Introduction: Current guidelines endorse the use of dexmedetomidine over propofol for light sedation of mechanically ventilated adult intensive care unit (ICU) patients. Previous studies have shown no significant differences in outcomes such as mortality and organ failure-free days. The Sedation Practice in Intensive Care Evaluation (SPICE III) study found a higher 90-day mortality in patients ≤ 65 years of age on dexmedetomidine, but no mechanism was determined. Methods: A post-hoc analysis of a multicenter, double-blind, randomized controlled trial. Adult medical and surgical ICU patients with sepsis requiring sedation while on mechanical ventilation and admitted between May 2013 through December 2018 were included. Patients were randomized in a 1:1 ratio to receive either dexmedetomidine or propofol infusions to achieve clinical directed target sedation for up to 14 days. Given the exploratory nature of the analysis, the significance level was set a priori at 0.20. Results: Multivariable regression models with a treatment and age interaction term were used to evaluate if age modified the association between treatment and outcomes. The primary outcome was 30-day mortality. Secondary outcomes included 90-day mortality, prevalence and duration of cardiac and renal dysfunction and delirium/coma-free days (DCFDs) for the 14-day study period, and ventilator-free days (VFDs) at 28 days. Dexmedetomidine arm had 214 patients of median age 59 (IQR:48-68) and 208 in the propofol arm of median age 60 (IQR:50-68). There was no clinically significant difference in study drug dosing or duration across age quartiles in either group. Age had a statistically significant interaction with treatment for 30-day mortality (P=0.14), where younger patients on dexmedetomidine had higher hazard of death. Age modified the effect of treatment on renal dysfunction prevalence (P=0.002), with higher odds of renal dysfunction for older patients on dexmedetomidine. No statistically significant age-treatment interaction was observed for other outcomes. Conclusions: There is no evidence of a consistent overall effect of age on mortality and organ dysfunctions based on choice of sedation in septic mechanically ventilated patients. The differential impact of dexmedetomidine for 30-day mortality and renal dysfunction warrants further study.
Mahmud et al. (Sun,) studied this question.