> Table of Contents > Hypokalemia
Hypokalemia
Joanne Dannenhoffer, MD
Frank J. Domino, MD
image BASICS
DESCRIPTION
Hypokalemia is defined as a serum potassium concentration <3.5 mEq/L (normal range, 3.5 to 5.0 mEq/L).
  • Mild hypokalemia (serum potassium 3.0 to 3.5 mEq/L)
  • Moderate hypokalemia (serum potassium 2.5 to 3.0 mEq/L)
  • Severe hypokalemia (serum potassium <2.5 mEq/L)
EPIDEMIOLOGY
Predominant sex: male = female
Incidence
  • Electrolyte abnormality is commonly encountered in clinical practice and in the elderly (1).
  • Found in >20% of hospitalized patients (when defined as potassium <3.6 mEq/L)
  • Higher incidence (5-20%) in individuals with eating disorders
  • >10% of inpatients with alcoholism
  • Higher incidence in patients with AIDS
  • Higher incidence in patients receiving diuretics
  • Associated risk after bariatric surgery
ETIOLOGY AND PATHOPHYSIOLOGY
Most common causes:
  • Decreased intake: deficient diet in alcoholics and elderly; anorexia nervosa
  • GI loss: vomiting, diarrhea, nasogastric tubes, laxative abuse, fistulas, villous adenoma, ureterosigmoidostomy, malabsorption, chemotherapy, radiation enteropathy, bulimia
  • Intracellular shift of potassium: metabolic alkalosis, insulin excess, &bgr;-adrenergic catecholamine excess (acute stress, &bgr;2-agonists), hypokalemic periodic paralysis, intoxications (theophylline, caffeine, barium, toluene)
  • Renal potassium loss
    • Drugs: diuretics (especially loop and thiazides), amphotericin B, aminoglycosides
    • Mineralocorticoid excess states: primary hyperaldosteronism; secondary hyperaldosteronism (congestive heart failure [CHF], cirrhosis, nephrotic syndrome, malignant hypertension, reninproducing tumors); renovascular hypertension; Bartter syndrome; Gitelman syndrome; congenital adrenogenital syndromes; exogenous mineralocorticoids (glycyrrhizic acid in licorice, carbenoxolone, steroids in nasal sprays); Liddle syndrome; vasculitis
    • Osmotic diuresis (e.g., poorly controlled diabetes)
    • Renal tubular acidosis (type I and II)
    • Magnesium depletion
  • Glucocorticoid excess states: Cushing syndrome, exogenous steroids, ectopic adrenocorticotrophic hormone production, II-&bgr;-hydroxysteroid dehydrogenase deficiency, refeeding syndrome
Genetics
Some rare, familial disorders can cause hypokalemia.
  • Familial hypokalemic periodic paralysis: hypokalemia after a high-carbohydrate or high-sodium meal or after exercise
  • Congenital adrenogenital syndromes
  • Liddle syndrome: increases K+ secretion
  • Familial interstitial nephritis
GENERAL PREVENTION
When initiating a diuretic, especially loop and thiazide diuretics, advice patients to increase their dietary potassium intake (see “Diet”).
COMMONLY ASSOCIATED CONDITIONS
  • Acute GI illnesses with severe vomiting or diarrhea
  • Increased risk of cardiac arrhythmias; atrial fibrillation (2,3)
  • Hypokalemia is a predictor of development of severe alcohol withdrawal syndrome (SWAS) (4).
image DIAGNOSIS
  • Patients with hypokalemia often have no symptoms, especially if the hypokalemia is mild (serum potassium 3.0 to 3.5 mEq/L).
  • Neuromuscular (most prominent manifestations)
    • Skeletal muscle weakness (proximal > distal muscles, lower limbs > upper limbs) may range from mild weakness to total paralysis, including respiratory muscles; it may lead to rhabdomyolysis and/or respiratory arrest in severe cases.
    • Smooth muscle involvement may lead to GI hypomotility, producing ileus and constipation.
  • Cardiovascular
    • Ventricular arrhythmias; higher risk if underlying CHF, left ventricular failure (LVF), cardiac ischemia
    • Increased risk of atrial fibrillation
    • Hypotension
    • Cardiac arrest
  • Renal: polyuria, polydipsia, nocturia owing to impaired ability to concentrate, myoglobinuria
  • Metabolic: hyperglycemia
PHYSICAL EXAM
Decreased skin turgor in dehydration, hypotension, orthostasis, pulmonary congestion/rales, peripheral edema in heart failure
DIFFERENTIAL DIAGNOSIS
  • Spurious hypokalemia occurs when blood with high WBC count (>100,000/mm3) is allowed to stand at room temperature (WBCs extract potassium from plasma).
