(Circulation. 1995;92:1644-1650.)
© 1995 American Heart Association, Inc.
Articles |
Differential Effects of Lidocaine on Defibrillation Threshold With Monophasic Versus Biphasic Shock Waveforms
From the University of Georgia College of Pharmacy and Medical College of Georgia School of Medicine (M.R.U.) (Augusta); and the University of Cincinnati Medical Center Colleges of Pharmacy and Medicine (M.R.U., M.S., T.F., M.G., M.L.M.), Cincinnati, Ohio.
Correspondence to Dr Michael Ujhelyi, Medical College of Georgia, Rm FI-1087, Augusta, GA 30912-2390.
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Abstract |
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Background Defibrillation waveforms and antiarrhythmic drugs have disparate effects on myocardial excitability and refractoriness, making it likely that antiarrhythmic drugs will interact with one waveform differently than with another. The aim of the present study was to determine if the increase in defibrillation threshold (DFT) induced by lidocaine is similar for electrical shocks with monophasic and biphasic waveforms.
Methods and Results Twenty-six pentobarbital-anesthetized farm-raised pigs were instrumented with pacing catheters and epicardial defibrillation electrodes. Each pig was assigned to one of four groups: (1) monophasic shock waveform and placebo (5% dextrose in water [D5W]) (n=7), (2) monophasic shock waveform and lidocaine (n=7), (3) biphasic shock waveform and placebo (D5W) (n=5), or (4) biphasic shock waveform and lidocaine (n=7). DFT was measured at baseline and subsequently during treatment (D5W or lidocaine). In the monophasic waveform groups, DFT increased from baseline in response to lidocaine by 92% (P<.0001), whereas DFT values in response to D5W did not change. In the biphasic waveform groups, DFT values did not change from baseline in response to lidocaine (P=NS), whereas DFT values from baseline in response to D5W significantly decreased by 29% (P=.04). In the monophasic waveform groups, the change in DFT from baseline in response to lidocaine was significantly different than the change from baseline in response to D5W (92±29% versus -0.5±29%, respectively) (P<.0002). In the biphasic waveform groups, however, the change in DFT from baseline in response to lidocaine was similar to the change from baseline in response to D5W (-5.66±15% versus -29±17%, respectively) (P=.48). Furthermore, the change in DFT from baseline in response to lidocaine differed significantly between monophasic and biphasic waveform groups (92±29% versus -5.66±15%) (P<.0002), whereas the change from baseline in response to D5W did not differ between monophasic and biphasic waveforms (-0.5±29% versus -29±17%) (P=.34).
Conclusions Compared with placebo groups, DFT values increased during lidocaine treatment to a much greater degree in the monophasic waveform group than in the biphasic waveform group receiving lidocaine. These data support our hypothesis that antiarrhythmic drugs can affect the defibrillation efficacy of monophasic waveforms differently than that of biphasic waveforms.
Key Words: defibrillation • waves • lidocaine • antiarrhythmia agents
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Many antiarrhythmic agents have been shown to affect the defibrillation threshold (DFT) of monophasic shocks.1 2 3 4 5 6 7 8 9 10 11 The exact mechanisms responsible for these effects are not known, although it appears that the effect of a drug on conduction velocity and/or repolarization has a significant role.2 12 Studies have consistently shown that drugs that prolong cardiac repolarization but do not affect conduction velocity (eg, cardiac potassium channel blockers, sodium channel activators) lower DFT.2 3 10 11 12 On the other hand, drugs that block cardiac sodium channels and do not prolong repolarization (eg, lidocaine, encainide, flecainide) increase the energy required for successful defibrillation.1 2 4 5 9 Drugs that slow conduction velocity and prolong repolarization time have little effect on DFT.2 Although these data indicate that the effect of a drug on a specific electrophysiological parameter can predict how it will affect defibrillation, there are little data to suggest that these global measurements of myocardial electrophysiology are directly causative of changes in monophasic defibrillation efficacy.
