Efficacy of palonosetron in comparison with other 5-HT3 antagonist drugs in preventing postoperative nausea and vomiting after otorhinolaryngological surgeries: A meta-analysis

Literature search

In the present investigation, we conducted a systematic review of the literature to identify all pertinent studies that align with our stated objectives and eligibility requirements. This review encompassed a comprehensive search of multiple databases, including PubMed, Science Direct, Embase, Scopus, and Google Scholar, up to December 2023. The specific keywords utilized in our study were "palanosteron," "post-operative nausea and vomiting," and "otorhinolaryngological surgeries." Through our thorough search process, we aimed to gather a diverse range of literature related to the efficacy and safety of palanosteron in the context of post-operative nausea and vomiting (PONV) specifically after otorhinolaryngological surgeries. Furthermore, our references include both the titles and full texts of studies that focus on the treatment of PONV, as well as comparative analyses of palanosteron with other pharmacological interventions in various global settings.

Eligibility criteria

To identify relevant studies examining the association between palonosetron and other medications for the prevention of postoperative nausea and vomiting (PONV), we systematically evaluated the titles and abstracts of numerous research articles. Only peer-reviewed articles published in English were included, while those in foreign languages were excluded. The eligibility criteria stipulated that studies must focus on drug interventions related to otorhinolaryngological surgeries and examine PONV treatment during two specific time frames: Early (0-24 hours) and Delayed (24-48 hours). Additionally, the studies had to report on the incidence of vomiting. We excluded any studies that had been conducted but not published in English, as well as those lacking information on palonosetron or relevant otorhinolaryngological surgeries. Furthermore, studies that did not present original research data were also omitted from consideration.

Extraction of data

Authors (AAA and BBB) independently retrieved all the related data from the included studies using a pre-defined, standardised data collection form and cross-checked the findings. Any disagreements between the investigators were resolved by reaching a consensus via discussion. The spreadsheet for data extraction included the following items: 1) Title; 2) name of the author; 3) year of publication; 4) study design; 5) risk of bias; 6) number of patients included; 7) duration of the drugs; 8) inclusion criteria; 9) exclusion criteria; 10) Type of drug; 11) Type of surgery; 12) dose of the drug etc.

The data were first extracted from tables or text. The corresponding authors of studies with incomplete or missing data were contacted to obtain the necessary information.

Quality of study using risk bias

Risk bias assessment is a critical step in meta-analysis because it helps evaluate the methodological quality and potential biases of the included studies. In the present study, the assessment of risk bias was conducted using the Cochrane Risk of Bias 2 (ROB2) tool software. 17, 18

Meta-analysis

In the present study, the statistical analysis was analysed using REVMAN 5.4 software. A fixed and random effect model was computed using Review Manager. The funnel plot was not feasible because there were only nine studies for palonosetron drugs. The I² statistic was employed to evaluate the degree of heterogeneity between trials, offering insight into the variability of results across studies. Values below 40% were deemed insignificant, reflecting minimal differences between study outcomes. I² values between 40% and 60% indicated moderate heterogeneity, where some variability existed but was not excessive. High heterogeneity, marked by I² values between 60% and 90%, suggested considerable differences between trials, potentially influenced by varying study designs, populations, or interventions. Results were conveyed in the MH pooled odds ratio (for PONV) with a 95% confidence interval (CI). The P value < 0.05 was contemplated statistically significant. The number needed to treat (NNT) for PONV incidence was determined for the pooled results. Wherever heterogeneity was found to be greater than 40%, results from “random effect modelling” were reported.

Literature search and study selection

A total of 348 scientific papers were discovered as a result of the primary search that was conducted using multiple scientific databases. The study was omitted from 130 repetitions, 10 titles with inappropriate information, and 8 papers which were not published in English. A total of 200 papers were thoroughly assessed for their abstracts; 30 of these papers were found to be related to the review subject at hand. 8 of these articles were found to meet the criteria for inclusion and were used in the analysis; the other 22 were eliminated due to insufficient data19, 20, 21, 22, 23, 24, 25, 26 (Figure 2).

Diagram 1

Illustration of flow chart diagram n of Palonosetron with other drugs in suppression of PONV in otorhinolaryngological surgeries

Study characteristics

The given (Table 1) showing the characteristics of the included studies.

Risk of bias

(Figure 3) shows the findings of the risk of bias assessment conducted using the Cochrane tool for the included studies. The risk bias was assessed using Rob2 tool. In the graph, each row represents a study and each column represents one type of bias. The colour represents the reviewer’s conclusion about the risk of each type of bias in each study. Red means a high risk of bias, yellow means an unclear risk of bias, and green means a low risk of bias. The overall risk of bias results showed most studies have low risk indicating that there are no significant concerns regarding the reliability and validity of the results in the present systematic review and meta-analysis.

