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| CLINICAL INVESTIGATION |
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| Year : 2007 | Volume
: 51
| Issue : 6 | Page : 510-514 |
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Antiemetic effects of granisetron versus dexamethasone in clonidine premedicated children undergoing strabismus surgery
Indu Sen1, GS Brar2, P Chari3
1 MD, Assistant Professor, Department of Anaesthesia & Intensive care and Post Graduate Institute of Medical Education & Research, Chandigarh, India
2 MS, Opthalmology, Assistant Professor, Department of Anaesthesia & Intensive care and Post Graduate Institute of Medical Education & Research, Chandigarh, India
3 MD, D. Ac, MAMS, FAMS, Ex-Professor & Head, Department of Anaesthesia & Intensive care and Post Graduate Institute of Medical Education & Research, Chandigarh, India
| Date of Acceptance | 20-Oct-2007 |
| Date of Web Publication | 20-Mar-2010 |
Correspondence Address:
Indu Sen
Post box No 1519, PGI Campus, Sector-12-A, Chandigarh-160012
India
 Source of Support: None, Conflict of Interest: None  | Check |
In a prospective, double blind, randomized trial, 120 children, aged 3-8 years,ASAI-II, undergoing strabismus repair were randomly divided into three groups (n = 40 each). Oral clonidine premedication (4gg.kg-1) was administered to all the patients two hours prior to surgery. Soon after induction of anaesthesia, Group G patients were administered intravenous granisetron (40gg.kg1 ), Group D intravenous dexamethasone (150gg.kg-1) and group S received 4ml normal saline. Postoperatively, children were continuously monitored and assessed half-hourly till discharge and then after 24 hours for vomiting and pain. The overall incidence of postoperative emesis was lower (15.4%) in the Group G compared with the Group D (21.6%) in the first 24 hours (P>0.05). The Group S had a highest incidence of postoperative vomiting ((37%) P value < 0.0324 compared to group G). The frequency of early vomiting was highest in the S group. Both G and D groups showed better control of delayed emetic episodes. We observed that in children who were premedicated with clonidine, both IV granisetron or dexamethasone were efficacious in reducing the incidence and severity of POV in day-care strabismus surgery. Keywords: POV, Ambulatory surgery, Strabismus surgery, Granisetron, Dexamethasone, Clonidine
How to cite this article:
Sen I, Brar G S, Chari P. Antiemetic effects of granisetron versus dexamethasone in clonidine premedicated children undergoing strabismus surgery. Indian J Anaesth 2007;51:510-4 |
How to cite this URL:
Sen I, Brar G S, Chari P. Antiemetic effects of granisetron versus dexamethasone in clonidine premedicated children undergoing strabismus surgery. Indian J Anaesth [serial online] 2007 [cited 2021 Mar 8];51:510-4. Available from: https://www.ijaweb.org/text.asp?2007/51/6/510/61189 |
 Introduction | |  |
Post-operative nausea and vomiting (PONV) continues to be a clinical problem with unacceptably high incidence. The reported incidence of PONV after strabismus surgery ranges from 44-88% without antiemetic prophylaxis [1],[2] . Oral clonidine is a safe and effective premedicant. [3] Granisetron is a long acting selective 5HT 3 receptor antagonist. Drug has been found to be safe and effective for antiemetic prophylaxis in children. [4],[5] In surgical settings, a single prophylactic dose of dexamethasone has been found to be cost effective antiemetic as compared to placebo. [6] Though all these drugs are commonly used in children, on literature review and medline search, we did not come across any study in paediatric patients undergoing strabismus repair where efficacy of granisetron or dexamethasone in clonidine premedicated children has been evaluated for the prevention of postoperative emesis.
