RECOVER 2.0 Worksheet

QUESTION ID: ALS-11

PICO Question:
In cats and dogs with CPA due to a shockable rhythm (P) does the use of a monophasic defibrillator (I) compared to a biphasic defibrillator (C) improve outcome (O)?

Outcomes:
Favorable neurologic outcome,Surrogate marker(s) of perfusion,Survival to Discharge,ROSC

Prioritized Outcomes (1= most critical; final number = least important):

1. Favorable neurologic outcome
2. Survival to discharge
3. ROSC
4. Surrogate markers of perfusion

Domain chairs: Gareth Buckley, Elizabeth Rozanski, Jake Wolf

Evidence evaluators: Jeannette Cremer, Christina Maglaras

Conflicts of interest: None

Search strategy: See attached document

Evidence Review:

Study Design		Reduced Quality Factors 0 = no serious, - = serious, - - = very serious				Positive Quality Factors 0 = none, + = one, ++ = multiple			Dichotomous Outcome Summary			Non-Dichotomous Outcome Summary Brief description	Overall Quality High, moderate, low, very low, none
No of studies	Study Type	RoB	Indirectness	Imprecision	Inconsistency	Large Effect	Dose-Response	Confounder	# Intervention with Outcome	# Control with Outcome	RR (95% CI)
Outcome: Favorable neurologic outcome
2	CT	0	-	0	-							Slight benefit for biphasic	Low
1	OS	-	-	0	0							Biphasic with improved CPC	Very low
0	ES
Outcome: Survival to discharge
3	CT	0	-	-	-	+						Slight benefit for biphasic	Moderate
1	OS	-	-	0	0	+						Biphasic with improved survival	High
2	ES	0	-	-	-							No difference	Low
Outcome: ROSC
5	CT	0	-	-	-							Slight benefit for biphasic	Moderate
1	OS	-	-	0	0							Biphasic with improved ROSC	High
9	ES	-	-	-	-							Slight benefit with BP	Low
Outcome: Surrogate markers of perfusion
0	CT
0	OS
6	ES	-	-	-	0	0							Very low

PICO Question Summary

Introduction

In patients with VF or pVT, successful defibrillation is necessary to achieve ROSC. The most common defibrillation waveforms in use are biphasic (BP) and monophasic (MP). In MP defibrillation, a high-energy unidirectional current is used, whereas BP defibrillation allows for lower-energy, bidirectional currents. Current veterinary and human guidelines recommend BP defibrillation when available over MP defibrillation because higher energy defibrillation has been associated with greater myocardial and other tissue injury.1–3

Consensus on science

Outcome 1: Favorable neurologic outcome For the most critical outcome of favorable neurologic outcome, two clinical trials (very low quality of evidence, downgraded for very serious indirectness and serious inconsistency), and one observational study (very low quality of evidence, downgraded for serious risk of bias and serious indirectness) were identified. A multi-center randomized, controlled trial of adults with out-of-hospital cardiac arrest demonstrated a higher percentage of patients with good cerebral performance category at the time of discharge (87% vs 53%, P=0.03) with BP therapy.4 Another clinical trial in adults with non-traumatic out-of-hospital cardiac arrest with VF were randomly allocated to receive either MP or BP defibrillation.5 No difference in neurologic outcome was noted between groups. An observational study of all adults with out-of-hospital cardiac arrest in Japan between 2005-2014 found improved neurologic outcome with BP defibrillation compared to MP defibrillation.6 Outcome 2: Survival to discharge Four clinical trials (the 2 mentioned above and two additional trials) in adults with out-of-hospital cardiac arrest evaluated survival to discharge between BP and MP defibrillation (very low quality of evidence, downgraded for very serious indirectness and serious inconsistency). The 2 previously mentioned studies showed no improvement in survival to discharge4,5 Similarly, the 2 additional clinical trials showed no benefit of BP over MP for this outcome.7,8 However, in the subset of patients in whom CPA was witnessed and when defibrillation was administered within 4-10 minutes in one study, improved survival was noted with BP defibrillation compared to MP defibrillation (BP 45% vs 31%, P=0.0002).7 In addition, 1 observational study demonstrated improved survival to 1 month with BP compared to MP defibrillation.6 Finally, 1 experimental swine study showed no difference in survival between BP and MP defibrillation in a prolonged VF model left untreated for the first 10 minutes.9 Outcome 3: ROSC Five clinical trials in people (very low quality of evidence, downgraded for very serious indirectness and serious inconsistency) evaluated this outcome. Three of the 5 OOH studies showed no improvement in frequency of ROSC with BP defibrillation compared to MP.5,7,10 Of the remaining 2 trials, one examined OOH CPA and one IH CPA, and both demonstrated significantly greater frequency of ROSC in patients treated with BP vs those treated with MP defibrillation.4,8 In one, a BP defibrillator was compared to two MP defibrillators, and ROSC frequency was higher with the BP (76%) than the MP (54%, P=0.024).8 In the other, 76% of patients were successfully defibrillated with BP vs 54% with MP (P=0.01).4 In addition, the previously described observational study showed higher frequency of ROSC with BP than MP.6 Nine experimental studies (4 in pigs and 5 in dogs) compared BP and MP defibrillation in various arrest models (very low quality of evidence, downgraded for serious risk of bias, serious indirectness, serious imprecision, and serious inconsistency). Overall, 5 studies showed no benefit of BP over MP in frequency of ROSC.9,11–13 Of the 4 remaining studies that showed a benefit of BP over MP, 3 were canine studies.14–17 Outcome 4: Surrogate markers of perfusion Six experimental studies in dogs and pigs evaluated this outcome (very low quality of evidence, downgraded for serious risk of bias, serious indirectness, and serious imprecision). Most identified less myocardial dysfunction, lower energy requirements, shorter periods of CPR, and lower values for markers of cardiac injury with BP therapy.9,11,12,18,19 One study in ten toy breed dogs found more severe ECG abnormalities, more persistently elevated cardiac biomarkers, and severely depressed left ventricular cardiac performance in the MP group compared to the BP group.15 However, all dogs included in the study survived.

