Increased Incidence of nausea and vomiting during the first 24 -48 hours post- operative period following surgery is defined as postoperative nausea and vomiting. The clinical term Post Operative Nausea and Vomiting (PONV) got popularized after the landmark review from Watcha and White in 1992 and became a medical subject heading in the National Library of Medicine in the year 1999.

Post operative nausea and vomiting, is an unpleasant experience subjectively and is also accompanied with grave complications such as aspiration, wound gaping, suture dehiscence in case of major abdominal surgeries^6.  PONV is also one of the causes for hospital readmission following day care/ambulatory surgeries ⁷

Some of predisposing factors  include age, gender of the patient, type of surgery, duration of surgery, smoking history⁴, history of motion sickness and anesthesia-related factors. Among anesthesia related factors, most common are General anesthesia technique, usage of Nitrous oxide, volatile anesthetics and opioids.

Following pain, it is the most frequent complication in the postoperative period². Previously, the incidence was estimated to be 80% ³ and has reduced with usage of various 5HT3 receptor antagonist.

PONV continues to be a concerning complication even in the age of advanced medicine and improved postoperative care. Therefore, more attention needs to be specified for its prevention³. So far, various pathways and mechanisms have been postulated. Still exact etiology has not  been adequately described ⁴. Multiple studies have also implicated for a greater insight and better understanding in the inhibition and treatment of post operative nausea and vomiting⁸ This induced the pursuance for a credible antiemetic which can address this issue in the patients

Various antiemetics are available at present include, (a)Dopamine antagonist such as Droperidol, metoclopramide, haloperidol, (b)H1 receptor antagonist, such as cyclizine, promethazine, (c)Anticholinergic drugs such as Atropine and hyoscine, (d) 5HT3 receptor antagonists such as Ondansetron, granisetron, Dolasetron, Tropisetron and (e) Steroids. Among these most currently used on day-to-day basis are Metoclopramide, Ondansetron and dexamethasone.

Lately FDA has approved Aprepitant which is an NK-1 receptor antagonist for its use as antiemetic. In the near future, other NK-1 receptor antagonists which are currently under trials are expected to enter the market¹⁰.

Currently 5HT3 receptor Antagonists are considered to be superior to other class of drugs, but none of them can be classified as potent enough to absolutely prevent the occurrence of post operative nausea and vomiting. Hence multifaceted intervention is advocated in high-risk patients susceptible to post operative nausea and vomiting¹¹.

Among 5HT3 receptor antagonists, the first generation drug Ondansetron is widely used as  first line of drug. Recent studies have demonstrated  that Second generation   drug palonosetron¹¹ was found to be the most effective drug¹². Hence this study was conducted to compare the efficacy of drug palonosetron against most commonly used antiemetic drug ondansetron.

Second generation drug palonosetron¹¹ was found to be the most effective drug¹².

AIMS AND OBJECTIVES

1. The goal of this double blinded interventional prospective study is to compare the efficacy of intravenous ondansetron (4 mg) versus intravenous palonosetron (75 mcg) in the prevention of post-operative nausea and vomiting in patients undergoing laparoscopic gynaecological surgery under general anaesthesia.
2. To compare the incidence of nausea and vomiting in both the drug groups.
3. To compare the need for requirement of rescue antiemetic in both the groups.
4. Adverse effects of the drugs.
5. Complications of the drugs.

This prospective, randomized, double-blind study was conducted over a period of 1 year at Subbaiah Institute of Medical Sciences, Shimoga. After obtaining institutional approval 80 patients aged above 18 yrs, belonging to ASA 1 and 2 posted for elective laparoscopic gynecological surgeries and those willing to be included in the study were  allotted to one of the 2 groups, Group O and Group P, with 40 patients in each group. Randomization was done  using randomly generated computerized table.

Pregnant females, patients with history of known cardiovascular disease or liver, renal, endocrine abnormalities and malignancy were excluded from the study. Any patient who had preexisting Nausea and vomiting, or those who received anti emetic prior to induction were also excluded from the study.

After pre anesthesia evaluation, patients were counselled and written informed consent was obtained from the patients. All the patients received tablet ranitidine 150 mg as premedication at night on the previous day of the surgical procedure and also on the morning of the surgery. Once the patient was shifted to operating room, standard ASA monitors were connected for monitoring. Intravascular access secured with large bore iv cannula.

The study medication, that is Palonosetron 75 mcg or 4 mg Ondansetron was given as intravenously just before induction of anesthesia according to the randomized computer chart.

