Acidosis

MED ICA L PROGRES S

Review Article

Medical Progress

M ANAGEMENT OF L IFE -T HREATENING A CID –B ASE D ISORDERS
Second of Two Parts
HORACIO J. ADROGUÉ, M.D., NICOLAOS E. MADIAS, M.D.

AND

ADVERSE CONSEQUENCES OF SEVERE ALKALEMIA

varying degrees to its generation.7,69-71 In turn, hypokalemia can have several adverse effects, including neuromuscular weakness; sensitization todigitalisinduced arrhythmias; polyuria; and increased ammonia production, which can heighten the risk of hepatic encephalopathy. Alkalemia stimulates anaerobic glycolysis and increases the production of lactic acid and ketoacids.6,17 Along with the alkalemic titration of plasma proteins and the hyperproteinemia accompanying chloride-responsive metabolic alkalosis, this effect contributes to thecharacteristic moderate elevation in the plasma anion gap.41,72 Although acute alkalemia can reduce the release of oxygen to the tissues by tightening the binding of oxygen to hemoglobin, chronic alkalemia negates this effect by increasing the concentration of 2,3diphosphoglyceric acid in red cells.69-71
MANAGEMENT OF LIFE-THREATENING ALKALOSES
Metabolic Alkalosis

Severe alkalemia (blood pH greaterthan 7.60) can compromise cerebral and myocardial perfusion by causing arteriolar constriction, an effect that is more pronounced in respiratory than in metabolic alkalosis (Table 2).69-71 Neurologic abnormalities may ensue, including headache, tetany, seizures, lethargy, delirium, and stupor. The associated reduction in the plasma concentration of ionized calcium probably contributes to thesemanifestations. Although it exerts a moderate positive inotropic effect on the isolated heart, alkalemia reduces the anginal threshold and predisposes the patient to refractory supraventricular and ventricular arrhythmias. This arrhythmogenic action is more pronounced in patients with underlying heart disease. Alkalemia depresses respiration, causing hypercapnia and hypoxemia. Such effects are oflittle consequence in patients with adequate ventilatory reserve, but they can be consequential in patients with compromised ventilation. Even mild alkalemia can frustrate efforts to wean patients from mechanical ventilation. Hypokalemia is an almost constant feature of alkalemic disorders, but it is more prominent in those of metabolic origin. Translocation of potassium into cells and renal andextrarenal losses contribute in

From the Department of Medicine, Baylor College of Medicine and Methodist Hospital, and the Renal Section, Veterans Affairs Medical Center, Houston (H.J.A.), and the Department of Medicine, Tufts University School of Medicine, and the Division of Nephrology and the Tupper Research Institute, New England Medical Center, Boston (N.E.M.). Address reprint requests toDr. Madias at the Division of Nephrology, New England Medical Center, Box 172, 750 Washington St., Boston, MA 02111. ©1998, Massachusetts Medical Society.

In the presence of an appropriate ventilatory response, severe alkalemia of metabolic origin requires that the plasma bicarbonate concentration exceed 45 mmol per liter.12 Just as in severe metabolic acidemia, the immediate goal of therapy ismoderation but not full correction of the alkalemia. Reducing plasma bicarbonate to less than 40 mmol per liter is an appropriate short-term goal, since the corresponding pH is on the order of 7.55 or lower. Most severe metabolic alkalosis is of the chloride-responsive form, the most common causes being loss of gastric acid and the administration of loop or thiazide diuretics.69,71 Thecharacteristic hypochloremic hyperbicarbonatemia results from the loss of hydrochloric acid in gastric secretions or from urinary excretion of excess ammonium chloride caused by these chloruretic diuretics. Substantial contraction of the volume of extracellular fluid as a result of diuretic-induced losses of sodium chloride can further amplify the resulting hyperbicarbonatemia by limiting the space of...