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Biphasic versus sequential pulse defibrillation: A direct comparison in pigs
Biphasic versus sequential pulse defibrillation: A direct comparison in pigs It has recently been demonstrated that both biphasic and sequential pulse defibrillation shocks are superior to monophasic defibrillation shocks in animals and humans. There is little information directly comparing these two waveforms when pulse characteristics, subject, and total electrode surface area are kept constant. Pigs were randomized in a cross-over design for triplicate determinations of defibrillation threshold using biphasic and sequential pulse shocks and both large and small epicardial electrodes. Anesthetized pigs weighing 18 to 28 kg had sets of defibrillating electrodes (TX-7) with total surface areas of 13 cm* (group 1, n = 16) and 26 cm2 (group 2, n = 16), respectively, attached to the heart. Leading edge delivered voltage, current, and energy were significantly lower with sequential pulse shocks than with biphasic shocks for both electrode sets (delivered energy means + standard error of the mean: 13.3 + 1.6 versus 22.4 + 3.0 joules, and 9.9 * 1.5 versus 14.2 F 1.6 joules, respectively). In addition, six of the pigs could not be defibrillated with 900 stored V using biphasic shocks, although all pigs were defibrillated with less than 800 stored V using sequential pulse defibrillation. We conclude that sequential pulse defibrillation using three defibrillating electrodes provides an important current delivery system not matched by biphasic shocks using two electrodes when subject, waveform characteristics, and total electrode surface area are kept constant. (AM HEART J 1992;124:97.)
Douglas 1,. Jones, PhD, George ,J. Klein, MD, FRCP(CI, and G. Kim Wood, AHT. London.
Ontario,
C’arzada
To provide maximum safety margins for patients with implantable defibrillators, it is necessary to optimize current delivery for defibrillation. Two basic strategies are being pursued to enhance defibrillation efficacy: improved hardware (battery, capacitor, or electrodes) and an improved current waveform (“sinusoidal” versus “trapezoidal” and “monophasic” versus,additional “phases”). Schuder et al.’ first tested t,he use of a biphasic square wave defibrillation pulse. Subsequently, several laboratories have demonstrated improved ethcacy of various waveforms incorporat ing hiphasic characteristicsZeG including studies &single cellsi-! An additional consideration was proposed by Bourland et al.,‘” who emphasized the advantage of both temporal and spatial current distribution (sequential pulse). We and others’“-ll
have consistently found reduced defibrillation requirements using sequential pulse shocks. Sequential pulse requires additional electrode(s) and an altered current path, which increases the number of electrodes on the heart and may thus reduce defibrillation energy requirements.‘“-lx The purpose of this report was to directly compare biphasic versus sequential pulse shocks using a paired comparison when subject, total electrode surface area, and pulse characteristics were the same for each modality. METHODS Animals
and surgery. Experiment.s were carried out on 32 pigs weighing from 18 to 28 kg. Animals were tranquilized with an intramuscular mixture of ketamine (400 mg, Rogarsetic,Rogar STB, London, Ontario, Canada) and diazepam(20 mg, Valium, Roche, Nutley, N.J.) for transportation t.o the laboratory. They received atropine (0.6 mg, intramuscularly) to prevent excessmucus secretion and then were intubated, placed on a Harvard respirator (Ealing ScienCfic, St. Laurent, Quebec,Canada), and respired at 10 to 15 breaths/min. Anesthesia was maintained with 0.5’, to 1.2‘, halothane(Somnothane,Hoescht,Markham, Ontario, Canada) blended with 1 L/min 02, 1 to 2 L/min filtered medical air, and 1 to 3 L/min NzO.Body temperature was monitored by an esophagealthermistor and controller (Yellow SpringsInstruments, Yellow Springs.Ohio) and was maintained hy controlling a circulating water
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Fig. 2. Diagrammatic representation of the defibrillation waveforms. The sequential pulse shock used two separate pathways designated by the top two traces. The biphasic pulse shock used a single pathway designated by the hot tom tracing. The two pulses A and C were 4.0 msec in duration separated by 0.2 msec (R). Leading edge voltages were of the same amplitude in each phase. The second pulse of biphasic shock had the anode-cathode orientation reversed.
Fig. 1. Diagrammatic representation of defibrillation electrode positions on the heart. A, Positions of electrodes for sequential pulse defibrillation. Electrodes A on the anterior right ventricle and C on the posterior right ventricle were cut in half, indicated by the line, so that the sum of their surface area equalled that of electrode B. For sequential pulse shocks, the first pulse was passed between electrodes A and B and the second pulse between electrodes C and B, with electrode B being the common cathode. B, Positions of electrodes for biphasic pulse defibrillation. Electrodes A on the mid right ventricle and B on the mid left ventricle were of equal surface area. Thus the total surface area of A and B for the biphasic pulse shock, was equal to the total surface area of electrodes A, B, and C used for sequential pulse shocks. Electrode B was the cathode for the first phase of the biphasic pulse shock and anode for the second phase.
blanket (K-pad, American Hospital, Mississauga, Ontario. Canada). The femoral artery was located through a cutdown incision, cannulated, and connected via a disposable pressure transducer (COBE, Bramalea, Ontario, Canada) to a reconder (VRl6, PPG Biomedical Syst,ems. Lenexa. Kans.). Each animal was randomly assigned to having biphasic, or sequential pulse defibrillation thresholds determined first. The chest was opened via a left thoracatomy in the fifth intercostal space. The heart was supported in a pericardial sling and defibrillating electrodes were attached tci the heart, two for biphasic shocks or three for sequential pulse shocks (Fig. I). The first group of 16 pigs had electrodes with a combined total surface area of 13 cm’. The second group of 16 pigs had electrodes with a combined total surface area of 26 cm”. For each group both biphasic
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Fig. 3. Leading edge voltages at defibrillation threshold measurements in the 16 pigs using electrodes of 13 cm? total surface area. Circles indicate defibrillation thresholds with this orientation were determined first. Squares indicate defibrillation thresholds with this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean values are the mid line above each description. End bars represent + the standard error of the mean. Significance is given as the t value. Correlation between thresholds using the different pulse techniques is given as r.
