From the Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, and SurVivaLink Corp, Minneapolis, Minn (J.E.B., A.M.D.).
Correspondence to Patrick J. Tchou, MD, Director, Clinical Cardiac Electrophysiology, Department of Cardiology/F15, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail tchoup{at}cesmtp.ccf.org
| Abstract |
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Methods and ResultsTwo groups of studies were performed. In group 1, 9 biphasic waveforms from a combination of 3 phase-1 tilt values (30%, 50%, and 70%) and 3 phase-2 leading-edge voltage values (0.5, 1.0, and 1.5 times the phase-1 leading-edge voltage, V1) were tested. Phase-2 pulse width was held constant at 3 ms in all waveforms. Two separate 60-µF capacitors were used in each phase. The energy value that would produce a 50% likelihood of successful defibrillation (E50) decreased with increasing phase-1 tilt and increased with increasing phase-2 leading-edge voltage except for the 30% phase-1 tilt waveforms. In group 2, 9 waveforms were identical to the waveforms in group 1, except for a 20-µF capacitor for phase 2. E50 decreased with increasing phase-1 tilt. Phase-2 leading-edge voltage of 1.0 to 1.5 V1 appeared to minimize E50 for phase-1 tilt of 50% and 70% but worsened E50 for phase-1 tilt of 30%. There was a significant correlation between E50 and residual membrane voltage at the end of phase 2, as calculated by the charge-burping model in both groups (group 1, R2=0.47, P<0.001; group 2, R2=0.42, P<0.001).
ConclusionsThe waveforms with 70% phase-1 tilt were more efficacious than those with 30% and 50%. The relationship of phase-2 leading-edge voltage to defibrillation efficacy depended on phase-2 capacitance. The charge-burping model predicted the optimal external biphasic waveform.
Key Words: defibrillation ventricles death, sudden
| Introduction |
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Recently, a quantitative "charge-burping" model has been proposed to explain the improved efficacy of biphasic over monophasic shocks.6 A recent study7 supported this model by demonstrating that minimum residual membrane voltage as calculated by the charge-burping model predicted the optimal internal biphasic waveform.
Defibrillation efficacy may also be improved by optimizing capacitance
values. On the basis of models of internal
defibrillation,8 9 optimal capacitance depends on
shock impedance and the chronaxy of the strength-duration curve.
Assuming a time constant of 2 to 4 ms and a mean impedance of 40
,
as reported in a previous swine external defibrillation
study,4 the optimum capacitance is calculated by
these theoretical models to be in the 50- to 100-µF
range.8 9 Hence, a 60-µF capacitor would be
within this optimal range to provide maximal external defibrillation
efficacy. Recent defibrillation studies10 11 12 13
have shown that the biphasic waveform with changing capacitance at
phase reversal may reduce the defibrillation threshold (DFT). However,
the optimal combination of phase-1 tilt and phase-2 leading-edge
voltage to maximize defibrillation efficacy has not been determined in
such a changing capacitor external waveform.
The purpose of this study was (1) to assess the contribution of phase-1 tilt and phase-2 leading-edge voltage in optimizing the small-capacitor (60/60-µF) biphasic waveform for external defibrillation, (2) to determine the optimal timing and voltage of phase reversal to maximize external defibrillation efficacy in biphasic waveform with changing capacitor at phase reversal (60/20-µF), and (3) to assess the ability of the charge-burping model to predict the optimal external defibrillation waveforms.
| Methods |
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Defibrillation Equipment and Protocol
The transthoracic defibrillation electrode system
consisted of adhesive pad electrodes, each with a surface area of 75
cm2, applied to the right high anterior shaved
thorax and to the left lower anterolateral shaved thorax. Pad
electrodes were connected to an external defibrillator custom-made by
SurVivaLink Corp. This custom external defibrillator delivered a
monophasic or biphasic, high-voltage, time-truncated, capacitative
discharge pulse. The defibrillator was equipped with 2 capacitor banks.
