Using inhaled anesthetics for sedation in critically ill COVID-19 patients in the ICU

SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival. Multicentre Open-label, Pragmatic, Randomized Controlled Trial and a Parallel Prospective (Non-randomized) Cohort Study

This study is testing if using inhaled anesthetics for sedation can help critically ill COVID-19 patients breathe better and recover faster while they are on a ventilator.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 800 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (Academic / other)
• Locations: 13 sites (Edmonton, Alberta and 12 other locations)
• Trial ID: NCT04415060 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of inhaled volatile anesthetics on ventilatory parameters and survival in critically ill patients suffering from COVID-19 or hypoxic respiratory failure. Participants will be mechanically ventilated and randomly assigned to receive either intravenous or inhaled sedation within 72 hours of starting treatment. The study aims to determine if inhaled agents can improve lung function and reduce the duration of mechanical ventilation. Patients will be monitored daily in the ICU and followed up for a year to assess outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who are mechanically ventilated and expected to remain so for at least one more day.

Not a fit: Patients who are not mechanically ventilated or those who do not require sedation for ventilation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance recovery rates and reduce the reliance on intravenous sedatives, improving overall patient outcomes in the ICU.

How similar studies have performed: Other studies have shown promising results with inhaled anesthetics in similar settings, suggesting potential benefits in this approach.

Eligibility criteria

Inclusion Criteria:

1. ≥ 18 years of age
2. Mechanically ventilated and expected to remain mechanically ventilated at the end of the next day
3. Receiving IV sedation by infusion or bolus for ≤72 hours to facilitate mechanical ventilation Transferred patients with escalating ventilation needs are eligible for recruitment within ≤72 hours of sedation commenced within the participating trial site that they were transferred to.

   Note: Intravenous sedation required to support mechanical ventilation includes use of one or more of the following agents: benzodiazepines, propofol, ketamine, barbiturates, alpha-2 agonist, opioids. Patients receiving intravenous opioids only i.e., fentanyl ≥ 50mcg/hour, hydromorphone ≥ 0.4mg/hour (or bolus q1h) for analgesia and sedation or agitation to assist mechanical ventilation are eligible for inclusion.
4. Mechanically ventilated patients +/- extracorporeal membrane oxygenation (extracorporeal life) support with:

   1. Proven or suspected (under investigation) COVID-19, or
   2. COVID-19 negative patients who have a PaO2FiO2 ratio ≤300 measured with arterial blood gas at least once during the 12 hours prior to enrollment.

Note: If arterial blood gas measurement is unavailable, the PaO2 can be imputed from the pulse oximetry measurement

Exclusion Criteria:

1. Contraindications to sedatives, such as propofol infusion syndrome or malignant hyperthermia;
2. Known allergy to any of the ingredients or components of the investigational products; sevoflurane or isoflurane;
3. Suspect or evidence of high intracranial pressure;
4. Severe brain injury that is likely to lead to sustained very low conscious levels or vegetative state
5. Severe neuromuscular disorder for example amyotrophic lateral sclerosis, Gullian Barre Syndrome that are the primary cause of needing ICU admission and mechanical ventilation
6. One-lung ventilation or pneumonectomy;
7. Ideal estimated tidal volume too low for delivery of inhaled agents. Target (6ml/kg) \< 200ml;
8. Use of inhaled prostacyclin which is contraindicated in the presence of a miniature vaporizer (i.e., Anesthesia Conserving Device). This agent has a high viscosity that leads to poor vaporization of the volatile agent. Note: Other inhaled pulmonary vasodilators such as nitric oxide can be safely administered in the presence of miniature vaporizers. Use of prostacyclin is permissible with an anesthesia machine and MADM;
9. Known pregnancy
10. Moribund patient not expected to survive \>12 hours

Where this trial is running

Edmonton, Alberta and 12 other locations

• University of Alberta Hospital — Edmonton, Alberta, Canada (Recruiting)
• Grey Nuns Community Hospital — Edmonton, Alberta, Canada (Recruiting)
• London Health Sciences Centre - University Hospital — London, Ontario, Canada (Recruiting)
• London Health Sciences Centre - Victoria Hospital — London, Ontario, Canada (Recruiting)
• The Ottawa Hospital — Ottawa, Ontario, Canada (Recruiting)
• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Recruiting)
• University Health Network - Toronto General Hospital — Toronto, Ontario, Canada (Recruiting)
• University Health Network - Toronto Western Hopsital — Toronto, Ontario, Canada (Recruiting)
• Centre Hospitalier de l'Université de Montréal — Montréal, Quebec, Canada (Recruiting)
• McGill University Health Centre - Royal Victoria Hospital — Montréal, Quebec, Canada (Recruiting)
• Hôpital Sacré-Coeur de Montréal — Montréal, Quebec, Canada (Recruiting)
• Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ) — Québec, Quebec, Canada (Active_not_recruiting)
• Universite de Sherbrooke — Sherbrooke, Quebec, Canada (Recruiting)

Study contacts

• Study coordinator: Angela Jerath, MD

Conditions Covid19; Hypoxic Respiratory Failure; sedation; ICU; volatile anesthetics