The Relation of Methemoglobin to the Cyanosis

We have stated in a preliminary report that the cyanosis observed in individuals treated with sulfanilamide is due to methemoglobin, and rarely, to sulfhemoglobin (1). We recognized at the time that attempts had been made to explain the presence of cyanosis on a different basis.. Marshall and Walzl (2) maintained that a black pigment derived from sulfanilamide, and present in the blood, was the cause of this cyanosis. A similar explanation was advanced by Ottenberg and Fox (3). They described the phenomenon of a bluish-purple pigment resulting when a colorless sulfanilamide solution was exposed to ultra violet light. We have confirmed this photochemical change of sulfanilamide. The results of our investigation are in agreement with those of Hartmann and his associates who showed that the cyanosis was related to methemoglobin formation and that methylene blue administered to cyanotic patients caused a disappearance of the cyanosis and a reduction in the concentration of methemoglobin (4). At this time we desire to present further evidence that the cyanosis is due solely to the presence of methemoglobin, and in rare instances, to sulfhemoglobin. We have also included the results of a study of individuals receiving sulfapyridine. Spectral distribution curves were obtained with the spectrophotometer, using normal human blood and the bloods of patients to whom sulfanilamide or sulfapyridine was being administered. In initiating such a study, we believed that if any pigment other than methemoglobin that might cause cyanosis were present, it would be detected in the spectral distribution curves.