A 45-year-old man comes to the emergency department due to shortness of breath that started 2 days ago and worsened last night. The patient has a history of hypertension for which he takes chlorthalidone, amlodipine, and labetalol. He ran out of his medications about 3 or 4 days ago. The patient smokes a pack of cigarettes daily and drinks 4 or 5 beers on the weekends. His last drink was 5 days ago. Temperature is 36.7 C (98.1 F), blood pressure is 220/110 mm Hg, pulse is 90/min, and respirations are 20/min. Oxygen saturation is 96% on 2 liters of oxygen via nasal cannula. Chest auscultation demonstrates bibasilar crackles and S4. Neurologic examination is normal. Funduscopic examination shows normal optic discs and occasional cotton-wool spots. Serum potassium is 5.0 mEq/L and creatinine is 2.1 mg/dL. The patient is admitted to the coronary care unit and prescribed intravenous furosemide and nitroprusside infusion with improvement of his symptoms. Two days later, the nurse finds him confused and agitated, and he has a generalized tonic-clonic seizure. Temperature is 36.7 C (98.1 F), blood pressure is 160/75 mm Hg, pulse is 110/min, and respirations are 28/min. Lungs are clear to auscultation, and no focal weakness is present. A basic metabolic panel obtained just prior to the seizure shows a new metabolic acidosis. Which of the following is the most likely cause of this patient's new neurologic findings?
Cyanide poisoning | |
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*Sodium nitrite + sodium thiosulfate is an alternate treatment but is contraindicated in carbon monoxide poisoning. | |
This patient has severe hypertension and associated acute end-organ complications: congestive heart failure (eg, bibasilar crackles, S4) and renal failure. These findings are consistent with hypertensive emergency, which may be treated with nitroprusside, a parenteral vasodilator that has quick onset and offset of action. Metabolism of nitroprusside releases nitric oxide, which induces arteriolar and venous vasodilation, and cyanide ions.
Cyanide toxicity can occur in patients receiving prolonged infusions of nitroprusside and is most common in patients with renal insufficiency. Cyanide inhibits oxidative phosphorylation, halting aerobic metabolism and forcing cells to switch to anaerobic metabolism. This leads to cellular hypoxia, lactic acid formation, and metabolic acidosis.
Because tissues cannot effectively use oxygen, organ dysfunction occurs. Neurologic manifestations include confusion, agitation, and seizures. Early acute toxicity is characterized by compensatory cardiorespiratory stimulation (eg, tachycardia, tachypnea). However, patients eventually develop bradycardia and hypotension, leading to cardiovascular collapse.
(Choice A) Alcohol withdrawal can result in rebound CNS overexcitation, leading to agitation and seizures. However, these manifestations usually begin within 48 hours of the last drink, whereas this patient's last drink was 5 days ago. In addition, withdrawal does not typically cause metabolic acidosis.
(Choice C) In hypertensive emergencies, mean arterial pressure should be lowered by 10%-20% in the first hour and by another 5%-15% over the next 23 hours. An excessive drop in blood pressure can lead to cerebral ischemia, with altered mental status and/or generalized seizures. However, this patient's blood pressure drop was not excessive.
(Choice D) Hypertensive encephalopathy occurs when a rapid and/or severe rise in blood pressure leads to cerebral edema. Neurologic symptoms may include agitation, confusion, and seizures but typically occur during the hypertensive emergency and abate after blood pressure is lowered. In contrast, this patient's neurologic examination was normal on admission, and his symptoms began after his blood pressure was lowered with nitroprusside.
(Choice E) Seizures can be the presenting symptom of an ischemic stroke, but focal neurologic signs are typically present. Given this patient's renal insufficiency, prolonged exposure to nitroprusside, and new metabolic acidosis, cyanide toxicity is a more likely cause of his nonfocal neurologic findings.
Educational objective:
Acute cyanide toxicity can occur in patients treated with nitroprusside, particularly if renal insufficiency is present. Clinical findings consistent with cyanide toxicity include metabolic acidosis, neurologic changes (eg, agitation, seizures), and cardiorespiratory stimulation (in early toxicity).