a b s t r a c t

Background: In the United States, over 350,000 cardiac arrests occur outside of the hospital and 209,000 occur in the hospital. Shockable rhythms such as ventricular fibrillation (VF) have a survival rate of 20-30% outside of the hospital setting. Dual Sequential Defibrillation has demonstrated success in terminating VF that is refrac- tory to multiple attempts using a single defibrillator.

Methods: The PubMed, and MEDLINE databases were reviewed in February of 2018 and literature reviewed on dual sequential defibrillation. The terms “dual”, “sequential”, “double sequential”, and “defibrillation” were added in the search builder. This search was limited to English-language articles. The results and their references were assessed for relevance to the topic and implications for dual sequential defibrillation in shockable cardiac arrest.

Result: Included search terms yielded 23 articles. Studies occurred in the emergency department and prehospital setting. There are two retrospective cohort studies and the majority of published studies are case reports/series. Sample size per study varied from 1 to 279 encounters.

Conclusion: Studies have shown success in using DSD to treat refractory VF. However, further studies are neces- sary to assess the efficacy and safety of DSD compared to the standard of care treating refractory VF.

(C) 2018

Introduction

Annually, over 350,000 cardiac arrests occur outside of the hospital and 209,000 occur in the hospital with a survival rate of 10% and 20%, respectively [1]. Survival rates vary by the type of abnormal rhythm causing the cardiac arrest. Shockable rhythms such as ventricular fibril- lation (VF) and pulseless Ventricular tachycardia have a survival rate of 21.4-29.3% outside of the hospital setting [2]. Current treatments guidelines are provided by the American Heart Association include basic life support (BLS) and Advanced cardiovascular life support [1]. Increase in survival is associated with witnessed cardiac arrest, by- stander cardiopulmonary resuscitation (CPR), Early defibrillation and return of spontaneous circulation (ROSC) [3]. The role of external defi- brillation is delivery of an electrical current to depolarize cardiac muscle cells, disrupt chaotic rhythms and re-establish sinus rhythm.

Refractory VF/VT occurs when there is persistent VF/VT despite defi- brillation attempts. Patients with refractory VF/VT have higher mortal- ity and Poor neurologic outcomes [4]. Often these rhythms may be resistant to standard American Heart Association ACLS guidelines and therefore newer techniques are being developed to treat this issue. In addition to defibrillations, current standard treatment for VF/VT

* Corresponding author at: Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, 2120 L St., Washington, DC 20037, United States.

E-mail address: [email protected] (A. Pourmand).

includes antiarrhythmic drugs such as lidocaine and amiodarone [5]. A recent study of esmolol showed some success in terminating refractory VF/VT and increasing ROSC compared to Standard therapy [6].

The practice of dual sequential defibrillation (DSD) has demon- strated promise in terminating VF refractory to multiple single device defibrillations and antiarrhythmic medications. This practice has a growing body of literature suggesting DSD has a role in acute emer- gency situation. This literature review provides an overview and discus- sion to elucidate the current understanding and outlook of DSD in resuscitative medicine.

Methods

The PubMed and MEDLINE databases were reviewed to assess the literature on Double sequential defibrillation. The terms “dual”, “se- quential”, “double sequential”, and “defibrillation” searched in the PubMed and MEDLINE search builder. Search results were further lim- ited to English language studies. Boolean operators and medical subject headings (MeSH) terms were used to combine search terms. Further lit- erature was discovered using the Google Scholar database with the same search terms and using the reference section of articles found through the PubMed search. The result revealed 23 matches. The results and their references were assessed for relevance to the topic and impli- cations for dual sequential defibrillation in shockable cardiac arrest.

https://doi.org/10.1016/j.ajem.2018.05.078

0735-6757/(C) 2018

refractory ventricular fibrillation“>Refractory ventricular fibrillation

Ventricular Fibrillation (VF) is an abnormal cardiac rhythm that can cause cardiac arrest. VF is often associated with a relatively higher chance of survival than other cardiac arrest rhythm such as pulseless electrical activity or asystole [7]. VF is caused by numerous underlying pathology, some examples are coronary heart disease, valvular heart disease, cardiomyopathy, electrolyte abnormalities, and congenital heart Rhythm disorder (Brugada syndrome, prolong QT) [8]. These con- ditions disrupt the normal flow of electricity in the heart leading to an erratic pattern, which results in a heart that is not able to properly per- fuse vital organs with blood.

The survival outcomes in refractory VF are 5.6-8.2% compared to non-refractory VF, which are 21.4-29.3% survival [2, 4, 9]. Refractory VF or shock resistant VF is defined as a rhythm that fails to achieve sustained ROSC after treatment with single defibrillation shocks and ad- ministration of anti-arrhythmic medication [10]. Refractory VF should be distinguished from recurrent VF (also known as Electrical storm), which is defined as greater than 3 episodes of VF in 24 h [11]. Practically, it is challenging to distinguish given that CPR guidelines state chest compressions should be resumed after defibrillation and this distorts rhythm for at least 2 additional minutes [12].

