Study Design Summary: Multicenter trial of 3904 ICU patients who were vented for less than 12 hours at time of randomization, split roughly 50/50 into control group which used other means of sedation such as propofol, benzodiazepines or other sedatives and intervention arm which receiving mainly dexmedetomidine as sedation, with primary outcome of all cause mortality at 90 days.
Notes: In the intervention group dexmedetomidine was used as the primary sedation agent, reduce agents of predefined low dose propofol or benzodiazepines in specific situations were allowed. The control group used propofol, benzodiazepines or other sedation agents and use of dexmedetomidine was discouraged but allowed as a rescue agent if needed. Antipsychotics were allowed in both groups. The intervention group had 97.7% of patients get dexmedetomidine, and 98.3% of patients in the control group got either propofol of midazolam, which is fairly good compliance overall for the size of the study
The demographics and baseline clinical characteristics of both groups at randomization was similar. This included age, APACHE II score, rates of sepsis, type of ICU admission, median RASS score and admission diagnosis.
The primary outcome of all cause mortality at 90 days was identical between the intervention vs control group (29.1% of both groups). Secondary outcomes including all cause mortality at 180 days, median days free of coma or delirium, and median ventilator free days were also not different between the groups.
The dexmedetomidine group required more rescue medication per the authors but this data is hard to discern from the paper and it is noted that both groups received multiple medications for sedation frequently. There is also a statement in the paper that there were more episodes of bradycardia and hypotension. While comparing the intervention to the control group the rates of bradycardia were 5.1% vs 0.5%, with “serious” bradycardia as 0.7% vs 0.05% for p=0.001. For hypotension rates were 2.7% vs 0.5%, and “serious” hypotension rates of 0.5% vs 0.05% for p=0.006. Asystole was 0.7% vs. 0.1%, P=0.003. However, even given these numbers the all cause mortality rate at 90 days was the same between the two groups.
“The biologic rationale for a potential benefit of dexmedetomidine is based on experimental evidence of protective effects against neuronal, myocardial, and renal injury, along with a reduction in inflammatory mediators after cardio- pulmonary bypass and reduced mortality in animal models.”
Study Conclusion: There was not an increased risk of death at 90 days in patients receiving dexmedetomidine compared to standard sedation agents, however, there were more adverse events in the dexmedetomidine group.
Fusion Beat Bottom Line Impression: This study demonstrated that dexmedetomidine does not improve 90 day mortality in patients when used as the primary sedation agent, there were increased adverse events with use of dexmedetomidine including bradycardia, hypotension and asystole, but all cause mortality at 90 days was the same between the two groups.
A Fusion Beat 