• Hypokalemia is defined as a plasma potassium (K⁺) concentration <3.5 mEq/L (normal 3.5–5 mEq/L). Causes include K⁺ loss or intracellular shifting. Symptoms range from arrhythmias to myalgias to respiratory depression.
• Hypokalemia may be a poor indicator of total body stores because of its asymmetric body distribution. Ninety-eight percent of the body's potassium is located intracellularly (75% in muscle, 6% in red blood cells, and 5% in the liver). The remaining 2% is located in the intravascular and extracellular compartments (2).
• Patients commonly present for surgery with low K⁺ levels, which is the most common electrolyte abnormality in hospitalized patients. Anaesthetists must be able to determine when and how a patient should be managed with such abnormalities.

• The majority of the body's potassium stores are located intracellularly.
• The membrane resting potential is an electrochemical gradient that plays a role in transport, signal transduction, myocardial pacemakers and contraction, and cell volume homeostasis. Consequently, there are several mechanisms that serve to maintain intravascular concentrations within a tight range.
  • The Na⁺–K⁺–ATPase enzyme pump (embedded in the cell membrane) moves 3 Na⁺ ions extracellularly and 2 K⁺ ions intracellularly. The exchange requires the expenditure of 1 adenosine triphosphate (ATP). The electrochemical gradient is manifested by an intracellular concentration of 150 mEq/L (intravascular concentration is ~3.5–5 mEq/L).
• Additional mechanisms: K⁺ concentrations between the two compartments are also affected by pH, insulin, and catecholamines or sympathomimetics with beta-adrenergic receptor activity.
  • pH: The Na⁺–H⁺ ion exchange facilitates buffering against alkalemia or acidemia. In alkalemia, H⁺ ions move extracellularly to offset the disturbance and Na⁺ moves intracellularly. This increase in intracellular Na⁺ stimulates the Na⁺–K⁺–ATPase, which results in a secondary intracellular shift of K⁺. Conversely, in acidemia, H⁺ ions move intracellularly, in exchange for Na⁺ moving extracellularly. This reduces intracellular shifting of K⁺ via the Na⁺–K⁺–ATPase (can result in hyperkalemia).
  • Insulin: Activates the Na⁺–K⁺–ATPase in cells, causing an intracellular shift of K⁺.
  • Beta-adrenergics: Activate adenylyl cyclase and increase cAMP levels, which then activate protein kinase A. Results in activation of calcium-gated K⁺ channels as well as Na⁺–K⁺–ATPase.
• K⁺ excretion: In addition to intracellular shifting, K⁺ levels are also regulated by the kidneys (90%), the gastrointestinal (GI) tract, and sweat. Aldosterone, a mineralocorticoid, lowers plasma K⁺ concentration at several levels in the renal tubule.

• Although the resting membrane potential is maintained by the Na⁺–K⁺–ATPase, certain cells exert their functional capacity via depolarization.
  • Pacemaker cells spontaneously depolarize to produce an electrical signal that travels to conduction cells and adjacent myocardial muscle cells in a domino-like fashion. Repolarization (Phase 3) is primarily via potassium efflux.
  • Myocardial muscle cells depolarize in response to adjacent pacemaker or muscle cells. Electrical depolarization is coupled to mechanical contraction and blood being pumped. Repolarization is mediated via potassium efflux; however, it is divided into an early (Phase 1) and late (Phase 3) phase by an extended plateau.
  • Nerve cells communicate and transmit their signal via electrical signaling that involves changes in resting membrane potential. Repolarization occurs via potassium efflux.

