Clinical manifestations and treatment of hypokalemia in adults
- David B Mount, MD
David B Mount, MD
- Assistant Professor of Medicine
- Harvard Medical School
- Section Editors
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor of Medicine
- University of Rochester School of Medicine and Dentistry
- Michael Emmett, MD
Michael Emmett, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Chief of Internal Medicine
- Baylor University Medical Center
Although hypokalemia can be transiently induced by the entry of potassium into the cells, most cases result from unreplenished gastrointestinal or urinary losses due, for example, to vomiting, diarrhea, or diuretic therapy [1-3]. (See "Causes of hypokalemia in adults".)
Potassium replacement is primarily indicated when hypokalemia is due to potassium loss, and there is a significant deficit in body potassium. It is also warranted for acute therapy in disorders such as hypokalemic or thyrotoxic periodic paralysis in which the hypokalemia is due to redistribution of potassium into the cells, often in association with significant symptoms. Potassium is given cautiously in redistributive hypokalemia since the hypokalemia is transient and the administration of potassium can lead to rebound hyperkalemia when the underlying process is corrected and potassium moves back out of the cells. The recommended regimens for acute therapy in this disorder are presented elsewhere. (See "Hypokalemic periodic paralysis", section on 'Acute treatment' and "Thyrotoxic periodic paralysis", section on 'Acute treatment'.)
Optimal therapy in patients with hypokalemia due to potassium loss is dependent upon the severity of the potassium deficit. In addition, somewhat different considerations are required to minimize continued urinary losses due to diuretic therapy, or less often, to primary hyperaldosteronism.
The clinical manifestations and treatment of hypokalemia will be reviewed here. The causes of and evaluation of patients with hypokalemia are discussed separately. (See "Causes of hypokalemia in adults" and "Evaluation of the adult patient with hypokalemia".)
MANIFESTATIONS OF HYPOKALEMIA
The severity of the manifestations of hypokalemia tends to be proportionate to the degree and duration of the reduction in serum potassium. Symptoms generally do not become manifest until the serum potassium is below 3.0 meq/L, unless the serum potassium falls rapidly or the patient has a potentiating factor, such as a predisposition to arrhythmia due to the use of digitalis. Symptoms usually resolve with correction of the hypokalemia.
- Mount DB, Zandi-Nejad K. Disorders of potassium balance. In: Brenner and Rector's The Kidney, Brenner BM (Ed), WB Saunders Co, Philadelphia 2008. p.547.
- Rose BD, Post TW. Hypokalemia. In: Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, Rose BD, Post TW (Eds), McGraw-Hill, New York 2001. p.836.
- Gennari FJ. Hypokalemia. N Engl J Med 1998; 339:451.
- Comi G, Testa D, Cornelio F, et al. Potassium depletion myopathy: a clinical and morphological study of six cases. Muscle Nerve 1985; 8:17.
- Shintani S, Shiigai T, Tsukagoshi H. Marked hypokalemic rhabdomyolysis with myoglobinuria due to diuretic treatment. Eur Neurol 1991; 31:396.
- Dominic JA, Koch M, Guthrie GP Jr, Galla JH. Primary aldosteronism presenting as myoglobinuric acute renal failure. Arch Intern Med 1978; 138:1433.
- Knochel JP. Neuromuscular manifestations of electrolyte disorders. Am J Med 1982; 72:521.
- Knochel JP, Schlein EM. On the mechanism of rhabdomyolysis in potassium depletion. J Clin Invest 1972; 51:1750.
- van Dinter TG Jr, Fuerst FC, Richardson CT, et al. Stimulated active potassium secretion in a patient with colonic pseudo-obstruction: a new mechanism of secretory diarrhea. Gastroenterology 2005; 129:1268.
- Blondon H, Béchade D, Desramé J, Algayres JP. Secretory diarrhoea with high faecal potassium concentrations: a new mechanism of diarrhoea associated with colonic pseudo-obstruction? Report of five patients. Gastroenterol Clin Biol 2008; 32:401.
- Yelamanchi VP, Molnar J, Ranade V, Somberg JC. Influence of electrolyte abnormalities on interlead variability of ventricular repolarization times in 12-lead electrocardiography. Am J Ther 2001; 8:117.
