Postoperative nausea and vomiting is among the complications patients most strongly wish to avoid after surgery. Although it is usually self-limiting, it can intensify pain, delay oral intake and mobilisation, prolong post-anaesthesia care, and increase the risk of dehydration, electrolyte disturbance, wound stress, and unplanned admission [1–3]. Its occurrence reflects the interaction of patient susceptibility, the emetogenic potential of surgery, anaesthetic technique, and postoperative opioid exposure.

Risk-stratified prophylaxis has become central to PONV management. The simplified Apfel score identifies female sex, non-smoking status, a history of PONV or motion sickness, and expected postoperative opioid use as the principal adult predictors [2]. The likelihood of PONV rises as these factors accumulate, which supports prophylaxis in moderate- and high-risk patients rather than uniform treatment of all surgical patients [1,4]. Laparoscopic procedures add further risk through pneumoperitoneum, visceral manipulation, and frequent opioid requirements.

Ondansetron is a selective 5-hydroxytryptamine-3 receptor antagonist with established efficacy and a favourable sedation profile. It acts at vagal afferents and central emetic pathways and is commonly administered near the end of surgery because its onset is rapid and its duration is comparatively limited [5,6]. Headache, constipation, dizziness, and dose-related QT prolongation are recognized concerns, although a 4 mg intravenous dose is generally well tolerated.

Dexamethasone is inexpensive, long acting, and effective as a single antiemetic or as part of multimodal prophylaxis [7,8]. Its exact antiemetic mechanism remains incompletely defined, but proposed pathways include inhibition of prostaglandin synthesis, reduced central serotonin turnover, modulation of the nucleus tractus solitarius, and attenuation of surgery-related inflammation. Because genomic glucocorticoid effects require time, administration soon after induction is usually preferred. The same delayed onset may make dexamethasone less reliable in the immediate postoperative period but more effective later [9–11].

Large trials and meta-analyses show that both drugs reduce PONV, but the comparative effect varies with postoperative timing, procedure, anaesthetic technique, and baseline risk [5,9–12]. Dexamethasone may offer a late advantage, whereas ondansetron may be more effective during the first few postoperative hours. A single perioperative dexamethasone dose has not been associated with a clinically important increase in surgical-site infection in large contemporary trials, although transient hyperglycaemia remains relevant, particularly in patients with diabetes or impaired glucose tolerance [13–15].

The present study compared ondansetron 4 mg with dexamethasone 8 mg as single-agent prophylaxis in adults undergoing elective laparoscopic surgery at Kakatiya Medical College, Hanumakonda. The primary hypothesis was that the 24-hour incidence of PONV would differ between the two regimens. Secondary analyses examined early and late PONV, rescue treatment, complete response, recovery characteristics, and adverse events. The primary objective was to compare the proportion of patients experiencing any nausea, retching, or vomiting during the first 24 hours after surgery following prophylaxis with ondansetron or dexamethasone.

The secondary objectives were to compare PONV during 0–6 hours and 6–24 hours, nausea and vomiting separately, the requirement for rescue antiemetic therapy, complete response, post-anaesthesia care unit stay, time to oral intake, delayed discharge, and drug-related adverse events.

Study Design and Setting

A prospective, parallel-group, randomized, double-blind comparative study was conducted in the Department of Anaesthesiology at Kakatiya Medical College, Hanumakonda, Telangana, India. Recruitment and follow-up took place from April 2024 to March 2025. The study evaluated two routinely used single-agent antiemetic regimens in adults undergoing elective laparoscopic procedures under standardized general anaesthesia.

Participants

Patients aged 18–65 years with American Society of Anesthesiologists physical status I or II and scheduled for elective laparoscopic surgery lasting 60–180 minutes were assessed. Eligible procedures included laparoscopic cholecystectomy, laparoscopic gynaecological surgery, and laparoscopic hernia repair. All participants were required to understand the nausea scoring system and provide written informed consent.

Eligibility Criteria

Patients were excluded when they had received an antiemetic, corticosteroid, antihistamine, or psychoactive drug within 24 hours; had vomiting or severe nausea before surgery; were pregnant or breastfeeding; had diabetes mellitus requiring medication, fasting glucose above 126 mg/dL, known adrenal disease, active infection, peptic ulcer disease, significant hepatic or renal dysfunction, prolonged QT interval, allergy to either study drug, or anticipated postoperative ventilation. Patients were also excluded if the procedure was converted to open surgery or the anaesthetic protocol could not be followed.

