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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Analgesic and sedative agents are universally used in intensive care unit &#40;ICU&#41; patients<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> as a cornerstone of the strategies applied to provide comfort and safety during their ICU stay by controlling pain and agitation&#46; This is particularly true for patients on mechanical ventilation &#40;MV&#41;&#44; where the reduction of the physiological response to stress exerted by sedation and analgesia allows healthcare practitioners to provide adequate patient care while promoting ventilator synchrony&#46; However&#44; sedatives and analgesics are not exempt from complications thus implementation of strategies to maximize their effectiveness and safety has become a priority for scientific societies and experts&#8217; committees of sedation and analgesia in ICU patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Sedative dose requirements are highly variable among ICU patients and particularly influenced by inter and intra-individual differences&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> Pathophysiology in the critically ill patients and individual specific characteristics such as age&#44; metabolic or genetics&#44; impact the drugs&#8217; metabolism and elimination<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">6&#44;7</span></a> and can render unpredictable responses to sedatives even when used at known safe doses&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The difficulty to achieve an adequate level of sedation despite the application of higher doses of sedatives&#47;analgesics along with agitation upon sedative discontinuation defined as <span class="elsevierStyleItalic">difficult sedation</span> &#40;DS&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> is a common clinical scenario and represents a challenge for the ICU specialists who are frequently forced to increase sedative dose or to add new agents&#44; which may increase the risks of toxicity and related complications&#46; DS in ICU patients is also associated with specific clinical&#44; haemodynamic&#44; endocrine and metabolic responses&#44; which negatively impact on patients&#8217; outcome&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Certain conditions have been related to sedation complications&#46; Among these&#44; harmful use of alcohol &#40;HUA&#41;&#44; reported in about 20&#8211;39&#37; of ICU patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10&#44;11</span></a> and chronic use of psychotropics have been both associated with increased risks of withdrawal syndrome&#44; particularly for patients under prolonged sedation &#40;PS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Considering this scenario&#44; we aimed to prospectively study the impact of HUA history on sedation and analgesia practices applied for ICU patients on MV&#44; as well as to assess its influence on patients&#8217; outcome and mortality&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">Prospective&#44; observational multicentre study of all adult patients consecutively admitted in 8 ICUs of public and university hospitals of Spain between November and December of 2007&#46; Patients were followed since admission until ICU discharge or death&#46; Patients derived to other ICU or participating in other clinical trials were excluded&#46; All study materials were approved by the Ethics Committee of the coordinating hospital &#40;Ref&#58; CEIC49&#47;2007&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Data were recorded from the patient or their relatives or clinical records &#40;in case patients were unable to report themselves&#41; including age&#44; gender&#44; cause for admission &#40;medical&#44; surgical or trauma&#41;&#44; Acute Physiology and Chronic Health Evaluation &#40;APACHE II&#41; and consumption habits such as tabaquism &#40;&#62;10<span class="elsevierStyleHsp" style=""></span>cigarettes&#47;day&#41;&#44; regular&#47;occasional use of illegal psychotropics &#40;IP&#41; during the previous year &#40;cocaine&#44; opioids derivatives&#44; cannabis&#44; psychostimulants&#44; psychedelics and other drugs&#41;&#44; regular use of prescribed psychotropics medications &#40;PPM&#41; during the last 3 months &#40;hypno-sedatives&#44; antidepressants&#44; neuroleptics&#44; antiepileptics&#41; and a quantitative evaluation of alcohol use according to Standard Drink Units &#40;SDU&#41; adapted for Spain<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a> considering as HUA weekly consumptions above 280<span class="elsevierStyleHsp" style=""></span>g &#40;28 SDU&#41; in men and 168<span class="elsevierStyleHsp" style=""></span>g &#40;17 SDU&#41; in women&#44; or 50<span class="elsevierStyleHsp" style=""></span>g &#40;5 SDU&#41; during the weekend or once a month as recommended by the World Health Organization &#40;WHO&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Analgesia and sedation practices were performed in accordance to the protocol of each participating ICU&#44; all following the sedation and analgesia guidelines published by the Sedation and Analgesia Work Group of the SEMICYUC in which preparation were actively involved &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Sedation level was evaluated using the Ramsay Scale<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a> &#40;4 centres&#41; and the Richmond Agitation&#8211;Sedation Scale &#40;RASS&#41;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a> &#40;4 centres&#41;&#44; while analgesia was monitored with a Pain Visual Analogic Scale &#40;VAS&#41; in patients able to communicate and&#47;or the Campbell Scale<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> in the rest of cases&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Sedation and analgesia data included the type of sedative and analgesic prescribed&#44; sedation duration &#40;short sedation &#40;SS&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>72<span class="elsevierStyleHsp" style=""></span>h&#59; prolonged sedation &#40;PS&#41;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>72<span class="elsevierStyleHsp" style=""></span>h&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a> and use of <span class="elsevierStyleItalic">sequential sedation</span> &#40;substitution of a medium-long half-life for a shorter half-life sedative&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a> Sedation&#47;analgesia complications were prospectively registered including <span class="elsevierStyleItalic">difficult sedation</span> &#40;DS&#41;&#44; <span class="elsevierStyleItalic">sedative failure</span> &#40;SF&#41; and <span class="elsevierStyleItalic">sedative withdrawal</span> &#40;<span class="elsevierStyleItalic">SW</span>&#41; defined by the Sedation and Analgesia Work Group of the