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Use of a Porcine Model to Evaluate the Risks and Benefits of Vasopressors in Propranolol Poisoning

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Abstract

Introduction

Vasopressors are a commonly used treatment in beta-blocker poisoning despite evidence they may be ineffective or harmful. The primary objective of the present study is to use previously collected data from two prior studies (high-dose insulin (HDI) versus vasopressin + epinephrine and a placebo-controlled HDI study) to compare survival between vasopressin + epinephrine and placebo. Secondary outcomes included a comparison with HDI as well as comparisons with hemodynamic parameters, including mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), and systemic vascular resistance (SVR).

Methods

Cardiogenic shock was induced in healthy pigs with a bolus of 0.5 mg/kg of intravenous propranolol followed by an infusion of 0.25 mg/kg/minute until the point of toxicity, defined as (0.75 × initial HR × initial MAP), at which point the infusion was reduced to 0.125 mg/kg/minute for 240 (vasopressin + epinephrine or HDI) or 360 minutes (placebo) or until death.

Results

Survival was significantly lower in pigs receiving vasopressin + epinephrine (0%, 0/5) than in pigs receiving placebo (50%, 2/4) (p < 0.01). Survival was significantly higher with HDI compared with both groups (100%, 5/5) (p < 0.01). All vasopressin + epinephrine pigs died within 100 minutes after reaching toxicity. Over the course of the resuscitation, we observed a statistically significant steady decrease in CO and HR in the vasopressin + epinephrine group compared with placebo (p < 0.01). In contrast, we observed a statistically significant change in MAP and SVR that followed a parabolic arc, with MAP and SVR rising significantly initially in the vasopressin + epinephrine group then rapidly falling until death (p < 0.01).

Conclusions

Mortality was higher with vasopressors compared with placebo in this porcine model of propranolol poisoning. Further studies are warranted to define the optimal timing and role of vasopressors in beta-blocker poisoning.

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Acknowledgments

The authors would like to recognize Dr. Joel Holger for his valued research mentorship. We would like to thank Kate Faltesek and Alex Adams as well; without their laboratory expertise, the execution of these studies would not have been possible. Finally, with admiration and sadness, we wish to thank and recognize Dr. Kristin Engebretsen. Our colleague, teacher, mentor, collaborator, and friend passed away during the processing of this study.

Sources of Funding

This project was funded by a grant from the American Academy of Clinical Toxicology and by the HealthPartners Research Foundation.

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Correspondence to Jon B Cole.

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Cole, J.B., Corcoran, J.N., Engebretsen, K.M. et al. Use of a Porcine Model to Evaluate the Risks and Benefits of Vasopressors in Propranolol Poisoning. J. Med. Toxicol. 16, 212–221 (2020). https://doi.org/10.1007/s13181-020-00758-8

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