• Users Online: 1616
  • Print this page
  • Email this page

Year : 2009  |  Volume : 53  |  Issue : 3  |  Page : 330-334 Table of Contents     

Prophylactic Granisetron Vs Pethidine for the Prevention of Postoperative Shivering: A Randomized Control Trial

1 D.N.B.Resident, Apollo Gleneagles Hospitals, Kolkata, India
2 Consultant, Apollo Gleneagles Hospitals, Kolkata, India

Date of Web Publication3-Mar-2010

Correspondence Address:
Asif lqbal
8/1 B, Mistri Para Lane, P.O. Entaly Kolkata- 14
Login to access the Email id

Source of Support: None, Conflict of Interest: None

PMID: 20640142

Rights and PermissionsRights and Permissions

Shivering-the "Big Little Problem" has an incidence of 60% in early recovery phase following general anaesthe­sia. A number of techniques have been tried to prevent postoperative shivering. Previous study showed that, ondansetron in higher doses reduces postoperative shivering. Therefore, this study was done to compare the efficacy of prophy­lactic granisetron, pethidine and placebo in preventing postoperative shivering.
Ninety patients aged 20-60yrs, ASA physical status I and II, scheduled for laparoscopic surgery under general anaesthesia were randomly allocated to receive either normal saline (Group S, n=30) as negative control, pethidine 25mg (Group P, n=30) as positive control or granisetron 40mcg.kg -1 (Group G, n=30) intravenously before induction. The anaesthesia was induced with fentanyl 2mcg.kg -1 , propofol 2mg.kg -1 and atracurium 0.5mg.kg -1 and maintained with sevoflurane 1-1.5%. Nasopharyngeal temperature was measured throughout the procedure. An investigator, blinded to the treatment group, graded postoperative shivering in a scale of 0 to 4. (0= no shivering, 1= piloerection or peripheral vasoconstriction but no visible shivering, 2= muscle activity in only one muscle group 3= muscle activity in more than one muscle group, 4= shivering involving the whole body). Prophylaxis was regarded as ineffective if shivering was greater than grade 3 and intravenous pethidine 25 mg was administered as rescue medication.
The three groups did not differ significantly regarding patient characteristics. The numbers of patients shivering on arrival in the recovery room at 15 minutes after operation were significantly less in Group P (7%) and Group G (17%) than in Group S (60%). Groups P and G differ significantly than in Group S (p<0.05).However, the difference between Groups P and G was not statistically significant (p>0.05). The prophylactic use of granisetron (40mcg.kg -1 ) and pethidine(25mg) intravenous were found to be effective in preventing postoperative shivering.

Keywords: Shivering; Postoperative; Granisetron; Pethidine

How to cite this article:
lqbal A, Ahmed A, Rudra A, Wankhede RG, Sengupta ST, Das T, Roy D. Prophylactic Granisetron Vs Pethidine for the Prevention of Postoperative Shivering: A Randomized Control Trial. Indian J Anaesth 2009;53:330-4

How to cite this URL:
lqbal A, Ahmed A, Rudra A, Wankhede RG, Sengupta ST, Das T, Roy D. Prophylactic Granisetron Vs Pethidine for the Prevention of Postoperative Shivering: A Randomized Control Trial. Indian J Anaesth [serial online] 2009 [cited 2020 Aug 3];53:330-4. Available from: http://www.ijaweb.org/text.asp?2009/53/3/330/60298

   Introduction Top

Post anaesthetic shivering is one of the most fre­quent problems in the early recovery phase following general anaesthesia [1],[2] . Considering clinical importance and frequency, postanaesthetic shivering was ranked as the sixth most important problem of current clinical anaesthesiology among 33 low morbidity clinical out­comes. [3] Previous studies have found that shivering oc­curs in the postoperative period in up to 60% of pa­tients [1],[2],[4] and varies according to age, sex, drugs used for anaesthesia and the duration for the surgery [4] .

