Lactic Acidosis and Albuterol

A quick diversion from GU.  I took care of a patient that was diagnosed with severe lactic acidosis (7.5mmol/l) secondary to albuterol (salbutamol) treatment. Who knew that albuterol can cause lactic acidosis!!!

Hyperlactatemia secondary to albuterol was originally described in 1980 in the British Journal of Clinical Pharmacology, although this was with intravenous albuterol. Chest reported the first case series of transient lactatemia associated with administration of inhaled albuterol. All patients cleared the lactic acidosis in 24 hours without intervention. In a prospective study in Emergency Medicine Journal, 18 asthmatic patients received four puffs of albuterol (100 ug/puff) at 10 minute intervals, by metered dose inhaler over a 2 hour period. Nine patients showed lactate levels >2.5 mmol/l and four patients had values > 4 mmol/l.

Lactatemia causes a anion gap metabolic acidosis which may increase the sensation of dyspnea compensatory hyperventilation and cardiovascular side effects. Type A lactic acidosis refers to circumstances where tissue oxygen delivery is inadequate (most common). Type B lactic acidosis occurs when there is no clinical evidence of reduction in tissue oxygen delivery and is usually secondary to tox (eg alcohols) and medications (eg metformin). Lactic acid is cleared through the liver and liver failure can cause lactatemia although there is usually another clinical condition leading to increased lactate production. Diabetic Ketoacidosis can also cause lactic acidosis in 10% of cases.

The cause of lactic acidosis secondary to albuterol is unknown. A proposed mechanism is that this is a type B lactic acidosis secondary to beta-2 receptor activation producing increased glycogenolysis and increased pyruvate. The pyruvate is converted to acetyl CoA, which enters the citric acid cycle. If pyruvate does not enter the citric acid cycle it can be converted to lactate, causing lactic acidosis. Other beta agonists may also cause a type b lactic acidosis.

Phillips, et al. Metabolic and cardiovascular side effects of the beta 2-adrenoceptor agonists salbutamol and rimiterol. Br J Clin Pharmacol. 1980 May;9(5):483-91.

Rodrigo GJ, Rodrigo C. Elevated plasma lactate level associated with high dose inhaled albuterol therapy in acute severe asthma. Emerg Med J. 2005 Jun;22(6):404-8.

Stratakos, et al. Transient lactic acidosis as a side effect of inhaled salbutamol. Chest. 2002 Jul;122(1):385-6.

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