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Biphasic and monophasic shocks for transthoracic defibrillation: a meta analysis of randomised controlled trials
Resuscitation 58 (2003) 9 /16 www.elsevier.com/locate/resuscitation
Review
Biphasic and monophasic shocks for transthoracic defibrillation: a meta analysis of randomised controlled trials Steven C. Faddy a,*, Jane Powell b, Jonathan C. Craig c a
Cardiology Department, St Vincent’s Hospital Sydney, Victoria St, Darlinghurst, NSW 2010, Australia b Neonatal Intensive Care Unit. Royal North Shore Hospital, Sydney, Australia c Department of Public Health and Community Medicine, University of Sydney, and the Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, Australia Received 17 January 2003; received in revised form 7 February 2003; accepted 7 February 2003
Abstract 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. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Ventricular fibrillation; Defibrillation; Cardiopulmonary resuscitation (CPR); Meta-analysis
Resumo Introduc¸a˜o: Nos desfibrilhadores implanta´veis usam-se por rotina ondas bifa´sicas. Mas teˆm sido adoptadas menos prontamente nos desfibrilhadores externos. Este estudo foi realizado para avaliar a efica´cia e os malefı´cios das ondas bifa´ sicas quando comparadas com as monofa´ sicas na desfibrilhac¸ a˜ o transtora´ cica dos doentes em fibrilhac¸ a˜ o ventricular (VF) ou taquicardia ventricular hemodinaˆ micamente insta´ vel. Me´ todo: O estudo incluiu ensaios randomizados controlados comparando a desfibrilhac¸a˜o externa monofa´sica ou bifa´sica para participantes com VF ou taquicardia ventricular hemodinaˆmicamente insta´veis. Foram incluı´dos na ana´lise sete ensaios (1129 doentes). Todos os ensaios foram realizados durante procedimentos electrofisiolo´ gicos ou teste de cardioversores/desfibrilhadores implanta´veis. Resultados: Quando comparados com os monofa´sicos de 200 J, os choques bifa´sicos de 200 J reduzem o risco de assistolia po´s primeiro choque ou de VF persistente em 81% (risco relativo (RR) 0.19; Intervalo Confianc¸a 95% (CI) 0.06 /0.60) para o primeiro choque. Reduzindo a energia das ondas bifa´sicas para 115-130 J a efica´cia e´ similar quando comparada com as ondas monofa´sicas de 200J (RR 1.07, CI 0.66 /1.74). Os choques bifa´sicos de baixa energia produzem menos lesa˜o mioca´rdica que os choques monofa´sicos de energia mais elevada conforme foi determinado pela
* Corresponding author. Tel.: /61-2-8382-3482; fax: /61-2-8382-2959. E-mail address: [email protected] (S.C. Faddy). 0300-9572/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0300-9572(03)00077-7
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deflecc¸a˜o do segmento ST apo´s o choque. Concluso˜es: As ondas bifa´sicas desfibrilham com efica´cia semelhante a energias mais baixas do que as ondas monofa´sicas standard 200 J e com maior efica´cia que os choques monofa´sicos da mesma energia. Os dados disponı´veis sugerem que a aplicac¸a˜ o de energia e voltagem mais baixas provocam menos lesa˜o mioca´rdica po´s-choque. # 2003 Elsevier Ireland Ltd. All rights reserved. Palavras chave: Fibrilhac¸a˜o ventricular; Desfibrilhac¸a˜o; Reanimac¸a˜o cardio-pulmonar (RCP); Meta-ana´lise
Resumen Introduccio´n : Las ondas bifa´sicas son usadas rutinariamente para los desfibriladores implantables. Estas ondas han sido menos usadas para desfibrilacio´n externa. Este estudio fue realizado para evaluar la eficacia y los riesgos de la ondas bifa´sicas en relacio´n con las monofa´sicas en la desfibrilacio´n transtora´cica de pacientes en fibrilacio´n ventricular (VF) o en taquicardia ventricular hemodinamicamente inestable. Me´todos : Los estudios incluyen ensayos controlados, randomizados que comparan la desfibrilacio´n externa bifa´sica con la monofa´sica para participantes con VF o taquicardia ventricular hemodinamicamente inestable. Se incluyeron 7 ensayos en este ana´lisis (1129 pacientes). Todos los ensayos fueron conducidos durante procedimientos electrofisiolo´gicos o pruebas de desfibrilador/cardioversor. Resultados : Las descargas bifa´sicas de 200 Joules, comparadas con descargas de 200 J monofa´sicos, redujeron el riesgo de ası´stole post primera descarga o VF persistente en 81% (riesgo relativo (RR) 0.19; con intervalo de confianza (CI) de 0.06 /0.60) para la primera descarga. Al reducir la energı´a de la onda bifa´sica a 115-130 J se consiguio´ igual efectividad comparada con descarga de 200 J monofa´sico (RR 1,07; CI o.66 /1.74). Las descargas bifa´sicas con menor energı´a producen menos dan˜o mioca´rdico que descargas monofa´sicas de mayor energı´a determinados por desniveles del segmento ST despue´s de la descarga. Conclusiones : Las ondas bifa´sicas desfibrilan con eficacia similar a menores energı´as que las ondas monofa´sicas esta´ndar de 200 J, y con mayor eficacia que descargas monofa´sicas de igual energı´a. Los datos disponibles sugieren que a menor energı´a y voltaje descargada habra´ menor lesio´n mioca´rdica post descarga. # 2003 Elsevier Ireland Ltd. All rights reserved. Palabras clave: Fibrilacio´n ventricular: Desfibrilacio´n; Reanimacio´n cardiopulmonar (RCP); Meta ana´lisis
1. Introduction Whether confronting hospital staff or first responders in the field, cardiac arrest demands prompt action, but has a poor prognosis. About 75% of victims will not survive initial resuscitation attempts and 91% die before hospital discharge [1]. Ventricular fibrillation (VF) is the initial ECG rhythm upon arrival of paramedics in 30/ 40% of out-of-hospital cardiac arrests (OHCA) [2 /5], but is estimated to be the cause of up to 85% of OHCA [5]. However, VF is potentially the most salvageable rhythm in cardiac arrest [1,6,7]. Electrical countershock is the definitive treatment, but the efficacy of shocks decreases dramatically with time. Defibrillation success falls from 80 to 98% after 30 s of VF to around 10% after 20 min [5,8]. Defibrillation waveform morphology is the latest major advance in external defibrillator development. Biphasic waveforms are characterised by an initial positive current flow followed by a reversal to negative current flow. Implantable cardioverter/defibrillators (ICD) with biphasic waveforms are able to defibrillate with less energy than monophasic waveforms [9 /11], requiring lower voltage and, hence, smaller and lighter battery and capacitor banks. Although biphasic waveforms are coming into more widespread use, there is a paucity of research using biphasic waveforms for transthoracic defibrillation. With few exceptions, the
studies performed to date are largely non-randomised and often without control groups. Transthoracic defibrillators with monophasic waveforms are still the type most used in current clinical practise. If trials of transthoracic defibrillation show similar benefits of biphasic waveforms as internal defibrillation trials have shown, there is potential to improve the poor outcomes associated with sudden cardiac death. More victims could be saved and the lesser degree of myocardial damage resulting from low energy shocks may improve the dismal long-term survival rate. In addition, external defibrillators (including AEDs) may become smaller, more portable and less expensive due to the reduced energy and voltage requirements. This systematic review was performed in order to evaluate the benefits and harms of biphasic waveforms over monophasic waveforms for the transthoracic defibrillation of patients in ventricular fibrillation or haemodynamically unstable ventricular tachycardia.