Treatment recommendation

We recommend using a biphasic defibrillator over a monophasic defibrillator in dogs and cats with shockable rhythms (strong recommendation, very low quality of evidence).

Justification of treatment recommendation

Multiple studies show improved neurologic outcome, survival to discharge, and ROSC with BP defibrillation compared to MP defibrillation. Many experimental studies in pigs and dogs show improved hemodynamics and decreased myocardial injury with BP defibrillation.

Knowledge gaps

While studies in people and experimental studies in pigs and dogs support the use of BP defibrillators over MP defibrillators, no clinical studies in dogs and no studies in cats have been performed. The effects of MP versus BP defibrillation waveform on outcome during CPR in dogs and cats with shockable rhythms is considered a low priority knowledge gap.

References:

1. Xie J, Weil MH, Sun S, et al. High-Energy Defibrillation Increases the Severity of Postresuscitation Myocardial Dysfunction. Circulation. 1997;96(2):683-688.

2. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142(16_suppl_2):S366-S468.

3. Fletcher DJ, Boller M, Brainard BM, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines: RECOVER clinical guidelines. J Vet Emerg Crit Care. 2012;22(s1):S102-S131.

4. Schneider T, Martens PR, Paschen H, et al. Multicenter, randomized, controlled trial of 150-J biphasic shocks compared with 200- to 360-J monophasic shocks in the resuscitation of out-of-hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) Investigators. Circulation. 2000;102(15):1780-1787.

5. Kudenchuk PJ, Cobb LA, Copass MK, et al. Transthoracic incremental monophasic versus biphasic defibrillation by emergency responders (TIMBER): a randomized comparison of monophasic with biphasic waveform ascending energy defibrillation for the resuscitation of out-of-hospital cardiac arrest due. Circulation. 2006;114(19):2010-2018.

6. Hagihara A, Onozuka D, Ono J, Nagata T, Hasegawa M. Interaction of defibrillation waveform with the time to defibrillation or the number of defibrillation attempts on survival from out-of-hospital cardiac arrest. Resuscitation. 2018;122:54-60.

7. Morrison LJ, Dorian P, Long J, et al. Out-of-hospital cardiac arrest rectilinear biphasic to monophasic damped sine defibrillation waveforms with advanced life support intervention trial (ORBIT). Resuscitation. 2005;66(2):149-157.

8. Martens PR, Russell JK, Wolcke B, et al. Optimal Response to Cardiac Arrest study: defibrillation waveform effects. Resuscitation. 2001;49(3):233-243.

9. Tang W, Weil MH, Sun S, et al. A comparison of biphasic and monophasic waveform defibrillation after prolonged ventricular fibrillation. Chest. 2001;120(3):948-954.