  • Thyrotoxicosis
DIAGNOSTIC TESTS & INTERPRETATION
  • Serum potassium <3.5 mEq/L (<3.5 mmol/L)
  • Disorders that may alter lab results: leukemia and other conditions with high WBCs
Initial Tests (lab, imaging)
  • EKG
  • If source of potassium loss not likely to be medications or GI tract: serum electrolytes, urinary potassium
  • Calculate plasma anion gap normal (anion gap = Na - [Cl + HCO3]); normal values, 12 ± 4 mEq/L. Must correct calculated anion gap for hypoalbuminemia. Increase calculated anion gap by 2.5 mEq/L for each 1 g/dL decrease in albumin <4 g/dL.
  • CT scan of adrenal glands if there is evidence of mineralocorticoid excess
Follow-Up Tests & Special Considerations
  • If excessive renal potassium loss (>20 mEq/day) and hypertension, plasma renin and aldosterone levels should be determined to differentiate adrenal from nonadrenal causes of hyperaldosteronism. If hypertension is absent and the patient is acidotic, renal tubular acidosis should be considered.
  • If hypertension is absent and serum pH is normal to alkalotic
    • High urine chloride (>10 mEq/day [>10 mmol/day])—diuretics or Bartter syndrome
    • Low urine chloride (<10 mEq/day [<10 mmol/day])—GI losses likely
  • ECG
    • Hypokalemia increases the myocyte resting potential, which increases the refractory period; this can lead to arrhythmias.
    • Flattening or inversion of T waves
    • Increased prominence of U waves (small, positive deflection after T wave, best seen in V2 and V3)
    • Depression of ST segment
    • Ventricular ectopia
Test Interpretation
In severe hypokalemia, necrosis of cardiac and skeletal muscle
image TREATMENT
GENERAL MEASURES
  • Underlying cause of hypokalemia should be identified.
  • For asymptomatic patients treated with oral replacement, outpatient follow-up is sufficient.
  • Patients with cardiac manifestations require IV replacement with cardiac monitoring in an intensive care setting.
P.533

MEDICATION
  • Nonemergent conditions (serum potassium >2.5 mEq/L [>2.5 mmol/L], no cardiac manifestations)
    • Oral therapy preferred: 40 to 120 mEq/day (40 to 120 mmol/day) in divided doses usually is adequate.
    • IV potassium should be given only when oral administration is not feasible (e.g., vomiting, postoperative state). Rate should not exceed 10 mEq/hr, and concentration should not exceed 40 mEq/L. Up to 40 mEq in 100 mL over 1 hour can be given safely through a central venous line. The patient's cardiac rhythm should be closely monitored.
    • Potassium chloride is suitable for all forms of hypokalemia.
    • Other potassium salts may be indicated if a coexisting disorder is present: potassium bicarbonate or bicarbonate precursor (gluconate, acetate, or citrate) in metabolic acidosis or phosphate in phosphate deficiency
  • Emergent situations (serum potassium <2.5 mEq/L [<2.5 mmol/L], arrhythmias), IV replacement: Rate of administration should not exceed 20 mEq/hr (20 mmol/hr); maximum recommended concentration, 60 mEq/L (60 mmol/L) of saline for peripheral administration. Administration through central venous lines preferred for rates above 20 mEq/hr.
  • Check serum magnesium and replace, if needed; cannot adequately replace potassium in a setting of low magnesium.
  • Precautions
    • Any form of potassium replacement carries the risk of hyperkalemia.
    • Serum potassium should be checked more frequently in groups at higher risk: the elderly, diabetic patients, and patients with renal insufficiency.
    • Patients receiving digitalis and patients with diabetic ketoacidosis in whom intracellular shift in potassium is expected after insulin therapy is initiated must have more aggressive replacement.
  • Significant possible interactions: Concomitant administration of potassium-sparing diuretics (spironolactone, triamterene, amiloride, ACE inhibitors) magnifies risk of hyperkalemia.
Geriatric Considerations
May need to correct magnesium depletion
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Patients receiving IV therapy should have cardiac monitoring and serum potassium level checked frequently (q4-6h).
  • Patients requiring potassium supplements should have serum potassium studied at intervals and magnesium level dictated by clinical judgment and patient compliance (5)[C].
