Article, Cardiology

Changing the management of refractory ventricular fibrillation: The consideration of earlier utilization of dual sequential defibrillation

a b s t r a c t

Dual sequential defibrillation has shown promise in the management of refractory ventricular fibrillation (RVF). In the recent past, there have been a number of reports on the topic with varying results. Some studies have concluded that DSD provides no benefit over standard defibrillation therapy of RVF in terms of survival and neurological outcome. In fact, termination of RVF and achieving return of spontaneous circulation (ROSC) are achieved quite frequently in patients with DSD. Unfortunately, DSD has been utilized very late in the course of resuscitation, likely masking a great deal of its potential benefit. Interventions at this later phase of resuscita- tion are much less likely to produce a beneficial outcome, regardless of their ability to impact the course of events. It is suggested that earlier use of DSD can potentially improve ROSC, ultimate survival, and neurological outcome. After a review of the existing literature on the topic, we will propose that DSD be considered for use at a much earlier time in the resuscitation of patients with RVF. In addition to the consideration of its use in resuscitation, clinicians and device manufacturers must also address the impact on the two defibrillation devices employed in DSD due to the potential for damage and resultant defibrillator dysfunction.

(C) 2019

Introduction

Ventricular fibrillation (VF) is a common presenting initial rhythm of sudden cardiac death and out-of-hospital cardiac arrest (OHCA) [1,2]. The management of VF arrest is well established within the advanced cardiovascular life support (ACLS) guidelines, with an emphasis on Early defibrillation and high quality cardiopulmonary resuscitation (CPR) [3]. When considering the severity of the condition, the manage- ment of VF arrest can be effective, with a survival rate between 20 and 30% [4]. In contrast, refractory ventricular fibrillation (RVF) is uncom- mon, the treatment is not well-established, and the mortality rate is very high, approaching 97% [1]. In fact, the definition of RVF is not well-established, but the most recent guidelines have defined it as per- sistent VF despite three standard defibrillation attempts and anti- arrhythmic administration [1].

Dual sequential defibrillation (DSD) involves the simultaneous use of two separate defibrillator devices. In this defibrillation strategy, both defibrillators are activated and connected to the patient using sep- arate defibrillation pads. When ready for actual electrical defibrillation, both devices are activated simultaneously by simply depressing the

* Corresponding author.

E-mail address: [email protected] (M. Sochor).

“shock” button at the same time. Fig. 1 demonstrates DSD used success- fully in an 18 year-old male patient with RVF; this DSD was delivered with 400 joules using two Philips MRX devices after more than 30 min of resuscitation and 11 standard defibrillatory shocks. The patient expe- rienced ROSC after this single DSD and was discharged from the hospital 4 days later with intact neurologic function.

DSD has been established for decades, but in the past five years there has been a growing body of literature regarding DSD as it pertains to OHCA and RVF management. We will review the current DSD literature, address some negative conclusions that have been made, and propose a change to the current RVF Management strategy.

Discussion

Over the past five years, there have been at least ten published case reports regarding the use of DSD in RVF [5-14]. Case after case of ex- traordinarily unlikely survival, the repeated failure of Standard therapy, and in some instances a remarkable recovery with baseline neurological function. With such compelling reports, the recent increase in scrutiny and published accounts regarding DSD is not surprising. In 2018 alone, we have seen four separately published literature reviews on the topic, interestingly providing very different conclusions [4,14-16].

https://doi.org/10.1016/j.ajem.2019.05.048

0735-6757/(C) 2019

546 M. Bero et al. / American Journal of Emergency Medicine 38 (2020) 545548

Fig. 1. Dual Sequential Defibrillation: Two simultaneous cardiac rhythm strips produced by 2 independent Philips MRX devices. Ventricular fibrillation is seen and terminated by DSD involving a total of 400 joules. Successful resuscitation of an 18 year-old male with witnessed ventricular fibrillation cardiac arrest. He received bystander care prior to EMS arrival. After 11 standard defibrillations over 36 min of resuscitation (high quality chest compressions, endotracheal intubation, intravenous epinephrine and amiodarone), the patient underwent DSD with a cumulative total of 400 joules via two Philips MRX devices. induced hypothermia was not applied. He was discharged on hospital day four with normal neurologic function. After a thorough cardiac evaluation, the etiology of his arrest was felt to be toxicologic, related to significant cocaine use the evening of the event.

