Lippincott Williams & Wilkins



Supplemental Table 20. Characteristics and main findings of included studies.A. Studies on predisposing and precipitating factorsArticleStudy DesignNumber of delirious / Total (%) Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualtiyAbelha 2012 ADDIN EN.CITE <EndNote><Cite><Author>Abelha</Author><Year>2012</Year><RecNum>2478</RecNum><DisplayText>[1]</DisplayText><record><rec-number>2478</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507739890">2478</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Abelha, F. J.</author><author>Fernandes, V.</author><author>Botelho, M.</author><author>Santos, P.</author><author>Santos, A.</author><author>Machado, J. C.</author><author>Barros, H.</author></authors></contributors><auth-address>Anesthesiology and Perioperative Care Unit, Surgical Department, Faculty of Medicine, University of Porto, Porto, Portugal, abelha@mail.telepac.pt.</auth-address><titles><title>Apolipoprotein E e4 allele does not increase the risk of early postoperative delirium after major surgery</title><secondary-title>J Anesth</secondary-title><alt-title>Journal of anesthesia</alt-title></titles><periodical><full-title>J Anesth</full-title><abbr-1>Journal of anesthesia</abbr-1></periodical><alt-periodical><full-title>J Anesth</full-title><abbr-1>Journal of anesthesia</abbr-1></alt-periodical><edition>2012/02/04</edition><dates><year>2012</year><pub-dates><date>Feb 01</date></pub-dates></dates><isbn>0913-8668</isbn><accession-num>22302107</accession-num><urls></urls><electronic-resource-num>10.1007/s00540-012-1326-5</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[1]Prospective Cohort26/173 (15%)PACUICDSC8 hrly??Major elective surgeryexpected hospital stay >48hrsNeurological or cardiac surgeryCNS conditionParkinsonDeliriumAntipsychotics useDrug/alcohol/opioid abuseNo informed consentAge ≥ 65 yearsEmergency surgeryCongestive Heart failure9.3 59.7 6.2(2.0 - 43.0)(6.7 – 530.5) (2.0 – 19.3)Delirium ICU incidence Logistic Regression++Comments: APOE4 allelle not associated with delirium (4% vs 17%, p=0.09)Delirium only measured during PACU admission. LOS PACU non-delirious patients 19 (15-23) hrs and LOS PACU delirous patiets 46 (19-78) hrs. Therefore risk of “immortal time bias”, the longer admitted (due to complications, severity of disease etc.) the higher the chance of becoming delirious Adjusted for ASA physical status,hyperlipidemia, ischaemic heart disease, RCRI, previous Lawton scale, Dependency in P-ADLAgarwal 2010 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BZ2Fyd2FsPC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48

