Bradley Wibrow1,2, F Eduardo Martinez3,4, Erina Myers5,6, Andrew Chapman7, Edward Litton8,9, Kwok M Ho8,7,10, Adrian Regli8,11,12, David Hawkins13, Andrew Ford8,14, Frank M P van Haren15,16,17, Simon Wyer18, Joe McCaffrey19, Alan Rashid20, Erin Kelty21, Kevin Murray21, Matthew Anstey5,8,22. 1. Intensive Care Unit, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. bradley.wibrow@health.wa.gov.au. 2. Medical School, University of Western Australia, Perth, WA, Australia. bradley.wibrow@health.wa.gov.au. 3. Intensive Care Unit, John Hunter Hospital, Newcastle, NSW, Australia. 4. School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia. 5. Intensive Care Unit, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. 6. School of Nursing, Midwifery, Health Sciences and Physiotherapy, Notre Dame University, Perth, WA, Australia. 7. Intensive Care Unit, Royal Perth Hospital, Perth, WA, Australia. 8. Medical School, University of Western Australia, Perth, WA, Australia. 9. Intensive Care Unit, St John of God Hospital, Subiaco, WA, Australia. 10. School of Veterinary and Life Sciences, Murdoch University, Perth, WA, Australia. 11. Intensive Care Unit, St John of God Murdoch Hospital, Murdoch, WA, Australia. 12. Medical School, The University of Notre Dame Australia, 19 Mouat Street, Fremantle, 6959, Australia. 13. Intensive Care Unit, Joondalup Health Campus, Joondalup, WA, Australia. 14. Royal Perth Hospital, Perth, WA, Australia. 15. Intensive Care Unit, St George Hospital, Sydney, Australia. 16. College of Health and Medicine, Australian National University, Canberra, Australia. 17. University of New South Wales Medicine and Health, Sydney, Australia. 18. Intensive Care Unit, Gosford and Wyong Hospitals, Gosford, Australia. 19. Intensive Care Unit, Barwon Health, Geelong, Australia. 20. Intensive Care Unit, Mater Hospital, Newcastle, Australia. 21. School of Population and Global Health, University of Western Australia, Perth, Australia. 22. School of Public Health, Curtin University, Perth, Australia.
Abstract
PURPOSE: Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients. METHODS: Multicentre, randomized, placebo-controlled, double-blind trial across 12 Australian ICUs recruiting patients from July 2016 to September 2019. Patients of at least 18 years requiring ICU admission with an expected length of stay (LOS) greater than 72 h; enrolled within 48 h of ICU admission. Indistinguishable liquid melatonin (4 mg; n = 419) or placebo (n = 422) was administered enterally at 21:00 h for 14 consecutive nights or until ICU discharge. The primary outcome was the proportion of delirium-free assessments, as a marker of delirium prevalence, within 14 days or before ICU discharge. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU) score. Secondary outcomes included sleep quality and quantity, hospital and ICU LOS, and hospital and 90-day mortality. RESULTS: A total of 847 patients were randomized into the study with 841 included in data analysis. Baseline characteristics of the participants were similar. There was no significant difference in the average proportion of delirium-free assessments per patient between the melatonin and placebo groups (79.2 vs 80% respectively, p = 0.547). There was no significant difference in any secondary outcomes including ICU LOS (median: 5 vs 5 days, p = 0.135), hospital LOS (median: 14 vs 12 days, p = 0816), mortality at any time point including at 90 days (15.5 vs 15.6% p = 0.948), nor in the quantity or quality of sleep. There were no serious adverse events reported in either group. CONCLUSION: Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of delirium compared to placebo. These findings do not support the routine early use of melatonin in the critically ill.
PURPOSE: Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients. METHODS: Multicentre, randomized, placebo-controlled, double-blind trial across 12 Australian ICUs recruiting patients from July 2016 to September 2019. Patients of at least 18 years requiring ICU admission with an expected length of stay (LOS) greater than 72 h; enrolled within 48 h of ICU admission. Indistinguishable liquid melatonin (4 mg; n = 419) or placebo (n = 422) was administered enterally at 21:00 h for 14 consecutive nights or until ICU discharge. The primary outcome was the proportion of delirium-free assessments, as a marker of delirium prevalence, within 14 days or before ICU discharge. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU) score. Secondary outcomes included sleep quality and quantity, hospital and ICU LOS, and hospital and 90-day mortality. RESULTS: A total of 847 patients were randomized into the study with 841 included in data analysis. Baseline characteristics of the participants were similar. There was no significant difference in the average proportion of delirium-free assessments per patient between the melatonin and placebo groups (79.2 vs 80% respectively, p = 0.547). There was no significant difference in any secondary outcomes including ICU LOS (median: 5 vs 5 days, p = 0.135), hospital LOS (median: 14 vs 12 days, p = 0816), mortality at any time point including at 90 days (15.5 vs 15.6% p = 0.948), nor in the quantity or quality of sleep. There were no serious adverse events reported in either group. CONCLUSION: Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of delirium compared to placebo. These findings do not support the routine early use of melatonin in the critically ill.
Authors: Sangeeta Mehta; Deborah Cook; John W Devlin; Yoanna Skrobik; Maureen Meade; Dean Fergusson; Margaret Herridge; Marilyn Steinberg; John Granton; Niall Ferguson; Maged Tanios; Peter Dodek; Robert Fowler; Karen Burns; Michael Jacka; Kendiss Olafson; Ranjeeta Mallick; Steven Reynolds; Sean Keenan; Lisa Burry Journal: Crit Care Med Date: 2015-03 Impact factor: 7.598
Authors: Guy M McKhann; Maura A Grega; Louis M Borowicz; Michon Bechamps; Ola A Selnes; William A Baumgartner; Richard M Royall Journal: Arch Neurol Date: 2002-09
Authors: Timothy D Girard; Pratik P Pandharipande; Shannon S Carson; Gregory A Schmidt; Patrick E Wright; Angelo E Canonico; Brenda T Pun; Jennifer L Thompson; Ayumi K Shintani; Herbert Y Meltzer; Gordon R Bernard; Robert S Dittus; E Wesley Ely Journal: Crit Care Med Date: 2010-02 Impact factor: 7.598
Authors: Judith S L Partridge; Finbarr C Martin; Danielle Harari; Jugdeep K Dhesi Journal: Int J Geriatr Psychiatry Date: 2012-10-30 Impact factor: 3.485
Authors: John W Devlin; Russel J Roberts; Jeffrey J Fong; Yoanna Skrobik; Richard R Riker; Nicholas S Hill; Tracey Robbins; Erik Garpestad Journal: Crit Care Med Date: 2010-02 Impact factor: 7.598