Article, Cardiology

Double sequential defibrillation for out-of-hospital refractory ventricular fibrillation: A scoping review

a b s t r a c t

Background: double sequential defibrillation has been proposed as a viable treatment option for patients in refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) out-of-hospital cardiac arrests . However, currently there is insufficient evidence to support a widespread implementation of this ther- apy.

Study objectives: The aim of this scoping review was to summarize the current available evidence of DSD for pa- tients with refractory VF/pVT OHCA as well as to identify gaps in the literature that may require further research. Methods: We conducted a Comprehensive literature search of MEDLINE via PubMed, Embase via Ovid, and Scopus on August 19, 2019. We also checked reference lists of relevant papers to identify additional studies. Any con- trolled clinical study design (randomized controlled trials and non-randomized controlled trials), and observa- tional studies (cohort studies and Case-control studies) providing information on resuscitative parameters, survival rates and neurological outcomes in adults (>= 18 years old) treated with DSD for refractory VF/pVT OHCA were included. Two investigators independently conducted the literature search, study selection, and data extraction.

Results: The search yielded 1612 unique records, of which 4 peer-reviewed articles were found relating to the re- search purpose, totaling 1061 patients of who 20.5% (n = 217) received DSD. Most studies evaluated if pre- hospital DSD was associated with improved survival to discharge after refractory VF/pVT. No randomized con- trolled trials were identified.

Conclusion: To date, it is difficult to conclude the real benefit of DSD for patients in refractory VF based on the available evidence. The findings of this scoping review suggest there is limited evidence to support at large- scale the use of DSD for refractory VF/pVT OHCA. Further research is needed to better characterize and under- stand the use of DSD for refractory VF/pVT, in order to implement best practices to maximize the effectiveness and efficiency of care.

(C) 2019

Introduction

Survival to hospital discharge and favorable neurological outcome, from refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) out-of-hospital cardiac arrest (OHCA), have dismal prognosis even when patients are treated by highly specialized emergency medi- cal services (EMS) providers [1,2]. The annual incidence of refractory VF can be up to 0.6 cases per 100,000 people and mortality can be as high as 97% [3,4]. VF/pVT are associated with the highest survival and predictive

? The authors whose names are listed below certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Additionally, it is my ethical obligation as a researcher, to report that each author has contributed to conducting the underlying research and drafting this manuscript.

* Corresponding author at: Department of Internal Medicine, Good Samaritan Hospital,

P.O. BOX: 4055, Aguadilla 00605, Puerto Rico.

E-mail address: [email protected] (D. Miraglia).

factor for Neurologically intact survival when compared with non- shockable cardiac arrest rhythms (pulseless electrical activity [PEA] and asystole) [5,6]. However, only up to 30% of patients with VF/pVT OHCA survive to discharge with good neurological function.

Currently, there are no efficacious treatments for patients who re- main in VF/pVT, and do not respond to standard defibrillation (SD) at- tempts [7,8]. Therefore, identifying the feasibility and effectiveness of new therapies for OHCA remains a high priority, particularly the role of double sequential defibrillation (DSD) for refractory VF/pVT. DSD has been proposed as an alternative Management strategy for recur- rent/refractory VF, as there appears to be a trend of promising outcomes [9-29]. The results and findings of these studies are important to de- velop better practices although the outcomes have varied widely, sug- gesting that further studies are necessary to better understand the potential impact of DSD for refractory VF/pVT.

The necessity of this review comes from not knowing what kind of information is available in published literature about pre-hospital use

https://doi.org/10.1016/j.ajem.2019.12.047

0735-6757/(C) 2019

of DSD. For these reasons, a scoping review was conducted, in order to systematically map the research done on pre-hospital DSD for refractory VF/pVT, as well as to identify gaps in the literature that may require fur- ther research. The following research questions were formulated: What is known from the literature about the efficacy of DSD for refractory VF/ pVT OHCA? What are the survival rates and neurological outcomes after survival to discharge? Henceforth, this scoping review will identify the feasibility of future work in this area from a variety of methodological perspectives. We also provide opportunity for discussions on this very important issue, including a quick reference that enables future re- search on this topic.

