Postoperative nausea and vomiting (PONV) remains one of the most distressing complications of anesthesia and surgery. Despite advances in anesthetic drugs and techniques, PONV continues to affect 20-30% of surgical patients overall, and up to 70% of high-risk patients undergoing laparoscopic procedures. Historically, during the “ether era,” the incidence of PONV was reported as high as 75-80%, making it one of the most feared postoperative complications after pain. Even today, many patients report PONV to be more unpleasant than postoperative pain itself, and its occurrence often undermines the patient’s surgical experience and prolongs hospital stay. The clinical significance of PONV extends beyond patient discomfort. Persistent nausea and vomiting can lead to dehydration, electrolyte imbalance, wound dehiscence, pulmonary aspiration, and rarely, esophageal rupture. In day-care and short-stay surgeries such as laparoscopic cholecystectomy, uncontrolled PONV is a common reason for unanticipated hospital admission, adding to healthcare costs and resource utilization. Therefore, the prevention of PONV is a critical determinant of recovery quality, patient satisfaction, and efficiency of perioperative care.[1] The pathophysiology of PONV is complex and multifactorial. Contributing factors include patient-related elements (female gender, younger age, nonsmoking status, history of motion sickness or previous PONV, obesity), anesthetic factors (volatile anesthetics, nitrous oxide, opioids, reversal agents), surgical procedures (laparoscopy, gynecological and middle ear surgery), and postoperative variables (pain, early ambulation, oral intake). Central to the emetic response is the chemoreceptor trigger zone (CTZ) located in the area postrema and the nucleus tractus solitarius in the medulla. These centers integrate afferent signals from the gastrointestinal tract, vestibular system, and higher cortical centers. Serotonin (5-hydroxytryptamine, 5-HT), acting on 5-HT3 receptors in the vagal afferents and CTZ, plays a pivotal role in initiating the vomiting reflex. Consequently, selective 5-HT3 receptor antagonists have emerged as the most effective and widely used class of antiemetics for both chemotherapy-induced nausea and PONV.[2] Among 5-HT3 receptor antagonists, ondansetron has been widely used for decades because of its favorable safety profile and proven efficacy. Administered intravenously in doses of 4-8 mg, ondansetron effectively reduces the incidence of PONV and is superior to traditional antiemetics such as metoclopramide, droperidol, or antihistamines, which are limited by adverse effects such as sedation, extrapyramidal symptoms, and dysphoria. However, the relatively short elimination half-life of ondansetron (3-5 hours) limits its duration of action, particularly in procedures associated with prolonged emetogenic risk.[3] Granisetron, a newer 5-HT3 antagonist, offers certain pharmacological advantages. It exhibits stronger receptor binding affinity and a longer half-life (8-12 hours), providing sustained antiemetic protection. Granisetron has been found more effective than ondansetron in preventing chemotherapy-induced nausea and vomiting and has shown promise in surgical settings as well. Studies have suggested that granisetron may provide superior efficacy in preventing both early and late PONV compared to ondansetron, although results remain inconsistent across different surgical populations.[4] Laparoscopic cholecystectomy, one of the most common minimally invasive surgeries worldwide, carries a particularly high incidence of PONV, ranging between 40% and 70%. Factors such as pneumoperitoneum, diaphragmatic irritation, increased intra-abdominal pressure, residual carbon dioxide, and postoperative opioid use all contribute to this risk. The need for effective, long-lasting, and safe antiemetic prophylaxis in laparoscopic cholecystectomy is therefore well established.[5] Aim To compare the antiemetic efficacy of ondansetron (80 μg/kg) and granisetron (40 μg/kg) in preventing postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy. Objectives 1. To compare the incidence and severity of postoperative nausea and vomiting between patients receiving ondansetron and those receiving granisetron. 2. To evaluate the duration of action and need for rescue antiemetics in both groups. 3. To observe and compare the adverse effects associated with ondansetron and granisetron.

