Enhancing Patient Safety in Refractory Ventricular Fibrillation: A Systematic Review of Double Sequential and Vector Change Defibrillation Barriers

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This systematic review addresses an important and timely question concerning the role of DSED and vector-change defibrillation in treating refractory ventricular fibrillation (VF). The paper is clearly structured and well written, providing a valuable synthesis of the available literature. However, there are some points that require clarification before publication.

For example, first the introduction should include a brief discussion of existing international guideline recommendations (ERC, AHA, ILCOR) to provide better context for the rationale behind this work.

Second the PRISMA flow diagram also requires clarification, as the screening stage is not fully transparent, and the reported numbers appear inconsistent.

Third, the limitations section should explicitly note that only two randomised controlled trials exist and that the majority of the included studies are small and heterogeneous. It should also note that none of the studies achieved the maximum Newcastle–Ottawa score.

These additions will improve transparency and ensure that the conclusions remain appropriately cautious.

Author Response

Comment 1: The introduction should include a brief discussion of existing international guideline recommendations (ERC, AHA, ILCOR) to provide better context for the rationale behind this work.

Response 1:
Thank you for this valuable suggestion. We agree with the reviewer’s comment and have revised the introduction to incorporate relevant information from recent international guidelines. Specifically, we have added a new second paragraph to the Introduction section (page 2, line 48), which states:
"According to the latest international guidelines from the European Resuscitation Council (ERC) and the American Heart Association (AHA), standard single-shock defibrillation is recommended for the management of shockable rhythms, including VF and pulseless ventricular tachycardia [4,5]. However, despite the occurrence of refractory VF in some clinical scenarios, neither organization currently provides specific recommendations regarding the use of alternative defibrillation techniques such as double sequential or vector change defibrillation [6]. The only relevant reference appears in the context of refractory cardiac arrest more broadly, where the use of extracorporeal cardiopulmonary resuscitation (eCPR) may be considered under specific conditions [4,5]."
This addition strengthens the rationale for the current review by highlighting the gap in current clinical guidance regarding alternative defibrillation strategies for refractory VF.

Comment 2: Second, the PRISMA flow diagram also requires clarification, as the screening stage is not fully transparent, and the reported numbers appear inconsistent.

Response 2: Thank you for this helpful observation. We agree with the reviewer’s comment and have revised the PRISMA flow diagram to enhance clarity and ensure consistency across all stages of screening. Specifically, the updated figure now explicitly accounts for the number of excluded records during each step and aligns all counts with the manuscript text.
This revision has been incorporated in the updated PRISMA figure, which appears on page 4, line 139 of the revised manuscript.

Comment 3: Third, the limitations section should explicitly note that only two randomised controlled trials exist and that the majority of the included studies are small and heterogeneous. It should also note that none of the studies achieved the maximum Newcastle–Ottawa score.

Response 3: Thank you for this important comment. We agree with the reviewer’s suggestions and have expanded the limitations section accordingly. Specifically, we have now included a statement clarifying that only two randomized controlled trials were identified, most included studies were small and clinically heterogeneous, and none achieved the maximum Newcastle–Ottawa Scale (NOS) quality score.
These additions appear in the Limitations section on page 13, line 470 of the revised manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

Please find the attachment.

Comments for author File: Comments.pdf

Comments on the Quality of English Language

Several sections need language enhancement. There a.re spelling errors in the Figure 1

Author Response

Comment 1: The title reflects the study type and essential component.

Response 1: Thank you for this positive observation. We are pleased that the title accurately reflects both the study type and the central topic addressed in the review.
No changes were required or made to the title in the revised version.
The title appears on page 1, line 2 of the manuscript.

Comment 2: It is interesting to see that the data search was completed in August 2025, and the manuscript was ready by September 2025. Considering the systematic review, it usually takes time to search all the required manuscripts from the mentioned database.

