Faculty Collaboration Database

Effect of Methylene Blue on a Porcine Model of Amlodipine Toxicity. J Med Toxicol 2020 Oct;16(4):398-404

Date

06/05/2020

Pubmed ID

32495116

Pubmed Central ID

PMC7554284

DOI

10.1007/s13181-020-00780-w

Scopus ID

2-s2.0-85086021076 (requires institutional sign-in at Scopus site)   5 Citations

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.

Author List

LeRoy JM, Boley SP, Corcoran JN, Engebretsen KM, Stellpflug SJ

Author

Justin N. Corcoran MD Assistant Professor in the Emergency Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amlodipine
Animals
Antidotes
Cardiotoxicity
Cardiovascular Diseases
Cardiovascular System
Disease Models, Animal
Hemodynamics
Methylene Blue
Norepinephrine
Sus scrofa
Time Factors