Age-Related Differences in Benzodiazepine Dosing for Mechanically Ventilated Pediatric ICU Patients: A Retrospective Cohort Study

Abstract

Objectives

Our primary objective was to determine differences in benzodiazepine doses given for tolerance of mechanical ventilation based on age cohorts in a pediatric intensive care unit (ICU) population. We hypothesized younger subjects would see increased doses of benzodiazepines.

Methods

This was a single center, retrospective cohort study of mechanically ventilated pediatric ICU patients receiving benzodiazepines. The primary outcome was a difference in midazolam and lorazepam dose intensity (mg/kg/day) between age cohorts. Primary outcomes were analyzed using an unadjusted linear mixed-effects model with random subject effect. If the model was significant, we performed multivariable regression analysis. When the overall adjusted model was significant, Tukey-adjusted pairwise comparisons were performed, and geometric mean ratio and 95% CI were estimated.

Results

The initial query returned 790 encounters across 747 unique subjects who received benzodiazepines. Dose intensity was calculated for midazolam and lorazepam. After adjusting for degree of illness, PIM3, and indication for mechanical ventilation, infants received, on average, 2.55 higher midazolam dose intensity ((1.30, 5.00), P < .01) than older childhood subjects and preschool-aged subjects received 2.95 higher midazolam dose intensity ((1.50, 5.81), P < .01) than older childhood subjects. Infants received 1.53 times higher lorazepam dose intensity than elementary-aged subjects ((1.03, 2.30), P = .03) and 1.98 times higher lorazepam dose intensity than older childhood subjects ((1.39, 2.82), P < .01).

Conclusions

Our study demonstrates among children receiving benzodiazepines to tolerate endotracheal intubation, children less than five years of age receive significantly higher benzodiazepine dose intensity than many of their older pediatric counterparts. Given the negative impact of sedative agents on developing brains and the increased risk of delirium with benzodiazepines, further investigation into variation in sedative dosing, including pharmacogenomics and differences in patient-centered clinical outcomes, is warranted.