Effect of Methylene Blue on a Porcine Model of Amlodipine Toxicity
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ORIGINAL ARTICLE
Effect of Methylene Blue on a Porcine Model of Amlodipine Toxicity Jenna M. LeRoy 1
&
Sean P. Boley 2 & Justin N. Corcoran 1 & Kristin M. Engebretsen 1 & Samuel J. Stellpflug 1
Received: 30 December 2019 / Revised: 7 April 2020 / Accepted: 28 April 2020 # American College of Medical Toxicology 2020
Abstract Introduction Calcium channel blocker (CCB) overdoses cause significant morbidity and mortality. Dihydropyridine CCBs cause peripheral vascular dilation and at high doses cardiac dysfunction. Amlodipine, a dihydropyridine, causes peripheral vasodilation from release of nitric oxide (NO) in addition to calcium channel blockade; NO scavenging is a potential treatment. Methylene blue (MB) inhibits NO directly and inhibits NO production. We compared the effects of MB versus norepinephrine (NE), with time to death as the primary outcome, in a porcine amlodipine toxicity model. Methods Animals were anesthetized and instrumented, and an amlodipine infusion was administered to mimic oral overdose. After 70 minutes, each group was resuscitated with normal saline. Animals in each group were then randomized to receive either MB or NE. Hemodynamic parameters, including mean arterial pressure and cardiac output, were recorded every 10 minutes. The primary outcome was survival time (Kaplan-Meier analysis and log-rank test). Results Interim analysis after 15 animals (7 MB, 8 NE) revealed that MB was clearly not superior to NE. Overall, 1 of 7 animals in the MB group survived to 300 minutes compared with 2 of 8 animals in the NE group. The median survival time was 100 minutes for the MB group and 177 minutes for the NE group. Survival time did not differ by group (log-rank test p = 0.29). Conclusion In this porcine model of amlodipine toxicity, methylene blue did not improve survival time compared with norepinephrine. Whether methylene blue is beneficial in combatting distributive shock in amlodipine toxicity remains unclear and requires further study. Keywords Amlodipine . Overdose . Methylene blue . Cardiovascular toxin . Pig
Introduction Cardiovascular medication overdose is associated with significant morbidity and mortality. The American Association of Poison Control Centers’ National Poison Data System has reported that serious outcomes related to cardiovascular drug exposures are rapidly increasing. Calcium channel blockers (CCBs) were associated with 5.2% of death cases in the 2017 report [1]. CCBs affect the heart and peripheral vasculature in varying amounts depending on type. Drugs in the dihydropyridine (DHP) class of CCBs impart their therapeutic Supervising Editor: Mark B. Mycyk, MD * Jenna M. LeRoy [email protected] 1
Department of Emergency Medicine, Regions Hospital, Saint Paul, MN, USA
2
Department of Emergency Medicine, United Hospital, Saint Paul, MN, USA
effect via peripheral vasodilation. In overdose, their effect remains primarily via peripheral vasodilation causing distributive shock, but there is loss of class specificity in severe cases; they can also cause cardiac toxicit
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