Response 2: Thank you very much for this thoughtful comment. We fully understand and agree with the reviewer’s observation that systematic reviews typically require a substantial amount of time for literature retrieval, screening, and analysis.
However, in our case, this process was accelerated due to prior academic work conducted by the lead author on a similar topic regarding the effectiveness of double sequential and vector change defibrillation.
This prior experience, along with unpublished internal data and familiarity with the relevant databases and search strategies, allowed for a more efficient identification and appraisal of eligible studies.
Despite the expedited timeline, we ensured that the systematic review process adhered strictly to PRISMA methodology and that all steps screening, eligibility assessment, and data extraction were thoroughly conducted.

Comment 3: In the abstract, avoid overstating clinical certainty (considering the limited number of RCTs).

Response 3: We thank the reviewer for this valuable comment and fully agree with the concern raised. Given the limited number of randomized controlled trials on this topic, we acknowledge that strong clinical conclusions should be avoided in the abstract.
Accordingly, we have revised the final sentence of the abstract to reflect a more cautious and balanced interpretation of the evidence. The updated phrasing now emphasizes the preliminary nature of the findings and the need for further high-quality research.
This revision appears in the Abstract section, on page 1, line 28, and now reads:
“DSED and VC defibrillation may offer potential benefits in managing RVF, but their use is hindered by significant practical, logistical, and methodological challenges. Due to the limited number of randomized trials, further high-quality studies with standardized definitions and safety endpoints are needed to clarify their clinical utility and inform implementation.”

Comment 4: Please use MeSH to refine the keywords.

Response 4: Thank you for this helpful suggestion. In response, we have revised the list of keywords to align with the official Medical Subject Headings (MeSH) terminology used by the National Library of Medicine.
The updated keywords now appear on page 1, line 31 of the manuscript and are as follows:
Ventricular Fibrillation; Defibrillators; Electric Countershock; Cardiac Arrest; Resuscitation; Treatment Outcome; Neurologic Manifestations.

Comment 5: The introduction could be tightened to focus on the knowledge gap driving the review. Also, the authors need to make sufficient references as part of the background information and rationale. It is better to avoid the main text included articles in the introduction (however, it is acceptable).

Response 5: We thank the reviewer for this constructive and thoughtful feedback. In response, we revised the Introduction to make it more concise and better focused on the knowledge gap regarding the lack of clinical guidance for alternative defibrillation strategies in refractory ventricular fibrillation (RVF). While streamlining the text, we ensured that the scientific rationale remained well-supported with appropriate references.

In addition, we introduced a new paragraph discussing the latest international guidelines issued by the European Resuscitation Council (ERC) and the American Heart Association (AHA). This addition was originally made in response to a related comment from Reviewer 1, but it also directly strengthens the background information and scientific justification requested in your comment. We believe it enhances the manuscript's clarity and contextual relevance.

We sincerely thank the reviewer for this thoughtful observation. In this particular case, we included certain studies in the Introduction because they offered essential background information that also supported the rationale for conducting the review. While we acknowledge that including studies later analyzed in the main text may not always be ideal, we believe their use here was justified and improved the clarity of the context.
We will certainly take this suggestion into account and avoid such overlap in future systematic reviews where feasible

The revised and more focused version of the Introduction now appears on pages 1–2, lines 37–69 and reads as follows:

Revised Introduction:

Cardiac arrest remains a leading cause of sudden death globally, with ventricular fibrillation (VF) being the most common shockable rhythm encountered [1]. It is categorized into out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA), each with distinct epidemiological patterns and management challenges [2]. Despite advancements in cardiopulmonary resuscitation (CPR) and defibrillation protocols, a significant proportion of patients develop refractory ventricular fibrillation (RVF)—defined as VF persisting after at least three failed shocks [2,3]. This condition necessitates exploring alternative defibrillation strategies to improve outcomes without compromising patient safety, particularly in high-acuity settings [1].

According to the latest guidelines from the European Resuscitation Council (ERC) and the American Heart Association (AHA), single-shock defibrillation is recommended for shockable rhythms, including VF and pulseless ventricular tachycardia [4,5]. However, neither organization currently provides specific guidance on alternative methods like double sequential or vector change defibrillation, despite their potential relevance in refractory VF [6]. The only related mention is in the broader context of refractory cardiac arrest, where eCPR may be considered under certain conditions [4,5].

