Correspondence

Treatment of Hypokalemia

N Engl J Med 1999; 340:154-155January 14, 1999

Article

To the Editor:

In his excellent review, Dr. Gennari (Aug. 13 issue)1 discusses the principles of potassium replacement in the management of hypokalemia. Although he advises caution in the use of intravenous potassium and makes recommendations about the rate of infusion, the importance of the vehicle for such infusions is not mentioned. We agree that the oral route is the safest for potassium supplementation, although intravenous replacement is justified in patients with arrhythmias or neuromuscular paralysis. One further important therapeutic principle concerns the use of glucose-free solutions during intravenous administration of potassium, as the following case report clearly illustrates.

A 35-year-old white woman presented with a two-day history of nausea, vomiting, and muscle weakness. She denied laxative or diuretic abuse. She had a history of nephrolithiasis. Examination revealed a blood pressure of 108/88 mm Hg and a pulse of 110 beats per minute; the chest and cardiovascular examination was normal. Muscle power was 3/5. Laboratory tests showed the following: a normal differential blood count; sodium, 137 mmol per liter; potassium, 1.6 mmol per liter; chloride, 108 mmol per liter; bicarbonate, 16 mmol per liter; anion gap, 13; blood urea nitrogen, 10 mg per deciliter; creatinine, 0.8 mg per deciliter; arterial blood pH, 7.32; partial pressure of carbon dioxide, 25 mm Hg; and partial pressure of oxygen, 93 mm Hg. Urinalysis revealed a pH of 7.5, a specific gravity of 1.005, and no white cells, protein, blood, or nitrites. Electrocardiography revealed prominent U waves. Renal ultrasonography and intravenous pyelography showed nephrocalcinosis.

The patient was treated in the emergency room with intravenous potassium (40 mmol per liter) in 5 percent glucose and oral potassium (40 mmol). Severe muscle weakness (grade 1/5) developed, and the potassium concentration was 1.2 mmol per liter. The patient was transferred to the intensive care unit for close monitoring. She received further doses of intravenous potassium (40 to 60 mmol per liter) in normal saline, and the potassium concentration increased to 3.6 mmol per liter. Distal renal tubular acidosis was subsequently diagnosed, and the patient was discharged with instructions to take 25 ml of potassium citrate and citric acid oral solution (Polycitra-K, Baker Norton Pharmaceuticals, Miami) four times daily.

This case illustrates the dangers of the administration of intravenous potassium in glucose-containing solutions during replacement therapy. Previous studies have also reported decreases in serum potassium and the appearance of life-threatening cardiac arrhythmias and worsening muscle weakness during the infusion of potassium with glucose in the treatment of hypokalemia.2,3 Similar decreases in potassium occur with the infusion of glucose alone both in healthy subjects and in subjects with hypokalemia. This is presumably caused by the enhanced insulin secretion stimulated by glucose, which results in the movement of potassium into cells.4,5 Initially, potassium-replacement therapy should consist of potassium administered in glucose-free solutions, since glucose may cause a further decrease in the serum potassium concentration, precipitating arrhythmias and neuromuscular paralysis.

Anupam Agarwal, M.D.
Charles S. Wingo, M.D.
University of Florida, Gainesville, FL 32610

5 References

1. 1

   Gennari FJ. Hypokalemia. N Engl J Med 1998;339:451-458
   Full Text | Web of Science | Medline

2. 2

   Kunin AS, Surawicz B, Sims EAH. 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;266:228-233
   Full Text | Web of Science | Medline

3. 3

   Griggs RC, Resnick J, Engel WK. Intravenous treatment of hypokalemic periodic paralysis. Arch Neurol 1983;40:539-540
   Web of Science | Medline

4. 4

   Holler JW. Potassium deficiency occurring during treatment of diabetic acidosis. JAMA 1946;131:1186-1189
   Web of Science | Medline

