title: Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Renal Division, University Hospital, Gent, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Schepkens
authors.forename: R
authors.initials: R
authors.lastname: Vanholder
authors.forename: J M
authors.initials: JM
authors.lastname: Billiouw
authors.forename: N
authors.initials: N
authors.lastname: Lameire
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced* / Q000401:mortality; D008297:Male; D012307:Risk Factors; D013148:Spironolactone / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D013148:Spironolactone; D003404:Creatinine