Annals of Emergency Medicine
Volume 49, Issue 6 , Pages 806-813 , June 2007

Sodium Thiosulfate or Hydroxocobalamin for the Empiric Treatment of Cyanide Poisoning?

  • Alan H. Hall, MD

      Affiliations

    • Toxicology Consulting and Medical Translating Services, Inc., Elk Mountain, WY
    • Department of Preventive Medicine and Biometrics, the University of Colorado Health Sciences Center, Denver, CO
    • Corresponding Author InformationAddress for correspondence: Alan H. Hall, MD, TCMTS, Inc., PO Box 184, Mile 5.0 Pass Creek Road, Elk Mountain, WY 82324; 307-348-7371, fax 307-348-7372
    • ,
  • Richard Dart, MD, PhD

      Affiliations

    • Rocky Mountain Poison and Drug Center, Denver Health, Denver, CO
    • Department of Surgery [Emergency Medicine], the University of Colorado Health Sciences Center, Denver, CO
    • Corresponding Author InformationAddress for reprints: Richard Hart, MD, PhD, Rocky Mountain Poison and Drug Center, 770 Bannock Street, MC 0180, Denver, CO 80204.
    • ,
  • Gregory Bogdan, PhD

      Affiliations

    • Rocky Mountain Poison and Drug Center, Denver Health, Denver, CO
    • Department of Pharmaceutical Sciences, the University of Colorado Health Sciences Center, Denver, CO.

Received 13 April 2006 ,Revised 31 August 2006 ,Accepted 25 September 2006.

