High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep. (January 2015)

• Record Type: Journal Article
• Authors: Haouzi, Philippe; Chenuel, Bruno; Sonobe, Takashi
• Is Part Of: Clinical toxicology. Volume 53:Number 1(2015)
• Page Start: 28
• Page End: 36
• Publication Date: 2015-01
• Subjects: Toxicology -- Periodicals; Toxicological emergencies -- Periodicals; 615.9
• DOI: 10.3109/15563650.2014.990976
• Languages: English
• ISSNs: 1556-3650

Abstract

<abstract> <title>Abstract</title> <p> <italic>Context.</italic> Severe H<sub>2</sub>S poisoning leads to death by rapid respiratory and cardiac arrest, the latter can occur within seconds or minutes in severe forms of intoxication. <italic>Objectives.</italic> To determine the time course and the nature of H<sub>2</sub>S-induced cardiac arrest and the effects of high-dose hydroxocobalamin administered after the end of sulfide exposure. <italic>Materials and methods.</italic> NaHS was infused in 16 sedated mechanically ventilated sheep to reach concentrations of H<sub>2</sub>S in the blood, which was previously found to lead to cardiac arrest within minutes <italic>following</italic> the cessation of H<sub>2</sub>S exposure. High-dose hydroxocobalamin (5 g) or saline solution was administered intravenously, 1 min after the cessation of NaHS infusion. <italic>Results.</italic> All animals were still alive at the cessation of H<sub>2</sub>S exposure. Three animals (18%) presented a cardiac arrest within 90 s and were unable to receive any antidote or vehicle. In the animals that survived long enough to receive either hydroxocobalamin or saline, 71% (5/7) died in the control group by cardiac arrest within 10 min. In all instances, cardiac arrest was the result of a pulseless electrical activity (PEA). In the group that received the antidote, intravenous injection of 5 g of hydroxocobalamin provoked an abrupt increase in blood pressure and blood flow; PEA was prevented in all instances. However, we could not find any evidence for a recovery in oxidative metabolism in the group receiving hydroxocobalamin, as blood lactate remained elevated and even continued to rise after 1 h, despite restored hemodynamics. This, along with an unaltered recovery of H<sub>2</sub>S kinetics, suggests that hydroxocobalamin did not act through a mechanism of H<sub>2</sub>S trapping. <italic>Conclusion.</italic> In this sheep model, there was a high risk for cardiac arrest, by PEA, persisting up to 10 min after H<sub>2</sub>S exposure. Very high dose of hydroxocobalamin (5 g), injected very early after the cessation of H<sub>2</sub>S exposure, improved cardiac contractility and prevented PEA.</p> </abstract>