and sequential pulse defibrillation thresholds were determined. A quadripolar patch electrode was sutured on the left ventricular epicardial outflow track for monitoring electrograms as well as ventricular fibrillation induction. Standard limb leads I and II were monitored on the VR16 recorder at 1 to 250 Hz. Fibrillation-defibrillation. Ventricular fibrillation was induced by passing 400 msec trains of 4 msec pulses at 60 Hz, timed to begin at the peak of the T wave during sinus rhythm. Current was increased in repeat attempts until ventricular fibrillation was induced. Once fibrillation was induced, a minimum of 10 seconds was allowed before defibrillation was attempted. lg Defibrillation was accomplished using shocks composed of two 4.0 msec pulses separated by 0.2 msec delivered from a Medtronic 2394 defibrillator (Medtronic, Inc., Minneapolis, Minn.) (Fig. 2). The initial stored voltage was set for 500 V. If this shock was unsuccessful in defibrillating the heart, the stored voltage was incremented in 100 V steps until the animal was rescued or the 900 stored V was unsuccessful, in which case internal paddle electrodes were used for rescue. The stored voltage of the next episode was started 100 V higher than the previous unsuccessful attempt. This process was repeated until the first shock of an episode defibrillated the heart or the 900 stored V failed to defibrillate the heart, in which case this unsuccessful shock was arbitrarily accepted as though it had been successful and the delivered peak voltage, current, and energy of that unsuccessful shock was used as a “minimum,” recognizing that this would reduce
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Fig. 4. Delivered leading edge current at defibrillation threshold measurements in the 16 pigs using electrodes of 13 cm2 total surface area. Circles indicate defibrillation thresholds with this orientation were determined first. Squares indicate defibrillation thresholds wit.h this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean values are the mid line above each description. End bars represent + the standard error of the mean. Significance is given as the t value. Correlation between thresholds using the different pulse techniques is given as r.
the estimated threshold. Then increments and decrements of 10 “; of the lowest successful 100 V increment shock were used until three determinationsso of the lowest successful voltage or three unsuccessful shocks at 900 stored V were obtained. If the first (500 V) shock successfully defibrillated the heart, the stored voltage of the next fibrillation episode was decreased by 100 V. Such 100 V decrements were repeated until the first shock failed to defibrillate the heart, in which case 100 V increments were used to rescue the pig. Subsequently, increments and decrements of 107 of the highest unsuccessful shock were used until 3 determinationszO were made of the lowest successful voltage. This assessment of defibrillation efficacy has been found to be accurate and highly reproducible while requiring fewer shocks than the dose-response curve.sl Once triplicate measurements were obtained with one lead orientation, the defibrillating leads were changed for triplicate determinations with the alternate orientation. At least 3 minutes separated ventricular fibrillation episodes. A custom-designed set of isolation amplifiers between the Medtronic defibrillator and the pig provided voltage and current output, which was fed to a 12 bit analog-to-digital (A/D) converter mount,ed in a personal computer sampling
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Fig. 5. Total delivered energy at defibrillation threshold measurements in the 16 pigs using electrodes of 13 cm’ total surface area. Circles indicate defibrillation t,hresholds with this orientation were determined first. Squares indicate defibrillation thresholds with this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean values are the mid line above each description. End bars represent IL the standard error of the mean. Significance is given as the t value. Correlation between thresholds using the different pulse techniques is given as r.
at 7 kHz. A custom-designed program calculated delivered peak voltage, currents, pulse durations, impedance, and total energy. RESULTS Small (13 cm*) electrodes.
At defibrillation threshold, the delivered leading edge peak voltages of the first shock phase using biphasic pulses were significantly greater than those delivered to the same animal when sequential pulse defibrillation shocks were used (Fig. 3). Of the 16 pigs, only three had a slightly (
0 SEQUENTIAL
BIPHASIC
Fig. 6. Delivered leading edge voltage at defibrillation threshold measurements in the 16 pigs using the electrodes of 26 cm2 total surface area. Circles indicate defibrillation thresholds with this orientation were determined first. Squares indicate defibrillation thresholds with this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean values are the mid line above each descript,ion. End bars represent t the standard error of the mean. Significance is given as the t value. Correlation between thresholds using the different pulse techniques is given as r
animal using sequential pulse shocks. Delivered energy using biphasic pulse shocks was also significantly higher than that using sequential pulse shocks (Fig. 5). For leading edge peak voltage, current, and delivered energy, there was no effect of the order of shocks. Larger (26 cm2) electrodes. The subsequent 16 pigs had a similar protocol using electrodes with double the surface area (26 cm”) of the previous group (13 cm”). The leading edge delivered voltages at threshold were again higher using the biphasic pulse technique (Fig. 6). In five animals, shocks with stored voltages of 900 V were unsuccessful in defibrillating the hearts. Of the other 11 pigs, three had slightly (< 60 V) lower peak voltages with biphasic pulse shocks, while the remainder had equal or great.er peak voltages with biphasic pulse compared with sequential pulse shocks. The accompanying delivered peak current was greater in 15 out of 16 pigs with t.hc biphasic pulse shocks (Fig. 7). Only one pig had a very slightly (0.2 A) lower peak current with biphasic pulse shocks. The total delivered energy was also lower with the sequential pulse shocks compared
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Fig. 8. Total delivered energy at defibrillation threshold measurementsin the 16pigs usingthe electrodesof 26 cm2 total surfacearea. Circles indicate defibrillation thresholds with this orientation were determined first. Squares in& cate defibrillation thresholds with this orientation were determined second.Open symbol indicates maximum valnesthat were not able to defibrillate the heart. Mean vallies are the mid line above each description, End bars represent i- the standard error of the mean.Significanceis given asthe t value. Correlation between thresholds using the different pulse techniques is given as r.
