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Melatonin in critically ill patients

We read the article (1) by K. Olofsson et al. with much interest. I believe evidence for the altered secretion in critically ill patients is accumulating (2—6). But unfortunately the studies directly demonstrating the usefulness of melatonin in the intensive care, is lacking apart from one pilot study (7). I would like to report one of several patients in whom we used melatonin for sleep disturbance in ICU. A 33-year-old healthy male patient was admitted to intensive care unit after a road traffic accident with significant chest injuries (flail chest, bilateral hemo-pneumo thoraces and lung contusions). He was managed with CPAP initially but subsequently required tracheal intubation and ventilation. He developed sepsis/ARDS during his stay in the ICU and was managed according to standard protocols. Initially, he was sedated with propofol and alfentanil and later with midazolam and morphine. He had a tracheostomy on the tenth day and respiratory weaning commenced. Weaning was prolonged despite good gas exchange and lung mechanics. He was agitated and had poor sleep at night despite temazepam and/or haloperidol, and often required propofol. During the daytime he was very drowsy and exhausted, requiring assisted ventilation. We started him on 5 mg of melatonin at night but it helped little on the first night. He slept for 8 h on the second night. He was drowsy but rousable to a loud voice in the morning. The melatonin dose was reduced to 2.5 mg. He remained settled at night and alert and cooperative during the daytime. Weaning was completed in 4 days and melatonin was continued for a further 3 days. Follow-up after 1 month in the clinic did not show any abnormalities. We used melatonin in 22 patients between 2001 and 2004. Because there are no guidelines regarding the indication or dosage of melatonin, we used our clinical judgment to guide our therapy. Generally, we consider melatonin if it is felt sleep disturbance/agitation is not responding to benzodiazepines and/or haloperidol and is interfering with the weaning. The usual starting dose is 5 mg and adjusted according to response normally to between 2.5 and 10 mg. Although we do not have any objective data regarding quantity and quality of sleep, our general observation is melatonin does help to improve the duration of sleep in most patients. We normally continue for 7—10 days. We have not seen any side-effects except drowsiness in some patients who need dose adjustment. This case report illustrates the potential benefit of melatonin in critically ill patients with sleep disturbance in ITU. Melatonin is manufactured (Penn Pharmaceuticals, Tredeger, Gwent, UK) to the same standard as other medicines and has a production certificate. However, like magnesium sulphate in pre-eclampsia, it has no product licence and is used at the clinician’s discretion. We need large control studies to establish the efficacy, dosage and safety of melatonin in sleep disturbance in ICU patients.