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Comparison of the hemodynamic effects of hydroxocobalamin and cobalt edetate at equipotent cyanide antidotal doses in conscious dogs

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Abstract

Objectives

The hemodynamic effects of two cyanide antidotes, hydroxocobalamin and cobalt edetate were compared.

Design

This experimental study was performed in chronically instrumented conscious dogs and at equipotent cyanide antidotal doses (hydroxocobalamin 70 mg·kg−1; cobalt edetate 10.5 mg·kg−1).

Results

Peak plasma cobalt concentrations did not differ in the two groups (412±183 vs 400±160 μmol·1−1). Hydroxocobalamin induced a slight increase in mean arterial pressure (+17±9%,p<0.05) and systemic resistance (+19±15%,p<0.05). In contrast, cobalt edetate induced an increase in heart rate (+78±33%,p<0.05), in cardiac output (+63±39%,p<0.05), and in maximum rise of left ventricular pressure (+33±15%,p<0.05), did not modify mean arterial pressure, and decreased systemic resistance (−36±15%,p<0.05). These hemodynamic effects were associated with an increase in plasma catecholamine concentrations (epinephrine: 2524±3025 vs. 58±37 pg·ml−1,p<0.05; norepinephrine: 1106±609 vs. 343±146 pg·ml−1,p<0.05), which in contrast remained unchanged after hydroxocobalamin administration. Cobalt edetate also induced an increase in blood glucose concentrations (9.9±1.9 vs. 6.1±1.2 mmol·l−1,p<0.05) and a moderate metabolic acidosis, whereas hydroxocobalamin did not. After adrenergic (α1,β) and cholinergic receptor blockade, cobalt edetate did not modify heart rate and various indices of cardiac function, suggesting that it has no direct cardiac effects.

Conclusion

Considering its lack of hemodynamically relevant effects, these results indicate that hydroxocobalamin is potentially a safer cyanide antidote than cobalt edetate.

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References

  1. Baud FJ, Barriot P, Toffis V, Riou B, Lecarpentier Y, Astier A, Bourdon R, Vicaut E, Bismuth C (1991) Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med 325:1761–1766

    Google Scholar 

  2. Michenfelder JD (1977) Cyanide release from sodium nitroprusside in the dog. Anesthesiology 46:196–201

    Google Scholar 

  3. Moore SJ, Norris JC, Walsh DA, Hume AS (1987) Antidotal use of methemoglobin forming cyanide antagonists in concurrent carbon monoxyde/cyanide intoxication. J Pharmacol Exp Ther 242:70–73

    Google Scholar 

  4. Friedberg KD, Shukla UR (1975) The efficiency of aquocobalamine as an antidote in cyanide poisoning when given alone or combined with sodium thiosulfate. Arch Toxicol 33:103–113

    Google Scholar 

  5. Rutkowsky JV, Roebuck BD, Smith RP (1986) Liver damage does not increase the sensitivity of mice to cyanide given acutely. Toxicology 38:305–314

    Google Scholar 

  6. Antal A (1894) Experimentelle Untersuchungen zur Therapie der Cyanvergiftungen. Ungar Arch Med 3:117–128

    Google Scholar 

  7. Paulet G (1958) Intoxication cyanhydrique et chelates de cobalt. J Physiol (Paris) 50:438–442

    Google Scholar 

  8. Evans CL (1964) Cobalt compounds as antidotes for hydrocyanic acid. Br J Pharmacol 23:455–475

    Google Scholar 

  9. Bartelheimer EW, Friedberg KD, Lendle L (1962) The potentialities of cobalt compounds for chemical reactions in relation to their toxicity and antidotal activity against hydrocyanic acid. Arch Int Pharmacodyn Ther 139:99–108

    Google Scholar 

  10. Nagler J, Provoost RA, Parizel G (1978) Hydrogen cyanide poisoning: Treatment with Cobalt EDTA. J Occup Med 20:414–416

    Google Scholar 

  11. Mushett CW, Kelley KL, Boxer GE, Rickards JC (1952) Antidotal efficacy of vitamin B12 (Hydroxo-cobalamin) in experimental cyanide poisoning. Proc Soc Exp Biol Med 81:234–237

    Google Scholar 

  12. Riou B, Baud FJ, Astier A, Barriot P, Lecarpentier Y (1990) In vitro demonstration of the antidotal efficacy of hydroxocobalamin in cyanide poisoning. J Neurosurg Anesthesiol 2:296–304

    Google Scholar 

  13. Brouard A, Blaisot B, Bismuth C (1987) Hydroxocobalamine in cyanide poisoning. J Toxicol Clin Exp 7:155–168

    Google Scholar 

  14. Riou B, Baud FJ, Renaud C, Bismuth C (1992) L'hydroxocobalamine. In: Baud FJ, Barriot P, Riou B (eds) Les antidotes. Masson, Paris, pp 175–193

    Google Scholar 

  15. Auzépy P, Veissière JF, Deparis M (1974) Choc anaphylactique dû à l'hydroxocobalamine. Nouv Presse Méd 3:152

    Google Scholar 

  16. Vatner SF (1978) Effects of anesthesia on cardiovascular control mechanisms. Environ Health Perspect 26:193–206

    Google Scholar 

  17. Gérard JL, Berdeaux A, Giudicelli JF (1989) Cardiac and hemodynamic profile of the new cardiotonic agent, DPI 201-106, in the conscious dog. Eur J Pharmacol 165:39–49

