Vascular access and extracorporeal circuit patency in continuous renal replacement therapy

array:23 ["pii" => "S0210569116302194" "issn" => "02105691" "doi" => "10.1016/j.medin.2016.09.011" "estado" => "S300" "fechaPublicacion" => "2016-12-01" "aid" => "987" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "copyrightAnyo" => "2016" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2016;40:572-85" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6157 "formatos" => array:3 [ "EPUB" => 164 "HTML" => 4866 "PDF" => 1127 ] ] "itemSiguiente" => array:17 [ "pii" => "S0210569116300663" "issn" => "02105691" "doi" => "10.1016/j.medin.2016.04.010" "estado" => "S300" "fechaPublicacion" => "2016-12-01" "aid" => "930" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2016;40:586-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3745 "formatos" => array:3 [ "EPUB" => 161 "HTML" => 2636 "PDF" => 948 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "Point of view" "titulo" => "Antimicrobial stewardship programs in the critical care setting" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "586" "paginaFinal" => "589" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Programas de administración de antimicrobianos en la unidad de cuidados intensivos" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2270 "Ancho" => 3325 "Tamanyo" => 303230 ] ] "descripcion" => array:1 [ "en" => "Antimicrobial stewardship program operating strategy." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Ruiz-Ramos, P. Ramirez" "autores" => array:2 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Ruiz-Ramos" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Ramirez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116300663?idApp=WMIE" "url" => "/02105691/0000004000000009/v1_201612020641/S0210569116300663/v1_201612020641/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0210569116301759" "issn" => "02105691" "doi" => "10.1016/j.medin.2016.07.009" "estado" => "S300" "fechaPublicacion" => "2016-12-01" "aid" => "965" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Med Intensiva. 2016;40:560-71" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5075 "formatos" => array:3 [ "EPUB" => 172 "HTML" => 3758 "PDF" => 1145 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Ultrasound-guided vascular cannulation in critical care patients: A practical review" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "560" "paginaFinal" => "571" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Canulación vascular eco-dirigida en pacientes críticos: una revisión práctica" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0035" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1603 "Ancho" => 3000 "Tamanyo" => 508164 ] ] "descripcion" => array:1 [ "en" => "US mapping before cannulation. (A) Patent vein, confirmed by full compressibility (arrows); (B) thrombosed common femoral vein, clearly seen enlarged and occupied by a large thrombus (t); a: common femoral artery. (C) vein valve; v: vein; (D) optimal vein diameter for central venous cannulation; (E) optimal vein diameter and distance from skin to vein for peripheral vein cannulation; (F) artery with two calcified atheromatous plaques (calipers)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. Blanco" "autores" => array:1 [ 0 => array:2 [ "nombre" => "P." "apellidos" => "Blanco" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173572716300601" "doi" => "10.1016/j.medine.2016.07.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572716300601?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116301759?idApp=WMIE" "url" => "/02105691/0000004000000009/v1_201612020641/S0210569116301759/v1_201612020641/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "Update in Intensive Care: Acute Kidney Injury" "titulo" => "Vascular access and extracorporeal circuit patency in continuous renal replacement therapy" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "572" "paginaFinal" => "585" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "F.J. González de Molina, M. Galindo, C. González, M.J. Broch, L. del Baño, A. Roglan" "autores" => array:6 [ 0 => array:4 [ "nombre" => "F.J." "apellidos" => "González de Molina" "email" => array:1 [ 0 => "fgonzalez@mutuaterrassa.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Galindo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "M.J." "apellidos" => "Broch" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "L." "apellidos" => "del Baño" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "A." "apellidos" => "Roglan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Intensiva, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Medicina Intensiva, Hospital Universitario Santa Lucía, Cartagena Murcia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Santander, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Medicina Intensiva, Hospital Universitari i Politécnic la Fe, Valencia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Medicina Intensiva, Hospital Morales Meseguer, Murcia, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Medicina Intensiva, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Acceso vascular y permeabilidad de los circuitos extracorpóreos en las técnicas de depuración renal continua" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1823 "Ancho" => 3337 "Tamanyo" => 359526 ] ] "descripcion" => array:1 [ "en" => "Algorithm for anticoagulation strategies in CRRT." ] ] ] "textoCompleto" => "IntroductionIn continuous renal replacement therapy (CRRT), the contact of blood with the extracorporeal circuit activates both the intrinsic and extrinsic pathways of plasma coagulation and of the platelets, leading to thrombin production, platelet aggregation, thrombus formation, and fibrin deposition. For these reasons, anticoagulation is necessary in CRRT to prevent clotting of the circuit and to maintain the permeability of the membrane to ensure appropriate daily dosing of the technique. The volume of blood circulating in the extracorporeal circuit ranges from 150ml to 250ml, depending on the surface area of the hemofilter. Repeated clotting without the possibility of blood return results in significant blood loss leading to anemia and multiple transfusions. Time in which the technique is interrupted (downtime) reduces the total dose administered respect to the prescribed dose, increases nursing workload, and increases costs. Catheter dysfunction is a common cause of circuit clotting. Choosing the right catheter and vascular access is fundamental to ensure adequate circuit function. This article reviews different strategies to prolong the patency of the circuit, discussing non-pharmacological strategies and the different anticoagulants used in CRRT, including unfractionated heparin, low-molecular-weight heparin, citrate, thrombin inhibitors, and platelet aggregation inhibitors.Vascular access for continuous renal replacement therapiesThe treatment of acute kidney failure with CRRT requires temporary vascular access. In the early days, CRRT used arteriovenous techniques, but these have been supplanted by venovenous techniques through double-lumen dialysis catheters. Despite the high quality of current catheters, catheters play a role in a high proportion of increased morbidity from CRRT due to complications during insertion, dysfunction (stenosis and/or thrombosis), and infection. The ideal catheter should be rapidly and easily accessible, should enable adequate flow, should be long lasting, and should keep complications to the minimum. This review will discuss the characteristics of catheters, the site and method of inserting them, and their complications.Characteristics of cathetersCatheters can be characterized by their geometry, material, inner diameter, and length. Geometry: The catheters used nowadays have a double lumen with or without separate distal tips. The proximal lumen is used for the access line and the distal lumen is used for the return line. One of the problems with these catheters is recirculation (the mixing of access and return blood), which decreases the effectiveness of the technique. Increasing the distance (2–3cm) between the access lumen and the return lumen and a design with lateral holes, both help to reduce recirculation.<a class="elsevierStyleCrossRef" href="#bib0405">1</a> The lumen of the catheter can have different designs (coaxial, split, double D, double O), although this does not seems to significantly influence the life of the circuit.<a class="elsevierStyleCrossRef" href="#bib0410">2</a>Materials: Nowadays polyurethane and silicone are used; both these materials are very flexible and cause little damage to the vessel wall. In critical patients, polyurethane is more common. Polyurethane catheters can last for several weeks; their main complication is thrombosis. Silicone catheters are used for long-term dialysis, usually with subcutaneous tunneling; this method of canalization makes them longer lasting (they can even last for months) and less prone to infection. Diameter: The inner diameter of a catheter determines how much blood can flow through it. Catheter diameter is usually measured in French (F) units, with 11–14F being the most appropriate for CRRT.<a class="elsevierStyleCrossRef" href="#bib0415">3</a>Length: The length of the catheter to be placed depends on the blood vessel used for the approach. If placed in the superior vena cava system through the jugular vein or right subclavian vein, it should measure 15–18cm. If placed in the inferior vena cava system through the femoral vein, it should measure 24–28cm3.Insertion and siteVenous accesses used for CRRT in critical patients should be easy and quick to insert as they are usually canalized at the bedside during the ICU stay. The catheter must be inserted under conditions of maximum asepsis, normally using percutaneous canalization or the Seldinger technique. Unlike chronic dialysis, CRRT for acute kidney failure in critical patients normally does not last for more than two weeks.<a class="elsevierStyleCrossRef" href="#bib0420">4</a> For this reason, the guidelines developed through the initiative Kidney Disease: Improving Global Outcomes (KDIGO)<a class="elsevierStyleCrossRef" href="#bib0425">5</a> recommend placing nontunneled catheters initially, and then replacing them with tunneled catheters if dialysis must be prolonged or if the patient requires frequent changes in venous access.<a class="elsevierStyleCrossRef" href="#bib0425">5</a> The choice of insertion site must aim to reduce complications such as infection, thrombosis, stenosis, and catheter malfunctioning. The most common sites of insertion are the femoral vein, internal jugular vein, and subclavian vein. Whether the right internal jugular or the femoral vein should be the first choice is a matter of controversy. The KDIGO<a class="elsevierStyleCrossRef" href="#bib0425">5</a> and the European Renal Best Practice (ERBP) of the European Dialysis Association<a class="elsevierStyleCrossRef" href="#bib0430">6</a> recommended avoiding femoral access when jugular access is available due to a supposed increased risk of infection. However, several studies, all of which were observational, have yielded discrepant results regarding the incidence of complications between femoral and jugular access,<a class="elsevierStyleCrossRefs" href="#bib0435">7–9</a> so the choice of insertion site remains a matter of individual preference, given the low level of scientific evidence. In 2008, the Cathedia study was published.<a class="elsevierStyleCrossRef" href="#bib0450">10</a> This prospective randomized multicenter trial comparing access through the femoral and internal jugular veins in critical patients undergoing CRRT found that canalization through the internal jugular vein did not reduce the risk of infection compared with femoral canalization except in patients with a high body mass index. In 2012, the same group published a study<a class="elsevierStyleCrossRef" href="#bib0455">11</a> with the patients in the Cathedia study who had required a second catheter in a site different from the first one. They found no differences between the two sites in catheter malfunction, colonization, or the efficacy of dialysis. In 2014, a single-center observational study evaluating 419 femoral catheters and 82 in other sites found that the rates of colonization and infection were similar, and the risk of infection was related to longer ICU stays, older age, and obesity.<a class="elsevierStyleCrossRef" href="#bib0460">12</a> In 2016, Bellomo et al.<a class="elsevierStyleCrossRef" href="#bib0465">13</a> analyzed the information about catheters obtained from the RENAL study,<a class="elsevierStyleCrossRef" href="#bib0420">4</a> in which 1508 patients were randomized and information about the catheter was available for 1399 (93%). The femoral vein (especially the right) was chosen in 937 (67%) patients, followed by the jugular (25%) and the subclavian (8%). The patients in whom the femoral vein was chosen had more severe disease and weighed less. The impact of the insertion site on the dose of treatment was limited, unlike the impact of catheter diameter, which was greater in femoral catheterizations than catheterizations in other sites. The authors concluded that the diameter of the catheter was more important for treatment dose than the site of catheterization.The left jugular vein follows a tortuous course toward the right atrium, and this can result in inadequate flow and filter malfunction; for this reason, this insertion site should be considered only after the right jugular and femoral veins.<a class="elsevierStyleCrossRef" href="#bib0415">3</a> The subclavian vein would be the last choice because it is prone to stenosis that would make it impossible to create an arteriovenous fistula if chronic dialysis were necessary.<a class="elsevierStyleCrossRef" href="#bib0415">3</a> Likewise, the possibility of stenosis of the iliac vein means that the femoral vein should be avoided if the patient might need a kidney transplant.Ultrasound guidance for central venous catheter placement has been recommended for years. The advantages are fewer complications such as bleeding, pneumothorax, and arterial wall puncture; moreover, ultrasound guidance makes it possible to avoid cannulation in thrombotic regions, reduces the incidence of catheter-related thrombosis, and results in lower costs by reducing the iatrogenic effects associated with blind insertion.<a class="elsevierStyleCrossRef" href="#bib0470">14</a>ComplicationsThe mechanical complications of catheter insertion include hematomas, pseudoaneurysms, vascular dissection, and arterial puncture; these complications occur in up to 5% of insertions. Other, less common complications include hemothorax, pneumothorax, pneumopericardium, retroperitoneal bleeding, tracheal puncture, chylothorax, anesthetic blockade of the brachial plexus, fat emboli, cardiac arrhythmias, and atrial rupture.<a class="elsevierStyleCrossRef" href="#bib0475">15</a> Chest X-rays are mandatory after catheter insertion in the jugular vein or subclavian vein. While the catheter is in use, the main complications are malfunctioning, thrombosis, and infection. Malfunction and thrombosis: These complications are caused by intraluminal thrombosis, catheter kinking, or malpositioning with occlusion of the catheter holes against the vessel wall. Malfunction manifests as increased pressure in the venous and arterial lines that results in inadequate treatment. Polyurethane catheters are more prone to thrombosis. The catheters are often sealed with heparin when not in use. One recent study comparing sealing with heparin versus sealing with citrate found that citrate was better at restoring flow to obstructed catheters and had a lower incidence of infection and hemorrhagic complications. Infection: Infection results from the contamination of the catheter lumen from the skin and its entrance into the blood flow or even from the hematogenous dissemination of pathogens from other foci of infection. The most common germs are coagulase negative Staphylococci and Staphylococcus aureus follow by gram-negative bacilli (particularly Pseudomonas aeruginosa). The incidence ranges from 3.8 to 6.6 episodes per 1000 days for nontunneled catheters and 1.6 to 5.5 episodes per 1000 days for tunneled catheters.<a class="elsevierStyleCrossRef" href="#bib0480">16</a> As for any other catheter, the risk factors for bacteremia are the frequency of catheter manipulation, the patient's severity, emergency insertion, the time the catheter remains in place, and the operator's experience. Various studies mentioned above have failed to show a higher incidence of infection in femoral catheters compared to jugular catheters. Among the fundamental measures to prevent infection, the most important are extreme asepsis during insertion, ultrasound guidance for insertion, keeping manipulation to a minimum (exclusive use for dialysis), and appropriate training for staff. The administration of local antibiotics to prevent infection is currently not recommended because it can favor fungal infection and resistance to antibiotics.<a class="elsevierStyleCrossRef" href="#bib0425">5</a>Optimization of patency in CRRT circuitsMaintaining the patency of the circuit during CRRT usually requires a pharmacological anticoagulation strategy. The ideal anticoagulant should have the following properties: (a) high antithrombotic potential with low risk of bleeding, (b) anticoagulation limited to the extracorporeal circuit, (c) quick and easy monitoring at the point of care, (d) possibility of prolonged use without undesired secondary effects, accumulation, or tachyphylaxis, and (e) an antidote that can reverse the effects immediately. Below we present the different strategies for optimizing the patency of the CRRT circuits (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Non-pharmacological strategiesIt is important for the CRRT to incorporate biocompatible materials and to be designed in way that limits the turbulent flow of blood. The biocompatibility of the membrane is especially important for preventing hemofilter coagulation. Negatively charged membranes have a greater capacity for adsorption of proteins and formed elements of blood, so they might not last as long as neutral membranes. Hemofilters with larger membrane surfaces present less resistance to blood flow, and this may also help them to last longer. Moreover, clotting is more likely to occur when blood flow through the circuit is interrupted or is slower. Other measures that favor the rheology of the circuit include prescribing a filtration fraction <25% in convection techniques, prioritizing diffusion rather than convection, and predilution to limit the concentration of blood in the filter by reducing the viscosity of the blood. The response to alarms must be rapid. The correct adjustment of the level in the bubble-trapping capsule can reduce the effect of contact between blood and air and minimize the risk of coagulation at this point. Establishing a protocol for the technique and ensuring that nursing staff are highly trained guarantee the best outcomes. The intermittent infusion of saline solution has not proven beneficial in prolonging the life of the circuit. Finally, as discussed above, it is very important to choose the best vascular access and the catheter with the best characteristics to ensure the correct flow of blood through the circuit and keep it from coagulating.<a class="elsevierStyleCrossRefs" href="#bib0485">17,18</a>We also need to consider situations in which the circuit will not require any type of anticoagulation, such as coagulopathies or platelet abnormalities. There are no studies that can establish evidence for specific cutoffs for determining the platelet count, activated partial thromboplastin time (aPTT), International Normalized Ratio (INR), fibrinogen, or other coagulation factors that would indicate the possibility of carrying out CRRT without anticoagulation. In recent years, experts have recommended the following values: thrombocytopenia with platelet count <50×109/L, aPTT >60s, INR >2, and disseminated intravascular coagulation. Similarly, patients with acute kidney failure who require systemic anticoagulation for their underlying disease (e.g., valve replacement, atrial fibrillation, or thromboembolic disease) do not usually require additional anticoagulation for CRRT.Pharmacological strategiesAnticoagulation for CRRT circuits with heparinIn 2007, the Beginning and Ending Supportive Therapy for the Kidney (B.E.S.T. kidney) investigators showed that up to 60% of CRRT procedures were done without any type of anticoagulation. When anticoagulation was prescribed, unfractionated heparin was the most commonly used.<a class="elsevierStyleCrossRef" href="#bib0495">19</a> In Spain, a survey done in 51 ICUs confirmed that 96% of the centers used heparin, 39.2% used prostacyclin, and only 5.8% used citrate.<a class="elsevierStyleCrossRef" href="#bib0500">20</a>Unfractionated heparinThis mixture of sulfated polysaccharides with molecular weights varying between 2kDa and 30kDa is the anticoagulant most commonly used in CRRT. Unfractionated heparin achieves its anticoagulant effect by bonding with antithrombin, favoring its bonding with thrombin (FII), and to a lesser extent by inhibiting activated factor X. To inhibit thrombin, it must bind both with thrombin itself and with antithrombin, although it does not need to bind with antithrombin to inhibit activated factor X. Its half-life ranges from 30min to up to 3h in cases with renal dysfunction. Its major advantages are (a) it is inexpensive; (b) prescribing physicians and the nurses in charge of the procedure are familiar with it; (c) it is easy to administer and to monitor (through aPTT); and (d) its effects can be reversed with protamine. There is no universally accepted protocol for its use, although various algorithms have been proposed for its administration during CRRT.<a class="elsevierStyleCrossRef" href="#bib0505">21</a> It is usually present in the solution primed from the system in variable concentrations (1000–5000IU per liter). Before connection to CRRT and after the evaluation of the patient's coagulation, a bolus (30IU/kg body weight) is usually administered through the arterial line; the recommended maintenance dose is 5–10IU/kg/h.The main problems associated with heparin are its dosing, bleeding, resistance, and heparin-induced thrombocytopenia. The problem with dosing heparin is that there is no direct relation between the dose of heparin and the aPTT, the duration of the filter, or hemorrhagic complications. Dosage is monitored through the aPTT, targeting levels between 1.5 and 2.0 times the baseline value (45–60s). The dose must be reduced drastically in patients with disseminated intravascular coagulation or thrombocytopenia. Every increase of 10s in the aPTT causes a 25% decrease in clots in the filter. The values of aPTT are partly dependent on the levels of coagulation factors associated with critical illness such as the variable clearing that the heparin itself undergoes when it is administered before filtering. Hemorrhagic events are the most common complication, affecting 10–50% of cases, depending on the type of population and the degree of anticoagulation.<a class="elsevierStyleCrossRef" href="#bib0510">22</a> Hemorrhagic complications are not strictly related to the dose of heparin administered, but they are strictly related to the aPTT. The risk of bleeding increases by 50% for each increment of 10s in the aPTT. The incidence of bleeding complications is underestimated because minor events often go unreported; major bleeding events are defined as intracranial hemorrhage, retroperitoneal hemorrhage, or hemorrhages that result in death or the transfusion of ≥2 units of packed red blood cells.Resistance to heparin is based on two pillars: (a) On the one hand, low levels of antithrombin III (AT-III), because this protein is consumed when the sepsis coagulation cascade is activated, and greater proteolytic degradation mediated by granulocyte elastase, the effect of which is increased by heparin itself. (b) On the other hand, the expression of heparin-binding proteins decreases heparin's effective concentration and thereby its anticoagulant effect.<a class="elsevierStyleCrossRef" href="#bib0515">23</a> Some centers opt for the administration of AT-III to favor anticoagulation and the durability of the circuit, but the cost-effectiveness remains to be determined. Acquired AT-III deficiency (AT-III <70%) can be supplemented by an initial bolus [AT-III bolus=Weight×(100−initial AT-III activity %)/1.5], following a continuous infusion (40UI/kg/d). The doses should be secondarily adjusted to maintain an AT-III activity level between 80% and 100%.<a class="elsevierStyleCrossRef" href="#bib0520">24</a>The incidence of heparin-induced thrombocytopenia (HIT) in ICU patients is very low, ranging from 0.3% to 0.5%.<a class="elsevierStyleCrossRef" href="#bib0525">25</a> The frequency of HIT in critically ill patients receiving heparin anticoagulation for CRRT still remain to be determined in prospective studies.<a class="elsevierStyleCrossRefs" href="#bib0530">26,27</a> It is advisable to determine the levels of antibodies to heparin platelet factor 4 (H/PF4) after calculating the 4T score (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0540">28</a> The most susceptible patients are those with a decrease >50% on the fourth day of receiving heparin. HIT should not be confused with the reversible thrombocytopenia that occurs after CRRT is started and ends when CRRT is stopped.<a class="elsevierStyleCrossRef" href="#bib0530">26</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Low-molecular-weight heparineLow-molecular-weight heparins with 18 saccharide units have a lower molecular weight (3600–6500kDa) than unfractionated heparin; therefore, they cannot simultaneously bond to thrombin and antithrombin, so the antithrombin activity is lost but the anti-factor Xa activity is maintained. Low-molecular-weight heparins are more effective than unfractionated heparin at decreasing fibrin deposits in the filter, and they start to act faster, activating fewer platelets and leukocytes. They are less dependent on antithrombin, bond less with proteins and cells, cause less activation of platelet factor-4, and result in a lower incidence of heparin-induced thrombocytopenia.<a class="elsevierStyleCrossRef" href="#bib0545">29</a> These characteristics, together with more predictable pharmacokinetics, make low-molecular-weight heparins safer and more reliable. Nevertheless, they are more expensive than unfractionated heparin, and monitoring their effects is more complex – not all centers can routinely determine anti-factor Xa levels. The different molecules of low-molecular-weight heparins have distinct pharmacokinetics, which is not interchangeable with their counterparts. The bioavailability, half-life, or clearance in plasma and degree of accumulation in acute kidney failure can vary significantly among the different molecules. A recent systematic review<a class="elsevierStyleCrossRef" href="#bib0550">30</a> concluded than no accumulation effect occurred with tinzaparin and dalteparin, but significant accumulation effects occurred with enoxaparin, bemiparin, and certoparin, even at prophylactic doses. The range of anti-factor Xa for their use has not been defined and is extrapolated from intermittent dialysis (iHD) between 0.2IU/ml and 0.4IU/ml. Unlike in iHD, the studies done in acute patients undergoing CRRT were done a long time ago, included few patients, and had heterogeneous objectives and designs, so it is difficult to draw conclusions. Low-molecular-weight heparins have been compared with unfractionated heparin<a class="elsevierStyleCrossRefs" href="#bib0555">31,32</a>; different doses of low-molecular-weight heparins have been compared<a class="elsevierStyleCrossRef" href="#bib0565">33</a>; and different low-molecular-weight heparins have been compared with each other<a class="elsevierStyleCrossRef" href="#bib0570">34</a> and with different anticoagulation strategies.<a class="elsevierStyleCrossRef" href="#bib0575">35</a> Two recent studies comparing the incidence of bleeding and the duration of the filter between enoxaparin and unfractionated heparin reported contradictory results. Garcés et al.<a class="elsevierStyleCrossRef" href="#bib0560">32</a> found similar filter life and anti-factor Xa ≥1.0IU/ml with enoxaparin, although the incidence of bleeding was higher. On the other hand, in a prospective controlled randomized crossover trial, Joannidis et al.<a class="elsevierStyleCrossRef" href="#bib0555">31</a> with anti-factor Xa levels between 0.25IU/ml and 0.30IU/ml found that the low-molecular-weight heparins (0.15mg/kg pre-filter bolus and 0.05mg/kg/h maintenance perfusion) conferred longer filter life without increasing the incidence of bleeding and were also a cost-effective option. For all these reasons, it is difficult to interpret low-molecular-weight heparins for use in CRRT. Both the dose and the anti-factor Xa target must be tailored in function of the low-molecular-weight heparin chosen and the patient's clinical characteristics.Anticoagulation with heparin-protamine (regional heparinization)First reported in the 1960s, regional anticoagulation combines pre-filter unfractionated heparin and post-filter protamine to counteract its effects (1mg protamine/100IU heparin). Its main indication was for patients in whom systemic anticoagulation was contraindicated. Its use has declined in parallel with the rise of citrate and increased knowledge about the side effects of protamine. Regional heparinization exposes patients to the risk of heparin-induced thrombocytopenia and the dose-dependent side effects of protamine: hypotension decreased cardiac output, anaphylaxis, pulmonary vasoconstriction with the risk of right ventricular failure, leukopenia, and a paradoxical effect on coagulation. This paradoxical effect is due to transient thrombocytopenia as well as platelet dysfunction (lower reactivity and thrombin-mediated aggregation). There is also a risk of a rebound anticoagulation effect because the half-life of heparin is longer than that of protamine; this effect is dose dependent and increases slightly with prolonged administration. Heparin-protamine complexes are taken up by the reticuloendothelial system, which fractionates them, rereleasing the heparin. This makes it difficult to titrate the appropriate doses of protamine to reverse its effects. It is more complex to monitor because the aPTT must be measured before and after the administration of the heparin and after reversion with protamine. Protamine should not be used with heparin-lined filters because it reverses the effects of the heparin. For all these reasons, regional anticoagulation with heparin-protamine is not recommended.<a class="elsevierStyleCrossRef" href="#bib0580">36</a>Regional anticoagulation with citrateThis type of anticoagulation is based on the pre-filter administration of a fluid with a certain concentration of citrate. Citrate chelates with the calcium in the blood and forms a citrate-calcium complex, thus impeding the formation of clots because calcium is a cofactor necessary for the activation of the coagulation cascade. The chelated calcium that is lost in the circuit is later replaced to maintain the ionized calcium in the patient's serum at normal levels. Most of the citrate administered is also removed through the effluent. The amount of citrate that passes into the patient's bloodstream is metabolized through the Krebs cycle in the liver, muscle tissue, and renal cortex. Thus, the circuit is anticoagulated without affecting the patient's coagulation and the life of the hemofilter is significantly prolonged, minimizing the risk of bleeding.Regional anticoagulation with citrate has been in use in intermittent dialysis for more than 20 years, where it has reduced bleeding events in patients with a high risk of bleeding. In recent years, different manufacturers have incorporated software in their CRRT monitors to simplify the calculations necessary for the administration of citrate and to enable automatic calcium compensation. This advance, together with the commercialization of specific fluids for anticoagulation with citrate, has reduced the complexity of this approach, increased its safety, and decreased its cost.<a class="elsevierStyleCrossRefs" href="#bib0585">37,38</a> There is currently a wide consensus that regional anticoagulation with citrate should be the first-choice option for anticoagulation in patients with high risk of bleeding.<a class="elsevierStyleCrossRefs" href="#bib0510">22,39,40,5</a>The main complications of citrate are alterations in the acid–base balance, hypocalcemia, and hypercalcemia. In the patient's body, the citrate–calcium complex is metabolized mainly in the liver, but the kidneys and skeletal muscle also contribute. Citrate is converted into sodium bicarbonate (1mmol of citrate is converted into 3mmol sodium bicarbonate), so the net result of the metabolism of the citrate–calcium complex is the incorporation of an alkali (sodium bicarbonate), which affects the acid–base balance. Hypocalcemia can result from insufficient replacement of the calcium that is chelated by the citrate, and hypercalcemia can result from excessive replacement (whether due to error or inadvertently maintaining continuous calcium infusion after suspending anticoagulation with citrate). Citrate also chelates magnesium, so magnesium levels must be closely monitored and supplemented to avoid hypomagnesemia. If the administration of citrate is excessive and the patient can metabolize it, the immediate consequences are hypernatremia and metabolic alkalosis.Citrate intoxication occurs when the patient cannot metabolize the citrate administered; this occurs in ischemic hepatitis (even before it is reflected in increased liver enzymes) or in decreased hepatic blood flow or severe peripheral hypoperfusion (cardiogenic shock and/or septic shock). It has been suggested that regional anticoagulation with citrate might be contraindicated in these patients. In this case, we would observe metabolic acidosis (with high anion gap) and a steep drop in the levels of ionic calcium in a patient with high total calcium, hypophosphatemia, and hypomagnesemia. The gold standard for the diagnosis for this complication is the direct measurement of the concentration of citrate in plasma; however, this determination is not usually available in daily practice. The laboratory determination used instead is the ratio of total calcium to ionic calcium. The normal value of this ratio is 2 (total calcium is normally the double of ionic calcium) and values ≥2.5 indicate intoxication. In these patients, the classical liver function parameters such as the transaminases and bilirubin are poor predictors of the development of citrate intoxication; the best predictors of this complication are serum lactate (≥3.4mmol/l) and prothrombin time (≤26% or ≥33s).<a class="elsevierStyleCrossRef" href="#bib0605">41</a> An increasing number of publications show adequate tolerance to anticoagulation with citrate in patients with compensated cirrhosis of the liver or acute liver failure<a class="elsevierStyleCrossRefs" href="#bib0600">40,42,43</a> since these patients do not have more metabolic complications. More frequent monitoring (every 4h) and higher target ranges of ionized calcium in the circuit (0.3–0.5mmol/l) are necessary to guarantee patient safety. This strategy is able to guarantee acceptable filter life by decreasing the contribution of citrate and the risk of intoxication.