C2005 Evidence Evaluation Template - Oct.14,...

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REMEMBER TO SAVE THE BLANK WORKSHEET TEMPLATE USING THE FILENAME FORMAT

WORKSHEET for PROPOSED Evidence-Based GUIDELINE RECOMMENDATIONSNOTE: Save worksheet using the following filename format: Taskforce.Topic.Author.Date.Doc where Taskforce is a=ACLS, b=BLS, p=Pediatric, n=neonatal and i=Interdisciplinary. Use 2 or 3 letter abbreviation for author’s name and 30Jul03 as sample date format.Worksheet Author: Karl B. Kern, MDUniversity of Arizona

Taskforce/Subcommittee: _X_BLS __ACLS __PEDS __ID __PROAD__Other:

Author’s Home Resuscitation Council: _X_AHA __ANZCOR __CLAR __ERC __HSFC__HSFC __RCSA ___IAHF ___Other:

Date Submitted to Subcommittee: Original: March 1, 2004; Revised: Aug 15, 2004, Final: Dec 12, 2004

STEP 1: STATE THE PROPOSAL. State if this is a proposed new guideline; revision to current guideline; or deletion of current guideline.Existing guideline, practice or training activity, or new guideline:

This is a re-evaluation of the current guideline.

Guidelines 2000 states: “Biphasic waveform defibrillation with shocks < 200 J is safe and has equivalent or higher efficacy for termination of ventricular fibrillation (VF) compared with higher-energy escalating monophasic-waveform shocks (Class IIa)” [p.I-60].

Further, the Guidelines 2000 state, “At this time no studies have reported experience with other biphasic waveforms in long-duration VF in out-of-hospital arrest. When such data becomes available, it will need to be assessed by the same evidence-evaluation process as used for the biphasic AED and this guidelines process.

The data indicates that biphasic waveform shocks of relatively low energy ( 200 J) are safe and have equivalent or higher efficacy for termination of VF compared with higher-energy escalating monophasic waveform shocks (Class IIa). The safety and efficacy data related to specific biphasic waveforms must be evaluated on an individual basis in both in-hospital (electrophysiology studies, ICD testing) and out-of-hospital settings [p. I-63].

The optimal energies for biphasic defibrillation have not been determined. Importantly, the biphasic first-shock energy level yielding the highest termination rate for VF is unknown. The percentage of patients who fail to respond to a first or successive biphasic shock at a constant energy of 200 J remains unknown. Do patients in

VF that is unresponsive to multiple "lower-energy" shocks then require higher-energy (escalating) biphasic shocks? Or will these patients require only repetition of low-energy biphasic shocks?

Research has not yet determined the optimal biphasic waveform. The potential advantages of new biphasic waveform variants, such as a rectilinear first pulse waveform, are also unknown.

Finally, it will be important to determine whether a waveform more effective for immediate outcomes (defibrillation) and short-term outcomes (spontaneous circulation, admission to the hospital) results in better long-term outcomes (survival to hospital discharge, survival for 1 year). These are critical questions in communities in which the interval from collapse to first shock remains long.

We cannot make a definitive recommendation for the energy for first and subsequent nonescalating biphasic defibrillation attempts. Current research confirms that biphasic shock energies 200 J are safe and effective. Even though both escalating- and nonescalating-energy defibrillators are available, there is insufficient data to recommend one approach over another.” [p. I-90-91].

Biphasic waveform defibrillators are conditionally acceptable—regardless of initial shock energy and regardless of the energy level of subsequent shocks (nonescalating) [p. I-148-9].

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Step 1A: Refine the question; state the question as a positive (or negative) hypothesis. State proposed guideline recommendation as a specific, positive hypothesis. Use single sentence if possible. Include type of patients; setting (in- /out-of-hospital); specific interventions (dose, route); specific outcomes (ROSC vs. hospital discharge).“Biphasic waveforms for use in transthoracic external defibrillation of VF cardiac arrest are more efficacious (higher rates of VF termination, ROSC, and survival) as well as safer (less adverse effects) than monophasic waveforms”. Step 1B: Gather the Evidence; define your search strategy. Describe search results; describe best sources for evidence.

Initial search term used was Biphasic Defibrillation. This produced numerous articles (AHA EndNote library = 68; Google = 13,300 Medline = 55; PubMed = 562. The Google search was obviously overwhelming and yielded mostly advertisement or industry sponsored sites. The PubMed search was most helpful when limited to ‘Biphasic Ventricular Defibrillation’ to include all clinical reports from Jan 1 2000 to present (n = 34). Even then 12/34 were for atrial fibrillation and 12/34 were for Internal defibrillation devices (ICDs).

Search term most productive was limiting it to the text word term, “Ventricular Defibrillation”List electronic databases searched (at least AHA EndNote 7 Master library [http://ecc.heart.org/], Cochrane database for systematic reviews and Central Register of Controlled Trials [http://www.cochrane.org/], MEDLINE [http://www.ncbi.nlm.nih.gov/PubMed/ ], and Embase), and hand searches of journals, review articles, and books.

Electronic searches were made using AHA EndNote 7 Master Library (July 2004); Google; Medline; PubMed, and Cochrane Central Register of Controlled Clinical trials. Hand search of all acquired articles references and all issues of Resuscitation from 2000 onward was also done.• State major criteria you used to limit your search; state inclusion or exclusion criteria (e.g., only human studies with control group? no animal studies? N subjects

> minimal number? type of methodology? peer-reviewed manuscripts only? no abstract-only studies?)

Eliminated all but ventricular defibrillation (no atrial fibrillation studies). ICD device studies were eliminated, though studies of transthoracic defibrillation performed during electrophysiology (EP) studies, including post ICD implantation testing were reviewed. Two defibrillation studies comparing biphasic vs monophasic waveforms during open heart surgery were also reviewed, but are not applicable to the above stated hypotheses, hence are not included in the summary grid. Only studies since Jan 2000 were included .(i.e. since the 2000 Guidelines), though the previous 2000 worksheet was reviewed for relevant citations.

• Number of articles/sources meeting criteria for further review: Create a citation marker for each study (use the author initials and date or Arabic numeral, e.g., “Cummins-1”). . If possible, please supply file of best references; EndNote 6+ required as reference manager using the ECC reference library.

54 studies were initially located, while 27 were obtained for detailed review (after eliminating ICD defibrillation studies and the open chest studies), including 11 clinical reports and 16 animal studies (all since Jan 1, 2000). Final grid included only studies of prolonged VF, primary endpoints, and no abstracts or secondary reports of previously included data sets.

STEP 2: ASSESS THE QUALITY OF EACH STUDYStep 2A: Determine the Level of Evidence. For each article/source from step 1, assign a level of evidence—based on study design and methodology.

Level of Evidence

Definitions(See manuscript for full details)

Level 1 Randomized clinical trials or meta-analyses of multiple clinical trials with substantial treatment effectsLevel 2 Randomized clinical trials with smaller or less significant treatment effectsLevel 3 Prospective, controlled, non-randomized, cohort studiesLevel 4 Historic, non-randomized, cohort or case-control studiesLevel 5 Case series: patients compiled in serial fashion, lacking a control groupLevel 6 Animal studies or mechanical model studiesLevel 7 Extrapolations from existing data collected for other purposes, theoretical analysesLevel 8 Rational conjecture (common sense); common practices accepted before evidence-based guidelines

http://www.ncbi.nlm.nih.gov/PubMed/

http://www.cochrane.org/

http://ecc.heart.org/

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Step 2B: Critically assess each article/source in terms of research design and methods. Was the study well executed? Suggested criteria appear in the table below. Assess design and methods and provide an overall rating. Ratings apply within each Level; a Level 1 study can be excellent or poor as a clinical trial, just as a Level 6 study could be excellent or poor as an animal study. Where applicable, please use a superscripted code (shown below) to categorize the primary endpoint of each study. For more detailed explanations please see attached assessment form.

Component of Study and Rating Excellent Good Fair Poor UnsatisfactoryDesign &

Methods

Highly appropriate sample or model, randomized, proper controls ANDOutstanding accuracy, precision, and data collection in its class

Highly appropriate sample or model, randomized, proper controlsOROutstanding accuracy, precision, and data collection in its class

Adequate, design, but possibly biased

ORAdequate under the circumstances

Small or clearly biased population or model

ORWeakly defensible in its class, limited data or measures

Anecdotal, no controls, off target end-points

ORNot defensible in its class, insufficient data or measures

Step 2C: Determine the direction of the results and the statistics: supportive? neutral? opposed?

DIRECTION of study by results & statistics: SUPPORT the proposal NEUTRAL OPPOSE the proposal

ResultsOutcome of proposed guideline superior, to a clinically important degree, to current approaches

Outcome of proposed guideline no different from current approach

Outcome of proposed guideline inferior to current approach

Step 2D: Cross-tabulate assessed studies by a) level, b) quality and c) direction (ie, supporting or neutral/ opposing); combine and summarize. Exclude the Poor and Unsatisfactory studies. Sort the Excellent, Good, and Fair quality studies by both Level and Quality of evidence, and Direction of support in the summary grids below. Use citation marker (e.g. author/ date/source). In the Neutral or Opposing grid use bold font for Opposing studies to distinguish them from merely neutral studies. Where applicable, please use a superscripted code (shown below) to categorize the primary endpoint of each study.

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Supporting Evidence Question: Are Biphasic waveforms more efficacious and safer than monophasic for transthoracic defibrillation?

All identified studies

Qua

lity

of E

vide

nce

Excellent

Good

Faddy 2003 E1

Morrison 2005Pre E2

VanAlem 2003 E2

Schwarz 2003 E1*

Schnieder 2000 E1, [A, B]

Higgins 2000 E1

Stothert 2004 E1, [E2

Carpenter 2003 E1: (BTE >MTE)E2: (BTE >MDS)

Tang 2001 E3

Fair Martens 2001 E1, [A] (BTE>MTE)

Zhang 2003 E1*Walker 2003 E1Clark 2002 E1Zhang 2001 E1Garcia 2000 E1Tang 2000 E3Niemann 2000b [E3]Leng 2000 [E3]

1 2 3 4 5 6 7 8Level of Evidence

A = Return of spontaneous circulation Of Note: Bold names are prolonged VF, non-bold names are very short VF B = Survival of event [ ] indicates a secondary endpoint result, which was often underpoweredC = Survival to hospital discharge * = open chest defibrillationD = Intact neurological survivalE = Other endpoint:

E1 = Termination of VF to any non-VF rhythm [Term VF]; E2 = Organized rhythm within 1 minute post shock [Organized]; E3 = Post resuscitation myocardial dysfunction, [ PRMD] (1=Terminate VF, 2=organized rhythm post shock, 3=PRMD)

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Neutral or Opposing Evidence!!Note: Many of the “Neutral” results here are secondary endpoints reported in the study, but known to be underpowered!!

Question: Are Biphasic waveforms more efficacious and safer than monophasic for transthoracic defibrillation?All identified studies

Qua

lity

of E

vide

nce

Excellent

Good

Morrison 2005Pre [A, B, C, D]

VanAlem 2003 [A,B,C,D]

Schnieder 2000 [C]

Higgins 2000 [E3]

Stothert 2004 [A]Tang 2001 A, B

Niemann 2000a E1, A, B, E3

FairMartens 2001 A, E1(BTE=MDS)

Bain 2001 E2(MTE = BTE)

Carpenter 2003 [C](MTE >BTE)

White 2001 A, C(MDS = BTE)

Niemann 2003a [E1]Niemann 2003b E1Niemann 2000b AGarcia 2000 ALeng 2000 A, B, [E3]


A = Return of spontaneous circulation C = Survival to hospital discharge E = Other endpoints (see above)B = Survival of event D = Intact neurological survival

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Question: Are Biphasic waveforms more efficacious and safer than monophasic for transthoracic defibrillation?

Open Chest studies only Supporting Evidence

Qua

lity

of E

vide

nce

Excellent

Good Schwarz 2003 E1*

Fair Zhang 2003 E1*


A = Return of spontaneous circulation Of Note: Bold names are prolonged VF, non-bold names are very short VF B = Survival of event [ ] indicates a secondary endpoint result which were often underpoweredC = Survival to hospital discharge * = open chest defibrillationD = Intact neurological survivalE = Other endpoint (1=Term VF, 2=organized rhythm post shock, 3=PRMD) (PRMD = post-resuscitation myocardial dysfunction)

Neutral or Opposing Evidence!! None

Qua

lity

of E

vide

nce

Excellent

Good

Fair



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Question: Are Biphasic waveforms more efficacious and safer than monophasic for transthoracic defibrillation?

Short duration VF (<90 seconds) Supporting Evidence

Qua

lity

of E

vide

nce

Excellent

Good Faddy 2003 E1 Higgins 2000 E1

FairWalker 2003 E1Clark 2002 E1Zhang 2001 E1Niemann 2000b [E3]Leng 2000 [E3]


A = Return of spontaneous circulation Of Note: Bold names are prolonged VF, non-bold names are very short VF B = Survival of event [ ] indicates a secondary endpoint result which were often underpoweredC = Survival to hospital discharge D = Intact neurological survivalE = Other endpoint (1=Terminate VF, 2=organized rhythm post shock, 3=PRMD)

Neutral or Opposing Evidence !!Many of the “Neutral” results here are secondary endpoints, reported in the study, but known to be underpowered!!

Qua

lity

of E

vide

nce

Excellent

GoodHiggins 2000 [E3]

Fair Bain 2001 E2(MTE = BTE)

Niemann 2000b A


A = Return of spontaneous circulation C = Survival to hospital discharge E = Other endpoints (see above)B = Survival of event D = Intact neurological survival = abstract 0nly

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Question: Are Biphasic waveforms more efficacious and safer than monophasic for transthoracic defibrillation for prolonged (>5 min) VF?

