Comparative Effectiveness of Dual- Versus Mono-Sedative Therapy on Opioid Administration, Sedative Administration, and Sedation Level in Mechanically Ventilated, Critically Ill Children

OBJECTIVE We estimated the effect of early initiation of dual therapy vs monotherapy on drug administration and related outcomes in mechanically ventilated, critically ill children. METHODS We used the electronic medical record at a single tertiary medical center to conduct an active comparator, new user cohort study. We included children <18 years of age who were exposed to a sedative or analgesic within 6 hours of intubation. We used stabilized inverse probability of treatment weighting to account for confounding at baseline. We estimated the average effect of initial dual therapy vs monotherapy on outcomes including cumulative opioid, benzodiazepine, and dexmedetomidine dosing; sedation scores; time to double the opioid or benzodiazepine infusion rate; initiation of neuromuscular blockade within the first 7 days of follow-up; time to extubation; and 7-day all-cause in-hospital death. RESULTS The cohort included 640 patients. Children receiving dual therapy received 0.03 mg/kg (95% CI, 0.02–0.04) more dexmedetomidine over the first 7 days after initiation of mechanical ventilation than did monotherapy patients. Dual therapy patients had similar sedation scores, time to double therapy, initiation of neuromuscular blockade, and time to extubation as monotherapy patients. Dual therapy patients had a lower incidence of death. CONCLUSIONS In this study, initial dual therapy compared with monotherapy does not reduce overall drug administration during mechanical ventilation. The identified effect of dual therapy on mortality deserves further investigation.