<a class="elsevierStyleCrossRef" href="#bib0620">44</a>We can conclude that there are no absolute contraindications for the use of citrate, although it must be employed with particular caution in clinical contexts characterized by severe liver failure/liver transplant or in situations of severe lactic acidosis secondary to hepatic hypoperfusion and severe intracellular hypoxia (septic or cardiogenic shock).Studies that compare citrate with other modalitiesThere is a growing body of literature to support favorable results for regional anticoagulation with citrate in CRRT. The strong points of this approach versus other anticoagulation strategies are the increased life of the filter and the decreased number of hemorrhagic complications. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows some of the most relevant and most recent studies that compare regional anticoagulation with citrate against other anticoagulation strategies.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Oudemans et al.<a class="elsevierStyleCrossRef" href="#bib0625">45</a> did a comparative analysis of the large randomized multicenter studies published through 2014 (CASH<a class="elsevierStyleCrossRef" href="#bib0630">46</a> from 2014, OVLG<a class="elsevierStyleCrossRef" href="#bib0635">47</a> from 2009, and Hetzel<a class="elsevierStyleCrossRef" href="#bib0640">48</a> from 2011). In the CASH study<a class="elsevierStyleCrossRef" href="#bib0630">46</a> citrate was compared to systemic anticoagulation with heparin in 139 patients. No differences were found in mortality or in recovery of renal function, but citrate was superior in terms of safety (fewer adverse effects, p<0.001), efficacy (longer filter life, p=0.02), and costs (p<0.001). The OLVG study<a class="elsevierStyleCrossRef" href="#bib0635">47</a> compared citrate with nadroparin in 200 patients. The efficacy of the two drugs was similar, but citrate was safer (fewer complications, p<0.001). In a secondary analysis in subgroups, citrate was particularly beneficial after surgery and in sepsis with multiple organ failure, where renal recovery and mortality were improved. The improved survival was attributed to a possible immunomodulating effect of citrate. This hypothesis is supported by experimental data showing that anticoagulation with citrate impedes the degranulation of polymorphonuclear leukocytes and the activation of thrombocytes induced by dialysis; these processes depend on ionic calcium and are blocked by the administration of citrate.<a class="elsevierStyleCrossRefs" href="#bib0645">49,50</a> In the Hetzel study,<a class="elsevierStyleCrossRef" href="#bib0640">48</a> citrate was compared against systemic heparin in 170 patients. No significant differences were found in the number of alterations in the acid–base balance or in the reduction of the levels of urea. The group that received citrate had longer filter life and a lower risk of bleeding. No differences in 30-day mortality were found. Hafner et al.<a class="elsevierStyleCrossRef" href="#bib0655">51</a> also compared citrate against systemic heparin. Both modalities were effective in controlling uremia, although the reduction in urea was larger in the citrate group; the authors attributed this difference to longer hemofilter life. The citrate group had slight alterations in the levels of pH, ionic calcium, and sodium; however, these alterations were not associated with adverse events and were all successfully resolved by modifying fluids according to protocol. In the economic analysis, citrate was cost-effective. In a meta-analysis of six randomized controlled trials with a total of 488 patients, Wu et al.<a class="elsevierStyleCrossRef" href="#bib0660">52</a> found that patients receiving citrate had a lower risk of bleeding without an increased incidence of alkalosis compared to patients in whom the circuits were anticoagulated with heparin. The efficacy and filter life were similar in the two groups. The authors concluded that citrate is at least as safe as heparin and significantly cheaper. Gattas et al.<a class="elsevierStyleCrossRef" href="#bib0665">53</a> recently carried out a prospective randomized multicenter trial comparing citrate versus heparin-protamine in 212 patients. The results showed longer filter lifespan and fewer adverse events in the citrate group. There were no differences in the number of transfusions, the duration of CRRT, length of stay, or mortality. There were also no differences in cytokine levels. Stucker et al.<a class="elsevierStyleCrossRef" href="#bib0670">54</a> found that citrate was superior to heparin as a method of anticoagulation in terms of dose and filter lifespan. Alterations in electrolytes and acid–base balance in the citrate group were uncommon, short-lived, and preventable with a strict protocol. There were no differences in short-term survival. Bai et al.<a class="elsevierStyleCrossRef" href="#bib0675">55</a> recently published a meta-analysis including the randomized controlled trials that compared heparin versus citrate in CRRT. The meta-analysis included a total of 992 patients in 11 studies; two of these used regional heparinization, and the rest used systemic heparinization. In the citrate group, there was a significant reduction in the risk of circuit loss and filter failure compared to the groups receiving regional heparinization or systemic heparinization. The risk of bleeding in the citrate group was significantly lower than in the systemic heparinization group and similar to that observed in the regional heparinization group. No differences were observed in survival. These authors concluded that given the low risk of circuit loss and filter failure, regional anticoagulation with citrate should be considered a better method of anticoagulation than heparin in critical patients without contraindications.In summary, regional anticoagulation with citrate can be considered efficacious and safer than anticoagulation with heparin. Citrate is associated with increased hemofilter lifespan and a lower risk of bleeding and multiple transfusions. Regional anticoagulation with citrate administered under strict protocols by properly trained staff is not associated with significant adverse events. More economic studies are necessary to evaluate its cost-effectiveness. The anti-inflammatory effects of citrate during CRRT and its impact on survival are controversial and should be evaluated in future studies.Thrombin inhibitorsDirect thrombin inhibitors (lepirudin, argatroban, bivalidurin) have proven efficacy as anticoagulants in critical patients with heparin-induced thrombocytopenia. However, most of the studies that support their use in CRRT are limited, retrospective, observational, and small. Heparin-induced thrombocytopenia results from the formation of antibodies against the heparin-platelet factor 4 complex, which secondarily activates the platelets and coagulation and eventually leads to increased thrombin formation.<a class="elsevierStyleCrossRef" href="#bib0680">56</a> The probability of heparin-induced thrombocytopenia can be predicted with the 4T score, which includes the degree of thrombocytopenia, time since the onset of the drop in platelet levels, presence of thrombosis or acute systemic symptoms, and presence of other causes of thrombocytopenia. Although the incidence of this complication in critical patients is low (0.3–0.5%),<a class="elsevierStyleCrossRef" href="#bib0525">25</a> it is associated with increased morbidity and mortality if its diagnosis is delayed, due to the prothrombotic situation it generates. In patients undergoing CRRT, heparin-induced thrombocytopenia can be suspected when the circuit becomes clotted early and repeatedly, even when citrate is used.<a class="elsevierStyleCrossRefs" href="#bib0685">57,58</a> Suspicion of heparin-induced thrombocytopenia requires treatment with heparin or heparin derivatives to be discontinued. No randomized studies have indicated the optimal anticoagulant in cases of heparin-induced thrombocytopenia. This choice will depend on local availability and experience in monitoring. Although citrate can be used for regional anticoagulation, these patients need thromboprophylaxis. These drugs inhibit free thrombin and thrombin bound in thrombi, and they do not react with antibodies against heparin. There are important differences in the pharmacokinetics of the three most studied direct thrombin inhibitors, and these are explained here below.LepirudinThis drug is metabolized by the kidneys. In patients with acute kidney failure, the half-life can be prolonged up to 50h, with the risk of the drug accumulating and increasing the risk of bleeding.<a class="elsevierStyleCrossRef" href="#bib0695">59</a> It is usually monitored through the aPTT, although the relationship between the levels of lepirudin and the aPTT is not linear. The most accurate test is ecarin clotting time, but this test is not available in all centers. Some cases of anaphylaxis have been reported. Lepirudin is perfused intravenously (0.005–0.01mg/kg/h) and the dose is adjusted in function of the time to ecarin clotting.<a class="elsevierStyleCrossRef" href="#bib0700">60</a> There is no specific antidote, but factor VIIa can be used in case of bleeding.<a class="elsevierStyleCrossRef" href="#bib0705">61</a> In 2014, Treschan et al.<a class="elsevierStyleCrossRef" href="#bib0710">62</a> published the results of a randomized double-blind study (ALicia) comparing lepirudin and argatroban in 28 critical postoperative patients with suspected heparin-induced thrombocytopenia and need for CRRT. The two drugs were equally efficacious in terms of circuit survival, but the lepirudin group had more episodes of bleeding.ArgatrobanA derivative of l-arginine, argatroban bonds reversibly to the catalytic site of thrombin without the need for a cofactor. It is metabolized by the liver (70%) and has a short half-life (31–59min), so it may be appropriate for critical patients with acute kidney failure without liver failure who need CRRT.<a class="elsevierStyleCrossRef" href="#bib0715">63</a> The recommended dose, based on a prospective study of 30 patients with heparin-induced thrombocytopenia, acute kidney failure, and CRRT, is a bolus of 100μg/kg followed by the perfusion of 1μg/kg/min; the dose is adjusted to reach a target pre-filter aPTT of 1.5–3 times the baseline level.<a class="elsevierStyleCrossRef" href="#bib0695">59</a> In patients with liver dysfunction, the half-life of the drug increased, making it necessary to reduce the dose, as in patients with multiple organ dysfunction (0.2–0.6μg/kg/min). There was an inversely proportional relation between the maintenance dose and severity scales; the closest correlation was with the Sequential Organ Failure Assessment (SOFA) (r=−90, p<0.001, dose μg/kg/min=2.18–0.09×SOFA).<a class="elsevierStyleCrossRef" href="#bib0695">59</a> Argatroban brought about an increase in filter lifespan comparable to that achieved with unfractionated heparin, but argatroban did not increase the risk of bleeding after heart surgery.<a class="elsevierStyleCrossRef" href="#bib0720">64</a> There is no specific antidote for argatroban, but an ex vivo study showed that factor VIIa can be used in cases of bleeding.<a class="elsevierStyleCrossRef" href="#bib0705">61</a> The KDIGO guidelines recommend using argatroban during CRRT before other thrombin inhibitors or factor Xa inhibitors in patients with heparin-induced thrombocytopenia that do not have severe liver failure.<a class="elsevierStyleCrossRef" href="#bib0425">5</a>BivalidurinBivalidurin reversibly inhibits thrombin. It has a short half-life (25min) and has the additional advantage over argatroban that its metabolism is enzymatic, so it can be used in patients with heparin-induced thrombocytopenia who have hepatic and renal dysfunction. Although the prescribing information does not list this indication, retrospective studies with few patients on the efficacy, safety, and dosing in these patients have shown good results.<a class="elsevierStyleCrossRef" href="#bib0725">65</a> The dose in patients on CRRT is 0.03–0.05mg/kg/h, which is adjusted in function of the pre-filter aPTT (1.5–2.5 times the baseline level). One prospective randomized double-blind study in 10 patients showed that the lifespan of the hemofilter was prolonged significantly compared to unfractionated heparin and to no anticoagulation.<a class="elsevierStyleCrossRef" href="#bib0730">66</a> Although no specific antidote is available, in cases with bleeding, factor VIIa can be administered.<a class="elsevierStyleCrossRef" href="#bib0705">61</a>Platelet aggregation inhibitorsProstacyclin (PGI2) is derived from the arachidonic acid in the vascular tissues and inhibits the final pathway of all mechanisms of cellular activation that lead to the adhesion, activation, liberation, and aggregation of the platelets. This effect is mediated by an increase in the intracellular levels of cyclic adenosine monophosphate (cAMP) secondary to the activation of the membrane's specific adenyl cyclase receptors.<a class="elsevierStyleCrossRef" href="#bib0735">67</a>EpoprostenolThe vasodilatory effects of this drug are short lasting (half-life 2min) whereas its antiplatelet effects last longer (2h). Some studies have analyzed the use of prostacyclin alone<a class="elsevierStyleCrossRefs" href="#bib0740">68,69</a> or combined with unfractionated heparin. The lifespan of the circuits was longer when it was used with unfractionated heparin (PGI2 4–5ng/kg/min with 2–3IU/kg/h unfractionated heparin).<a class="elsevierStyleCrossRef" href="#bib0750">70</a> Herrera et al.<a class="elsevierStyleCrossRef" href="#bib0755">71</a> reported that circuit lifespan was similar with epoprostenol and unfractionated heparin but the risk of bleeding with epoprostenol was lower. Hemodynamic instability was the most common adverse effect associated with PGI2, and it was directly related to the dose used. The main drawback is the risk of arterial hypotension, and this can be minimized by progressively increasing the dose. The cost has come down since a generic version of this drug became available.NafamostatNafamostat, a prostacyclin analog, is a synthetic serine protease inhibitor that inhibits various coagulation factors (thrombin, factor Xa, factor XIIa, kallikrein) and components of the complement system, as well as platelet aggregation. It has a low molecular weight and a short half-life (5–8min). It is eliminated through the circuit, limiting systemic anticoagulation and lowering the risk of bleeding. Few data (only from Japan and Korea) are available about its use in CRRT because it is not available in the United States or Europe. Retrospective<a class="elsevierStyleCrossRef" href="#bib0760">72</a> and prospective<a class="elsevierStyleCrossRef" href="#bib0765">73</a> studies have demonstrated the efficacy and safety of nafamostat (fewer bleeding episodes and transfusions). However, Baek et al.<a class="elsevierStyleCrossRef" href="#bib0760">72</a> founder longer filter lifespan without anticoagulation than with nafamostat (27.5 vs. 19.8h), and Lee et al.<a class="elsevierStyleCrossRef" href="#bib0765">73</a> found a nonsignificant trend toward longer circuit lifespan with nafamostat than with no anticoagulation. Moreover, significant secondary effects such as anaphylaxis, agranulocytosis, and hyperkalemia have been reported.Finally in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> are summarized the main key points of this review about vascular access and circuit patency in continuous renal replacement therapy.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>ConclusionsVascular access placement and filter patency (anticoagulation) is a fundamental issue strictly related to dialysis delivery and should be carefully evaluated for each patient and CRRT modalities. Non-tunneled polyurethane catheters with a double lumen are the appropriate vascular access for CRRT in acute kidney failure. The vein used for the catheter insertion should be chosen taking into account the patients’ clinical characteristics. The catheter should be placed under ultrasound guidance and with adherence to infection-control policies. Citrate anticoagulation may be used for all patients without contraindications. Heparin as a first choice is still feasible in patients without high risk of bleeding, especially for units with less or no experience in citrate anticoagulation. In patients with heparin-induced thrombocytopenia, the administration of thrombin inhibitors (argatroban) or factor Xa inhibitors (danaparoid or fondaparinux) is highly recommended. The evidence available about the safety and efficacy of thrombin inhibitors and platelet aggregation inhibitors is insufficient to recommend their use in routine practice.FundingThere has been no funding for the realization of this writing.Conflict of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:3 [ "identificador" => "sec0010" "titulo" => "Vascular access for continuous renal replacement therapies" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Characteristics of catheters" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Insertion and site" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Complications" ] ] ] 2 => array:3 [ "identificador" => "sec0030" "titulo" => "Optimization of patency in CRRT circuits" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Non-pharmacological strategies" ] 1 => array:3 [ "identificador" => "sec0040" "titulo" => "Pharmacological strategies" "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0045" "titulo" => "Anticoagulation for CRRT circuits with heparin" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Unfractionated heparin" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Low-molecular-weight heparine" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Anticoagulation with heparin-protamine (regional heparinization)" ] ] ] 1 => array:3 [ "identificador" => "sec0065" "titulo" => "Regional anticoagulation with citrate" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Studies that compare citrate with other modalities" ] ] ] 2 => array:3 [ "identificador" => "sec0075" "titulo" => "Thrombin inhibitors" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Lepirudin" ] 1 => array:2 [ "identificador" => "sec0085" "titulo" => "Argatroban" ] 2 => array:2 [ "identificador" => "sec0090" "titulo" => "Bivalidurin" ] ] ] 3 => array:3 [ "identificador" => "sec0095" "titulo" => "Platelet aggregation inhibitors" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0100" "titulo" => "Epoprostenol" ] 1 => array:2 [ "identificador" => "sec0105" "titulo" => "Nafamostat" ] ] ] ] ] ] ] 3 => array:2 [ "identificador" => "sec0110" "titulo" => "Conclusions" ] 4 => array:2 [ "identificador" => "sec0115" "titulo" => "Funding" ] 5 => array:2 [ "identificador" => "sec0120" "titulo" => "Conflict of interest" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-05-30" "fechaAceptado" => "2016-09-19" "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1823 "Ancho" => 3337 "Tamanyo" => 359526 ] ] "descripcion" => array:1 [ "en" => "Algorithm for anticoagulation strategies in CRRT." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "The 4Ts score is the sum of the values for each of the 4 categories. Scores of 1–3 are considered to correspond to a low, 4–5 intermediate, and 6–8 high probability of HIT." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Category \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 Points \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 Point \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">0 Point \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Platelet count fall >50% and platelet nadir ≥20×109/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Platelet count 30–50% or platelet nadir 10–19×109/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Platelet count fall <30% or platelet nadir <10×109/L \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Timing of the decrease in platelet count \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clear onset days 5–10 or platelet fall ≤1 day (prior heparin exposure within 30 days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consistent with days 5–10 fall, but not clear (e.g., missing platelet counts); onset after day 10; or fall ≤1 day (prior heparin exposure 30–100 days ago) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Platelet count ≤4 days without recent exposure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thrombosis or other sequelae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">New thrombosis (confirmed); skin necrosis; acute systemic reaction postintravenous unfractionated heparin bolus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Progressive or recurrent thrombosis; non-necrotizing (erythematous) skin lesions; suspected thrombosis (not proven) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other causes of thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None evident \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Possible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Definite \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1266453.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical estimation of the probability of HIT (The 4Ts score).<a class="elsevierStyleCrossRef" href="#bib0540">28</a>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AKI, acute kidney injury; C, citrate; Syst. hept, systemic heparin; Reg. hep, regional heparin (heparin-protamine); RR, relative risk; CI, confidence interval; RRT, renal replacement therapy." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N° patients: citrate vs. heparine \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N° centers \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inclusion criteria \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Exclusion criteria \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Monchi et al., 2004<a class="elsevierStyleCrossRef" href="#bib0770">74</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:8 Syst. hep: 12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Liver cirrhosis. High risk of bleeding. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Longer filter life in the citrate group (p=0.0007). Higher transfusion rate in the heparin group (p=0.0008). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kutsogiannis et al., 2005<a class="elsevierStyleCrossRef" href="#bib0775">75</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:16 Syst. hep: 14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Liver failure. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significantly longer filter life in the citrate group (p<0.001). Lower RR of bleeding with citrate than with heparin (RR=0.14; 95% CI: 0.02–0.96; p=0.05). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bagshaw et al., 2005<a class="elsevierStyleCrossRef" href="#bib0780">76</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:54 Syst. hep: 29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chronic dialysis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Significantly longer filter life in the citrate group (p<0.001). Regional anticoagulation with citrate well tolerated without significant complications in acid–base balance or electrolytes. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Betjes et al., 2007<a class="elsevierStyleCrossRef" href="#bib0785">77</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:21 Syst. hep: 27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Need for RRT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acute liver failure. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Similar filter lifespan in the two groups. No significant adverse metabolic events in the citrate group. More bleeding events (p<0.01) and transfusions (p=0.01) in the heparin group. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fealy et al., 2007<a class="elsevierStyleCrossRef" href="#bib0790">78</a> (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:10 Reg. hep: 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acute or chronic liver failure. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Longer circuit life in the citrate group (p=0.77). No bleeding episodes in either group. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oudemans-van Straaten et al., 2009<a class="elsevierStyleCrossRef" href="#bib0635">47</a> (OLVG study) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C: 97 Syst. hep: 103 (nadroparin) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Liver cirrhosis, chronic dialysis, heparin-induced thrombocytopenia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Similar efficacy. Citrate was safer (fewer complications p<0.001). Secondary analyses of surgical patients and patients with multiple organ failure showed better recovery of renal function and lower mortality in the citrate group. Possible immunomodulating effect? \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hetzel et al., 2011<a class="elsevierStyleCrossRef" href="#bib0640">48</a> (Hetzel study) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:87 Syst. hep: 83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metabolic alkalosis, pregnancy, breast feeding, chronic dialysis, heparin-induced thrombocytopenia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No significant differences in the number of acid–base balance alterations or in urea levels. Longer filter life in the citrate group (p<0.001) and lower risk of bleeding. No differences in 30-day survival. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tiranathanagul et al., 2011<a class="elsevierStyleCrossRef" href="#bib0795">79</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:10 Syst. hep: 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acute or chronic liver failure. Dialysis in the previous 24h, hypercalcemia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Longer circuit life in the citrate group. After measuring the pre- and post-filter levels of myeloperoxidase of the polymorphonuclear leukocytes, they concluded that citrate therapy could also reduce membrane-induced bioincompatibility phenomena (p<0.01). Citrate seemed to help control the inflammatory response and systemic oxidative stress (decrease in IL8 levels, p<0.05). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Schilder et al., 2014 (48) (CASH study) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C: 66 Syst. hep:73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Need for RRT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High risk of bleeding, heparin-induced thrombocytopenia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No differences in mortality or recovery of renal function. Citrate was superior in terms of safety (fewer adverse events, p<0.001), efficacy (longer filter life, p=0.02), and costs (p<0.001). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Brain et al., 2014<a class="elsevierStyleCrossRef" href="#bib0800">80</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:19 Syst. hep: 11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Weight <30kg, pregnancy or breast feeding. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Longer filter life in the citrate group (p=0.004). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stucker et al., 2015<a class="elsevierStyleCrossRef" href="#bib0670">54</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:54 Syst. hep: 49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Liver failure, high risk of bleeding, heparin-induced thrombocytopenia. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">As a method of circuit anticoagulation, citrate was superior to heparin in terms of dose (p=0.005) and filter lifespan (p=0.004). In the citrate group, alterations in electrolytes and in acid–base balance were uncommon, transitory, and preventable with a strict protocol. There were no differences in short-term survival. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hafner et al., 2015<a class="elsevierStyleCrossRef" href="#bib0655">51</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:60 Syst. hep: 50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI and indication of RRT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The two modalities were effective in controlling uremia, but the reduction in urea after 3 or 4 days was significantly greater in the citrate group (p<0.0001); this difference was attributed to longer filter life. The citrate group had higher levels of pH, lower levels of ionic Ca, and higher levels of Na, without associated adverse effects (p<0.0001); these alterations were successfully resolved by modifying flow according to protocol. Circuit lifespan was significantly longer in the citrate group. Citrate was cost-effective. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gattas et al., 2015<a class="elsevierStyleCrossRef" href="#bib0665">53</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C:105 Reg. hep: 107 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AKI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Liver failure, pregnancy, breast feeding, heparin-induced thrombocytopenia, chronic dialysis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Longer filter life (p<0.0004) and fewer adverse effects (p<0.01) in the citrate group. No differences in the number of transfusions, the duration of treatment, length of stay, or mortality. Similar effects on cytokine levels. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1266454.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Studies comparing regional anticoagulation with citrate versus other anticoagulation strategies." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1. Non-tunneled polyurethane catheters with a double lumen are the appropriate vascular access for CRRT in acute kidney failure. Tunneled silicone catheters represent an alternative that is generally reserved for longer treatments or for patients with problematic venous access. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2. The right internal jugular vein or the femoral veins are the access sites of choice. The subclavian vein should be avoided due to the high risk of thrombosis and stenosis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3. The location, diameter, geometry, and length of the catheter should be tailored to physical and clinical characteristics of the patient. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4. Dialysis catheters should be placed under ultrasound guidance to minimize the iatrogenic effects of insertion. Malfunction, thrombosis, and infection are complications that can be prevented by proper care of the catheter. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5. When not in use, catheters should be sealed with an antithrombotic solution. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6. Non-pharmacological measures are useful strategies for optimizing the patency of the circuit. These include correct venous access, appropriate settings of blood flow and filtration fraction, prior dilution, favoring diffusion over convection, ensuring thorough training of staff, using protocols, and monitoring the technique closely. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7. Unfractionated heparin continues to be the anticoagulation strategy most frequently employed in CRRT. It is an effective anticoagulation strategy, but there are problems with dosing and increased risk of bleeding. There may also be a certain degree of resistance to heparin, and this strategy can result in heparin-induced thrombocytopenia. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8. Despite repeated clotting of the filter, forgoing anticoagulation of the circuit continues to be a common option in patients with high risk of bleeding in centers where regional anticoagulation with citrate is not available. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9. Regional anticoagulation with citrate has proven very effective. It is associated with increased filter lifespan and decreased risk of bleeding and need for multiple transfusions. This strategy should be the first choice in patients with increased risk of bleeding. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10. Regional anticoagulation with citrate requires strict protocols and thorough staff training to ensure patient safety. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11. In patients without high risk of bleeding, citrate, unfractionated heparin, and low-molecular-weight heparins have all proven efficacious. The choice of strategy will depend on the patient's clinical condition and contraindications, as well as on the center's experience and protocols. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12. Unfractionated heparin or low-molecular-weight heparins are probably the best alternatives in patients with low risk of bleeding in whom citrate administration is contraindicated. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13. In patients with heparin-induced thrombocytopenia, the administration of thrombin inhibitors (argatroban) or factor Xa inhibitors (danaparoid or fondaparinux) is highly recommended. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">14. Regional anticoagulation with heparin-protamine is not currently recommended. The evidence available about the safety and efficacy of epoprostenol and other platelet aggregation inhibitors and thrombin inhibitors is insufficient to recommend their use in routine practice. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1266452.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Key points." