Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial

Area of Science:

• Critical Care Medicine
• Pharmacology
• Sleep Science

Background:

• Delirium is a frequent and distressing complication in critically ill patients, linked to worse outcomes.
• Previous studies on melatonin for delirium prevention have yielded inconsistent results.
• Effective preventative strategies for delirium in intensive care units (ICUs) are needed.

Purpose of the Study:

• To investigate if early enteral administration of melatonin reduces delirium prevalence in critically ill patients.
• To assess the impact of melatonin on sleep quality, length of stay, and mortality in the ICU.

Main Methods:

• A multicentre, randomized, placebo-controlled, double-blind trial involving 847 critically ill patients across 12 Australian ICUs.
• Patients received either 4 mg of liquid melatonin or a placebo enterally within 48 hours of ICU admission for 14 nights or until discharge.
• Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU), with the primary outcome being the proportion of delirium-free assessments within 14 days.

Main Results:

• No significant difference was observed in the proportion of delirium-free assessments between the melatonin (79.2%) and placebo (80%) groups (p=0.547).
• Secondary outcomes, including ICU and hospital length of stay, sleep quality, and 90-day mortality, also showed no significant differences between the groups.
• No serious adverse events were reported in either the melatonin or placebo arms.

Conclusions:

• Enteral melatonin initiated early in critically ill patients did not decrease the prevalence of delirium compared to placebo.
• The findings do not support the routine early use of melatonin for preventing delirium in the ICU.
• Further research may be needed to explore melatonin's role in specific subgroups or at different timings.