Sedation / Analgesia / Delirium

Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill patient. Crit Care Med 2002;30:119-41. Combines expert opinion and literature review to make recommendations. This topic is due for updated guidelines.
PMID: 11902253

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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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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Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286:2703-10. This early study helped establish the methodology for studying ICU delirium while documenting the immense scope of the problem. Over 80% of patients experienced delirium during their ICU stay, 10% of whom were still delirious at hospital discharge. Nearly 40% of patients who were alert or easily aroused and followed commands were delirious, suggesting delirium is easily overlooked. Training manuals and other downloadable materials in 12 languages are available at: www.icudelirium.org
PMID: 11730446
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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 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 co-morbidities, 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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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 than currently approved by the FDA. 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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Jackson JC, Girard TD, Gordon SM, ,et al. Long-term cognitive and psychological outcomes in the awakening and breathing controlled trial. Am J Respir Crit Care Med. 2010; 2010 Mar 18. Single-center randomized a priori analysis within the larger multicenter “ABC” Trial, assessed cognitive, psychological, and functional/quality-of-life measures at 3 and 12 months after discharge. Results suggest no difference in patients treated with daily “wake up and breathe” protocol, challenging the suspicion that decreasing sedation in critical illness may have a negative impact on patients’ psychological wellbeing.
PMID: 20299535
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Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009;373:1874-82. The first RCT to assess early mobilization of intubated adult patients during daily interruption of sedation. Ambitious intervention protocol allowed for progression from range of motion exercises to assisted transfers, ADLs, and ambulation as tolerated. Treatment group had statistically significant improvement in multiple outcomes including return to independent functional status (35% vs 59%), fewer days of delirium, shorter duration of mechanical ventilation, and lower incidence of ICU acquired paresis.
PMID: 19446324
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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
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