A randomised trial of the pro-phylactic use of melatonin in critically ill patients to evaluate if this leads to a reduction in incidence of delirium (Pro-MEDIC study)

Inclusion criteria: Patients admitted to the Intensive Care Unit, identified by the treating intensivist as expected to have an ICU length of stay >72 hours. Patients must be enrolled within 48 hours of their ICU admission. Exclusion criteria: 1 Patients already on melatonin before their admission to ICU 2 Prior hypersensitivity reaction to any of the components of the study drug 3 Patients expected to be discharged within 72 hrs of their ICU admission 4 Non English speaking 5 Expected or inevitable death within next 48 hours 6 Patients that are not expected to improve adequately to be able to be assessed with a CAM‐ICU score during their ICU stay 7 Patients that are not able to be assessed due to neurological problems that would affect their ability to participate in a CAM‐ICU assessment (as judged by treating physician) 8 No enteral route – melatonin not available in intravenous formulation 9 Pregnancy or breastfeeding. 10. Hepatic impairment defined as Alanine Transferase (ALT) >500 IU/L, previous liver transplant or liver cirrhosis categories Childs‐Pugh B and C. Delirium Melatonin (4mg) to be given once daily at 21:00 (oral or nasogastric medication) to intensive care patients who have an expected ICU length of stay >72 hrs. Patients must be enrolled within 48 hrs of their admission. Given for 14 days or until ICU discharge (whichever is shorter). The decision on whether nasogastric or oral route is used will be left up to the patient and bedside nurse. Melatonin is inexpensive with an excellent safety profile and is widely used in the community. It is a natural hormone stimulated by low light, peaking during the main sleep period. It helps regulate the sleep‐wake cycle, which is a problem in ICU. Serum melatonin levels are lower post surgery, in delirious post surgical patients and in those administered opioids. Drops in melatonin levels and fluctuations in its metabolite 6‐SMT are associated with delirium. Administered by bedside ICU nurse and adherence will be monitored by the examining the patients medication chart Delirium free assessments (as measured by CAM‐ICU score) Severity of delirium as measured by CAM‐S score;Mortality;Length of ICU stay ‐ this will be assessed by the principal investigator or research co‐ordinator at each site using computer results systems linked to medical records;Hospital length of stay ‐ this will be assessed by the principal investigator or research co‐ordinator at each site using computer results systems linked to medical records or medical records themselves;Ventilator days ‐ this is recorded in ICU systems already and will be extracted by the research co‐ordinator or principal investigator;Physical restraints ‐ yes/no each day during ICU stay or 14 days (whichever is shorter) ‐ nursing staff will report whether they used physical restraints that day;Anti‐psychotics ‐ these will be recorded as total dose each day ‐ recorded on case report form;Economic cost ‐ cost consequence analysis using cost of length of stay in ICU if there is a reduction in length of stay in the intervention group;Sleep quality ‐ total sleep time by polysomnography;Sleep quality ‐ sleep efficiency on polysomnography;Sleep quality ‐ percentage REM sleep by polysomnography;Sleep quality ‐ arousal index by polysomnography