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Sedation / Analgesia / Delirium

Guidelines

Devlin JW, Skrobik Y, Gélinas C et al. Clinical Practice Guidelines for the Prevention and Management of Pain/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med 2018; 46:e825-e873

PMID: 30113379

Comparison Between Administration Methods

Kollef MH, Levy NT, Ahrens TS, et al. Use of continuous vs. bolus IV sedation. Chest 1998;114:541-8. Surveillance study of 157 patients on ventilator found bolus sedation resulted in shorter duration of mechanical ventilation, and ICU and hospital stays.

PMID: 9726743

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Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342:1471-7. RCT found daily interruption of sedation in a MICU population resulted in shorter duration of mechanical ventilation and ICU stay, less total dose of sedation, and less use of diagnostic tests to work-up impaired mental status compared to the control group. No increase in short term adverse outcomes in the intervention group identified but patients were not evaluated for subtle or long-term adverse outcomes.

PMID: 10816184

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Mehta S, Burry L, Cook D, et al. SLEAP Investigators. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 2012; 308:1985-92. Multicenter trial randomized 430 critically ill, mechanically ventilated adults to protocolized sedation vs protocolized sedation plus daily sedation interruption. There was no difference in time to successful extubation, length of ICU stay, length of hospital stay, or incidence of delirium. The daily sedation interruption group received higher doses of sedatives and opiates, and required greater nursing care based on a visual analog scale.

PMID: 23180503

Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010;375:475-80. In 140 patients randomized to sedation vs no sedation, a no-sedation strategy led to 4 fewer days of mechanical ventilation and 10 fewer ICU days at one month, but required extra personnel to comfort a significant number of patients who were managed without sedation.

PMID: 20116842

Girard T, Kress J, Fuchs B, et al. Efficacy and safety of paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awake and Breathing Controlled trial): a randomized controlled trial. Lancet 2008;371:126-34. This RCT found the combination of daily sedation holiday and daily weaning trials resulted in reduced ventilator days and reduced mortality compared to daily weaning trials alone (HR 0.68, p = .01, NNT to save one life 7).

PMID: 18191684

Comparison Between Agents

Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009; 301:489-99. This study is noteworthy for finding use of dexmedetomidine reduced the prevalence of delirium (54% vs 77% with midazolam) and for providing further evidence of the safety of using dexmedetomidine at higher doses and longer duration. There was no difference in the primary outcome, time spent at target level of sedation. Duration of mechanical ventilation was shorter with dexmedetomidine but length of ICU stay was similar.

PMID: 19188334

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Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012; 307:1151-60. This article is noteworthy for being the first to directly compare sedation with propofol vs. dexmedetomidine in patients requiring prolonged mechanical ventilation. Duration of mechanical ventilation (including invasive and noninvasive) did not differ between dexmedetomidine and propofol (97 hrs vs 118 hrs, p = 0.24).  As with previous studies, dexmedetomidine shortened the duration of mechanical ventilation compared to midazolam. Time spent at target sedation was similar for all medications.

PMID: 22436955

Delirium in the ICU

Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-62. This study confirmed a high prevalence of ICU delirium (over 80% as identified by I-CAM) and was the first to show delirium is an independent risk factor for mortality. Specifically, ICU delirium was associated with 3-fold higher 6-month mortality. After adjusting for comorbidities, illness severity, coma, and use of sedatives and analgesics, delirium was also associated with prolonged ICU and hospital stays, as well as cognitive impairment at hospital discharge.

PMID: 15082703

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Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369:1306-16. A prospective two center study of patients with respiratory failure or shock found that at 3 months 40% of patients had deficits in cognition similar to those seen in moderate traumatic brain injury, and 26% had deficits similar to mild Alzheimer’s disease. A similar pattern was evident at 12 months. Duration of delirium was associated with worse cognitive and executive function at both time points. Type of sedative and analgesic medications was not associated with degree of subsequent cognitive deficit.

PMID: 24088092

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Skrobik Y, Duprey MS, Hill NS et al. Low-dose nocturnal dexmedetomidine prevents ICU delirium: A randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2018; 197:1147-1156. Two-center, double-blind, placebo-controlled trial randomized 100 delirium-free critically ill adults receiving sedatives to receive nocturnal (9:30 p.m. to 6:15 a.m.) intravenous dexmedetomidine or placebo until ICU discharge. Primary outcomes were delirium assessed using the Intensive Care Delirium Screening Checklist every 12 hours throughout the ICU admission and sleep evaluated each morning by the Leeds Sleep Evaluation Questionnaire. A higher proportion in the dexmedetomidine group remained free of delirium (80% vs. 54% for placebo) but patient-reported sleep quality did not differ. While promising results, further studies should be done to confirm findings.

PMID: 29498534

Girard TD, Exline MC, Carson SS et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med. 2018; 379:2506-2516. This study randomized 566 patients with acute respiratory failure or shock and hypoactive (89%) or hyperactive delirium (11%) to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The primary endpoint was the number of days alive without delirium or coma during the 14-day intervention period. Compared to placebo, neither haloperidol or ziprasidone increased the number of days alive without delirium or coma during the 14-day intervention period. Outcomes did not differ in the smaller subset of patients with agitated delirium.

PMID: 30346242

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Last Reviewed: June 2019