2. Methods MEDLINE (1966 /Sep 2002), EMBASE (1985 /Sep 2002) and the Cochrane Controlled Trials Register (3rd quarter 2002) were searched using medical subject
S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16
heading (MeSH) terms (ventricular fibrillation, sudden death, electric countershock), relevant textwords (monophasic, biphasic) and limited to randomised controlled trials using an optimally sensitive search strategy [12,13]. Manual searching of reference lists cited in original articles, relevant journals (Journal of the American College of Cardiology, Circulation, Resuscitation, Prehospital Emergency Care), and proceedings of major cardiology meetings between 1985 and 1999 (American Heart Association, American College of Cardiology) was also performed. Contact was made with known investigators to identify studies that may have been overlooked or remained unpublished. Studies were considered for inclusion if they were randomised controlled trials of biphasic and monophasic waveforms in the setting of patients with ventricular fibrillation or ventricular tachycardia requiring electrical cardioversion. Animal studies were not considered. Two types of primary outcome were assessed. When the biphasic and monophasic waveforms were of equal energy (e.g. 200 J) first shock failure (asystole or persistent ventricular fibrillation) was compared. When the biphasic and monophasic shocks were of different energy, both first shock failure and the weighted mean differences in delivered energy and voltage were assessed. First shock failure was used to demonstrate similar efficacy of the different energies, with the difference in delivered energy and voltage demonstrating the ability to achieve this similar success rate with lower output from the defibrillator. Secondary outcomes included endpoints thought to be markers of myocardial damage such as ST segment changes and time from first shock to restoration of a haemodynamically stable supraventricular rhythm. Two reviewers independently assessed the methodological quality of each trial. Disagreements were resolved by discussion. Quality assessments were based on the methodological description of each primary study. Studies were grouped according to whether they reported a random or quasi-random method of treatment allocation, allocation concealment, adequate blinding of outcomes and intention to treat analysis. Quantitative analyses of outcomes were based on trials with independent study groups. Relative risk (RR) and risk difference (RD) were calculated for individual studies and then pooled using a random effects model. The measure of effect producing the least statistical heterogeneity was used to summarise the data. Heterogeneity was assessed for compatibility with the assumption of uniform relative risk using the Q statistic. In addition, weighted mean difference (WMD) in delivered energy and voltage were evaluated for studies comparing waveforms of different energies. There were too few studies to fully explore sources of heterogeneity between
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studies. Data from crossover studies were not included [14,15].
3. Results 3.1. Literature search Of 813 potentially relevant citations, nine papers describing seven randomised trials comparing biphasic and monophasic waveforms for human transthoracic defibrillation were identified (Table 1). All of the primary studies were conducted during electrophysiology procedures or implantable cardioverter/defibrillator testing with well-trained personnel in attendance. There were 398 patients included in the pooled analysis comparing waveforms of the same nominal energy [16 /18], 545 in the pooled analysis of first shock efficacy for 200 J monophasic and lower energy biphasic waveforms [18,19], and 614 in the pooled analysis of delivered energy and voltage. Several biphasic waveforms were used. Details of experimental and control waveforms are given in Table 1. The average age of individual study populations ranged from 61 to 68 years. Individual studies comprised between 73 and 90% males. The average weight of patients was 81 /82 kg. Coronary artery disease was present in 69 /84% of patients in individual primary studies. A wide variety of cardioactive drugs were in use. No deaths were recorded during the study period in any of the primary studies. Table 2 describes the methodological qualities of the primary studies included in the final analyses. All studies were stated to be randomised but methods were described in only five. Allocation concealment was adequately described in just three studies. Intention-totreat analysis was generally not stated. In one study, patients were excluded from analysis because of ‘incorrect randomisation’ and ‘violation of study protocol’ [20], which was clearly not intention-to-treat analysis. One study was presented in abstract form only [16]. 3.2. First shock failure First shock failure was assessed from studies of short duration VF/VT performed during electrophysiology studies. Compared to 200 J monophasic shocks, 200 J biphasic shocks reduced the risk of asystole or persistent VF after the first shock by 81% (RR /0.19, 95%CI: 0.06 /0.60) (Fig. 1). The pooled analysis showed no significant heterogeneity (x2 /0.67, 2df, P /0.7).
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Table 1 Characteristics of trials of monophasic versus biphasic transthoracic defibrillation Study ID
No. analysed
Study design
Participants
Inclusion criteria
Intervention
Outcomes
Echt, 1993 [16] Greene, 1993 [17]
120
Parallel Parallel
EPS for investigation of ventricular arrhythmias OHCA survivors undergoing EPS
200 200 200 200
J J J J
Gurvich Edmark Gurvich Edmark
First shock failure
171
Bardy, 1996 [19]
430
Parallel
649/11 years 89% male 649/11 years 90% male 829/15 kg 659/12 years 78% male 819/16 kg
OHCA survivors undergoing 130 ICD testing 115 200 360
J J J J
BTE BTE MDS MDS
Reddy, 1997 [21]
30
Mittal, 1999 [20]
184
Parallel
629/11 years 75% male 819/17 kg 639/14 years 78% male
Higgins, 2000 [18]
154
Parallel
OHCA survivors undergoing 130 J BTE ICD testing 115 J BTE 200 J MDS ICD surgery and testing, EPS 120 J experimental biphasic 200 J MDS EPS, evaluation of ICD 130 J BTE 200 J BTE 200 J MDS
First shock failure Difference in delivered energy ST segment 10 s post shock ST segment 10 s post shock
Crossover
689/12 years 81% male 819/15 kg
First shock failure
First shock failure
First shock failure Difference in delivered energy
Mean9/S.D. unless otherwise stated. Abbreviations: OHCA, out-of-hospital cardiac arrest; EPS, electrophysiology study; ICD, implantable cardioverter/defibrillator; BTE, biphasic truncated exponential; MTE, monophasic truncated exponential; MDS, monophasic damped sine.
Table 2 Quality of trials of monophasic versus biphasic transthoracic defibrillation Study
Method of randomisation Blinding and allocation concealment
Outcomes assessment and measurement
Intention-to- Loss to foltreat low up
Notes
Echt, 1993 [16] Greene, 1993 [17]
States ‘randomised in Not stated blinded fashion’. Randomised by defibrilla- Investigator and tor. outcome assessor
First shock failure: Unclear.
