Nausea and vomiting are the most prevalent and distressing adverse effects in the postoperative phase, with incidence varying between 20% and 30% [1,2]. Laparoscopic surgeries are associated with a 40% to 70% incidence of postoperative nausea and vomiting (PONV) [3–6]. PONV can result in several complications that impede recovery and hence lead to an escalation of hospital care costs. Various guidelines have established the contribution of risk factors and strategies to reduce the risk of PONV [7,8].

Though various drugs are being used to prevent PONV, the 5-hydroxytryptamine-3 receptor antagonists (5-HT3A) have a proven efficacy as the first line antiemetics. Amongst the 5-HT3A, ondansetron is the oldest and most commonly used antiemetic. However, its drawback is the need for repeated dosages, as its duration of action is short. Still, ondansetron is commonly used as it costs less than other 5-HT3As. Palonosetron is another drug in the class, with a 70 to 100 times higher affinity for receptor binding and a prolonged half-life of 40 hours [9,10]. Its therapeutic effect lasts up to 72 hours after a single intravenous dose [11]. After successful clinical safety to prevent postchemotherapy nausea and vomiting, the U.S. Food and Drug Administration (FDA) in 2008 approved palonosetron 0.075 mg for prevention of PONV up to 24 hours postsurgery in adults [10,11]. Various trials have compared the safety and efficacy of ondansetron and palonosetron, especially in laparoscopic surgery, often with variable conclusions.

In 2018, Liu et al. [12] conducted a meta-analysis comprising nine studies to evaluate the efficacy and safety of palonosetron and ondansetron in laparoscopic surgery under general anesthesia. The meta-analysis reported that palonosetron was not more efficacious than ondansetron in preventing early PONV. However, it was more efficacious in preventing vomiting after laparoscopic surgery. Various other patient-related (age, sex, smoking status, previous history of motion sickness or PONV) and perioperative factors (opioid use, the timing and dosage of antiemetic administration, the type of anesthetic drug used, and the type of surgery) may influence the incidence of PONV [1]. However, since these factors were not analyzed in detail, no conclusive statement was made regarding the choice of antiemetic therapy.

Several similar randomized controlled trials (RCTs) have been performed after the above meta-analysis. There is a need to review the evidence in light of these additional studies. The objective of the current systematic review was to assess whether the findings of the prior meta-analysis remain valid or if there is an update to prove the comparable effectiveness or safety of palonosetron compared to ondansetron.

We performed this review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement [13]. We preregistered our protocol in PROSPERO (registration No. CRD42023426193). The PICOST criteria were defined as P (population), patients undergoing laparoscopic surgery under general anesthesia; I (intervention), use of intravenous palonosetron for prophylaxis of PONV; C (control), intravenous ondansetron; O (outcome), efficacy and safety of palonosetron and ondansetron; S (study design), RCTs; T (time frame), January 2008 to April 2023. We performed electronic database searches using PubMed, Google Scholar, Semantic Scholar, and Cochrane Library databases for articles in English literature. Studies other than laparoscopic surgeries and which did not report PONV were excluded. Only the most recent or larger sample size was considered if the same study population was included in more than one article. Studies published in a language other than English, in vitro and animal studies, letters to the editor, reviews, book chapters, and studies with missing or insufficient data were excluded because of potential publication bias.

Search strategy

The comprehensive search strategy involved reviewing all relevant studies using the combination of terms ‘Palonosetron AND Ondansetron.’ The search strategy is presented in Supplementary Table 1. After removing duplicates, we also scanned reference lists of included articles for further possible additional studies.

Data abstraction

Two reviewers (JK, BL) independently analyzed all the included studies. The initial shortlisting was done on the title and abstract, and the shortlisted articles were then analyzed in detail. Discrepancies were resolved by discussion with a third reviewer. We extracted data using a standardized data abstraction form for the following variables: author, year of publication, the total number of patients, age, sex distribution, the dosage of the drug, time of drug administration, duration of surgery, duration of anesthesia, episodes of nausea and vomiting, and adverse effects. The kappa statistic was calculated to assess inter-rater reliability.