| Methods | | |
After approval by hospital ethics committee and parents/guardians informed consent, we conducted a prospective randomized double blind trial in 120 healthychildren of either sex, aged 3-8 years,undergoing elective strabismus correction surgery.Patients with known hypersensitivity to serotonin antagonists & those who had received antiemetics (eg. phenothiazines, scopolamine) or steroids 24 hours prior to surgery were excluded. However, we included patients with previous history of motion sickness and POV, because they are the ones who are likely to get maximum benefit from prophylactic antiemetic therapy.All the children fasted 6 hours for solids and 3 hours for liquids. Premedication consisted of oral clonidine (4tg.kg -1 ) two hours prior to surgery. Peri-operative monitoring included heart rate, oxygen saturation, electrocardiography, noninvasive blood pressure and end-tidal carbon dioxide concentration (EtCO 2 ). Induction of anaesthesia was done with either sleep dose of intravenous propofol or halothane inhalation (in children not willing for intravenous cannulation), followed by atracurium (0.5mg.kg -1 ) to facilitate endotracheal intubation.Ventilation was controlled mechanically and was adjusted to keep EtCO 2 35-40 mmHg using a mixture of 70% nitrous oxide in oxygen and halothane.All children received 1tg.kg -1 fentanyl at induction and no more opioids were given during or after the operation.
Using a closed envelope technique, children were randomly assigned to one of the three groups to receive 4 ml of an intravenous solution before surgical procedure started. This solution consisted of granisetron 40gg.kg -1 (Group G), dexamethasone 150gg.kg -1 (Group D) or 4ml normal saline (Group S). For postoperative analgesia IV paracetamol 15mg.kg -1 was administered intra-operatively to all the children. At the completion of surgery, neostigmine (0.05 mg.kg -1 ) and glycopyrrolate (0.01 mg.kg -1 ) were given intravenously to reverse muscle paralysis. Sedation was assessed by the University of Michigan Sedation Scale {UMSS [7] (Appendix I)} The events in the recovery room (vomiting, pain, antiemetics & analgesics requirements) were continuously monitored and recorded every half hourly for four hours or until the patient achieved the discharge criteria. Intensity of nausea was also noted whenever reported by the children. All observations were made by an anaesthesiologist, who was not aware of patients' group assignments.The number of episodes of vomiting or retching were recorded as no vomiting (0), one emetic episode (1), two or more bouts of vomiting (2). All emetic episodes were noted by the blinded anaesthesiologist in first four hours and by parents/guardians in next 20 hours. Vomiting occurring within first four hours was considered as early vomiting and from 4-24 hour as delayed vomiting. Rescue antiemetic therapy consisted of intravenous metoclopramide (0.2mg.kg -1 ), till the patient could take oral feeds, and tablet metoclopramide afterwards. Need for intravenous metoclopramide as rescue antiemetic was recorded. Pain was evaluated by incidence and {FLACC scale (Appendix II)} [8]. A score of 7 or >7 was considered severe, 3-6 = moderate and < 3 = minimal. Rescue analgesia was given when the pain score was >3. Oral intake was restrained for 2 hours after recovery from anaesthesia. Duringthis period, small quantities of clear liquids were allowed on child's request.[Additional file 1]
The discharge criteria were based on the criteria for fast tracking out patients after ambulatory surgery.Time to meet discharge criteria was recorded. However, it is our institute policy to keep all the patients in PACU for four hours post-surgery. At the time of discharge tablet paracetamol SOS was prescribed and the telephone numbers of all the guardians were noted.All patients were routinely examined by the ophthalmologist in the evening clinic on first postoperative day. Guardians were provided with a postcard each and were requested to handover the same to the operating surgeon, after recording the occurrence of vomiting episodes. Pain,anti-emetics & analgesics requirements after discharge and details of untoward events were assessed by interviewing the parent/guardian.[Additional file 2]
Statistical Analysis: Assuming that average incidence of postoperative emesis following strabismus surgery is 70%, to have 80% power (oo = 0.05), to detect a reduction to 35%, one would need to study 31 patients per group. Keeping in mind the drop-outs, we planned to study 40 patients in each group. Demographic and clinical data in three groups were analyzed using independent samples t-test or the Mann Whitney-U test where appropriate. The occurrence of postoperative emetic episodes, rescue antiemetic therapy and rescue analgesic therapy were analyzed with the Chi-square test or the Fisher Exact test. The number of episodes of vomiting that occurred were measured by a standard analysis of variance (ANOVA). The occurrence of vomiting after discharge was analyzed using a contingency table. P value of <0.05 was considered significant.All values were expressed as mean + S.D. and number (%).
