Effects of deep sedation under mechanical ventilation on cognitive outcome in patients undergoing surgery for oral and maxillofacial cancer and microvascular reconstruction

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Terada, S. Inoue, M. Konda, J. Egawa, J. Ueda, T. Kirita, M. Kawaguchi" "autores" => array:7 [ 0 => array:3 [ "nombre" => "Y." "apellidos" => "Terada" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "S." "apellidos" => "Inoue" "email" => array:1 [ 0 => "seninoue@naramed-u.ac.jp" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Konda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "J." "apellidos" => "Egawa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "J." "apellidos" => "Ueda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "T." 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"apellidos" => "Kawaguchi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Anesthesiology and Division of Intensive Care, Nara Medical University, Japan" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8522, Japan" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efectos de la sedación profunda bajo ventilación mecánica sobre los resultados cognitivos en pacientes sometidos a cirugía por cáncer oral y maxilofacial con reconstrucción microvascular" ] ] "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" => 864 "Ancho" => 1421 "Tamanyo" => 39827 ] ] "descripcion" => array:1 [ "en" => "A scatter diagram showing the relation between the number of impaired cognitive test and patient's age." ] ] ] "textoCompleto" => "IntroductionCognitive impairment after intensive care unit (ICU) admission has been recognized as one of symptoms of post-intensive care syndrome (PICS).<a class="elsevierStyleCrossRef" href="#bib0135">1</a> High-dose deep sedation has been suggested to play an important role of development of cognitive impairment.<a class="elsevierStyleCrossRefs" href="#bib0140">2,3</a> It was also suggested that strategies for reducing sedation levels in the ICU do not seem to be associated with worse cognitive and psychological status among ICU survivors.<a class="elsevierStyleCrossRef" href="#bib0150">4</a> However, multiple factors should contribute to its development. It has been suggested that critical illness per se may develop brain damage by complicated status and situations such as increased level of cytokines in the brain, hypoxemia, hypotension, hyper- and hypo-glycemia, and sedatives, etc.<a class="elsevierStyleCrossRef" href="#bib0155">5</a> Thus, the impact of heavy sedation as a single cause on development of cognitive impairment in ICU patients remains unclear.Despite the evidence suggesting beneficial effects of lighter sedation strategy, many ICUs still continue to use high dose sedation practices for managing patient on mechanical ventilation.<a class="elsevierStyleCrossRefs" href="#bib0160">6,7</a> One of the reasons of such practices is because postoperative management for specific surgeries, especially reconstruction with microvascular anastomosis, conventionally immobilization with deep sedation is considered necessary for a certain period to avoid possible mechanical strain to the transplanted tissues although there is still no evidence available to support this practice.<a class="elsevierStyleCrossRefs" href="#bib0170">8,9</a> It is supposed that these patients are the population whose cognitive function can be affected by deep sedation itself rather than co-existing critical illness and ICU admission.In this study, we investigated whether 3 days deep sedation protocol could decline cognitive function in mechanically ventilated non-critical patients, who underwent surgery for oral and maxillofacial cancer and microvascular reconstruction.Patients and methodsThis observational cohort study was approved (August 19, 2013) by the Ethics Committee of Nara Medical University Hospital (Kashihara, Japan; study number 715) and the revision was approved on August 31, 2016. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000019914) on August 30, 2013 and the revision was registered on August 9, 2016. Written informed consent was obtained from all individual participants included in this study. The reason why the revision was required is because participant's eligibility was changed midway through. We initially recruited participants from both Departments of Otorhinolaryngology, which required 2 days sedation, and Oral and Maxillofacial Surgery, which required 3 days sedation and intended to compare the two groups. However, we quit recruiting participants from Department of Otorhinolaryngology because otolaryngologists modified and have not yet determined their postoperative care for this kind of surgery. Consequently, all patients from Departments of Otorhinolaryngology that had participated until then were excluded from the study.Patients were eligible for inclusion in the study if they were scheduled for elective oral and maxillofacial surgery and were 40–85 yr of age, which was changed to 50–85 yr of age in the revised protocol. Additional inclusion criteria were American Society of Anesthesiologists physical status I–III, fluency in Japanese, ability to read, and absence of serious hearing or visual impairments that would preclude neuropsychological testing. The following exclusion criteria were applied: a history of neurological or mental illness, baseline Mini Mental State Examination (MMSE) score below 24.Complete medical history, physical examination findings, electrocardiograms, chest X-ray, blood examination, and pulmonary function test were performed for all patients. All the operations and postoperative managements were performed by the same surgical and intensive care team. Cognitive function was assessed two days preoperatively and three weeks postoperatively using a battery of seven neuropsychological tests: the MMSE, Trail Making Test (Parts A and B), Digit Span (forward and backward), and Grooved Pegboard Test (dominant).<a class="elsevierStyleCrossRefs" href="#bib0180">10,11</a> Regarding Grooved Pegboard Test, significant impairment in the non-dominant hand test was predicted because the radial forearm flap was usually harvested from the non-dominant arm, which may impair a smooth movement of the hand. Therefore, non-dominant hand Grooved Pegboard Test was not included. As described previously, cognitive impairment was defined as a decline of 20% from preoperative test scores in at least two of these tests.<a class="elsevierStyleCrossRef" href="#bib0190">12</a> Cognitive function was assessed by the same intensivists. All cognitive tests were performed in the same hospital room.Methods of anesthetic induction and maintenance and tracheal intubation were not standardized for each patient. Usually, general anesthesia was induced with intravenous propofol (1–2.5mgkg−1) and fentanyl (1–2μgkg−1) or remifentanil (0.2–0.3μgkg−1min−1). Tracheal intubation was facilitated using rocuronium (0.6–0.9mgkg−1) with laryngoscopy. Anesthesia was maintained with sevoflurane (1–1.5%) and 40% oxygen and air mixture. Fentanyl (1–2μgkg−1h−1) or remifentanil (0.1–0.2μgkg−1min−1) were used for analgesia. Rocuronium (0.2–0.3mgkg−1h−1) was used for muscle relaxation. Fluid management was also at the discretion of the attending anesthetist. Usually, 500–1000ml of colloid (6% hydroxyethyl starch) was infused in the first 1h followed by 2–4mlkg−1h−1 of crystalloid. Transfusion was performed if necessary, in which hemoglobin level was maintained between 7 and 10g/gL. Tracheostomy was performed prior to tumor resection. Most patients had unilateral or bilateral neck dissections and excision of the primary tumor with immediate reconstruction. The radial forearm flap was usually harvested usually from the non-dominant arm. After completion of microvascular anastomosis, continuous administration of prostaglandin E1 (10ngkg−1min−1) was started through a central venous line.After surgery, patients were transferred to the ICU and remained sedated under mechanical ventilation with the head maintained in a neutral position and elevated 30–40 degree. Patients were sedated with propofol (2–3mgkg−1h−1), fentanyl (0.2–0.3μgkg−1h−1), and dexmedetomidine (0.4–0.7μgkg−1h−1 to maintain deep sedation (Richmond Agitation-Sedation Scale [RASS]-4 or -5).<a class="elsevierStyleCrossRef" href="#bib0195">13</a> We combined different agents to maximize efficacy and minimize adverse effects, with expecting that these combinations have significant benefits over single agents in spite of the absence of strong evidence. Basically, a protocol-based sedation in consideration of pre-emptive analgesia was provided by trained nurses. Dobtamine was used to keep systolic blood pressure>110mmHg. Patients received hydrocortisone 100mg on anesthetic induction and several further doses at 12h intervals. The reconstructive surgeons monitored the color of transferred flaps every 2h and cleaned the oral cavity every 6h until the morning of postoperative day 3. When the target sedation level was not maintained, midazolam (5mg) was temporally administered. On the morning of postoperative day 3, sedative administration was terminated but fentanyl was still administered for postoperative pain management although the dose was decreased (0.04–0.06μgkg−1h−1). Patients were weaned from mechanical ventilation after patients regained consciousness and discharged from the ICU.StatisticsCognitive impairment after ICU sedation has been reported to vary approximately between 20 and 60%.