The study medication was prepared by the research personnel and conducting anesthesiologist

Standard general      anesthesia technique was followed for all the patients. All patients received Inj.Glycopyrrolate 0.2mg IV as premedication. Intravenous induction was done with Inj.Propofol 2mg/kg and analgesia was provided by Inj.Fentanyl 2 mcg/kg IV. Muscle relaxation was achieved with Inj Vecuronium 0.1mg/kg IV. Bag mask ventilation was continued till adequate muscle relaxation, then patient was intubated with appropriate size ET tube, cuff inflated tube secured and ventilation maintained with IPPV. Anaesthesia was maintained with titrated concentration of Sevoflurane, Oxygen and air in the ratio of 1:1, and intermittent dose of Vecuronium 0.01 mg/kg every 30 min. At the end of surgery all patients were given Inj neostigmine 0.05mg/kg along with ing glycopyrrolate for reversal of muscle relaxation. Extubation was done after adequate recovery from muscle relaxants and anesthesia. Patients were shifted to post operative care unit for further monitoring. Duration of anesthesia and surgery were also recorded.

After surgery, all patients were monitored for 24 hours . the occurrences of nausea, retching, and vomiting were observed during the time interval between 0 to  2^nd  hr, 2^nd to 6^th  hr, and 6^th  to 24 hr,. Patients with single episode of vomiting at any time during the follow up period received inj Metaclopromide 10mg IV as rescue medication. The need for rescue medication was also observed. Patients who were free of nausea, retching and vomiting were considered as complete responders. Within the first 24 hours following surgery, side effects of the study medicine such as headache, stomach discomfort, constipation, and dizziness were also observed.

STATISTICAL ANALYSIS

The statistical analysis was done by using SPSS version 25.0. Microsoft Word and Excel have been used for generating graphs and tables. For discrete data, the values were represented as numbers and percentages, and to test the association between the groups; the chi-square test was used. For continuous data, the data values were expressed as mean and standard deviation, and to test the mean difference between the groups.

TABLE 1- AGE DISTRIBUTION AMONG THE STUDY POPULATION

The table 1 shows age wise distribution among group O and P. The mean age in Group O and Group P was 39.2 ± 11.75 and 40.92± 11.29 respectively. The p value 0.505 showed no statistical significance among both groups.

TABLE 2 - DISTRIBUTION OF ASA GRADES IN TWO GROUPS

The table 2 shows distribution of ASA grades in Group O & Group P. The p value 1.000 showed no statistical significance with regard to ASA grade distribution among both the groups.

TABLE 3- DISTRIBUTION OF PROCEDURE TIME BETWEEN THE GROUPS

The average duration of general anaesthesia in Group O is 155.75 minutes where as in Group P is 152.82 minutes. The average time of surgical procedure in Group O is 130.67 minutes where as in Group P is 127.52 minutes. All of them were not statistically significant.

TABLE 4 - COMPARISON OF INCIDENCE OF NAUSEA WITHIN 24 HOURS OF POST OPERATIVE PERIOD IN BOTH THE GROUPS

From 0 -2 hours : 27.5% patients in group O had nausea where as 25% patients experienced nausea in group P which is not statistically significant as p value is 0.799

From 2 6 hours: in group O 42.5% and in group P 17.5% experienced nausea during this period. This reduction in the incidence of nausea in group P is statistically significant with p value 0.015.

From 6-24 hours: 35% in group O and 5% in group P had nausea with the p value 0.001 which is statistically significant.

The reduction in the incidence of PONV in group P during 2-6 and 6-24 hours postoperative period is statistically significant with the p values < 0.05.

TABLE 5 - COMPARISON OF INCIDENCE OF RETCHING WITHIN 24 HOURS OF POST OPERATIVE PERIOD IN BOTH THE GROUP

From 0 -2 hours: in group O 10% patients and 7.5% patients in group P had retching during this period and p value is 1 which is not statistically significant.

From 2                   6 hours: 2.5% patients in both the groups O and P experienced retching and the p value of 1 is not statistically significant.

From 6                   24 hours: none of the patients had retching during this period in both the groups.

TABLE 6       - COMPARISON OF INCIDENCE OF VOMITING WITHIN 24 HOURS OF POST OPERATIVE PERIOD IN BOTH THE GROUPS

From 0 2 hours: 20 % of the patients in group O and 10% of the patients in group P had vomiting. P value is o.348 which is not statistically significant.

From 2 6 hours: 22.5% in group O and 10% in group P experienced vomiting. P value is 0.225 which is not significant statistically.

From 6-24 hours : 27.5% patients in group O and 1% of the patients in group P had vomiting and the p value is 0.005 which is statistically significant.

Though group P had lesser incidence of vomiting during 0-2 and 2-6 hour post operative period as compared to group O, it is not statistically significant.