It is unknown, however, if antiarrhythmic agents can affect the defibrillation efficacy of biphasic shocks. It is known that biphasic DFT values are approximately 30% to 45% lower than monophasic waveforms, which may be explained by the different electrophysiological actions that these waveforms exert on the myocardium.13 14 15 16 17 For example, biphasic shocks directly excite less fibrillating tissue than monophasic shocks at a given stimulus strength.13 18 Biphasic shocks are also less likely to reinitiate ventricular fibrillation very soon after the original fibrillation front was annihilated.17 Furthermore, the electrophysiological state of the myocardium appears to be less disorganized after biphasic shocks than after monophasic shocks. This is evident by a greater degree of conduction velocity slowing and refractory period dispersion produced by monophasic shocks.17 19 20 This heterogeneity of conduction and refractoriness can produce the substrate for reentrant rhythms (eg, ventricular fibrillation) immediately after shock, which can result in failed defibrillation.
Because of the different electrophysiological effects of biphasic and monophasic shocks, it is likely that pharmacological agents that can affect tissue refractoriness or conduction velocity can affect the defibrillation efficacy of monophasic and biphasic waveforms differently. Lidocaine slows conduction velocity without prolongation of refractoriness and is known to increase DFT with a monophasic waveform.2 12 21 22 Further slowing of conduction velocity produced by lidocaine may allow for reinitiation of fibrillation waveforms from early postshock activations that arise shortly after monophasic shocks. Thus, higher shock energies may be needed to terminate all postshock activations. Because biphasic shocks terminate ventricular fibrillation with less residual conduction slowing, we hypothesized that there will be a smaller increase in DFT during lidocaine treatment when defibrillation is performed with biphasic rather than with monophasic shocks.
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Methods |
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Animal Preparation and Surgical Instrumentation
Domestic farm pigs weighing between 25 and 30 kg were used in this investigation. All procedures were approved by the University of Cincinnati Institution Animal Care and Use Committee before we conducted this investigation. On the day before the procedure, the animals were fasted overnight. On the morning of the investigation, the animals were premedicated with ketamine (15 mg/kg) administered intramuscularly. Subsequently, pentobarbital (25 mg/kg) was administered intravenously for initial anesthesia induction. After intubation with an endotracheal cuffed tube, the animals were mechanically ventilated with a large-animal Harvard Apparatus pump ventilator. A level plane of anesthesia was subsequently maintained throughout the study period with pentobarbital (demonstrated to not affect DFT)23 (75 to 150 mg IV every 30 to 60 minutes as needed). The femoral vein, external jugular vein, and femoral artery were cannulated for catheterization, drug infusion, and blood collection. A combination monophasic action potential/pacing catheter (EP Technologies) was placed via the external jugular vein into the right ventricular apex under fluoroscopic guidance to record monophasic action potential duration and for right ventricular pacing. A 5F pigtail Millar pressure-sensing catheter was placed via the femoral artery into the aortic arch, approximately 3 to 5 cm from the aortic valve, under fluoroscopic guidance for blood pressure monitoring. Surface ECG leads were placed on the four limbs for monitoring of leads II and aVF. The chest was opened with a median sternotomy. One 14-cm2 and one 28-cm2 titanium mesh patch electrodes (models A and L 67, respectively, Cardiac Pacemakers Inc) were sutured onto the surface of the pericardium. The large electrode was placed over the anterior and lateral wall of the right ventricle, which was perpendicular to the small electrode placed over the lateral, posterior, and apical wall of the left ventricle. The electrodes were interfaced with an external defibrillator in which the right ventricular patch served as the anode. The defibrillator was capable of delivering a monophasic or biphasic truncated waveform at a 65° fixed-tilt with a pulse duration between 5 and 8 and 8 and 12 ms, respectively. The biphasic waveform of this device is 60% positive and 40% negative. The output of this device is determined by preset voltage adjustments (1-V increments) (Ventak ECD, Cardiac Pacemakers Inc). Two unipolar epicardial screw electrodes (model 4312, Cardiac Pacemakers Inc) were fixed on the left ventricle—one at the apex and the other approximately 25 to 30 mm cranial in the same longitudinal plane—left ventricular unipolar electrogram recordings. The chest was reapproximated after these procedures, and chest tubes were placed into the pleural space and drained via suction. Arterial blood gases were measured every 20 to 30 minutes to maintain an arterial pH between 7.37 and 7.45, PaO2 between 80 and 120 mm Hg, and PaCO2 between 35 and 45 mm Hg. Sodium and potassium concentrations were measured every 30 minutes to maintain a serum sodium concentration between 135 and 144 mEq/L and a serum potassium concentration between 3.4 and 4.4 mEq/L (Nova 1, Baxter). The potassium concentrations remained above 3.4 mEq/L after the initial instrumentation phase of the study. Body temperature was monitored via a rectal probe and maintained at 37° to 38°C with a surgical thermal blanket. Adequate hydration was maintained with lactated Ringer's solution at a rate of 2 mL/kg per hour.
