A 22 year-old woman presented with sudden-onset shortness of breath and five days of progressively worsening rhinorrhea and cough. She was tachycardic and tachypneic, with diffuse inspiratory and expiratory wheezes bilaterally. Oxygen saturation was 78% on room air. Accessory muscle use was observed. Lactate was 2.4 mEq/L. Chest radiograph was unremarkable. After treatment with albuterol-ipratropium, methylprednisolone, and IV magnesium, oxygen saturations improved. Continuous albuterol nebulizers were then administered. Repeat lactate four hours later was 7.5 mEq/L, with serum bicarbonate 15 mmol/L and pH 7.31. Albuterol was discontinued, and the lactic acidosis resolved.
Discussion:
Lactic acidosis is one of the most common causes of metabolic acidosis in the inpatient setting and is frequently encountered by general internists. This phenomenon occurs due to overproduction or underutilization of lactate, for which several pathologic mechanisms exist. Lactate is generated from pyruvate via the glycolytic pathway of glucose metabolism. It is converted into carbon dioxide and water, glucose, or alanine. Typically, a balance between production and utilization of lactate is maintained; however, lactate can accumulate due to either increased production or decreased breakdown of pyruvate.
Impaired tissue oxygenation is the most frequent cause of increased lactate production, leading to type A lactic acidosis. Conversely, type B lactic acidosis occurs without indication of systemic hypoperfusion and is hypothesized to be secondary to regional ischemia or toxin-mediated disruption of cellular metabolism. Patients with diabetes mellitus, human immunodeficiency virus, severe alcoholism, malignancy, and mitochondrial disorders are at increased risk of type B lactic acidosis. In addition, several medications—including albuterol, antiretrovirals, biguanides, iron, isoniazid, linezolid, propofol, and salicylates—have been implicated in disturbing mitochondrial protein synthesis and inducing toxin-mediated type B lactic acidosis. Withdrawal of the offending agent is helpful in remediating toxin-mediated type B lactic acidosis.
Though well documented in literature, albuterol is often unrecognized as a cause of lactic acidosis by general internists. A beta-2 adrenergic receptor agonist, albuterol enhances glycogenolysis and gluconeogenesis, leading to increased glucose catabolism to pyruvate. Meanwhile, augmented lipolysis and accumulation of free fatty acids suppress pyruvate dehydrogenase activity, shifting pyruvate from the Krebs cycle to production of lactate.
Conclusions:
Lactic acidosis is a common metabolic disturbance in hospitalized patients and has a wide array of etiologies. By recognizing pharmacologic agents such as albuterol as a cause of lactic acidosis, general internists can prevent unnecessary and costly evaluations and resolve certain acid-base disturbances simply via drug discontinuation.