Oral melatonin decreases need for sedatives and analgesics in critically ill patients

INTRODUCTION. The analgesic/sedative therapy is necessary notwithstanding presents important side effects. Critically ill frequently present alterations of the circadian rhythm, delirium and agitation episodes with the risk of receiving additional sedation. The dramatically reduced endogenous blood melatonin level (both in the basal levels and in night peaks) could play a role in this context. OBJECTIVES. Reducing the need for sedatives and analgesic drugs by the oral administration of melatonin in high-risk critically ill [1] treated with conscious sedation [2]. METHODS. Double-blind RCT between placebo and Melatonin (3 9 2 mg), administered daily at 8 and 12 p.m. from the third ICU day until discharge. Inclusion criteria: ageC18 years, SAPSII[32 points, expected mechanical ventilation (MV) C4, practicability of gastroenteric tract. All patients were treated according to the local guidelines: propofol or midazolam during the first 48 h, immediate introduction of enteral sedation with hydroxyzine (until 600 mg/die) and supplementary lorazepam (until 16 mg/die) if necessary. Therapy was titrated at least three times a day, in order to obtain a conscious sedation (RASS = 0) as soon as possible. RESULTS. 96 patients enrolled: age 72 [60–77] years, SAPS II 41 [34–54] points,MV11 [6– 22] days. Diagnosis: 17 pancreatitis, 37 acute lung diseases, 23 acute heart diseases, 19 other. The analgesic/sedative therapy during the first 3 ICU days (clinical stabilization) was not different between groups. Melatonin administration determined: early weaning from sedatives and analgesics (Fig. 1; p = 0.0005); significant decrease in total administered doses of hydroxyzine: 2,700 (100–8,050) versus 300 (0–2100), p\0.001; BDZP equivalents: 1 (0–105) versus 0 (0–8), p\0.001; haloperidol: 0 (0–15.9) versus 0 (0–3), p\0.001; propofol: 20 (0–980) versus 0 (0–40), p\0.001; opiates: 2.5 (0–82.5) versus 0 (0–20), p\0.001; decrease of pain events (VNR[3): 28.6 versus 23.7%, p\0.001; anxiety (VNR[3): 34.3 versus 29.8%, p\0.001; agitation (longer than 1 h): 34.3 versus 32.2%, p\0.001; decrease in physical restraints use: 41.8 versus 31.1%, p\0.001; higher RASS: 0 [-1–0] versus 0 [0–0],p = 0.003. CONCLUSIONS. Oral melatonin significantly decreased the need for sedative and analgesic drugs in critically ill high-risk patients treated with awake sedation (Clinicaltrial.gov n NCT00470821). REFERENCES. 1. Iapichino G, et al. Crit Care Med 2006;34:1039–1043. 2. Cigada M, et al. J Criti Care 2008;23:349–353