Among the proposed strategies, double sequential external defibrillation (DSED) and vector change (VC) defibrillation are gaining attention. DSED administers two rapid, sequential shocks from separate defibrillators, while VC alters pad placement to change current direction through the myocardium [7–9]. Preliminary evidence from observational studies and small randomized trials suggests both may increase return of spontaneous circulation (ROSC), especially in OHCA [10,11].

Despite early promise, widespread use of DSED and VC is limited. Barriers include the need for dual defibrillators, shock coordination delays, lack of standard protocols, and reliance on trained personnel—all potentially compromising timely defibrillation and safety [3,12]. Furthermore, heterogeneity in study designs, inconsistent RVF definitions, small sample sizes, and limited reporting of neurological outcomes hinder evidence generalizability [13–15].

Given these issues, the effectiveness and safety of DSED and VC remain debated. This systematic review synthesizes current evidence on their use in RVF and critically evaluates the practical, logistical, and methodological barriers to implementation. Emphasis is placed on the implications for patient safety and the need to inform future clinical practice.

We hope these changes address the reviewer’s recommendations and enhance the scientific clarity and contextual relevance of the manuscript.

Comment 6: I appreciate the authors for the PROSPERO registration. However, for transparency, the verification link must be provided in the IRB section.

Response 6: Thank you for your helpful comment. The review protocol has been submitted for registration in the PROSPERO database (ID: 1144647) and is currently undergoing processing. As the record has not yet been published in the public registry, a verification link is not available at this stage

Comment 7: The authors mentioned the PRISMA checklist as a supplementary file 1. However, I could not find it. Only the quality assessment checklist is available.

Response: We thank the reviewer for this observation. We apologize for the oversight in the initial submission. We have now included the completed PRISMA 2020 checklist as Supplementary File 1, titled:
“Supplementary file 1.1 – PRISMA_2020_checklist.docx”
This file provides itemized information on how all PRISMA requirements were addressed in the manuscript.

Comment 8: Please modify the eligibility criteria. Be specific about what you have included (types of studies). Because it is unclear.

Response 8: Thank you for this constructive comment. We have revised the “Eligibility Criteria” section to explicitly state the types of eligible study designs, including randomized controlled trials, cohort studies, and case series. This clarification ensures greater transparency regarding study selection. The updated text can be found on Page 2, Line 85.

Revised Text (Page 2, Line 85):

Eligibility Criteria
Studies were included if they were primary clinical investigations, such as randomized controlled trials (RCTs), prospective or retrospective cohort studies, or case series involving adult patients (aged ≥18 years) who experienced refractory ventricular fibrillation (RVF) during cardiac arrest. Eligible studies assessed the use of DSED or VC defibrillation and reported at least one of the following outcomes: return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, or barriers to implementation, with a particular focus on patient safety.

Comment 9: Figure 1 conveys wrong information. I strongly believe there are errors and a lack of transparency.

Response 9: Thank you for this valuable comment. We agree with the reviewer’s observation and have revised the PRISMA 2020 flow diagram to correct the inconsistencies and improve transparency. The updated figure now accurately reflects the number of records at each stage of the screening and selection process and is consistent with the described methodology in the manuscript.
This revised diagram has been incorporated into the manuscript on page 3, line 106, and we have also attached the updated file titled “PRISMA_2020_flow_diagram_new_SRs_v1(18.9).docx” as a supplementary file for clarity and completeness.

Comment 10: Also, only duplicate studies between the databases are 3?

Response 10:
Thank you for highlighting this point. Following the reviewer’s comment, we re-examined the database outputs using both citation manager tools and manual screening. We confirm that only three duplicate records were identified and removed prior to screening. This is consistent with the revised PRISMA 2020 flow diagram, which has been updated for transparency and accuracy.

Comment 11: The eligibility criteria must be clearly reflected in the flow-chart.

Response 11: Thank you for your valuable comment. We agree that transparency regarding eligibility criteria is essential. In response, we have revised the PRISMA flow diagram to explicitly categorize the reasons for exclusion at the eligibility stage, clearly reflecting the inclusion and exclusion criteria described in the methods section.

Comment 12: Where is the detailed PICO(T)? Considering the clinical scenario, a clear PICOT is mandatory.