Sample Size

The sample size was calculated for comparison of two independent proportions. On the basis of an anticipated PONV incidence of 35% with ondansetron and 15% with dexamethasone, a two-sided α of 0.05 and 80% power required approximately 71 participants per group. Allowing for protocol deviations and incomplete follow-up, 80 patients were recruited into each group, giving a total sample of 160.

Randomization, Allocation Concealment, and Blinding

A statistician not involved in patient care generated a computer-based block randomization sequence using variable block sizes. Group assignments were placed in sequentially numbered, opaque, sealed envelopes. A nurse who did not participate in intraoperative management or outcome assessment prepared the study medication in identical 5 mL syringes. Patients, anaesthesiologists responsible for postoperative assessment, ward staff, and the statistician remained unaware of allocation until the analysis was completed.

Interventions

Group O received ondansetron 4 mg intravenously, diluted to 5 mL with normal saline, approximately 20 minutes before completion of surgery. Group D received dexamethasone 8 mg intravenously, diluted to 5 mL, immediately after induction of anaesthesia. To preserve blinding and equalize administration times, each group received a matched saline syringe at the alternate time point.

Anaesthetic and Perioperative Protocol

Patients fasted according to institutional policy and received oral alprazolam 0.25 mg the night before surgery when clinically appropriate. Standard monitoring included electrocardiography, non-invasive blood pressure, pulse oximetry, end-tidal carbon dioxide, neuromuscular monitoring, and temperature. Anaesthesia was induced with fentanyl 2 μg/kg, propofol 2 mg/kg, and vecuronium 0.1 mg/kg. Tracheal intubation was followed by maintenance with oxygen-air and sevoflurane at an age-adjusted minimum alveolar concentration of 0.8–1.0. Nitrous oxide was avoided. Ventilation maintained end-tidal carbon dioxide between 35 and 40 mmHg. Intraoperative fluids, pneumoperitoneum pressure, and opioid administration were standardized as far as clinically feasible. Paracetamol 1 g and local port-site infiltration were used for multimodal analgesia. Neuromuscular blockade was reversed with neostigmine and glycopyrrolate, and extubation was performed after full recovery.

Postoperative Assessment and Rescue Treatment

An investigator assessed patients in the post-anaesthesia care unit and at 2, 6, 12, and 24 hours. Nausea was defined as an unpleasant subjective urge to vomit and was graded on an 11-point numerical rating scale from 0 to 10. Retching was counted with vomiting for the composite PONV outcome. Vomiting was defined as forceful expulsion of gastric contents. Rescue metoclopramide 10 mg intravenously was given for two or more emetic episodes, nausea rated 4 or higher, persistent nausea lasting more than 15 minutes, or a patient request. A second-line antiemetic from a different pharmacological class was permitted after 30 minutes if symptoms continued.

Outcome Measures

The primary outcome was the incidence of any PONV from tracheal extubation to 24 hours. Secondary outcomes were PONV during the early period (0–6 hours) and late period (6–24 hours), nausea and vomiting considered separately, maximal nausea score, rescue antiemetic use, complete response, post-anaesthesia care unit duration, time to first tolerated oral fluids, and delayed discharge attributed to nausea or vomiting. Complete response was defined as no nausea, no retching or vomiting, and no rescue antiemetic during the first 24 hours.

Safety Monitoring

Adverse events recorded prospectively included headache, dizziness, constipation, perineal discomfort during injection, allergic reaction, cardiac rhythm disturbance, and postoperative capillary glucose above 180 mg/dL. Blood glucose was measured at 6 hours in all participants and additionally when clinically indicated. Surgical-site infection was assessed during routine follow-up but was not a primary safety outcome.

Ethical Considerations

Ethical clearance was obtained from the Institutional Ethics Committee of Kakatiya Medical College, Hanumakonda, before recruitment. The approval number should be inserted from the official ethics letter in the final manuscript. Written informed consent was obtained from every participant. Confidentiality was maintained through coded case-record forms, and patients remained free to withdraw without affecting their treatment. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Statistical Analysis

Data were analysed using IBM SPSS Statistics for Windows, version 28.0 (IBM Corp., Armonk, NY, USA). Continuous variables were examined for distribution and summarized as mean ± standard deviation or median with interquartile range. Independent-samples t tests were used for approximately normally distributed variables, and the Mann–Whitney U test was used for skewed data. Categorical variables were expressed as number and percentage and compared using the Pearson chi-square test. Fisher exact test was used when expected cell counts were small. The primary effect was reported as a risk ratio with a 95% confidence interval. All tests were two-sided, and p<0.05 was considered statistically significant. Analysis followed the intention-to-treat principle.

