Volatile Anaesthetics in COVID-19 – a pilot study

Rationale:
Recent small studies in ARDS patients indicate that the use of volatile anaesthetic agents can improve oxygenation and decrease levels of a marker of epithelial injury and of some inflammatory markers, when compared with intravenous sedation. We hypothesize that using inhaled volatile anaesthetic agents as the primary sedative during mechanically ventilation in patients with COVID-19-associated ARDS improves gas exchange, ventilatory support requirements, and time to extubation.

Objective:
To investigate the feasibility of inhaled volatile anaesthetic agents in reducing the severity of COVID-19-associated ARDS.

Study design:
Single-centre, pragmatic, open-label, double cross-over randomised controlled pilot trial.

Study population:
Patients with COVID-19 requiring mechanical ventilation.

Intervention:
The administration of inhaled isoflurane for sedation, compared to intravenous sedation. In this pilot study, patients will intermittent receive inhaled or intravenous sedation, according to the randomisation scheme.

Pilot study primary endpoints:
Change in PaO2/FiO2 (P/F) ratio, oxygenation index, and ventilation parameters

Safety endpoints:
Haemodynamic stability, acute liver injury, acute kidney injury

Secondary endpoints:
In-hospital mortality, P/F ratio and oxygenation index at various time points, time to extubation, length of stay in the ICU, length of stay in the hospital, major complications (sepsis, renal failure, MI, stroke, requirement for ECMO, delirium, atrial fibrillation, and myocardial injury).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The burden to the patients is minimal: while this intervention is being tested, patients will be already sedated for mechanical ventilation. Furthermore, only routine care data will be used in this pilot study, and there will be no post-discharge follow-up.
Because of its common routine use in clinical anaesthesia, there is extensive experience with the use of isoflurane. The risks of the intervention are considered low and are mainly related the potential side effects of isoflurane, with a lowering effect on blood pressure the most likely (and very much controllable) side-effect.

Using inhaled volatile anaesthetic agents as the primary sedative during mechanically ventilation in patients with COVID-19-associated ARDS improves gas exchange and ventilatory support requirements

24, 48, 72 hours, hospital discharge

The administration of inhaled isoflurane for sedation, compared to intravenous sedation. In this pilot study, patients will intermittent receive inhaled or intravenous sedation, according to the randomisation scheme.