Study Design
The experiment consisted of two phases in which
DFT and
electrophysiological parameters
were measured initially during a baseline phase that was immediately
followed by the treatment phase (placebo of 5% dextrose in water
[D5W] or lidocaine). The animals were assigned to one of
four groups according to defibrillation waveform and treatment: (1)
monophasic shock waveform and placebo (D5W) (n=7), (2)
monophasic shock waveform and lidocaine (n=7), (3) biphasic shock
waveform and placebo (D5W) (n=5), or (4) biphasic shock
waveform and lidocaine (n=7). The baseline phase was started 30 minutes
after completion of instrumentation. Treatment phase began immediately
after the completion of the baseline phase where the drugs,
D5W or lidocaine (8 mg/mL), were administered as a
10-minute loading dose (20 mg/kg of lidocaine) followed by a continuous
infusion (20 mg/kg per hour of lidocaine).1
D5W served as control and was given at the same infusion
rate as if lidocaine were infused. DFT and other measurements were
initiated 10 minutes after the end of the loading dose (20 minutes
after initiation of loading dose). Blood samples were obtained every 20
minutes during the drug phase for analysis of lidocaine
concentrations. An immunoassay method (Abbott TDx, Abbott Laboratories)
was used to measure lidocaine concentrations.
Defibrillation Threshold Determination
Ventricular
fibrillation was induced by delivering,
to the right ventricle, a stimulus drive train with a 100-ms cycle
length for 2 seconds at a stimulus amplitude of 10 V (Model S8800,
Grass Instruments). Fibrillation with hemodynamic
collapse was allowed to continue for 5 to 8 seconds before
defibrillation. Defibrillation shocks were applied with truncated
exponential waveform of preset energy levels. Defibrillation trials
were performed at a minimum of every 4 minutes but not until heart rate
and blood pressure returned to within 10% of baseline values. To
quantify DFT, a step-up–and–down method was used.24
This
method incorporates an all-or-nothing response variable (successful
versus failed defibrillation) at each delivered energy. An initial
estimate of the DFT was determined, starting at 600 V and decreasing
the defibrillation voltage by 20% until defibrillation failed.
Subsequently, the voltage level for the following defibrillation trial
was increased by single 10% increments until defibrillation was
successful. This was followed by decremental voltage levels of 10%
until defibrillation fails. This protocol continued until there were at
least four reversals in direction and 15 defibrillation trials. All
failed defibrillation trials were quickly followed by a rescue shock of
100 V more than the failed attempt. Energy, impedance, pulse width, and
peak current delivered to the myocardium were measured by
the defibrillator and subsequently printed. These values are accurate
to within 10% of oscilloscope measurements (Ventak ECD literature,
Cardiac Pacemakers Inc).
Electrophysiological and
Hemodynamic Parameters
All electrophysiological
measurements were obtained at the start of DFT protocol (20 minutes
after beginning drug infusion-postdistribution phase), 30 minutes after
the start of DFT protocol, and at the end of DFT protocol for both
baseline and drug treatment phases. These values were then averaged for
each study phase. The ECG leads II and aVF, two left
ventricular unipolar ECGs, endocardial monophasic action
potentials, and aortic blood pressure were monitored and recorded
on an eight-channel monitor (7E, Grass Instruments) at a paper speed of
100 mm/s. The QRS and QT intervals during sinus rhythm and right
ventricular pacing at 350-ms cycle length were obtained
from surface ECG leads II and aVF from five consecutive
beats. Ventricular pacing was continued for 15 seconds
before measurement of these ECG parameters.