Dual sequential defibrillation is not a new concept; animal studies on the topic were underway as early as the 1940s, with evidence to sug- gest that sequential shocks lowered the defibrillation threshold [4,17]. Clinical use of external electrical cardioversion was not recommended until the 1960s [18,19]. In the 1990s and 2000s, we began to see case re- ports demonstrating the success of dual sequential cardioversion in the setting of Refractory atrial fibrillation [19,20]. In 1994, Hoch et al. pub- lished some of the first literature regarding the use of dual sequential defibrillation in the setting of refractory ventricular fibrillation, demon- strating great success of the technique in the electrophysiology lab [21]. And now, in recent years, we have seen many reports on the topic of DSD in the setting of OHCA and RVF.

There are three main theorized mechanisms of DSD that attempt to explain its benefit over standard defibrillation. Firstly, with DSD there is a higher amount of energy delivered to the myocardium, and higher en- ergy administration has demonstrated higher rates of conversion from VF [22]. Secondly, DSD provides multiple delivered vectors of energy, with studies demonstrating a higher VF conversion rate compared to single shocks delivering the same amount of energy [23]. Thirdly, the timing of the sequential defibrillations, specifically the minimally asyn- chronous nature of the shocks delivered, is also theorized to help in- crease the success rate of VF conversion by increasing the duration of the defibrillating current flowing through the myocardium [6,10,24]. It is possible that all three of these mechanisms contribute during an at- tempt at DSD.

Despite these well-studied mechanisms demonstrating a theoretical benefit to DSD, the available literature on DSD and its utility in the set-

unlikely to be effective. According to a recent review of RVF manage- ment, it is estimated that for each two-minute round of CPR, the proba- bility of a successful defibrillation decreases by 14% [1]. Thus, the conclusion made by Emerson et al. is predictable and likely misleading; they found no difference in the rate of achieving ROSC because, after 10 defibrillation attempts, there is likely no difference to be had.

The study by Emerson et al. is by no means the only example of DSD

being used late in an arrest. Table 1 demonstrates the consistent later use of DSD throughout the available literature. The articles are listed by publication date and it is clear that despite the benefit of time and, theoretically an increased awareness of the technique, DSD is still being attempted very late in the course of an arrest. While there are re- ported cases of success using DSD late in an arrest, there is evidence sug- gesting that earlier use of DSD leads to better outcomes [14]. Hajjar et al. produced a case report as well as a review on the topic. When pooling data from twelve different case reports and series, they determined that DSD terminated RVF 76.9% of the time and obtained ROSC in 53.9% of cases [14,26-28]. These numbers are all the more impressive when considering the consistent late use of DSD in the calculated data, with an average of 6 single shocks and 31.4 min of arrest time prior to DSD attempt. Hajjar et al. also provided data comparing DSD cases with favorable versus unfavorable neurological outcomes, determining that patients with survival and good neurological outcome had a

Table 1 Summary of DSD application from selected literature: time to performance and number of preceding standard defibrillations.

ting of RVF has produced varying conclusions regarding its clinical effi- cacy. The mixed results and the many negative conclusions regarding

Article (date published)

Number of standard shocks before DSD attempt

Arrest time prior to DSD attempts (minutes)