Methods

We followed the PRISMA-ScR (Preferred reporting items for system- atic reviews and Meta-analysis extension for scoping reviews) guide- lines developed according to published guidance, by the EQUATOR Network (Enhancing the Quality and Transparency of Health Research), for the development of reporting guidelines [30] and the scoping review methods manual developed by the Joanna Briggs Institute [31]. A formal scoping review protocol was drafted. The five key phases developed by the authors to maintain a transparent method for data collection, analy- sis and interpretation where the following: 1) identifying the research question; 2) identifying relevant studies; 3) selecting studies; 4) charting the data; and 5) collecting, summarizing, and reporting the results.

Data sources and searches

We searched the following electronic bibliographic databases on Au- gust 19, 2019: MEDLINE via PubMed, Embase via Ovid, and Scopus. We also checked reference lists of relevant papers to identify additional stud- ies. The search was repeated on September 10, 2019 to capture any arti- cles published during the Review process. Adhering to the research question, we decided to conduct a broad search, as including more spe- cific search terms would, in our case, be associated with a higher risk of missing wrongly indexed studies in the literature. We used EndNote to remove internal (within a database), and external (between databases) duplicates. In order to identify ongoing clinical trials we searched the In- ternational Clinical Trials Registry Platform (ICTRP) (http://www.who. int/ictrp/en/), which includes entries in (ClinicalTrials.gov) on Septem- ber 10, 2019.

We used the PRESS (Peer Review of Electronic Search Strategies) checklist to develop the research strategy we used for this study [32]. Our search strategy was based on the use of text words only (text- word search). A search was performed using the following keywords: (“refractory ventricular fibrillation” or “RVF” or “pre-hospital cardiac ar- rest” or “out-of-hospital cardiac arrest” or “cardiac arrest” or “heart ar- rest” or “OHCA”) and (“double defibrillation” or “dual defibrillation” or “double simultaneous defibrillation” or “double sequential defibrilla- tion” or “DD” or “DSD”) and (“conventional cardiopulmonary resuscita- tion” or “cardiopulmonary resuscitation” or “resuscitation” or “CPR”).

Studies selection

We used the PCC (Population, Concept, and Context) framework to delineated eligibility criteria [33]. Two reviewers checked the titles, ab- stracts, or type of each of the identified articles. We included any con- trolled clinical study design (randomized controlled trials and non- randomized controlled trials) and observational studies (cohort studies and case-control studies) with a control group (i.e. patients not receiv- ing DSD) which provided information on resuscitative parameters, sur- vival rates and neurological outcomes in adults (>=18 years old), who were treated with DSD, and needed resuscitation for refractory VF/ pVT OHCA.

No publication date, or publication status restrictions were imposed. We did not consider articles that fell under the following exclusion

criteria: languages other than English, editorials, comments, conference abstracts, duplicate studies, case reports, case-series, reviews, meta- analyses, or were conducted on Pediatric populations, pregnancy, dealt with electrophysiology and provoked cardiac arrest. After elimi- nating the excluded abstracts, we acquired the full texts of the chosen articles, which were then rescreened and reevaluated for eligibility by using the same exclusion criteria. Any disagreement regarding inclusion or exclusion criteria was resolved via discussion. Fig. 1 shows the study selection procedure.

Data extraction

The charting form was developed during the review process from the selected full-text studies and was created by two investigators using a pre-defined standardized form that was piloted on 2 articles in order to ensure it would gather the correct information. Microsoft Excel was utilized for this stage. Two reviewers then charted data, discussed results, and updated the data charting form. Variables ex- tracted for data charting included the first author, year of publication, study designs, focus of the paper, sample size, population characteris- tics, interventions, and key outcomes. We did no critically appraise studies or confirm abstracted data with study investigators. Table 1-2 summarize details of the pre-hospital observational studies on DSD se- lected for inclusion according to demographics, presentation, resuscita- tive parameters, and outcomes.

As the authors compiled the data for Tables 1-2, 1 article was re- moved from the study because it looked at registry data from the San Antonio Fire Department (SAFD) OHCA quality assurance/quality im- provement (QA/QI) database between January 2013 and December 2015 [29]. One of the included studies had previously looked on this data registry during the same time period to describe their experience with DSD, but its primary outcome measure was different [25]. The discarded article was approved by the authors before the analysis was completed. This study is included in Tables 1-2 as a quick reference but was not included in our qualitative analysis. Following data extrac- tion, a narrative synthesis was undertaken to describe the articles in- cluded in terms of the type of study, the intervention delivered to the participants, as well as the outcomes in the study. We focused on 2 key themes based on the research question of the scoping review, which were: survival rates and neurological outcomes [34].