Each capacitor bank was used for a phase of a monophasic or biphasic
shock, with independent phase capacitance values in the range of 10 to
300 µF, in 10-µF steps. Each capacitor bank was charged to a
maximum of 4000 V and was programmed to deliver a pulse with
predetermined initial voltage, capacitance, pulse width or tilt, and
polarity. Together, the 2 capacitor banks delivered a biphasic shock.
The defibrillator acquired data from current and voltage meters, and it
sampled each meter at 10 kHz. All reported experimental
parameters were measured and calculated from these waveform
data acquired during the delivery of the shocks.
Ventricular fibrillation was induced with 60-Hz alternating current (15 V) applied for 4 seconds through the RV electrode. The test biphasic waveform was delivered at 10 seconds after initiation of alternating current. The right high anterior pad was used as the cathode for phase 1. If ventricular fibrillation was not terminated by the test biphasic waveform, a monophasic rescue shock (450 to 900 V) was delivered via the RV electrode. A recovery period of at least 3 minutes was allowed between episodes of fibrillation. Fibrillation was not reinitiated until heart rate and blood pressure had returned to the preshock values.
E50 and V50
Defibrillation efficacies of different waveforms were compared
through the determination of E50 and
V50 for each waveform, where
E50 and V50 were defined as
the estimated energy and voltage values that would produce a 50%
likelihood of successful defibrillation. The protocol to determine
E50 and V50 used a Bayesian
approach.18 Ten defibrillation shocks were
delivered with each waveform. The first shock had a 1650-V phase-1
leading-edge voltage. Subsequent shocks had the voltage decremented or
incremented, depending on the success or failure of the preceding
shock, respectively. The voltage changes in the sequence of
defibrillation test shocks were 350, 200, 150, 150, 100, 100, 50, 50,
and 0 V. This approach has been demonstrated to obtain an estimate of
V50 with an error of
<10%.18 The E50 for
stored and delivered energy were calculated at
V50.
Defibrillation Waveforms
Nine biphasic waveforms were tested in each group. The
description of each waveform in groups 1 and 2 is detailed in Figures 1
and 2
,
respectively. The 9 waveforms in each group were tested in random order
in each experiment.
|
|
Residual Membrane Voltage
Calculation of residual membrane voltage for the purpose of
testing the charge-burping hypothesis was performed according to the
method described by Kroll6 and detailed in the
Appendix.
Statistical Analysis
Group data were expressed as mean±SD. Repeated-measures 1-way
ANOVA was used to compare defibrillation parameters among
the 9 waveforms in each group. Pairwise comparisons were performed by
the method of contrasts.19 ANCOVA was used
between the E50 for delivered energy and the
normalized absolute residual membrane voltage at the end of phase 2 in
each group. The null hypothesis was rejected for
P<0.05.
| Results |
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Defibrillation Energy
Figure 3
shows the
E50 of delivered energy in each waveform. For
30% phase-1 tilt waveforms, the E50 of the
30/0.5 phase-1 leading-edge voltage (V1) waveform
was the lowest compared with the 30/1.0 V1
(P=0.0001) and the 30/1.5 V1 waveforms
(P=0.0002). Similar to 30% phase-1 tilt waveforms, the
50/0.5 V1 and the 70/0.5 V1
waveforms generated the lowest E50 within their
corresponding 50% and 70% phase-1 tilt waveforms (50/0.5
V1 versus 50/1.0 V1,
P=0.0151; versus 50/1.5 V1,
P=0.0001; 70/0.5 V1 versus 70/1.0
V1, P=0.0438; versus 70/1.5
V1, P=0.0028). Thus, the waveforms
with phase-2 leading-edge voltage equal to half of phase-1 leading-edge
voltage had the lowest E50 of delivered energy in
all 3 tilts tested in these experiments.
