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\u201377] years, SAPS II 41 [34\u201354] points,MV11 [6\u2013
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\u20138,050) versus 300 (0\u20132100), p\0.001; BDZP equivalents: 1 (0\u2013105) versus 0 (0\u20138), p\0.001; haloperidol: 0 (0\u201315.9) versus 0 (0\u20133), p\0.001; propofol: 20 (0\u2013980) versus 0 (0\u201340), p\0.001; opiates: 2.5 (0\u201382.5) versus 0 (0\u201320), 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\u20130] versus 0 [0\u20130],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\u20131043. 2. Cigada M, et al.
J Criti Care 2008;23:349\u201335