RECOVER 2.0 Worksheet

QUESTION ID: ALS-12

PICO Question:
In cats and dogs with CPA due to a shockable rhythm (P) does the use of standard dose fixed energy shocks (I) compared with escalating energy shocks (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 neuro outcome
2. Survival to discharge
3. ROSC
4. Surrogate markers of perfusion

Domain chairs: Gareth Buckley, Elizabeth Rozanski, Jake Wolf

Evidence evaluators: Virginie Wurlod, Claudio Correa Natalini

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 neuro outcome
1	CT	0	- -	0	0								Low
1	OS	-	-	0	0							No control group. Similar to hx control	Very low
Outcome: Survival to discharge
2	CT	0	- -	0	0							No difference in survival, but likely not powered	Low
2	OS	-	-	0	0							No clear difference	Very low
Outcome: ROSC
3	CT	-	-	-	0							No difference in ROSC	Low
2	OS	0	-	–	-							No clear difference	Low
9	ES	-	-	-	-							No clear difference	Low
Outcome: Surrogate markers of perfusion
0	CT
0	OS
5	ES	0	-	-	-							No difference	Low

PICO Question Summary

Introduction

High defibrillation energy has been associated with increased myocardial injury during the post-resuscitation period. 1 However, unsuccessfully defibrillated patients with ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) invariably fail to achieve ROSC. Two energy strategies have been suggested for repeated biphasic defibrillation: a fixed energy strategy (commonly repeated doses of 150 J in adult humans) and an escalating energy strategy (commonly 200-300-360 J in adult humans).2 Current veterinary guidelines state that an escalating defibrillation energy protocol, compared to a fixed energy protocol, may be considered when using both biphasic and monophasic defibrillators.3 The American Heart Association guidelines for human advanced life support suggest that either fixed or escalating defibrillation energy protocols may be considered.4

Consensus on science

Outcome 1: Favorable neurologic outcome For the most critical outcome of favorable neurologic outcome, one clinical trial in humans was identified (low quality of evidence due to very serious indirectness)5 The clinical trial found no difference in neurologic outcome or survival in adults with out-of-hospital cardiac arrest treated with an escalating versus fixed energy protocol; however, it was not powered to do so. While the study showed no difference in conversion rates of a single initial biphasic shock at 150 vs. 200J, the authors did show that with repeated shocks, escalating doses (200-300-360J) resulted in a higher conversion frequency (36.6% vs 24.7%, P=0.035) and higher VF termination frequency than a fixed, lower dose (150-150-150J) regimen (82.5% vs 71.2%, P=0.027).5 One observational study in humans (very low quality of evidence, downgraded due to serious risk of bias and serious indirectness) did not contain a control group, but found that low-energy fixed biphasic shocks could result in similar neurologic outcomes, survival to discharge, and ROSC as those historically reported with escalating monophasic therapy.6 Outcome 2: Survival to discharge For the outcome of survival to discharge, in addition to the Stiell et al. trial described above, a second clinical trial in adults with in-hospital cardiac arrest directly compared low-energy, fixed shocks (150 J) and high-energy, escalating shocks (200-300-360 J) (low quality of evidence due to very serious indirectness).2 If ROSC was not achieved after the third shock in the fixed shock group, they were converted to high-energy, escalating shocks. No difference in survival (24 hour, 7 day, or 30 day), ROSC, or first shock termination was noted between groups. However, a rhythm conversion rate of 39% was noted after failed lower shocks when the dose was then escalated to 360 J on the fourth shock. Therefore, the authors recommended starting at the low initial shock dose and then switching to high energy (360J) if the patient was not successfully defibrillated after the first shock. In addition to the White study described above, one additional observational study (very low quality of evidence, downgraded due to serious risk of bias and serious indirectness) in adults with out-of-hospital cardiac arrest with presumed cardiac etiology showed no difference in survival between those treated with a fixed protocol of 360 J versus those treated with an escalating protocol of 200 to 360 J.7 Outcome 3: ROSC In addition to the clinical and observational trials described above, 1 experimental swine study compared fixed dose biphasic defibrillation (150J) with escalating dose defibrillation (200-300-360J).8 This study found higher successful defibrillation and ROSC in the escalation therapy group compared to the fixed therapy group (15/18 pigs versus 5/17 pigs, P < 0.002). Nine pigs in the fixed energy group were successfully defibrillated when converted to the escalating therapy group after three fixed shocks.