Definition of dual sequential defibrillation

Dual or double sequential defibrillation is the application of two de- fibrillators that provide two shocks to a patient in refractory arrhyth- mias. The timing of delivering the sequential defibrillation is not clearly defined as techniques differ. The DSD techniques include defi- brillation with a 1 to 2 second delay, overlapping shocks or completely synchronized. In the out of hospital setting, fully synchronized defibril- lation is a challenge given the devices are not electrically connected, therefore true timing cannot be determined [13].

Two defibrillator types are used in the prehospital setting. The orig- inal device was the monophasic defibrillator, which delivers 200-360 joules of energy in a single direction. Introduced in the 1990’s, the bi- phasic defibrillator delivers bidirectional energy of 100-200 J. Wang et al. in a meta-analysis reported the biphasic and monophasic did not dif- fer in out of hospital cardiac arrests in terms of survival rate to hospital discharge [14]. However, patients resuscitated with Biphasic shocks were more likely to be Neurologically intact upon leaving the hospital based on Cerebral Performance Category [15]. Clinicians use the

CPC system to stratify the neurological level for cardiac arrest patients.

[16] The effectiveness of Biphasic defibrillation is postulated to be the use of multiple vectors. The myocyte vectors are not depolarized in a single direction during VF and the bidirectional waveform in biphasic devices maximizing the amount of depolarizing myocytes in cardiac muscle [15]. An additional benefit of the biphasic is the lower energy re- sults in less post-shock myocardial damage [17].

Currently DSD is predominantly performed after multiple attempts of unsuccessful single device defibrillation. Growing clinical and theo- retical evidence suggests the use of sequential shocks may alter the ter- mination threshold and provide increased success in terminating refractory VF [18]. There are two ways the second set of pads can be ap- plied to a patient. (Fig. 1A, B). With the first set in the anterior right chest and lateral left chest, with the second set either adjacent to the first set or in the anterior/posterior position. Charge both devices, en- sure everyone is clear of the patient, press the shock button on both de- vices (either simultaneously or sequentially) and immediately resume CPR.

Levels of evidence

Animal models

The subject of DSD has been researched since the 1940’s in animal models and is an ongoing debate among researchers [19]. In 1986, the use of double and triple sequential defibrillation was trialed in dogs with induced VF that were with or without myocardial infarcts. The study concluded the use of sequential shocks would lower defibrillation threshold. The total energy and voltage required to terminate VF, and restore normal sinus was lower using DSD [20]. In 1994, VF was induced in closed-chested dogs and termination was attempted with either sin- gle or sequential overlapping electrical pulses of various energy levels (50 J, 100 J, 150 J). The study found the highest success in terminating VF to sinus with use of 150 J in sequential pulses [18].

Cohort study

Ross et al. conducted a retrospective cohort study on out of hospital cardiac arrests in a large urban emergency medical service (EMS) sys- tem between January 2013 and December 2015. Of the 3470 patients, 302 met inclusion criteria, which selected for patients in both recurrent and refractory VF treated with at least 4 single defibrillations as the

Fig. 1. A. illustrates the addition of another set of pads next to the original set in an anterior-lateral orientation. B. illustrates the anterior posterior orientation with the anterior pad placed over the precordium or apex, and the posterior pad is placed on the back in the left or right infrascapular region.

control or administration of DSD as the experimental group. The pri- mary outcome was Favorable neurologic outcome as defined by CPC 1 and 2 (1 = Good cerebral performance: conscious, alert, able to work, might have mild neurologic or psychological deficit; 2 = Moderate ce- rebral disability: conscious, sufficient cerebral function for independent activities of daily life) [8, 20]. The secondary outcomes include ROSC rates, Survival to hospital admission or survival to hospital discharge. Of the 302, 23 had incomplete data and were excluded, 229 received single 200 J defibrillation and 50 received a total of 400 J DSD. In the DSD group, a single person pushed both button simultaneously to de- liver the 400 J. The orientation of the pads was one in the anterolateral and one in the anterior posterior orientation. Overall, the study showed no statistical difference in primary or secondary outcomes [21].