|
When one compares the waveforms using the optimal phase-2 leading-edge voltage (0.5 V1) for each phase-1 tilt, the E50 for the 30/0.5 V1 waveform was higher than the corresponding E50 of the 50/0.5 V1 (P=0.0482) and the 70/0.5 V1 waveforms (P=0.0168). There was no significant difference in E50 between the 50/0.5 V1 and the 70/0.5 V1 waveforms (P=0.6625). In a similar manner, the E50 in the 30/1.0 V1 waveform was higher than that of the 50/1.0 V1 (P=0.0001) and the 70/1.0 V1 waveforms (P=0.0001). There was again no significant difference between the E50 of the 50/1.0 V1 and the 70/1.0 V1 waveforms (P=0.3836). For waveforms with phase-2 leading-edge voltage of 1.5 V1, the E50 in the 30/1.5 V1 waveform was higher than the 70/1.5 V1 waveform (P=0.0019). Thus, the waveform with phase-1 tilt of 50% or 70% had lower E50 of delivered energy than the waveform with the phase-1 tilt of 30% when phase-2 leading-edge voltage was constant.
Membrane Voltage
The residual membrane voltages at the end of phase 2, based on the
charge-burping model for the test waveforms, are shown in Table 1
. The
theoretical cell membrane response curves are illustrated as the thin
lines in Figure 1
. As predicted by this model and illustrated in Figure 1
, the residual membrane voltage at the end of phase 2 for each fixed
phase-1 tilt increased with increasing phase-2 leading-edge voltage.
According to the charge-burping hypothesis, optimal DFT energies are
obtained when phase 2 of the shock minimizes any residual cell membrane
voltage. Figure 4
shows the relationship
between E50 of delivered energy and residual
membrane voltage at the end of phase 2. There is a significant
correlation between the residual membrane voltage at the end of phase 2
and the measured E50 of delivered energy.
|
Group 2
Complete DFT data sets were obtained from 10 swine (35±6 kg). The
waveform characteristics and the DFT parameters are
detailed in Table 2
.
|
Defibrillation Energy
Figure 5
shows the
E50 of delivered energy in each waveform. For
30% phase-1 tilt waveforms, the E50 in the
30/0.5 V1 waveform was lower than in the 30/1.5
V1 waveform (P=0.0253). There was no
difference in E50 between the 30/1.0
V1 and 30/1.5 V1 waveforms
(P=0.0656). In contrast to the 30% phase-1 tilt waveforms,
the 50% and 70% phase 1 tilt waveforms had lower
E50 at phase-2 leading-edge voltages of 1.0
V1 (50/0.5 V1 versus 50/1.0
V1, P=0.0391; 70/0.5
V1 versus 70/1.0 V1,
P=0.0414). However, the differences in
E50 between the 50/0.5 V1
and 50/1.5 V1 waveforms (P=0.071) and
between the 70/0.5 V1 and 70/1.5
V1 waveforms (P=0.087) did not reach
statistical significance. Thus, the lowest E50 of
delivered energy appeared to be associated with waveforms having longer
phase-1 durations (50% and 70%) and larger phase-2 leading-edge
voltages (1.0 V1).
|
When one compares the waveforms of differing tilts but the same 0.5 V1 phase-2 leading-edge voltage, the E50 for the 30/0.5 V1 waveform was higher than the corresponding E50 of the 70/0.5 V1 waveform (P=0.0095) but not different from that of the 50/0.5 V1 waveform (P=0.1373). There was no significant difference in E50 between the 50/0.5 V1 and the 70/0.5 V1 waveforms (P=0.2496). For waveforms with phase-2 leading-edge voltage of 1.0 V1, the E50 in the 30/1.0 V1 waveform was higher than that of the 50/1.0 V1 (P=0.0001) and the 70/1.0 V1 waveforms (P=0.0001). There was again no significant difference between the E50 of the 50/1.0 V1 and the 70/1.0 V1 waveforms (P=0.2596). In a similar manner, for waveforms with phase-2 leading-edge voltage of 1.5 V1, the E50 in the 30/1.5 V1 waveform was higher than the 50/1.5 V1 waveform (P=0.0001) and the 70/1.5 V1 waveform (P=0.0001). Thus, the waveform with the phase-1 tilt of 50% or 70% had lower E50 of delivered energy than the waveforms with the phase-1 tilt of 30% for each phase-2 leading-edge voltage.