Treatment recommendation

We recommend that for dogs and cats with shockable arrest rhythms, if an initial standard dose (2 J/kg) electrical defibrillation is unsuccessful the second and subsequent shocks be delivered at a dose of 2x the initial dose (4 J/kg). (strong recommendation, low quality of evidence).

Justification of treatment recommendation

The 2 human clinical trials reviewed for the PICO question provide compelling evidence that in adult humans, there is no difference in the efficacy of the first electrical defibrillation between standard biphasic dosing (150J) and high energy biphasic dosing (200J). Therefore, we recommend that the standard dosing regimen for monophasic and biphasic dosing continue to be used for the initial shock in dogs and cats with shockable arrest rhythms. However, if the initial shock is unsuccessful, the evidence from the clinical trials and the one experimental swine study reviewed for this PICO question suggest that at a minimum, doubling the initial dose for subsequent shocks improves the efficacy of subsequent electrical defibrillations. Additional dose escalation may be beneficial, but the dose at which risk outweighs benefit is unknown and thus the committee chose not to recommend energy in doses over twice the initial dose.

Knowledge gaps

The optimal defibrillation energy dosing and escalation protocols for dogs and cats have not been studied. Previous studies have only examined a small subset of defibrillation dosing strategies targeted at adult humans.

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. Anantharaman V, Tay SY, Manning PG, et al. A multicenter prospective randomized study comparing the efficacy of escalating higher biphasic versus low biphasic energy defibrillations in patients presenting with cardiac arrest in the in-hospital environment. Open Access Emerg Med. 2017;9:9-17.

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. 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.

5. Stiell IG, Walker RG, Nesbitt LP, et al. BIPHASIC Trial: a randomized comparison of fixed lower versus escalating higher energy levels for defibrillation in out-of-hospital cardiac arrest. Circulation. 2007;115(12):1511-1517.

6. White RD, Hankins DG, Atkinson EJ. Patient outcomes following defibrillation with a low energy biphasic truncated exponential waveform in out-of-hospital cardiac arrest. Resuscitation. 2001;49(1):9-14.

7. Olsen JA, Brunborg C, Steinberg M, et al. Survival to hospital discharge with biphasic fixed 360 joules versus 200 escalating to 360 joules defibrillation strategies in out-of-hospital cardiac arrest of presumed cardiac etiology. Resuscitation. 2019;136:112-118.

8. Niemann JT, Rosborough JP, Walker RG. A model of ischemically induced ventricular fibrillation for comparison of fixed-dose and escalating-dose defibrillation strategies. Acad Emerg Med. 2004;11(6):619-624.

Supplemental:

Outcome: Favorable neurologic outcome

1 Clinical Trial

Stiell et al., 2007: BIPHASIC Trial: A randomized comparison of fixed lower versus escalating higher energy levels for defibrillation in OOHCA

● AEDs randomly programmed to provide either fixed lower energy regiment of 150 J for all shocks or escalating higher energy regimen of 200 J, 300 J, 360 J

● 221 patients enrolled, however only 106 received 2 or more shocks (and therefore were directly compared)

● No difference in single shock, but significant for termination of VF and conversion to organized rhythm with escalating therapy. Not powered to detect a survival difference or neuro outcome

1 Observational Studies

White et al., 2001: Patient outcomes following defibrillation with a low energy biphasic truncated exponential waveform in OOHCA

● Evaluation of non-escalating low-energy AEDs in adults with OOHCA and VF delivered by first-arriving personnel

● No control group

● 46% survived to discharge and were neurologically intact (CPC 1), which they said is comparable to previous experience with high energy, escalating shock therapy

3 Experimental Studies

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

● VF induced in 20 pigs receiving MV. After 10 minutes, randomized to receive either 150 J biphasic waveform shocks or escalating monophasic waveform shocks

