title: Impact of oral melatonin on critically ill adult patients with ICU sleep deprivation: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Sleep deprivation is common in critically ill patients in intensive care units (ICU). It can result in delirium, difficulty weaning, repeated nosocomial infections, prolonged ICU length of stay and increased ICU mortality. Melatonin, a physiological sleep regulator, is well known to benefit sleep quality in certain people, but evidence for the effectiveness in ICU sleep disturbance is limited.
  
  
  METHODS
  This study has a prospective, randomized, double-blind, controlled, parallel-group design. Eligible patients are randomly assigned to one of the two treatment study groups, labelled the 'melatonin group' or the 'placebo group'. A dose of 3 mg of oral melatonin or placebo is administered at 9:00 pm on four consecutive days. Earplugs and eye masks are made available to every participant. We plan to enrol 198 patients. The primary outcome is the objective sleep quality measured by the 24-hour polysomnography. The secondary outcomes are the subjective sleep quality assessed by the Richards Campbell Sleep Questionnaire, the anxiety level evaluated by the Visual Analogue Scale-Anxiety, the number of delirium-free days in 8 and 28 days, the number of ventilation-free days in 28 days, the number of antibiotic-free days, ICU length of stay, the overall ICU mortality in 28 days and the incidence and severity of the side effects of melatonin in ICU patients. Additionally, the body stress levels, oxidative stress levels and inflammation levels are obtained via measuring the plasma melatonin, cortisone, norepinephrine, malonaldehyde(MDA), superoxide dismutase(SOD), interleukin-6 (IL-6) and interleukin-8 (IL-8)concentrations.
  
  
  CONCLUSIONS
  The proposed study will be the first randomized controlled study to use the polysomnography, which is the gold standard of assessing sleep quality, to evaluate the effect of melatonin on the sleep quality and circadian rhythms of ICU patients. The results may recommend a new treatment for ICU patients with sleep deprivation that is safe, effective and easily implementable in daily practice.
  
  
  BACKGROUND
  This study was registered with ClinicalTrials (NCT; registration number: ChiCTR-TRC-14004319) on 4 March 2013.
authors.forename: Huawei
authors.initials: H
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: Guobin
authors.initials: G
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.forename: Jiajia
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, 20A Fu Xing Men Wai Da Jie, Xicheng District, Beijing 100038, China. xxm_fxyy@sina.cn.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Xi
mesh_terms: D000284:Administration, Oral; D015415:Biomarkers / Q000097:blood; D002681:China; D002940:Circadian Rhythm / Q000187:drug effects; D002985:Clinical Protocols; D016638:Critical Illness; D004311:Double-Blind Method; D017052:Hospital Mortality; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D018836:Inflammation Mediators / Q000097:blood; D007362:Intensive Care Units; D007902:Length of Stay; D008550:Melatonin / Q000008:administration & dosage* / Q000009:adverse effects; D018384:Oxidative Stress; D017286:Polysomnography; D011446:Prospective Studies; D012107:Research Design; D012890:Sleep / Q000187:drug effects*; D012892:Sleep Deprivation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006993:Hypnotics and Sedatives; D018836:Inflammation Mediators; D008550:Melatonin