10. van Alem AP, Chapman FW, Lank P, Hart AAM, Koster RW. A prospective, randomised and blinded comparison of first shock success of monophasic and biphasic waveforms in out-of-hospital cardiac arrest. Resuscitation. 2003;58(1):17-24.

11. Tang W, Weil MH, Sun S, et al. The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function. J Am Coll Cardiol. 1999;34(3):815-822.

12. Leng CT, Paradis NA, Calkins H, et al. Resuscitation after prolonged ventricular fibrillation with use of monophasic and biphasic waveform pulses for external defibrillation. Circulation. 2000;101(25):2968-2974.

13. Scott BD, Kallok MJ, Birkett C, Kieso RA, Kerber RE. Transthoracic defibrillation: effect of dual-pathway sequential pulse shocks and single-pathway biphasic pulse shocks in a canine model. Am Heart J. 1993;125(1):99-109.

14. Clark CB, Zhang Y, Davies LR, Karlsson G, Kerber RE. Transthoracic biphasic waveform defibrillation at very high and very low energies: a comparison with monophasic waveforms in an animal model of ventricular fibrillation. Resuscitation. 2002;54(2):183-186.

15. Lee SG, Moon HS, Hyun C. The efficacy and safety of external biphasic defibrillation in toy breed dogs. J Vet Emerg Crit Care. 2008;18(4):362-369.

16. Clark CB, Zhang Y, Davies LR, Karlsson G, Kerber RE. Pediatric transthoracic defibrillation: biphasic versus monophasic waveforms in an experimental model. Resuscitation. 2001;51(2):159-163.

17. Flaker GC, Schuder JC, McDaniel WC, Stoeckle H, Dbeis M. Superiority of biphasic shocks in the defibrillation of dogs by epicardial patches and catheter electrodes. Am Heart J. 1989;118(2):288-291.

18. Tang W, Weil MH, Sun S, et al. The effects of biphasic waveform design on post-resuscitation myocardial function. J Am Coll Cardiol. 2004;43(7):1228-1235.

19. Osswald S, Trouton TG, O’Nunain SS, et al. Relation between shock-related myocardial injury and defibrillation efficacy of monophasic and biphasic shocks in a canine model. Circulation. 1994;90(5):2501-2509.

Supplemental:

Outcome: Favorable neurologic outcome

2 Clinical Trials

Kudenchuk et al., 2006: Transthoracic incremental monophasic versus biphasic defibrillation by emergency responders

● Adults with non-traumatic OOH VF were randomly allocated to monophasic or biphasic waveforms

● No difference in presence of VF or organized rhythm, survival to discharge, or neuro outcome

Schneider et al., 2000: Multicenter, randomized, controlled trial of 150 J biphasic shocks compared with 200 to 360 J monophasic shocks in the resuscitation of OOHCA victims

● AEDs randomized according to waveform on daily basis in 4 EDs

● Higher ROSC with biphasic and good neuro outcome, but no difference in survival

1 Observational Studies

Hagihara et al., 2018: Interaction of defibrillation waveform with the time to defibrillation or the number of defibrillation attempts on survival from OOHCA

● Evaluation of all OOHCA in Japan from 2005-2014

● Improved ROSC, 1 month survival and CPC score with biphasic compared to monophasic

0 Experimental Studies

Outcome: Survival to discharge

4 Clinical Trials

Schneider et al., 2000: Multicenter, randomized, controlled trial of 150 J biphasic shocks compared with 200 to 360 J monophasic shocks in the resuscitation of OOHCA victims

● AEDs randomized according to waveform on daily basis in 4 EDs

● Higher ROSC with biphasic and good neuro outcome, but no difference in survival

Morrison et al., 2005: OOHCA rectilinear biphasic to monophasic damped sine defibrillation waveforms with ALS intervention trial (ORBIT)

● OHCA requiring at least one shock treated by ALS paramedics

● No difference in ROSC, survival to discharge. However, within 4-10 minutes of bystander witnessed, improved survival with biphasic

Martens et al., 2001: Optimal response to cardiac arrest study: defibrillation waveforms effects

● AEDs randomized according to waveform on daily basis in 4 EDs for adults with VF and cardiac etiology

● No difference in refibrillation, survival to admission or discharge. Improved ROSC pre-hospital with biphasic compared to one form of monophasic

1 Observational Studies

Hagihara et al., 2018: Interaction of defibrillation waveform with the time to defibrillation or the number of defibrillation attempts on survival from OOHCA

