HormonesMelatonin

Sleep disorders precede and increase the risk of sepsis-associated delirium, with melatonin dysregulation mediating this relationship

In a prospective cohort of 99 ICU patients with sepsis, sleep disorders preceded SAD onset with a duration-dependent effect and were associated with a 1.45-7.69-fold higher risk of delirium across multiple analyses. Lower melatonin concentrations correlated with worse multidimensional sleep impairment, and mediation analysis showed that melatonin reduction occurring alongside sleep disturbances was associated with SAD development (ACME = -0.110, P = 0.024).

Last updated: Jul 28, 2026โ€ข0 RCTsโ€ข๐Ÿ“– Read as article โ†’

Evidence Score

Evidence Score34/100
Human RCTโ˜†โ˜†โ˜†โ˜†โ˜†
Meta-analysisโ˜†โ˜†โ˜†โ˜†โ˜†
Mechanismโ˜…โ˜…โ˜…โ˜…โ˜…
Safetyโ˜…โ˜…โ˜…โ˜…โ˜†
Confidencelow

Study Evidence

Study 1. Association Among Melatonin Dysregulation, Sleep Disorders, and Sepsis-Associated Delirium: A Prospective Cohort Study with Mediation Analysis.

observational

Zhao L, Cui Q, Dong S, Yan Q, Yang F, Shi H, Wang Y, Liu J, Li Y ยท Neurocritical care (2026)

Participants: N/A
Duration: Not specified in abstract
Intervention: Observational assessment of sleep quality (RCSQ) and melatonin concentrations
Outcome: Sepsis-associated delirium (SAD) incidence, sleep quality, melatonin levels
Effect Size: Odds ratio range 1.45-7.69 for delirium risk; ฮฒ = 7.65-13.10 for melatonin-sleep impairment; ACME = -0.110
Population: 99 ICU patients with sepsis

Result:

PubMed: 42469580DOI: 10.1007/s12028-026-02594-0

Mechanism Graph

Sepsis induces sleep disturbances and melatonin dysregulation
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Lower melatonin concentrations impair sleep continuity and overall sleep quality
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Sleep disorders precede SAD onset with duration-dependent effect
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Melatonin reduction mediates the link between sleep disruption and SAD development

Limitations

  • โš Observational design cannot establish causality
  • โš Potential influence of unmeasured confounders (e.g., sedation, critical illness severity) not fully excluded
  • โš Small sample size (n=99) limits generalizability

Frequently Asked Questions

What is the relationship between sleep disorders and sepsis-associated delirium?โ–ผ

Sleep disorders precede SAD onset with a duration-dependent effect and are associated with a 1.45- to 7.69-fold higher risk of delirium.

How does melatonin dysregulation contribute to SAD?โ–ผ

Lower melatonin concentrations correlate with worse sleep quality and continuity, and melatonin reduction at the onset of sleep disturbances mediates the development of SAD.

Was the effect of sedation controlled for in this study?โ–ผ

Yes, the biphasic melatonin suppression in SAD patients was independent of sedation exposure (P > 0.05).

What statistical methods were used to adjust for confounding?โ–ผ

Multivariable logistic analysis, propensity score matching, inverse probability weighting, mixed-effects models, Bayesian analysis, and mediation analysis were used.

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References

  1. 1.Zhao L, Cui Q, Dong S, Yan Q, Yang F, Shi H, Wang Y, Liu J, Li Y. "Association Among Melatonin Dysregulation, Sleep Disorders, and Sepsis-Associated Delirium: A Prospective Cohort Study with Mediation Analysis.." Neurocritical care, 2026. PMID: 42469580 DOI: 10.1007/s12028-026-02594-0
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