Hydromorphone-based Analgosedation in the PICU: A Pilot Study

Background: More than 100,000 children in the US require invasive mechanical ventilation (IMV) in the pediatric intensive care unit (PICU) each year with exposure to analgesic and sedative medications [1]. Sedative exposure is linked to prolongation of IMV, increased hospital length of stay (LOS), and delirium. Evidence shows improvement in outcomes with an analgosedation approach, prioritizing opiates and minimizing benzodiazepine exposure [2]. However, there is little guidance as to which opioid is optimal; most PICUs currently use fentanyl [3]. We hypothesize that hydromorphone would be preferable due to more rapid onset and fewer side effects [4]. The objective of this pilot study was to evaluate feasibility of a hydromorphone-based analgosedation protocol (HM-ASP), as compared to a fentanyl-based ASP (F-ASP) in critically ill children on IMV.

Methods: Pre/post-interventional study in an academic PICU, comparing F-ASP (retrospective, June-Dec 2019) to HM-ASP (prospective, Jan-March 2020). Inclusion criteria included age birth to <21 years, and IMV of at least 4 hours duration. Outcomes (auto-extubation, mortality, duration of IMV, LOS, delirium, agitation, cumulative benzodiazepine and opiate exposure within the first 5 days of IMV) were reviewed.

Results: 67 patients met inclusion criteria for the pre-intervention F-ASP cohort; 30 patients met inclusion criteria for the post-intervention HM-ASP. Demographics between the 2 cohorts were similar. The ASP was successfully implemented in 93% of eligible patients. Outcomes in the HM-ASP cohort were similar and trended towards benefit [Fig 1]. HM-ASP was associated with decrease in: total midazolam use (0.76 to 0.14 mg/kg, p=0.13), mean duration of IMV (5.53 to 2.84 days, p=0.14), PICU LOS (mean 17.1 to 9.4 days, p=0.09), and decrease in delirium (1.19 to 0.69 days, p=0.08). Despite a decrease in overall sedation exposure, there was no increase in: cumulative opiate exposure (6.4 mg/kg vs. 5.9 mg/kg in morphine equivalents, p=0.77), agitation (6.0% vs 6.7%, p>0.99), auto-extubations (n=0 in both), or mortality (n=2 vs 0, p>0.99).

Conclusion: HM-ASP is feasible and safe for use in children on IMV. This pilot study demonstrated overall improvement in short-term patient outcomes when compared to F-ASP, but due to limited power, results did not reach statistical significance. Further large-scale studies are necessary to demonstrate efficacy and long-term sustainability.