Prophylactic use of intravenous ondansetron versus ketamine - midazolam combination for prevention of shivering during spinal anesthesia: A randomized double-blind placebo-controlled trial


Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


Background: The aim of this study was to compare the efficacy intravenous (IV) ondansetron with ketamine plus midazolam for the prevention of shivering during spinal anesthesia (SA).
Materials and Methods: Ninety patients, aged 18–65 years, undergoing lower extremity orthopedic surgery were included in the present study. SA was performed in all patients with hyperbaric bupivacaine 15 mg. The patients were randomly allocated to receive normal saline (Group C), ondansetron 8 mg IV (Group O) or ketamine 0.25 mg/kg IV plus midazolam 37.5 µg/kg IV (Group KM) immediately after SA. During surgery, shivering scores were recorded at 5 min intervals. The operating room temperature was maintained at 24°C.
Results: The incidences of shivering were 18 (60%) in Group C, 6 (20%) in Group KM and 8 (26.6%) in Group O. The difference between Groups O and Group KM with Group C was statistically significant (P < 0.05). No significant difference was noted between Groups KM with Group O in this regard (P > 0.05). Peripheral and core temperature changes throughout surgery were not significantly different among three groups (P > 0.05). Incidence (%) of hallucination was not significantly different between the three groups (0, 3.3, 0 in Group O, Group KM, Group C respectively, P > 0.05).
Conclusion: Prophylactic use of ondansetron 8 mg IV was comparable to ketamine 0.25 mg/kg IV plus midazolam 37.5 µg/kg IV in preventing shivering during SA.