Figure 2

Risk of bias

Figure 3

Overall risk of the present study

Quantitative meta-analysis

Postoperative nausea and vomiting (PONV) is a significant concern for patient care, ranking as the second most common issue after pain. A pivotal 1992 review by Watcha and White introduced the widespread use of the term PONV, which later became an official medical subject heading in the National Library of Medicine in 1999. 27 Proactively addressing PONV enhances patient outcomes, despite the fact that it often resolves without intervention. However, PONV can occasionally cause serious complications, such as aspiration of gastric contents, suture disruption, esophageal rupture, subcutaneous emphysema, or pneumothorax. Additionally, untreated PONV can extend a patient's hospital stay. For patients at high risk of developing PONV, the recommended approach involves administering a combination of antiemetic drugs with different mechanisms of action. This approach provides better prophylaxis and reduces drug side effects compared to single therapies. In this study, a combination of 5-HT3 antagonists, including ondansetron, palonosetron, and dexamethasone, was used, building on previous research demonstrating the superior efficacy of such combinations. Specifically, co-treatment with dexamethasone and ondansetron proved more effective than the single use of ramosetron in preventing PONV in patients undergoing middle ear surgeries.28

Further research, Chatterjee and colleagues reported that using palonosetron and dexamethasone together reduced the incidence of PONV from 56% to 23%, compared to single-drug therapy.29 These findings strongly support the use of dexamethasone in combination with 5-HT3 receptor antagonists as an integral part of PONV prophylaxis, particularly in high-risk patients.

For this study, we have selected 8 published articles for analyzing the “comparison of efficacy” of Palonosetron with other similar drugs for preventing “Post Operative Nausea and Vomiting” (PONV) after otorhinolaryngological surgeries.

Group A was the treatment of palonosetron whereas Group B was treated with different drugs such as Ondansetron, Dexamethasone, and Tropisteron. In the present study, the results of PONV incidences showed significantly lower. Similarly, the results of PONV in Sharma et al. and Kumar et al. showed higher incidences in studies such as. 21, 22, 23

In this investigation, the incidence of PONV of all the drugs post otorhinolaryngological surgeries is exhibited in (Figure 3). The fixed effect model was used in this study when the heterogeneity was <50% and the >50% heterogeneity was used for the random effect model.

Comprehensively, investigations of this study disclosed insignificant variations when compared to palonosetron with other drugs (p = 0.18) with a pooled estimate of 0.53 and positive confidence intervals for both the lower and upper confidence ranges (0.21, 1.35 respectively) (Table 2 and Figure 5).

Figure 4

Forest plot for the overall outcome of palonosetron compared with other drugs in early (0-24h) and delayed (24-48h) PONV

The outcome of an early PONV incidence exhibited a significant difference with a P value < 0.05 when compared to palonosetron with other drugs although delayed PONV response exhibited an insignificant difference with a P value > 0.05. (Table 2)

The Forest plots representing the confidence intervals, p-values, and heterogeneity of palonosetron compared with other drugs are illustrated in Figure 3, Figure 4, Figure 5, providing a visual summary of the study's results. These plots display the range of effects across various trials, offering insight into the consistency (or variability) of outcomes. Each trial's effect size is depicted as a square, with lines extending to indicate the confidence interval (CI). P-values are included to assess the statistical significance of the findings. While some heterogeneity is observed in the meta-analysis, the I² score—a statistical measure of the degree of variation between studies—indicates that this variability is notable. Heterogeneity in meta-analyses can arise from several factors, including differences in study timeframes, variations in treatments administered, experimental design discrepancies, sample sizes, and the ethnic backgrounds of the populations studied. These factors contribute to variability in outcomes, which is common in clinical trials that aggregate results from diverse settings. Addressing heterogeneity is crucial, as it can influence the interpretation of the meta-analysis findings and impact the overall conclusions regarding the drug's efficacy.

Figure 5

Forest plot for the outcome of palonosetron compared with other drugs in early (0-24h) PONV

Figure 6

Forest plot for the outcome of palonosetron compared with other drugs in early (24-48h) PONV

The research reports on the palonosetron and its comparison with other medicines in preventing PONV after various surgeries were less. Preet Mohinder Singh et al. reported that Palonosetron treatment was found to be more statistically significant than placebo in preventing vomiting and nausea in the early and delayed stages in patients who have undergone elective surgery with general anaesthesia.

