Dott. M. M. Ciammaichella
Dirigente Medico
SC Medicina Interna I° per l'Urgenza
(Direttore: Dott. G. Cerqua)
A.C.O. S. Giovanni – Addolorata, Roma, Italia


 

HYPERKALEMIA

 

KEY-WORDS: Hyperkalemia

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INTRODUCTION
CLINICAL
WORKUP
TREATMENT
MEDICATION
FOLLOW-UP
MISCELLANEOUS
BIBLIOGRAPHY

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INTRODUCTION

Background: Hyperkalemia is a potentially life-threatening illness which can be difficult to diagnose clinically because of the paucity of reliable signs and symptoms. The physician must have a high suspicion in patients who are at risk for this disease process and quickly perform an ECG to ascertain whether electrocardiographic signs of hyperkalemia are present.

Pathophysiology: Potassium is one of the body's major ions. Nearly 98% is intracellular with the concentration gradient maintained by the Na/K ATPase pump. The ratio of intracellular to extracellular potassium is important in determining the cellular membrane potential. Small changes in the extracellular potassium level can have profound effects on the function of the cardiovascular and neuromuscular systems. The normal potassium level is 3.5-5.0 mEq/L and total body potassium stores are approximately 50 meq/kg (3500 mEq in a 70-kg person).

Minute to minute control of potassium is controlled by intracellular to extracellular exchange, mostly by the sodium-potassium pump which is controlled by insulin and beta-2 receptors. Long term potassium balance is achieved by a balance of gastrointestinal intake and renal potassium excretion. Hyperkalemia is defined as a potassium level greater than 5.5 mEq/L. The range for a mild condition is 5.5-6.0 mEq/L, moderate 6.1- 7.0 mEq/L and severe 7.0+ mEq/L.

Hyperkalemia resultsfrom the following:

1. Decreased or impaired potassium excretion as seen with acute or chronic renal failure (most common), potassium sparing diuretics, urinary obstruction, sickle cell disease, Addison's disease, and SLE.

2. Additions of potassium into extracellular space as seen with potassium supplements (oral or IV potassium, salt substitutes), rhabdomyolysis, and hemolysis (i.e., venipuncture, blood transfusions, burns, tumor lysis).

3. Transmembrane shifts (shifting potassium from the intracellular to extracellular space) as seen with acidosis and medication effects (acute digitalis toxicity, beta blockers, succinylcholine).

4. Factitious or pseudohyperkalemia as seen with improper blood collection (ischemic blood draw from venipuncture technique), laboratory error, leukocytosis, and thrombocytosis.


Frequency:

  • In the US: Hyperkalemia is diagnosed in 1-8% of hospitalized patients.

Mortality/Morbidity:

  • The primary cause of morbidity and mortality is potassium's effect on cardiac function.
  • Reported death rates rate range up to 67% if severe hyperkalemia is untreated.
Sex: Male = Female

 

 

CLINICALPATHOPHYSIOLOGY

History:

  • The findings of hyperkalemia can be subtle since complaints may be vague.
  • Hyperkalemia is frequently discovered as an incidental laboratory finding.
  • Cardiac and neurological complaints predominate.
  • Patients may be asymptomatic or complain of generalized fatigue, weakness, paresthesias, paralysis or palpitations.
  • Hyperkalemia should be suspected in any patient with a predisposition toward an elevated potassium.
    • Acute or chronic renal failure, dialysis
    • Trauma, including crush injuries (rhabdomyolysis) or burns
    • Ingestion of foods high in potassium, such as bananas, oranges, high protein diets, tomatoes and salt substitutes
    • Medications such as potassium supplements, potassium sparing diuretics, NSAIDs and beta blockers. Digoxin toxicity can also predispose to hyperkalemia.

Physical:

  • Evaluation of vital signs is essential to determine hemodynamic stability and the presence of cardiac arrhythmias related to the hyperkalemia.
  • Cardiac examination may reveal extrasystoles, pauses or bradycardia.
  • Neurological examination may reveal diminished deep tendon reflexes or decreased motor strength.
  • In rare cases, muscular paralysis and hypoventilation may be seen.
  • Search for stigmata of renal failure such as edema and dialysis sites (e.g., A-V fistulas or tenkoff catheters).
  • Look for signs of trauma that suggest rhabdomyolysis.

