title: Treatment of acute metabolic acidosis: a pathophysiologic approach.
abstract: Acute metabolic acidosis is associated with increased morbidity and mortality because of its depressive effects on cardiovascular function, facilitation of cardiac arrhythmias, stimulation of inflammation, suppression of the immune response, and other adverse effects. Appropriate evaluation of acute metabolic acidosis includes assessment of acid-base parameters, including pH, partial pressure of CO(2) and HCO(3)(-) concentration in arterial blood in stable patients, and also in central venous blood in patients with impaired tissue perfusion. Calculation of the serum anion gap and the change from baseline enables the physician to detect organic acidoses, a common cause of severe metabolic acidosis, and aids therapeutic decisions. A fall in extracellular and intracellular pH can affect cellular function via different mechanisms and treatment should be directed at improving both parameters. In addition to supportive measures, treatment has included administration of base, primarily in the form of sodium bicarbonate. However, in clinical studies of lactic acidosis and ketoacidosis, bicarbonate administration has not reduced morbidity or mortality, or improved cellular function. Potential explanations for this failure include exacerbation of intracellular acidosis, reduction in ionized Ca(2+), and production of hyperosmolality. Administration of tris(hydroxymethyl)aminomethane (THAM) improves acidosis without producing intracellular acidosis and its value as a form of base is worth further investigation. Selective sodium-hydrogen exchanger 1 (NHE1) inhibitors have been shown to improve haemodynamics and reduce mortality in animal studies of acute lactic acidosis and should also be examined further. Given the important effects of acute metabolic acidosis on clinical outcomes, more intensive study of the pathogenesis of the associated cellular dysfunction and novel methods of treatment is indicated.
authors.affiliation: Division of Nephrology, Veterans Health Administration Greater Los Angeles Heathcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA. jkraut@ucla.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kraut
authors.forename: Nicolaos E
authors.initials: NE
authors.lastname: Madias
mesh_terms: D000138:Acidosis / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D000208:Acute Disease; D001784:Blood Gas Analysis; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017923:Sodium-Hydrogen Exchangers / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D017923:Sodium-Hydrogen Exchangers