with the biphasic shocks in 14 out of the 16 animals (Fig. 8). In several of the animals the energy requirements more than doubled using biphasic pulse shocks. In five of the animals, delivered energies greater than 37 joules were repeatedly unsuccessful in terminating ventricular fibrillation using biphasic pulse shocks. These same pigs required less than 25 joules for successful defibrillation using sequential pulse shocks. Despite these differences, there was a significant correlation between the two measurements.
waveform, and pulse characteristics are the same. The postulate that the sequential pulse technique merely provided a “simulated biphasic stimulus shock” can not explain this result, as the true biphasic pulse with the same pulse characteristics did not have the same result. The postulate that the advantage of sequential pulse over monophasic pulse is because of the increased number of electrodes and therefore the electrode surface area is increased, is not tenable, as the total electrode surface areas were equal. Indeed, if anything, there should have been a slight advantage to the biphasic shock as the total active electrode surface area during actual current delivery was 33 P’;. higher with the biphasic pulse shock compared with sequential pulse shocks, and increased electrode surface area has been associated with decreased defibrillation requirements.l”-‘s Several recent studies* have found improvements
o-
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7. Delivered leading edge current at defibrillation threshold measurements in the 16 pigs using the electrodes of 26 cm? total surface area. Circles indicate defibrillation thresholds with this orientation were determined first. Squares indicate defibrillation thresholds with this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean valuesare the mid line aboveeachdescription. End bars represent + the standard error of the mean. Significance isgiven asthe t value. Correlation betweenthresholds using the different pulse techniques is given as r.
DISCUSSION
The main finding of this study is that the sequential pulse technique required less voltage, current, and delivered energy compared with the biphasic pulse technique when total electrode surface area,
-References
1. 1 through
8. 16, and
2” through
28.
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of biphasic shocks over monophasic shocks, although not all lead orientations show such benefit.““. “; Additional characteristics of the biphasic waveform may also play a role in defibrillation efficacy.s, s4.“s. sg In the present study we used equal pulse durations and equal leading edge peak voltages. For the heart, equal pulse durations have been shown to be advantageous over short first or short second pu1ses.s.s4,sBm31 There is little information regarding leading edge voltages, although high ratios of first-to-second pulse leading edge voltages are also disadvantageous.s, 7.s5s2g,“e On the other hand, for the engineer there may be a design advantage in using a single capacitor source where the leading edge voltage of the second pulse can be set to the cut-off voltage of the first pulse. This characteristic has most recently been investigated.i6. 2”-30,32-34A limitation of such a design relates to the mechanism by which the switch between polarities is made. If a set duration of the first pulse is used, the amplitude of the second pulse leading edge voltage may be small if large electrodes wit.h low impedances are used. Such high first-to-second pulse ratios have been found to be disadvantageous.“. 7y“. “g. ‘x’ Alternatively, if a specific “tilt” or cut-off voltage is used, the pulse duration may be very short if large electrodes are used. Short first pulse shocks have also been found to be disadvantageous.“, 95.2g-31 This would not be expected to be the sole explanation for the difference in impedance caused by halving the one active electrode, which altered the impedance of the pathway on average lessthan 20 “C, while the difference in peak current at the defibrillation threshold averaged approximately 50 “iI. There are conflict ing results32-34on the relative advantages of single versus double capacitor shocks. Even the results from the same laboratory differ,33* 34 perhaps dependent upon the types of electrodes used or upon the position of the electrodes. Nevertheless, the optimum waveform needs to be determined. Such factors may have contributed to the inability to defibrillate five pigs using large patches and biphasic pulses, while only one pig could not be defibrillated using the smaller patches in the present study. When sequential pulse shocks were used, at least one of the electrodes involved in active current delivery was a smaller electrode. Alternatively, these differences may simply reflect individual animal variation as the correlation coefficient between animals was consistently significant. It was noteworthy that despite the high values for these six pigs when using biphasic shocks, each animal was able to be defibrillated reproducibly at substantially lower values using the sequential pulse technique. These data suggest that an advantage in defibrilla-
American
July 1992 Heart Journal
tion efficacy is conferred by using both temporally and spatially distributed shocks. It remains to be determined if adding a biphasic waveform to the sequential pulse shock will further enhance defihrillation efficacy. The authors thank Drs. R. Mehra and M. .I. Kallok for proved ing electrodes and defibrillators. Thanks are also due to S. Hunt for typing the manuscript. REFERENCES
