The Effects of Melatonin Supplementation on Sleep Quality and Assessment of the Serum Melatonin in ICU Patients: A Randomized Controlled Trial

Abstract

Objectives: To evaluate whether the use of exogenous melatonin affects sleep, reduces the prevalence of delirium, and decreases the need for analgosedation and to assess whether serum melatonin indices correlate with exogenous administration in critically ill patients. Design: Double-blind, randomized, placebo-controlled study. Setting: Multicenter ICUs of two tertiary hospitals. Patients: A total of 203 adult patients who were admitted to the ICU and administered with analgesics and/or sedatives. Interventions: Oral melatonin (10 mg) or placebo for up to seven consecutive nights. Measurements and Main Results: The number of observed sleeping hours at night was assessed by the bedside nurse. Sleep quality was evaluated using the Richards Campbell Questionnaire Sleep (RCSQ). The prevalence of delirium, pain, anxiety, adverse reactions, duration of mechanical ventilation, length of ICU and hospital stays, and doses of sedative and analgesic drugs administered were recorded. The use of analgesics and sedatives was assessed daily. Melatonin levels were determined by enzyme-linked immunosorbent assay. Based on the RCSQ results, sleep quality was assessed to be better in the melatonin group than that in the placebo group with a mean (sd) of 69.7 (21.2) and 60.7 (26.3), respectively (p = 0.029). About 45.8% and 34.4% of participants in the melatonin and placebo groups had very good sleep (risk ratio, 1.33; 95% CI, 0.94–1.89), whereas 3.1% and 14.6% had very poor sleep (risk ratio, 0.21; 95% CI, 0.06–0.71), respectively. No significant difference was observed regarding the days free of analgesics or sedatives, the duration of night sleep, and the occurrence of delirium, pain, and anxiety. Melatonin serum peak levels at 2 am were 150 pg/mL (range, 125–2,125 pg/mL) in the melatonin group and 32.5 pg/mL (range, 18.5–35 pg/mL) in the placebo group (p < 0.001). Conclusions: Melatonin was associated with better sleep quality, which suggests its possible role in the routine care of critically ill patients in the future.

Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis

“…1 ), with a total of 17,140 participants [ 34 – 113 ]. Included trials were comprised of 54 (67.5%) pharmacological or sedation intervention studies [ 34 – 36 , 38 – 40 , 42 – 45 , 47 , 49 – 51 , 55 – 57 , 59 – 63 , 67 – 69 , 71 , 73 – 76 , 78 , 79 , 81 , 82 , 85 – 87 , 89 , 90 , 92 – 94 , 97 – 100 , 102 , 103 , 105 – 108 , 110 , 112 , 113 ] with 14,224 participants, 25 (31.3%) studies of non-pharmacological single or multi-component interventions with 2904 participants [ 37 , 41 , 46 , 48 , 52 , 53 , 57 , 58 , 64 – 66 , 70 , 72 , 77 , 80 , 83 , 84 , 88 , 91 , 95 , 96 , 101 , 104 , 109 , 111 ], and 1 study (1.2%) included a combination non-pharmacological with a pharmacological intervention with 12 participants [ 54 ]. Key features of all included trials are presented in detail in eTable 2.…”

“…Nine interventions studied in 31 trials ( N = 10,270) [ 34 – 36 , 38 , 40 , 44 , 50 , 51 , 55 , 56 , 59 , 63 , 67 , 69 , 71 , 73 , 74 , 76 , 79 , 81 , 82 , 85 , 89 , 93 , 97 , 98 , 102 , 103 , 107 , 113 ] connected to the evidence network for ICU length of stay (Table 1 , Fig. 2 C, eTable 5); 28% (10/36) of the pairwise comparisons included direct evidence.…”

Summary of Contact With Dr. Marik. Pulmonary Medicine and Critical Care. Eastern Virginia Medical School - Usa.

“…• Melatonin (slow release): Begin with 0.3 mg and increase as tolerated to 2 mg at night. [43][44][45][46][47][48][49][50] • Zinc 30-50 mg/day (elemental zinc). [23,30,32,33,[51][52][53][54][55] • B complex vitamins [56][57][58][59][60] • Ivermectin for postexposure prophylaxis (see ClinTrials.gov NCT04422561).…”

“…• Melatonin 10 mg at night (the optimal dose is unknown) [50] • Vitamin D3 2000-4000 IU/day. Calcifediol 0.2 mg is an alternative.…”

“…• Vitamin C 500-1000 mg q 6 hourly and Quercetin 250-500 mg BID (if available) • Zinc 75-100 mg/day • Melatonin 10 mg at night (the optimal dose is unknown) [50] • Vitamin D3 20,000-60,000 IU single oral dose. Calcifediol 0.2-0.5 mg is an alternative.…”