Source:Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial.
–499; doi:10.1001/jama.2009.56

The authors of this multinational, randomized, double-blinded trial compared the safety and efficacy of continuous dexmedetomidine to midazolam for sedation in mechanically ventilated adults. Enrolled patients were intubated and mechanically ventilated for less than 96 hours prior to start of study drug, and had an anticipated ventilation and sedation duration of at least three more days. Exclusion criteria were extensive and included pregnancy, severe brain pathology, acute liver failure, dialysis dependence, ischemic heart disease or cardiomyopathy, and those with persistent shock.

Sedation was managed using a nurse-implemented algorithm including daily drug interruption to target a light sedation goal. The Richmond Agitation-Sedation Scale1 (RASS) was used with a target score from −2 to 1. This is a score widely used in adult ICU patients. The score ranges from −5, which is completely unarousable to voice or touch, to +4, which is combative, violent, and danger to self or others.

Study patients were randomized two to one with 244 receiving dexmedetomidine and 122 receiving midazolam. The mean maintenance infusion dose of dexmedetomidine was 0.8 mcg/kg/hr but ranged from 0.2 to 1.14 mcg/kg/hr; 80% of study patients received the infusion >1 day. The mean age of all enrolled patients was approximately 62 years, with most (75%) treated for severe sepsis.

Dexmedetomidine- and midazolam-treated patients spent the same percentage of time in the target RASS range (77% vs 75%). Patients receiving dexmedetomidine had significantly less delirium (54% vs 77%) and a shorter median time to extubation (3.7 vs 5.6 days). Median intensive care unit length of stay was similar (5.9 vs 7.6 days). Patients receiving dexmedetomidine were significantly more likely to receive rescue open label midazolam (63% vs 49%), but not fentanyl boluses. The dexmedetomidine-treated patients were more likely to develop bradycardia (42% vs 19%) and less likely to develop tachycardia (25.4% vs 44.3%) and hypertension that required therapy (18.9% vs 29.5%). Rates of hypotension were similar.

The authors conclude that dexmedetomidine was effective in providing sedation to adult ventilated patients and was associated with shorter duration of intubation and less delirium.

Dr Munkwitz has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Pediatric patients require sedation for chemical restraint during mechanical ventilation, for diverse procedures, and to prevent patient harm from self-extubation, catheter removal, and even falling out of bed. Sedation places pediatric patients at risk for cardio-respiratory depression. In a mechanically ventilated patient this can result in prolonged mechanical ventilation,2 with increased risk of ventilator-associated pneumonias as well as swallowing difficulty and oral aversion after extubation among infants.

Agents commonly used for sedation are benzodiazepines, chloral hydrate, barbiturates, propofol, and opiates; all can produce undesirable side effects. Dexmedetomidine is used in pediatric patients to provide effective and safe sedation in both spontaneously breathing patients and mechanically...

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