Clinical effects of oral melatonin in high-risk critically ill

INTRODUCTION. Endogenous blood melatonin in critical patients is often dramatically low, in both basal levels and night peaks. Exogenous supplementation could determine hypnogogue, immunomodulating and antioxidant effects. Prolonged administration (possible undesirable effects: sleepiness, bronchospasm, accumulation) has not previously been described in critically ill. OBJECTIVES. Evaluating safety and clinical effects of oral melatonin in high-risk critically ill [1] treated with conscious sedation [2]. METHODS. Double-blind RCT between placebo andmelatonin (3 mg92), administered daily at 8 and 12 pm from the third ICU day until discharge. Inclusion criteria: age C 18, SAPS II[32, expected mechanical ventilation (MV) C 4, practicability of gastroenteric tract. Statistical analysis performedwithmixed-effects regressionmodels for repeatedmeasures (Stata 11). RESULTS. 96 patients enrolled: age 72 [60\u201377] years, SAPS II 41 [34\u201354] pts,MV11 [6\u201322] days. Diagnosis: 17 pancreatitis, 37 acute lung diseases, 23 acute heart diseases, 19 other. Melatonin fastened sepsis resolution and ventilation weaning; it also guaranteed hemodynamic stability and helped restoring a quite normal circadian rhythm (Table 1). Differences in length of stay, days of MV and ICU/hospital mortality were not statistically significant. Undesirable effects were not reported. CONCLUSIONS. Melatonin administration was shown safe regarding cardio-respiratory and neurological stability. It determined fastened sepsis resolution in both lab measurements (WBC, PLT, bilirubin) and clinical observations (SOFA, septic state) probably due to its immunomodulative action and reactive oxygen species scavenging. The Melatonin group had faster ventilation weaning; nurse-observed decreased sleep hours in the morning/afternoon and increased in the night highlighted a quite restored circadian rhythm. GRV was not different, as the need for bronchodilators; no excessive sleepiness was shown. No differences in MV days, ICU days or ICU/hospital mortalitywere reported, being this study notpowered for these outcomes. In two post-hoc analyses, Melatonin decreased MV days (p = 0.013 in patients treated [7 days) and ICU mortality (p = 0.047 inpatients treated[40 days), suggesting the necessity of newand adequately powered studies for long-term ICU patients. (Clinicaltrial.gov n_ NCT00470821