There was a statistically significant difference in the percentage of witnessed arrests between the groups of this study with 38% in DSD group versus 54.6% in the control group. A variable known to influence outcomes of resuscitation in VF/VT include age, sex, rate of bystander CPR and witness of arrest [3]. This resulted in a selection bias because a 2010 meta-analysis found the difference in survival for witness’s ar- rest to be 13.5% versus 6.4% in non-witnessed arrest. The author of this study discussed the limitations of the study including the selection bias as a confounder, the low population number and the inability to dif- ferentiate recurrent versus refractory VF. Refractory and recurrent is often used interchangeably in literature but distinguishing them may be beneficial to properly study the effectiveness of DSD. The result is the data skewed toward no difference if recurrent VF is being mischaracterized as refractory VF [21].

A similar retrospective cohort study by Emmerson et al. between July 2015 and December 2016 in London with 220 out of hospital car- diac arrest patients (45 treated with DSD and 175 treated with single defibrillations) found no significance in pre-hospital ROSC, ROSC at hos- pital admission and survival to discharge between the control and ex- perimental groups. The study protocol aimed at no more than 6 single defibrillation shocks prior to DSD. Ultimately, an average of 10 single de- fibrillation shocks delivered before employing DSD and the time to DSD and ROSC was not recorded. The DSD group had 60% of arrests witnessed and the control group had 79.4% witnessed creating a selec- tion bias similar to Ross et al. The study reported omission of recurrent VF but stated it cannot guarantee all recurrent VF was excluding. The study reinforces the need for isolating refractory VF/VT through analysis of strips and clarifying definitions to enable studying DSD in truly refrac- tory VF cases [22].

Case reports

The first reported application of DSD in human dates back to 1994 with a retrospective case series of 5 patients out of 2990 patients over a 3-year period experiencing refractory ventricular fibrillation. Prior to attempt DSD, patients received 7 to 20 single defibrillation shocks. DSD was delivered externally 0.5 to 4.5 s apart by means of two defibril- lators and all 5 (100%) patients reverted back to normal sinus rhythm [23]. DSD is regaining attention in recent year with several case reports and case series attempting to expand understanding of this practice.

Cabanas et al., discussed a retrospective case series between 2008 and 2010. The study was based on a prehospital protocol to use DSD in patients with VF after 5 unsuccessful single defibrillation shocks. The study included 10 patients (9 males and 1 female) with a median age of 76.5 years. The initial cardiac rhythms were VF in 6 patients, asystole in 3 patients, and pulseless electrical activity in 1 patient. In the 10 patients, the median number of single shocks prior to DSD was

6.5 and ranged from 6 to 11. The median was 2 shocks delivered by DSD prior to successful termination of refractory rhythm. VF terminated after DSD in 7 cases (70%), of the 7 only 3 (42.3%) patients had ROSC in the field. Of the 10 patients, none (0%) survived to hospital discharge. However, the median resuscitation time was 51-min, ranging from 45 to 62 min [24].

Another retrospective case series by Cortez et al. studied prehospital patients from 2010 to 2014. The study included 12 out of 2428 cardiac arrest patients. Of the 2428, 499 where in shockable VF/VT rhythms and of that number 12 had refractory VF/VT. The median time till DSD attempted was 27 min and the number of single shocks before DSD is undocumented. Of the 12, 9 (75%) terminated to sinus, but only 3

(25%) had ROSC. Of the 3, only 2 (17%) left the hospital neurologically

intact with CPC of 1 [25].

A variable in successful outcomes of resuscitation is the timing, therefore timely application of DSD is required to assess efficacy. For ex- ample, in Cortez et al., it took an average of 27 min to employ DSD ver- sus 51 min in Cabanas et al. In addition, the median prehospital resuscitation time was also shorter at 32 min in Cortez et al., versus 51 min in Cabanas et al. In Cortez, 2 patients were discharge with CPC of 1, whereas in Cabanas none survived to discharge. Timing of DSD em- ployment is a potential contributor to the outcome discrepancies be- tween these two case series [24, 25].

Merlin et al. conducted a retrospective case series of patients in the out of hospital setting who received DSD from January 1, 2015 to April 30, 2015. During this period, paramedics employed DSD after three un- successful single defibrillations of VF. The mean age of the 7 patients treated with DSD was 62, with a mean resuscitation time of 34.3 min be- fore the first DSD. The mean number of single shocks was 5.4 prior to DSD ranging from 3 to 9, with a mean of 2 DSD shocks delivered. VF con- verted to normal sinus after DSD in 5 cases (57.1%) with 4 patients sur- viving to admission (43%) and 3 patients surviving to discharge with no or minimal neurologic disability (28.6%) [26].

DSD has also been described in the in hospital arrest setting. In a case report by Sena et al., a 56-year-old woman was admitted for concern of an acute coronary syndrome. She became unresponsive and cardiac monitor exhibited VF. Hospital CPR protocol was initiated with delivery of four rounds of defibrillation using a 200 J biphasic defibrillator. After these unsuccessful attempts, DSD using two defibrillators at 300 J each or 600 J in total was attempted. A second set of defibrillator pads were placed in an anteroposterior position directly adjacent to the first set of pads. The defibrillators were activated simultaneously and the pa- tient reverted to normal sinus rhythm with return of spontaneous circu- lation (ROSC). The patient regained consciousness and was discharge from the hospital in neurologically intact after 7 days [27].

