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Association Among Melatonin Dysregulation, Sleep Disorders, and Sepsis-Associated Delirium: A Prospective Cohort Study with Mediation Analysis

Zhao L, Cui Q, Dong S, Yan Q, Yang F, Shi H, Wang Y, Liu J et al.

Neurocritical care, 2026

99 participants

Abstract

Background: Sepsis-associated delirium (SAD) is a life-threatening complication in the intensive care unit (ICU). Although sleep disturbances are common in sepsis, their relationship with SAD remains poorly understood. We investigated the link between sleep disturbances, melatonin dysregulation, and SAD.

Methods: In this prospective cohort study, we longitudinally assessed 99 patients with sepsis. Sleep quality was evaluated using the Richards-Campbell Sleep Questionnaire (RCSQ) and melatonin concentration, and multivariable logistic analysis, propensity score matching (PSM), inverse probability weighting (IPW), mixed-effects models, Bayesian, and mediation analysis to adjust for confounding factors to evaluate the relationship of melatonin with sleep disorder and SAD.

Results: Sleep disorders preceded SAD onset with a duration-dependent effect (P 0.05). Mediation analysis demonstrated substantial mediating effects of melatonin concentrations measured at sleep disturbance onset (ADE = 0.60, P < 0.001), and melatonin reduction occurring alongside sleep disturbances was associated with SAD development [average causal mediation effects (ACME) = - 0.110, P = 0.024].

Conclusions: This study provides preliminary evidence that disrupted sleep patterns and altered melatonin secretion may contribute to the development of SAD in ICU patients. While our findings support melatonin not only as a risk factor for sleep disruption and SAD, but also as a biologically plausible candidate…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 99 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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