Consultation

It is suggested that a scoping review should include the consultation of experts in the area of research [35]. Consultation was not included in this study due the approach being relatively new in the pre-hospital management of cardiac arrest.

Results

Study populations and settings

Our initial database search identified 1612 records. We first removed 598 duplicates and then eliminated 996 papers following inspection of the titles and abstracts. We read the full text of each of the remaining 18 articles. This selection procedure resulted in 4 primary research stud- ies relating to the research purpose (Tables 1-2) [25-28]. No random- ized clinical trials were identified, although two are ongoing in Canada as noted on ClinicalTrials.gov. Identifier (NCT number): NCT03249948 and NCT04080986. All articles were published between 2016 and 2019. One study was performed in United Kingdom [26], 1 was per- formed in Canada [28], and 2 were performed in US [25,27]. Considering demographics, all articles identified patients as having refractory VF/ pVT OHCA at some point during the cardiac arrest. The sample sizes of the patients that received DSD ranged from 45 to 71, the percentage of males ranged from 76.0% to 93.2%, and the mean age of the patients

Records identified through database and manual searching (n = 1612)

Records after duplicates removed

(n = 1014)

Records excluded (n = 996)

Titles/abstracts screened (n = 1014)

Full-test articles excluded with reasons

(n = 14)

Full-text articles assessed for eligibility

(n = 18)

Fig. 1. PRISMA flow-chart illustrating the study Selection process on DSD for refractory VF/pVT OHCA.

Studies included in scoping review

(n = 4)

Included

ranged from 59 to 62 years. About half of the cardiac arrests were witnessed, received bystander cardiopulmonary resuscitation (CPR), and the majority were attended by EMS providers.

Focus and outcomes

There were dramatically heterogeneous study characteristics within the field of pre-hospital DSD. This expressed itself in both in patient pop- ulation and DSD procedure. There was also substantial heterogeneity of outcome measurement across studies. A standard protocol for the use of

DSD was not uniform across studies. In all studies patients remained re- fractory to at least 3 SD shocks before they received DSD. All studies compared the use of DSD to SD for refractory VF OHCA in adult patients (>=18 years old). One study explored the relationship between the type of defibrillation (SD vs. DSD), the number of defibrillation attempts pro- vided and the outcomes of VF termination and ROSC for patients pre- senting in refractory VF [28]. Two studies focused on the association of DSD with survival after refractory VF [26,27]. The other evaluated if pre-hospital DSD was associated with favorable neurological outcome at discharge [25]. All studies reported ROSC, 3 studies reported survival

Table 1

Characteristics of patients in refractory VF arrest before receiving DSD

Author, year Study design Setting Country

Patients,n

Received DSD, n

Age,y

Male,n (%)

witnessed arrest, n (%)

Bystander CPR, n (%)

Time to CPRa

VF patients, n (%)b

SD shocks

Ross et al. 2016 RCS OHCA

279

50

59.4

38 (76.0)

19 (38.0)

15 (30.0)

Emmerson et al. 2017 RO OHCA

220

45

59.8

42 (93.2)

23 (51.1)

32 (71.1)

39 (86.7) c

10.2

Cheskes et al. 2019 RO OHCA

252

51

61.8

43 (84.3)

34/50 (68.0)

25/50 (50.0)

Mapp et al. 2019 Matched

USA case-control OHCA

128

25

58.3

20 (88.0)

15 (60.0)

8 (32.0)

4.5 (4-6.75)d

Beck et al. 2019 RO OHCA

310

71

62.2

61 (84.5)

56 (78.8)

38 (53.5)

64 (94.1)c

4.5

USA [25]

UK [26]

Canada [28]

[29]

USA [27]

CPR = cardiopulmonary resuscitation; DSD = double sequential defibrillation; ellipses (…) = data not available; M = male; OHCA = out-of-hospital cardiac arrest; RCS = retrospective cohort study; RO = retrospective observational; SD = standard defibrillation; VF = ventricular fibrillation.

Notes: The studies by Ross et al. and Mapp et al. included the same patient population, but reported different outcomes. Notes: Total percentages are referred to studies with available data.

All continuous variables are reported as mean unless specified otherwise.

a Time to CPR is reported in minutes.

b Refer to initial rhythm.

c Refer to shockable (VF/pVT).

d Reported as median (IQR). Data only available for 2014 and 2015.

