Inhaled sedatives could reduce lung inflammation, shorten the duration of ventilation and potentially improve survival

A team from Lawson Health Research Institute are being funded by the Government of Ontario’s COVID-19 Rapid Research Fund to study whether inhaled sedatives can replace those that are delivered intravenously in COVID-19 patients requiring ventilation. The multi-centre clinical trial aims to address a global shortage of intravenous (IV) sedatives while improving patient outcomes.

“When COVID-19 patients develop severe respiratory failure and need to be ventilated, they require sedation. While IV sedatives are currently used, there is concern about global drug shortages, particularly if there’s a second wave of COVID-19 in the fall,” explains Dr. Marat Slessarev, Scientist at Lawson and Critical Care Physician at London Health Sciences Centre (LHSC). “Even if we have enough ventilators, we won’t be able to ventilate patients without sedatives.”

The clinical trial, being co-led by Dr. Slessarev and Dr. Angela Jerath at Sunnybrook Health Sciences Centre, will study the replacement of IV sedatives with inhaled sedatives. Inhaled sedatives, also called volatiles, are widely available due to their use in operating rooms to sedate patients during surgery. While they have not been routinely used to sedate patients needing ventilation, early studies suggest they could be safe and even more effective than IV sedatives.

“Preliminary studies in non-COVID patients with severe respiratory failure suggest that inhaled sedatives can reduce lung inflammation, shorten the duration of ventilation and potentially improve survival. Inhaled sedatives could therefore reduce the pandemic’s strain on ventilator capacity while improving patient outcomes,” says Dr. Slessarev. “Since these drugs are safe, cheap and readily available, they can easily be used to address IV sedative shortages if found effective.”

The researchers will recruit approximately 800 patients from across Canada and the United States including patients from LHSC. Each patient will be randomized to receive either IV sedatives or inhaled sedatives. Patient outcomes such as survival and length of ventilation will be compared between the two groups to determine which method of sedation is most effective.

Given many survivors of critical illness experience cognitive impairment for months or even years after an intensive care unit (ICU) stay, the team is also planning a sub-study to assess whether one method of sedation results in better cognitive outcomes after treatment.

In addition to funding from the Government of Ontario, the study is being supported with funding from the Canadian Institutes of Health Research (CIHR), London Health Sciences Foundation and Sunnybrook Health Sciences Centre.

Robert DeLaet is a Consultant, Communications & External Relationsat Lawson Health Research Institute.

“This is the largest trial of its kind. If inhaled sedatives can shorten the length of ventilation or improve survival in patients with serve respiratory failure, this could cause a paradigm shift in the way we sedate patients in intensive care units (ICUs) around the world,” notes Dr. Slessarev.