Management of hypokalemia in the hospital

I. Problem/Condition.

Hypokalemia is the most common electrolyte problem encountered by hospitalists, occurring in about 20% of patients sometime during their hospitalization.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

There are over 20 clinical etiologies of hypokalemia. It is useful to think about etiologies in three general categories: cellular shifts, extra-renal losses and renal losses (Table I).

Mechanism Clinical conditions
Poor potassium intake Beer potomania
Cellular shifts Hypokalemic periodic paralysis, metabolic alkalosis, hyperthyroidism, insulin use, beta-adrenergics (pharmacologic or intrinsic)
Extra-renal loss Diarrhea, vomiting, excessive sweating, plasmapheresis, dialysis
Renal loss Renal tubular acidosis, salt-wasting nephropathies, Bartter’s syndrome, Gitelman’s syndrome, delivery to distal nephron of non-reabsorbable anions (ketoacids, bicarbonate, toluene, penicillins), excess mineralocorticoid, hypomagnesemia, drugs (diuretics, amphotericin, platinum)

A cellular shift of potassium from the extracellular to the intracellular compartment may result in hypokalemia. This occurs with metabolic alkalosis, with insulin or beta-agonist administration, with hyperthyroidism, and in the periodic paralysis syndromes. In general, the magnitude of the hypokalemia that accompanies cellular shifts is modest. In healthy volunteers, a single dose of aerosolized albuterol lowers serum potassium by 0.2-0.4 milliequivalents/L (mEq/L), and this effect may persist for several hours.

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In delirium tremens, serum potassium may decline by 1 mEq/L due to the effects of high levels of intrinsic beta-agonists (primarily epinephrine and norepinephrine). When patients with delirium tremens present with serum potassium less than 2.5 mEq/L, this is almost always due to the additive effects of other etiologies (such as vomiting, alkalosis associated with volume depletion, and hypomagnesemia).

In distinction to other diseases that cause intracellular shift of potassium, the hypokalemia seen with the periodic paralysis syndromes (hypokalemic periodic paralysis, thyrotoxic periodic paralysis, and Andersen syndrome) may result in very low levels of serum potassium (less than 2.5 mEq/L).

Extra-renal losses of potassium occur with vomiting and diarrhea. The potassium content in diarrhea is much higher than in vomitus (20-50 mEq/l vs. 5-10 mEq/L), but hypokalemia associated with vomiting is usually much more profound than that with diarrhea. This is because vomiting is much more frequently associated with metabolic alkalosis and volume depletion. These two conditions result in inappropriate renal loss of potassium; a more minor effect is the intracellular shift of potassium that accompanies vomiting-associated alkalosis. Rare extrarenal causes of hypokalemia include the chronic poor potassium intake sometimes seen in chronic beer drinkers who also have hyponatremia (beer potomania), excessive sweating, plasmapheresis, and dialysis.

Renal loss etiologies of hypokalemia include diseases of the kidney (renal tubular acidosis, salt losing nephropathies, Bartter syndrome, and Gitelman syndrome); states associated with delivery of non-reabsorbable anions to the distal nephron (such as ketoacids, bicarbonate, toluene, and penicillins); states of excess mineralocorticoids (Conn’s syndrome, Cushing’s syndrome, corticosteroid administration); hypomagnesemia; and certain drugs (diuretics, amphotericin, and platinum).

B. Describe a diagnostic approach/method to the patient with this problem

In over 90% of hospitalized patients, hypokalemia is associated with one of three clinical conditions: diuretic use, vomiting, or diarrhea. Thus for the hospitalist, the cause of hypokalemia does not usually present diagnostic uncertainty. Even though patients often have more than one cause of hypokalemia, potassium supplementation and treatment of the major underlying cause (discontinuing diuretics, treatment of vomiting or diarrhea) corrects the hypokalemia.

A practical approach to the hospitalized patient with hypokalemia is to initiate treatment and defer laboratory investigation of etiology if the patient has vomiting, diarrhea, or used diuretics. In the absence of one of these etiologies, and in the patient in whom treatment does not correct the hypokalemia, then a more detailed laboratory investigation is warranted.