The primary outcome was efficacy (incidence of nausea and vomiting) of palonosetron and ondansetron. This was based on outcomes at three time points postoperatively, such as T1 (0–2 hours), T2 (2–6 hours), T3 (6–24 hours). The secondary outcome was palonosetron and ondansetron’s safety (incidence of all adverse effects).

Risk of bias and GRADE assessment

Risk of Bias 2.0 (Cochrane) was used to analyze the risk of bias within the included studies [14]. Two independent reviewers (RA, BL) assessed the risk of bias, and any inconsistency was resolved by a discussion. Robvis tool was used to generate traffic light plots to display the risk of bias visually [15].

The GRADE (Grading of the Recommendations, Assessment, Development, and Evaluations) approach was used to analyze the certainty of the evidence for each of the meta-analytic outcomes [16].

Statistical analysis: meta-analysis

The meta-analysis was conducted for dichotomous data with relative risk with a 95% confidence interval as a summary metric. The trial results were combined using the random-effects model (DerSimonian and Laird technique). When the number of events was zero, a continuity correction was applied by adding a small constant (typically 0.5) to each cell in the contingency tables. Heterogeneity was assessed with the Q-statistic and Moran’s I² and interpreted qualitatively as low (25%–50%), moderate (50%–75%), or high (75%–100%). These results were subsequently summarized and visually represented using forest plots.

Subgroup analyses in efficacy outcome were performed according to the type of surgery (gynecological and cholecystectomy), type of general anesthetic agent (sevoflurane and isoflurane), dose of antiemetic agent (0.075-mg palonosetron/4-mg ondansetron and 0.075-mg palonosetron/8-mg ondansetron) and time of antiemetic agent (before intubation or before extubation). Using a funnel plot, we assessed small-study effects, including publication bias. We also examined each funnel plot using Egger’s asymmetry test with the “metabias” command to check for potential publication bias. The statistical analyses were performed using STATA version 17 (StataCorp LLC), with the assistance of the “metan” and “meta esize” packages. All p values were two-tailed, and the statistical significance level was set at 0.05.

Study results

The process of study identification has been depicted in PRISMA (Fig. 1). We shortlisted a total of 79 articles for full-text reading. Of these, 21 articles were included in the systematic review. The kappa statistic for the literature selection was 0.70, indicating substantial agreement between the reviewers. For data extraction, the kappa statistic was 0.83, indicating excellent agreement.

Figure 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram.

Study characteristics

All the included studies were published between 2011 and 2022. The total number of participants in the palonosetron group was 1,022 (201 males, 648 females, and 173 unspecified). The ondansetron group had 1,021 participants (179 males, 727 females, and 115 unspecified). Table 1 reveals the characteristics of the included studies [17–37] and the heterogeneity in terms of type of laparoscopic surgery, general anesthesia agents, dose and timing of antiemetic administration, and rescue drugs. The incidence of PONV and adverse effects in the included studies is presented in Supplementary Tables 2 and 3.

Table 1 . Characteristic data of the included studies.