References 

  1. Alarie Y. Toxicity of fire smoke. Crit Rev Toxicol. 2002;2:259–289
  2. Canfield D, Chatuverdi A, Dubowski K. Carboxyhemoglobin and blood cyanide concentrations in relation to aviation accidents. Aviat Space Environ Med. 2005;76:978–980
  3. Chatuverdi A, Sanders D. Aircraft fires, smoke toxicity, and survival. Aviat Space Environ Med. 1996;67:275–278
  4. Stefanidou M, Athanaselis S. Toxicological aspects of fire. Vet Hum Toxicol. 2004;46:196–199
  5. Borron SW, Baud FJ. Toxicity, cyanide: updated May 18, 2006. Available at: http://www.emedicine.com/emerg/topic118.htm. Accessed June 26, 2006.
  6. Lee-Chiong TL. Smoke inhalation injury. Postgrad Med. 1999;105:55–62
  7. Rotenberg JS. Cyanide as a weapon of terror. Pediatr Ann. 2003;32:236–240
  8. Keim ME. Terrorism involving cyanide: the prospect of improving preparedness in the prehospital setting. Prehospital Disaster Med. 2006;21:s56–s60
  9. Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Public Health Service. Cyanide toxicity. Am Fam Physician. 1993;48:107–114
  10. Hall AH, Rumack BH. Clinical toxicology of cyanide. Ann Emerg Med. 1986;15:1067–1074
  11. Bowden CA, Krenzelok EP. Clinical applications of commonly used contemporary antidotes: a US perspective. Drug Saf. 1997;16:9–47
  12. Hall A, Kulig K, Rumack B. Suspected cyanide poisoning in smoke inhalation: complications of sodium nitrite therapy. J Toxicol Clin Toxicol. 1989;9:3–9
  13. Hall AH, Rumack BH. Hydroxycobalamin/sodium thiosulfate as a cyanide antidote. J Emerg Med. 1987;5:115–121
  14. Megarbane B, Delahaye A, Goldgran-Toledano D, et al. Antidotal treatment of cyanide poisoning. J Chin Med Assoc. 2003;66:193–203
  15. Brouard A, Blaisot B, Bismuth C. Hydroxocobalamine in cyanide poisoning. J Toxicol Clin Exp. 1987;7:155–168
  16. Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med. 2001;37:635–641
  17. Santiago I. Gas poisoning. An Sist Sanit Navar. 2003;26(suppl 1):173–180
  18. Baskin SI, Horowitz AM, Nealley EW. The antidotal action of sodium nitrite and sodium thiosulfate against cyanide poisoning. J Clin Pharmacol. 1992;32:368–375
  19. Perrson H. Sodium thiosulfate. In:  Meredith TJ,  Haines JA,  Berger J-C, et al. editor. IPCS/CEC Evaluation of Antidotes Series, Vol. 2: Antidotes for Poisoning by Cyanide. Cambridge, UK: Cambridge University Press; 1993;p. 43–64
  20. Bismuth C. Hydroxocobalamin. In:  Meredith TJ,  Haines JA,  Berger J-C, et al. editor. IPCS/CEC Evaluation of Antidotes Series, Vol. 2: Antidotes for Poisoning by Cyanide. Cambridge, UK: Cambridge University Press; 1993;p. 65–77
  21. Hantson P, Benaissa L, Baud F. Smoke poisoning. Presse Med. 1999;28:1949–1954
  22. Personne M, Kulling P. Vitamin B12-variant in cyanide poisoning: hydroxycobalamin is a new effective antidote. Lakartidningen. 1997;94:877–878
  23. Lau FL. Emergency management of poisoning in Hong Kong. Hong Kong Med J. 2000;6:288–292
  24. Kuroki Y, Endo Y, Masatono K, et al. Non-approved antidotes in Japan: foreign antidotes imported for poisoning countermeasures at the Summit 2000. Chudoku Kenkyu. 2001;14:259–267
  25. Møeller S, Hemmingsen C. Science and practice: case reports: cyanide poisoning. Ugeskr Laeger. 2003;165:2579–2580
  26. Mushett CW, Kelley KL, Boxer GE, et al. Antidotal efficacy of vitamin B12a (hydroxo-cobalamin) in experimental cyanide poisoning. Proc Soc Exp Biol Med. 1952;81:234–237
  27. Astier A, Baud FJ. Complexation of intracellular cyanide by hydroxocobalamin using a human cellular model. Hum Exp Toxicol. 1996;15:19–25
  28. Van den Berg MP, Merkus P, Romeijn SG, et al. Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous delivery in rats and humans. J Drug Target. 2003;11:325–331
  29. Faure J, Vincent M, Benabid A, et al. Treatment with hydroxocobalamin for hypercyanemia and hypercyanuria following compression of the sciatic nerve in the rabbit. C R Soc Biol (Paris). 1977;171:1221–1226
  30. Vincent M, Vincent F, Marka C, et al. Cyanide and its relationship to nervous suffering: physiopathological aspects of intoxication. Clin Toxicol. 1981;18:1519–1527