1. Historical information important in the diagnosis of this problem

Historical inquiry of primary importance includes ascertaining an accurate medication list, and determining whether or not the patient has had vomiting and/or diarrhea. Certain historical features may suggest one of the more unusual causes of hypokalemia, such as a history of recent onset hypertension in Conn’s syndrome, a history of renal stones in renal tubular acidosis, or glue-sniffing in toluene poisoning.

Muscle weakness may accompany serum potassium of less than 2.5 mEq/L due to any etiology, but significant muscle weakness is uncommon and suggests the possibility of one of the periodic paralysis syndromes.

In the periodic paralysis syndromes, muscle weakness is typically worse proximally and in lower extremities. With these syndromes, episodes of weakness and hypokalemia are often precipitated by exercise, stress, or high carbohydrate meals. Most, but not all, patients with thyrotoxic periodic paralysis are Asian men who have had symptoms of hyperthyroidism for several months.

Though the periodic paralysis syndromes are rare, they are important to recognize for two reasons. First, these patients often experience hyperkalemia during the recovery phase of their illness as potassium shifts back into the extracellular compartment, and therefore more cautious potassium replacement is warranted. Secondly, preventive therapies are available and may be offered to these patients to prevent or ameliorate subsequent episodes. Thus, patients with hypokalemia and acute muscle weakness should be carefully questioned about the presence of previous episodes of muscle weakness and symptoms of hyperthyroidism (such as weight loss, tremor, and palpitations).

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Severe hypokalemia (serum potassium less than 2.5 mEq/l) may be accompanied by muscle weakness and ileus, but in general the physical examination is usually not helpful diagnostically in hospitalized patients with hypokalemia. The exception to this is patients with one of the periodic paralysis syndrome. These patients typically have proximal motor weakness and hyporeflexia in the presence of a normal level of consciousness.

Patients with vomiting often have findings of volume depletion (tachycardia, low blood pressure, fall in blood pressure with standing), and these findings would suggest the need for volume repletion in addition to potassium administration. Rare causes of hypokalemia may be accompanied by such physical examination signs such as abdominal striae and centripetal obesity in Cushing’s syndrome.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

As noted above, laboratory investigation into the etiology of hypokalemia may be deferred if the patient has vomiting, diarrhea, or used diuretics. In patients in whom the etiology is less obvious, determination of acid-base status (pH from an arterial blood gas) and an estimate of urine potassium secretion are the first diagnostic steps.

Determining renal potassium excretion is most accurately done with a 24-hour collection. In the presence of hypokalemia, 24-hour potassium loss of more than 30 mEq suggests some component of inappropriate renal loss. Random urine potassium measurements can result in misleading results.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Specific diagnoses are suggested by examining the blood pH and urine potassium secretion (Table II).

Table II.
  Acidosis Alkalosis
24 hr urine K > 30 mEq diabetic ketoacidosis, renal tubular acidosis current diuretic use, Barter’s syndrome, mineralocorticoid excess
24 hr urine K < 30 mEq gastrointestinal loss due to diarrhea, villous adenoma, laxative abuse

surreptitious vomiting, occasional laxative abuse, previous diuretic use

Calculation of the potassium/creatinine ratio on a random specimen may also be useful. Urine potassium/creatinine of more than 13 mEq/gram creatinine (1.5 mEq/mmol creatinine) suggests renal potassium loss. Lower values are seen in conditions associated with cellular shifts, poor intake, and extra-renal loss (Table I).

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Although hypokalemia may be accompanied by electrocardiographic abnormalities (depression of ST segments, loss of T wave amplitude, and increase in U wave amplitude), the degree of hypokalemia that is associated with these changes is quite variable. Thus, as opposed to hyperkalemia, T-wave changes seen on the 12-lead electrocardiogram (EKG) do not often guide the decision about treatment of hypokalemia. However, rhythm monitoring may be useful to detect arrhythmias associated with hypokalemia.