No.	Study	Year	Efficacy (E)/Safety (S)	Type of LS	GA agent	Nitrous oxide	Propofol	Rescue drug (mg)	Palonosetron					Ondansetron
									No. of participants	Male	Female	Dose (mg)/time		No. of participants	Male	Female	Dose (mg)/time
1	Park et al. [17]	2011	E, S	Gynecological	Sevoflurane	Used	Used	Metoclopramide 10	45	0	45	0.075/BI		45	0	45	8/BI
2	Bajwa et al. [18]	2011	E, S	Gynecological	Sevoflurane	NM	Used	Ondansetron 4	30	0	30	0.075/BI		30	0	30	8/BI
3	Swaika et al. [19]	2011	E	Cholecystectomy	Sevoflurane	Used	NM	Ondansetron 4	29	0	29	0.075/BE		29	0	29	8/BE
4	Kim et al. [20]	2013	E, S	Gynecological	Sevoflurane	Used	Used	NM	50	0	50	0.075/BI		50	0	50	8/BIa)
5	Kim et al. [21]	2013	E, S	NM	Sevoflurane	NM	Used	Metoclopramide 10/dexamethasone 8	36	0	36	0.075/BI		35	0	35	4/BI
6	Gupta et al. [22]	2014	S	Cholecystectomy	Isoflurane	Used	Used	Metoclopramide 10	40	18	22	0.075/BI		40	19	21	4/BI
7	Joshi et al. [23]	2014	E	NM	Isoflurane	Used	NM	Metoclopramide 10	50	20	30	0.075/BI		50	15	35	4/BI
8	Bhalla et al. [24]	2015		Cholecystectomy	Isoflurane	Used	NM	Dexamethasone 8	50	24	:26	0.075/BI		50	20	30	4/BI
9	Sureshkumar et al. [25]	2016	E, S	NM	Sevoflurane	Used	Used	Metoclopramide 10	50	15	35	0.075/BI		50	17	33	4/BI
10	Singh et al. [26]	2016	S	Cholecystectomy	NM	Used	Used	Metoclopramide 10	45	40	5	0.075/BI		45	37	8	8/BI
11	Kuragayala et al. [27]	2016	E	NM	NM	Used	Used	Metoclopramide 10	25	NM	NM	0.075/BE		25	NM	NM	8/BE
12	Kumar et al. [28]	2018	E	Cholecystectomy	Isoflurane	Used	NM	Metoclopramide 10	50	7	43	0.075/BI		50	10	40	8/BI
13	Davis et al. [29]	2019	E, S	NM	Isoflurane	Used	Used	Metoclopramide 10	65	0	65	0.075/BI		65	0	65	8/BI
14	Carvalho Braga et al. [30]	2019	E	Cholecystectomy	Sevoflurane	NM	Used	Metoclopramide 10	41	0	41	0.075/BI		41	0	41	4/BI and every 8 hr after surgery
15	Verma et al. [31]	2020	E, S	Cholecystectomy	Isoflurane	Used	NM	Metoclopramide 10	30	0	30	0.075/BI		30	0	30	8/BI
16	Elrashidy et al. [32]	2020		Gastrectomy	Sevoflurane	NM	Used	Metoclopramide 10	50	14	36	0.075/BI		50	11	39	4/BI
17	Davolos et al. [33]	2021	E	Cholecystectomy	Sevoflurane	NM	Used	Dimenhydrinate	106	30	76	0.075/BI		106	19	87	8/BI and every 8 hr after surgery
18	Debnath et al. [34]	2022	E	Cholecystectomy	Sevoflurane	Used	Used	Metoclopramide 10	90	NM	NM	0.075/BI		90	NM	NM	8/BI
19	Chauhan et al. [35]	2022	E	NM	Isoflurane	Used	Used	NM	30	13	17	0.075/BI		30	15	15	8/BI
20	Yadav et al. [36]	2022	E, S	Gynecological	Sevoflurane	Used	Used	Metoclopramide 10	45	0	45	0.075/BI		45	0	45	8/BI
21	Balyan et al. [37]	2022	E, S	Gynecological	Sevoflurane	NM	Used	Ondansetron 4	65	0	65	0.075/BI		65	0	65	8/BI

LS, laparoscopic surgery; GA, general anesthesia; BI, before intubation; NM, not mentioned; BE, before extubation..

^a)Ondansetron 16 mg (8 mL) was added in intravenous patient-controlled analgesia and was continuously infused..

Meta-analysis

Four of the 21 studies did not report PONV outcomes in the pre-identified time frames. Hence, we included the remaining 17 studies for efficacy assessment. Ten of these 21 studies did not report any adverse effects. Therefore, we used the remaining 11 studies for safety assessment.