<a class="elsevierStyleCrossRefs" href="#bib0140">2,3</a> For the purpose of a sample-size calculation, we assumed the incidence of cognitive impairment as high as 25% and its 95% confident interval as wide as 50%. The reason of its wide setting of the confident interval was because there was a possibility of no incidence of cognitive impairment. We estimated that 12 patients were required to satisfy this assumption. Considering misestimation of the baseline confident interval, we added 5 participants. Consequently, 17 participants were recruited.Depending on the data distribution, results are presented as mean (standard deviation [SD]) or median [interquartile range]. Comparisons of change between pre- and post-evaluation were made using the paired t-test or the Wilcoxon test. A correlation between the number of declined cognitive test and age was assessed using Spearman's rank correlation test. A p-value of <0.05 was considered statistically significant for all analyses. Analyses were computed using R (version 3.0.3, R Foundation for Statistical Computing, Vienna, Austria).ResultsOne hundred and five consecutive patients (>20 years old) who underwent surgery for oral and maxillofacial cancer and microvascular reconstruction under general anesthesia between September 2013 and August 2016 at Nara Medical University Hospital were initially enrolled. Of those, several patients from Departments of Otorhinolaryngology participated this study; however, 49 patients in all were finally excluded from the study because of the above reason. Of 56 patients from Departments of Oral and Maxillofacial Surgery, written informed consent was obtained from 31 patients; however, 3 patients refused the second evaluation, 6 could not undergo the second evaluation because of our inconvenience, 1 could not accomplish the second evaluation because of the effects of sedatives for palliative therapy, 1 was excluded because microvascular reconstruction was not necessary, and 3 was excluded because they were younger than 50 years old although they accomplished the pre- and post-evaluations. Eventually, 17 patients completed both cognitive evaluations and were included in this study (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Patient characteristics, duration of sedation, and doses of analgosedatives are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. One patient required a revision of microvascular anastomosis and additional 3 days sedation. All the remaining patients had uneventful intraoperative and postoperative courses. The pre-cognitive evaluation was performed on preoperative day 2 (range 1–2). The post-cognitive evaluation was conducted on postoperative day 23 (range 21–30).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Regarding the incidence of cognitive impairment, 5 of 17 patients (29%) showed the defined cognitive impairment (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2A</a>). In this connection, the patient, who required additional sedation, showed no decline in any tests. Patients data with dividing into patients who developed and no developed cognitive impairment are shown on the right side of <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. In regard with performing statistical tests, it was likely that our population was too small to satisfy any statistical power for comparing patients who developed and no developed cognitive impairment. Consequently, statistical tests were not conducted. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2B</a> shows the number of patients showing a decline of each cognitive test. Except MMSE test, several patients showed a decline of each test. Regarding the association between the number of impaired cognitive test and patient's age, a significant correlation was not observed (rho=−0.163, 95% CI=−0.597 to 0.345, p=0.5324) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>The median scores on all six cognitive tests are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a>. No significant difference between pre- and post-cognitive evaluations was observed in any tests.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>DiscussionOn the whole, scores in any cognitive tests did not significantly differ after discharge from the ICU compared with before admission. Looking at each patient result, however, the rate of patients showed a decline of >20% from pre-cognitive evaluation scores in at least two of six tests was 29% of all the patients. These results indicate that deep sedation during several days even under non-critical status can impair the medium term cognitive function in some patients.The strength of this study is to conduct and compare neurophysiological test performance before ICU admission and after discharge. A major limitation of the studies investigating the effect of ICU admission on cognitive outcome is that a baseline assessment of cognitive status before admission is lacking.<a class="elsevierStyleCrossRef" href="#bib0155">5</a> We used multiple cognitive tests probing different domains, including MMSE (screening), Trail Making Test Part A (attention), Trail Making Test Part B (executive function), Digit Span Test (verbal working memory), and Grooved Pegboard Test (motor function). According to a consensus statement, the Rey Auditory Verbal Learning Test, Trail Making Test A/B, and Grooved Pegboard Test are recommended as core components of a comprehensive neuropsychological battery.<a class="elsevierStyleCrossRef" href="#bib0180">10</a> In our preliminary studies, we included the Rey Auditory Verbal Learning Test; however, it was excluded from the main trial as it took a long time to complete and was stressful for some postoperative patients. In current results, MMSE as a dementia screening test was intact. However, it has been suggested that screening tests such as the MMSE do not have the sensitivity to examine for Postoperative cognitive dysfunction (POCD).<a class="elsevierStyleCrossRef" href="#bib0200">14</a> On the contrary, cognitive function was broadly impaired such as domains of attention, executive function, verbal working memory, and motor function. It has been suggested that even minor mood changes may have a negative impact on motivation and ability to complete neuropsychological testing.<a class="elsevierStyleCrossRef" href="#bib0205">15</a> If important changes in mood or anxiety occur after surgery, it is possible that the performance in the neuropsychological tests was adversely affected. However, the fact that almost 30% of patient showed cognitive impairment demands close attention even if the above concern is considered. In this study, non-dominant hand Grooved Pegboard Test was not included for the reason mentioned before. However, more patients might have shown cognitive impairment if this test had been included if the flap had been harvested from the other part of the body, because taking one more test would increase opportunities to show a decline of more than 20% from preoperative test scores.Although several mechanisms for cognitive impairment after ICU admission have been postulated as mentioned before,<a class="elsevierStyleCrossRef" href="#bib0155">5</a> the etiology of this type of cognitive impairment is still unclear. The results of most studies reviewed suggested that critical illness and ICU treatment are associated with cognitive impairment.<a class="elsevierStyleCrossRef" href="#bib0155">5</a> Of those, high-dose deep sedation has been suggested to play an important role of development of cognitive impairment<a class="elsevierStyleCrossRefs" href="#bib0140">2,3</a>; however, it is still unclear deep sedation status with critical illness or deep sedation status by exposure to analgosedatives plays a main role. Several pre-clinical studies have shown that anesthetic or sedative agents have toxic effects on the central nerve system.<a class="elsevierStyleCrossRefs" href="#bib0210">16–18</a> In addition, considering that our participants were in relatively non-critical status, it is likely that exposure to analgosedatives and immobilization adversely, at least partially, affected cognitive outcome in our population. According to the report of the Second International Perioperative Neurotoxicity Workshop, there is still considerable controversy over whether specific anesthetic agents increase the risk of cognitive impairment.<a class="elsevierStyleCrossRefs" href="#bib0225">19,20</a> Besides, sedation was provided by a protocol-based sedation using co-administration of three analgosedatives. Therefore, it is difficult to determine which specific analgosedative agent did affect the cognitive outcome. On the other hand, a combination of sedatives caused a greater increase in the rate of neuronal damage than either drug alone.<a class="elsevierStyleCrossRef" href="#bib0235">21</a> A sedation protocol based on a single analgosedative agent might have had less impact on cognitive outcome. Looking back on the backgrounds of patients who developed cognitive impairment, the doses of propofol and midazolam used seems larger although the dose of dexmedetomidine seems similar compared with patients who did not develop cognitive impairment. It is concluded that benzodiazepine administration is an important and potentially modifiable risk factor for transitioning into delirium.<a class="elsevierStyleCrossRef" href="#bib0140">2</a> Additionally, some, but not all, clinical studies demonstrated that propofol led to delirium.<a class="elsevierStyleCrossRef" href="#bib0140">2</a> Considering that increasing duration of delirium was an independent predictor of worse cognitive impairment,<a class="elsevierStyleCrossRef" href="#bib0155">5</a> these drags might have contributed to development of cognitive impairment in our patients. As for dexmedetomidine, this drug has been reported to have ability to attenuate propofol-induced neurotoxicity.<a class="elsevierStyleCrossRef" href="#bib0240">22</a> Different doses of dexmedetomidine might have produced a different result. However, these comments may be too speculative.POCD is common following non-cardiac surgery. In a prospective multicenter trial of as many as a thousand patients undergoing non-cardiac surgery, POCD was present in 26% of patients one week postoperatively and in 10% of patients three months postoperatively.