Supporting Evidence

Qua

lity

of E

vide

nce

Excellent

GoodMorrison 2005Pre E2

VanAlem 2003 E2

Schnieder 2000 E1, [A, B]

Stothert 2004 E1, [E2


Tang 2001 E3

Fair Martens 2001 E1, [A] (BTE>MTE) Garcia 2000 E1

Tang 2000 E3



Neutral or Opposing Evidence !!Many of the “Neutral” results here are secondary endpoints, reported in the study, but known to be

underpowered!!

Qua

lity

of E

vide

nce

Excellent

Good

Morrison 2005Pre[A, B, C, D]

VanAlem 2003 [A,B,C,D]

Schnieder 2000 [C]

Tang 2001 A, B


Fair Martens 2001 A, E1(BTE=MDS)

Stothert 2004 [A

Carpenter 2003 [C](MTE >BTE)

White 2001 A, C(MDS = BTE)

Niemann 2003a [E1]

Niemann 2003b E1

Garcia 2000 A

Leng 2000 A, B, [E3]


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Question: Are Biphasic waveforms more efficacious and safer than monophasic for transthoracic defibrillation for prolonged (>5 min) VF? --Primary Endpoints Only--

Supporting Evidence

Qua

lity

of E

vide

nce

Excellent

Good

Morrison 2005Pre E2

VanAlem 2003 E2

Schnieder 2000 E1

Stothert 2004 E1, [


Tang 2001 E3

Fair Martens 2001 E1 (BTE>MTE) Garcia 2000 E1

Tang 2000 E3



Neutral EvidenceMany of the “Neutral” results here are secondary endpoints, reported in the study, but known to be underpowered!!

Qua

lity

of E

vide

nce

Excellent

Good Tang 2001 A, B


FairMartens 2001 A, E1(BTE=MDS) White 2001 A, C

(MDS = BTE)

Garcia 2000 A

Leng 2000 A, B

Niemann 2003b E1



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Question: Are Biphasic waveforms more efficacious and safer than monophasic for transthoracic defibrillation for prolonged (>5 min) VF? --Primary Endpoints Only—FINAL Version (No 2nd reports of same data)

Supporting Evidence

Qua

lity

of E

vide

nce

Excellent

Good

Morrison 2005Pre E2

VanAlem 2003 E2

Schnieder 2000 E1

Stothert 2004 E1


Tang 2001 E3

Fair Garcia 2000 E1Tang 2000 E3


A = Return of spontaneous circulation Of Note: Bold names are prolonged VF, non-bold names are very short VF B = Survival of event [ ] indicates a secondary endpoint result which were often underpoweredC = Survival to hospital discharge D = Intact neurological survivalE = Other endpoint (1=Term VF, 2=organized rhythm post shock, 3=PRMD)

Neutral Evidence Many of the “Neutral” results here are secondary endpoints, reported in the study, but known to be underpowered!!

Qua

lity

of E

vide

nce

Excellent

Good Tang 2001 A, B


Fair White 2001 A, C(MDS = BTE)

Garcia 2000 A

Leng 2000 A, B

Niemann 2003b E1


A = Return of spontaneous circulation C = Survival to hospital discharge E = Other endpoints (see above)B = Survival of event D = Intact neurological survival = abstract 0nly

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STEP 3. DETERMINE THE CLASS OF RECOMMENDATION. Select from these summary definitions.CLASS CLINICAL DEFINITION REQUIRED LEVEL OF EVIDENCE

Class IDefinitely recommended. Definitive, excellent evidence provides support.

• Always acceptable, safe• Definitely useful • Proven in both efficacy & effectiveness• Must be used in the intended manner for proper clinical indications.

• One or more Level 1 studies are present (with rare exceptions) • Study results consistently positive and compelling

Class II:Acceptable and useful

• Safe, acceptable• Clinically useful• Not yet confirmed definitively

• Most evidence is positive• Level 1 studies are absent, or inconsistent, or lack power • No evidence of harm

• Class IIa: Acceptable and usefulGood evidence provides support

• Safe, acceptable• Clinically useful • Considered treatments of choice

• Generally higher levels of evidence• Results are consistently positive

• Class IIb: Acceptable and usefulFair evidence provides support

• Safe, acceptable • Clinically useful• Considered optional or alternative Treatments

• Generally lower or intermediate levels of evidence• Generally, but not consistently, positive results

Class III: Not acceptable, not useful, may be harmful

• Unacceptable• Not useful clinically• May be harmful.

• No positive high level data• Some studies suggest or confirm harm.

Indeterminate• Research just getting started.• Continuing area of research• No recommendations until further research

• Minimal evidence is available• Higher studies in progress • Results inconsistent, contradictory• Results not compelling

STEP 3: DETERMINE THE CLASS OF RECOMMENDATION. State a Class of Recommendation for the Guideline Proposal. State either a) the intervention, and then the conditions under which the intervention is either Class I, Class IIA, IIB, etc.; or b) the condition, and then whether the intervention is Class I, Class IIA, IIB, etc.

“Biphasic waveforms for use in transthoracic external defibrillation of VF cardiac arrest are more efficacious (higher rates of VF termination, ROSC, and survival) as well as safer (less adverse effects) than monophasic waveforms”.

Indicate if this is a __Condition or XXX InterventionFinal Class of recommendation:

__ Class I-Definitely Recommended XXX Class IIa-Acceptable & Useful; good evidence__ Class IIb-Acceptable & Useful; fair evidence __ Class III – Not Useful; may be harmful__ Indeterminate-minimal evidence or inconsistent

REVIEWER’S PERSPECTIVE AND POTENTIAL CONFLICTS OF INTEREST: Briefly summarize your professional background, clinical specialty, research training, AHA experience, or other relevant personal background that define your perspective on the guideline proposal. List any potential conflicts of interest involving consulting, compensation, or equity positions related to drugs, devices, or entities impacted by the guideline proposal. Disclose any research funding from involved companies or interest groups. State any relevant philosophical, religious, or cultural beliefs or longstanding disagreements with an individual.

I am a Professor of Medicine at the University of Arizona where I am an Interventional Cardiologist. I have a long standing interest and research career in CPR. I am a Scientific Advisory Board member for several companies with interests in defibrillation including Revivant Corporation (affiliated with Zoll Medical) and Medtronic Emergency Response Systems. Both arrangements are based on an hourly fee schedule for work performed, without any ties to company stock or performance. I know most of the individuals doing resuscitation research, but do not believe that I have any philosophical, religious, or cultural disagreements or bias that would interfere with an honest appraisal of resuscitation science regardless of it origin.

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REVIEWER’S FINAL COMMENTS AND ASSESSMENT OF BENEFIT / RISK: Summarize your final evidence integration and the rationale for the class of recommendation. Describe any mismatches between the evidence and your final Class of Recommendation. “Mismatches” refer to selection of a class of recommendation that is heavily influenced by other factors than just the evidence. For example, the evidence is strong, but implementation is difficult or expensive; evidence weak, but future definitive evidence is unlikely to be obtained. Comment on contribution of animal or mechanical model studies to your final recommendation. Are results within animal studies homogeneous? Are animal results consistent with results from human studies? What is the frequency of adverse events? What is the possibility of harm? Describe any value or utility judgments you may have made, separate from the evidence. For example, you believe evidence-supported interventions should be limited to in-hospital use because you think proper use is too difficult for pre-hospital providers. Please include relevant key figures or tables to support your assessment.

The evidence comparing biphasic versus monophasic waveform defibrillation is fairly extensive with one meta-analysis, a number of clinical reports, and numerous animal studies. Studies of Transthoracic defibrillation after short duration VF (< 2 min) and long duration VF (> 5 min), as well as open chest defibrillation were all reviewed. The long duration VF studies are most pertinent to out-of-hospital cardiac arrest, but the other studies also add value as the overall benefit of biphasic waveforms is examined in this worksheet.

Open chest studies of internal defibrillation, one clinical (Schwarz 2003) and one animal (Zhang 2003) both found that a biphasic waveform was more successful in terminating VF than a monophasic waveform.

Short-term VF (including studies from 10 sec to 2 min of VF) are generally those performed in the EP laboratory for testing of implanted ICD devices. Some animal studies also used short term VF.

Faddy et al. is the only available meta-analysis comparing biphasic vs monophasic defibrillation waveforms (Faddy 2003). Seven prospective, randomized, controlled trials were identified, but only 6 were included since the definition of the meta analysis primary endpoint for "first shock failure" included remaining in VF or asystole, the seventh study was not usable since its primary endpoint was "VF termination" to any non-VF, including asystole, post shock. Unfortunately this excluded study was the only one that was done for prolonged (out-of-hospital) VF. Hence, the meta analysis includes all studies done in the EP lab with short-duration VF (10 to 30 seconds in duration). Though this is supportive data for biphasic defibrillation, I believe the time has arrived to look more carefully ONLY at longer duration VF (5-10 minutes!!) compatible with out-of-hospital cardiac arrest. Therefore, I believe this meta analysis is of limited usefulness in proving superiority of biphasic waveform defibrillation for out-of-hospital ventricular fibrillation cardiac arrest.

Summary of Faddy et al:N = 1129 VF Duration = “short” (no actual times given)Level of Evidence: 2

Quality: Good Supportive for “E1” (first shock failure) and “E3” (less ST segment changes post shock)

Higgins et al. is a prospective, randomized, double-blind, controlled clinical trial comparing monophasic vs two different strengths of biphasic wavefrom defibrillation (Higgins 2000). The patients were undergoing EP testing with ICD placements. Mean time of VF was 19 seconds (Short-term VF). Primary endpoint was 1st shock efficacy, defined as termination of VF without the need for further cardioversion or defibrillation shocks. First shock success was best for the 200J biphasic waveform. Conclusions: For short-term, brief VF 200J Biphasic was superior in terminating VF than either 130J Biphasic or 200J monophasic (MDS). No differences in post shock hemodynamics were found. Applicability of data for OOH VFCA patients is suspect due to the short duration VF (19 sec). 200J Mono 130J Biphasic 200J Bisphasic

'n' (total 154) 68 47 39

1st Shock efficacy 61 (90%) 39 (83%) 39 (100%)

SummaryN = 154 VF Duration = 19 secondsLevel of Evidence: 2

Quality: Good Supportive for “E1” (termination of VF); Neutral for “E3” (post shock hemodynamics)

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Bain et al. is a prospective, randomized, blinded clinical trial of MTE vs BTE waveform defibrillation (first shock) success. However, each subject was tested for both types of waveform. The randomization was for which waveform would be tested first, in the sequence of testing. This is different than being randomized to one waveform or the other! No differerence in the primary endpoint (first shock success) was seen between the two waveforms (97% vs 100%). No data is given comparing the two groups at baseline (since they are exactly the same patients (!) and no description of any statistical analysis is provided. The endpoint was similar (but not exactly) to what other such studies have done, namely "considered successful… if the defibrillation shock resulted in a supraventricular or paced rhythm within 5 sec after the shock". A major problem here is the short VF time prior to shock. This study was done at the time of EP studies for ICD implantation, rather than in an OOH population suffering VFCA. Hence, the mean time of VF prior to shock was only 11 seconds. Therfore, the applicability of these results to the OOH scenario is suspect.

MTE BTE p "n" 115 115 1st Shock success 112 (97%) 115 (100%) NS

Summary:N = 118; VF Duration = 11 SecondsLevel of Evidence: 2

Quality: Fair (Randomization was to the order of testing of both waveforms, not one or the other)Neutral for “E1” (1st shock success)

Some animal studies also used short-term VF.

Walker et al. is a prospective, but non-randomized, series of multiple defibrillation trials per animal (20/animal in Protocol 1 and 16/animal in Protocol 2) (Walker et al. 2003). Total number of animals; n = 14; total number of defibrillation trials = 852!! VF induced-electrically was short duration (15s in Protocol 1 and 30s in Protocol 2). There were actually two different studies:

Protocol 1: MDS (LP-12@200J), MTE (HS-300@200J), and BTE (LP-12@150J)

Protocol 2: Four Biphasic WaveformsA: Heart Stream ForeRunner (150J, 150J, 150J)B: MPC LifePack 12 (200J, 300J, 360J)C: Survivalink FirstSave AED (‘low, high, high’)D: Zoll M Series (120J, 150J, 200J)—rectilinear

Impedance was changed from the natural 40Ω to 90Ω with an in-series external 50Ω resistor. Half of the studies were done with the natural impedance and half with the increased impedance. The primary endpoint was defibrillation efficacy (E1: termination of VF after 1; < 2, and < 3shocks. The use of such an inline resistor has created significant controversy surrounding this study. Protocol 1 showed that for defibrillation success BTE > MDS [Odds ratio = 11.5 (8.3 – 15.8)]; BTE > MTE [OR = 53.7 (30.6 – 94.2)]; MDS > MTE [OR = 4.7 (2.8 – 7.8)]. Protocol 2 showed that with the “natural” (low) impedance there was no difference in shock success among the four different biphasic waveforms. With the increased impedances there were differences, ranked from the best to worst as B > C > D = A. The limitations and controversies surrounding this paper center on the following:

1. Artificial increases in impedance. Jones et al. published detailed letter to editor (Resuscitation 2003;53:365-367) outlining their objections to the methodology of increasing impedance with an in-series external resistor. The widely different results seen with this methodology compared to the clinical experience was highlighted as evidence that this technique does not giving meaningful results, at least not interpretable for clinical application or usefulness. Walker et al (the authors) rebut these criticisms by stating that absolute efficacy comparisons were never the intent, but rather only “relative” efficacy (Resuscitation 2003;53:367-371).

2. Short duration VF (Only 15s in Protocol 1 and 30s in Protocol 2).

3. Multiple episodes of VF and defibrillation testing in each animal. The comparison of defibrillation efficacy after 19 previous VF/Defib tests is never shown to be compatible with such efficacy tested de novo the first time.

