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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Dahlström U.
        • Karlsson E.
        Captopril and spironolactone therapy for refractory congestive heart failure.
        Am J Cardiol. 1993; 71: 29A-33A
        • van Vilet A.
        • Donker A.J.M.
        • Nauta J.J.P.
        • Verheugt F.W.A.
        Spironolactone in congestive heart-failure refractory to high-dose loop diuretic and low-dose angiotensin-converting enzyme inhibitor.
        Am J Cardiol. 1993; 71: 21A-28A
        • Sato A.
        • Suzuki Y.
        • Saruta T.
        Effects of spironolactone and angiotensin-converting-enzyme inhibitor on left ventricular hypertrophy in patients with essential hypertension.
        Hypertens Res. 1999; 22: 17-22
        • RALES Investigators
        The effect of spironolactone on morbidity and mortality in patients with severe heart failure.
        N Engl J Med. 1999; 341: 709-717
        • Odawara M.
        • Asano M.
        • Yamashita K.
        Life-threatening hyperkalaemia caused by angiotensin-converting enzyme inhibitors and diuretics.
        Diabetic Med. 1997; 14: 169-170
        • Weiner I.D.
        • Wingo C.S.
        J Am Soc Nephrol. 1998; 9: 1535-1543
        • Siamopoulos K.C.
        • Elisaf M.
        • Katopodis K.
        Iatrogenic hyperkalaemia—points to consider in diagnosis and management.
        Nephrol Dial Transplant. 1997; 13: 2402-2406
        • Rado J.P.
        Posture as a contributing factor to beta-blockade induced hyperkalaemia.
        Eur J Clin Pharmacol. 1985; 28: 359-360
        • Ritz E.
        • Kettner A.
        • Bommer J.
        Digitalis intoxication and hyperkalaemia in hemodialysed patients.
        Int J Artif Organs. 1981; 4: 149-150
        • Georges B.
        • Beguin C.
        • Jadoul M.
        Spironolactone and congestive heart failure.
        Lancet. 2000; 355: 1369-1370
        • RALES Investigators
        Effectiveness of spironolactone added to an angiotensin-converting-enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure.
        Am J Cardiol. 1996; 78: 902-907
        • CONSENSUS Trial Study Group
        Effects of enalapril on mortality in severe congestive heart failure.
        N Engl J Med. 1987; 316: 1429-1435
        • Jarman P.R.
        • Kehely A.M.
        • Mather H.M.
        Hyperkalaemia in diabetes.
        Postgrad Med J. 1995; 71: 551-552
      1. Bonnet F, Thivolet CH. Reversible hyperkalaemia at the initiation of ACE inhibitors in a young diabetic patient with latent hyporeninemic hypoaldosteronism. Diabetes Care. 1996;19:781. Letter.

        • Large D.M.
        • Laing I.
        • Carr P.H.
        • Davies M.
        Hyperkalaemia in diabetes mellitus—potential hazards of coexisting hyporeninemic hypoaldosteronism.
        Postgrad Med J. 1984; 60: 370-373
        • Dietz R.
        • Nagel F.
        • Osterziel K.J.
        Angiotensin-converting enzyme inhibitors and renal function in heart failure.
        Am J Cardiol. 1992; 70: 119C-125C
        • Zimran A.
        • Kramer M.
        • Plaskin M.
        • Hershko C.
        Incidence of hyperkalaemia induced by indomethacin in a hospital population.
        BMJ. 1985; 291: 107-108
        • Meier D.E.
        • Myers W.M.
        • Swenson R.
        • Bennet W.M.
        Indomethacin-associated hyperkalaemia in the elderly.
        J Am Geriatr Soc. 1983; 31: 371-373
        • Galler M.
        • Folkert V.W.
        • Schlondorff D.
        Reversible acute renal insufficiency and hyperkalaemia following indomethacin therapy.
        JAMA. 1981; 246: 154-155