Although IV fluids resolved his AKI, prerenal in etiology given the calculated FENa at 0.5%, his lactate levels continued to uptrend to a peak of 4.0 mmol/L complicated by elevated blood pressure (BP) > 150/100 mm Hg. Given his thoracic aneurysm, his BP was treated with metoprolol tartrate and amlodipine 10 mg daily. The patient remained asymptomatic with no evidence of ischemia or sepsis.
We suspected the nebulizer treatments to be the etiology of the patient’s hyperlactatemia and subsequent anion-gap metabolic acidosis. His scheduled albuterol and ipratropium nebulizer treatments were discontinued, and the patient experienced rapid resolution of his anion gap and hyperlactatemia to 1.2 mmol/L over 24 hours. On discontinuation of the nebulization therapy, mild wheezing was noted on physical examination. The patient reported no symptoms and was at his baseline. The patient finished his antibiotic course for his community-acquired pneumonia and was discharged in stable condition with instructions to continue his previously established home COPD medication regimen of umeclidinium/vilanterol 62.5/25 mcg daily and albuterol metered-dose inhaler as needed.
Discussion
Short-acting β-agonists, such as albuterol, are widely used in COPD and are a guideline-recommended treatment in maintenance and exacerbation of asthma and COPD.1 Short-acting β-agonist adverse effects (AEs) include nausea, vomiting, tremors, headache, and tachycardia; abnormal laboratory results include hypocalcemia, hypokalemia, hypophosphatemia, hypomagnesemia, and hyperglycemia.2,3 Albuterol-induced hyperlactatemia and lactic acidosis also are known but often overlooked and underreported AEs.
In a randomized control trial, researchers identified a positive correlation between nebulized albuterol use and hyperlactatemia in asthmatics with asthma exacerbation.4 One systematic review identified ≤ 20% of patients on either IV or nebulized high-dose treatments with selective β2-agonists may experience hyperlactatemia.5 However, aerosolized administration of albuterol as opposed to IV administration is less likely to result in AEs and abnormal laboratory results given decreased systemic absorption.3
Hyperlactatemia and lactic acidosis are associated with increased morbidity and mortality.6 Lactic acidosis is classified as either type A or type B. Type A lactic acidosis is characterized by hypoperfusion as subsequent ischemic injuries lead to anaerobic metabolism and elevated lactate. Diseases such as septic, cardiogenic, and hypovolemic shock are often associated with type A lactic acidosis. Type B lactic acidosis, however, encapsulates all nonhypoperfusion-related elevations in lactate, including malignancy, ethanol intoxication, and medication-induced lactic acidosis.7,8
In this case, the diagnosis was elusive as the patient had multiple comorbidities. His history included COPD, which is associated with elevated lactate levels.5 However, his initial laboratory workup did not show an anion gap, confirming a lack of an underlying acidotic process on admission. Because the patient was admitted for pneumonia, a known infectious source, complicated by an acute elevation in lactate, sepsis must be and was effectively ruled out. The patient also reported alcohol use during his admission, which confounded his presentation but was unlikely to impact the etiology of his lactic acidosis, given the unremarkable β-hydroxybutyrate and serum alcohol levels.