Dexmedetomidine vs propofol in intensive care unit patients

Abstract

Dexmedetomidine is indicated as a sedative agent in intensive care units (ICUs). While several clinical trials and two meta-analyses have compared this agent with propofol or midazolam, the results were variable depending on the specific end-point (e.g., duration of mechanical ventilation, ICU mortality, maintaining a target depth of sedation, incidence of delirium episodes, length of hospital stay). Hence, the effectiveness of this new agent vs the comparators seems to be controversial. Trial sequential analysis (TSA) is a statistical technique that can estimate the optimal, cumulative number of patients that would be needed to generate a conclusive result. We therefore applied a TSA model to the most recent meta-analysis evaluating dexmedetomidine. A total of 10 randomized controlled trials were included in our analysis. According to our results, the comparison of dexmedetomidine vs propofol showed no proof of incremental effectiveness for the end-points of length of ICUs stay and incidence of delirium episodes. In contrast, futility (i.e., proof of no incremental effectiveness) was demonstrated for the end-point of mechanical ventilation. Hence, the results for the comparison of dexmedetomidine vs propofol were inconclusive for the first two end-points; on the other hand, conclusiveness was reached for the third end-point. We conclude that the place of dexmedetomidine in therapy of critically ill patients is very uncertain and further controlled trials are still needed.

Keywords: Dexmedetomidine; Propofol; Midazolam; Sedation; Intensive care unit; Mechanical ventilation; Hospital stay; Meta-analysis; Trial sequential analysis

Core tip: Dexmedetomidine, a sedative agent for critically ill patients, has been studied in several randomized trials and in two meta-analyses. The clinical results were conflicting because of the diversity of the end-points and the small size of most studies. Since trial sequential analysis can improve the interpretation of controversial meta-analyses, we applied this technique to dexmedetomidine. According to our results, the comparison of dexmedetomidine vs propofol showed no proof of incremental effectiveness (for length of intensive care unit (ICU) stay and incidence of delirium) or of no incremental effectiveness (for duration of mechanical ventilation). Hence, the therapeutic role of dexmedetomidine in ICU is still uncertain.