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The new definitions of SEPSIS and SEPTIC SHOCK: What do they give us? An answer
Las nuevas definiciones de SEPSIS y CHOQUE SÉPTICO: ¿Qué nos ofrecen? Una respuesta
M. Singer
University College London, London, UK
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"tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "44" "paginaFinal" => "52" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Monitorizando la microcirculación en el paciente séptico: ¿en qué punto estamos?" ] ] "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" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1804 "Ancho" => 2434 "Tamanyo" => 183671 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Different StO<span class="elsevierStyleInf">2</span> patterns in response to a vascular occlusion test (VOT) in healthy subjects and septic shock. Figure A shows a normal StO<span class="elsevierStyleInf">2</span> response to a VOT, whereas figure B shows an altered response in a septic shock patient. Note that, independently of the baseline absolute StO<span class="elsevierStyleInf">2</span> value, the response to ischemia is different. The DeO<span class="elsevierStyleInf">2</span> slope is slower, and a longer period in order to reach a predetermined ischemic threshold (i.e. 40%)<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">34</span></a> is needed. The vascular reactivity is also impaired, leading to a slower StO<span class="elsevierStyleInf">2</span> recovery rate (ReO<span class="elsevierStyleInf">2</span>), and a blunted hyperemic response before returning to baseline StO<span class="elsevierStyleInf">2</span>.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Gruartmoner, J. Mesquida, C. Ince" "autores" => array:3 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Gruartmoner" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Mesquida" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Ince" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116302650?idApp=WMIE" "url" => "/02105691/0000004100000001/v3_201702170036/S0210569116302650/v3_201702170036/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S021056911630050X" "issn" => "02105691" "doi" => "10.1016/j.medin.2016.03.008" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "917" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2017;41:38-40" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6576 "formatos" => array:3 [ "EPUB" => 190 "HTML" => 4859 "PDF" => 1527 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Point of view</span>" "titulo" => "New definition of sepsis and septic shock: What does it give us?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "38" "paginaFinal" => "40" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nueva definición de sepsis y <span class="elsevierStyleItalic">shock</span> séptico: ¿qué nos ofrece?" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 920 "Ancho" => 1473 "Tamanyo" => 57919 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Mortality rate in relation to the variation of the SIRS score between day 2 and day 1.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Rodríguez, I. Martín-Loeches, J.C. Yébenes" "autores" => array:3 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez" ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Martín-Loeches" ] 2 => array:2 [ "nombre" => "J.C." "apellidos" => "Yébenes" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021056911630050X?idApp=WMIE" "url" => "/02105691/0000004100000001/v3_201702170036/S021056911630050X/v3_201702170036/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Point of view</span>" "titulo" => "The new definitions of SEPSIS and SEPTIC SHOCK: What do they give us? An answer" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "41" "paginaFinal" => "43" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "M. Singer" "autores" => array:1 [ 0 => array:3 [ "nombre" => "M." "apellidos" => "Singer" "email" => array:1 [ 0 => "m.singer@ucl.ac.uk" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "University College London, London, UK" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Las nuevas definiciones de SEPSIS y CHOQUE SÉPTICO: ¿Qué nos ofrecen? Una respuesta" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Can I thank Dr Rodriguez and colleagues<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> for engendering debate and discussion on the new Sepsis-3 definitions.