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:80 [ 0 => array:3 [ "identificador" => "bib0405" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood recirculation in temporary central catheters for acute hemodialysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Leblanc" 1 => "S. Fedak" 2 => "G. Mokris" 3 => "E.P. Paganini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Nephrol" "fecha" => "1996" "volumen" => "45" "paginaInicial" => "315" "paginaFinal" => "319" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8738663" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0410" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparison of the Niagara and Medcomp catheters for continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "N. Fealy" 1 => "I. Kim" 2 => "I. Baldwin" 3 => "A. Schneider" 4 => "R. Bellomo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/0886022X.2012.757823" "Revista" => array:6 [ "tituloSerie" => "Ren Fail" "fecha" => "2013" "volumen" => "35" "paginaInicial" => "308" "paginaFinal" => "313" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23356529" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0415" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vascular access for continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Vijayan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1525-139X.2008.00553.x" "Revista" => array:6 [ "tituloSerie" => "Semin Dial" "fecha" => "2009" "volumen" => "22" "paginaInicial" => "133" "paginaFinal" => "136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19426415" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0420" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intensity of continuous renal-replacement therapy in critically ill patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "RENAL Replacement Therapy Study Investigators" 1 => "R. Bellomo" 2 => "A. Cass" 3 => "L. Cole" 4 => "S. Finfer" 5 => "M. Gallagher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0902413" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2009" "volumen" => "361" "paginaInicial" => "1627" "paginaFinal" => "1638" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19846848" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0425" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "KDIGO clinical practice guideline for acute kidney injury" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2012" "volumen" => "2" "paginaInicial" => "1" "paginaFinal" => "138" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4671525" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0430" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis, prevention and treatment of haemodialysis catheter-related bloodstream infections (CRBSI): a position statement of European Renal Best Practice (ERBP)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Vanholder" 1 => "B. Canaud" 2 => "R. Fluck" 3 => "M. Jadoul" 4 => "L. Labriola" 5 => "A. Marti-Monros" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "NDT Plus" "fecha" => "2010" "volumen" => "3" "paginaInicial" => "234" "paginaFinal" => "246" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0435" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Central venous catheter-related infection in a prospective and observational study of 2,595 catheters" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Lorente" 1 => "C. Henry" 2 => "M.M. Martín" 3 => "A. Jiménez" 4 => "M.L. Mora" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc3824" "Revista" => array:6 [ "tituloSerie" => "Crit Care" "fecha" => "2005" "volumen" => "9" "paginaInicial" => "R631" "paginaFinal" => "R635" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16280064" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0440" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[discussion 234–5]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The incidence of infectious complications of central venous catheters at the subclavian, internal jugular, and femoral sites in an intensive care unit population" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.S. Deshpande" 1 => "C. Hatem" 2 => "H.L. Ulrich" 3 => "B.P. Currie" 4 => "T.K. Aldrich" 5 => "C.W. Bryan-Brown" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2005" "volumen" => "33" "paginaInicial" => "13" "paginaFinal" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15644643" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0445" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of insertion site on central venous catheter colonization and bloodstream infection rates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.R. Gowardman" 1 => "I.K. Robertson" 2 => "S. Parkes" 3 => "C.M. Rickard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-008-1046-3" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2008" "volumen" => "34" "paginaInicial" => "1038" "paginaFinal" => "1045" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18317732" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0450" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: a randomized controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.-J. Parienti" 1 => "M. Thirion" 2 => "B. Mégarbane" 3 => "B. Souweine" 4 => "A. Ouchikhe" 5 => "A. Polito" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.299.20.2413" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2008" "volumen" => "299" "paginaInicial" => "2413" "paginaFinal" => "2422" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18505951" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0455" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vascular access sites for acute renal replacement in intensive care units" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.E. Dugué" 1 => "S.P. Levesque" 2 => "M.-O. Fischer" 3 => "B. Souweine" 4 => "J.-P. Mira" 5 => "B. Megarbane" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2215/CJN.06570711" "Revista" => array:6 [ "tituloSerie" => "Clin J Am Soc Nephrol" "fecha" => "2012" "volumen" => "7" "paginaInicial" => "70" "paginaFinal" => "77" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22076877" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0460" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Initial and extended use of femoral versus nonfemoral double-lumen vascular catheters and catheter-related infection during continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.-R. Chua" 1 => "A.G. Schneider" 2 => "N.L. Sherry" 3 => "N. Lotfy" 4 => "M.J. Chan" 5 => "J. Galtieri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.ajkd.2014.04.022" "Revista" => array:6 [ "tituloSerie" => "Am J Kidney Dis" "fecha" => "2014" "volumen" => "64" "paginaInicial" => "909" "paginaFinal" => "917" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24882583" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0465" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Femoral access and delivery of continuous renal replacement therapy dose" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Bellomo" 1 => "J. Mårtensson" 2 => "S. Lo" 3 => "K.-M. Kaukonen" 4 => "A. Cass" 5 => "M. Gallagher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000439581" "Revista" => array:6 [ "tituloSerie" => "Blood Purif" "fecha" => "2016" "volumen" => "41" "paginaInicial" => "11" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26485539" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0470" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International evidence-based recommendations on ultrasound-guided vascular access" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Lamperti" 1 => "A.R. Bodenham" 2 => "M. Pittiruti" 3 => "M. Blaivas" 4 => "J.G. Augoustides" 5 => "M. Elbarbary" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-012-2597-x" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2012" "volumen" => "38" "paginaInicial" => "1105" "paginaFinal" => "1117" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22614241" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0475" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complications of central venous catheterization" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.E. Kusminsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jamcollsurg.2007.01.039" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Surg" "fecha" => "2007" "volumen" => "204" "paginaInicial" => "681" "paginaFinal" => "696" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17382229" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0480" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vascular access related infections in hemodialysis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.K. Saxena" 1 => "B.R. Panhotra" 2 => "A.S. Al-Mulhim" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Saudi J Kidney Dis Transplant" "fecha" => "2005" "volumen" => "16" "paginaInicial" => "46" "paginaFinal" => "71" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0485" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors affecting circuit patency and filter “life.”" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "I. Baldwin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/0000102081" "Revista" => array:7 [ "tituloSerie" => "Contrib Nephrol" "fecha" => "2007" "volumen" => "156" "paginaInicial" => "178" "paginaFinal" => "184" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17464125" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S2215036615002175" "estado" => "S300" "issn" => "22150366" ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0490" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical review: patency of the circuit in continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Joannidis" 1 => "H.M. Oudemans-van Straaten" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc5937" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2007" "volumen" => "11" "paginaInicial" => "218" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17634148" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0495" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Uchino" 1 => "R. Bellomo" 2 => "H. Morimatsu" 3 => "S. Morgera" 4 => "M. Schetz" 5 => "I. Tan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-007-0754-4" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2007" "volumen" => "33" "paginaInicial" => "1563" "paginaFinal" => "1570" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17594074" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0500" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Survey on the management of acute renal failure and renal replacement techniques in Spanish intensive care units" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "el Grupo de Trabajo de Cuidados Intensivos Nefrológicos de la SEMICYUC" "etal" => false "autores" => array:3 [ 0 => "A. Úbeda-Iglesias" 1 => "D. Herrera-Rojas" 2 => "C. Gómez-González" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medin.2014.04.001" "Revista" => array:6 [ "tituloSerie" => "Med Intensiva" "fecha" => "2015" "volumen" => "39" "paginaInicial" => "84" "paginaFinal" => "89" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24881964" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0505" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Revised algorithm for heparin anticoagulation during continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H. Dickie" 1 => "L. Tovey" 2 => "W. Berry" 3 => "M. Ostermann" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Crit Care" "fecha" => "2015" "paginaInicial" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12617736" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0510" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anticoagulation strategies in continuous renal replacement therapy: can the choice be evidence based?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H.M. Oudemans-van Straaten" 1 => "J.P.J. Wester" 2 => "A.C.J.M. de Pont" 3 => "M.R.C. Schetz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-005-0044-y" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2006" "volumen" => "32" "paginaInicial" => "188" "paginaFinal" => "202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16453140" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0515" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical review: anticoagulation for continuous renal replacement therapy – heparin or citrate?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H.M. Oudemans-van Straaten" 1 => "J.A. Kellum" 2 => "R. Bellomo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc9358" "Revista" => array:6 [ "tituloSerie" => "Crit Care" "fecha" => "2011" "volumen" => "15" "paginaInicial" => "202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21345279" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1054139X15001615" "estado" => "S300" "issn" => "1054139X" ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0520" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acquired deficit of antithrombin and role of supplementation in septic patients during continuous veno-venous hemofiltration" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Lafargue" 1 => "O. Joannes-Boyau" 2 => "P.M. Honoré" 3 => "B. Gauche" 4 => "H. Grand" 5 => "C. Fleureau" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MAT.0b013e31815cc3bf" "Revista" => array:6 [ "tituloSerie" => "ASAIO J" "fecha" => "2008" "volumen" => "54" "paginaInicial" => "124" "paginaFinal" => "128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18204328" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0525" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heparin-induced thrombocytopenia in intensive care patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Selleng" 1 => "S. Selleng" 2 => "A. Greinacher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-0028-1092872" "Revista" => array:6 [ "tituloSerie" => "Semin Thromb Hemost" "fecha" => "2008" "volumen" => "34" "paginaInicial" => "425" "paginaFinal" => "438" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18956282" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0530" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The incidence of thrombocytopenia associated with continuous renal replacement therapy in critically ill patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.A. Ferreira" 1 => "D.W. Johnson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/0886022X.2015.1057799" "Revista" => array:6 [ "tituloSerie" => "Ren Fail" "fecha" => "2015" "volumen" => "37" "paginaInicial" => "1232" "paginaFinal" => "1236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26108135" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0535" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The clinical diagnosis of heparin-induced thrombocytopenia in patients receiving continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C.E. Holmes" 1 => "J.C. Huang" 2 => "C. Cartelli" 3 => "A. Howard" 4 => "J. Rimmer" 5 => "M. Cushman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11239-008-0228-8" "Revista" => array:6 [ "tituloSerie" => "J Thromb Thrombolysis" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "406" "paginaFinal" => "412" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18488144" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0540" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Cuker" 1 => "P.A. Gimotty" 2 => "M.A. Crowther" 3 => "T.E. Warkentin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2012-07-443051" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2012" "volumen" => "120" "paginaInicial" => "4160" "paginaFinal" => "4167" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22990018" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0545" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Hirsh" 1 => "T.E. Warkentin" 2 => "S.G. Shaughnessy" 3 => "S.S. Anand" 4 => "J.L. Halperin" 5 => "R. Raschke" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2001" "volumen" => "119" "paginaInicial" => "64S" "paginaFinal" => "94S" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11157643" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0550" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A systematic review on the accumulation of prophylactic dosages of low-molecular-weight heparins (LMWHs) in patients with renal insufficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "F. Atiq" 1 => "P.M.L.A. van den Bemt" 2 => "F.W.G. Leebeek" 3 => "T. van Gelder" 4 => "J. Versmissen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00228-015-1880-5" "Revista" => array:6 [ "tituloSerie" => "Eur J Clin Pharmacol" "fecha" => "2015" "volumen" => "71" "paginaInicial" => "921" "paginaFinal" => "929" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26071276" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0555" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enoxaparin vs. unfractionated heparin for anticoagulation during continuous veno-venous hemofiltration: a randomized controlled crossover study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Joannidis" 1 => "J. Kountchev" 2 => "M. Rauchenzauner" 3 => "N. Schusterschitz" 4 => "H. Ulmer" 5 => "A. Mayr" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-007-0719-7" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2007" "volumen" => "33" "paginaInicial" => "1571" "paginaFinal" => "1579" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17563874" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0560" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enoxaparin versus unfractioned heparin as anticoagulant for continuous venovenous hemodialysis: a randomized open-label trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.O. Garcés" 1 => "J.A. Victorino" 2 => "F.S. Thomé" 3 => "L.M. Röhsig" 4 => "E. Dornelles" 5 => "M. Louzada" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/08860221003606281" "Revista" => array:6 [ "tituloSerie" => "Ren Fail" "fecha" => "2010" "volumen" => "32" "paginaInicial" => "320" "paginaFinal" => "327" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20370447" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0565" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anticoagulation with low molecular weight heparin (Fragmin) during continuous hemodialysis in the intensive care unit" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.F. Jeffrey" 1 => "A.A. Khan" 2 => "J.T. Douglas" 3 => "E.J. Will" 4 => "A.M. Davison" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Artif Organs" "fecha" => "1993" "volumen" => "17" "paginaInicial" => "717" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8215953" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0570" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nadroparin versus dalteparin anticoagulation in high-volume, continuous venovenous hemofiltration: a double-blind, randomized, crossover study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.C. de Pont" 1 => "H.M. Oudemans-van Straaten" 2 => "K.J. Roozendaal" 3 => "D.F. Zandstra" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2000" "volumen" => "28" "paginaInicial" => "421" "paginaFinal" => "425" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10708177" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0575" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of the antithrombotic effects of heparin, enoxaparin and prostacycline in continuous hemofiltration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D. Journois" 1 => "D. Safran" 2 => "M.H. Castelain" 3 => "D. Chanu" 4 => "C. Drévillon" 5 => "G. Barrier" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Fr Anesthèsie Rèanimation" "fecha" => "1990" "volumen" => "9" "paginaInicial" => "331" "paginaFinal" => "337" ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0580" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "European Best Practice Guidelines Expert Group on Hemodialysis, European Renal Association. Section V. Chronic intermittent haemodialysis and prevention of clotting in the extracorporal system" ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2002" "volumen" => "17" "numero" => "Suppl. 7" "paginaInicial" => "63" "paginaFinal" => "71" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12386229" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0585" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "And the winner is: regional citrate anticoagulation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.S.C. Bouman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e318194df2e" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2009" "volumen" => "37" "paginaInicial" => "764" "paginaFinal" => "765" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19325378" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0590" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Z. Zhang" 1 => "N. Hongying" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-011-2438-3" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2012" "volumen" => "38" "paginaInicial" => "20" "paginaFinal" => "28" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22124775" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0595" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anticoagulation for continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.J. Tolwani" 1 => "K.M. Wille" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1525-139X.2008.00545.x" "Revista" => array:6 [ "tituloSerie" => "Semin Dial" "fecha" => "2009" "volumen" => "22" "paginaInicial" => "141" "paginaFinal" => "145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19426417" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0600" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Review and guidelines for regional anticoagulation with citrate in continuous hemofiltration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H. Oudemans-van Straaten" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Neth J Crit Care" "fecha" => "2004" "volumen" => "8" "paginaInicial" => "146" "paginaFinal" => "156" ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0605" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Schultheiß" 1 => "B. Saugel" 2 => "V. Phillip" 3 => "P. Thies" 4 => "S. Noe" 5 => "U. Mayr" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc11485" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2012" "volumen" => "16" "paginaInicial" => "R162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22913794" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0610" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation Threshold (L-CAT) observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Slowinski" 1 => "S. Morgera" 2 => "M. Joannidis" 3 => "T. Henneberg" 4 => "R. Stocker" 5 => "E. Helset" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13054-015-1066-7" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2015" "volumen" => "19" "paginaInicial" => "349" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26415638" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0615" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sustained low-efficiency dialysis with regional citrate anticoagulation in medical intensive care unit patients with liver failure: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Lahmer" 1 => "M. Messer" 2 => "S. Rasch" 3 => "A. Beitz" …2 ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcrc.2015.06.006" "Revista" => array:6 [ "tituloSerie" => "J Crit Care" "fecha" => "2015" "volumen" => "30" "paginaInicial" => "1096" "paginaFinal" => "1100" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0620" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid–base status and phosphate supplementation needs" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2369-14-232" "Revista" => array:5 [ "tituloSerie" => "BMC Nephrol" "fecha" => "2013" "volumen" => "14" "paginaInicial" => "232" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0625" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Citrate for continuous renal replacement therapy: safer, better and cheaper" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13054-014-0661-3" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2014" "volumen" => "18" "paginaInicial" => "661" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0630" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13054-014-0472-6" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2014" "volumen" => "18" "paginaInicial" => "472" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0635" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Citrate anticoagulation for continuous venovenous hemofiltration" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e3181953c5e" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2009" "volumen" => "37" "paginaInicial" => "545" "paginaFinal" => "552" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0640" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfq575" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2011" "volumen" => "26" "paginaInicial" => "232" "paginaFinal" => "239" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0645" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduction of granulocyte activation during hemodialysis with regional citrate anticoagulation: dissociation of complement activation and neutropenia from neutrophil degranulation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "1996" "volumen" => "7" "paginaInicial" => "234" "paginaFinal" => "241" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0650" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low polymorphonuclear cell degranulation during citrate anticoagulation: a comparison between citrate and heparin dialysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "1997" "volumen" => "12" "paginaInicial" => "1387" "paginaFinal" => "1393" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0655" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Implementation of continuous renal replacement therapy with regional citrate anticoagulation on a surgical and trauma intensive care unit: impact on clinical and economic aspects-an observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40560-015-0102-7" "Revista" => array:5 [ "tituloSerie" => "J Intensive Care" "fecha" => "2015" "volumen" => "3" "paginaInicial" => "35" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0660" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.ajkd.2011.11.030" "Revista" => array:6 [ "tituloSerie" => "Am J Kidney Dis" "fecha" => "2012" "volumen" => "59" "paginaInicial" => "810" "paginaFinal" => "818" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0665" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized controlled trial of regional citrate versus regional heparin anticoagulation for continuous renal replacement therapy in critically ill adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0000000000001004" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2015" "volumen" => "43" "paginaInicial" => "1622" "paginaFinal" => "1629" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0670" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13054-015-0822-z" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2015" "volumen" => "19" "paginaInicial" => "91" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0675" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Citrate versus heparin anticoagulation for continuous renal replacement therapy: an updated meta-analysis of RCTs" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-015-4099-0" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2015" "volumen" => "41" "paginaInicial" => "2098" "paginaFinal" => "2110" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0680" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heparin-induced thrombocytopenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Esp Cardiol" "fecha" => "2007" "volumen" => "60" "paginaInicial" => "1071" "paginaFinal" => "1082" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0685" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc6937" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2008" "volumen" => "12" "paginaInicial" => "R84" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0690" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Repeated premature hemofilter clotting during regional citrate anticoagulation as indicator of heparin induced thrombocytopenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000366125" "Revista" => array:6 [ "tituloSerie" => "Blood Purif" "fecha" => "2014" "volumen" => "38" "paginaInicial" => "127" "paginaFinal" => "130" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0695" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Argatroban for anticoagulation in continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e3181932394" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2009" "volumen" => "37" "paginaInicial" => "105" "paginaFinal" => "110" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0700" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anticoagulation options for patients with heparin-induced thrombocytopenia requiring renal support in the intensive care unit" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/0000102110" "Revista" => array:6 [ "tituloSerie" => "Contrib Nephrol" "fecha" => "2007" "volumen" => "156" "paginaInicial" => "259" "paginaFinal" => "266" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0705" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recombinant activated factor VII effectively reverses the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin ex vivo as measured using thromboelastography" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MBC.0b013e328201c9a9" "Revista" => array:6 [ "tituloSerie" => "Blood Coagul Fibrinolysis" "fecha" => "2007" "volumen" => "18" "paginaInicial" => "547" "paginaFinal" => "553" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0710" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13054-014-0588-8" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2014" "volumen" => "18" "paginaInicial" => "588" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0715" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heparin-induced thrombocytopenia during renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1492-7535.2004.01108.x" "Revista" => array:6 [ "tituloSerie" => "Hemodial Int" "fecha" => "2004" "volumen" => "8" "paginaInicial" => "295" "paginaFinal" => "303" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0720" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of argatroban: experiences in continuous renal replacement therapy in critically ill patients after cardiac surgery" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jtcvs.2013.11.051" "Revista" => array:6 [ "tituloSerie" => "J Thorac Cardiovasc Surg" "fecha" => "2014" "volumen" => "147" "paginaInicial" => "1918" "paginaFinal" => "1924" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0725" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety, efficacy, and dosing requirements of bivalirudin in patients with heparin-induced thrombocytopenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1592/phco.28.9.1115" "Revista" => array:6 [ "tituloSerie" => "Pharmacotherapy" "fecha" => "2008" "volumen" => "28" "paginaInicial" => "1115" "paginaFinal" => "1124" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0730" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bivalirudin versus unfractionated heparin for prevention of hemofilter occlusion during continuous renal replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1592/phco.30.11.1117" "Revista" => array:6 [ "tituloSerie" => "Pharmacotherapy" "fecha" => "2010" "volumen" => "30" "paginaInicial" => "1117" "paginaFinal" => "1126" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0735" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prostaglandin E1: the endogenous physiological regulator of platelet mediated blood coagulation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Prostaglandins Leukot Essent Fatty Acids" "fecha" => "1989" "volumen" => "35" "paginaInicial" => "189" "paginaFinal" => "195" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0740" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous haemofiltration in acute renal failure with prostacyclin as the sole anti-haemostatic agent" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-002-1249-y" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2002" "volumen" => "28" "paginaInicial" => "586" "paginaFinal" => "593" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0745" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of prostacyclin (epoprostenol) as anticoagulant in continuous renal replacement therapies: efficacy, security and cost analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Nephrol" "fecha" => "2006" "volumen" => "19" "paginaInicial" => "648" "paginaFinal" => "655" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0750" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anticoagulation with prostacyclin and heparin during continuous venovenous hemofiltration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "1994" "volumen" => "22" "paginaInicial" => "1774" "paginaFinal" => "1781" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0755" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of isolated epoprostenol or associated to heparin for the maintenance of the patency of the continuous renal replacement technical circuits" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Med Intensiva" "fecha" => "2006" "volumen" => "30" "paginaInicial" => "314" "paginaFinal" => "321" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0760" "etiqueta" => "72" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of nafamostat mesylate in continuous renal replacement therapy among patients at high risk of bleeding" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/0886022X.2011.647293" "Revista" => array:6 [ "tituloSerie" => "Ren Fail" "fecha" => "2012" "volumen" => "34" "paginaInicial" => "279" "paginaFinal" => "285" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0765" "etiqueta" => "73" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ability of nafamostat mesilate to prolong filter patency during continuous renal replacement therapy in patients at high risk of bleeding: a randomized controlled study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0108737" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2014" "volumen" => "9" "paginaInicial" => "e108737" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0770" "etiqueta" => "74" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-003-2047-x" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2004" "volumen" => "30" "paginaInicial" => "260" "paginaFinal" => "265" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0775" "etiqueta" => "75" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1523-1755.2005.00342.x" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2005" "volumen" => "67" "paginaInicial" => "2361" "paginaFinal" => "2367" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib0780" "etiqueta" => "76" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is regional citrate superior to systemic heparin anticoagulation for continuous renal replacement therapy? A prospective observational study in an adult regional critical care system" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcrc.2005.01.001" "Revista" => array:6 [ "tituloSerie" => "J Crit Care" "fecha" => "2005" "volumen" => "20" "paginaInicial" => "155" "paginaFinal" => "161" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 76 => array:3 [ "identificador" => "bib0785" "etiqueta" => "77" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regional citrate versus heparin anticoagulation during venovenous hemofiltration in patients at low risk for bleeding: similar hemofilter survival but significantly less bleeding" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Nephrol" "fecha" => "2007" "volumen" => "20" "paginaInicial" => "602" "paginaFinal" => "608" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 77 => array:3 [ "identificador" => "bib0790" "etiqueta" => "78" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A pilot randomized controlled crossover study comparing regional heparinization to regional citrate anticoagulation for continuous venovenous hemofiltration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Artif Organs" "fecha" => "2007" "volumen" => "30" "paginaInicial" => "301" "paginaFinal" => "307" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 78 => array:3 [ "identificador" => "bib0795" "etiqueta" => "79" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1744-9987.2011.00996.x" "Revista" => array:6 [ "tituloSerie" => "Ther Apher Dial" "fecha" => "2011" "volumen" => "15" "paginaInicial" => "556" "paginaFinal" => "564" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 79 => array:3 [ "identificador" => "bib0800" "etiqueta" => "80" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomised trial of software algorithm driven regional citrate anticoagulation versus heparin in continuous renal replacement therapy: the Filter Life in Renal Replacement Therapy pilot trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Crit Care Resusc" "fecha" => "2014" "volumen" => "16" "paginaInicial" => "131" "paginaFinal" => "137" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02105691/0000004000000009/v1_201612020641/S0210569116302194/v1_201612020641/en/main.assets" "Apartado" => array:4 [ "identificador" => "60883" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Puesta al día en Medicina Intensiva: Acute Kidney Injury" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/02105691/0000004000000009/v1_201612020641/S0210569116302194/v1_201612020641/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116302194?idApp=WMIE"]