SEMICYUC<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">MV total time&#44; data on weaning and tracheostomy&#44; ICU length of stay &#40;LOS&#41; and patients&#8217; outcome &#40;Exitus&#47;Alive&#41; was also registered&#46; Information on other adverse effects associated with sedation and analgesia such as vasopressor rate&#44; arrhythmias&#44; infections&#44; etc&#46;&#44; were not collected&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Impact of HUA on complications of sedation and clinical outcome was analyzed only for patients who required MV beyond 24<span class="elsevierStyleHsp" style=""></span>h&#46; Descriptive results were calculated based on the total number of valid cases and are presented for continuous variables as mean &#40;SD&#41; and median and interquartile range &#40;IR P25&#8211;P75&#41; in case of non-normal distribution and as frequencies for categorical variables&#46; Categorical variables underwent univariate analysis using Pearson&#39;s Chi-squared test and Fisher&#39;s test in case of lower frequencies than expected&#46; Continuous variables were compared with the Student <span class="elsevierStyleItalic">t</span> test &#40;normal distribution&#41; and <span class="elsevierStyleItalic">U</span>-Mann&#8211;Whitney test&#44; considering a <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 value as statistically significant&#46; For the multivariate analysis&#44; a multinomial &#40;categorical dependent factors&#41; and linear regression models &#40;continuous factors&#41; were used to determine the effect of each factor on the sedation complications and risk probabilities&#46; Variables identified as significantly different between HUA and no HUA groups were included in the multivariate analysis to determine their impact on the prevalence of SF and WS&#46; DS was not included in the analysis since SF and WS are part of this clinical entity&#46; Results are presented as odds ratios &#40;OR&#41; along with 95&#37; confidence intervals &#40;95&#37; CI&#41; thus considering as possible risk factor those with an OR<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1 and a protective factor those with an OR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#46; All statistical analysis was performed with SPSS 13&#46;0<span class="elsevierStyleSup">&#174;</span> for Windows&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Total cohort</span><p id="par0060" class="elsevierStylePara elsevierViewall">A total of 509 patients were admitted to the 8 participating ICUs during study period and 38 of them were excluded &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Total study sample &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>471&#41; was 58&#46;9 &#40;17&#46;2&#41; years old&#44; mostly male &#40;66&#46;9&#37;&#41;&#44; with a <span class="elsevierStyleItalic">medical</span> cause for admission &#40;52&#46;2&#37;&#41; and a mean APACHE II of 13&#46;2 &#40;8&#46;3&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">A 16&#46;7&#37; of cases were considered as HUA and 20&#37; of all patients were smokers&#46; PPM and IP were reported in 19&#46;3&#37; and 4&#46;4&#37; of patients&#44; respectively&#46; A total of 244 &#40;51&#46;8&#37;&#41; patients received MV and 119 &#40;23&#46;4&#37;&#41; did so for &#8805;24<span class="elsevierStyleHsp" style=""></span>h constituting the study group&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study group</span><p id="par0070" class="elsevierStylePara elsevierViewall">Demographic characteristics and consumption habits of the study group are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Most patients were male &#40;68&#46;9&#37;&#41; and had a medical cause of admission &#40;53&#46;9&#41;&#59; mean age was 57&#46;0 &#40;17&#46;9&#41; years old and APACHEII was 18&#46;8 &#40;7&#46;2&#41;&#59; half &#40;50&#46;5&#37;&#41; of the patients referred consumption of at least one psychotropic&#44; being tobacco &#40;27&#46;7&#37;&#41; and HUA &#40;25&#46;2&#37;&#41; the most frequently reported&#46; PPM were reported in 15&#46;1&#37; of patients and hypno-sedatives &#40;9&#46;2&#37;&#41; where the most commonly prescribed&#44; being benzodiazepines &#40;7&#46;5&#37;&#41; the more frequent type&#46; Of the IP users&#44; 75&#37; were also&#44; with cocaine &#40;4&#46;2&#37;&#41; and cannabis &#40;3&#46;3&#37;&#41; as the preferred drugs&#46; A 75&#37; of IP users were also tobacco or alcohol consumers&#46; Use of PPM was reported in 15&#46;1&#37; of patients being hypno-sedatives &#40;benzodiazepines 81&#46;5&#37;&#41; and antidepressants &#40;SSRI 50&#37;&#41; the most commonly prescribed&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Sedation&#47;analgesia practices and outcome variables</span><p id="par0075" class="elsevierStylePara elsevierViewall">Combination of sedatives and analgesics was the most frequent sedation pattern observed &#40;89&#46;9&#37;&#41;&#44; with a 10&#46;1&#37; and 6&#46;7&#37; of patients receiving analgesia or sedation alone&#44; while simultaneous use of two or more sedatives was observed in 35&#46;2&#37; of cases &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Shorter sedation times &#40;SS<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>72<span class="elsevierStyleHsp" style=""></span>h&#41; was registered in 60&#46;5&#37; of patients and a 39&#46;4&#37; required PS&#46; The strategy of sequential sedation was applied for 20&#46;1&#37; of patients and SW and SF were observed in 24 &#40;20&#46;1&#37;&#41; and 17 &#40;14&#46;2&#37;&#41; of them&#44; respectively&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Most patients were intubated outside the ICU &#40;83&#37;&#41;&#46; Median length of MV was of 138 &#40;69&#8211;290&#41;<span class="elsevierStyleHsp" style=""></span>h and 70&#46;5&#37; of patients required of MV &#8805;72<span class="elsevierStyleHsp" style=""></span>h&#46; Re-intubation was necessary in 6&#37; of cases and a tracheostomy was performed in 15&#37; of patients at an average of 10&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;1 days after admission&#46; Mean ICU&#39;s LOS was 13&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;6 days and mortality rate was of 27&#46;7&#37;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">HUA vs&#46; No-HUA</span><p id="par0085" class="elsevierStylePara elsevierViewall">According to the SDUs assessment&#44; a total of 30 patients &#40;25&#46;2&#37;&#41; were categorized as HUA &#40;<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#41;&#46; No differences in demographics&#44; severity&#44; and cause of admission or history of psychotropic consumption were observed compared with No-HUA patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Overall&#44; HUA patients required longer sedation and analgesia times&#44; and a higher proportion of them were under PS &#40;86&#46;7&#37; vs&#46; 