(931) Effect of Bolus Doses Prior to Uptitration of Continuous Fentanyl/Midazolam Infusions for Sedation

Introduction: Analgosedation has demonstrated improved patient outcomes and reduced mechanical ventilation (MV) time, but there are no guidelines on titrating infusions. Upfront bolus dosing may shorten time to steady state concentrations and avoid excess up-titration on continuous infusions thus preventing drug accumulation, adverse drug reactions, and addition of other sedatives. This study compared the efficacy and safety of bolus doses prior to up-titration of fentanyl and midazolam infusions in MV patients in the medical intensive care unit (MICU).

Methods: This retrospective, cohort study evaluated 77 MICU patients pre- (N=48) and post-implementation (N=29) of education on fentanyl and midazolam intermittent doses prior to up-titration between July 2021 and July 2022. Patients with concurrent neuromuscular blocking agents, uncontrolled seizures, catastrophic stroke of National Institutes of Health Stroke Scale >20, intracranial hemorrhage, or COVID-19 as the primary diagnosis were excluded. Secondary outcomes included number of concomitant sedatives and sedation intensity scale (SIS). Safety outcomes included acute kidney injury (AKI), abnormal liver function, and death during MV.

Results: There was no difference in baseline prior-to-admission medications, ICU admission reason, or number of sedatives prior to study drug infusion. Median duration of MV showed no difference (133 hours vs 137 hours, p=0.725). There was also no difference in number of concomitant sedatives (p=0.5975), most often propofol, dexmedetomidine, and then ketamine. No difference was found in the daily SIS or safety outcomes of AKI (73% vs 59%, p=0.15), abnormal liver function (35% vs 21%, p=0.20), or death during MV (38% vs 31%, p=0.34). When looking at just fentanyl SIS, the study group had a statistically significant lower fentanyl SIS on days 2 and 4, with 3.3 units and 3.0 units lower, respectively.

Conclusions: Bolus dosing of fentanyl and midazolam for sedation prior to up-titration is safe and may be associated with lower usage of fentanyl with continuous infusions of at least 2 days. Low protocol adherence may be improved upon as only 83% of the 29 patients in the study group had a bolus protocol ordered and of those 83% of patients, only 1/3 of patients had a protocol adherence rate >75%.