Efficacy assessment

Nausea

The overall pooled risk ratio indicated that those patients who received palonosetron were significantly less likely to develop nausea. As compared to ondansetron, this reduction was seen at all-time points (n = 15 [45%] at T1, 12 [46%] at T2, and 8 [48%] at T3). The effect of heterogeneity was low at T1 and T2 and moderate at T3 (Fig. 2).

Figure 2. Forest plots of efficacy. T1, 0–2 hours; T2, 2–6 hours; T3, 6–24 hours; CI, confidence interval; DL, DerSimonian and Laird approach.

Vomiting

The overall pooled risk ratio revealed that those patients who received palonosetron were significantly less likely to develop vomiting by 54% (n = 15) at T1 and 44% (n = 9) at T3 phases. Patients receiving palonosetron were 24% (n = 12) less likely to develop vomiting at the T2 phase. However, it was statistically not significant. The effect of heterogeneity was low (Fig. 2).

Subgroup analysis

The pooled risk ratio by subgroups is presented in Table 2.

Table 2 . The risk ratio of subgroup analysis.

Variable	Risk ratio (95% CI)
	T1	T2	T3
Type of surgery
Gynecological (N)	0.54 (0.31–0.94)	0.52 (0.26–1.03)	0.60 (0.36–1.00)
Cholecystectomy (N)	0.54 (0.21–1.37)	0.78 (0.54–1.12)	0.76 (0.31–1.88)
Gynecological (V)	0.97 (0.30–3.13)	0.61 (0.19–1.92)	0.67 (0.29–1.55)
Cholecystectomy (V)	0.40 (0.18–0.93)	0.83 (0.55–1.26)	0.66 (0.38–1.15)
Anesthesia agent
Sevoflurane (N)	0.54 (0.34–0.86)	0.58 (0.37–0.90)	0.60 (0.28–1.27)
Isoflurane (N)	0.53 (0.35–0.80)	0.43 (0.29–0.64)	0.49 (0.35–0.68)
Sevoflurane (V)	0.61 (0.31–1.21)	0.86 (0.61–1.20)	0.72 (0.44–1.17)
Isoflurane (V)	0.26 (0.11–0.59)	0.34 (0.14–0.84)	0.42 (0.22–0.79)
Dose of antiemetic, ondansetron (mg)
0.075 vs. 8 (N)	0.57 (0.37–0.87)	0.53 (0.39–0.71)	0.52 (0.39–0.69)
0.075 vs. 4 (N)	0.45 (0.27–0.75)	0.41 (0.16–1.07)	0.58 (0.09–3.61)
0.075 vs. 8 (V)	0.39 (0.22–0.70)	0.70 (0.48–1.01)	0.48 (0.31–0.74)
0.075 vs. 4 (V)	0.37 (0.13–1.05)	0.96 (0.45–2.07)	1.50 (0.59–3.83)
Timing of antiemetic
Before intubation (N)			0.52 (0.39–0.69)
Before extubation (N)			0.27 (0.09–0.86)
Before intubation (V)	0.39 (0.22–0.70)	0.70 (0.48–1.01)	0.48 (0.31–0.74)
Before extubation (V)	2.00 (0.55–7.24)	1.00 (0.37–2.74)	0.26 (0.03–2.33)
Safety (irrespective of time phases)
Headache	0.80 (0.52–1.22)
Constipation	1.79 (0.99–3.22)
Dizziness	0.90 (0.63–1.29)
Drowsiness	1.10 (0.67–1.82)

CI, confidence interval; N, nausea; V, vomiting; T1, 0–2 hours; T2, 2–6 hours; T3, 6–24 hours..

Impact of dose of antiemetic on postoperative nausea and vomiting incidence

In the 0.075-mg palonosetron vs. 8-mg ondansetron subgroup, the pooled risk reduction of nausea and vomiting was significant in palonosetron at all-time phases except vomiting at the T2 phase.