Causes:

  • Pseudohyperkalemia:

    Hemolysis (in lab tube) (most common)

    Thrombocytosis

    Leukocytosis

    Venipuncture technique (i.e., ischemic blood draw from prolonged tourniquet application)
  • Redistribution:

    Acidosis

    Insulin deficiency

    Beta blocker drugs

    Acute digoxin intoxication or overdose

    Succinylcholine

    Arginine hydrochloride

    Hyperkalemic familial periodic paralysis
  • Excessive Endogenous Potassium Load:

    Hemolysis

    Rhabdomyolysis

    Internal hemorrhage
  • Excessive Exogenous Potassium Load:

    Parenteral administration

    Excess in diet

    Potassium supplements

    Salt substitutes
  • Diminished Potassium Excretion:

    Decreased glomerular filtration rate (acute or end-stage chronic renal failure)

    Decreased mineral corticoid activity

    Defect in tubular secretion (renal tubular acidosis II and IV)

    Drugs (i.e., NSAIDs, cyclosporine, potassium-sparing diuretics

  • Laboratory error

 

 



WORKUP

Lab Studies:

  • Potassium level
    • The relationship between serum potassium and symptoms is not consistent. For example, patients with a chronically elevated potassium level may be asymptomatic at much higher levels than other patients. The rapidity of change in the potassium level is what influences the symptoms seen at various potassium levels.
  • BUN and creatinine for evaluation of renal status
  • Calcium level if patient has renal failure since hypocalcemia can exacerbate cardiac rhythm disturbances
  • Glucose level in patients with diabetes mellitus
  • Digoxin level if the patient is on a digitalis medication
  • Arterial blood gas (ABG) if acidosis is suspected

Other Tests:

  • Continuous cardiac monitoring is indicated for evaluation of rhythm disturbances.
  • An electrocardiogram (ECG) is essential and can be instrumental in diagnosing hyperkalemia in the appropriate clinical setting. ECG changes have a sequential progression of effects, which roughly correlate with the potassium level. The following ECG findings may be observed:
    • Early changes of hyperkalemia include peaked T waves, shortened QT interval and ST segment depression.
    • The above changes are following by bundle branch blocks causing a widening of the QRS complex, increases in the PR interval and decreased amplitude of the P wave.
    • Eventually, the P wave disappears and the QRS morphology widens to resemble a sine wave with ventricular fibrillation or asystole ultimately occurring.
    • ECG findings generally correlate with the potassium level but potentially life-threatening arrhythmias can occur without warning at almost any level of hyperkalemia.
  • Cortisol and aldosterone levels to check for mineralcorticoid deficiency when other causes are ruled out

 


TREATMENT

Emergency Department Care:

  • When the diagnosis is suspected or laboratory values indicative of hyperkalemia are received, continuous ECG monitoring with frequent vital sign checks should be performed.
  • The initial management includes assessment of the ABCs and prompt evaluation of the patient's cardiac status with an ECG.
  • Discontinue any potassium-sparing drugs or dietary potassium.
  • If the hyperkalemia is severe (potassium > 7.0 mEq/l) and/or the patient is symptomatic, treatment should be started before diagnostic investigation of the underlying cause. Treatment should be individualized based upon the patient's presentation, potassium level and ECG. Not all patients should receive every medication listed in the therapy section. Patients with mild hyperkalemia, for example, may only need to have excretion enhanced.
Consultations: Consult a nephrologist or the dialysis team for either severe symptomatic hyperkalemia or patients with renal failure. Admit these patients to an intensive care unit.

 

 

MEDICATION

Treatment is directed at stabilizing the myocardium, shifting potassium from the extracellular environment to the intracellular compartment and promoting the renal excretion and gastrointestinal loss of potassium.

Drug Category: Electrolyte supplements - These agents are used to treat hyperkalemia and reduce the risk of ventricular fibrillation caused by hyperkalemia.