64&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Midazolam was the preferred sedative &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; in HUA group while no differences among use of other agents when compared with the No-HUA group were observed&#46; The simultaneous use of &#8805;2 sedatives and&#47;or the sequential application of sedatives were significantly more frequent in the HUA group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Similarly&#44; the number of patients in the HUA group presenting DS tripled that of the No-HUA group &#40;60&#37; vs&#46; 18&#37;&#41;&#44; and the incidence of sedation complications such as SF &#40;40&#37; vs&#46; 5&#46;6&#37;&#41; and SW &#40;46&#46;7&#37; vs&#46; 11&#46;2&#37;&#41; was 8 and 4 times higher in the HUA group&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">HUA was also associated with longer periods on MV &#40;250&#59; &#40;125&#46;2&#8211;319&#46;3&#41; vs&#46; 99&#59; &#40;49&#46;5&#8211;229&#41; hours&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and LOS &#40;8&#46;2&#59; &#40;4&#46;12&#8211;15&#46;3&#41; vs&#46; 12&#46;6 &#40;6&#46;3&#8211;22&#46;9&#41;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; days when compared with No-HUA group&#46; However&#44; no differences were found regarding mortality &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Multivariate logistic regression analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41; identified history of HUA &#40;OR&#58; 59&#46;4&#59; 5&#46;9&#8211;595&#46;8&#41;&#44; use of IP &#40;OR&#58; 33&#46;1&#59; 1&#46;8&#8211;597&#46;5&#41; and PS &#40;OR&#58; 32&#46;7&#59; 2&#46;09&#8211;512&#46;0&#41; as significant risk factors for SF&#46; Incidence of SW was also influenced by HUA &#40;OR&#58; 5&#46;3&#59; 1&#46;87&#8211;15&#46;1&#41; as well as the simultaneous requirement of &#8805;2 sedatives during ICU&#39;s stay &#40;OR&#58; 4&#46;9&#59; 1&#46;8&#8211;13&#46;2&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">The present work is&#44; to our knowledge&#44; the first multicentre study of prospective nature that demonstrates that history of HUA may negatively impact on the sedation and analgesia&#39;s related complications in MV critically ill patients&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">One out of 4 patients was categorized as HUA&#44; similar to data reported in United States<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> and Spanish national surveys&#44; but higher than data from ICU settings&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10&#44;11</span></a> The retrospective nature and the different diagnostic criteria used in most of the evidence available could account for such differences&#46; The definition of HUA according to the WHO recommendations &#40;SDU adapted for Spanish population&#41; may present some advantages over other instruments such as the Alcohol Use Disorders Identification Test<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a> &#40;AUDIT&#41; or the CAGE questionnaire<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> in the critical care setting&#46; The SDU is an objective&#44; easy and quick way to quantify the alcohol intake that may ease the investigation of a patient&#39;s alcohol consumption habits by the critical care specialist who frequently lacks the time and training to carry out complex questionnaires&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Similar to previous reports&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> there were no differences in the type of admission diagnosis among HUA and no HUA patients&#46; However and contrarily to published series<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10&#44;11</span></a> HUA patients of this study were not younger nor predominantly male&#59; different geo-demographical characteristics of the studies setting may account for the difference&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Sedation and analgesia</span><p id="par0130" class="elsevierStylePara elsevierViewall">One-third of the study population required of the simultaneous administration of &#8805;2 sedatives in order to achieve adequate sedation&#46; Similarly&#44; SF was reported in 14&#46;2&#37; of the cases&#46; The incidence of SF shows important variations across the evidence&#44; &#40;i&#46;e&#46; midazolam SF 25&#8211;33&#37;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> or propofol 3&#8211;34&#37;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a>&#41;&#44; due to the lack of a clear consensus on the definition of the maximal dose for some of the most used sedatives in ICU&#46; Doses ranging between 4 and 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h have been recommended by several scientific societies as the maximal safe dose for propofol since higher infusions have been associated with direct toxicity defined as propofol infusion syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">25</span></a> This demarcation is less clear for midazolam thus the maximum dose reported in the available evidence ranges from 0&#46;2 to 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#46; In absence of a clear definition of a toxicity syndrome directly associated with midazolam&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> the ranges considered to define sedative failure in this study were those recommended by the SEMICYUC&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Sedative withdrawal rate observed in our study &#40;20&#46;1&#37;&#41; was lower than the reported by other authors &#40;20&#8211;80&#37; in critically ill patients undergoing sedation and analgesia beyond a week&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> but again&#44; differences in SW definition and case-mix<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> may account for conflicting results&#46; Diagnosis of SW was established by study investigators whenever the presence of specific and easily recognizable clinical signs and symptoms such as insomnia&#44; anxiety&#44; agitation&#44; nausea&#44; delirium and seizures were observed at the time of sedatives&#8217; reduction or discontinuation &#40;in the absence of pain or other organic causes&#41;&#46; The use of standard definitions such as DSM-IV<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> or several questionnaires&#47;interviews designed to identify SW might be limited in the ICU setting since their implementation requires an adequate level of patients&#8217; consciousness and&#47;or preserved verbal&#44; motor&#44; hearing and visual abilities&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Sequential sedation&#44; a strategy aimed to avoid the adverse effects of accumulation of sedatives&#44; was implemented in 1 of every 4 patients&#46; Authors did not find relevant evidence in literature to compare with&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">HUA