Comparison of dexmedetomidine with propofol/midazolam in sedation of long-stay intensive care patients: a prospective randomized, controlled, multicenter trial
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KeywordsMechanical Ventilation Midazolam Dexmedetomidine Deep Sedation Pivotal Trial
Sedation is a major problem in long-stay intensive care patients despite use of sedation stops and scores. We hypothesized that the α2-adrenoceptor agonist dexmedetomidine (DEX) is at least equivalent to standard-of-care sedation (SOC), and may reduce the length of ICU stay and improve other clinically relevant outcomes.
We performed a pilot (n = 85), phase III, multicenter, prospective, randomized, double-blind, double-dummy, active comparator (SOC: either propofol or midazolam) study to define the feasibility and size of a pivotal trial. Patients with expected ICU stays ≥48 hours and a need for sedation for at least 24 hours after randomization were included within the first 72 hours of ICU stay. The maximum duration of study sedation was 14 days, with a 45-day follow-up from randomization. Sedation was Richmond Agitation Sedation Scale (RASS)-score targeted, with daily sedation stops.
Forty-one patients received DEX and 44 SOC (28 propofol). The goal was moderate (RASS 0 to -3) sedation in most patients (78% in DEX and 80% in SOC). Patients were at the target RASS 55% (DEX) and 57% (SOC) of the sedation time (not significant): for RASS target 0 to -3, 68% (DEX) and 64% (SOC) of the time (not significant) and for RASS target -4, 31% (DEX) and 63% (SOC), respectively (P = 0.006). Median time from admission/randomization to ICU discharge was similar (DEX 6.6/5.7 days, SOC 6.7/5.5 days, not significant). Mechanical ventilation was shorter for DEX with RASS target 0 to -3 (DEX 70.2 hours, SOC 92.5 hours, P = 0.027), and patients' ability to communicate (multidimensional visual analog scale) was better with DEX (P < 0.001). Occurrence rates and number of patients with overall and serious adverse events were similar.
DEX is well tolerated and comparable with SOC in long-term sedation, but not suitable as the sole agent for deep sedation. DEX enhances the patient's ability to communicate. Its effects on relevant outcomes (for example, duration of mechanical ventilation) should be tested in a large randomized controlled trial.