Effect of Methylene Blue on a Porcine Model of Amlodipine Toxicity

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

Journal of medical toxicology : official journal of the American College of Medical Toxicology - 16(2020), 4 vom: 03. Okt., Seite 398-404

Sprache:

Englisch

Beteiligte Personen:

LeRoy, Jenna M [VerfasserIn]
Boley, Sean P [VerfasserIn]
Corcoran, Justin N [VerfasserIn]
Engebretsen, Kristin M [VerfasserIn]
Stellpflug, Samuel J [VerfasserIn]

Links:

Volltext

Themen:

1J444QC288
Amlodipine
Antidotes
Cardiovascular toxin
Comparative Study
Journal Article
Methylene Blue
Methylene blue
Norepinephrine
Overdose
Pig
Research Support, Non-U.S. Gov't
T42P99266K
X4W3ENH1CV

Anmerkungen:

Date Completed 26.07.2021

Date Revised 15.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s13181-020-00780-w

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM310747724