Table 2

Characteristics of DSD in refractory VF arrest and subsequent outcomes

Author, year DSD pads placement Country

DSD shocks

Time to DSDa

Joules

VF terminated, n (%)

ROSC, n (%)

resuscitation timea

Survivalb, n (%)

CPC <= 2c, n (%)

Ross et al. 2016 AP or AL

400

16 (32.0)

4 (8.0)

3 (6.0)

Emmerson et al. 2017 AP or AL

2.5

720

17 (37.8)

3 (6.7)

Cheskes et al. 2019 AP

2.2

400

39 (76.5)

9 (17.5)

Mapp et al. 2019 AP or AL

400

5 (20.0)

4 (16.0)

3 (12.0)

Beck et al. 2019 AP or AL

2.2

720

28 (39.4)

10 (14.3)

USA [25]

UK [26]

Canada [28]

USA [29]

USA [27]

AL = anterior-lateral; AP = anterior-posterior; CPC = cerebral performance category; DSD = double sequential defibrillation; ellipses (…) = data not available; ROSC = return of spon- taneous circulation; VF = ventricular fibrillation.

Notes: Total percentages are referred to studies with available data.

a Time to DSD shocks and resuscitation are reported in minutes.

b Refers to survival to hospital discharge.

c Refers to CPC at the time of discharge.

to hospital discharge [25-27], 1 study reported survival to hospital ad- mission, but not to discharge [28], and 1 study reported favorable neuro- logical outcome at discharge [25]. No study reported 30-day survival, long-term survival (6-12 months) or long-term Favorable neurological outcomes. Table 3 outlines details about the primary outcome and re- sults of the observational studies in pre-hospital DSD.

The first pre-hospital observational study in DSD was published by Ross et al. in 2016. The primary outcome of the study was Neurologically intact survival to hospital discharge; no statistically significant differ- ence (p = .317) was found between SD group (11.4%) and DSD group (6.0%) (OR 0.50, 95% CI 0.15-1.72). There were no statistically signifi- cant in the secondary outcomes of ROSC by EMS, survival to hospital ad- mission, and survival to hospital discharge [25]. The following year an observational cohort study was published by Emmerson et al. The main outcomes of interest included pre-hospital ROSC, sustained ROSC to hospital, and survival to hospital discharge. In the DSD group 17 of 45 patients (37.8%) achieved pre-hospital ROSC, and 10 (58.8%) of these sustained ROSC to hospital admission. Three of 43 patients sur- vived to hospital discharge, representing a 7% overall survival rate and a 30% survival rate among those who sustained ROSC to hospital. No sig- nificant difference in ROSC and survival rates were found between the two groups; Ultimately, the study did not find any clear benefit of DSD use in the treatment of refractory VF. This study did not report favorable neurological outcome [26].

Recently 2 observational studies on DSD for VF/pVT OHCA were pub- lished. Beck et al. evaluated ROSC, Survival to hospital admission, sur- vival to 72 h, and survival to hospital discharge. This study found that ROSC was lower for DSD group vs. SD group (39.4% vs. 60.3%, adjusted OR 0.46, 95% CI 0.25-0.87) and no significant difference in survival to discharge was found between DSD group and SD group (14.3% vs 20.9%, adjusted OR 0.63, 95% CI 0.27-1.45). This study did not report fa- vorable neurological outcome [27]. Lastly, Caheskes et al. found that in overall VF termination into ROSC were similar among DSD group and SD group (17.6% vs. 21.4%, RR 0.8, 95% CI 0.4-1.6). The most significant finding of this study was associated with improved rates of VF termina- tion for those receiving DSD vs. SD (29.4% vs. 17.5%, RR 1.7, 95% CI 1.1-2.6) and ROSC (15.7% vs. 5.4%, RR 2.9, 95% CI 1.4-5.9) when early

defibrillation attempts were considered (defibrillation attempt 4-8). This study did not report on survival and favorable neurological out- come to hospital discharge [28].

Discussion

Even though Resuscitative medicine has advanced significantly in re- cent decades, there has been no significant improvement in the likelihood of survival to hospital discharge, long-term survival (6-12 months) and favorable neurological outcomes in cardiac arrest patients. In 2016, the

overall estimated survival to hospital discharge in the United States (US) in the ROC Epistry database after EMS-treated cardiac arrest was 11.4%, survival after VF was 30.0%, and when bystander-witnessed VF was 37.4% for patients of any age [1]. The low survival rate and poor func- tional outcomes have been shown to be significantly associated with older age, the degree of comorbid illness, ischemic burden, acute throm- botic events imposed during resuscitation, and delay in initiation of CPR and administration of defibrillation for shockable arrhythmias [6,36,37].

