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

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.