5. 5

   Farber SJ, Pellegrino ED, Conan NJ, Earle DP. Observations on plasma potassium level of man. Am J Med Sci 1951;221:678-687
   Web of Science | Medline

To the Editor:

In his review of hypokalemia, Gennari does not mention that several precautions are necessary at the time of blood sampling to ensure that the plasma potassium concentration is measured accurately. Neglect of these aspects can lead to the minimization or even concealment of clinically relevant hypokalemia. Most important, fist clenching must not be used to aid venipuncture because it can markedly elevate the plasma potassium concentration.1-3 Plasma measurements of potassium yield slightly lower and less variable values than serum measurements of potassium.1,3,4 Hemolysis must be avoided in order to prevent a spurious elevation of the plasma or serum potassium concentration.3 Orthostasis also raises the plasma potassium concentration.3 Blood samples for the measurement of potassium are often obtained in the morning, when a daily dose of any diuretic is likely to be taken; thus, hypokalemia that develops later in the day may be overlooked.3

J. Ian S. Robertson, M.D.
Elmbank, Manse Rd., Bowling,, Glasgow G60 5AA, United Kingdom

4 References

1. 1

   Brown JJ, Chinn RH, Davies DL, et al. Falsely high plasma potassium values in patients with hyperaldosteronism. BMJ 1970;2:18-20
   CrossRef | Web of Science | Medline

2. 2

   Don BR, Sebastian A, Cheitlin M, Christiansen M, Schambelan M. Pseudohyperkalemia caused by fist clenching during phlebotomy. N Engl J Med 1990;322:1290-1292
   Full Text | Web of Science | Medline

3. 3

   Singh BN, Hollenberg NK, Poole-Wilson PA, Robertson JI. Diuretic-induced potassium and magnesium deficiency: relation to drug-induced QT prolongation, cardiac arrhythmias and sudden death. J Hypertens 1992;10:301-316
   CrossRef | Web of Science | Medline

4. 4

   Hyman D, Kaplan NM. The difference between serum and plasma potassium. N Engl J Med 1985;313:642-642
   Web of Science | Medline

Author/Editor Response

Dr. Gennari replies:

To the Editor: Drs. Agarwal and Wingo make a valuable point regarding the importance of avoiding the use of glucose-containing solutions in the treatment of hyperkalemia. The ability of glucose administration to lower the serum potassium concentration is well recognized and can certainly reverse any beneficial effect of administered potassium.

Dr. Robertson's comments about the potential effects of the technique of blood sampling on the serum potassium concentration, although correct, are of little importance in the search for hypokalemia. Hemolysis or fist clenching more commonly leads to the incorrect diagnosis of hyperkalemia. In the United States, laboratories always report whether hemolysis is present, and venipuncture specialists instruct patients not to clench their fists during blood sampling. Patients with diuretic-induced hypokalemia have low serum potassium concentrations regardless of the time of sampling. If serum potassium concentrations are only transiently reduced after each day's dose of diuretic, then clinically significant potassium depletion is not present.

F. John Gennari, M.D.
University of Vermont College of Medicine, Burlington, VT 05401

Citing Articles (3)

Citing Articles

1. 1

   D WILLIAMS, R SMITH, W MALLON. (2008) Severe hypokalemia, paralysis, and AIDS-associated Isospora Belli diarrhea. Journal of Emergency Medicine
   CrossRef

2. 2

   Jean-Philippe Lafrance, Martine Leblanc. (2005) Metabolic, Electrolytes, and Nutritional Concerns in Critical Illness. Critical Care Clinics 21:2, 305-327
   CrossRef

3. 3

   Giuseppe Famularo, Fabio Massimo Corsi, Manlio Giacanelli. (1999) Iatrogenic Worsening of Hypokalemia and Neuromuscular Paralysis Associated with the Use of Glucose Solutions for Potassium Replacement in a Young Woman with Licorice Intoxication and Furosemide Abuse. Academic Emergency Medicine 6:9, 960-964
   CrossRef