Biphasic Shocks Compared with Monophasic Damped Sine Wave Shocks for Direct Ventricular Defibrillation during Open Heart Surgery

This multicenter study was conducted at the University of Innsbruck (Innsbruck, Austria), the University of Washington School of Medicine, Seattle, Washington), and the Hope Heart Institute (Seattle, Washington) between February 2000 and January 2001. Ethics committees at each participating institution approved the investigational protocol, and written informed consent was obtained from all patients. Eligible patients were aged at least 18 yr and scheduled to undergo cardiothoracic surgery with hypothermic cardioplegia. Patients were excluded if they had an ICD or had epicardial ICD electrode patches in place.

Shortly after induction of anesthesia, left ventricular wall thickness was measured in a cross-section view just below the mitral valve at the papillary muscle using transesophageal echocardiography. Standard cardiopulmonary bypass techniques with moderate core hypothermia were used, with supplemental topical cooling applied in most cases. Continuous monitoring of arterial perfusion pressure and core temperature by pulmonary artery catheter or esophageal temperature probe was performed, and these variables were recorded for study purposes just prior to removal of the aortic clamp. On removal of the aortic clamp, the assigned waveform was delivered in a step-up protocol to the patients in whom ventricular fibrillation (VF) developed. Presence of VF was established by direct visualization of the myocardium and electrocardiographic waveform display.

Presurgical information collected for each patient included classification of the presenting cardiac condition, history of arrhythmia, current cardiac medications, the patient's American Society of Anesthesiologists physical status, and the type of cardiothoracic surgical procedure planned. Electrocardiographic recordings for the study were begun before aortic clamp removal and continued throughout the delivery of the shock sequence. Arterial blood samples for blood chemical analyses were obtained before cardiopulmonary bypass and immediately after removal of the aortic clamp.

At enrollment, each patient was randomly assigned via  a block design to one of two treatment groups. The control group received monophasic damped sine wave shocks (fig. 1A) generated by a LIFEPAK®12 defibrillator/monitor (Medtronic Physio-Control Corp., Redmond, WA). The defibrillator has 50-μF capacitance, 21-mH inductance, and internal resistance of 11 Ω. The experimental group received biphasic truncated exponential waveform shocks (fig. 1B) generated by a Biphasic LIFEPAK®12 defibrillator/monitor. Attributes of this biphasic waveform have been published elsewhere. 3The shock protocols were identical for the two treatment groups. Patients with VF received progressively stronger shocks of 2, 5, 7, 10, and 20 J (one shock per energy level) until defibrillation occurred. If VF persisted after the 20-J shock of the assigned waveform, a 20-J crossover shock of the other waveform was given. The surgeon, who delivered the shocks, and the electrocardiogram overreader were blinded to the waveform type. Only the anesthesiologist, who opened the randomization envelope, knew which waveform was being applied. All study shocks were delivered to the epicardial surface through two 5.1-cm-diameter (20.4-cm²) circular paddles. In cases in which the crossover shock also failed to terminate VF, further treatment of the patient was at the physician's discretion.

The study electrocardiograms were reviewed later by a cardiothoracic anesthesiologist not associated with any other aspect of the study. Cardiac rhythms before and after each shock were classified by rhythm type. A successful shock was defined in the study protocol as one that terminated VF for at least 10 s.

Previous clinical studies of damped sine waveform defibrillation with internal paddles suggest that a shock energy of 5 J has between 48% and 91% probability of success. 16–21Based on these reports, the current investigation was designed around a primary end point comparison of cumulative defibrillation effectiveness between the two waveforms for shocks of 5 J or less. The triangular sequential analysis method of Whitehead 22was used to minimize the sample size and still accurately define the risks of both type I and type II errors. To set the study design parameters, the cumulative success rates for monophasic and biphasic shocks of 5 J or less were assumed to be 60% and 81%, respectively. The study was sized to provide a statistical power of 0.90 and a two-sided α of 0.05. To ensure a sufficient sample size for construction of comparative dose–response curves, the first interim analysis was scheduled when data from 72 patients (approximately 36 per group) had been collected. Subsequent interim analyses were scheduled when data for each block of 20 patients (approximately 10 per group) had been collected.

For each patient, the defibrillation threshold (the lowest successful shock energy), the cumulative energy received, and the number of shocks delivered were determined. The delivered peak current for each biphasic shock was estimated from the energy setting, the measured defibrillation impedance, and known characteristics of the shock delivery circuit. The peak current of each monophasic shock was not available because the monophasic defibrillators used in this study do not measure defibrillation impedance.

