Acute Electrocardiographic ST Segment Elevation May Predict Hypotension in a Swine Model of Severe Cyanide Toxicity

Abstract

Cyanide causes severe cardiac toxicity resulting in tachycardia, hypotension, and cardiac arrest; however, the clinical diagnosis can be difficult to make. A clinical finding that may precede or predict cyanide-induced hypotension may be a trigger to provide treatment earlier and improve outcomes in cyanide toxicity. Our primary objective was to determine if there is a clinically significant change in ST segment deviation measured on ECG during intravenous cyanide infusion that may predict cyanide-induced hypotension. As part of a larger study comparing antidotes for cyanide-induced shock, 30 swine were anesthetized and monitored and then intoxicated with a continuous cyanide infusion until severe hypotension (50 % of baseline mean arterial pressure) occurred. ECGs were obtained at baseline, every 5 min during infusion, and at the development of hypotension. Repeated measures of analysis of variance were used to determine significance. The mean weight for the 30 swine at baseline was 48 kg (range 45-52), pulse rate 86 beats/min (range 55-121), and systolic blood pressure 109 mmHg (range 90-121). The mean time to hypotension was 31 min (range 16-39). The mean amount of cyanide infused was 5 mg/kg (range 2.5-6.3 mg/kg). All animals (30/30) had ECG changes in repolarization or depolarization during cyanide infusion. Significant rhythm, repolarization, and conduction changes from baseline were observed prior to severe hypotension (p<0.05). Normal sinus rhythm and sinus tachycardia were the most common rhythms preceding hypotension. We observed ST segment elevation in leads V3, V4, III, and aVF and ST segment depression in leads aVL and aVR. The most pronounced ST segment elevation was observed in leads V3 and V4. We also detected significant changes with increased pulse rate, prolonged PR interval, and shortened QTc interval. Other significant changes were increased T axis and reduced QRS axis. We detected ST segment deviations occurring just before the onset of cyanide-induced hypotension in our swine model. Leads V3 and V4 had the most pronounced with ST elevation, but we also detected electrocardiographic ST elevation inferiorly. Shortening of the QTc and lengthening of the PR interval were also detected before hypotension.

Intramuscular administration of glyoxylate rescues swine from lethal cyanide poisoning and ameliorates the biochemical sequalae of cyanide intoxication

“…Therefore, this study’s main objectives were to (1) assess glyoxylate’s efficacy in swine, an FDA-approved preclinical animal model that is favorable for human dosing because of the similarity to human anatomy, physiology, genome, and size ( Swindle et al , 2012 ), and (2) evaluate if the putative biochemical mechanisms of glyoxylate are conserved in large mammalian models. We used survival following exposure to a highly lethal cyanide dose as a primary outcome in addition to physiological and laboratory parameters, similar to those monitored during the care of critically ill patients, as secondary outcomes ( Bebarta et al , 2010 ; Fortin et al , 2010 ; Hendry-Hofer et al , 2020 ; Muncy et al , 2012 ). Pharmacokinetic studies and metabolite profiling were also conducted to characterize the countermeasure biochemically.…”