In patients with severe hypokalemia (potassium less than 2.5 mEq/L), the presence of serious arrhythmias (such as ventricular tachycardia or rapid atrial fibrillation) is often used to assist with decisions about the rapidity of treatment. In patients in whom one of the periodic paralysis syndromes is suspected, the EKG may be useful diagnostically, since a prolonged QT interval is characteristically seen in Andersen syndrome and not seen in hypokalemic periodic paralysis or thyrotoxic periodic paralysis. Thyroid function testing is useful for those patients with suspected thyrotoxic periodic paralysis.

III. Management of hypokalemia in the hospital

A. Management

A useful approach to treating hypokalemia in the hospital begins by asking three questions: (1) at what level of hypokalemia should I treat this patient? (2) what agent should I use? and (3) what is the best route of administration? Though there is some evidence-based literature that offers guidance, many recommendations about treatment of hypokalemia are based on expert opinion.

(1) At what level of hypokalemia should I treat this patient?

The decision to treat hypokalemia depends on two factors: (1) whether or not the patient has symptoms of hypokalemia and (2) what co-morbid conditions are present. Any degree of hypokalemia that is accompanied by a serious arrhythmia (ventricular tachycardia, rapid atrial fibrillation) or significant muscle weakness should usually be treated. In hypokalemic patients without serious arrhythmias or significant muscle weakness, the degree of hypokalemia that necessitates treatment depends mostly on co-morbid clinical conditions.

In otherwise healthy persons, arrhythmias rarely occur and then only with values of serum potassium less than 3.0 mEq/L. Rhabdomyolysis has been reported in patients with serum potassium less than 2.5 mEq/L, and diaphragmatic muscle paralysis and death in patients with hypokalemic periodic paralysis with serum potassium less than 2.0 mEq/L.

Therefore, in otherwise healthy persons who do not have symptoms of hypokalemia, serum potassium values of less than 3.0 mEq/L are usually treated. The literature suggests that in patients with cirrhosis, serum potassium values less than 3.5 mEq/L may precipitate hepatic encephalopathy. Thus experts recommend supplemental potassium in cirrhotic patients with serum potassium less than 3.5 mEq/L, and in patients with established hepatic encephalopathy who have serum potassium less than 4.0 mEq/L.

In patients undergoing coronary artery bypass, serum potassium levels less than 4.0 mEq/L have been associated with increased mortality. In the setting of an acute myocardial infarction, serum potassium levels less than 3.5 mEq/L and greater than 4.5 mEq/L have been associated with increased mortality. In these settings, many experts recommend correction of serum potassium values of less than 4.0 mEq/L, being careful to avoid over replacement which might result in a potassium level greater than 4.5 mEq/L.

Ambulatory patients with congestive heart failure who take non-potassium sparing diuretics have an excess mortality and sudden cardiac death, and thus many cardiologists recommend achieving a serum potassium level of 4.0 mEq/L or greater in patients with congestive heart failure.

Epidemiologic data suggests that optimal levels of serum potassium in ambulatory patients with hypertension may be 4.0 mEq/L; though this does not apply to the hospital setting, it might influence decisions about discharge medications and communication with healthcare providers who will care for the patient after discharge. General guidelines for treatment of hypokalemia for given clinical conditions are summarized in Table III.

Table III.
Clinical Condition Serum potassium, mEq/L
Acute myocardial infarction, anesthesia for coronary artery surgery < 4.0
Hepatic encephalopathy, congestive heart failure with arrhythmia < 4.0
Cirrhosis or acute hepatic failure without encephalopathy < 3.5
Congestive heart failure without arrhythmia < 3.5
Otherwise healthy < 3.0

(2) What agent should I use?

Except in rare circumstances, potassium chloride is the agent of choice. In patients with renal tubular acidosis and hypokalemia, potassium bicarbonate is preferred, and in the setting of hypophosphatemia, potassium phosphate may be used. Potassium-containing foods are a cheap alternative therapy, but most potassium in foods is predominantly potassium phosphate or citrate, which are only 40% as effective as potassium chloride in correcting hypokalemia. Thus large quantities of these foods are needed to correct significant degrees of hypokalemia. This is usually not practical in the hospital.