Not stated
Not stated
Abstract
Not stated
0/171 (0%)
Bardy, 1996 [19]
Weighted randomisation without replacement. Allocation concealment unclear. States order of shock randomised. Allocation concealment unclear. Simple block randomisation. Allocation concealment unclear. Randomised by defibrillator.
First shock failure : Coded ECG strip analysed. Code later broken to reveal study group. First shock failure: Unclear. Delivered energy : Output from defibrillator. ST segment : Digital calipers. ST segment : Two interpreters using digital callipers and digitised ECG. First shock failure : Unclear. Delivered energy : Interface unit connected to computer. First shock failure : Coded ECG strip analysed. Code later broken to reveal study group. Delivered energy : Output from defibrillator.
Not stated
30/460 (7%)
Not stated
3/33 (9%)
No
Not stated
Not stated
27/181 (15%)
Reddy, 1997 [21] Mittal, 1999 [20] Higgins, 2000 [18]
Outcome assessor
Outcome assessors
Not stated
Investigator and outcome assessor
Compared to 200 J monophasic shocks, lower energy biphasic shocks have a similar chance of resulting in persistent VF or asystole after the first shock (RR / 1.07, 95% CI: 0.66 /1.74) (Fig. 2). The wide confidence intervals, however, demonstrate weak evidence for
Antero-posterior electrode placement
equivalence of these waveforms. Although evidence of equivalence is promising, it is not yet definitive. Pooling of studies comparing 200 J monophasic and low energy biphasic waveforms showed no significant heterogeneity (x2 /1.12, 1df, P/0.29).
S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16
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Fig. 1. Efficacy of first shock in reversing VF for 200 J monophasic and biphasic shocks; (a) relative risk reduction, (b) risk difference (absolute risk reduction).
3.3. Delivered energy and voltage Three studies in electrophysiology patients measured delivered energy and voltage with 200 J monophasic and lower energy biphasic waveforms. In achieving equivalent efficacy, 130 J biphasic shocks delivered a mean of 80.5 J (95% CI: 70.3 /90.7 J) less energy [18 /20] and required 1016.4 (95% CI: 971.0 /1061.7) fewer volts across the capacitors [19]. Similarly, 115 J biphasic waveforms delivered 98.0 J (95% CI: 96.7 /99.3 J) less energy and required 1079.0 (95% CI: 1033.6 /1124.4) fewer volts to achieve equivalent efficacy as the 200 J monophasic waveform [19]. The 120 J impedance-compensating biphasic waveform and anterior/posterior electrode placement resulted in first-shock failure less frequently than a 200 J monophasic waveform (RR /0.15, 95% CI: 0.02 /1.19), although this difference was not statistically significant
[20]. In achieving this effect, the biphasic waveform delivered 76.0 J (63%) less energy (95% CI: 72.0 /80.0 J) and 1251.0 (58%) fewer volts (95% CI: 1186.4 /1315.6 V). This study showed a statistically significant but clinically unimportant difference in impedance between the two study groups. Fig. 3 shows the mean ST segment deflection from two studies that measured ST segments after 200 J monophasic and lower energy biphasic shocks [19,21]. Funnel plots were derived but there were too few studies in each analysis to adequately investigate for the presence or effects of publication bias.
4. Discussion After short durations of VF/VT, biphasic defibrillation waveforms result in asystole or persistent VF/VT
Fig. 2. Efficacy of first shock in reversing VF for 200 J monophasic shocks compared to lower energy biphasic shocks.
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Fig. 3. ST segment deflection in two studies (mean9/95% confidence interval).
less frequently than monophasic waveforms of the same energy, or at similar rates with less delivered energy as the standard 200 J monophasic waveform currently employed. Low energy biphasic shocks result in less severe ST segment changes, possibly indicating a lesser degree of post-shock myocardial damage. The primary studies comparing 200 J biphasic and monophasic shocks reported significantly better first shock efficacy following biphasic shocks. However, this review assessed the adverse outcome, persistent VF or asystole. Two of the three primary studies failed to show significant superiority of biphasic waveforms with respect to adverse outcomes (Fig. 1a), largely due to small sample sizes. The pooled analysis, however, was able to demonstrate a significant advantage of biphasic waveforms over monophasic with respect to persistent VF or asystole. The results of these trials suggest that in-hospital cardiac arrest, where episodes of VF and haemodynamically unstable VT are diagnosed and treated relatively quickly, may be treated more successfully with biphasic defibrillation waveforms than the standard monophasic waveforms currently employed. The studies included in this review all dealt with arrhythmias of between 10 and 30 s duration. It is uncertain whether these results can be extended to out-of-hospital cardiac arrest (OHCA) where there are average delays of up to 13 min between collapse and defibrillation [1,5,22,23]. Three animal studies have investigated the use of biphasic waveforms in both short and long duration VF/ VT [24 /26]. All showed that biphasic waveforms had a 30 /56% lower defibrillation threshold than monophasic waveforms for short duration VF/VT. These studies also demonstrated a 38/56% lower defibrillation threshold for biphasic waveforms after long duration VF/VT of up
to 10 min. Another study performed on pigs showed a superior rate of return of spontaneous circulation after 8 min of VF and 1 min of simulated CPR with biphasic shocks compared to monophasic shocks of the same energy (RR /7.0, 95% CI: 0.96 /50.93) [27]. In short, available data on long duration VF/VT from animal studies shows that biphasic waveforms are superior to monophasic for transthoracic defibrillation of established arrythmias. It is reasonable to extrapolate these results to long duration VF/VT in humans and suggest that biphasic waveforms will result in higher rates of spontaneous circulation. Randomised controlled trials of these waveforms in prehospital treatment of VF/VT are necessary, but available data suggests that biphasic waveforms will perform no worse than monophasic. Future studies should adhere to the Utstein reporting guidelines [28] for OHCA. These guidelines have been in operation since 1991 and define one resuscitation outcome as the presence of a perfusing rhythm, at least temporarily, after shock. Studies reporting post-shock asystole as successful ‘defibrillation’ have the potential to bias comparisons of biphasic and monophasic waveforms in otherwise rigorous randomised trials, thus confusing any true benefits of biphasic waveform defibrillation. A recent randomised study performed in out-ofhospital cardiac arrest victims demonstrated superior defibrillation in patients treated with an impedancecompensating biphasic waveform defibrillator compared to three monophasic defibrillators [29]. This study could not be included in our meta-analysis, however, because the investigators have included reversion of VF/VT to asystole as a successful shock. Our review defined reversion to asystole as a failed shock. Secondary outcomes in this study did, however, include return of spontaneous circulation. Biphasic waveforms resulted in higher rates of spontaneous circulation compared to monophasic (81 vs 52%, P /0.001) and higher rates of hospital admission, but did not improve long term survival. The study comparing the 120 J impedance-compensating biphasic waveform with a 200 J monophasic waveform [20] was not included in the pooled analysis of lower energy biphasic waveforms. Inclusion of this study resulted in significant statistical heterogeneity, which may be related to the antero-posterior electrode placement used. Further investigation is required before a link between electrode placement and biphasic waveform efficacy can be established. Two studies investigated ST segment deflection as a measure of myocardial injury by measuring the ST segment 80 ms after the J-point, referenced to the preceding TP interval (10 s after successful shock). Although both studies were very similar in design and methods, one measured ST elevation resulting from transthoracic defibrillation shocks and the other mea-