Membrane Voltage
The absolute residual membrane voltage at the end of phase 2 based
on the charge-burping model for the test waveforms are shown in Table 2
. The theoretical cell membrane response curves are illustrated as the
thin lines in Figure 2
. Figure 6
shows
the relationship between E50 of delivered energy
and absolute residual membrane voltage at the end of phase 2. Similar
to group 1, there is a significant correlation between the absolute
residual membrane voltage at the end of phase 2 and the measured
E50 of delivered energy.
|
| Discussion |
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Residual Membrane Voltage
Recently, a quantitative charge-burping model has been
proposed.6 In this model, the optimal phase 1 of
the biphasic waveform should be identical to the optimal monophasic
waveform, while the optimal phase 2 discharges the residual
charges left on the cell membranes by phase 1.6 A
study by Swerdlow et al7 supported this model by
demonstrating that the optimal ratio of phase-1 pulse width to phase-2
pulse width depended on the relationship between the time constant of
the shocking system and the time constant of myocardial cell membranes.
This result was predicted by the charge-burping model. In this study,
we calculated the membrane response curves in each waveform using the
same charge-burping model.6 There was a
significant correlation between the absolute residual membrane voltage
at the end of phase 2 and the E50 of delivered
energy in both groups (Figure 4
and 6
). This result suggests that
minimizing the residual membrane voltage at the end of phase 2 as
calculated by the charge-burping model correlates with the optimal
phase 2 for generating the lowest delivered energy. The original
charge-burping model postulated that biphasic waveforms may have little
advantage over monophasic ones for external
defibrillation.6 This hypothesis was based on the
concept that internal defibrillation creates large voltage gradients in
the heart, especially near the shocking electrodes, whereas external
defibrillation would create relatively homogeneous voltage
gradients within the heart. A few early experimental
studies20 21 supported this hypothesis. Recent
external defibrillation studies,3 4 5 however,
have found that biphasic waveforms do indeed improve defibrillation
efficacy. Furthermore, our study suggests that the charge-burping model
reasonably predicted the defibrillation efficacy of a particular
phase-1 waveform in combination with various phase-2 pulses. Thus, it
would appear that discharging the residual membrane voltage at the end
of phase 1 may still be important even with external
defibrillation.
Phase-2 Leading-Edge Voltage
One recent internal defibrillation study22
compared defibrillation efficacy among 3 biphasic waveforms with equal
phase-1 tilt at 65% but shorter phase-2 pulse width or smaller phase-2
leading-edge voltage. Defibrillation energy requirements were
significantly increased for the waveform with a smaller phase-2
leading-edge voltage, whereas a short phase-2 pulse width did not
influence defibrillation efficacy. This result suggested that the
amplitude of phase-2 leading-edge voltage may be a more critical
determinant than the phase-2 pulse width for defibrillation success of
biphasic waveforms in humans.22
Although the 0.5 V1 phase-2 leading-edge voltage always had the lowest DFT in the 60/60-µF shocks (group 1), this relationship did not persist in the 60/20-µF waveforms (group 2). For the optimal phase-1 tilts in group 2, the best phase-2 leading-edge voltages were higher in the 1.0 to 1.5 V1 range. Thus, when smaller phase-2 capacitors are used, the optimal phase-2 leading-edge voltage is higher than those waveforms when the same phase-1 and phase-2 capacitors are used.