I. Schuder JC, Stoeckle MD, Dolan AM. Transthoracic ventricular defibrillation with square-wave stimuli, one-half cycle, one cycle, and multicycle waveforms. Circ Res 1964;15:258-64. 2. Schuder tJC, Gold JH, Stoeckle MD, Roberts SA, McDaniel WC, Moellinger DW. Defibrillation in the calf with bidirectional trapezodial wave shocks applied via chronically implanted epicardial electrodes. Trans Am Sot Artif Intern Organs 1981;37:467-70. :i. dories JL, ,Jones RE: Improved defibrillator waveform safety factor with biphasic waveform. Am J Physiol 1983;245(Heart Circ Physiol 14l:H60-5. 4. Winkle RA, Mead RH, Ruder MA, et al. Improved low energy defibrillation efficacy in man using biphasic truncated exponential waveform. AM HEART ,J 1989;117:122-7. 5. Tang ASL, Yabe S, Wharton JM, Dolker M, Smith WM, ldeker RE. Ventricular defibrillation using biphasic waveforms: the importance of phasir duration. .J Am Co11 Cardiol 1989: 13:207-14. 6. Chapman PD, Vetter JW, Souza JJ, Troup PJ, Wetherbee JX, Hoffman RG. Comparative efficacy of monophasic and biphasic truncated exponential shocks for non-thoracotomy internal defibrillation in does. J Am Co11 Cardiol 1988:12:739-45. 7. Jones .JL, Lepeschkin l?, Jones RE, Rush S. Response of cutured myocardial cells to countershock type electric field stimulation. Am J Physiol 1978;240(Heart Circ Physiol 91: H214-22. 8. *Jones JL, Jones RE. Decreased defibrillator induced dysfunction with biphasic rectangular waveform. Am cJ Physiol 1984; 247(Heart Circ Phvsiol 16):H792-6. 9. Jones JL, -Jones RI?, Balasky G. Microlesion formation in myocardial cells by high-intensity electric field stimulation. Am J Physiol 1987;253(Heart Circ Physiol 18):H480-6. 10. Bourland JD, Tacker WA, Wessale JL, Kallok MJ, Graf JE, Geddes LA. Sequential pulse defibrillation for implantable defibrillators. Med Instrum 1986;20:138-42. 11. dories DL, Klein Gd, Kallok MJ. Improved defibrillation threshold with sequential pulse energy delivered to differenr lead orientiations in pigs. Am J Cardiol 1985;55:821-5. 12. *Jones DL, Sohla A, Bourland JD, Tacker WA, Kallok MJ. Klein GJ. Internal ventricular defibrillation with sequential pulse counter shock in pigs: comparison with single pulses and effects of pulse separation. PACE 1987;10:497-502. 13. dones DL, Klein GJ, Guiraudon GM, et al. Internal cardiac defibrillation in man: pronounced improvement with sequential pulse delivery to two different lead orientiations. Circulation 1986;73:484-91. G, Green HL. Pro14. Bardv GH, Ivey TD, Allen MD, Johnson spective comparison of sequential pulse and single pulse defibrillation using two different clinically available systems in man. J Am Co11 Cardiol 1985;14:165-71. of direct current detibrill;i. Ewy GA, Horan WJ. Effectiveness lation: role of paddle size. II. A.~I HEART -7 1977;93:674-5. defibrillation 16. Dixon EG, Tang ASL, Wolf PD, et al. Improved threshold with large contoured epicardial electrodes and biphasic waveforms. Circulation 1987;76:1176-84. 17. Kallok MJ, Bourland JD, Tacker WA, Jones DL, Klein G.1. Wessale JL. Optimization of epicardial electrode size and implant site for reduced sequential pulse defibrillation thresholds. Med Instrum 1985;20:36-9.
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18. Jones DL, Klein GJ, Guiraudon GM, Sharma AD. Sequential pulse defibrillation in humans: orthogonal sequential pulse defibrillation with epicardial electrodes. J Am Co11 Cardiol 1988;11:590-6. 19. Rattes MF, Jones DL, Sohla A, Sharma AD, Jarvis E, Klein GJ. Defibrillation with the sequential pulse technique: reproducibilitv with repeated shocks. AM HEART J 1986;111:874-8. 20. dories Di,, Fujim;ra 0, Klein GJ. Minimum replications to estimate average threshold energy for defibrillation. Med Instrum 1988;11:298-303. 21. .Jones DL, Irish WD, Klein GJ. Defibrillation efficacy: comparison of defibrillation threshold versus dose-response curve determination. Circ Res 1991;69:45-51. 22. Gurvich NL, Markarychev VA. Defibrillation of the heart with biphasic electrical impulses. Kardiologiia 1967;7:109-12. 23. Schuder JC, Gold JH, Stoeckle H, McDaniel WC, Cheung KN. Transthoracic ventricular defibrillation in the 100 kg calf with symmetrical one-cycle bidirectional rectangular wave stimuli. IEEE Trans Biomed Eng 1983;30:415-22. 24. Bardy GH, Ivey TD. Allen MD, Johnson G, Mehra R, Greene HL. A prospective randomized evaluation of biphasic versus monophasic waveform pulses on defibrillation efficacy in humans. J Am Co11 Cardiol 1989;14:728-33. “5. ‘Thakur R. Souza J, Wetherbee J, Chapman P. Leading edge volrage ratio is an important determinatant of biphasic waveform defibrillation efficacy [Abstract]. ,J Am Co11 Cardiol 199O;IS:Al,~. 26. Zhou S, Wolf PD. Smith WM. Ideker R. Comparison of activation patterns after unsuccessful biphasic and monophasic bhol ks [Abstract]. .J Am Co11 Cardiol 1990;15:72A.
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27. Bardy GH, Allen MD, Johnson G. Mehra R, Greene HL. The effect of electrode systems and current pathways on biphasic waveform defibrillation efficacy in man [Abstract]. J Am Co11 Cardiol 1990;15:72A. 28. Mehra R, DeGroot P, Norenberg S. Reduction of transvenous defibrillation thresholds with an asymmetric biphasic pulse IAbstractl. Circulation 1988:78:11-218. 29. Feeser S& Kavanagh KM, Ideker RE. Evidence of two mechanisms for defibrillation with biphasic truncated exponential waveforms [Abstract]. Circulation 1989;8O:II-532. 30. Chapman PD, Vetter JW. Souza JJ, Wetherbee JN, Troup PJ. Comparison of monophasic with single and dual capacitor biphasic waveforms for nonthroacotomy canine internal defibrillation. J Am Co11 Cardiol 1989;14:242-5. 31. Schuder JC, McDaniel WC, Stoeckle H, Dbeis M, Flaker GC. Optimal biphasic waveform morphology for canine defibrillation with a transvenous catheter and subcutaneous patch system [Abstract]. Circulation 1988;78:11-219. BA, Franz MR. Sequential pulse internal 32. Fain ES, Sweeney defibrillation: is there an advantage to “switched” current pathways? Abf HEART .J 1989;118:717-24. 33. Kavanaeh KM. Tanp ASL. Rollins DL. Smith WM. Ideker RE. Compar&on of the iGter&l defibrillation thresholb for monophasic and double and single capacity biphasic wave forms .J Am Co11 Cardioi 1989;14:1343-9. 34. Feeser SA, Tang ASL, Kavanagh KM, Rollins DL, Smith WM, Wolf PD, Ideker RE. Strength-duration and probability of success curves for defibrillation with biphasic waveforms. Circulation 1990:82:2128-41.
