Effectiveness of intramuscularly administered cyanide antidotes on methemoglobin formation and survival.
Successful first aid therapy for cyanide intoxication is dependent upon immediate administration of antidotes which directly or indirectly interact with the cyanide ion to remove it from circulation. Owing to the severe respiratory, cardiovascular and convulsive episodes following acute cyanide intoxication, the most practical approach is to administer antidotes by intramuscular injection. Exceptionally rapid methemoglobin formers-hydroxylamine hydrochloride (HH) and dimethylaminophenol (DMAP)-are usually able to prevent the lethal effect of cyanide following intramuscular injections in doses sufficient to induce 20% methemoglobin (HH = 20 mg kg-1 and DMAP = 2 mg kg-1). Sodium nitrite, the methemoglobin inducer approved for military use, must be administered by intravenous infusion because it is not an effective cyanide antidote by the intramuscular route. In the normal unintoxicated animal an intramuscular injection of 20 mg kg-1 sodium nitrite will form 20% methemoglobin; however, in acute cyanide intoxication the associated severe bradycardia appears to limit the rate of absorption and thus the rapid formation of methemoglobin. If the bradycardia is prevented or reversed by atropine, the rate of absorption of sodium nitrite and the formation of methemoglobin is able to reverse the otherwise lethal effects of cyanide. Thus, an intramuscularly administered combination of 20 mg kg-1 sodium nitrite and 1 mg kg-1 atropine sulfate, rapidly absorbed from the intramuscular site, appears to achieve the same degree of effectiveness against acute cyanide intoxication as intramuscularly administered HH or DMAP. It would appear from these studies that HH, DMAP and sodium nitrite with atropine are all potentially effective intramuscular antidotes for acute cyanide poisoning.
Vick
J A
JA
Division of Research and Testing, Food and Drug Administration, Washington, DC 20204, USA.
Von Bredow
J D
JD
D000627:Aminophenols / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage* / Q000494:pharmacology*; D003486:Cyanides / Q000037:antagonists & inhibitors* / Q000506:poisoning*; D004159:Diphenylamine / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000008:administration & dosage / Q000494:pharmacology; D007273:Injections, Intramuscular; D008706:Methemoglobin / Q000096:biosynthesis* / Q000187:drug effects*; D016019:Survival Analysis
D000627:Aminophenols; D000931:Antidotes; D003486:Cyanides; D006898:Hydroxylamines; D019811:Hydroxylamine; D008706:Methemoglobin; D004159:Diphenylamine; C020292:4-dimethylaminophenol