ACE Inhibitor Overdose

Angiotensin converting enzyme inhibitor overdose usually causes mild to moderate hypotension, but large ingestions can cause refractory vasodilatory shock, hyperkalaemia and acute kidney injury. Angioedema can occur at any dose.

ACE inhibitors are among the most prescribed drugs. Serious toxicity is uncommon and typically seen with ingestions of lisinopril above 200 mg, or at lower doses in patients with volume depletion or renal impairment. Co-ingestion with other antihypertensives is more dangerous.

Risk factors for harm. Hypovolaemia, renal impairment, heart failure, concurrent diuretics or potassium supplements, and co-ingestion of other antihypertensives.

Course. Onset within 1 to 6 hours, with peak hypotension at 6 to 12 hours; effects last 24 to 48 hours.

Pathophysiology.

Inhibition of angiotensin converting enzyme reduces angiotensin II and aldosterone, causing vasodilatation and loss of efferent arteriolar tone, so glomerular filtration falls and potassium rises.

Bradykinin accumulation causes angioedema.

• Dizziness, postural hypotension, weakness, headache and nausea.
• Hypotension and bradycardia in severe poisoning; occasional shock.
• Hyperkalaemia, oliguria and acute kidney injury.
• Angioedema of the lips, tongue and airway; cough.

Red flags.

• Systolic blood pressure under 90 mmHg despite fluids.
• Potassium over 6.5 mmol/L or ECG changes of hyperkalaemia.
• Angioedema with airway involvement.

• History of the drug, dose, formulation and co-ingestants; paracetamol and salicylate levels.
• Blood pressure, ECG, electrolytes (potassium), urea and creatinine, glucose, lactate and venous gas.
• Urine output; repeated potassium and creatinine over 24 hours.
• Airway assessment for angioedema.

Differential diagnosis. Other antihypertensive overdose, calcium channel blocker overdose, hereditary or acquired angioedema, anaphylaxis, hypovolaemia and sepsis.

• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour of a large ingestion if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Hypotension: lie flat, give intravenous 0.9% sodium chloride 10 to 20 mL/kg, then noradrenaline 0.05 micrograms/kg/minute intravenously if fluids fail, titrated to a mean arterial pressure of 65 mmHg or higher. Maximum 1 microgram/kg/minute. Give by central line; monitor blood pressure, extravasation and arrhythmia. Refractory shock may respond to vasopressin 0.01 to 0.04 units/minute.
• Hyperkalaemia with ECG changes: calcium gluconate 10% 30 mL intravenously over 10 minutes, repeated after 10 minutes if ECG changes persist. Maximum 3 doses. Monitor ECG continuously and extravasation. Avoid in digoxin toxicity.
• Insulin 10 units (soluble) intravenously with glucose 25 g (50 mL of 50%) over 15 minutes. Maximum 2 doses; repeat every 30 to 60 minutes as needed. Monitor glucose hourly for 6 hours (hypoglycaemia is common, especially in renal failure); reduce insulin to 5 units in severe renal impairment.
• Salbutamol 10 to 20 mg nebulised over 10 minutes. Maximum 20 mg for each dose. Monitor heart rate, tremor and potassium; use caution in ischaemic heart disease and arrhythmia.
• Angioedema: adrenaline (1 in 1000) 0.5 mg (0.5 mL) intramuscularly, repeated after 5 minutes if needed. Maximum 3 doses. Monitor airway, heart rate and blood pressure. Use caution in coronary artery disease and hypertension. Bradykinin mediated angioedema may not respond; icatibant 30 mg subcutaneously once, repeated after 6 hours if needed (maximum 3 injections in 24 hours; monitor injection site reactions and cardiac events; avoid in recent stroke or acute ischaemic heart disease). Secure the airway early by senior staff, and avoid antihistamine and steroid reliance.
• Haemodialysis for severe hypotension with renal failure or intractable hyperkalaemia, which removes lisinopril and enalaprilat.
• Observe for at least 6 hours (24 hours for large ingestions or renal impairment), with blood pressure, potassium and creatinine rechecked before discharge.

Monitoring. Blood pressure, potassium and creatinine every 6 hours; ECG; urine output.

Referral and escalation. Poisons information centre for large ingestions; intensive care for shock, hyperkalaemia or airway compromise; nephrology for renal replacement therapy.

Special groups. Pregnancy: ACE inhibitors are foetotoxic, so review the prescription after recovery. Older adults: higher risk of kidney injury.