Hypokalemia

Hypokalemia (low serum potassium) is a common electrolyte disorder that is typically caused by potassium loss (e.g., due to diarrhea, vomiting, or diuretic medication). Mild hypokalemia may be asymptomatic or cause mild nonspecific symptoms such as nausea, muscle weakness, and fatigue. Severe deficiency can cause cardiac arrhythmias and death. Treatment consists of oral or IV supplementation in conjunction with treatment of the underlying cause. In concurrent hypomagnesemia, which may lead to refractory hypokalemia, the simultaneous repletion of magnesium and potassium is necessary.

See also “Hyperkalemia.”

• Serum potassium (K⁺) level < 3.5 mEq/L ^[1]
• Severe hypokalemia: K⁺ level < 2.5 mEq/L

Hypokalemia is most often caused by renal or gastrointestinal potassium loss. Other electrolyte imbalances (e.g., hypomagnesemia), alkalosis, and several medications can also have an impact on potassium homeostasis.

• Potassium is an important factor in maintaining the resting membrane potential.
• ↓ Extracellular K⁺ concentration → resting membrane potential becomes more negative than -90 mV) → ↓ excitability ^[3]
• Alkalosis can impact potassium balance via intracellular shifts and vice versa. ^[4]
  • Alkalosis → ↓ extracellular H⁺ → stimulation of the Na⁺/H⁺ antiporter (transfers H⁺ out of the cells in exchange for Na⁺) → ↑ intracellular Na⁺ → ↑ sodium gradient stimulates the Na⁺/K⁺-ATPase (transfers K⁺ into the cells in exchange for Na⁺) → ↓ extracellular K⁺ concentration
  • Hypokalemia → ↓ extracellular K⁺ concentration → ↓ potassium gradient inhibits the Na⁺/K⁺-ATPase → ↓ extracellular Na⁺ → ↓ sodium gradient inhibits the Na⁺/H⁺ antiporter → ↓ extracellular H⁺ → alkalosis
  • Exception: In renal tubular acidosis, findings include hypokalemia and metabolic acidosis!

K⁺ acts like H⁺: Hypokalemia leads to alkalosis and vice versa!

Particularly acute extracellular changes in concentration influence excitability! Chronic changes lead to intracellular compensation!

• Hypomagnesemia can impact potassium balance via the following mechanisms of increased renal loss: ^[5]
  • Magnesium serves as a cofactor in Na⁺/K⁺-ATPases → hypomagnesemia disrupts the Na⁺/K⁺-ATPase in the basolateral membrane of the proximal convoluted loop of Henle → ↓ Na⁺ reabsorption → ↑ luminal Na⁺ → ↑ Na⁺ reabsorption and ↑ K⁺ secretion by the principal cells distally
  • Apical ROMK channels in principal cells are inhibited by intracellular magnesium. With low levels of magnesium available, the ROMK channels are not inhibited, resulting in increased K⁺ secretion.

Hypomagnesemia can lead to refractory hypokalemia!

Patients may be asymptomatic, particularly if the deficiency is mild. Symptoms usually occur if serum K⁺ levels are < 3.0 mEq/L and/or decrease rapidly. ^[2]

• Cardiovascular manifestations
  • Symptoms of cardiac arrhythmias (e.g., palpitations, irregular pulse, syncope)
  • Hypotension
• Neuromuscular manifestations
  • Muscle cramps and spasms ^[6]
  • Muscle weakness, paralysis
  • Respiratory failure secondary to paralysis of the respiratory muscles
  • Rhabdomyolysis
  • Decreased deep tendon reflexes
• Gastrointestinal manifestations
  • Nausea, vomiting ^[6]
  • Constipation or ileus
  • Fatigue
• Other manifestations
  • Hyperglycemia ^[7]
  • Polyuria ^[8]
  • Symptoms of underlying causes, including:
    • Dehydration in gastroenteritis
    • Tachycardia and tremors in alcohol withdrawal
    • Symptoms of thyrotoxicosis
    • Symptoms of digoxin toxicity in patients treated with digoxin ^[9]

Hypokalemia (and hyperkalemia) can cause cardiac arrhythmia and may lead to ventricular fibrillation!

All patients require an ECG and laboratory studies to confirm the diagnosis and rule out concurrent electrolyte abnormalities. Further diagnostic tests depend on the suspected underlying etiology.