● No difference in survival, ROSC, or neuro alertness score

● Better myocardial function with biphasic shocks

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

Berg et al., 2005: Better outcome after pediatric defibrillation dosage than adult dosage in a swine model of pediatric VF

● 7 min untreated VF in piglets randomized to biphasic pediatric escalating dose or biphasic adult dose escalating dose

● Improved survival with good neuro outcome with pediatric shocks. Improved cTnT and LV EF in lower dose. No difference in ROSC or survival

Outcome: Survival to discharge

2 Clinical Trials

Stiell et al., 2007: BIPHASIC Trial: A randomized comparison of fixed lower versus escalating higher energy levels for defibrillation in OOHCA

● AEDs randomly programmed to provide either fixed lower energy regiment of 150 J for all shocks or escalating higher energy regimen of 200 J, 300 J, 360 J

● 221 patients enrolled, however only 106 received 2 or more shocks (and therefore were directly compared)

● No difference in single shock, but significant for termination of VF and conversion to organized rhythm. Not powered to detect a survival difference or neuro outcome

Anantharam et al., 2017: A multicenter prospective randomized study comparing the efficacy of escalating higher biphasic versus low biphasic energy defibrillators in patients presenting with cardiac arrest in the in hospital environment

● 235 adults with in hospital VF/VT that received either low energy shocks (150 J) or high energy escalating shocks, If ROSC not achieved by the third shock, patients crossed over to the high energy shock

● No difference in first shock termination and ROSC or survival (24 hour, 7 day, or 30 day)

● Conversion rate of 39% at 360 J after failed lower shocks and recommended increasing from 150-200 J to 360 J quickly if not successfully defibrillated in first instance

3 Observational Studies

White et al., 2001: Patient outcomes following defibrillation with a low energy biphasic truncated exponential waveform in OOHCA

● Evaluation of non-escalating low-energy AEDs in adults with OOHCA and VF delivered by first-arriving personnel

● No control group

● 46% survived to discharge and were neurologically intact (CPC 1), which they said is comparable to previous experience with high energy, escalating shock therapy

Hoyme et al., 2020: Improved survival to hospital discharge in pediatric IHCA using 2 J/kg as first defibrillation dose for initial pulseless ventricular arrhythmia

● Children with IHCA and VF/pVT. Compared <1.7 J/kg, 1.7-2.5 J/kg, and >2.5 J/kg

● First dose other than 1.7-2.5 J/kg are associated with lower survival to hospital discharge in children < 12 and first doses >2.5 had lower survival and ROSC in children < 18 with VF. Only examined initial shock, not escalating shocks

Olsen et al., 2019: Survival to hospital discharge with biphasic fixed 360 J v 200 escalating to 360 J defibrillation strategies in OOHCA of presumed cardiac etiology

● Escalating group included 360 patients with 883 shocks versus 478 patients and 1736 shocks in fixed high energy

● No difference in survival to hospital discharge

0 Experimental Studies

Outcome: ROSC

3 Clinical Trials

Stiell et al., 2007: BIPHASIC Trial: A randomized comparison of fixed lower versus escalating higher energy levels for defibrillation in OOHCA

● AEDs randomly programmed to provide either fixed lower energy regiment of 150 J for all shocks or escalating higher energy regimen of 200 J, 300 J, 360 J

● 221 patients enrolled, however only 106 received 2 or more shocks (and therefore were directly compared)

● No difference in single shock, but significant for termination of VF and conversion to organized rhythm. Not powered to detect a survival difference or neuro outcome

Anantharam et al., 2017: A multicenter prospective randomized study comparing the efficacy of escalating higher biphasic versus low biphasic energy defibrillators in patients presenting with cardiac arrest in the in hospital environment

● 235 adults with in hospital VF/VT that received either low energy shocks (150 J) or high energy escalating shocks, If ROSC not achieved by the third shock, patients crossed over to the high energy shock

● No difference in first shock termination and ROSC or survival (24 hour, 7 day, or 30 day)

● Conversion rate of 39% at 360 J after failed lower shocks and recommended increasing from 150-200 J to 360 J quickly if not successfully defibrillated in first instance

