Use of Inhaled Volatile Anesthetics for Longer Term Critical Care Sedation: A Pilot Randomized Controlled Trial

Abstract

Objectives: Assess feasibility, barriers to recruitment, and safety of volatile-based sedation in longer term sedation patients in North American ICUs with limited or no experience with volatile sedation. Design: Open-label, pilot randomized clinical trial performed between October 2013 and September 2018. Setting: Four Canadian ICUs across two academic tertiary and quaternary hospitals. Patients: Sixty adults anticipated needing sedation and invasive ventilation beyond 48 hours with tidal volumes greater than 350 mL, expected 6-month mortality risk less than 50%, no evidence of high intracranial pressure, or drug contraindications (malignant hyperthermia, allergy). Interventions: 2:1 randomization to inhaled volatile sedation using isoflurane or standard midazolam and/or propofol IV sedation. Measurement and Main Results: Primary outcome of safety and feasibility was assessed by staff satisfaction scores using a five-point Likert scale and serum fluoride measurements. Secondary clinical outcomes included time to extubation, quality of sedation, opioid use, cardiorespiratory parameters, vasopressor and antipsychotic drug use, and 3-month cognitive outcome measured using telephone interview for cognitive status. From 2,210 screened patients, 308 met eligibility criteria secondary to many not requiring sedation, extubation planned within 48 hours, high risk of death, or low tidal ventilation. Of 308 patients, 60 were randomized to isoflurane (n = 41) or IV (n = 19) sedation secondary to lack of substitute decision-maker or physician consent. Duration of inhaled isoflurane and IV sedation were median of 114 and 88 hours, respectively. Nine isoflurane patients crossed into the IV arm secondary to mainly hypercarbia from low tidal ventilation. Nursing and respiratory therapy staff satisfaction scores were quantitatively similar between both sedation approaches. Serum fluoride levels rose with duration of isoflurane sedation but were not associated with altered kidney function. There were no significant differences in secondary clinical outcomes. Conclusions: We showed adequate preliminary safety and acceptability of inhaled volatile anesthetics for long-term sedation.