The defibrillation effectiveness of the two waveforms was quantified in terms of cumulative success at 5 J, mean threshold energy, mean cumulative energy, and mean number of shocks required. In addition, the dose–response relation for each waveform was approximated from the cumulative number of patients successfully defibrillated at or below each energy level (the cumulative percent success). Logistic regression was used to create a best-fit curve between data points for each waveform.

The relation between the two dose–response curves was analyzed with a Cox proportional hazards model. For all other analyses, continuous variables were compared with the Student t  test, and binary variables were compared with the Fisher exact test. Differences were considered significant for P < 0.05.

Of 251 enrolled patients, 98 received one or more defibrillation shocks of the biphasic or monophasic waveform. Of these, the University of Innsbruck enrolled 210 subjects, Providence Medical Center enrolled 18, and the University of Washington enrolled 23. Eighty, 10, and 8 subjects received shocks at these study centers, respectively. Three of the 98 patients were removed from the data set because they had preshock rhythms that were not VF, as determined by independent review of the electrocardiogram after the surgical procedure (two were ventricular tachycardia, one was asystole). Four additional patients were removed for protocol deviations occurring during the first two protocol shocks of 2 and 5 J. The remaining 91 patients were included in the data analysis of the primary end point (cumulative percent success at 5 J). Two of the 91 patients included in the primary end point analysis had a protocol deviation in the shock sequence after the 5-J shock and therefore were excluded from the calculation of the mean threshold energy, mean cumulative energy, and mean number of shocks required and from the dose–response analyses. There were no significant differences between the biphasic and the monophasic treatment groups in average age, number of men and women, or any of the categories of presurgical information collected (table 1), nor were there significant differences between the two groups in the data related to surgical treatment (table 2).

A total of 50 patients were randomly assigned to the biphasic shock group, and 41 were assigned to the monophasic shock group. Eight patients assigned to the biphasic shock group received a 20-J monophasic crossover shock, which defibrillated the ventricles in three cases, or 37.5% (table 3). Of note, in one case, after repeated unsuccessful monophasic shocks of up to 50 J with the 5.1-cm-diameter paddles, the ventricles were defibrillated by a monophasic shock delivered with larger-diameter paddles. Eight patients assigned to the monophasic shock group each received a 20-J biphasic crossover shock, which also defibrillated the ventricles in three cases, or 37.5% (table 3). Two other patients in the monophasic shock group should have received a 20-J crossover shock but did not; their data were not included in the crossover analysis. There was no significant difference in the success rates of the biphasic and the monophasic crossover shocks. In all crossover patients, further shocks or other medical interventions eventually resulted in a functional cardiac rhythm.

The biphasic waveform was substantially more effective than the monophasic waveform for direct epicardial defibrillation. Cumulative defibrillation success at 5 J, the primary end point of the study, was significantly higher in the biphasic shock group than in the monophasic shock group (25 of 50 vs.  9 of 41 defibrillated;P = 0.011). The biphasic shock group required significantly lower threshold energy (6.8 ± 5.0 [SD] vs.11.0 ± 6.7 J;P = 0.003), less cumulative energy (12.6 ± 12.3 vs.  23.4 ± 16.0 J;P = 0.002), and fewer shocks (2.5 ± 1.2 vs.  3.5 ± 1.4;P = 0.002). The energy dose–response curves illustrate the higher percent success with the biphasic waveform (fig. 2).

The mean delivered peak current for the biphasic shock group was calculated to be 5.6 A at the mean threshold energy (6.8 J) and the mean measured defibrillation impedance of 45 ± 9 Ω (range, 30–79 Ω). The mean delivered peak current for the monophasic shock group was 10.6 A at the mean threshold energy (11.0 J). This mean current was estimated by assuming that the monophasic shock group had the same mean impedance as that measured for the biphasic shock group.

Over the range of energy levels studied, the estimated hazard ratio from the Cox proportional hazards model was 1.64 (95% confidence interval, 1.02–2.65). This means, in comparing a patient given a monophasic shock that failed to defibrillate at the specific energy level to a patient given a biphasic shock that failed at the same level, the biphasic-shocked patient will be, on average, 1.64 times more likely than the monophasic-shocked patient to be successfully defibrillated at the next energy level.

By all our measures of effectiveness (cumulative success at 5 J, mean threshold energy, mean cumulative energy, and mean number of shocks), the biphasic waveform is more effective than the monophasic waveform for direct epicardial defibrillation with paddles. These findings are consistent with those from clinical studies of transchest defibrillation 1–6and cardioversion 7,8and of defibrillation with ICDs, 9–13all of which have described clinical advantages associated with biphasic waveform shocks.