In the 0.075-mg vs. 4-mg ondansetron subgroup, there was a reduction in nausea by palonosetron at all-time phases. However, it was statistically significant only at T1. The palonosetron group showed a lower risk of vomiting during the T1 and T2 phases but a higher risk during the T3 phase; however, these differences were not statistically significant. The effect of heterogeneity was moderate in the subgroup analysis.

Impact of time of antiemetic administration on postoperative nausea and vomiting incidence

The palonosetron had significantly less nausea at the T3 phase and vomiting in all-time phases when given before intubation, with low heterogeneity.

Impact of inhalational anesthetic agent on postoperative nausea and vomiting incidence

The subgroup analysis revealed that when isoflurane was used, there was a significant reduction in nausea and vomiting incidence in the palonosetron group compared to ondansetron at all-time phases. However, the same was not seen with sevoflurane. The heterogeneity was low.

Impact of different types of laparoscopic surgery on postoperative nausea and vomiting incidence

The pooled risk reduction for nausea in gynecological surgery and vomiting in cholecystectomy surgery was statistically significant in the palonosetron group at the T1 phase. No significant difference was observed between groups at T2 and T3 phases. The heterogeneity was low to moderate in subgroup analysis, and no significant difference was observed.

Safety assessment

Eleven studies were included in a meta-analysis of overall safety. The commonest adverse effects reported were headache (n = 11), dizziness (n = 10), constipation (n = 7), and drowsiness (n = 3). The overall safety profile of palonosetron and ondansetron was comparable, with moderate heterogeneity in studies (Fig. 3). Pooled analysis to discern patterns in the most prevalent adverse effects revealed that headache and dizziness were comparatively less, while constipation and drowsiness were comparatively high in the palonosetron group; however, these differences were not statistically significant (Table 2).

Figure 3. Forest plots of safety. CI, confidence interval; DL, DerSimonian and Laird approach.

Publication bias

Funnel plot analysis showed asymmetry for T1, T2, and T3 vomiting; however, Egger’s test was nonsignificant (p = 0.86, p = 0.21, and p = 0.61). Funnel plot symmetry was observed for T1, but T2 and T3 nausea showed asymmetry. However, Egger’s test was nonsignificant (p = 0.71 and p = 0.28). Funnel plots showed symmetry for safety (p = 0.61, Egger’s test). Overall, funnel plot analysis did not identify evidence of substantial publication bias (Supplementary Figs. 1, 2).

Risk of bias and GRADE assessment

Out of 21 included studies, 13 studies revealed a low risk of bias, and the remaining eight studies exhibited some concerns (Fig. 4). The quality of evidence in the present study was found to be high, while studies were modest in sample size (25–106 participants per group). The level of importance of the generated evidence was found to be critical (Fig. 4).

Figure 4. Risk of bias and GRADE Grading of the Recommendations, Assessment, Development, and Evaluations) assessment. CI, confidence interval; RR, risk ratio.

PONV poses a considerable therapeutic challenge, the cause being multifactorial, including anesthetic, operative, and patient-related factors [38,39]. A vast literature exists regarding the prevention and management of PONV, with ongoing controversies over the preferential use of newer-generation antiemetics. In the context of laparoscopic surgeries, as the incidence of PONV is notably elevated, prevention and management are further complicated [40]. Hence, the current review provides pooled evidence of the efficacy and safety of palonosetron in comparison to ondansetron in laparoscopic surgeries.

By pooling individual patient data from 17 trials, the pooled reduction of postoperative nausea (45%–48%) and vomiting (24%–54%) was significant in palonosetron compared to ondansetron. The long plasma half-life of the palonosetron and higher affinity for the 5-HT receptor than ondansetron explain the higher efficacy [41,42]. Another reason for increasing the efficacy of palonosetron in comparison to ondansetron could be that the optimal dose of ondansetron (i.e., 4 mg/8 mg intravenous every 8 hours) was not used. Metoclopramide of 10 mg was the most commonly used rescue drug. The palonosetron group required less rescue antiemetic intervention compared to ondansetron in patients undergoing laparoscopic surgeries. Hence, all these favor palonosetron. Although the heterogeneity of the studies was low, the comparison between both drugs at optimal and potent doses lacks certainty due to the scarcity of information in published studies.