- Guo J, Massaeli H, Xu J, et al. Extracellular K+ concentration controls cell surface density of IKr in rabbit hearts and of the HERG channel in human cell lines. J Clin Invest 2009; 119:2745.
- Nia AM, Gassanov N, Ortega M, Er F. Drunk potassium channels. Europace 2011; 13:1352.
- Siegel D, Hulley SB, Black DM, et al. Diuretics, serum and intracellular electrolyte levels, and ventricular arrhythmias in hypertensive men. JAMA 1992; 267:1083.
- Mujais SK, Katz AL. Potassium deficiency. In: The Kidney: Physiology and Pathophysiology, Seldin DW, Giebisch G (Eds), Lippincott Williams & Wilkins, 2000. p.1615.
- Goldstein SA. K2P potassium channels, mysterious and paradoxically exciting. Sci Signal 2011; 4:pe35.
- Ma L, Zhang X, Chen H. TWIK-1 two-pore domain potassium channels change ion selectivity and conduct inward leak sodium currents in hypokalemia. Sci Signal 2011; 4:ra37.
- Chen EH, Hollander JE. When do patients need admission to a telemetry bed? J Emerg Med 2007; 33:53.
- Drew BJ, Califf RM, Funk M, et al. Practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association scientific statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized Electrocardiology and the American Association of Critical-Care Nurses. Circulation 2004; 110:2721.
- Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000; 160:2429.
- Huang CL, Kuo E. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol 2007; 18:2649.
- Yang L, Frindt G, Palmer LG. Magnesium modulates ROMK channel-mediated potassium secretion. J Am Soc Nephrol 2010; 21:2109.
- Whang R, Flink EB, Dyckner T, et al. Magnesium depletion as a cause of refractory potassium repletion. Arch Intern Med 1985; 145:1686.
- Zydlewski AW, Hasbargen JA. Hypothermia-induced hypokalemia. Mil Med 1998; 163:719.
- Schaefer M, Link J, Hannemann L, Rudolph KH. Excessive hypokalemia and hyperkalemia following head injury. Intensive Care Med 1995; 21:235.
- Ahmed I, Chilimuri SS. Fatal dysrhythmia following potassium replacement for hypokalemic periodic paralysis. West J Emerg Med 2010; 11:57.
- Lu KC, Hsu YJ, Chiu JS, et al. Effects of potassium supplementation on the recovery of thyrotoxic periodic paralysis. Am J Emerg Med 2004; 22:544.
- Lin SH, Lin YF. Propranolol rapidly reverses paralysis, hypokalemia, and hypophosphatemia in thyrotoxic periodic paralysis. Am J Kidney Dis 2001; 37:620.
- Beal AL, Deuser WE, Beilman GJ. A role for epinephrine in post-traumatic hypokalemia. Shock 2007; 27:358.
- Cronin D, Kaliaperumal C, Kumar R, Kaar G. Dyskalaemia following diffuse axonal injury: case report and review of the literature. BMJ Case Rep 2012; 2012.
- Pomeranz S, Constantini S, Rappaport ZH. Hypokalaemia in severe head trauma. Acta Neurochir (Wien) 1989; 97:62.
- Amin DN, Henry JA. Propranolol administration in theophylline overdose. Lancet 1985; 1:520.
- Darbar D, Smith M, Mörike K, Roden DM. Epinephrine-induced changes in serum potassium and cardiac repolarization and effects of pretreatment with propranolol and diltiazem. Am J Cardiol 1996; 77:1351.
- Kim GH, Han JS. Therapeutic approach to hypokalemia. Nephron 2002; 92 Suppl 1:28.
- Crop MJ, Hoorn EJ, Lindemans J, Zietse R. Hypokalaemia and subsequent hyperkalaemia in hospitalized patients. Nephrol Dial Transplant 2007; 22:3471.
- Sterns RH, Cox M, Feig PU, Singer I. Internal potassium balance and the control of the plasma potassium concentration. Medicine (Baltimore) 1981; 60:339.
