Patrick C Ng1,2,3, Tara B Hendry-Hofer4, Matthew Brenner5, Sari B Mahon5, Gerry R Boss6, Joseph K Maddry7,8, Vikhyat S Bebarta4,9. 1. USAF En route Care Research Center, 59 MDW/ST Joint Base San Antonio Lackland AFB, San Antonio, TX, USA. Patrick.c.ng.mil@mail.mil. 2. Department of Emergency Medicine, Brooke Army Medical Center, Joint Base San Antonio, San Antonio, TX, USA. Patrick.c.ng.mil@mail.mil. 3. Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Patrick.c.ng.mil@mail.mil. 4. Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 5. Beckman Laser Institute, University of California, Irvine, Irvine, CA, USA. 6. Department of Medicine, University of California, San Diego, La Jolla, CA, USA. 7. Department of Emergency Medicine, Brooke Army Medical Center, Joint Base San Antonio, San Antonio, TX, USA. 8. US Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, TX, USA. 9. Office of the Chief Scientist, 59MDW/ST Joint Base San Antonio Lackland AFB, San Antonio, TX, USA.
Abstract
INTRODUCTION: Cyanide is a deadly poison, particularly with oral exposure where larger doses can occur before symptoms develop. Prior studies and multiple governmentagencies highlight oral cyanide as an agent with the potential for use in a terrorist attack. Currently, there are no FDA approved antidotes specific to oralcyanide. An oral countermeasure that can neutralize and prevent absorption of cyanide from the GI tract after oral exposure is needed. Our objective was toevaluate the efficacy of oral sodium thiosulfate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity. METHODS: Swine (45-55kg) were instrumented, sedated, and stabilized. Potassium cyanide (8 mg/kg KCN) in saline was delivered as a one-time bolus via an orogastric tube. Three minutes after cyanide, animals randomized to the treatment group received sodium thiosulfate (510 mg/kg, 3.25 M solution) via orogastric tube. Our primary outcome was survival at 60 minutes after exposure. We compared survival between groups by log-rank, Mantel-Cox analysis and trended labs and vital signs. RESULTS: At baseline and time of treatment all animals had similar weights, vital signs, and laboratory values. Survival at 60 min was 100% in treated animals compared to 0% in the control group (p=0.0027). Animals in the control group became apneic and subsequently died by 35.0 min (20.2,48.5) after cyanide exposure. Mean arterial pressure was significantly higher in the treatment group compared to controls (p=0.008). Blood lactate (p=0.02) and oxygen saturation (p=0.02) were also significantly different between treatment and control groups at study end. CONCLUSION: Oral administration of sodium thiosulfate improved survival, blood pressure, respirations, and blood lactate concentrations in a large animal model of acute oral cyanide toxicity.
INTRODUCTION: Cyanide is a deadly poison, particularly with oral exposure where larger doses can occur before symptoms develop. Prior studies and multiple governmentagencies highlight oral cyanide as an agent with the potential for use in a terrorist attack. Currently, there are no FDA approved antidotes specific to oralcyanide. An oral countermeasure that can neutralize and prevent absorption of cyanide from the GI tract after oral exposure is needed. Our objective was toevaluate the efficacy of oral sodium thiosulfate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity. METHODS: Swine (45-55kg) were instrumented, sedated, and stabilized. Potassium cyanide (8 mg/kg KCN) in saline was delivered as a one-time bolus via an orogastric tube. Three minutes after cyanide, animals randomized to the treatment group received sodium thiosulfate (510 mg/kg, 3.25 M solution) via orogastric tube. Our primary outcome was survival at 60 minutes after exposure. We compared survival between groups by log-rank, Mantel-Cox analysis and trended labs and vital signs. RESULTS: At baseline and time of treatment all animals had similar weights, vital signs, and laboratory values. Survival at 60 min was 100% in treated animals compared to 0% in the control group (p=0.0027). Animals in the control group became apneic and subsequently died by 35.0 min (20.2,48.5) after cyanide exposure. Mean arterial pressure was significantly higher in the treatment group compared to controls (p=0.008). Blood lactate (p=0.02) and oxygen saturation (p=0.02) were also significantly different between treatment and control groups at study end. CONCLUSION: Oral administration of sodium thiosulfate improved survival, blood pressure, respirations, and blood lactate concentrations in a large animal model of acute oral cyanide toxicity.
Authors: Carlos Guido Musso; Paula Enz; Flavia Vidal; Rodolfo Gelman; Luis Di Giuseppe; Pablo Bevione; Leonardo Garfi; Ricardo Galimberti; Luis Algranati Journal: Saudi J Kidney Dis Transpl Date: 2008-09
Authors: Tara B Hendry-Hofer; Patrick C Ng; Alyssa E Witeof; Sari B Mahon; Matthew Brenner; Gerry R Boss; Vikhyat S Bebarta Journal: J Med Toxicol Date: 2018-12-11
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Authors: Patrick C Ng; Tara B Hendry-Hofer; Alyssa E Witeof; Matthew Brenner; Sari B Mahon; Gerry R Boss; Vikhyat S Bebarta Journal: Comp Med Date: 2018-09-12 Impact factor: 0.982
Authors: Penelope R Brock; Rudolf Maibach; Margaret Childs; Kaukab Rajput; Derek Roebuck; Michael J Sullivan; Véronique Laithier; Milind Ronghe; Patrizia Dall'Igna; Eiso Hiyama; Bénédicte Brichard; Jane Skeen; M Elena Mateos; Michael Capra; Arun A Rangaswami; Marc Ansari; Catherine Rechnitzer; Gareth J Veal; Anna Covezzoli; Laurence Brugières; Giorgio Perilongo; Piotr Czauderna; Bruce Morland; Edward A Neuwelt Journal: N Engl J Med Date: 2018-06-21 Impact factor: 91.245
Authors: Matthew Brenner; Sarah M Azer; Kyung-Jin Oh; Chang Hoon Han; Jangwoen Lee; Sari B Mahon; Xiaohua Du; David Mukai; Tanya Burney; Mayer Saidian; Adriano Chan; Derek I Straker; Vikhyat S Bebarta; Gerry R Boss Journal: J Clin Toxicol Date: 2017-06-27