S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16
sured ST depression (Fig. 3). It would appear that the use of adhesive defibrillation pads to measure the ECG led to measurement of non-standard ECG recordings. Bardy et al. [19] claim their ECG approximated Lead II while Reddy et al. [21] claimed they were measuring an approximation of V5. Quantitative analysis of these results is clearly not justified. However, it is reasonable to infer that 200 J monophasic waveforms have a far more profound effect on ST segments, which may reflect temporary myocardial injury. There have not been any studies performed comparing biochemical cardiac markers following biphasic or monophasic defibrillation. The primary studies analysed in this review were conducted during electrophysiology procedures and there was little underlying risk of defibrillation shocks failing to revert the short duration arrythmias. Ventricular fibrillation/tachycardia associated with out-ofhospital cardiac arrest is unable to be reverted to a haemodynamically stable rhythm in as many as 90.9% of cases [30]. Applying the 81% relative risk reduction seen in the review, it would be possible to reduce this failure rate to as little as 17.2%, representing return of spontaneous circulation in as many as 73% of patients. The absolute risk reduction in this low-risk population was calculated to be 9% (Fig. 1b), which, when applied to the poorest published OHCA figures, also suggests that a rate of ROSC of at least 73% could be achieved. The realism of these assumptions and the effect on longterm survival will only be demonstrated by large randomised trials in the prehospital setting. Despite early predictions, the spread of automatic external defibrillators (AEDs) in the community has been somewhat slower than expected. This has been blamed in part on the size, weight and cost of the instruments. Biphasic waveforms allow defibrillation with less energy and voltage. A decrease in the size of batteries and capacitor banks, as well as allowing electronic switching instead of solid-state, will allow AEDs to become smaller, lighter and ultimately, less expensive. It is hoped that this will facilitate a far more widespread distribution of these devices in the community in general and in public places in particular. A limitation of the review is the use of first shock failure as the primary outcome. Although this was guided by the previously published literature, the efficacy of multiple biphasic shocks compared to multiple monophasic shocks will need to be determined in large randomised trials of long duration VF/VT. Another limitation is the method of inducing ventricular arrhythmias. Each of the studies included in the review investigated electrically induced VF/VT, which has been shown to require less energy to defibrillate than ischaemia-induced arrhythmias [31,32]. Human cardiac arrest generally occurs because a critical mass of myocardium is not being adequately perfused. Cardiac disease is estimated to be the underlying cause of sudden
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death in 66/74% of sudden cardiac deaths [22,33]. Electrically induced arrhythmia is an extremely rare cause of cardiac arrest. Previous studies of varying methodological quality have suggested that biphasic waveforms have an additional benefit over monophasic for long duration VF [25,26,34] but that arrhythmias of ischaemic origin have higher defibrillation thresholds than electrically induced VF/VT [31,32]. The true benefits of biphasic waveforms in OHCA will remain unclear until randomised controlled trials are conducted in patients with long duration VF of ischaemic origin.
5. Conclusion Biphasic defibrillation waveforms revert short duration VF/VT to a haemodynamically stable rhythm more often than monophasic waveforms of the same energy. With lower delivered energy, biphasic waveforms can defibrillate with similar efficacy to higher-energy monophasic waveforms. Low-energy biphasic waveforms result in less severe ST segment changes. Although not conclusively proven in studies of out-ofhospital cardiac arrest, biphasic defibrillation waveforms have the potential to improve the disappointing survival rate from sudden cardiac death.
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S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16 with a transvenous lead system. J Am Coll Cardiol 1999;30(1):233 /6. Natale A, Sra J, Krum D, et al. Comparison of biphasic and monophasic pulses: does the advantage of biphasic shocks depend on the waveshape? Pacing Clin Electrophysiol 1995;18(7):1354 / 61. Kroll MW, Anderson KM, Supino CG, Adams TP. Decline in defibrillation thresholds. Pacing Clin Electrophysiol 1993;16(1 Pt 2):213 /7. Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence-Based Medicine */How to Practice and Teach EBM. Edinburgh: Churchill Livingstone, 1998:37 /78. Mulrow CD, Oxman AD, editors. Locating and selecting studies. Cochrane Collaboration Handbook [updated September 1997]; Section 5. In: The Cochrane Library [database on disk and CDROM]. The Cochrane Collaboration. Oxford: Update Software; 1997, Issue 4. Augostini RS, Tchou PJ, Love C, et al. Multicentre trial of a biphasic external defibrillation waveform (Abstract). Pacing Clin Electrophysiol 1999;22:827. Bardy GH, Gliner BE, Kudenchuk PJ, et al. Truncated biphasic pulses for transthoracic defibrillation. Circulation 1995;91(6):1768 /74. Echt DS, Greene HL, Kudenchuk PJ et al. and the biphasic defibrillation waveform investigators. Biphasic waveform is more efficacious than monophasic waveform for transthoracic cardioversion (Abstract). Pacing Clin Electrophysiol 1993;16;1914. Greene HL, DiMarco JP, Kudenchuk PJ, et al. Comparison of monophasic and biphasic defibrillation pulse waveforms for transthoracic cardioversion. Am J Cardiol 1995;75(16):1135 /9. Higgins SL, Herre JM, Epstein AE et al. for the Physio-Control Biphasic Investigators. A comparison of biphasic and monophasic shocks for external defibrillation. Prehospital Emerg Care 2000;4:305 /313. Bardy GH, Marchlinski FE, Sharma AD, et al. Multicentre comparison of truncated biphasic shocks and standard damped sine wave monophasic shocks for transthoracic ventricular defibrillation. Circulation 1996;94(10):2507 /14. Mittal S, Ayati S, Stein KM et al. for the Zoll Investigators. Comparison of a novel rectilinear biphasic waveform with a damped sine wave monophasic waveform for transthoracic ventricular defibrillation. J Am Coll Cardiol 1999;34(5):1595 / 1601. Reddy RK, Gleva MJ, Gliner BE, et al. Biphasic transthoracic defibrillation causes fewer ST-segment changes after shock. Ann Emerg Med 1997;30(2):127 /34. Holmberg M, Holmberg S, Herlitz J, Gardelov B for the Swedish cardiac Arrest Registry. Survival after cardiac arrest outside hospital in Sweden. Resuscitation 1998; 36(1):29 /36. Hoekstra JW, Banks JR, Martin DR, et al. Effect of firstresponder automated defibrillation on time to therapeutic inter-
