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Abstract
Introduction Intraperitoneal dexamethasone has been reported to be effective to reduce the incidence of postoperative nausea and vomiting (PONV). Therefore, this meta-analysis will analyse the efficacy and safety of intraperitoneal dexamethasone on PONV following laparoscopy.
Methods and analysis Electronic databases (eg, Cochrane Library, PubMed, Excerpta Medica Database, Web of Science, National Institute of Informatics, Oriental Medicine Advanced Searching Integrated System and China National Knowledge Infrastructure) and clinical trial registries will be systematically searched from their inception to 1 October 2022. After the study and data collection processes, we will identify randomised controlled trials that reported details of intraperitoneal dexamethasone on PONV following laparoscopy to conduct a meta-analysis. We will perform the study process and data collection separately. The collected data will be statistically analysed using Review Manager 5.4 software. The risk of bias will be assessed using the Cochrane risk-of-bias tool 2. The Grading of Recommendations Assessment, Development and Evaluation certainty assessment, and a trial sequential analysis will be conducted to ensure the accuracy of this meta-analysis.
Ethics and dissemination Ethical approval and patient consent are not required since this study is a systematic review and meta-analysis. The findings of this meta-analysis will be submitted to a peer-reviewed journal for publication.
PROSPERO registration number CRD42022362924.
- anaesthetics
- surgery
- adult anaesthesia
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
This research will be the first meta-analysis to analyse the efficacy and safety of intraperitoneal dexamethasone on PONV following laparoscopy.
A trial sequential analysis will be conducted to ensure the accuracy of this meta-analysis.
The uncertain quality, sample size and heterogeneity of the included studies may limit the representativeness and determination of the results summarised in this meta-analysis.
Introduction
Postoperative nausea and vomiting (PONV) continue to affect patients who had undergone surgery, negatively impacting postoperative outcomes, such as delaying postanaesthesia care and discharge, decreasing patient satisfaction, and increasing overall hospital costs.1 2 PONV affects up to 80% of high-risk patients within 24 hours after surgery because of patient-related factors, surgical procedures and perioperative medications, such as opioids.3 Following the emergence of enhanced recovery after surgery, the importance of antiemetic prophylaxis in perioperative care has increased.4 Dexamethasone, a glucocorticoid, plays a significant role in this phase and is considered as a first-line agent for treating PONV prophylaxis.5 6 Although there are still concerns regarding the safety of dexamethasone infection owing to its immunosuppressive and glucose-rising effects, dexamethasone has equal or even better efficacy in reducing the incidence of PONV along with the advantages of low cost and longer effectiveness than those of other preventive agents.7–10
Laparoscopic surgery, including gynaecological laparoscopy and cholecystectomy, may be associated with an increased risk of PONV, and achieving good results with a single antiemetic method is difficult.11–14 Dexamethasone contributes to reducing the risk of PONV following laparoscopic surgery and is usually administered by intravenous injection according to previous research on PONV prophylaxis.15 16 Recently, an uncommon delivery method of intraperitoneal injection has emerged in clinical practice, and many studies on this delivery method have mainly focused on the field of intraperitoneal local anaesthetics for postlaparoscopic analgesia.17–19 However, some studies documenting the use of intraperitoneal glucocorticoids have reported an association with a lower incidence of PONV after laparoscopic surgery.20 21 Dexamethasone is a glucocorticoid, commonly delivered intravenously, and its effect on preventing PONV has been confirmed by previous studies.7 22–24 Accordingly, we propose that intraperitoneal dexamethasone may also yield a good or better effect in preventing PONV.
Ismail et al25 reported that 8 mg intraperitoneal dexamethasone for PONV prophylaxis was more effective than the same dose of intravenous dexamethasone. It is promising that intraperitoneal dexamethasone might be perceived as a more optimal method for treating PONV prophylaxis. However, clinical practice recommendations strong enough to guide the administration of intraperitoneal dexamethasone for PONV prophylaxis after laparoscopic surgery are lacking. Thus, we aim to complement the relevant evidence by performing a systematic review and meta-analysis to assess the efficacy and safety of intraperitoneal dexamethasone for PONV prophylaxis following laparoscopy.
Methods and analysis
This systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022362924). This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.26
Eligibility criteria
We will identify adult patients who underwent laparoscopy without restrictions on age, sex or laparoscopic type. They will be divided into an intraperitoneal group, comprising those who were administered intraperitoneal dexamethasone, and a control group, where intravenous dexamethasone, placebo or no intervention was used to prevent PONV following laparoscopy. The core outcome set and recommendations recorded in the Core Outcome Measures in Effectiveness Trials database for PONV research will be considered for inclusion of all outcomes (https://www.comet-initiative.org/Studies/Details/545). The primary outcome we will investigate is the occurrence of PONV recorded during the first 24 hours after laparoscopy. Secondary outcomes will be the incidence of other postoperative complications, postoperative Visual Analogue Scale (VAS) pain scores and total rescue analgesic consumption during the 24 hours after surgery. Moreover, only randomised controlled trials (RCTs) will be included in the meta-analysis. Studies with the following characteristics will be excluded: duplicate literature, insufficient original data, discrepancy in literature type and inferior quality publications.
