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OtherPractice

Electrolyte disturbance with diuretics and ACEIs

Michael R. Kolber, Scott Garrison and Ricky D. Turgeon
Canadian Family Physician July 2016, 62 (7) 569;
Michael R. Kolber
Associate Professor in the Department of Family Medicine at the University of Alberta in Edmonton.
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Scott Garrison
Associate Professor in the Department of Family Medicine at the University of Alberta in Edmonton.
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Ricky D. Turgeon
Clinical pharmacist at Vancouver General Hospital in British Columbia.
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Clinical question

What is the risk of electrolyte disturbances with diuretics and angiotensin-converting enzyme inhibitors (ACEIs) and when should we check levels?

Bottom line

Moderate hyponatremia (sodium [Na] < 130 mmol/L) and hypokalemia (potassium [K] < 3.2 mmol/L) occur in about 4% of thiazide users; hyperkalemia (K > 5.4 mmol/L) occurs in 4% of ACEI (and angiotensin receptor blocker) users. Limited evidence suggests checking electrolyte levels 2 to 4 weeks after starting or increasing doses of these agents, and at least annually thereafter.

Evidence

  • The ALLHAT substudy1 (n = 19 731 with normal baseline K levels) found the following results at 1 year.

    -Overall, 3.5% of those taking chlorthalidone (12.5 to 25 mg), 0.2% of those taking lisinopril (10 to 40 mg), and 0.3% of those taking amlodipine (2.5 to 10 mg) had K levels less than 3.2 mmol/L; 1.2% of those taking chlorthalidone, 3.6% of those taking lisinopril, and 1.9% of those taking amlodipine had K levels greater than 5.4 mmol/L. Further, 8% of those taking chlorthalidone were taking K supplements at 5 years.2

  • The SHEP study3 of 4736 patients taking chlorthalidone (12.5 to 25 mg) or placebo found, within 4.5 years, 3.9% and 4.1% of those taking chlorthalidone had K levels below 3.2 mmol/L and Na levels below 130 mmol/L, respectively (vs 0.8% and 1.3% for placebo, respectively).

  • The HYVET trial4 (indapamide vs placebo) excluded patients with abnormal K levels; compared with placebo, K levels were 0.05 mmol/L lower with indapamide at 2 years (Na levels were not reported).

  • Chlorthalidone (12.5 to 25 mg) decreases K levels an average of 0.2 to 0.4 mmol/L5,6 (about 0.1 to 0.2 mmol/L more than the same dose of hydrochlorothiazide).6

  • Angiotensin receptor blockers have rates of hyperkalemia similar to those for ACEIs.7

Context

  • Diuretics are inexpensive first-line agents for patients with uncomplicated hypertension.8

  • Limited evidence suggests that thiazide-induced hypokalemia or hyponatremia occur within the first days to weeks of therapy9,10 but can also develop years later.11

  • Hypokalemia and hyponatremia risk factors include being female1,12 and increasing age12 or diuretic dose.12

  • Mild hypokalemia is often asymptomatic, but symptoms can include weakness, myalgia, and cardiac arrhythmia.13

  • Moderate to severe hyponatremia (Na < 130 mmol/L) can cause lethargy, dizziness, nausea, and confusion.14

Implementation

Common nondrug causes of hypokalemia include vomiting, diarrhea, renal losses, congestive heart failure, or systemic alkalosis. If patients have hypokalemia from diuretics, adding ACEIs15 or using K-sparing diuretics (like amiloride)16 can help maintain normokalemia. Consider primary aldosteronism and Cushing syndrome in patients with hypertension who have hypokalemia before medical therapy.

Notes

Tools for Practice articles in Canadian Family Physician (CFP) are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in CFP are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice{at}cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

  • Competing interests

    None declared

  • The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

  • Copyright© the College of Family Physicians of Canada

References

  1. 1.↵
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    . Clinical significance of incident hypokalemia and hyperkalemia in treated hypertensive patients in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Hypertension 2012;59(5):926-33.
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    1. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group
    . Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288(23):2981-97.
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    1. SHEP Cooperative Research Group
    . Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265(24):3255-64.
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    1. Barber J,
    2. McKeever TM,
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    7. et al
    . Diuretic induced hyponatraemia in elderly hypertensive women. J Hum Hypertens 2002;16(9):631-5.
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    . Hypokalemia. N Engl J Med 1998;339(7):451-8.
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Canadian Family Physician: 62 (7)
Canadian Family Physician
Vol. 62, Issue 7
1 Jul 2016
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Electrolyte disturbance with diuretics and ACEIs
Michael R. Kolber, Scott Garrison, Ricky D. Turgeon
Canadian Family Physician Jul 2016, 62 (7) 569;

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