    Google Scholar 

  18. Bourdon R (1988) Fondements théoriques des méthodes spectroscopiques appliquées au dosage des composés inorganiques dans les liquides biologiques. Rev Fr Lab 177:37–71

    Google Scholar 

  19. Causon RC, Carruthers ME, Rodnight R (1981) Assay of plasma catecholamines by liquid chromatography with electromechanical detection. Anal Biochem 116:223–226

    Google Scholar 

  20. Baud FJ, Barriot P, Toffis V, Astier A, Ledantec P, Riou B, Julien H, Bismuth C (1990) Démonstration de l'effet complexant de l'hydroxocobalamine chez l'intoxiqué par cyanures. J Toxicol Clin Exp 10:193–194 (Abstract)

    Google Scholar 

  21. Marrs TC (1987) The choice of cyanide antidotes. In: Ballantyne B, Marrs TC (eds) Clinical and experimental toxicology of cyanides. Wright, Bristol, pp 383–401

    Google Scholar 

  22. Riou B, Gérard JL, Drieu la Rochelle C, Bourdon R, Berdeaux A, Giudicelli JF (1991) Hemodynamic effects of hydroxocobalamin in conscious dogs. Anesthesiology 74:552–558

    Google Scholar 

  23. Beregi JP, Riou B, Lecarpentier Y (1991) Effects of hydroxocobalamin on rat cardiac papillary muscle. Intensive Care Med 17:175–177

    Google Scholar 

  24. Hilmann B, Bardham KD, Bain JTB (1974) The use of cobalt edetate (Kelocyanor) in cyanide poisoning. Postgr Med J 50:171–174

    Google Scholar 

  25. Naughton M (1974) Acute cyanide poisoning. Anaesth Intensive Care 4:351–356

    Google Scholar 

  26. Bryson DD (1978) Cyanide poisoning. Lancet II:92

    Google Scholar 

  27. Pontal PG, Bismuth C, Garnier R, Pronczuck di Garbino J (1982) Therapeutic attitude in cyanide poisoning. Retrospective study of 24 non-lethal cases. Vet Hum Toxicol 24: [Suppl 1] 90–94

    Google Scholar 

  28. Klimmek R, Fladerer H, Szinicz L, Weger N, Kiese M (1979) Effects of 4-dimethylaminophenol and Co2EDTA on circulation, respiration, and blood homeostasis in dogs. Arch Toxicol 42:75–84

    Google Scholar 

  29. Gilbert JC; Glantz SA (1989) Determinants of left ventricular filling and the diastolic pressure-volume relation. Circ Res 64:827–852

    Google Scholar 

  30. Lanier WL, Stangland KJ, Scheithauer BW, Milde JH, Michenfelder JD (1987) The effects of dextrose infusion and head position on neurologic outcome after complete cerebral ischemia in primates: Examination of a model. Anesthesiology 66:39–48

    Google Scholar 

  31. Pulsinelli WA, Waldman S, Rawlinson D, Plum F (1982) Moderate hyperglycemia augments ischemic brain damage: A neuropathologic study in the rat. Neurology 32:1239–1246

    Google Scholar 

  32. Randall WC (1977) Neural regulation of the heart. Oxford University Press, New York, pp. 15–129

    Google Scholar 

  33. Fabiato A, Fabiato F (1978) Calcium-induced release of calcium from the sarcoplasmic reticulum of skinned cells from adult human, dog, cat, rabbit, rat and frog hearts and from fetal and newborn ventricles. Ann NY Acad Sci 307:491–522

    Google Scholar 

  34. Bismuth C, Cantineau JP, Pontal P et al (1984) Priorité de l'oxygénation dans l'intoxication cyanhydrique. J Toxicol Méd 4:107–121

    Google Scholar 

  35. Hall AH, Rumack BH (1987) Hydroxocobalamin/sodium thiosulfate as a cyanide antidote. J Emerg Med 5:115–121

    Google Scholar 

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Authors and Affiliations

  1. Laboratoire de Pharmacologie, Université Paris Sud, Le Kremlin-Bicêtre, France

    B. Riou, A. Berdeaux, E. Pussard & J. -F. Giudicelli

  2. Département d'Anesthésie-Réanimation, CHU Pitié-Salpétrière, Université Paris VI, 47-83 Boulevard de l'Hôpital, F-75651, Paris Cedex 13, France

    B. Riou

Authors
  1. B. Riou
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  2. A. Berdeaux
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  3. E. Pussard
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  4. J. -F. Giudicelli
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Additional information

Dr. B. Riou was supported by the Fondation pour la Recherche Médicale. This study was presented in part at the 5th International Trauma and Critical Care Society Symposium, Amsterdam, June 11–12, 1992

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Riou, B., Berdeaux, A., Pussard, E. et al. Comparison of the hemodynamic effects of hydroxocobalamin and cobalt edetate at equipotent cyanide antidotal doses in conscious dogs. Intensive Care Med 19, 26–32 (1993). https://doi.org/10.1007/BF01709274

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  • DOI: https://doi.org/10.1007/BF01709274

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