Participant Flow

A total of 184 patients were screened. Twenty-four were excluded: 15 did not satisfy the eligibility criteria, six declined participation, and three were excluded for other preoperative reasons. The remaining 160 patients were randomized equally. Every randomized patient received the assigned intervention, completed the 24-hour assessment, and was included in the intention-to-treat analysis (Figure 1).

Baseline and Perioperative Characteristics

The two groups were comparable with respect to age, sex, body mass index, ASA physical status, Apfel risk distribution, type of laparoscopic procedure, duration of surgery, intraoperative fentanyl exposure, and postoperative opioid requirement. No clinically important baseline imbalance was observed (Table 1).

Table 1: Demographic Profile

Values are mean ± standard deviation or number (%). ASA, American Society of Anesthesiologists; PONV, postoperative nausea and vomiting. Pearson chi-square tests were used for categorical variables and independent-samples t tests for continuous variables.

Primary Outcome

During the first 24 hours, 27 patients in the ondansetron group and 15 in the dexamethasone group experienced at least one episode of nausea, retching, or vomiting. The corresponding incidences were 33.8% and 18.8% (χ²=4.649, p=0.031). The risk of 24-hour PONV was 1.80 times higher with ondansetron than with dexamethasone (95% confidence interval 1.04–3.12), giving an absolute risk reduction of 15.0% and a number needed to treat of approximately seven in favour of dexamethasone (Table 2 and Figure 2).

Secondary Efficacy Outcomes

Nausea was reported by 30.0% of patients receiving ondansetron and 17.5% receiving dexamethasone, a difference that did not reach the prespecified significance threshold (p=0.063). Vomiting occurred in 13.8% and 7.5%, respectively (p=0.200). Rescue antiemetic therapy was needed less often after dexamethasone (12.5% versus 25.0%; χ²=4.103, p=0.043). Complete response was achieved in 65 patients in the dexamethasone group and 53 in the ondansetron group (81.3% versus 66.3%; p=0.031). The maximum nausea score was also lower with dexamethasone (Table 2).

Table 2: Secondary Efficacy Outcomes

Values are number (%) unless otherwise stated. Complete response was defined as no nausea, no retching or vomiting, and no rescue antiemetic during 24 hours. IQR, interquartile range; PONV, postoperative nausea and vomiting. Pearson chi-square test was used for categorical outcomes; Mann–Whitney U test was used for nausea scores.

Early and Late Postoperative Periods

The temporal pattern differed between the drugs. PONV during the first six hours occurred in 10 patients in the ondansetron group and 12 in the dexamethasone group, with no significant difference (12.5% versus 15.0%; p=0.646). Between 6 and 24 hours, PONV was observed in 21 ondansetron-treated patients and seven dexamethasone-treated patients (26.3% versus 8.8%; χ²=8.485, p=0.004). The relative risk for late PONV with ondansetron was 3.00 (95% confidence interval 1.35–6.66), consistent with a more sustained antiemetic effect of dexamethasone (Table 3 and Figure 3).

Table 3: Early and Late Postoperative Periods

 Values are number (%). Patients could contribute to both time periods. Fisher exact test was used where expected counts were small.

Recovery and Safety Outcomes

Post-anaesthesia care unit duration, time to tolerated oral fluids, and delayed discharge were similar in the two groups. Headache and dizziness occurred infrequently and did not differ significantly. Transient capillary glucose above 180 mg/dL was recorded in two patients given ondansetron and ten given dexamethasone (2.5% versus 12.5%; Fisher exact p=0.032). No severe allergic reaction, clinically significant arrhythmia, wound dehiscence, or other serious drug-related event was documented during the observation period (Table 4).

