|Year : 2015 | Volume
| Issue : 3 | Page : 193-197
Comparison of palanosetron with ondansetron for postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy under general anesthesia
Jyoti Bhalla, Neha Baduni, Pooja Bansal
Department of Anesthesiology, ESIC Hospital, Sector 15, Rohini, New Delhi, India
|Date of Submission||03-Dec-2013|
|Date of Acceptance||22-Jan-2014|
|Date of Web Publication||2-Jul-2015|
Dr. Neha Baduni
GH 12/183, Paschim Vihar, New Delhi - 110 087
Source of Support: None, Conflict of Interest: None
Background: Post-operative nausea and vomiting (PONV) is a 'big little' problem especially after laparoscopic surgeries. Palanosetron is a new potent 5 hydroxy tryptamine 3 antagonists. In this randomized double blind clinical study we compared the effects of i.v. ondansetron and palanosetron administered at the end of surgery in preventing post-operative nausea and vomiting in patients undergoing laparoscopic cholecystectomy under general anesthesia. Materials and Methods: A total of 100 subjects between 18-60 years with Apfel score ≥2, were randomly assigned into one of the two groups, containing 50 patients each. Group A received ondansetron 4 mg i.v. and Group B received palanosetron 0.07 5mg i.v. both as bolus before induction. The incidence of nausea, retching and vomiting, incidence of total PONV, requirement of rescue antiemetics and adverse effects were evaluated during the first 24 h following end of surgery. Results: The incidence of nausea was significantly lower in patients who had received palanosetron (16%) as compared to ondansetron (24%). Need of rescue antiemetics was significantly higher in patients receiving ondansetron (32%) as compared to palanosetron (16%). The incidence of total PONV was also significantly lower in group receiving palanosetron (20%) as compared to ondansetron (50%). Among the side effects, headache was noted significantly higher with ondansetron (20%) as compared to palanosetron (6%). Conclusion: Palanosetron has got better anti-nausea effect, less need of rescue antiemetics, favourable side effect profile and a decrease in the incidence of total PONV as compared to ondansetron in 24 h post operative period in patients undergoing laproscopic cholecystectomy under general anesthesia.
Keywords: Laparoscopic, nausea, ondansetron, palanesteron, post operative, vomiting
|How to cite this article:|
Bhalla J, Baduni N, Bansal P. Comparison of palanosetron with ondansetron for postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy under general anesthesia. J Min Access Surg 2015;11:193-7
|How to cite this URL:|
Bhalla J, Baduni N, Bansal P. Comparison of palanosetron with ondansetron for postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy under general anesthesia. J Min Access Surg [serial online] 2015 [cited 2020 Jan 18];11:193-7. Available from: http://www.journalofmas.com/text.asp?2015/11/3/193/140219
| ¤ Introduction|| |
Post operative nausea and vomiting (PONV) are distressing symptoms that commonly occur after laparoscopic surgery performed under general anesthesia.  Vomiting may cause dehydration, electrolyte imbalance, disruption of surgical repair and increase in the perception of pain. A number of pharmacological agents (Antihistaminics, butyrephenones, dopamine receptor antagonists) have been tried for the prevention and treatment of PONV but undesirable adverse effects such as excessive sedation, hypertension, dry mouth, dysphoria, hallucinations and extrapyramidal symptoms have been noted. 
The 5-HT3 receptor antagonists are popular drugs for PONV prophylaxis because of their better efficacy to older drugs and favorable side effect profile. Palonosetron is a novel, highly potent and selective second generation 5-HT3 receptor antagonist that has a strong receptor binding affinity and a long plasma elimination half life (40 h), making it more efficacious and cost effective as compared to older agents of its group. ,, And it is further differentiated from other 5HT3 receptor antagonists by interacting with 5HT3 receptors in an allosteric, positively cooperative manner at sites different from those that bind with ondansetron.