Estadísticas

Update in Intensive Care: Acute Kidney Injury

Vascular access and extracorporeal circuit patency in continuous renal replacement therapy

Acceso vascular y permeabilidad de los circuitos extracorpóreos en las técnicas de depuración renal continua

F.J. González de Molinaa,

Autor para correspondencia

fgonzalez@mutuaterrassa.es

Corresponding author.

, M. Galindob, C. Gonzálezc, M.J. Brochd, L. del Bañoe, A. Roglanf

a Servicio de Medicina Intensiva, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain

b Servicio de Medicina Intensiva, Hospital Universitario Santa Lucía, Cartagena Murcia, Spain

c Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Santander, Spain

d Servicio de Medicina Intensiva, Hospital Universitari i Politécnic la Fe, Valencia, Spain

e Servicio de Medicina Intensiva, Hospital Morales Meseguer, Murcia, Spain

f Servicio de Medicina Intensiva, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Leído

18906

Veces
se ha leído el artículo

4414

Total PDF

14492

Total HTML

Compartir estadísticas

 array:23 [
  "pii" => "S0210569116302194"
  "issn" => "02105691"
  "doi" => "10.1016/j.medin.2016.09.011"
  "estado" => "S300"
  "fechaPublicacion" => "2016-12-01"
  "aid" => "987"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; y SEMICYUC"
  "copyrightAnyo" => "2016"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "sco"
  "cita" => "Med Intensiva. 2016;40:572-85"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 6157
    "formatos" => array:3 [
      "EPUB" => 164
      "HTML" => 4866
      "PDF" => 1127
    ]
  ]
  "itemSiguiente" => array:17 [
    "pii" => "S0210569116300663"
    "issn" => "02105691"
    "doi" => "10.1016/j.medin.2016.04.010"
    "estado" => "S300"
    "fechaPublicacion" => "2016-12-01"
    "aid" => "930"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "sco"
    "cita" => "Med Intensiva. 2016;40:586-9"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 3745
      "formatos" => array:3 [
        "EPUB" => 161
        "HTML" => 2636
        "PDF" => 948
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Point of view</span>"
      "titulo" => "Antimicrobial stewardship programs in the critical care setting"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "586"
          "paginaFinal" => "589"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Programas de administraci&#243;n de antimicrobianos en la unidad de cuidados intensivos"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 2270
              "Ancho" => 3325
              "Tamanyo" => 303230
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Antimicrobial stewardship program operating strategy&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "J&#46; Ruiz-Ramos, P&#46; Ramirez"
          "autores" => array:2 [
            0 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Ruiz-Ramos"
            ]
            1 => array:2 [
              "nombre" => "P&#46;"
              "apellidos" => "Ramirez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116300663?idApp=WMIE"
    "url" => "/02105691/0000004000000009/v1_201612020641/S0210569116300663/v1_201612020641/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S0210569116301759"
    "issn" => "02105691"
    "doi" => "10.1016/j.medin.2016.07.009"
    "estado" => "S300"
    "fechaPublicacion" => "2016-12-01"
    "aid" => "965"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; y SEMICYUC"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "ssu"
    "cita" => "Med Intensiva. 2016;40:560-71"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 5075
      "formatos" => array:3 [
        "EPUB" => 172
        "HTML" => 3758
        "PDF" => 1145
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
      "titulo" => "Ultrasound-guided vascular cannulation in critical care patients&#58; A practical review"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "560"
          "paginaFinal" => "571"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Canulaci&#243;n vascular eco-dirigida en pacientes cr&#237;ticos&#58; una revisi&#243;n pr&#225;ctica"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0035"
          "etiqueta" => "Figure 4"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr4.jpeg"
              "Alto" => 1603
              "Ancho" => 3000
              "Tamanyo" => 508164
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">US mapping before cannulation&#46; &#40;A&#41; Patent vein&#44; confirmed by full compressibility &#40;arrows&#41;&#59; &#40;B&#41; thrombosed common femoral vein&#44; clearly seen enlarged and occupied by a large thrombus &#40;t&#41;&#59; a&#58; common femoral artery&#46; &#40;C&#41; vein valve&#59; v&#58; vein&#59; &#40;D&#41; optimal vein diameter for central venous cannulation&#59; &#40;E&#41; optimal vein diameter and distance from skin to vein for peripheral vein cannulation&#59; &#40;F&#41; artery with two calcified atheromatous plaques &#40;calipers&#41;&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "P&#46; Blanco"
          "autores" => array:1 [
            0 => array:2 [
              "nombre" => "P&#46;"
              "apellidos" => "Blanco"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S2173572716300601"
        "doi" => "10.1016/j.medine.2016.07.002"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572716300601?idApp=WMIE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116301759?idApp=WMIE"
    "url" => "/02105691/0000004000000009/v1_201612020641/S0210569116301759/v1_201612020641/en/main.assets"
  ]
  "en" => array:16 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Update in Intensive Care&#58; Acute Kidney Injury</span>"
    "titulo" => "Vascular access and extracorporeal circuit patency in continuous renal replacement therapy"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "572"
        "paginaFinal" => "585"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "F&#46;J&#46; Gonz&#225;lez de Molina, M&#46; Galindo, C&#46; Gonz&#225;lez, M&#46;J&#46; Broch, L&#46; del Ba&#241;o, A&#46; Roglan"
        "autores" => array:6 [
          0 => array:4 [
            "nombre" => "F&#46;J&#46;"
            "apellidos" => "Gonz&#225;lez de Molina"
            "email" => array:1 [
              0 => "fgonzalez&#64;mutuaterrassa&#46;es"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "M&#46;"
            "apellidos" => "Galindo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "C&#46;"
            "apellidos" => "Gonz&#225;lez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "M&#46;J&#46;"
            "apellidos" => "Broch"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "L&#46;"
            "apellidos" => "del Ba&#241;o"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "A&#46;"
            "apellidos" => "Roglan"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:6 [
          0 => array:3 [
            "entidad" => "Servicio de Medicina Intensiva&#44; Hospital Universitari M&#250;tua Terrassa&#44; Terrassa&#44; Barcelona&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Medicina Intensiva&#44; Hospital Universitario Santa Luc&#237;a&#44; Cartagena Murcia&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Medicina Intensiva&#44; Hospital Universitario Marqu&#233;s de Valdecilla&#44; Santander&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Servicio de Medicina Intensiva&#44; Hospital Universitari i Polit&#233;cnic la Fe&#44; Valencia&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Servicio de Medicina Intensiva&#44; Hospital Morales Meseguer&#44; Murcia&#44; Spain"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Servicio de Medicina Intensiva&#44; Hospital de la Santa Creu i Sant Pau&#44; Barcelona&#44; Spain"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Acceso vascular y permeabilidad de los circuitos extracorp&#243;reos en las t&#233;cnicas de depuraci&#243;n renal continua"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1823
            "Ancho" => 3337
            "Tamanyo" => 359526
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Algorithm for anticoagulation strategies in CRRT&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In continuous renal replacement therapy &#40;CRRT&#41;&#44; the contact of blood with the extracorporeal circuit activates both the intrinsic and extrinsic pathways of plasma coagulation and of the platelets&#44; leading to thrombin production&#44; platelet aggregation&#44; thrombus formation&#44; and fibrin deposition&#46; For these reasons&#44; anticoagulation is necessary in CRRT to prevent clotting of the circuit and to maintain the permeability of the membrane to ensure appropriate daily dosing of the technique&#46; The volume of blood circulating in the extracorporeal circuit ranges from 150<span class="elsevierStyleHsp" style=""></span>ml to 250<span class="elsevierStyleHsp" style=""></span>ml&#44; depending on the surface area of the hemofilter&#46; Repeated clotting without the possibility of blood return results in significant blood loss leading to anemia and multiple transfusions&#46; Time in which the technique is interrupted &#40;downtime&#41; reduces the total dose administered respect to the prescribed dose&#44; increases nursing workload&#44; and increases costs&#46; Catheter dysfunction is a common cause of circuit clotting&#46; Choosing the right catheter and vascular access is fundamental to ensure adequate circuit function&#46; This article reviews different strategies to prolong the patency of the circuit&#44; discussing non-pharmacological strategies and the different anticoagulants used in CRRT&#44; including unfractionated heparin&#44; low-molecular-weight heparin&#44; citrate&#44; thrombin inhibitors&#44; and platelet aggregation inhibitors&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Vascular access for continuous renal replacement therapies</span><p id="par0010" class="elsevierStylePara elsevierViewall">The treatment of acute kidney failure with CRRT requires temporary vascular access&#46; In the early days&#44; CRRT used arteriovenous techniques&#44; but these have been supplanted by venovenous techniques through double-lumen dialysis catheters&#46; Despite the high quality of current catheters&#44; catheters play a role in a high proportion of increased morbidity from CRRT due to complications during insertion&#44; dysfunction &#40;stenosis and&#47;or thrombosis&#41;&#44; and infection&#46; The ideal catheter should be rapidly and easily accessible&#44; should enable adequate flow&#44; should be long lasting&#44; and should keep complications to the minimum&#46; This review will discuss the characteristics of catheters&#44; the site and method of inserting them&#44; and their complications&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Characteristics of catheters</span><p id="par0015" class="elsevierStylePara elsevierViewall">Catheters can be characterized by their geometry&#44; material&#44; inner diameter&#44; and length&#46; <span class="elsevierStyleItalic">Geometry</span>&#58; The catheters used nowadays have a double lumen with or without separate distal tips&#46; The proximal lumen is used for the access line and the distal lumen is used for the return line&#46; One of the problems with these catheters is recirculation &#40;the mixing of access and return blood&#41;&#44; which decreases the effectiveness of the technique&#46; Increasing the distance &#40;2&#8211;3<span class="elsevierStyleHsp" style=""></span>cm&#41; between the access lumen and the return lumen and a design with lateral holes&#44; both help to reduce recirculation&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">1</span></a> The lumen of the catheter can have different designs &#40;coaxial&#44; split&#44; double D&#44; double O&#41;&#44; although this does not seems to significantly influence the life of the circuit&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleItalic">Materials&#58;</span> Nowadays polyurethane and silicone are used&#59; both these materials are very flexible and cause little damage to the vessel wall&#46; In critical patients&#44; polyurethane is more common&#46; Polyurethane catheters can last for several weeks&#59; their main complication is thrombosis&#46; Silicone catheters are used for long-term dialysis&#44; usually with subcutaneous tunneling&#59; this method of canalization makes them longer lasting &#40;they can even last for months&#41; and less prone to infection&#46; <span class="elsevierStyleItalic">Diameter</span>&#58; The inner diameter of a catheter determines how much blood can flow through it&#46; Catheter diameter is usually measured in French &#40;F&#41; units&#44; with 11&#8211;14<span class="elsevierStyleHsp" style=""></span>F being the most appropriate for CRRT&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleItalic">Length&#58;</span> The length of the catheter to be placed depends on the blood vessel used for the approach&#46; If placed in the superior vena cava system through the jugular vein or right subclavian vein&#44; it should measure 15&#8211;18<span class="elsevierStyleHsp" style=""></span>cm&#46; If placed in the inferior vena cava system through the femoral vein&#44; it should measure 24&#8211;28<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Insertion and site</span><p id="par0020" class="elsevierStylePara elsevierViewall">Venous accesses used for CRRT in critical patients should be easy and quick to insert as they are usually canalized at the bedside during the ICU stay&#46; The catheter must be inserted under conditions of maximum asepsis&#44; normally using percutaneous canalization or the Seldinger technique&#46; Unlike chronic dialysis&#44; CRRT for acute kidney failure in critical patients normally does not last for more than two weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">4</span></a> For this reason&#44; the guidelines developed through the initiative Kidney Disease&#58; Improving Global Outcomes &#40;KDIGO&#41;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">5</span></a> recommend placing nontunneled catheters initially&#44; and then replacing them with tunneled catheters if dialysis must be prolonged or if the patient requires frequent changes in venous access&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">5</span></a> The choice of insertion site must aim to reduce complications such as infection&#44; thrombosis&#44; stenosis&#44; and catheter malfunctioning&#46; The most common sites of insertion are the femoral vein&#44; internal jugular vein&#44; and subclavian vein&#46; Whether the right internal jugular or the femoral vein should be the first choice is a matter of controversy&#46; The KDIGO<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">5</span></a> and the European Renal Best Practice &#40;ERBP&#41; of the European Dialysis Association<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">6</span></a> recommended avoiding femoral access when jugular access is available due to a supposed increased risk of infection&#46; However&#44; several studies&#44; all of which were observational&#44; have yielded discrepant results regarding the incidence of complications between femoral and jugular access&#44;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">7&#8211;9</span></a> so the choice of insertion site remains a matter of individual preference&#44; given the low level of scientific evidence&#46; In 2008&#44; the <span class="elsevierStyleItalic">Cathedia</span> study was published&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">10</span></a> This prospective randomized multicenter trial comparing access through the femoral and internal jugular veins in critical patients undergoing CRRT found that canalization through the internal jugular vein did not reduce the risk of infection compared with femoral canalization except in patients with a high body mass index&#46; In 2012&#44; the same group published a study<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">11</span></a> with the patients in the <span class="elsevierStyleItalic">Cathedia</span> study who had required a second catheter in a site different from the first one&#46; They found no differences between the two sites in catheter malfunction&#44; colonization&#44; or the efficacy of dialysis&#46; In 2014&#44; a single-center observational study evaluating 419 femoral catheters and 82 in other sites found that the rates of colonization and infection were similar&#44; and the risk of infection was related to longer ICU stays&#44; older age&#44; and obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">12</span></a> In 2016&#44; Bellomo et al<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">13</span></a> analyzed the information about catheters obtained from the RENAL study&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">4</span></a> in which 1508 patients were randomized and information about the catheter was available for 1399 &#40;93&#37;&#41;&#46; The femoral vein &#40;especially the right&#41; was chosen in 937 &#40;67&#37;&#41; patients&#44; followed by the jugular &#40;25&#37;&#41; and the subclavian &#40;8&#37;&#41;&#46; The patients in whom the femoral vein was chosen had more severe disease and weighed less&#46; The impact of the insertion site on the dose of treatment was limited&#44; unlike the impact of catheter diameter&#44; which was greater in femoral catheterizations than catheterizations in other sites&#46; The authors concluded that the diameter of the catheter was more important for treatment dose than the site of catheterization&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The left jugular vein follows a tortuous course toward the right atrium&#44; and this can result in inadequate flow and filter malfunction&#59; for this reason&#44; this insertion site should be considered only after the right jugular and femoral veins&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">3</span></a> The subclavian vein would be the last choice because it is prone to stenosis that would make it impossible to create an arteriovenous fistula if chronic dialysis were necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">3</span></a> Likewise&#44; the possibility of stenosis of the iliac vein means that the femoral vein should be avoided if the patient might need a kidney transplant&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Ultrasound guidance for central venous catheter placement has been recommended for years&#46; The advantages are fewer complications such as bleeding&#44; pneumothorax&#44; and arterial wall puncture&#59; moreover&#44; ultrasound guidance makes it possible to avoid cannulation in thrombotic regions&#44; reduces the incidence of catheter-related thrombosis&#44; and results in lower costs by reducing the iatrogenic effects associated with blind insertion&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Complications</span><p id="par0035" class="elsevierStylePara elsevierViewall">The mechanical complications of catheter insertion include hematomas&#44; pseudoaneurysms&#44; vascular dissection&#44; and arterial puncture&#59; these complications occur in up to 5&#37; of insertions&#46; Other&#44; less common complications include hemothorax&#44; pneumothorax&#44; pneumopericardium&#44; retroperitoneal bleeding&#44; tracheal puncture&#44; chylothorax&#44; anesthetic blockade of the brachial plexus&#44; fat emboli&#44; cardiac arrhythmias&#44; and atrial rupture&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">15</span></a> Chest X-rays are mandatory after catheter insertion in the jugular vein or subclavian vein&#46; While the catheter is in use&#44; the main complications are malfunctioning&#44; thrombosis&#44; and infection&#46; <span class="elsevierStyleItalic">Malfunction and thrombosis&#58;</span> These complications are caused by intraluminal thrombosis&#44; catheter kinking&#44; or malpositioning with occlusion of the catheter holes against the vessel wall&#46; Malfunction manifests as increased pressure in the venous and arterial lines that results in inadequate treatment&#46; Polyurethane catheters are more prone to thrombosis&#46; The catheters are often sealed with heparin when not in use&#46; One recent study comparing sealing with heparin versus sealing with citrate found that citrate was better at restoring flow to obstructed catheters and had a lower incidence of infection and hemorrhagic complications&#46; <span class="elsevierStyleItalic">Infection&#58;</span> Infection results from the contamination of the catheter lumen from the skin and its entrance into the blood flow or even from the hematogenous dissemination of pathogens from other foci of infection&#46; The most common germs are coagulase negative <span class="elsevierStyleItalic">Staphylococci</span> and <span class="elsevierStyleItalic">Staphylococcus aureus</span> follow by gram-negative bacilli &#40;particularly <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#41;&#46; The incidence ranges from 3&#46;8 to 6&#46;6 episodes per 1000 days for nontunneled catheters and 1&#46;6 to 5&#46;5 episodes per 1000 days for tunneled catheters&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">16</span></a> As for any other catheter&#44; the risk factors for bacteremia are the frequency of catheter manipulation&#44; the patient&#39;s severity&#44; emergency insertion&#44; the time the catheter remains in place&#44; and the operator&#39;s experience&#46; Various studies mentioned above have failed to show a higher incidence of infection in femoral catheters compared to jugular catheters&#46; Among the fundamental measures to prevent infection&#44; the most important are extreme asepsis during insertion&#44; ultrasound guidance for insertion&#44; keeping manipulation to a minimum &#40;exclusive use for dialysis&#41;&#44; and appropriate training for staff&#46; The administration of local antibiotics to prevent infection is currently not recommended because it can favor fungal infection and resistance to antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">5</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Optimization of patency in CRRT circuits</span><p id="par0040" class="elsevierStylePara elsevierViewall">Maintaining the patency of the circuit during CRRT usually requires a pharmacological anticoagulation strategy&#46; The ideal anticoagulant should have the following properties&#58; &#40;a&#41; high antithrombotic potential with low risk of bleeding&#44; &#40;b&#41; anticoagulation limited to the extracorporeal circuit&#44; &#40;c&#41; quick and easy monitoring at the point of care&#44; &#40;d&#41; possibility of prolonged use without undesired secondary effects&#44; accumulation&#44; or tachyphylaxis&#44; and &#40;e&#41; an antidote that can reverse the effects immediately&#46; Below we present the different strategies for optimizing the patency of the CRRT circuits &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Non-pharmacological strategies</span><p id="par0045" class="elsevierStylePara elsevierViewall">It is important for the CRRT to incorporate biocompatible materials and to be designed in way that limits the turbulent flow of blood&#46; The biocompatibility of the membrane is especially important for preventing hemofilter coagulation&#46; Negatively charged membranes have a greater capacity for adsorption of proteins and formed elements of blood&#44; so they might not last as long as neutral membranes&#46; Hemofilters with larger membrane surfaces present less resistance to blood flow&#44; and this may also help them to last longer&#46; Moreover&#44; clotting is more likely to occur when blood flow through the circuit is interrupted or is slower&#46; Other measures that favor the rheology of the circuit include prescribing a filtration fraction &#60;25&#37; in convection techniques&#44; prioritizing diffusion rather than convection&#44; and predilution to limit the concentration of blood in the filter by reducing the viscosity of the blood&#46; The response to alarms must be rapid&#46; The correct adjustment of the level in the bubble-trapping capsule can reduce the effect of contact between blood and air and minimize the risk of coagulation at this point&#46; Establishing a protocol for the technique and ensuring that nursing staff are highly trained guarantee the best outcomes&#46; The intermittent infusion of saline solution has not proven beneficial in prolonging the life of the circuit&#46; Finally&#44; as discussed above&#44; it is very important to choose the best vascular access and the catheter with the best characteristics to ensure the correct flow of blood through the circuit and keep it from coagulating&#46;<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">17&#44;18</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">We also need to consider situations in which the circuit will not require any type of anticoagulation&#44; such as coagulopathies or platelet abnormalities&#46; There are no studies that can establish evidence for specific cutoffs for determining the platelet count&#44; activated partial thromboplastin time &#40;aPTT&#41;&#44; International Normalized Ratio &#40;INR&#41;&#44; fibrinogen&#44; or other coagulation factors that would indicate the possibility of carrying out CRRT without anticoagulation&#46; In recent years&#44; experts have recommended the following values&#58; thrombocytopenia with platelet count &#60;50<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;L&#44; aPTT &#62;60<span class="elsevierStyleHsp" style=""></span>s&#44; INR &#62;2&#44; and disseminated intravascular coagulation&#46; Similarly&#44; patients with acute kidney failure who require systemic anticoagulation for their underlying disease &#40;e&#46;g&#46;&#44; valve replacement&#44; atrial fibrillation&#44; or thromboembolic disease&#41; do not usually require additional anticoagulation for CRRT&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pharmacological strategies</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Anticoagulation for CRRT circuits with heparin</span><p id="par0055" class="elsevierStylePara elsevierViewall">In 2007&#44; the Beginning and Ending Supportive Therapy for the Kidney &#40;B&#46;E&#46;S&#46;T&#46; kidney&#41; investigators showed that up to 60&#37; of CRRT procedures were done without any type of anticoagulation&#46; When anticoagulation was prescribed&#44; unfractionated heparin was the most commonly used&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">19</span></a> In Spain&#44; a survey done in 51 ICUs confirmed that 96&#37; of the centers used heparin&#44; 39&#46;2&#37; used prostacyclin&#44; and only 5&#46;8&#37; used citrate&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">20</span></a></p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Unfractionated heparin</span><p id="par0060" class="elsevierStylePara elsevierViewall">This mixture of sulfated polysaccharides with molecular weights varying between 2<span class="elsevierStyleHsp" style=""></span>kDa and 30<span class="elsevierStyleHsp" style=""></span>kDa is the anticoagulant most commonly used in CRRT&#46; Unfractionated heparin achieves its anticoagulant effect by bonding with antithrombin&#44; favoring its bonding with thrombin &#40;FII&#41;&#44; and to a lesser extent by inhibiting activated factor X&#46; To inhibit thrombin&#44; it must bind both with thrombin itself and with antithrombin&#44; although it does not need to bind with antithrombin to inhibit activated factor X&#46; Its half-life ranges from 30<span class="elsevierStyleHsp" style=""></span>min to up to 3<span class="elsevierStyleHsp" style=""></span>h in cases with renal dysfunction&#46; Its major advantages are &#40;a&#41; it is inexpensive&#59; &#40;b&#41; prescribing physicians and the nurses in charge of the procedure are familiar with it&#59; &#40;c&#41; it is easy to administer and to monitor &#40;through aPTT&#41;&#59; and &#40;d&#41; its effects can be reversed with protamine&#46; There is no universally accepted protocol for its use&#44; although various algorithms have been proposed for its administration during CRRT&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">21</span></a> It is usually present in the solution primed from the system in variable concentrations &#40;1000&#8211;5000<span class="elsevierStyleHsp" style=""></span>IU per liter&#41;&#46; Before connection to CRRT and after the evaluation of the patient&#39;s coagulation&#44; a bolus &#40;30<span class="elsevierStyleHsp" style=""></span>IU&#47;kg body weight&#41; is usually administered through the arterial line&#59; the recommended maintenance dose is 5&#8211;10<span class="elsevierStyleHsp" style=""></span>IU&#47;kg&#47;h&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The main problems associated with heparin are its dosing&#44; bleeding&#44; resistance&#44; and heparin-induced thrombocytopenia&#46; The problem with dosing heparin is that there is no direct relation between the dose of heparin and the aPTT&#44; the duration of the filter&#44; or hemorrhagic complications&#46; Dosage is monitored through the aPTT&#44; targeting levels between 1&#46;5 and 2&#46;0 times the baseline value &#40;45&#8211;60<span class="elsevierStyleHsp" style=""></span>s&#41;&#46; The dose must be reduced drastically in patients with disseminated intravascular coagulation or thrombocytopenia&#46; Every increase of 10<span class="elsevierStyleHsp" style=""></span>s in the aPTT causes a 25&#37; decrease in clots in the filter&#46; The values of aPTT are partly dependent on the levels of coagulation factors associated with critical illness such as the variable clearing that the heparin itself undergoes when it is administered before filtering&#46; Hemorrhagic events are the most common complication&#44; affecting 10&#8211;50&#37; of cases&#44; depending on the type of population and the degree of anticoagulation&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">22</span></a> Hemorrhagic complications are not strictly related to the dose of heparin administered&#44; but they are strictly related to the aPTT&#46; The risk of bleeding increases by 50&#37; for each increment of 10<span class="elsevierStyleHsp" style=""></span>s in the aPTT&#46; The incidence of bleeding complications is underestimated because minor events often go unreported&#59; major bleeding events are defined as intracranial hemorrhage&#44; retroperitoneal hemorrhage&#44; or hemorrhages that result in death or the transfusion of &#8805;2 units of packed red blood cells&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Resistance to heparin is based on two pillars&#58; &#40;a&#41; On the one hand&#44; low levels of antithrombin III &#40;AT-III&#41;&#44; because this protein is consumed when the sepsis coagulation cascade is activated&#44; and greater proteolytic degradation mediated by granulocyte elastase&#44; the effect of which is increased by heparin itself&#46; &#40;b&#41; On the other hand&#44; the expression of heparin-binding proteins decreases heparin&#39;s effective concentration and thereby its anticoagulant effect&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">23</span></a> Some centers opt for the administration of AT-III to favor anticoagulation and the durability of the circuit&#44; but the cost-effectiveness remains to be determined&#46; Acquired AT-III deficiency &#40;AT-III &#60;70&#37;&#41; can be supplemented by an initial bolus &#91;AT-III bolus<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Weight<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>&#40;100<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>initial AT-III activity &#37;&#41;&#47;1&#46;5&#93;&#44; following a continuous infusion &#40;40<span class="elsevierStyleHsp" style=""></span>UI&#47;kg&#47;d&#41;&#46; The doses should be secondarily adjusted to maintain an AT-III activity level between 80&#37; and 100&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">24</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The incidence of heparin-induced thrombocytopenia &#40;HIT&#41; in ICU patients is very low&#44; ranging from 0&#46;3&#37; to 0&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">25</span></a> The frequency of HIT in critically ill patients receiving heparin anticoagulation for CRRT still remain to be determined in prospective studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">26&#44;27</span></a> It is advisable to determine the levels of antibodies to heparin platelet factor 4 &#40;H&#47;PF4&#41; after calculating the 4T score &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">28</span></a> The most susceptible patients are those with a decrease &#62;50&#37; on the fourth day of receiving heparin&#46; HIT should not be confused with the reversible thrombocytopenia that occurs after CRRT is started and ends when CRRT is stopped&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">26</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Low-molecular-weight heparine</span><p id="par0080" class="elsevierStylePara elsevierViewall">Low-molecular-weight heparins with 18 saccharide units have a lower molecular weight &#40;3600&#8211;6500<span class="elsevierStyleHsp" style=""></span>kDa&#41; than unfractionated heparin&#59; therefore&#44; they cannot simultaneously bond to thrombin and antithrombin&#44; so the antithrombin activity is lost but the anti-factor Xa activity is maintained&#46; Low-molecular-weight heparins are more effective than unfractionated heparin at decreasing fibrin deposits in the filter&#44; and they start to act faster&#44; activating fewer platelets and