Hyperkalemia

Hyperkalemia — a serum potassium above 5.0 mEq/L — is one of the most immediately life-threatening electrolyte disorders in clinical practice. It kills through cardiac arrhythmia: peaked T waves progress to PR prolongation, then QRS widening, then a sine wave pattern, then ventricular fibrillation or asystole.

The critical clinical principle is that the EKG, not the potassium level, determines urgency. A potassium of 6.2 mEq/L with a normal EKG is a different clinical situation than a potassium of 5.8 mEq/L with wide QRS complexes. The EKG reflects the effect of hyperkalemia on the myocardium — and that effect depends on the rate of rise, the baseline potassium, and concurrent electrolyte abnormalities.

Hyponatremia, hypocalcemia, and acidosis all potentiate the cardiac toxicity of hyperkalemia. A patient with a potassium of 5.9 mEq/L who is also hypocalcemic and acidotic is at higher risk than the number alone suggests. Always interpret the potassium in the context of the full electrolyte panel and the EKG.

Before treating hyperkalemia, confirm it is real. Pseudohyperkalemia is a falsely elevated potassium caused by potassium release from cells during or after blood collection. It is common and frequently missed.

Hemolysis is the most common cause — red blood cells rupture during venipuncture, especially with difficult draws, small-gauge needles, or prolonged tourniquet time, releasing intracellular potassium into the sample. Thrombocytosis (platelet count above 500,000) and leukocytosis (WBC above 100,000) can also cause pseudohyperkalemia as platelets and white cells release potassium during clotting.

If pseudohyperkalemia is suspected, repeat the potassium on a fresh, atraumatic sample — ideally without a tourniquet. A plasma potassium (collected in a heparinized tube, which prevents clotting) will be lower than the serum potassium in true thrombocytosis-related pseudohyperkalemia. If the repeat is normal and the patient has no EKG changes, no treatment is needed.

Hyperkalemia results from three mechanisms: decreased renal excretion, transcellular shift of potassium from intracellular to extracellular space, and — rarely in isolation — excess intake.

Decreased renal excretion is the most common mechanism in clinical practice. The kidney is responsible for excreting 90% of daily potassium load. Any cause of reduced GFR — AKI, CKD, or reduced effective arterial blood volume — impairs potassium excretion. Medications that block the renin-angiotensin-aldosterone system (ACE inhibitors, ARBs, aldosterone antagonists like spironolactone) reduce aldosterone-mediated potassium excretion. Potassium-sparing diuretics (triamterene, amiloride) block the epithelial sodium channel in the collecting duct, reducing potassium secretion. Type IV renal tubular acidosis — hypoaldosteronism, most commonly from diabetic nephropathy — is a classic cause of mild, persistent hyperkalemia.

Transcellular shift moves potassium out of cells without changing total body potassium. Acidosis is the most clinically important cause — for every 0.1-unit fall in pH, potassium rises by approximately 0.5–0.7 mEq/L as hydrogen ions enter cells and potassium exits to maintain electroneutrality. Insulin deficiency (as in diabetic ketoacidosis) removes a key driver of cellular potassium uptake. Beta-2 adrenergic blockade reduces cellular potassium uptake. Tissue necrosis — rhabdomyolysis, tumor lysis syndrome, massive hemolysis — releases large amounts of intracellular potassium.

Excess intake alone rarely causes hyperkalemia in patients with normal renal function — the kidney can excrete a large potassium load efficiently. It becomes clinically relevant when combined with impaired excretion: a patient with CKD stage 4 who eats a high-potassium diet, or a patient on an ACE inhibitor who receives a large potassium supplement.

The treatment of hyperkalemia follows three sequential steps: membrane stabilization, transcellular shift, and elimination. These are not interchangeable — they work through different mechanisms and have different time courses.

Membrane stabilization with calcium is the first and most urgent intervention when EKG changes are present. Calcium gluconate (or calcium chloride, which delivers more elemental calcium but is more caustic) does not lower the potassium — it raises the threshold potential of cardiac myocytes, counteracting the depolarizing effect of hyperkalemia. The effect begins within minutes and lasts 30–60 minutes. It buys time for the other interventions to work. Calcium should be given whenever there are EKG changes — peaked T waves, PR prolongation, QRS widening — regardless of the potassium level.

Transcellular shift moves potassium back into cells temporarily. Insulin (typically 10 units regular insulin IV) drives potassium into cells via the Na-K-ATPase pump. It must always be paired with dextrose (25–50 g IV) to prevent hypoglycemia — except in patients with glucose above 250 mg/dL. The effect begins within 15–30 minutes and lasts 4–6 hours. Inhaled albuterol (10–20 mg nebulized) also drives potassium into cells via beta-2 receptor stimulation and is additive to insulin. Sodium bicarbonate shifts potassium in the setting of metabolic acidosis but is less reliable as a standalone intervention.

Elimination removes potassium from the body. Loop diuretics (furosemide) increase renal potassium excretion in patients with adequate renal function and urine output. Sodium polystyrene sulfonate (Kayexalate) and patiromer are cation exchange resins that bind potassium in the GI tract — their onset is hours, making them unsuitable for acute management but useful for ongoing control. Hemodialysis is the most effective and reliable method of potassium removal and is indicated in severe hyperkalemia with renal failure, refractory cases, or hemodynamic instability.

Acute treatment of hyperkalemia addresses the immediate threat — it does not fix the underlying cause. After stabilization, the focus shifts to identifying and correcting the precipitant and preventing recurrence.

Review the medication list. ACE inhibitors, ARBs, aldosterone antagonists, potassium-sparing diuretics, NSAIDs, and trimethoprim are among the most common contributors. In patients with CKD or heart failure who require RAAS blockade, the risk-benefit balance must be reassessed — but these medications should not be reflexively discontinued without considering the cardiovascular and renal protective benefits.

Dietary potassium restriction is appropriate for patients with CKD or persistent hyperkalemia — typically below 2,000–2,500 mg per day. High-potassium foods include bananas, oranges, potatoes, tomatoes, beans, and salt substitutes (which often contain potassium chloride). Salt substitutes are a frequently overlooked source of potassium in patients who are trying to reduce sodium intake.

Patiromer and sodium zirconium cyclosilicate (SZC) are newer potassium binders with more predictable pharmacokinetics and better tolerability than sodium polystyrene sulfonate. They are appropriate for chronic management of hyperkalemia in patients with CKD or heart failure on RAAS inhibitors — and they have enabled continuation of RAAS therapy in patients who previously had to discontinue it due to hyperkalemia.