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> This is a valuable exercise not only to raise queries and thoughts, but also to clarify misconceptions. Below, using a combination of science and data, I shall gently pick apart each of their assertions to demonstrate the flaws and inconsistencies in their arguments.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The main reason why SIRS was not included in the operationalization of the new sepsis definition was actually based on pathophysiology. The SIRS criteria are not particularly good in distinguishing a normal and appropriate host response to an infection from an inappropriate response resulting in a more serious infection. A bad cold will thus qualify as ‘sepsis’ in the old terminology if accompanied, for example, by fever >38<span class="elsevierStyleHsp" style=""></span>°C and a heart rate above 90<span class="elsevierStyleHsp" style=""></span>bpm. The new definition however describes a dysregulated, life-threatening host response that results in organ dysfunction. Whereas few patients die from a cold, despite having two or more SIRS criteria, a SOFA score ≥2 related to the acute episode does indeed represent organ dysfunction and is associated with a >10% risk of dying.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The semantic argument posed by Rodriguez et al. of 7-in-8 patients admitted to ICU with infection-related organ failure having SIRS misses the point. Rather, the 1-in-8 who did not have the requisite SIRS criteria would not have qualified as having sepsis under the old definition despite having infection-related organ failure serious enough to require critical care, and to result in death in 16%.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> By comparison, the new criteria are necessarily all-inclusive as these mandate new onset organ dysfunction.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The Bone paradigms have served a useful purpose but are now outdated. There was complete consensus among the Task Force, which specifically included many experts in sepsis pathophysiology, that sepsis represents much, much more than just an inflammatory (pro- and anti-) response. The failure of multiple immunomodulatory trials is testament to this fact. We surely need to take into account other pathways (metabolic, hormonal, bioenergetics, endothelial, etc.) responsible for producing organ dysfunction and not focus simply upon inflammation.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Dr Rodriguez and colleagues cite studies that relate the number of SIRS criteria to mortality risk. However, a rise in mortality from 7% to 17% for patients having 2 as opposed to the maximum 4 SIRS criteria does not match up to the difference in mortality ranging from 18% for 1 organ dysfunction, progressing stepwise to 68% for 5 organ dysfunctions.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> Furthermore, the mortality risk relating to the number of SIRS criteria in emergency room and ward patients is approximately three times lower than the equivalent SIRS score in ICU patients.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> A mortality risk predicated on organ dysfunction (using SOFA, LODS or qSOFA) is far more consistent, nothwithstanding the patient's hospital location.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">I am unaware of any hospital using SIRS criteria alone to trigger a Sepsis Code activation. If so, the poor ward response teams would be overwhelmed with multiple emergency referrals, running to see most hospital patients with a raised white count and a temperature above 38.3 °C! Many such patients are not infected,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> let alone need unnecessary antibiotics. With increasing concerns about antibiotic resistance and the need for good stewardship, we must be circumspect in throwing antibiotics around needlessly. Basing antibiotic prescriptions on SIRS criteria alone is thus worrisome. All major studies, e.g. the Surviving Sepsis Campaign registry<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> and the Spanish multicentre before-after educational program study,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> have focused on patients admitted to critical care rather than general ward patients. Such patients already had organ dysfunction to merit ICU admission.