leukocytes&#46; They are less dependent on antithrombin&#44; bond less with proteins and cells&#44; cause less activation of platelet factor-4&#44; and result in a lower incidence of heparin-induced thrombocytopenia&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">29</span></a> These characteristics&#44; together with more predictable pharmacokinetics&#44; make low-molecular-weight heparins safer and more reliable&#46; Nevertheless&#44; they are more expensive than unfractionated heparin&#44; and monitoring their effects is more complex &#8211; not all centers can routinely determine anti-factor Xa levels&#46; The different molecules of low-molecular-weight heparins have distinct pharmacokinetics&#44; which is not interchangeable with their counterparts&#46; The bioavailability&#44; half-life&#44; or clearance in plasma and degree of accumulation in acute kidney failure can vary significantly among the different molecules&#46; A recent systematic review<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">30</span></a> concluded than no accumulation effect occurred with tinzaparin and dalteparin&#44; but significant accumulation effects occurred with enoxaparin&#44; bemiparin&#44; and certoparin&#44; even at prophylactic doses&#46; The range of anti-factor Xa for their use has not been defined and is extrapolated from intermittent dialysis &#40;iHD&#41; between 0&#46;2<span class="elsevierStyleHsp" style=""></span>IU&#47;ml and 0&#46;4<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46; Unlike in iHD&#44; the studies done in acute patients undergoing CRRT were done a long time ago&#44; included few patients&#44; and had heterogeneous objectives and designs&#44; so it is difficult to draw conclusions&#46; Low-molecular-weight heparins have been compared with unfractionated heparin<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">31&#44;32</span></a>&#59; different doses of low-molecular-weight heparins have been compared<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">33</span></a>&#59; and different low-molecular-weight heparins have been compared with each other<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">34</span></a> and with different anticoagulation strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">35</span></a> Two recent studies comparing the incidence of bleeding and the duration of the filter between enoxaparin and unfractionated heparin reported contradictory results&#46; Garc&#233;s et al&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">32</span></a> found similar filter life and anti-factor Xa &#8805;1&#46;0<span class="elsevierStyleHsp" style=""></span>IU&#47;ml with enoxaparin&#44; although the incidence of bleeding was higher&#46; On the other hand&#44; in a prospective controlled randomized crossover trial&#44; Joannidis et al&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">31</span></a> with anti-factor Xa levels between 0&#46;25<span class="elsevierStyleHsp" style=""></span>IU&#47;ml and 0&#46;30<span class="elsevierStyleHsp" style=""></span>IU&#47;ml found that the low-molecular-weight heparins &#40;0&#46;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg pre-filter bolus and 0&#46;05<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h maintenance perfusion&#41; conferred longer filter life without increasing the incidence of bleeding and were also a cost-effective option&#46; For all these reasons&#44; it is difficult to interpret low-molecular-weight heparins for use in CRRT&#46; Both the dose and the anti-factor Xa target must be tailored in function of the low-molecular-weight heparin chosen and the patient&#39;s clinical characteristics&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Anticoagulation with heparin-protamine &#40;regional heparinization&#41;</span><p id="par0085" class="elsevierStylePara elsevierViewall">First reported in the 1960s&#44; regional anticoagulation combines pre-filter unfractionated heparin and post-filter protamine to counteract its effects &#40;1<span class="elsevierStyleHsp" style=""></span>mg protamine&#47;100<span class="elsevierStyleHsp" style=""></span>IU heparin&#41;&#46; Its main indication was for patients in whom systemic anticoagulation was contraindicated&#46; Its use has declined in parallel with the rise of citrate and increased knowledge about the side effects of protamine&#46; Regional heparinization exposes patients to the risk of heparin-induced thrombocytopenia and the dose-dependent side effects of protamine&#58; hypotension decreased cardiac output&#44; anaphylaxis&#44; pulmonary vasoconstriction with the risk of right ventricular failure&#44; leukopenia&#44; and a paradoxical effect on coagulation&#46; This paradoxical effect is due to transient thrombocytopenia as well as platelet dysfunction &#40;lower reactivity and thrombin-mediated aggregation&#41;&#46; There is also a risk of a rebound anticoagulation effect because the half-life of heparin is longer than that of protamine&#59; this effect is dose dependent and increases slightly with prolonged administration&#46; Heparin-protamine complexes are taken up by the reticuloendothelial system&#44; which fractionates them&#44; rereleasing the heparin&#46; This makes it difficult to titrate the appropriate doses of protamine to reverse its effects&#46; It is more complex to monitor because the aPTT must be measured before and after the administration of the heparin and after reversion with protamine&#46; Protamine should not be used with heparin-lined filters because it reverses the effects of the heparin&#46; For all these reasons&#44; regional anticoagulation with heparin-protamine is not recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">36</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Regional anticoagulation with citrate</span><p id="par0090" class="elsevierStylePara elsevierViewall">This type of anticoagulation is based on the pre-filter administration of a fluid with a certain concentration of citrate&#46; Citrate chelates with the calcium in the blood and forms a citrate-calcium complex&#44; thus impeding the formation of clots because calcium is a cofactor necessary for the activation of the coagulation cascade&#46; The chelated calcium that is lost in the circuit is later replaced to maintain the ionized calcium in the patient&#39;s serum at normal levels&#46; Most of the citrate administered is also removed through the effluent&#46; The amount of citrate that passes into the patient&#39;s bloodstream is metabolized through the Krebs cycle in the liver&#44; muscle tissue&#44; and renal cortex&#46; Thus&#44; the circuit is anticoagulated without affecting the patient&#39;s coagulation and the life of the hemofilter is significantly prolonged&#44; minimizing the risk of bleeding&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Regional anticoagulation with citrate has been in use in intermittent dialysis for more than 20 years&#44; where it has reduced bleeding events in patients with a high risk of bleeding&#46; In recent years&#44; different manufacturers have incorporated software in their CRRT monitors to simplify the calculations necessary for the administration of citrate and to enable automatic calcium compensation&#46; This advance&#44; together with the commercialization of specific fluids for anticoagulation with citrate&#44; has reduced the complexity of this approach&#44; increased its safety&#44; and decreased its cost&#46;<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">37&#44;38</span></a> There is currently a wide consensus that regional anticoagulation with citrate should be the first-choice option for anticoagulation in patients with high risk of bleeding&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">22&#44;39&#44;40&#44;5</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The main complications of citrate are alterations in the acid&#8211;base balance&#44; hypocalcemia&#44; and hypercalcemia&#46; In the patient&#39;s body&#44; the citrate&#8211;calcium complex is metabolized mainly in the liver&#44; but the kidneys and skeletal muscle also contribute&#46; Citrate is converted into sodium bicarbonate &#40;1<span class="elsevierStyleHsp" style=""></span>mmol of citrate is converted into 3<span class="elsevierStyleHsp" style=""></span>mmol sodium bicarbonate&#41;&#44; so the net result of the metabolism of the citrate&#8211;calcium complex is the incorporation of an alkali &#40;sodium bicarbonate&#41;&#44; which affects the acid&#8211;base balance&#46; Hypocalcemia can result from insufficient replacement of the calcium that is chelated by the citrate&#44; and hypercalcemia can result from excessive replacement &#40;whether due to error or inadvertently maintaining continuous calcium infusion after suspending anticoagulation with citrate&#41;&#46; Citrate also chelates magnesium&#44; so magnesium levels must be closely monitored and supplemented to avoid hypomagnesemia&#46; If the administration of citrate is excessive and the patient can metabolize it&#44; the immediate consequences are hypernatremia and metabolic alkalosis&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Citrate intoxication occurs when the patient cannot metabolize the citrate administered&#59; this occurs in ischemic hepatitis &#40;even before it is reflected in increased liver enzymes&#41; or in decreased hepatic blood flow or severe peripheral hypoperfusion &#40;cardiogenic shock and&#47;or septic shock&#41;&#46; It has been suggested that regional anticoagulation with citrate might be contraindicated in these patients&#46; In this case&#44; we would observe metabolic acidosis &#40;with high anion gap&#41; and a steep drop in the levels of ionic calcium in a patient with high total calcium&#44; hypophosphatemia&#44; and hypomagnesemia&#46; The gold standard for the diagnosis for this complication is the direct measurement of the concentration of citrate in plasma&#59; however&#44; this determination is not usually available in daily practice&#46; The laboratory determination used instead is the ratio of total calcium to ionic calcium&#46; The normal value of this ratio is 2 &#40;total calcium is normally the double of ionic calcium&#41; and values &#8805;2&#46;5 indicate intoxication&#46; In these patients&#44; the classical liver function parameters such as the transaminases and bilirubin are poor predictors of the development of citrate intoxication&#59; the best predictors of this complication are serum lactate &#40;&#8805;3&#46;4<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41; and prothrombin time &#40;&#8804;26&#37; or &#8805;33<span class="elsevierStyleHsp" style=""></span>s&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">41</span></a> An increasing number of publications show adequate tolerance to anticoagulation with citrate in patients with compensated cirrhosis of the liver or acute liver failure<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">40&#44;42&#44;43</span></a> since these patients do not have more metabolic complications&#46; More frequent monitoring &#40;every 4<span class="elsevierStyleHsp" style=""></span>h&#41; and higher target ranges of ionized calcium in the circuit &#40;0&#46;3&#8211;0&#46;5<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41; are necessary to guarantee patient safety&#46; This strategy is able to guarantee acceptable filter life by decreasing the contribution of citrate and the risk of intoxication&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">44</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">We can conclude that there are no absolute contraindications for the use of citrate&#44; although it must be employed with particular caution in clinical contexts characterized by severe liver failure&#47;liver transplant or in situations of severe lactic acidosis secondary to hepatic hypoperfusion and severe intracellular hypoxia &#40;septic or cardiogenic shock&#41;&#46;</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Studies that compare citrate with other modalities</span><p id="par0115" class="elsevierStylePara elsevierViewall">There is a growing body of literature to support favorable results for regional anticoagulation with citrate in CRRT&#46; The strong points of this approach versus other anticoagulation strategies are the increased life of the filter and the decreased number of hemorrhagic complications&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows some of the most relevant and most recent studies that compare regional anticoagulation with citrate against other anticoagulation strategies&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Oudemans et al&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">45</span></a> did a comparative analysis of the large randomized multicenter studies published through 2014 &#40;CASH<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">46</span></a> from 2014&#44; OVLG<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">47</span></a> from 2009&#44; and Hetzel<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">48</span></a> from 2011&#41;&#46; In the CASH study<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">46</span></a> citrate was compared to systemic anticoagulation with heparin in 139 patients&#46; No differences were found in mortality or in recovery of renal function&#44; but citrate was superior in terms of safety &#40;fewer adverse effects&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; efficacy &#40;longer filter life&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; and costs &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The OLVG study<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">47</span></a> compared citrate with nadroparin in 200 patients&#46; The efficacy of the two drugs was similar&#44; but citrate was safer &#40;fewer complications&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In a secondary analysis in subgroups&#44; citrate was particularly beneficial after surgery and in sepsis with multiple organ failure&#44; where renal recovery and mortality were improved&#46; The improved survival was attributed to a possible immunomodulating effect of citrate&#46; This hypothesis is supported by experimental data showing that anticoagulation with citrate impedes the degranulation of polymorphonuclear leukocytes and the activation of thrombocytes induced by dialysis&#59; these processes depend on ionic calcium and are blocked by the administration of citrate&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">49&#44;50</span></a> In the Hetzel study&#44;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">48</span></a> citrate was compared against systemic heparin in 170 patients&#46; No significant differences were found in the number of alterations in the acid&#8211;base balance or in the reduction of the levels of urea&#46; The group that received citrate had longer filter life and a lower risk of bleeding&#46; No differences in 30-day mortality were found&#46; Hafner et al&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">51</span></a> also compared citrate against systemic heparin&#46; Both modalities were effective in controlling uremia&#44; although the reduction in urea was larger in the citrate group&#59; the authors attributed this difference to longer hemofilter life&#46; The citrate group had slight alterations in the levels of pH&#44; ionic calcium&#44; and sodium&#59; however&#44; these alterations were not associated with adverse events and were all successfully resolved by modifying fluids according to protocol&#46; In the economic analysis&#44; citrate was cost-effective&#46; In a meta-analysis of six randomized controlled trials with a total of 488 patients&#44; Wu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">52</span></a> found that patients receiving citrate had a lower risk of bleeding without an increased incidence of alkalosis compared to patients in whom the circuits were anticoagulated with heparin&#46; The efficacy and filter life were similar in the two groups&#46; The authors concluded that citrate is at least as safe as heparin and significantly cheaper&#46; Gattas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">53</span></a> recently carried out a prospective randomized multicenter trial comparing citrate versus heparin-protamine in 212 patients&#46; The results showed longer filter lifespan and fewer adverse events in the citrate group&#46; There were no differences in the number of transfusions&#44; the duration of CRRT&#44; length of stay&#44; or mortality&#46; There were also no differences in cytokine levels&#46; Stucker et al<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">54</span></a> found that citrate was superior to heparin as a method of anticoagulation in terms of dose and filter lifespan&#46; Alterations in electrolytes and acid&#8211;base balance in the citrate group were uncommon&#44; short-lived&#44; and preventable with a strict protocol&#46; There were no differences in short-term survival&#46; Bai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">55</span></a> recently published a meta-analysis including the randomized controlled trials that compared heparin versus citrate in CRRT&#46; The meta-analysis included a total of 992 patients in 11 studies&#59; two of these used regional heparinization&#44; and the rest used systemic heparinization&#46; In the citrate group&#44; there was a significant reduction in the risk of circuit loss and filter failure compared to the groups receiving regional heparinization or systemic heparinization&#46; The risk of bleeding in the citrate group was significantly lower than in the systemic heparinization group and similar to that observed in the regional heparinization group&#46; No differences were observed in survival&#46; These authors concluded that given the low risk of circuit loss and filter failure&#44; regional anticoagulation with citrate should be considered a better method of anticoagulation than heparin in critical patients without contraindications&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In summary&#44; regional anticoagulation with citrate can be considered efficacious and safer than anticoagulation with heparin&#46; Citrate is associated with increased hemofilter lifespan and a lower risk of bleeding and multiple transfusions&#46; Regional anticoagulation with citrate administered under strict protocols by properly trained staff is not associated with significant adverse events&#46; More economic studies are necessary to evaluate its cost-effectiveness&#46; The anti-inflammatory effects of citrate during CRRT and its impact on survival are controversial and should be evaluated in future studies&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Thrombin inhibitors</span><p id="par0130" class="elsevierStylePara elsevierViewall">Direct thrombin inhibitors &#40;lepirudin&#44; argatroban&#44; bivalidurin&#41; have proven efficacy as anticoagulants in critical patients with heparin-induced thrombocytopenia&#46; However&#44; most of the studies that support their use in CRRT are limited&#44; retrospective&#44; observational&#44; and small&#46; Heparin-induced thrombocytopenia results from the formation of antibodies against the heparin-platelet factor 4 complex&#44; which secondarily activates the platelets and coagulation and eventually leads to increased thrombin formation&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">56</span></a> The probability of heparin-induced thrombocytopenia can be predicted with the 4T score&#44; which includes the degree of thrombocytopenia&#44; time since the onset of the drop in platelet levels&#44; presence of thrombosis or acute systemic symptoms&#44; and presence of other causes of thrombocytopenia&#46; Although the incidence of this complication in critical patients is low &#40;0&#46;3&#8211;0&#46;5&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">25</span></a> it is associated with increased morbidity and mortality if its diagnosis is delayed&#44; due to the prothrombotic situation it generates&#46; In patients undergoing CRRT&#44; heparin-induced thrombocytopenia can be suspected when the circuit becomes clotted early and repeatedly&#44; even when citrate is used&#46;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">57&#44;58</span></a> Suspicion of heparin-induced thrombocytopenia requires treatment with heparin or heparin derivatives to be discontinued&#46; No randomized studies have indicated the optimal anticoagulant in cases of heparin-induced thrombocytopenia&#46; This choice will depend on local availability and experience in monitoring&#46; Although citrate can be used for regional anticoagulation&#44; these patients need thromboprophylaxis&#46; These drugs inhibit free thrombin and thrombin bound in thrombi&#44; and they do not react with antibodies against heparin&#46; There are important differences in the pharmacokinetics of the three most studied direct thrombin inhibitors&#44; and these are explained here below&#46;</p><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Lepirudin</span><p id="par0135" class="elsevierStylePara elsevierViewall">This drug is metabolized by the kidneys&#46; In patients with acute kidney failure&#44; the half-life can be prolonged up to 50<span class="elsevierStyleHsp" style=""></span>h&#44; with the risk of the drug accumulating and increasing the risk of bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">59</span></a> It is usually monitored through the aPTT&#44; although the relationship between the levels of lepirudin and the aPTT is not linear&#46; The most accurate test is ecarin clotting time&#44; but this test is not available in all centers&#46; Some cases of anaphylaxis have been reported&#46; Lepirudin is perfused intravenously &#40;0&#46;005&#8211;0&#46;01<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#41; and the dose is adjusted in function of the time to ecarin clotting&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">60</span></a> There is no specific antidote&#44; but factor VIIa can be used in case of bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">61</span></a> In 2014&#44; Treschan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">62</span></a> published the results of a randomized double-blind study &#40;ALicia&#41; comparing lepirudin and argatroban in 28 critical postoperative patients with suspected heparin-induced thrombocytopenia and need for CRRT&#46; The two drugs were equally efficacious in terms of circuit survival&#44; but the lepirudin group had more episodes of bleeding&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Argatroban</span><p id="par0140" class="elsevierStylePara elsevierViewall">A derivative of <span class="elsevierStyleSmallCaps">l</span>-arginine&#44; argatroban bonds reversibly to the catalytic site of thrombin without the need for a cofactor&#46; It is metabolized by the liver &#40;70&#37;&#41; and has a short half-life &#40;31&#8211;59<span class="elsevierStyleHsp" style=""></span>min&#41;&#44; so it may be appropriate for critical patients with acute kidney failure without liver failure who need CRRT&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">63</span></a> The recommended dose&#44; based on a prospective study of 30 patients with heparin-induced thrombocytopenia&#44; acute kidney failure&#44; and CRRT&#44; is a bolus of 100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg followed by the perfusion of 1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;min&#59; the dose is adjusted to reach a target pre-filter aPTT of 1&#46;5&#8211;3 times the baseline level&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">59</span></a> In patients with liver dysfunction&#44; the half-life of the drug increased&#44; making it necessary to reduce the dose&#44; as in patients with multiple organ dysfunction &#40;0&#46;2&#8211;0&#46;6<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#47;min&#41;&#46; There was an inversely proportional relation between the maintenance dose and severity scales&#59; the closest correlation was with the Sequential Organ Failure Assessment &#40;SOFA&#41; &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;90&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; dose &#956;g&#47;kg&#47;min<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;18&#8211;0&#46;09<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>SOFA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">59</span></a> Argatroban brought about an increase in filter lifespan comparable to that achieved with unfractionated heparin&#44; but argatroban did not increase the risk of bleeding after heart surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">64</span></a> There is no specific antidote for argatroban&#44; but an ex vivo study showed that factor VIIa can be used in cases of bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">61</span></a> The KDIGO guidelines recommend using argatroban during CRRT before other thrombin inhibitors or factor Xa inhibitors in patients with heparin-induced thrombocytopenia that do not have severe liver failure&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Bivalidurin</span><p id="par0145" class="elsevierStylePara elsevierViewall">Bivalidurin reversibly inhibits thrombin&#46; It has a short half-life &#40;25<span class="elsevierStyleHsp" style=""></span>min&#41; and has the additional advantage over argatroban that its metabolism is enzymatic&#44; so it can be used in patients with heparin-induced thrombocytopenia who have hepatic and renal dysfunction&#46; Although the prescribing information does not list this indication&#44; retrospective studies with few patients on the efficacy&#44; safety&#44; and dosing in these patients have shown good results&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">65</span></a> The dose in patients on CRRT is 0&#46;03&#8211;0&#46;05<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#44; which is adjusted in function of the pre-filter aPTT &#40;1&#46;5&#8211;2&#46;5 times the baseline level&#41;&#46; One prospective randomized double-blind study in 10 patients showed that the lifespan of the hemofilter was prolonged significantly compared to unfractionated heparin and to no anticoagulation&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">66</span></a> Although no specific antidote is available&#44; in cases with bleeding&#44; factor VIIa can be administered&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">61</span></a></p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Platelet aggregation inhibitors</span><p id="par0150" class="elsevierStylePara elsevierViewall">Prostacyclin &#40;PGI2&#41; is derived from the arachidonic acid in the vascular tissues and inhibits the final pathway of all mechanisms of cellular activation that lead to the adhesion&#44; activation&#44; liberation&#44; and aggregation of the platelets&#46; This effect is mediated by an increase in the intracellular levels of cyclic adenosine monophosphate &#40;cAMP&#41; secondary to the activation of the membrane&#39;s specific adenyl cyclase receptors&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">67</span></a></p><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Epoprostenol</span><p id="par0155" class="elsevierStylePara elsevierViewall">The vasodilatory effects of this drug are short lasting &#40;half-life 2<span class="elsevierStyleHsp" style=""></span>min&#41; whereas its antiplatelet effects last longer &#40;2<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; Some studies have analyzed the use of prostacyclin alone<a class="elsevierStyleCrossRefs" href="#bib0740"><span class="elsevierStyleSup">68&#44;69</span></a> or combined with unfractionated heparin&#46; The lifespan of the circuits was longer when it was used with unfractionated heparin &#40;PGI2 4&#8211;5<span class="elsevierStyleHsp" style=""></span>ng&#47;kg&#47;min with 2&#8211;3<span class="elsevierStyleHsp" style=""></span>IU&#47;kg&#47;h unfractionated heparin&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">70</span></a> Herrera et al&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">71</span></a> reported that circuit lifespan was similar with epoprostenol and unfractionated heparin but the risk of bleeding with epoprostenol was lower&#46; Hemodynamic instability was the most common adverse effect associated with PGI2&#44; and it was directly related to the dose used&#46; The main drawback is the risk of arterial hypotension&#44; and this can be minimized by progressively increasing the dose&#46; The cost has come down since a generic version of this drug became available&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Nafamostat</span><p id="par0160" class="elsevierStylePara elsevierViewall">Nafamostat&#44; a prostacyclin analog&#44; is a synthetic serine protease inhibitor that inhibits various coagulation factors &#40;thrombin&#44; factor Xa&#44; factor XIIa&#44; kallikrein&#41; and components of the complement system&#44; as well as platelet aggregation&#46; It has a low molecular weight and a short half-life &#40;5&#8211;8<span class="elsevierStyleHsp" style=""></span>min&#41;&#46; It is eliminated through the circuit&#44; limiting systemic anticoagulation and lowering the risk of bleeding&#46; Few data &#40;only from Japan and Korea&#41; are available about its use in CRRT because it is not available in the United States or Europe&#46; Retrospective<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">72</span></a> and prospective<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">73</span></a> studies have demonstrated the efficacy and safety of nafamostat &#40;fewer bleeding episodes and transfusions&#41;&#46; However&#44; Baek et al<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">72</span></a> founder longer filter lifespan without anticoagulation than with nafamostat &#40;27&#46;5 vs&#46; 19&#46;8<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; and Lee et al<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">73</span></a> found a nonsignificant trend toward longer circuit lifespan with nafamostat than with no anticoagulation&#46; Moreover&#44; significant secondary effects such as anaphylaxis&#44; agranulocytosis&#44; and hyperkalemia have been reported&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Finally in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> are summarized the main key points of this review about vascular access and circuit patency in continuous renal replacement therapy&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0170" class="elsevierStylePara elsevierViewall">Vascular access placement and filter patency &#40;anticoagulation&#41; is a fundamental issue strictly related to dialysis delivery and should be carefully evaluated for each patient and CRRT modalities&#46; Non-tunneled polyurethane catheters with a double lumen are the appropriate vascular access for CRRT in acute kidney failure&#46; The vein used for the catheter insertion should be chosen taking into account the patients&#8217; clinical characteristics&#46; The catheter should be placed under ultrasound guidance and with adherence to infection-control policies&#46; Citrate anticoagulation may be used for all patients without contraindications&#46; Heparin as a first choice is still feasible in patients without high risk of bleeding&#44; especially for units with less or no experience in citrate anticoagulation&#46; In patients with heparin-induced thrombocytopenia&#44; the administration of thrombin inhibitors &#40;argatroban&#41; or factor Xa inhibitors &#40;danaparoid or fondaparinux&#41; is highly recommended&#46; The evidence available about the safety and efficacy of thrombin inhibitors and platelet aggregation inhibitors is insufficient to recommend their use in routine practice&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0175" class="elsevierStylePara elsevierViewall">There has been no funding for the realization of this writing&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:7 [
        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        1 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Vascular access for continuous renal replacement therapies"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Characteristics of catheters"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Insertion and site"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Complications"
            ]
          ]
        ]
        2 => array:3 [
          "identificador" => "sec0030"
          "titulo" => "Optimization of patency in CRRT circuits"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Non-pharmacological strategies"
            ]
            1 => array:3 [
              "identificador" => "sec0040"
              "titulo" => "Pharmacological strategies"
              "secciones" => array:4 [
                0 => array:3 [
                  "identificador" => "sec0045"
                  "titulo" => "Anticoagulation for CRRT circuits with heparin"
                  "secciones" => array:3 [
                    0 => array:2 [
                      "identificador" => "sec0050"
                      "titulo" => "Unfractionated heparin"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0055"
                      "titulo" => "Low-molecular-weight heparine"
                    ]
                    2 => array:2 [
                      "identificador" => "sec0060"
                      "titulo" => "Anticoagulation with heparin-protamine &#40;regional heparinization&#41;"
                    ]