Source of Data Data were collected from patients undergoing elective laparoscopic cholecystectomy under general anesthesia at TNMC & BYL Nair Charitable Hospital, Mumbai, during the study period. Study Design A single-center, prospective, randomized, double-blind, parallel-group interventional study was conducted. Study Location Department of Anaesthesia, TNMC & BYL Nair Charitable Hospital, Mumbai. Study Duration The study was conducted over two years, from December 2015 to November 2017. Sample Size A total of 160 patients were included, divided equally into two groups: • Group A (n = 80): Patients received granisetron 40 μg/kg intravenously. • Group B (n = 80): Patients received ondansetron 80 μg/kg intravenously. Inclusion Criteria • Adult patients aged 20-60 years. • ASA physical status I or II. • Patients scheduled for elective laparoscopic cholecystectomy under general anesthesia. Exclusion Criteria • Patients with renal, hepatic, metabolic, or neuromuscular disorders. • Known allergy to study drugs. • History of motion sickness or previous PONV. • Patients not meeting inclusion criteria. Procedure and Methodology All patients underwent thorough pre-anesthesia evaluation. Written informed consent was obtained. Patients were randomized into two groups using sealed envelope technique. Study drugs were administered as a short intravenous infusion five minutes before induction. Premedication included glycopyrrolate (0.004 mg/kg), midazolam (0.03 mg/kg), and fentanyl (2 μg/kg). Induction was achieved with propofol (2 mg/kg) followed by succinylcholine (2 mg/kg) to facilitate endotracheal intubation. Anesthesia was maintained with oxygen (50%), air (50%), propofol infusion (3-5 mg/kg/h), and vecuronium (0.08 mg/kg loading followed by 0.02 mg/kg maintenance). Pneumoperitoneum was established with CO₂ to maintain intra-abdominal pressure of 12-15 mmHg, and patients were positioned in reverse Trendelenburg. A nasogastric tube was inserted after intubation and removed at the end of surgery. Analgesia was provided with diclofenac 75 mg intramuscularly. At the conclusion of surgery, neuromuscular blockade was reversed with neostigmine (0.05 mg/kg) and glycopyrrolate (0.008 mg/kg). Patients were monitored in the recovery room and ward for 24 hours postoperatively. PONV was assessed at 1, 4, 9, 12, 18, and 24 hours using direct questioning. Rescue antiemetic (metoclopramide 10 mg IV) was administered if >2 episodes of retching or >1 episode of vomiting occurred. Sample Processing Demographic data, duration of surgery, drug doses, incidence and severity of nausea/vomiting, recovery time, clinical recovery score, and adverse effects (headache, dizziness, constipation, hypersensitivity reactions) were recorded. Statistical Methods Data were analyzed using SPSS version 23.0. Quantitative variables were expressed as mean ± SD and compared using Student’s t-test. Qualitative variables were expressed as proportions and analyzed using chi-square test or Fisher’s exact test where applicable. A p-value < 0.05 was considered statistically significant. Data Collection Observations were systematically recorded in pre-structured case record forms. Frequency of nausea, vomiting, retching, requirement for rescue antiemetics, adverse drug reactions, and clinical recovery scores were documented and analyzed for both groups

Table 1: Age-wise Distribution of Patients Age Group (yrs) Group A (Granisetron) n (%) Group B (Ondansetron) n (%) Test of Significance p-value 21-30 66 (82.5%) 63 (78.8%) χ² = 0.42 0.51 31-40 7 (8.8%) 9 (11.3%) 41-50 6 (7.5%) 8 (10.0%) 51-60 1 (1.3%) 0 (0.0%) Total 80 (100%) 80 (100%) In this study, the majority of patients in both treatment groups belonged to the younger age category of 21-30 years, with 82.5% in the granisetron group and 78.8% in the ondansetron group. Smaller proportions of patients were distributed across the 31-40 year age group (8.8% vs. 11.3%), the 41-50 year group (7.5% vs. 10.0%), and only one patient in the granisetron group (1.3%) fell into the 51-60 year range, while none in the ondansetron group were in this bracket. Statistical analysis (χ² = 0.42, p = 0.51) confirmed that the age distribution between the two groups was comparable, with no significant difference observed. Table 2: Gender Distribution of Patients Gender Group A (Granisetron) n (%) Group B (Ondansetron) n (%) Test of Significance 95% CI p-value Male 13 (16.3%) 17 (21.3%) χ² = 0.56 -4.9% to 14.9% 0.45 Female 67 (83.8%) 63 (78.8%) Total 80 (100%) 80 (100%) Females predominated in both study arms, comprising 83.8% in the granisetron group and 78.8% in the ondansetron group, while males accounted for 16.3% and 21.3% respectively. The difference in gender distribution was not statistically significant (χ² = 0.56, 95% CI: -4.9% to 14.9%, p = 0.45), indicating that both groups were balanced in terms of sex composition. This reflects the higher prevalence of laparoscopic cholecystectomy among women, which is consistent with epidemiological data on gallstone disease. Table 3: Weight-wise Distribution of Patients Weight (kg) Group A (Granisetron) n (%) Group B (Ondansetron) n (%) Test of Significance 95% CI p-value 45-60 61 (76.3%) 53 (66.3%) χ² = 2.07 -2.8% to 22.7% 0.15 61-70 18 (22.5%) 34 (42.5%) >70 1 (1.3%) 1 (1.3%) Total 80 (100%) 80 (100%) Most patients in both groups weighed between 45-60 kg, with 76.3% in the granisetron