Efficacy and Safety of Analgesics and Sedatives during Radiofrequency Catheter Ablation of Atrial Fibrillation: A Network Meta-Analysis

Background: Atrial fibrillation is the most common tachyarrhythmia, while catheter ablation is an effective therapy for atrial fibrillation. However, pain and nervousness may occur during the procedure. Moreover, a consensus has still not been reached on which is the best kind of analgesic and sedative to use in these procedures. Therefore, we conducted a network meta-analysis to evaluate the efficacy and safety of analgesics and sedatives used in catheter ablation for atrial fibrillation. Methods: We searched PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, and Baidu Wenku document download website for randomized controlled trials from their inception to February 26, 2023. Only studies that made comparisons among analgesics or sedatives and involved patients with atrial fibrillation undergoing radiofrequency catheter ablation were included. The efficacy endpoints were Ramsay sedation scores and visual analog scale scores during the radiofrequency catheter ablation for atrial fibrillation. The safety endpoints were the incidence of respiratory depression, hypotension, nausea, and vomiting. Pairwise comparisons and frequency method analyses were conducted. Results were reported as odds ratio (OR), mean difference (MD), and corresponding 95% confidence intervals (CIs). We assessed the risk bias of the studies in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Results: Out of the 709 articles initially retrieved, 14 studies, with a total of 1156 participants, were included. In terms of efficacy, patients receiving dexmedetomidine during radiofrequency ablation for atrial fibrillation had higher Ramsay sedation scores than those receiving midazolam plus fentanyl, or its derivatives (MD –0.88, 95% CI [–0.04 to –0.72]). Compared with morphine, dezocine (MD 1.88, 95% CI [1.16 to 2.60]), hydromorphone (MD 4.07, 95% CI [3.56 to 4.58]), butorphanol (MD 3.18, 95% CI [2.38 to 3.96]), and fentanyl or its derivatives (MD 1.57, 95% CI [1.25 to 1.89]) had a better analgesic effect. In terms of safety, propofol (OR 16.46; 95% CI [1.54 to 175.95]) and midazolam plus fentanyl or its derivatives (OR 7.02; 95% CI [1.33 to 36.99]) significantly increased the incidence of respiratory depression compared with dexmedetomidine plus fentanyl or its derivatives. Dexmedetomidine plus fentanyl or its derivatives reduced the incidence of nausea and vomiting compared with fentanyl alone (OR 4.74; 95% CI [1.01 to 22.22]). Propofol was associated with a lower incidence of nausea and vomiting than hydromorphone (OR 0.01; 95% CI [0.00 to 0.59]) and fentanyl or its derivatives (OR 0.01; 95% CI [0.00 to 0.51]). There was no statistically significant difference in the incidence of hypotension between any two strategies. Conclusions: Hydromorphone and butorphanol had better analgesic effects than fentanyl or its derivates. Dexmedetomidine had better sedative effects. In terms of safety, dexmedetomidine, oxymorphone, and butorphanol were superior. It is necessary to explore the regimen that can consider both the effectiveness and safety during radiofrequency catheter ablation for atrial fibrillation (AF). The PROSPERO Registration: This study was registered with PROSPERO, number: CRD42023403661.


INTRODUCTION Rationale
3 Describe the rationale for the review in the context of existing knowledge.

Objectives 4
Provide an explicit statement of the objective(s) or question(s) the review addresses.

Eligibility criteria 5
Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses.
Information sources 6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies.Specify the date when each source was last searched or consulted.

Search strategy 7
Present the full search strategies for all databases, registers and websites, including any filters and limits used.

Selection process 8
Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

Data collection process 9
Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

Data items 10a
List and define all outcomes for which data were sought.Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.
10b List and define all other variables for which data were sought (e.g.participant and intervention characteristics, funding sources).Describe any assumptions made about any missing or unclear information.

Study risk of bias assessment
11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.

Effect measures
12 Specify for each outcome the effect measure(s) (e.g.risk ratio, mean difference) used in the synthesis or presentation of results.

Synthesis methods
13a Describe the processes used to decide which studies were eligible for each synthesis (e.g.tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item 5)).
13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.
All data are organized in Excel in tabular form.
13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.
13d Describe any methods used to synthesize results and provide a rationale for the choice(s).If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.
13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g.subgroup analysis, meta-regression).
13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results.

Reporting bias assessment
14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).

Certainty assessment
15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome.
The first manuscript is not reported.We can supplement this in subsequent submissions.

Study selection
16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.
16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.

Study characteristics
17 Cite each included study and present its characteristics.Lines 167-168.

Risk of bias in studies
18 Present assessments of risk of bias for each included study.Lines 168-169.

Results of individual studies
19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g.confidence/credible interval), ideally using structured tables or plots.

Results of syntheses 20a
For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies.
Lines 190-192,212 -216,239-231,259-260,274-278. 20b Present results of all statistical syntheses conducted.If metaanalysis was done, present for each the summary estimate and its precision (e.g.confidence/credible interval) and measures of statistical heterogeneity.If comparing groups, describe the direction of the effect.
20c Present results of all investigations of possible causes of heterogeneity among study results.
20d Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results.
Heterogeneity was low and sensitivity analysis was not performed.

Eligibility criteria
3 Specify the inclusion and exclusion criteria for the review.Yes Information sources 4 Specify the information sources (e.g.databases, registers) used to identify studies and the date when each was last searched.

Yes
Risk of bias 5 Specify the methods used to assess risk of bias in the included studies.Yes

Synthesis of results
6 Specify the methods used to present and synthesize results.Yes

Included studies 7
Give the total number of included studies and participants and summarise relevant characteristics of studies.

8
Present results for main outcomes, preferably indicating the number of included studies and participants for each.If meta-analysis was done, report the summary estimate and confidence/credible interval.If comparing groups, indicate the direction of the effect (i.e. which group is favoured).

Limitations of evidence 9
Provide a brief summary of the limitations of the evidence included in the review (e.g.study risk of bias, inconsistency and imprecision).

Interpretation 10
Provide a general interpretation of the results and important implications.Yes OTHER Funding 11 Specify the primary source of funding for the review.Yes Registration 12 Provide the register name and registration number.Yes From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.MetaArXiv.2020, September 14.DOI: 10.31222/osf.io/v7gm2.For more information, visit: www.prisma-statement.org