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Year : 2019  |  Volume : 3  |  Issue : 3  |  Page : 166-169

The effect of low-dose granisetron on shivering in subarachnoid block

Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Brawijaya University/Dr. Saiful Anwar, General Hospital, Malang, Indonesia

Date of Submission21-Nov-2019
Date of Acceptance21-Nov-2019
Date of Web Publication23-Jan-2020

Correspondence Address:
Dr. Isngadi Isngadi
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Brawijaya University/Dr. Saiful Anwar, General Hospital, Ijen Nirwana Residence B5/19, Malang
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/BJOA.BJOA_4_19

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Background: Shivering has many negative effects on the postanesthesia patient. Shivering is regulated by serotonin. The serotonin antagonists such as ondansetron and granisetron are widely used to prevent nausea and vomiting. Ondansetron is used in regional and general anesthesia, while granisetron is widely used in chemotherapy. This study aimed to determine the effect of low-dose granisetron on the incidence of shivering in postspinal anesthesia. Patients and Methods: The study conducted at Dr. Saiful Anwar General Hospital, Malang, Indonesia. Twenty-three patients divided into two groups: Group C (control) received no premedication and Group G (granisetron) received low-dose granisetron 10 μg/kg. The shivering grade and shivering intensity were recorded every 5 min in the first 1-h postanesthesia. The data were analyzed using t-test, regression test, and effective contribution test. Results: The shivering incidence in Group K was 71.9% and Group G was 9.4% (P = 0.018). The control group experienced shivering Grade I, II, III, and IV. Granisetron group only experienced shivering Grade I and II. Conclusion: The administration of low-dose granisetron before the spinal anesthesia significantly reduced the incidence of shivering in adult patients with no side effects.

Keywords: Granisetron, low-dose, shivering, spinal anesthesia

How to cite this article:
Isngadi I, Jaya W, Fardian D. The effect of low-dose granisetron on shivering in subarachnoid block. Bali J Anaesthesiol 2019;3:166-9

How to cite this URL:
Isngadi I, Jaya W, Fardian D. The effect of low-dose granisetron on shivering in subarachnoid block. Bali J Anaesthesiol [serial online] 2019 [cited 2021 Feb 27];3:166-9. Available from: https://www.bjoaonline.com/text.asp?2019/3/3/166/276624

  Introduction Top

Subarachnoid block anesthesia or spinal anesthesia has many advantages.[1] This technique is safe and often used in lower abdominal surgery. Even though it is safe, regional anesthesia may cause complications in the thermoregulation system.[2] Shivering often happens after spinal anesthesia. Shivering is an unconscious and rhythmic movement involving several groups of muscles. The increase of muscle activity generates the elevation of oxygen consumption, lactic acidosis, and carbon dioxide production. Shivering is regulated by amine serotonin compounds (5-HT).[3] The shivering incidence is about 20%–60% in adult patients with spinal anesthesia.[3] Shivering triggers postoperative wound severity and increases intraocular or intracranial pressure. It also increases the metabolic rate by 100%–130%.[4] Shivering is dangerous for patients who suffer from cardiopulmonary diseases.[5]

Anesthetic agents such as clonidine, magnesium sulfate, ketamine, tramadol, ondansetron, and dexamethasone are often used as a premedication. However, these drugs have not significantly reduced the incidence of shivering.[6] Opioid and nonopioid drugs are widely used to reduce the incidence of shivering, but they have several side effects, including hypotension, hypertension, sedation, respiratory depression, and nausea or vomiting.[7]

Serotonin antagonist potentially reduces the incidence of shivering in patients with spinal anesthesia. Granisetron and ondansetron are classified as serotonin antagonist drugs. Ondansetron commonly used as a premedication in regional and general anesthesia.[8] Granisetron prevents postoperative nausea and vomiting (PONV) in postchemotherapy. The previous study showed that granisetron is better than ondansetron because it has a longer half-life and has fewer side effects.[9] The aim of the study is to determine the effect of low-dose granisetron on shivering incidence in postspinal anesthesia.