DIET
In patients with mild hypokalemia (potassium, 3.0 to 3.5 mEq/L [3.0 to 3.5 mmol/L]) not caused by GI losses, dietary supplementation may be sufficient; potassium-rich foods include oranges, bananas, cantaloupes, prunes, raisins, dried beans, dried apricots, and squash.
PATIENT EDUCATION
  • Instructions for appropriate diet
  • If potassium supplementation is necessary, stress the need for compliance.
PROGNOSIS
  • Associated with higher morbidity and mortality because of cardiac arrhythmias
  • Ease of correction of hypokalemia and need for prolonged treatment rest on the primary cause; if it can be eliminated (e.g., resolution of diarrhea, discontinuation of diuretics, removal of adrenal tumor), hypokalemia can be expected to resolve and no further treatment is indicated.
REFERENCES
1. Hanlon JT, Semla TP, Schmader KE. Medication misadventures in older adults: literature from 2013. J Am Geriatr Soc. 2014;62(10):1950-1953.
2. Krijthe BP, Heeringa J, Kors JA, et al. Serum potassium levels and the risk of atrial fibrillation: the Rotterdam Study. Int J Cardiol. 2013;168(6): 5411-5415.
3. Tran CT, Bundgaard H, Ladefoged SD, et al. Potassium dynamics are attenuated in hyperkalemia and a determinant of QT adaptation in exercising hemodialysis patients. J Appl Physiol (1985). 2013; 115(4):498-504.
4. Goodson CM, Clark BJ, Douglas IS. Predictors of severe alcohol withdrawal syndrome: a systematic review and meta-analysis. Alcohol Clin Exp Res. 2014;38(10):2664-2677.
5. Unwin RJ, Luft FC, Shirley DG. Pathophysiology and management of hypokalemia: a clinical perspective. Nat Rev Nephrol. 2011;7(2):75-84.
Additional Reading
&NA;
  • Arsenault KA, Yusuf AM, Crystal E, et al. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013;(1):CD003611.
  • Asmar A, Mohandas R, Wingo CS. A physiologic-based approach to the treatment of a patient with hypokalemia. Am J Kidney Dis. 2012;60(3):492-497.
  • Ben Salem C, Hmouda H, Bouraoui K. Drug-induced hypokalaemia. Curr Drug Saf. 2009;4(1):55-61.
  • Chan KE, Lazarus JM, Hakim RM. Digoxin associates with mortality in ESRD. J Am Soc Nephrol. 2010;21(9):1550-1559.
  • Ernst ME, Moser M. Use of diuretics in patients with hypertension. N Engl J Med. 2009;361(22): 2153-2164.
  • Facchini M, Sala L, Malfatto G, et al. Low-K+ dependent QT prolongation and risk for ventricular arrhythmia in anorexia nervosa. Int J Cardiol. 2006; 106(2):170-176.
  • Jones E. Hypokalemia. N Engl J Med. 2004;350(11): 1156.
  • Osadchii OE. Mechanisms of hypokalemia-induced ventricular arrhythmogenicity. Fundam Clin Pharmacol. 2010;24(5):547-559.
  • Palmer BF. A physiologic-based approach to the evaluation of a patient with hypokalemia. Am J Kidney Dis. 2010;56(6):1184-1190.
  • Zietse R, Zoutendijk R, Hoorn EJ. Fluid, electrolyte and acid-base disorders associated with antibiotic therapy. Nat Rev Nephrol. 2009;5(4):193-202.
See Also
&NA;
  • Hyperkalemia
  • Algorithm: Hypokalemia
Codes
&NA;
ICD10
E87.6 Hypokalemia
Clinical Pearls
&NA;
  • In patients without heart disease, a low potassium level will rarely cause cardiac disturbances. In an otherwise healthy patient, gentle repletion using oral potassium or an increase in potassium-rich foods should be adequate.
  • In patients with cardiac ischemia, heart failure, or left ventricular hypertrophy, even mild to moderate hypokalemia can cause arrhythmias. These patients should receive potassium repletion as well as cardiac monitoring.
  • To safely prevent hypokalemia in diabetic and renal insufficiency patients, ensure adequate dietary potassium intake with foods rich in potassium, including spinach, tomatoes, broccoli, squash, potatoes, bananas, cantaloupe, and oranges. Avoid potassium-sparing diuretics, if possible.
  • Uncorrected hypomagnesemia can hinder the correction of hypokalemia. Check magnesium levels and replete as necessary.