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How Much Should We Worry?

Lawrence C. Reardon, MD, MPH; David S. Macpherson, MD, MPH

Arch Intern Med. 1998;158:26-32.

Background  Hyperkalemia is a potentially life-threatening complication resulting from the use of angiotensin-converting enzyme (ACE) inhibitors; data to guide the intensity of monitoring for or responding to hyperkalemia in outpatients are limited.

Methods  Case-control methodological procedures were used to identify risk factors for hyperkalemia. Outpatients prescribed ACE inhibitors during 1992 and 1993 at a Veterans Affairs medical center general medicine clinic were identified. Case patients had a potassium level higher than 5.1 mmol/L on the day of clinic visit while using an ACE inhibitor; controls had a potassium level lower than 5.0 mmol/L on the day of clinic visit while using an ACE inhibitor and had no elevated potassium level during the study period. Predictor variables measured included type and dosage of ACE inhibitor; serum chemistries; comorbidities; concurrent drug use; and age. Case patients were followed up for 1 year after the index episode of hyperkalemia. Follow-up variables included changes in therapy with ACE inhibitor, maximum potassium for each change, and mortality.

Results  Of 1818 patients using ACE inhibitors, 194 (11%) developed hyperkalemia. Results of laboratory studies indicating a serum urea nitrogen level higher than 6.4 mmol/L (18 mg/dL), creatinine level higher than 136 µmol/L (1.5 mg/dL), congestive heart failure, and long-acting ACE inhibitors were independently associated with hyperkalemia; concurrent use of loop or thiazide diuretic agent was associated with reduced risk. After 1 year of follow-up, 15 (10%) of 146 case patients remaining on a regimen of an ACE inhibitor developed severe hyperkalemia (potassium level >6.0 mmol/L). A serum urea nitrogen level higher than 8.9 mmol/L (25 mg/dL) and age more than 70 years were independently associated with subsequent severe hyperkalemia.

Conclusions  Mild hyperkalemia is common in medical outpatients using ACE inhibitors, especially in those with renal insufficiency or congestive heart failure. However, once hyperkalemia is identified during the use of ACE inhibitors, subsequent severe hyperkalemia is uncommon in patients younger than 70 years with normal renal function.

From the Department of Medicine, University of Pittsburgh, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pa. Dr Reardon is deceased.

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