  Patients and Methods Top

This study is an experimental double-blind, randomized clinical trial. The study was carried out at the Central Surgical Installation of Dr. Saiful Anwar Hospital Malang. The study protocol was approved by the Health Research Ethical Clearance Committee of Dr. Saiful Anwar General Hospital. The subjects of this study were 32 patients who underwent elective surgery in spinal anesthesia. The patients provided written consent to be included in the study. The inclusion criteria included patients who received spinal anesthesia, aged 18–40 years, body mass index 20–30 kg/m 2, the American Society of Anesthesiologists physical status I and II, the operation region between the abdominal region to the lower leg, and the maximum operating duration is 2 h. Patients who experienced granisetron side effects, massive bleeding, and spinal block failure were excluded from this study.

Patients were randomized into two groups: the Group C (control group, n = 16) and the Group G (granisetron group, n = 16). Group G received low-dose granisetron 10 μg/kg body weight (intravenous [IV]) before anesthesia. Room temperature was maintained between 20°C and 23°C. Spinal anesthesia was performed using the 27-G Quincke needle at the L3–L4 or L4–L5 segment using 15 mg of 0.5% Bupivacaine Heavy. Blood pressure, pulse rate, and tympanic temperature were measured every 5 min for the first 60 min. When the blood pressure decreases more than 20% from the baseline, ephedrine (5–10 mg) was given, and the patient was excluded from the study. The presence of shivering is recorded. If patients experienced shivering, Meperidine 0.5 mg/kg body weight (IV) was given.

Data were analyzed statistically using t-test, regression test, and effective contribution test (standard error [SE]) using SPSS 19 software IBM Corp. Released 2010. IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp. P < 0.05 was considered statistically significant.

  Results Top

The subjects for this study were 32 patients who underwent an elective surgery with spinal anesthesia. The characteristics of the patients are shown in [Table 1]. The mean age of the patients was 28.75 ± 7.69 years in the Group C and 32.87 ± 6.96 years in the Group G. All the data were normal and homogeneous.
Table 1: Characteristics of the patients (n=16)

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The shivering incidence in Group C and Group G showed a significant difference. In the first 5 min, the shivering incidence in Group C was 50%, while in Group G, it was 6.3% [Table 2]. The shivering incidence in Group C continues to increase until 60 min postanesthesia. Overall, Group C experienced shivering up to 71.9%, while in Group G, shivering was 9.4% (P < 0.05).
Table 2: The incidence of shivering postanesthesia (n=16)

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Based on the regression test, low-dose granisetron and observation time influence the shivering incidence (P < 0.05). An effective contribution test (SE test) was carried out to find the contribution of each factor to the shivering incidence. Based on the SE test, the administration of granisetron made the largest effective contribution (93.46%). Low-dose granisetron influences the reduction of shivering incidence with R2 = 0.93. The shivering intensity is divided into four grades based on the Crossley and Mahajan Scale [Table 3]. Control group experienced shivering Grade I, II, III, and IV. Granisetron group only experienced shivering Grade I and II. No side effects found in the granisetron group. However, one patient from the control group experienced nausea and vomiting.
Table 3: Frequency distribution of shivering during surgery

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  Discussion Top

Group C experienced shivering up to 71.9%, while in Group G, shivering was 9.4% (P < 0.05). The shivering incidence in Group K continued until the 60th-min postanesthesia. The previous study explained that the possibility of shivering incidence in the adult patient is about 20%–60%.[3] In regional anesthesia, the sympathetic nerve blocking leads the vasodilation in the blocked area. Furthermore, the vasocontraction threshold above the blocked area is decreased by 0.5°C. Due to that, the body heat transfers from the body core to the peripheral.[4] This process causes heat production–heat loss imbalance and triggers hypothermia. Hypothermia because of neuraxial anesthesia occurs through three phases: redistribution, body heat loss to the environment, and the inhibition of the temperature regulation center.[10]

The study showed that in the first 30 min, the redistribution of the body heat to the peripheral caused hypothermia. Both neuraxial and granisetron reduce the shivering incidence, but granisetrons's effect is more significant. The shivering incidence starts to elevate in the 45th-min postanesthesia. The elevation occurs because the hypothermia already enters the second phase, the heat loss to the environment. In the neuraxial block, the body heat formation is inhibited, especially in the blocked area. The thermoregulation system responses to such conditions by generate shivering. Shivering is also influenced by patient's morphometry, surgery duration, evaporation, and operating room temperature.[10]

Granisetron significantly reduces the incidence of shivering. Shivering is related to thermoregulation and regulated by serotonin (5-HT). The uses of serotonin directly in the preoptic region and anterior hypothalamus change the thermosensitive neuron activity.[11] The preoptic region of the hypothalamus secretes serotonin to activate the heat-producing pathway. Granisetron is a 5-HT3 antagonist drug and has a similar structure to serotonin (5-HT).[12],[13] The 5-HT3 antagonist's drug will inhibit serotonin absorption in the preoptic region.[7] The study showed a similar result to Eldaba and Amr's study.[3] In their study, the low-dose granisetron 10 μg/kg body weight was able to reduce the incidence of shivering in children patients.[3] The previous study by Kabade et al.[14] using granisetron 40 μg/kg body weight showed that granisetron reduces the incidence of shivering in adult patients. Granisetron is better than ondansetron because it prevents Grade III and IV shivering. In the previous study, ondansetron only prevents Grade I, II, and III shivering.[8]

This study also observed the presence of side effects arising from the granisetron administration. The granisetron group did not experience side effects, but there was one patient who experienced PONV in the control group. The appearance of nausea and vomiting can be caused by hypotension shortly after spinal anesthesia, which is related to hypoxemia or hypoperfusion in the chemoreceptor trigger zone area or vomiting center.[15]

  Conclusion Top

The administration of low-dose granisetron as spinal anesthesia premedication significantly reduced the incidence of shivering and reduced the degree or intensity of shivering postspinal anesthesia. There were no side effects due to the administration of granisetron as premedication.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Khanduri KC. Regional Anaesthesia Techniques for Orthopaedic Surgery. Med J Armed Forces India. 2008;64:108–10. doi:10.1016/S0377-1237(08)80048-2.  Back to cited text no. 1
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. 2
Eldaba AA, Amr YM. Premedication with granisetron reduces shivering during spinal anaesthesia in children. Anaesth Intensive Care 2012;40:150-3.  Back to cited text no. 3
Lenhardt R. Body temperature regulation and anesthesia. Handb Clin Neurol 2018;157:635-44.  Back to cited text no. 4
Schwarzkopf KR, Hoff H, Hartmann M, Fritz HG. A comparison between meperidine, clonidine and urapidil in the treatment of postanesthetic shivering. Anesth Analg 2001;92:257-60.  Back to cited text no. 5
Bhattacharya PK, Bhattacharya L, Jain RK, Agarwal RC. Post Anaesthesia Shivering (PAS). Indian J Anaesth 2003;47:88-93.  Back to cited text no. 6
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Lopez MB. Postanaesthetic shivering – From pathophysiology to prevention. Rom J Anaesth Intensive Care 2018;25:73-81.  Back to cited text no. 7
Nallam SR, Cherukuru K, Sateesh G. Efficacy of Intravenous ondansetron for prevention of postspinal shivering during lower segment cesarean section: A double-blinded randomized trial. Anesth Essays Res 2017;11:508-13.  Back to cited text no. 8
[PUBMED]  [Full text]  
Chidambaram A, Bylappa K, Somasekaram P. A Comparative Study Of Ondansetron And Granisetron For Prevention Of Nausea And Vomiting Following Laparoscopic Surgeries. The Internet Journal of Anesthesiology. 2010;29:1-7.  Back to cited text no. 9
Arkiliç CF, Akça O, Taguchi A, Sessler DI, Kurz A. Temperature monitoring and management during neuraxial anesthesia: An observational study. Anesth Analg 2000;91:662-6.  Back to cited text no. 10
Ishiwata T. Role of serotonergic system in thermoregulation in rats. J Phys Fit Sport Med 2014;3:445-50.  Back to cited text no. 11
Rojas C, Stathis M, Thomas AG, Massuda EB, Alt J, Zhang J, et al. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg 2008;107:469-78.  Back to cited text no. 12
Machu TK. Therapeutics of 5-HT3 receptor antagonists: Current uses and future directions. Pharmacol Ther 2011;130:338-47.  Back to cited text no. 13
Kabade S, Venkatesh Y, Karthik S, Kumar V. Comparative study of granisetron versus pethidine for the prevention of perioperative shivering under spinal anesthesia. Karnataka AnaesthJ 2016;2:14.  Back to cited text no. 14
Wong CA. Complication and Side Effect of Central Neuraxial Technique; in Spinal and Epidural Anesthesia. New York: McGraw-Hill; 2007.  Back to cited text no. 15


  [Table 1], [Table 2], [Table 3]


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