A similar in-hospital case reported by Gerstein et al. involved a 66- year-old man with an acute inferior ST-elevation myocardial infarction who went into VF. CPR was initiated with a biphasic 200 J device for 72 min. A total of 15 single defibrillation attempts occurred before DSD was tried. After the second DSD attempt, normal sinus rhythm was established with ROSC. Ultimately, the patient had anoxic brain in- jury and did not survive due to the prolonged CPR [28].

Several studies presented single case reports of cardiac arrest that occurred outside of the hospital [29-34]. The result was resuscitations using DSD reverted from VF to normal sinus rhythm with ROSC and complete neurological recovery in each case. A notable difference be- tween these cases is the amount of single defibrillation attempts before attempting DSD. Sheikh et al. received 3 single 200 J defibrillations, two in anterolateral position and one in anteroposterior position, before re- ceiving DSD [29]. Bell et al. had 4 attempts with single defibrillations be- fore the use of two 200 J biphasic successfully terminated VF after 27 min. The patient has a recurrence of VF 60 s later and DSD was suc- cessful again [30]. Leacock et al. had 5 single defibrillations before the use of two 200 J defibrillators was attempted [31]. Lybeck et al. had 7 at- tempts with a single defibrillator before DSD was employed with 200 J biphasic and 360 J monophasic devices delivered within 1 s [32]. In Tawil et al., the patient received 7 single biphasic 200 J defibrillation at- tempts before DSD with two biphasic devices at a total of 400 J was attempted. ROSC occurred after 3 DSD shocks and this patient was later discharged neurologically intact after 61 min of resuscitative ef- forts. The number of shocks needed to terminate VF/VT is an indepen- dent risk factor for survival to hospital discharge [33]. A patient

requiring greater than or equal to 3 shocks is associated with less favor- able outcomes [35]. In Johnston et al. a 28-year-old female with Long QT syndrome had a cardiac arrest witnessed by her husband who initiated CPR immediately. She had 6 biphasic single defibrillations using 200 J before attempting DSD with two 200 J defibrillators. She recovered fully and was discharge neurologically intact [34] (Table 1).

Device and patient safety

A case report by Gerstein et al. reports the first known case of dam- age to a defibrillator linked to DSD. The case involves a 41-year-old man presenting to his Primary care clinic with electrocardiogram (ECG) ab- normalities. The physician sent him to the emergency department and an ECG displayed VT or supraventricular tachycardia secondary to left cardiac vessel occlusion. The patient received antiarrhythmic and

defibrillation with a Zoll M Series CCT biphasic 200 J. This first shock was ineffective and a Physio-Control LIFEPAK LP15 360 J biphasic defi- brillator was attempted. After both brands failed, DSD was attempted twice with two Zoll brand devices used simultaneously. Finally, DSD was attempted with two of the Physio-Control LIFEPAK LP15 and was again unsuccessful [36].

Next day, one of the LIFEPAK devices failed self-test and was non- functioning. The event code indicated the third shock delivered from the prior day, which occurred in parallel with the use of the Zoll device. DSD is an off-label use and manufactures for the devices involved in this case have no safety standards or guidance surrounding this practice. The leading theory behind how the damage occurred was there was cross talk between devices that resulted in the device sending electricity to the other device instead of to the patient. DSD is increasingly being used and a few large EMS agencies have integrated it into their

Table 1

Studies/reports on dual sequential defibrillation

Author Design No. Details Findings

Ross et al. Retrospective

Cohort study

279 229 received single 200 J defibrillation and 50 received DSD with a total of 400 J DSD.

Overall, the study showed no statistical difference in primary or secondary outcomes between DSD and single defibrillation. The study was subject to selection bias favoring outcomes for the control.

Emmerson et al.

Retrospective Cohort study

220 175 received single 200 J defibrillation and 45 received two 200 J defibrillations in sequence for a total of 400 J. Average of 10 single shocks delivered prior to DSD

Overall, the study showed no statistical difference in primary or secondary outcomes between DSD and single defibrillation. The study was subject to selection bias. The study discusses limitations and missing important data such as time to employment of DSD.

Hoch et al. Case series 5 1994 case of 5 patients out of 2990 patients over a 3-year period

experiencing refractory ventricular fibrillation. Two defibrillators delivered DSD to these 5 patients.

All 5 (100%) patients reverted back to normal sinus rhythm after multiple attempts at single defibrillation.

