Tetanizing prepulse: A novel strategy to mitigate implantable cardioverter-defibrillator shock-related pain

Abstract

Background: Skeletal muscle activation has been implicated as the source of pain associated with implantable cardioverter-defibrillator shocks. We hypothesized that the skeletal muscle response to defibrillatory shocks could be attenuated with a tetanizing prepulse immediately before biphasic shock delivery.

Objective: The purpose of this study was to test the ability of tetanizing prepulses to reduce the skeletal muscle activation associated with defibrillation.

Methods: Seven adult pigs were studied. A left ventricular coil and subcutaneous dummy can in the right thorax were used to deliver either pure biphasic waveforms or test waveforms consisting of a tetanizing pulse of high-frequency alternating current (HFAC) ramped to an amplitude of 5-100 V over 0.25-1 second, immediately followed by a biphasic shock of approximately 9 J (ramped HFAC and biphasic [rHFAC+B]). We used limb acceleration and rate of force development as surrogate measures of pain. Test and control waveforms were delivered in sinus rhythm and induced ventricular fibrillation to test defibrillation efficacy.

Results: Defibrillation threshold energy was indistinguishable between rHFAC+B and pure biphasic shocks. Peak acceleration and rate of force development were reduced by 72% ± 7% and 71% ± 22%, respectively, with a 25-V, 1-second rHFAC+B waveform compared with pure biphasic shocks. Notably, rHFAC+B with a 9-J biphasic shock produced significantly less skeletal muscle activation than a 0.1-J pure biphasic shock.

Conclusion: A putative source of implantable cardioverter-defibrillator shock-related pain can be mitigated using a tetanizing prepulse followed by biphasic shock. Human studies will be required to assess true pain reduction with this approach.

Keywords: Defibrillation; Implantable cardioverter-defibrillator; Pain; Skeletal muscle.

Figure 1

Experimental setup: Waveforms (A) are applied to the animal (B) through a custom-built amplifier. A force transducer and accelerometer yield measurements (C) of acceleration (top) and RoFD (bottom). Asterisks indicate peak values for RoFD and acceleration. (A) and (C) illustrate application and measurement of a pure biphasic waveform.

Figure 2

Waveforms: Standard biphasic waveform (A) with 4 ms per phase and 66 % tilt and rHFAC+B (B) shown with 250 ms duration and 25 V amplitude ramp. Biphasic waveforms are identical in A and B (amplitude= 480 V).

Figure 3

Comparison of Biphasic (A) and rHFAC+B (D). Both Acceleration (B,E) and RoFD (C,F) decreased by about a factor of four when using rHFAC+B (peak values indicated with asterisks) compared with biphasic alone.

Figure 4

Summary Relationships: Peak acceleration (A) and RoFD (B) versus ramp amplitude for ramp durations of 0.25 s (red, dotted), 0.5 s (green, dashed), and 1 s (blue, solid). (n=6) For each duration, as ramp amplitude increases the peak values of RoFD and acceleration decrease to a minimum at a ramp amplitude of about 25 V and then increase or remain unchanged afterwards.

Figure 5

Pain threshold comparison: Peak acceleration (A) and RoFD (B) for standard biphasic waveforms (red dots and blue Xs) versus estimated waveform energy. All values were normalized to the maximum (9 J) shock. Red dots and blue Xs are from two different animals. The black open squares are responses from six animals to rHFAC+B with a 25 V amplitude, 1 s duration ramp followed by the maximum 9 J biphasic shock. Dashed line at 0.1 J represents reported pain threshold for defibrillation. Acceleration and RoFD fall off below 0.1–1 J and remain relatively constant above this threshold.

Figure 6

Defibrillation: Biphasic (A) and rHFAC+B (B) waveforms were both able to defibrillate in n=6 animals. The success rate was the same for both waveforms in four animals (C) and did not change significantly (p=0.978) over all six. ECG traces are blanked in grey boxes due to electrical artifacts from the applied fields. Note that there are two animals that remained at 50%.