Ventricular conduction velocity was determined by QRS
duration during right ventricular pacing at 350-ms cycle
length and by the activation interval between the two unipolar left
ventricular electrograms during right
ventricular pacing at 350 ms. Activation times of the left
ventricular electrograms were considered to be the point
where the first deflection was more than 5 mm in height from baseline
for each electrode. The morphology of the left ventricular
electrograms were closely examined to ensure that the direction of
conduction did not change. A change in morphology occurred in two pigs
(one animal in the D5W monophasic group and one in the
lidocaine monophasic group), which resulted in the omission of these
values. Myocardial repolarization was assessed by
simultaneous monophasic action potential duration and by JT
interval during sinus rhythm and right ventricular pacing
at a pacing cycle length of 350 ms. Right ventricular
effective refractory period was determined by pacing the right
ventricle for eight beats using a stimulus intensity twice the
diastolic threshold at a cycle length of 350 ms followed by
one premature extrastimulus. The drive train was repeated after a
2-second pause, and the extrastimuli coupling interval was decreased by
2 ms until ventricular capture failed.
Data Analysis
DFT response for each test was modeled based on
response at each
energy level within a treatment phase. The entire range of energy and
voltage used in the testing phase was divided into eight bins. Then,
the percentage of defibrillation success for each bin was calculated
(ie, six shocks were placed in an energy bin of 3.5 to 3.75 J, and four
[or 66%] resulted in successful defibrillation). From this, an
energy-voltage dose-response curve was constructed with a nonlinear
model that describes the relation between the probability of
defibrillation success and the energy bin value. The energy predicting
20%, 50%, and 90% success were calculated from the fitted curve.
Because the step-up–and–down method of DFT testing is most
sensitive
for predicting 50% success (ED50), only this
parameter was reported. An iterative computer program
(MERFFIT, Cardiac Pacemaker Inc) was used to perform
these computations. Electrophysiological
measurements were made by a blinded investigator with a digitizing pad
interfaced with a computer program (Sigma Scan, Jandel Scientific).
A
paired t test was used to test differences within a group
from baseline to treatment phase (measurements using the animal as its
own control). Between-group comparisons were made with a
repeat-measures ANOVA with two sets of orthogonal contrast. The two
sets of orthogonal contrast were used to partition the degrees of
freedom for time (baseline and treatment phases) by group interaction.
One set of orthogonal contrast compared the difference between group 1
(monophasic waveform and placebo) and group 2 (monophasic waveform and
lidocaine) and the difference between group 3 (biphasic waveform and
placebo) and group 4 (biphasic waveform and lidocaine). These data made
inferences on the effect of treatment on a certain method of
defibrillation. The second set of orthogonal contrasts compared group 1
and group 3, and group 2 and group 4. These data made inferences on the
effect of waveform for a given treatment. Because we only had 3
df, we could not perform all comparisons in one orthogonal
set. Thus, we had to use two orthogonal sets. To remain conservative,
we corrected for multiple comparisons (ie, two orthogonal sets) using
Bonferroni test, where the P values were multipled by the
number of comparisons (two), while 
remained set at .05. Changes in
electrophysiological parameters
from baseline to drug treatment were compared with the use of a paired
t test. The significance level was set at
P<.05.
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Results |
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Defibrillation Threshold
Baseline mean DFT values in the animals defibrillated with a monophasic waveform were 38% higher than mean baseline DFT values (ED50) in the animals defibrillated with a biphasic waveform (7.23±1.7 [n=14] versus 4.45±1.56 J [n=12], P<.0001). During the treatment phase, an infusion of D5W had no significant effect on DFT (7.34±1.87 to 7.30±1.59 J) in animals defibrillated with a monophasic shock; however, DFT values decreased significantly during D5W infusion in the animals defibrillated with a biphasic shock (5.28±1.55 to 3.74±1.04 J, P=.04) (Table 1
).
Lidocaine,
on the other hand, increased DFT values from baseline in the monophasic
shock group (7.11±1.51 to 13.6±3.4 J, P<.0001), but
lidocaine did not significantly change DFT values from baseline in the
animals defibrillated with biphasic shocks (3.86±1.27 to
3.60±1.41 J,
P=NS) (Table 1).
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Between-group
differences were determined by using repeated
measures, which standardized the data to accommodate for the
differences in baseline DFT values among the groups. Within the animals
defibrillated with monophasic shocks, lidocaine significantly increased
DFT by 92% from baseline values compared with a 0.5% decrease in DFT
during D5W (P<.0002). In the animals
defibrillated with biphasic shocks, DFT values decreased during
lidocaine by 5.66% compared with a 29.1% decrease during
D5W (P=.48) (Fig 1). The DFT
change from baseline to lidocaine differed significantly between
monophasic and biphasic waveform groups (92±29% versus
-5.66±15%,
respectively) (P<.0002), whereas the change from baseline
to D5W did not differ between monophasic and biphasic
waveforms (-0.5±29% versus -29±17%,
P=.34) (Fig 1).
