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ORIGINAL ARTICLE
Year : 2014  |  Volume : 8  |  Issue : 2  |  Page : 197-201  

Palonosetron, Ondansetron, and Granisetron for antiemetic prophylaxis of postoperative nausea and vomiting - A comparative evaluation


1 Department of Anesthesiology and Critical Care, N.S.C.B. Subharti Medical College, Swami Vivekananda Subharti University, Subhartipuram, NH-58, Meerut, Uttar Pradesh, India
2 Department of Radio-diagnosis, Imaging and Interventional Radiology, N.S.C.B. Subharti Medical College, Swami Vivekananda Subharti University, Subhartipuram, NH-58, Meerut, Uttar Pradesh, India

Date of Web Publication16-Jun-2014

Correspondence Address:
Prof. Kumkum Gupta
108, Chanakyapuri, Shastri Nagar, Meerut - 250 004, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0259-1162.134503

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   Abstract 

Background: Postoperative nausea and vomiting is commonly associated with adverse consequences and hamper the postoperative recovery in spite of the availability of many antiemetic drugs and regimens for its prevention. The study was aimed to compare the prophylactic effects of intravenously administered palonosetron, ondansetron, and granisetron on prevention of postoperative nausea and vomiting after general anesthesia.
Materials and Methods: This prospective, double-blind study, comprised 120 adult consented patients of ASA grade I and II of either gender, was carried out after approval of Institutional Ethical Committee. Patients were randomized into three equal groups of 40 patients each in double-blind manner. Group P received inj. palonosetron (0.075 mg), group O received inj. ondansetron (4 mg), and group G received inj. granisetron (2 mg) intravenously five minutes before induction of anesthesia. The need for rescue antiemetic, episode of postoperative nausea and vomiting, and side effects were observed for 12 hours in the post-anesthesia care unit. At the end of study, results were compiled and statistical analysis was done by using ANOVA, Chi-square test, and Kruskal Wallis Test. Value of P < 0.05 was considered significant.
Results: The incidence of nausea and vomiting was maximal during the first four hours postoperatively. The complete control of postoperative nausea and vomiting for first 12 hours was achieved in 30% patients of ondansetron group, 55% patients of granisetron group, and 90% patients of palonosetron group. Safety profile was more with palonosetron.
Conclusion: Palonosetron was comparatively highly effective to prevent the PONV after anesthesia due to its prolonged duration of action than ondansetron and granisetron.

Keywords: Granisetron, ondansetron, palonosetron, postoperative nausea and vomiting


How to cite this article:
Gupta K, Singh I, Gupta PK, Chauhan H, Jain M, Rastogi B. Palonosetron, Ondansetron, and Granisetron for antiemetic prophylaxis of postoperative nausea and vomiting - A comparative evaluation. Anesth Essays Res 2014;8:197-201

How to cite this URL:
Gupta K, Singh I, Gupta PK, Chauhan H, Jain M, Rastogi B. Palonosetron, Ondansetron, and Granisetron for antiemetic prophylaxis of postoperative nausea and vomiting - A comparative evaluation. Anesth Essays Res [serial online] 2014 [cited 2021 Oct 28];8:197-201. Available from: https://www.aeronline.org/text.asp?2014/8/2/197/134503


   Introduction Top


Postoperative nausea and vomiting (POVN) is considered one of the most unpleasant postoperative discomforts and lead to serious complications of aspiration of gastric contents, suture dehiscence, esophageal rupture, subcutaneous emphysema, or pneumothorax. The incidence of PONV is 30-40% in normal population and touches a peak of 75-80% in certain high-risk groups. [1] With the use of lesser emetogenic anesthetic techniques and advent of newer drugs for the prophylaxis of postoperative nausea and vomiting, the incidence of PONV has come down by 50%, especially with the use of non-opioid medication for pain relief.

Postoperative nausea and vomiting is defined as nausea and/or vomiting occurring within 24 hours after surgery. Patient characteristics, type of surgical procedure, duration of anesthesia, and surgery are few of the important determinants for risk of PONV. There is involvement of three nerves and seven neurotransmitters for activation of vomiting center, which makes the prophylaxis and treatment complex. The antiemetic premedication can reduce the rate of postoperative nausea and vomiting. Numerous pharmacological agent, regimens, and techniques were evolved from time to time, but they have limited efficacy due to various side effects. [2]

5-hydroxytryptamine subtype 3 (5-HT3) receptor antagonist are effective antiemetic drugs with more safety and favorable side effect profile as they lack the sedation, dysphoria, and extra-pyramidal side effects of other commonly used antiemetics. Ondansetron is the first 5-HT3 antagonist, used alone or in combination for the prophylaxis due to its lower cost. Granisetron is highly selective, potent, and produces irreversible block of 5-HT3 receptors. Palonosetron is the second generation 5-HT3 antagonist with unique chemical structure and longer half- life of 40 hours. [3],[4],[5],[6],[7],[8]

The present double-blind, randomized prospective study was aimed to compare the antiemetic efficacy, duration of action, and side effects of palonosetron, ondansetron, and granisetron for antiemetic prophylaxis of postoperative nausea and vomiting after laparoscopic cholecystectomy under general anesthesia.


