eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Hypokalemia: Follow-up

Author: Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Coauthor(s): Rosemary Ouseph, MD, Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine; Leslie Ford, MD, Assistant Professor of Medicine, Kidney Disease Program, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Aug 5, 2009

Follow-up

Further Inpatient Care

• Further inpatient care consists of monitoring serum potassium levels and adjusting supplements. Once a cause has been determined for hypokalemia and the condition has been treated as per the diagnosis, ensuring that treatment plans are adequate is imperative. Recall that potassium can shift in and out of cells under several influences. Therefore, several determinations of serum potassium level after presumably adequate replacement are indicated to ensure that serum potassium levels achieve normalcy.
• After potassium has been replenished, checking again for several days to determine whether potassium has stabilized or has started falling again is equally important. For example, if an individual presents with nausea and vomiting and hypokalemia, the physician might understandably attribute the hypokalemia to the nausea and vomiting. However, if after replenishment, the patient once again develops hypokalemia without nausea and vomiting, then considering other possible causes of hypokalemia is necessary. Additionally, if a need for ongoing potassium supplementation is anticipated for the patient (eg, a patient on long-term diuresis for hypertension), then ensuring that the prescribed daily potassium supplement is adequate to maintain a normal serum potassium level is important.
• Evaluate for more unusual secondary causes. If an unusual cause of hypokalemia is suggested, due to either specific clinical features or failing to observe a response to the initial therapy, evaluation can at least begin while the patient is hospitalized. However, evaluation often can be completed in an outpatient setting.
  • If occult diuretic or laxative use is suspected, establishing proof of this is best accomplished in the hospital, with patients in a relatively controlled environment. In this setting, 24-hour urine measurements of sodium and potassium excretion, measurement of serum potassium at frequent intervals, and supervision of intake and output are possible. Ongoing potassium losses in the face of a negative urine and serum screen for diuretics suggest another diagnosis.
  • If patients are hypertensive, then the next steps would be determining serum renin activity and aldosterone and cortisol levels; obtaining a 24-hour urine measurement for aldosterone, cortisol, sodium, and potassium; initiating a captopril renal scan to investigate the possibility of renal artery stenosis; and performing a CT scan of the abdomen to investigate for a possible adrenal adenoma. A high cortisol level suggests Cushing disease. Evaluate for pituitary or adrenal causes. If renin and aldosterone levels are both elevated, this points more strongly to renal artery stenosis.
  • If the index of suspicion is high enough, then perform a renal arteriogram and renal vein renin determination to look for significant renal artery stenosis as a cause of hypertension and hypokalemia. A high aldosterone level with low renin activity suggests primary hyperaldosteronism. If the patient is hypertensive but the aldosterone level is low, this suggests one of the more unusual congenital forms of hypertension, such as Liddle syndrome, where a mutation in the epithelial sodium channel produces uncontrollable sodium reabsorption or glucocorticoid-remediable hypertension. This scenario also could be produced by licorice ingestion or ingestion of a steroid with mineralocorticoid activity, such as prednisone or fludrocortisone.
  • If patients are not hypertensive but have hypokalemic metabolic alkalosis, then possibilities include Bartter syndrome or Gitelman syndrome if diuretic use and bulimia have been excluded. If patients have metabolic acidosis, the most common cause is diarrhea. If this is not present, then the most likely possibility is a distal renal tubular acidosis, as might be seen with amyloid or amphotericin use or with glue sniffing.

Further Outpatient Care

• For otherwise healthy patients undergoing what appears to be an acute episode causing hypokalemia, such as severe diarrhea, no further follow-up care is required.
• For patients who are likely to develop hypokalemia again (eg, on diuretic therapy), periodic monitoring of serum potassium levels is essential. If not performed during hospitalization, then outpatient follow-up care with tests such as 24-hour urine cortisol and aldosterone is acceptable.