group and 66.3% in the ondansetron group. A higher proportion of patients in the ondansetron group (42.5%) were in the 61-70 kg range compared to 22.5% in the granisetron group, while very few patients exceeded 70 kg (1.3% in each group). Although there was some variation in weight categories, statistical testing (χ² = 2.07, p = 0.15, 95% CI: -2.8% to 22.7%) showed no significant difference between groups, suggesting effective randomization and comparability with respect to body weight Table 4: ASA Grade-wise Distribution of Patients ASA Grade Group A (Granisetron) n (%) Group B (Ondansetron) n (%) Test of Significance 95% CI p-value I 62 (77.5%) 66 (82.5%) χ² = 0.59 -7.4% to 17.4% 0.44 II 18 (22.5%) 14 (17.5%) Total 80 (100%) 80 (100%) Assessment of ASA physical status revealed that the majority of patients in both groups were ASA Grade I (77.5% in the granisetron group vs. 82.5% in the ondansetron group), with the remainder being ASA Grade II (22.5% vs. 17.5%). Statistical evaluation (χ² = 0.59, p = 0.44, 95% CI: -7.4% to 17.4%) indicated no significant difference between the groups. This confirms that the baseline health status of patients was comparable and that both groups predominantly comprised patients with relatively low anesthetic risk.

Table 1 - Age-wise distribution: Most participants in both arms were young adults (21-30 yrs: 82.5% vs 78.8%), and age strata were statistically comparable (χ²=0.42, p=0.51). A youthful cohort is typical in laparoscopic cholecystectomy (LC) PONV trials because symptomatic cholelithiasis often presents in the 20-40 yr band for women, and many centers preferentially schedule ASA I-II patients for day-care LC. Prior randomized studies comparing 5-HT3 antagonists in LC Sharma M et al.(2024)[6] likewise enrolled predominantly younger adults and did not find baseline age imbalances between groups, supporting that randomization achieved demographic equivalence and that age is unlikely to confound antiemetic efficacy comparisons. Table 2 - Gender distribution: Females predominated in both groups (83.8% vs 78.8%) with no significant between-group difference (χ²=0.56, 95% CI of difference −4.9% to 14.9%, p=0.45). Female preponderance mirrors epidemiology (higher gallstone disease burden in women) and aligns with PONV risk models in which female sex is a strong independent predictor. Multiple trials summarized in literature review Bhat I.(2024)[7] & Naeem M et al.(2021)[8] also report female-heavy LC cohorts and still show balanced sex distributions across randomized antiemetic arms-exactly as seen here-minimizing sex-related bias in outcome estimates. Table 3 - Weight-wise distribution: Weight bands were broadly similar between groups (45-60 kg: 76.3% vs 66.3%; 61-70 kg: 22.5% vs 42.5%; >70 kg: 1.3% each), with a non-significant overall difference (χ²=2.07, p=0.15; 95% CI for risk difference −2.8% to 22.7%). Prior LC antiemetic trials typically include normal-to-overweight patients and exclude extremes of BMI; distribution is consistent with those datasets. Because obesity can modulate PONV risk and drug PK/PD, demonstrating no material imbalance in weight classes-like in Mangu HR et al.(2021)[9] & Bayoumi HM et al.(2025)[10] cohorts-supports internal validity when comparing rescue antiemetic need or emesis rates across groups. Table 4 - ASA grade distribution: ASA I-II status dominated (I: 77.5% vs 82.5%; II: 22.5% vs 17.5%), again without a significant difference (χ²=0.59, p=0.44). This echoes the methodological norms of previous LC PONV RCTs-restricting to ASA I-II to limit perioperative confounding (hemodynamic instability, opioid requirements, delayed gastric emptying) and to enable same-day discharge paradigms. Studies synthesised in review Bayoumi HM et al.(2025)[10] similarly report ASA I-II-heavy samples and emphasize that comparable ASA mix across arms is crucial before attributing differences in early/late PONV to the antiemetic rather than baseline fitness. Kumar J et al.(2024)[11]

The present randomized controlled study comparing ondansetron (80 μg/kg) and granisetron (40 μg/kg) in patients undergoing laparoscopic cholecystectomy demonstrated that both agents were effective in preventing postoperative nausea and vomiting (PONV). However, granisetron showed a trend towards greater efficacy, with a lower incidence of nausea, vomiting, and reduced requirement for rescue antiemetics, particularly during the later postoperative period. Both drugs were well tolerated, with minimal adverse effects. Thus, granisetron may be considered a more favorable option than ondansetron for routine prophylaxis of PONV in laparoscopic cholecystectomy due to its longer duration of action and sustained antiemetic effect. LIMITATIONS OF THE STUDY 1. The study was conducted in a single tertiary care center, which may limit generalizability of findings. 2. Only ASA I and II patients aged 20-60 years were included; results may not be applicable to higher-risk surgical populations. 3. The follow-up period was limited to 24 hours, and late PONV beyond this window was not assessed. 4. Factors such as dietary habits, menstrual cycle phase in females, and genetic variability in drug metabolism were not evaluated, though they may influence PONV incidence. 5. A fixed weight-based dosing regimen was used; pharmacokinetic variability in obese or underweight patients may not have been fully captured.

