Sedating with Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects on Ventilatory Parameters and Survival
SAVE-ICU
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PURPOSE
The purpose of SAVE‑ICU is to determine whether using inhaled anesthetic agents for ICU sedation leads to better patient outcomes—including mortality, ventilator‑free days, ICU‑free days, and quality of life—compared to conventional intravenous sedatives. It additionally seeks to understand how sedation type influences cognitive, psychiatric, neurologic, and inflammatory outcomes in survivors of critical illness.
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PROGRESS
100%
patients enrolled
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FUTURE
The SAVE‑ICU trial will provide the first large‑scale evidence on the effectiveness and safety of inhaled anesthesia for long‑term ICU sedation outside the operating room. Its results may influence global critical‑care sedation practices, guide drug‑shortage contingency planning, and inform future research on brain injury, inflammation, and recovery after ARDS—especially in COVID‑19 and post‑pandemic ICU populations.
What is SAVE-ICU?
The SAVE‑ICU trial is a large, multicentre, open‑label randomized controlled study evaluating whether inhaled volatile anesthetic–based sedation (sevoflurane or isoflurane) improves outcomes for mechanically ventilated ICU patients with COVID‑19 or other causes of hypoxic respiratory failure compared with standard intravenous sedation. It also includes a parallel prospective cohort for patients who cannot be randomized due to resource or technical limitations.
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Why is this important?
Severe COVID‑19 and ARDS cause profound respiratory failure requiring mechanical ventilation and prolonged sedation. During the pandemic, global shortages of intravenous sedatives highlighted an urgent need for safe alternatives. Inhaled anesthetics may not only fill a supply gap but also offer physiologic benefits—such as improved oxygenation, anti‑inflammatory effects, and faster ventilator liberation—potentially reducing complications and improving survival. The trial aims to determine whether these advantages translate into better clinical and long‑term outcomes.
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What is involved in the study?
Participants are randomized 1:1 to receive either inhaled volatile sedation or standard intravenous sedation within 72 hours of starting sedation. They are followed daily in the ICU for up to 30 days, until discharge or death. Additional follow‑ups occur at 30, 60, 90, and 365 days using health‑system databases and telephone assessments, including quality of life and disability measures. Optional sub‑studies include neuro‑cognitive testing, MRI‑based neuroimaging, and immuno‑thrombotic biomarker profiling.
Study Arms
Intervention Arm: Inhaled Volatile Sedation
Participants randomized to this arm receive sedation using inhaled volatile anesthetics—either sevoflurane or isoflurane, depending on local availability. These agents are delivered through a vaporizing device integrated into the mechanical ventilator circuit (MADM, AnaConDa, or an anesthesia machine). Sedation is titrated to standard ICU sedation targets, and participants remain on inhaled sedation until the clinical team discontinues sedation or until death.
Control Arm: Intravenous Sedation
Participants randomized to this arm receive intravenous (IV) sedative medications, such as propofol, benzodiazepines, ketamine, opioids, or alpha‑2 agonists, following standard ICU sedation practices and guideline‑based protocols. Volatile anesthetics are not permitted in this arm. Sedation is adjusted to the same clinical targets as the intervention arm​.