<a class="elsevierStyleCrossRef" href="#bib0245">23</a> Therefore, our results might have been an identical phenomenon of POCD. To distinguish whether our findings were derived from POCD or cognitive impairment by high dose deep sedation in the ICU, we should have needed same surgical patients who had not required sedation and immobilization in the ICU. However, it has been reported that cognitive impairment after ICU discharge is correlated with duration of mechanical ventilation and psychophysiological disorder is positively associated with more days of sedation in the ICU.<a class="elsevierStyleCrossRefs" href="#bib0250">24,25</a> Therefore, it is possible that the additional days of sedation under mechanical ventilation in the ICU contributed to cognitive impairment after ICU discharge in our patients. Regarding the long-term cognitive outcome like 3 months or 1 year later, we should have evaluated it; however, it is regrettable that we did not for personal reasons.There are several limitations to this study. First, our study was a single arm trial missing the control group, which means patients who underwent surgery without additional days of sedation under mechanical ventilation. If we had set a control group, we might have made a more appropriate judgment on the effect of additional days of sedation on cognitive outcome. However, it would have required to change the postoperative management protocol at the commencement of the study. As another limitation, age was not associated with cognitive impairment after ICU discharge in our study in spite of several previous suggestions. Our study population consisted of patients over 50 years old with the mean age of 62. Relatively older age in our population might have masked the effect of age on cognitive outcome. Otherwise, for patients over a certain age, the effect of high dose deep sedation on cognitive outcome may depend on patient's susceptibility rather than age. Lastly, the considerable number of patients were excluded from the study. In addition, it has been suggested that plausible assumptions regarding outcomes of patients lost to follow-up could change the interpretation of results of relevant randomized controlled trials.<a class="elsevierStyleCrossRef" href="#bib0260">26</a> Especially, patients who refused the second evaluation might have showed cognitive impairment because such patients may have wished to conceal their cognitive impairment.<a class="elsevierStyleCrossRef" href="#bib0205">15</a> Therefore, more percentage of participants might have showed cognitive impairment after discharge from ICU.In conclusion, the medium-term cognitive function was impaired in some patients, who underwent deep sedation during several days continuing from maxillomandibular oral surgery with microvascular reconstruction. However, it is still unclear whether this cognitive impairment was due to an epiphenomenon of POCD or additional several days sedation under mechanical ventilation in the ICU.FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Author contribution<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">Dr. Terada helped to design the study and prepared the manuscript.</li><li class="elsevierStyleListItem" id="lsti0010">Dr. Konda helped to design the study and prepared the manuscript.</li><li class="elsevierStyleListItem" id="lsti0015">Dr. Inoue designed the study and prepared the manuscript.</li><li class="elsevierStyleListItem" id="lsti0020">Dr. Egawa helped to design the study and prepared the manuscript.</li><li class="elsevierStyleListItem" id="lsti0025">Dr. Ueda helped to design the study and prepared the manuscript.</li><li class="elsevierStyleListItem" id="lsti0030">Dr. Kirita helped to design the study and prepared the manuscript.</li><li class="elsevierStyleListItem" id="lsti0035">Dr. Kawaguchi helped to design the study and reviewed the manuscript.</li><li class="elsevierStyleListItem" id="lsti0040">All authors approved the final manuscript.</li></ul>Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1141381" "titulo" => "Abstract" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Patients" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Intervention" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Variables of interest" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1072342" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1141380" "titulo" => "Resumen" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "abst0040" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0045" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0050" "titulo" => "Pacientes" ] 3 => array:2 [ "identificador" => "abst0055" "titulo" => "Intervenciones" ] 4 => array:2 [ "identificador" => "abst0060" "titulo" => "Variables de interés" ] 5 => array:2 [ "identificador" => "abst0065" "titulo" => "Resultados" ] 6 => array:2 [ "identificador" => "abst0070" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1072343" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistics" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Author contribution" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack388848" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-07-04" "fechaAceptado" => "2017-11-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1072342" "palabras" => array:5 [ 0 => "Sedation" 1 => "Intensive care unit" 2 => "Cognitive impairment" 3 => "Cognitive test" 4 => "Sedatives" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1072343" "palabras" => array:5 [ 0 => "Sedación" 1 => "Unidad de cuidados intensivos" 2 => "Alteración cognitiva" 3 => "Prueba cognitiva" 4 => "Sedantes" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveCognitive impairment after intensive care unit (ICU) admission is becoming increasingly recognized. High-dose deep sedation has been suggested to play an important role in the development of cognitive impairment. However, the impact of heavy sedation as a single cause in the development of cognitive impairment in ICU patients remains unclear. In this study we investigated whether a three-day deep sedation protocol could reduce cognitive function in mechanically ventilated non-critical patients. DesignA prospective observational study was carried out. PatientsA total of 17 surgical patients were studied. InterventionNone. Variables of interestCognitive function before and after ICU admission. ResultsThirty-one patients requiring three days of sedation after microvascular reconstruction were initially enrolled in the study. Sedation in the ICU was maintained with propofol and dexmedetomidine combined with fentanyl. Cognitive function was assessed using a battery of 6 neuropsychological tests two days before surgery and three weeks after surgery. Finally, a total of 17 patients were included in the analysis. Cognitive impairment (defined as a decline of >20% from the pre-admission cognitive evaluation scores in at least two of 6 tests) was observed in 5 of the 17 patients (29%). However, there were no significant differences between the pre- and post-admission cognitive evaluations in 6 tests. ConclusionsMiddle-term cognitive function can be impaired in some patients subjected to deep sedation during several days following maxillary–mandibular oral surgery with microvascular reconstruction." "secciones" => array:7 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Patients" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Intervention" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Variables of interest" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoCada vez existe un mayor consenso sobre la afectación cognitiva tras el ingreso en la unidad de cuidados intensivos (UCI). Se ha sugerido que la sedación profunda con dosis elevada desempeña un papel importante en el desarrollo de la alteración cognitiva. Sin embargo, todavía existen dudas sobre el impacto de este tipo de sedación como causa única del desarrollo de alteraciones cognitivas en pacientes ingresados en la UCI. En este estudio, investigamos si la aplicación de un protocolo de sedación profunda durante 3 días disminuía la función cognitiva en pacientes no críticos bajo ventilación mecánica. DiseñoSe llevó a cabo un estudio observacional prospectivo. PacientesSe estudió a un total de 17 pacientes quirúrgicos. IntervencionesNinguna. Variables de interésFunción cognitiva antes y después del ingreso en la UCI. ResultadosEn este estudio se incluyó inicialmente a 31 pacientes que requerían 3 días de sedación tras una reconstrucción microvascular. Se mantuvo la sedación en la UCI con propofol y dexmedetomidina en combinación con fentanilo. Se evaluó la función cognitiva mediante un grupo de 6 pruebas neurofisiológicas antes de la intervención y 3 días después de esta. Por último, se incluyó a un total de 17 pacientes en el análisis. Se observó alteración cognitiva (definida como una reducción>20% frente a las puntuaciones de la evaluación cognitiva previa al ingreso en al menos 2 de las 6 pruebas) en 5 de los 17 pacientes (29%). Sin embargo, no se observaron diferencias significativas entre las evaluaciones previas y posteriores al ingreso en 6 pruebas. ConclusionesLa función cognitiva a medio plazo puede verse afectada en algunos pacientes sometidos a sedación profunda durante varios días tras una cirugía oral maxilar-mandibular con reconstrucción microvascular." "secciones" => array:7 [ 0 => array:2 [ "identificador" => "abst0040" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0045" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0050" "titulo" => "Pacientes" ] 3 => array:2 [ "identificador" => "abst0055" "titulo" => "Intervenciones" ] 4 => array:2 [ "identificador" => "abst0060" "titulo" => "Variables de interés" ] 5 => array:2 [ "identificador" => "abst0065" "titulo" => "Resultados" ] 6 => array:2 [ "identificador" => "abst0070" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1780 "Ancho" => 2333 "Tamanyo" => 282440 ] ] "descripcion" => array:1 [ "en" => "Patient inclusion and exclusion." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 864 "Ancho" => 1421 "Tamanyo" => 39827 ] ] "descripcion" => array:1 [ "en" => "A scatter diagram showing the relation between the number of impaired cognitive test and patient's age." ] ] 2 => 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" => "Data are presented as median [interquartile range] or mean (standard deviation) as indicated.BMI=body mass index" "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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Overall population (n=17) \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">Cognitive impairment (n=5) \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">No cognitive impairment (n=12) \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">Age (yr) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55±2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64±10 \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">Sex (F/M) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/7 \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">Hight (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">163.3±10.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">171±2.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">160±10.4 \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">Weight (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58.3±13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">66.8±7.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54.8±13.7 \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">BMI (kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.7±3.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22.9±2.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.2±3.5 \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">Duration of anesthesia (min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">929 [808–1022] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">929 [911–941] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">932 [770–1022] \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">Duration of surgery (min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">786 [665–893] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">786 [759–848] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">782 [645–895] \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">Intraoperative fentanyl (μg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1406±492 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1310±261 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1446±567 \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">Duration of sedation in ICU (h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55.5 [54–59] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 [53.5–55] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56.5 [54.4–63.3] \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">Duration of mechanical ventilation in ICU (h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56.5 [55.9–60.4] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56.5 [56–56.5] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58 [55.9–65.6] \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">Fentanyl for sedation (μg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3449±961 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3037±169 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3620±1106 \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">Propofol for sedation (mg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6450±2247 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7950±1444 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5825±2266 \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">Dexmedetomidine for sedation (μg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2003±652 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2148±620 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1943±682 \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">Midazolam for sedation (mg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 [5–20] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 [10–30] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 [5–16.3] \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947747.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Patient characteristics, intraoperative data, duration of sedation, and doses of analgosedatives." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2A" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table 2" "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "In this study, cognitive impairment was defined as a decline of 20% from pre-cognitive evaluation scores in at least two of seven tests." "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">Number of tests \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">Number of patients \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">0 test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=8 \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">1 test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=4 \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 tests \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947746.png" ] ] ] ] "descripcion" => array:1 [ "en" => "The number of patients showing a decline of 20% from pre-cognitive evaluation scores." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 2B" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table 2" "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=""><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">Name of the test \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">Number of patients showing a decline \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">Mini Mental State Examination \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=0 \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">Trail Making Test Part A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=4 \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">Trail Making Test Part B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=3 \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">Digit Span Forward Test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=1 \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">Digit Span Backward Test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=3 \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">Dominant hand Pegboard Test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947748.png" ] ] ] ] "descripcion" => array:1 [ "en" => "The number of patients showing a decline of each cognitive test." ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Data are presented as median [interquartile range].MMSE=Mini Mental State Examination; TMT A=Trail Making Test Part A; TMT B=Trail Making Test Part B." "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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Baseline \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">3 weeks after surgery \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">p value \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">MMSE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29 [28–30] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 [29–30] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4258 \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">TMT A (s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39 [29–52] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42 [33–56] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5171 \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">TMT B (s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">102 [87–118] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">89 [70–120] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7119 \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">Digit Span Forward \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 [6–7] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 [6–7] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8203 \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">Digit Span Backward \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 [4–5] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 [4–6] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8984 \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">Dominant hand Pegboard (s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73 [63–81] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77 [62–89] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2069 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947745.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Cognitive test results at baseline and three weeks postoperatively." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0135" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The truth about consequences – post-intensive care syndrome in intensive care unit survivors and their families" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.A. Harvey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e318258e943" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2012" "volumen" => "40" "paginaInicial" => "2506" "paginaFinal" => "2507" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22809925" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0140" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of sedation on cognitive function in mechanically ventilated patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. 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Effects of deep sedation under mechanical ventilation on cognitive outcome in patients undergoing surgery for oral and maxillofacial cancer and microvascular reconstruction

Efectos de la sedación profunda bajo ventilación mecánica sobre los resultados cognitivos en pacientes sometidos a cirugía por cáncer oral y maxilofacial con reconstrucción microvascular

Y. Teradaa, S. Inouea,

Corresponding author

seninoue@naramed-u.ac.jp

Corresponding author.