Initial evaluation

Laboratory studies ^[1]

• Electrolytes and kidney function
  • BMP
    • Low serum K⁺ levels
    • Renal function tests
    • Other electrolytes
  • Serum calcium, magnesium, phosphate
• Blood gas (venous or arterial): : may show metabolic alkalosis
• Urinary potassium: Consider measuring to narrow down underlying etiology. ^[10][11][12]
  • Methods
    • Spot urine: rapid assessment, indicated in urgent cases , less reliable than 24-hour collections
    • 24-hour urine collection: less practical, indicated for chronic cases and uncertain diagnoses, more accurate than spot urine
  • Findings
    • Renal loss; : spot urine > 15–20 mEq/L (24-hour collection > 15 mEq/L) ^[1][11]
    • Extrarenal loss; : spot urine < 15–20 mEq/L (24-hour collection < 15 mEq/L) ^[12]

Consider confirming abnormal serum potassium levels with a repeat blood draw.

ECG findings in hypokalemia ^[2][13]

• Mild to moderate hypokalemia
  • T-wave flattening or inversion
  • ST depression
  • Prolonged PR interval
• Moderate to severe hypokalemia
  • Presence of U waves: small waveform following the T wave that is often absent but becomes more pronounced in hypokalemia or bradycardia ^[2]
  • T and U wave fusion
  • QT prolongation ^[13]
• Dysrhythmias
  • Premature atrial and ventricular complexes
  • Sinus bradycardia
  • Paroxysmal atrial or junctional tachycardia
  • Ventricular dysrhythmias, e.g., Torsades de pointes
  • PEA/asystole

To remember that low potassium may result in a flattened T wave, think of: "No pot, no tea (T)!"

Identification of underlying etiology

• Review the patient's history and medication list to help identify potential causes of hypokalemia.
• If the etiology is still unclear, further testing can help determine the underlying etiology.
• Imaging is not routinely required but may be necessary if certain underlying etiologies are suspected. ^[1]

Approach

Most patients require potassium chloride (KCl) repletion, management of concurrent electrolyte abnormalities (see “Electrolyte repletion”), and treatment of the underlying cause. See “Potassium replacement” for further details on repletion regimens for hypokalemia, treatment goals, warnings, and adverse effects.

• Severe hypokalemia (< 2.5 mEq/L) and/or high risk of recurrent severe hypokalemia
  • KCl: IV repletion PLUS oral repletion if tolerated ^[15][16][17]
    • Rate of repletion should not exceed 10–20 mEq/hour through a peripheral IV. ^[15][17]
    • Higher doses (up to 40 mEq/hour) must be administered through a central line.
    • Order continuous cardiac monitoring for IV potassium infusions over 10 mEq/hour.
    • Check potassium levels every 2–4 hours or after a maximum of 60 mEq (combined total from oral and IV sources) has been repleted.
  • Consider admission to ICU, continuous cardiac monitoring, and central line placement.
• Moderate hypokalemia (2.5–2.9 mEq/L)
  • KCl: Oral repletion; is preferred unless the patient is unable to tolerate PO, has severe symptoms, or has ECG changes in hypokalemia. ^[16]
  • Disposition is usually determined by treatment of the underlying disorder.
• Mild hypokalemia (3.0–3.5 mEq/L) with easily reversible cause
  • Prioritize treatment of the underlying condition (e.g., GI fluid losses).
  • Consider oral supplementation, e.g., KCl
  • Consider increasing dietary potassium intake. ^[18]
  • Patients can usually be discharged after stabilization.

High concentrations of IV potassium can cause local venous irritation and potentially lead to cardiac arrhythmias. Limit the rate of infusion according to the type of IV access and place patients on a continuous cardiac monitor.

Correction of hypokalemia is a common cause of hyperkalemia in hospitalized patients; monitor K⁺ levels frequently in patients receiving potassium repletion. ^[16][17]

In patients with hypokalemia, avoid solutions containing dextrose, which can increase insulin secretion and worsen hypokalemia. ^[15]

Treatment of underlying condition

See “Etiology of hypokalemia.”