</p><p id="par0035" class="elsevierStylePara elsevierViewall">It is also important to stress that the sepsis definitions, and the criteria that describe them, are not intended to dictate clinical management. A sick, hypotensive yet fluid-resuscitated patient requiring vasopressors should not be treated any differently if his lactate is 2.1 (fulfilling the new septic shock criteria) rather than 1.9 (not ‘septic shock’). Likewise, manifestations of organ dysfunction, e.g. hypotension, oliguria, dyspnoea, should obviously be actively treated without waiting for the clinician to perform a formal SOFA score and then proclaiming ‘Eureka’.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The advantage of the SOFA score for operationalizing sepsis is that it utilizes simple physiological and biochemical tests that should be routinely performed in any sick patient where the clinician is concerned about organ dysfunction. However, the timing of SOFA scoring should be retrospective for coding, research and epidemiology purposes, and after the presumptive diagnosis of infection has been confirmed or refuted. We have offered a much more robust categorization than previously provided. This is sorely needed to improve upon a highly inconsistent epidemiology where sepsis and septic shock means different things to different people. This heterogeneity results in widely differing incidences and mortality rates. Such spurious differences impacts on epidemiology, quality improvement programs, and clinical trial design.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">I would also challenge the notion that international guideline campaigns implemented around the previous definitions have “dramatically decreased” mortality. These claims usually rely either on complicated statistical manipulations or huge increases in the denominator with a corresponding dilutional effect – the Will Rogers Phenomenon. For example, one US study reported a fall in severe sepsis mortality from 40% to 27% between 2000 and 2007.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a> Yet, in the same period the number of cases of severe sepsis rose massively from 300,270 to 781,725, and the actual number of total deaths nearly doubled. A similar national ICD-10 database study has recently been published from Germany;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> in seven years (from 2007 to 2013) mortality from severe sepsis and septic shock fell from 49.5% to 43.6% yet the number of cases tripled and total deaths also doubled. Hardly the claimed “dramatic decrease” Dr Rodriguez and colleagues attest! Correcting for illness severity, there has been some improvement in mortality over time, as shown by recent Australasian<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> and UK national data,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> yet this improvement is less marked for sepsis than for patients with non-septic critical illness (Shankar-Hari M., personal communication).</p><p id="par0050" class="elsevierStylePara elsevierViewall">With respect to quickSOFA can I respectfully suggest the authors read the detail provided in both the main definitions paper<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> and the accompanying paper by Seymour et al.?<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> Twenty-eight commonly collected physiological and biochemical variables (including the SIRS criteria and lactate) were evaluated; regression analysis identified the three qSOFA criteria as the best determinants of mortality risk, and a respiratory rate cut-off of 22<span class="elsevierStyleHsp" style=""></span>breaths/min was superior to the SIRS respiratory rate cut-off of 20. Unlike the totally arbitrary selection by Bone et al. of the SIRS cut-offs,<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> qSOFA was developed from data collected on hundreds of thousands of patients. They also misunderstand the point of qSOFA: we wrote that “<span class="elsevierStyleItalic">adult patients with suspected infection can be rapidly identified</span> (with qSOFA) <span class="elsevierStyleItalic">as being more likely to have poor outcomes typical of sepsis</span>.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a>” We were also at pains to stress in the paper that qSOFA is <span class="elsevierStyleUnderline">not</span> part of the new definition of sepsis, as re-emphasized in a recent editorial,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> but “<span class="elsevierStyleItalic">be used to prompt clinicians to further investigate for organ dysfunction, to initiate or escalate therapy as appropriate, and to consider referral to critical care or increase the frequency of monitoring, if such actions have not already been undertaken. The task force considered that positive qSOFA criteria should also prompt consideration of possible infection in patients not previously recognized as infected.