The sodium nitroprusside (SNP) is often used in pediatric intensive care units because of its strongly antihypertensive properties¹⁾ and various pharmacokinetic advantages²⁾. However, cyanide toxicity, the most lethal complication, can occur after SNP treatment. Antidotal therapy is the treatment of choice in cases of cyanide poisoning. In general, exchange transfusion can be useful in poisoning cases because it activates the detoxification systems and removes some of the toxic agents from the blood more rapidly than does antidote therapy. Here, we report the first case of a 2-month-old infant whose SNP-induced cyanide poisoning was successfully treated by exchange transfusion rather than by the use of antidotes.

A 2-month-old male infant was brought to the emergency room due to cough, fever, and dyspnea. At the time of presentation to the emergency room, the following vital signs were recorded: blood pressure, 95/40 mmHg; pulse rate, 187/min; respiration rate, 66/min; and body temperature, 37.8℃. Oxygen saturation was 80% in room air. A chest X-ray revealed consolidation in the right lung. Venous blood gas analysis showed the following results: pH, 7.23; carbon dioxide partial pressure (pCO₂), 65 mmHg; and oxygen partial pressure (pO₂), 18 mmHg. The white blood cell (WBC) count and hemoglobin level were 8,300/mm³ and 10.7 g/dL, respectively. The C-reactive protein (CRP) level was markedly increased (111 mg/L). The infant developed serious dyspnea and failed to maintain oxygen saturation; he subsequently underwent mechanical ventilation after being hospitalized in the intensive care unit. He was diagnosed to have aspiration pneumonia and was treated with antibiotics and an anti-inflammatory dose of steroids.

Several hours after admission, his blood pressure increased to 110/70 mmHg. To control his blood pressure, treatment with nitroglycerin was started. However, 2 days after admission, the infant's blood pressure further increased to 120/80 mmHg after methylprednisolone pulse therapy, which was administered to control pneumonia that had worsened and progressed to acute respiratory distress syndrome. Despite nitroglycerin infused to its maximal level, the infant's blood pressure failed to normalize. Thus, SNP was started and maintained with 2.4 µg/(kg·min) until SNP-induced cyanide poisoning was diagnosed (on the ninth day of hospitalization). In an evaluation study for hypertension, there was no evidence of kidney or heart disease. On the seventh day after admission, extubation was performed, and arterial blood gas analysis finding was within the normal range. By the eighth day of hospitalization, SNP continued to be infused at a rate of 2 µg/(kg·min), and arterial blood gas analysis revealed high anion gap metabolic acidosis with compensatory respiratory alkalosis (pH, 7.44; pCO₂, 19 mmHg; pO₂, 120 mmHg; and bicarbonate level, 11 mmol/L); however, respiratory distress symptoms were not observed.

However, 1 day later, on the ninth day of admission, the respiratory rate increased gradually, and the patient showed symptoms of air hunger, moaning sound, nasal flaring, and irritability. The heart rate increased to 190/min. And the patient had myoclonic seizures. The infant's skin was cherry-red in color, and arterial blood gas analysis revealed a worsening of the high anion gap metabolic acidosis (pH, 7.27; pCO₂, 12 mmHg; pO₂, 281 mmHg; and bicarbonate level, 5 mmol/L). Although the plasma lactic acid level exhibited a marked increase to 122 mmol/L, lung sounds were normal, and a chest X-ray revealed improvement in the pneumonic infiltration. No evidence of sepsis or severe sepsis was found; there was no fever, normal WBC count (7,280/mm³) and hypertension rather than hypotension. The infection or inflammation was controlled (CRP was markedly decreased to 3.5 mg/dL). Thus, SNP toxicity was diagnosed, and SNP infusion was stopped. Since a suitable antidote drug was not available, we performed an exchange transfusion immediately after SNP toxicity was diagnosed. After one volume of exchange transfusion, the acidosis improved to a pH of 7.44, a pCO₂ of 25 mmHg, a pO₂ of 118 mmHg, and a bicarbonate level of 17 mmol/L. However, tachypnea was still observed and the pCO₂ level was low. Plasma lactate was markedly decreased but not yet normalized (40 mmol/L). Consequently, a second volume of exchange transfusion was administered. Thereafter, the blood gas and plasma bicarbonate levels normalized (pH, 7.43; pCO₂, 35 mmHg; and bicarbonate level, 23 mmol/L), plasma lactate was further decreased (31 mmol/L), the respiratory rate stabilized, and the patient improved clinically (Fig. 1). The infant was discharged from the hospital on the 20th day after hospitalization without any neurological deficits.