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ventions during out-of-hospital cardiac arrest. The Multicenter High Dose Epinephrine Study Group. Ann Emerg Med 1993;22(8):1247 /53. Walcott GP, Melnick SB, Chapman FW, et al. Relative efficacy of monophasic and biphasic waveforms for transthoracic defibrillation after short and long durations of ventricular fibrillation. Circulation 1998;98(20):2210 /5. Halperin H, Leng C, Paradis N, et al. Defibrillation with monophasic and biphasic waveforms in prolonged cardiac arrest. Circulation 1998;98:I-173. Walcott GP, Melnick SB, Chapman FW, et al. Comparison of monophasic and biphasic waveforms for external defibrillation in an animal model of cardiac arrest and resuscitation (Abstract). J Am Coll Cardiol 1995;25(2 Suppl. A):405A. Scheatzle MD, Menegazzi JJ, Allen TL, Durham SB. Evaluation of biphasic transthoracic defibrillation in an animal model of prolonged ventricular fibrillation. Acad Emerg Med 1999;6(9):880 /6. Anonymous. Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the ‘Utstein style’. Prepared by a Task Force of Representatives from the European Resuscitation Council, American Heart Association, Heart and Stroke Foundation of Canada, Australian Resuscitation Council. Resuscitation 1991;22(1):1 /26. Schneider T, Martens PR, Paschen H et al. for the Optimized Response to Cardiac Arrest (ORCA) Investigators. Multicenter, randomised, controlled trial of 150-J biphasic shocks compared with 200- to 360-J monophasic shocks in the resuscitation of outof-hospital cardiac arrest victims. Circulation 2000;102:1780 / 1787. Stiell IG, Wells GA, De Maio VJ et al. for the OPALS study group. Modifiable factors associated with improved cardiac arrest survival in a multicentre basic life support/defibrillation system: OPALS study phase I results. Ann Emerg Med 1999;33(1):44 /50. Killingsworth CR, Walcott GP, Churchwell SR, et al. Comparison of biphasic waveform transthoracic defibrillation thresholds for electrically induced and spontaneous ventricular fibrillation in a dog model of acute ischaemia and reperfusion [Abstract]. Circulation 1998;98:I-173. Killingsworth CR, Walcott GP, Smith WS, et al. Biphasic waveform transthoracic defibrillation thresholds for spontaneous ventricular fibrillation in a porcine model of acute ischaemia [Abstract]. J Am Coll Cardiol 1999;33(2 Suppl. A):370A. Holmberg M, Holmberg S, Herlitz J. The problem of out-ofhospital cardiac arrest prevalence of sudden death in Europe today. Am J Cardiol 1999;83(5B):88D /90D. Tang W, Weil MH, Sun S, et al. Defibrillation with low-energy biphasic waveform reduces the severity of post-resuscitation myocardial dysfunction after prolonged cardiac arrest [Abstract]. Crit Care Med 1999;27(1 Suppl.):A43.
Review
Biphasic and monophasic shocks for transthoracic defibrillation: a meta analysis of randomised controlled trials Steven C. Faddy a,*, Jane Powell b, Jonathan C. Craig c a
Cardiology Department, St Vincent’s Hospital Sydney, Victoria St, Darlinghurst, NSW 2010, Australia b Neonatal Intensive Care Unit. Royal North Shore Hospital, Sydney, Australia c Department of Public Health and Community Medicine, University of Sydney, and the Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, Australia Received 17 January 2003; received in revised form 7 February 2003; accepted 7 February 2003
Abstract 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. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Ventricular fibrillation; Defibrillation; Cardiopulmonary resuscitation (CPR); Meta-analysis
Resumo Introduc¸a˜o: Nos desfibrilhadores implanta´veis usam-se por rotina ondas bifa´sicas. Mas teˆm sido adoptadas menos prontamente nos desfibrilhadores externos. Este estudo foi realizado para avaliar a efica´cia e os malefı´cios das ondas bifa´ sicas quando comparadas com as monofa´ sicas na desfibrilhac¸ a˜ o transtora´ cica dos doentes em fibrilhac¸ a˜ o ventricular (VF) ou taquicardia ventricular hemodinaˆ micamente insta´ vel. Me´ todo: O estudo incluiu ensaios randomizados controlados comparando a desfibrilhac¸a˜o externa monofa´sica ou bifa´sica para participantes com VF ou taquicardia ventricular hemodinaˆmicamente insta´veis. Foram incluı´dos na ana´lise sete ensaios (1129 doentes). Todos os ensaios foram realizados durante procedimentos electrofisiolo´ gicos ou teste de cardioversores/desfibrilhadores implanta´veis. Resultados: Quando comparados com os monofa´sicos de 200 J, os choques bifa´sicos de 200 J reduzem o risco de assistolia po´s primeiro choque ou de VF persistente em 81% (risco relativo (RR) 0.19; Intervalo Confianc¸a 95% (CI) 0.06 /0.60) para o primeiro choque. Reduzindo a energia das ondas bifa´sicas para 115-130 J a efica´cia e´ similar quando comparada com as ondas monofa´sicas de 200J (RR 1.07, CI 0.66 /1.74). Os choques bifa´sicos de baixa energia produzem menos lesa˜o mioca´rdica que os choques monofa´sicos de energia mais elevada conforme foi determinado pela
* Corresponding author. Tel.: /61-2-8382-3482; fax: /61-2-8382-2959. E-mail address: [email protected] (S.C. Faddy). 0300-9572/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0300-9572(03)00077-7
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S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16
deflecc¸a˜o do segmento ST apo´s o choque. Concluso˜es: As ondas bifa´sicas desfibrilham com efica´cia semelhante a energias mais baixas do que as ondas monofa´sicas standard 200 J e com maior efica´cia que os choques monofa´sicos da mesma energia. Os dados disponı´veis sugerem que a aplicac¸a˜ o de energia e voltagem mais baixas provocam menos lesa˜o mioca´rdica po´s-choque. # 2003 Elsevier Ireland Ltd. All rights reserved. Palavras chave: Fibrilhac¸a˜o ventricular; Desfibrilhac¸a˜o; Reanimac¸a˜o cardio-pulmonar (RCP); Meta-ana´lise
Resumen Introduccio´n : Las ondas bifa´sicas son usadas rutinariamente para los desfibriladores implantables. Estas ondas han sido menos usadas para desfibrilacio´n externa. Este estudio fue realizado para evaluar la eficacia y los riesgos de la ondas bifa´sicas en relacio´n con las monofa´sicas en la desfibrilacio´n transtora´cica de pacientes en fibrilacio´n ventricular (VF) o en taquicardia ventricular hemodinamicamente inestable. Me´todos : Los estudios incluyen ensayos controlados, randomizados que comparan la desfibrilacio´n externa bifa´sica con la monofa´sica para participantes con VF o taquicardia ventricular hemodinamicamente inestable. Se incluyeron 7 ensayos en este ana´lisis (1129 pacientes). Todos los ensayos fueron conducidos durante procedimientos electrofisiolo´gicos o pruebas de desfibrilador/cardioversor. Resultados : Las descargas bifa´sicas de 200 Joules, comparadas con descargas de 200 J monofa´sicos, redujeron el riesgo de ası´stole post primera descarga o VF persistente en 81% (riesgo relativo (RR) 0.19; con intervalo de confianza (CI) de 0.06 /0.60) para la primera descarga. Al reducir la energı´a de la onda bifa´sica a 115-130 J se consiguio´ igual efectividad comparada con descarga de 200 J monofa´sico (RR 1,07; CI o.66 /1.74). Las descargas bifa´sicas con menor energı´a producen menos dan˜o mioca´rdico que descargas monofa´sicas de mayor energı´a determinados por desniveles del segmento ST despue´s de la descarga. Conclusiones : Las ondas bifa´sicas desfibrilan con eficacia similar a menores energı´as que las ondas monofa´sicas esta´ndar de 200 J, y con mayor eficacia que descargas monofa´sicas de igual energı´a. Los datos disponibles sugieren que a menor energı´a y voltaje descargada habra´ menor lesio´n mioca´rdica post descarga. # 2003 Elsevier Ireland Ltd. All rights reserved. Palabras clave: Fibrilacio´n ventricular: Desfibrilacio´n; Reanimacio´n cardiopulmonar (RCP); Meta ana´lisis