, M. Kondaa, J. Egawaa, J. Uedab, T. Kiritab, M. Kawaguchia

a Department of Anesthesiology and Division of Intensive Care, Nara Medical University, Japan

b Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8522, Japan

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    "titulo" => "Effects of deep sedation under mechanical ventilation on cognitive outcome in patients undergoing surgery for oral and maxillofacial cancer and microvascular reconstruction"
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        "titulo" => "Efectos de la sedaci&#243;n profunda bajo ventilaci&#243;n mec&#225;nica sobre los resultados cognitivos en pacientes sometidos a cirug&#237;a por c&#225;ncer oral y maxilofacial con reconstrucci&#243;n microvascular"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cognitive impairment after intensive care unit &#40;ICU&#41; admission has been recognized as one of symptoms of post-intensive care syndrome &#40;PICS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a> High-dose deep sedation has been suggested to play an important role of development of cognitive impairment&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;3</span></a> It was also suggested that strategies for reducing sedation levels in the ICU do not seem to be associated with worse cognitive and psychological status among ICU survivors&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> However&#44; multiple factors should contribute to its development&#46; It has been suggested that critical illness per se may develop brain damage by complicated status and situations such as increased level of cytokines in the brain&#44; hypoxemia&#44; hypotension&#44; hyper- and hypo-glycemia&#44; and sedatives&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> Thus&#44; the impact of heavy sedation as a single cause on development of cognitive impairment in ICU patients remains unclear&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite the evidence suggesting beneficial effects of lighter sedation strategy&#44; many ICUs still continue to use high dose sedation practices for managing patient on mechanical ventilation&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#44;7</span></a> One of the reasons of such practices is because postoperative management for specific surgeries&#44; especially reconstruction with microvascular anastomosis&#44; conventionally immobilization with deep sedation is considered necessary for a certain period to avoid possible mechanical strain to the transplanted tissues although there is still no evidence available to support this practice&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">8&#44;9</span></a> It is supposed that these patients are the population whose cognitive function can be affected by deep sedation itself rather than co-existing critical illness and ICU admission&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In this study&#44; we investigated whether 3 days deep sedation protocol could decline cognitive function in mechanically ventilated non-critical patients&#44; who underwent surgery for oral and maxillofacial cancer and microvascular reconstruction&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Patients and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This observational cohort study was approved &#40;August 19&#44; 2013&#41; by the Ethics Committee of Nara Medical University Hospital &#40;Kashihara&#44; Japan&#59; study number 715&#41; and the revision was approved on August 31&#44; 2016&#46; This study was registered with the University Hospital Medical Information Network Clinical Trials Registry &#40;UMIN000019914&#41; on August 30&#44; 2013 and the revision was registered on August 9&#44; 2016&#46; Written informed consent was obtained from all individual participants included in this study&#46; The reason why the revision was required is because participant&#39;s eligibility was changed midway through&#46; We initially recruited participants from both Departments of Otorhinolaryngology&#44; which required 2 days sedation&#44; and Oral and Maxillofacial Surgery&#44; which required 3 days sedation and intended to compare the two groups&#46; However&#44; we quit recruiting participants from Department of Otorhinolaryngology because otolaryngologists modified and have not yet determined their postoperative care for this kind of surgery&#46; Consequently&#44; all patients from Departments of Otorhinolaryngology that had participated until then were excluded from the study&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Patients were eligible for inclusion in the study if they were scheduled for elective oral and maxillofacial surgery and were 40&#8211;85 yr of age&#44; which was changed to 50&#8211;85 yr of age in the revised protocol&#46; Additional inclusion criteria were American Society of Anesthesiologists physical status I&#8211;III&#44; fluency in Japanese&#44; ability to read&#44; and absence of serious hearing or visual impairments that would preclude neuropsychological testing&#46; The following exclusion criteria were applied&#58; a history of neurological or mental illness&#44; baseline Mini Mental State Examination &#40;MMSE&#41; score below 24&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Complete medical history&#44; physical examination findings&#44; electrocardiograms&#44; chest X-ray&#44; blood examination&#44; and pulmonary function test were performed for all patients&#46; All the operations and postoperative managements were performed by the same surgical and intensive care team&#46; Cognitive function was assessed two days preoperatively and three weeks postoperatively using a battery of seven neuropsychological tests&#58; the MMSE&#44; Trail Making Test &#40;Parts A and B&#41;&#44; Digit Span &#40;forward and backward&#41;&#44; and Grooved Pegboard Test &#40;dominant&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">10&#44;11</span></a> Regarding Grooved Pegboard Test&#44; significant impairment in the non-dominant hand test was predicted because the radial forearm flap was usually harvested from the non-dominant arm&#44; which may impair a smooth movement of the hand&#46; Therefore&#44; non-dominant hand Grooved Pegboard Test was not included&#46; As described previously&#44; cognitive impairment was defined as a decline of 20&#37; from preoperative test scores in at least two of these tests&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> Cognitive function was assessed by the same intensivists&#46; All cognitive tests were performed in the same hospital room&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Methods of anesthetic induction and maintenance and tracheal intubation were not standardized for each patient&#46; Usually&#44; general anesthesia was induced with intravenous propofol &#40;1&#8211;2&#46;5<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span>&#41; and fentanyl &#40;1&#8211;2<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span>&#41; or remifentanil &#40;0&#46;2&#8211;0&#46;3<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span>&#41;&#46; Tracheal intubation was facilitated using rocuronium &#40;0&#46;6&#8211;0&#46;9<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span>&#41; with laryngoscopy&#46; Anesthesia was maintained with sevoflurane &#40;1&#8211;1&#46;5&#37;&#41; and 40&#37; oxygen and air mixture&#46; Fentanyl &#40;1&#8211;2<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleSup">&#8722;1</span>&#41; or remifentanil &#40;0&#46;1&#8211;0&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span>&#41; were used for analgesia&#46; Rocuronium &#40;0&#46;2&#8211;0&#46;3<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleSup">&#8722;1</span>&#41; was used for muscle relaxation&#46; Fluid management was also at the discretion of the attending anesthetist&#46; Usually&#44; 500&#8211;1000<span class="elsevierStyleHsp" style=""></span>ml of colloid &#40;6&#37; hydroxyethyl starch&#41; was infused in the first 1<span class="elsevierStyleHsp" style=""></span>h followed by 2&#8211;4<span class="elsevierStyleHsp" style=""></span>ml<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleSup">&#8722;1</span> of crystalloid&#46; Transfusion was performed if necessary&#44; in which hemoglobin level was maintained between 7 and 10<span class="elsevierStyleHsp" style=""></span>g&#47;gL&#46; Tracheostomy was performed prior to tumor resection&#46; Most patients had unilateral or bilateral neck dissections and excision of the primary tumor with immediate reconstruction&#46; The radial forearm flap was usually harvested usually from the non-dominant arm&#46; After completion of microvascular anastomosis&#44; continuous administration of prostaglandin E1 &#40;10<span class="elsevierStyleHsp" style=""></span>ng<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span>&#41; was started through a central venous line&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">After surgery&#44; patients were transferred to the ICU and remained sedated under mechanical ventilation with the head maintained in a neutral position and elevated 30&#8211;40 degree&#46; Patients were sedated with propofol &#40;2&#8211;3<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleSup">&#8722;1</span>&#41;&#44; fentanyl &#40;0&#46;2&#8211;0&#46;3<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleSup">&#8722;1</span>&#41;&#44; and dexmedetomidine &#40;0&#46;4&#8211;0&#46;7<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleSup">&#8722;1</span> to maintain deep sedation &#40;Richmond Agitation-Sedation Scale &#91;RASS&#93;-4 or -5&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a> We combined different agents to maximize efficacy and minimize adverse effects&#44; with expecting that these combinations have significant benefits over single agents in spite of the absence of strong evidence&#46; Basically&#44; a protocol-based sedation in consideration of pre-emptive analgesia was provided by trained nurses&#46; Dobtamine was used to keep systolic blood pressure<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>110<span class="elsevierStyleHsp" style=""></span>mmHg&#46; Patients received hydrocortisone 100<span class="elsevierStyleHsp" style=""></span>mg on anesthetic induction and several further doses at 12<span class="elsevierStyleHsp" style=""></span>h intervals&#46; The reconstructive surgeons monitored the color of transferred flaps every 2<span class="elsevierStyleHsp" style=""></span>h and cleaned the oral cavity every 6<span class="elsevierStyleHsp" style=""></span>h until the morning of postoperative day 3&#46; When the target sedation