1. Saeed R, Hamza HA, Liaqat A, Safdar M, Idrees M, Rehman A. Comparison of Ondansetron and Granisetron in Prevention of Post-Operative Nausea and Vomiting Following Laparoscopic Cholecystectomy. Annals of Punjab Medical College. 2023 Mar 31;17(1):97-101. 2. Pradhan S, Dhakal S. Comparative Study of Ondansetron and Granisetron for Preventing Post-Operative Nausea and Vomiting in Laparoscopic Cholecystectomy under General Anesthesia. Nepal Journal of Medical Sciences. 2021 Dec 31;6(2):4-11. 3. Khubzan WD, Albagieh MH, Nathif RA, Alshamrani WM, Alharbi NS, Sharahili RA, Alsaeed NM, Mahfouz MM. Comparison between ondansetron and granisetron in preventing nausea and vomiting after laparoscopic cholecystectomy: A systematic review and meta-analysis. Saudi Medical Journal. 2025 Jul;46(7):721. 4. Taneja P, Bansal Y, Ohri A. Comparative study on ondansetron with Granisetron in the prevention of postoperative nausea and vomiting in subjects undergoing laparoscopic cholecystectomy under general anesthesia. Acta Scientific Pharmaceutical Sciences (ISSN: 2581-5423). 2021 Mar;5(3). 5. Kishore CP, Rao MS, Kooran SP, Arora RK, Roy AB. Comparative study of ondansetron, granisetron and granisetron with dexamethasone for prevention of postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy. Indian Journal of Clinical Anaesthesia. 2021;8(2):236-42. 6. Sharma M, Sapkota S, Sharma S, Shakya S. A Comparative study on efficacy of Granisetron and Ondansetron in the Prevention of Post-Operative Nausea and Vomiting after Laparoscopic surgery. Devdaha Medical Journal. 2024 Mar 30;6(1):39-45. 7. Bhat I. Prevention Of Post-Operative Nausea And Vomiting In Females Following Laparoscopic Cholecystectomy: Is Ramosetron Superior To Granisetron?. The Internet Journal of Anesthesiology. 2024 Jun 7. 8. Naeem M, Tabassum R, Khaskheli MS, Awan AH, Meraj M, Irfan R. Granisetron versus ondansetron for prevention of post-operative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy. Journal of Pharmaceutical Research International. 2021 Dec 11;33(54B):11-7. 9. Mangu HR, Kamal M, Kadiyala V, Mukkara M, Samantaray A. Comparison of Efficacy of Granisetron, Ondansetron and Dexamethasone in Prevention of Postoperative Nausea and Vomiting. International Journal. 2021 Jul;4(4):722. 10. Bayoumi HM, Abdelaziz DH, Boraii S, Bendas ER, El Said NO. Intraperitoneal Granisetron for Post‐Laparoscopic Cholecystectomy Pain Management: A Double‐Blinded, Randomized Controlled Trial. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2025 Sep;45(9):547-56. 11. Kumar J, Alagarsamy R, Lal B, Rai AJ, Joshi R, Karna ST, Shakti P, Verma DK, Yadav V, Goel P, Yunus M. Comparison of efficacy and safety between palonosetron and ondansetron to prevent postoperative nausea and vomiting in patients undergoing laparoscopic surgery: a systematic review and meta-analysis. Journal of Minimally Invasive Surgery. 2024 Dec 15;27(4):202.