Impact of oral melatonin on critically ill adult patients with ICU sleep deprivation: study protocol for a randomized controlled trial

Abstract

BackgroundSleep 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/DesignThis 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.DiscussionThe 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.Trial registrationThis study was registered with ClinicalTrials (NCT; registration number: ChiCTR-TRC-14004319) on 4 March 2013.

The effect of chronotherapy on delirium in critical care – a systematic review

“…Although it is too early to recommend the use of melatonin or melatonergic agents as a prophylactic treatment of delirium, melatonin has been licensed in the UK for the short‐term treatment of insomnia in adults who are aged 55 and over (Bellapart and Boots, ; NICE, ). With significant chronotherapeutic benefits of improved sleep quality and latency, morning alertness and increased quality of life, this may also provide a clinically relevant alternative to conventional sedative‐hypnotic agents currently being used in critical care (Lemoine and Zisapel, ; Huang et al ., ). This is especially relevant for older patients in whom use of conventional agents may adversely affect cognition, memory, sleep structure and increase their risk of delirium (Glass et al ., ).…”

Effect of oral melatonin and wearing earplugs and eye masks on nocturnal sleep in healthy subjects in a simulated intensive care unit environment: which might be a more promising strategy for ICU sleep deprivation?

“…Sleep deprivation is a major concern in critically ill patients in the ICU, and is characterized by poor subjective sleep quality, a paucity of restorative sleep stages and loss of circadian rhythms. [ 1 ] Because of frequent arousals and awakenings, sleep in the ICU has a higher proportion of none-rapid eye movement (NREM) sleep stage 1 and 2 (or light sleep), and reduced restorative slow wave (SW) and rapid eye movement (REM) sleep [ 2 ], and might bring many adverse consequences, including impaired immune function, difficult weaning from mechanical ventilation, delirium and severe morbidity [ 3 ].…”

Emerging Role of Melatonin and Melatonin Receptor Agonists in Sleep and Delirium in Intensive Care Unit Patients

“…24 In this study, Huang and colleagues plan to enroll 198 critically ill patients who will be randomized to receive 3 mg of melatonin or placebo for 4 days. The primary outcome will be to assess the effects of melatonin on the 24-hour sleep-wake cycle and subjective sleep quality.…”