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ADDIN EN.CITE.DATA [2]Prospective Cohort63/82 (77%)Burn ICUCAM-ICU24 hrly??>24 hrs MVBurn injuriesNeurological conditionPostanoxic encephalopathyMoribundImpaired hearingDelirious previous day Comatose previous dayBenzodiazepines dose <24 hrOpiates dose <24 hrMethadone dose <24 hrBaseline Component26.5 44.9 6.8 0.5 0.70.6(11.9-58.9)(19-105.8)(3.1-15.0)(0.4-0.6) (0.5-0.9)(0.3-1.0) (ns)Daily transition towards deliriumLogistic Regression (GEE + Markov)++CommentsOR presented using 25th and 75th percentile values as comparators (for continuous variables)Benzodiazepines in mg midazolam equivalents and opiates in mg fentanyl equivalentsPrincipal component analysis was used to calculate a single value incorporating age, acute physiology component of the APACHE, history of alcohol/substance abuse, burn percentage and presence of an inhalation injury for use in Logistic Regression. Aldemir 2001 ADDIN EN.CITE <EndNote><Cite><Author>Aldemir</Author><Year>2001</Year><RecNum>2480</RecNum><DisplayText>[3]</DisplayText><record><rec-number>2480</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507741482">2480</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Aldemir, M.</author><author>Ozen, S.</author><author>Kara, I. H.</author><author>Sir, A.</author><author>Bac, B.</author></authors></contributors><auth-address>Department of General Surgery, Dicle University, Faculty of Medicine, Diyarbakir, Turkey. maldemir21@</auth-address><titles><title>Predisposing factors for delirium in the surgical intensive care unit</title><secondary-title>Crit Care</secondary-title><alt-title>Critical care (London, England)</alt-title></titles><periodical><full-title>Crit Care</full-title><abbr-1>Critical care (London, England)</abbr-1></periodical><alt-periodical><full-title>Crit Care</full-title><abbr-1>Critical care (London, England)</abbr-1></alt-periodical><pages>265-70</pages><volume>5</volume><number>5</number><edition>2001/12/12</edition><keywords><keyword>Adult</keyword><keyword>Age Distribution</keyword><keyword>Delirium/diagnosis/*etiology</keyword><keyword>Emergencies</keyword><keyword>Female</keyword><keyword>Health Status</keyword><keyword>Humans</keyword><keyword>*Intensive Care Units</keyword><keyword>Length of Stay</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Postoperative Complications</keyword><keyword>Prospective Studies</keyword><keyword>Sex Distribution</keyword></keywords><dates><year>2001</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1364-8535 (Print)&#xD;1364-8535</isbn><accession-num>11737901</accession-num><urls></urls><custom2>PMC83853</custom2><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3]Prospective Cohort90/818 (11%)SurgicalICUDSM-III 24hrlyResearchAll patientsNoneRespiratory diseaseInfectionFeverHypotensionAnemiaHypocalcemiaHyponatremiaElevated serum urea nitrogenElevated hepatic enzymesHyperamylasemiaHyperbilirubinemiaMetabolic acidosis30.618.014.319.85.430.98.24.66.343.48.74.5(9.5-98.4)(3.5-90.8)(4.1-49.3)(5.3-74.3)(1.6-17.8)(5.8-163.2)(2.5-26.4)(1.4-15.6)(1.2-32.2)(4.2-442.7)(2.0-37.7)(1.1-17.7)ICU Delirium OccurrenceForward StepwiseLogistic Regression+Q: Quality, PACU= Postanesthesia care unit, ICDSC: Intensive Care Delirium Screening Checklist, hrly: hourly, hrs: hours, CNS: Central Nervous System, ICU: Intensive Care, LOS: Length of Stay, CAM-ICU: Confusion Assessment Method for use in the ICU, MV: mechanical ventilation, GEE: Generelazid Estimated Equations, DSM-IV: Diagnostic Statistic Manual version IV, SICU: surgical ICU, ASA: American Society of Anesthesiologists, RCRI: revised cardiac risk index, P-ADL: Personal activities of daily livingArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityAngles 2008 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbmdsZXM8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA [5]Prospective cohort70/115 (61%)Surgical ICUCAM-ICU12 hrlyResearchTrauma patientsAge > 50 yearsAdmission ≥ 24 hoursAge ≤ 50 yearsDied in SICUHistory of dementiaTransferred from jail or in active police custodyVent-free daysChest injury (chest AIS score ≥ 3)AgeInitial GCS scoreBenzo-free daysTBIDeep sedation, hours RASS low (≤ -3)0.790.281.10.850.840.650.99(0.65-0.96)(0.09-0.83)(1.01-1.1)(0.68-1.07) (ns)(0.66-1.09) (ns)(0.22-1.87) (ns)(0.98-1.02) (ns)Delirium IncidenceLogistic Regression+Colombo 2012 ADDIN EN.CITE <EndNote><Cite><Author>Colombo</Author><Year>2012</Year><RecNum>1839</RecNum><DisplayText>[6]</DisplayText><record><rec-number>1839</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232808">1839</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Colombo, R.</author><author>Corona, A.</author><author>Praga, F.</author><author>Minari, C.</author><author>Giannotti, C.</author><author>Castelli, A.</author><author>Raimondi, F.</author></authors></contributors><auth-address>Intensive Care Unit, Azienda Ospedaliera Luigi Sacco, University of Milan, Italy.</auth-address><titles><title>A reorientation strategy for reducing delirium in the critically ill. Results of an interventional study</title><secondary-title>Minerva Anestesiol.</secondary-title></titles><periodical><full-title>Minerva Anestesiol.</full-title></periodical><pages>1026-1033</pages><volume>78</volume><number>9</number><dates><year>2012</year><pub-dates><date>2012/9</date></pub-dates></dates><isbn>0375-9393</isbn><urls><related-urls><url>;[6]B/A80/314 (26%)MixedICUCAM-ICU 12hrlyResearchAll patientsCognitive disordersDementiaPsychosisDisability after strokeMoribundAgeMidazolam + opiate infusionReorientation strategy1.03 2.1 0.5(1.0-1.1) (2.2-4.0) (0.3-0.9) Time to delirium Cox Regression(Hazard Ratio) +CommentsIntervention: reorientation strategyNo blinding in different phases of the studyDubois 2001 ADDIN EN.CITE <EndNote><Cite><Author>Dubois</Author><Year>2001</Year><RecNum>378</RecNum><DisplayText>[7]</DisplayText><record><rec-number>378</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232720">378</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dubois, M. J.</author><author>Bergeron, N.</author><author>Dumont, M.</author><author>Dial, S.</author><author>Skrobik, Y.</author></authors></contributors><titles><title>Delirium in an intensive care unit: a study of risk factors</title><secondary-title>Intensive Care Med.</secondary-title></titles><periodical><full-title>Intensive Care Med.</full-title></periodical><pages>1297-1304</pages><volume>27</volume><number>8</number><keywords><keyword>ICU Rehab 2016</keyword></keywords><dates><year>2001</year><pub-dates><date>2001/8</date></pub-dates></dates><isbn>0342-4642</isbn><urls><related-urls><url>;[7]ProspectiveCohort40/198 (19%)Mixed ICUDSM-IV screening ICDSC 24hrlyBedside Nurse>24hrsMoribund No informed consentHypertensionSmokingBilirubine (per 10% increase)EpiduralMorphine dose 0.01-7.1mg Morphine dose 7.2-18.6mg Morphine dose 18.6-331.6mg 2.6 2.2 1.2 3.5 7.8 9.2 6.0 (1.1-5.7)(0.9-4.9)(1.03-1.4)(1.2-10.4)(1.8-34.4)(2.2-39.0)(1.4-25.4)Delirium Incidence first 5 days ICULogistic Regression+CommentsLaboratory data: proportion of days with abnormal values from admission to day delirium occurredOpioids in parenteral morphine equivalents, benzodiazepines as lorazepam equivalents. Delirious patients mean daily equivalent dosage during delirium phase. Non-delirious patients mean dose using all 5 days. ICU: intensive care, CAM-ICU: Confusion Assessment Method for use in ICU, hrly: hourly, hrs:hours, ISS: injury severity score, GCS: Glasgow Coma Scale, MOF: Multi Organ Failure, ns: non-significant, SICU: surgical intensive care unit, AIS: abbreviated injury scale, TBI: traumatic brain injury, RASS: Richmond Agitation-Sedation Scale, B/A: before after intervention study, MV: mechanically ventilated.ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityEly 2007 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FbHk8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA [8]Prospective Cohort47/53(89%)MedicalICUCAM-ICU12hrlyResearch teamMV>24hrsNoneAPOE4 presentAge, yearsAPACHE IIComa days, quintilesSepsis/ARDS/pneumoniaTotal dose lorazepam, mg 7.31.01.01.31.71.0(1.8-29.5) (0.98-1.1)(ns)(0.9-1.1) (ns)(1.1-1.6)(0.6-5.3) (ns)(1.0-1.0) (ns)ICU delirium daysLogistic Regression(Proportional Odds)++Girard 2012 ADDIN EN.CITE <EndNote><Cite><Author>Girard</Author><Year>2012</Year><RecNum>2531</RecNum><DisplayText>[9]</DisplayText><record><rec-number>2531</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508780434">2531</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Girard, T. D.</author><author>Ware, L. B.</author><author>Bernard, G. R.</author><author>Pandharipande, P. P.</author><author>Thompson, J. L.</author><author>Shintani, A. K.</author><author>Jackson, J. C.</author><author>Dittus, R. S.</author><author>Ely, E. W.</author></authors></contributors><auth-address>Vanderbilt University School of Medicine, Nashville, TN 37232-8300, USA. timothy.girard@vanderbilt.edu</auth-address><titles><title>Associations of markers of inflammation and coagulation with delirium during critical illness</title><secondary-title>Intensive Care Med</secondary-title><alt-title>Intensive care medicine</alt-title></titles><alt-periodical><full-title>Intensive Care Medicine</full-title></alt-periodical><pages>1965-73</pages><volume>38</volume><number>12</number><edition>2012/08/21</edition><keywords><keyword>Aged</keyword><keyword>Biomarkers</keyword><keyword>Blood Coagulation Disorders/*blood</keyword><keyword>Delirium/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Inflammation/*blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Multivariate Analysis</keyword><keyword>Prospective Studies</keyword><keyword>Respiration, Artificial</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2012</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0342-4642</isbn><accession-num>22903241</accession-num><urls></urls><custom2>PMC3606929</custom2><custom6>NIHMS401688</custom6><electronic-resource-num>10.1007/s00134-012-2678-x</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[9]ProspectiveCohort107/138(78%)Medical ICUCAM-ICU24hrlyResearch teamMV>12 hrsMoribundAfter cardiac arrestNeurological diseaseMV ≥ 2 weeksMMP-9 (ng/mL)sTNFR1 (pg/mL)Protein C (% control)0.42.1 0.4(0.2-0.8)(1.2-3.6)(0.2-0.9)Delirium day after biomarker assessmentLogistic Regression(GEE)++CommentsOR represents odds of being delirious day after biomarker measurement with increase in biomarker concentration from the 25th to the 75th percentileAdjusted for age, APACHE II APS, admission with severe sepsisGuillamondegui 2011 ADDIN EN.CITE <EndNote><Cite><Author>Guillamondegui</Author><Year>2011</Year><RecNum>2031</RecNum><DisplayText>[10]</DisplayText><record><rec-number>2031</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232819">2031</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Guillamondegui, Oscar D.</author><author>Richards, Justin E.</author><author>Ely, E. Wesley</author><author>Jackson, James C.</author><author>Archer, Kristin R.</author><author>Archer-Swygert, Kristin</author><author>Norris, Patrick R.</author><author>Obremskey, William T.</author></authors></contributors><auth-address>Division of Trauma and Surgical Critical Care, Vanderbilt University Medical Center, Nashville, Tennessee, USA. oscar.guillamondegui@vanderbilt.edu</auth-address><titles><title>Does hypoxia affect intensive care unit delirium or long-term cognitive impairment after multiple trauma without intracranial hemorrhage?</title><secondary-title>J. Trauma</secondary-title></titles><periodical><full-title>J. Trauma</full-title></periodical><pages>910-915</pages><volume>70</volume><number>4</number><dates><year>2011</year><pub-dates><date>2011/4</date></pub-dates></dates><isbn>0022-5282</isbn><urls><related-urls><url> Papers/G/Guillamondegui et al. 2011 - Does hypoxia affect intensive care unit del ... tive impairment after multiple trauma without intracranial hemorrhage.pdf</url></pdf-urls></urls><electronic-resource-num>10.1097/TA.0b013e3182114f18</electronic-resource-num></record></Cite></EndNote>[10]Prospective Cohort55/97(57%)TraumaICUCAM-ICU12hrly ??ISS > 15Intracranial hemorrhageNo continuous oxygen saturation data.Ventilator daysPulse (Emergency Department)1.21.02(1.1-1.3)(1.00-1.04)Delirium ICU OccurenceLogistic Regression++CommentsAdjusted for ISS, Saturation ≤90% for ≥ 5minutes, blood transfusions, blood pressure at emergency department Heyman 2007 ADDIN EN.CITE <EndNote><Cite><Author>Heymann</Author><Year>2007</Year><RecNum>2620</RecNum><DisplayText>[11]</DisplayText><record><rec-number>2620</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508783336">2620</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Heymann, A</author><author>Sander, M</author><author>Krahne, D</author><author>Deja, M</author><author>Weber-Carstens, S</author><author>MacGuill, M</author><author>Kastrup, M</author><author>Wernecke, KD</author><author>Nachtigall, I</author><author>Spies, CD</author></authors></contributors><titles><title>Hyperactive delirium and blood glucose control in critically ill patients</title><secondary-title>Journal of International Medical Research</secondary-title></titles><periodical><full-title>Journal of International Medical Research</full-title></periodical><pages>666-677</pages><volume>35</volume><number>5</number><dates><year>2007</year></dates><isbn>0300-0605</isbn><urls></urls></record></Cite></EndNote>[11]Retrospective Cohort55/196(28%)ICU+IMCUDDS8hrlyBedside nurseAll patientsDeep sedation (RASS≤-3)Psychiatric diseasesCognitive disordersSevere braininjuries (GCS≤8)HyperglycemiaAPACHE IISOFAHAP/VAPAlcohol abusePolytraumaTISS4.23.1 1.21.11.58.02.37.22.314.52.71.1(1.4-12.1)(1.6-6.1) (HR)(1.1-1.3)(1.0-1.1) (HR)(1.2-1.7)(2.7-24.1)(1.3-4.1) (HR)(1.7-29.6)(1.2-4.7) (HR)(3.3-64.9)(1.4-5.5) (HR)(1.0-1.1) (HR)ICU + IMCU Hyperactive Delirium Occurrence Logistic RegressionCox Regression (Hazard Ratio)+CommentsDDS not validated against DSM-IV criteria (possibly detection bias)Outcome of hyperactive delirium defined as DDS > 7Due to retrospective study (with prospective delirium assessment) missing data in 137/333 patients (leaving 196 patients)ICU: intensive care unit, CAM-ICU: Confusion Assessment Method for use in ICU, hrly= hourly, MV: mechanically ventilated, APACHE (APS): Acute Physiology and Chronic Health Evaluation (Acute Physiology Score), ARDS: acute respiratory distress syndrome, GEE: Generelazid Estimated Equations, ISS: Injury Severity Score, hrs: hours, IMCU: intermediate care unit, DDS: delirium detection score, RASS: Richmond Agitation and Sedation Score, GCS: Glasgow Coma Scale, H-/VAP: Hospital/Ventilator Associated Pneumonia, TISS:Therapeutic Intervention Scoring System, HR: hazard ratio, ns=non-significant, IQCODE: Informant Questionnaire on Cognitive Decline in the Elderly.ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityHsieh 2013 ADDIN EN.CITE <EndNote><Cite><Author>Hsieh</Author><Year>2013</Year><RecNum>2616</RecNum><DisplayText>[12]</DisplayText><record><rec-number>2616</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508783169">2616</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Hsieh, SJ</author><author>Soto, Graciela J</author><author>Pittignano, Vincent</author><author>Martinez, Mirian</author><author>Chen, Julie</author><author>Ferguson, Nadia C</author><author>Cheng, Angela</author><author>Hope, Aluko A</author><author>Leung, Sharon</author><author>Gong, Michelle N</author></authors></contributors><titles><title>Acute respiratory distress syndrome increases the risk of delirium in critically ill patients</title><secondary-title>C55. ACUTE RESPIRATORY DISTRESS SYNDROME</secondary-title></titles><pages>A4468-A4468</pages><dates><year>2013</year></dates><publisher>Am Thoracic Soc</publisher><isbn>1073-449X</isbn><urls></urls></record></Cite></EndNote>[12]Prospective CohortMulticenter244/564 (43%)Mixed ICUCAM-ICU24 hrlyResearch TeamAdult patientsNon-Englisch or non-Spanish languageDevelopmental delayEnd-stage dementiaARDS status Not Intubated, no ARDS Intubated, no ARDS Intubated, with ARDSAgeCharlson Comorbidity IndexAPACHE IVDementiaNon-English languageAlcohol abuseIllicit drug useSevere sepsisAny benzodiazepineAny opiateAny propofolAny steroidRef1.986.551.001.211.226.762.202.421.971.111.931.144.161.06(1.16-3.40)(1.56-27.54)(0.99-1.02) (ns)(0.78-1.89) (ns)(1.08-1.37)(2.57-17.75)(1.26- 3.84)(1.09-5.37)(0.73-5.32) (ns)(0.58-2.13) (ns)(1.09-3.41)(0.64-2.01) (ns)(2.41-7.20)(0.63-1.79) (ns)Delirium PrevalenceLogistic Regression+ICU: intensive care unit, CAM-ICU: Confusion Assessment Method for use in ICU, hrly= hourly, ARDS: acute respiratory distress syndrome, APACHE (APS): Acute Physiology and Chronic Health Evaluation (Acute Physiology Score), ns=non-significant, IQCODE: Informant Questionnaire on Cognitive Decline in the Elderly.ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityKamdar 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYW1kYXI8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA [14]Prospective cohort34/64(53,1%)Mixed ICUCAM-ICUtwice dailyResearch TeamAge ≥ 18 yearsAdmission to ICUMV > 24 hoursBeing in the process of weaning from MV Degenerative neurological diseasePrior known psychiatric conditionsRecent psychiatric events including suicide attemptsHistory of drug addiction or alcoholismCompromised level of consciousness (GCS ≤ 8 or RASS < -3) at beginning of studyPresence of tracheostomyAgeSOFA scoreAPACHE II scoreNeurological causeSexp-value 0.01p-value 0.03p-value 0.01p-value 0.01p-value 0.93 (ns)Incidence of deliriumPrincipal component analysis+CommentsNo odds ratio’s or confidence intervals providedLimpawattana 2016 ADDIN EN.CITE <EndNote><Cite><Author>Limpawattana</Author><Year>2016</Year><RecNum>2621</RecNum><DisplayText>[15]</DisplayText><record><rec-number>2621</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508783448">2621</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Limpawattana, Panita</author><author>Panitchote, Anupol</author><author>Tangvoraphonkchai, Kawin</author><author>Suebsoh, Naluttaporn</author><author>Eamma, Wanaporn</author><author>Chanthonglarng, Bunruam</author><author>Tiamkao, Somsak</author></authors></contributors><titles><title>Delirium in critical care: a study of incidence, prevalence, and associated factors in the tertiary care hospital of older Thai adults</title><secondary-title>Aging &amp; mental health</secondary-title></titles><periodical><full-title>Aging &amp; mental health</full-title></periodical><pages>74-80</pages><volume>20</volume><number>1</number><dates><year>2016</year></dates><isbn>1360-7863</isbn><urls></urls></record></Cite></EndNote>[15] Prospective Cohort44/99 (44,4%)Medical ICUCAM-ICU24 hrlyResearch Team≥65 years of ageReadmission to ICUNo informed consentComa (RASS score < -3)Severe aphasiaSevere hearing impairmentPrevious strokeBed change > 3Physical restraintsUse of bladder catheterOn mechanical ventilators6.35 15.7521.462.030.86(1.64-24.55)(1.31-188.95)(4.6-100.16)(0.49-8.39) (ns)(0.26-2.9) (ns)Prevalence and incidence of deliriumLogistic Regression+CommentsNot entirely suitable for multivariate analysis because of the small sample sizeICU: intensive care unit, CAM-ICU: Confusion Assessment Method for use in ICU, hrly= hourly, ARDS: acute respiratory distress syndrome, RCSQ: Richards-Campbell Sleep Questionnaire, ns=non-significant, MV: mechanically ventilated, SOFA: Sequential Organ Failure Assessment, APACHE: Acute Physiology and Chronic Health Evaluation, RASS: Richmond Agitation and Sedation Score.ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityLin 2008 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaW48L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA [17]Prospective cohort68/90 (75,6%)Medical ICUCAM-ICUtwice daily≥65 years of ageRASS score ≥ -3Admission in previous 24 hoursReadmission to ICUNo. of sedatives usedAgeLength of stayAPACHE IIRASSCOPDStrokeDays of ventilator useNo. of anesthetic analgesics usedTotal no. of medications usedDuration of trachea useUse of steroids before ICU admissionDuration of dehydrationSensory impairmentMalnutrition0.780.981.010.921.0615.872.161.100.053.530.930.012.100.36NA(0.45-1.33) (ns)(0.89-1.08) (ns)(0.99-1.03) (ns)(0.80-1.05) (ns)(0.62-1.82) (ns)(0.90-278.61) (ns)(0.34-12.76) (ns)(0.84-1.44) (ns)(0.00-0.54)(1.12-11.15)(0.60-1.43) (ns)(0.00-0.32)(1.15-3.84)(0.06-2.10) (ns)NADelirium incidenceLogistic Regresiion+McNicoll 2003 ADDIN EN.CITE <EndNote><Cite><Author>McNicoll</Author><Year>2003</Year><RecNum>22</RecNum><DisplayText>[18]</DisplayText><record><rec-number>22</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232699">22</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McNicoll, Lynn</author><author>Pisani, Margaret A.</author><author>Zhang, Ying</author><author>Ely, E. Wesley</author><author>Siegel, Mark D.</author><author>Inouye, Sharon K.</author></authors></contributors><auth-address>Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. lmcnicoll@</auth-address><titles><title>Delirium in the intensive care unit: occurrence and clinical course in older patients</title><secondary-title>J. Am. Geriatr. Soc.</secondary-title></titles><periodical><full-title>J. Am. Geriatr. Soc.</full-title></periodical><pages>591-598</pages><volume>51</volume><number>5</number><keywords><keyword>ICU Rehab 2015</keyword></keywords><dates><year>2003</year><pub-dates><date>2003/5</date></pub-dates></dates><isbn>0002-8614</isbn><urls><related-urls><url>(Apr-17-08).pdf</url></related-urls><pdf-urls><url>All Papers/M/McNicoll et al. 2003 - Delirium in the intensive care unit - occurrence and clinical course in older patients.pdf</url></pdf-urls></urls></record></Cite></EndNote>[18]ProspectiveCohort83/118(70%)Medical ICUCAM-ICU24hrlyResearch team≥65 years of ageNo informed consentTransfer from another ICUAphasia/advanced dementiaDeath before first interviewDementia1.3(1.1-1.6)Hospital Delirium Occurrence Logistic Regression(Risk Ratio)++CommentsDementia was defined as MBDRS ≥3 and the IQCODE ≥3.31 or MBDRS ≥3.5 or IQCODE ≥3.5Outcome is occurrence of delirium during initial ICU stay plus up to 7 days after transfer from ICUAdjusted for Charlson Comorbidity Index, APACHE II, impairment in ADLs, invasive procedures other than MVICU: intensive care unit, CAM-ICU: Confusion Assessment Method for use in ICU, hrly= hourly, MV: mechanically ventilated, ns=non-significant, RASS: Richmond Agitation and Sedation Score, APACHE: Acute Physiology and Chronic Health Evaluation, COPD: chronic obstructive pulmonary disease, NA: not applicable, MBDRS:Modified Blessed Dementia Rating Scale, IQCODE: Informant Questionnaire on Cognitive Decline for the Elderly, ADL: Activity of Daily Living.ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityMehta 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWh0YTwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl

