Effectiveness of intramuscularly administered cyanide antidotes and the rate of methemoglobin formation

Successful first aid therapy for cyanide intoxication is dependent upon the immediate administration of antidotes which directly or indirectly interact with the cyanide ion to remove it from circulation. Exceptionally rapid methemoglobin formers (hydroxylamine hydrochloride 'HA) and Dimethylaminophenol (DMAP) are usually able to prevent the lethal effect of cyanide following intramuscular injections in doses sufficient to induce 20% methemoglobin (HA = 20 mg/kg and DMAP= 2 mg/kg). Sodium nitrite, the methemoglobin inducer approved by the FDA and is available for military use, must be administered by intravenous infusion since it is not an effective cyanide antidote by the intramuscular route. In the normal un-intoxicated animal an intramuscular injection of 20 mg/kg sodium nitrite will form 20% methemoglobin at a rapid rate; however, in the presence of acute cyanide intoxication the associated severe bradycardia appears to limit the rate of absorption of sodium nitrite from the intramuscular site which prevents the rapid formation of sufficient methemoglobin to counteract cyanide intoxication.