   Materials and Methods Top


After approval by the Institutional Ethical Committee and written informed consent, 120 adult patients of American Society of Anesthesiologist physical status I and II, aged 18-58 years of either gender, scheduled for elective laparoscopic cholecystectomy under general anesthesia, were enrolled for present study. All the patients underwent pre-anesthetic assessment before enrollment. Patients with history of systemic hypertension, endocrine or metabolic disorders, hepatic or renal disease, cardio-pulmonary dysfunction, patients with gastro-intestinal disorders, psychiatric diseases, and morbid obesity were excluded from study. Other exclusion criterions were pregnant and menstruating females, history of motion sickness or those who had taken antiemetic drugs within 24 hours before surgical procedures.

The total 120 patients were equally divided into three groups of 40 patients according to a computer-generated random table. Patients of group P were given injection palonosetron (0.075 mg), patients of group O were given injection ondansetron (4 mg), and patients of group G were given injection granisetron (2 mg), intravenously along with premedication, five minutes before induction of general anesthesia. The study drug preparation was done by an assistant who was unaware to the study protocol and was not involved in the study for any further evaluation of patients.

All patients were given tab alprazolam 0.25 mg and tab ranitidine 150 mg the night before surgery and were kept fasting for eight hours prior surgery. On arrival to operation-theater, routine monitoring of heart rate, systemic arterial blood pressure, pulse oximetry (SpO 2 ), electrocardiogram (ECG) was started. After securing intravenous line, infusion of lactate Ringer was started. Patients were premedicated with intravenous midazolam (0.05 mg kg -1 ), fentanyl (2 μg kg -1 ), and glycopyrrolate (0.2 mg) followed by study medication according to group allocation five minutes prior to induction of general anesthesia.

After pre-oxygenation, induction was done with propofol (2 mg kg -1 ), and tracheal intubation was facilitated with vecuronium bromide 0.08 mg kg -1 . Anesthesia was maintained with isoflurane, N 2 O (60%) in oxygen. All patients were mechanically ventilated to maintain the EtCO2 between 35-40 mm Hg. Additional analgesia during the surgery was achieved with fentanyl (25 μg). At the end of surgery, the residual neuromuscular blockade was antagonized with appropriate doses of neostigmine (0.05 mg kg -1 ) and glycopyrrolate (0.01 mg kg -1 ). Extubation was performed when respiration was adequate and patient was able to obey simple commands.

The baseline systemic arterial blood pressure, pulse rate, and SpO2 were recorded followed by after premedication, after induction and then at five min intervals till one hour and then at every 15 min till the end of surgery. They were monitored for any hypotension, hypertension, arrhythmias, hypoxemia, and bronchial spasm. Hemodynamic changes occurring during study period were managed with volume expansion, vasopressor or atropine, if required.

Postoperatively, nausea or emetic episode were recorded by the nursing staff without knowledge of which group of anti-emetic drug was given to the patients. The side effects like headache, dizziness, and drowsiness were also noted. Postoperatively, the patients were given intramuscular injection of diclofenac sodium (75 mg) for postoperative analgesia.

Nausea was defined as an urge to vomit, and vomiting was defined as the forceful expulsion of gastric contents from the mouth. Patients were asked about nausea and vomiting at 2, 4, 6, and 12 hours. Complete response was defined as no nausea, retching or vomiting, and no need of rescue antiemetic medication within 12 hours in postoperative period. If required, rescue anti-emetic metoclopramide 5 mg was given intramuscularly. The total number of complete responders was recorded.

For the study, the minimum sample size required was 32 patients in each group for type 1 error of 0.01 and power of 90% to ensure statistically significant results. Assuming a 5% dropout rate, total 120 patients were enrolled for better validation of results. The recorded data are systematically compiled in tabulated manner as mean ± SD and analyzed by Stat graphics Centurion, using one-way ANOVA and Chi-square test. Comparison between groups for postoperative nausea and vomiting score was performed by using the Kruskal Wallis test. P < 0.05 was considered as statistically significant.


   Results Top


The study was successfully conducted on 120 adult consented patients for their postoperative assessment of PONV. All the three groups were comparable for their demographic profiles with respect to age, sex, BMI and ASA physical status and duration of laparoscopic cholecystectomy. [Table 1].
Table 1: Demographic profiles of patients (n-120)

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Preoperatively, the baseline heart rate and systemic blood pressure were comparable among the three groups with no statistically significant difference. The heart rate and systemic blood pressure did not show any significant difference among the groups after intubation at 5 minutes, 15 minutes, and 45 minutes, and at the end of surgical procedures.