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Both items #2 & #3 highlight that this comparison is not truly representative of the use of such different biphasic waveforms in the OOH clinical arena.

Summary:N = 14 VF Duration = 15 seconds or 30 secondsLevel of Evidence: 6

Quality: Fair (Controversial) Supportive for “E1” endpoint

Clark et al. published a prospective, randomized, swine (18-26 kg) study of defibrillation efficacy following short duration VF comparing biphasic and monophasic waveforms (Clark 2002). The study was limited in the number of animals studied. (“n” = 13; each animal studied numerous times at different shock energy levels). Randomization was two-fold: 1st to Monophasic or biphasic, 2nd to sequence of which energy level shock to use. VF duration = 15 seconds. Primary endpoint was E1: Termination of VF at 5 sec post shock (any other Non-VF “success”)

Results:

70J/20 kg pig = 3.5 J/kg 150J/75 kg man = 2 J/kg100J/20 kg pig = 5 J/kg 200J/75 kg man = 2.7 J/kg200J/20 kg pig = 10 J/kg 300J/75 kg man = 4 J/kg300J/20 kg pig = 15 J/kg 360J/75 kg man = 4.8 J/kg360/20 kg pig = 18 J/kg

Conclusions: Biphasic waveforms (BTE) were superior to monophasic (MTE) at low energies levels for terminating VF.Limitations/Controversies:

Short duration VF (15 seconds)Multiple studies with each animalEndpoint only VF termination/No outcome measures

Summary:N = 13 swine VF Duration = 15 seconds Level of Evidence: 6

Quality: Fair (each animal studies numerous times with both waveforms) Supportive for E1 (termination of VF)

Zhang et al. published a prospective, ‘randomized’ (order of biphasic vs monophasic shocks) swine (15-25 kg) study with and without halothane induced left ventricular dysfunction (Zhang 2001). Study included “n” = 23, each animal acted as its own control for

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both conditions of no LV dysfunction and LV dysfunction and for receiving both waveform types (Mono and Biphasic). VF duration = 20 seconds. Primary endpoint: VF termination (no details given)

Results:

Conclusions:Biphasic waveforms maintain their superiority over monophasic with and without concurrent LV Dysfunction. LV dysfunction did not affect defib success

Limitations/Controversies:1. Acute halothane induced LV dysfunction—does this really mimic the clinical scenario? Others have published that LV dysfunction decreases the Defib success, but these data did not find such. 2. Very brief VF (20 sec)3. MTE rather than MDS used (MTE known to be less efficacious than MDS). Summary:

N = 23 swine VF Duration = 20 seconds Level of Evidence: 6

Quality: Fair (each animal acted as own control before and after “LV Dysfx produced with high dose anesthetic)

Supportive for 1° endpoint: VF Termination

Niemann et al. published a prospective, randomized, non-blinded swine study for defibrillation efficacy comparing Mono vs Biphasic waveforms. The study “n” = 21; (each animal had both 30s and 90s VF trial). Randomization was done for waveform treatment (Mono vs Bi). VF duration = 30 seconds; then following recovery each studied again after 90 seconds of VF. Primary endpoint: VF termination and return of pulse. Secondary endpoints: ST segment changes; post shock hemodynamicsstudied (Niemann 2000).

Results:Mono Biphasic ‘p’

30 sec VF group:n (# tests) 10 11VF Termination 6 (60%) 7 (63%) NSST ∆s 6/8 (75%) 1/10 (10%) .013

Mono Biphasic ‘p’90 sec VF group:

n (# tests) 8 11VF Termination 5 (63%) 9 (82%) NSST ∆s 6/8 (75%) 2/10 (20%) .054

Summary of VF termination data: Mono 11/18 (61%); Biphasic 16/22 (73%). No Difference. Likewise, no difference in ROSC was found.

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Conclusions1. Biphasic comparable to Monophasic for VF termination after relatively brief VF (30s and 90s)

2. Biphasic produced less ST segment ∆s.

Limitations/Controversies:1. Short duration of VF (30s and 90s only)2. Clinical meaning of ST ∆s measured at 10s to 30s after shock (?)3. Monophasic waveform tested was MTE, MDS is used more clinically

Summary:N = 21 swineVF Duration = 30 seconds or 90 seconds Level of Evidence: 6

Quality: Good Neutral for 1° endpoint (VF Termination and ROSC); and Supportive for a 2° endpoint (less ST segment change)

Leng et al. published a prospective, randomized canine study for defibrillation success and survival after short duration and long duration VF (Leng 2000). The study was “n” = 26 (13 MDS and 13 Biphasic). Randomization was to the waveform (Mono vs Bi). VF duration: 10 seconds; then 10 minutes. Each animal underwent both studies—(see limitations). Primary endpoints: Defibrillation thresholds (DFT), and overall resuscitation outcomes. Study ‘deaths’ were defined as refractory VF, cross-over rescue shocks, or no ROSC (LVSBP of >50 mmHg for at least 1 min). Secondary endpoints: Test effects of countershocks on myocardial function

Results:

Conclusions:

1. DFTs are lower with Biphasic then Mono after 10 sec of VF

Limitations/Controversies:

1. Two studies in one (short and prolonged VF)

Summary:N = 26 swineVF Duration = 10 seconds (then 10 minutes-reported later under polonged VF studies) Level of Evidence: 6

Quality: Fair Supportive for a 1° outcome of a lower DFT with biphasic

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Most pertinent are the studies of prolonged VF defibrillation. There are 7 clinical trials and 5 animal studies.

van Alem et al. published the first truly blinded trial of out-of-hospital (OOH) defibrillation comparing Biphasic vs Monophasic (MDS) (van Alem 2003). The devices were randomized, not the patients. The primary endpoint was defibrillation with an organized rhythm within 1 min of shock. This is different from other studies including the ORCA and ORBIT trials. The second endpoint was termination of VF at 5 sec post shock (Similar to ORCA primary endpoint). Similar success was seen for termination of VF here (98%) as in the ORCA trial (96%). Different results were noted for the monophasic arms, thought to be due to different monophasic waveforms (MDS here and MTE (80%) in ORCA.). No difference in ROSC, Admission to Hosp, or Hosp Discharge were found, though the study was never powered to detect such. Hence, the true significance to the primary endpoint (vs the secondary endpoint used in previous studies) is uncertain. It did not predict better clinical outcome, albeit this was a small (n = 120 patients) study. Of note, no data given as to concurrent CPR protocols. (CPR or Shock first etc, though it is suspected that chest compressions were not required nor given prior to defibrillation attempts)

Results MDS waveform(n=69) BTE waveform(=51) P-value RR (95% CI)

Shock success, 31 (45%) 35 (69%) 0.01 1.53 (1.11_/2.10)Termination of VF at 5 s 63 (91%) 50 (98%) 0.12 1.07 (0.99_/1.14)Return of spontaneous circulation, 45 (65%) 31 (61%) 0.62 0.93 (0.70_/1.23)Admission to hospital, 33 (48%) 20 (40%) 0.35 0.82 (0.54_/1.25)Discharge from the hospital, 13 (19%) 7 (14%) 0.46 0.73 (0.31_/1.70)

It should be noted that the outcome data are contaminated by different waveform defibrillation attempts (uncontrolled by the arriving EMS providers after the original AED randomization).

SummaryN = 120VF Duration = 8 minutes (Call to first shock)Level of Evidence: 2Quality: Good Supportive for an “E2” endpoint of organized rhythm post shock and Neutral for Outcome endpoints (“A-D”)

Schneider et al. published the ORCA trial (Schneider 2000). This trial was the first randomized, prospective, controlled (albeit not blinded) clinical trial comparing biphasic vs monophasic AEDs in a realistic (mean time from call to first shock was 9 min), out-of-hospital setting. The primary endpoint was termination of VF at 5 sec post shock after a series of 3 shocks (and included any non-VF rhythm as "success" specifically asystole or PEA as well as SVT etc.) Secondary endpoints (underpowered) included first shock success, 2 shock success, ROSC, survival to hospital admission, and survival to discharge. The weaknesses of this study include the lack of blinding, the use of two different monophasic waveforms (MDS = 21%; and MTE = 79%), and the relatively small numbers (total 'n' = 115). The not unanticipated result is that biphasic was more successful than monophasic for termination of VF. The surprising finding is that the biphasic waveform group had a significantly higher ROSC rate (0.001) and survival to hospital admission rate (0.02, …but only in the intention to treat analysis; 0.27 in the 'on treatment' analysis). These improved outcomes have not previously been documented.

Monophasic Biphasic p 'n' 67 48 Defib efficacy 1st Shock 44 (66%) 44 (92%) 0.001 3 shocks 49 (73%) 46 (96%) 0.002 ROSC 35 (52%) 39 (81%) 0.001 Surv to Hosp Admit 31 (46%) 33 (69%) 0.02 Surv to Hosp DC 18 (27%) 16 (33%) 0.45

This study is very persuasive in favor of biphasic over monophasic for out-of-hospital VF CA treatment.

[Separate review published in the Ann Emerg Med Nov 2001by J. T. Niemann, MD]

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Background: “Secondary to advantages in energy requirements, size, and weight, biphasic waveforms have replaced monophasic waveforms for implantable defibrillators. However, to date, prospective clinical studies of biphasic shocks have been performed only in highly controlled, in-hospital settings. The role of low-energy biphasic waveforms in sudden cardiac arrest needs to be investigated in out-of-hospital settings as well.Methods and findings: Automatic external defibrillators (AEDs) delivering 150-J biphasic shocks or traditional 200- to 360-J monophasic shocks were prospectively randomized daily in 4 emergency medical services systems. Data for 338 patients experiencing out-of-hospital cardiac arrest were analyzed. One hundred fifteen patients had a cardiac disorder, with ventricular fibrillation, and received AED treatment.The mean time from the emergency call to the first shock was 8.9 minutes. The 150-J biphasic waveform defibrillated at higher rates, resulting in return of spontaneous circulation in a greater percentage of patients achieving return of spontaneous circulation. The rates of survival to hospital admission and discharge did not differ between patients treated with the biphasic and monophasic AEDs. However, discharged patients resuscitated with biphasic shocks were more likely to have good cerebral performance.Conclusions: In patients with out-of-hospital cardiac arrest, an appropriately dosed low-energy impedance-compensating biphasic-waveform strategy produces better defibrillation performance than does the use of escalating high-energy monophasic shocks. The 150-J biphasic waveform AED also results in a greater rate of return of spontaneous circulation and better neurologic status at discharge.Comment: This is the first study of sufficient size in a population with out-of-hospital sudden cardiac death to demonstrate a difference between conventional monophasic waveform defibrillation shocks and lower energy biphasic waveform shocks. The devices used for biphasic defibrillation were all the same. The defibrillators for monophasic waveform countershock were from 2 different manufacturers and included both a truncated exponential waveform and a damped sine waveform. The specific defibrillators for the monophasic group were not considered separately in the data analysis. This should be considered when interpreting the results of the study. Two of the monophasic defibrillators used in the study, although meeting specific standards, have not had a particularly impressive track record. Whenever a new device or technique is considered superior to “conventional” technology, an outcome favoring the new may result from it truly being better or the fact that it was compared with the least effective conventional intervention.The Utstein template for reporting outcomes of out-of-hospital cardiac arrest has become standard. Three major outcomes or end points are incorporated into the template: restoration of spontaneous circulation, survival to admission, and survival to hospital discharge. This study failed to demonstrate that biphasic defibrillation resulted in a greater admission or discharge rate. In interpreting the results of this study, it is also important to consider the purpose of defibrillation, namely, to terminate ventricular fibrillation. This study clearly demonstrated that biphasic defibrillation resulted in a greater rate of ventricular fibrillation termination with fewer shocks and a higher rate of restoration of spontaneous circulation. Because a defibrillator has only one purpose, to expect a greater rate of hospital admission or discharge may be exceeding intentions and expectations. This should be considered a positive study favoring biphasic defibrillation, but keep in mind that the best of monophasic waveforms was not used in the control group”.

Summary:N = 115; VF Duration = 9 minutes (call to first shock)Level of Evidence: 2Quality: Good (Randomization was per waveforms, not per patient, not blinded)Supportive for “E” and “A-B” endpoints

Neutral or Opposing for C

Morrison et al. have provided a ‘pre-print’ of their ORBIT trial (accepted for publication in Resuscitation) entitled “Comparison of Rectilinear Biphasic defibrillation to monophasic damped sine defibrillation in advanced cardiac life support for out-of-hospital cardiac arrest”. This is a prospective, randomized (by block), controlled trial of the effectiveness of rectilinear biphasic waveform defibrillation compared to monophasic damped sine defibrillation in out-of-hospital cardiac arrest. Randomization was by station (block design) and there was no attempt to blind the EMS providers. Primary endpoint was “defibrillation success” after < 3 shocks, defined as conversion to an organized rhythm 5 seconds after shock (this is the same primary endpoint as with the ORCA trial). The primary endpoint was analysed in three patient subgroups, i.e. all patients, patients iniitally presenting with VF or VT, and patients iniitally presenting with non-shockable rhythms but developing such during course of therapy. Secondary endpoints (known to be underpowered) included conversion after one shock, return of spontaneous circulation, survival to arrival at the Emergency Department, survival to 24-hours, survival to 30 days, and cerebral performance category at hospital discharge. The weaknesses of the study are the borderline differences found in analyzing all patients (only differences noted in the “initially shockable”) and the lack of blinding. The subgroup of those with initially shockable rhythms was larger than the previously reported clinical series (total ‘n’ = 169; whereas ORCA total ‘n’ was 115 and van alem study total ‘n’ was 120). In those with initial VF or VT the ‘defibrillation success’ was significantly better with the RLB waveform (p=.01). However, no difference was seen among all patients (p=.05, with a p value needed of .048 per authors).

