Ibrahim Murad G, Bellomo Rinaldo, Hart Graeme K, Norman Trevor R, Goldsmith Donna, Bates Samantha, Egi Moritoki
Department of Intensive Care and Department of Medicine, University of Melbourne, Austin Hospital, Melbourne, VIC, Australia.
Crit Care Resusc. 2006 Sep;8(3):187-91.
Patients in the intensive care unit often suffer from lack of sleep at night. We hypothesised that nocturnal melatonin may increase observed nocturnal sleep in tracheostomised patients.
Double-blind, randomised, placebo-controlled pilot study.
ICU of a tertiary hospital.
Thirty-two ICU patients with tracheostomy who were not receiving continuous sedation.
We administered either oral melatonin (3mg) or placebo at 20:00. We collected pre- and post-dosage blood samples on Days 1 and 3 to confirm drug delivery. Primary outcome measure was number of hours of observed sleep at night, assessed by the bedside nurse. Secondary outcome measures included comparison of the incidence of agitation, assessed by score on the Riker Sedation-Agitation Scale, and requirement for sedatives or haloperidol to settle agitation.
Pre-treatment melatonin levels in the two groups were similarly low: 4.8 pg/mL (95% CI, 2.4-7.5) for melatonin versus 2.4 (95% CI, 1.6-3.2) for placebo (P=0.13). Post-treatment, melatonin levels increased significantly in the melatonin group compared with the placebo group (3543 pg/mL versus 3 pg/mL; P<0.0001). However, subsequent observed nocturnal sleep was similar in the two groups: 240 minutes (range, 75-331.3) for melatonin v 243.4 minutes (range, 0-344.1) for placebo (P=0.98). Observed diurnal sleep was also similar: 138.7 minutes (range, 50-230) with melatonin v 104 minutes (range, 0-485) for placebo (P=0.42). The incidence of agitation was non-significantly higher in the melatonin group (31% v 7%; P=0.11), while the requirement for extra sedation or use of haloperidol was slightly higher in the placebo group (57% versus 46%; P=0.56).
Melatonin is well absorbed, and a standard dose increases blood levels approximately 1000-fold. However, in this pilot assessment, these high levels failed to increase observed nocturnal sleep or induce other observable benefits in tracheostomised ICU patients.
重症监护病房的患者夜间常睡眠不足。我们推测夜间服用褪黑素可能会增加气管切开患者的夜间睡眠时间。
双盲、随机、安慰剂对照的试点研究。
一家三级医院的重症监护病房。
32例未接受持续镇静的气管切开重症监护病房患者。
我们在20:00给予口服褪黑素（3mg）或安慰剂。在第1天和第3天采集给药前和给药后的血样以确认药物递送情况。主要结局指标是床边护士评估的夜间观察到的睡眠时间。次要结局指标包括通过里克尔镇静 - 躁动量表评分评估的躁动发生率比较，以及使用镇静剂或氟哌啶醇来缓解躁动的需求。
两组治疗前褪黑素水平同样较低：褪黑素组为4.8 pg/mL（95%CI，2.4 - 7.5），安慰剂组为2.4（95%CI，1.6 - 3.2）（P = 0.13）。治疗后，褪黑素组的褪黑素水平与安慰剂组相比显著升高（3543 pg/mL对3 pg/mL；P < 0.0001）。然而，随后两组观察到的夜间睡眠时间相似：褪黑素组为240分钟（范围，75 - 331.3），安慰剂组为243.4分钟（范围，0 - 344.1）（P = 0.98）。观察到的日间睡眠时间也相似：褪黑素组为138.7分钟（范围，50 - 230），安慰剂组为104分钟（范围，0 - 485）（P = 0.42）。褪黑素组的躁动发生率略高于安慰剂组（31%对7%；P = 0.11），而安慰剂组额外使用镇静剂或氟哌啶醇的需求略高于褪黑素组（57%对46%；P = 0.56）。
褪黑素吸收良好，标准剂量可使血药浓度升高约1000倍。然而，在这项试点评估中，这些高血药浓度未能增加气管切开的重症监护病房患者观察到的夜间睡眠时间或带来其他可观察到的益处。