Information sources and search strategy
Electronic databases will be screened from inception to 1 October 2022, including the Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE via PubMed, Excerpta Medica Database (Embase) via Ovid, Web of Science Core Collection, China National Knowledge Infrastructure (CNKI), National Institute of Informatics (CiNii) and Oriental Medicine Advanced Searching Integrated System (OASIS). We will also attempt to retrieve grey literature by screening the European Grey Literature (OpenSIGLE) database and Google Scholar, which will be independent of language restrictions. We will subsequently search the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov and Chinese Clinical Registry (ChiCTR) to avoid unnecessary omissions during the literature search. Published RCTs documenting the effects of intraperitoneal dexamethasone on PONV following laparoscopy will be included. We will follow the Peer Review of Electronic Search Strategies (PRESS) guidelines and include a peer reviewer focused on the search strategy to help develop a comprehensive and precise search strategy eventually.27 Advanced search structure will be created by conceptualising the PICO question’s elements (P, patient; I, intervention; C, comparison; O, outcome) with controlled language (MeSH) and natural language.28 Following the elements of the PICO question, we will use the search terms that include ‘laparoscopy,’ ‘intraperitoneal,’ ‘dexamethasone,’ ‘placebo,’ ‘intravenous’ and ‘postoperative nausea and vomiting.’ The PubMed search items using wild cards and truncation are listed in table 1. We will also choose the filter (article type) to increase precision to collect the required RCTs. The full search items that will be used for all databases, registers and websites are shown in online supplemental material 1. If necessary, some adjustments will be made to the search terms used in the enrolled databases, registers and websites.
Supplemental material
The PubMed search items for study selection
Study and data collection
The study collection process will be independently conducted by two authors (NX and LL) after obtaining the studies from all electronic databases. Any duplicates detected by the EndNote X9 software (The Thomson Corporation Corp, Stanford, Connecticut, USA) will be deleted. The titles and abstracts of the remaining studies will be reviewed for relevance according to the eligibility criteria. Following the removal of ineligible studies, the full texts of the studies will be assessed to determine whether they should be included. A PRISMA diagram will be used to show the study collection process. Based on a data extraction table, including the baseline information of the included studies, methodological characteristics, study population and specific details of outcomes for both groups, two authors (NX and LL) will independently complete the data collection process. Any disagreements identified during the study and data collection process will be addressed by a consensus meeting.
Study quality assessment
The risk of bias assessment for individual studies included in this meta-analysis will be conducted separately by us using the Cochrane revised risk-of-bias tool (RoB2).29 Three levels of risk of bias will be determined: low, some concerns and high. We will mainly analyse the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, selection of the reported results and overall bias. RoB2 assessment spreadsheet (ROB2_IRPG_beta_v9), downloaded from https://www.riskofbias.info/, will be used to generate the related figures demonstrating the risk of bias for the included studies.29
Grading Recommendations Assessment, Development, and Evaluation (GRADE) certainty assessment
GRADE certainty assessment for the primary outcome will adhere to the GRADE approach.30 The six aspects detected in the certainty assessment will focus on study design, risk of bias, inconsistency, indirectness, imprecision and other considerations. The four levels of evidence quality will be classified as high, moderate, low or very low. We will use the GRADE profiler (V.3.6.1) to produce a table of evidence profiles depicting the results of the GRADE certainty assessment.31
Statistical analysis
Statistical analyses in this meta-analysis will be based on the collected data, and relevant calculations will be performed using the Review Manager software (RevMan, V.5.4. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration). For dichotomous variables, the risk ratio (RR) will be pooled as the effect size, calculated using a 95% CI. For continuous variables, we will employ the mean difference (MD) and 95% CI to assess the effect. The I2 value will be used to assess the degree of heterogeneity among the included studies. We will refer to I2 value to decide when to perform the meta-analysis. When there is excessively significant heterogeneity among the studies (I2 >75%), the meta-analysis will be deemed impossible. Fixed-effects model analysis will be conducted if the I2 value is below 25%; otherwise, a random-effects model analysis will be conducted. Considering that there may not be sufficient literature reporting the eligible comparators and interventions to complete a meta-analysis, we will utilise a narrative synthesis to demonstrate clinical outcomes based on the reporting guidelines of synthesis without meta-analysis when necessary.32
Subgroup analysis
If the collected data are sufficient, we will perform subgroup analyses to investigate how sex, age, laparoscopic type and doses of dexamethasone administered by intraperitoneal injection influence the results of this meta-analysis.
Sensitivity analysis
If obvious heterogeneity (I2 >50%) is detected in any domain included in our meta-analysis, we will perform sensitivity analyses to investigate the source of heterogeneity by sequentially excluding each study and remeasuring the pooled data for the remaining included studies. When the retrieved studies show a high risk of bias, a sensitivity analysis will be conducted to rule them out.
Patient and public involvement
No patients were enrolled in this study since this is a meta-analysis based on published studies. This systematic review protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD42022362924). This meta-analysis will be submitted to a peer-reviewed journal for publication.
Publication bias
A funnel plot generated using the Review Manager software (V.5.4) for the primary outcome will be visually estimated to demonstrate the risk of publication bias. The alternative is to use the Stata 15.1 software (StataCorp LP, College Station, Texas, USA) to perform Egger’s test to quantitatively assess publication bias.
Trial sequential analysis (TSA)
To avoid the adverse impact caused by random errors (type I or II) on the findings of this meta-analysis,33 we will additionally perform a TSA to ensure the accuracy of this meta-analysis using the TSA software, V.0.9.5.10 Beta (Centre for Clinical Intervention Research, Copenhagen).
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors NX: Conceptualised and designed the study. NX and LL: Literature and data selection. LC: Inconsistency handling. NX: Supervision. NX, LL and KJ: Critical revision of the manuscript for important intellectual content. All authors: Analysed the feasibility and writing of this protocol, contributed to the protocol and approved the final version of this manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.