Published: 2017-01-23

Adjuvant effect of melatonin on anesthesia induced by thiopental sodium in human subjects

Sengottaian Sivakumar, Bhavya Krishna


Background: Melatonin has unique properties of anxiolysis, hypnosis, and analgesia without impairing psychomotor skills. We studied the dose requirements of thiopentone for induction of general anesthesia following administration of oral melatonin compared to that of placebo.

Methods: The study is a prospective randomized double-blinded study conducted at Sri Ramachandra Medical College, which included 44 patients of ASA status I and II in the age group of 16 to 55 years who underwent elective surgical procedures under general anesthesia. Patients were randomly allocated to 2 groups by drawing lots. Group A received T. Melatonin 0.2mg/kg and Group B received placebo 120 minutes prior to induction of anesthesia. The baseline heart rate, blood pressure, Spo2 and Ramsay sedation score were noted down. After adequate preoxygenation, all patients received Injection Fentanyl 2 mcg/kg followed by Inj. Thiopentone 2.5% which was titrated to loss of eyelash reflex. The dose of thiopentone required was noted down in both the groups. Hemodynamic parameters (HR, Systolic and diastolic BP) were monitored prior to induction and every 3 minutes for the first 10 minutes.

Results: Both the groups were comparable with regard to age, weight and ASA status. Ramsay sedation score prior to induction of anesthesia was not significantly different in both the groups.

The mean dose of Thiopentone required in Group A (Melatonin) was 138.64±6.3 mg and 223.86±5.3 mg in Group B (Placebo) with P value 0.000. The mean per Kg dose requirement of Thiopentone in Group A was 2.54±0.64mg and 4.56±0.67mg in Group B (placebo) with P value 0.000. Hemodynamic parameters were similar in both the groups.

Conclusions: Administration of melatonin 0.2mg/kg body weight significantly reduced the induction dose of Thiopentone.


Adults, General anesthesia, Melatonin, Surgery, Thiopentone

Full Text:



Gordon N. The therapeutics of melatonin: a paediatric perspective. Brain Dev. 2000;22:213-17.

Herxheimer A. Does melatonin help people sleep? Br Med J. 2006;332:373-4.

Arendt J. The Pineal Gland and Pineal Tumours. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al., editors. Endotext [Internet]. South Dartmouth (MA):, Inc.; 2000

Dietary supplement fact sheets. National institute of health. Available at: factsheets/list-all/Melatonin/.

Sánchez-Barceló EJ, Mediavilla MD, Tan DX, Reiter RJ. Clinical uses of melatonin: evaluation of human trials. Curr Med Chem. 2010;17:2070-95.

Slominski A, Tobin DJ, Zmijewski MA, Wortsman J, Paus R. Melatonin in the skin: synthesis, metabolism and functions. Trends Endocrinol Metab. 2008;19:17-24.

Burgess HJ, Revell VL, Molina TA, Eastman CI. Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg. J Clin Endocrinol Metab. 2010;95:1-7.

Galano A, Tan DX, Reiter RJ. Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res. 2011;51:1-16.

Mukherjee D, Roy SG, Bandyopadhyay A, Chattopadhyay A, Basu A, Mitra E, et al. Melatonin protects against isoproterenol-induced myocardial injury in the rat: antioxidative mechanisms. J Pineal Res. 2010;48:251-62.

Dauchy RT, Blask DE, Dauchy EM, Davidson LK, Tirrell PC, Greene MW, et al. Antineoplastic effects of melatonin on a rare malignancy of mesenchymal origin: melatonin receptor-mediated inhibition of signal transduction, linoleic acid metabolism and growth in tissue-isolated human leiomyosarcoma xenografts. J Pineal Res. 2009;47:32-42.

Otmani S, Demazières A, Staner C, Jacob N, Nir T, Zisapel N, et al. Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers. Hum Psychopharmacol. 2008;23:693-705.

Luthringer R, Muzet M, Zisapel N, Staner L. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009;24:239-49.

Wade AG, Ford I, Crawford G, McConnachie A, Nir T, Laudon M, et al. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med. 2010;8:51.

Lee BJ, Parrott KA, Ayres JW, Sack RL. Design and evaluation of an oral controlled release delivery system for melatonin in human subjects. Int J Pharmaceutics. 1995;124:119-27.

Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S. Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry. 2009;17:166-9.

Lee BJ, Ryu SG, Cui JH. Formulation and release characteristics of hydroxypropyl methylcellulose matrix tablet containing melatonin. Drug Dev Ind Pharm. 1999;25:493-501.

Paul MA, Miller JC, Gray GW, Love RJ, Lieberman HR, Arendt J. Melatonin treatment for eastward and westward travel preparation. Psychopharmacology (Berl). 2010;208:377-86.

Lane EA, Moss HB. Pharmacokinetics of melatonin in man: first pass hepatic metabolism. J Clin Endocrinol Metab. 1985;61:1214-6.

Di WL, Kadva A, Johnston A, Silman R. Variable Bioavailability of Oral Melatonin (letter) N Engl J Med. 1997;336:1028-9.

DeMuro RL, Nafziger AN, Blask DE, Menhinick AM, Bertino JS Jr. The absolute bioavailability of oral melatonin. J Clin Pharmacol. 2000;40:781-4.

Waldhauser F, Waldhauser M, Lieberman HR, Deng MH, Lynch HJ, Wurtman RJ. Bioavailability of Oral Melatonin in Humans. Neuroendocrinology. 1984;39:307.

Fourtillan JB, Brisson AM, Gobin P, Ingrand I, Decourt JP, Girault J. Bioavailability of melatonin in humans after day-time administration of D(7) melatonin. Biopharm Drug Dispos. 2000;21:15-22.

Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336:186-95.

Kopin IJ, Pare CM, Axelrod J, Weissbach H. The fate of melatonin in animals. J Biol Chem. 1961;236:3072-5.

Naguib M, Hammond DL, Schmid PG 3rd, Baker MT, Cutkomp J, Queral L, et al Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol Br. J. Anaesth. 2003;90(4):504-7.

Samarkandi AH. The comparative dose-response effects of melatonin and midazolam for premedication of adult patients: a double-blinded, placebo-controlled study. Anesth Analg. 2000;91(2):473-9.

Acil M, Basgul E, Celiker V, Karagöz AH, Demir B, Aypar U. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Eur J Anaesthesiol. 2004;21(7):553-7.

Miyoshi H, Ono T, Sumikawa K. Melatonin reduces minimum alveolar concentration for isoflurane in rats. Anesthesiology. 2001;95:A-113.

Kain ZN, MacLaren J, McClain BC, Saadat H, Wang SM, Mayes LC, et al. Safely used oral melatonin in children with themaximum dose of 0.4 mg/kg without any major side-effects and emergence in children undergoing anesthesia and surgery. Anesthesiology. 2009;111:44-9.

Ionescu D, Badescu C, Ilie A, Miclutia I, Iancu C, Ion D, et al. Melatonin as pre medication for laparoscopic cholecystectomy: A double blind, placebo controlled study. South Afr J Anaesth Analg. 2008;14:8-11.

Melatonin. Monograph. Altern Med Rev 2005;10:326-36.

Capuzzo M, Zanardi B, Schiffino E, Buccoliero C, Gragnaniello D, Bianchi S, et al. Melatonin does not reduce anxiety more than placebo in the elderly undergoing surgery. Anesth Analg 2006;103:121-3.