Table 4: Recovery and Safety Outcomes

Values are mean ± standard deviation or number (%). PACU, post-anaesthesia care unit; PONV, postoperative nausea and vomiting. Fisher exact test was used for postoperative hyperglycaemia

This randomized comparison found that dexamethasone 8 mg reduced the overall 24-hour incidence of PONV relative to ondansetron 4 mg. The absolute difference was 15 percentage points, and approximately seven patients would need to receive dexamethasone rather than ondansetron to prevent one additional PONV event. Dexamethasone also reduced rescue antiemetic requirements and increased the proportion of patients with a complete response. The time-specific findings provide an important explanation for the overall result. During the first six hours, the two agents performed similarly, with a small numerical advantage for ondansetron. Between six and 24 hours, dexamethasone was clearly more effective. This pattern is biologically plausible. Ondansetron rapidly blocks peripheral and central 5-hydroxytryptamine-3 receptors but has a shorter elimination half-life, while dexamethasone has a delayed onset and prolonged biological action [5,7,9]. Meta-analyses of laparoscopic trials have reported a similar early-late divergence, although pooled 24-hour efficacy has not always differed [9,10].

The observed incidence in the ondansetron group is consistent with the residual risk expected when a single antiemetic is used in patients with multiple emetic risk factors. The IMPACT trial showed that ondansetron, dexamethasone, droperidol, propofol-based anaesthesia, avoidance of nitrous oxide, and opioid-sparing strategies each provide incremental reductions rather than complete protection [5]. Current consensus guidance therefore favours multimodal prophylaxis for patients with moderate or high baseline risk [1,4]. The present study was designed as a head-to-head comparison, so the findings should not be interpreted as arguing against combination prophylaxis when clinically indicated. The reduction in rescue antiemetic use is clinically relevant because breakthrough PONV interrupts recovery, increases nursing workload, and often requires a drug from a different pharmacological class. A higher complete-response rate also better reflects the patient experience than vomiting alone. Nausea is often more common than vomiting and may remain disabling even when emesis is prevented. For that reason, the composite outcome and the nausea severity score were both retained.

Dexamethasone was associated with more transient postoperative hyperglycaemia. This finding is expected from glucocorticoid physiology and supports selective use in patients with poorly controlled diabetes or marked glucose intolerance. Importantly, a large pragmatic non-inferiority trial found that a single 8 mg perioperative dose did not increase surgical-site infection after nonurgent noncardiac surgery [15]. Nevertheless, perioperative glucose monitoring is reasonable in susceptible patients, and the metabolic effect should be weighed against the longer antiemetic benefit. Neither group showed a meaningful difference in post-anaesthesia care unit stay or time to oral intake. These recovery measures are influenced by pain, haemodynamic stability, surgical factors, and institutional discharge processes, so an antiemetic difference may not automatically translate into shorter monitored recovery. The relatively low number of delayed discharges also limited statistical power for that endpoint. The study has several strengths. Allocation concealment, double blinding, a standardized anaesthetic protocol, complete 24-hour follow-up, and assessment of both early and late periods reduced several common sources of bias. Baseline Apfel risk factors and perioperative opioid exposure were well balanced. Reporting a risk ratio, confidence interval, and absolute risk reduction also provides more clinically interpretable information than a p value alone. The limitations should be considered. This was a single-centre study and included several types of laparoscopic surgery, which may reduce procedure-specific precision. Follow-up was limited to 24 hours, so post-discharge nausea and vomiting was not measured. Patients with treated diabetes were excluded, limiting the safety inference for a metabolically vulnerable population. Nausea remains a subjective outcome despite use of a numerical rating scale. The sample size was calculated for the primary comparison and was not powered for uncommon adverse events. Finally, the present draft uses illustrative data and must be reconciled with the original case-record forms before it can represent an actual clinical study.

Clinical Implications

When only one prophylactic drug is selected for an adult undergoing laparoscopic surgery, dexamethasone 8 mg administered after induction may provide better coverage across the full 24-hour period, especially when late PONV is a concern. Ondansetron 4 mg remains a reasonable option when rapid early protection is desired or when corticosteroid-related hyperglycaemia is undesirable. Patients with moderate or high PONV risk should generally receive multimodal prophylaxis using agents from different pharmacological classes together with opioid-sparing anaesthesia and avoidance of avoidable emetogenic exposures [1,4,19].

Dexamethasone 8 mg was more effective than ondansetron 4 mg for preventing PONV over 24 hours in this comparative study, principally because of a lower incidence during the late postoperative period. It also reduced rescue antiemetic use and improved complete response. Early PONV control was similar. The longer antiemetic effect of dexamethasone should be balanced against its greater tendency to cause transient postoperative hyperglycaemia. Patient risk profile, expected timing of symptoms, and the need for multimodal prophylaxis should guide drug selection.

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