Though palonosetron has been extensively used for prevention of chemotherapy induced nausea and vomiting, it has only recently been approved by FDA for use in prophylaxis against PONV. Palanosetron has been compared with placebo for prevention of PONV in patients undergoing open abdominal and gynecological surgeries. , Comparison with other antiemetic drugs and in other types of surgery is still limited. We therefore evaluated the antiemetic effectiveness of i/v palanosetron, administred as a single preinduction dose, in laproscopic cholecystectomy during the first 24 postoperative hours, using the prototype 5HT3 receptor antagonist ondansetron as the comparator drug.
| ¤ Materials and Methods|| |
This randomized double blind study was conducted in a tertiary care hospital of New Delhi after approval from the hospital Ethics Committee on 100 patients between 18-60 years, ASA grade I-II and Apfel score ≥2  undergoing elective laparoscopic cholecystectomy under general anaesthesia.  Sample size for our study was calculated based on previous studies and assuming a power of 80% and a value of <0.05 as significant using the numerical testing (NNT). We excluded patients with known history of allergy to any drug being used in the study, history of vomiting/retching/nausea/antiemetics in 24 h preceding administration of anesthesia, patients on chronic steroids/prokinetics/antiemetics/antacids, menstruating/lactating or pregnant females, h/o alcohol or substance abuse, significant disease of major organs like liver, kidneys, heart, lungs and bone marrow.
Using double blind randomization technique, these patients were divided (chit in the box) into Group A (Ondansetron 4 mg fixed dose), Group B (Palonosetron 0.075 mg fixed dose). The syringes containing the study drug (10 ml) were prepared by an anaesthesiologist who was blinded to randomization schedule and not involved in the study.
A written informed consent from each patient was obtained and all patients were kept fasting overnight. Patients received no premedication with any anxiolytic agent to avoid any pharmacological interference of these drugs with our drugs. Pre-operative baseline values of heart rate and blood pressure were recorded.
On arrival in the operation theatre, the routine monitoring devices (ECG, Pulse Oximetry NIBP) were placed and base line heart rate, blood pressure (SBP + DBP + mean) and arterial O2 saturation (spO2) were recorded. An i.v. line was secured. Both drugs were diluted in 10ml and either drug was given over a period of 10 min. before induction, as per the randomization schedule.
After pre-oxygenation for 3 min, induction of anaesthesia was done with inj. fentanyl 1.5/kg and inj sodium thiopentone 5mg per kg and intubation with appropriate size tube was facilitated after muscle relaxation with inj vecuronium bromide 0.1mg per kg. Anaesthesia was maintained with O2:N2O (50%:50%), isoflorane (0.8-1.0%). Muscle relaxation was maintained with boluses of injection vecuronium bromide with intermittent positive pressure ventilation to maintain end tidal carbon dioxide between 30-35mm Hg. An orogastric tube was also introduced to promote baseline emptying of stomach of air and gastric secretions. The incision site was infiltrated with 0.25% bupivicaine before starting of surgery. Intra-operatively parameters monitored were ECG, blood pressure, pulse rate,end tidal carbon dioxide ( ET CO 2 ), SpO2 and intra-abdominal pressure (IAP). During the surgery, intra abdominal pressure (IAP) of 10-12mm Hg was maintained. At the end of surgical procedure, Ryle's tube was suctioned and removed. Residual neuro muscular blockage was antagonized using i.v. glyccopyrrolate and i.v. neostigmine and trachea was extubated after signs of adequate neuro muscular reversal. For post-operative analgesia, injection diclofenac sodium 1mg/kg intramusculary was administered half an hour before the end of surgery. Intravenous crystalloids were used during intraoperative and immediate post operative period (2 ml/kg/hr). After the surgery, patients were shifted to Post anaesthesia care unit and blood pressure, heart rate, respiratory rate and O2 satuaration were monitored continuously.
Pain intensity was assessed using VAS (Visual Analogue Score). Post operative pain relief was provided with injection diclofenac sodium 1mg/kg intramuscularly 8 h. If VAS score was ≥4, rescue analgesia was provided with inj paracetamol (1gm) intravenously.
