Low-Dose Buprenorphine Initiations During Opioid and Sedative Weaning in Mechanically Ventilated Neurocritical Care...

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.

We conducted a retrospective matched cohort/case-control study of adults in the neurocritical care unit (NCCU) receiving parenteral opioids while on IMV ≥ 24 h. Patients receiving low-dose BUP initiation (≤ 2 mg cumulative in the first 8 h 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 intravenous (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].

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). The intensive care unit (ICU) length of stay was similar (30.2 ± 18.6 vs. 31.8 ± 14.9 days; p = 0.385).

In this pilot retrospective matched cohort study, low-dose BUP initiation as part of an opioid/sedative-weaning strategy was feasible and associated with higher documented time-in-target RASS, reduced opioid/sedative exposure, and faster IMV liberation without documented POW. Given the small sample size, co-interventions, retrospective design, and residual confounding, these findings should be considered hypothesis-generating and require prospective validation.