Response 12: Thank you for this valuable comment. We agree that the explicit presentation of the PICOT framework enhances transparency and methodological rigor. Accordingly, we have added a new subsection titled "2.2 PICOT Framework" on page 30, line 90, clearly outlining the population, intervention, comparison, outcomes, and time frame of the review question.

Comment 13: Including different quality assessment tools for each study type is highly appreciated. However, please check again whether it is a standard way or not.

Response 13: Thank you for your positive feedback and thoughtful observation. We confirm that using study-type-specific quality assessment tools is a standard and widely accepted methodology in systematic reviews. Specifically, we employed the Newcastle–Ottawa Scale (NOS) for non-randomized studies and the Cochrane RoB 2 tool for randomized controlled trials, as recommended by the Cochrane Handbook for Systematic Reviews of Interventions and other methodological guidelines. This approach has been clarified in the Methods section, page 10, line 209, to enhance transparency and scientific rigor.

Comment 14: Table 1 lists “NR” (not reported) for neurological outcomes in several studies, but the text does not explicitly quantify how many studies failed to report them.

Response 14: Thank you for this insightful comment. We have revised the manuscript to explicitly indicate that neurological outcomes were reported in only six of the included studies. Specifically, we have added the following sentence to the Comparative Effectiveness of DSED, VC, and Conventional Defibrillation section (Page 11, Line 366):
“However, only six studies explicitly reported neurological outcomes, limiting the strength of conclusions regarding post-arrest neurological recovery [9,16,17,21,22,24].”
This addition improves transparency and addresses the concern regarding incomplete outcome reporting.

Comment 15: There is no pooled or comparative analysis  not even a simple weighted average for ROSC or survival. A narrative synthesis is acceptable, but presenting summary percentages would strengthen the interpretation.”

Response 15: Thank you for pointing this out. We agree with this comment. Therefore, we have added a narrative summary of ROSC percentages across studies to strengthen interpretability, while avoiding formal pooling due to high heterogeneity in study designs and outcome definitions. This addition can be found in the revised manuscript on page 11, paragraph 3.5, lines 379–384, where we now state.

Comment 16: Given the low certainty and lack of pooled analysis, the discussion must not overinterpret the findings. Phrases such as “urgent need for integration of DSED-specific training into resuscitation curricula” imply a policy recommendation that may not be justified.

Response 16: Thank you for this important observation. We agree with the comment and have revised the phrasing to reflect a more cautious and evidence-aligned interpretation. Specifically, we have removed the policy-leaning language and rephrased the statement to avoid overstatement.

The updated sentence is now found on page 11, paragraph 3, lines 367–369 and reads as follows:
“Given the current lack of standardized instruction, future research should explore whether integrating DSED-specific training into resuscitation curricula could enhance provider preparedness and improve safety.”

We believe this revised phrasing more accurately reflects the current evidence and avoids implying premature recommendations.

 

 

Reviewer 3 Report

Comments and Suggestions for Authors This is a systematic review of DSED/VC for refractory VF with focused on its barriers. It is interesting to focus on its barriers while previous systematic reviews mainly focused on its efficacy.   Major: The authors mentions that the aim of this study are to examine the practical, logstical and methodological barriers to the implementation. Is there a reason for separating the barriers into practical, logistical, and methodological? The way of describing has changed among the Introduction, Discussion, and Conclusion. If you are considering them separately, please explicitly state which barrier corresponds to which section.   The search term doesn't include “vector change.” Is it not needed?   L353-367 Is the content described here based on the discussion from this review? Were there any studies that raised concerns about implementing DSED due to regional disparities?   Minor Fig. 1 contains several errors. The spelling of “eligibility” in the Screening box is incorrect, the number is missing, the box to its right has an extra ‘i’ in “Did not report outcomes of interest,” and there are two boxes labeled “Full-text articles included after eligibility assessment.”   L261 Is the 13.7-second delay a defibrillation delay? Or a resuscitation interruption?  