The net effect of lidocaine on DFT was a mean DFT value that was 93%
(92%-[-]0.5%) higher than placebo with monophasic shocks
(the
difference between the percentage DFT change from baseline to lidocaine
and percentage DFT change from baseline to D5W) versus DFT
values that were 23% ([-]5.66%-[-]29%)
higher than placebo
with biphasic shocks (Table 1
and Fig 2).
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Electrophysiological
Parameters
The mean and SD electrophysiological
values are reported in Table 2 for all groups. Baseline
values for each parameter did not differ between the four
groups (P>0.51). In no animals receiving D5W
were changes seen in any of the
electrophysiological measurements.
Lidocaine administration resulted in significant slowing of
ventricular conduction velocity, as evidenced by a
prolongation in QRS interval and left ventricular
activation times during right ventricular pacing, in both
waveform groups. Lidocaine also decreased the repolarization interval,
as evidenced by a reduction in JTc during sinus rhythm, JT
interval during pacing, and action potential duration during pacing.
These indexes of repolarization were of smaller magnitude than the
slowing of conduction and revealed significance for the paced JT
interval and action potential duration at 90% repolarization in both
the monophasic and biphasic groups. Right ventricular
effective refractory period was significantly increased by a small
magnitude in both waveform groups.
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Lidocaine Concentrations
The dose of lidocaine achieved
steady serum concentrations and did
not vary by more than 10% beyond the 20-minute point, which was the
point in time that the DFT study protocol started. These concentrations
ranged between 12 and 13 µg/mL in both waveform groups. Furthermore,
the mean area under the lidocaine plasma concentration-time curve was
similar in both groups (1812 versus 1750 µg/mL per minute; biphasic
versus monophasic groups, respectively) and thus cannot be used to
explain the DFT differences seen between groups (Fig 2).
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Discussion |
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It is well established that antiarrhythmic drugs can significantly alter the energy required for successful defibrillation.25 This information, however, applies only to defibrillation shocks with monophasic waveforms. Before the present study, no data existed regarding the influence of antiarrhythmic drugs on DFT with biphasic waveforms. However, it is rational to believe that antiarrhythmic drugs may affect DFT values according to defibrillation waveform because of inherent electrophysiological differences between monophasic and biphasic shock waveforms.13 Because a large percentage of patients with implantable cardioverter defibrillators also receive antiarrhythmic drugs,26 we performed the present study to determine if there was an antiarrhythmic drug–defibrillation waveform interaction. The major new finding of this investigation was that the increase in DFT during lidocaine therapy is fourfold lower with a biphasic than with a monophasic shock waveform.
Interaction Between Defibrillation Waveforms and
Lidocaine
We chose lidocaine as our model probe because its effects on
DFT
with monophasic shocks are well characterized. Furthermore, we chose a
lidocaine dosage that has been shown to consistently increase
DFT values to ensure that a drug effect was evident in the monophasic
group. DFT values (with monophasic shocks) are known to increase
significantly when lidocaine concentrations exceed 4 to 5
µg/mL.27 As lidocaine concentrations increase so do DFT
values, where DFT values are 100% higher than baseline values at
concentrations of 10 µg/mL.2 27 In the present
study
with a swine model of defibrillation, lidocaine increased DFT by 93%
in the monophasic waveform group compared with placebo
(D5W) at plasma lidocaine concentrations near 12 µg/mL.