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PgB=

ADDIN EN.CITE.DATA [19]Prospective CohortNested in SLEAP trialMulticenter226/420 (53,8%)Mixed ICUICDSC24 hrlyBedside nurseMV ≥ 48 hoursContinuous IV opioid and/or benzodiazepine infusionCardiac arrestTraumatic brain injuryNeuromuscular blockersEnrolled in a related trialPreviously enrolled in SLEAPLacking commitment to maximal therapyAge < 40 41-65 66-80 > 80APACHE II <19 19-24 24-29 >29TabaccoAlcohol (≥ 2 drinks/day)Neurologic conditionCardiac diseaseRandomization groupComaRenal replacementPhysical restraintTotal midazolam (1mg increase)Total fentanyl (0,1 mg increase)Antipsychotic use in ICURef0.920.910.85Ref0.940.980.641.4010180.861.330.940.551.051.870.9981.01.67Ref(0.59-1.43) (ns)(0.53-1.56) (ns)(0.38-1.88) (ns)Ref(0.63-1.42) (ns)(0.63-1.55) (ns)(0.38-1.09) (ns)(0.96-2.06) (ns)(0.69-1.99) (ns)(0.52-1.41) (ns)(0.64-2.76) (ns)(0.68-1.29) (ns)(0.25-1.22) (ns)(0.63-1.73) (ns)(1.33-2.63)(0.997-1.0)(1.0-1.0) (ns)(1.01-2.77)Delirium prevalenceCox proportional hazards regression analysis+Morandi 2011 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3JhbmRpPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48

