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Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine.
Clin Toxicol (Phila) 2019; 57(3):189-196CT

Abstract

INTRODUCTION

Hydrogen sulfide (H2S) is found in petroleum, natural gas, and decaying organic matter. Terrorist groups have attempted to use it in enclosed spaces as a chemical weapon. Mass casualty scenarios have occurred from industrial accidents and release from oil field sites. There is no FDA approved antidote for sulfide poisoning. We have previously reported that intravenous cobinamide is effective for sulfide poisoning. A rapid-acting antidote that is easy to administer intramuscularly (IM) would be ideal for use in a prehospital setting. In this study, we assessed survival in sulfide-poisoned swine treated with IM cobinamide.

METHODS

Eleven swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. After stabilization, anesthesia was adjusted such that animals ventilated spontaneously with a FiO2 of 0.21. Sodium hydrosulfide (NaHS, 8 mg/mL) was infused intravenously at 0.9 mg/kg.min until apnea or severe hypotension. Animals were randomly assigned to receive cobinamide (4 mg/kg), or no treatment at the apnea/hypotension trigger. The NaHS infusion rate was sustained for 1.5 min post trigger, decreased to 0.2 mg/kg.min for 10 min, and then discontinued.

RESULTS

The amount of NaHS required to produce apnea or hypotension was not statistically different in both groups (cobinamide: 9.0 mg/kg ±6.1; saline: 5.9 mg/kg ±5.5; mean difference: -3.1, 95% CI: -11.3, 5.0). All of the cobinamide treated animals survived (5/5), none of the control (0/6) animals survived (p < .01). Mean time to return to spontaneous ventilation in the cobinamide treated animals was 3.2 (±1.1) min. Time to return to baseline systolic blood pressure (±5%) in cobinamide-treated animals was 5 min.

CONCLUSION

Intramuscular cobinamide was effective in improving survival in this large swine model of severe hydrogen sulfide toxicity.

Authors+Show Affiliations

a Rocky Mountain Poison and Drug Center , Denver Health and Hospital Authority , Denver , CO , USA.b Department of Emergency Medicine , University of Colorado, School of Medicine , Aurora , CO , USA.c Medical Toxicology and the Department of Emergency Medicine , San Antonio Military Medical Center , San Antonio , TX , USA.d Beckman Laser Institute , University of California, Irvine , Irvine , CA , USA.d Beckman Laser Institute , University of California, Irvine , Irvine , CA , USA.e USAF En Route Care Research Center , US Army Institute of Surgical Research , San Antonio , TX , USA.f Division of Pulmonary and Critical Care Medicine , Pennsylvania State University, College of Medicine , Hershey , PA , USA.g Department of Medicine , University of California, San Diego , La Jolla , CA , USA.h Laboratory Services Branch , Clinical Research Division, Wilford Hall Ambulatory Surgical Center , San Antonio , TX , USA.e USAF En Route Care Research Center , US Army Institute of Surgical Research , San Antonio , TX , USA.b Department of Emergency Medicine , University of Colorado, School of Medicine , Aurora , CO , USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30430872

Citation

Ng, Patrick C., et al. "Intramuscular Cobinamide Versus Saline for Treatment of Severe Hydrogen Sulfide Toxicity in Swine." Clinical Toxicology (Philadelphia, Pa.), vol. 57, no. 3, 2019, pp. 189-196.
Ng PC, Hendry-Hofer TB, Garrett N, et al. Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine. Clin Toxicol (Phila). 2019;57(3):189-196.
Ng, P. C., Hendry-Hofer, T. B., Garrett, N., Brenner, M., Mahon, S. B., Maddry, J. K., ... Bebarta, V. S. (2019). Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine. Clinical Toxicology (Philadelphia, Pa.), 57(3), pp. 189-196. doi:10.1080/15563650.2018.1504955.
Ng PC, et al. Intramuscular Cobinamide Versus Saline for Treatment of Severe Hydrogen Sulfide Toxicity in Swine. Clin Toxicol (Phila). 2019;57(3):189-196. PubMed PMID: 30430872.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine. AU - Ng,Patrick C, AU - Hendry-Hofer,Tara B, AU - Garrett,Norma, AU - Brenner,Matthew, AU - Mahon,Sari B, AU - Maddry,Joseph K, AU - Haouzi,Philippe, AU - Boss,Gerry R, AU - Gibbons,Thomas F, AU - Araña,Allyson A, AU - Bebarta,Vikhyat S, Y1 - 2018/11/15/ PY - 2018/11/16/pubmed PY - 2018/11/16/medline PY - 2018/11/16/entrez KW - Cobinamide KW - hydrogen sulfide toxicity KW - resuscitation KW - swine SP - 189 EP - 196 JF - Clinical toxicology (Philadelphia, Pa.) JO - Clin Toxicol (Phila) VL - 57 IS - 3 N2 - INTRODUCTION: Hydrogen sulfide (H2S) is found in petroleum, natural gas, and decaying organic matter. Terrorist groups have attempted to use it in enclosed spaces as a chemical weapon. Mass casualty scenarios have occurred from industrial accidents and release from oil field sites. There is no FDA approved antidote for sulfide poisoning. We have previously reported that intravenous cobinamide is effective for sulfide poisoning. A rapid-acting antidote that is easy to administer intramuscularly (IM) would be ideal for use in a prehospital setting. In this study, we assessed survival in sulfide-poisoned swine treated with IM cobinamide. METHODS: Eleven swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. After stabilization, anesthesia was adjusted such that animals ventilated spontaneously with a FiO2 of 0.21. Sodium hydrosulfide (NaHS, 8 mg/mL) was infused intravenously at 0.9 mg/kg.min until apnea or severe hypotension. Animals were randomly assigned to receive cobinamide (4 mg/kg), or no treatment at the apnea/hypotension trigger. The NaHS infusion rate was sustained for 1.5 min post trigger, decreased to 0.2 mg/kg.min for 10 min, and then discontinued. RESULTS: The amount of NaHS required to produce apnea or hypotension was not statistically different in both groups (cobinamide: 9.0 mg/kg ±6.1; saline: 5.9 mg/kg ±5.5; mean difference: -3.1, 95% CI: -11.3, 5.0). All of the cobinamide treated animals survived (5/5), none of the control (0/6) animals survived (p < .01). Mean time to return to spontaneous ventilation in the cobinamide treated animals was 3.2 (±1.1) min. Time to return to baseline systolic blood pressure (±5%) in cobinamide-treated animals was 5 min. CONCLUSION: Intramuscular cobinamide was effective in improving survival in this large swine model of severe hydrogen sulfide toxicity. SN - 1556-9519 UR - https://www.unboundmedicine.com/medline/citation/30430872/Intramuscular_cobinamide_versus_saline_for_treatment_of_severe_hydrogen_sulfide_toxicity_in_swine_ L2 - http://www.tandfonline.com/doi/full/10.1080/15563650.2018.1504955 DB - PRIME DP - Unbound Medicine ER -