- Adrogué HJ, Lederer ED, Suki WN, Eknoyan G. Determinants of plasma potassium levels in diabetic ketoacidosis. Medicine (Baltimore) 1986; 65:163.
- Wang CC, Shiang JC, Huang WT, Lin SH. Hypokalemic paralysis as primary presentation of Fanconi syndrome associated with Sjögren syndrome. J Clin Rheumatol 2010; 16:178.
- Hoorn EJ, Zietse R. Combined renal tubular acidosis and diabetes insipidus in hematological disease. Nat Clin Pract Nephrol 2007; 3:171.
- Kassirer JP, Schwartz WB. The response of normal man to selective depletion of hydrochloric acid. Factors in the genesis of persistent gastric alkalosis. Am J Med 1966; 40:10.
- KASSIRER JP, BERKMAN PM, LAWRENZ DR, SCHWARTZ WB. THE CRITICAL ROLE OF CHLORIDE IN THE CORRECTION OF HYPOKALEMIC ALKALOSIS IN MAN. Am J Med 1965; 38:172.
- Villamil MF, Deland EC, Henney RP, Maloney JV Jr. Anion effects on cation movements during correction of potassium depletion. Am J Physiol 1975; 229:161.
- Sopko JA, Freeman RM. Salt substitutes as a source of potassium. JAMA 1977; 238:608.
- Aselton PJ, Jick H. Short-term follow-up study of wax matrix potassium chloride in relation to gastrointestinal bleeding. Lancet 1983; 1:184.
- Kopyt N, Dalal F, Narins RG. Renal retention of potassium in fruit. N Engl J Med 1985; 313:582.
- Wahr JA, Parks R, Boisvert D, et al. Preoperative serum potassium levels and perioperative outcomes in cardiac surgery patients. Multicenter Study of Perioperative Ischemia Research Group. JAMA 1999; 281:2203.
- Shapiro W, Taubert K. Letter: Hypokalaemia and digoxin-induced arrhythmias. Lancet 1975; 2:604.
- Keith NM, Osterberg AE, Burchell HB. Some effects of potassium salts in man. Ann Intern Med 1942; 16:879.
- Nicolis GL, Kahn T, Sanchez A, Gabrilove JL. Glucose-induced hyperkalemia in diabetic subjects. Arch Intern Med 1981; 141:49.
- Sterns RH, Feig PU, Pring M, et al. Disposition of intravenous potassium in anuric man: a kinetic analysis. Kidney Int 1979; 15:651.
- KUNIN AS, SURAWICZ B, SIMS EA. Decrease in serum potassium concentrations and appearance of cardiac arrhythmias during infusion of potassium with glucose in potassium-depleted patients. N Engl J Med 1962; 266:228.
- Abramson E, Arky R. Diabetic acidosis with initial hypokalemia. Therapeutic implications. JAMA 1966; 196:401.
- Hamill RJ, Robinson LM, Wexler HR, Moote C. Efficacy and safety of potassium infusion therapy in hypokalemic critically ill patients. Crit Care Med 1991; 19:694.
- Pullen H, Doig A, Lambie AT. Intensive intravenous potassium replacement therapy. Lancet 1967; 2:809.
- Kruse JA, Carlson RW. Rapid correction of hypokalemia using concentrated intravenous potassium chloride infusions. Arch Intern Med 1990; 150:613.
- MANIFESTATIONS OF HYPOKALEMIA
- Severe muscle weakness or rhabdomyolysis
- Cardiac arrhythmias and ECG abnormalities
- Renal abnormalities
- Glucose intolerance
- PATHOGENESIS OF SYMPTOMS
- DIAGNOSIS AND EVALUATION
- General issues
- - Hypomagnesemia and redistributive hypokalemia
- Estimation of the potassium deficit
- - Uncontrolled diabetes
- Potassium preparations
- - Intravenous therapy
- Ongoing losses and the steady state
- Potassium-sparing diuretics
- Mild to moderate hypokalemia
- Severe or symptomatic hypokalemia
- - Intravenous potassium repletion
- Adverse effects of intravenous potassium
- Recommended approach
- Careful monitoring
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS