Premedication with granisetron reduces shivering during spinal anaesthesia in children.
Abstract: This study evaluates the effect of prophylactic granisetron on the incidence of postoperative shivering after spinal anaesthesia in children. Eighty children, American Society of Anesthesiologists physical status I to II and aged two to five years were scheduled for surgery of the lower limb under spinal anaesthesia. The children were randomised to receive 10 [micro]g/kg granisetron diluted in 10 ml saline 0.9% intravenously (group 1, n=40) or placebo (10 ml 0.9% saline, group 2, n=40) to be given over five minutes just before spinal puncture. Shivering, core temperature and the levels of motor and sensory block were assessed. No patients shivered in group 1. However, six patients shivered in Group 2 (P=0.025). There were no significant differences in the other measured variables between the groups. Granisetron is an effective agent to prevent shivering after spinal anaesthesia in children from two to five years of age.

Key Words: spinal anaesthesia, shivering, children, granisetron
Article Type: Report
Subject: Pediatric anesthesia (Management)
Granisetron (Dosage and administration)
Authors: Eldaba, A.A.
Amr, Y.M.
Pub Date: 01/01/2012
Publication: Name: Anaesthesia and Intensive Care Publisher: Australian Society of Anaesthetists Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 Australian Society of Anaesthetists ISSN: 0310-057X
Issue: Date: Jan, 2012 Source Volume: 40 Source Issue: 1
Topic: Event Code: 200 Management dynamics Computer Subject: Company business management
Geographic: Geographic Scope: Australia Geographic Code: 8AUST Australia
Accession Number: 280719634
Full Text: Shivering during spinal anaesthesia has been well described, although it has a lower incidence in children over one year of age (10 to 16%) (1,2) than in adults (40 to 60%)3. Post-anaesthetic shivering increases patient discomfort, may aggravate postoperative pain and increases oxygen utilisation.

The neurotransmitter serotonin (5-HT3) plays a role in the control of perioperative shivering by its action in the pre-optic anterior hypothalamic region (4-6). The 5-HT3 receptor antagonists are effective in reducing post-anaesthetic shivering after general and spinal anaesthesia in adults (7,8). However, there is less information on their efficacy in reducing shivering after spinal anaesthesia in children, although it would be reasonable to assume antiserotonin drugs are effective in preventing this side-effect in this age group. In particular, there are no data on the effect of granisetron on postoperative shivering in the paediatric patient population.

This study aimed to test the hypothesis that pretreatment with intravenous granisetron would be effective in reducing postoperative shivering after spinal anaesthesia in children aged two to five years.

MATERIALS AND METHODS

This study was approved by the institutional ethics committee of the Faculty of Medicine, Tanta University, Egypt (approval number 124/ 04/ 10) and written informed consent was obtained from the parents of all patients studied. This study was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12611001059954). Eighty children, American Society of Anesthesiologists physical status I to II, aged two to five years and scheduled for lower limb surgery under spinal anaesthesia were entered into this double-blind, randomised, placebo-controlled trial.

Exclusion criteria included parental refusal of consent, coagulopathy, spinal congenital anomalies, neurological abnormality, allergy to local anaesthetics, surgery scheduled to last for more than 90 minutes, hypo- or hyperthyroidism and those who needed an intraoperative blood transfusion.

Patients were randomised to one of two groups to receive either granisetron 10 [micro]g/kg intravenously diluted in 10 ml saline, or 10 ml saline (placebo group). Randomisation was performed using a computer-based random number generator in permutated blocks of varying sizes and the assignment entered in sealed envelopes that were not opened until informed consent was obtained. The drug was mixed and administered by a nurse who took no further part in the study. The patient, parent, anaesthetist, observer gathering data and nurses taking care of the patient in the perioperative period remained blinded to the group assignment.

After standard fasting times, all children had topical anaesthetic EMLA[R] (AstraZeneca Pty Ltd, Cairo, Egypt) applied to the dorsum of both hands one hour before surgery. Midazolam 0.5 mg/kg was given orally as a preoperative sedation 30 minutes prior to the anaesthesia. A peripheral intravenous line was inserted on arrival in the operating theatre and the assigned study drug was administered over a five minute period just before spinal puncture.

Spinal puncture was done in the lateral decubitus position with a midline approach at L4 to 5. We used 25 gauge 55 mm Quincke spinal needles. Correct placement of the spinal needle was verified by a free flow of cerebrospinal fluid. Hyperbaric bupivacaine 0.5% (0.5 mg/kg) was used to achieve subarachnoid block. Monitoring of children included pulse oximetry, non-invasive blood pressure, electrocardiography and core temperature by tympanic probe. The children were sedated with intravenous thiopentone 2 mg/kg. If any subject cried or moved the upper body and hands to interfere with the procedure, 1 [micro]g/kg fentanyl was given as a supplemental analgesia and sedation.