vs&#46; No-HUA</span><p id="par0145" class="elsevierStylePara elsevierViewall">HUA patients were sedated for longer periods&#44; required more frequently the simultaneous use of &#8805;2 sedatives and presented higher rates of sedation complications than No-HUA patients&#46; Moreover&#44; HUA was identified as an independent risk factor for the development of SF and SW&#46; Similar results were reported in the study of De Wit et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> where critical patients with psychotropic consumption history needed 2&#46;5 times more sedatives and 5 times more analgesics to obtain similar sedation level as well longer infusion periods than patients without history of consumption&#46; The need for higher doses of sedatives and analgesics observed in HUA patients might be explained by a possible cross-tolerance mechanism between sedatives and alcohol&#44; as well as to an increased metabolism of these substances through the action of p450 enzyme&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> The same underlying mechanisms could also explain the higher incidence of SW&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a> Although alcohol has no specific receptors as benzodiazepines or barbiturates do&#44; all three substances exert their action through the stimulation of GABA A receptors &#40;reduce brain excitability<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a> while inhibiting glutamate&#39;s N-methyl-<span class="elsevierStyleSmallCaps">d</span>-aspartate &#40;NMDA&#41; receptors<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> &#40;excitatory&#41;&#46; Chronic exposure to any of these agents may induce to a series of compensatory mechanisms at the cellular receptor level producing a gradual decrease in GABA receptors &#40;down-regulation&#41; and increasing NMDA ones &#40;up-regulation&#41; in such a way that balance is only restored in the presence of such psychotropic agents&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a> Prolonged use of benzodiazepines enhances the GABA&#47;NMDA unbalance&#44; making necessary to increase sedative agents&#8217; dose to reach&#47;maintain the adequate levels of sedation&#46; Similarly&#44; reduction or discontinuation of these agents may disrupt the balance&#44; increasing brain excitability which together with the interruption of the inhibitory effect&#44; is manifested as the known symptoms and signs of withdrawal&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">In the present study&#44; HUA patients required longer periods of MV&#46; This finding was not found by De Wit et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> who described that despite the increased risk for need of MV&#44; alcoholic patients did no required prolonged times of MV&#44; except for those presenting with withdrawal syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">36</span></a> Similarly to data reported by Suchyta et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> in our series&#44; HUA patients presented longer ICU LOS&#46; These findings have not been replied in other retrospective investigations with different case mixes&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> PS and the need for higher number and&#47;or doses of sedatives consistently found in patients with chronic use of psychotropics may play a role in the prolongation of MV and ICU stay times&#46; Oversedation has been associated with prolonged time on MV and complications such as pneumonia&#44; barotrauma&#44; upper digestive haemorrhage&#44; bacteraemia&#44; or venous thrombosis among others&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a> On the other hand&#44; and similarly to other reports&#44;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10&#44;11&#44;36</span></a> HUA was not associated with higher rates of mortality in ICU patients&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">One of the main limitations of the present study is that&#44; in order to attain an easy and rapid detection in the ICU setting&#44; criteria used for classification of &#8220;psychotropic consumption&#8221; were less strict than those used in other studies&#44; which may contribute to a possible overestimation of psychotropic use rates&#46; However&#44; several studies in the hospital and out-of-hospital setting have shown that detection of drug dependence is frequently under-diagnosed with rates ranging from 10 to 86&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> This may be particularly true in the context of critically ill patients&#44; where the implementation of standard criteria for disease classifications<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> and screening tools may be hampered by factors such as the lack of critical care physicians specific training in drug dependencies&#44; the need for urgent care&#44; and the frequently imprecise sources of information available in this setting &#40;subjective information from relatives or incomplete medical records&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The study was conducted in 2007&#46; Sedation and analgesia practices may have changed since then hampering the validity of data presented in this manuscript with today&#39;s practice&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The implementation of sedation and analgesia protocols were responsibility of each of the participating centres as well as for the diagnosis of SW or SF that was performed according to the clinical criteria of investigators&#46; The knowledge of history of HUA could have influenced beforehand the sedation strategy implemented and diagnosis of WS by the attending physician affecting the internal validity of the study&#46; However it is important to recognize that all the study investigators are active members of the Spanish National Sedation and Analgesia Work Group of SEMICYUC which may influence the highly consonance of sedoanalgesia practices described in this study with the recommended by scientific societies&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">We are also aware that the definition of SW used in the present study may lead to a false overrepresentation of this clinical profile due to the inclusion of misdiagnosed ICU delirium cases in mechanically ventilated patients&#44; a syndrome that although sharing some of the clinical symptoms has different pathophysiologic mechanisms and outcomes&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Despite the multicentre design&#44; the low number of patients and events per variable finally included advise to take cautiously results found in multivariate analysis&#46; Similarly&#44; although statistically significant&#44; the impact of IPP on sedation practices and complications should be re-evaluated due to the low number of cases&#46; The different case-mix &#40;age&#44; social background&#44; etc&#46;&#41; of the included patients in the different participating centres may also hamper external validity of the results making them not applicable to other hospitals with different characteristics&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In conclusion&#44; HUA patients may be at higher risk of requiring prolonged sedation and the use of higher doses of sedatives and analgesics&#44; increasing the risk of sedation failure and withdrawal that could ultimately impact negatively on their outcome&#46; Early identification of HUA patients might be advisable in patients admitted to ICUs since these patients are in higher risk of sedation failure and withdrawal and could benefit from strategies oriented to the prevention of these complications&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Purpose"