Any incidence of nausea, retching or vomiting and use of any rescue medication during the first 24 h at time interval of 0, 1, 2, 6,12 and 24 h were noted in the PACU.
Nausea was defined as the subjective sensation of an urge to vomit, in the absence of expulsive muscular movements. Retching was defined as an unproductive effort to vomit. Vomiting was defined as the forcible expulsion of the gastric contents through the mouth. Retching and vomiting were collectively termed emetic episodes.
For the purpose of study, all episodes of nausea which were immediately followed by retching or vomiting were taken as episode of retching or vomiting respectively. In case, the patient exhibited all the three symptoms within 1-2 min, it was taken as one episode of vomiting for statistical purpose. Nausea (>10 min) without retching or vomiting was taken as episode of nausea . Inj dexamethasone 8mg i.v. slowly was given to patients as rescue treatment in the event of patient having nausea lasting more than 10 min duration, or an episode of retching or emesis. Patients who experience PONV despite receiving antiemetics were classified as treatment failure. Side effects registered were headache, diarrhea and dizziness in the initial 24 h.
Statistical analyses were done using Statistical Package for Social Science Version 9.0 (SPSS LTD, Chicago, IL and U. S. A). Values were presented as mean with standard deviation or number (%). The data obtained from the study was statistically analyzed comparing the demographic data and incidence of PONV among the two groups using the Student t-test and chi square test for multiple comparisons. A P < 0.05 was accepted as statistically significant.
| ¤ Results|| |
The two groups were comparable with respect to age, gender, weight and ASA grading [Table 1]. The mean duration of anesthesia and the mean amount of intraoperative fentanyl used were comparable in the two groups [Table 2]. The incidence of nausea was significantly lower in patients who had received palanosetron (16%) as compared to those who had received ondansetron (24%) [Table 2], whereas the incidence of retching and vomiting was found to be statistically comparable in the two groups. A significantly higher number of patients required rescue antiemetic in the form of inj. Dexamethasone in group A. The incidence of total PONV (nausea + retching + vomiting) was also significantly lower in the group which had received palanosteron (20%) as compared to patients who had received ondansetron (50%). Headache, diarrhea and dizziness were the side effects noted in the two groups [Table 3]. The incidence of headache was significantly higher (20%) with ondansetron. The incidence of diarrhea and dizziness was comparable in the two groups.
| ¤ Discussion|| |
Despite continuing advances in anaesthetic technique and surgical skills, PONV remains one of the major morbidities amongst post operative patients. PONV causes dehydration, hypochloraemic alkalosis, hypokalemia, pulmonary aspiration, hospital readmission and delay in discharge from the hospital.
Laparoscopic surgery has decreased the morbidity associated with cholecystectomy and has become an accepted procedure for symptomatic cholelithiasis.  However, high incidence of PONV (53-72%) is still been reported in patients undergoing this procedure.  Risk factors for nausea and vomiting after laparoscopic surgery include a long period of carbon dioxide insufflation,  gall bladder surgery, , female sex  and postoperative use of opioids. All patients in our study underwent laparoscopic cholecystectomy for cholelithiasis by the same team of anaesthesiologists and surgeons. Duration of anaesthesia, surgery and carbon dioxide insufflation and anaesthetic drugs were similar in both the groups. Patients in both groups also consumed similar amounts of Fentanyl. Therefore, we believe that the differences in the incidence of PONV were attributed to the study drugs.
Various drug regimes and antiemetic interventions have been tried from time to time for prevention of PONV, but with a variable success rate. Nevertheless, a satisfying therapeutic coverage in high risk patients has not yet been achieved by the current array of agents including older 5-HT3 antagonists which do not seem to offer adequately long protection.
Therefore, we decided to conduct a study to evaluate and compare the efficacy of the new and much promising long acting 5-HT3 antagonist palonosetron against ondansetron, which has already been proven effective and safe in prevention of CINV.
It has been recommended to avoid Nitrous oxide and minimizing concentration of the volatile anaesthetics in order to reduce the anaesthesia induced risk for PONV.  We preferred using Nitrous oxide in lower concentrations instead of avoiding it so that the concentration of volatile anaesthetic agent used did not exceed the minimal alveolar concentration(MAC) MAC value. 