We performed this study with lidocaine concentrations higher than that
used clinically for treating ventricular
tachycardia but similar to concentrations seen after bolus
infusions during cardiac arrest and resuscitation.28 The
greater increase in DFT seen at higher levels also provides greater
statistical power and allowed us to perform this study with fewer
animals. Thus, it is evident that our swine model of defibrillation is
similar to the dog model when evaluating the interaction between
lidocaine and defibrillation efficacy with a monophasic defibrillation
waveform. Furthermore, our swine model was able to show that biphasic
shocks had DFT values that were 38% lower than monophasic shocks,
which is similar to values reported in previous human and animal (swine
and canine) models.14 15 16
Data from the present study indicate that antiarrhythmic drugs affect DFT values based on the shape of the defibrillation shock waveform. The animals that received lidocaine and monophasic shocks had DFT values that were 92% higher than those during the baseline phase, which is consistent with previous studies. On the other hand, lidocaine did not significantly affect the DFT values with biphasic shocks. A new and unexpected finding was a significant reduction in DFT values (29%) from baseline to placebo phase in the biphasic shock waveform group. The decrease in DFT with biphasic shocks cannot be attributed to experimental procedures, anesthetic agent, number of defibrillations, or the amount of time the preparation was in use since these variables were the same for each waveform group. The disparate DFT effects between waveform groups also cannot be explained by changes in electrophysiological parameters since baseline values were similar and the magnitude of change induced by lidocaine was also similar between the monophasic and biphasic groups. In the present study, lidocaine significantly slowed ventricular conduction velocity in both waveform groups. Lidocaine also decreased the time to repolarization as demonstrated by a significant reduction in the JT interval during right ventricular pacing and a decrease in the monophasic action potential duration in both waveform groups. The magnitude of the decrease in repolarization time is smaller than the slowing of conduction velocity but is consistent with previous reported data in both human and animal studies.1 2 29 30 Thus, the only difference was the use of a biphasic waveform. It appears, therefore, that multiple biphasic shocks within a short time period may cause DFT values to decrease. When correcting for this variability, lidocaine was shown to increase DFT values from baseline by 93% (percentage DFT change from baseline to lidocaine minus the percentage DFT change from baseline to placebo) in the monophasic group and by 23% in the biphasic group. Therefore, the magnitude by which lidocaine increased DFT values was fourfold greater in the monophasic waveform group than in the biphasic group.
Proposed Mechanisms
The mechanisms by which lidocaine
increases DFT values are
unclear. It has been suggested that changes in either
ventricular depolarization or repolarization are
causative.2 3 10 11 12
Although these
electrophysiological effects have been
shown to predict the effect of a drug on DFT, only one study has
directly correlated electrophysiological
changes (QTc interval prolongation) to reduction in
DFT.3 This relation has not been corroborated by
others.2 12 31 32 A lack of
correlation between increased
DFT values and decreased conduction velocity was evident in our
previous study in which lidocaine added to moricizine therapy caused
the DFT values to increase in a synergistic manner, but QRS duration
was prolonged only in an additive manner.1 Further
confusing the interpretation of previous data are studies demonstrating
that adenosine and allopurinol can affect DFT values even
though these agents do not affect ventricular conduction
velocity or repolarization.33 34 Thus, the
electrophysiological effects of
antiarrhythmic drugs measured during sinus rhythm and
ventricular pacing can usually predict how the drug will
affect DFT using monophasic shocks, but these global indicators of
myocardial electrophysiology have not been demonstrated to be directly
causative.
Therefore, other mechanisms must be operative. There are two theories of failed defibrillation: (1) the shock stimulus was not strong enough to excite more than 90% of the myocardium (critical mass) and thus annihilate the original fibrillation wave front or (2) the shock stimulus annihilates the initial fibrillation wave front but induces an electrophysiological state after shock that results in the generation of a new fibrillation activation front.17 18 19 20 35 36 37 38 39 40 It is unlikely that sodium channel–blocking agents increase DFT by decreasing the excitability of the ventricular myocyte, since it has been shown that tetrodotoxin (a potent sodium channel blocker) does not impair the ability of the shock to excite myocardial tissues.41 In addition, mapping studies have shown that monophasic shocks are able to activate/excite a greater portion of myocardium at a given stimulus strength than biphasic shocks.13 18 Thus, if the effects of lidocaine were due to a drug-induced decrease in tissue excitability, then biphasic shock should fall below the 90% critical tissue mass cutoff sooner than monophasic shocks, since both waveforms must excite the same critical mass (>90%) to annihilate the original fibrillation front.17 We observed the opposite findings, suggesting that lidocaine affects DFT values via mechanisms that are not related to a decrease in the magnitude of shock-induced tissue excitation.
