Hyperkalemia: Potassium Imbalance

• Potassium is the main intracellular cation.
• Intracellular K+ is maintained at high concentrations around 120mmol/l via active K+ intake and active Na+ expulsion by the Na+/K+ ATPase pump.
• Plasma K+ concentration is maintained at a low 3.5-5mmol/l.
• Potassium intake is exclusively dietary.
• The kidney is the main regulator of potassium balance, eliminating 90-95% of ingested K+, with the remainder excreted in feces and sweat.

Hyperkalemia

• Hyperkalemia occurs when plasma potassium is > 5 mmol/l.
• Must first rule out pseudo hyperkalemia, caused by K+ transfer to the extracellular sector from:
  • Hemolysis during a difficult blood draw with a tight tourniquet.
  • Wrist pumping during blood draw.
  • Delayed sample centrifugation.
  • Major hyperleukocytosis (> 100,000 elements/mm²).
• Hyperkalemia is common and represents a diagnostic and therapeutic emergency.

Diagnostics

• ECG shows diffuse progressive changes:
  • Tall, peaked, symmetrical T waves.
  • Reduced P wave amplitude progressing to disappearance.
  • Prolonged PR interval (AV block).
  • Widened QRS complex (intraventricular block).
  • Ventricular arrhythmias: VT or flutter, VF, then cardiac arrest.

Neuromuscular Manifestations

• Includes paresthesia of extremities and perioral region.
• Muscular hypotonia with weakness.
• Flaccid and symmetrical paralysis.
• Cranial nerve palsy and impaired deep sensation.

Biology

• Positive diagnosis requires a blood ionogram showing kalemia ≥ 5 mmol/l.
• Always rule out pseudo hyperkalemia:
  • Hemolysis during a difficult blood draw with a tight tourniquet.
  • Wrist pumping during blood draw.
  • Delayed sample centrifugation.
  • Major hyperleukocytosis (>100,000 elements/mm²).

Etiological Diagnosis

• Excess intake: rare if outside of chronic renal failure (CRF).
  • From oral or IV administration of massive K+ doses or rapid infusion.
  • Or massive transfusion.

Cellular Transfer

• Acute acidosis causes extracellular K+ transfer as H+ enters cells.
  • Kalemia increases by 0.5 mmol/l per 0.1 decrease in arterial pH.
• Uncontrolled diabetes mellitus:
  • Insulin deficit causes hyperkalemia. Insulin stimulates intracellular K+ transfer by activating the Na+/K+ ATPase pump.

Cellular Destruction

• Includes rhabdomyolysis and crush syndrome.
  • Also extensive burns, hemolysis, hypothermia, tumor lysis, and post-op revascularization syndrome.
• Medications inhibit the Na+/K+ ATPase pump, such as:
  • Digitalis.
  • Beta-blockers.
  • Alpha-adrenergic antagonists.

Issue with Renal Excretion of K+

• Can be related to:
  • Reduced glomerular filtration rate: acute renal failure or chronic renal failure.
• Acute Renal Failure:
  • Oligoanuric or anuric ARF is the most frequent cause hyperkalemia.
• Chronic Renal Failure:
  • K+ homeostasis is maintained until advanced CRF due to adaptations.
• Digestive secretion:
  • K+ secretion by the colon up to 30% of intake.
• Renal :
  • Secretion of K+ in the collecting duct of remaining nephrons.
• Adrenal insufficiency.
• Potassium retaining Medications :
  • ACE inhibitors (ACEi)
  • Angiotensin II receptor antagonists (ARAII)
  • Spironolactone.
  • Unfractionated Heparin ( decreasing angiotensin II receptors in the adrenal glomerulosa).

Treatment

• Obtain an ECG looking for electrical signs of hyperkalemia.
• Etiological diagnosis involves:
  • Ruling out pseudo hyperkalemia.
  • Assessing potassium intake.
  • Looking for factors that favor hyperkalemia.
  • Checking for cell lysis.
  • Testing for hypoaldosteronism.
• Treatment depends on the cause, severity, and risk of recurrence.

