Determinants of hypokalemia following hypertonic sodium bicarbonate infusion

The hypokalemic response to alkali infusion has been attributed to the resulting extracellular fluid (ECF) expansion, urinary potassium excretion, and internal potassium shifts, but the dominant mechanism remains uncertain. Hypertonic NaHCO₃ infusion (1 N, 5 mmol/kg) to unanesthetized dogs with normal acid-base status or one of the four chronic acid-base disorders decreased plasma potassium concentration ([K⁺]_p) at 30 min in all study groups (Δ[K⁺]_p, - 0.16 to - 0.73 mmol/L), which remained essentially unaltered up to 90-min postinfusion. ECF expansion accounted for only a small fraction of the decrease in ECF potassium content, (K⁺)_e. Urinary potassium losses were large in normals and chronic respiratory acid-base disorders, limited in chronic metabolic alkalosis, and minimal in chronic metabolic acidosis, yet, ongoing kaliuresis did not impact the stability of [K⁺]_p. All five groups experienced a reduction in (K⁺)_e at 30-min postinfusion, Δ(K⁺)_e remaining unchanged thereafter. Intracellular fluid (ICF) potassium content, (K⁺)_i, decreased progressively postinfusion in all groups excluding chronic metabolic acidosis, in which a reduction in (K⁺)_e was accompanied by an increase in (K⁺)_i. We demonstrate that hypokalemia following hypertonic NaHCO₃ infusion in intact animals with acidemia, alkalemia, or normal acid-base status and intact or depleted potassium stores is critically dependent on mechanisms of internal potassium balance and not ECF volume expansion or kaliuresis. We envision that the acute NaHCO₃ infusion elicits immediate ionic shifts between ECF and ICF leading to hypokalemia. Thereafter, maintenance of a relatively stable, although depressed, [K⁺]_e requires that cells release potassium to counterbalance ongoing urinary potassium losses.