Hyperkalemia in Outpatients Using ACE Inhibitors
ABSTRACT & COMMENTARY
Synopsis: In patients taking ACE inhibitors, the factors that predicted the development of severe hyperkalemia included age over 70 years, BUN greater than 25 mg/dL, serum creatinine greater than 1.4 mg/dL, and blood glucose greater than 190 mg/dL.
Source: Reardon LC, Macpherson DS. Arch Intern Med 1998;158:26-32.
Angiotensin-converting enzyme inhibitors (ACEI) are used in many clinical conditions ranging from hypertension and congestive heart failure to diabetic nephropathy. Hyperkalemia is a known complication with ACEI and occurs most often in those with renal insufficiency. Severe hyperkalemia (K ³ 6.0 mEq/L), while rare, can be life-threatening. How often should potassium levels be monitored in patients receiving ACEI? If hyperkalemia occurs, should ACEI be continued? To answer the question "How much should we worry?" the authors retrospectively studied 1) the prevalence and risk factors for hyperkalemia in medical outpatients (male veterans) receiving ACEI; 2) subsequent course of hyperkalemia; and 3) risk of severe hyperkalemia ³ 6.0 mEq/L and related mortality.
A case-control study design was used to identify risk factors for hyperkalemia. Normokalemic (K £ 5 mEq/L) and hyperkalemic case patients (K > 5.1 mEq/L) were identified from outpatients prescribed ACEI at a VA medical center during a two-year study period. Variables studied included type and dose of ACEI, chemistries, concurrent drug use, and comorbid conditions. Case patients with hyperkalemia were followed up for one year, and follow-up study variables included change in ACEI therapy, potassium levels, and mortality.
A total of 1818 patients received ACEI during the two-year period. There were 194 case and control patients each. Equal numbers were hypertensive in the two groups. There were more severe diabetics (16%; P = 0.007), and BUN and creatinine levels were higher (22 mg/dL and 1.3 mg/dL, respectively) in the case patients compared to controls. Hyperkalemia (K > 5.1 mEq/L) was identified in 11% of case patients. Moderate hyperkalemia (K ³ 5.6 mEq/L) occurred in 2% (37 of 1818 patients), and severe hyperkalemia (K ³ 6.0 mEq/L) was uncommon (3 of 1818 patients; 0.17%). Independent factors that predicted hyperkalemia are shown in the table.
Table
Independent Factors Predicting Hyperkalemia with ACEI
| Factor | Increased Odds Ratio | Decreased Odds Ratio |
| BUN> 18 mg/dL Serum Creatinine |
2.5 | |
| 1.1-1.5mg/dL | 1.5 | |
| >1.6mg/dL | 1.6 | |
| Use of Long-acting ACEI | 2.8 | |
| CHF | 2.6 | |
| Diurectic use Thiazide Loop |
0.4 0.4 |
In case patients with hyperkalemia who remained on an ACEI for the one-year follow-up period (155 of 194 case patients), severe hyperkalemia (K > 6 mEq/L) occurred in 10%, as compared with 4% in whom ACEI were stopped or dosage was reduced.
The factors that predicted the development of subsequent severe hyperkalemia in those remaining on ACEI were:
1. age > 70 years (odd ratio, 5.4)
2. BUN > 25 mg/dL (odds ratio, 4.5)
3. serum creatinine > 1.4 mg/dL
4. blood glucose > 190 mg/dL
The predictors of increased mortality during follow-up in the case hyperkalemic patients were a serum potassium level of 6.3 mEq/L rather than 6.0 mEq/L, increased BUN greater than 28 mg/dL, and serum creatinine greater than 1.5 mg/dL (P < 0.003 for all variables).
COMMENT BY KAMALJIT SETHI, MD
It is helpful to know that severe hyperkalemia (K > 6.0 mEq/L) is uncommon with ACEI, just as mild hyperkalemia (K 5.1-5.5 mEq/L) is fairly common. Despite its design limitation (retrospective, case-controlled), this study suggests that the elderly and those with renal insufficiency should be monitored more closely if ACEI are to be continued once hyperkalemia occurs. The following are reasonable guidelines to reduce the risk of hyperkalemia for patients over age 70 or when serum creatinine greater than 1.5 mg/dL and ACEI are indicated.
1. ACEI: Among the long-acting ACEI, fosinopril is the agent of choice because of dual renal and hepatic excretion. Short-acting captopril may also be used. Of the long-acting ACEI, fosinopril has the least renal accumulation and, thus, the highest safety margin from the renal standpoint.
2. Dose: Fosinopril-no dose reduction. Start with 5-10 mg; Captopril-Start with 6.25 mg dose.
3. Hyperkalemia: a) If it occurs, consider K+ restriction to 60-80 mEq/L.
b) Non-potassium sparing diuretics can be used, such as furosemide and hydrochlorthiazide. Volume depletion should be avoided.
c) Kayexelate can be used in doses of 15-30 g/d.
d) If K is greater than 5.1 mEq/dL, monitor monthly. If K is greater than 5.5 mEq/dL, ACEI should be discontinued until K can be controlled and is £ 5 mEq/dL.
4. Azotemia: Increase in serum creatinine of up to 0.5 mg/dL is acceptable, if it stabilizes and ACEI can be continued. If increase is greater than 0.5 mg/dL, further evaluation is needed.
Early progressive azotemia may point to renal artery stenosis. Renal perfusion scan may be helpful. Bilateral renal artery stenosis is a contraindication to ACEI use.
Dosage of all ACEI except fosinopril will need to be reduced and adjusted to level of renal function.
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