Excessive methaemoglobinaemia and multi-organ failure following 4-DMAP antidote therapy☆

Abstract 

This report describes the clinical history of a patient intoxicated with methyl isocyanate (MIC), a toxic agent first receiving attention in 1984 after a mass accident in a pesticide plant in Bhopal, India, and treated with the cyanide-specific antidote 4-DMAP. The numerous clinical conditions requiring 39-day intensive care treatment included ARDS, renal and hepatic failure, haemolysis, bone marrow depression, septic encephalopathy and critical illness polyneuropathy. The most outstanding condition, however, was a methaemoglobinemia of 86.7%, which was predominantly related to the use of 4-DMAP, although uptake of MIC may have been a significant contributing factor. Since significant cyanide intoxication could be excluded clinically and by laboratory testing in the initial phase of emergency treatment, most of the clinical effects were due to the side-effects of the antidote therapy. Due to intensive therapy, the patient survived without any neurological or organ deficit. This case shows that antidotes should be used cautiously in cases where uncertainties about the nature of the underlying toxic agent exist. This may prevent severe side-effects associated with antidote therapy, e.g. 4-DMAP, if there is—as in our case—a mismatch between the toxic agent and the antidote.

Keywords: Methyl isocyanate, Cyanide, 4-Dimethyl amino phenol, Toxicity, Methaemoglobin, Multiple organ failure