Drug Name

Calcium Chloride or Calcium Gluconate - This is the first drug to be used for severe hyperkalemia (potassium over 7.0 mEq/L) when the ECG also manifests significant abnormalities such as widening of the QRS interval, loss of the p wave, or cardiac arrhythmias. Most clinicians do not treat an ECG which only demonstrates peaked T waves with calcium emergently. Calcium increases the threshold potential and restores the relationship with the elevated resting membrane potential that is seen in hyperkalemia.
One ampule of calcium chloride has approximately three times as much calcium as calcium gluconate. The onset of action is less than 5 min and lasts about 30-60 min. A repeat dose may be given if the ECG changes have not normalized.

Adult Dose

Calcium gluconate: 10 mL of a 10% soln IV over 2 min
Calcium chloride: 5 mL of a 10% soln IV over 2 min
The doses should be titrated with constant monitoring of ECG changes during administration.

Pediatric Dose

Calcium chloride: 0.2 mL/kg/dose of a 10% soln IV over 5 minutes up to the maximum dose of 5 mL
Calcium gluconate: 100 mg/kg (1 mL/kg) of a 10% soln IV over 3-5 minutes up to a maximum dose of 10 mL
Stop the infusion if bradycardia develops.

Contraindications

In the patient with hyperkalemia who also has digoxin toxicity, calcium preparations can enhance the effects of the cardiac glycoside by causing arrhythmias and should therefore be avoided.
Do not administer to patients with hypercalcemia.

Interactions

Calcium may also decrease the effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones. Administered IV, calcium antagonizes the effects of verapamil.
It may react with phosphorous to cause deposition of cancellus material.

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Exercise caution when administering to digitalized patients and those with respiratory failure or acidosis and with severe hyperphosphatemia.

Drug Category: Antidotes - Insulin is given with glucose to facilitate the uptake of glucose into the cell bringing potassium with it.


Drug Name

Dextrose - Glucose and insulin temporarily shift potassium intracellularly with these effects occurring within the first 30 min of administration.

Adult Dose

1-2 amps D50W and 5-10 u of regular insulin IV

Pediatric Dose

0.5 g/kg (2 mL/kg) of a 25% dextrose solution with 0.1 u/kg regular insulin (1 unit regular insulin per 5 g of glucose) IV over 30 minutes

Contraindications

Do not administer glucose in the diabetic patient who already has an elevated blood sugar.

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Hypertonic dextrose solutions when administered via peripheral veins may cause thrombosis.
Exercise caution in patients diagnosed with subclinical diabetes mellitus, or carbohydrate intolerance.
Monitor fluid balance, glucose, electrolytes, and acid-base balance closely.


Drug Name

Insulin - Insulin stimulates the cellular uptake of potasium within 20-30 min. Glucose should be administered along with the insulin to prevent hypoglycemia with blood sugar levels being monitored frequently.

Adult Dose

IV: 5-10 u of regular insulin and 1-2 amps of D50W bolus

Pediatric Dose

0.5 g/kg (2 mL/kg) of a 25% dextrose solution with 0.1 u/kg regular insulin (1 unit regular insulin per 5 g of glucose) IV over 30 minutes

Contraindications

Avoid use in patients diagnosed with hypoglycemia.

Pregnancy

A - Safe in pregnancy

Precautions

Monitor glucose carefully. Dose adjustments of insulin may be necessary in patients diagnosed with renal and hepatic dysfunction.

Drug Category: Alkalinizing agents - Increases the pH which results in a temporary potassium shift from the extracellular to the intracellular environment. These agents also enhance the effectiveness of insulin in patients with acidemia.


Drug Name

Sodium Bicarbonate - The bicarbonate ion produced when it dissociates neutralizes the hydrogen ions and raises urinary and blood pH. Its onset of action is within minutes and lasts approximately 15-30 min. The blood pH should be monitored to avoid excess alkalosis.

Adult Dose

1 mEq/kg, up to 50-100 mEq through a slow IV push or a continuous IV drip.

Pediatric Dose

1-2 mEq/kg IV over 5-10 minutes
Monitor ABGs to avoid arterial pH over 7.55.

Contraindications

Avoid use in patients diagnosed with alkalosis, hypernatremia, hypocalcemia, and severe pulmonary edema.

Interactions

This treatment may decrease the therapeutic levels of lithium, chlorpropamide, methotrexate, tetracyclines, and salicylates due to urinary alkalinization.

