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At a rectal temperature of 25 degrees C, six patients undergoing hypothermic cardiopulmonary bypass received intravenous infusions of sodium nitroprusside (SNP) at a rate of 7.3 +/- 1.7 micrograms/kg/min for 20 minutes. Total SNP dose per patient was 11.0 +/- 1.1 mg. Blood samples for serum cyanide (CN-), red blood cell cyanide (RBC CN-), and thiocyanate (SCN-) determinations were drawn immediately before SNP infusion. These determinations were repeated at the end of the infusion, at the start of rewarming, and at a rectal temperature greater than 34 degrees C and 1, 4 (five subjects), and 24 hours (three subjects) thereafter. Extracorporeal blood flow was held constant at 2.4 L/min/m2 and mean arterial pressure was maintained between 50 to 100 mm Hg with phenylephrine (3.62 +/- 0.75 mg) during SNP infusion and trimethaphan (37.8 +/- 15.6 mg) after the end of the infusion. There was a significant increase in RBC CN- after the SNP infusion that lasted until the subjects were rewarmed. One subject developed a peak RBC CN- level of 0.8 microgram/ml. Plasma CN- levels changed little throughout and SCN- levels were elevated only after rewarming. The nonenzymatic release of free CN- from SNP was not inhibited by hypothermia, while the enzymatic detoxification of CN- to SCN- may have been delayed.