High-Dose vs. Low-Dose Melatonin: The Quest for Circadian Regulation in the ICU
Delirium remains one of the most significant challenges in modern intensive care medicine, particularly among patients requiring mechanical ventilation. Characterized by an acute onset of cognitive dysfunction, fluctuating levels of consciousness, and inattention, it affects up to 80 percent of patients in the intensive care unit (ICU). The consequences are profound, ranging from increased mortality and prolonged hospital stays to long-term cognitive impairment resembling Alzheimer’s disease. Given the potential role of circadian rhythm disruption in the pathogenesis of delirium, melatonin—an endogenous hormone regulating sleep-wake cycles—has been a subject of intense research. However, the DEMEL trial, recently published in Intensive Care Medicine, provides a sobering look at whether pharmacological melatonin supplementation can truly move the needle in delirium prevention.