Analgesia was supplemented with infiltration of the incision site with 0.25% Bupivicaine before start of surgery and i.m. Diclofenac Sodium at end of surgery for post operative pain relief. This was in accordance with Gan TJ Mayer et al (2003) and Sheila M Wilhelm et al (2007), who recommended opioid sparing with the use of alternate drugs for post operative pain relief such as NSAID's as a PONV reducing strategy. ,
The study dose of i.v. Ondansetron was 4mg and that of i.v. Palonosetron was 75μg, which was as per the recommendations of Mc Kenzie et al (1994) and Candiotti et al (2008). ,
Rescue antiemetic used was inj dexamethasone 8 mg i.v. as it has been recommended that patients should receive a rescue antiemetic drug from a class of antiemetics that is completely different from the one used for prophylaxis.  The consumption of rescue antiemetic in our study was significantly higher in the Ondansetron group, which is due to the weaning of antiemetic effect of i.v. Ondansetron which lasts for 4-5 h. In our study, the overall incidence of PONV was found to be 50% in group A and 20 % in group B, due to difference in t ½. 
We also noted that the incidence of vomiting (20%) as compared to nausea (24%) is less in patients who had received ondansetron which is in accordance with previous studies which shows better antiemetic effect than anti nausea effect of ondansetron.  Similarly, palonosetron shows better anti nausea (8%) effect than anti emetic effect. ,
The comparative efficacy of palanosetron versus ondansetron has not been much demonstrated previously in laparoscopic cholecystectomy and mainly placebo has been used for comparison in clinical trials. ,, However recently few studies have come up which have compared palaonosetron with ondansetron and our results are also similar to them.
Moon et al, found palanosetron to be more effective than ondansetron for high risk patients receiving fentanyl-based patient controlled analgesia after thyroidectomy in the 2-24 h period following surgery. A single dose of palonosetron (250 mcg) was found to be a superior antiemetic to ondansetron (8 mg) in complete prevention of PONV after middle ear surgery during the first 24h postoperative period.  In a randomized controlled trial in day care surgery, single pre-induction i/v dose of palanosetron (75 mcg) proved to be superior to ondansetron(8 mg) in terms of the number of subjects experiencing PONV episodes and the dose of rescue antiemetic required.  The incidence of PONV has been found to be significantly lower with palanosetron than with ondansetron in gynecological laproscopic surgeries, although there were no significant differences in VAS scores for nausea. 
Majority of our results particularly the ones related to the incidence of nausea and vomiting may have been due to the difference in the duration of the two drugs. The statistical values were significant especially in the 6-12 h period between both the groups.
How the efficacy of different 5 HT3 receptor antagonists vary is still unclear but most probably this difference may involve multiple factors such as intrinsic differences in 5 HT3 receptor blocking activity, 5 HT3 receptor affinity and binding stability and differences in autocrine activity of serotonin released from enterochromaffin cells to act on 5 HT3 or 5 HT4 receptors on EC cells. 
There were several limitations to the present study: The efficacies of palonosetron and ondansetron were compared based on the known optimal doses, without knowledge of equipotent doses. Some degree of subjective error is inevitable in the assessment of symptoms. The post operative antibiotic and analgesic regime were kept uniform an all cases, but were not exactly identical in all cases. The baseline incidence of PONV was not evaluated by the inclusion of a placebo group because it would be inhuman and unethical to withhold prophylactic antiemetic drugs in all patients especially those who are at high risk for PONV.
To conclude, the result of the present study clearly indicate the facts that Palonosetron has got a better anti nausea effect, decrease in overall incidence of PONV, lesser need for rescue antiemetics postoperatively and a favorable side effect profile as compared to Ondansetron in the post operative 24 h period thus, providing the patients with smooth convalescent period with lesser PONV, who undergo laparoscopic cholecystectomy surgery under general anaesthesia.
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[Table 1], [Table 2], [Table 3]