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            1 => array:2 [
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              "titulo" => "Methods"
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              "identificador" => "abst0015"
              "titulo" => "Results"
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              "identificador" => "abst0020"
              "titulo" => "Conclusions"
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              "titulo" => "Statistical analysis"
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          "titulo" => "Results"
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              "titulo" => "Total cohort"
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              "titulo" => "Study group"
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                  "identificador" => "sec0035"
                  "titulo" => "Sedation&#47;analgesia practices and outcome variables"
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                  "identificador" => "sec0040"
                  "titulo" => "HUA vs&#46; No-HUA"
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          "titulo" => "Discussion"
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              "titulo" => "Sedation and analgesia"
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              "identificador" => "sec0055"
              "titulo" => "HUA vs&#46; No-HUA"
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          "titulo" => "Conflict of interest"
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          "identificador" => "xack213661"
          "titulo" => "Acknowledgments"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-04-09"
    "fechaAceptado" => "2015-06-29"
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          "palabras" => array:5 [
            0 => "Harmful use of alcohol"
            1 => "Sedation therapeutic failure"
            2 => "Difficult sedation"
            3 => "Sedative withdrawal"
            4 => "Mechanical ventilation"
          ]
        ]
      ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:5 [
            0 => "Consumo en&#243;lico de riesgo"
            1 => "Fracaso terap&#233;utico de la sedaci&#243;n"
            2 => "Sedaci&#243;n dif&#237;cil"
            3 => "Privaci&#243;n de la sedaci&#243;n"
            4 => "Ventilaci&#243;n mec&#225;nica"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate the impact of a history of harmful use of alcohol &#40;HUA&#41; on sedoanalgesia practices and outcomes in patients on mechanical ventilation &#40;MV&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective&#44; observational multicentre study was made of all adults consecutively admitted during 30 days to 8 Spanish ICUs&#46; Patients on MV &#62;24<span class="elsevierStyleHsp" style=""></span>h were followed-up on until discharge from the ICU or death&#46; Data on HUA&#44; smoking&#44; the use of illegal &#40;IP&#41; and medically prescribed psychotropics &#40;MPP&#41;&#44; sedoanalgesia practices and their related complications &#40;sedative failure &#91;SF&#93; and sedative withdrawal &#91;SW&#93;&#41;&#44; as well as outcome&#44; were prospectively recorded&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 23&#46;4&#37; &#40;119&#47;509&#41; of the admitted patients received MV &#62;24<span class="elsevierStyleHsp" style=""></span>h&#59; 68&#46;9&#37; were males&#59; age 57&#46;0 &#40;17&#46;9&#41; years&#59; APACHE II score 18&#46;8 &#40;7&#46;2&#41;&#59; with a medical cause of admission in 53&#46;9&#37;&#46; Half of them consumed at least one psychotropic agent &#40;smoking 27&#46;7&#37;&#44; HUA 25&#46;2&#37;&#59; MPP 9&#46;2&#37;&#59; and IP 7&#46;6&#37;&#41;&#46; HUA patients more frequently required PS &#40;86&#46;7&#37; vs&#46; 64&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; and the use of &#62;2 sedatives &#40;56&#46;7&#37; vs&#46; 28&#46;1&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; HUA was associated to an eightfold &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and fourfold &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; increase in SF and SW&#44; respectively&#46; In turn&#44; the duration of MV and the stay in the ICU was increased by 151<span class="elsevierStyleHsp" style=""></span>h &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; and 4&#46;4 days &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; respectively&#44; when compared with the non-HUA group&#46; No differences were found in terms of mortality&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">HUA may be associated to a higher risk of SF and WS&#44; and can prolong MV and the duration of stay in the ICU in critical patients&#46; Early identification could allow the implementation of specific sedation strategies aimed at preventing these complications&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar el impacto del consumo en&#243;lico de riesgo &#40;HUA&#41; en las pr&#225;cticas de sedoanalgesia y la evoluci&#243;n de pacientes en ventilaci&#243;n mec&#225;nica &#40;MV&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo observacional multic&#233;ntrico de todos los adultos ingresados consecutivamente durante 30 d&#237;as en 8 UCIs espa&#241;olas&#46; Los pacientes en MV &#62;24<span class="elsevierStyleHsp" style=""></span>h fueron evaluados hasta el alta de UCI o <span class="elsevierStyleItalic">exitus</span>&#46; Se registr&#243; el HUA&#44; consumo de tabaco&#44; psic&#243;tropos ilegales &#40;IP&#41; o bajo prescripci&#243;n m&#233;dica &#40;MPP&#41; las pr&#225;cticas de sedoanalgesia y sus complicaciones asociadas &#40;Fracaso de Sedaci&#243;n&#47;SF y S&#237;ndrome de Privaci&#243;n&#47;SW&#41; as&#237; como datos sobre la evoluci&#243;n cl&#237;nica&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El 23&#46;4&#37; &#40;119&#47;509&#41; de los ingresados&#44; requirieron VM &#8805;24<span class="elsevierStyleHsp" style=""></span>h&#58; Varones 