                  ]
                ]
                1 => array:3 [
                  "identificador" => "sec0065"
                  "titulo" => "Regional anticoagulation with citrate"
                  "secciones" => array:1 [
                    0 => array:2 [
                      "identificador" => "sec0070"
                      "titulo" => "Studies that compare citrate with other modalities"
                    ]
                  ]
                ]
                2 => array:3 [
                  "identificador" => "sec0075"
                  "titulo" => "Thrombin inhibitors"
                  "secciones" => array:3 [
                    0 => array:2 [
                      "identificador" => "sec0080"
                      "titulo" => "Lepirudin"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0085"
                      "titulo" => "Argatroban"
                    ]
                    2 => array:2 [
                      "identificador" => "sec0090"
                      "titulo" => "Bivalidurin"
                    ]
                  ]
                ]
                3 => array:3 [
                  "identificador" => "sec0095"
                  "titulo" => "Platelet aggregation inhibitors"
                  "secciones" => array:2 [
                    0 => array:2 [
                      "identificador" => "sec0100"
                      "titulo" => "Epoprostenol"
                    ]
                    1 => array:2 [
                      "identificador" => "sec0105"
                      "titulo" => "Nafamostat"
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "sec0110"
          "titulo" => "Conclusions"
        ]
        4 => array:2 [
          "identificador" => "sec0115"
          "titulo" => "Funding"
        ]
        5 => array:2 [
          "identificador" => "sec0120"
          "titulo" => "Conflict of interest"
        ]
        6 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-05-30"
    "fechaAceptado" => "2016-09-19"
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1823
            "Ancho" => 3337
            "Tamanyo" => 359526
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Algorithm for anticoagulation strategies in CRRT&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The 4Ts score is the sum of the values for each of the 4 categories&#46; Scores of 1&#8211;3 are considered to correspond to a low&#44; 4&#8211;5 intermediate&#44; and 6&#8211;8 high probability of HIT&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Category&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 Points&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 Point&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">0 Point&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Platelet count fall &#62;50&#37; and platelet nadir &#8805;20<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Platelet count 30&#8211;50&#37; or platelet nadir 10&#8211;19<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Platelet count fall &#60;30&#37; or platelet nadir &#60;10<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Timing of the decrease in platelet count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clear onset days 5&#8211;10 or platelet fall &#8804;1 day &#40;prior heparin exposure within 30 days&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Consistent with days 5&#8211;10 fall&#44; but not clear &#40;e&#46;g&#46;&#44; missing platelet counts&#41;&#59; onset after day 10&#59; or fall &#8804;1 day &#40;prior heparin exposure 30&#8211;100 days ago&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Platelet count &#8804;4 days without recent exposure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thrombosis or other sequelae&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">New thrombosis &#40;confirmed&#41;&#59; skin necrosis&#59; acute systemic reaction postintravenous unfractionated heparin bolus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Progressive or recurrent thrombosis&#59; non-necrotizing &#40;erythematous&#41; skin lesions&#59; suspected thrombosis &#40;not proven&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other causes of thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None evident&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Definite&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1266453.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical estimation of the probability of HIT &#40;The 4Ts score&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">28</span></a></p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AKI&#44; acute kidney injury&#59; C&#44; citrate&#59; Syst&#46; hept&#44; systemic heparin&#59; Reg&#46; hep&#44; regional heparin &#40;heparin-protamine&#41;&#59; RR&#44; relative risk&#59; CI&#44; confidence interval&#59; RRT&#44; renal replacement therapy&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&#176; patients&#58; citrate vs&#46; heparine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&#176; centers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Exclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Monchi et al&#46;&#44; 2004<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">74</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;8<br>Syst&#46; hep&#58; 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Liver cirrhosis&#46; High risk of bleeding&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Longer filter life in the citrate group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0007&#41;&#46; Higher transfusion rate in the heparin group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0008&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kutsogiannis et al&#46;&#44; 2005<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">75</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;16<br>Syst&#46; hep&#58; 14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Liver failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significantly longer filter life in the citrate group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Lower RR of bleeding with citrate than with heparin &#40;RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;14&#59; 95&#37; CI&#58; 0&#46;02&#8211;0&#46;96&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bagshaw et al&#46;&#44; 2005<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">76</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;54<br>Syst&#46; hep&#58; 29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chronic dialysis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Significantly longer filter life in the citrate group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Regional anticoagulation with citrate well tolerated without significant complications in acid&#8211;base balance or electrolytes&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Betjes et al&#46;&#44; 2007<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">77</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;21<br>Syst&#46; hep&#58; 27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Need for RRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Acute liver failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Similar filter lifespan in the two groups&#46; No significant adverse metabolic events in the citrate group&#46; More bleeding events &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and transfusions &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in the heparin group&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fealy et al&#46;&#44; 2007<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">78</span></a><br>&#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;10<br>Reg&#46; hep&#58; 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Acute or chronic liver failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Longer circuit life in the citrate group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;77&#41;&#46; No bleeding episodes in either group&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oudemans-van Straaten et al&#46;&#44; 2009<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">47</span></a> &#40;OLVG study&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58; 97<br>Syst&#46; hep&#58; 103<br>&#40;nadroparin&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Liver cirrhosis&#44; chronic dialysis&#44; heparin-induced thrombocytopenia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Similar efficacy&#46; Citrate was safer &#40;fewer complications <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Secondary analyses of surgical patients and patients with multiple organ failure showed better recovery of renal function and lower mortality in the citrate group&#46; Possible immunomodulating effect&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hetzel et al&#46;&#44; 2011<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">48</span></a> &#40;Hetzel study&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;87<br>Syst&#46; hep&#58; 83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Metabolic alkalosis&#44; pregnancy&#44; breast feeding&#44; chronic dialysis&#44; heparin-induced thrombocytopenia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No significant differences in the number of acid&#8211;base balance alterations or in urea levels&#46; Longer filter life in the citrate group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and lower risk of bleeding&#46; No differences in 30-day survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tiranathanagul et al&#46;&#44; 2011<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">79</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;10<br>Syst&#46; hep&#58; 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Acute or chronic liver failure&#46; Dialysis in the previous 24<span class="elsevierStyleHsp" style=""></span>h&#44; hypercalcemia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Longer circuit life in the citrate group&#46; After measuring the pre- and post-filter levels of myeloperoxidase of the polymorphonuclear leukocytes&#44; they concluded that citrate therapy could also reduce membrane-induced bioincompatibility phenomena &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; Citrate seemed to help control the inflammatory response and systemic oxidative stress &#40;decrease in IL8 levels&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Schilder et al&#46;&#44; 2014 &#40;48&#41; &#40;CASH study&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58; 66<br>Syst&#46; hep&#58;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Need for RRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High risk of bleeding&#44; heparin-induced thrombocytopenia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No differences in mortality or recovery of renal function&#46; Citrate was superior in terms of safety &#40;fewer adverse events&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; efficacy &#40;longer filter life&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; and costs &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Brain et al&#46;&#44; 2014<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">80</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;19<br>Syst&#46; hep&#58; 11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Weight &#60;30<span class="elsevierStyleHsp" style=""></span>kg&#44; pregnancy or breast feeding&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Longer filter life in the citrate group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stucker et al&#46;&#44; 2015<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">54</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;54<br>Syst&#46; hep&#58; 49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Liver failure&#44; high risk of bleeding&#44; heparin-induced thrombocytopenia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">As a method of circuit anticoagulation&#44; citrate was superior to heparin in terms of dose &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41; and filter lifespan &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#46; In the citrate group&#44; alterations in electrolytes and in acid&#8211;base balance were uncommon&#44; transitory&#44; and preventable with a strict protocol&#46; There were no differences in short-term survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hafner et al&#46;&#44; 2015<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">51</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;60<br>Syst&#46; hep&#58; 50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI and indication of RRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The two modalities were effective in controlling uremia&#44; but the reduction in urea after 3 or 4 days was significantly greater in the citrate group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#59; this difference was attributed to longer filter life&#46; The citrate group had higher levels of pH&#44; lower levels of ionic Ca&#44; and higher levels of Na&#44; without associated adverse effects &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#59; these alterations were successfully resolved by modifying flow according to protocol&#46; Circuit lifespan was significantly longer in the citrate group&#46; Citrate was cost-effective&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gattas et al&#46;&#44; 2015<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">53</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&#58;105<br>Reg&#46; hep&#58; 107&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AKI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Liver failure&#44; pregnancy&#44; breast feeding&#44; heparin-induced thrombocytopenia&#44; chronic dialysis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Longer filter life &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0004&#41; and fewer adverse effects &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in the citrate group&#46; No differences in the number of transfusions&#44; the duration of treatment&#44; length of stay&#44; or mortality&#46; Similar effects on cytokine levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1266454.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Studies comparing regional anticoagulation with citrate versus other anticoagulation strategies&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#46; Non-tunneled polyurethane catheters with a double lumen are the appropriate vascular access for CRRT in acute kidney failure&#46; Tunneled silicone catheters represent an alternative that is generally reserved for longer treatments or for patients with problematic venous access&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&#46; The right internal jugular vein or the femoral veins are the access sites of choice&#46; The subclavian vein should be avoided due to the high risk of thrombosis and stenosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&#46; The location&#44; diameter&#44; geometry&#44; and length of the catheter should be tailored to physical and clinical characteristics of the patient&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&#46; Dialysis catheters should be placed under ultrasound guidance to minimize the iatrogenic effects of insertion&#46; Malfunction&#44; thrombosis&#44; and infection are complications that can be prevented by proper care of the catheter&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&#46; When not in use&#44; catheters should be sealed with an antithrombotic solution&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&#46; Non-pharmacological measures are useful strategies for optimizing the patency of the circuit&#46; These include correct venous access&#44; appropriate settings of blood flow and filtration fraction&#44; prior dilution&#44; favoring diffusion over convection&#44; ensuring thorough training of staff&#44; using protocols&#44; and monitoring the technique closely&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7&#46; Unfractionated heparin continues to be the anticoagulation strategy most frequently employed in CRRT&#46; It is an effective anticoagulation strategy&#44; but there are problems with dosing and increased risk of bleeding&#46; There may also be a certain degree of resistance to heparin&#44; and this strategy can result in heparin-induced thrombocytopenia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8&#46; Despite repeated clotting of the filter&#44; forgoing anticoagulation of the circuit continues to be a common option in patients with high risk of bleeding in centers where regional anticoagulation with citrate is not available&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9&#46; Regional anticoagulation with citrate has proven very effective&#46; It is associated with increased filter lifespan and decreased risk of bleeding and need for multiple transfusions&#46; This strategy should be the first choice in patients with increased risk of bleeding&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10&#46; Regional anticoagulation with citrate requires strict protocols and thorough staff training to ensure patient safety&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11&#46; In patients without high risk of bleeding&#44; citrate&#44; unfractionated heparin&#44; and low-molecular-weight heparins have all proven efficacious&#46; The choice of strategy will depend on the patient&#39;s clinical condition and contraindications&#44; as well as on the center&#39;s experience and protocols&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12&#46; Unfractionated heparin or low-molecular-weight heparins are probably the best alternatives in patients with low risk of bleeding in whom citrate administration is contraindicated&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13&#46; In patients with heparin-induced thrombocytopenia&#44; the administration of thrombin inhibitors &#40;argatroban&#41; or factor Xa inhibitors &#40;danaparoid or fondaparinux&#41; is highly recommended&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">14&#46; Regional anticoagulation with heparin-protamine is not currently recommended&#46; The evidence available about the safety and efficacy of epoprostenol and other platelet aggregation inhibitors and thrombin inhibitors is insufficient to recommend their use in routine practice&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1266452.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Key points&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:80 [
            0 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Blood recirculation in temporary central catheters for acute hemodialysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Leblanc"
                            1 => "S&#46; Fedak"
                            2 => "G&#46; Mokris"
                            3 => "E&#46;P&#46; Paganini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Nephrol"
                        "fecha" => "1996"
                        "volumen" => "45"
                        "paginaInicial" => "315"
                        "paginaFinal" => "319"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8738663"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparison of the Niagara and Medcomp catheters for continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "N&#46; Fealy"
                            1 => "I&#46; Kim"
                            2 => "I&#46; Baldwin"
                            3 => "A&#46; Schneider"
                            4 => "R&#46; Bellomo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/0886022X.2012.757823"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ren Fail"
                        "fecha" => "2013"
                        "volumen" => "35"
                        "paginaInicial" => "308"
                        "paginaFinal" => "313"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23356529"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vascular access for continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Vijayan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1525-139X.2008.00553.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Dial"
                        "fecha" => "2009"
                        "volumen" => "22"
                        "paginaInicial" => "133"
                        "paginaFinal" => "136"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19426415"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intensity of continuous renal-replacement therapy in critically ill patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "RENAL Replacement Therapy Study Investigators"
                            1 => "R&#46; Bellomo"
                            2 => "A&#46; Cass"
                            3 => "L&#46; Cole"
                            4 => "S&#46; Finfer"
                            5 => "M&#46; Gallagher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0902413"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2009"
                        "volumen" => "361"
                        "paginaInicial" => "1627"
                        "paginaFinal" => "1638"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19846848"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "KDIGO clinical practice guideline for acute kidney injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Kidney Disease&#58; Improving Global Outcomes &#40;KDIGO&#41; Acute Kidney Injury Work Group"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2012"
                        "volumen" => "2"
                        "paginaInicial" => "1"
                        "paginaFinal" => "138"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4671525"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis&#44; prevention and treatment of haemodialysis catheter-related bloodstream infections &#40;CRBSI&#41;&#58; a position statement of European Renal Best Practice &#40;ERBP&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Vanholder"
                            1 => "B&#46; Canaud"
                            2 => "R&#46; Fluck"
                            3 => "M&#46; Jadoul"
                            4 => "L&#46; Labriola"
                            5 => "A&#46; Marti-Monros"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "NDT Plus"
                        "fecha" => "2010"
                        "volumen" => "3"
                        "paginaInicial" => "234"
                        "paginaFinal" => "246"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Central venous catheter-related infection in a prospective and observational study of 2&#44;595 catheters"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "L&#46; Lorente"
                            1 => "C&#46; Henry"
                            2 => "M&#46;M&#46; Mart&#237;n"
                            3 => "A&#46; Jim&#233;nez"
                            4 => "M&#46;L&#46; Mora"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/cc3824"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2005"
                        "volumen" => "9"
                        "paginaInicial" => "R631"
                        "paginaFinal" => "R635"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16280064"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "&#91;discussion 234&#8211;5&#93;"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The incidence of infectious complications of central venous catheters at the subclavian&#44; internal jugular&#44; and femoral sites in an intensive care unit population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;S&#46; Deshpande"
                            1 => "C&#46; Hatem"
                            2 => "H&#46;L&#46; Ulrich"
                            3 => "B&#46;P&#46; Currie"
                            4 => "T&#46;K&#46; Aldrich"
                            5 => "C&#46;W&#46; Bryan-Brown"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2005"
                        "volumen" => "33"
                        "paginaInicial" => "13"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15644643"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influence of insertion site on central venous catheter colonization and bloodstream infection rates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;R&#46; Gowardman"
                            1 => "I&#46;K&#46; Robertson"
                            2 => "S&#46; Parkes"
                            3 => "C&#46;M&#46; Rickard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-008-1046-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2008"
                        "volumen" => "34"
                        "paginaInicial" => "1038"
                        "paginaFinal" => "1045"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18317732"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy&#58; a randomized controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;-J&#46; Parienti"
                            1 => "M&#46; Thirion"
                            2 => "B&#46; M&#233;garbane"
                            3 => "B&#46; Souweine"
                            4 => "A&#46; Ouchikhe"
                            5 => "A&#46; Polito"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.299.20.2413"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2008"
                        "volumen" => "299"
                        "paginaInicial" => "2413"
                        "paginaFinal" => "2422"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18505951"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vascular access sites for acute renal replacement in intensive care units"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;E&#46; Dugu&#233;"
                            1 => "S&#46;P&#46; Levesque"
                            2 => "M&#46;-O&#46; Fischer"
                            3 => "B&#46; Souweine"
                            4 => "J&#46;-P&#46; Mira"
                            5 => "B&#46; Megarbane"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.06570711"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2012"
                        "volumen" => "7"
                        "paginaInicial" => "70"
                        "paginaFinal" => "77"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22076877"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Initial and extended use of femoral versus nonfemoral double-lumen vascular catheters and catheter-related infection during continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46;-R&#46; Chua"
                            1 => "A&#46;G&#46; Schneider"
                            2 => "N&#46;L&#46; Sherry"
                            3 => "N&#46; Lotfy"
                            4 => "M&#46;J&#46; Chan"
                            5 => "J&#46; Galtieri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.ajkd.2014.04.022"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis"
                        "fecha" => "2014"
                        "volumen" => "64"
                        "paginaInicial" => "909"
                        "paginaFinal" => "917"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24882583"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Femoral access and delivery of continuous renal replacement therapy dose"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Bellomo"
                            1 => "J&#46; M&#229;rtensson"
                            2 => "S&#46; Lo"
                            3 => "K&#46;-M&#46; Kaukonen"
                            4 => "A&#46; Cass"
                            5 => "M&#46; Gallagher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000439581"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood Purif"
                        "fecha" => "2016"
                        "volumen" => "41"
                        "paginaInicial" => "11"
                        "paginaFinal" => "17"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26485539"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International evidence-based recommendations on ultrasound-guided vascular access"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Lamperti"
                            1 => "A&#46;R&#46; Bodenham"
                            2 => "M&#46; Pittiruti"
                            3 => "M&#46; Blaivas"
                            4 => "J&#46;G&#46; Augoustides"
                            5 => "M&#46; Elbarbary"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-012-2597-x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2012"
                        "volumen" => "38"
                        "paginaInicial" => "1105"
                        "paginaFinal" => "1117"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22614241"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Complications of central venous catheterization"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;E&#46; Kusminsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jamcollsurg.2007.01.039"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Surg"
                        "fecha" => "2007"
                        "volumen" => "204"
                        "paginaInicial" => "681"
                        "paginaFinal" => "696"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17382229"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vascular access related infections in hemodialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;K&#46; Saxena"
                            1 => "B&#46;R&#46; Panhotra"
                            2 => "A&#46;S&#46; Al-Mulhim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Saudi J Kidney Dis Transplant"
                        "fecha" => "2005"
                        "volumen" => "16"
                        "paginaInicial" => "46"
                        "paginaFinal" => "71"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors affecting circuit patency and filter &#8220;life&#46;&#8221;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "I&#46; Baldwin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/0000102081"
                      "Revista" => array:7 [
                        "tituloSerie" => "Contrib Nephrol"
                        "fecha" => "2007"
                        "volumen" => "156"
                        "paginaInicial" => "178"
                        "paginaFinal" => "184"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17464125"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S2215036615002175"
                          "estado" => "S300"
                          "issn" => "22150366"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical review&#58; patency of the circuit in continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Joannidis"
                            1 => "H&#46;M&#46; Oudemans-van Straaten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/cc5937"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2007"
                        "volumen" => "11"
                        "paginaInicial" => "218"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17634148"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Continuous renal replacement therapy&#58; a worldwide practice survey&#46; The beginning and ending supportive therapy for the kidney &#40;B&#46;E&#46;S&#46;T&#46; kidney&#41; investigators"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Uchino"
                            1 => "R&#46; Bellomo"
                            2 => "H&#46; Morimatsu"
                            3 => "S&#46; Morgera"
                            4 => "M&#46; Schetz"
                            5 => "I&#46; Tan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-007-0754-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2007"
                        "volumen" => "33"
                        "paginaInicial" => "1563"
                        "paginaFinal" => "1570"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17594074"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Survey on the management of acute renal failure and renal replacement techniques in Spanish intensive care units"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "el Grupo de Trabajo de Cuidados Intensivos Nefrol&#243;gicos de la SEMICYUC"
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; &#218;beda-Iglesias"
                            1 => "D&#46; Herrera-Rojas"
                            2 => "C&#46; G&#243;mez-Gonz&#225;lez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.medin.2014.04.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Intensiva"
                        "fecha" => "2015"
                        "volumen" => "39"
                        "paginaInicial" => "84"
                        "paginaFinal" => "89"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24881964"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Revised algorithm for heparin anticoagulation during continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "H&#46; Dickie"
                            1 => "L&#46; Tovey"
                            2 => "W&#46; Berry"
                            3 => "M&#46; Ostermann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2015"
                        "paginaInicial" => "19"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12617736"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anticoagulation strategies in continuous renal replacement therapy&#58; can the choice be evidence based&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "H&#46;M&#46; Oudemans-van Straaten"