The dose–response curve generated for the biphasic waveform shocks used in our study (fig. 2) provides important clinical guidance for selection of appropriate defibrillation energy levels during cardiac surgery. For 5.1-cm-diameter paddles, an initial shock of 5 J is a reasonable choice when minimization of threshold energy and cumulative energy is desired, although a greater number of shocks may ultimately be required. Conversely, an initial shock of 10–20 J is a reasonable choice when more rapid defibrillation with a minimal number of shocks is desired. In general, selection of biphasic shocks of half the energy usually used with monophasic shocks will result in approximately the same defibrillation success rate. For example, 5-J biphasic shocks achieved virtually the same success rate (52%) as 10-J damped sine wave shocks (51%).

The peak currents calculated for our study provide additional insight into the clinical advantage of biphasic defibrillation. The possibility of electrical injury from defibrillation shocks of a given waveform increases as peak current increases, 23–27regardless of energy. 28,29Therefore, the clinical objective of minimizing damage is most appropriately considered in terms of minimizing current.

In our study, the mean peak current for successful defibrillation in the biphasic shock group (5.6 A) was approximately 47% lower than that for the monophasic shock group (10.6 A). The biphasic defibrillators used in this study defibrillate with less current for two reasons. First, at the impedances typically seen with epicardial defibrillation, these biphasic defibrillators deliver approximately 30% less current than monophasic defibrillators at the same energy setting. Second, biphasic shocks defibrillate with less energy. These observations imply that, regardless of whether a lower, equivalent, or even somewhat higher energy setting is used, shocks from these biphasic defibrillators offer a wider margin of safety than shocks from the monophasic defibrillators.

The relative difference in effectiveness between biphasic and monophasic shocks in our study is similar to that reported for clinical studies of ICD shocks. For example, Neuzner et al.  13reported a clinical study comparing biphasic shocks with monophasic trapezoidal waveform shocks, which originally were used for ICDs and are always truly monophasic. Those biphasic shocks achieved higher success rates than the monophasic shocks at all levels from 2 to 25 J. For example, for 15-J shocks, the defibrillation success rate for the biphasic shock was 83%, and the defibrillation success rate for the monophasic shock was 27%.

Our study design allowed shocks up to a maximum energy of 20 J. Therefore, the shapes of the dose–response curves for shocks greater than 20 J have not been established. In patients in whom the crossover shock was unsuccessful, additional shocks of 20 J or greater succeeded in all cases (including one case that involved larger paddles). Therefore, we believe that the curves will continue to increase.

The role of electrode size in clinical direct defibrillation with biphasic shocks has not yet been established. However, the results of one animal study (direct defibrillation in pigs) by Zhang et al.  14showed that defibrillation success with biphasic shocks was higher than with monophasic shocks (7–20 J) when smaller paddles (15.9 cm²) were used but not when larger paddles (44.2 cm²) were used. Although clinical application of the animal study results is necessarily limited, we interpret their study to suggest that biphasic waveforms may provide particular protective benefit when small paddles must be used, such as for mini-incisions of the thorax.

In our study, the success rate with monophasic shocks of 5 J or less was 22%, which is substantially lower than the 48–91% success rates reported for monophasic waveforms of 5 J or less in earlier studies of direct defibrillation. 16–21Also in our study, monophasic shocks of up to 20 J did not defibrillate 25% (10 of 41) of the patients but were reported to fail in 1.5% (8 of 535 patients) in those earlier studies. However, direct comparison of our monophasic waveform results with those of earlier studies is problematic because important aspects of patient characteristics, study protocols, and surgical procedures were not always provided in the earlier reports. The earlier studies may have used different criteria for determining which patients received shocks (e.g. , patients with ventricular tachycardia may have been shocked), may have repeated shocks at the same low energy levels, and may have used different sized electrode paddles. Also, the patients may have been taking different antiarrhythmic drugs, some of which are now known to decrease or increase defibrillation thresholds. 30Cardiac surgery techniques have evolved, for example, from using simple extracorporeal hypothermia to using cardioplegic perfusion, with unknown effects on defibrillation success. In addition, subtle differences between various versions of damped sine waveforms could affect shock effectiveness. 31In sum, we believe that our results represent defibrillation success rates under current surgical conditions.

Although previous clinical studies have compared biphasic and monophasic shocks for transchest defibrillation and cardioversion and for defibrillation with ICDs, none has compared those waveforms for direct defibrillation with paddles. Our study thus completes the set of comparisons of biphasic and monophasic waveform shocks for defibrillation of VF. Based on all the clinical comparisons of biphasic versus  monophasic damped sine waveform shocks now reported, we believe that biphasic defibrillators offer the clinical advantage of terminating ventricular arrhythmias with lower energy and current, which consequently may reduce the risk of myocardial damage.

The authors thank Ian H. Wright, M.D. (Clinical Assistant Professor, Department of Anesthesiology, University of Washington, Seattle, Washington), for his careful and expert overreading of all electroencephalographic recordings.