● Evaluation of all OOHCA in Japan from 2005-2014

● Improved ROSC, 1 month survival and CPC score with biphasic compared to monophasic

1 Experimental Studies

Tang et al., 2001: A comparison of biphasic and monophasic waveform defibrillation after prolonged VF

● VF induced in 20 pigs. Untreated VF for 10 minutes and then randomized with 3 150 J biphasic shocks or 200-300-360 J monophasic shocks

● No difference in ROSC or survival. Less impaired myocardial function post-resuscitation with biphasic

Tang et al., 2004: The effects of biphasic waveform design on post-resuscitation myocardial function

● Randomized 4 groups of pigs with 7 minutes of electrically induced VF. Randomized to low energy biphasic truncated defibrillation at 150 or 200 J or high energy biphasic at 200 or 360 J

● No difference in survival or neuro alertness score amongst four groups. Lower ROSC with BTEH 200 J

● Animals with BTEL required fewer shocks, less CPR, and less energy. Myocardial function (CO, SV, EF, MAP) best for lower energy

Outcome: ROSC

5 Clinical Trials

Kudenchuk et al., 2006: Transthoracic incremental monophasic versus biphasic defibrillation by emergency responders

● Adults with non-traumatic OOH VF were randomly allocated to monophasic or biphasic waveforms

● No difference in presence of VF or organized rhythm, survival to discharge, or neuro outcome.

Schneider et al., 2000: Multicenter, randomized, controlled trial of 150 J biphasic shocks compared with 200 to 360 J monophasic shocks in the resuscitation of OOHCA victims

● AEDs randomized according to waveform on daily basis in 4 EDs

● Higher ROSC with biphasic and good neuro outcome, but no difference in survival

Morrison et al., 2005: OOHCA rectilinear biphasic to monophasic damped sine defibrillation waveforms with ALS intervention trial (ORBIT)

● OHCA requiring at least one shock treated by ALS paramedics

● No difference in ROSC, survival to discharge. However, within 4-10 minutes of bystander witnessed, improved survival with biphasic

● Higher success in conversion to organized rhythm with first shock in BP (increased probability by 57%)

Martens et al., 2001: Optimal response to cardiac arrest study: defibrillation waveforms effects

● AEDs randomized according to waveform on daily basis in 4 EDs for adults with VF and cardiac etiology

● No difference in refibrillation, survival to admission or discharge. Improved ROSC pre-hospital with biphasic compared to one form of monophasic

van Alem et al., 2003: A prospective, randomised and blinded comparison of first shock success of monophasic and biphasic waveforms in OOHCA

● Compared AEDs with monophasic and biphasic waveforms in adults with OOHCA (both received an initial shock of 200 J)

● Higher first success rate of conversion to an organized rhythm for BP. No difference in termination of VF at 5 seconds, survival, or ROSC

1 Observational Studies

Hagihara et al., 2018: Interaction of defibrillation waveform with the time to defibrillation or the number of defibrillation attempts on survival from OOHCA

● Evaluation of all OOHCA in Japan from 2005-2014

● Improved ROSC, 1 month survival and CPC score with biphasic compared to monophasic

11 Experimental Studies

Tang et al., 2001: A comparison of biphasic and monophasic waveform defibrillation after prolonged VF

● VF induced in 20 pigs. Untreated VF for 10 minutes and then randomized with 3 150 J biphasic shocks or 200-300-360 J monophasic shocks

● No difference in ROSC or survival.

Tang et al., 1999: The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function

● 20 pigs with induced VF with either 4 or 7 minutes of untreated VF randomized to three 150 J biphasic shocks or escalating monophasic shocks

● Biphasic associated with less myocardial dysfunction compared to escalating monophasic. No difference in ROSC

Tang et al., 2004: The effects of biphasic waveform design on post-resuscitation myocardial function

● Randomized 4 groups of pigs with 7 minutes of electrically induced VF. Randomized to low energy biphasic truncated defibrillation at 150 or 200 J or high energy biphasic at 200 or 360 J

● No difference in survival or neuro alertness score amongst four groups. Lower ROSC with BTEH 200 J

Clark et al., 2002: Transthoracic biphasic waveform defibrillation at very high and very low energies: a comparison with monophasic waveforms in an animal model of VF

● 13 swine with electrically induced VF that received monophasic and biphasic shocks in random order