Cabanas et al.

Cortez et al.

Merlin et al.

Case series 10 10 patients (9 males and 1 female) with a median age of 76.5. In the 10 patients, the median number of single shocks was 6.5 and average of 2 shocks was delivered by DSD prior to successful termination. The median resuscitation time was 51-min.

Case series 12 12 out of 2428 cardiac arrest patients. Of the 2428, 499 where in shockable VF/VT rhythms and of that number 12 had refractory VF/VT. The median time till DSD was attempted was 27 min.

Case series 7 DSD was employed by paramedics after three unresponsive episodes of VF to single defibrillation. The mean resuscitation time was 34.3 min before first DSD. The mean number of single shocks was 5.4 prior to DSD ranging from 3 to 9, with a mean of 2 DSD shocks delivered.

VF terminated after DSD in 7 cases and only 3 (42.3%) patients had ROSC in the field. Of the 10 patients, 0 (0%) survived to hospital discharge.

Of the 12, 9 terminated to sinus (75%), but only 3 (25%) had ROSC. Of the 3, only 2 (17%) left the hospital neurologically intact with CPC of 1.

VF converted to normal sinus after DSD in 5 cases (57.1%) with 4 patients surviving to admission (43%) and 3 patients surviving to discharge with no or minimal neurologic disability (28.6%).

Sena et al. Case report 1 56-year-old female in hospital became unresponsive and went into

VF. Hospital CPR protocol was initiated with delivery of four rounds of defibrillation using a 200 J biphasic defibrillator. After these unsuccessful attempts, DSD using two defibrillators at 300 J each or 600 J in total was attempted.

The result was resuscitations using DSD reverted from VF to normal sinus rhythm with ROSC and complete neurological recovery.

Gerstein et al.

Leacock et al.

Lybeck et al.

Case report 1 66-year-old man had an acute inferior ST-elevation myocardial infarction out of the hospital went into VF. CPR was initiated with a biphasic 200 J devices for 72 min. A total of 15 single defibrillation attempts occurred before DSD was tried.

Case report 1 51-year-old male with a non-ST elevation MI. 5 single defibrillations attempted before the use of two 200 J defibrillators

Case report 1 40-year-old male struck his chest against a pole during a basketball game and had sudden out-of-hospital cardiac arrest. 7 attempts with a single defibrillator before DSD was employed with 200 J biphasic and a 360 J monophasic devices delivered within 1 s.

After the second DSD attempt, normal sinus rhythm was established with ROSC. However, the patient had Anoxic brain injury and did not survive due to the prolonged CPR.

The result was resuscitations using DSD reverted from VF to normal sinus rhythm with ROSC and complete neurological recovery.

The result was resuscitations using DSD reverted from VF to normal sinus rhythm with ROSC and complete neurological recovery.

Tawil et al. Case report 1 54-year-old male suffered from out of hospital cardiac arrest. DSD

was attempted after 7 single biphasic 200 J defibrillation attempts before DSD with two biphasic devices at a total of 400 J was attempted.

The result was resuscitations using DSD reverted from VF to normal sinus rhythm with ROSC and complete neurological recovery.

Johnston et al.

Gerstein et al.

Case report 1 A 28-year-old female with long QT syndrome had a cardiac arrest witnessed by her husband who initiated CPR immediately. 6 biphasic 200 J single defibrillations were used before attempting DSD with two 200 J defibrillators.

Case Report 1 A 41-year-old male with EKG showing VT secondary to coronary syndrome. DSD was attempted and one device was damaged and nonfunctioning the following day.

The result was resuscitations using DSD reverted from VF to normal sinus rhythm with ROSC and complete neurological recovery in each case.

The report recommends for patient safety that additional testing by manufacturers with DSD. Also, protocol to evaluate for function after use in DSD can avert harm to patients.

Bell et al. Case report 1 A 53-year-old male with EKG showing refractory VF secondary to

coronary syndrome. DSD with two biphasic 200 J devices was attempted after 18 min and after 4 single defibrillation attempts with ROSC achieved at 27 min. VF recurred 60 s later and DSD was successful a second time.

The result was resuscitations using DSD reverted from VF to normal

sinus rhythm with ROSC and complete neurological recovery.

Sheikh et al.

Case report 1 A 79-year-old male with EKG showing VT secondary to coronary syndrome. 3 biphasic 200 J single defibrillations were used before attempting DSD with two 200 J defibrillators.

The result was resuscitations using DSD reverted from VT to normal sinus rhythm with ROSC and placement of an automatic implantable defibrillator.

protocols. It is possible the defibrillator malfunction was unrelated to DSD but given that is a rare event DSD must be considered [36].