Anantharam et al., 2017: Role of peak current in conversion of patients with VF

● Adults older than 21 with non-traumatic VF or pVT and randomized (cluster, envelope randomization) to either low energy (150 J) or escalating higher energy (both biphasic)

● However, low energy still received escalating if still in VF after two shocks. Also measured transthoracic impedance

● No difference in ROSC (not powered to evaluate). Primarily evaluated TTI

2 Observational Studies

White et al., 2001: Patient outcomes following defibrillation with a low energy biphasic truncated exponential waveform in OOHCA

● Evaluation of non-escalating low-energy AEDs in adults with OOHCA and VF delivered by first-arriving personnel

● No control group

● 46% survived to discharge and were neurologically intact (CPC 1), which they said is comparable to previous experience with high energy, escalating shock therapy. ROSC achieved in 28 out of 35

Hoyme et al., 2020: Improved survival to hospital discharge in pediatric IHCA using 2 J/kg as first defibrillation dose for initial pulseless ventricular arrhythmia

● Children with IHCA and VF/pVT. Compared <1.7 J/kg, 1.7-2.5 J/kg, and >2.5 J/kg

● First dose other than 1.7-2.5 J/kg are associated with lower survival to hospital discharge in children < 12 and first doses >2.5 had lower survival and ROSC in children < 18 with VF. Only examined initial shock, not escalating shocks

9 Experimental Studies

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

● No difference in ROSC, survival

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

● VF induced in 20 pigs receiving MV. After 10 minutes, randomized to receive either 150 J biphasic waveform shocks or escalating monophasic waveform shocks

● No difference in survival, ROSC, or neuro alertness score

Niemann et al., 2004: A model of ischemically induced VF for comparison of fixed-dose and escalating-dose defibrillation strategies

● 46 swine with VF via balloon occlusion of coronary artery. 1-5 minutes of VF and countershocks with biphasic waveform. Randomized to receive low energy (150 J) or escalating higher energy (200-300-360 J) shocks

● Improved successful defibrillation and ROSC in escalating group (5/17 v. 15/18) with fewer than 3 shocks. 9 animals in group one successfully defibrillated when converted to group 2

Berg et al., 2004: Attenuated adult biphasic shocks compared with weight-based monophasic shocks in a swine model of prolonged pediatric VF

● 7 min untreated VF in piglets randomized to either biphasic escalating shocks or weight based (2-4 J/kg)

● For 24 kg piglets, higher survival with good neuro outcome and LVEF 1-4 hours after ROSC in the attenuated biphasic adult shocks. Both had escalating structures

Berg et al., 2005: Better outcome after pediatric defibrillation dosage than adult dosage in a swine model of pediatric VF

● 7 min untreated VF in piglets randomized to biphasic pediatric escalating dose or biphasic adult dose escalating dose

● No difference in ROSC or survival

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

Flaker et al., 1990: The effect of multiple shocks on canine cardiac defibrillation

● Dogs with induced VF and subject to either monophasic or biphasic defibrillation at 7, 12, 13, or 18 J

● Low energy shocks created a sensitizing effect on cardiac tissue, allowing more successful defibrillation with repeated shocks

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

Outcome: Surrogate markers of perfusion

0 Clinical Trials

0 Observational Studies

5 Experimental Studies

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

● VF induced in 20 pigs receiving MV. After 10 minutes, randomized to receive either 150 J biphasic waveform shocks or escalating monophasic waveform shocks

● Better myocardial function with biphasic shocks

Berg et al., 2005: Better outcome after pediatric defibrillation dosage than adult dosage in a swine model of pediatric VF

● 7 min untreated VF in piglets randomized to biphasic pediatric escalating dose or biphasic adult dose escalating dose

● Improved cTnT and LV EF in lower dose.

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

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

Berg et al., 2004: Attenuated adult biphasic shocks compared with weight-based monophasic shocks in a swine model of prolonged pediatric VF

● 7 min untreated VF in piglets randomized to either biphasic escalating shocks or weight based (2-4 J/kg)

● For 24 kg piglets, higher survival with good neuro outcome and LVEF 1-4 hours after ROSC in the attenuated biphasic adult shocks. Both had escalating structures

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 first shock success, second, or third. No difference in CPR time or hemodynamic variables post-resuscitation