                            1 => "J&#46;P&#46;J&#46; Wester"
                            2 => "A&#46;C&#46;J&#46;M&#46; de Pont"
                            3 => "M&#46;R&#46;C&#46; Schetz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-005-0044-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2006"
                        "volumen" => "32"
                        "paginaInicial" => "188"
                        "paginaFinal" => "202"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16453140"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical review&#58; anticoagulation for continuous renal replacement therapy &#8211; heparin or citrate&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46;M&#46; Oudemans-van Straaten"
                            1 => "J&#46;A&#46; Kellum"
                            2 => "R&#46; Bellomo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/cc9358"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2011"
                        "volumen" => "15"
                        "paginaInicial" => "202"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21345279"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1054139X15001615"
                          "estado" => "S300"
                          "issn" => "1054139X"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acquired deficit of antithrombin and role of supplementation in septic patients during continuous veno-venous hemofiltration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Lafargue"
                            1 => "O&#46; Joannes-Boyau"
                            2 => "P&#46;M&#46; Honor&#233;"
                            3 => "B&#46; Gauche"
                            4 => "H&#46; Grand"
                            5 => "C&#46; Fleureau"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MAT.0b013e31815cc3bf"
                      "Revista" => array:6 [
                        "tituloSerie" => "ASAIO J"
                        "fecha" => "2008"
                        "volumen" => "54"
                        "paginaInicial" => "124"
                        "paginaFinal" => "128"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18204328"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Heparin-induced thrombocytopenia in intensive care patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46; Selleng"
                            1 => "S&#46; Selleng"
                            2 => "A&#46; Greinacher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1055/s-0028-1092872"
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Thromb Hemost"
                        "fecha" => "2008"
                        "volumen" => "34"
                        "paginaInicial" => "425"
                        "paginaFinal" => "438"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18956282"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The incidence of thrombocytopenia associated with continuous renal replacement therapy in critically ill patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;A&#46; Ferreira"
                            1 => "D&#46;W&#46; Johnson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/0886022X.2015.1057799"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ren Fail"
                        "fecha" => "2015"
                        "volumen" => "37"
                        "paginaInicial" => "1232"
                        "paginaFinal" => "1236"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26108135"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The clinical diagnosis of heparin-induced thrombocytopenia in patients receiving continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46;E&#46; Holmes"
                            1 => "J&#46;C&#46; Huang"
                            2 => "C&#46; Cartelli"
                            3 => "A&#46; Howard"
                            4 => "J&#46; Rimmer"
                            5 => "M&#46; Cushman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11239-008-0228-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Thromb Thrombolysis"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "paginaInicial" => "406"
                        "paginaFinal" => "412"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18488144"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Cuker"
                            1 => "P&#46;A&#46; Gimotty"
                            2 => "M&#46;A&#46; Crowther"
                            3 => "T&#46;E&#46; Warkentin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2012-07-443051"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2012"
                        "volumen" => "120"
                        "paginaInicial" => "4160"
                        "paginaFinal" => "4167"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22990018"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Heparin and low-molecular-weight heparin&#58; mechanisms of action&#44; pharmacokinetics&#44; dosing&#44; monitoring&#44; efficacy&#44; and safety"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Hirsh"
                            1 => "T&#46;E&#46; Warkentin"
                            2 => "S&#46;G&#46; Shaughnessy"
                            3 => "S&#46;S&#46; Anand"
                            4 => "J&#46;L&#46; Halperin"
                            5 => "R&#46; Raschke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2001"
                        "volumen" => "119"
                        "paginaInicial" => "64S"
                        "paginaFinal" => "94S"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11157643"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A systematic review on the accumulation of prophylactic dosages of low-molecular-weight heparins &#40;LMWHs&#41; in patients with renal insufficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "F&#46; Atiq"
                            1 => "P&#46;M&#46;L&#46;A&#46; van den Bemt"
                            2 => "F&#46;W&#46;G&#46; Leebeek"
                            3 => "T&#46; van Gelder"
                            4 => "J&#46; Versmissen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00228-015-1880-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Clin Pharmacol"
                        "fecha" => "2015"
                        "volumen" => "71"
                        "paginaInicial" => "921"
                        "paginaFinal" => "929"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26071276"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Enoxaparin vs&#46; unfractionated heparin for anticoagulation during continuous veno-venous hemofiltration&#58; a randomized controlled crossover study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Joannidis"
                            1 => "J&#46; Kountchev"
                            2 => "M&#46; Rauchenzauner"
                            3 => "N&#46; Schusterschitz"
                            4 => "H&#46; Ulmer"
                            5 => "A&#46; Mayr"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-007-0719-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2007"
                        "volumen" => "33"
                        "paginaInicial" => "1571"
                        "paginaFinal" => "1579"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17563874"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Enoxaparin versus unfractioned heparin as anticoagulant for continuous venovenous hemodialysis&#58; a randomized open-label trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;O&#46; Garc&#233;s"
                            1 => "J&#46;A&#46; Victorino"
                            2 => "F&#46;S&#46; Thom&#233;"
                            3 => "L&#46;M&#46; R&#246;hsig"
                            4 => "E&#46; Dornelles"
                            5 => "M&#46; Louzada"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/08860221003606281"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ren Fail"
                        "fecha" => "2010"
                        "volumen" => "32"
                        "paginaInicial" => "320"
                        "paginaFinal" => "327"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20370447"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anticoagulation with low molecular weight heparin &#40;Fragmin&#41; during continuous hemodialysis in the intensive care unit"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46;F&#46; Jeffrey"
                            1 => "A&#46;A&#46; Khan"
                            2 => "J&#46;T&#46; Douglas"
                            3 => "E&#46;J&#46; Will"
                            4 => "A&#46;M&#46; Davison"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Artif Organs"
                        "fecha" => "1993"
                        "volumen" => "17"
                        "paginaInicial" => "717"
                        "paginaFinal" => "720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8215953"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nadroparin versus dalteparin anticoagulation in high-volume&#44; continuous venovenous hemofiltration&#58; a double-blind&#44; randomized&#44; crossover study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;C&#46; de Pont"
                            1 => "H&#46;M&#46; Oudemans-van Straaten"
                            2 => "K&#46;J&#46; Roozendaal"
                            3 => "D&#46;F&#46; Zandstra"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "28"
                        "paginaInicial" => "421"
                        "paginaFinal" => "425"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10708177"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0575"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of the antithrombotic effects of heparin&#44; enoxaparin and prostacycline in continuous hemofiltration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D&#46; Journois"
                            1 => "D&#46; Safran"
                            2 => "M&#46;H&#46; Castelain"
                            3 => "D&#46; Chanu"
                            4 => "C&#46; Dr&#233;villon"
                            5 => "G&#46; Barrier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Fr Anesth&#232;sie R&#232;animation"
                        "fecha" => "1990"
                        "volumen" => "9"
                        "paginaInicial" => "331"
                        "paginaFinal" => "337"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "European Best Practice Guidelines Expert Group on Hemodialysis&#44; European Renal Association&#46; Section V&#46; Chronic intermittent haemodialysis and prevention of clotting in the extracorporal system"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2002"
                        "volumen" => "17"
                        "numero" => "Suppl&#46; 7"
                        "paginaInicial" => "63"
                        "paginaFinal" => "71"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12386229"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0585"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "And the winner is&#58; regional citrate anticoagulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46;S&#46;C&#46; Bouman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0b013e318194df2e"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "37"
                        "paginaInicial" => "764"
                        "paginaFinal" => "765"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19325378"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Z&#46; Zhang"
                            1 => "N&#46; Hongying"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-011-2438-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2012"
                        "volumen" => "38"
                        "paginaInicial" => "20"
                        "paginaFinal" => "28"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22124775"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anticoagulation for continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;J&#46; Tolwani"
                            1 => "K&#46;M&#46; Wille"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1525-139X.2008.00545.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Dial"
                        "fecha" => "2009"
                        "volumen" => "22"
                        "paginaInicial" => "141"
                        "paginaFinal" => "145"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19426417"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Review and guidelines for regional anticoagulation with citrate in continuous hemofiltration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "H&#46; Oudemans-van Straaten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Neth J Crit Care"
                        "fecha" => "2004"
                        "volumen" => "8"
                        "paginaInicial" => "146"
                        "paginaFinal" => "156"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0605"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure&#58; a prospective observational study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Schulthei&#223;"
                            1 => "B&#46; Saugel"
                            2 => "V&#46; Phillip"
                            3 => "P&#46; Thies"
                            4 => "S&#46; Noe"
                            5 => "U&#46; Mayr"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/cc11485"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2012"
                        "volumen" => "16"
                        "paginaInicial" => "R162"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22913794"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0610"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure&#58; the Liver Citrate Anticoagulation Threshold &#40;L-CAT&#41; observational study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Slowinski"
                            1 => "S&#46; Morgera"
                            2 => "M&#46; Joannidis"
                            3 => "T&#46; Henneberg"
                            4 => "R&#46; Stocker"
                            5 => "E&#46; Helset"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13054-015-1066-7"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2015"
                        "volumen" => "19"
                        "paginaInicial" => "349"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26415638"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sustained low-efficiency dialysis with regional citrate anticoagulation in medical intensive care unit patients with liver failure&#58; a prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Lahmer"
                            1 => "M&#46; Messer"
                            2 => "S&#46; Rasch"
                            3 => "A&#46; Beitz"
                             …2
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jcrc.2015.06.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Crit Care"
                        "fecha" => "2015"
                        "volumen" => "30"
                        "paginaInicial" => "1096"
                        "paginaFinal" => "1100"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution&#58; effects on acid&#8211;base status and phosphate supplementation needs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2369-14-232"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Nephrol"
                        "fecha" => "2013"
                        "volumen" => "14"
                        "paginaInicial" => "232"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0625"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Citrate for continuous renal replacement therapy&#58; safer&#44; better and cheaper"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13054-014-0661-3"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2014"
                        "volumen" => "18"
                        "paginaInicial" => "661"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0630"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury&#58; a multi-center randomized clinical trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13054-014-0472-6"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2014"
                        "volumen" => "18"
                        "paginaInicial" => "472"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0635"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Citrate anticoagulation for continuous venovenous hemofiltration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0b013e3181953c5e"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "37"
                        "paginaInicial" => "545"
                        "paginaFinal" => "552"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0640"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration&#58; a prospective randomized multicentre trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfq575"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2011"
                        "volumen" => "26"
                        "paginaInicial" => "232"
                        "paginaFinal" => "239"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0645"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reduction of granulocyte activation during hemodialysis with regional citrate anticoagulation&#58; dissociation of complement activation and neutropenia from neutrophil degranulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "1996"
                        "volumen" => "7"
                        "paginaInicial" => "234"
                        "paginaFinal" => "241"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0650"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low polymorphonuclear cell degranulation during citrate anticoagulation&#58; a comparison between citrate and heparin dialysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "1997"
                        "volumen" => "12"
                        "paginaInicial" => "1387"
                        "paginaFinal" => "1393"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0655"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Implementation of continuous renal replacement therapy with regional citrate anticoagulation on a surgical and trauma intensive care unit&#58; impact on clinical and economic aspects-an observational study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s40560-015-0102-7"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Intensive Care"
                        "fecha" => "2015"
                        "volumen" => "3"
                        "paginaInicial" => "35"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0660"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regional citrate versus heparin anticoagulation for continuous renal replacement therapy&#58; a meta-analysis of randomized controlled trials"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.ajkd.2011.11.030"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis"
                        "fecha" => "2012"
                        "volumen" => "59"
                        "paginaInicial" => "810"
                        "paginaFinal" => "818"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0665"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A randomized controlled trial of regional citrate versus regional heparin anticoagulation for continuous renal replacement therapy in critically ill adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0000000000001004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2015"
                        "volumen" => "43"
                        "paginaInicial" => "1622"
                        "paginaFinal" => "1629"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0670"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy&#58; a randomized controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13054-015-0822-z"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2015"
                        "volumen" => "19"
                        "paginaInicial" => "91"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0675"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Citrate versus heparin anticoagulation for continuous renal replacement therapy&#58; an updated meta-analysis of RCTs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-015-4099-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2015"
                        "volumen" => "41"
                        "paginaInicial" => "2098"
                        "paginaFinal" => "2110"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0680"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Heparin-induced thrombocytopenia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Esp Cardiol"
                        "fecha" => "2007"
                        "volumen" => "60"
                        "paginaInicial" => "1071"
                        "paginaFinal" => "1082"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0685"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-PF4&#47;heparin antibodies associated with repeated hemofiltration-filter clotting&#58; a retrospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/cc6937"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2008"
                        "volumen" => "12"
                        "paginaInicial" => "R84"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0690"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Repeated premature hemofilter clotting during regional citrate anticoagulation as indicator of heparin induced thrombocytopenia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000366125"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood Purif"
                        "fecha" => "2014"
                        "volumen" => "38"
                        "paginaInicial" => "127"
                        "paginaFinal" => "130"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0695"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Argatroban for anticoagulation in continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0b013e3181932394"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "37"
                        "paginaInicial" => "105"
                        "paginaFinal" => "110"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0700"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anticoagulation options for patients with heparin-induced thrombocytopenia requiring renal support in the intensive care unit"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/0000102110"
                      "Revista" => array:6 [
                        "tituloSerie" => "Contrib Nephrol"
                        "fecha" => "2007"
                        "volumen" => "156"
                        "paginaInicial" => "259"
                        "paginaFinal" => "266"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0705"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recombinant activated factor VII effectively reverses the anticoagulant effects of heparin&#44; enoxaparin&#44; fondaparinux&#44; argatroban&#44; and bivalirudin ex vivo as measured using thromboelastography"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MBC.0b013e328201c9a9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood Coagul Fibrinolysis"
                        "fecha" => "2007"
                        "volumen" => "18"
                        "paginaInicial" => "547"
                        "paginaFinal" => "553"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0710"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Argatroban versus Lepirudin in critically ill patients &#40;ALicia&#41;&#58; a randomized controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13054-014-0588-8"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2014"
                        "volumen" => "18"
                        "paginaInicial" => "588"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0715"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Heparin-induced thrombocytopenia during renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1492-7535.2004.01108.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hemodial Int"
                        "fecha" => "2004"
                        "volumen" => "8"
                        "paginaInicial" => "295"
                        "paginaFinal" => "303"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0720"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of argatroban&#58; experiences in continuous renal replacement therapy in critically ill patients after cardiac surgery"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jtcvs.2013.11.051"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Thorac Cardiovasc Surg"
                        "fecha" => "2014"
                        "volumen" => "147"
                        "paginaInicial" => "1918"
                        "paginaFinal" => "1924"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0725"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety&#44; efficacy&#44; and dosing requirements of bivalirudin in patients with heparin-induced thrombocytopenia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1592/phco.28.9.1115"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacotherapy"
                        "fecha" => "2008"
                        "volumen" => "28"
                        "paginaInicial" => "1115"
                        "paginaFinal" => "1124"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0730"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bivalirudin versus unfractionated heparin for prevention of hemofilter occlusion during continuous renal replacement therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1592/phco.30.11.1117"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacotherapy"
                        "fecha" => "2010"
                        "volumen" => "30"
                        "paginaInicial" => "1117"
                        "paginaFinal" => "1126"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0735"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prostaglandin E1&#58; the endogenous physiological regulator of platelet mediated blood coagulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Prostaglandins Leukot Essent Fatty Acids"
                        "fecha" => "1989"
                        "volumen" => "35"
                        "paginaInicial" => "189"
                        "paginaFinal" => "195"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0740"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Continuous haemofiltration in acute renal failure with prostacyclin as the sole anti-haemostatic agent"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-002-1249-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2002"
                        "volumen" => "28"
                        "paginaInicial" => "586"
                        "paginaFinal" => "593"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0745"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of prostacyclin &#40;epoprostenol&#41; as anticoagulant in continuous renal replacement therapies&#58; efficacy&#44; security and cost analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Nephrol"
                        "fecha" => "2006"
                        "volumen" => "19"
                        "paginaInicial" => "648"
                        "paginaFinal" => "655"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0750"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anticoagulation with prostacyclin and heparin during continuous venovenous hemofiltration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "1994"
                        "volumen" => "22"
                        "paginaInicial" => "1774"
                        "paginaFinal" => "1781"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0755"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of isolated epoprostenol or associated to heparin for the maintenance of the patency of the continuous renal replacement technical circuits"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Intensiva"
                        "fecha" => "2006"
                        "volumen" => "30"
                        "paginaInicial" => "314"
                        "paginaFinal" => "321"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0760"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of nafamostat mesylate in continuous renal replacement therapy among patients at high risk of bleeding"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/0886022X.2011.647293"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ren Fail"
                        "fecha" => "2012"
                        "volumen" => "34"
                        "paginaInicial" => "279"
                        "paginaFinal" => "285"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0765"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ability of nafamostat mesilate to prolong filter patency during continuous renal replacement therapy in patients at high risk of bleeding&#58; a randomized controlled study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0108737"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2014"
                        "volumen" => "9"
                        "paginaInicial" => "e108737"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0770"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Citrate vs&#46; heparin for anticoagulation in continuous venovenous hemofiltration&#58; a prospective randomized study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-003-2047-x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2004"
                        "volumen" => "30"
                        "paginaInicial" => "260"
                        "paginaFinal" => "265"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0775"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1523-1755.2005.00342.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2005"
                        "volumen" => "67"
                        "paginaInicial" => "2361"
                        "paginaFinal" => "2367"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0780"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is regional citrate superior to systemic heparin anticoagulation for continuous renal replacement therapy&#63; A prospective observational study in an adult regional critical care system"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jcrc.2005.01.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Crit Care"
                        "fecha" => "2005"
                        "volumen" => "20"
                        "paginaInicial" => "155"
                        "paginaFinal" => "161"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0785"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regional citrate versus heparin anticoagulation during venovenous hemofiltration in patients at low risk for bleeding&#58; similar hemofilter survival but significantly less bleeding"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Nephrol"
                        "fecha" => "2007"
                        "volumen" => "20"
                        "paginaInicial" => "602"
                        "paginaFinal" => "608"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0790"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A pilot randomized controlled crossover study comparing regional heparinization to regional citrate anticoagulation for continuous venovenous hemofiltration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Artif Organs"
                        "fecha" => "2007"
                        "volumen" => "30"
                        "paginaInicial" => "301"
                        "paginaFinal" => "307"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0795"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1744-9987.2011.00996.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ther Apher Dial"
                        "fecha" => "2011"
                        "volumen" => "15"
                        "paginaInicial" => "556"
                        "paginaFinal" => "564"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0800"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Randomised trial of software algorithm driven regional citrate anticoagulation versus heparin in continuous renal replacement therapy&#58; the Filter Life in Renal Replacement Therapy pilot trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Resusc"
                        "fecha" => "2014"
                        "volumen" => "16"
                        "paginaInicial" => "131"
                        "paginaFinal" => "137"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/02105691/0000004000000009/v1_201612020641/S0210569116302194/v1_201612020641/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "60883"
    "tipo" => "SECCION"
    "es" => array:2 [
      "titulo" => "Puesta al d&#237;a en Medicina Intensiva&#58; Acute Kidney Injury"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "es"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/02105691/0000004000000009/v1_201612020641/S0210569116302194/v1_201612020641/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116302194?idApp=WMIE"
]

