Review Article | Published:

Treatment of acute metabolic acidosis: a pathophysiologic approach

Nature Reviews Nephrology volume 8, pages 589601 (2012) | Download Citation

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 CO2 and HCO3 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 Ca2+, 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.

Key points

  • Metabolic acidosis is a common acid–base disorder that can have a notable impact on cellular function and can be associated with poor clinical outcomes

  • Evaluation includes measurement of acid–base parameters in arterial blood in stable patients, and in central venous blood in patients with markedly impaired tissue perfusion, measurement of serum electrolytes, and calculation of anion gap and osmolal gap

  • As a fall in intracellular and extracellular pH affects cellular function, measures should be taken to improve both parameters, particularly when pH is <7.1

  • Administration of base in the form of sodium bicarbonate has not been shown to improve cellular function or reduce mortality associated with lactic acidosis or ketoacidosis and is associated with adverse effects

  • Administration of other forms of base such as THAM, or use of other methods of delivering base such as dialysis, might improve acid–base parameters without the adverse effects of intravenous bicarbonate

  • As acidosis could affect cellular function through additional mechanisms such as activation of sodium–hydrogen exchanger 1, inhibition of this transporter might be beneficial

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Acknowledgements

The authors' work is supported in part by research funds from the Veterans Administration.

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Affiliations

  1. Division of Nephrology, Veterans Health Administration Greater Los Angeles Heathcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA

    • Jeffrey A. Kraut
  2. Department of Medicine, Division of Nephrology, St Elizabeth's Medical Center, 736 Cambridge Street Boston, MA 02135, USA

    • Nicolaos E. Madias

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The authors contributed equally to all aspects of this manuscript.

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The authors declare no competing financial interests.

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Correspondence to Jeffrey A. Kraut.

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https://doi.org/10.1038/nrneph.2012.186