Results

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MDS RLB ‘p’‘n’ (Shockable group) 83 86“shock success” (%) 33.7% 52.3% .011st shock conversion 12.2% 22.9% ..07ROSC (%) 47.0% 46.5% NSSurvival to 24-Hours (%) 26.8% 30.6% NSSurvival to Hospital DC (%) 7.3% 9.4% .NSSurvival to 30 days (%) 7.3% 8.3% NSCerebral category “1”at discharge (%) 50.0% 57.1% NS

Summary:N = 169 (Initially shockable group); VF Duration ~ 8 minutes (call to first shock)Level of Evidence: 2Quality: Good (Randomization was per station [not per patient], not blinded)Supportive for “E” (only among those with initial VF/VT)

Neutral or Opposing for “A, B, C and D” endpoints

Martens et al. published a second look at the data from the ORCA trial (Martens 2001). This study is a secondary subgroup analysis from the ORCA data previously published in Circulation. The major issue here is the lack of any original or new data and the small numbers in the subgroups. MDS waveform group had only 13 patients (MTE was 48, and the Biphasic subgroup was 54). Defibrillation efficacy (termination of VF at 5 sec post shock) was superior with Biphasic compared to MTE, but similar comparisons to MDS were rountinely underpowered and hence the p value non-significant. The most impressive example of this shortcoming was the outcome (ROSC) results where the monophasic subgroups had identical ROSC rates at 54%. Biphasic had a ROSC rate of 76%, which in the analysis was significantly different from the MTE (n=48) group, but not different from the MDS (n=13) group.

In summary, the data analsysis is substantially limited by small numbers, and the overall information is not new having been previously reported in Circulation.

Summary:N = 435; VF Duration = 8-10 minutes (call to analysis of VF)Level of Evidence: 2

Quality: Suspect (subgroup analysis to look for differences is limited by very small numbers (i.e. 13 in MDS subgroup)Supportive “E” endpoints (as well as for “A-D” for MTE) but Neutral for “A-D” for MDS

Not included in the final analysis grid.

Stothert et al have a study in press (PreHosp Emerg Care Nov 2004) which is a observational, population-based, historically controlled report comparing biphasic versus monophasic shock success in out-of-hospital cardiac arrest patients (Stothert 2004). “N” = 294, including the historical control monophasic group of 153. The primary endpoint was first shock success (termination of VF) with secondary endpoints of post shock organized rhythm, and ROSC. Results: Rectilinear Biphasic Monophasic p

1st Shock success 95/141 (67%) 75/153 (49%) 0.0025 (OR = 2.14 [1.33-3.42]< 3 shocks success 116/141 (82%) 110/153 (72%) 0.05 (OR = 1.80 [1.03-3.13]

Pts defib to ROSC 50/141 (35) 40/153 (26%) 0.11 (OR = 1.55 [0.94-2.54]

Conclusions: Rectilinear Biphasic waveform produced more first and three shock success at terminating VF than did the monophasic waveform, but no difference in outcome (ROSC), an underpowered secondary endpoint, was seen.

Summary:N = 294; VF Duration = 5:49±2:23 min response time for ALS paramedic teamLevel of Evidence: 4Quality: Good

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Supportive for “E1” and “E2” endpoints Neutral for A

Carpenter et al. published a retrospective cohort series showing that MDS and BTE waveforms were similar in their termination of VF, while both were significantly better than the MTE (Carpenter 2003). At 60 sec post shock, the BTE produced more organized rhythms (“E2” endpoint defined as "a minimum of 2 consecutive ventricular complexes of similar morphology within a 5 sec interval with an absense of chaotic electrical activity" [NO PULSE was required.] ).

Organized rhythm at 60 sec post shock: MDS 25%; MTE 27%; BTE 40% (p <0.01 MDS vs BTE) Still in VF:

MDS 49%; MTE 60%; BTE 41% (p<0.01 MTE vs BTE)

Of interest is the proportion successfully defibrillated (VF terminated) after 1, 2 or 3 shocks among the three groups. 1 shock 2 shocks 3 shocks

MDS: 84%; 92%, 96% MTE: 63%, 75%, 85% BTE: 90%, 96%, 97%

MTE was sigificantly less (p<0.01) for all three shocks than either MDS or BTE. No difference between MDS or BTE at any shock

Secondary endpoints included ROSC (No differences), survival to hospital admission (no differences), but was better for survival to hospital discharge in the MTE group vs the BTE group (MTE [39.7%] vs BTE [20%; p<0.01). The authors comment that they are uncertain as to the validity of this last finding (p.195). This study used a variety of BTE waveforms (majority were Phillips impedance compensating fixed 150 J dose BTE (86%); a minority were PhysioControl escalating (200-200-360 J) BTE (14%). All BTE data were combined. No comparison data between the two forms of BTE is provided. It is difficult to reconcile the results with BTE and MDS being better at eliminating VF than MTE but MTE resulting in twice as much survival to discharge than BTE. It calls into question what is the proper endpoint in evaluating defibrillate waveform efficacy. Does it matter if the first shock or even the first three shocks fail to defibrillate if eventually the best outcome is unrelated to such early results??

Summary: N = 366

Level of Evidence: 4VF Duration = 7-8 minutes (collapse to BLS arrival)Quality: Good (for an “E” endpoint) = Termination of VFNeutral for “E” above between BTE and MDS, but both better than MTE (Supportive),Negative for “C” as MTE was better for survival to discharge than BTE

White et al. published a small retrospective, observational study of patient outcomes following defibrillation with Biphasic (non-escalating, IC 150 J) waveform AEDs compared to a historical control which used an earlier monophasic MDS AED (White 2001). Very little comparison data is provided (a single paragraph in Results, with no tabulated data or figure). My compilation of the data is as follows: Monophasic MDS AEDs Biphasic non-escalating, IC low energy AEDs)

Witnessed VF (n) 70 35 ROSC with shock only 23 (33%) 14 (38%) ROSC (on scene) Total 54 (77%) 28 (80%) Discharged home 32 (46%) 16 (46%)

No statistical analysis given.

Conclusions:

No difference in outcome with the use of a biphasic non-escalating low energy (150J) AED (compared to the historical results using a monophasic (MDS) AED).

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Summary:N = 105; VF Duration = 5-6 minutes (call to shock time)Level of Evidence: 5

Quality: Fair (very little data given on the comparison of the two groups. No stats analysis provided.) Neutral: (A-D) “no decrease in outcome with the use of biphasic non-escalating low energy defib”

Animal studies that used a prolonged VF model:

Tang et al. published a prospective, randomized swine (40-45 kg) study (“n” = 20), VF duration = 10 min untreated (Tang 2001). Randomized to either 3 biphasic shocks (150J) or 3 monophasic (200J, 300J, 360J) and to epi or no epi.. Primary endpoints: ROSC (mean BP>60 mmHg for 5 min), 72 hour survival, and post resuscitation LV function (TTE measurements).

Results:Monophasic Biphasic ‘p’

N 10 10Wt 42 kg 43 kg NSROSC 7/10 8/10 NS72 Hr Surv 7/10 8/10 NS

Pos Resuscitation Myocardial Dysfunction:

No Epi use

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After Epi use

Conclusions:Lower energy Biphasic shocks were as effective as higher energy conventional monophasic shocks for ROSC after 10 min

of untreated VF. Less post resuscitation myocardial dysfunction was seen after biphasic defibrillation compared with monophasic defibrillation. No differences in outcomes.


1. Doses (J/kg) are large here (almost twice the clinical dose) 150J/45 kg pig (biphasic) = 3.3 J/kg vs 150/75 kg man = 2 J/kg; 360J/45 kg pig (mono) = 8 J/kg vs 360/75 kg man = 4.8 J/kg

2. TEE difficult in pigs/no other PRMD measurements 3. Authors did not reproduce their previous work showing epinephrine worsens PRMD (see figures)

Summary: N = 20 swine

VF Duration = 10 minLevel of Evidence = 6Quality: Good (1° endpoint: ROSC; 2° endpoint: PRLV function)

Neutral for 1° endpoint: ROSC; Supportive for the 2° endpoint (PRMD)

Garcia et al. published a prospective, ‘randomized’ (each animal underwent 4 different protocols, the order of which was random), swine (20-30 kg) study to determine the effect of CPR vs no CPR on the efficacy of MDS vs BTE defibrillation efficacy (Garcia 2000). “N” = 20 animals (80 different tests of defibrillation efficacy). VF duration = 6 min. Primary endpoints were termination of VF (any other non-VF rhythm) and resumption of perfusing rhythm (ROSC)

Four randomized treatmentsA) 6 min CPR/then defib with 100J MDSB) 6 min unRxed VF/ then defib with 100J MDSC) 6 min CPR/then defib with 100J BTED) 6 min unRxed VF/ then defib with 100J BTE

Results:

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Conclusions:

Defibrillation efficacy is enhanced by CPR when using a Biphasic waveform (BTE), but not with a MDS waveform. ROSC occurs only with CPR preceding defib with either waveform after 6 min of VF.

Limitations/Controversies

Randomized, but not blinded to waveform used.

Summary:N = 20 swine (80 ‘tests’) VF Duration = 6 minutes Level of Evidence: 6

Quality: Fair (each animal underwent 4 separate periods of testing) Supportive for 1° endpoint: VF Termination

Tang et al published in 2000 a series of swine studies comparing the effect of monophasic vs biphasic waveform defibrillation on post resuscitation myocardial dysfunction after progressive periods of VFCA (Tang 2000). “N” = Unknown (data not provided!—20+ [from JACC 1999 article: the 4 and 7 min VF data]). Subjects: swine (40-45 kg [from JACC]). Randomization was to waveform (Mono vs Biphasic) with each sub-study a different VF duration (presumably). VF (untreated) duration: three different sub-studies with 4 min VF, 7 min VF, and 10 min VF. Primary endpoint: LV ejection fraction (determined with TEE)

Results:

Conclusions:

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Biphasic waveform defibrillation results in less post resuscitation myocardial dysfunction than monophasic waveform defibrillation, whether after 4, 7 or 10 min of untreated VF.


This is a ‘summary report’ of several experiments “lumped” together. Unfortunately, the data needed to assure compatibility of all the three time subgroups is not provided. Indeed, much of the usual data is not provided here, including total “n”, etc. This limits the reader from fully interpreting these results.

Summary:N = Unknown (data not provided; 20+)VF Duration = 4,7 and 10 minutes Level of Evidence: 6

Quality: Fair (much of the study detail is not provided) Supportive for 1° endpoint of PRLV Ejection Fraction

Niemann et al published a prospective, randomized swine study of Monophasic vs Biphasic waveforms for defibrillation after 5 min of untreated VF (Neimann 2000). “N” = 38 swine (29±4 kg). Randomization was per animal to one of the two waveforms (each animal treated and tested only once). VF duration = 5 min. (no CPR prior to 1st shock; CPR was provided if the countershock resulted in a non-VF, non-perfusing rhythm SBP <50 mmHg)

Primary endpoints: 1) 1st shock success (termination of VF to any non-VF rhythm) 2) 1st series of 3 shocks success (same definition of success) 3) Frequency of perfusing rhythm within 30s of shock without CPR performed 4) Frequency of perfusing rhythm any time after cardiac arrest

Results:

Table 2. Countershock Success After Five Minutes of Ventricular Fibrillation

Differences between groups were not statistically significant.

Monophasic Biphasic ‘p’

“n” 18 20 NSROSC after 1st Shock 2 (11%) 1 (5%) NSTermination of VF 17 (94%) 20 (100%) NSPEA after 1st Shock 15 (83%) 18 (90%) NSROSC after CPR 15 (100%) 17 (94%) NSTotal ROSC 17 (94%) 18 (90%) NS

Conclusions:1. Monophasic high dose (stacked) shocks are equivalent to low dose (fixed) biphasic shocks, and vice versa.2. ROSC after 1st shock following untreated 5 min of VF rarely results in ROSC3. CPR after shock induced PEA highly successful in establishing ROSC

Limitations/Controversies:1. Human doses for swine (75 kg vs 29 kg subjects)2. No longer-term outcome data

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Summary:N = 38 swineVF Duration = 5 minutes Level of Evidence: 6

Quality: Good Neutral for 1° endpoint of Countershock success and Outcome (ROSC)

Leng et al. published a prospective, randomized canine study for defibrillation success and survival after short duration and long duration VF (Leng 2000). “N” = 26 (13 MDS and 13 Biphasic). Randomization was to the waveform (Mono vs Bi). VF duration: 10 seconds; then 10 minutes (each animal underwent both studies—see limitations). Primary endpoints: Test the DFTs and overall resuscitation outcomes. Study ‘deaths’ were refractory VF, cross over rescue shocks, or no ROSC (LVSBP of >50 mmHg for at least 1 min). Secondary endpoints: Test effects of countershocks on myocardial function

Results:

Table 2. Study Endpoints after Prolonged (10 min) VF MP (n=13) BP (n=13) Refractory VF 0 1 Crossover deaths 3 0 Fatal Complications 0 11

No ROSC 4 1 Total Study deaths 7 3 (2) 2

Values are number of animals (n) from group (N). 1 Catheter perforation and hemorrhage. 2 P=0.05 when fatal technical complication was excluded.

Total Survival: Monophasic Biphasic

5/13 10/13 [NS per FET]

Conclusions:

1. DFTs are lower with Biphasic then Mono after 10 min of VF

2. Biphasic may have a significant impact on resuscitation from prolonged VF


1. No actual statistical difference in outcome in this experimental study (1° endpoint)

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Summary:N = 26 swineVF Duration = 10 seconds then 10 minutes Level of Evidence: 6

Quality: Good Supportive for a 1° of DFT; and Neutral for 1° endpoint of Outcome (survival) .

