Inhaled Volatile Sedation vs IV Sedation in Mechanically Ventilated Patients: A Systematic Review

Introduction: Sedation is crucial in handling mechanically ventilated patients in the ICU. Emerging alternatives, i.e., inhaled volatile anesthetics (IVA) (such as isoflurane, sevoflurane, and desflurane) to traditional intravenous (IV) sedatives like propofol or midazolam have shown promise in various Randomized controlled Trials (RCTs). We aimed to systematically review RCTs that compared IVA with IV sedation to assess their clinical efficacy, safety, and ICU-related outcomes.


Methods: We conducted a thorough search in PubMed, Embase and Scopus. We only included RCTs comparing any IVA vs IV sedation in adults (>18 years) who were on mechanical ventilation in ICUs, and reporting relevant clinical outcomes. Finally, 19 studies, including RCTs and post-hoc analyses, were included.


Results: Volatile sedation improved several patient-centered outcomes. In a 301-patient RCT, isoflurane increased ICU-Free Days (ICU-FD) (17.3 vs 13.8 days, p=0.028) without a difference in Ventilator free days (VFD) (19.8 vs 18.5, p=0.454). Wake-up and extubation times were significantly shorter: one trial reported median spontaneous breathing onset at 26 vs 375 min (p < 0.001, sevoflurane vs propofol), and another found extubation delays of 33.6±13.1 vs 326.1±360.2 min (p < 0.01). Respiratory parameters including PaO2/FiO2, PaCO2, and pH showed no consistent differences between groups. In ARDS patients, both isoflurane and propofol led to similar oxygenation improvements. Sedation quality was comparable based on RASS targets. Safety profiles were similar: no increased rates of hypotension, delirium, or organ dysfunction. One study noted lower incidence of renal replacement therapy with isoflurane (p=0.011). Mortality rates were not significantly different between groups in any single study.


Conclusions: Inhaled volatile anesthetics are a safe and effective alternative to traditional IV sedation in mechanically ventilated ICU patients. In all RCTs, volatile agents achieved non-inferior sedation control with faster wake-ups, extubating times, and similar outcomes in delirium, adverse events, and mortality. Still, most trials were single-center and underpowered for patient-centered outcomes. Larger, multicenter RCTs are needed to validate their role further and optimize sedation strategies in the ICU.