title: Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection.
abstract: OBJECTIVE
  The 2 antidotes for acute cyanide poisoning in the United States must be administered by intravenous injection. In the out-of-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study is to determine whether sodium nitrite and sodium thiosulfate are effective cyanide antidotes when administered by intramuscular injection.
  
  
  METHODS
  We used a randomized, nonblinded, parallel-group study design in 3 mammalian models: cyanide gas inhalation in mice, with treatment postexposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all 3 models were lethal in the absence of therapy.
  
  
  RESULTS
  We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the 2 drugs rescued 73% of the rabbits and 80% of the pigs. In all 3 species, survival in treated animals was significantly better than in control animals (log rank test, P<.05). In the pigs, the drugs attenuated an increase in the plasma lactate concentration within 5 minutes postantidote injection (difference: plasma lactate, saline solution-treated versus nitrite- or thiosulfate-treated 1.76 [95% confidence interval 1.25 to 2.27]).
  
  
  CONCLUSIONS
  We conclude that sodium nitrite and sodium thiosulfate administered by intramuscular injection are effective against severe cyanide poisoning in 3 clinically relevant animal models of out-of-hospital emergency care.
authors.affiliation: Department of Emergency Medicine, University of Colorado, School of Medicine, Aurora, CO.
authors.forename: Vikhyat S
authors.initials: VS
authors.lastname: Bebarta
authors.affiliation: Battelle Memorial Institute, Columbus, OH.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brittain
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chan
authors.affiliation: Medical Toxicology and the Department of Emergency Medicine, San Antonio Military Medical Center/59 MDW, San Antonio, TX.
authors.forename: Norma
authors.initials: N
authors.lastname: Garrett
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California, Irvine, Irvine, CA.
authors.forename: David
authors.initials: D
authors.lastname: Yoon
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California, Irvine, Irvine, CA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Burney
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California, Irvine, Irvine, CA.
authors.forename: David
authors.initials: D
authors.lastname: Mukai
authors.affiliation: Battelle Memorial Institute, Columbus, OH.
authors.forename: Michael
authors.initials: M
authors.lastname: Babin
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Renate B
authors.initials: RB
authors.lastname: Pilz
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California, Irvine, Irvine, CA.
authors.forename: Sari B
authors.initials: SB
authors.lastname: Mahon
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California, Irvine, Irvine, CA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brenner
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Gerry R
authors.initials: GR
authors.lastname: Boss
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D003486:Cyanides / Q000506:poisoning*; D004195:Disease Models, Animal; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D011817:Rabbits; D011897:Random Allocation; D012977:Sodium Nitrite / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D034421:Sus scrofa; D013885:Thiosulfates / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000931:Antidotes; D003486:Cyanides; D013885:Thiosulfates; C017717:sodium thiosulfate; D012977:Sodium Nitrite