In conclusion, the evidence in favor of biphasic vs monophasic waveforms for defibrillation is supported by both internal and external defibrillation studies including studies of both short-term and long-term VF. Careful examination of such studies shows that the most consistent endpoint for which there is supportative data is ‘termination of VF.” Biphasic waveforms consistently terminates VF more frequently than monophasic in clinical and animal studies of open chest defibrillation and closed chest external transthoracic defibrillation of both short-term VF (<2 min of VF) and longer-term VF (>5 min of VF).

In short-term VF transthoracic studies a meta-analysis and one recent (2000) study both favored biphasic waveforms for termination of VF. All five animal studies were supportative of biphasic waveforms for the outcomes of either termination of VF or less post defibrillation complications. No study of external defibrillation of short-term VF showed monophasic superior to biphasic, though several studies found no difference between the two waveforms for defibrillation to an organized rhythm or return of spontaneous circulation.

The vast majority of clinical transthoracic defibrillation studies for longer-term VF found biphasic superior to monophasic for termination of VF, defibrillation to an organized rhythm, or less post defibrillation complications. One study (Schnieder) found improved ROSC and survival to admission with biphasic compared to monophasic. However, the other studies found no difference between waveform useage for outcome measures including return of spontaneous circulation, survival of the event, survival to hospital discharge, or intact neurological survival. Of note, most often such outcome measures were secondary endpoints in relatively small clinical trials, and therefore were underpowered to find such outcome differences. Hence, the value of such outcome results are suspect. Only one clinical trial found monophasic better than biphasic for survival to hospital discharge (Carpenter 2003). These authors themselves questioned the validity of that particular finding.

A final analysis using only primary endpoints in completed, published (or in-press) studies shows that both clinical (n=4) and animal (n=3) reports support the premise that biphasic waveforms are superior to monophasic waveforms for terminating long-term (> 5 min) VF and lowering ther incidence of post defibrillation complications, specifically hemodynamic compromise. No study shows superiority in outcome for either waveform, but as mentioned all studies are underpowered to detect this endpoint.

Preliminary draft/outline/bullet points of Guidelines revision: Include points you think are important for inclusion by the person assigned to write this section. Use extra pages if necessary.

Publication: Guidelines 2000 Chapter: Part 4 Pages: I-63 2nd column/lines 15-22 I-63 2nd column/lines 23-30

Topic and subheading: Waveforms and Energy Levels

Change the current wording from, ‘At this time no studies have reported experience with other biphasic waveforms in long-duration VF in out-of-hospital arrest. When such data becomes available, it will need to be assessed by the same evidence-evaluation process as used for the biphasic AED and this guidelines process. [p. I-63; lines 15-22].

Now should read: “Since the 2000 Guidelines for CPR and ECC additional clinical (levels 2 & 4) and experimental (level 6) data suggest that both low energy (<200J) and higher energy (200J-360J) shocks with biphasic waveforms are more effective for termination of ventricular fibrillation than are monophasic

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waveforms. Outcomes (return of spontaneous circulation, survival to hospital admission, survival to hospital discharge, and neurologically normal survival) were not different in 5 clinical studies, though a 6th clinical trial did find improved ROSC and 24-hour survival (but not survival to discharge) with a biphasic waveform (Schnieder et al.).”

Change the current wording from, ‘The data indicates that biphasic waveform shocks of relatively low energy ( 200 J) are safe and have equivalent or higher efficacy for termination of VF compared with higher-energy escalating monophasic waveform shocks (Class IIa). The safety and efficacy data related to specific biphasic waveforms must be evaluated on an individual basis in both in-hospital (electrophysiology studies, ICD testing) and out-of-hospital settings [p. I-63].

Now should read: “The data indicates that biphasic waveform shocks of relatively low energy ( 200 J) and higher energy (200J to 360J) are safe and have equivalent or higher efficacy for termination of VF compared with 200J to 360J energy escalating monophasic waveform shocks (Class IIa). The comparative safety and efficacy related to specific biphasic waveforms and energy doses must be evaluated on an individual basis in both in-hospital (electrophysiology studies, ICD testing) and out-of-hospital settings [p. I-63].

Citation List

Full Citation*See detailed comments above on key citations.

Bain 2001 Bain, A. C., C. D. Swerdlow, et al. (2001). "Multicenter study of principles-based waveforms for external defibrillation.[see comment]." Annals of Emergency Medicine 37(1): 5-12.

STUDY OBJECTIVE: The efficacy of a shock waveform for external defibrillation depends on the waveform characteristics. Recently, design principles based on cardiac electrophysiology have been developed to determine optimal waveform characteristics. The objective of this clinical trial was to evaluate the efficacy of principles-based monophasic and biphasic waveforms for external defibrillation. METHODS: A prospective, randomized, blinded, multicenter study of 118 patients undergoing electrophysiologic testing or receiving an implantable defibrillator was conducted. Ventricular fibrillation was induced, and defibrillation was attempted in each patient with a biphasic and a monophasic waveform. Patients were randomly placed into 2 groups: group 1 received shocks of escalating energy, and group 2 received only high-energy shocks. RESULTS: The biphasic waveform achieved a first-shock success rate of 100% in group 1 (95% confidence interval [CI] 95.1% to 100%) and group 2 (95% CI 94.6% to 100%), with average delivered energies of 201+/-17 J and 295+/-28 J, respectively. The monophasic waveform demonstrated a 96.7% (95% CI 89.1% to 100%) first-shock success rate and average delivered energy of 215+/-12 J for group 1 and a 98.2% (95% CI 91.7% to 100%) first-shock success rate and average delivered energy of 352+/-13 J for group 2. CONCLUSION: Using principles of electrophysiology, it is possible to design both biphasic and monophasic waveforms for external defibrillation that achieve a high first-shock efficacy.

Comment in: Ann Emerg Med. 2001 Jan;37(1):59-60; PMID: 11145773

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Carpenter 2003

Clark 2002

Carpenter, J., T. D. Rea, et al. (2003). "Defibrillation waveform and post-shock rhythm in out-of-hospital ventricular fibrillation cardiac arrest." Resuscitation 59(2): 189-96.

BACKGROUND: The importance of the defibrillation waveform on the evolving post-shock cardiac rhythm is uncertain. The primary objective of this study was to evaluate cardiac rhythms following the first defibrillation shock, comparing biphasic truncated exponential (BTE), monophasic damped sinusoidal (MDS), and monophasic truncated exponential (MTE) waveforms in patients experiencing out-of-hospital ventricular fibrillation cardiac arrest (OHCA). METHODS: We reviewed the automated external defibrillator (AED) and emergency medical services (EMS) records of 366 patients who suffered OHCA and were treated with defibrillation shocks by first-tier emergency responders between 1 January 1999 and 31 August 2002 in King County, Washington. The post first shock rhythms were determined at 5, 10, 20, 30, and 60 s and compared according to defibrillation waveform. RESULTS: The MDS and BTE waveforms were associated with significantly higher frequency of defibrillation than the MTE waveform, though only the BTE association persisted to 30 and 60 s. No difference in defibrillation rates was detected between MDS and BTE waveforms. By 60 s, an organized rhythm was present in a greater proportion for BTE (40.0%) compared with MDS (25.4%, P=0.01) or MTE (26.5%, P=0.07). CONCLUSION: In this retrospective cohort investigation, MDS and BTE waveforms had higher first shock defibrillation rates than the MTE waveform, while patients treated with the BTE waveform were more likely to develop an organized rhythm within 60 s of the initial shock. The results of this investigation, however, do not provide evidence that these surrogate advantages are important for improving survival. Additional investigation is needed to improve the understanding of the role of waveform and its potential interaction with other clinical factors in order to optimize survival in OHCA.

Clark, C. B., Y. Zhang, et al. (2002). "Transthoracic biphasic waveform defibrillation at very high and very low energies: a comparison with monophasic waveforms in an animal model of ventricular fibrillation." Resuscitation 54(2): 183-6.

The purpose of this study was to compare truncated exponential biphasic waveform versus truncated exponential monophasic waveform shocks for transthoracic defibrillation over a wide range of energies. Biphasic waveforms are more effective than monophasic shocks for defibrillation at energies of 150-200 Joules (J) but there are few data available comparing efficacy and safety of biphasic versus monophasic defibrillation at energies of <150 J or >200 J. Thirteen adult swine (weighing 18-26 kg, mean 20 kg) were deeply anesthetized and intubated. After 15 s of electrically-induced ventricular fibrillation (VF), each pig received truncated exponential monophasic shocks (10 ms) and truncated exponential biphasic shocks (5/5 ms) in random order. Energy doses ranged from 70 to 360 J. Success was defined as termination of VF at 5 s post-shock. For both biphasic and monophasic waveforms success rate rose as energy was increased. Biphasic waveform shocks (5/5 ms) were superior to 10 ms monophasic waveform shocks at the very low energy levels (at 70 J, biphasic: 80+/-9%, monophasic; 32+/-11% and at 100 J, biphasic; 96+/-3% and monophasic 39+/-11%, both P < 0.01). No significant differences in shock success were seen between biphasic and monophasic waveform shocks at 200 J or higher energy levels. Shock success of > 75% was achieved with 200 J (10 J/kg) for both waveforms. Pulseless electrical activity (PEA) or ventricular asystole occurred in 4 animals receiving monophasic shocks and 1 animal receiving biphasic shocks.

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Faddy 2003

Garcia 2000

Biphasic waveform shocks (5/5 ms) for transthoracic defibrillation were superior to monophasic shocks (10 ms) at low energy levels. Percent success increased with increasing energies. PEA occurred infrequently with either waveform.

Faddy, S. C., J. Powell, et al. (2003). "Biphasic and monophasic shocks for transthoracic defibrillation: a meta analysis of randomised controlled trials." Resuscitation 58(1): 9-16.

INTRODUCTION: Biphasic waveforms are routinely used for implantable defibrillators. These waveforms have been less readily adopted for external defibrillation. This study was performed in order to evaluate the efficacy and harms of biphasic waveforms over monophasic waveforms for the transthoracic defibrillation of patients in ventricular fibrillation (VF) or haemodynamically unstable ventricular tachycardia. METHODS: Studies included randomised controlled trials comparing monophasic and biphasic external defibrillation for participants with VF or hemodynamically unstable ventricular tachycardia. Seven trials (1129 patients) were included in the analysis. All trials were conducted during electrophysiology procedures or implantable cardioverter/defibrillator testing. RESULTS: Compared with 200 J monophasic shocks, 200 J biphasic shocks reduced the risk of post-first shock asystole or persistent VF by 81% (relative risk (RR) 0.19; 95% confidence intervals (CI) 0.06-0.60) for the first shock. Reducing the energy of the biphasic waveform to 115-130 J resulted in similar effectiveness compared with the monophasic waveform at 200 J (RR 1.07, CI 0.66-1.74). Low energy biphasic shocks produce less myocardial injury than higher energy monophasic shocks as determined by ST segment deflection after shock. CONCLUSIONS: Biphasic waveforms defibrillate with similar efficacy at lower energies than standard 200 J monophasic waveforms, and greater efficacy than monophasic shocks of the same energy. Available data suggests that lower delivered energy and voltage result in less post-shock myocardial injury.

Garcia, L. A., J. J. Allan, et al. (2000). "Interactions between CPR and defibrillation waveforms: effect on resumption of a perfusing rhythm after defibrillation." Resuscitation 47(3): 301-5.

BACKGROUND: Cardiopulmonary resuscitation (CPR) improves survival from cardiac arrest. The interactions between CPR and the new biphasic (BiP) defibrillation waveforms have not been defined. Our purpose was to compare the effect of CPR versus no CPR during BiP and damped sinusoidal (DS) shocks on the termination of ventricular fibrillation (VF) and the resumption of a perfusing rhythm. METHODS: We studied 20 pigs; VF was induced electrically and allowed to persist for 6 min. During VF episodes each pig received (in random order): (a) 6 min of full CPR (continuous ventilation and closed chest mechanical compression (Thumper, Michigan Instruments)) followed by DS defibrillation at 100 J; (b) no CPR, DS defibrillation; (c) 6 min of full CPR and BiP defibrillation at 100 J; and (d) no CPR, BiP defibrillation. RESULTS: BiP shocks with CPR terminated VF in 83% of attempts versus 45% without CPR (15/18 and 5/11 respectively, P<0.05). DS shocks with CPR were successful in terminating VF in 53% of attempts; DS shocks without CPR were successful in 44% (8/15 and 7/16, respectively, P=NS). No animal achieved a perfusing rhythm after shocks of either waveform if CPR did not precede the shocks during the 6-min VF period, whereas if CPR was administered during VF 46% (11/24) of the combined BiP/DS shocks restored a perfusing rhythm (P<0.01).

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Higgins 2000

Leng 2000

CONCLUSION: In this experimental long duration VF model, CPR was essential for a perfusing rhythm after termination of VF by shocks with either waveform. CPR facilitated the termination of VF and resumption of a perfusing rhythm after biphasic waveform defibrillation but not after damped sinusoidal waveform defibrillation.

Higgins, S. L., J. M. Herre, et al. (2000). "A comparison of biphasic and monophasic shocks for external defibrillation. Physio-Control Biphasic Investigators.[erratum appears in Prehosp Emerg Care 2001 Jan-Mar;5(1):78]." Prehospital Emergency Care 4(4): 305-13.