Pregnancy

A - Safe in pregnancy

Precautions

The rapid administration of this medication may result in paradoxical CSF, intracellular acidosis, hypokalemia, impaired O2 delivery, and hypocalcemia. Other complications, such as hypernatremia, overshoot alkalosis, and hyperosmolality, may also occur.
It is important to exercise caution in individuals susceptible to electrolyte imbalances such as patients with CHF, cirrhosis, or renal failure. Avoid extravasation since sodium bicarbonate can cause tissue necrosis.

Drug Category: Beta Agonists - Promote cellular reuptake of K+, possibly via the cyclic gAMP receptor cascade.


Drug Name

Albuterol - It is an adrenergic agonist that also increases plasma insulin concentrations. The increase in insulin may in turn help in shifting potasium into the intracellular space.
It has been found to lower the K+ level by 0.5-1.5 mEq/L and can be very beneficial in renal failure patients where fluid overload is a concern. The onset of action is 30 min and the duration of action is 2-3 h.

Adult Dose

2.5 mg mixed with 3 mg NS via high flow nebulizer q 20 min as tolerated

Pediatric Dose

<1 yr: 0.05-0.15 mg/kg/dose with 3 mg NS nebulized 1-5 yr: 1.25-2.5 mg/dose with 3 mg NS nebulized 5-12 yr: 2.5 mg/dose with 3 mg NS nebulized >12 yr: 2.5-5 mg/dose with 3 mg NS nebulized

Contraindications

Avoid its use in patients with hypersensitivity to albuterol or adrenergic amines.

Interactions

Beta-adrenergic blockers antagonize the effects of this medication.
The cardiovascular effects of this medication may increase when administered concurrently with MAO inhibitors, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents.

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Use with caution in patients diagnosed with hyperthyroidism, diabetes mellitus, or cardiovascular disorders.
Watch for tachycardia, nervousness and other signs of beta agonists side effects.

Drug Category: Diuretics - These agents cause the loss of potassium through the kidney.


Drug Name

Furosemide - The effect of diuretics are slow and frequently take an hour to begin. They lower the potassium level by an inconsistent amount.

Adult Dose

40 mg IV push
The dose may need to be doubled in renal failure.

Pediatric Dose

IV: 0.5-2 mg/kg/dose; do not exceed 2 mg/kg/dose in neonates or 6 mg/kg/dose in infants and children

Contraindications

Avoid use in patients with anuria.

Interactions

Metformin decreases furosemide concentrations. Conversely, furosemide interferes with the hypoglycemic effect of antidiabetic agents. It also antagonizes the muscle relaxing effect of tubocurarine.
Auditory toxicity appears to be increased with the concurrent use aminoglycosides and furosemide. Hearing loss of varying degrees may occur.
The anticoagulant activity of warfarin may be enhanced, when taken concurrently with this medication.
Increased plasma lithium levels and toxicity are possible when taken concurrently with this medication.

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Avoid the use in patients who are hypoveolemic and monitor for evidence of blood, renal, or hepatic dysfunction.
Loop diuretics may increase the urinary excretion of magnesium and calcium.

Drug Category: Binding Resins - Promote exchange of K+ for Na+ in the gastrointestinal system.


Drug Name

Sodium Polystyrene Sulfonate  - Exchanges sodium for potassium and binds it in the gut, primarily in the large intestine and decreases total body potassium. The onset of action after oral administration ranges from 2-12 h, and is longer when administered rectally.
Lowers K+ over 1-2 h with a duration of action of 4-6 h. The potassium level drops by approximately 0.5-1.0 mEq/L. Multiple doses of kayexalate are usually necessary.

Adult Dose

25-50 g mixed with 100 ml of 20% sorbitol PO or PR

Pediatric Dose

1 g/kg/dose PO or PR

Interactions

Systemic alkalosis may occur if administered concurrently with magnesium hydroxide, aluminum carbonate or similar antacids and laxatives.

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Use caution when administering to patients who can be adversely affected by a small increase in sodium loads such as severe hypertension, severe congestive heart failure, and marked edema.
Constipation, with the possibility of fecal impaction may occur. Rare instances of colonic necrosis have been reported.


