Buprenorphine for Iatrogenic Opioid Dependence in Neurocritical Care: Effects on Sedation, Ventilator Liberation, and Clinical Outcomes

Background/Objective: Iatrogenic opioid dependence, withdrawal, and opioid accumulation can impede neurologic assessment and delay liberation from invasive mechanical ventilation (IMV) in neurocritical care. We evaluated whether low-dose buprenorphine (BUP) initiation was associated with improved sedation and ventilator outcomes. Methods: We conducted a retrospective matched cohort/case-control study of adults in the neurocritical care unit (NCCU) receiving parenteral opioids while on IMV ≥ 24 hr. Patients receiving low-dose BUP initiation (≤ 2 mg cumulative in the first 8 hr with ≥ 1 sublingual dose; n = 19) were matched by demographics and diagnosis to patients not receiving BUP (NO-BUP; n = 18). Outcomes included ventilator days/time to liberation, daily IV morphine milligram equivalents (MME), time-in-target range Richmond Agitation-Sedation Scale (RASS − 2 to 0), continuous sedative infusion exposure, opioid withdrawal, and BUP-attributable adverse events (precipitated opioid withdrawal [POW] or respiratory depression). Results: BUP patients had fewer ventilator days than NO-BUP patients (17.7 ± 13.9 vs 29.3 ± 13.9 days; mean difference − 11.65, 95% CI -20.9 to -2.4; Cohen’s d = 0.84; p =  0.008) and earlier median liberation (16.0 vs 23.5 days; p =  0.021). After BUP initiation, daily IV MME decreased (597.6 ± 617.5 to 6.8 ± 18.3 mg; p =  0.001), target RASS time increased (63.9 ± 27.8% to 81.6 ± 22.0%; p =  0.0001), and continuous sedative infusions declined (73.7% to 31.6%; p =  0.021). No BUP patient experienced POW or respiratory depression temporally related to BUP; opioid withdrawal occurred in 0/19 BUP vs 6/18 NO-BUP patients (33.3%; p =  0.008). ICU length of stay was similar (30.2 ± 18.6 vs 31.8 ± 14.9 days; p =  0.385). Mortality occurred in 0/19 BUP vs 5/18 NO-BUP (27.8%; p =  0.020). Conclusions: In this retrospective, diagnosis-matched NCCU cohort, low-dose BUP initiation was feasible and associated with improved sedation targets, reduced opioid/sedative exposure, and faster IMV liberation without observed precipitated withdrawal. Findings are hypothesis-generating given retrospective design, small sample size, heterogeneous diagnoses, and potential residual confounding from adjunctive medications.