BACKGROUND AND OBJECTIVE: The ability of a shock to defibrillate the heart depends on its waveform and energy. Past studies of biphasic truncated exponential (BTE) shocks for external defibrillation focused on low energy levels. This prospective, randomized, double-blind clinical trial compared the first-shock efficacies of 200-joule (J) BTE, 130-J BTE, and 200-J monophasic damped sine wave shocks. METHODS: Ventricular fibrillation (VF) was induced in 115 patients during evaluation of implantable cardioverter-defibrillator function and 39 patients during electrophysiologic evaluation of ventricular arrhythmias. After 19 +/- 10 seconds of VF, a randomized transthoracic shock was administered. Mean first-shock success rates of the three groups were compared using a "Tukey-like" statistical test, adjusting for multiple comparisons. Blood pressures and arterial oxygen saturations were measured before VF induction and 30, 90, and 150 seconds after successful defibrillation. RESULTS: First-shock success rates were 61/68 (90%) for 200-J monophasic, 39/39 (100%) for 200-J biphasic, and 39/47 (83%) for 130-J biphasic shocks. The 200-J biphasic shocks were simultaneously superior in first-shock efficacy to both 200-J monophasic and 130-J biphasic shocks (experimentwise error rate, alpha < 0.01). There was no significant difference between the efficacies of 200-J monophasic and 130-J biphasic shocks, nor was there any significant difference between the three groups in hemodynamic parameters after successful shocks. CONCLUSIONS: Biphasic shocks of 200 J provide better first-shock defibrillation efficacy for short-duration VF than 200-J monophasic and 130-J biphasic shocks and thus may allow earlier termination of VF in cardiac arrest patients.

Leng, C. T., N. A. Paradis, et al. (2000). "Resuscitation after prolonged ventricular fibrillation with use of monophasic and biphasic waveform pulses for external defibrillation." Circulation 101(25): 2968-74.

BACKGROUND: Survival after prolonged ventricular fibrillation (VF) appears severely limited by 2 major factors: (1) low defibrillation success rates and (2) persistent post-countershock myocardial dysfunction. Biphasic (BP) waveforms may prove capable of favorably modifying these limitations. However, they have not been rigorously tested against monophasic (MP) waveforms in clinical models of external defibrillation, particularly where rescue from prolonged VF is the general rule. METHODS AND RESULTS: We randomized 26 dogs to external countershocks with either MP or BP waveforms. Hemodynamics were assessed after shocks applied during sinus rhythm, after brief VF (>10 seconds), and after resuscitation from prolonged VF (>10 minutes). Short-term differences in percent change in left ventricular +dP/dt(max) (MP -16+/-28%, BP +9.1+/-24%; P=0.03) and left ventricular -dP/dt(max) (MP -37+/-26%, BP -18+/-20%; P=0.05) were present after rescue from brief VF, with BP animals exhibiting less countershock-induced dysfunction. After

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Martens 2001

Morrison 2005(Pre-print)

prolonged VF, the BP group had lower mean defibrillation thresholds (107+/-57 versus 172+/-88 J for MP, P=0.04) and significantly shorter resuscitation times (397+/-73.7 versus 488+/-74.3 seconds for MP, P=0.03). CONCLUSIONS: External defibrillation is more efficacious with BP countershocks than with MP countershocks. The lower defibrillation thresholds and shorter resuscitation times associated with BP waveform defibrillation may improve survival after prolonged VF arrest.

Martens, P. R., J. K. Russell, et al. (2001). "Optimal Response to Cardiac Arrest study: defibrillation waveform effects.[see comment]." Resuscitation 49(3): 233-43.

INTRODUCTION: Advances in early defibrillation access, key to the "Chain of Survival", will depend on innovations in defibrillation waveforms, because of their impact on device size and weight. This study compared standard monophasic waveform automatic external defibrillators (AEDs) to an innovative biphasic waveform AED. MATERIAL AND METHODS: Impedance-compensated biphasic truncated exponential (ICBTE) and either monophasic truncated exponential (MTE) or monophasic damped sine (MDS) AEDs were prospectively, randomly assigned by date in four emergency medical services. The study design compared ICBTE with MTE and MDS combined. This subset analysis distinguishes between the two classes of monophasic waveform, MTE and MDS, and compares their performance to each other and to the biphasic waveform, contingent on significant overall effects (ICBTE vs. MTE vs. MDS). Primary endpoint: Defibrillation efficacy with < or =3 shocks. Secondary endpoints: shock efficacy with < or =1 shock, < or =2 shocks, and survival to hospital admission and discharge. Observations included return of spontaneous circulation (ROSC), refibrillation, and time to first shock and to first successful shock. RESULTS: Of 338 out-of-hospital cardiac arrests, 115 had a cardiac aetiology, presented with ventricular fibrillation, and were shocked by an AED. Defibrillation efficacy for the first "stack" of up to 3 shocks, for up to 2 shocks and for the first shock alone was superior for the ICBTE waveform than for either the MTE or the MDS waveform, while there was no difference between the efficacy of MTE and MDS. Time from the beginning of analysis by the AED to the first shock and to the first successful shock was also superior for the ICBTE devices compared to either the MTE or the MDS devices, while again there was no difference between the MTE and MDS devices. More ICBTE patients achieved ROSC pre-hospital than did MTE patients. While the rates of ROSC were identical for MTE and MDS patients, the difference between ICBTE and MDS was not significant. Rates of refibrillation and survival to hospital admission and discharge did not differ among the three populations. CONCLUSIONS: ICBTE was superior to MTE and MDS in defibrillation efficacy and speed and to MTE in ROSC. MTE and MDS did not differ in efficacy. There were no differences among the waveforms in refibrillation or survival.

Comment in: Resuscitation. 2001 Jun;49(3):231; PMID: 11723997

Morrison L.J., P. Dorian, et al (2005 pre-print). “Comparison of Rectilinear Biphasic Defibrillation to Monophasic Damped Sine Defibrillation In Advanced Cardiac Life Support For Out-Of-Hospital Cardiac Arrest.” Resuscitation (in press).BACKGROUND. Although biphasic defibrillation waveforms appear to be superior to monophasic waveforms in terminating VF, their relative benefits in out-of-hospital resuscitation are incompletely understood. Prior comparisons of defibrillation waveform efficacy in out-of-hospital cardiac arrest (OHCA) are confined to patients presenting in a shockable rhythm and resuscitated by first responders (basic life

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Niemann 2004

support). This effectiveness study compared monophasic and biphasic defibrillation waveform for conversion of ventricular arrhythmias in all OHCA treated with advance life support (ALS). METHODS AND RESULTS. This prospective randomized controlled trial compared the rectilinear biphasic (RLB) waveform with the monophasic damped sine (MDS) waveform, using step-up energy levels. The study enrolled OHCA patients requiring at least one shock delivered by ALS providers, regardless of initial presenting rhythm. Shock success was defined as conversion at 5 seconds to organized rhythm after 1 to 3 escalating shocks. We report efficacy results for the cohort of patients treated by ALS paramedics who presented with an initially shockable rhythm who had not received a shock from a first responder(MDS: n=83; RLB: n=86). Shock success within the first three ascending energy shocks for RLB (120J, 150J, 200J) was superior to MDS (200J, 300J, 360J) for patients initially presenting in a shockable rhythm (52% vs. 34%, p=0.01). First shock conversion was 23% and12%, for RLB and MDS, respectively (p=0.07). There were no significant differences in return of spontaneous circulation (47% vs. 47%), survivalto 24 hours (31% vs. 27%), and survival to discharge (9% vs. 7%). Mean 24 hour survival rates of bystander witnessed events showed differences between waveforms in the early circulatory phase at 4-10 minutes post event; (mean (SD) RLB 0.45 (0.07) vs. MDS 0.31 (0.06), p = 0.0002) and demonstrated decline as time to first shock increased to 20 minutes. CONCLUSION. Shock success to an organized rhythm comparing step-up protocol for energy settings demonstrated the RLB waveform was superior to MDS in ALS treatment of OHCA. Survival rates for both waveforms are consistent with current theories on the circulatory and metabolic phases of out-of-hospital cardiac arrest.

Neimann, J. T., J. P. Rosbourgh, et al. (2004). " A model of ischemically induced ventricular fibrillation for comparison of fixed-dose and escalating-dose defibrillation strategies." Acad Emerg Med 11(6): 619-624.

OBJECTIVE: Fixed – and escalating defibrillation protocols are both in clinical use. Clinical observations suggest that the probability of successful defibrillation is not constant across a population of patients with ventricular fibrillation (VF). Common animal models of electrically induced VF do not represent a clinical VF etiology or reproduce clinical heterogeneity in defibrillation probability. The authors hypothesized that a model of ischemically induced VF would exhibit heterogeneous defibrillation shock strength requirements and that an escalating-dose strategy would more effectively achieve prompt defibrillation. METHODS: Forty-six swine were randomized to fixed, lower-energy (150 J) Transthoracic shocks (group 1) or escalating, higher-energy (200 J-300 J-360 J) shocks (group 2). VF was induced by balloon occlusion of a coronary artery. After 1 or 5 minutes of VF, countershocks with a biphasic waveform were administered. The primary endpoint was successful defibrillation (termination of VF for 5 seconds) with < 3 shocks. RESULTS: VF was induced with occlusion or after reperfusion in 35 animals. Only five of 17 group 1 animals (29%, 95% CI = 10-56) could be defibrillated with <3 shocks; 15 of 18 group 2 animals (83%, 95% CI = 59-96) were defibrillated with < 3 shocks (p<0.002 vs. group 1). Nine of the group 1 animals (75%) that could not be defibrillated with 150-J shocks were rescued with < 3 shocks ranging from 200 to 360 J. CONCLUSIONS: In this ischemic VF animal model, defibrillation shock strength requirements varied among individuals, and when defibrillation was difficult, an escalating-dose strategy

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Niemann 2000a

Niemann 2000b

was more effective for prompt defibrillation than fixed, lower-energy shocks. Monophasic and biphasic waveforms were equally effective in terminating prolonged VF

Niemann, J. T., D. Burian, et al. (2000). "Monophasic versus biphasic transthoracic countershock after prolonged ventricular fibrillation in a swine model.[see comment]." Journal of the American College of Cardiology 36(3): 932-8.

OBJECTIVE: We sought to compare the defibrillation efficacy of a low-energy biphasic truncated exponential (BTE) waveform and a conventional higher-energy monophasic truncated exponential (MTE) waveform after prolonged ventricular fibrillation (VF). BACKGROUND: Low energy biphasic countershocks have been shown to be effective after brief episodes of VF (15 to 30 s) and to produce few postshock electrocardiogram abnormalities. METHODS: Swine were randomized to MTE (n = 18) or BTE (n = 20) after 5 min of VF. The first MTE shock dose was 200 J, and first BTE dose 150 J. If required, up to two additional shocks were administered (300, 360 J MTE; 150, 150 J BTE). If VF persisted manual cardiopulmonary resuscitation (CPR) was begun, and shocks were administered until VF was terminated. Successful defibrillation was defined as termination of VF regardless of postshock rhythm. If countershock terminated VF but was followed by a nonperfusing rhythm, CPR was performed until a perfusing rhythm developed. Arterial pressure, left ventricular (LV) pressure, first derivative of LV pressure and cardiac output were measured at intervals for 60 min postresuscitation. RESULTS: The odds ratio of first-shock success with BTE versus MTE was 0.67 (p = 0.55). The rate of termination of VF with the second or third shocks was similar between groups, as was the incidence of postshock pulseless electrical activity (15/18 MTE, 18/20 BTE) and CPR time for those animals that were resuscitated. Hemodynamic variables were not significantly different between groups at 15, 30 and 60 min after resuscitation. CONCLUSIONS: Monophasic and biphasic waveforms were equally effective in terminating prolonged VF with the first shock, and there was no apparent clinical disadvantage of subsequent low-energy biphasic shocks compared with progressive energy monophasic shocks. Lower-energy shocks were not associated with less postresuscitation myocardial dysfunction.

Comment in: J Am Coll Cardiol. 2001 May;37(6):1753-4; PMID: 11345396

Niemann, J. T. , D. Burian, et al. (2000). ”Transthoracic monophasic and biphasic defibrillation in a swine model: a comparison of efficacy, ST segment changes, and postshock hemodynamics. Resuscitation 47:51-58. OBJECTIVE: Biphasic waveforms for transthoracic defibrillation (DF) have been tested extensively after brief (15 s) episodes of VF in animal models and in patients undergoing electrophysiologic testing. The purpose of this study was to compare the effects mono- and biphasic waveforms for DF on postdefibrillation ST segments and left ventricular pressure, markers of myocardial injury, after more extended periods of VF (30 and 90 s). METHODS AND RESULTS: 21 anesthetized and instrumented swine were randomized to truncated exponential monophasic or biphasic waveform DF. VF was induced electrically and 30 s later, DF with the

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Niemann 2003a

designated waveform was attempted with a shock dose of 200 J. If unsuccessful, 300 J and then 360 J were administered if necessary. Following return to control hemodynamic values and normalization of the surface ECG, VF was again induced and, after 90 s, DF was attempted as in the 30 s VF period. CPR was not performed during VF and each animal was countershocked with only one waveform for both VF episodes. Waveforms were compared for frequency of first shock defibrillation success, surface ECG indicators of myocardial injury (ST segment changes at 10, 20, and 30 s after countershock) and time to return to pre-VF hemodynamics after successful DF, an indicator of postshock ventricular function. Successful first shock conversion rates at 30 and 90 s were 60 and 63% for monophasic and 64 and 82% for biphasic (NS). Biphasic DF after 30 s produced ST segment changes (measured 10 s after DF) in 1:10 animals while six of eight animals in the monophasic group showed ST segment changes (P_0.013). After 90 s of VF, ST segment changes were observed in 6:8 in the monophasic group and 2:10 in the biphasic group (P_0.054). Differences in the time to hemodynamic recovery (return to control peak left ventricular pressure) were not observed between biphasic and monophasic waveforms after 30 or 90 s of VF. CONCLUSION : Monophasic and biphasic Transthoracic defibrillation are equally effective in terminating VF of 30 and 90 s duration and restoring a perfusing rhythm. The biphasic waveform produced less ECG evidence of transient myocardial injury. However, there was no difference in the rate of return to control hemodynamics. ST segment changes following countershock of VF of brief duration are transient and of questionable significance.