</span>”<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> We also wrote “<span class="elsevierStyleItalic">It is crucial, however, that failure to meet 2 or more qSOFA or SOFA criteria should not lead to a deferral of investigation or treatment of infection or to a delay in any other aspect of care deemed necessary by the practitioners”</span>.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> The beauty of qSOFA – acknowledging that it does need prospective validation in different healthcare settings – is that it can be performed by any healthcare practitioner at the bedside in just 1–2<span class="elsevierStyleHsp" style=""></span>min – unlike SIRS testing that requires an intrinsic delay of even several hours while blood tests are performed to measure white count and PaCO<span class="elsevierStyleInf">2</span>.</p><p id="par0055" class="elsevierStylePara elsevierViewall">I would also remind Dr Rodriguez and colleagues that all the studies claiming benefit from “essential therapeutic measures such as early administration of antibiotics” were all performed on patients with existing organ dysfunction, if not full-blown shock. The ‘essential’ nature of this particular argument is also challenged and undermined by a recent metaanalysis<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a> and even more recent prospective studies contesting this particular dogma.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">15,16</span></a> What is truth, indeed?</p><p id="par0060" class="elsevierStylePara elsevierViewall">Finally, they question the new clinical characterization of septic shock. I would sincerely hope that hyperlactataemia persisting after initial resuscitation does not define a terminal event, as Rodriguez and colleagues suggest. From the Surviving Sepsis Campaign registry of 28,150 patients admitted to ICUs with infection-related organ failure and adequate fluid-resuscitation, upon which we based our criteria, mortality was 42.3% in patients having both hypotension (MAP<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>mmHg) and persisting hyperlactataemia (>2<span class="elsevierStyleHsp" style=""></span>mmol/l).<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> Mortality was considerably lower in patients meeting only one or none of these criteria, i.e. 25.7% with hyperlactataemia alone, 30.1% with fluid-resistant hypotension alone, and 25% with organ dysfunction despite a normal lactate and blood pressure. The ‘unexpected low mortality’ they note in recent clinical septic shock trials is actually not unexpected when the criteria used to define shock in these trials are more closely examined. Take for instance, the Early Goal-Directed Therapy studies where a lactate >4 irrespective of fluid resuscitation, or refractory hypotension (systolic BP<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>90<span class="elsevierStyleHsp" style=""></span>mm Hg or MAP<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>mm Hg despite resuscitation with at least 1<span class="elsevierStyleHsp" style=""></span>l of intravenous fluid) determined study inclusion.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">18–20</span></a> ‘Shock’ in many of these patients was rapidly reversed with fluid alone and did not need vasopressors, mechanical ventilation or renal replacement therapy. However, only 15–20% of patients entered into these trials fulfilled the much tighter clinical criteria required by the new septic shock definition. Our systematic review showed multiple criteria have been used in the literature to describe septic shock.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> This however generated a ten-fold variation in incidence and a four-fold variation in mortality. We thus need to talk the same language to make sensible national, international or temporal comparisons.</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 2 => array:2 [ "identificador" => "xack268846" "titulo" => "Acknowledgements" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-10-17" "fechaAceptado" => "2016-10-23" "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "(in press)" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New definition of SEPSIS and SEPTIC SHOCK: what gives us?