level was not maintained&#44; midazolam &#40;5<span class="elsevierStyleHsp" style=""></span>mg&#41; was temporally administered&#46; On the morning of postoperative day 3&#44; sedative administration was terminated but fentanyl was still administered for postoperative pain management although the dose was decreased &#40;0&#46;04&#8211;0&#46;06<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleSup">&#8722;1</span>&#41;&#46; Patients were weaned from mechanical ventilation after patients regained consciousness and discharged from the ICU&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistics</span><p id="par0045" class="elsevierStylePara elsevierViewall">Cognitive impairment after ICU sedation has been reported to vary approximately between 20 and 60&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;3</span></a> For the purpose of a sample-size calculation&#44; we assumed the incidence of cognitive impairment as high as 25&#37; and its 95&#37; confident interval as wide as 50&#37;&#46; The reason of its wide setting of the confident interval was because there was a possibility of no incidence of cognitive impairment&#46; We estimated that 12 patients were required to satisfy this assumption&#46; Considering misestimation of the baseline confident interval&#44; we added 5 participants&#46; Consequently&#44; 17 participants were recruited&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Depending on the data distribution&#44; results are presented as mean &#40;standard deviation &#91;SD&#93;&#41; or median &#91;interquartile range&#93;&#46; Comparisons of change between pre- and post-evaluation were made using the paired t-test or the Wilcoxon test&#46; A correlation between the number of declined cognitive test and age was assessed using Spearman&#39;s rank correlation test&#46; A <span class="elsevierStyleItalic">p</span>-value of &#60;0&#46;05 was considered statistically significant for all analyses&#46; Analyses were computed using R &#40;version 3&#46;0&#46;3&#44; R Foundation for Statistical Computing&#44; Vienna&#44; Austria&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">One hundred and five consecutive patients &#40;&#62;20 years old&#41; who underwent surgery for oral and maxillofacial cancer and microvascular reconstruction under general anesthesia between September 2013 and August 2016 at Nara Medical University Hospital were initially enrolled&#46; Of those&#44; several patients from Departments of Otorhinolaryngology participated this study&#59; however&#44; 49 patients in all were finally excluded from the study because of the above reason&#46; Of 56 patients from Departments of Oral and Maxillofacial Surgery&#44; written informed consent was obtained from 31 patients&#59; however&#44; 3 patients refused the second evaluation&#44; 6 could not undergo the second evaluation because of our inconvenience&#44; 1 could not accomplish the second evaluation because of the effects of sedatives for palliative therapy&#44; 1 was excluded because microvascular reconstruction was not necessary&#44; and 3 was excluded because they were younger than 50 years old although they accomplished the pre- and post-evaluations&#46; Eventually&#44; 17 patients completed both cognitive evaluations and were included in this study &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Patient characteristics&#44; duration of sedation&#44; and doses of analgosedatives are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; One patient required a revision of microvascular anastomosis and additional 3 days sedation&#46; All the remaining patients had uneventful intraoperative and postoperative courses&#46; The pre-cognitive evaluation was performed on preoperative day 2 &#40;range 1&#8211;2&#41;&#46; The post-cognitive evaluation was conducted on postoperative day 23 &#40;range 21&#8211;30&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Regarding the incidence of cognitive impairment&#44; 5 of 17 patients &#40;29&#37;&#41; showed the defined cognitive impairment &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2A</a>&#41;&#46; In this connection&#44; the patient&#44; who required additional sedation&#44; showed no decline in any tests&#46; Patients data with dividing into patients who developed and no developed cognitive impairment are shown on the right side of <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; In regard with performing statistical tests&#44; it was likely that our population was too small to satisfy any statistical power for comparing patients who developed and no developed cognitive impairment&#46; Consequently&#44; statistical tests were not conducted&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 2B</a> shows the number of patients showing a decline of each cognitive test&#46; Except MMSE test&#44; several patients showed a decline of each test&#46; Regarding the association between the number of impaired cognitive test and patient&#39;s age&#44; a significant correlation was not observed &#40;rho<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;163&#44; 95&#37; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;597 to 0&#46;345&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;5324&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The median scores on all six cognitive tests are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a>&#46; No significant difference between pre- and post-cognitive evaluations was observed in any tests&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">On the whole&#44; scores in any cognitive tests did not significantly differ after discharge from the ICU compared with before admission&#46; Looking at each patient result&#44; however&#44; the rate of patients showed a decline of &#62;20&#37; from pre-cognitive evaluation scores in at least two of six tests was 29&#37; of all the patients&#46; These results indicate that deep sedation during several days even under non-critical status can impair the medium term cognitive function in some patients&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The strength of this study is to conduct and compare neurophysiological test performance before ICU admission and after discharge&#46; A major limitation of the studies investigating the effect of ICU admission on cognitive outcome is that a baseline assessment of cognitive status before admission is lacking&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> We used multiple cognitive tests probing different domains&#44; including MMSE &#40;screening&#41;&#44; Trail Making Test Part A &#40;attention&#41;&#44; Trail Making Test Part B &#40;executive function&#41;&#44; Digit Span Test &#40;verbal working memory&#41;&#44; and Grooved Pegboard Test &#40;motor function&#41;&#46; According to a consensus statement&#44; the Rey Auditory Verbal Learning Test&#44; Trail Making Test A&#47;B&#44; and Grooved Pegboard Test are recommended as core components of a comprehensive neuropsychological battery&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> In our preliminary studies&#44; we included the Rey Auditory Verbal Learning Test&#59; however&#44; it was excluded from the main trial as it took a long time to complete and was stressful for some postoperative patients&#46; In current results&#44; MMSE as a dementia screening test was intact&#46; However&#44; it has been suggested that screening tests such as the MMSE do not have the sensitivity to examine for Postoperative cognitive dysfunction &#40;POCD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">14</span></a> On the contrary&#44; cognitive function was broadly impaired such as domains of attention&#44; executive function&#44; verbal working memory&#44; and motor function&#46; It has been suggested that even minor mood changes may have a negative impact on motivation and ability to complete neuropsychological testing&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> If important changes in mood or anxiety occur after surgery&#44; it is possible that the performance in the neuropsychological tests was adversely affected&#46; However&#44; the fact that almost 30&#37; of patient showed cognitive impairment demands close attention even if the above concern is considered&#46; In this study&#44; non-dominant hand Grooved Pegboard Test was not included for the reason mentioned before&#46; However&#44; more patients might have shown cognitive impairment if this test had been included if the flap had been harvested from the other part of the body&#44; because taking one more test would increase opportunities to show a decline of more than 20&#37; from preoperative test scores&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Although several mechanisms for cognitive impairment after ICU admission have been postulated as mentioned before&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> the etiology of this type of cognitive impairment is still unclear&#46; The results of most studies reviewed suggested that critical illness and ICU treatment are associated with cognitive impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> Of those&#44; high-dose deep sedation has been suggested to play an important role of development of cognitive impairment<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;3</span></a>&#59; however&#44; it is still unclear deep sedation status with critical illness or deep sedation status by exposure to analgosedatives plays a main role&#46; Several pre-clinical studies have shown that anesthetic or sedative agents have toxic effects on the central nerve system&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">16&#8211;18</span></a> In addition&#44; considering that our participants were in relatively non-critical status&#44; it is likely that exposure to analgosedatives and immobilization adversely&#44; at least partially&#44; affected cognitive outcome in our population&#46; According to the report of the Second International Perioperative Neurotoxicity Workshop&#44; there is still considerable controversy over whether specific anesthetic agents increase the risk of cognitive impairment&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">19&#44;20</span></a> Besides&#44; sedation was provided by a protocol-based sedation using co-administration of three analgosedatives&#46; Therefore&#44; it is difficult to determine which specific analgosedative agent did affect the cognitive outcome&#46; On the other hand&#44; a combination of sedatives caused a greater increase in the rate of neuronal damage than either drug alone&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> A sedation protocol based on a