The quantity of potassium needed to correct hypokalemia depends on several variables (total body water, acid-base status, and ongoing renal or extra-renal losses) and is difficult to predict with accuracy for most hospitalized patients. In normal volunteers, 75 mEq of potassium results in a rise of potassium by 1.0-1.5 mEq/L. A practical approach for hospitalized patients is to anticipate that 40 mEq of potassium chloride will raise serum potassium by 0.5-1.0 mEq/L, knowing that individual variation will necessitate frequent measurements and re-estimation of total body potassium needs.

(3) What is the best route of administration?

Oral potassium chloride raises potassium within 60 minutes, and is cheaper and safer than giving potassium intravenously. Furthermore, larger quantities can be given with each dose. Thus, oral administration is usually preferred over the intravenous route. In patients who are unable to take orally administrated potassium, and in the rare patient in who more rapid correction of potassium is indicated (serious arrhythmia, diaphragmatic paralysis resulting in respiratory failure), potassium should be given intravenously.

When given intravenously it is preferable to mix it in non-dextrose containing solutions. This is because intravenous dextrose is accompanied by endogenous insulin secretion, this results in an intracellular potassium shift and can delay correction of hypokalemia. Most experts recommend continuous cardiac rhythm monitoring when intravenous infusion rates of potassium exceed 10 mEq/hour.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

Treatment of hypokalemia can be accompanied by “overshoot” hyperkalemia. In one large teaching hospital this occurred in 16% of their hypokalemic patients and was most likely to occur in patients with hematologic malignancies and those who were receiving concomitant parenteral nutrition or magnesium supplementation. Nearly one-third of these patients had peak potassium of greater than 6.0 mEq/L. Frequent measurement of serum potassium during replacement may help to prevent this complication. Compared to physician-ordered potassium replacement, nurse-driven potassium replacement protocols have been shown to result in more timely correction of hypokalemia and less overshoot hyperkalemia.

Rebound hyperkalemia is frequently seen after treatment of the periodic paralysis syndromes (over 50% of the time in some series). Many experts recommend treating the periodic paralysis syndromes with smaller potassium doses (30 mEq), making frequent measurements of serum potassium, and limiting total potassium replacement to 90 mEq in the first 24 hours.

Mount, DB, Skorecki, K,, Chertow, GM,, Marsden, PA,, Tall, MW,, Yu, ASL. “Chapter 18. Disorders of potassium balance.”. Brenner and Rector's The Kidney, 10 ed.. 2016. pp. 559-600.

Gorbatkin, SM,, Schlanger, L,, Bailey, JL, McKean, SC,, Ross, JJ,, Dressler, DD,, Brotman, DJ,, Ginsberg, JS. “Chapter 250. Potassium and magnesium disorders.”. Principles and Practice of Hospital Medicine. 2012.

Crop, MJ,, Hoorn, EJ,, Lindemans, J,, Zietse, R. “Hypokalaemia and subsequent hyperkalaemia in hospitalized patients”. Nephrol Dial Transplant. vol. 22. 2007. pp. 3471-3477.

Coca, SG,, Perazella, MA,, Buller, GK. “The cardiovascular implications of hypokalemia.”. Am J Kidney Dis. vol. 45. 2005. pp. 233-247.

Goyal, A,, Spertus, JA,, Gosch, K. “Serum potassium levels and mortality in acute myocardial infarction.”. JAMA. vol. 307. 2012. pp. 157-164.

Owen, P,, Monahan, MF,, MacLaren, R. “Implementing and assessing an evidence-based electrolyte dosing order form in the medical ICU.”. Intensive Crit Care Nurs. vol. 24. 2008. pp. 8-19.

Hoekstra, M,, Vogelzang, M,, Drost, JT. “Implementation and evaluation of a nurse-centered computerized potassium regulation protocol in the intensive care unit–a before and after analysis.”. BMC Med Inform Decis Mak. 2010.