DSD can be explained by one major problem with the current body of

literature: DSD is being attempted very late in the course of RVF and car- diac arrest. There are a number of reasons to explain why this occurs. Though the awareness of DSD as a management option is growing, it is likely still lacking. Additionally, there are no standard guidelines to aid in the management of RVF, nor is there a standardized definition of RVF. Regardless of the reason for its late use in arrest, this “delayed application” is likely masking a large degree of its potential benefit. For example, Emerson et al. retrospectively reviewed OHCA cases in London, specifically patients who received DSD by the London ambu- lance service from July 2015 to December 2016. They concluded that DSD did not improve the rate of achieving ROSC compared to standard management of RVF [25]. Patients in the Emerson study, however, re- ceived an average of 10 standard defibrillations before DSD was attempted. Any defibrillation attempt this late in an arrest is extremely

Leacock (April 2014) 5 25

Cabanas (March 2015) 8.1 (mean) 36.8 (mean)

Gerstein (April 2015) 15 72

Lybeck (May 2015) 7 38

Ross (June 2016) Not reported Not reported

Merlin (August 2016) 5.4 (mean) 34.3 (mean)

Cortez (August 2016) 5 (mean) 27.5 (mean)

Sena (September 2016) 4 Not reported

Johnston (October 2016) 6 23

Boehm (November 2016) 5 15

Emmerson (August 2017) 10 (mean) Not reported

El Tawil (December 2017) 7 Not reported

Hajjar (August 2018) 8 22

Bell (September 2018) 4 17

Zabel (November 2018) 5 26

Mapp (December 2018) Data incomplete Not reported Beck (February 2019) 4.5 Not reported

M. Bero et al. / American Journal of Emergency Medicine 38 (2020) 545548 547

significantly shorter time prior to DSD attempt during their arrests (mean of 24.0 min vs. 34.3 min). A recent Letter to the editor by Clem- ency et al. reminds us that the pooling of data from case reports and case series can lead to overly optimistic conclusions [16], but still this data is potentially promising.

Contradictory to this evidence, some studies have concluded that DSD provides no benefit over standard management in the setting of RVF. This is true of Ross et al. who reviewed 3470 cases of OHCA man- aged by the San Antonio Fire Department between January 2013 and December 2015. When reviewing cases of RVF, defined in their study as receiving DSD or at least 4 standard defibrillations, they found no benefit to DSD over standard therapy. Specifically, they found no differ- ence in survival or favorable neurological outcome between the two groups [29]. It is well established, however, that these outcomes are heavily dependent on other factors, such as witnessed arrest and by- stander CPR [30,31]. More recent review of the literature has pointed out a selection bias within the data used by Ross et al., showing that the DSD group had significantly fewer witnessed arrest and less by- stander CPR [4]. Quality of CPR and the limiting of chest compression in- terruption are also important variables that cannot be easily measured or quantified; these factors are likely to contribute more to survival and neurological outcome as the length of an arrest increases. Unfortu- nately, Ross et al. failed to report an average number of standard defi- brillations prior to DSD attempt nor did they note arrest time prior to DSD attempt, making it difficult to make meaningful conclusions. De- spite these shortcomings, the data and conclusions provided by Ross et al. were heavily cited in a recent literature review by Simon et al., again concluding that DSD has not demonstrated benefit over standard therapy with regard to survival and neurological outcome [15]. These conclusions, based on data with confounding factors and missing key el- ements, have likely contributed to the lack acceptance of DSD as a man- agement option in the setting of RVF.

Similar studies with late use of DSD continue to provide us with neg- ative conclusions regarding this topic. Mapp et al. recently produced a matched case-control study on the topic [32]. Unfortunately, much like the article by Ross et al. previously mentioned, this study concludes that DSD provides no benefit over standard therapy despite a very sim- ilar limitations, including selection bias and absence of key elements needed to make a fair conclusion. Continuing into 2019, Beck et al. has provided yet another retrospective study concluding that DSD provides no benefit over standard therapy [33]. Once again this conclusion is made while lacking key elements in the data, impacted by selection bias, and disadvantaged by late use of DSD.