• Review medications that may be affecting potassium balance, e.g., β2 agonists, laxatives.
• Diuretic-induced hypokalemia (e.g., loop diuretics or thiazides) ^[1]
  • Discontinue the diuretic or reduce the dose and combine with potassium-sparing diuretics, e.g., spironolactone.
  • Rehydrate with normal saline if the patient has both volume depletion and contraction alkalosis.
• Start oral or IV magnesium for patients with hypomagnesemia.
• Treat nausea and vomiting and provide fluid resuscitation for dehydration and hypovolemia.
• Consider aggressive potassium repletion for conditions at high risk of relapsing or refractory hypokalemia, e.g., DKA, high-dose insulin therapy, refeeding syndrome.
• Consider specialist consult (e.g., nephrology, endocrinology, dietician) as directed by the suspected underlying etiology.

Potassium supplementation will be ineffective if concurrent hypomagnesemia is left untreated (see “Magnesium repletion”).

Patients with a continued source of potassium loss (e.g., those on diuretics) may require long-term potassium supplementation. ^[15]

1. Kardalas E, Paschou SA, Anagnostis P, Muscogiuri G, Siasos G, Vryonidou A. Hypokalemia: a clinical update. Endocrine Connections. 2018; 7 (4): p.R135-R146. doi: 10.1530/ec-18-0109 . | Open in Read by QxMD
2. Domino FJ. The 5-Minute Clinical Consult 2011. Lippincott Williams & Wilkins ; 2010
3. Marini JJ, Wheeler AP. Critical Care Medicine. Lippincott Williams & Wilkins ; 2010
4. Ronco C, Bellomo R, Kellum JA. Critical Care Nephrology. Elsevier Health Sciences ; 2009
5. Greenberg A. Primer on Kidney Diseases E-Book. Elsevier Health Sciences ; 2009
6. Levis JT. ECG diagnosis: hypokalemia.. Perm J. 2012; 16 (2): p.57. doi: 10.7812/tpp/12-015 . | Open in Read by QxMD
7. Gleadle J, Li J, Yong T. Clinical Investigations at a Glance. John Wiley & Sons ; 2017
8. Viera AJ, Wouk N. Potassium disorders: Hypokalemia and hyperkalemia. Am Fam Physician. 2015; 92 (6): p.487-495.
9. 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): p.492-497. doi: 10.1053/j.ajkd.2012.01.031 . | Open in Read by QxMD
10. Gennari FJ. Hypokalemia. N Engl J Med. 1998; 339 (7): p.451-458. doi: 10.1056/nejm199808133390707 . | Open in Read by QxMD
11. Magee CC, Tucker JK, Singh AK. Core Concepts in Dialysis and Continuous Therapies. Springer ; 2016
12. Mehta M, Mathews A. The Hospitalist Manual. PMPH-USA ; 2010
13. Liamis G. Diabetes mellitus and electrolyte disorders. World J Clin Cases. 2014; 2 (10): p.488. doi: 10.12998/wjcc.v2.i10.488 . | Open in Read by QxMD
14. Lote CJ. Principles of Renal Physiology. Springer Science & Business Media ; 2000
15. Bryson PD. Comprehensive Reviews in Toxicology. CRC Press ; 1996
16. Porth C. Essentials of Pathophysiology. Lippincott Williams & Wilkins ; 2011
17. Aronson PS, Giebisch G. Effects of pH on Potassium: New Explanations for Old Observations. Journal of the American Society of Nephrology. 2011; 22 (11): p.1981-1989. doi: 10.1681/asn.2011040414 . | Open in Read by QxMD
18. Unwin RJ, Luft FC, Shirley DG. Pathophysiology and management of hypokalemia: a clinical perspective. Nature Reviews Nephrology. 2011; 7 (2): p.75-84. doi: 10.1038/nrneph.2010.175 . | Open in Read by QxMD
19. Agabegi SS, Agabegi ED. Step-Up To Medicine. Lippincott Williams & Wilkins ; 2013
20. Lederer E. Hypokalemia. In: Batuman V, Hypokalemia. New York, NY: WebMD. http://emedicine.medscape.com/article/242008-overview. Updated: December 29, 2016. Accessed: February 9, 2017.
21. Mount DB. Clinical manifestations and treatment of hypokalemia in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-treatment-of-hypokalemia-in-adults?source=search_result&search=hypokalemia&selectedTitle=1~150#H3819731.Last updated: January 7, 2016. Accessed: February 9, 2017.