Postanaesthetic shivering is not only distressing to patients, but can lead to physiological changes such as increased tissue oxygen consumption and carbon dioxide production, resulting in raised minute ventila­tion and cardiac output [5] . Moreover, the elderly with limited cardiopulmonary reserve may suffer form lactic acidosis, mixed venous oxygen desaturation, and hy­poxemia [4],[5],[6] . A number of pharmacological intervention have been studied for the treatment and prophylaxis of shivering, including clonidine, ketamine, doxapram, tramadol, pethidine and other opioids [6],[7],[8],[9] . Among the pharmacological agents, pethidine has been shown to be one of the most effective treatment [10],[11] .Although its

mechanism of action is not completely understood, it probably acts directly on the thermoregulatory centre [12] or via opioid receptors [13] . Serotonin (5-Hydrox­ytryptamine), a biological amine found in the brain and spinal cord, has a role in neurotransmission and studies suggest that the serotonergic system has a role in con­trol of postanaesthetic shivering [9] . Granisetron, 5-HT 3 receptor antagonist, has been shown to be effective in the prevention of emetic symptoms [14],[15] . The best of our knowledge, there is no study in India regarding the use of granisetron as a prophylactic agent against postop­erative shivering. The aim of the study was to compare the efficacy of prophylactic granisetron on postanaesthetic shivering in comparison to pethidine an agent which is known to be effective in the treatment and prevention of postanaesthetic shivering [10] .

   Methods Top

Following institutional review board approval and after obtaining written informed consent, a prospec­tive, randomized, double-blind, placebo-controlled study was undertaken. The power of the study was calculated based on the number of the patients who shivered, setting a significant level of p = 0.05, it was calculated that a group size of 30 patients allowed de­tection of a difference between groups with a power of 80%. Therefore, we took 90 patients aged 20 yr to 60yr, ASA physical status I and II, undergoing laparoscopic surgery. Patients with cardiopulmonary disease, psychological disorder, and with body tem­perature more than 38 0 C or less than 36.5 0 C were excluded from the study. Procedures which might re­quire administration of blood and blood products and anticipated duration more than 180 min were also ex­cluded from the study.

The patients were randomly (enveloped random­ization) allocated to receive normal saline (Group S, n = 30) as negative control, pethidine 25mg (Group P, n=30) as positive control or granisetron 40mcg.kg -1 (Group G, n = 30) as study agent intravenously before induction of anaesthesia.

The prepared drug was diluted to a volume of 5 ml and presented as coded syringes by anaesthesiologists who were not involved in the man­agement of patients.[Additional file 1]

The anaesthetic management of the patients were standardized. Heart rate, non-invasive blood pressure, oxygen saturation and end tidal carbon dioxide recorded during the surgery. Nasopharyngeal temperature (as we do not have tympanic probe) was measured as core body temperature immediately after induction of ana­esthesia and continued till the completion of surgery. Operation room temperature and recovery room tem­perature standardized by centrally air-conditioning with laminar flow and hepafilter.

Anaesthesia was induced with fentanyl 2mcg.kg­1, propofol 2mg.kg -1 and atracurium 0.5mg.kg -1 was given to facilitate orotracheal intubation. Anaesthesia was maintained with 1-1.5% sevoflurane in oxygen and air, ventilator was adjusted to maintain end tidal car­bon dioxide between 4.6 and 5.2 kPa throughout the procedure. Muscle relaxation for pneumoperitonium and surgical procedure was provided with additional doses of atracurium. During laparoscopy, intra-abdomi­nal pressure was maintained at 1.3 to 1.8 kPa by car­bon dioxide insufflator. Residual neuromuscular block­ade was antagonized with neostigmine 0.05 mg.kg -1 and glycopyrrolate 8-10 mcg.kg -1 . When the patient respi­ratory efforts were adequate and he or she responded to verbal commands, the trachea was extubated. The type and duration of anaesthesia and surgery were re­corded.

In the recovery room, all patients were monitored, received oxygen through facemask and were covered with cotton blanket. An anaesthesiologist unaware of the study drug observed the patients for shivering, pain, nausea and vomiting. Heart rate, non-invasive blood pressure, oxygen saturation and nasopharyngeal tem­perature were measured and recorded on admission to the recovery room at 15 minute. The shivering was graded using a scale similar to that validated by Tsai and Chu [16] [Table 1]. Any possible side effects of the study drug (i.e. nausea, vomiting, hypotension, tachy­cardia, dry mouth, and dizziness) were recorded. Pa­tient with nausea and vomiting were treated with metoclopramide 10mg. If the patient shivered accord­ing to at least grade 3 the prophylaxis was regarded as ineffective and intravenous pethidine 25 mg was ad­ministered as rescue agent [17] .

The incidence of shivering and side effects were compared using the Chi square test. The results were reported as mean ± SD. p < 0.05 was considered sta­tistically significant.

   Results Top

The three groups were comparable regarding dis­tribution of age, weight, height, gender, duration of ana­esthesia, duration of operation and ASA physical sta­tus [Table 2].

The number of patients with postoperative shiv­ering on arrival in the recovery room, 15 minutes after arrival, were significantly less in Group G and Group P than in Group S (p<0.05) in [Table 3]. There was no statistically significant difference between Group P and G (p > 0.05) in [Table 3]. In Group S, 18 patients shiv­ered at grade=3 and were subsequently treated with pethidine 25 mg intravenously as rescue agent. How­ever, in Group G and Group P only 6 and 2 patients reached grade 3 shivering respectively [Table 3].How­ever, there were no significant differences in the core temperature amongst the patients before and after the anaesthesia [Table 4].

Five patients in Group S and seven patients in Group P had nausea and vomiting (p>0.05) but no pa­tients of Group G complained of nausea and vomiting. None of the patients had episodes of oxygen desaturation or respiratory depression during the study. None of the patient in the study groups had cardiovas­cular complication.

   Discussion Top

In this study, we found that granisetron 40mcg.kg -1 was as effective as pethidine 25mg in preventing shiv­ering related to general anaesthesia.

During postoperative period, shivering is a fre­quent and understandable complication of general ana­esthesia [18] and the incidence has been shown around 56%-66% following general anaesthesia [1],[2],[4] . In our study, we also found 60% of patients in Control group had shivering after general anaesthesia. Shivering in­crease metabolic activity and oxygen consumption. It may also cause arterial hypoxia and lactic acidosis. Furthermore, it may interfere with the monitoring of an electrocardiogram [16],[19], . All of these make the preven­ tion of shivering important especially in elderly patients with a low cardiopulmonary reserve [16] .

It has been mentioned that hypothermia may cause postanaesthetic shivering by alteration of thermoregu­latory mechanism [12] .However, no relationship has been shown between axillary temperature and occurrence of shivering. [12] In our study there were no significant differences in nasopharyngeal temperature among the groups.

A number of factors including age, duration of surgery, temperature of the operating room, and infu­sion solution, are risk factors for hypothermia and shiv­erring [13] . For this reason, in our study patients over the age of 60 years were excluded [13] . The temperature of operation room was maintained at 24 0 C and infusions of cold crystalloid solution were avoided.

Various drugs have been used to treat or prevent postoperative shivering but the ideal treatment has not yet been found. 5-hydroxytryptamine may influence both heat production and heat loss pathways [13] . Ondansetron (4 and 8 mg) and dolasetron (1mg.kg -1 ) , 5-HT 3 an­tagonists have been effectively used in treatment of postoperative shivering [4],[20] .Powell and Colleagues [4] re­ported that after general anaesthesia, shivering was determined in 57%, 33% and 15% of patients in con­trol, ondansetron 4mg and 8mg respectively. Similarly, Bock and colleagues [20] mentioned in their study report that dolasetron 1mg.kg -1 decreases the incidence of shivering from 62% to 27%. The incidence of shivering (27%) in patients who received dolasetron in their study was more than the incidence of shivering in the patients those who received granisetron in our study (17%), however, the difference is not statistically significant.

Pethidine has been shown to be one of the most effective treatments to prevent postoperative shiver­ing [10],[11] . In our study, two patients shivered after pro­phylactic pethidine, however the mechanism of pethi­dine to reduce shivering is not clear. The study using naloxone indicated that pethidine may act via k recep­tor than µ opioid receptors to prevent shivering. The anti-shivering action of pethidine was inhibited by high dose naloxone, which blocks both µ and k receptors, but not by low dose of naloxone which block only µ receptors [10]. . A disadvantage of pethidine is that it can cause respiratory depression in the presence of previ­ously administered opioids or anaesthetics. Moreover, nausea and vomiting are also important side effect of pethidine.

In conclusion, pethidine can cause some side ef­fects such as respiratory depression, hypotension, and postoperative nausea and vomiting. Therefore, prophy­lactic granisetron 40mcg.kg -1 intravenously may be ad­ministered without causing the adverse effect in patient with high expectancy of shivering and postoperative nausea and vomiting ranked sixth and second in mor­bidity clinical outcome. [3]

