Nitroprusside and cyanide.

Sir,—An otherwise excellent and thorough report by Vesey, Cole and Simpson (1976) fails to acknowledge or refute a hypothesis which has already appeared in this Journal (Smith and Kruszyna, 1976a) about the mechanism by which cyanide is released from nitroprusside in vivo, and the significance of that reaction for blood cyanide concentrations. We are delighted with the confirmation that "The red cell cyanide content (after nitroprusside) has no apparent toxicological significance." As we have noted previously, it is biologically inactive because it is bound in the form of cyanmethaemoglobin (Smith and Kruszyna, 1974, 1976b). produces cyanide poisoning via a reaction with hemo-globin. Cyanide and thiocyanate concentrations following sodium nitroprusside infusion in man. Br. Sir,—We apologize for failing to acknowledge the interesting findings of Smith and Kruszyna (1974, 1976a) in our recent communication to this Journal (Vesey, Cole and Simpson, 1976). Their work is an important contribution to our understanding of the breakdown of sodium nitro-prusside (SNP) in vivo and probably explains a number of our observations. We were intending to make what we hoped would be a more intelligent comment on completion of work in vivo and in vitro, now in progress. The fact that we found 98% of the total blood cyanide (HCN) in the erythrocytes (RBC) of patients immediately following the infusion of SNP is consistent with their conclusion that haemoglobin is involved in the breakdown of SNP (Smith and Kruszyna, 1974). Our reason for suggesting that red blood cell HCN is of no toxicological significance at the concentrations we reported was that some of these values, which were for patients suffering no toxic effects, were greater than reported whole blood HCN concentrations for persons who died from cyanide poisoning. We cannot comment yet on the form in which HCN is retained in the red cell, but on the basis of Smith and Kruszyna's results only a fraction of this (about 20%) would be attached to the methaemoglobin produced in the reduction of SNP (Smith and Kruszyna, 1976b). Our findings in vitro are similarly consistent with their hypothesis. Fresh human blood, incubated for 2 h at 37 °C, yielded 95% of the theoretical amount of HCN with SNP concentrations which might be expected clinically (5-25 [unol/litre; 1.5-7.5 mg/litre). Of this 93% was found in the red cells and 7% in plasma. When the same quantity of washed red cells was incubated with the same concentrations of SNP in …