| Results | | |
Nine of the 120 patientsenrolled were excluded from the data analysis because of protocol alteration or incomplete data. Patients in the three groups were comparable with regards to age, weight and history of motion sickness/ POV. Anaesthesia time, administration of propofol vs halothane for induction, intraoperative haemodynamic variables, duration of surgery, number of muscles repaired and quantity of intravenous fluids administered intraoperatively were also compared.[Table 1]
Complete response defined as no POV and no administration of rescue antiemetic medication during the first 24 hours afteranaesthesia was seen in 75.7%, (84.6% in granisetron group, 78.4% in dexamethasone group and 62.9% in saline group, P< .0324 for G vs S). Incidence of early and delayed vomiting alongwith need for rescue antiemetics is shown in [Table 2].
Children receiving granisetron vomited less frequently than those receiving dexamethasone or saline. The overall incidence of emesis was higher in S group (37%) than in D and G group (21.6% & 15.4%) respectively. Analysis of results at various time intervals showed that 7 episodes of vomiting were observed in first hour after surgery in S group as compared to 4 & 3 episodes in D and G groups respectively. Combination of granisetron or dexamethasone with oral clonidine resulted in significant reduction in the number of patients experiencing delayed vomiting. In the late postoperative period, no patient in the D and G group vomited whereas 3 episodes of vomiting were documented in S group. Severe emesis occurred in only one patient in S group. A smaller percentage of patients received rescue antiemetics in G & D group as compared to S group. (5.1 %, 5.4% & 23% respectively). Severe emesis occurred in only one patient in S group [Table 3].
The pain scores in the three groups at all times did not show any difference and need for rescue analgesia did not differ. The average time to attain discharge criteria were comparable in D & G groups. One patient in S group had to be observed for longer period (>4hr) and was admitted on the request of parents. Eight patients (S3, D-1, G- 4) had constipation on first postoperative day. No other clinically significant deleterious effects with regards to headache, dizziness, drowsiness or sedation were noticed in any of the children.
| Discussion | | |
The etiology and consequences of postoperative emesis are complex and multi-factorial. [2],[9],[10],[11],[12],[13],[14],[15] The patients undergoing ophthalmologic surgeries involving manipulation of extraocular muscles are more prone to develop postoperative nausea and vomiting because of oculoemetic reflex. [9] Given the detrimental effects of postoperative vomiting and inherent risk of this complication related to ophthalmological surgeries, any factor that would decrease the incidence or prevalence of POV would be highly useful. The concept of balanced antiemesis has been put forth in the recent years & multi-modal management approach has been suggested. [16] This includes combination therapy with antiemetic medications acting at different neuroreceptor sites, less emetogenic anaesthesia techniques, adequate intravenous hydration and adequate pain control. However, the results of numerous antiemetics studied for prevention of PONV are divergent and inconsistentand high costs of antiemetic drugs limit their use. [1],[2],[3],4[],[5],[6],[9],[10],[11],[12],[13],[14],[15].
In this double-blind randomized trial, overall incidence of postoperative emesis was 24.3%, and we had included patients with history of motion sickness and previous POV. Patients with an acute complete response (ACR), defined as no emetic episodes and no rescue medication within 24 h of study drug administration were 84.6% in granisetron group, 78.4% in dexamethasone group and 62.9% in saline group (P < .0324 for G vs S ). Considering the high likelihood of developing postoperative emesis without prophylaxis in patients undergoing strabismus correction surgeries, we did not consider it ethical to include a placebo arm in the study. All the patients received oral clonidine which is a safe and effective premedicant and also reduces the incidence of vomiting. [3],[12] An anecdotal report has revealed that there were no deaths in 11 toddlers ingesting clonidine accidentally in doses of 10-150gg.kg -1 . [17] Handa etal have shown that pretreatment with oral clonidine 4gg.kg -1 enhances the antiemetic effects of propofol when compared with midazolam 0.4 mg.kg -1 . [18] Though, Gulhas et al [19] could not find any such difference in a similar study comparing oral clonidine 4gg.kg -1 with placebo. Incidence of vomiting in our clonidine saline group was 37%, where we had included patients with previous history of postoperative vomiting. Untoward haemodynamic effects of clonidine premedication for eg. bradycardia (heart rate < 60/min) requiring pharmacological management were not observed. Demographic profile, surgical procedure, duration of anaesthesia and surgery were comparable in the three groups. Few of our patients were induced with halothane as they did not want to be pricked even after the application of EMLA cream. The number of patients induced with propofol versus halothane were comparable amongst three groups.
