Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases

Am J Med. 2001 Apr 15;110(6):438-41. doi: 10.1016/s0002-9343(01)00642-8.


Purpose: The beneficial effects of spironolactone are additive to those of ACE inhibitors among patients with heart failure and/or hypertension; however, it is essential to identify patients prone to develop serious hyperkalemia during combined treatment and to evaluate the associated morbidity and mortality.

Subjects and methods: We studied 25 patients treated with ACE inhibitors and spironolactone who were admitted to the emergency room with a serum potassium level > 6 mmol/L. Patients were followed up for at least one month after admission.

Results: The mean age of the patients (11 males, 14 females) was 74 +/- 13 years. Five patients were diabetics. On admission, the serum potassium was 7.7 +/- 0.7 mmol/L and the serum creatinine was 3.8 +/- 1.8 mg/dL; these values were significantly higher than the most recent follow-up laboratory measurements (4.6 +/- 0.5 mmol/L and 1.9 +/- 1.2 mg/dL, respectively) obtained at 13 +/- 5 weeks before admission. The arterial pH on admission was 7.3 +/- 0.1 and the plasma bicarbonate was 18 +/- 5 mmol/L. The main causes for acute renal failure were dehydration (n = 12) and worsening heart failure (n = 9). The mean daily dose of spironolactone was 57 +/- 32 mg and 12 patients were concomitantly treated with other drugs that may cause hyperkalemia. Two patients died, and 2 patients were resuscitated but survived. Hemodialysis was necessary in 17 patients; 12 patients were admitted to the intensive care unit. The mean duration of hospitalization was 12 +/- 6 days. Two patients needed to be started on maintenance hemodialysis therapy.

Conclusion: A combination of ACE inhibitors and spironolactone should be considered with caution and monitored closely in patients with renal insufficiency, diabetes, older age, worsening heart failure, a risk for dehydration, and in combination with other medications that may cause hyperkalemia. A daily spironolactone dose of 25 mg should not be exceeded.

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Creatinine / blood
  • Diuretics / administration & dosage
  • Diuretics / adverse effects*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Humans
  • Hyperkalemia / chemically induced*
  • Hyperkalemia / mortality
  • Male
  • Risk Factors
  • Spironolactone / administration & dosage
  • Spironolactone / adverse effects*


  • Angiotensin-Converting Enzyme Inhibitors
  • Diuretics
  • Spironolactone
  • Creatinine