Response to Letter Regarding Article, “BIPHASIC Trial: A Randomized Comparison of Fixed Lower Versus Escalating Higher Energy Levels for Defibrillation in Out-of-Hospital Cardiac Arrest”
We appreciate the interest of Tang and colleagues, who have made substantial contributions to advancing care for patients with cardiac arrest. We provide additional information here to clarify the issues they raise, beginning with their last point.
The letter expresses concern about an imbalance between groups1 in the incidence of asystole as an initial rhythm. However, the multishock groups, on which the primary end point is based, are nearly balanced: 2 of 55 versus 0 of 51 patients initially in asystole.
The letter expresses concern about aggregating first and subsequent shocks in the primary analysis. An abstract of our study reported separate results for subsequent shocks in which energy levels differ most between groups, revealing a larger advantage for higher-energy shocks: ventricular fibrillation termination, 71% for 150 J versus 85% for 300 to 360 J (P=0.01); conversion, 24% versus 43% (P<0.01).2
Another stated concern is that the automated external defibrillators studied were modified. They were not; study sites used their existing standard LIFEPAK 500 automated external defibrillators, providing protocol choices starting as low as 150 J and increasing to as high as 360 J. Although the Philips automated external defibrillators discussed by Tang and colleagues are limited to a fixed 150-J protocol, many automated external defibrillators allow various protocol choices, including 150 J fixed. Because most devices support multiple protocols and evidence to recommend 1 protocol over another remained lacking, our study addressed an important question: When multiple protocols are available, which should be chosen?
The letter suggests that the lower peak current of the 150-J shocks we studied compared with different 150-J shocks discussed in the letter reduces defibrillation effectiveness. This would be true only if the waveform shape were the same. Compared with the 100-μF shocks discussed in the letter, the longer time-constant 200-μF shocks we studied provide higher average current for any given peak current. Consequently, as established in the literature, higher-capacitance waveforms defibrillate with less peak current.3
Most defibrillators increase energy by increasing shock intensity (current and voltage) rather than changing waveform shape or duration. We evaluated the effect of shock intensity without changing waveform and found that a protocol using higher intensities for subsequent shocks produced better heart rhythm outcomes than one maintaining a lower intensity. The principle demonstrated by our results would apply to any other waveform unless either (1) the first energy level succeeded for 100% of all shocks or (2) increasing the intensity above that of the first shock caused the peak current to exceed the level at which clinically significant myocardial injury appears. Multiple clinical studies report relatively low biphasic ventricular fibrillation termination rates (<75%) and subsequent shock success lower than the first shock success, providing ample evidence to rule out condition 1 for any defibrillator previously studied, including the 150-J defibrillator discussed in the letter.4 Condition 2 has not been verified for other automated external defibrillators, but the lack of any finding of increased harm in our escalating-energy group compared with the fixed-energy group shows that it is not an issue for the defibrillator tested.
Although our study does have limitations, it provides the first clinical data comparing biphasic energy protocols, and we believe the principle our results demonstrate should be considered when clinical protocols are selected.
R.G. Walker, Dr Chapman, and P. Lank are employees of and hold stocks and options in Medtronic Inc. Dr Christenson has received funding from the Resuscitation Outcomes Consortium, National Institutes of Health, and Canadian Institutes of Health Research Funded Consortium. British Columbia Ambulance Service has a contract with Medtronic Inc. Dr Sookram serves on the speakers’ bureau for Hoffman LaRoche. Dr Berringer has received honorarium from Sabex Pharmaceuticals. Dr Stiell, L.P. Nesbitt, D. Cousineau, Dr Bradford, and Dr Wells report no conflicts.
Stiell IG, Walker RG, Nesbitt LP, Chapman FW, Cousineau D, Christenson J, Bradford P, Sookram S, Berringer R, Lank P, Wells GA. BIPHASIC trial: a randomized comparison of fixed lower versus escalating higher energy levels for defibrillation in out-of-hospital cardiac arrest. Circulation. 2007; 115: 1511–1517.
Stiell IG, Walker R, Nesbitt L, Chapman F, Cousineau D, Christenson J, Bradford P, Sookram S, Lank P, Wells G. A randomized controlled trial of fixed versus escalating energy levels for defibrillation. Resuscitation. 2006; 69: 52. Abstract.