Niemann, J. T., D. Garner, et al. (2003). "Left ventricular function after monophasic and biphasic waveform defibrillation: the impact of cardiopulmonary resuscitation time on contractile indices." Academic Emergency Medicine 10(1): 9-15.

Previous work has suggested that low-energy biphasic waveform defibrillation (BWD) is followed by less post-resuscitation left ventricular (LV) dysfunction when compared with higher-energy monophasic waveform defibrillation (MWD). To the best of the authors' knowledge, the effect of cardiopulmonary resuscitation (CPR) duration and total ischemia time on LV function after countershock, controlling for waveform type, has not been evaluated. OBJECTIVE: To determine the effect of CPR duration on LV function after MWD and BWD. METHODS: VF was electrically induced in anesthetized and instrumented swine. After 5 minutes of VF, the animals were randomized to MWD (n = 22) or one of two BWDs (n = 46). If countershock terminated VF but was followed by a nonperfusing rhythm, conventional manual CPR without drug therapy was performed until restoration of spontaneous circulation (ROSC), defined as a systolic arterial pressure >60 mm Hg for 10 minutes without vasopressor support. Systolic LV pressure (LVP), LV dP/dt (first derivative of pressure measured over time), and cardiac output (CO) were measured at intervals for 60 minutes postresuscitation. CPR times (times to ROSC) and hemodynamic variables for the three groups were compared. Multivariable linear regression was performed to assess the contribution of defibrillation waveform, total joules, and CPR time on LVP, LV dP/dt, and CO at 15, 30, and 60 minutes postresuscitation. RESULTS: When analyzed as groups, significant differences in median number of shocks to terminate VF, total joules, or CPR time were not observed between waveform groups. Regression analysis demonstrated that increasing CPR time was associated with a

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Niemann 2003b

Schneider 2000

significant effect on indices of LV function at 15 and 30 minutes postresuscitation. Global LV function was not influenced by waveform type or total joules. CONCLUSIONS: Adjustment for CPR time, a determinant of total myocardial ischemia time, is necessary when defibrillation waveforms are compared for their effect on postresuscitation cardiac function and short-term outcome.

Niemann, J. T., D. Garner, et al. (2003). "Transthoracic impedance does not decrease with rapidly repeated countershocks in a swine cardiac arrest model." Resuscitation 56(1): 91-5.

STUDY PURPOSE: Successful defibrillation is dependent upon the delivery of adequate electrical current to the myocardium. One of the major determinant of current flow is transthoracic impedance. Prior work has suggested that impedance falls with repeated shocks during sinus rhythm. The purpose of this study was to evaluate changes in transthoracic impedance with repeated defibrillation shocks in an animal model of cardiac arrest due to ventricular fibrillation (VF). METHODS: VF was electrically induced in anesthetized swine. After 5 min of untreated VF, monophasic or biphasic waveform defibrillation was attempted using a standard sequence of 'stacked shocks' (200, 300, then 360 J, if necessary) administered via adhesive electrodes. If one of the first three shocks failed to convert VF, conventional CPR was initiated and defibrillation (360 J) attempted 1 min later. Strength-duration curves for delivered voltage and current were measured during each shock and transthoracic impedance calculated. Animals requiring a minimum of four shocks were selected for study inclusion. Impedance data from sequential shocks were analyzed using mixed linear models to account for the repeated-measures design and the variability of the initial impedance of individual animals. RESULTS: Thirteen animals (monophasic waveform, n=7, biphasic waveform, n=6) required at least four shocks to terminate VF (range 4-6). Transthoracic impedance did not change from the first shock in the 13 animals (46+/-8 Omega) to the fourth shock (46+/-9 Omega). In animals receiving more than four shocks, transthoracic impedance likewise did not change significantly from the first to the last shock, which terminated VF. The lack of a significant change in impedance was also observed when animals were analyzed according to defibrillation waveform. CONCLUSION: Transthoracic impedance does not change significantly with repeated shocks in a VF cardiac arrest model. This is likely due to the lack of reactive skin and soft tissue hyperemia and edema observed in non-arrest models.

Schneider, T., P. R. Martens, et al. (2000). "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 102(15): 1780-7.

BACKGROUND: In the present study, we compared an automatic external defibrillator (AED) that delivers 150-J biphasic shocks with traditional high-energy (200- to 360-J) monophasic AEDs. METHODS AND RESULTS: AEDs were prospectively randomized according to defibrillation waveform on a daily basis in 4 emergency medical services systems. Defibrillation efficacy, survival to hospital admission and discharge, return of spontaneous circulation, and neurological status at discharge (cerebral performance category) were compared. Of 338 patients with out-

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Schwarz 2003

Shorofsky 2000

of-hospital cardiac arrest, 115 had a cardiac etiology, presented with ventricular fibrillation, and were shocked with an AED. The time from the emergency call to the first shock was 8.9+/-3.0 (mean+/-SD) minutes. CONCLUSIONS: The 150-J biphasic waveform defibrillated at higher rates, resulting in more patients who achieved a return of spontaneous circulation. Although survival rates to hospital admission and discharge did not differ, discharged patients who had been resuscitated with biphasic shocks were more likely to have good cerebral performance.

Schwarz, B., T. A. Bowdle, et al. (2003). "Biphasic shocks compared with monophasic damped sine wave shocks for direct ventricular defibrillation during open heart surgery." Anesthesiology 98(5): 1063-9.

BACKGROUND: Biphasic waveform shocks are more effective than monophasic shocks for transchest ventricular defibrillation, atrial cardioversion, and defibrillation with implantable defibrillators but have not been studied for open chest, intraoperative defibrillation. This prospective, blinded, randomized clinical study compares biphasic and monophasic shock effectiveness and establishes intraoperative energy dose-response curves. METHODS: Patients undergoing cardiothoracic surgery with bypass cardioplegia were randomly assigned to the monophasic or biphasic shock group. Ventricular fibrillation occurring after aortic clamp removal was treated with escalating energies of 2, 5, 7, 10, and 20 J until defibrillation occurred. If ventricular fibrillation persisted, a 20-J crossover shock of the other waveform was used. RESULTS: Cumulative defibrillation success at 5 J, the primary end point of the study, was higher in the biphasic group than in the monophasic group (25 of 50 vs. 9 of 41 defibrillated; P = 0.011). In addition, the biphasic group required lower threshold energy (6.8 vs. 11.0 J; P = 0.003), less cumulative energy (12.6 vs. 23.4 J; P = 0.002), and fewer shocks (2.5 vs. 3.5; P = 0.002). Crossover-shock effectiveness did not differ between groups. Dose-response curves show biphasic shocks to have higher cumulative success rates at all energies tested. CONCLUSIONS: Biphasic shocks are substantially more effective than monophasic shocks for direct defibrillation. The dose-response curve guides selection of first-shock energy for traditional step-up protocols. Starting at 5 J optimizes for lowest threshold and cumulative energy, whereas 10 or 20 J optimizes for more rapid defibrillation and fewer shocks.

Shorofsky, S. R. and M. R. Gold (2000). "Effect of second-phase duration on the strength-duration relation for human transvenous defibrillation." Circulation 102(18): 2239-42.

BACKGROUND: The mechanism by which biphasic waveforms improve defibrillation efficacy is unclear. In addition, the optimal shape of the biphasic waveforms remains controversial. Animal experiments suggest that prolonging the duration of the second phase longer than the first worsens defibrillation thresholds (DFT). The purpose of this study was to determine the strength-duration relation for the second phase of a biphasic defibrillation waveform in humans. METHODS AND RESULTS: This was a prospective, randomized study of biphasic DFT in 36 patients; a uniform dual-coil transvenous lead system was used. In each patient, 3 DFTs were determined with the pulse duration for the second phase of the defibrillation waveform varying between 1 and 18 ms. The duration of the first phase was fixed at 6 ms and the capacitance was 150 microF. There was a significant increase in the leading edge

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Stothert 2004

Tang 2000

voltage at DFT only when the second-phase pulse duration was decreased to 1 ms. There was no increase in DFT voltage even when the second-phase pulse duration was increased from 2 to 18 ms. Similar relations were observed for stored energy, leading edge current, or phase 2 energy. The normalized average current delivered during phase 2 decreased monotonically with increasing phase 2 duration. CONCLUSIONS: In humans, the biphasic DFT voltage or energy is increased only when the second phase of the waveform is <2 ms. The DFT voltage is insensitive to increasing the second phase of the defibrillator waveform to as long as 18 ms, or 3 times the duration of the first phase of the waveform.

Stothert, J. C., T. S. Hatcher, et al. (2004). "Rectilinear biphasic waveform defibrillation of out-of-hospital cardiac arrest." Prehospital Emergency Care.

BACKGROUND: The rectilinear biphasic (RLB) waveform has been shown to effectively defibrillate short-duration ventricular fibrillation (VF)_ at significantly lower energies than a monophasic damped sine (MDS) waveform. This article reports RLB waveform defibrillation effectiveness for patients presenting in VF during out-of-hospital cardiac arrest when compared to historical MDS effectiveness. METHODS: External RLB defibrillators were deployed in the Omaha Fire Department’s emergency medical services (EMS) system. The RLB defibrillators delivered an escalating three shock sequence of 120, 150, 200 J. The results observed during the first year of full deployment were compared with the results observed during the previous year when only MDS defibrillators were deployed in the system. The MDS defibrillators delivered an escalating three-shock sequence of 200, 300, and 360 J. Defibrillation was defined as termination of VF for at least 5 seconds after a defibrillation shock. RESULTS: There were 141 adult patients presenting in VF without trauma during the first year using RLB defibrillators. By comparison, there were 153 adult patients during the comparable year using MDS defibrillators. The 120 J RLB shocks had a significantly higher first-shock rate of successful VF termination (67%, 95% CI: 59%-75%) compared with the initial 200J MDS shocks (48%. 95% CI: 40%-57%, p<0.0025); odds ratio 2.14 [1.33-3.42]). The number of patients who were defibrillated to a return of spontaneous circulation with a sinus rhythm was significantly greater (25, 95% CI: 18-33%) when using the RLB defibrillator compared with using the MDS defibrillator (15%, 95% CI: 10%-22%, p = 0.05; odds ratio 1.85 [1.04-3.31]). CONCLUSION: The RLB defibrillator terminated the VF of patients in out-of-hospital cardiac arrest with superior rates using significantly less energy compared with historical rates for a higher-energy MDS defibrillator.

Tang, W., M. H. Weil, et al. (2000). "Low-energy biphasic waveform defibrillation reduces the severity of postresuscitation myocardial dysfunction." Critical Care Medicine 28(11 Suppl): N222-4.

Both clinical and experimental studies have demonstrated substantial impairment of ventricular function after resuscitation from cardiac arrest. Indeed, postresuscitation myocardial dysfunction has been implicated as a potentially important mechanism, accounting for fatal outcomes after successful resuscitation in 70% of victims within the first 72 hrs. Recent experimental studies implicated the total electrical energy delivered during defibrillation as an important correlate with the severity of postresuscitation myocardial dysfunction and postresuscitation survival.

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Tang 2004(Biphasic onlyNOT USED)

Tang 2001

This prompted us to investigate the option of using lower electrical energy biphasic waveform defibrillation. We compared the effects of low-energy biphasic waveform defibrillation with conventional monophasic waveform defibrillation after a short (4 mins), intermediate (7 mins), or prolonged (10 mins) interval of untreated ventricular fibrillation. Biphasic waveform defibrillation with a fixed energy of 150 joules proved to be as effective as conventional monophasic damped sine waveform defibrillation for restoration of spontaneous circulation, with significantly lower delivered energy. This was associated with significantly less severity of postresuscitation myocardial dysfunction. The low-energy biphasic waveform defibrillation is, therefore, likely to be the future direction of transthoracic defibrillation in settings of cardiopulmonary resuscitation.

Tang, W., M. H. Weil, et al. (2004). "The effects of biphasic waveform design on post-resuscitation myocardial function." Journal of the American College of Cardiology 43(7): 1228-35.

OBJECTIVES: This study examined the effects of biphasic truncated exponential waveform design on survival and post-resuscitation myocardial function after prolonged ventricular fibrillation (VF). BACKGROUND: Biphasic waveforms are more effective than monophasic waveforms for successful defibrillation, but optimization of energy and current levels to minimize post-resuscitation myocardial dysfunction has been largely unexplored. We examined a low-capacitance waveform typical of low-energy application (low-energy biphasic truncated exponential [BTEL]; 100 microF, < or =200 J) and a high-capacitance waveform typical of high-energy application (high-energy biphasic truncated exponential [BTEH]; 200 microF, > or =200 J). METHODS: Four groups of anesthetized 40- to 45-kg pigs were investigated. After 7 min of electrically induced VF, a 15-min resuscitation attempt was made using sequences of up to three defibrillation shocks followed by 1 min of cardiopulmonary resuscitation. Animals were randomized to BTEL at 150 J or 200 J or to BTEH at 200 J or 360 J. RESULTS: Resuscitation was unsuccessful in three of the five animals treated with BTEH at 200 J. All other attempts were successful. Significant therapy effects were observed for survival (p = 0.035), left ventricular ejection fraction (p < 0.001), stroke volume (p < 0.001), fractional area change (p < 0.001), cardiac output (p = 0.044), and mean aortic pressure (p < 0.001). Hemodynamic outcomes were negatively associated with energy and average current but positively associated with peak current. Peak current was the only significant predictor of survival (p < 0.001). CONCLUSIONS: Maximum survival and minimum myocardial dysfunction were observed with the low-capacitance 150-J waveform, which delivered higher peak current while minimizing energy and average current.

Tang, W., M. H. Weil, et al. (2001). "A comparison of biphasic and monophasic waveform defibrillation after prolonged ventricular fibrillation." Chest 120(3): 948-54.