1. Introduction Whether confronting hospital staff or first responders in the field, cardiac arrest demands prompt action, but has a poor prognosis. About 75% of victims will not survive initial resuscitation attempts and 91% die before hospital discharge [1]. Ventricular fibrillation (VF) is the initial ECG rhythm upon arrival of paramedics in 30/ 40% of out-of-hospital cardiac arrests (OHCA) [2 /5], but is estimated to be the cause of up to 85% of OHCA [5]. However, VF is potentially the most salvageable rhythm in cardiac arrest [1,6,7]. Electrical countershock is the definitive treatment, but the efficacy of shocks decreases dramatically with time. Defibrillation success falls from 80 to 98% after 30 s of VF to around 10% after 20 min [5,8]. Defibrillation waveform morphology is the latest major advance in external defibrillator development. Biphasic waveforms are characterised by an initial positive current flow followed by a reversal to negative current flow. Implantable cardioverter/defibrillators (ICD) with biphasic waveforms are able to defibrillate with less energy than monophasic waveforms [9 /11], requiring lower voltage and, hence, smaller and lighter battery and capacitor banks. Although biphasic waveforms are coming into more widespread use, there is a paucity of research using biphasic waveforms for transthoracic defibrillation. With few exceptions, the
studies performed to date are largely non-randomised and often without control groups. Transthoracic defibrillators with monophasic waveforms are still the type most used in current clinical practise. If trials of transthoracic defibrillation show similar benefits of biphasic waveforms as internal defibrillation trials have shown, there is potential to improve the poor outcomes associated with sudden cardiac death. More victims could be saved and the lesser degree of myocardial damage resulting from low energy shocks may improve the dismal long-term survival rate. In addition, external defibrillators (including AEDs) may become smaller, more portable and less expensive due to the reduced energy and voltage requirements. This systematic review was performed in order to evaluate the benefits and harms of biphasic waveforms over monophasic waveforms for the transthoracic defibrillation of patients in ventricular fibrillation or haemodynamically unstable ventricular tachycardia.
2. Methods MEDLINE (1966 /Sep 2002), EMBASE (1985 /Sep 2002) and the Cochrane Controlled Trials Register (3rd quarter 2002) were searched using medical subject
S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16
heading (MeSH) terms (ventricular fibrillation, sudden death, electric countershock), relevant textwords (monophasic, biphasic) and limited to randomised controlled trials using an optimally sensitive search strategy [12,13]. Manual searching of reference lists cited in original articles, relevant journals (Journal of the American College of Cardiology, Circulation, Resuscitation, Prehospital Emergency Care), and proceedings of major cardiology meetings between 1985 and 1999 (American Heart Association, American College of Cardiology) was also performed. Contact was made with known investigators to identify studies that may have been overlooked or remained unpublished. Studies were considered for inclusion if they were randomised controlled trials of biphasic and monophasic waveforms in the setting of patients with ventricular fibrillation or ventricular tachycardia requiring electrical cardioversion. Animal studies were not considered. Two types of primary outcome were assessed. When the biphasic and monophasic waveforms were of equal energy (e.g. 200 J) first shock failure (asystole or persistent ventricular fibrillation) was compared. When the biphasic and monophasic shocks were of different energy, both first shock failure and the weighted mean differences in delivered energy and voltage were assessed. First shock failure was used to demonstrate similar efficacy of the different energies, with the difference in delivered energy and voltage demonstrating the ability to achieve this similar success rate with lower output from the defibrillator. Secondary outcomes included endpoints thought to be markers of myocardial damage such as ST segment changes and time from first shock to restoration of a haemodynamically stable supraventricular rhythm. Two reviewers independently assessed the methodological quality of each trial. Disagreements were resolved by discussion. Quality assessments were based on the methodological description of each primary study. Studies were grouped according to whether they reported a random or quasi-random method of treatment allocation, allocation concealment, adequate blinding of outcomes and intention to treat analysis. Quantitative analyses of outcomes were based on trials with independent study groups. Relative risk (RR) and risk difference (RD) were calculated for individual studies and then pooled using a random effects model. The measure of effect producing the least statistical heterogeneity was used to summarise the data. Heterogeneity was assessed for compatibility with the assumption of uniform relative risk using the Q statistic. In addition, weighted mean difference (WMD) in delivered energy and voltage were evaluated for studies comparing waveforms of different energies. There were too few studies to fully explore sources of heterogeneity between
11
studies. Data from crossover studies were not included [14,15].
3. Results 3.1. Literature search Of 813 potentially relevant citations, nine papers describing seven randomised trials comparing biphasic and monophasic waveforms for human transthoracic defibrillation were identified (Table 1). All of the primary studies were conducted during electrophysiology procedures or implantable cardioverter/defibrillator testing with well-trained personnel in attendance. There were 398 patients included in the pooled analysis comparing waveforms of the same nominal energy [16 /18], 545 in the pooled analysis of first shock efficacy for 200 J monophasic and lower energy biphasic waveforms [18,19], and 614 in the pooled analysis of delivered energy and voltage. Several biphasic waveforms were used. Details of experimental and control waveforms are given in Table 1. The average age of individual study populations ranged from 61 to 68 years. Individual studies comprised between 73 and 90% males. The average weight of patients was 81 /82 kg. Coronary artery disease was present in 69 /84% of patients in individual primary studies. A wide variety of cardioactive drugs were in use. No deaths were recorded during the study period in any of the primary studies. Table 2 describes the methodological qualities of the primary studies included in the final analyses. All studies were stated to be randomised but methods were described in only five. Allocation concealment was adequately described in just three studies. Intention-totreat analysis was generally not stated. In one study, patients were excluded from analysis because of ‘incorrect randomisation’ and ‘violation of study protocol’ [20], which was clearly not intention-to-treat analysis. One study was presented in abstract form only [16]. 3.2. First shock failure First shock failure was assessed from studies of short duration VF/VT performed during electrophysiology studies. Compared to 200 J monophasic shocks, 200 J biphasic shocks reduced the risk of asystole or persistent VF after the first shock by 81% (RR /0.19, 95%CI: 0.06 /0.60) (Fig. 1). The pooled analysis showed no significant heterogeneity (x2 /0.67, 2df, P /0.7).
