Kelleher Art Burgess, O'Donovan Mark, O'Doherty Deborah, Lavery Ros, Lehane Elaine, Saab Mohamad M
Catherine McAuley School of Nursing and Midwifery, University College Cork, Cork, Ireland.
College of Medicine and Health, University College Cork, Cork, Ireland.
PLoS One. 2025 Sep 8;20(9):e0332031. doi: 10.1371/journal.pone.0332031. eCollection 2025.
Melatonin supplements and melatonin receptor agonists are linked to reduced delirium in the Intensive Care Unit (ICU) which we hypothesised may affect the length of stay (LOS) in ICU or in hospital. In this review, we identified and critically appraised the literature on the effect of exogenous melatonin and melatonin receptor agonists on the ICU and/or hospital LOS among adults admitted to the ICU.
Six electronic databases and three trial registries were searched for randomised controlled trials (RCTs). Screening, risk of bias assessment, quality appraisal, and level of evidence assessment were conducted and cross-checked by two reviewers independently. Meta-analyses with disease-specific subgroups were conducted to assess the mean difference in LOS for exogenous melatonin and melatonin receptor agonists compared with a placebo.
Twenty RCTs were reviewed with 14 having a low risk of bias. For ICU LOS (18 studies) there was significant statistical heterogeneity (I2 = 73%); compared with placebo the 95% prediction interval for the mean difference was -3.18 and 1.39 days. For hospital stay (12 studies, I2 = 79%) the 95% prediction interval ranged from -6.68 to 3.52. Removing two statistical outliers, and correcting for publication bias, there was no overall statistically significant difference in mean ICU LOS (p-value = 0.298) or mean hospital LOS (p-value = 0.456). The subgroup analysis found statistically significant improvements for those who underwent coronary artery bypass graft surgery (ICU LOS -0.47 days, 95% CI: -0.78 to -0.16, p-value = 0.003); and patients with COVID-19 (hospital LOS -3.90 days, 95% CI: -6.28 to -1.51, p-value = 0.001).
There was a very low certainty of evidence that melatonin and melatonin receptor agonists were associated with reductions in ICU and hospital LOS in ICU patients overall. However, further research is needed for surgical patients and those with pneumonia.
褪黑素补充剂和褪黑素受体激动剂与重症监护病房（ICU）谵妄减少有关，我们推测这可能会影响ICU或医院的住院时间（LOS）。在本综述中，我们检索并批判性评价了关于外源性褪黑素和褪黑素受体激动剂对入住ICU的成年人的ICU和/或医院住院时间影响的文献。
检索六个电子数据库和三个试验注册库以查找随机对照试验（RCT）。由两名审阅者独立进行筛选、偏倚风险评估、质量评估和证据水平评估，并相互核对。进行特定疾病亚组的荟萃分析，以评估外源性褪黑素和褪黑素受体激动剂与安慰剂相比住院时间的平均差异。
共审查了20项RCT，其中14项偏倚风险较低。对于ICU住院时间（18项研究），存在显著的统计学异质性（I2 = 73%）；与安慰剂相比，平均差异的95%预测区间为-3.18至1.39天。对于住院时间（12项研究，I2 = 79%），95%预测区间为-6.68至3.52。去除两个统计异常值并校正发表偏倚后，ICU平均住院时间（p值 = ）或平均住院时间（p值 = ）没有总体统计学显著差异。亚组分析发现，接受冠状动脉搭桥手术的患者（ICU住院时间 -0.47天，95% CI：-0.78至-）有统计学显著改善；和COVID-19患者（住院时间 -3.90天，95% CI：-6.28至-）。
总体而言，证据的确定性非常低，表明褪黑素和褪黑素受体激动剂与ICU患者的ICU和医院住院时间减少有关。然而，手术患者和肺炎患者需要进一步研究。 （注：原文中部分p值未完整给出，译文保留原文格式）