Discussion

The efforts are ongoing to optimize ACLS protocol and increase the survival rate of patients unresponsive to current standards of care. Large urban EMS agencies have begun to integrate dual sequential defi- brillation into Resuscitation protocols [21, 24] DSD has been an effective technique in treatment of refractory VF in many cases around the country.

Evidence supports that early intervention with defibrillation corre- late with better outcomes [3]. Cortez et al. employed DSD after a mean 27 min and had better outcomes using DSD in comparison to Cabanas et al., which employed DSD after a mean of 51 min [24, 25]. The reported cases and series range from 3 to 15 single defibrillators before DSD was attempted [26-34]. Hasegawa et al. reports the success of defibrillation tapers off after multiple attempts and after three attempts survival out- comes decrease [35]. This poses a dilemma because classification of re- fractory VF requires three attempts at single defibrillation. Case reports have published showing success after 1 to 3 attempts with DSD. VF was reverted to sinus after a median of 2 attempts. Ross et al. found no sig- nificant difference in outcomes between the use of DSD and single defi- brillation in a cohort analysis. However, the study had a selection bias that favored outcomes for control group and despite this had no signif- icant difference in outcomes. Emphasis on timely incorporation of DSD into protocols would be beneficial given the outcomes measured are based not only on ROSC, but neurological preservation [21].

The underlying mechanism of DSD is not fully understood. Leading theories divide the mechanism into three components that likely have interplay. The components are duration, vector direction and energy. One theory proposes the defibrillation threshold is lowered with simul- taneous or near simultaneous shocks because cardiac cells are in various stage of depolarize, repolarization and rest. The increase duration of shock allows for depolarization of missed cells that continue to propa- gate disorganized rhythms [18, 23]. Another theory postulates DSD maximizes on the vectors and allows for more cardiac mass to depolar- ize [18, 20, 23, 37]. This allows for increased likelihood of a shock aligning with the excitable cardiac cells. In refractory VF high-energy defibrillation may be required to successfully terminate VF as it may overcome factors such as suboptimal pad placement, anatomy differ- ences and transthoracic impedance [38, 39]. Previously, weight was thought to be an independent risk factor for unsuccessful defibrillation due to the barrier created between the heart and external defibrillation, however this was found not to be a variable in a prehospital study using biphasic defibrillation [40]. It is likely the mechanism is a combination of these factors and understanding the mechanism of DSD may be useful in optimizing the timing of shock delivery.

The practice of DSD is corroborated by human and animal studies using sequential or overlapping shocks. The exact importance of magni- tude versus direction of energy applied for termination of arrhythmias remains unclear [20, 23]. The survival rate in refractory DSD is only

5.6-8.2% compared to 21.4-29.3% in shockable VF [2, 4, 9]. Refractory VF is associated with underlying pathology that is acute or chronic is- chemic. This causes scarring of the myocardium and predisposed indi- viduals to a persisting arrhythmia [8]. The practice of transporting these patients was the standard of care for a time. However, evidence concludes resuscitation in the field is associated with better outcomes than patients transported to hospital [3]. Currently, standard interven- tions used in the VT/VF vary based on the clinical scenario, setting, (in or out of hospital) and available resources. The treatment involves com- binations of the following: CPR, defibrillation, medications, relocation of defibrillator pads, cardiac catheterization, surgical interventions and protocols to minimize oxygen requirement such as inducing hypother- mia in patients [41].

Patient safety was highlighted in Gerstein et al. after a device failed the day after being used in DSD. This was the first and only reported case of device malfunction, but the rise in this practice should incentiv- ize manufactures to include DSD in future quality testing. The report concludes approaches to averting potential damage to defibrillators and danger to patients. Recommendations to providers include adding protocol to evaluate function of device after off label use such as DSD [36].

Conclusions

Survival rates remain low in refractory of VF and current standards should continue to explore other treatment options. The emergence of the practice of DSD in treating refractory VF requires establishing guide- lines surrounding the practice. Most of the data to date is based on case establish reports and series showing some successful resuscitation with intact neurological outcome. Overall, well-designed and high quality case control or double-blinded randomized trial will be necessary to completely elucidate the efficacy and role of DSD.

Author disclosure statement

No competing financial interests exist.