single analgosedative agent might have had less impact on cognitive outcome&#46; Looking back on the backgrounds of patients who developed cognitive impairment&#44; the doses of propofol and midazolam used seems larger although the dose of dexmedetomidine seems similar compared with patients who did not develop cognitive impairment&#46; It is concluded that benzodiazepine administration is an important and potentially modifiable risk factor for transitioning into delirium&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a> Additionally&#44; some&#44; but not all&#44; clinical studies demonstrated that propofol led to delirium&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a> Considering that increasing duration of delirium was an independent predictor of worse cognitive impairment&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> these drags might have contributed to development of cognitive impairment in our patients&#46; As for dexmedetomidine&#44; this drug has been reported to have ability to attenuate propofol-induced neurotoxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a> Different doses of dexmedetomidine might have produced a different result&#46; However&#44; these comments may be too speculative&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">POCD is common following non-cardiac surgery&#46; In a prospective multicenter trial of as many as a thousand patients undergoing non-cardiac surgery&#44; POCD was present in 26&#37; of patients one week postoperatively and in 10&#37; of patients three months postoperatively&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">23</span></a> Therefore&#44; our results might have been an identical phenomenon of POCD&#46; To distinguish whether our findings were derived from POCD or cognitive impairment by high dose deep sedation in the ICU&#44; we should have needed same surgical patients who had not required sedation and immobilization in the ICU&#46; However&#44; it has been reported that cognitive impairment after ICU discharge is correlated with duration of mechanical ventilation and psychophysiological disorder is positively associated with more days of sedation in the ICU&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">24&#44;25</span></a> Therefore&#44; it is possible that the additional days of sedation under mechanical ventilation in the ICU contributed to cognitive impairment after ICU discharge in our patients&#46; Regarding the long-term cognitive outcome like 3 months or 1 year later&#44; we should have evaluated it&#59; however&#44; it is regrettable that we did not for personal reasons&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">There are several limitations to this study&#46; First&#44; our study was a single arm trial missing the control group&#44; which means patients who underwent surgery without additional days of sedation under mechanical ventilation&#46; If we had set a control group&#44; we might have made a more appropriate judgment on the effect of additional days of sedation on cognitive outcome&#46; However&#44; it would have required to change the postoperative management protocol at the commencement of the study&#46; As another limitation&#44; age was not associated with cognitive impairment after ICU discharge in our study in spite of several previous suggestions&#46; Our study population consisted of patients over 50 years old with the mean age of 62&#46; Relatively older age in our population might have masked the effect of age on cognitive outcome&#46; Otherwise&#44; for patients over a certain age&#44; the effect of high dose deep sedation on cognitive outcome may depend on patient&#39;s susceptibility rather than age&#46; Lastly&#44; the considerable number of patients were excluded from the study&#46; In addition&#44; it has been suggested that plausible assumptions regarding outcomes of patients lost to follow-up could change the interpretation of results of relevant randomized controlled trials&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">26</span></a> Especially&#44; patients who refused the second evaluation might have showed cognitive impairment because such patients may have wished to conceal their cognitive impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> Therefore&#44; more percentage of participants might have showed cognitive impairment after discharge from ICU&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion&#44; the medium-term cognitive function was impaired in some patients&#44; who underwent deep sedation during several days continuing from maxillomandibular oral surgery with microvascular reconstruction&#46; However&#44; it is still unclear whether this cognitive impairment was due to an epiphenomenon of POCD or additional several days sedation under mechanical ventilation in the ICU&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Author contribution</span><p id="par0160" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><p id="par0110" class="elsevierStylePara elsevierViewall">Dr&#46; Terada helped to design the study and prepared the manuscript&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><p id="par0115" class="elsevierStylePara elsevierViewall">Dr&#46; Konda helped to design the study and prepared the manuscript&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><p id="par0120" class="elsevierStylePara elsevierViewall">Dr&#46; Inoue designed the study and prepared the manuscript&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><p id="par0125" class="elsevierStylePara elsevierViewall">Dr&#46; Egawa helped to design the study and prepared the manuscript&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><p id="par0130" class="elsevierStylePara elsevierViewall">Dr&#46; Ueda helped to design the study and prepared the manuscript&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><p id="par0135" class="elsevierStylePara elsevierViewall">Dr&#46; Kirita helped to design the study and prepared the manuscript&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><p id="par0140" class="elsevierStylePara elsevierViewall">Dr&#46; Kawaguchi helped to design the study and reviewed the manuscript&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><p id="par0145" class="elsevierStylePara elsevierViewall">All authors approved the final manuscript&#46;</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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            1 => "Unidad de cuidados intensivos"
            2 => "Alteraci&#243;n cognitiva"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cognitive impairment after intensive care unit &#40;ICU&#41; admission is becoming increasingly recognized&#46; High-dose deep sedation has been suggested to play an important role in the development of cognitive impairment&#46; However&#44; the impact of heavy sedation as a single cause in the development of cognitive impairment in ICU patients remains unclear&#46; In this study we investigated whether a three-day deep sedation protocol could reduce cognitive function in mechanically ventilated non-critical patients&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective observational study was carried out&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Patients</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 17 surgical patients were studied&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Intervention</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">None&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Variables of interest</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Cognitive function before and after ICU admission&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Thirty-one patients requiring three days of sedation after microvascular reconstruction were initially enrolled in the study&#46; Sedation in the ICU was maintained with propofol and dexmedetomidine combined with fentanyl&#46; Cognitive function was assessed using a battery of 6 neuropsychological tests two days before surgery and three weeks after surgery&#46; Finally&#44; a total of 17 patients were included in the analysis&#46; Cognitive impairment &#40;defined as a decline of &#62;20&#37; from the pre-admission cognitive evaluation scores in at least two of 6 tests&#41; was observed in 5 of the 17 patients &#40;29&#37;&#41;&#46; However&#44; there were no significant differences between the pre- and post-admission cognitive evaluations in 6 tests&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Middle-term cognitive function can be impaired in some patients subjected to deep sedation during several days following maxillary&#8211;mandibular oral surgery with microvascular reconstruction&#46;</p></span>"
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        "resumen" => "<span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Objetivo</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Cada vez existe un mayor consenso sobre la afectaci&#243;n cognitiva tras el ingreso en la unidad de cuidados intensivos &#40;UCI&#41;&#46; Se ha sugerido que la sedaci&#243;n profunda con dosis elevada desempe&#241;a un papel importante en el desarrollo de la alteraci&#243;n cognitiva&#46; Sin embargo&#44; todav&#237;a existen dudas sobre el impacto de este tipo de sedaci&#243;n como causa &#250;nica del desarrollo de alteraciones cognitivas en pacientes ingresados en la UCI&#46; En este estudio&#44; investigamos si la aplicaci&#243;n de un protocolo de sedaci&#243;n profunda durante 3 d&#237;as disminu&#237;a la funci&#243;n cognitiva en pacientes no cr&#237;ticos bajo ventilaci&#243;n mec&#225;nica&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Dise&#241;o</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se llev&#243; a cabo un estudio observacional prospectivo&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Pacientes</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se estudi&#243; a un total de 17 pacientes quir&#250;rgicos&#46;</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Intervenciones</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Ninguna&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Variables de inter&#233;s</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Funci&#243;n cognitiva antes y despu&#233;s del ingreso en la UCI&#46;</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Resultados</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">En este estudio se incluy&#243; inicialmente a 31 pacientes que requer&#237;an 3 d&#237;as de sedaci&#243;n tras una reconstrucci&#243;n microvascular&#46; Se mantuvo la sedaci&#243;n en la UCI con propofol y