S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16
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Table 1 Characteristics of trials of monophasic versus biphasic transthoracic defibrillation Study ID
No. analysed
Study design
Participants
Inclusion criteria
Intervention
Outcomes
Echt, 1993 [16] Greene, 1993 [17]
120
Parallel Parallel
EPS for investigation of ventricular arrhythmias OHCA survivors undergoing EPS
200 200 200 200
J J J J
Gurvich Edmark Gurvich Edmark
First shock failure
171
Bardy, 1996 [19]
430
Parallel
649/11 years 89% male 649/11 years 90% male 829/15 kg 659/12 years 78% male 819/16 kg
OHCA survivors undergoing 130 ICD testing 115 200 360
J J J J
BTE BTE MDS MDS
Reddy, 1997 [21]
30
Mittal, 1999 [20]
184
Parallel
629/11 years 75% male 819/17 kg 639/14 years 78% male
Higgins, 2000 [18]
154
Parallel
OHCA survivors undergoing 130 J BTE ICD testing 115 J BTE 200 J MDS ICD surgery and testing, EPS 120 J experimental biphasic 200 J MDS EPS, evaluation of ICD 130 J BTE 200 J BTE 200 J MDS
First shock failure Difference in delivered energy ST segment 10 s post shock ST segment 10 s post shock
Crossover
689/12 years 81% male 819/15 kg
First shock failure
First shock failure
First shock failure Difference in delivered energy
Mean9/S.D. unless otherwise stated. Abbreviations: OHCA, out-of-hospital cardiac arrest; EPS, electrophysiology study; ICD, implantable cardioverter/defibrillator; BTE, biphasic truncated exponential; MTE, monophasic truncated exponential; MDS, monophasic damped sine.
Table 2 Quality of trials of monophasic versus biphasic transthoracic defibrillation Study
Method of randomisation Blinding and allocation concealment
Outcomes assessment and measurement
Intention-to- Loss to foltreat low up
Notes
Echt, 1993 [16] Greene, 1993 [17]
States ‘randomised in Not stated blinded fashion’. Randomised by defibrilla- Investigator and tor. outcome assessor
First shock failure: Unclear.
Not stated
Not stated
Abstract
Not stated
0/171 (0%)
Bardy, 1996 [19]
Weighted randomisation without replacement. Allocation concealment unclear. States order of shock randomised. Allocation concealment unclear. Simple block randomisation. Allocation concealment unclear. Randomised by defibrillator.
First shock failure : Coded ECG strip analysed. Code later broken to reveal study group. First shock failure: Unclear. Delivered energy : Output from defibrillator. ST segment : Digital calipers. ST segment : Two interpreters using digital callipers and digitised ECG. First shock failure : Unclear. Delivered energy : Interface unit connected to computer. First shock failure : Coded ECG strip analysed. Code later broken to reveal study group. Delivered energy : Output from defibrillator.
Not stated
30/460 (7%)
Not stated
3/33 (9%)
No
Not stated
Not stated
27/181 (15%)
Reddy, 1997 [21] Mittal, 1999 [20] Higgins, 2000 [18]
Outcome assessor
Outcome assessors
Not stated
Investigator and outcome assessor
Compared to 200 J monophasic shocks, lower energy biphasic shocks have a similar chance of resulting in persistent VF or asystole after the first shock (RR / 1.07, 95% CI: 0.66 /1.74) (Fig. 2). The wide confidence intervals, however, demonstrate weak evidence for
Antero-posterior electrode placement
equivalence of these waveforms. Although evidence of equivalence is promising, it is not yet definitive. Pooling of studies comparing 200 J monophasic and low energy biphasic waveforms showed no significant heterogeneity (x2 /1.12, 1df, P/0.29).
S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16
13
Fig. 1. Efficacy of first shock in reversing VF for 200 J monophasic and biphasic shocks; (a) relative risk reduction, (b) risk difference (absolute risk reduction).
3.3. Delivered energy and voltage Three studies in electrophysiology patients measured delivered energy and voltage with 200 J monophasic and lower energy biphasic waveforms. In achieving equivalent efficacy, 130 J biphasic shocks delivered a mean of 80.5 J (95% CI: 70.3 /90.7 J) less energy [18 /20] and required 1016.4 (95% CI: 971.0 /1061.7) fewer volts across the capacitors [19]. Similarly, 115 J biphasic waveforms delivered 98.0 J (95% CI: 96.7 /99.3 J) less energy and required 1079.0 (95% CI: 1033.6 /1124.4) fewer volts to achieve equivalent efficacy as the 200 J monophasic waveform [19]. The 120 J impedance-compensating biphasic waveform and anterior/posterior electrode placement resulted in first-shock failure less frequently than a 200 J monophasic waveform (RR /0.15, 95% CI: 0.02 /1.19), although this difference was not statistically significant
[20]. In achieving this effect, the biphasic waveform delivered 76.0 J (63%) less energy (95% CI: 72.0 /80.0 J) and 1251.0 (58%) fewer volts (95% CI: 1186.4 /1315.6 V). This study showed a statistically significant but clinically unimportant difference in impedance between the two study groups. Fig. 3 shows the mean ST segment deflection from two studies that measured ST segments after 200 J monophasic and lower energy biphasic shocks [19,21]. Funnel plots were derived but there were too few studies in each analysis to adequately investigate for the presence or effects of publication bias.
4. Discussion After short durations of VF/VT, biphasic defibrillation waveforms result in asystole or persistent VF/VT
Fig. 2. Efficacy of first shock in reversing VF for 200 J monophasic shocks compared to lower energy biphasic shocks.
