Melatonin use and the risk of 30‐day mortality among US veterans with sepsis: A retrospective study

Prior research suggests melatonin has beneficial effects that could improve survival among sepsis patients. This exploratory analysis sought to compare 30-day survival among melatonin treated and untreated patients with sepsis. A retrospective cohort study was conducted among patients with a primary inpatient admission diagnosis for sepsis utilizing the International Classification of Diseases, versions 9 and 10, Clinical Modification (ICD-9-CM and ICD-10-CM) diagnosis codes between 2000 and 2021. Propensity score weighting was utilized, accounting for demographic, clinical, and laboratory factors. Weighted Cox models were estimated for 30-day in-hospital and 30-day overall survival. A total of 9386 patients were included in the study with 593 exposed to melatonin within the first day of hospitalization. Propensity score weighted Cox models reveal melatonin was associated with a 37.9% decreased risk of 30-day in-hospital mortality (HR = 0.621; 95% CI = [0.415-0.931]) and a 33.5% decreased risk of 30-day overall mortality (HR = 0.665; 95% CI = [0.493-0.897]). Factors associated with higher risk of both in-hospital and overall mortality include male sex, white race, age, higher Charlson comorbidity burden, sodium and potassium levels, intensive care unit stay, invasive ventilation, and vasopressor use. Higher serum albumin levels are associated with lower mortality risks. Among patients diagnosed with sepsis, exposure to melatonin was associated with a lower in-hospital and 30-day mortality. Additional research is warranted to fully understand the role of melatonin in sepsis.