Douglas 1,. Jones, PhD, George ,J. Klein, MD, FRCP(CI, and G. Kim Wood, AHT. London.
Ontario,
C’arzada
To provide maximum safety margins for patients with implantable defibrillators, it is necessary to optimize current delivery for defibrillation. Two basic strategies are being pursued to enhance defibrillation efficacy: improved hardware (battery, capacitor, or electrodes) and an improved current waveform (“sinusoidal” versus “trapezoidal” and “monophasic” versus,additional “phases”). Schuder et al.’ first tested t,he use of a biphasic square wave defibrillation pulse. Subsequently, several laboratories have demonstrated improved ethcacy of various waveforms incorporat ing hiphasic characteristicsZeG including studies &single cellsi-! An additional consideration was proposed by Bourland et al.,‘” who emphasized the advantage of both temporal and spatial current distribution (sequential pulse). We and others’“-ll
have consistently found reduced defibrillation requirements using sequential pulse shocks. Sequential pulse requires additional electrode(s) and an altered current path, which increases the number of electrodes on the heart and may thus reduce defibrillation energy requirements.‘“-lx The purpose of this report was to directly compare biphasic versus sequential pulse shocks using a paired comparison when subject, total electrode surface area, and pulse characteristics were the same for each modality. METHODS Animals
and surgery. Experiment.s were carried out on 32 pigs weighing from 18 to 28 kg. Animals were tranquilized with an intramuscular mixture of ketamine (400 mg, Rogarsetic,Rogar STB, London, Ontario, Canada) and diazepam(20 mg, Valium, Roche, Nutley, N.J.) for transportation t.o the laboratory. They received atropine (0.6 mg, intramuscularly) to prevent excessmucus secretion and then were intubated, placed on a Harvard respirator (Ealing ScienCfic, St. Laurent, Quebec,Canada), and respired at 10 to 15 breaths/min. Anesthesia was maintained with 0.5’, to 1.2‘, halothane(Somnothane,Hoescht,Markham, Ontario, Canada) blended with 1 L/min 02, 1 to 2 L/min filtered medical air, and 1 to 3 L/min NzO.Body temperature was monitored by an esophagealthermistor and controller (Yellow SpringsInstruments, Yellow Springs.Ohio) and was maintained hy controlling a circulating water
97
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4mertcan
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.miy 1992 Heart Jaurnn~
6 * L-c-< :: ::
~
;
H I
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1 m
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:j :: ::: ::: ::;::: ::1:: :::::: j :: ;I:: :;::
:::: 1: i::: :1f:1
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Fig. 2. Diagrammatic representation of the defibrillation waveforms. The sequential pulse shock used two separate pathways designated by the top two traces. The biphasic pulse shock used a single pathway designated by the hot tom tracing. The two pulses A and C were 4.0 msec in duration separated by 0.2 msec (R). Leading edge voltages were of the same amplitude in each phase. The second pulse of biphasic shock had the anode-cathode orientation reversed.
Fig. 1. Diagrammatic representation of defibrillation electrode positions on the heart. A, Positions of electrodes for sequential pulse defibrillation. Electrodes A on the anterior right ventricle and C on the posterior right ventricle were cut in half, indicated by the line, so that the sum of their surface area equalled that of electrode B. For sequential pulse shocks, the first pulse was passed between electrodes A and B and the second pulse between electrodes C and B, with electrode B being the common cathode. B, Positions of electrodes for biphasic pulse defibrillation. Electrodes A on the mid right ventricle and B on the mid left ventricle were of equal surface area. Thus the total surface area of A and B for the biphasic pulse shock, was equal to the total surface area of electrodes A, B, and C used for sequential pulse shocks. Electrode B was the cathode for the first phase of the biphasic pulse shock and anode for the second phase.
blanket (K-pad, American Hospital, Mississauga, Ontario. Canada). The femoral artery was located through a cutdown incision, cannulated, and connected via a disposable pressure transducer (COBE, Bramalea, Ontario, Canada) to a reconder (VRl6, PPG Biomedical Syst,ems. Lenexa. Kans.). Each animal was randomly assigned to having biphasic, or sequential pulse defibrillation thresholds determined first. The chest was opened via a left thoracatomy in the fifth intercostal space. The heart was supported in a pericardial sling and defibrillating electrodes were attached tci the heart, two for biphasic shocks or three for sequential pulse shocks (Fig. I). The first group of 16 pigs had electrodes with a combined total surface area of 13 cm’. The second group of 16 pigs had electrodes with a combined total surface area of 26 cm”. For each group both biphasic
Volume
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h t = - 3. r = 0.
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8160 7477
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0
SEQUENTIAL
BIPHASIC tz-7.l406
Fig. 3. Leading edge voltages at defibrillation threshold measurements in the 16 pigs using electrodes of 13 cm? total surface area. Circles indicate defibrillation thresholds with this orientation were determined first. Squares indicate defibrillation thresholds with this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean values are the mid line above each description. End bars represent + the standard error of the mean. Significance is given as the t value. Correlation between thresholds using the different pulse techniques is given as r.