TABLE 7 - COMPARISON OF INCIDENCE OF HEADACHE, DIZZINESS AND CONSTIPATION IN BOTH THE GROUPS

The incidence of headache was 15% (6 Patients) in ondansetron group and 5% (2 Patients) in palonosetron group.
The two groups were comparable with P value of 0.264 which is not significant.

TABLE 8 - COMPARISON OF NEED FOR RESCUE MEDICATION WITHIN  24 HOURS OF POST OPERATIVE PERIOD IN BOTH THE GROUPS

From 0  2 hours: 7.5% patients in group O and 2.5% patients in group P required rescue medication, p value is 0.608 which is not statistically significant. From 2  6 hours: 7.5% patients in group O and 2.5% patients in group P required rescue medication, p value is 0.608 which is not statistically significant. From 6  24 hours: 20% patients in group O and 5% patients in group P required rescue medication during this period. P value is 0.091 which is not statistically significant.

Even today Postoperative nausea and vomiting is a distressing complication to the patients in the postoperative period despite advent of new generation of antiemetics. Due to a complex mechanism of pathogenesis, it still remains a matter of concern for anesthesiologists. PONV in the postoperative period can lead to untoward complications such as dehydration, aspiration, unforeseen hospital admission, delayed wound healing, and wound dehiscence, leading to delayed discharge from the hospital¹³.

The pathophysiology of PONV is multiplex involving numerous receptors and pathways. The chemoreceptor trigger zone, vagal mucosal pathway in gastrointestinal system, vestibular system neuronal pathways, reflex afferent pathways from cerebral cortex and  afferents from midbrain are the five main pathways that activate nausea and vomiting. Stimulation these pathways can initiate PONV through cholinergic, histaminergic, serotonergic or dopaminergic receptors¹⁵.

Currently 5HT3 receptor antagonists are used as first line choice in the prophylaxis of nausea and vomiting due to their higher margin of safety and tolerable side effects. Among this ondansetron is the first drug of choice. Ondansetron is the first generation 5HT3 receptor antagonists and it acts by blocking the depolarizing action of serotonin exerted through 5HT3 receptors on vagal afferents in the gastro intestinal tract as well as in NTS (Nucleus tractus solitaries) and CTZ (chemoreceptor trigger zone). Its side effects include headache, dizziness, mild constipation, abdominal discomfort¹⁶.

Palonosetron is a second generation 5HT3 receptor antagonists. It is the longest acting 5HT3 receptor antagonist with the elimination half life of 40 hours approximately due its highest affinity for the receptor site. It is the only drug of its class that has been approved by US FDA for delayed chemotherapy induced nausea and vomiting. It is metabolized in the liver and kidney ( by CYP2D6, CYP3A4 AND CYP1A2) and excreted by kidney. common side effects of inj palonosetron include headache, fatigue, dizziness, abdominal pain, QT prolongation was seen when given along with moxifloxacin, erythromycin, anti-psychotics, antidepressants etc¹⁷.

In our study, the incidence of nausea, retching, vomiting at 24 hours post procedure in Ondansetron group was 35%, 0% and 27.5% and 2%, 0% and 1% in Palonosetron group respectively. The incidence of nausea and vomiting was higher at a period between 2hrs and 6hrs post procedure. The incidence of nausea is 42.5% in Ondansetron group and 17.5 % in Palonosetron group during this period. 22.5% in Ondansetron group and 10% in Palonosetron group had vomiting at this period. The incidence of vomiting was seen highest between 6-24 hour post operative period i.e 27.5% in ondansetron group where as it was 1% in palonosetron group during this period. All the patients with vomiting were given  Inj Metaclopromide 10 mg as rescue medication.

The complete responders in Ondansetron group are 57.5 % and in Palonosetron group are 75 %. Adverse events like headache, dizziness and constipation were reported in both the groups throughout the study but       it was of no statistical significance.

F J Davolos et al¹⁸., (2020) compared palonosetron (0.075mg) and ondansetron (8mg) for prophylaxis of post operative nausea and vomiting in laparoscopic cholecystectomy. This randomized controlled trial was conducted in 212 patients randomized into 2 equal groups. One group received ondansetron (8mg) and another received palonosetron (0.075mg) intravenously just before the induction of anesthesia. Patients were monitored for 24 hours post operatively for incidence of PONV at the intervals of 0-2, 2-6, 6-12, 12-24 hours.

