Sodium oxybate versus midazolam for end-of-life continuous deep sedation: a randomised controlled trial

At the end of life, some patients with refractory suffering require deep continuous sedation. Based on the pharmacological properties, we hypothesised that sodium oxybate may offer advantages in these particular situations by preventing sedation lightening, a limitation reported with midazolam, the currently recommended agent.This trial aimed to compare the efficacy of sodium oxybate and midazolam for deep continuous sedation at the end of life.

This single-centre, single-blind, parallel-group, randomised trial tested sodium oxybate versus midazolam for this indication. The primary outcome was the treatment success defined as the ability to achieve and maintain a Richmond agitation-sedation scale less than or equal to -4.Patients, admitted to the acute palliative care unit, were randomly assigned to receive one standard dose of sodium oxybate followed by the maintenance or a titration dose of midazolam with subsequent maintenance. Patients were blinded to group assignments. Analysis was performed using an intention-to-treat approach. This study was registered at ClinicalTrials.gov (NCT05085873).

Between 14 October 2021 and 9 October 2023, 22 patients were included. Treatment success was 100% (95% CI 71.5% to 100%) in the sodium oxybate group versus 0% (95% CI 0% to 28.5%) in the midazolam group (p<0.0001). No severe adverse events were reported.

This first end-of-life randomised controlled trial comparing midazolam with another sedative suggests that sodium oxybate may offer more stable continuous deep sedation, with fewer fluctuations in sedation depth. These findings support the potential for improving patient comfort in this specific context.