Severe lactic acidosis caused by sodium nitroprusside in a newborn with congenital heart disease

Objective: Sodium nitroprusside (SNP) is an antihypertensive drug used frequently in the critical care setting. Coadminstration of the antidote sodium thiosulfate usually prevents increases in cyanide concentrations during anesthesia or long-term SNP infusion (1). We report on a newborn with congenital heart disease who developed severe lactic acidosis due to the administration of SNP despite concomitant medication with sodium thiosulfate.

Case report: A 3800g-female newborn was admitted to our hospital because of complex congenital heart disease (double inlet left ventricle, dysplasia of the right ventricle, atrial and ventricular septal defects with right ventricular outlet, transposition of the great arteries, hypoplastic ascending aorta). Due to the presence of hypoplastic ascending aorta treatment consisted of the administration of prostaglandin E1 to allow for adequate systemic perfusion via the patent ductus arteriosus. Because of a mismatch between pulmonary and systemic blood flow continuous treatment with SNP was started to shift perfusion from the pulmonary bed to the systemic circulation by reducing the afterload. To avoid iatrogenic intoxication with cyanide the patient received concomitant medication with sodium thiosulfate (ratio SNP/sodium thiosulfate of 1:10).

On day 6 of SNP medication the patient developed profound lactic acidosis (ph: 7,26, pO2 48,5mmHg, pCO2 21,3mmHg, lactate 19 mmol/l, base excess –16,4 mmol/l). SNP was stopped; the patient was intubated and ventilated with FiO2 100%. Due to rapid resolution of lactic acidosis no specific antidote (dimethylaminophenol – DMAP) was given; a substantial increase in the difference of arterio-venous oxygen saturation was also seen. Toxicological analysis which was done 24h after the development of lactic acidosis still showed elevated levels of thiocyanate (41mg/l; therapeutic <30mg/l).

Conclusion: Despite concomitant administration of sodium thiosulfate SNP may cause severe lactic acidosis due to the accumulation of cyanide with consecutive inactivation of cytochrome oxidase a-3 and blockade of cellular aerobic metabolism. The prolonged administration of SNP may have affected the detoxification capacity of the enzyme rhodanese which converts cyanide and thiosulfate into thiocyanate. Furthermore, rhodanese is predominantly located at a mitochondrial site, while thiosulfate – due to low lipophilicity – has limited intracellular distribution (2). This inequity in distribution in conjunction with prolonged SNP medication may have caused severe cyanide intoxication in our patient.

References

1. Hall VA, Guest JM. Sodium nitroprusside-induced cyanide intoxication and prevention with sodium thiosulfate prophylaxis. Am J Crit Care 1992; 1:19–25

2. Baskin SI, Porter DW, Rockwood GA, Romano JA, Patel HC, Kiser RC, Cook CM, Ternay AL. In vitro and in vivo comparison of sulphur donors as antidotes to acute cyanide intoxication. J Appl Toxicol 1999; 19:173–183