Author Response

Comment 1:

The authors mention that the aim of this study is to examine the practical, logistical, and methodological barriers to the implementation. Is there a reason for separating the barriers into practical, logistical, and methodological? The way of describing has changed among the Introduction, Discussion, and Conclusion. If you are considering them separately, please explicitly state which barrier corresponds to which section.

Response 1:

We sincerely thank the reviewer for this constructive comment, which helped us clarify and better define the conceptual framework of the study. Following the reviewer’s suggestion, we carefully reconsidered the classification of barriers and concluded that logistical barriers are inherently part of the practical domain, as they refer to real-world operational factors affecting implementation.

Therefore, the revised manuscript now distinguishes two main categories of barriers only — practical and methodological. This modification enhances both clarity and internal consistency across all sections.

The following sections were updated accordingly:

• Abstract: page 1, column 1, line 11

• Introduction: page 1, column 2, line 37

• Discussion: page 16, column 1, line 385

• Conclusions: page 13, column 2, line 489

In the Introduction, we also added a defining statement for transparency:

“Practical barriers refer to real-world factors affecting clinical application, while methodological barriers concern limitations in study design and reporting.”

These changes ensure conceptual coherence and provide a clearer framework for interpreting the findings throughout the manuscript.

Comment 2:

The search term doesn't include “vector change.” Is it not needed?

Response 2:

We thank the reviewer for this valuable observation. The term “vector change” was not included as a separate keyword because it is not indexed as an independent MeSH term in PubMed, Scopus, or CINAHL. Relevant studies referring to vector change defibrillation are indexed under broader categories such as “Defibrillators,” “Electric Countershock,” and “Ventricular Fibrillation.”

Accordingly, our search strategy and keyword selection already encompassed this terminology through the following MeSH terms:

Ventricular Fibrillation; Defibrillators; Electric Countershock; Cardiac Arrest; Resuscitation; Treatment Outcome; Neurologic Manifestations.

These terms adequately capture all relevant studies addressing both double sequential and vector change defibrillation. Therefore, the addition of “vector change” as a separate search term was not required, and no modification to the Methods section was necessary.

Comment 3:

L353–367: Is the content described here based on the discussion from this review? Were there any studies that raised concerns about implementing DSED due to regional disparities?

Response 3:

We thank the reviewer for this comment. The content in lines 353–367 is derived from the synthesized discussion of the included studies rather than author interpretation. No study explicitly reported regional or geographic disparities affecting the implementation of DSED. The evidence primarily addressed practical barriers, such as limited training, lack of standardized protocols, and coordination challenges, as well as methodological heterogeneity across studies.

Since the included literature did not identify regional inequality as a relevant factor, no modification to the manuscript was required.

Comment 4:

Figure 1 contains several errors. The spelling of “eligibility” in the Screening box is incorrect, the number is missing, the box to its right has an extra ‘i’ in “Did not report outcomes of interest,” and there are two boxes labeled “Full-text articles included after eligibility assessment.”

Response 4:

We thank the reviewer for these detailed observations. The PRISMA flow diagram (Figure 1) has been fully revised to correct all identified issues. Specifically, the spelling of “eligibility” has been corrected, the missing number in the Screening box has been added, the redundant text containing the extra “i” was removed, and the duplicate “Full-text articles included after eligibility assessment” box was eliminated.

The updated figure now accurately represents the study selection process in accordance with PRISMA 2020 standards and aligns with the numbers and descriptions reported in the Methods and Results sections.

Comment 5:

L261: Is the 13.7-second delay a defibrillation delay? Or a resuscitation interruption?

Response 5:

We thank the reviewer for this valuable comment. The 13.7-second delay reported in the simulation study refers to the interval between the first and second shocks delivered during double sequential external defibrillation (DSED). It represents the inter-shock delay required to coordinate the two defibrillators, rather than a delay in initiating defibrillation or an interruption of ongoing resuscitation efforts.

In other words, this value reflects the brief time difference between the two sequential shocks, not a pause in CPR or other treatment activities. Therefore, no modification to the manuscript was necessary, but we appreciate the opportunity to clarify this point for accuracy.

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors,

Thank you for making the revisions according to the comments.

Wish you all the best

Reviewer 3 Report

Comments and Suggestions for Authors

The authors appropriately revised the manuscript