Información del artículo

ISSN: 02105691
Idioma original: Inglés

DOI:10.1016/j.medin.2016.09.011

Datos actualizados diariamente

año/Mes	Html	Pdf	Total

2024 Noviembre	17	17	34
2024 Octubre	181	58	239
2024 Septiembre	245	76	321
2024 Agosto	301	71	372
2024 Julio	251	59	310
2024 Junio	210	83	293
2024 Mayo	214	53	267
2024 Abril	189	51	240
2024 Marzo	166	55	221
2024 Febrero	218	47	265
2024 Enero	225	59	284
2023 Diciembre	230	58	288
2023 Noviembre	257	61	318
2023 Octubre	236	71	307
2023 Septiembre	210	59	269
2023 Agosto	163	41	204
2023 Julio	176	47	223
2023 Junio	144	40	184
2023 Mayo	154	56	210
2023 Abril	164	29	193
2023 Marzo	175	78	253
2023 Febrero	152	60	212
2023 Enero	178	47	225
2022 Diciembre	122	47	169
2022 Noviembre	155	72	227
2022 Octubre	176	57	233
2022 Septiembre	132	55	187
2022 Agosto	131	64	195
2022 Julio	136	58	194
2022 Junio	129	36	165
2022 Mayo	109	63	172
2022 Abril	159	53	212
2022 Marzo	187	74	261
2022 Febrero	126	55	181
2022 Enero	184	92	276
2021 Diciembre	146	56	202
2021 Noviembre	144	63	207
2021 Octubre	172	96	268
2021 Septiembre	111	62	173
2021 Agosto	188	79	267
2021 Julio	127	61	188
2021 Junio	97	57	154
2021 Mayo	144	76	220
2021 Abril	378	164	542
2021 Marzo	210	56	266
2021 Febrero	198	52	250
2021 Enero	194	41	235
2020 Diciembre	174	37	211
2020 Noviembre	114	34	148
2020 Octubre	105	53	158
2020 Septiembre	106	43	149
2020 Agosto	112	51	163
2020 Julio	110	70	180
2020 Junio	149	33	182
2020 Mayo	140	27	167
2020 Abril	172	39	211
2020 Marzo	93	23	116
2020 Febrero	189	49	238
2020 Enero	78	34	112
2019 Diciembre	99	28	127
2019 Noviembre	125	37	162
2019 Octubre	86	29	115
2019 Septiembre	94	38	132
2019 Agosto	76	24	100
2019 Julio	104	41	145
2019 Junio	66	15	81
2019 Mayo	95	44	139
2019 Abril	69	35	104
2019 Marzo	83	59	142
2019 Febrero	76	33	109
2019 Enero	70	43	113
2018 Diciembre	124	41	165
2018 Noviembre	374	153	527
2018 Octubre	592	34	626
2018 Septiembre	207	12	219
2018 Agosto	52	21	73
2018 Julio	88	12	100
2018 Junio	126	16	142
2018 Mayo	124	10	134
2018 Abril	213	21	234
2018 Marzo	411	15	426
2018 Febrero	267	14	281
2018 Enero	163	26	189
2017 Diciembre	269	16	285
2017 Noviembre	63	21	84
2017 Octubre	52	19	71
2017 Septiembre	53	16	69
2017 Agosto	39	19	58
2017 Julio	44	16	60
2017 Junio	55	21	76
2017 Mayo	76	31	107
2017 Abril	79	37	116
2017 Marzo	63	4	67
2017 Febrero	4	7	11
2017 Enero	23	15	38
2016 Diciembre	35	32	67
2016 Noviembre	0	1	1

Mostrar todo

Indexada en:

Síguenos:

Suscribirse:

Estadísticas

Indexada en:

Síguenos:

Suscribirse:

Estadísticas

Suscríbase a la newsletter