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Fig. 3. ST segment deflection in two studies (mean9/95% confidence interval).
less frequently than monophasic waveforms of the same energy, or at similar rates with less delivered energy as the standard 200 J monophasic waveform currently employed. Low energy biphasic shocks result in less severe ST segment changes, possibly indicating a lesser degree of post-shock myocardial damage. The primary studies comparing 200 J biphasic and monophasic shocks reported significantly better first shock efficacy following biphasic shocks. However, this review assessed the adverse outcome, persistent VF or asystole. Two of the three primary studies failed to show significant superiority of biphasic waveforms with respect to adverse outcomes (Fig. 1a), largely due to small sample sizes. The pooled analysis, however, was able to demonstrate a significant advantage of biphasic waveforms over monophasic with respect to persistent VF or asystole. The results of these trials suggest that in-hospital cardiac arrest, where episodes of VF and haemodynamically unstable VT are diagnosed and treated relatively quickly, may be treated more successfully with biphasic defibrillation waveforms than the standard monophasic waveforms currently employed. The studies included in this review all dealt with arrhythmias of between 10 and 30 s duration. It is uncertain whether these results can be extended to out-of-hospital cardiac arrest (OHCA) where there are average delays of up to 13 min between collapse and defibrillation [1,5,22,23]. Three animal studies have investigated the use of biphasic waveforms in both short and long duration VF/ VT [24 /26]. All showed that biphasic waveforms had a 30 /56% lower defibrillation threshold than monophasic waveforms for short duration VF/VT. These studies also demonstrated a 38/56% lower defibrillation threshold for biphasic waveforms after long duration VF/VT of up
to 10 min. Another study performed on pigs showed a superior rate of return of spontaneous circulation after 8 min of VF and 1 min of simulated CPR with biphasic shocks compared to monophasic shocks of the same energy (RR /7.0, 95% CI: 0.96 /50.93) [27]. In short, available data on long duration VF/VT from animal studies shows that biphasic waveforms are superior to monophasic for transthoracic defibrillation of established arrythmias. It is reasonable to extrapolate these results to long duration VF/VT in humans and suggest that biphasic waveforms will result in higher rates of spontaneous circulation. Randomised controlled trials of these waveforms in prehospital treatment of VF/VT are necessary, but available data suggests that biphasic waveforms will perform no worse than monophasic. Future studies should adhere to the Utstein reporting guidelines [28] for OHCA. These guidelines have been in operation since 1991 and define one resuscitation outcome as the presence of a perfusing rhythm, at least temporarily, after shock. Studies reporting post-shock asystole as successful ‘defibrillation’ have the potential to bias comparisons of biphasic and monophasic waveforms in otherwise rigorous randomised trials, thus confusing any true benefits of biphasic waveform defibrillation. A recent randomised study performed in out-ofhospital cardiac arrest victims demonstrated superior defibrillation in patients treated with an impedancecompensating biphasic waveform defibrillator compared to three monophasic defibrillators [29]. This study could not be included in our meta-analysis, however, because the investigators have included reversion of VF/VT to asystole as a successful shock. Our review defined reversion to asystole as a failed shock. Secondary outcomes in this study did, however, include return of spontaneous circulation. Biphasic waveforms resulted in higher rates of spontaneous circulation compared to monophasic (81 vs 52%, P /0.001) and higher rates of hospital admission, but did not improve long term survival. The study comparing the 120 J impedance-compensating biphasic waveform with a 200 J monophasic waveform [20] was not included in the pooled analysis of lower energy biphasic waveforms. Inclusion of this study resulted in significant statistical heterogeneity, which may be related to the antero-posterior electrode placement used. Further investigation is required before a link between electrode placement and biphasic waveform efficacy can be established. Two studies investigated ST segment deflection as a measure of myocardial injury by measuring the ST segment 80 ms after the J-point, referenced to the preceding TP interval (10 s after successful shock). Although both studies were very similar in design and methods, one measured ST elevation resulting from transthoracic defibrillation shocks and the other mea-
S.C. Faddy et al. / Resuscitation 58 (2003) 9 /16
sured ST depression (Fig. 3). It would appear that the use of adhesive defibrillation pads to measure the ECG led to measurement of non-standard ECG recordings. Bardy et al. [19] claim their ECG approximated Lead II while Reddy et al. [21] claimed they were measuring an approximation of V5. Quantitative analysis of these results is clearly not justified. However, it is reasonable to infer that 200 J monophasic waveforms have a far more profound effect on ST segments, which may reflect temporary myocardial injury. There have not been any studies performed comparing biochemical cardiac markers following biphasic or monophasic defibrillation. The primary studies analysed in this review were conducted during electrophysiology procedures and there was little underlying risk of defibrillation shocks failing to revert the short duration arrythmias. Ventricular fibrillation/tachycardia associated with out-ofhospital cardiac arrest is unable to be reverted to a haemodynamically stable rhythm in as many as 90.9% of cases [30]. Applying the 81% relative risk reduction seen in the review, it would be possible to reduce this failure rate to as little as 17.2%, representing return of spontaneous circulation in as many as 73% of patients. The absolute risk reduction in this low-risk population was calculated to be 9% (Fig. 1b), which, when applied to the poorest published OHCA figures, also suggests that a rate of ROSC of at least 73% could be achieved. The realism of these assumptions and the effect on longterm survival will only be demonstrated by large randomised trials in the prehospital setting. Despite early predictions, the spread of automatic external defibrillators (AEDs) in the community has been somewhat slower than expected. This has been blamed in part on the size, weight and cost of the instruments. Biphasic waveforms allow defibrillation with less energy and voltage. A decrease in the size of batteries and capacitor banks, as well as allowing electronic switching instead of solid-state, will allow AEDs to become smaller, lighter and ultimately, less expensive. It is hoped that this will facilitate a far more widespread distribution of these devices in the community in general and in public places in particular. A limitation of the review is the use of first shock failure as the primary outcome. Although this was guided by the previously published literature, the efficacy of multiple biphasic shocks compared to multiple monophasic shocks will need to be determined in large randomised trials of long duration VF/VT. Another limitation is the method of inducing ventricular arrhythmias. Each of the studies included in the review investigated electrically induced VF/VT, which has been shown to require less energy to defibrillate than ischaemia-induced arrhythmias [31,32]. Human cardiac arrest generally occurs because a critical mass of myocardium is not being adequately perfused. Cardiac disease is estimated to be the underlying cause of sudden
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death in 66/74% of sudden cardiac deaths [22,33]. Electrically induced arrhythmia is an extremely rare cause of cardiac arrest. Previous studies of varying methodological quality have suggested that biphasic waveforms have an additional benefit over monophasic for long duration VF [25,26,34] but that arrhythmias of ischaemic origin have higher defibrillation thresholds than electrically induced VF/VT [31,32]. The true benefits of biphasic waveforms in OHCA will remain unclear until randomised controlled trials are conducted in patients with long duration VF of ischaemic origin.
5. Conclusion Biphasic defibrillation waveforms revert short duration VF/VT to a haemodynamically stable rhythm more often than monophasic waveforms of the same energy. With lower delivered energy, biphasic waveforms can defibrillate with similar efficacy to higher-energy monophasic waveforms. Low-energy biphasic waveforms result in less severe ST segment changes. Although not conclusively proven in studies of out-ofhospital cardiac arrest, biphasic defibrillation waveforms have the potential to improve the disappointing survival rate from sudden cardiac death.
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