Experimental paperCardioplegia defibrillation of circulatory and metabolic phase ventricular fibrillation in a swine modelzsstarf;
Introduction
Ventricular fibrillation (VF) remains an important worldwide cause of sudden cardiac arrest. It has previously been shown that animals can be resuscitated from induced ventricular fibrillation with potassium cardioplegia (Kplegia), with or without calcium reversal.1, 2, 3, 4 Hypothesized benefits include conversion of wasteful VF to asystole with decrease in ventricular myocardial energy usage,5 and possible spontaneous resumption of sinus rhythm after reversal of the hyperkalemic state obviating the need for electrical defibrillation and possible associated myocardial stunning.2, 4 Our previous observations of termination of electrical phase VF with Kplegia in a swine model suggest further exploration of this novel therapy for more prolonged VF is warranted.4
Human studies suggest patients may benefit from a period of chest compressions prior to defibrillation for VF arrest greater than 5 min duration.6, 7 Chest compressions may serve to resupply vital nutrients such as oxygen prior to defibrillation and return of spontaneous circulation (ROSC). It is possible such patients could also benefit from transient Kplegia to decrease myocardial nutrient demand during this critical resuscitation period.
The optimal dosing and timing of potassium and calcium intravenous (IV) infusions for Kplegia-assisted resuscitation of VF is unknown. The purpose of this series of three randomized blinded placebo controlled experiments was to explore three increasing potassium dosing and timing protocols to treat three increasing durations of prolonged VF to assess for the greatest benefit, if any, in comparison to a standard resuscitation approach based on a variety of outcome measures.
Section snippets
Methods
We conducted a series of three randomized, blinded, placebo controlled trials of potassium followed by calcium infusion in a swine VF arrest model. The Institutional Animal Care and Use Committee (protocol 15127224) approved the study, and it was performed in compliance with the Guide for the Care and Use of Laboratory Animals.8 Thirty two mixed-breed domestic swine (Sus scrofa) with mean mass 26.0 kg were used. The swine included males and females in a 1:1 ratio in each experiment. Three
Study protocol
We sedated the animals with intramuscular ketamine (10 mg/kg) and xylazine (4 mg/kg). We then established IV access via a peripheral ear vein using a 20 g catheter. We established a surgical plane of anesthesia using a rapid IV infusion of fentanyl (0.05 mg/kg), maintaining this with a continuous titrated infusion of the same (0.03–0.100 mg/kg/hr), and we paralyzed the animals with vecuronium (4 mg initial bolus IV with additional 2 mg boluses as needed).
We intubated the animals by direct laryngoscopy
Measurements
The amplitude-spectral area (AMSA) is a quantitative waveform measurement associated with successful defibrillation, ROSC, and survival.10, 11 KPlegia is expected to decrease AMSA in association with temporary asystole induction, but AMSA could subsequently improve in association with any beneficial energy dynamics. We calculated AMSA for animals in VF using a 3 s ECG epoch obtained 20 s after VF induction and then during the 7 s cessation of chest compressions each minute beginning just before
Analysis
We performed univariate comparisons of interval data between the Kplegia and placebo groups using the nonparametric Hodges–Lehmann confidence interval for median shift. If exact confidence interval statistics could not be computed, then we used asymptotic estimates and checked with bootstrapped estimates. We compared binomial data such as the number of animals achieving ROSC using Fisher’s exact test.
We constructed random-effects mixed linear regression models to assess CPP from just before the
Results
Major results are listed in Table 1 including: the number of animals that achieved chemical or electrical defibrillation, the average number of shocks required if the later, the total number of animals achieving ROSC, and the number with recurrent cardiac arrest. Table 1 also lists: the number of animals requiring norepinephrine infusion, the time to norepinephrine initiation post ROSC, and the number of animals surviving to protocol completion one hour post ROSC. None of these results were
Discussion
We previously demonstrated that potassium plegia with calcium reversal, “Kplegia,” can terminate electrical phase VF chemically in an electrically induced VF porcine model.4 The purpose of this series of experiments was to explore higher potassium doses and durations of Kplegia for termination of longer duration VF.
We progressively increased the duration of untreated VF from 6 to 12 min in 3 experiments, and simultaneously increased the potassium dose and duration of Kplegia. Our goals were to
Conclusions
We have found two regimens of Kplegia to be comparable to a contemporary control therapy in the resuscitation of electrically induced circulatory phase VF arrest. A Kplegia regimen with two higher doses of potassium was ineffective for resuscitation of metabolic phase VF arrest. Further experimentation is necessary to optimize and fully assess the potential benefit of this novel resuscitative strategy for VF arrest.
Conflicts of interest statement
None.
Disclosures
The LUCAS device that was used in this experiment was loaned to Dr. Menegazzi by Joilife. None of the authors have any financial interest in Jolife. The Zoll monitor-defibrillator that was used in this experiment was loaned to Dr. Menegazzi. None of the authors have any financial interest in Zoll. The authors have nothing else to disclose in relation to this particular investigation.
Support
The project described was supported by grants from the Laerdal Foundation for Acute Medicine and the Zoll Foundation, and Award Number 5K12HL109068 (KAM) from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. Study sponsors had no role in any aspect of the design, execution, or dissemination of this
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Previous Presentation: American Heart Association Resuscitation Science Symposium (RESS) Annual Meeting, Chicago, IL, November 10, 2018.