Combination of Melatonin and Non-pharmacological Strategies on Delirium Prevention in ICU – A Randomized Controlled Trial

INTRODUCTION: Prevalence of delirium in Indian ICUs accounts to about 68% with inpatient mortality about 30%.(1) Physiological alterations and dynamic ICU environment may disrupt sleep, thus precipitating ICU delirium.(2) Therefore, promoting sleep with sleep bundles by combining melatonin(3) with non-pharmacological measures like ear plugs and eye mask may be beneficial to reduce ICU delirium.(4) OBJECTIVES: To determine the effectiveness of combining melatonin and non-pharmacological measures like ear plugs and eye mask prophylactically to reduce the occurrence of delirium in ICU patients and to determine its impact on sleep. MATERIALS AND METHODS: After institutional scientific and ethical committee approval, the study was registered under CTRI with reference number CTRI/2024/01/061285. With written informed consent, 66 adult patients admitted to ICU, expected to stay in the ICU for 24 h or more, able to communicate verbally, understand sleep questionnaire and satisfying the inclusion/exclusion criteria were randomised into the Melatonin and the Control group (33 patients each). The Melatonin group received 3mg of oral Melatonin along with ear plugs and eye mask at 21.00 hrs for first three consecutive nights of ICU stay or hospital stay. Both the groups received routine care including, early mobilisation, physiotherapy, daily family engagement, minimising night activities/procedures. Their CAM-ICU, RCSQ (Richards-Campbell Sleep Questionnaire) scores and ear plugs-eye mask effectiveness and comfort were recorded daily. p value of <0.05 was considered as statistically significant after assuming all the rules of statistical tests. RESULTS: There was no difference in the demographics between the two groups. The CAM-ICU showed a significant difference on Day 3 (P = 0.02) with more patients in the control group experiencing delirium. There was noteworthy improvement in all parameters of sleep in the Melatonin group with global RCSQ score of 66.94 ± 9.14 vs 57.59 ±11.45 in the control group (P = 0.001). Night time sleep also showed betterment in the melatonin group of 5.09 ± 0.95 hrs vs 3.92 ±1.03 hrs in the control group. Day time sleep, LOS in ICU and hospital and mortality were unaffected. With time, subjects found ear plugs easier to use, and eye mask more comfortable, more effective and easier to use (p< 0.05). While univariate analysis revealed LOS in ICU (2.91 ±1.38 vs 3.12 ±1.24 days) and LOS in hospital (4.85 ± 2.88 vs 5.97 ± 2.79 days) to be a prominent factor for delirium, age was found to influence sleep in both univariate and multivariate analyses. DISCUSSION/CONCLUSION: A sleep bundle comprising of oral melatonin with non-pharmacological measures were employed by us and showed favourable outcomes similar to many studies.(3,4,5) Eye masks were better tolerated compared to ear plugs, however, both were effective and their use at night could be encouraged. Multi-component interventions in other studies have successfully reduced delirium incidence and promoted sleep.(6,7) In conclusion, melatonin, ear plugs and eye mask not only reduce the incidence of delirium, but also improve the quality of sleep in the ICU considerably.