RESUMO
Objective: To evaluate the feasibility of conducting a prospective randomised controlled trial (pRCT) comparing remifentanil and fentanyl as adjuncts to sedate mechanically ventilated patients. Design: Single-center, open-labelled, pRCT with blinded analysis. Setting: Australian tertiary intensive care unit (ICU). Participants: Consecutive adults between June 2020 and August 2021 expected to receive invasive ventilation beyond the next day and requiring opioid infusion were included. Exclusion criteria were pregnant/lactating women, intubation >12 h, or study-drug hypersensitivity. Interventions: Open-label fentanyl and remifentanil infusions per existing ICU protocols. Outcomes: Primary outcomes were feasibility of recruiting ≥1 patient/week and >90 % compliance, namely no other opioid infusion used during the study period. Secondary outcomes included complications, ICU-, ventilator- and hospital-free days, and mortality (ICU, hospital). Blinded intention-to-treat analysis was performed concealing the allocation group. Results: 208 patients were enrolled (mean 3.7 patients/week). Compliance was 80.6 %. More patients developed complications with fentanyl than remifentanil: bradycardia (n = 44 versus n = 21; p < 0.001); hypotension (n = 78 versus n = 53; p < 0.01); delirium (n = 28 versus n = 15; p = 0.001). No differences were seen in ICU (24.3 % versus 27.6 %,p = 0.60) and hospital mortalities (26.2 % versus 30.5 %; p = 0.50). Ventilator-free days were higher with remifentanil (p = 0.01). Conclusions: We demonstrated the feasibility of enrolling patients for a pRCT comparing remifentanil and fentanyl as sedation adjuncts in mechanically ventilated patients. We failed to attain the study-opioid compliance target, likely because of patients with complex sedative/analgesic requirements. Secondary outcomes suggest that remifentanil may reduce mechanical ventilation duration and decrease the incidence of complications. An adequately powered multicentric phase 2 study is required to evaluate these results.
