Analgesia-first sedation in critically ill adults: A U.S. pilot, randomized controlled trial

• Published in: Journal of critical care 2019-10, Vol.53, p.107-113
• Main Authors: Tanios, Maged, Nguyen, Huan Mark, Park, Hyunsoon, Mehta, Sangeeta, Epstein, Scott K., Youssef, Fady, Beltran, Antonio, Flores, Gabe, Sidhom, Ramy, Sehgal, Arunpal, Leo, James, Devlin, John W.
• Format: Article
• Language: English
• Subjects: Analgesia; Analgesics; Anesthesia; Clinical trials; Evidence-based medicine; Fentanyl; Intensive care; Intubation; Mortality; Narcotics; Pain management; Patients; Pilot study; Randomized controlled trial; Sedation; Ventilators; Weaning
• ISSN: 0883-9441; 1557-8615
• DOI: 10.1016/j.jcrc.2019.06.008

To determine the feasibility of conducting a multicenter ICU RCT of AFS compared to either protocol-directed sedation (PDS) or both PDS and daily sedation interruption (DSI) in North America. This single-center RCT compared AFS [fentanyl (bolus ± infusions) to reach CPOT ≤2; if RASS ≥1, CPOT ≤2 and additional fentanyl failed to reach RASS goal (−2 to 0), low-dose propofol (up to 6 h) was given] with either PDS or both PDS and DSI daily in adults mechanically ventilated (MV) ≥48 h. Relevant feasibility, safety, and clinical outcomes were defined and evaluated. 90 of 160 eligible patients were enrolled [AFS = 27; PDS = 28; PDS + DSI = 31]; rate = 3/month. Time from intubation to randomization was 17.5 ± 11.6 h. Study days fully adherent to the study intervention [AFS = 95%; PDS = 99%; PDS + DSI = 96%] and time spent in the first 48 h after randomization without pain (CPOT ≤2)[AFS = 82%; PDS = 78%; PDS + DSI = 77%] and at goal RASS[AFS = 88%; PDS = 83%; PDS + DSI = 95%] were high and similar. Nurse-perceived [median (IQR)] study workload (10-point VAS) was higher with AFS [4(2–6)] than PDS [1(1–3)] or PDS + DSI [2(1–5)]; p = .002). Unplanned extubation was rare (AFS = 1; PDS = 0; PDS + DSI = 1). Days [median (IQR)] free of MV in the 28d after intubation [AFS 24(23,26); PDS 24(20,26); PDS + DSI 24(21,26)] was not different (p = .62). A multicenter RCT evaluating AFS is feasible to conduct in North America. •Analgesia-first sedation (AFS) has not been evaluated in a randomized trial in North America where ICU practices are different from Europe.•Enrollment, intervention adherence, and achievement of pain/sedation goals, were similar between the AFS and control groups.•Nurse and respiratory care practitioner-perceived patient workload were greater with AFS but did not exceed the feasibility benchmark.•Patient self-extubation and breakthrough propofol use were very low in the AFS group.•A multicenter study comparing AFS to traditional sedation strategies in North America appears feasible to conduct.