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ADDIN EN.CITE.DATA [21]Prospective CohortNested in VALID study?/?(?%)Medical ICUCAM-ICU24hrlyResearch TeamAll patientsICU LOS >3daysCardiac arrestSevere chronic lung diseaseElective cardiothoracic surgery Uncomplicated overdoseDied/discharged ≤48hrs25-OHD, nmol/LAgeAPACHE II1.01.01.1(0.99-1.0) (ns)(0.95-1.0) (ns)(1.03-1.2)Delirium day after 25-OHD measurementLogistic Regression++CommentsBlood for measurement of serum 25-OHD concentration collected within 24hrs of ICU admissionTotal sample 120 patients of whom unknown percentage died/comatose day after 25-OHD measurement, so unknown sample in presented analysisOuimet 2007 ADDIN EN.CITE <EndNote><Cite><Author>Ouimet</Author><Year>2007</Year><RecNum>2206</RecNum><DisplayText>[22]</DisplayText><record><rec-number>2206</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232830">2206</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ouimet, Sébastien</author><author>Kavanagh, Brian P.</author><author>Gottfried, Stewart B.</author><author>Skrobik, Yoanna</author></authors></contributors><auth-address>Department of Medicine, University of Montreal, Montreal, Canada.</auth-address><titles><title>Incidence, risk factors and consequences of ICU delirium</title><secondary-title>Intensive Care Med.</secondary-title></titles><periodical><full-title>Intensive Care Med.</full-title></periodical><pages>66-73</pages><volume>33</volume><number>1</number><dates><year>2007</year><pub-dates><date>2007/1</date></pub-dates></dates><isbn>0342-4642</isbn><urls><related-urls><url> Papers/O/Ouimet et al. 2007 - Incidence, risk factors and consequences of ICU delirium.pdf</url></pdf-urls></urls><electronic-resource-num>10.1007/s00134-006-0399-8</electronic-resource-num></record></Cite></EndNote>[22]Prospective Cohort243/764(32%)MixedICUICDSC1-8hrlyBedsideAll patientsMoribundComatose >5 days/until deathHypertension (History)Alcoholism (History)APACHE IIIatrogenic ComaPain (assessed by NRS)Anxiety1.92.01.053.70.91.8(1.3-2.6)(1.3-3.3)(1.03-1.1)(2.3-5.9)(0.8-0.97)(1.04-3.4)ICU Delirium OccurrenceLogistic Regression++ICU: intensive care unit, ICDSC: Intensive Care Delirium Screening Checklist, hrly: hourly, MV: Mechanical ventilated, IV: intravenous, APACHE: Acute Physiology and Chronic Health Evaluation, ns=non-significant, CAM-ICU: Confusion Assessment Method for use in the ICU, IGF-1: insulin growth factor-1, hrs: hours, LOS: Length of stay, 25-OHD:25-OH Vitamin D, ICDSC: Intensive Care Delirium Screening Checklist, NRS: Numeric Rating Scale (for pain assessment). ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityPandharipande 2006 ADDIN EN.CITE <EndNote><Cite><Author>Pandharipande</Author><Year>2006</Year><RecNum>376</RecNum><DisplayText>[23]</DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232720">376</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pandharipande, Pratik</author><author>Shintani, Ayumi</author><author>Peterson, Josh</author><author>Pun, Brenda Truman</author><author>Wilkinson, Grant R.</author><author>Dittus, Robert S.</author><author>Bernard, Gordon R.</author><author>Ely, E. Wesley</author></authors></contributors><titles><title>Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients</title><secondary-title>Anesthesiology</secondary-title></titles><periodical><full-title>Anesthesiology</full-title></periodical><pages>21-26</pages><volume>104</volume><number>1</number><keywords><keyword>ICU Rehab 2016</keyword></keywords><dates><year>2006</year><pub-dates><date>2006</date></pub-dates></dates><isbn>0003-3022</isbn><urls><related-urls><url>;[23]Prospective Cohort?/198(?%)Medical or Coronary ICUCAM-ICU24hrlyResearch TeamMVNeurological diseasePersistent comaLack of 2 consecutive cognitive assessmentsLorazepamMidazolamFentanylMorphinePropofolAPACHE IIAgeAntipsychoticsAnticholinergic drugsCross products1.21.71.21.11.21.061.02nsnsns(1.1-1.4)(0.9-3.2) (ns)(1.0-1.5) (ns)(0.9-1.2) (ns)(0.9-1.7) (ns)(1.02-1.1)(1.00-1.03)Daily transition towards deliriumLogistic Regression (GEE + Markov)++CommentsTotal of 696 observations from 198 patients were included in analysisAnticholinergic drugs: atropine, diphenhydramine, bupropion hydrochloride, metoclopramide, prochlorperazine, promethazine)Odds Ratio for medication intpereted as: every unit dose of lorazepam in loge milligrams previous day increases risk with 20% for transition towards deliriumAdjusted for mental status previous day, age, sex, visual and hearing deficits, history of dementia, depression (assessed by Geriatric Depression Scale short form, modified APACHE II (minus GCS), sepsis, history of neurologic disease, hematocrit at baseline, daily serum glucoseCross-product sedative drug and mental status previous day to assess if previous cognitive status modifies the risk of the medicationCross-product lorazepam and each of the other sedative and analgesic drugs to assess if combined use of the two drugs increases riskPandharipande 2008 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYW5kaGFyaXBhbmRlPC9BdXRob3I+PFllYXI+MjAwODwv

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ADDIN EN.CITE.DATA [24]Prospective Cohort68/97(70%)Surgical or Trauma ICUCAM-ICU24hrlyBedsideMV > 24hrsNeurological diseaseHearing lossMoribundPersistent comaAnestheticsH2 BlockersLorazepamMidazolamFentanylMorphine0.51.50.52.81.90.4 (0.2-1.2) (ns)(0.8-2.6) (ns)(0.2-1.3) (ns)(1.4-5.3) (0.99-3.6)(ns)(0.2-0.8)Daily transition towards deliriumLogistic Regression (GEE + Markov)++CommentsPrincipal component analysis was used to combine age, body mass index, Charlson Comorbidity Inedex, APACHE II score and presence of sepsis into two summary components for use in Logistic Regression to preserve power.Adjusted for mental status previous day, two summary components, daily use (yes/no) of each psychoactive drugPisani 2007 ADDIN EN.CITE <EndNote><Cite><Author>Pisani</Author><Year>2007</Year><RecNum>2564</RecNum><DisplayText>[25]</DisplayText><record><rec-number>2564</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508780435">2564</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pisani, M. A.</author><author>Murphy, T. E.</author><author>Van Ness, P. H.</author><author>Araujo, K. L.</author><author>Inouye, S. K.</author></authors></contributors><auth-address>Pulmonary &amp; Critical Care Section, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8057, USA. Margaret.Pisani@yale.edu</auth-address><titles><title>Characteristics associated with delirium in older patients in a medical intensive care unit</title><secondary-title>Arch Intern Med</secondary-title><alt-title>Archives of internal medicine</alt-title></titles><periodical><full-title>Arch Intern Med</full-title><abbr-1>Archives of internal medicine</abbr-1></periodical><alt-periodical><full-title>Arch Intern Med</full-title><abbr-1>Archives of internal medicine</abbr-1></alt-periodical><pages>1629-34</pages><volume>167</volume><number>15</number><edition>2007/08/19</edition><keywords><keyword>Aged</keyword><keyword>*Delirium/diagnosis/therapy</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Intensive Care Units</keyword><keyword>Male</keyword><keyword>Prospective Studies</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug 13-27</date></pub-dates></dates><isbn>0003-9926 (Print)&#xD;0003-9926</isbn><accession-num>17698685</accession-num><urls></urls><electronic-resource-num>10.1001/archinte.167.15.1629</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[25]Prospective Cohort214/304(70%)Medical ICUCAM-ICU24hrlyChartreviewResearch ≥60 years of ageNo informed consentTransferred from another ICUInability to communicate <ICULOS ICU < 24hrsDementia (IQCODE>3.3)Benzodiazepines <ICU Creatinine > 2mg/dLArterial pH <7.356.33.42.12.1(2.9-13.8)(1.6-7.0)(1.1-4.0)(1.1-3.9)Delirium first 48hoursLogistic Regression++CommentsInternal validation final model using bootstrapping procedure ICU: Intensive Care unit, CAM-ICU: Confusion Assessment Method for use in the ICU, MV: mechanical ventilated, APACHE II: Acute Physiology and Chronic Health Evaluation, ns: non significant, GEE: GEE: Generalized Estimated Equations, GCS: Glasgow coma Scale, hrly: hourly, hrs:hours, LOS: Length of stay, IQCODE: Informant Questionnaire on Cognitive Decline for the Elderly. ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityPandharipande 2009 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYW5kaGFyaXBhbmRlPC9BdXRob3I+PFllYXI+MjAwOTwv