The data among the included studies had wide variations, such as differences in dose and timing of antiemetic administration, inhalational anesthetic agents, and types of surgery. Recognizing that the etiology of PONV is multifactorial, the efficacy might be altered depending on the factors mentioned earlier. Thereby, the subgroup analysis was aimed at assessing the influence of these factors on palonosetron efficacy.

In our subgroup analysis, we assessed if anesthetic, operative, and patient-related factors affect the efficacy of palonosetron. We found that 0.075 mg palonosetron was significantly more effective than the 8 mg ondansetron in most phases except vomiting at the T2 phase. Only one study by Davolos et al. [33], which was the largest and hence also had the maximum weightage (42.4%), had an equal efficacy between 8-mg ondansetron (intravenously every 8 hours) and 0.075-mg palonosetron (single dose). Similarly, ondansetron 4 mg showed a significant reduction in vomiting in the late phase in comparison to palonosetron. This could be misleading as only the study of Carvalho et al. [30] was included in this subgroup in which an ondansetron dose of 4 mg was given before intubation, followed by 8-hourly administration. Additionally, the study revealed that the rescue antiemetic requirement was higher in the ondansetron group [30]. Overall, it could be concluded that a single dose of 0.075-mg palonosetron outweighs the ondansetron of 8 mg or 4 mg in efficacy on single or regular administration.

The timing of an antiemetic drug is an important determinant of its effect. When administered before intubation, palonosetron demonstrated a notable reduction in nausea and vomiting across all-time phases. Conversely, when administered before extubation, its efficacy was less than that of ondansetron in the early hours. This emphasizes the fact that the optimal time of 6 hours is needed to exhibit the full potency of palonosetron, unlike the ondansetron, which attains peak effect in 15 to 30 minutes following administration.

The interaction between an anesthetic and antiemetic use and type of anesthesia is also an important consideration. In the current review, patients who received palonosetron along with isoflurane anesthesia had significantly less vomiting (74%, 66%, and 58%) as compared to those with sevoflurane anesthesia (39%, 14%, and 28%) across the three time points. At the same time, some previous studies have reported no difference between isoflurane, sevoflurane, or desflurane in lumbar disc surgery with regard to influence on PONV frequency or severity. However, others have observed a temporal association with a late peak of PONV observed in patients given isoflurane [43]. In contrast, Apfel et al. [38] reported that volatile anesthetics are the leading contributory factor to early (0–2 hours) PONV. In arthroscopic daycare surgeries, a higher frequency of PONV was seen in patients administered sevoflurane. This was postulated to be due to the quicker awakening, higher pain scores, or interaction with exhausted soda lime, leading to the production of inducers of PONV like formaldehyde [44]. In our systematic review, too, we observed that in patients undergoing surgery under sevoflurane anesthesia, palonosetron failed to reach a statistical significance, especially in vomiting than ondansetron. Further, it may be prudent to use a combination of propofol and inhalational anesthetics to decrease the early PONV, compared to volatile anesthetics only [45].

The subgroup analysis of six trials of cholecystectomy and five trials of gynecological surgery revealed that the reduction in nausea in gynecological surgery and vomiting in cholecystectomy surgery was significant in the first 2 hours. Could the change in CO₂ peritoneal insufflation or abdominal pressure difference be attributed to the results, or do they hold no significance? This ponders further research on the difference in incidence rates of PONV between the types of laparoscopic surgeries.

