Hydroxocobalamin and Sodium Thiosulfate Versus Sodium Nitrite and Sodium Thiosulfate in the Treatment of Acute Cyanide Toxicity in a Swine (Sus scrofa) Model

Bebarta, Vikhyat S.; Tanen, David A.; Lairet, Julio; Dixon, Patricia; Valtier, Sandra; Bush, Anneke C.

doi:10.1016/j.annemergmed.2009.09.020

Cited by 64 publications

(44 citation statements)

References 22 publications

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“…A potassium cyanide mixture (3 %, normal saline) was infused at 0.16 mg/kg/min until severe hypotension occurred, which we defined as a 50 % reduction in baseline mean arterial pressure for 1 min. In our previous experiments, we found this dose effective in causing severe hypotension and 100 % lethal if untreated, but allowing animals to recover with antidotal treatment [5].…”

Section: Methodsmentioning

confidence: 99%

“…Invasive hemodynamic parameters and core temperature were measured with a pulmonary artery catheter and monitor [5]. Aortic pressure was measured continuously through the femoral artery.…”

Section: Methodsmentioning

confidence: 99%

“…Both routes provide rapid toxicity, but intravenous delivery ensured a more controlled exposure to the animals, while minimizing the risk to research staff from undetected leaks in the ventilation system [12,13]. We minimized this limitation by establishing a clinical end point of severe hypotension and ensuring that toxic levels similar to those observed in humans were achieved [5]. We have used potassium cyanide for this and our previous study; however, the potassium infused is small, approximately 1 mEq of potassium infused over 30 min.…”

Section: Limitationsmentioning

confidence: 99%

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

et al. 2012

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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.

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Section: Methodsmentioning

confidence: 99%

“…Invasive hemodynamic parameters and core temperature were measured with a pulmonary artery catheter and monitor [5]. Aortic pressure was measured continuously through the femoral artery.…”

Section: Methodsmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

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

et al. 2012

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“…The recommended dose of 70 mg/kg leads to a typical, initial adult dose of 5 g administered over 15 min, followed by an additional 5 g over 15 min to 2 h if indicated by the patient's clinical condition [40]. However, in cardiac arrest or severe hypotension, animal studies support a faster infusion rate over only 1-3 min without apparent adverse effects [41].…”

Section: How Is Hydroxocobalamin Administered?mentioning

confidence: 99%

Case Files of the University of Massachusetts Toxicology Fellowship: Does This Smoke Inhalation Victim Require Treatment with Cyanide Antidote?

Hamad¹,

Babu

Bebarta

2016

J. Med. Toxicol.

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Cyanide toxicity is common after significant smoke inhalation. Two cases are presented that provide framework for the discussion of epidemiology, pathogenesis, presenting signs and symptoms, and treatment options of inhalational cyanide poisoning. An evidence-based algorithm is proposed that utilizes point-of-care testing to help physicians identify patients who benefit most from antidotal therapy.

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“…[11][12][13] In previous studies examining the efficacy of hydroxocobalamin to treat cyanide toxicity in a swine model of acute severe cyanide toxicity, it also improved blood pressure, heart rate, and lactate levels. 14,15 Hydroxocobalamin has been shown to improve blood pressure likely through nitric oxide scavenging, when administered in a small volume, and may be an ideal resuscitation treatment prior to the availability of blood. 16 Severe hemorrhage has been associated with high nitric oxide states, and nitric oxide scavenging has been shown to be beneficial.…”

mentioning

confidence: 99%

A Prospective, Randomized Trial of Intravenous Hydroxocobalamin Versus Whole Blood Transfusion Compared to No Treatment for Class III Hemorrhagic Shock Resuscitation in a Prehospital Swine Model

Bebarta

Garrett

Boudreau

et al. 2015

Academic Emergency Medicine

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Objectives: The objective was to compare systolic blood pressure (sBP) over time in swine that have had 30% of their blood volume removed (Class III shock) and treated with intravenous (IV) whole blood or IV hydroxocobalamin, compared to nontreated control animals.Methods: Thirty swine (45 to 55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Animals were hemorrhaged a total of 20 mL/kg over a 20-minute period. Five minutes after hemorrhage, animals were randomly assigned to receive 150 mg/ kg IV hydroxocobalamin solubilized in 180 mL of saline, 500 mL of whole blood, or no treatment. Animals were monitored for 60 minutes thereafter. A sample size of 10 animals per group was determined based on a power of 80% and an alpha of 0.05 to detect an effect size of at least a 0.25 difference (>1 standard deviation) in mean sBP between groups. sBP values were analyzed using repeated-measures analysis of variance (RANOVA). Secondary outcome data were analyzed using repeated-measures multivariate analysis of variance (RMANOVA).Results: There were no significant differences between hemodynamic parameters of IV hydroxocobalamin versus whole blood versus control group at baseline (MANOVA; Wilks' lambda; p = 0.868) or immediately posthemorrhage (mean sBP = 47 mm Hg vs. 41 mm Hg vs. 37 mm Hg; mean arterial pressure = 39 mm Hg vs. 28 mm Hg vs. 34 mm Hg; mean serum lactate = 1.2 mmol/L vs. 1.4 mmol/L vs. 1.4 mmol/L; MANOVA; Wilks' lambda; p = 0.348). The outcome RANOVA model detected a significant difference by time between groups (p < 0.001). Specifically, 10 minutes after treatment, treated animals showed a significant increase in mean sBP compared to nontreated animals (mean sBP = 76.3 mm Hg vs. 85.7 mm Hg vs. 51.1 mm Hg; p < 0.001). RMANOVA modeling of the secondary data detected a significant difference in mean arterial pressure, heart rate, and serum lactate (p < 0.001). Similar to sBP, 10 minutes after treatment, treated animals showed a significant increase in mean arterial pressure compared to nontreated animals (mean arterial pressure = 67.7 mm Hg vs. 61.4 mm Hg vs. 40.5 mm Hg). By 10 minutes, mean heart rate was significantly slower in treated animals compared to nontreated animals (mean heart rate = 97.3 beats/min vs. 95.2 beats/min vs. 129.5 beats/min; p < 0.05). Serum lactate, an early predictor of shock, continued to rise in the control group, whereas it did not in treated animals. Thirty minutes after treatment, serum lactate values of treated animals were significantly lower compared to nontreated animals (p < 0.05). This trend continued throughout the 60-minute observation period such that 60-minute values for lactate were 1.4 mmol/L versus 1.1 mmol/L versus 3.8 mmol/L. IV hydroxocobalamin produced a statistically significant increase in systemic vascular resistance compared to control, but not whole blood, with a concomitant decrease in cardiac output.

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Hydroxocobalamin and Sodium Thiosulfate Versus Sodium Nitrite and Sodium Thiosulfate in the Treatment of Acute Cyanide Toxicity in a Swine (Sus scrofa) Model

Cited by 64 publications

References 22 publications

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

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

Case Files of the University of Massachusetts Toxicology Fellowship: Does This Smoke Inhalation Victim Require Treatment with Cyanide Antidote?

A Prospective, Randomized Trial of Intravenous Hydroxocobalamin Versus Whole Blood Transfusion Compared to No Treatment for Class III Hemorrhagic Shock Resuscitation in a Prehospital Swine Model

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