Comparison of sufentanil and fentanyl for delirium outcomes in mechanically ventilated surgical intensive care unit patients: an exploratory multicenter randomized trial

Purpose: Delirium is common among mechanically ventilated intensive care unit (ICU) patients and is associated with adverse outcomes. Although opioid analgesia is central to sedation management, its effect on delirium remains uncertain. This study compared delirium outcomes between sufentanil- and fentanyl-based analgesia in mechanically ventilated surgical ICU patients.Methods: In this prospective, multicenter, randomized exploratory trial conducted at three tertiary hospitals, adults requiring invasive mechanical ventilation and continuous opioid-based analgesia were randomized at enrollment in a 1:1 ratio to receive sufentanil or fentanyl. Delirium was assessed at least twice daily using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). The primary outcome was delirium incidence during the ICU stay. Secondary outcomes included delirium duration, prolonged delirium (≥3 days), and other clinical outcomes. Delirium-related analyses were performed in a modified intention-to-treat population.Results: A total of 252 patients were screened for eligibility: 217 were randomized to sufentanil (n=120) or fentanyl (n=97), and 199 were evaluable for delirium outcomes. Delirium occurred in 53 of 113 patients (46.9%) in the sufentanil group and 51 of 86 patients (59.3%) in the fentanyl group (relative risk for fentanyl vs. sufentanil, 1.26; 95% confidence interval [CI], 0.97–1.64; P=0.083). Delirium duration was shorter in the sufentanil group than in the fentanyl group (1.9±3.2 days vs. 2.9±3.9 days, P=0.034), and prolonged delirium (≥3 days) was less frequent (20.4% vs. 34.9%, P=0.022). In an exploratory multivariable analysis, opioid type was not significantly associated with delirium occurrence (adjusted odds ratio [aOR], 1.65; 95% CI, 0.88–3.09; P=0.118). Among patients who developed delirium, fentanyl use was associated with prolonged delirium (aOR, 2.35; 95% CI, 1.00–5.48; P=0.049). Other major clinical outcomes were comparable between the groups.Conclusion: Overall delirium incidence did not differ significantly between sufentanil- and fentanyl-based analgesia. However, secondary analyses suggested that delirium duration may be shorter with sufentanil.Trial Registration: Registered in the Clinical Research Information Service (CRIS No. PRE20260212-006).