Patient with acute hypoxic respiratory failure (including those with COVID-19) require sedation to tolerate intubation and mechanical ventilation. Historically, these patients were sedated using intravenous sedatives (e.g. propofol, midazolam). While intravenous sedatives are easy to administer, they rely on liver and kidney metabolism for clearance from the body and their blood concentrations cannot be easily measured and therefore accurately titrated in individual critically ill patients. Given that liver and kidney functions are often impaired in critically ill patients, clearance of intravenous sedatives in individual patients is unpredictable. As a results, continuous administration of intravenous sedatives can lead to build up of these agents and their metabolites in patients’ blood, leading to prolonged sedation, delirium, delayed liberation from mechanical ventilation and longer ICU stays.

In contrast, inhaled anesthetic sedatives do not form active metabolites, are cleared from the body through the lungs, and their blood concentrations can be continuously monitored at the bedside using exhaled gas analysers. Additional benefits of inhaled anesthetic sedatives include dilation of airways, which helps improve gas exchange and help with secretion clearance, and reduction of inflammation, which reduces lung injury. In prior studies, these properties of inhaled anesthetic sedatives translated into shorter time to extubation, reduced lung inflammation, and shorter duration of mechanical ventilation and ICU length of stay. In the context of the pandemic, stocks and supplies of intravenous sedatives were running low, and inhaled anesthetic sedatives provide an alternative means for sedation of patients who require mechanical ventilation for hypoxic respiratory failure.

Inhaled anesthetic sedatives are used routinely every day to provide sedation to patients in the operating rooms worldwide. However, their delivery in the intensive care units (ICUs) requires additional equipment because ICUs ventilators are not equipped with special vaporizers that are found in the operating rooms. Most hospitals participating in the SAVE-ICU RCT are using miniature vaporizers to deliver inhaled sedatives to the patients and special scavenging equipment to capture unused gas. We also use bedside gas analyzers to measure levels of inhaled sedatives that are delivered to the patient, which provides additional safety to make sure that we are not under- or over-dosing individual patients with inhaled sedatives.