Indicators of Severe Hyperkalemia

• Presence of electrical signs on ECG, where even mild changes can rapidly progress to severe arrhythmias.
• Clinical signs of hyperkalemia.
• Underlying conditions, such as acute renal failure. Chronic renal failure can protect against hyperkalemia risks.

Aims of Treatment

• Correct hyperkalemia immediately.
• Simultaneously correct acidosis and hyponatremia, which potentiate hyperkalemia effects on the heart.

Cardiac Protection methods

• Calcium.
  • Does not alter kalemia.
  • Essential for patients with hyperkalemia displaying ECG changes.
  • Direct membrane antagonist of hyperkalemia (hyperpolarizes the membrane depolarized by hyperkalemia).
  • Give 1 amp of calcium salts IV over 5 minutes and repeat until ECG effect is seen.
  • Calcium chloride has better bioavailability but is more toxic to peripheral veins than calcium gluconate.
  • Immediate but temporary effect, repeat after 5 minutes with ECG monitoring.
  • Calcium is contraindicated in patients taking digitalis with Mg salts preferred.

Transfer of Potassium Intracellularly

• Glucose-Insulin Solution:
  • Insulin stimulates cellular K+ uptake by stimulating the Na+/K+ ATPase pump.
  • Use 10 IU of insulin per 50g of glucose (max 16 IU to avoid receptor saturation).
  • Ex: Infuse 500 cc of D10W (10% dextrose) with 10 IU insulin over 30 minutes, or 500 cc of D15W with 15 IU insulin.
  • Avoid infusing 30% dextrose for risk of hyperglycemia and vein toxicity.
  • Glucose infusions are paired with potassium supplementation to avoid hypoglycemia, unless pre-existing hyperglycemia.
  • Reduces kalemia by 0.7 to 1 mmol/l in 1-2 hours.
• Beta-Adrenergic Agonists:
  • Mainly salbutamol activates the Na+/K+ ATPase pump.
  • Use 10-20 mg in 4cc NS via nebulizer over 10 minutes.
  • Limited use in coronary patients due to risks of tachycardia and angina.
  • Synergistic effect with insulin lowers kalemia by 1.2 to 1.5 mmol/I.
• Alkalinization:
  • Sodium bicarbonate is no longer recommended for hyperkalemia due to risks of volume overload if patient is volume overloaded, vein toxicity, failure to correct chronic acidosis, and incompatibility with monotherapy.

Methods of Eliminating Potassium Excess

• Loop/Thiazide Diuretics:
  • Increases urinary K+ excretion.
  • Effect is delayed and modest with renal insufficiency.
  • Useful if there is volume overload.
• Ion Exchange Resin:
  • Exchanges K+ with another ion in the digestive mucosa.
  • 4+ hour delay before action.
  • Use 30-90 g daily via 2-6 doses 3-4 times daily.
  • Given rectally can risk digestive necrosis.
  • Not an emergency treatment and indicated for moderate chronic hyperkalemia.
• Extracorporeal Clearance:
  • Most effective and rapid technique for durable kalemia reduction.
  • During the 1st hour of high efficiency dialysis (HMD) using a low-K+ dialysate pulls 30-40 mmol of K+.
• A 4-hour dialysis session usually normalizes kalemia.
  • An 8-hour dialysis is required when rapidly progressive hyperkalemia results from a difficult-to-control cause, like rhabdomyolysis.
  • Indicated with life threatening hyperkalemia with electrical signs and oliguric ARF.
• Other measures:
  • Low K+ diet
  • Stop hyperkalemia-inducing treatments such as K+-sparing diuretics, ACE inhibitors, and ARBs (in patients with recent initiation and dehydration).
  • Correct Extracellular Volume Deficit by increasing distal Na+ delivery and renal K+ excretion and restore stable hemodynamics.
  • Correct metabolic acidosis.

Hypokalemia

• Defined by plasma potassium < 3.5 mmol/l.
• Often discovered incidentally and clinically silent.
• The kidneys are often responsible for hypokalemia.
• A diagnostic and therapeutic emergency because of its impact on the myocardium.