   References Top

1.Buggy D, Higgens P, Moran C, O'Donovan F, Mc Carroll M. Clonidine at induction reduces shivering after gen­eral anesthesia. Can J Anaesth 1997; 44: 263-7.  Back to cited text no. 1      
2.Piper SN, Rohm KD, Suttner SW, Maleck WH, Kranke P, Boldt J. A comparison of nefopam and clonidine for the prevention of postanesthetic shivering: A comparative, double blind and placebo controlled dose ranging study. Anaesthesia 2004; 59: 559-64.  Back to cited text no. 2      
3.Macario A, Weinger M, Truong P, Lee M. Which clini­cal anesthesia outcomes are both common and impor­tant to avoid? The perspective of a panel of expert an­esthesiologists. Anesth Analg 1999;88:1085- 91.  Back to cited text no. 3      
4.Powell R, Buggy D. Ondansetron given before induc­tion of anesthesia reduces shivering after general anes­thesia. Anesth Analg 2000; 90: 1413-7.  Back to cited text no. 4      
5.Crossley AWA. Peri-operative shivering. Anaesthesia 1999; 47: 193-5.  Back to cited text no. 5      
6.Ciofo MJ, Clerque f, Devilliers C, et al. Changes in ven­tilation, oxygen uptake and carbon dioxide output dur­ing recovery from isoflurane anesthesia. Anesthesiol­ogy 1989; 70:737-41.  Back to cited text no. 6      
7.Piper SN, Maleck WH, Boldt J, suttner SW, Schmidt CC, Reich DGP. A comparison of clonidine, meperidine and placebo in preventing postanesthetic shivering. Anesth Analg2000; 90: 954-7.  Back to cited text no. 7      
8.Kranke P, Eberhart LH, Roewer N, Tramer MR. Pharma­cological treatment of postoperative shivering a quan­titative systemic review of randomized controlled trials. Anesth Analg 2002; 94: 453-60.  Back to cited text no. 8      
9.Alfonsi P. Postanesthetic shivering epidemiology, patho­physiology and approaches to prevention and manage­ment. Drugs 2001; 61: 2193-205.  Back to cited text no. 9      
10.Wrench IJ, Cavill G, Ward JEH, Crossley AWA. Com­parison between alfentanil, pethidine and placebo in the treatment of postanesthetic shivering. Br J Anaesth 1997; 79:541-2.  Back to cited text no. 10      
11.Terasako K, Yamamoto M. Comparison between pentazo­cine, pethidine and placebo in the treatment of postanes­thetic shivering. Acta Anaesthesiol Scand 2000; 44:311-2.  Back to cited text no. 11      
12.Vanderstappen I, Vanermeerch E, Vanacker B, Mattheussen M, Herijgers P, Van Aken H. The effect of prophylactic clonidine on postoperative shivering: a large prospective double-blind study. Anaesthesia 1996;51:351-5.  Back to cited text no. 12      
13.Witte JD, Sessler DI. Perioperative shivering physi­ology and pharmacology. Anesthesiology 2002; 96: 467-84.  Back to cited text no. 13      
14.Fuji Y, Tanka H, Toyooka H. Granisetron prevents nau­sea and vomiting during spinal anesthesia for cae­sarean section. Acta Anaesthesiol Scand 1998; 42: 312-5.  Back to cited text no. 14      
15.Biswas BN, Rudra A. Comparison of granisetron and granisetron plus dexamethasone for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Acta Anaesthesiol Scand 2003; 47: 79-83.  Back to cited text no. 15      
16.Tsai Ye, Chu KS. A comparison of tramadol, amitryptiline and meperidine for post epidural anesthetic shivering in parturient. Anesth analg 2001; 93:1288-92.  Back to cited text no. 16      
17.Sagir O, Gulhas N, Yucel TA, Begee Z, Ersoy O. Control of shivering during regional anesthesia:prophylactic ketamine and granisetron. Acta Anaesiol Scand 2007; 51:44-4.  Back to cited text no. 17      
18.Kranke P, Eberhart LH, Roewer N, Tramer MR. Single dose parenteral pharmacological interventions for the prevention of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg 2004; 99: 718-27.  Back to cited text no. 18      
19.Chan AM, Ng KF, Tong EW, Jan GS. Control of shiver­ing under regional anesthesia in obstetric patients with tramadol. Can J Anaesth 1999; 46: 253-8.  Back to cited text no. 19      
20.Bock M, Sinner B,Gottlicher M, Simon E, Martin E, Motsch J. Involvement of serotonergic pathways in pos­tanesthetic cold defence: dolasetron prevents shiver­ing. J Thermal Biol 2002;27:159-66.  Back to cited text no. 20      


  [Table 1], [Table 2], [Table 3], [Table 4]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Article Tables

 Article Access Statistics
    PDF Downloaded590    
    Comments [Add]    

Recommend this journal