STUDY OBJECTIVE: To compare the effects of biphasic defibrillation waveforms and conventional monophasic defibrillation waveforms on the success of initial defibrillation, postresuscitation myocardial function, and duration of survival after prolonged duration of untreated ventricular fibrillation (VF), including the effects of epinephrine. DESIGN: Prospective, randomized, animal study. SETTING: Animal laboratory and university-affiliated research and educational institute. PARTICIPANTS: Domestic pigs. INTERVENTIONS: VF was induced in 20

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van Alem 2003

Walker 2003

anesthetized domestic pigs receiving mechanical ventilation. After 10 min of untreated VF, the animals were randomized. Defibrillation was attempted with up to three 150-J biphasic waveform shocks or a conventional sequence of 200-J, 300-J, and 360-J monophasic waveform shocks. When reversal of VF was unsuccessful, precordial compression was performed for 1 min, with or without administration of epinephrine. The protocol was repeated until spontaneous circulation was restored or for a maximum of 15 min. MEASUREMENTS AND RESULTS: No significant differences in the success of initial resuscitation or in the duration of survival were observed. However, significantly less impairment of myocardial function followed biphasic shocks. Administration of epinephrine reduced the total electrical energy required for successful resuscitation with both biphasic and monophasic waveform shocks. CONCLUSIONS: Lower-energy biphasic waveform shocks were as effective as conventional higher-energy monophasic waveform shocks for restoration of spontaneous circulation after 10 min of untreated VF. Significantly better postresuscitation myocardial function was observed after biphasic waveform defibrillation. Administration of epinephrine after prolonged cardiac arrest decreased the total energy required for successful resuscitation.

van Alem, A. P., F. W. Chapman, et al. (2003). "A prospective, randomised and blinded comparison of first shock success of monophasic and biphasic waveforms in out-of-hospital cardiac arrest." Resuscitation 58(1): 17-24.

BACKGROUND: Evidence suggests that biphasic waveforms are more effective than monophasic waveforms for defibrillation in out-of-hospital cardiac arrest (OHCA), yet their performance has only been compared in un-blinded studies. METHODS AND RESULTS: We compared the success of biphasic truncated exponential (BTE) and monophasic damped sine (MDS) shocks for defibrillation in OHCA in a prospective, randomised, double blind clinical trial. First responders were equipped with MDS and BTE automated external defibrillators (AEDs) in a random fashion. Patients in ventricular fibrillation (VF) received BTE or MDS first shocks of 200 J. The ECG was recorded for subsequent analysis continuously. The success of the first shock as a primary endpoint was removal of VF and required a return of an organized rhythm for at least two QRS complexes, with an interval of <5 s, within 1 min after the first shock. The secondary endpoint was termination of VF at 5 s. VF was the initial recorded rhythm in 120 patients in OHCA, 51 patients received BTE and 69 received MDS shocks. The success rate of 200 J first shocks was significantly higher for BTE than for MDS shocks, 35/51 (69%) and 31/69 (45%), P=0.01. In a logistic regression model the odds ratio of success for a BTE shock was 4.01 (95% CI 1.01-10.0), adjusted for baseline cardiopulmonary resuscitation, VF-amplitude and time between collapse and first shock. No difference was found with respect to the secondary endpoint, termination of VF at 5 s (RR 1.07 95% CI: 0.99-1.11) and with respect to survival to hospital discharge (RR 0.73 95% CI: 0.31-1.70). CONCLUSION: BTE-waveform AEDs provide significantly higher rates of successful defibrillation with return of an organized rhythm in OHCA than MDS waveform AEDs.

Walker, R. G., S. B. Melnick, et al. (2003). "Comparison of six clinically used external defibrillators in swine.[see comment]." Resuscitation 57(1): 73-83.

BACKGROUND: External defibrillation has long been practiced with two types of monophasic waveforms, and now four biphasic waveforms are also widely

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White 2001

available. Although waveforms and clinical dosing protocols differ among defibrillators, no studies have adequately compared performance of the monophasic or the biphasic waveforms. This is the first study to compare defibrillation efficacy among biphasic external defibrillators, and does so as part of a study comparing all commonly available waveforms using their respective manufacturer-provided and clinically used doses. METHODS AND RESULTS: Efficacy of six waveforms was tested in 852 short-duration ventricular fibrillation episodes in 14 swine. Protocol 1: 200-J monophasic damped sine (MDS) and monophasic truncated exponential (MTE) shocks were compared to 150-J biphasic shocks in six swine at the low-impedance of these animals. Protocol 2: Four commercially available biphasic defibrillators were compared using their respective manufacturer-recommended dose protocols in eight swine at low and simulated high-impedance. At low-impedance, all biphasic shocks achieved near-perfect success, while efficacy was significantly lower for MDS (67%) and MTE (30%) shocks. In protocol 2, first-shock success rates of the four biphasic defibrillators were uniformly high (97, 100, 100, and 94%) for low-impedance shocks, and decreased for high-impedance shocks (62, 92, 82, and 64%). There were statistically significant differences in efficacy among devices. CONCLUSIONS: Commonly used MDS and MTE waveforms provide markedly dissimilar efficacies. Despite impedance-compensation schemes in biphasic defibrillators, impedance has an impact on their efficacy. At high-impedance, modest efficacy differences exist among clinically available biphasic defibrillators, reflecting differences in both waveforms and manufacturer-provided doses.

Comment in: Resuscitation. 2003 Dec;59(3):365-7; author reply 367-71; PMID: 14659607

White, R. D., D. G. Hankins, et al. (2001). "Patient outcomes following defibrillation with a low energy biphasic truncated exponential waveform in out-of-hospital cardiac arrest." Resuscitation 49(1): 9-14.

PRIMARY OBJECTIVE: To determine the outcome of patients with out-of-hospital cardiac arrest and ventricular fibrillation as the presenting rhythm while using automated external defibrillators (AEDs) that delivered non-escalating, impedance-compensated low-energy (150 J) shocks. MATERIALS and METHODS: AEDs delivering low-energy biphasic truncated exponential (BTE) shocks were employed in an emergency medical services (EMS) system in which first-arriving personnel - police, firefighters or paramedics - delivered the initial shocks. Patients were classified according to their response to shocks: restoration of sustained spontaneous circulation (ROSC) without need for epinephrine and other advanced life support (ALS) interventions; and ALS, those requiring epinephrine in all instances. The primary end-point was neurologically-intact discharge survival. Secondary end-points were ROSC with shocks only and the call-to-shock time interval. RESULTS: Of 42 patients with VF arrest treated with BTE shocks, 35 were bystander-witnessed. Of these 35, 14 (38%) regained a sustained ROSC on-scene with shocks only, needing no epinephrine for ROSC. All 14 survived to discharge home. Of the remaining 21 patients needing ALS intervention, only two (9.5%) survived to discharge. Overall, 16/35 patients (46%) survived to discharge home, an outcome comparable to our experience with patients treated with escalating high-energy monophasic waveform shocks. CONCLUSIONS: Low-energy (150 J) non-escalating biphasic truncated exponential waveform shocks terminate VF in out-of-hospital cardiac arrest with high efficacy; patient outcome is comparable with that observed with escalating high-

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Zhang 2003

Zhang 2001

energy monophasic shocks. Low-energy shocks, in addition to high efficacy, may confer the advantage of less shock-induced myocardial dysfunction, though this will be difficult to define in the clinical circumstance of long-duration VF provoked by a pre-existing diseased myocardial substrate.

Zhang, Y., L. R. Davies, et al. (2003). "Open-chest epicardial "surgical" defibrillation: biphasic versus monophasic waveform shocks." Pacing & Clinical Electrophysiology 26(3): 711-8.

The aim of the study was to compare biphasic versus monophasic shocks for open-chest epicardial defibrillation. Transthoracic biphasic waveform shocks require less energy to terminate ventricular fibrillation compared to monophasic waveform shocks. However, if biphasic shocks are effective for open-chest epicardial ("surgical") defibrillation has not been established. Twenty-eight anesthetized adult swine (15-25 kg) underwent a midline sternotomy. Ventricular fibrillation was electrically induced. After 15 seconds of ventricular fibrillation, each pig in group 1 (n = 16) randomly received damped sinusoidal monophasic epicardial shocks and truncated exponential biphasic epicardial shocks from large (44.2 cm2) paddle electrodes at eight energy levels (2-50 J). Pigs in group 2 (n = 12) received monophasic and truncated exponential biphasic shocks from small (15.9 cm2) paddle electrodes. In group 1 (large paddle electrodes), the overall percent shock success rose from 15 +/- 9% at 2 J to 97 +/- 3% at 50 J. In this group there was no significant difference in percent of shock success between damped sinusoidal monophasic and biphasic waveform shocks. In group 2 (small paddle electrodes), biphasic shocks yielded a significantly higher percent of shock success than monophasic shocks at mid-energy levels from 7 to 20 J (all P < 0.01). With small surgical paddle electrodes, biphasic waveform shocks demonstrated a significantly higher percent of shock success rate compared to monophasic waveform shocks. With large paddle electrodes, the two waveforms were equally effective.

Zhang, Y., G. Karlsson, et al. (2001). "Biphasic and monophasic transthoracic defibrillation in pigs with acute left ventricular dysfunction." Resuscitation 50(1): 95-101.

OBJECTIVE: Our purpose was to compare biphasic versus monophasic shock success for VF termination in a porcine model of acute left ventricular (LV) dysfunction. BACKGROUND: For the termination of ventricular fibrillation (VF), transthoracic biphasic waveform shocks achieve higher success rates than monophasic shocks. However, the effectiveness of biphasic versus monophasic defibrillation in a setting of left ventricular dysfunction has not been reported. METHODS: In 23 open-chest adult swine (15-25 kg), LV dysfunction [> or =25% decline in cardiac output (CO)] was induced by continuous inhalation of halothane (1-1.75%). Each pig randomly received transthoracic biphasic and monophasic shocks at three energy levels (30, 50 and 100 J) in two conditions: baseline and LV dysfunction. Halothane effect on left ventricular size and contraction was measured by echocardiography in three additional swine. RESULTS: With halothane, pigs demonstrated a decline in CO (baseline 4.16+/-0.19, halothane 2.72+/-0.19 l/min, P<0.01), mean arterial pressure (baseline 107.2+/-3.5, halothane 80.1+/-3.4 mmHg, P<0.01) and increased left ventricular end-diastolic pressure (baseline 6.4+/-0.9,

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Zhang 2003(Tri vs Bi only:NOT USED)

halothane 12.7+/-0.8 mmHg, P<0.01). LV diameters increased and fractional shortening fell. During baseline, biphasic shocks achieved significantly greater success (termination of VF) compared to monophasic waveforms (100 J: biphasic 83.3+/-9.5 versus monophasic 38.9+/-9.5%, P<0.01; 50 J: biphasic 67.1+/-8.8 versus monophasic 11.8+/-5.7%, P<0.01; 30 J: biphasic: 31.9+/-6.4 versus monophasic 0+/-0%, P<0.01). The superiority of the biphasic waveform to terminate VF was retained during LV dysfunction at all energy levels (100 J: biphasic 78.3+/-7.3 versus monophasic 37.5+/-8.1%, P<0.01; 50 J: biphasic 65.5+/-11.5 versus monophasic 11.7+/-5.9%, P<0.01; 30 J: biphasic: 40.6+/-8.0 versus monophasic 3.1+/-3.1%, P<0.01). Within both waveforms, there were no significant differences in percent shock success at any energy level comparing baseline with LV dysfunction. CONCLUSION: In this porcine model of acute LV dysfunction, biphasic waveform shocks were not only superior to monophasic waveform shocks for termination of VF during baseline, but retained superiority to monophasic waveform shocks when LV dysfunction was present.

Zhang, Y., R. S. Ramabadran, et al. (2003). "Triphasic waveforms are superior to biphasic waveforms for transthoracic defibrillation: experimental studies." Journal of the American College of Cardiology 42(3): 568-75.

OBJECTIVES: Our objective was to evaluate the efficacy of triphasic waveforms for transthoracic defibrillation in a swine model. BACKGROUND: Triphasic shocks have been found to cause less post-shock dysfunction than biphasic shocks in chick embryo studies. METHODS: After 30 s of electrically induced ventricular fibrillation (VF), each pig in part I (n = 32) received truncated exponential biphasic (7.2/7.2 ms) and triphasic (4.8/4.8/4.8 ms) transthoracic shocks. Each pig in part II (n = 14) received biphasic (5/5 ms) and triphasic shocks (5/5/5 ms). Three selected energy levels (50, 100, and 150 J) were tested for parts I and II. Pigs in part III (n = 13) received biphasic (5/5 ms) and triphasic (5/5/5 ms) shocks at a higher energy (200 and 300 J). Although the individual pulse durations of these shocks were equal, the energy of each pulse varied. Nine pigs in part I also received shocks where each individual pulse contained equal energy but was of a different duration (biphasic 3.3/11.1 ms; triphasic 2.0/3.2/9.2 ms). RESULTS: Triphasic shocks of equal duration pulses achieved higher success than biphasic shocks at delivered low energies: <40 J: 38 +/- 5% triphasic vs. 19 +/- 4% biphasic (p < 0.01); 40 to <50 J: 66 +/- 7% vs. 42 +/- 7% (p < 0.01); and 50 to <65 J: 78 +/- 4% vs. 54 +/- 5% (p < 0.05). Shocks of equal energy but different duration pulses achieved relatively poor success for both triphasic and biphasic waveforms. Shock-induced ventricular tachycardia (VT) and asystole occurred less often after triphasic shocks. CONCLUSIONS: Triphasic transthoracic shocks composed of equal duration pulses were superior to biphasic shocks for VF termination at low energies and caused less VT and asystole.

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