 

 

FOLLOW-UP

Further Inpatient Care:

  • Continuous cardiac monitoring for patients who are hyperkalemic. Definitive therapy is dialysis in patients with renal failure or where pharmacological therapy is not working.
  • Monitor serial potassium levels.
  • Resolve acid-base problems.
  • Correct co-existent electrolyte disturbances.
  • Treat digoxin toxicity, if present.

Further Outpatient Care:

  • Adjust diet to decrease potassium dietary load.
  • Adjust medications that predispose or exacerbate hyperkalemia.
  • Repeat potassium level tests in two to three days.
  • Re-evaluate renal function if signs of renal insufficiency.

Transfer:

  • If unable to correct the hyperkalemia with pharmacological therapy and dialysis is not available, the patient should be stabilized and transferred to a center where dialysis can be performed.

Deterrence/Prevention:

  • Avoid foods high in potassium.
  • Avoid medications that predispose to hyperkalemia.

Complications:

  • Life-threatening cardiac arrhythmias
  • Hypokalemia may result from the treatment of hyperkalemia

Prognosis:

  • Full resolution with correction of the underlying etiology
  • Reduction of plasma potassium should begin within the first hour of initiation of treatment.

Patient Education:

  • Pursue diet modification.
  • Discontinue use of medications that may worsen hyperkalemia.

  • Encourage adherence to dialysis schedule if the patient is noncompliant.

 


MISCELLANEOUS

Medical/Legal Pitfalls:

  • Assess and treat the patient, not the potassium level. Ascertain whether the elevated potassium level is real or factitious.
  • Continuous ECG monitoring if the patient is found to be hyperkalemic.
  • An ECG is essential to assess for cardiac conduction disturbances related to hyperkalemia.
  • Severe hyperkalemia with ECG changes is a life-threatening emergency. Calcium chloride is the initial treatment of choice to stabilize the cardiac membrane and can be given more than once if the ECG continues to demonstrate an abnormally widened QRS complex
  • Medications such as calcium, insulin, glucose and sodium bicarbonate are temporizing measures. Definitive loss of excess potassium can only be obtained with resin binding agents, dialysis or increased renal excretion. Begin administration of a resin-binding agent soon after the other drugs have been given.
  • Watch for over-correction of potassium level.
  • In diabetic ketoacidosis (DKA), and in many other types of metabolic acidosis, the potassium level is elevated secondarily to acidemia. Once the clinician initiates therapy for DKA, the potassium level will decrease.

  • Evaluate for digitalis toxicity if the patient is taking digoxin.

 

 



BIBLIOGRAPHY

  • Allon M, Dunlay R, Copkney C: Nebulised albuterol for acute hyperkalemia in patients on hemodialysis. Annals of Internal Medicine 1989; 110: 426-429.
  • Commerford PJ, Lloyd EA: Arrhythmias in patients with drug toxicity, electrolyte, and endocrine disturbances. Medical Clinics of North America 1984; 68: 1051-1078.
  • Mandal AK: Hypokalemia and Hyperkalemia. Medical Clinics of North America 1997; 81(3): 611-639.
  • Mitch WE, Wilcox CS: Disorders of body fluids, sodium and potassium in chronic renal failure. Am J Med 1982 Mar; ID - AM 00750/AM/NIADDK(3): 536-50.
  • Moore ML, Bailey RR: Hyperkalaemia in patients in hospital. N Z Med J 1989 Oct 25; 102(878): 557-8.
  • Nijsten MWN, de Smet BJGL, Dofferhoff ASM: Psuedohyperkalemia and Platelet Counts (letter). New England Journal of Medicine 1991; 325: 1107.
  • Oster JR, Perez GO, Vaamonde CA: Relationship between blood pH and potassium and phosphorus during acute metabolic acidosis. Am J Physiol 1978 Oct; 235(4): F345-51.
  • Pruitt BA, Goddwin CW, Vaughan GM, et al: The metabolic problems of the burn patient. Acta Chir Scand 1985; 522: 119-139.
  • Williams ME: Hyperkalemia. Critical Care Clinic 1991; 7: 155-174.
  • Zull DN: Disorders of Potassium Metabolism. Emergency Medicine Clinics of North America 1989; 7(4): 771-794