After the introduction of selective 5-HT 3 receptor antagonist ondansetron, several of its congeners have appeared, namely, granisetron, tropisetron, dolasetron and ramosetron. Of these granisetron received FDA approval for use in the prevention of PONV in August 2002. [20] Granisetron is claimed to be superior to traditional antiemetic agents for prevention of PONV [13] . In the present study, in an adjusted cohort of > 100 POV-free patients (PFP),Granisetron-clonidineand dexamethasone-clonidine combination proved to be more effective to clonidine-saline combination (84.6 ,78.4% and 37%). Dose of study antiemetics chosen were based upon results of previously published studies on paediatric strabismus surgery under general anaesthesia [3],[6],[15]. Thus, the difference in incidence and severity of vomiting can be attributed to class of study drugs administered. However, routine use of granisetron has been criticized because of the high cost. Antiemetic prophylaxis with single dose of dexamethasone is known to decrease incidence of PONV. [6] Splinter et al [21] while comparing the effects of ondansetron alone vs dexamethasone with ondansetron found that incidence of postoperative vomiting was reduced to 9% in combination group. Their patients received oral midazolam premedication 20-30 minutes before surgery. Incidence of vomiting in our combination groups is 15.4 & 21.6%. These results are comparable to other studies considering that 21.6 % patients had previous history of POV or motion sickness. [4],[11],[13],[14] .
In the recovery room, the vital signs and pain scores were similar in the three groups. Since the initial prophylaxis in this study included a 5HT 3 antagonist or dexamethasone, we instituted rescue antiemetic therapy from a different class, i.e. intravenous metoclopramide. [22],[23] None of our patients required a second dose of metoclopramide.
We recognize the limitations of our study. Few of our patients were induced with halothane as they did not want to be pricked even after the application of EMLA cream. But the number of patients induced with propofol versus halothane was not statistically significant amongst three groups and none of our patients received propofol infusion for the maintenance of anaesthesia. Secondly, due to non-availability of paediatric laryngeal mask airways (when the study was conducted), all our children were intubated endotracheally, using non-depolarizing muscle relaxant (atracurium) and were reversed with neostigmine at the completion of procedure. However, this was a common factor in all the three groups. Currently, we are using spontaneous ventilation techniques with paediatric LMA insertion for airway management in squint repair surgeries, and this has further reduced the incidence of postoperative emesis. Thirdly, all our patients were extubated within one hour whereas time of onset of action of dexamethasone is two hours. [24] Probably, preoperative administration of dexamethasone in this group of patients may be more effective in reducingthe incidence of POV. Lastly, as both verbal expression of discomfort as well as retrospective reporting of experiences is unreliable, assessment of nausea is difficult in children. Hence, only postoperative emesis was statistically evaluated in our study.
In conclusion, we observed that both IV granisetron or dexamethasone when combined with oral clonidine were equally efficacious in reducing the incidence and severity of POV in day-care strabismus surgery. The need for rescue antiemetics was lower in the combination treatment groups. All the patients, who received intraoperative antiemetic therapy could be discharged home within the proposed time of four hours. This may have economic implications. Both granisetron and dexamethasone were equally efficacious in the prevention of delayed POV. However low costs of dexamethasone and clonidine make this combination a preferred choice in the present cost-conscious scenario. Further studies in large group of clonidine premedicated children using a combination of granisetron and dexamethasone along with a propofol-based anaesthetic may help to achieve the target of zero postoperative emesis. Dose and time of administration of antiemetics in such combinations need to be defined.
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[Table 1], [Table 2], [Table 3]
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