Palonosetron performed better than ramosetron in all three measures during the delayed phase, but none of these variables showed statistical significance during the early phase. Palonosetron showed exceptional vomiting inhibition (VI) and complete response (CR) than granisetron in the initial stage but in the delayed phase palonosetron showed no statistical significance in variables other than CR which are higher effective for Palonosetron.

In investigating the incidence of PONV associated with Palonosetron in comparison with various other medications in the course of elective surgeries performed under general anaesthesia, Xiong et al. 2015, reported that Palonosetron was more effective than ondansetron in suppressing early postoperative nausea (PON) by 49%, late PON by 47%, and late postoperative vomiting (POV) by 59%. However, no significant difference was observed in diminishing early POV between the two drugs.30 Preet et al. 2016 reported a meta-analysiswith 22 trials on Palanosetron, and compared with ondansetron drug. The results showed that Palanosetron showed better improvement than ondansetron in all groups.31 Kim et al. 2017 reported the meta-analysis of preventive of PONV using Palanosetron and compared with Ramosetron. The results revealed no definite difference in PONV prevention between the two drugs that are tested.32 Eun Jin et al. 2016 reported that there are no distinguishable variations in the efficacy of Palonosetron and Ramosetron in the prevention of PON, POV, and PONV when compared with other medications during elective surgeries performed under general anaesthesia. An administration of 5-HT3 receptor antagonist during the early portion of the operation, Palonosetron showed higher efficacy than Ramosetron.33 Nevertheless, when administered towards the conclusion of the surgical procedure, ramosetron had superior efficacy compared to palonosetron. No discernible disparities in headache or dizziness were seen between those who received palonosetron and those who received ramosetron.

Palonosetron is unique among 5-HT3 antagonists due to its high receptor binding affinity and prolonged half-life, which enables it to provide long-lasting protection against both acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV). Unlike earlier 5-HT3 antagonists, such as ondansetron and granisetron, palonosetron is highly selective for the 5-HT3 receptors and demonstrates a different pharmacodynamic profile. It exhibits allosteric inhibition, leading to a change in the receptor’s conformation and increased internalization, which reduces receptor availability and enhances its antiemetic effect. Palonosetron has minimal interaction with other neurotransmitter receptors, which contributes to its relatively low incidence of side effects, such as headache or constipation. It is well-absorbed following intravenous administration, reaching peak plasma concentrations rapidly, with a volume of distribution indicative of extensive tissue distribution. Palonosetron is primarily metabolized by the CYP2D6 enzyme, with additional contributions from CYP3A4 and CYP1A2 pathways, and is eliminated through both renal and hepatic routes. Its long duration of action makes it particularly effective in preventing delayed nausea and vomiting, a significant advantage in managing patients undergoing highly emetogenic chemotherapy.

Palonosetron’s clinical implications in PONV management go beyond its pharmacokinetic profile. Compared to first-generation 5-HT3 antagonists like ondansetron and dolasetron, palonosetron demonstrates superior efficacy, particularly in preventing delayed PONV, which typically occurs more than 24 hours post-surgery. Its unique allosteric binding and positive cooperativity with the 5-HT3 receptor may contribute to this enhanced and sustained efficacy. Furthermore, studies have shown that palonosetron may reduce the overall incidence of nausea, which is often more challenging to control than vomiting, thus improving patient comfort and satisfaction. Additionally, palonosetron is often compared with other classes of antiemetics, such as neurokinin-1 (NK1) receptor antagonists (e.g., aprepitant) and corticosteroids (e.g., dexamethasone). While NK1 receptor antagonists are also effective in managing both acute and delayed PONV, palonosetron’s side effect profile tends to be more favorable, with fewer reports of headache, constipation, and fatigue. Its minimal drug interactions also make it a safer option for polypharmacy patients. When used in combination with other antiemetics like dexamethasone, palonosetron has been shown to provide synergistic effects, further reducing the incidence of PONV compared to monotherapy with older 5-HT3 receptor antagonists. Despite these advantages, its cost remains a limiting factor, especially in resource-constrained settings, where cheaper alternatives may still be prioritized.

The efficacy of Palonosetron in comparison to other 5-HT3 antagonists for PONV after otorhinolaryngological surgeries can be influenced by several factors. Patient characteristics such as age, gender, BMI, and history of PONV or motion sickness are critical, as they affect susceptibility to PONV. The type of surgery (e.g., sinus surgery or tonsillectomy) and the anesthetic technique, particularly the use of general anesthesia and opioids, also play significant roles. Drug dosage, timing of administration, and the length of observation post-surgery impact the efficacy comparison, especially since Palonosetron has a longer half-life than other 5-HT3 antagonists. Study design factors such as randomization, blinding, and study size can introduce bias, while pharmacological differences between the drugs, including receptor affinity and side effect profiles, also contribute.