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ADDIN EN.CITE.DATA [26]Prospective Cohort nested in MENDS trial?/97(?%)Medical and Surgical ICUCAM-ICU24hrlyBedsideMVNeurological diseaseActive seizure disorderChild-Pugh Class B/C cirrhosisAlcohol abuseActive myocardial ischemia2nd or 3rd degree heart blockSevere dementiaPregnancySevere hearing lossNo informed consentTryptophan/LNAA ratioTyrosine/LNAA ratioPhenylalanine/LNAA ratioAgeModified APACHE IIIQCODEDexmedetomidine <24hrsLorazepam <24hrsFentanyl <24hrsMental status <24hrsp-valuep-valuep-valuep-valuep-valuep-valuep-valuep-valuep-valuep-value<0.05<0.05ns<0.052x<0.05nsnsnsns1x<0.05Transition towards delirium day after (day 2 and day 4) measurementLogistic Regression (GEE + Markov)++CommentsNo data on total number of observations, nor on number of patients who became deliriousNo effect estimates/confidence intervals providedBlood samples collected on study days 1 and 3Three separate models for each factor. Each model adjusted for age, IQCODE, modified APACHE II (minus GCS), Dexmedetomidine -, Lorazepam - , Fentanyl on previous day, mental status previous dayModified APACHE II non-significant in Phenylalanine/LNAA ratio model, Fentanyl<24hrs non-significant in both Tyrosine- and Phenylalanine/LNAA ratio modelPisani 2009 ADDIN EN.CITE <EndNote><Cite><Author>Pisani</Author><Year>2009</Year><RecNum>2565</RecNum><DisplayText>[27]</DisplayText><record><rec-number>2565</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508780435">2565</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pisani, M. A.</author><author>Murphy, T. E.</author><author>Araujo, K. L.</author><author>Slattum, P.</author><author>Van Ness, P. H.</author><author>Inouye, S. K.</author></authors></contributors><auth-address>Department of Internal Medicine, Pulmonary and Critical Care Section, and the Program on Aging, Yale University School of Medicine, USA. margaret.pisani@yale.edu</auth-address><titles><title>Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population</title><secondary-title>Crit Care Med</secondary-title><alt-title>Critical care medicine</alt-title></titles><alt-periodical><full-title>Critical care medicine</full-title></alt-periodical><pages>177-83</pages><volume>37</volume><number>1</number><edition>2008/12/04</edition><keywords><keyword>Aged</keyword><keyword>Analgesics, Opioid/*adverse effects</keyword><keyword>Benzodiazepines/*adverse effects</keyword><keyword>Delirium/*epidemiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>*Intensive Care Units</keyword><keyword>Male</keyword><keyword>Prospective Studies</keyword><keyword>Time Factors</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0090-3493</isbn><accession-num>19050611</accession-num><urls></urls><custom2>PMC2700732</custom2><custom6>NIHMS117966</custom6><electronic-resource-num>10.1097/CCM.0b013e318192fcf9</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[27]Prospective Cohort239/304(79%)Medical ICUCAM-ICU24hrlyChartreviewResearch ≥60 years of ageNo informed consentTransferred from another ICUInability to communicate <ICULOS ICU < 24hrsPersistent comaBenzodiazepine/opioid useDementia (IQCODE>3.3)HaloperidolModified APACHE II1.61.21.41.01(1.3-2.1) (1.1-1.3) (1.2-1.5) (1.00-1.02)Duration first delirium episode in ICUPoisson Regression(Rate Ratio)+CommentsEnd of delirium episode with two consecutive days without deliriumModified APACHE II (minus GCS)Not clear if benzodiazepine exposure is before delirium episodeInternal validation final model using bootstrapping procedureICU: Intensive Care unit, CAM-ICU: Confusion Assessment Method for use in the ICU, MV: mechanical ventilated, APACHE II: Acute Physiology and Chronic Health Evaluation, ns: non significant, GEE: GEE: Generalized Estimated Equations, GCS: Glasgow coma Scale, hrly: hourly, hrs:hours, LOS: Length of stay, IQCODE: Informant Questionnaire on Cognitive Decline for the Elderly.ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualitySchreiber 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TY2hyZWliZXI8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy

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ADDIN EN.CITE.DATA [28]Prospective CohortMulticenter274/330(83%)MixedICUCAM-ICU24hrlyResearchMVAcute lung injury Illness with life expectancy < 6 monthsCognitive impairmentCommunication barriersNo fixed addressTransferred from other hospital and ALI > 24 hoursMV > 5 days before onset ALIPrevious lung resection Age < 40 years 40-60 years > 60 yearsMaleHome use of opioidsAPACHE II scoreDaily SOFA scoreDaily sepsis statusCorticosteroid administrationCorticosteroid doseBenzodiazepine administrationBenzodiazepine doseRef1.812.521.341.111.011.031.061.520.971.321.02(1.26-2.62)(1.62-3.87)(0.96-1.86) (ns)(0.97-1.27) (ns)(1.00-1.03)(0.99-1.07) (ns)(0.79-1.41) (ns)(1.05-2.21)(0.89-1.07) (ns)(0.93-1.89) (ns)(0.99-1.04) (ns)Transition from a normal state into delirium the next dayLogistic Regression (First-order Markov model)++Serafim 2012 ADDIN EN.CITE <EndNote><Cite><Author>Serafim</Author><Year>2012</Year><RecNum>2582</RecNum><DisplayText>[29]</DisplayText><record><rec-number>2582</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508780435">2582</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Serafim, R. B.</author><author>Dutra, M. F.</author><author>Saddy, F.</author><author>Tura, B.</author><author>de Castro, J. E.</author><author>Villarinho, L. C.</author><author>da Gloria Santos, M.</author><author>Bozza, F. A.</author><author>Rocco, J. R.</author></authors></contributors><auth-address>Ventilatory Care Unit, Copa D&apos;Or Hospital, Rio de Janeiro, Brazil. rodrigobserafim@.</auth-address><titles><title>Delirium in postoperative nonventilated intensive care patients: risk factors and outcomes</title><secondary-title>Ann Intensive Care</secondary-title><alt-title>Annals of intensive care</alt-title></titles><periodical><full-title>Ann Intensive Care</full-title><abbr-1>Annals of intensive care</abbr-1></periodical><alt-periodical><full-title>Ann Intensive Care</full-title><abbr-1>Annals of intensive care</abbr-1></alt-periodical><pages>51</pages><volume>2</volume><number>1</number><edition>2013/01/01</edition><dates><year>2012</year><pub-dates><date>Dec 31</date></pub-dates></dates><isbn>2110-5820</isbn><accession-num>23272945</accession-num><urls></urls><custom2>PMC3544687</custom2><electronic-resource-num>10.1186/2110-5820-2-51</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[29]Prospective Cohort43/465(9%)Surgical ICUCAM12hrlyBedside RASS > -3MVPregnancyInability to verbalizeHearing or visual impairmentNo informed consentAgeAPACHE II APSBenzodiazepine use first 24hrEmergency surgeryTrauma patient1.041.12.38.16.2(1.02-1.1)(1.04-1.2)(1.04-5)(3.6-18.1)(4.1-6.5)ICU delirium occurrenceLogistic Regression++CommentsDelirium assessment in all non-mechanically ventilated patients using the CAMSeymour 2012 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TZXltb3VyPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48