dexmedetomidina en combinaci&#243;n con fentanilo&#46; Se evalu&#243; la funci&#243;n cognitiva mediante un grupo de 6 pruebas neurofisiol&#243;gicas antes de la intervenci&#243;n y 3 d&#237;as despu&#233;s de esta&#46; Por &#250;ltimo&#44; se incluy&#243; a un total de 17 pacientes en el an&#225;lisis&#46; Se observ&#243; alteraci&#243;n cognitiva &#40;definida como una reducci&#243;n<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20&#37; frente a las puntuaciones de la evaluaci&#243;n cognitiva previa al ingreso en al menos 2 de las 6 pruebas&#41; en 5 de los 17 pacientes &#40;29&#37;&#41;&#46; Sin embargo&#44; no se observaron diferencias significativas entre las evaluaciones previas y posteriores al ingreso en 6 pruebas&#46;</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conclusiones</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">La funci&#243;n cognitiva a medio plazo puede verse afectada en algunos pacientes sometidos a sedaci&#243;n profunda durante varios d&#237;as tras una cirug&#237;a oral maxilar-mandibular con reconstrucci&#243;n microvascular&#46;</p></span>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">Overall population &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&#41;&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">Cognitive impairment &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&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">No cognitive impairment &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&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">Age &#40;yr&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&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">Sex &#40;F&#47;M&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#47;7&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">Hight &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">163&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">171<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">160<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;4&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">Weight &#40;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;7&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">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&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">Duration of anesthesia &#40;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">929 &#91;808&#8211;1022&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">929 &#91;911&#8211;941&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">932 &#91;770&#8211;1022&#93;&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">Duration of surgery &#40;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">786 &#91;665&#8211;893&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">786 &#91;759&#8211;848&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">782 &#91;645&#8211;895&#93;&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">Intraoperative fentanyl &#40;&#956;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1406<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>492&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1310<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>261&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1446<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>567&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">Duration of sedation in ICU &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55&#46;5 &#91;54&#8211;59&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54 &#91;53&#46;5&#8211;55&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#46;5 &#91;54&#46;4&#8211;63&#46;3&#93;&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">Duration of mechanical ventilation in ICU &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#46;5 &#91;55&#46;9&#8211;60&#46;4&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#46;5 &#91;56&#8211;56&#46;5&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58 &#91;55&#46;9&#8211;65&#46;6&#93;&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">Fentanyl for sedation &#40;&#956;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3449<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>961&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3037<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>169&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3620<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1106&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">Propofol for sedation &#40;mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6450<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2247&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7950<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1444&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5825<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2266&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">Dexmedetomidine for sedation &#40;&#956;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2003<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>652&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2148<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>620&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1943<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>682&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">Midazolam for sedation &#40;mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#91;5&#8211;20&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#91;10&#8211;30&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#91;5&#8211;16&#46;3&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1947747.png"
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Patient characteristics&#44; intraoperative data&#44; duration of sedation&#44; and doses of analgosedatives&#46;</p>"
        ]
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      3 => array:8 [
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
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          "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">In this study&#44; cognitive impairment was defined as a decline of 20&#37; from pre-cognitive evaluation scores in at least two of seven tests&#46;</p>"
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            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">Number of tests&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">Number of patients&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">0 test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&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">1 test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&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 tests&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">The number of patients showing a decline of 20&#37; from pre-cognitive evaluation scores&#46;</p>"
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                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">Name of the test&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">Number of patients showing a decline&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&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">Trail Making Test Part A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&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">Trail Making Test Part B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&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">Digit Span Forward Test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&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">Digit Span Backward Test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&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">Dominant hand Pegboard Test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Data are presented as median &#91;interquartile range&#93;&#46;</p><p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">MMSE<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Mini Mental State Examination&#59; TMT A<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Trail Making Test Part A&#59; TMT B<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Trail Making Test Part B&#46;</p>"
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              "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="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8203&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">Digit Span Backward&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#91;4&#8211;5&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#91;4&#8211;6&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8984&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73 &#91;63&#8211;81&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77 &#91;62&#8211;89&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2069&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Cognitive test results at baseline and three weeks postoperatively&#46;</p>"
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Article information

ISSN: 21735727
Original language: English

DOI:10.1016/j.medine.2019.01.001

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2024 November	17	13	30
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2023 October	90	30	120
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2023 August	29	17	46
2023 July	42	25	67
2023 June	43	15	58
2023 May	50	34	84
2023 April	57	20	77
2023 March	96	28	124
2023 February	92	29	121
2023 January	69	11	80
2022 December	99	23	122
2022 November	103	35	138
2022 October	138	23	161
2022 September	81	25	106
2022 August	75	40	115
2022 July	31	24	55
2022 June	72	18	90
2022 May	67	32	99
2022 April	38	25	63
2022 March	62	41	103
2022 February	79	17	96
2022 January	62	34	96
2021 December	71	37	108
2021 November	69	36	105
2021 October	137	62	199
2021 September	63	24	87
2021 August	75	37	112
2021 July	26	28	54
2021 June	36	30	66
2021 May	56	49	105
2021 April	162	60	222
2021 March	76	28	104
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2020 December	55	21	76
2020 November	59	16	75
2020 October	62	30	92
2020 September	51	15	66
2020 August	33	16	49
2020 July	36	18	54
2020 June	47	21	68
2020 May	43	6	49
2020 April	48	15	63
2020 March	26	19	45
2020 February	64	55	119
2020 January	46	17	63
2019 December	45	21	66
2019 November	59	32	91
2019 October	124	23	147
2019 September	30	20	50
2019 August	30	17	47
2019 July	31	24	55
2019 June	23	11	34
2019 May	51	34	85
2019 April	5	4	9
2019 March	1	4	5
2019 February	0	10	10
2019 January	0	0	0

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