Sensory block was assessed 10 minutes after injection of bupivacaine by bilateral pinprick test at each dermatome to elicit grimace or acknowledgement of pain. Motor block was assessed using the Bromage scale (9) recording the ability to flex hip, knee and ankle. Shivering was assessed using a modified scale from Tsai and Chu (0 = no shivering, 1=mild fasciculations on face and neck, 2=visible tremor involving more than one muscle group, 3=gross muscle activity involving the whole body) (10).

Core temperature by tympanic thermometer and shivering were recorded before spinal puncture and 15, 30, 60 and 90 minutes after spinal puncture. All intravenous fluids during surgery were warmed to 37[degrees]C and the temperature of the operating room was kept at 27[degrees]C. The sample size was calculated using the following assumptions: the incidence of shivering in the control group would be 15% in keeping with a previous study11. Power analysis identified 40 patients per group, required to detect 25% difference between groups with a power 80% and a significance level of 0.05.

Comparison of demographic data between groups was done by Student's t-test. Comparison between groups was done by Fisher's exact test (two-tailed). Repeated data on the same participants (core temperature, heart rate, non-invasive blood pressure) were analysed by repeated measures (analysis of variance). P <0.05 was considered statistically significant.

RESULTS

Demographic data, duration of surgery and volume of infused fluid are presented in Table 1. The two groups were comparable with respect to age, weight and volume of fluid given intraoperatively.

Nine subjects cried or moved the upper body and hands during the procedure and received 1 [micro]g/kg fentanyl (five patients in the control group and four patients in the granisetron group). There was a 100% success rate in achieving sensory and motor block within 10 minutes after spinal injection.

With respect to the motor block, 35 children in group 1 and 33 children in group 2 showed motor block grade three; five children in group 1 and seven children in group 2 showed motor block grade two (P=0.75). With respect to sensory block, the range in all children in both groups was between T4 and T7. Ten children in group 1 and 12 children in group 2 showed a sensory block to T4, while the sensory block reached T7 in 11 children in group 1 and 10 children in group 2. The other children in both groups were in between these levels.

There was no significant difference in core temperature (Table 1), heart rate, blood pressure and oxygen saturation between the groups at any time. Shivering did not occur in any patient in group 1; it occurred in six patients in group 2 (Table 1, P=0.025). All patients who showed shivering received intravenous pethidine 0.5 mg/kg to stop the shivering, which was effective in all cases.

DISCUSSION

These findings indicate that granisetron was effective in reducing shivering. There was no incidence of shivering in the granisetron group, while it occurred in six patients in the control group despite the absence of any significant difference in core temperature or block characteristics between both groups.

The exact mechanism of post-spinal shivering has not been fully elucidated. Hypotheses include internal redistribution of heat from the core to the peripheral compartment (12-14), loss of thermoregulatory vasoconstriction below the level of the blockade (which leads to increase heat loss from body surfaces) or altered thermoregulation characterised by a small decrease in vasoconstriction and a slight increase in the sweating threshold. Interestingly, the major difference in thermal control between adults and children is that in children the surface area per kilogram is larger than adults, together with thinner skin and lower fat content that allows a higher heat loss (15).

There are several risk factors for shivering during spinal anaesthesia such as age, level of sensory block, temperature of the operating room, wound exposure and amount and temperature of infusion fluids (16). In this study, there were no significant differences between the groups in any of those factors.

Various drugs have been used to prevent postoperative shivering. The ideal drug has not yet been found, although 5-hydroxytryptamine may influence both heat production and heat loss pathways (17). Powell and Buggy (6) reported that shivering was observed in 57, 33 and 15% of patients receiving placebo, ondansetron 4 mg, and ondansetron (18) mg respectively. Also, Bock and colleagues18 reported that dolasetron 1 mg.[kg.sup.-1] decreased 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 who received granisetron in the study of Iqbal and colleagues19 (17%). So, we decided using granisetron in our study for its potentillay greater beneficial effect.

Other pharmacological agents have been used for the treatment and prevention of shivering including tramadol, midazolam, ketamine, pethidine and clonidine (1,11,19).