Inpatient & Outpatient Medications

• Oral potassium chloride
  • This should be given as indicated. Maintain the patient, if necessary, on a fixed regimen.
  • Potassium chloride is absorbed easily and can be given several times per day if needed, especially if high-dose diuretic therapy is required.
• Potassium-sparing diuretics
  • Generally, use potassium-sparing diuretics only in patients with normal renal function who are prone to significant hypokalemia.
  • Some evidence indicates that spironolactone is particularly useful in patients with cirrhosis and patients with heart failure. Exercise caution in using potassium-sparing diuretics in either of these populations. Frequent determination of potassium levels is mandatory.
  • Often, individuals with cirrhosis or congestive heart failure have subtle decreases in renal function that might not be apparent based on routine lab work. In addition, patients with heart failure often are treated with ACE inhibitors, another class of drugs that inhibits renal potassium excretion.
  • The combination of mild renal insufficiency, an ACE inhibitor, a potassium-sparing diuretic, and a potassium supplement can very easily result in life-threatening hyperkalemia. Although these combinations can be used, frequent follow-up care is necessary.
  • Treatment with the more selective aldosterone receptor inhibitor eplerenone is associated with fewer side effects than treatment with spironolactone and may be more efficacious in treating hypertension associated with primary hyperaldosteronism.¹⁹
  • Treatment with eplerenone in the setting of congestive heart failure after acute myocardial infarction was associated with improved mortality and a low incidence of hyperkalemia.²⁰
• Angiotensin-converting enzyme inhibitors
  • ACE inhibitors have gained significantly in popularity due to demonstration of their tolerability and benefit in a variety of disease conditions. These drugs are amazingly well tolerated by large groups of individuals.
  • Cough is the most common complaint, but other types of adverse effects commonly seen with other antihypertensives, such as exercise intolerance, fatigue, dry mouth, impotence, and drowsiness, are not reported as commonly.
  • In particular, these drugs have demonstrable clinical benefit for the treatment of hypertension, congestive heart failure, and a variety of kidney diseases, including diabetic nephropathy.
  • The combination of ACE inhibitors with thiazide or loop diuretics is excellent because they ameliorate some of the hypokalemia that can occur with diuretic use.
  • Nonetheless, the provisos listed regarding potassium-sparing diuretics apply here. In patients with renal insufficiency and on potassium supplements or potassium-sparing diuretics, use of ACE inhibitors can lead to lethal hyperkalemia.

Transfer

• Transfer generally is not required unless patients experience untreatable cardiac arrhythmias, digoxin toxicity, or paralysis and no facilities are available for monitoring. In general, even severe hypokalemia can be treated successfully in most medical centers.

Deterrence/Prevention

• Some authors advocate the routine use of potassium supplementation in patients with congestive heart failure. Undoubtedly, most patients will require potassium supplementation because they will be taking loop diuretics. However, recall the caveats concerning the use of potassium supplements, ACE inhibitors, and potassium-sparing diuretics in patients with subclinical renal failure.