References

1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al, American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Executive summary: Heart Disease and Stroke Statistics-2016 update: a report from the Amer- ican Heart Association. Circulation 2016;133(4):447-54.
2. Daya MR, Schmicker RH, Zive DM, Rea TD, Nichol G, Buick JE, et al, Resuscitation Outcomes Consortium Investigators. Out-of-hospital Cardiac arrest survival improv- ing over time: results from the Resuscitation Outcomes Consortium (ROC). Resusci- tation 2015;91:108-15.
3. Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out-of-hos- pital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2010;3(1):63-81.
4. Sakai T, Iwami T, Tasaki O, Kawamura T, Hayashi Y, Rinka H, et al. Incidence and out- comes of out-of-hospital cardiac arrest with shock-resistant ventricular fibrillation: data from a large population-based cohort. Resuscitation 2010;81(8):956-61.
5. Kudenchuk PJ, Brown SP, Daya M, Morrison LJ, Grunau BE, Rea T, Aufderheide T, Powell J, Leroux B, Vaillancourt C, Larsen J, Wittwer L, Colella MR, Stephens SW, Gamber M, Egan D, Dorian P, Resuscitation Outcomes Consortium Investigators. Re- suscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC- ALPS): rationale and methodology behind an out-of-hospital cardiac arrest antiar- rhythmic drug trial. Am Heart J 2014 May;167(5) [653-9.e4].
6. Driver BE, Debaty G, Plummer DW, Smith SW. Use of esmolol after failure of stan- dard cardiopulmonary resuscitation to treat patients with refractory ventricular fi- brillation. Resuscitation 2014;85(10):1337-41.
7. Morrison LJ, Neumar RW, Zimmerman JL, Link MS, Newby LK, McMullan Jr PW, et al, American Heart Association Emergency Cardiovascular Care Committee, Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on

   P. Strategies for improving survival after in-hospital cardiac arrest in the United States: 2013 consensus recommendations: a consensus statement from the Ameri- can Heart Association. Circulation 2013;127(14):1538-63.

   Hayashi M, Shimizu W, Albert CM. The spectrum of epidemiology underlying sud- den cardiac death. Circ Res 2015;116(12):1887-906.

