Abstract Rationale Opioids are integral to ICU sedation but may delay ventilator liberation by suppressing respiratory drive. Transitioning from intravenous to enteral opioids is increasingly used, yet its effect on mechanical-ventilation duration and ICU length of stay (LOS) remains uncertain. Evidence on the impact of enteral opioid transition particularly the timing of initiation remains scarce. Our study evaluates whether the initiation and timing of enteral opioid therapy among mechanically ventilated, non-surgical ICU patients are associated with prolonged mechanical ventilation and ICU LOS. Methods We performed a retrospective cohort study for adults (≥18 years old) admitted to medical ICUs between January 2020 and December 2023 who required invasive mechanical ventilation and received any opioid. Surgical, NICU, and PICU admissions were excluded. Patients were categorized based on the route and timing of opioid administration: Intravenous (IV) fentanyl only, early enteral (≤72 hours), and late enteral (72 hours) following intubation. Primary outcomes were ventilator duration and ICU LOS. Multivariable linear regression adjusted for age, sex, race, Charlson Comorbidity Index, substance-use disorder, and prior outpatient opioid prescriptions. Results Among 4,497 patients (mean age 60 ± 16.7 yr; 44% female), 88.1% received IV fentanyl only, 6.3% early enteral, and 5.6% late enteral opioids. Mean outcomes increased incrementally across exposure groups: ventilator days 4.1 ± 6.2 (IV only) vs 6.1 ± 7.8 (early) vs 11.4 ± 7.2 (late); ICU LOS 5.5 ± 4.6 vs 7.2 ± 5.9 vs 10.5 ± 6.3. After adjustment, enteral opioid use remained independently associated with longer ventilation and ICU stay early enteral +2.10 (95% CI 1.33-2.87) ventilator days and +1.71 (1.13-2.29) ICU days; late enteral +7.26 (6.44-8.07) ventilator days and +4.96 (4.35-5.57) ICU days. Ventilator dependence at discharge increased from 4.6% (IV only) to 12.4% (early) and 18.7% (late) (p 0.0001). Conclusions Enteral opioid exposure particularly when initiated 72 hours after intubation was associated with significantly longer ventilation, prolonged ICU stay, and higher odds of ventilator dependence at discharge, independent of baseline factors. Earlier enteral transitions showed smaller effects, suggesting partial confounding by illness severity, though a physiologic contribution to delayed weaning is plausible via respiratory-drive suppression, sedation carry-over, and ileus. These findings highlight the need for cautious enteral-opioid use during sedation transitions. Future studies should utilize severity-adjusted, time-to-event or propensity-weighted analyses to assess causality and guide opioid-use strategies aimed at reducing mechanical-ventilation duration. This abstract is funded by: None
Abdullah et al. (Fri,) studied this question.
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