The results from the study showed highest incidence of PONV was between 2-6 hours post operatively in ondansetron group (43.4%) as compared with palonosetron group 36.8% with P value <0.05 which is statistically significant. there was no remarkable difference  between both the groups statistically in the incidence of post operative nausea and vomiting and the need of rescue medication during  other time intervals. It was observed that palonosteron group was superior to ondansetron in the prevention of PONV.

After analysing the results from our study, we conclude that Palonosetron 75 mcg is more efficacious than Ondansetron 4 mg in preventing PONV in patients undergoing laparoscopic gynaecological surgeries.

Limitations of the study-

This study was conducted in only female patients hence further test will be needed to compare its effect in males. The study also needs to be conducted in ENT ophthal surgeries were the incidence of PONV is highest. Further test will be required to analyse its effect in chemotherapy

1. Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology. 1992 Jul;77(1):162
2. Shaikh SI, Nagarekha D, Hegade G, Marutheesh M. Postoperative nausea and vomiting: A simple yet complex problem. Anesth Essays 2016;10(3):388 96.
3. Maharaj CH, Kallam SR, Malik A, Hassett P, Grady D, Laffey JG. Preoperative intravenous fluid therapy decreases postoperative nausea and pain in high risk patients. Anesth Analg. 2005 Mar;100(3):675
4. Ghosh S, Pal A, Acharya A, Biswas C, Ghosh TR, Ghosh S. Palonosetron and palonosetron plus dexamethasone to prevent postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: A prospective, randomized, double- blind comparative Anesth Essays Res. 2011 Dec;5(2):134 7.
5. Chung F, Mezei G. Factors contributing to a prolonged stay after ambulatory Anesth Analg. 1999 Dec;89(6):1352 9.
6. Gold BS, Kitz DS, Lecky JH, Neuhaus JM. Unanticipated admission to the hospital following ambulatory surgery. JAMA. 1989 Dec 1;262(21):3008
7. Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, et Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014 Jan;118(1):85 113.
8. Patel L, Lindley C. Aprepitant--a novel NK1-receptor antagonist. Expert Opin 2003 Dec;4(12):2279 96.
9. Candiotti KA, Kovac AL, Melson TI, Clerici G, Joo Gan T. A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Three Different Doses of Palonosetron Versus Placebo for Preventing Postoperative Nausea and Vomiting. Anesth Analg. 2008 Aug;107(2):445
10. Kovac AL, Eberhart L, Kotarski J, Clerici G, Apfel C, Palonosetron 04-07 Study Group. A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo in preventing postoperative nausea and vomiting over a 72-hour Anesth Analg. 2008 Aug;107(2):439 44.
11. Davolos FJC, Modolo NS, Braz LG, Nascimento Junior P do. Palonosetron versus ondansetron for prophylaxis of postoperative nausea and vomiting in laparoscopic cholecystectomy: a non- inferiority randomized controlled trial. Braz J Anesthesiol Engl Ed. 2021 Jul;S0104001421002761.
12. Bhargava T, Sahu S, Singh TK, Shrivastava D, Kumar A, Mohammad D, et al. Comparison of palonosetron and ondansetron in preventing postoperative nausea and vomiting in renal transplantation recipients: a randomized clinical trial. Braz J Anesthesiol Engl Ed [Internet]. 2021 Aug 16; Available from: https://sciencedirect.com/science/article/pii/S01040014210031 6X
13. Elrashidy AA, Elsherif M, Elhag W, Abdelaziem O, Abdelaziem S, Abdel-Rahman RS. Palonosetron versus Ondansetron as Prophylaxis against Postoperative Nausea and Vomiting (PONV) after Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Open J Anesthesiol. 2020 Oct 26;10(10):349 60.
14. Verma S, Chand T, Singh MK. Comparative study between ondansetron & palonosetron in prevention of post operative nausea vomiting operated under general anaesthesia: A randomised double blind Indian J Clin Anaesth. 2020 Jul 15;7(2):245 50.
15. Aydin A, Kaçmaz M, Boyaci A. Comparison of ondansetron, tropisetron, and palonosetron for the prevention of postoperative nausea and vomiting after middle ear surgery. Curr Ther Res. 2019;91:17
16. Sharma S, Khanna S, Das J, Mehta Y, Handa KK. A randomized study to compare palonosetron with ondansetron for prevention of postoperative nausea and vomiting following middle ear surgeries. J Anaesthesiol Clin 2019;35(2):182 7.
17. Carvalho Braga EL, Figueiredo NV, Barrucand L, Cavalcanti IL. Use of palonosetron and ondansetron in the prophylaxis of postoperative nausea and vomiting in women 60 years of age or older undergoing laparoscopic cholecystectomy: A randomised double-blind study. Eur J Anaesthesiol 2019 Mar;36(3):241 2.