• Hypokalemia is defined as a serum [K⁺] <3.5 mEq/L. This disturbance is the result of either reduced total body stores or redistribution into the intracellular space.
• Reduced total body stores may result from reduced intake or increased excretion (renal or extrarenal).
  • Reduced intake: The minimum daily requirement is 40–50 mEq/day
  • Increased renal excretion: Type I and II renal tubular acidosis, diuretic therapy, carbonic anhydrase inhibitors, ureterosigmoidostomy, posthypercapnia, increased mineralocorticoid activity (aldosterone), and hemodialysis
  • Increased extrarenal excretion: Diarrhea, vomiting and nasogastric suction, increased sweat loss, and laxative abuse
• Intracellular shifting can occur perioperatively via alkalemia, exogenous insulin administration, and beta-adrenergics.
  • Alkalemia: Hyperventilation results in hypocarbia, and can be caused perioperatively by controlled mechanical ventilation (increased respiratory rate or tidal volume), stimulation, or pain. Another cause is excessive bicarbonate administration.
  • Exogenous insulin may be administered for glucose control. Hyperalimentation may increase endogenous insulin release.
  • Beta-adrenergics may be administered as catecholamines or sympathomimetics (epinephrine, dobutamine, isoproterenol, and ephedrine). Nebulizers and inhalers for the treatment of COPD or asthma. Thyrotoxicosis causes excessive beta-adrenergic stimulation.
• Clinical manifestations of hypokalemia result from hyperpolarization of cell membranes, as well as from prolongation of action potentials and refractory periods. Thus, it primarily affects cardiac, skeletal muscle, GI, and renal systems.
  • Cardiac: Dysrhythmias (premature atrial contractions, premature ventricular contractions, AV block, ventricular tachycardia, ventricular fibrillation), conduction defects (increased PR and QT intervals, reduced T wave amplitude, T wave inversion or U waves, and ST segment depression), and potentiation of digitalis toxicity.
  • Skeletal muscle: Weakness, paralysis, rhabdomyolysis, fasciculations, and tetany (typically do not manifest until the serum [K⁺] is <3 mEq/L)
  • GI: Ileus, constipation
  • Renal: Metabolic alkalosis, nephrogenic diabetes insipidus, impaired urinary concentrating abilities, increased NH₃ production, and hypokalemic nephropathy.
• Acute changes are less well tolerated than chronic changes.
• Correlation between serum and total body K⁺ is not exact and may be difficult to extrapolate. It is estimated that in chronic hypokalemia reduced plasma levels of 1 mEq/L can equal a total body deficit of 200–400 mEq (1).

• Mild hypokalemia (3.0–3.5 mEq/L) does not typically require urgent correction (2).
• [K⁺] <3.0 mEq/L often requires K⁺ replacement. Of note, values greater than or equal to 2.6 mEq/L have not been shown to increase morbidity or mortality in patients undergoing anesthesia.
• [K⁺] between 2.0 and 2.5 mEq/L are likely to cause arrhythmias and muscular weakness; furthermore, it can potentiate the effects of neuromuscular blocking agents and can delay recovery.
• Potassium replacement. Oral and IV preparations are available. Perioperative correction often involves IV KCl preparations. The maximum recommended rate of infusion is 10–20 mEq/hour (peripheral IV: 10 mEq/hour; central line access 20 mEq/hour). Higher rates of administration carry the risk of hyperkalemia or arrhythmias.
• Magnesium replacement should be concurrently performed.
• Delay or proceed? The decision to delay for further optimization versus proceeding depends upon:
  • Urgency of surgery. Urgent or emergent surgery may be performed with careful EKG monitoring and avoidance of hyperventilation, alkalosis, and beta-adrenergics. K⁺ replacement should be undertaken. In the event that arrhythmias or EKG changes manifest, boluses of 1 mEq may be administered while monitoring for resolution.
  • Acute versus chronic onset. When patients present preoperatively with hypokalemia, a determination of its onset should be attempted. Review old laboratory values.
  • Clinical manifestations should be assessed
  • EKG changes
  • Need for perioperative hyperventilation. Intracranial surgical procedures may require intracranial pressure optimization via hyperventilation (hypocarbia). Additionally, the use of mannitol or furosemide to provide "brain relaxation" can further decrease potassium levels (excreted by the kidneys). Attempts to correct potassium should be undertaken prior to surgery. In the event that the patient's clinical condition deteriorates, proceed as discussed above for urgent/emergent surgery.
  • Need for beta-adrenergic agents

• Hyperkalemia
• Buffering Systems
• Cardiac Action Potential
• QT Prolongation

276.8 Hypopotassemia

E87.6 Hypokalemia

Matthew C. Gertsch , MD

Nina Singh-Radcliff , MD