● Successful defibrillation increased with increasing energy. Biphasic superior at lower energy; no significant difference at higher energy levels

Lee et al., 2008: The efficacy and safety of external biphasic defibrillation in toy breed dogs

● Evaluated 10 toy breed dogs with BP versus MP

● BP required 30% less shock energy and was more effective at converting at all time points than MP. All dogs survived

Niemann et al., 2000: Monophasic versus biphasic transthoracic countershock after prolonged VF in a swine model

● Swine randomized to receive either monophasic truncated exponential shocks or low-energy (150 J) monophasic shocks

● No difference in ROSC, CPR time, or hemodynamic variables

Leng et al., 2000: Resuscitation after prolonged VF with use of monophasic and biphasic waveform pulses for external defibrillation

● Randomized 26 dogs to monophasic or biphasic waveforms with induced VF

● Less myocardial dysfunction with biphasic. Shorter resuscitation times for biphasic with prolonged CPA, but no difference in ROSC

Zhang et al., 2003: Open-chest epicardial surgical defibrillation

● 28 pigs with induced VF randomized to monophasic or biphasic epicardial, open chest defibrillation

● With small surgical paddles, greater shock success rate with BP. No difference with large paddles

Clark et al., 2001: Pediatric transthoracic defibrillation: biphasic versus monophasic waveforms in an experimental model

● 27 piglets with induced VF and administered BP and MP shocks

● BP had better termination of VF than MP

Flaker et al., 1989: Superiority of biphasic shocks in the defibrillation of dogs by epicardial patches and catheter electrodes

● Patches implanted on LV and RV of 28 dogs with induced VF and 7 dogs with transvenous catheter with electrodes. Administered BP and MP shocks

● BP superior at some energy levels for patches; with the catheter electrodes, BP universally more effective at terminating rhythm and ROSC

Scott et al., 1993: Transthoracic defibrillation: effect of dual-pathway sequential pulse shocks and single-pathway biphasic pulse shocks in a canine model

● Three groups of dogs administered shocks of variable duration, voltage, and polarity for MP and BP

● No difference between them at any level

Outcome: Surrogate markers of perfusion

0 Clinical Trials

0 Observational Studies

6 Experimental Studies

Tang et al., 2001: A comparison of biphasic and monophasic waveform defibrillation after prolonged VF

● VF induced in 20 pigs. Untreated VF for 10 minutes and then randomized with 3 150 J biphasic shocks or 200-300-360 J monophasic shocks

● No difference in ROSC or survival. Less impaired myocardial function post-resuscitation with biphasic

Niemann et al., 2000: Monophasic versus biphasic transthoracic countershock after prolonged VF in a swine model

● Swine randomized to receive either monophasic truncated exponential shocks or low-energy (150 J) monophasic shocks

● No difference in ROSC, CPR time, or hemodynamic variables

Tang et al., 1999: The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function

● 20 pigs with induced VF with either 4 or 7 minutes of untreated VF randomized to three 150 J biphasic shocks or escalating monophasic shocks

● Biphasic associated with less myocardial dysfunction compared to escalating monophasic

Tang et al., 2004: The effects of biphasic waveform design on post-resuscitation myocardial function

● Randomized 4 groups of pigs with 7 minutes of electrically induced VF. Randomized to low energy biphasic truncated defibrillation at 150 or 200 J or high energy biphasic at 200 or 360 J

● Animals with BTEL required fewer shocks, less CPR, and less energy. Myocardial function (CO, SV, EF, MAP) best for lower energy

Leng et al., 2000: Resuscitation after prolonged VF with use of monophasic and biphasic waveform pulses for external defibrillation

● Randomized 26 dogs to monophasic or biphasic waveforms with induced VF

● Less myocardial dysfunction with biphasic. Shorter resuscitation times for biphasic with prolonged CPA

Lee et al., 2008: The efficacy and safety of external biphasic defibrillation in toy breed dogs

● Evaluated 10 toy breed dogs with BP versus MP

● BP required 30% less shock energy, cardiac biomarkers elevated and sustained for longer periods in MP group and ECG changes more severe and longer in MP group. LV cardiac performance severely depressed in MP group

Osswald et al., 1994: Relation between shock related myocardial injury and defibrillation efficacy of monophasic and biphasic shocks in a canine model

● Different waveforms tested in 12 dogs using implantable devices

● BP associated with less injurious effects on myocardial oxidative metabolism and hemodynamic performance