68&#46;9&#37;&#59; Edad 57&#46;0 &#40;17&#46;9&#41; a&#241;os&#59; APACHEII 18&#46;8 &#40;7&#46;2&#41;&#59; Ingreso por causa medica 53&#46;9&#37;&#46; La mitad consum&#237;an al menos un psicotr&#243;pico &#40;tabaco&#58; 27&#46;7&#37;&#59; HUA&#58; 25&#46;2&#37;&#59; PPM&#58; 9&#46;2&#37;&#59; PI&#58; 7&#46;6&#37;&#41;&#46; Los pacientes con HUA requirieron m&#225;s frecuentemente PS &#40;86&#46;7&#37; vs&#46; 64&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; y doble sedaci&#243;n &#40;56&#46;7&#37; vs&#46; 28&#46;1&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; El HUA se asoci&#243; a incidencias 8 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; y 4 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; veces superiores de SF y SW y prolong&#243; en 151 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; horas y 4&#46;4 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; d&#237;as&#44; el tiempo de VM y estancia media en UCI respectivamente respecto al grupo no-HUA&#46; No se encontraron diferencias en la mortalidad&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El HUA podr&#237;a asociarse a un mayor riesgo de SF y WS y prolongar los tiempos de MV y LOS en los pacientes cr&#237;ticos&#46; Su identificaci&#243;n precoz permitir&#237;a implementar estrategias espec&#237;ficas de sedaci&#243;n orientadas a prevenir estas complicaciones&#46;</p></span>"
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            "titulo" => "Resultados"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Process of patients&#8217; inclusion&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendations</span>&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"><span class="elsevierStyleHsp" style=""></span>Sedation in critically ill patients should be initiated only after adequate analgesia has been provided&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"><span class="elsevierStyleHsp" style=""></span>Regular assessment of sedation and analgesia level should be performed in critically ill patients using validated scales at least every 4<span class="elsevierStyleHsp" style=""></span>h&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"><span class="elsevierStyleHsp" style=""></span>The administration of sedatives and analgesics should be done according to regularly redefined sedation goals for each patient and using the minimal effective dose during the shorter possible time in order to avoid the adverse effects derived from agent&#39;s accumulation&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"><span class="elsevierStyleHsp" style=""></span>The implementation of protocols&#44; clinical guidelines or algorithms to guide the initiation&#44; adjustment and discontinuation of sedatives and analgesics is strongly recommended&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"><span class="elsevierStyleItalic">Definitions</span>&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"><span class="elsevierStyleHsp" style=""></span>Length of sedation&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"><span class="elsevierStyleHsp" style=""></span>Short sedation &#40;SS&#41;&#58; sedation during less than 72<span class="elsevierStyleHsp" style=""></span>h&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"><span class="elsevierStyleHsp" style=""></span>Prolonged sedation &#40;PS&#41;&#58; sedation during 72<span class="elsevierStyleHsp" style=""></span>h or more&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"><span class="elsevierStyleItalic">Sedation complications&#58;</span>&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"><span class="elsevierStyleHsp" style=""></span>Difficult sedation&#58; includes those situations of sedative failure &#40;failure to achieve desired sedation level after maximal dosage&#41;&#44; tolerance &#40;the need of increasing doses to achieve the same sedation level&#41; and&#44; sedative withdrawal &#40;presence of symptoms that occurs upon the abrupt discontinuation or a decrease in the sedative dose&#41;&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"><span class="elsevierStyleHsp" style=""></span>Sedative failure &#40;SF&#41;&#58; the inability to achieve the desired level of sedation at doses &#62;0&#46;25<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h of midazolam or &#62;4&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h of propofol &#40;provided adequate analgesia&#41;&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"><span class="elsevierStyleHsp" style=""></span>Sedative withdrawal &#40;SW&#41;&#58; as agitation after the abrupt interruption&#47;reduction of sedative dose in absence of pain and&#47;or metabolic alterations&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">HUA&#44; harmful use of alcohol&#59; <span class="elsevierStyleItalic">n</span>&#44; number&#59; &#37;&#44; percentage&#59; SD&#44; standard deviation&#46;</p>"
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                  <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">&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">Study population &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>119&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HUA</th><th class="td" title="table-head  " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><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="" 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">No-HUA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>89&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><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></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Demographic and psychotropics use</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&#46;0 &#40;17&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&#46;7 &#40;17&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;0 &#40;18&#46;8&#41;&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;48&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"><span class="elsevierStyleHsp" style=""></span>APACHE II mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&#46;8 &#40;7&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;7 &#40;7&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&#46;2 &#40;7&#46;5&#41;&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;47&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"><span class="elsevierStyleHsp" style=""></span>Male <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82 &#40;68&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59 &#40;66&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23 &#40;76&#46;7&#41;&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;36&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"><span class="elsevierStyleHsp" style=""></span>Tabaquism <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;27&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;28&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;26&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;00&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"><span class="elsevierStyleHsp" style=""></span>Harmful use of alcohol <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30 &#40;25&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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"><span class="elsevierStyleHsp" style=""></span>Medical prescription <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18 &#40;15&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;15&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;00&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hypnosedatives <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;9&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;9&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;10&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;00&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Antidepressants n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;9&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;00&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Neuroleptics <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;4&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;00&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"><span class="elsevierStyleHsp" style=""></span>Illegal psychotropics <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;10&#46;0&#41;&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;28&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cocaine <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;16&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cannabis <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Opiate derivatives <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Psychostimulants <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Psychedelics and other drugs <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Cause of admission</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Medical <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64 &#40;53&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47 &#40;52&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;56&#46;7&#41;&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;45&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"><span class="elsevierStyleHsp" style=""></span>Surgical <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41 &#40;34&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;37&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;26&#46;7&#41;&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;45&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"><span class="elsevierStyleHsp" style=""></span>Trauma <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;11&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;10&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;16&#46;7&#41;&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;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparison of demographic and psychotropic use variables between groups&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">HUA&#44; harmful use of alcohol&#59; <span class="elsevierStyleItalic">n</span>&#44; number&#59; &#37;&#44; percentage&#59; SD&#44; standard deviation&#59; IR &#40;interquartile range P25&#8211;P75&#41;&#59; ICU&#44; intensive care unit&#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="" valign="top" scope="col">&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">Global study population &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>119&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HUA</th><th class="td" title="table-head  " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><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="" 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">No-HUA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>89&#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">HUA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><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></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleBold">Sedation and analgesia procedures</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sedation &#40;total&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">115 &#40;96&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">88 &#40;98&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27 &#40;90&#46;0&#41;&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;90&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sedation alone <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sedation and analgesia <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">107 &#40;89&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80 &#40;89&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27 &#40;90&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;00&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#62;2 Sedatives simultaneously <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42 &#40;35&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;28&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;56&#46;7&#41;&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;01&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sequential sedation <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24 &#40;20&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;15&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;33&#46;3&#41;&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;03&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Midazolam <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">69 &#40;57&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46 &#40;51&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23 &#40;76&#46;7&#41;&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;01&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Propofol <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66 &#40;55&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48 &#40;53&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18 &#40;60&#46;0&#41;&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;67&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Analgesia &#40;total&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111 &#40;93&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81 &#40;91&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&#46;0 &#40;100&#41;&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;19&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Analgesia alone <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;10&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;00&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#62;2 