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ADDIN EN.CITE.DATA [30]Prospective Cohort nested in ABC trial?/140(?)Medical ICUCAM-ICU24hrlyResearchMV > 12hrsCardiac arrestVentilated ≥ 2 weeksMoribundNeurological diseaseNo informed consentChange in sedative dosing:Benzodiazepine, mg/hrPropofol, mcg/kg/minDaytime sedative dosing:Benzodiazepine, mg/hrPropofol, mcg/kg/min2.51.411663.2(1.0-6.3) (ns)(0.8-2.5) (ns)(16-82719)(1.0-10.6)(ns)Transition towards delirium day after exposureLogistic Regression(GEE + Markov)++CommentsTotal of 485 patient days observed with observed delirium in 160 (33%) days. Results based on complete case analysis with n=272 patient days Adjusted for age, modified SOFA (with removal of neurological component) and mental status day of exposureThe OR reflect change in odds of being delirious next day with change in exposure from 10th percentile to 90th percentile value.10th-90th percentiles for exposure variables respectively (-0.19 – 0.25), (-7.7 – 5.7), (0, 2.4), (0, 40.1)ICU: Intensive Care unit, CAM(-ICU): Confusion Assessment Method (for use in the ICU), MV: mechanical ventilated, ALI: acute lung injury, APACHE II (-APS): Acute Physiology and Chronic Health Evaluation II (Acute Physiology Score), SOFA: Sequential Organ Failure Assessment, ns: non significant, GEE: Generalized Estimated Equations, hrly: hourly, hrs:hours, hr: hour, LOS: Length of stay, RASS: Richmond Agitation and Sedation Scale, HR: hazard ratioArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityShehabi 2013 ADDIN EN.CITE <EndNote><Cite><Author>Shehabi</Author><Year>2013</Year><RecNum>1707</RecNum><DisplayText>[31]</DisplayText><record><rec-number>1707</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232801">1707</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shehabi, Yahya</author><author>Bellomo, Rinaldo</author><author>Reade, Michael C.</author><author>Bailey, Michael</author><author>Bass, Frances</author><author>Howe, Belinda</author><author>McArthur, Colin</author><author>Murray, Lynne</author><author>Seppelt, Ian M.</author><author>Webb, Steve</author><author>Others,</author></authors></contributors><titles><title>Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study</title><secondary-title>Crit. Care Med.</secondary-title></titles><periodical><full-title>Crit. Care Med.</full-title></periodical><pages>1983-1991</pages><volume>41</volume><number>8</number><keywords><keyword>PAD-ES Agitation/Sedation Manuscript</keyword></keywords><dates><year>2013</year><pub-dates><date>2013</date></pub-dates></dates><publisher>LWW</publisher><isbn>0090-3493</isbn><urls><related-urls><url>;[31]Prospective CohortMulticenter114/259(44%)Mixed ICUCAM-ICU4hrlyResearchMV ≤24hrsMV expected >24hrsSedative/analgesicsNeurological impairmentPsychiatric illnessBurnsDementiaPalliative careUnable to communicateEarly deep sedation Cumulative dose of Dexmedetomidine first 48hrAPACHE IIAgeMaleOperativeElectiveCardiacRespiratorySepsisGastrointestinalVasopressorsDialysis1.01.41.01.011.41.11.31.20.91.20.91.21.0(0.9-1.0) (ns)(1.1-1.8)(0.96-1.0) (ns)(1.00-1.03)(0.9-2.0) (ns)(0.6-1.0) (ns)(0.7-2.6) (ns)(0.6-2.3) (ns)(0.5-1.7) (ns)(0.7-2.3) (ns)(0.5-1.9) (ns)(0.7-1.9) (ns)(0.6-1.8) (ns)Time to delirium in 28-day period after first 48hrs of ICU admissionCox Regression(Hazard Rations)++CommentsCAM-ICU performed only in RASS range of -2 to +1 so risk of detection bias of deliriumHR interpret chance of achieving desired outcome (shorter time to delirium), so HR of 1.4 is 40% increased chance of shorter time to deliriumShi 2010 ADDIN EN.CITE <EndNote><Cite><Author>Shi</Author><Year>2010</Year><RecNum>2589</RecNum><DisplayText>[32]</DisplayText><record><rec-number>2589</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508780435">2589</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shi, C. M.</author><author>Wang, D. X.</author><author>Chen, K. S.</author><author>Gu, X. E.</author></authors></contributors><auth-address>Department of Anesthesiology and Surgical Intensive Care, Peking University First Hospital, Beijing, China.</auth-address><titles><title>Incidence and risk factors of delirium in critically ill patients after non-cardiac surgery</title><secondary-title>Chin Med J (Engl)</secondary-title><alt-title>Chinese medical journal</alt-title></titles><periodical><full-title>Chin Med J (Engl)</full-title><abbr-1>Chinese medical journal</abbr-1></periodical><alt-periodical><full-title>Chin Med J (Engl)</full-title><abbr-1>Chinese medical journal</abbr-1></alt-periodical><pages>993-9</pages><volume>123</volume><number>8</number><edition>2010/05/26</edition><keywords><keyword>Aged</keyword><keyword>*Critical Illness</keyword><keyword>Delirium/*epidemiology/etiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Postoperative Complications</keyword><keyword>Prospective Studies</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2010</year><pub-dates><date>Apr 20</date></pub-dates></dates><isbn>0366-6999 (Print)&#xD;0366-6999</isbn><accession-num>20497703</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[32]Prospective Cohort73/164(45%)Surgical ICUNu-DESC24hrlyBedside Research (ward)All patientsPsychiatric diseasesGlucocorticoids>5dys within 1yrNeurosurgeryAdrenal gland disease/surgeryNeed of glucocorticoids MoribundAge (/10years increase)History of strokeAPACHE IISerum cortisol (first postoperative day)2.64.51.43.4(1.4-4.9)(1.2-16.5)(1.2-1.6)(1.7-6.8)Postoperative Delirium Occurrence up to day 7Logistic Regression+CommentsDelirium assessment with the Nu-DESC which is validated in non-mechanically ventilated ICU patientsSimons 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaW1vbnM8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA [33]RetrospectiveCohort998/3198(31,2%)MixedICUCAM-ICU12hrlyBedsideAll patientsICU admission after >30 days of hospital admissionSex (male)Age (per year)InfectionSedationSeason Spring Summer Autumn WinterDiagnostic category Surgical Medical Trauma NeurologicAPACHE II28-day photoperiod1.031.023.373.78Ref1.001.060.88Ref0.903.113.701.101.00(0.85-1.23) (ns)(1.01-1.02)(2.74-4,15)(3.14-4.56)(0.79-1.26) (ns)(0.77-1.46) (ns)(0.62-1.26) (ns)(0.72-1.13) (ns)(1.82-5.32)(2.72-5.02)(1.09-1.12)(1.00-1.00) (ns)ICU Delirium IncidenceLogistic Regression+ICU: Intensive Care unit, CAM(-ICU): Confusion Assessment Method (for use in the ICU), MV: mechanical ventilated, APACHE II(-APS): Acute Physiology and Chronic Health Evaluation II (Acute Physiology Score), ns: non significant, GEE: Generalized Estimated Equations, hrly: hourly, hrs:hours, hr: hour, LOS: Length of stay, RASS: Richmond Agitation and Sedation Scale, HR: hazard ratio, Nu-DESC: Nursing Delirium Screening ScaleArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualitySkrobik 2013 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ta3JvYmlrPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48

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ADDIN EN.CITE.DATA [34]ProspectiveCohort64/99(65%)MixedICUICDSC8hrlyBedsideICU LOS > 24 hrsReceiving IV midazolam and/orIV fentanylCerebral anoxiaCNS lesion that could cause or mimic comaGender maleAgeAPACHE II scoreBody Mass IndexSmokingAlcohol consumptionHepatic dysfunctionRenal dysfunctionIV midazolam levelsIV fentanyl levelsnsnsnsnsnsnsnsnsnsp=0.34p=0.34p=0.90p=0.49p=0.33p=0.61p=0.07p=0.26p=0.001p=0.40ICU Delirium IncidenceCox Regression Model+CommentsNo Odds Ratios or Confidence Intervals given, only p-valuesIV midazolam levels were significantly lower in patients with delirium than in patients without deliriumTime to first occurrence of delirium was not associated with the presence (p=0.3) of midazolam or midazolam dose (p=0.4)Svenningsen 2013 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdmVubmluZ3NlbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1ll

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ADDIN EN.CITE.DATA [35]Prospective CohortMulticenter416/640(65%)Mixed ICUCAM-ICU12hrlyResearchAll patientsLOS ICU <48hrsInability to communicateReadmission to ICU >24hrsRASS change >2 Propofol bolusPropofol continuousMidazolam bolusMidazolam continuousAlfentanil 5.21.50.90.70.41.5(3.8-7.1)(0.4-1.0) (ns)(0.7-1.2) (ns)(0.4-1.2) (ns)(0.2-0.7)(1.08-2.2)ICU Delirium IncidenceLogistic regression+Comments41 patients already delirious at ICU admission whom were not included in logistic regression analysis due to outcome of incident deliriumInterpret OR Alfentanil as compared to no opiates, OR propofol bolus/continuous and midazolam bolus/continuous compared to no sedativesAdjusted for: gender, age (in quartiles), SAPS II, ICU Center, ICU setting (medical/surgical)No adjustments for repeated measurements! Poor statistical method!van Rompaey 2009 ADDIN EN.CITE <EndNote><Cite><Author>Van Rompaey</Author><Year>2009</Year><RecNum>1709</RecNum><DisplayText>[36]</DisplayText><record><rec-number>1709</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232801">1709</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Van Rompaey, Bart</author><author>Elseviers, Monique M.</author><author>Schuurmans, Marieke J.</author><author>Shortridge-Baggett, Lillie M.</author><author>Truijen, Steven</author><author>Bossaert, Leo</author></authors></contributors><auth-address>University of Antwerp, Faculty of Medicine, Division of Nursing Science and Midwifery, Universiteitsplein 1, 2610 Wilrijk, Belgium. bart.vanrompaey@ua.ac.be</auth-address><titles><title>Risk factors for delirium in intensive care patients: a prospective cohort study</title><secondary-title>Crit. Care</secondary-title></titles><periodical><full-title>Crit. Care</full-title></periodical><pages>R77</pages><volume>13</volume><number>3</number><keywords><keyword>PAD-ES Agitation/Sedation Manuscript</keyword></keywords><dates><year>2009</year><pub-dates><date>2009/5/20</date></pub-dates></dates><publisher>ccforum.</publisher><isbn>0270-7462</isbn><urls><related-urls><url> Papers/V/Van Rompaey et al. 2009 - Risk factors for delirium in intensive care patients - a prospective cohort study.pdf</url></pdf-urls></urls><electronic-resource-num>10.1186/cc7892</electronic-resource-num></record></Cite></EndNote>[36]Prospective CohortMulticenter155/523 (30%)Mixed ICUNEECHAM24hrlyLOS >24hrsGCS>10MV at inclusionNo informed consent>3 Alcohol units/dayCognitive impairmentMedical admissionPsychoactive medication in ICUArtificial airway >3 medication perfusionsLack of windowsIsolationLack of visits3.2 2.4 4.0 3.3 8.1 2.7 2.4 2.9 3.7 (1.3-8.0)(1.2-4.8)(1.5-11.0)(1.5-11.2)(1.2-55.1)(1.1-7.1)(1.3-4.5)(1.0-8.4)(1.8-7.9)ICU delirium OccurrenceLogistic Regression+Commentsno blinding of outcome assessment and subjective risk factorsICU: Intensive Care unit, ICDSC: Intensive Care Delirium Screening Checklist, LOS: length of stay, CNS: central nervous system, APACHE II(-APS): Acute Physiology and Chronic Health Evaluation II (Acute Physiology Score), IV: intravenous, ns: non significant, CAM(-ICU): Confusion Assessment Method (for use in the ICU), RASS: Richmond Agitation and Sedation Scale, NEECHAM: Neelon and Champagne Confusion Scale, GCS: Glasgow Coma Scale, MV: mechanical ventilated, hrly: hourly, hrs: hours, hr: hourArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityVeiga 2012 ADDIN EN.CITE <EndNote><Cite><Author>Veiga</Author><Year>2012</Year><RecNum>2053</RecNum><DisplayText>[37]</DisplayText><record><rec-number>2053</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232821">2053</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Veiga, Dalila</author><author>Luis, Clara</author><author>Parente, Daniela</author><author>Fernandes, Vera</author><author>Botelho, Miguela</author><author>Santos, Patricia</author><author>Abelha, Fernando</author></authors></contributors><auth-address>Department of Anesthesiology, Centro Hospitalar de S?o Jo?o, Porto, Portugal.</auth-address><titles><title>Postoperative delirium in intensive care patients: risk factors and outcome</title><secondary-title>Rev. Bras. Anestesiol.</secondary-title></titles><periodical><full-title>Rev. Bras. Anestesiol.</full-title></periodical><pages>469-483</pages><volume>62</volume><number>4</number><dates><year>2012</year><pub-dates><date>2012/7</date></pub-dates></dates><isbn>0034-7094</isbn><urls><related-urls><url>(12)70146-0</url><url>(12)70146-0</url></related-urls><pdf-urls><url>All Papers/V/Veiga et al. 2012 - Postoperative delirium in intensive care patients - risk factors and outcome.pdf</url></pdf-urls></urls><electronic-resource-num>10.1016/S0034-7094(12)70146-0</electronic-resource-num></record></Cite></EndNote>[37]Prospective Cohort128/680(19%)PACUICDSC8hrlyHospital stay <48hrsNo informed consentCardiac/neurological surgeryCNS/Parkinson’s diseaseDelirium/antipsychotics useDrug/alcohol/opioid abuseReadmission to PACUPersistent ComaAgeASA III/IVEmergency surgeryFresh Frozen Plasma1.052.22.71.7(1.04-1.1)(1.3-4.0)(1.6-4.5)(1.3-2.2)PACU Delirium IncidenceLogistic Regression++CommentsDelirium assessments only performed in the PACU. Median (IQR) LOS PACU for patients without delirium 19 (16-30) and with delirium 40 (18-87). Difference observed in this study could be explained merely due to increased length of stay (due to disease severity/complications) with increased time to develop deliriumWhitlock 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaGl0bG9jazwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+

