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/design: 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.

Discussion: 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.

Trial registration: This study was registered with ClinicalTrials (NCT; registration number: ChiCTR-TRC-14004319) on 4 March 2013.

Figures

Figure 1

A bedside flowchart for pain management in ICU patients.1Consider the patient not cooperative if: RASS < -2/CAM-ICU+/communication or linguistic barriers. 2Verbal Numeric Rating (VNR) 0 = no pain, 10 = maximal conceivable pain. Ask:“Can you quantify your pain between 0 and 10?”. Consider at rest and breakthrough pain (e.g. = coughing, tracheo-bronchial aspiration). 3Consider the evaluation as reliable if it takes into account the subjective parameters the patients uses to evaluate their pain: cultural, religious and familial aspects, expectation for secondary benefits. 4Behavioral Pain Scale (BPS) 0 = absence of pain, 12 = maximal pain. -Facial expression: 1. Relaxed/2. Partially tightened/3. Fully tightened/ 4. Grimacing. -Upper limbs: 1. No movement/2. Partially bent/3. Fully bent with finger flexion/4. Permanently retracted. -Compliance to ventilation: 1. Toleration movement/ 2. Coughing but tolerating ventilation for most of the time/ 3. Fighting ventilator/4. Unable to control ventilation.

Figure 2

A bedside flowchart for agitation management in ICU patients.1Always aim for RASS target =0/-1 (patient awake and tranquil, well adapted despite invasive tool and critical condition). RASS target may be between -2 to -4 if required by clinical conditions. 2Sepsis, hypo-perfusion, hypo/hyperglycemia, hypoxia, fever, electrolyte imbalance, alkalosis/acidosis. 3Mode of ventilation; bladder catheter positioning; bronchial aspiration.

Figure 3

A bedside flowchart for delirium management in ICU patients.1Sepsis, hypo-perfusion, hypo/hyperglycemia, hypoxia, fever, electrolyte imbalance, alkalosis/acidosis. 2None pharmacological protocol. Orientation: Use patient’s visual and auditory aids, Encourage communication calling the patient by name, Availability of patient’s personal belongings, Coherence between physicians and staff intervention, Use music or TV during the daytime. Environment: Lights off during the night, on during the daytime, Orient patients’ beds to allow vision of sunlight, Discourage sleep during the daytime, Patient mobilization and physiotherapy during the daytime, Control excessive noise during the daytime, Avoid medical and nursing procedures during the night. 3Consider to stop or decrease deliriogenic therapy: anticholinergic drug, metoclopramide, inhibitor of protonic pump, promethazine, etc.

Figure 4

The trial procedures flow sheet. ICU, Intensive care unit; PSG, Polysomnography; RCSQ, Richards Campbell sleep questionnaire; SOFA, Sequential organ failure assessment; VAS-A, Visual analogue scale-anxiety.