Document Detail


Hydroxocobalamin and sodium thiosulfate versus sodium nitrite and sodium thiosulfate in the treatment of acute cyanide toxicity in a swine (Sus scrofa) model.
MedLine Citation:
PMID:  19944487     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
STUDY OBJECTIVE: Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate. METHODS: Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance. RESULTS: Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar. CONCLUSION: Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.
Authors:
Vikhyat S Bebarta; David A Tanen; Julio Lairet; Patricia S Dixon; Sandra Valtier; Anneke Bush
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-11-27
Journal Detail:
Title:  Annals of emergency medicine     Volume:  55     ISSN:  1097-6760     ISO Abbreviation:  Ann Emerg Med     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-29     Completed Date:  2010-04-19     Revised Date:  2010-05-25    
Medline Journal Info:
Nlm Unique ID:  8002646     Medline TA:  Ann Emerg Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  345-51     Citation Subset:  AIM; IM    
Copyright Information:
Copyright (c) 2009 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.
Affiliation:
Medical Toxicology, University of Texas Health Sciences Center, San Antonio, TX, USA. vikbebarta@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Acidosis / chemically induced,  drug therapy
Animals
Antidotes / administration & dosage,  therapeutic use*
Blood Pressure / drug effects
Cyanides / poisoning*
Disease Models, Animal
Drug Therapy, Combination
Female
Hydroxocobalamin / therapeutic use*
Hypotension / chemically induced,  drug therapy
Lactates / blood
Male
Monitoring, Physiologic
Sodium Nitrite / therapeutic use*
Sus scrofa
Thiosulfates / therapeutic use*
Time Factors
Chemical
Reg. No./Substance:
0/Antidotes; 0/Cyanides; 0/Lactates; 0/Thiosulfates; 13422-51-0/Hydroxocobalamin; 7632-00-0/Sodium Nitrite; 7772-98-7/sodium thiosulfate
Comments/Corrections
Comment In:
Ann Emerg Med. 2010 Jun;55(6):582; author reply 582-3   [PMID:  20494232 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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