Ozaki M, Kurz A, Sessler DI, Lenhardt R, Schroeder M, Moayeri A, et al. Thermoregulatory thresholds during epidural and spinal anesthesia. Anesthesiology 1994;81:282-8.  Back to cited text no. 1
Jeon YT, Jeon YS, Kim YC, Bahk JH, Do SH, Lim YJ. Intrathecal clonidine does not reduce post-spinal shivering. Acta Anaesthesiol Scand 2005;49:1509-13.  Back to cited text no. 2
Ciofolo MJ, Clergue F, Devilliers C, Ben Ammar M, Viars P. Changes in ventilation, oxygen uptake, and carbon dioxide output during recovery from isoflurane anesthesia. Anesthesiology 1989;70:737-41.  Back to cited text no. 3
Guffin A, Girard D, Kaplan JA. Shivering following cardiac surgery: Hemodynamic changes and reversal. J Cardiothorac Anesth 1987;1:24-8.  Back to cited text no. 4
Buggy D, Higgins P, Moran C, O'Donovan F, McCarroll M. Clonidine at induction reduces shivering after general anaesthesia. Can J Anaesth 1997;44:263-7.  Back to cited text no. 5
Glosten B, Hynson J, Sessler DI, McGuire J. Preanesthetic skin-surface warming reduces redistribution hypothermia caused by epidural block. Anesth Analg 1993;77:488-93.  Back to cited text no. 6
Ikeda T, Kazama T, Sessler DI, Toriyama S, Niwa K, Shimada C, et al. Induction of anesthesia with ketamine reduces the magnitude of redistribution hypothermia. Anesth Analg 2001;93:934-8.  Back to cited text no. 7
Sagir O, Gulhas N, Toprak H, Yucel A, Begec Z, Ersoy O. Control of shivering during regional anaesthesia: Prophylactic ketamine and granisetron. Acta Anaesthesiol Scand 2007;51:44-9.  Back to cited text no. 8
Hopkin DA. Postoperative spasticity and shivering. Anaesthesia 1984;39:725-6.  Back to cited text no. 9
Kurz A, Sessler DI, Annadata R, Dechert M, Christensen R, Bjorksten AR. Midazolam minimally impairs thermoregulatory control. Anesth Analg 1995;81:393-8.  Back to cited text no. 10
Honarmand A, Safavi MR. Comparison of prophylactic use of midazolam, ketamine, and ketamine plus midazolam for prevention of shivering during regional anaesthesia: A randomized double-blind placebo controlled trial. Br J Anaesth 2008;101:557-62.  Back to cited text no. 11
Gardner C, Perren M. Inhibition of anaesthetic-induced emesis by a NK1 or 5-HT3 receptor antagonist in the house musk shrew, Suncus murinus. Neuropharmacology 1998;37:1643-4.  Back to cited text no. 12
Dawson NJ, Malcolm JL. Initiation and inhibition of shivering in the rat: Interaction between peripheral and central factors. Clin Exp Pharmacol Physiol 1982;9:89-93.  Back to cited text no. 13
Hindle AT. Recent developments in the physiology and pharmacology of 5-hydroxytryptamine. Br J Anaesth 1994;73:395-407.  Back to cited text no. 14
Kelsaka E, Baris S, Karakaya D, Sarihasan B. Comparison of ondansetron and meperidine for prevention of shivering in patients undergoing spinal anesthesia. Reg Anesth Pain Med 2006;31:40-5.  Back to cited text no. 15
Tsai YC, Chu KS. A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients. Anesth Analg 2001;93:1288-92.  Back to cited text no. 16
Wilson E, David A, MacKenzie N, Grant IS. Sedation during spinal anaesthesia: Comparison of propofol and midazolam. Br J Anaesth 1990;64:48-52.  Back to cited text no. 17
Buggy DJ, Crossley AW. Thermoregulation, mild perioperative hypothermia and postanaesthetic shivering. Br J Anaesth 2000;84:615-28.  Back to cited text no. 18
Hendolin H, Länsimies E. Skin and central temperatures during continuous epidural analgesia and general anaesthesia in patients subjected to open prostatectomy. Ann Clin Res 1982;14:181-6.  Back to cited text no. 19
Frank SM, Beattie C, Christopherson R, Norris EJ, Rock P, Parker S, et al. Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia. Anesthesiology 1992;77:252-7.  Back to cited text no. 20
Matsukawa T, Sessler DI, Christensen R, Ozaki M, Schroeder M. Heat flow and distribution during epidural anesthesia. Anesthesiology 1995;83:961-7.  Back to cited text no. 21
Dal D, Kose A, Honca M, Akinci SB, Basgul E, Aypar U. Efficacy of prophylactic ketamine in preventing postoperative shivering. Br J Anaesth 2005;95:189-92.  Back to cited text no. 22
Sharma DR, Thakur JR. Ketamine and shivering. Anaesthesia 1990;45:252-3.  Back to cited text no. 23
Kinoshita T, Suzuki M, Shimada Y, Ogawa R. Effect of low-dose ketamine on redistribution hypothermia during spinal anesthesia sedated by propofol. J Nippon Med Sch 2004;71:92-8.  Back to cited text no. 24
Hales JR. Skin arteriovenous anastomoses, their control and role in thermoregulation. In: Johansen K, Burggren W, editors. Cardiovascular Shunts: Phylogenetic, Ontogenetic and Clinical Aspects. Copenhagen, Denmark: Munksgaard; 1985. p. 433-51.  Back to cited text no. 25
Adam RD, Victor M, Ropper AH. Motor paralysis. In: Adam RD, Victor M, Ropper AH, editors, Principles of Neurology. 6th ed. New York: Mc Graw Hill Inc.; 1997. p. 45-63.  Back to cited text no. 26
Matsukawa T, Hanagata K, Ozaki M, Iwashita H, Koshimizu M, Kumazawa T. I.m. midazolam as premedication produces a concentration-dependent decrease in core temperature in male volunteers. Br J Anaesth 1997;78:396-9.  Back to cited text no. 27
Tarhan O, Canbay O, Celebi N, Uzun S, Sahin A, Coskun F, et al. Subhypnotic doses of midazolam prevent nausea and vomiting during spinal anesthesia for cesarean section. Minerva Anestesiol 2007;73:629-33.  Back to cited text no. 28
Bauer KP, Dom PM, Ramirez AM, O'Flaherty JE. Preoperative intravenous midazolam: Benefits beyond anxiolysis. J Clin Anesth 2004;16:177-83.  Back to cited text no. 29
Sessler DI. Temperature monitoring. In: Miller RD, editor. Anesthesia. New York: Churchill Livingstone; 1994. p. 1363-82.  Back to cited text no. 30
Guyton AC. Body temperature, temperature regulation and fever. In: Guyton AC, editor. Textbook of Medical Physiology. 6th ed. Philadelphia: WB Saunders; 1991. p. 886-98.  Back to cited text no. 31
Diemunsch P, Conseiller C, Clyti N, Mamet JP. Ondansetron compared with metoclopramide in the treatment of established postoperative nausea and vomiting. The French Ondansetron Study Group. Br J Anaesth 1997;79:322-6.  Back to cited text no. 32
Safavi MR, Honarmand A. Low dose intravenous midazolam for prevention of PONV, in lower abdominal surgery – Preoperative vs intraoperative administration. Middle East J Anaesthesiol 2009;20:75-81.  Back to cited text no. 33