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ADDIN EN.CITE.DATA [38]NestedProspectiveCohort73/310(23,5%)Cardio-thoracicICUCAM-ICU12hrlyBedsideCardiothoracic surgeryGeneral anesthesiaIncreased risk for intraoperative awarenessSurgery with wake-up testUnable to provide informed consentPre-existing dementiaStroke with residual neurological deficitsNested cohort:ASA score 4 (vs 1,2 and 3)EuroSCORE (per 1 point)Packed RBC’s (per 1 unit)Average maintenance ETAC (per 0,1 aaMAC increase)2,881,201,260,70(1,18-6,94)(1,07-1,36)(1,10-1,43)(0,53-0,92)ICU Delirium IncidenceLogistic Regression++CommentsSingle-center substudy of the BAG-RECALL trialUsed a a Bayesian stochastic search variable selection approach to select variablesWolters 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Xb2x0ZXJzPC9BdXRob3I+PFllYXI+MjAxNTwvWWVhcj48

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ADDIN EN.CITE.DATA [39]ProspectiveCohort535/1112(48%)MixedICUCAM-ICU+Chart review24hrlyBedsideResearchICU LOS >24 hrsTransfer from other ICU or hospitalNeurological disorderDelirium assessment not possibleCorticosteroid administrationCorticosteroid dose1.081.00(0.89-1.32) (ns)(0.99-1.01) (ns)Transition into deliriumLogistic Regression++Yoshitaka 2013 ADDIN EN.CITE <EndNote><Cite><Author>Yoshitaka</Author><Year>2013</Year><RecNum>2610</RecNum><DisplayText>[40]</DisplayText><record><rec-number>2610</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1508780436">2610</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yoshitaka, S.</author><author>Egi, M.</author><author>Morimatsu, H.</author><author>Kanazawa, T.</author><author>Toda, Y.</author><author>Morita, K.</author></authors></contributors><auth-address>Department of Anesthesiology and Resuscitology, Okayama University Medical School, 2-5-1 Shikatachou, Okayama, Okayama700-8525, Japan.</auth-address><titles><title>Perioperative plasma melatonin concentration in postoperative critically ill patients: its association with delirium</title><secondary-title>J Crit Care</secondary-title><alt-title>Journal of critical care</alt-title></titles><alt-periodical><full-title>Journal of critical care</full-title></alt-periodical><pages>236-42</pages><volume>28</volume><number>3</number><edition>2013/01/15</edition><keywords><keyword>Apache</keyword><keyword>Aged</keyword><keyword>Chi-Square Distribution</keyword><keyword>Comorbidity</keyword><keyword>*Critical Illness</keyword><keyword>Delirium/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Intensive Care Units</keyword><keyword>Male</keyword><keyword>Melatonin/*blood</keyword><keyword>Middle Aged</keyword><keyword>Postoperative Period</keyword><keyword>Prospective Studies</keyword><keyword>Risk Factors</keyword><keyword>Statistics, Nonparametric</keyword></keywords><dates><year>2013</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0883-9441</isbn><accession-num>23312124</accession-num><urls></urls><electronic-resource-num>10.1016/j.jcrc.2012.11.004</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[40]Prospective Cohort13/40(33%)SurgicalICUCAM-ICU5 times1 Physician>20 years of ageLOS ICU > 48hrsElective surgeryEmergency surgeryCardiopulmonary bypass Brain surgeryPsychosis/dementiaSubstance/alcohol abuseVision/hearing impairmentNo Informed consentAgeAPACHE IIPostoperative epidural Postoperative MVDuration of operationΔ melatonin 1hr postoperative1.21.80.314.11.00.5(1.02-1.4)(1.09-2.9)(0.0-3.4) (ns)(0.4-519.2) (ns)(0.99-1.01) (ns)(0.3-0.99)Delirium incidence (up to day 2 postoperative)Logistic Regression++CommentsΔ melatonin 1hr postoperative is difference with preoperative melatonin concentration in pg/mLPACU: Post Anesthesia Care Unit, ICDSC: Intensive Care Delirium Screening Checklist, CNS: Central Nervous System, ASA: American Society of Anesthesiologists, IQR: interquartile range, ICU: Intensive Care unit, CAM-ICU: Confusion Assessment Method for use in the ICU, EuroSCORE: European System for Cardiac Operative Risk Evaluation, RBC: red blood cell, ETAC: end tidal anesthetic concentration, aaMAC: age-adjusted minimum alveolar concentration, LOS: Length of stay, APACHE II: Acute Physiology and Chronic Health Evaluation II, MV: mechanical ventilated, ns: non significant, hrly: hourly, hrs:hours, hr: hour, OR: Odds Ratio, AUC: Area under the Curve,ArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityZhang 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaGFuZzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl

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ADDIN EN.CITE.DATA [41]ProspectiveCohort54/223(24,2%)MixedICUCAM-ICU8hrlyBedsideGCS > 10RASS ≥ -3ICU LOS > 48 hrsAcute structural brain diseaseDo-not-resuscitation orderDelirious at ICU admissionAgeSexAPACHE IIIntubated (vs non-intubated)Living alonePhysical restraintAlcohol drinkingSmokingHospital LOS before ICU1.000.671.131.501.752.802.230.941.01(0.97-1.04) (ns)(0.27-1.62) (ns)(1.06-1.21)(0.56-4.04) (ns)(0.51-5.94) (ns)(0.99-7.90) (ns)(0.84-5.98) (ns)(0.32-2.79) (ns)(0.97-1.05) (ns)ICU Delirium IncidenceLogistic Regression++ICU: Intensive Care unit, CAM-ICU: Confusion Assessment Method for use in the ICU, GCS: Glasgow Coma Scale, RASS: Richmond Agitation and Sedation Scale, LOS: Length of stay, APACHE II: Acute Physiology and Chronic Health Evaluation II, ns: non significant, hrly: hourly, hrs:hours, hr: hourArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityZaal 2012 ADDIN EN.CITE <EndNote><Cite><Author>Zaal</Author><Year>2012</Year><RecNum>89</RecNum><DisplayText>[42]</DisplayText><record><rec-number>89</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232703">89</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zaal, Irene J.</author><author>Slooter, Arjen J. C.</author></authors></contributors><auth-address>Department of Intensive Care Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands. i.j.zaal-2@umcutrecht.nl</auth-address><titles><title>Delirium in critically ill patients: epidemiology, pathophysiology, diagnosis and management</title><secondary-title>Drugs</secondary-title></titles><periodical><full-title>Drugs</full-title></periodical><pages>1457-1471</pages><volume>72</volume><number>11</number><keywords><keyword>ICU Rehab 2015</keyword></keywords><dates><year>2012</year><pub-dates><date>2012/7/30</date></pub-dates></dates><isbn>0012-6667</isbn><urls><related-urls><url> Papers/Z/Zaal and Slooter 2012 - Delirium in critically ill patients - epidemiology, pathophysiology, diagnosis and management.pdf</url></pdf-urls></urls><electronic-resource-num>10.2165/11635520-000000000-00000</electronic-resource-num></record></Cite></EndNote>[42]B/A62/130(48%)MixedICUCAM-ICU+Chart Review24hrlyResearchAll patientsICU LOS<24hrsPersistent ComaSingle-Room ICUMaximum SOFA scoreAPACHE IIAge FemaleEmergency admissionCharlson Comorbidity Index ≥1Charlson Comorbidity Index ≥3Surgical AdmissionMedical AdmissionNeurological Admission0.71.10.981.011.01.71.42.11.81.12.0(0.5-0.9) (1.1-1.2) (0.96-1.0) (1.0-1.02) (0.8-1.4) (ns)(0.9-3.1) (ns)(1.0-2.1) (ns)(1.4-3.3)(1.1-2.9)(0.7-1.8) (ns)(1.2-3.1)Total number of delirium days during ICUPoisson Regression(Rate Ratio)+CommentsIntervention: transition from traditional ICU with wards and a single-room ICU with, among others, improved daylight and improved orientationOR Charslon Comorbidty index interpret as compared to Charlson Comorbidity Index of 0. OR Surgical/Medical/Neurological admission compared to cardiovascular admissionNo blindingGirard 2008 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HaXJhcmQ8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA [43]RCTMulticenter?/335(?)Medical ICUCAM-ICU24hrlyResearchMV > 12hrsCardiac arrestVentilated ≥ 2 weeksMoribundNeurological diseaseNo informed consentPaired sedation and ventilator weaning protocol vs sedation per usual care plus daily ventilator weaning 2 vs 3 (ns)Total number of delirium days during ICU, median++Pandharipande 2007 ADDIN EN.CITE <EndNote><Cite><Author>Pandharipande</Author><Year>2007</Year><RecNum>1722</RecNum><DisplayText>[44]</DisplayText><record><rec-number>1722</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232802">1722</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pandharipande, Pratik</author><author>Cotton, Bryan A.</author><author>Shintani, Ayumi</author><author>Thompson, Jennifer</author><author>Costabile, Sean</author><author>Truman Pun, Brenda</author><author>Dittus, Robert</author><author>Ely, E. Wesley</author></authors></contributors><auth-address>Vanderbilt University School of Medicine [corrected] Department of Anesthesia/Critical Care Medicine, 1121 21st Ave So, Nashville MAB 526, TN [corrected] 37212, USA.</auth-address><titles><title>Motoric subtypes of delirium in mechanically ventilated surgical and trauma intensive care unit patients</title><secondary-title>Intensive Care Med.</secondary-title></titles><periodical><full-title>Intensive Care Med.</full-title></periodical><pages>1726-1731</pages><volume>33</volume><number>10</number><keywords><keyword>PAD-ES Agitation/Sedation Manuscript</keyword></keywords><dates><year>2007</year><pub-dates><date>2007/10</date></pub-dates></dates><publisher>Springer</publisher><isbn>0342-4642</isbn><urls><related-urls><url> Papers/P/Pandharipande et al. 2007 - Motoric subtypes of delirium in mechanically ventilated surgical and trauma intensive care unit patients.pdf</url></pdf-urls></urls><electronic-resource-num>10.1007/s00134-007-0687-y</electronic-resource-num></record></Cite></EndNote>[44]RCTMulticenter83/106(81%)MixedICUCAM-ICU12hrlyResearchMV > 24hrsNeurological diseaseActive seizure disorderChild-Pugh Class B/C cirrhosisAlcohol abuseActive myocardial ischemia2nd or 3rd degree heart blockSevere dementiaPregnancySevere hearing lossNo informed consentSedation dexmedetomidine up to 120 hrs vs lorazepam sedation up to 120 hrs9 vs 7 (ns)3 vs 4 (ns)79% vs 82% (ns)Delirium free days, medianDelirium days, medianDelirium prevalence, %++Riker 2009 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SaWtlcjwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl

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ADDIN EN.CITE.DATA [45]RCTMulticenter225/375(60%)MixedICUCAM-ICU24 hrlyResearchMV for less <96hrsAnticipated MV >3dTrauma/burnsDialysisPregnancy/lactationEpidural/spinal analgesiaCNS pathologyAcute hepatitis/liver diseaseChild-Pugh Class C cirrhosisHepatitisActive myocardial ischemia2nd or 3rd degree heart blockleft ventricular EF < 30%HR < 50/min, SBP<90mmHgNo informed consentSedation with dexmedetomidine (I) vs midazolam (C) up to 30days to achieve light sedation54% vs 77% p<0.00133% vs 55% p=0.030 3 vs 2 p=0.002Delirium prevalence, %Delirium incidence, %Delirium-free days, mean++CommentsPrevalence including patients with delirium at study enrollment 138 (I) and 70 (C) leaving respectively 76 (I) and 40 (C) patients for incidence measureB/A: Before/after study, ICU: Intensive Care unit, CAM-ICU: Confusion Assessment Method for use in the ICU, MV: mechanical ventilated, APACHE II: Acute Physiology and Chronic Health Evaluation II, ns: non significant, hrly: hourly, hrs:hours, hr: hour, LOS: Length of stay, CNS: Central Nervous System, OR: Odds Ratio, SOFA: Sequential Organ Failure Assessment, RCT: randomized controlled trial, EF: ejection fraction, HR: heartrate, SBP: systolic blood pressure, I: intervention, C: controlArticleStudy DesignNumber of delirious / Total (%)Type ICMethod Delirium AssessmentInclusionExclusionRisk FactorEffect estimate Risk FactorOutcomeModelQualityRuokonen 2009 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SdW9rb25lbjwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+

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ADDIN EN.CITE.DATA [46]RCTMulticenter15/85(18%)MixedICUCAM-ICU24hrly ResearchLOS ICU <72hrsMV Sedation need>24hrsICU stay >48hrsAcute neurological disorderMAP<55mmHg, HR<50/min2nd or 3rd degree heart blockHepatic SOFA >2Pregnancy/lactationVision/hearing lossUse ?2-agnosit at inclusionNo informed consentDexmedetomidine sedation vs standard care (propofol or midazolam)44% vs 25% p=0.035Delirium Occurence, %(combined CAM-ICU positive and adverse event)+CommentsDelirium not assessed at inclusion. Delirium secondary outcome (not powered)More CAM-ICU assessments in intervention group because of less deep sedation, consequently higher risk of CAM-ICU positive assessment measureSchweickert 2009 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TY2h3ZWlja2VydDwvQXV0aG9yPjxZZWFyPjIwMDk8L1ll

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ADDIN EN.CITE.DATA [47]RCTMulticenter?/104(?)Mixed ICUCAM-ICU24hrlyResearchMV <72hrsSedatedMV need >24hrsBaseline functional independenceNeuromuscular diseaseCardiac arrestRaised intracranial pressureAbsent limbs6month survival<50%No informed consentEarly exercise and mobilsation vs standard care (both with daily sedation interruption)2 vs 4 p=0.03033% vs 57% p=0.0202 vs 4 p=0.02028% vs 41% p=0.010ICU delirium days, mdTime ICU with delirium,%Hospital delirium days,mdHospital with delirium,%++Van Rompaey 2012 ADDIN EN.CITE <EndNote><Cite><Author>Van Rompaey</Author><Year>2012</Year><RecNum>106</RecNum><DisplayText>[48]</DisplayText><record><rec-number>106</rec-number><foreign-keys><key app="EN" db-id="v9razzrwmtv29zeet5tvadzm9d5dffdd0s55" timestamp="1507232704">106</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Van Rompaey, Bart</author><author>Elseviers, Monique M.</author><author>Van Drom, Wim</author><author>Fromont, Veronique</author><author>Jorens, Philippe G.</author></authors></contributors><titles><title>The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients</title><secondary-title>Crit. Care</secondary-title></titles><periodical><full-title>Crit. Care</full-title></periodical><pages>R73</pages><volume>16</volume><number>3</number><keywords><keyword>ICU Rehab 2015</keyword></keywords><dates><year>2012</year><pub-dates><date>2012/5/4</date></pub-dates></dates><isbn>0270-7462</isbn><urls><related-urls><url> Papers/V/Van Rompaey et al. 2012 - The effect of earplugs during the night on th ... perception - a randomized controlled trial in intensive care patients.pdf</url></pdf-urls></urls><electronic-resource-num>10.1186/cc11330</electronic-resource-num></record></Cite></EndNote>[48]RCT/136Mixed ICUNEECHAM8hrlyBedsideLOS >24hrsGCS>10Hearing impairmentDementia/confusion/deliriumSedation useEarplugs (I)SOFAAgeSmoking0.51.091.031.9(0.3-0.8)(1.01-1.2)(1.01-1.05)(1.1-3.5)Time to delirium/mild confusionCox Regression (HR)+ICU: Intensive Care unit, CAM-ICU: Confusion Assessment Method for use in the ICU, MV: mechanical ventilated, APACHE II: Acute Physiology and Chronic Health Evaluation II, ns: non significant, hrly: hourly, hrs:hours, hr: hour, LOS: Length of stay, HR: hazard ratio, GCS: Glasgow Coma Scale, NEECHAM: Neelon and Champagne Confusion Scale, SOFA: Sequential Organ Failure Assessment, RCT: randomized controlled trial, HR: heartrate, MAP: mean arterial ressure, I: intervention, C: controlReferences ADDIN EN.REFLIST 1.Abelha FJ, Fernandes V, Botelho M, Santos P, Santos A, Machado JC, Barros H: Apolipoprotein E e4 allele does not increase the risk of early postoperative delirium after major surgery. 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