European Journal of Anaesthesiotogy 2005; 22: 189-196 © 2005 European Society of Anaesthesioiogy ISSN 0265-0215 Original Article Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study A. Samarkandi*, M. Naguib^, W. Riad*, A. Thalaj*, W. Alotibi*, E Aldammas*, A. Albassam^ King Saud Unwersity, Departments of Anesthesia and 'Surgery, Riyadh, Saudi Arabia; 'University of Iowa College of Medicine, Department of Anesthesia, Iowa City, IA, USA Summary Background and abjective: Unlike midazolam, melatonin premedication is not associated with cognitive impairment in adults despite its anxiolytic properties. The use of melatonin as a premedicant in children has not been reported. This randomized, double-blind, placebo-controlled study compared the perioperative effects of different doses of melatonin and midazolam in children. Methods: Seven groups of children (« = 15 in each) were randomly assigned to receive one of the following premedicants. Midazolam 0.1, 0.25 or 0.5mgkg~^ orally, melatonin 0.1, 0.25 or 0.5mgkg~^ orally each mixed in 15 mg kg acetaminophen, or placebo only (15 mg kg acetaminophen). Anxiety and temperament were evaluated before and after administration of the study drug, on separation from parents and on the intro- duction of the anaesthesia mask. At week 2 postoperatively, the behaviour of the children was measured by the Post Hospitalization Behaviour Questionnaire. Results: Melatonin or midazolam each in doses of 0.25 or 0.5 mgkg~^ were equally effective as premedicants in alleviating separation anxiety and anxiety associated with the introduction of the anaesthesia mask. A trend was noted for midazolam to prolong recovery times as the dosage increased. The use of melatonin was associ- ated with a lower incidence {P = 0.049) of excitement at 10 min postoperatively, and a lower incidence (P = 0.046) of sleep disturbance at week 2 postoperatively than that observed with midazolam and control groups. No postoperative excitement was noted in the melatonin groups at 20, 30 and 45 min. Discussion: Melatonin was not only as effective as midazolam in alleviating preoperative anxiety in children, but it was also associated with a tendency towards faster recovery, lower incidence of excitement postoperativeiy and a lower incidence of sleep disturbance at week 2 postoperatively. Keywords: ADJUVANTS. ANAESTHESIA, midazoiam, melatonin; ANAESTHESIA, DRUG THERAPY, premedication; PAEDIATRICS; RANDOMIZED CONTROLLED TRIALS; ANXIETY, separation. A large body of evidence indicates that the pineal hormone melatonin (N-acetyl-5-methoxytryptamine) has several important physiological functions, includ- ing regulation of circadian rhythms [11, regulation of the reproductive axis 12] and antioxidant activity [3]. Correspondence to: Prnf. Mohamed Naguib, University of Texas MD Anderson Cancer Ontcr, Department ol Anesrhesiology and Pain Medicine, 1515 Holcombe Boulevard. Unit -^2, Houston, TX 77()3(), USA. Tel: +1 3! 9 3'i6 7471; Fax: +1 2940 Accepted for publication May 2004 EJA 1930 However, it is perhaps the best known by medical and lay personnel alike for its hypnotic actions. The hyp- notic effects of melatonin are considered an integral component of its physiological role. For instance, intravenous (i.v.) administration of large doses of melatonin to rats resulted in hypnotic effects similar to that observed with equipotent doses of thiopental and propofol [4]. Oral melatonin is used to enhance both the onset and quality of sleep (51, alleviate jet lag 16], for premedication of adult patients [7,81 and for treatment of sleep disorders in adults [91 as well