Limitations
The characteristics of the defibrillation waveform in this
study depended on shock impedance. The typical patient impedance for
external shock is 60 to 80
,3 5 23 but the
shock impedance in our study was
40
. Although the optimal
phase-1 tilt value is 70% with a phase-1 pulse width of 3.0 ms in this
study, this phase-1 pulse width will be longer in a clinical setting
because of the higher impedance. Thus, these results may need to be
verified in humans because of this difference impedance.
Conclusions
The major findings of the present study are as follows: (1)
the 60/60-µF biphasic waveform with combination of phase-1 70% tilt
and phase-2 leading-edge voltage of 0.5 times phase-1 leading-edge
voltage provided the maximal defibrillation efficacy, (2) the
60/20-µF capacitor biphasic waveform with combination of phase-1 50%
and 70% tilt and phase-2 leading-edge voltage of 1.0 and 1.5 times
phase-1 leading-edge voltage provided the optimal defibrillation
efficacy, and (3) the residual membrane voltage as calculated by the
charge-burping model predicted the optimal small-capacitor external
defibrillation biphasic waveform.
|
| Acknowledgments |
|---|
| Footnotes |
|---|
| Appendix 1 |
|---|
|
|
|---|
2 Independent of
1
2) is the
duration that leaves as little residual membrane potential remaining on
a cell affected by phase 1 (
1) as possible.
Ideally, affected cells are set back to "relative ground" with
2.
Generalized charge-burping theory for external defibrillation is based
on the Kroll cardiac cell response model illustrated in Figure 7
. The Kroll design equations are
extended to account for the transthoracic resistance and a
charge-burping
2 that is independent of
1. The generalized burping theory is based on
incorporating an independent capacitor system for
2.
In the transthoracic extension of the Kroll model, the
resistance variables are RS=resistance of the
defibrillator (including the electrode-electrolyte interface),
RTC=resistance of the thoracic cage,
RCW=resistance of the chest wall,
RLP=resistance of the lungs in parallel,
RLS=resistance of the lungs in series, and
RH=resistance of the heart.
RB represents the combined parallel and
series resistances of the patient's body. Also,
C1 represents the
1 capacitor system, C2
represents the
2 capacitor system, and
the pair Cm and Rm
represent the membrane series capacitance and resistance of a
single cell. The node VS represents the
voltage between the electrodes, and Vm denotes
the voltage across the cell membrane.
The discharge of a capacitor system is modeled by
V=V1e-t/
1
for an initial C1 capacitor system with a
leading-edge voltage of V1. Using the abstract
circuit of Figure 7
, an equation for Vm may be
determined to be
![]() | (1) |
S and
B
are nonlinear resistance representations of the
transthoracic resistive elements,
m=RmCm
represents the time constant of the myocardial cell in the
circuit model, and
1=(RS+RB)
· C1 represents the time constant of
1. The ordinary differential equation (ODE) in
Equation 1
1, in terms of phase-1 cell potential
Vm1, is
![]() | (2) |
For
2, an analysis identical to
Equations 1
, and 2
is derived. The differences are 2-fold. First, a
biphasic waveform reverses the flow of current through the
myocardium during
2. Reversing the
flow of current in the circuit model changes the sign on the current.
The sign changes on the right hand side of Equation 1
. Second, the
2 part of the waveform is assumed to be
independent of
1. Therefore, the
2 ODE incorporates an independent leading-edge
voltage, V2, for the
2
portion of the pulse. Let
2 represent
the
2 time constant. With these
considerations, the
2 ODE becomes
![]() | (3) |
1, the (initial) value
for Vm2 is
Vm2 (0)=Vm1
(d
1)=V
1 where
d
1 is the overall time of discharge for
1 and V
1 is the
voltage left on the cell at the end of
1.
Applying the initial condition to equation 3
![]() | (4) |
2 for those cells that
were not depolarized by
1. Equation 4
2, denoted
by d
2. Arranging the exponential functions
to 1 side and taking the logarithm of both sides, we solve for
d
2 to get
![]() | (5) |
Received July 7, 1998; revision received July 28, 1998; accepted July 30, 1998.
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