Analgesics simultaneously <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;14&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;13&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;16&#46;7&#41;&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;23&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Morphine <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66 &#40;55&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47 &#40;52&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19 &#40;63&#46;3&#41;&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;39&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fentanyl <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26 &#40;21&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19 &#40;21&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;23&#46;3&#41;&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;82&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Remifentanil <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36 &#40;30&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27 &#40;30&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;30&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleBold">Time with sedatives and&#47;or analgesia</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Prolonged sedation <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47 &#40;39&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;28&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;56&#46;7&#41;&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;018&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"><span class="elsevierStyleHsp" style=""></span>Short sedation <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72 &#40;60&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64 &#40;71&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13 &#40;43&#46;3&#41;&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;002&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"><span class="elsevierStyleHsp" style=""></span>Sedation time &#40;h&#41; median &#40;IR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83&#46;0 &#40;157&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&#46;0 &#40;105&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">171&#46;5 &#40;226&#41;&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;002&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Midazolam time &#40;h&#41; median &#40;IR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">107 &#40;53&#46;5&#8211;262&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;0 &#40;7&#46;5&#8211;98&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&#46;5 &#40;46&#46;7&#8211;316&#46;7&#41;&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;01&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Propofol &#40;h&#41; median &#40;IR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#46;5 &#40;21&#46;2&#8211;78&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;0 &#40;5&#46;5&#8211;42&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&#46;5 &#40;19&#46;2&#8211;104&#46;2&#41;&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;06&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"><span class="elsevierStyleHsp" style=""></span>Analgesia time &#40;h&#41; median &#40;IR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">96&#46;0 &#40;48&#8211;135&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87&#46;0 &#40;43&#46;5&#8211;181&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">187&#46;5 &#40;93&#46;5&#8211;322&#41;&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;009&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Morphine time &#40;h&#41; median &#40;IR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97&#46;5 &#40;48&#46;7&#8211;259&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&#46;0 &#40;11&#46;5&#8211;107&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&#46;50 &#40;33&#46;2&#8211;320&#41;&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;08&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fentanyl time &#40;h&#41; median &#40;IR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93 &#40;46&#46;5&#8211;169&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70&#46;5 &#40;35&#46;2&#8211;157&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">144 &#40;72&#8211;164&#41;&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;98&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Remifentanil time &#40;h&#41; median &#40;IR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81 &#40;40&#46;5&#8211;127&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63 &#40;31&#46;5&#8211;91&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">96 &#40;48&#8211;157&#41;&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;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleBold">Complications of sedation</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Difficult sedation <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34 &#40;28&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;18&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18 &#40;60&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&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"><span class="elsevierStyleHsp" style=""></span>Sedative withdrawal <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24 &#40;20&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;11&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;46&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&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"><span class="elsevierStyleHsp" style=""></span>Sedative failure <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;14&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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    ]
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              "identificador" => "bib0220"
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                  "contribucion" => array:1 [
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                          "etal" => false
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                  "contribucion" => array:1 [
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
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                            1 => "C&#46;J&#46; Beck"
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                        "fecha" => "2008"
                        "volumen" => "34"
                        "paginaInicial" => "2264"
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                            "web" => "Medline"
                          ]
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              "identificador" => "bib0255"
              "etiqueta" => "11"
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