Thus, the second mechanism seems more likely. Increased dispersion of refractoriness may be one mechanism by which postshock activations can propagate.35 36 37 38 39 40 Antiarrhythmic drugs that are potent sodium channel blockers can increase the dispersion of refractoriness.42 43 44 Drugs that decrease action potential duration can also increase dispersion of refractoriness.45 Myocardium that has a large dispersion in refractoriness is likely to have regions where an impulse will not be conducted in one direction but will conduct in a different direction (anisotropic conduction), increasing the probability for the formation of a reentrant circuit and failed defibrillation. We postulate that lidocaine (a sodium channel–blocking agent that decreases action potential duration) increases the degree of refractory period dispersion during defibrillation, allowing for propagation of postshock activations. Thus, higher shock energies (which reduce the dispersion of repolarization) are needed to terminate these activations, resulting in high DFT values.46
The explanations may also be why lidocaine affects biphasic shocks differently than monophasic shock. Data from mapping and in vitro studies suggest that biphasic waveforms do not produce as much dispersion of refractoriness and electrical heterogeneity after shock as do monophasic shocks.13 17 18 19 20 40 This may be the mechanism for lower DFT values seen with biphasic shocks in the absence of antiarrhythmic drugs. Therefore, it is conceivable that lidocaine is less likely to increase the dispersion of refractoriness when biphasic shocks are applied because this waveform appears to cause less electrophysiological disturbance (eg, conduction block, dispersion of refractoriness) than monophasic waveforms after shock.19 20 This may explain the smaller increase in DFT values during lidocaine with biphasic shocks versus monophasic shocks observed in the present study.
Study Limitations
We used a swine model with a healthy
cardiovascular system. It is unknown if these findings
can be directly extrapolated to infarcted hearts, myopathic hearts, or
other defibrillation lead systems (eg, transvenous). It is likely,
however, that these findings in a swine model are predictive of human
defibrillation, since it has been shown that antiarrhythmic agents that
increase DFT values in whole animal models increase DFT and/or cause
ventricular fibrillation to be refractory to defibrillation
in humans with cardiovascular
disease.1 2 3 4 5 6 7 8 9 10 11 12 45 46 47 48 49 50 51 52 53 54 55
A recent meta-analysis has
confirmed these observations, showing a very close correlation between
animal models of defibrillation and clinical data observed in
humans.56 Moreover, a retrospective analysis
indicates that antiarrhythmic agents are a responsible factor in
producing high DFT values in patients with implanted
defibrillators.57
We studied a single lidocaine dose that sustained blood concentrations that were well above clinically accepted levels for the treatment of ventricular tachycardia but similar to levels seen after bolus infusions during cardiac arrest and resuscitation.28 We believe that similar findings would have occurred at lower doses, although there would have been less statistical power to detect differences between waveforms because of smaller differences in DFT values.
Clinical Implications
The clinical importance of elevated DFT
values was established
when the incidence of sudden cardiac death in patients with high DFT
values (>25 J) was reported to be sixfold greater than in patients
with lower DFT values (<25 J).58 Thus, if the DFT is
increased beyond the capacity of the defibrillator, the patient will
not be resuscitated. The above issues have become a daily problem in
the management of arrhythmia patients, since antiarrhythmic
drugs have been shown to affect DFT and are used concomitantly in
approximately 50% to 70% of patients with implanted
defibrillators.26 With the advent of transvenous
defibrillation lead systems, the available "safety margin" may be
less because of the higher DFT values inherent to this lead system.
Therefore, there has been a trend toward increasing the use of devices
with biphasic shock waveforms to reduce DFT values. This is the first
report of the interaction of antiarrhythmic drugs and biphasic shock
waveforms. The results of this study imply that elevation of DFT by
antiarrhythmic drugs may be less of a concern when using defibrillators
with biphasic shock waveforms.
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Acknowledgments |
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This work was supported by a Grant-In-Aid from the American Heart Association Ohio Affiliate (SW 92-22-1). Support of this study in the form of defibrillation equipment was provided by Cardiac Pacemaker Inc (St Paul, Minn). The authors are indebted to Richard A. Walsh, MD, for his support during this project and his critical review of the manuscript. The authors are also grateful of the statistical support provided by Marybeth Johnson, PhD, and the technical support provided by Gary Flesher.
Received December 29, 1994; revision received March 21, 1995; accepted March 26, 1995.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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Echt DS, Black JN, Barbey JT, Coxe DR, Cato E.
Evaluation of antiarrhythmic drugs on defibrillation energy
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3.
Dorian P, Wang M, David I, Feindel C. Oral
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