A Randomized Controlled Trial Comparing Inhaled Isoflurane Via the Anaesthetic Conserving Device (Sedaconda ® ACD) with Propofol for Sedation of Invasively Ventilated ICU Patients
التفاصيل البيبلوغرافية
العنوان:
A Randomized Controlled Trial Comparing Inhaled Isoflurane Via the Anaesthetic Conserving Device (Sedaconda ® ACD) with Propofol for Sedation of Invasively Ventilated ICU Patients
Background: Small studies indicate that isoflurane may be useful for sedation during invasive ventilation of ICU patients. There are no published large prospective efficacy trials. Methods: This phase 3, non-inferiority trial evaluated the efficacy and safety of ≤54 hours of isoflurane via the anaesthetic conserving device (ACD) compared with propofol in invasively ventilated ICU patients (30-day follow-up). Primary endpoint was percentage of time in Richmond Agitation–Sedation Scale (RASS) range –1 to –4; the predefined non-inferiority margin was 15% below the propofol mean. Secondary endpoints: opioid requirements, spontaneous breathing during sedation, time to wake-up and extubation, adverse events, ventilator-, ICU-, coma- and delirium-free days, and 30-day mortality. Findings: 301 patients were randomized to isoflurane (n=150) or propofol (n=151). Least-squares mean percentage of time (95% CI) in RASS target range was 90·7% (86·8–94·6) for isoflurane and 91·1% (87·2–95·0) for propofol. With isoflurane, opioid requirements were reduced by 29% (ANOVA, p=0·004) throughout and spontaneous breathing more frequent on Day 1 (50·3% vs 37·0%, GLMM, p=0·013). Extubation and wake-up times were short, and wake-up time was significantly shorter after isoflurane on Day 2 (median [IQR]: 20 [10–30] vs 30 [11–120] minutes; Cox regression p=0·001). No significant differences in serious adverse events, ventilator-, ICU-, coma- and delirium-free days or mortality. Interpretation: Isoflurane via the ACD for sedation of ICU patients was efficacious, non-inferior to propofol, with lower opioid use, more spontaneous breathing, and shorter wake-up time. Trial Registration: EudraCT#: 2016-004551-67Funding . This study was funded by Sedana Medical AB. Funding: This study was funded by Sedana Medical AB. Declaration of Interest: AM: Consultancy fees: Sedana Medical AB. TV: Grant support: B Braun. UG: Lecture fees: MT Monitor Technik, Getinge; reimbursement of clinical study expenses: Bayer Healthcare. TB: Lecture fees and travel costs: Sedana, Lowenstein Medical, Drager Medical. PK: Personal fees: Sedana Medical AB. MD: Lecture fees and travel costs: Cytosorbents Europe GmbH. PS: Employee and shareholder: Sedana Medical AB. JW, HB, KS, RK, AF, SCT, JS, HV, MB: Nothing to declare. Ethical Approval: The study was conducted in accordance with International Conference on Harmonisation Good Clinical Practice standards and the Declaration of Helsinki. Ethical approval for this study was provided by the ethics committees in Germany (Ethikkommission der Arztekammer des Saarlandes