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Rodríguez" 1 => "I. Martín-Loeches" 2 => "J.C. Yébenes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "MedIntensiva" "fecha" => "2016" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0110" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The third international consensus definitions for Sepsis and Septic Shock (Sepsis-3)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Singer" 1 => "C.S. Deutschman" 2 => "C.W. Seymour" 3 => "M. Shankar-Hari" 4 => "D. Annane" 5 => "M. Bauer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Med Assoc" "fecha" => "2016" "volumen" => "315" "paginaInicial" => "801" "paginaFinal" => "810" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0115" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.M. Kaukonen" 1 => "M. Bailey" 2 => "S. Suzuki" 3 => "D. Pilcher" 4 => "R. Bellomo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Med Assoc" "fecha" => "2014" "volumen" => "311" "paginaInicial" => "1308" "paginaFinal" => "1316" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0120" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "(in press)" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differences in impact of definitional elements on mortality precludes international comparisons of sepsis epidemiology-a cohort study illustrating the need for standardized reporting" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Shankar-Hari" 1 => "D.A. Harrison" 2 => "K.M. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 10 | 10 | 20 |
| 2024 Octubre | 68 | 56 | 124 |
| 2024 Septiembre | 82 | 49 | 131 |
| 2024 Agosto | 95 | 58 | 153 |
| 2024 Julio | 73 | 35 | 108 |
| 2024 Junio | 105 | 83 | 188 |
| 2024 Mayo | 94 | 30 | 124 |
| 2024 Abril | 107 | 45 | 152 |
| 2024 Marzo | 100 | 31 | 131 |
| 2024 Febrero | 139 | 49 | 188 |
| 2024 Enero | 125 | 52 | 177 |
| 2023 Diciembre | 105 | 34 | 139 |
| 2023 Noviembre | 96 | 53 | 149 |
| 2023 Octubre | 101 | 32 | 133 |
| 2023 Septiembre | 77 | 40 | 117 |
| 2023 Agosto | 29 | 11 | 40 |
| 2023 Julio | 45 | 32 | 77 |
| 2023 Junio | 32 | 24 | 56 |
| 2023 Mayo | 46 | 37 | 83 |
| 2023 Abril | 38 | 21 | 59 |
| 2023 Marzo | 66 | 43 | 109 |
| 2023 Febrero | 48 | 33 | 81 |
| 2023 Enero | 39 | 27 | 66 |
| 2022 Diciembre | 63 | 47 | 110 |
| 2022 Noviembre | 54 | 48 | 102 |
| 2022 Octubre | 58 | 35 | 93 |
| 2022 Septiembre | 109 | 49 | 158 |
| 2022 Agosto | 123 | 57 | 180 |
| 2022 Julio | 87 | 60 | 147 |
| 2022 Junio | 101 | 46 | 147 |
| 2022 Mayo | 81 | 45 | 126 |
| 2022 Abril | 94 | 49 | 143 |
| 2022 Marzo | 141 | 96 | 237 |
| 2022 Febrero | 97 | 44 | 141 |
| 2022 Enero | 84 | 61 | 145 |
| 2021 Diciembre | 71 | 57 | 128 |
| 2021 Noviembre | 88 | 59 | 147 |
| 2021 Octubre | 98 | 92 | 190 |
| 2021 Septiembre | 48 | 45 | 93 |
| 2021 Agosto | 72 | 58 | 130 |
| 2021 Julio | 37 | 48 | 85 |
| 2021 Junio | 51 | 43 | 94 |
| 2021 Mayo | 74 | 74 | 148 |
| 2021 Abril | 203 | 107 | 310 |
| 2021 Marzo | 134 | 72 | 206 |
| 2021 Febrero | 107 | 58 | 165 |
| 2021 Enero | 105 | 40 | 145 |
| 2020 Diciembre | 91 | 42 | 133 |
| 2020 Noviembre | 93 | 30 | 123 |
| 2020 Octubre | 106 | 41 | 147 |
| 2020 Septiembre | 117 | 31 | 148 |
| 2020 Agosto | 77 | 23 | 100 |
| 2020 Julio | 50 | 34 | 84 |
| 2020 Junio | 78 | 22 | 100 |
| 2020 Mayo | 81 | 18 | 99 |
| 2020 Abril | 71 | 37 | 108 |
| 2020 Marzo | 69 | 22 | 91 |
| 2020 Febrero | 150 | 38 | 188 |
| 2020 Enero | 133 | 43 | 176 |
| 2019 Diciembre | 109 | 37 | 146 |
| 2019 Noviembre | 161 | 36 | 197 |
| 2019 Octubre | 110 | 31 | 141 |
| 2019 Septiembre | 146 | 37 | 183 |
| 2019 Agosto | 144 | 35 | 179 |
| 2019 Julio | 148 | 48 | 196 |
| 2019 Junio | 116 | 24 | 140 |
| 2019 Mayo | 151 | 59 | 210 |
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| 2019 Marzo | 149 | 53 | 202 |
| 2019 Febrero | 101 | 50 | 151 |
| 2019 Enero | 100 | 50 | 150 |
| 2018 Diciembre | 110 | 34 | 144 |
| 2018 Noviembre | 166 | 57 | 223 |
| 2018 Octubre | 118 | 31 | 149 |
| 2018 Septiembre | 63 | 16 | 79 |
| 2018 Agosto | 54 | 18 | 72 |
| 2018 Julio | 43 | 20 | 63 |
| 2018 Junio | 65 | 17 | 82 |
| 2018 Mayo | 30 | 10 | 40 |
| 2018 Abril | 48 | 20 | 68 |
| 2018 Marzo | 43 | 15 | 58 |
| 2018 Febrero | 38 | 14 | 52 |
| 2018 Enero | 74 | 27 | 101 |
| 2017 Diciembre | 37 | 19 | 56 |
| 2017 Noviembre | 50 | 22 | 72 |
| 2017 Octubre | 37 | 15 | 52 |
| 2017 Septiembre | 46 | 19 | 65 |
| 2017 Agosto | 49 | 18 | 67 |
| 2017 Julio | 54 | 23 | 77 |
| 2017 Junio | 54 | 26 | 80 |
| 2017 Mayo | 76 | 46 | 122 |
| 2017 Abril | 88 | 10 | 98 |
| 2017 Marzo | 3 | 14 | 17 |
| 2017 Febrero | 39 | 43 | 82 |
| 2017 Enero | 5 | 7 | 12 |
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