Diagnostic Indications

• ECG can show:
  • Diffuse ventricular repolarization disorders: U waves, flattened or inverted T waves, T-U wave double hump, ST segment depression, and prolonged QT interval.
  • Severe Rhythm Disturbances: atrial fibrillation, ventricular extrasystoles, ventricular tachycardia, ventricular fibrillation, and torsades de pointes.

Muscular Issues

• Striated muscle hypotonia, cramps, myalgias, tetany with associated hypomagnesemia, rhabdomyolysis if severe (K+ < 2mmol/l), paresis or ascending paralysis (lower limbs then respiratory muscles).
• Smooth muscle: gastrointestinal dysmotility, constipation, paralytic ileus, dysuria, and urinary retention.

Renal Signs

• Acute hypokalemia: no renal consequences.
• Chronic hypokalemia can cause:
  • Polyuria-polydipsia syndrome from decreased urine concentration due to tubular resistance to ADH where hypokalemia reduces aquaporin action.
  • Metabolic alkalosis from proximal HCO3- reabsorption, it is the most common metabolic disorder associated with hypokalemia.
  • Chronic interstitial nephritis with hypokalemia.

Biology

• Diagnosis is based on blood ionogram showing Serum potassium ≤ 3.5 mmol/l.

Etiological Diagnosis

• Potassium depletion by suppressing exogenous intake is rare because potassium is distributed widely in foods.
  • The rare instances include parentaral nutrition without potassium supplementation also abusive administration of ion exchange resins & severe undernutrition.
• Cellular Transfer:
  • Metabolic alkalosis is accompanied by hypokalemia as H+ entry drives K+ out.
  • Insulin stimulates the intracellular transfer of K+.
  • Beta-adrenergic stimulation from endogenous adrenaline release or beta2-agonist administration causes K+ transfer.
• Digestive Losses:
• Kaliuresis < 20 mmol/24 h points to extrarenal potassium loss.
  • Causes range from acute or chronic diarrhea.
  • Also villous tumors, digestive fistulas, vomiting, and gastric aspiration.
• Renal Loss:
  • Kaliuresis ≥ 20 mmol/24 h indicates renal potassium loss:
  • Can be associated with hypertension HTA:
    • Primary hyperaldosteronism from adrenal adenoma.
    • Secondary hyperaldosteronism via renal artery stenosis.
    • Also malignant hypertension, renin-secreting tumors, hypercorticism, Cushing’s syndrome, and corticosteroid therapy.
  • Not associated with hypertension:
  • Congenital tubulopathies like Gitelman's, Bartter's syndrome, tubular acidosis - also diuretics of the loop or thiazide family. Also look towards secondary hyperaldosteronism without hypertension (heart failure, cirrhosis, nephrotic syndrome) and polyuria.

Diagnostic approach

• Measure serum potassium < 3.5 mmol/l
• Rule out hypokalemia due to K+ transfer
• Evaluate renal K behaviour.
• Kaliuresis > 20 mmol/24hrs indicates inadequate renal compensation and points to renal losses.

Treatment

• Aim to correct K+ deficit and stop ongoing K+ losses.
• Causal treatment to correct the issue:
  • Stop hypokalemia inducing medications.
  • Treat any digestive disorders.
  • Correct hypomagnesemia or apply surgical intervention for adrenal adenomas.

Symptomatic treatment:

• Consists of potassium dietary adjustments and K supplements where needed to compensate any losses.
• Limit on going losses of K through K sparing diuretics and treat underlying conditions for best results.

Indications

• Management depends on level and presence of comorbidites:
  • Hypokalemia of 2.5-3mmol/L without other symptoms: Oral potassium supplementation can be enough with high amounts of potassium.
• Chlorure de K+ treatment
  • Potassium infusion based on ECG and symptoms.
• Severe Hypokalemia: 2.5mmol/L with symptoms then supplementation required
• Chlorure de K infusion
  • Be cautious not to be over 1g/hr otherwise side effects can occur.