and sequential pulse defibrillation thresholds were determined. A quadripolar patch electrode was sutured on the left ventricular epicardial outflow track for monitoring electrograms as well as ventricular fibrillation induction. Standard limb leads I and II were monitored on the VR16 recorder at 1 to 250 Hz. Fibrillation-defibrillation. Ventricular fibrillation was induced by passing 400 msec trains of 4 msec pulses at 60 Hz, timed to begin at the peak of the T wave during sinus rhythm. Current was increased in repeat attempts until ventricular fibrillation was induced. Once fibrillation was induced, a minimum of 10 seconds was allowed before defibrillation was attempted. lg Defibrillation was accomplished using shocks composed of two 4.0 msec pulses separated by 0.2 msec delivered from a Medtronic 2394 defibrillator (Medtronic, Inc., Minneapolis, Minn.) (Fig. 2). The initial stored voltage was set for 500 V. If this shock was unsuccessful in defibrillating the heart, the stored voltage was incremented in 100 V steps until the animal was rescued or the 900 stored V was unsuccessful, in which case internal paddle electrodes were used for rescue. The stored voltage of the next episode was started 100 V higher than the previous unsuccessful attempt. This process was repeated until the first shock of an episode defibrillated the heart or the 900 stored V failed to defibrillate the heart, in which case this unsuccessful shock was arbitrarily accepted as though it had been successful and the delivered peak voltage, current, and energy of that unsuccessful shock was used as a “minimum,” recognizing that this would reduce
ra 0.8221 N=
1%
SEQUENTIAL
BIPHASIC
Fig. 4. Delivered leading edge current at defibrillation threshold measurements in the 16 pigs using electrodes of 13 cm2 total surface area. Circles indicate defibrillation thresholds with this orientation were determined first. Squares indicate defibrillation thresholds wit.h this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean values are the mid line above each description. End bars represent + the standard error of the mean. Significance is given as the t value. Correlation between thresholds using the different pulse techniques is given as r.
the estimated threshold. Then increments and decrements of 10 “; of the lowest successful 100 V increment shock were used until three determinationsso of the lowest successful voltage or three unsuccessful shocks at 900 stored V were obtained. If the first (500 V) shock successfully defibrillated the heart, the stored voltage of the next fibrillation episode was decreased by 100 V. Such 100 V decrements were repeated until the first shock failed to defibrillate the heart, in which case 100 V increments were used to rescue the pig. Subsequently, increments and decrements of 107 of the highest unsuccessful shock were used until 3 determinationszO were made of the lowest successful voltage. This assessment of defibrillation efficacy has been found to be accurate and highly reproducible while requiring fewer shocks than the dose-response curve.sl Once triplicate measurements were obtained with one lead orientation, the defibrillating leads were changed for triplicate determinations with the alternate orientation. At least 3 minutes separated ventricular fibrillation episodes. A custom-designed set of isolation amplifiers between the Medtronic defibrillator and the pig provided voltage and current output, which was fed to a 12 bit analog-to-digital (A/D) converter mount,ed in a personal computer sampling
100
Jones. Klein,
and Wood
American
t = - 3
200 SEQUENTIAL
r = 0.
BI PHASIC
Heart
July 1992 Journal
454 5018
N = 18
Fig. 5. Total delivered energy at defibrillation threshold measurements in the 16 pigs using electrodes of 13 cm’ total surface area. Circles indicate defibrillation t,hresholds with this orientation were determined first. Squares indicate defibrillation thresholds with this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean values are the mid line above each description. End bars represent IL the standard error of the mean. Significance is given as the t value. Correlation between thresholds using the different pulse techniques is given as r.
at 7 kHz. A custom-designed program calculated delivered peak voltage, currents, pulse durations, impedance, and total energy. RESULTS Small (13 cm*) electrodes.
At defibrillation threshold, the delivered leading edge peak voltages of the first shock phase using biphasic pulses were significantly greater than those delivered to the same animal when sequential pulse defibrillation shocks were used (Fig. 3). Of the 16 pigs, only three had a slightly (
0 SEQUENTIAL
BIPHASIC
Fig. 6. Delivered leading edge voltage at defibrillation threshold measurements in the 16 pigs using the electrodes of 26 cm2 total surface area. Circles indicate defibrillation thresholds with this orientation were determined first. Squares indicate defibrillation thresholds with this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean values are the mid line above each descript,ion. End bars represent t the standard error of the mean. Significance is given as the t value. Correlation between thresholds using the different pulse techniques is given as r
animal using sequential pulse shocks. Delivered energy using biphasic pulse shocks was also significantly higher than that using sequential pulse shocks (Fig. 5). For leading edge peak voltage, current, and delivered energy, there was no effect of the order of shocks. Larger (26 cm2) electrodes. The subsequent 16 pigs had a similar protocol using electrodes with double the surface area (26 cm”) of the previous group (13 cm”). The leading edge delivered voltages at threshold were again higher using the biphasic pulse technique (Fig. 6). In five animals, shocks with stored voltages of 900 V were unsuccessful in defibrillating the hearts. Of the other 11 pigs, three had slightly (< 60 V) lower peak voltages with biphasic pulse shocks, while the remainder had equal or great.er peak voltages with biphasic pulse compared with sequential pulse shocks. The accompanying delivered peak current was greater in 15 out of 16 pigs with t.hc biphasic pulse shocks (Fig. 7). Only one pig had a very slightly (0.2 A) lower peak current with biphasic pulse shocks. The total delivered energy was also lower with the sequential pulse shocks compared
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Aiphasic
uersus sequential
40
t L: -
-
3.
pulse defibrillation
101
7125
r 3 0 . 5606
10
3 2 a
35
-
30
-
25
-
20
-
15
-
10
-
2 +
t
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+
51 = -
5 . 6481
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OBIPHASIC
SEQUENTIAL
16
Fig.