Although SNP has been used safely to treat many neonates³⁾, infants⁴⁾ and children⁵⁾, cyanide intoxication should be considered if unexplained tachypnea, tachycardia, lactic acidosis, irritability, and seizures occur after SNP administration⁶⁾. Reported risk factors associated with cyanide toxicity from SNP administration include prolonged infusion duration and/or high doses of SNP⁷⁾, as indicated by several cases of cyanide toxicity in patients who had received more than 2 µg/(kg·min) SNP or had been infused for more than 24 hours5, ⁸⁾. Moreover, children and neonates may be more susceptible to cyanide toxicity because of lower thiosulfate storage levels⁹⁾. In the present case, the infant had several risk factors for SNP infusion-associated cyanide toxicity; specifically, he was very young (2 months old) and had received a high dose [>2 µg/(kg·min)] of SNP for several days.

In this case, the infant showed the classical symptoms and signs of cyanide toxicity, i.e., tachycardia, tachypnea without respiratory problems, unexplained metabolic acidosis, irritability, and seizures. It was not possible to measure the blood cyanide concentrations in our hospital, but the plasma lactate concentrations were 122 mmol/L. Plasma lactate concentrations that exceed 10 mmol/L correlate with blood cyanide concentrations that exceed 40 µmol/L¹⁰⁾, and it has been shown that clinical toxicity appears when the blood cyanide concentration exceeds 40 µmol/L¹¹⁾. In adults, the fatal level of cyanide is generally considered to exceed 100-115 µmol/L¹⁰⁾. Although nitroglycerin induced lactic acidosis might contribute to some portions of the patient's plasma lactate, his symptoms and sings were very typical to cyanide toxicity, we made a diagnosis of SNP-induced cyanide toxicity consequently. A key strategy to manage cyanide poisoning is to administer sulfur donors; sodium thiosulfate is usually used in clinical practice¹²⁾. However, antidotes were not immediately available to us. Albumin can exhibit enzyme-like behavior and use bound elemental sulfur to detoxify cyanide13, ¹⁴⁾. Thus, to supply sulfur donors and remove the cyanide and thiocyanate, we performed exchange transfusion.

Since exchange transfusion activates the detoxification systems and can clear some toxins from the blood more rapidly than antidotes, it can be useful for poisoning cases. Exchange transfusion has been used successfully to treat neonates or infants who have been poisoned with salicylate¹⁵⁾, theophyllin¹⁶⁾, phenobarbital¹⁷⁾, and other agents. A study in cats revealed that blood exchange transfusion is also an effective way to treat acute cyanide poisoning¹⁸⁾. While the usefulness of blood exchange transfusion for pediatric cases of cyanide or nitroprusside poisoning has not yet been reported, we reasonably assumed that exchange transfusion would also be efficacious for cyanide poisoning. This is because exchange transfusion not only removes cyanide and thiocyanide from the blood but also activates the detoxification systems by supplying blood with abundant amounts of sulfur moieties. More importantly, exchange transfusion replaces cyanide-contaminated erythrocytes with fresh erythrocytes, thereby improving the blood's oxygen carrying capacity more rapidly than does antidote therapy. Therefore, we believe that exchange transfusion might be an effective therapeutic modality in a critical case of cyanide poisoning.

Cyanide poisoning causes cessation of oxidative phosphorylation and induces histotoxic anoxia, especially of the central nervous and cardiovascular systems; at high levels, it can lead to death. Exchange transfusion causes complications in 5% to 10% of infants even though the risk of death from the procedure is only 0.3/100 procedures¹⁹⁾. In weighing the risks and benefits of using exchange transfusion therapy, we considered our patient to be at a serious risk from cyanide poisoning (based on classic cyanide poisoning signs and a markedly high level of plasma lactate without renal or heart problems or evidence of sepsis) and concluded that exchange transfusion provided more benefits than risks. Therefore, the infant received two rounds of exchange transfusion, after which his plasma lactic acid levels dropped markedly, the irritability and seizures disappeared, and his blood pCO₂ levels and vital signs normalized. No complications of exchange transfusion were observed.

In summary, while exchange transfusion is not considered as the primary treatment option for treating SNP infusion-associated cyanide poisoning, it may be an effective alternative modality for treating this condition if antidotes are not available.