8. Yannopoulos D, Bartos JA, Martin C, Raveendran G, Missov E, Conterato M, Frascone RJ, Trembley A, Sipprell K, John R, George S, Carlson K, Brunsvold ME, Garcia S, Aufderheide TP. Minnesota Resuscitation Consortium’s advanced perfusion and re- perfusion cardiac life support strategy for out-of-hospital refractory ventricular fi- brillation. J Am Heart Assoc 2016;5(6):e003732 pii.
9. Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A. Amiodarone as com- pared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med 2002 Mar 21;346(12):884-90 [Erratum in: N Engl J Med 2002;347(12):955].
10. Exner DV, Pinski SL, Wyse DG, Renfroe EG, Follmann D, Gold M, et al, Antiarrhythmics Versus Implantable Defibrillators. Electrical storm presages nonsudden death: the antiarrhythmics versus implantable defibrillators (AVID) trial. Circulation 2001;103(16):2066-71.
11. Pierce AE, Roppolo LP, Owens PC, Pepe PE, Idris AH. The need to resume chest com- pressions immediately after defibrillation attempts: an analysis of post-shock rhythms and duration of pulselessness following out-of-hospital cardiac arrest. Re- suscitation 2015;89:162-8.
12. Deakin CD, Kerber RE. Dual sequential defibrillation: does one plus one equal two? Resuscitation 2016;108:A1-2.
13. Wang CH, Huang CH, Chang WT, Tsai MS, Liu SS, Wu CY, et al. Biphasic versus Monophasic defibrillation in out-of-hospital cardiac arrest: a systematic review and meta-analysis. Am J Emerg Med 2013;31(10):1472-8.
14. Schneider T, Martens PR, Paschen H, Kuisma M, Wolcke B, Gliner BE, Russell JK, Weaver WD, Bossaert L, Chamberlain D. Multicenter, randomized, controlled trial of 150-J biphasic shocks compared with 200- to 360-J monophasic shocks in the re- suscitation of out-of-hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) investigators. Circulation 2000;102(15):1780-7.
15. Ajam K, Gold LS, Beck SS, Damon S, Phelps R, Rea TD. Reliability of the cerebral per- formance category to classify neurological status among survivors of ventricular fi- brillation arrest: a cohort study. Scand J Trauma Resusc Emerg Med 2011;19:38.
16. van Alem AP, Chapman FW, Lank P, Hart AA, Koster RW. A prospective, randomised and blinded comparison of first shock success of monophasic and biphasic wave- forms in out-of-hospital cardiac arrest. Resuscitation 2003;58(1):17-24.
17. Kerber RE, Spencer KT, Kallok MJ, Birkett C, Smith R, Yoerger D, Kieso RA. Overlap- ping sequential pulses. A new waveform for Transthoracic defibrillation. Circulation 1994;89(5):2369-79.
18. Wiggers CJ. The physiologic basis for Cardiac resuscitation from ventricular fibrilla- tion-method for serial defibrillation. Am Heart J 1940;20:413-22.
19. Chang MS, Inoue H, Kallok MJ, Zipes DP. Double and triple sequential shocks reduce Ventricular defibrillation threshold in dogs with and without myocardial infarction. J Am Coll Cardiol 1986;8(6):1393-405.
20. Ross EM, Redman TT, Harper SA, Mapp JG, Wampler DA, Miramontes DA. Dual defi- brillation in out-of-hospital cardiac arrest: a retrospective cohort analysis. Resuscita- tion 2016;106:14-7.
21. Emmerson AC, Whitbread M, Fothergill RT. Double sequential defibrillation therapy for out-of-hospital cardiac arrests: the London experience. Resuscitation 2017;117: 97-101.
22. Hoch DH, Batsford WP, Greenberg SM, Mcpherson CM, Rosenfeld LE, Marieb M, et al. Double sequential external shocks for refractory ventricular fibrillation. J Am Coll Cardiol 1994;23(5):1141-5.
23. Cabanas JG, Myers JB, Williams JG, De Maio VJ, Bachman MW. Double sequential ex- ternal defibrillation in out-of-hospital refractory ventricular fibrillation: a report of ten cases. Prehosp Emerg Care 2015;19(1):126-30.
24. Cortez E, Krebs W, Davis J, Keseg DP, Panchal AR. Use of double sequential external defibrillation for refractory ventricular fibrillation during out-of-hospital cardiac ar- rest. Resuscitation 2016;108:82-6.
25. Merlin MA, Tagore A, Bauter R, Arshad FH. A case series of double sequence defibril- lation. Prehosp Emerg Care 2016;20(4):550-3.
26. Sena RC, Eldrich S, Pescatore RM, Mazzarelli A, Byrne RG. Refractory ventricular fi- brillation successfully cardioverted with dual sequential defibrillation. J Emerg Med 2016;51(3):e37-40.
27. Gerstein NS, Shah MB, Jorgensen KM. Simultaneous use of two defibrillators for the conversion of refractory ventricular fibrillation. J Cardiothorac Vasc Anesth 2015;29 (2):421-4.
28. Sheikh H, Xie E, Austin E. Double sequential cardioversion for refractory ventricular tachycardia: a case report. CJEM 2018:1-5.
29. Bell CR, Szulewski A, Brooks SC. Make it two: a case report of dual sequential exter- nal defibrillation. CJEM 2017:1-6.
30. Leacock BW. Double simultaneous defibrillators for refractory ventricular fibrilla- tion. J Emerg Med 2014;46(4):472-4.
31. Lybeck AM, Moy HP, Tan DK. Double sequential defibrillation for refractory ventric- ular fibrillation: a case report. Prehosp Emerg Care 2015;19(4):554-7.
32. El Tawil C, Mrad S, Khishfe BF. Double sequential defibrillation for refractory ventric- ular fibrillation. Am J Emerg Med 2017;35(12):1985.e3-4.
33. Johnston M, Cheskes S, Ross G, Verbeek PR. Double sequential external defibrillation and survival from out-of-hospital cardiac arrest: a case report. Prehosp Emerg Care 2016;20(5):662-6.
34. Hasegawa M, Abe T, Nagata T, Onozuka D, Hagihara A. The number of prehospital defibrillation shocks and 1-month survival in patients with out-of-hospital cardiac arrest. Scand J Trauma Resusc Emerg Med 2015;23:34.
35. Gerstein NS, McLean AR, Stecker EC, Schulman PM. External defibrillator damage as- sociated with attempted synchronized dual-dose cardioversion. Ann Emerg Med 2018;71(1):109-12.
36. Jones DL, Klein GJ, Guiraudon GM, Sharma AD. Sequential pulse defibrillation in humans: orthogonal sequential pulse defibrillation with epicardial electrodes. J Am Coll Cardiol 1988;11(3):590-6.
37. Deakin CD, Ambler JJ, Shaw S. Changes in transthoracic impedance during sequential biphasic defibrillation. Resuscitation 2008;78(2):141-5.
38. Link MS, Atkins DL, Passman RS, Halperin HR, Samson RA, White RD, Cudnik MT, Berg MD, Kudenchuk PJ, Kerber RE. Part 6: electrical therapies: automated external defibrillators, defibrillation, cardioversion, and pacing: 2010 American Heart Associ- ation Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(18 Suppl. 3):S706-19.
39. White RD, Blackwell TH, Russell JK, Jorgenson DB. Body weight does not affect defi- brillation, resuscitation, or survival in patients with out-of-hospital cardiac arrest treated with a nonescalating biphasic waveform defibrillator. Crit Care Med 2004; 32(9 Suppl):S387-92.
40. Bastiaenen R, Hedley PL, Christiansen M, Behr ER. Therapeutic hypothermia and ventricular fibrillation storm in early repolarization syndrome. Heart Rhythm 2010;7(6):832-4.