Pethidine has been shown to be one of the most effective agents to prevent postoperative shivering (20,21). The anti-shivering action of pethidine is also not completely understood (20). The major concern of pethidine is that it can cause respiratory depression, especially in the presence of previously administered anaesthetics and especially in children. A higher incidence of postoperative nausea and vomiting are also important side-effects of pethidine (21).

Clonidine may be associated with hypotension and sedation (11,19). Also, tramadol is associated with more frequent incidence of side-effects such as nausea, vomiting and dizziness. Hallucinations are a well-known side-effect of ketamine, which may limit its use (1). In contrast, 5-HT3 antagonists appear to be relatively free of side-effects although this has not been confirmed in large studies.

A possible limitation of this study is the incidence of shivering in the control group. In another study an incidence of 3.5% was found, with a significantly lower incidence in children who received a caudal anaesthesia (22). This is a much lower reported incidence than the one used by the authors and could potentially influence the power analysis.

CONCLUSION

Our findings suggest that granisetron is an effective agent to reduce shivering in children from two to five years of age after spinal anaesthesia.

REFERENCES

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(12.) Matsukawa T, Sessler DI, Christensen R, Ozaki M, Schroeder M. Heat flow and distribution during epidural anesthesia. Anesthesiology 1995; 83:961-967.

(13.) Kurz A, Sessler DI, Schroeder M, Kurz M. Thermoregulatory response thresholds during spinal anaesthesia. Anesth Analg 1993; 77:721-726.

(14.) Ozaki M, Kurz A, Sessler DI, Lenhardt R, Schroeder M, Moayeri A et al. Thermoregulatory thresholds during epidural and spinal anaesthesia. Anesthesiology 1994; 81:282-288.

(15.) Buggy DJ, Grossley AWA. Thermoregulation, mild perioperative and post-anaesthetic shivering. Br J Anaesth 2000; 84:615-628.

(16.) Williams RK, Adams DC, Black IH. While we wait. Anesth Analg 2011; 112:1239-1241.

(17.) Kranke P, Eberhart LH, Roewer N, Tramer MR. Postoperative shivering in children: a review on pharmacologic prevention and treatment. Paediatr Drugs 2003; 5:373-383.

(18.) Bock M, Sinner B, Gottlicher M, Simon E, Martin E, Motsch J. Involvement of serotonergic pathways in postanaesthetic cold defence: dolasetron prevents shivering. J Thermal Biol 2002; 27:159-166.

(19.) Iqbal A, Ahmed A, Rudra A, Wankhede RG, Sengupta S, Das T et al. Prophylactic granisetron versus pethedine for the prevention of postoperative shivering: A randomized control trial. Indian J Anaesth 2009; 53:330-334.

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(21.) Terasako K, Yamamoto M. Comparison between pentazocine, pethidine and placebo in the treatment of post-anaesthetic shivering. Acta Anaesthesiol Scand 2000; 44:311-312.

(22.) Akin A, Esmaoglu A, Boyaci A. Postoperative shivering in children and causative factors. Paediatr Anaesth 2005; 15:1089-1092.

A. A. ELDABA *, Y. M. AMR ([dagger]) Department of Anesthesia, Tanta University Hospital, Tanta, Egypt

* MD, Lecturer.

([dagger]) MD, Assistant Professor.

Address for correspondence: Dr Y. M. Amr, Anesthesia Department, Tanta University Hospital, Tanta University, Tanta 31257, Egypt. Email: yasser.amr@gmail.com

Accepted for publication on October 24, 2011.
Table 1
Demographic data, core temperature, level of sensory and motor
block and incidence of shivering in both groups

                               Group 1,           Group 2,
                               n=40               n=40

Age, y, mean (range)           3.9 (2-5)          3.8 (2-5)
Weight, kg, mean [+ or -] SD   15.4 [+ or -] 0.5  15.2 [+ or -] 0.7
Volume of intravenous fluids,  156 [+ or -] 17    151 [+ or -] l5
  ml, mean [+ or -] SD
Core temperature,
    mean [+ or -] SD
  Before spinal anaesthesia,   37 [+ or -] 0.1    36.9 [+ or -] 0.2
    [degrees]C
  After spinal anaesthesia,    36 [+ or -] 0.2    36.1 [+ or -] 0.3
    [degrees]C
Sensory and motor block
  Sensory block level
    T4                         10                 12
    T7                         11                 10
  Motor block
    Grade 2                    5                  7
    Grade 3                    35                 33
Shivering in both groups
  Before spinal anaesthesia    0                  0
  After spinal anaesthesia *
    Grade 2                    0                  4
    Grade 3                    0                  2

* Significant difference between groups, P=0.025.
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