Anesthetic Pharmacology Section Editor: James G. Bovill The Effects of Melatonin Premedication on Propofol and Thiopental Induction Dose–Response Curves: A Prospective, Randomized, Double-Blind Study Mohamed Naguib, MB, BCh, MSc, FFARCSI, MD* Abdulhamid H. Samarkandi, MB, BS, KSUF, FFARCSI† Mohamed A. Moniem, MD† Emad El-Din Mansour, MD† Ahmad A. Alshaer, MD† Hasan A. Al-Ayyaf, MB, BCh† Awatif Fadin, MB, BCh† Saleh W. Alharby, MB, BS, FRCS (Glas)‡ BACKGROUND: The effect of melatonin on the intraoperative requirements for IV anesthetics has not been documented. We studied the effect of melatonin premedi- cation on the propofol and thiopental dose–response curves for abolition of responses to verbal commands and eyelash stimulation. METHODS: This prospective, randomized, double-blind study included 200 adults with ASA physical status I. Patients received either 0.2 mg/kg melatonin or a placebo orally for premedication (n = 100 per group). Approximately 50 min later, subgroups of 10 melatonin and 10 placebo patients were administered various doses of propofol (0.5, 1.0, 1.5, 2.0, or 2.4 mg/kg) or thiopental (2.0, 3.0, 4.0, 5.0, or 6.0 mg/kg) for anesthetic induction. The ability of each patient to respond to the command, “open your eyes,” and the disappearance of the eyelash reflex were assessed 60 s after the end of the injection of propofol or thiopental. Dose–response curves were determined by probit analysis. RESULTS: Melatonin premedication decreased thiopental ED 50 values for loss of re- sponse to verbal command and eyelash reflex from 3.4 mg/kg (95%confidence interval, 3.2–3.5 mg/kg) and 3.7 mg/kg (3.5–3.9 mg/kg) to 2.7 mg/kg (2.6 –2.9 mg/kg) and 2.6 mg/kg (2.5–2.7 mg/kg), respectively (P  0.05). Corresponding propofol ED 50 values decreased from 1.5 mg/kg (1.4 –1.6 mg/kg) and 1.6 mg/kg (1.5–1.7 mg/kg) to 0.9 mg/kg (0.8 – 0.96 mg/kg) and 0.9 mg/kg (0.8 – 0.95 mg/kg), respectively (P  0.05). CONCLUSIONS: Melatonin premedication significantly decreased the doses of both propofol and thiopental required to induce anesthesia. (Anesth Analg 2006;103:1448 –52) The pineal hormone melatonin (N-acetyl-5- methoxytryptamine) regulates a variety of physiolog- ical processes, including circadian, cardiovascular, reproductive, and neuroendocrine functions, and en- hances immune responses (1–3). However, it is the hypnotic effects of melatonin that are considered an integral component of its physiological role (4,5). Administration of melatonin facilitates sleep onset and improves the quality of sleep (6 – 8). Premedicants decrease the intraoperative require- ments for IV anesthetics (9 –11). Although we previ- ously demonstrated that melatonin is an effective premedicant in both adult and pediatric surgical pa- tients (12–14), the effect of melatonin on the require- ments of IV anesthetics to induce anesthesia has not been documented. To that end, we designed and performed a prospective, randomized, double-blind study to evaluate the effect of melatonin premedica- tion on the dose–response curves of propofol and thiopental calculated for the two commonly used end-points: abolition of response to verbal commands and loss of eyelash reflex. METHODS After obtaining IRB approval from King Khalid University Hospital (Riyadh, Saudi Arabia) and writ- ten informed patient consent, we enrolled 200 adult patients of both sexes who met the criteria for ASA physical status I. Patients who had taken benzodiaz- epines, opioid drugs, or other sedative drugs within 1 mo of the planned date of surgery were excluded. Patients were randomly assigned to four groups (n = 50 patients per group) (according to a computer- generated list) based on whether they would receive 0.2 mg/kg melatonin premedication or placebo (sa- line) and the type of induction drug used (propofol or thiopental). The randomization list was maintained by the pharmacy. Before surgery, patients were trans- ported to an isolated, quiet room in the operating From the *Department of Anesthesiology and Pain Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and Departments of †Anesthesia and ‡Surgery, King Saud University, Riyadh, Saudi Arabia. Accepted for publication August 17, 2006. Supported by institutional and/or departmental sources. The results of this study were presented at the ASA Annual Meeting, Chicago, Illinois, October 14 –18, 2006. Address correspondence and reprint requests to Mohamed Naguib, MB, BCh, MSc, FFARCSI, MD, Department of Anesthesi- ology and Pain Medicine, University of Texas M.D. Anderson Cancer Center, Unit 409, 1400 Holcombe Boulevard, Houston, TX 77030. Address e-mail to naguib@mdanderson.org. Copyright © 2006 International Anesthesia Research Society DOI: 10.1213/01.ane.0000244534.24216.3a Vol. 103, No. 6, December 2006 1448