745: EFFECT OF BOLUS DOSES PRIOR TO UP-TITRATION OF FENTANYL OR MIDAZOLAM FOR SEDATION

Abstract

Introduction: Fentanyl and midazolam are highly lipophilic agents commonly used as continuous infusions for sedation. Based on the pharmacokinetics, a bolus dose could shorten the time to achieve steady state concentrations before being maintained with an increase in the continuous infusion. Upfront bolus dosing may avoid excessive up-titration to a maximum rate leading to drug accumulation, adverse reactions, and addition of other sedatives. The purpose of this study is to compare the efficacy and safety of bolus doses versus no bolus doses prior to up-titration of fentanyl and midazolam continuous infusions for sedation in mechanically ventilated adult patients in the medical intensive care unit (MICU). Methods: This retrospective cohort study looked at adults receiving fentanyl or midazolam infusions for sedation for at least 24 hours admitted to the MICU at North Shore University Hospital from October 2021 to April 2022. The 2 cohorts are patients pre- and post-implementation of education on fentanyl and midazolam bolus doses. Patients were excluded if they were receiving concurrent neuromuscular blocking agents, had concurrent diagnosis of uncontrolled seizures, catastrophic stroke, intracranial hemorrhage, or COVID-19 as the primary diagnosis. The primary outcome of the study is duration of mechanical ventilation (MV). Results: Thirty-six patients were analyzed with 25 in the control group and 11 in the study group. More patients in the study group had history of leukemia (8% vs 45%, p=0.018) and a higher number of sedatives prior to study drug infusion (p=0.0383). There was no difference in the median duration of MV (6 vs 9 days, p=0.1179). The control group had a statistically significant lower sedation intensity score on days 1 and 2 of sedation that on average was 9.6 and 8.5 units lower, respectively. Outcomes including number of concomitant sedatives, in-hospital mortality and time to Richmond Agitation Sedation Scale (RASS) goal were not statistically significant. Adverse events were similar between groups. Conclusions: Low protocol adherence and small sample size limit the interpretation of results. Thus, larger studies would be required to assess if there is a difference in MV using the bolus vs no bolus dose titration. Next steps include further data collection and protocol reinforcement.