Plasma melatonin levels in hip fracture patients with and without delirium: A confirmation study

Melatonin plays a major role in maintaining circadian rhythm. Changes in melatonin metabolism might lead to circadian rhythm disturbances which are often observed in delirious patients. To assess if high morning plasma melatonin concentrations were associated with delirium. Consecutive hip fracture patients aged ≥65 years were included. Delirium was assessed daily with the Confusion Assessment Blood samples were collected at 11.00am on weekdays during first week of hospitalization. Melatonin was analyzed by liquid chromatography-tandem mass spectrometry. We analyzed 389 samples of 144 participants [mean age 84.0, 70 experienced delirium]. A Generalized Estimating Equations (GEE) model with outcome melatonin level in highest tertile ( >3.36 pg/ml) and covariates delirium group (i.e. never, before, during, post delirium), cognitive impairment, age, sex and anesthesia type, was constructed. Highest melatonin levels were associated with postoperative samples (Odds Ratio(OR) 2.11 compared to preoperative samples; 95% Confidence Interval(CI) 1.17–3.82, p = 0.01) and higher age (OR 1.05 per year; CI 1.01–1.11, p = 0.03), but not with delirium group(p = 0.35). Undergoing surgery and aging in general may induce changes in melatonin metabolism. Future research should focus on daily multiple melatonin measurements to determine whether melatonin supplementation might be beneficial for delirium treatment or prevention.