Fig. 8. Total delivered energy at defibrillation threshold measurementsin the 16pigs usingthe electrodesof 26 cm2 total surfacearea. Circles indicate defibrillation thresholds with this orientation were determined first. Squares in& cate defibrillation thresholds with this orientation were determined second.Open symbol indicates maximum valnesthat were not able to defibrillate the heart. Mean vallies are the mid line above each description, End bars represent i- the standard error of the mean.Significanceis given asthe t value. Correlation between thresholds using the different pulse techniques is given as r.
with the biphasic shocks in 14 out of the 16 animals (Fig. 8). In several of the animals the energy requirements more than doubled using biphasic pulse shocks. In five of the animals, delivered energies greater than 37 joules were repeatedly unsuccessful in terminating ventricular fibrillation using biphasic pulse shocks. These same pigs required less than 25 joules for successful defibrillation using sequential pulse shocks. Despite these differences, there was a significant correlation between the two measurements.
waveform, and pulse characteristics are the same. The postulate that the sequential pulse technique merely provided a “simulated biphasic stimulus shock” can not explain this result, as the true biphasic pulse with the same pulse characteristics did not have the same result. The postulate that the advantage of sequential pulse over monophasic pulse is because of the increased number of electrodes and therefore the electrode surface area is increased, is not tenable, as the total electrode surface areas were equal. Indeed, if anything, there should have been a slight advantage to the biphasic shock as the total active electrode surface area during actual current delivery was 33 P’;. higher with the biphasic pulse shock compared with sequential pulse shocks, and increased electrode surface area has been associated with decreased defibrillation requirements.l”-‘s Several recent studies* have found improvements
o-
SEQUENTIAL
BIPHASIC
7. Delivered leading edge current at defibrillation threshold measurements in the 16 pigs using the electrodes of 26 cm? total surface area. Circles indicate defibrillation thresholds with this orientation were determined first. Squares indicate defibrillation thresholds with this orientation were determined second. Open symbol indicates maximum values that were not able to defibrillate the heart. Mean valuesare the mid line aboveeachdescription. End bars represent + the standard error of the mean. Significance isgiven asthe t value. Correlation betweenthresholds using the different pulse techniques is given as r.
DISCUSSION
The main finding of this study is that the sequential pulse technique required less voltage, current, and delivered energy compared with the biphasic pulse technique when total electrode surface area,
-References
1. 1 through
8. 16, and
2” through
28.
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Jones, Klein,
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of biphasic shocks over monophasic shocks, although not all lead orientations show such benefit.““. “; Additional characteristics of the biphasic waveform may also play a role in defibrillation efficacy.s, s4.“s. sg In the present study we used equal pulse durations and equal leading edge peak voltages. For the heart, equal pulse durations have been shown to be advantageous over short first or short second pu1ses.s.s4,sBm31 There is little information regarding leading edge voltages, although high ratios of first-to-second pulse leading edge voltages are also disadvantageous.s, 7.s5s2g,“e On the other hand, for the engineer there may be a design advantage in using a single capacitor source where the leading edge voltage of the second pulse can be set to the cut-off voltage of the first pulse. This characteristic has most recently been investigated.i6. 2”-30,32-34A limitation of such a design relates to the mechanism by which the switch between polarities is made. If a set duration of the first pulse is used, the amplitude of the second pulse leading edge voltage may be small if large electrodes wit.h low impedances are used. Such high first-to-second pulse ratios have been found to be disadvantageous.“. 7y“. “g. ‘x’ Alternatively, if a specific “tilt” or cut-off voltage is used, the pulse duration may be very short if large electrodes are used. Short first pulse shocks have also been found to be disadvantageous.“, 95.2g-31 This would not be expected to be the sole explanation for the difference in impedance caused by halving the one active electrode, which altered the impedance of the pathway on average lessthan 20 “C, while the difference in peak current at the defibrillation threshold averaged approximately 50 “iI. There are conflict ing results32-34on the relative advantages of single versus double capacitor shocks. Even the results from the same laboratory differ,33* 34 perhaps dependent upon the types of electrodes used or upon the position of the electrodes. Nevertheless, the optimum waveform needs to be determined. Such factors may have contributed to the inability to defibrillate five pigs using large patches and biphasic pulses, while only one pig could not be defibrillated using the smaller patches in the present study. When sequential pulse shocks were used, at least one of the electrodes involved in active current delivery was a smaller electrode. Alternatively, these differences may simply reflect individual animal variation as the correlation coefficient between animals was consistently significant. It was noteworthy that despite the high values for these six pigs when using biphasic shocks, each animal was able to be defibrillated reproducibly at substantially lower values using the sequential pulse technique. These data suggest that an advantage in defibrilla-
American
July 1992 Heart Journal
tion efficacy is conferred by using both temporally and spatially distributed shocks. It remains to be determined if adding a biphasic waveform to the sequential pulse shock will further enhance defihrillation efficacy. The authors thank Drs. R. Mehra and M. .I. Kallok for proved ing electrodes and defibrillators. Thanks are also due to S. Hunt for typing the manuscript. REFERENCES