In the present study, only 32 patients (27%) suffered from nausea and 28 patients (23%) showed tendency of postoperative vomiting. The incidence of postoperative nausea and vomiting was maximal during the first four hours and was more in the patients of ondansetron group as compared to patients of palonosetron and granisetron group.

The incidence of nausea in ondansetron group was seen in 12 patients (30%) at 0-4 hours; in palonosetron group, it was seen only in two patients (5%) while six patients (15%) of granisetron group has suffered from nausea. The difference among the three groups was statistically highly significant (P < 0.01). Incidence at 4-12 hours was observed in eight patients (20%) of ondansetron group, only one patient (2.5%) of palonosetron group as compared to three patients (7.5%) of granisetron group. The difference among the groups was statistically significant (P < 0.05) [Table 2].
Table 2: Incidence of nausea (n-120)

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Incidence of vomiting episode at 0-4 hours were observed in 10 patients (25%) of ondansetron group, two patients (5%) of palonosetron group, and six patients (15%) of granisetron group. The difference among the groups was statistically highly significant (P < 0.01). At 4-12 hours, seven patients (17.5%) of ondansetron group suffered from vomiting as compared to only one patient (2.5%) in palonosetron group and two patients (5%) of granisetron group. The difference among the three groups was statistically significant (P < 0.05) [Table 3].
Table 3: Incidence of vomiting (n-120)

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The number of complete responders was three in group O, 34 in group P, and 23 in group G over the postoperative period of 12 hours. The difference among the group was statistically highly significant. Complete control of postoperative nausea and vomiting (PONV) for 12 hours after administration of study drug was achieved in 30% patients of ondansetron group, 55% patients of granisetron group, and 90% patient of palonosetron group [Table 4].
Table 4: Postoperative response of nausea and vomiting (n-120)

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The incidences of side effects were more in patients of ondansetron group, but with no statistical significant difference among the groups. None of the patient showed any allergic reaction or any other side effects due to study medication [Table 5].
Table 5: Comparative evaluation of side effects (n-120)

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   Discussion Top


The present study showed that antiemetic prophylaxis with 5-hydroxytryptamine subtype 3 (5-HT3) antagonist provided clinically effective prevention of postoperative nausea and vomiting with statistically significant difference in their efficacy and duration of action. There were only few episodes of headache and dizziness, which were resolved as time relapsed without any specific treatment.

Postoperative nausea and vomiting is defined as nausea and/or vomiting occurring within 24 hours after surgery. Vomiting involves co-ordination of the respiratory, gastro-intestinal and abdominal musculature, and is controlled by the vomiting center, which is situated in the lateral reticular formation close to tractus solitarius in the brain stem. The chemoreceptor trigger zone (CTZ) in the area postrema is rich in dopamine, opioid, and serotonin or 5-hydroxytryptamine receptors.

The etiology of the PONV is complex and multifactorial. Preoperative anxiety, positive pressure ventilation, inhalational anesthetic agents, and nitrous oxide increase the risk of PONV. Anesthetic agents initiate the vomiting reflex by stimulating the central 5-HT3 receptors on the chemoreceptor trigger zone (CTZ). PONV is more common in younger age group and in obese patients. [9],[10],[11],[12] Apfel et al. considered laparoscopic surgery, female gender, non-smokers, a history of PONV, motion sickness, and postoperative opioid therapy as important independent causal factors for PONV. [13]

Antiemetic drugs tend to have more prominent action at one or two receptors while 5-HT3 receptor antagonists are highly specific and selective for acting against nausea and vomiting by binding to the serotonin 5-HT3 receptor in the chemoreceptor trigger zone (CTZ) and at vagal efferent in the gastrointestinal tracts. [14],[15] The present study showed that the palonosetron and granisetron were statistically superior to ondansetron for control of PONV and the difference was statistically highly significant in first 12 hrs (P < 0.05). During the present study, anesthetic and surgical factors were well controlled, so that any difference in emesis free episodes can be attributed to the study drugs and goes in accordance with the studies conducted by Tramθr et al. [16] and Gigilla et al. [17]

The optimal dose of palonosetron is 0.075 mg and is more effective in preventing nausea and vomiting for a longer period of time with a single dosing, which makes it more cost-effective.

In our study, the complete response was 86.6% with granisetron and 90% with palonosetron, which is in accordance with the study of Bhattacharyya et al. [18] Clinical recovery score and recovery time were comparatively lower in patients of ondansetron group as compared to patients of granisetron group with no significant difference.

In the present study, we did not include any control group receiving placebo as PONV is not controlled by placebo. It was suggested that if active drugs are available, placebo-controlled trials are unethical as PONV is very much distressing after major surgery. [19] Evidence-based management of postoperative nausea and vomiting also justifies the use of prophylactic antiemetic medication for the prevention of postoperative nausea and vomiting.


