Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial.

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.

Service delivery model of extracorporeal membrane oxygenation in an Australian regional hospital.

BACKGROUND: The role of extracorporeal membrane oxygenation (ECMO) for adults in regional centres with low numbers of patients receiving ECMO is unclear. A robust service delivery model may assist in the quality provision of ECMO. OBJECTIVE: To describe a novel ECMO service delivery model in a regional Australian hospital, reporting on patient characteristics and outcomes before and after its implementation. METHODS: An observational cohort study of all patients receiving ECMO at the University Hospital Geelong intensive care unit before and after implementation of a new ECMO clinical service model. The program included intensivist training in cannulation and care for ECMO patients, nurse accreditation in ECMO maintenance, and establishing a relationship with an ECMO centre caring for a high number of patients. Data included ECMO caseload, circuit configuration, complications, durations of therapy, and survival to ECMO weaning and ICU and hospital discharge. RESULTS: During the 14-year period for which we collected data, 61 adults received ECMO: 21 (35%) before and 40 (65%) after implementation of the structured program. The median annual case rate increased significantly between periods from two (range, 0-5 cases) to 10 (range, 5-13 cases) (P < 0.01). Other changes from before to after implementation included more medical indications for ECMO (48% v 80%; P < 0.01), higher peripheral cannulation configuration (57% v 98%; P < 0.01) and greater intensivist involvement as cannulation proceduralists (29% v 80%; P < 0.01). There were no significant differences between cohorts in ECMO weaning or duration, complication rates or ICU or in-hospital mortality. CONCLUSIONS: Provision of ECMO in a tertiary regional hospital within a multifaceted clinical service model is feasible and safe. Partnership with a centre providing ECMO for a high number of patients during service development and delivery is desirable.