Headache was the most commonly reported adverse effect, although the exact mechanism is unknown and multifactorial. This may be because of weak 5-HT1 antagonistic action. The constipation and drowsiness were comparatively high in the palonosetron group, although insignificant. Increased constipation in palonosetron can be attributed to the higher affinity for 5-HT3A, which prolongs the duration of gut transit and suppresses the postprandial colonic motor function [46]. Other reported adverse effects were myalgia (n = 3), itching (n = 2), pain (n = 1), anxiety (n = 1), dry mouth (n = 1), fever (n = 1), and chest tightness (n = 1). None of the observed adverse effects necessitated additional intervention, as they were all self-limiting. The anesthetist and surgeon should be aware of all these possible adverse effects.

In 2011, the U.S. FDA warned about ondansetron usage, causing abnormal cardiac rhythms by QT interval prolongation, whereas palonosetron appears to be safe in this regard [47]. Surprisingly, none of the studies commented on the baseline corrected QT interval and its prolongation after administration of the antiemetic. Furthermore, ondansetron was associated with 29 reported cases of serotonin syndrome [48]. As per the FDA review. In contrast, no instances of serotonin syndrome have been linked to the use of palonosetron. These findings imply that palonosetron has a more advantageous safety profile; nevertheless, a comprehensive evaluation of adverse effects as research endpoints is required to warrant this observation.

Limitations of the study persist despite the availability of numerous similar RCTs on this subject, preventing a comprehensive general conclusion. The reported data were variable and lacked uniformity regarding the time phase, details on anesthetic agents, baseline patient risk, intensity of PONV, and timing of rescue medication administration. These factors all influence the precise assessment of the efficacy and safety of the antiemetic. Subgroup analysis to determine the influence of all risk factors on PONV was not feasible due to limited reporting. The rescue drugs used in the present review were metoclopramide, ondansetron, and dexamethasone. Due to wide variation in the use of rescue drugs and lack of reporting on their influence on PONV incidence among the included studies, a detailed analysis was not possible. The assessment of patient satisfaction lacked uniformity, with different studies employing diverse scales for evaluation. Additionally, the studies did not adequately consider or discuss the cost aspect. Hence, future trials should consider and report the Apfel score for baseline risk, duration of surgery, and information on proemetic and antiemetic drugs that influence the PONV incidence.

Despite the effectiveness of palonosetron, it is noteworthy that it did not completely eliminate PONV. The potent dose and cost of ondansetron should be compared with palonosetron to reach obvious conclusions. This highlights the need for further exploration and development of more potent antiemetic or combination treatments bespoke to particular patient groups to reduce PONV incidence. The use of propofol as an inducing agent and total intravenous anesthesia negating the nitrous oxide might further reduce the PONV incidence in high-risk patients.

The current systematic review and meta-analysis found high-quality evidence to suggest that palonosetron exhibits superior efficacy within the first 24 hours postoperatively and requires less rescue antiemetic intervention compared to ondansetron in patients undergoing laparoscopic surgeries. Both palonosetron and ondansetron demonstrate nearly comparable safety profiles. If palonosetron is given before intubation, it is better for reducing PONV events. None of the studies in our review evaluated cardiac safety, and it remains a major limitation.

Ethics statement

This meta-analysis relies exclusively on secondary data from previously published studies, involving no new data collection or direct interaction with human subjects. Therefore, this study was deemed exempt from requiring IRB approval or informed consent.

Authors’ contributions

Conceptualization, Formal analysis, Methodology, Visualization: JK, RA, BL, AJR, RJ, STK, PS, VY

Data curation, Investigation: JK, RA, BL, PS

Writing–original draft: JK, RA, BL, AB

Writing–review & editing: AJR, DKV, VY, PG, MY

All authors read and approved the final manuscript.

Conflict of interest

All authors have no conflicts of interest to declare.

Funding/support

None.

Data availability

The data presented in this study are available upon reasonable request to the corresponding author.

Supplementary materials

Supplementary materials can be found via https://doi.org/10.7602/jmis.2024.27.4.202