  31. Mizoule J. Study of the Antidotal Action of Hydroxocobalamin. Paris, France: Université de Paris: Faculté de Pharmacie; 1966;
  32. Posner MA, Tobey RE, McElroy H. Hydroxocobalamin therapy of cyanide intoxication in guinea pigs. Anesthesiology. 1976;44:157–160
  33. Krapez JR, Vesey CJ, Adams L, et al. Effects of cyanide antidotes used with sodium nitroprusside infusions: sodium thiosulphate and hydroxocobalamin given prophylactically to dogs. Br J Anaesth. 1981;53:793–804
  34. Rose CL, Chen KK, Harris PN. Mercuric cyanide poisoning and its treatment in dogs. Proc Soc Exp Biol Med (New York). 1964;116:371–373
  35. Ivankovich AD, Braverman B, Kanuru RP, et al. Cyanide antidotes and methods of their administration in dogs: a comparative study. Anesthesiology. 1980;52:210–216
  36. Paulet G, Olivier M. On the subject of the therapeutic value of hydroxocobalamin in hydrocyanic acid poisoning. Ann Pharm Fr. 1963;21:133–137
  37. Paulet G. On the subject of the treatment of cyanide poisoning with chelates of cobalt. Urgence Med Chirurg. 1965;II:611–613
  38. Borron S, Stonerook M, Reid K. Efficacy of hydroxocobalamin for the treatment of acute cyanide poisoning in adult beagle dogs. Clin Toxicol. 2006;44:5–15
  39. Posner MA, Rodkey FL, Tobey RE. Nitroprusside-induced cyanide poisoning: antidotal effect of hydroxocobalamin. Anesthesiology. 1976;44:330–335
  40. Borron S, Barriot P, Imbert M, et al. Hydroxocobalamin for empiric treatment of smoke inhalation-associated cyanide poisoning: results of a prospective study in the prehospital setting. Ann Emerg Med. 2005;46:S77
  41. Fortin JL, Ruttiman M, Domanski L, et al. Prehospital use of hydroxocobalamin for smoke inhalation in the Paris fire brigade. Clin Toxicol. 2006;44:37–44
  42. Forsyth JC, Mueller PD, Becker CE, et al. Hydroxocobalamin as a cyanide antidote: safety, efficacy, and pharmacokinetics in heavily smoking normal volunteers. J Toxicol Clin Toxicol. 1993;31:277–294
  43. Borron SW, Megarbane B, Baud F. Hydroxocobalamin is an effective antidote in severe acute cyanide poisoning in man. Int J Toxicol. 2004;23:399–400
  44. Bromley J, Hughes BG, Leong DC, et al. Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. Ann Pharmacother. 2005;39:1566–1569
  45. Fortin J, Waroux S, Ruttiman M. Hydroxocobalamin for poisoning caused by ingestion of potassium cyanide. Clin Toxicol. 2005;43:731
  46. Weng TI, Fang CC, Lin SM, et al. Elevated plasma cyanide level after hydroxocobalamin infusion for cyanide poisoning. Am J Emerg Med. 2004;22:492–493
  47. Espinoza OB, Perez M, Ramirez MS. Bitter cassava poisoning in eight children: a case report. Vet Hum Toxicol. 1992;34:65
  48. Bismuth C, Cantineau JP, Pontal P, et al. Priority of oxygenation in cyanide poisoning. J Toxicol Med. 1984;4:107–121
  49. Motin J, Bouletreau P, Rouzioux JM. Severe cyanide poisoning treated successfully with hydroxocobalamin. J Med Strasbourg. 1970;1:717–722
  50. Yacoub M, Faure J, Morena H, et al. Acute cyanide poisoning: current data on the metabolism of cyanide and treatment with hydroxocobalamin. Eur J Toxicol Environ Hyg. 1974;7:22–29
  51. Lutier F, Dusoleil P, de Montgros J. Action of a massive dose of hydroxocobalamin in acute cyanide poisoning: apropos of a case. Arch Mal Prof. 1971;32:683–686
  52. Racle JP, Chausset R, Dissait F. Acute cyanide poisoning: biological, toxicological, clinical, and therapeutic aspects. Rev Med Clermont Ferrand. 1976;5:371–382
  53. Bourrelier J, Paulet G. Hydrocyanic poisoning following severe burns by fused sodium cyanate: 3 cases treated with EDTACO2. Presse Med. 1971;79:1013–1014
  54. Jouglard J, Nava G, Botta A, et al. Regarding an acute poisoning with potassium cyanide treated with hydroxocobalamin. Marseille Med. 1974;12:617–624
  55. Bismuth C, Baud FJ, Djeghout H, et al. Cyanide poisoning from propionitrile exposure. J Emerg Med. 1987;5:191–195