Our scoping review revealed that the majority of studies that have

been conducted on pre-hospital DSD have evaluated ROSC, survival to hospital admission, survival to discharge, and 1 study has evaluated neurological outcome at discharge, but no study has reported 30-day survival or long-term survival (6-12 months), neither short-term favor- able neurological outcomes nor long-term favorable neurological outcomes. Similarly, there were variations in the amount of energy de- livered and differences in protocols for when DSD was used for refrac- tory VF/pVT amount studies. In addition, all studies except one failed to report the time from collapse to DSD. Overall, DSD was applied as late as the 6 shocks as it was often used only after failed SD attempts. In the current literature, a major limitation discovered is the paucity of research and lack of literature to support this therapy. We identified these as the main important gaps in the available literature. Further- more, our review revealed that all studies included were observational in nature and were conducted in small cohorts of patients. Despite these limitations, the findings from this review highlight an area of re- search that may contribute to improve survival for people in refractory VF/pVT OHCA, but this would need to be investigated in a more robust manner.

Double defibrillation is the use of two defibrillators at their highest allowed energy setting to treat refractory VF. One set of pads is placed anterolateral-position and the second set of pads can be either placed ad- jacent to the first set or in the antero-posterior position. Shocks are then delivered simultaneously or near simultaneously. Double defibrillation can either be sequential or simultaneous, depending on the duration of the defibrillation potential and the intershock interval between the two defibrillator shocks [13,18]. Currently, there is no clinical evidence sug- gesting sequential or simultaneous is more effective. However, double external defibrillation can terminate ventricular tachyarrhythythmias and has been successful in terminating refractory VF during routine elec- trophysiology studies [9].

The first mention of this technique was from electrophysiology teams at Yale-New Haven Hospital and St. Francis Hospital [9]. The teams theorized that the double sequential shocks lead to more effec- tive energy delivery to overcome the increasing defibrillatory threshold or possibly decrease transthoracic impedance. In theory, the application of DSD would lead to the delivery of more energy to overcome the in- creasing defibrillatory threshold [38,39]. Nevertheless, the problem

Table 3

Outlines details about the primary outcome and results of the observational studies in pre-hospital DSD for refractory VF

Author, year Country

Patients population Primary outcome Results

Ross et al. 2016 USA [25]

Emmerson et al. 2017

London [26]

Cheskes et al. 2019 Canada [28]

Mapp et al. 2019 USA [29]

Beck et al. 2019 USA [27]

This was a retrospective cohort study that included 279 OHCA adult patients (>=18 years old). Fifty patients were treated with DSD (intervention) between January 2013 and December 2015 and were compared to 229 patients who received only SD. Patients were considered for DSD following 3 unsuccessful conventional defibrillation attempts. DSD was delivered with 2 sequential 200 J shocks in the AP and anterior pad positions.

This was a retrospective study that included 220 OHCA adult patients (>=18 years old). Forty-five were treated with DSD (intervention) between July 2015 and December 2016 and were compared to 175 patients who received only SD. Patients were considered for DSD if they remained in VF following a minimum of 5 consecutive SD attempts and 2 doses of IV amiodarone (300 mg and 150 mg).

Before being treated with DSD, 33 patients received N6 standard shocks, 7 patients had b6 standard shocks, and 5 received exactly 6 standard shocks. After receiving DSD, 11 patients (24%) were given further SD attempts (ranging from 1 to 9 shocks). This was a retrospective study of prospectively collected data that included 252 OHCA adult patients (>=18 years old). Fifty-one patients were treated with DSD (intervention) over a three-year period beginning on January 1, 2015 and were compared to 201 patients who received only SD. Patients were considered for DSD if they presented in VF and received at least a minimum of 3 conventional defibrillations. DSD shocks were provided in a rapid sequential manner (single paramedic pressing the shock button on the original defibrillator followed by pressing the shock button of the second defibrillator).

This was a matched case-control study between January 2013 and December 2015 that included 128 OHCA adult patients (>=18 years old).

Sixty-four patients who survived to hospital admission were matched with sixty-four controls that did not. Twelve of 64 patient that survived to hospital admission received DSD and 13 of 64 patients that did not survive to hospital admission received DSD. The stablished protocol directed the lead paramedic to consider DSD after administering three 200 J conventional defibrillations. AL pad placement combined with AP pad placement were used for DSD.