I. Schuder JC, Stoeckle MD, Dolan AM. Transthoracic ventricular defibrillation with square-wave stimuli, one-half cycle, one cycle, and multicycle waveforms. Circ Res 1964;15:258-64. 2. Schuder tJC, Gold JH, Stoeckle MD, Roberts SA, McDaniel WC, Moellinger DW. Defibrillation in the calf with bidirectional trapezodial wave shocks applied via chronically implanted epicardial electrodes. Trans Am Sot Artif Intern Organs 1981;37:467-70. :i. dories JL, ,Jones RE: Improved defibrillator waveform safety factor with biphasic waveform. Am J Physiol 1983;245(Heart Circ Physiol 14l:H60-5. 4. Winkle RA, Mead RH, Ruder MA, et al. Improved low energy defibrillation efficacy in man using biphasic truncated exponential waveform. AM HEART ,J 1989;117:122-7. 5. Tang ASL, Yabe S, Wharton JM, Dolker M, Smith WM, ldeker RE. Ventricular defibrillation using biphasic waveforms: the importance of phasir duration. .J Am Co11 Cardiol 1989: 13:207-14. 6. Chapman PD, Vetter JW, Souza JJ, Troup PJ, Wetherbee JX, Hoffman RG. Comparative efficacy of monophasic and biphasic truncated exponential shocks for non-thoracotomy internal defibrillation in does. J Am Co11 Cardiol 1988:12:739-45. 7. Jones .JL, Lepeschkin l?, Jones RE, Rush S. Response of cutured myocardial cells to countershock type electric field stimulation. Am J Physiol 1978;240(Heart Circ Physiol 91: H214-22. 8. *Jones JL, Jones RE. Decreased defibrillator induced dysfunction with biphasic rectangular waveform. Am cJ Physiol 1984; 247(Heart Circ Phvsiol 16):H792-6. 9. Jones JL, -Jones RI?, Balasky G. Microlesion formation in myocardial cells by high-intensity electric field stimulation. Am J Physiol 1987;253(Heart Circ Physiol 18):H480-6. 10. Bourland JD, Tacker WA, Wessale JL, Kallok MJ, Graf JE, Geddes LA. Sequential pulse defibrillation for implantable defibrillators. Med Instrum 1986;20:138-42. 11. dories DL, Klein Gd, Kallok MJ. Improved defibrillation threshold with sequential pulse energy delivered to differenr lead orientiations in pigs. Am J Cardiol 1985;55:821-5. 12. *Jones DL, Sohla A, Bourland JD, Tacker WA, Kallok MJ. Klein GJ. Internal ventricular defibrillation with sequential pulse counter shock in pigs: comparison with single pulses and effects of pulse separation. PACE 1987;10:497-502. 13. dones DL, Klein GJ, Guiraudon GM, et al. Internal cardiac defibrillation in man: pronounced improvement with sequential pulse delivery to two different lead orientiations. Circulation 1986;73:484-91. G, Green HL. Pro14. Bardv GH, Ivey TD, Allen MD, Johnson spective comparison of sequential pulse and single pulse defibrillation using two different clinically available systems in man. J Am Co11 Cardiol 1985;14:165-71. of direct current detibrill;i. Ewy GA, Horan WJ. Effectiveness lation: role of paddle size. II. A.~I HEART -7 1977;93:674-5. defibrillation 16. Dixon EG, Tang ASL, Wolf PD, et al. Improved threshold with large contoured epicardial electrodes and biphasic waveforms. Circulation 1987;76:1176-84. 17. Kallok MJ, Bourland JD, Tacker WA, Jones DL, Klein G.1. Wessale JL. Optimization of epicardial electrode size and implant site for reduced sequential pulse defibrillation thresholds. Med Instrum 1985;20:36-9.
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18. Jones DL, Klein GJ, Guiraudon GM, Sharma AD. Sequential pulse defibrillation in humans: orthogonal sequential pulse defibrillation with epicardial electrodes. J Am Co11 Cardiol 1988;11:590-6. 19. Rattes MF, Jones DL, Sohla A, Sharma AD, Jarvis E, Klein GJ. Defibrillation with the sequential pulse technique: reproducibilitv with repeated shocks. AM HEART J 1986;111:874-8. 20. dories Di,, Fujim;ra 0, Klein GJ. Minimum replications to estimate average threshold energy for defibrillation. Med Instrum 1988;11:298-303. 21. .Jones DL, Irish WD, Klein GJ. Defibrillation efficacy: comparison of defibrillation threshold versus dose-response curve determination. Circ Res 1991;69:45-51. 22. Gurvich NL, Markarychev VA. Defibrillation of the heart with biphasic electrical impulses. Kardiologiia 1967;7:109-12. 23. Schuder JC, Gold JH, Stoeckle H, McDaniel WC, Cheung KN. Transthoracic ventricular defibrillation in the 100 kg calf with symmetrical one-cycle bidirectional rectangular wave stimuli. IEEE Trans Biomed Eng 1983;30:415-22. 24. Bardy GH, Ivey TD. Allen MD, Johnson G, Mehra R, Greene HL. A prospective randomized evaluation of biphasic versus monophasic waveform pulses on defibrillation efficacy in humans. J Am Co11 Cardiol 1989;14:728-33. “5. ‘Thakur R. Souza J, Wetherbee J, Chapman P. Leading edge volrage ratio is an important determinatant of biphasic waveform defibrillation efficacy [Abstract]. ,J Am Co11 Cardiol 199O;IS:Al,~. 26. Zhou S, Wolf PD. Smith WM. Ideker R. Comparison of activation patterns after unsuccessful biphasic and monophasic bhol ks [Abstract]. .J Am Co11 Cardiol 1990;15:72A.
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27. Bardy GH, Allen MD, Johnson G. Mehra R, Greene HL. The effect of electrode systems and current pathways on biphasic waveform defibrillation efficacy in man [Abstract]. J Am Co11 Cardiol 1990;15:72A. 28. Mehra R, DeGroot P, Norenberg S. Reduction of transvenous defibrillation thresholds with an asymmetric biphasic pulse IAbstractl. Circulation 1988:78:11-218. 29. Feeser S& Kavanagh KM, Ideker RE. Evidence of two mechanisms for defibrillation with biphasic truncated exponential waveforms [Abstract]. Circulation 1989;8O:II-532. 30. Chapman PD, Vetter JW. Souza JJ, Wetherbee JN, Troup PJ. Comparison of monophasic with single and dual capacitor biphasic waveforms for nonthroacotomy canine internal defibrillation. J Am Co11 Cardiol 1989;14:242-5. 31. Schuder JC, McDaniel WC, Stoeckle H, Dbeis M, Flaker GC. Optimal biphasic waveform morphology for canine defibrillation with a transvenous catheter and subcutaneous patch system [Abstract]. Circulation 1988;78:11-219. BA, Franz MR. Sequential pulse internal 32. Fain ES, Sweeney defibrillation: is there an advantage to “switched” current pathways? Abf HEART .J 1989;118:717-24. 33. Kavanaeh KM. Tanp ASL. Rollins DL. Smith WM. Ideker RE. Compar&on of the iGter&l defibrillation thresholb for monophasic and double and single capacity biphasic wave forms .J Am Co11 Cardioi 1989;14:1343-9. 34. Feeser SA, Tang ASL, Kavanagh KM, Rollins DL, Smith WM, Wolf PD, Ideker RE. Strength-duration and probability of success curves for defibrillation with biphasic waveforms. Circulation 1990:82:2128-41.