This much we know – successful defibrillation becomes less and less likely as the duration of arrest increases. When considering the litera- ture we have available and the consistently later use of DSD in the set- ting of RVF, we feel it is difficult to demonstrate Survival benefit or improvement in neurological outcome provided by DSD alone. Despite its later use, we do have data demonstrating the ability of DSD to termi- nate RVF and obtain ROSC. Furthermore, we have evidence to suggest that earlier use of DSD may improve survival and favorable neurological outcome. There is no denying that publication bias is likely a significant contributor to this favorable data regarding DSD. The totality of the data we have available to us is poor, providing minimal guidance on RVF management. Esmolol has been suggested as a way to combat the neg- ative effects of excessive catacholamines in a prolonged VF arrest, but this topic is also lacking in supporting evidence [34]. ECMO is an impor- tant consideration and has shown some promise in the setting of RVF, though in a very specific patient population [35,36]. ECMO is obviously an extremely invasive management pathway that carries considerable risks and complications [37,38]. When considering the lack of other op- tions and the very high mortality rate of RVF, it seems only reasonable to attempt any non-invasive management options, such as dual sequential defibrillation.

Therefore, we propose consideration of a change in defibrillation

strategy for RVF as follows:

  • ventricular fibrillation unresponsive to two standard defibrillation at- tempts should be considered RVF

o third and subsequent defibrillation attempts for RVF should use DSD

  • If a second defibrillator is not immediately available after two unsuc- cessful single shock attempts, pad placement should be changed to at- tempt an alternate vector as noted in Fig. 2

o the delivered energy should be appropriately increased

o once a second defibrillator is available, DSD can be considered

There are a number of obstacles to consider regarding this proposed change to the management of VF arrest. First and foremost, any poten- tial negative effects or Safety concerns should be addressed. In general, there have been very few reported instances of harm regarding DSD. Myocardial injury or dysfunction related to the increased amount of de- livered energy would be a reasonable concern, but studies have demon- strated that there is no increased damage with increased energy [22]. One important study to consider is Gerstein et al., who reported a case

Fig. 2. Depiction of DSD Pad Placement: A. Base-Apex. B. Anterior-Posterior. C. Combined Base-Apex and Anterior-Posterior.

548 M. Bero et al. / American Journal of Emergency Medicine 38 (2020) 545548

of DSD in which one of the defibrillator devices was later found to be non-functional [39]. It was concluded that the DSD attempt caused an electrical shortage within the device and manufacturer repairs were needed. The manufacturer made it clear that these devices are not de- signed for DSD, and such off-label use and subsequent damage or repair would not be covered by warranty. Apart from hospital cost concerns, this case report also uncovers an issue of patient safety when consider- ing the possible harm that may occur to a patient in need of defibrilla- tion from a non-functional device. Another important issue to consider regarding DSD is the availability of a second defibrillator early in an arrest. While our proposal for early use of DSD in the setting of RVF seems manageable in a hospital setting with ample equipment, it is more challenging in cases of out-of-hospital cardiac arrest (OHCA). Clearly these issues of safety standards and equipment availability will need to be addressed prior to considering earlier use of DSD.

Conclusion

In conclusion, we suggest consideration of a potential change to the management of RVF with an emphasis on the early use of dual sequen- tial defibrillation, ideally utilizing DSD as the third defibrillation at- tempt. The available literature has consistently used DSD very late in the course of an arrest, likely masking its true effect. Despite this later use, we have evidence demonstrating the ability of DSD to terminate RVF and obtain ROSC, and the data suggests that its early use may lead to better outcomes. Patient safety and device integrity issues, however, must be addressed prior to widespread implementation of this strategy. Study of DSD used earlier in arrest is needed to more clearly explore its impact…and to provide information to make informed decisions re- garding cardiac arrest defibrillation management.

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