This was a retrospective study that included 310 out of hospital cardiac arrest adult patients

(>=18 years old). Seventy-one patients were treated with DSD (intervention) between January 2013 and December 2016 and were compared to 239 patients who received only SD. Patients were considered for DSD if they were in VF refractory to 3 or more defibrillation attempts. Typical pad placement was AL and AP. There were no limits to the number of applied DSD shocks.

This study evaluated if pre-hospital dual defibrillation (DD) is associated with better neurologically intact survival in out-of-hospital cardiac arrest.

This study described the survival outcomes of OHCA patients treated by ambulance clinicians using a local DSD protocol in an attempt to resolve refractory VF.

This study explored the relationship between type of defibrillation (standard vs DSD), the number of defibrillation attempts provided and the outcomes of VF termination and ROSC for patients presenting in refractory VF.

This study evaluated whether pre-hospital DSD is associated with improved survival to hospital admission in the setting of refractory VF/pVT.

This study evaluated the association of DSD with survival after Refractory VF/VT OHCA.

There was no statistically significant difference in the primary outcome of neurologically intact survival between the DSD group (6.0%) and the standard defibrillation group (11.4%) (p = .317) (OR 0.50,

95% CI 0.15-1.72).

Forty-five patients were treated with DSD. A third (37.8%) obtained a pre-hospital ROSC. Three of 43 patients survived to be discharged from hospital, representing a 7% overall survival rate and a 30% survival rate among those who sustained ROSC to hospital. They observed similar ROSC and survival rates among those who received standard defibrillation only.

VF termination was similar between DSD and SD (76.5% vs. 78.1%, RR 1.0, 95% CI: 0.8-1.2). In the

shock-based analysis, when Early defibrillation attempts were considered (defibrillation attempt 4-8), VF termination was higher for those receiving

DSD compared to SD (29.4% vs. 17.5%, RR 1.7, 95% CI

1.1-2.6). VF termination to ROSC was similar between DSD and SD (17.6% vs. 21.4%, RR 0.8, 95% CI

0.4-1.6). When early defibrillation attempts were considered (defibrillation attempt 4-8), ROSC was higher for those receiving DSD compared to SD (15.7% vs. 5.4%, RR 2.9, 95% CI 1.4-5.9). When late

defibrillation attempts were considered (defibrillation attempt 9-17), VF termination was higher for those receiving DSD compared to SD (31.2% vs. 17.1%, RR 1.8, 95% CI 1.1-3.0), but ROSC

was rare regardless of defibrillation strategy. Survival to hospital admission occurred in 48.0% of DSD patients and 50.5% of the conventional therapy patients (p N .99, OR 0.91, 95% CI 0.40-2.1).

Pre-hospital ROSC occurred in 20.0% of the DSD patients and 40.8% of the conventional therapy patients (p = .07, OR 0.36, 95% CI 0.14-1.06).

Survival to hospital discharge occurred in 16.0% of the DSD patients vs. 23.3% of the conventional therapy patients (p = .59, OR 0.63, 95% CI 0.22-1.9). Neurologically intact survival to hospital discharge occurred in 12.0% of the DSD patients vs. 19.4% of the conventional therapy patients (p = .56, OR 0.57, 95% CI 0.17-2.1).

ROSC was lower for DSD than standard defibrillation: (39.4% vs. 60.3%, adjusted OR 0.46, 95% CI 0.25-0.87). There were no differences in survival to hospital admission (35.2% vs. 49.2%, adjusted OR: 0.57, 95% CI 0.30-1.08), survival to 72h (21.4% vs. 32.3%, adjusted OR 0.52, 95% CI

0.26-1.10), or survival to hospital discharge (14.3% vs. 20.9%, adjusted OR 0.63, 95% CI 0.27-1.45).

AL = anterior-lateral; AP = anterior-posterior; DD = dual defibrillation; DSD = double sequential defibrillation; OHCA = out-of-hospital cardiac arrest; ROSC = return of spontaneous circulation; SD = standard defibrillation; VF = ventricular fibrillation; VT = ventricular tachycardia.

Notes: All authors have suggested there may be a role of DSD for refractory VF although the timing of delivery, level of energy, and best pad position have not been elucidated.

may not be an energy problem. The exact mechanism of how DSD result in successful defibrillation in patients with refractory VF remains un- known. However, there are a few hypothesized theories why this method of defibrillation may be more successful.