  56. Perro G, Cutillas M, Maachi B, et al. Plasma lactate levels and the calculated anion gap are not predictive of cyanide poisoning in fire burns. Brûlures. 2002;3:13–15
  57. Curry SC, Connor DA, Raschke RA. Effect of the cyanide antidote hydroxocobalamin on commonly ordered serum chemistry studies. Ann Emerg Med. 1994;24:65–67
  58. Gourlain H, Caliez C, Laforge M, et al. Study of the mechanisms involved in hydroxocobalamin interference with determination of some biochemical parameters. Ann Biol Clin (Paris). 1994;52:121–124
  59. Vest P, Renaudeau C, Tellal S, et al. Interference of hydroxocobalamin treatment on common biochemical determinations. Ann Biol Clin (Paris). 2002;60:57–64
  60. Beaudeux JL, Flourie F, Peynet J, et al. Hydroxocobalamin and sodium thiosulfate interfere negatively with measurement of creatine kinase activity. Clin Chem. 1994;40:2120–2121
  61. Auzepy P, Veissieres JF, Deparis M. Anaphylactic shock due to hydroxocobalamine. [letter] Nouv Presse Med. 1974;3:152
  62. Branco-Ferreira M, Clode MH, Pereira-Barbosa MA, et al. Anaphylactic reaction to hydroxycobalamin. Allergy. 1997;52:118–119
  63. Dally S, Gaultier M. Anaphylactic shock caused by hydroxocobalamin. Nouv Presse Med. 1976;5:1917
  64. Hovding G. Anaphylactic reaction after injection of vitamin B12. BMJ. 1968;3:102
  65. James J, Warin RP. Sensitivity to cyanocobalamin and hydroxocobalamin. BMJ. 1971;2:262
  66. Heyworth-Smith D, Hogan PG. Allergy to hydroxycobalamin, with tolerance of cyanocobalamin. Med J Aust. 2002;177:162–163
  67. Vidal C, Lorenzo A. Anaphylactoid reaction to hydroxycobalamin with tolerance of cyanocobalamin. Postgrad Med J. 1998;74:702
  68. Uhl W, Nolting A, Golor G, et al. Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study. Clin Toxicol. 2006;44:17–28
  69. Breton D, Jouvet P, de Blic J, et al. Toxicity of fire smoke: apropos of 2 pediatric cases. Arch Fr Pediatr. 1993;50:43–45
  70. Hug E, Marenzi A. Binding of hydrocyanic acid by red blood cells which contain methemoglobin. C R Soc Biol. 1933;114:84–86
  71. Paulet G. Current state of treatment for cyanide poisoning. Arch Mal Prof. 1984;45:185–192
  72. Hug E. L’intoxication par l’acide cyanhydrique [Poisoning by hydrocyanic acid: antidotal action of methylene blue, sodium nitrite, and sodium sulfide (Na2S)]. Comptes Rend Soc Biol. 1932;111:89–90
  73. Paulet G, Dassonville J. The value of dimethylaminophenol (DMAP) in treatment of cyanhydride poisoning: experimental study. J Toxicol Clin Exp. 1985;5:105–111
  74. Renard C, Borron SW, Renaudeau C, et al. Sodium thiosulfate for acute cyanide poisoning: study in a rat model. Ann Pharm Fr. 2005;63:154–161
  75. Chin RG, Calderon Y. Acute cyanide poisoning: a case report. J Emerg Med. 2000;18:441–445
  76. Nakatani T, Kosugi Y, Mori A, et al. Changes in the parameters of oxygen metabolism in a clinical course recovering from potassium cyanide. Am J Emerg Med. 1993;11:213–217
  77. Cheok SS. Acute cassava poisoning in children in Sarawak. Trop Doct. 1978;8:99–101
  78. Lam KK, Lau FL. An incident of hydrogen cyanide poisoning. Am J Emerg Med. 2000;18:172–175
  79. Osterloh J, Hall AH. Hydroxocobalamin analysis and pharmacokinetics. [letter] Clin Toxicol. 1997;35:409–411
  80. Ivankovich AD, Braverman B, Stephens TS, et al. Sodium thiosulfate disposition in humans: relation to sodium nitroprusside toxicity. Anesthesiology. 1983;58:11–17
  81. Evans CL. Cobalt compounds as antidotes for hydrocyanic acid. Br J Pharmacol Chemother. 1964;23:455–475

 Supervising editor: Donald M. Yealy, MDFunding and support: Dr. Hall’s work on this article was supported in part by EMD Pharmaceuticals, Inc., Durham, NC, an affiliate of Merck KGaA and the US developer of the cyanide antidote hydroxocobalamin (Cyanokit). Drs. Hall, Dart, and Bogdan are members of the Cyanokit Advisory Board of EMD Pharmaceuticals, Inc.Publication dates: Available online November 13, 2006.

PII: S0196-0644(06)02276-1

doi: 10.1016/j.annemergmed.2006.09.021

Annals of Emergency Medicine
Volume 49, Issue 6 , Pages 806-813 , June 2007

Article Tools