Complications

• Cardiovascular complications are clinically the most important harbingers of significant morbidity or mortality from hypokalemia.
  • Although hypokalemia has been implicated in the development of atrial arrhythmias and ventricular arrhythmias, ventricular arrhythmias have received the most attention. Increased susceptibility to cardiac arrhythmias is observed with hypokalemia in the following settings:
    • Congestive heart failure
    • Underlying ischemic heart disease/acute myocardial ischemia
    • Aggressive therapy for hyperglycemia, such as with diabetic ketoacidosis
    • Digitalis therapy
    • Methadone therapy²¹
    • Conn syndrome²²
  • Low potassium intake has been implicated as a risk factor for the development of hypertension and/or hypertensive end-organ damage.
  • Hypokalemia leads to altered vascular reactivity, likely due to the effects of potassium depletion on the expression of adrenergic receptors, angiotensin receptors, and mediators of vascular relaxation. The result is enhanced vasoconstriction and impaired relaxation, which may play a role in the development of diverse clinical sequelae, such as ischemic central nervous system events or rhabdomyolysis.
• Muscle weakness, depression of the deep-tendon reflexes, and even flaccid paralysis can complicate hypokalemia. Rhabdomyolysis can be provoked, especially with vigorous exercise.  However, rhabdomyolysis has also been seen as a complication of severe hypokalemia, complicating primary hyperaldosteronism in the absence of exercise.²³
• Abnormalities of renal function often accompany acute or chronic hypokalemia.
  • This may include nephrogenic diabetes insipidus.
  • It also may include metabolic alkalosis due to impaired bicarbonate excretion and enhanced ammonia genesis.
  • Another may be cystic degeneration and interstitial scarring.
• Hypokalemia decreases gut motility, leading to or exacerbating an ileus.
• Hypokalemia also is a contributory factor in the development of hepatic encephalopathy in the setting of cirrhosis.
• Hypokalemia has a dual effect on glucose regulation.
  • Hypokalemia decreases insulin release.
  • It also decreases peripheral insulin sensitivity.
  • Clinical evidence suggests that the hypokalemic effect of thiazide is the causative factor in thiazide-associated diabetes mellitus.²⁴
• Hypokalemia has widespread actions in many organ systems, which, over time, result in cardiovascular disease.
  • Hypokalemia or potassium deficiency contributes to the development of hypertension.
  • Altered glucose metabolism due to impaired insulin release and peripheral sensitivity leads to altered lipid metabolism and endothelial cell dysfunction, increasing the risk of overt atherosclerosis.
  • The combined endothelial and vascular smooth-muscle cell dysfunction enhances vasoconstriction, increasing the likelihood of end-organ ischemia.
  • Treatment of hypertension with diuretics without due attention to potassium homeostasis exacerbates the development of end-organ damage by fueling the metabolic abnormalities.
  • These patients are then at higher risk for lethal hypokalemia under stress conditions such as myocardial infarction, septic shock, or diabetic ketoacidosis.

Prognosis

• The prognosis for hypokalemia depends entirely on the underlying cause. An acute episode due to diarrhea has an excellent prognosis. Hypokalemia due to a congenital disorder such as Bartter syndrome has a poor to nonexistent potential for successful treatment.

Patient Education

• Instruct patients on symptoms of hypokalemia or hyperkalemia.
  • Palpitations or notable cardiac arrhythmias
  • Muscle weakness
  • Increasing difficulty with diabetes control
  • Polyuria
• Instruct patients on the effects of medications, specifically, which of their drugs will produce serum potassium abnormalities in either direction. For example, tell patients to discontinue diuretics if nausea and vomiting or diarrhea occurs and to call the physician if such gastrointestinal losses persist. Depending on patients' underlying disease or diseases, sudden fluid losses can result in either hypokalemia or hyperkalemia if diuretics, potassium supplements, or antihypertensives are continued.
• Instruct patients on diet. High sodium intake tends to enhance renal potassium losses. Therefore, instruct patients about a low-sodium, high-potassium diet.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Low Potassium.

Miscellaneous

Medicolegal Pitfalls

• ECG monitoring is imperative for severe hypokalemia (<2 mg/dL in otherwise healthy individuals or <3 mg/dL in patients with known or suspected cardiac disease). With a sudden shift of potassium into the cells (eg, with insulin therapy for diabetic ketoacidosis), even individuals with healthy hearts can develop lethal arrhythmias. Continuously monitor patients on digoxin or those with digoxin toxicity.
• Cases of suspected inadequate intake as a cause of hypokalemia generally indicate abuse by self or others. Consider psychiatric evaluation for suspected alcoholism or an eating disorder. Consider referral to abuse authorities if neglect (particularly in the case of an elderly person) or intentional child abuse is suspected.
• Remember that the combination of potassium supplements, ACE inhibitors, angiotensin receptor blockers, and potassium-sparing diuretics has the potential to produce severe hyperkalemia. Patients taking drugs that can alter serum potassium levels require periodic follow-up care. The greater the number of medical problems and the greater the number of drugs, the more frequent the follow-up care should be. Failure to check potassium levels after alteration of 1 of these drugs could allow the patient to develop a lethal complication.

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