First, higher energy is delivery to overcome the increasing defibrillatory threshold. Consequently, it improves success on subsequent

defibrillation [13,38,39]. One of the most common concerns in using DSD is the potential injury from more energy and the damage of the defibrilla- tors, although unusual, it is possible, even though several studies have shown safety in patients receiving 200 J and 360 J biphasic energy from each defibrillator for conversion of refractory VF [9-29]. Second, it is sug- gested that the first shock lowers the defibrillation threshold, thus

increasing the second shock’s success. It is also suggested that alternate vectors of defibrillation provided by the second set of pads may be a factor in vector change success [9,40]. Lastly, it is very unlikely that the shocks are delivered at the same time. Rather, this near-simultaneous defibrilla- tion may be creatinga longer duration of defibrillation exposure that re- sults in successful defibrillation. Nonetheless, there is minimal scientific explanation and data supporting the most effective method for pad place- ment and energy level selection [9].

No clinical association can be inferred between the use of DSD for VF/ pVT OHCA and our scoping review. However, the individual results of the studies included in our scoping review can certainly be interpreted in the context of the limitations described in the discussion section of each article. Our aim was to simply present the differences in studies characteristics, and what is known from the literature about DSD for re- fractory VF/pVT OHCA as well as to identify gaps in the literature that may require further research. Conclusions about DSD for VF/pVT OHCA cannot be made due to the nature of this scoping review. Furthermore, the methods and results of these studies could lend themselves to a sys- tematic review and meta-analysis although heterogeneity may be a sig- nificant issue; thus, more rigorous outcome measures are needed to determine the real benefit of DSD for VF/pVT OHCA.

Study limitations

The primary limitation of the scoping review methodology is the lack of quality assessment of the included articles. However, the goal of a scoping review is simply to identify research that has been con- ducted, not necessarily to assess quality [35]. This scoping review has some limitations. First, all included studies were observational in na- ture. All the studies listed two or three limitations in the discussion sec- tion of the article, so the overall quality of evidence for the predictors we identified was low. Second, our review was based on the analysis of ob- servational studies thus making it impossible to exclude the possibility of potential bias. Third, results from some studies were inconsistent and no reported outcomes such as, survival to discharge, and favorable neurological outcome. In addition, all studies except one failed to report the time from collapse to DSD. Finally, there were variations in the pro- tocol, and treatment of the patients amount studies. In terms of method- ology, this review was limited to three databases and articles published in English. These criteria may have biased the results and limited the substantial evidence.

Conclusion

Our scoping review mapped the observational studies published in the literature on DSD for refractory VF/pVT OHCA. The findings of this scoping review suggest there is a lack of literature and limited evidence to support at large-scale the use of DSD for refractory VF/pVT OHCA. Further research is needed to better characterize and understand the use of DSD for refractory VF/pVT, in order to implement best practices to maximize the effectiveness and efficiency of care. These trends of in- conclusive evidence on DSD will be evaluated by 2 randomized control trials (RCTs). The DOSE VF pilot study and the DOSEVF study. The DOSEVF trial will address continued resuscitation using SD, resuscita- tion involving DSD, and resuscitation involving vector change defibrilla- tion, in patients presenting with refractory VF during OHCA, but results will be not available until 2022. Up-to-date data will be available on completion of ongoing randomized trials.

Perspective

We plan to conduct a systematic review and meta-analysis in a sec- ond research to evaluate the efficacy of DSD for patients with refractory VF/pVT OHCA.

Declaration of competing interest

None of the authors have conflicts of interest to disclose.

Acknowledgments

The authors would like to thank the library staff from the Veterans Affairs Caribbean Healthcare System Library Service for assistance with producing the search strategy.

Author contributions

All authors conceived the study design. DM and LM performed the initial database search. Duplicates were removed by DM. Titles and ab- stracts were appraised for eligibility by two authors (DM and LM). DM, LM and JA completed the review and analysis. All authors contributed to the manuscript. All authors read and approved the final manuscript. DM takes responsibility for the paper as a whole.

Funding

This project did not receive any funding support.

Availability of data and materials

All data generated or analyzed during this study are included in this paper.

Consent for publication

Not applicable.

Ethics approval and consent to participate

This study uses only data that have already been published and does not need any ethical approval.

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