Montelukast and Delirium Risk During Intensive Care Unit (ICU) Stay: Findings from a Cohort Study

Background: Delirium is a frequent complication in critically ill patients and is associated with increased mortality, prolonged hospitalization, and long-term cognitive impairment. Montelukast, a leukotriene receptor antagonist commonly used in respiratory diseases, has been associated with neuropsychiatric adverse effects, including delirium. Evidence regarding its safety in critically ill adults is limited. This study aimed to investigate the association between montelukast use during ICU stay and the development of delirium and further evaluate its safety in the ICU. Methods: This retrospective cohort study was conducted at King Abdulaziz Medical City, Saudi Arabia, between January 2018 and December 2021. Adult critically ill patients (18– 79 years) who were admitted to ICUs for respiratory symptoms and categorized based on montelukast exposure during ICU stay. The primary outcome was assessing the incidence of delirium during ICU stay. Secondary outcomes included delirium duration, recurrence of delirium, delirium-free days, ventilator-free days, length of stay (LOS), safety outcomes (liver and kidney injury), 30-day and in-hospital mortality. Propensity score (PS) matching with a 1:4 ratio was performed to minimize baseline differences between the groups. Results: Out of 1590 screened patients, 1469 were included, and 44 received montelukast during ICU stay. After PS matching (1:4), montelukast use was associated with a significantly higher incidence of delirium (OR 4.66, 95% CI 1.63 to 13.34; P < 0.004). Among patients who developed delirium, mixed delirium was the most frequent subtype in the montelukast group (50% vs 12.5% in controls). There were no notable differences found in terms of delirium-free days, recurrence of delirium, liver or kidney injury, length of stay, ventilator-free days, or overall mortality. Conclusion: Our study demonstrates an association between montelukast use during ICU admission and a higher incidence of delirium. Prospective randomized studies are needed to confirm these findings. Keywords: delirium, delirium-free days, montelukast, respiratory diseases, critical illness, intensive care unit, ICU