   Conclusion Top


The present study showed that antiemetic prophylaxis with 5-hydroxytryptamine subtype 3 (5-HT3) antagonist provided clinically effective prevention of postoperative nausea and vomiting with statistically significant difference in their efficacy and duration of action. Palonosetron is better drug for antiemetic prophylaxis of PONV in patients undergoing laparoscopic cholecystectomy under general anesthesia as compared to ondansetron and granisetron due to its prolonged duration and minimal side effects.

 
   References Top

1.Islam S, Jain PN. Postoperative nausea and vomiting (PONV): A review article. Indian J Anaesth 2004;48:253-8.  Back to cited text no. 1
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2.Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003;97:62-71.  Back to cited text no. 2
    
3.Loewen PS, Marra CA, Zed PJ. 5-HT3 receptor antagonist vs traditional agents for the prophylaxis of postoperative nausea and vomiting. Can J Anesth 2000;47:1008-18.  Back to cited text no. 3
    
4.Gan TJ. Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: Are they all the same? CNS Drugs 2005;19:225-38.  Back to cited text no. 4
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5.Ho KY, Gan TJ. Pharmacology, pharmacogenetics, and clinical efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Curr Opin Anaesthesiol 2006;19:606-11.  Back to cited text no. 5
    
6.Basu A, Saha D, Hembrom BP, Roy A, Naaz A. Comparison of palonosetron, granisetron and ondansetron as antiemetics for prevention of postoperative nausea and vomiting in patients undergoing middle ear surgery. J Indian Med Assoc 2011;109:327-9.  Back to cited text no. 6
    
7.White PF, Scuderi PE. Prevention of postoperative nausea and vomiting (PONV): A dose-ranging study involving palonosetron, a potent 5-HT3 receptor antagonist. Anesthesiology 2005;103:A703.  Back to cited text no. 7
    
8.Swaika S, Pal A, Chatterjee S, Saha D, Dawar N. Ondansetron, ramosetron or palonosetron: Which is a better choice of antiemetic to prevent postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy? Anesthesia Essays Res 2011;52:182-6.  Back to cited text no. 8
    
9.Wang SM, Kain ZN. Preoperative anxiety and postoperative nausea and vomiting in children: Is there an association? Anesth Analg 2000;90:571-5.  Back to cited text no. 9
    
10.Gan TJ. Risk factors for postoperative nausea and vomiting. Anesth Analg 2006;102:1884-98.  Back to cited text no. 10
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11.Pierre S, Como G, Benais H, Apfel CC. A risk score-dependent anti-emetic approach effectively reduces postoperative nausea and vomiting- A continuous quality improvement initiative. Can J Anesth 2004;51:320-5.  Back to cited text no. 11
    
12.Leslie K, Myles PS, Chan MT, Paech MJ, Peyton P, Forbes A, et al. Risk factors for severe postoperative nausea and vomiting in a randomized trial of nitrous Oxide-based vs. nitrous oxide-free anesthesia. Br J Anaesth 2008;101:498-505.  Back to cited text no. 12
    
13.Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350:2441-51.  Back to cited text no. 13
    
14.Gralla R, Lichinister M, VanDer VS. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately Emetogenic chemotherapy: Results of double-blind randomized Phase III trial comparing single doses of palanosetron with ondansetron. Ann Oncol 2003;14:1570-7.  Back to cited text no. 14
    
15.Bajwa SS, Bajwa SK, Kaur J, Sharma V, Singh A, Goraya SP, et al. Palonosetron: A novel approach to control postoperative nausea and vomiting in day care surgery. Saudi J Anaesth 2011;5:19-24.  Back to cited text no. 15
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16.Tramer MR. A rational approach to control postoperative nausea and vomiting: Evidence from systemic reviews. Part II Recommendations for prevention and treatment and research agenda. Acta Anaesthesiol Scand 2001;45:14-9.  Back to cited text no. 16
    
17.Gigilla CA, Soares H. Granisetron is equivalent to Ondansetron for prophylaxis of chemotherapy induced nausea and vomiting. Cancer 2000;89:2301-8.  Back to cited text no. 17
    
18.Bhattacharyya DP, Dawn S, Nayak S, Roy PR, Acharya A, Dey RK. A comparative study between palonosetron and granisetron to prevent postoperative nausea and vomiting after laparoscopic cholecystectomy. J Anaesth Clin Pharmacol 2010;26:480-3.  Back to cited text no. 18
    
19.Aspinall RL, Goodman NW. Denial of effective treatment and poor quality of clinical information in placebo controlled trials of ondansetron for postoperative nausea and vomiting: A review of published trials. BMJ 1995;311:844-6.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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