Selective ß2-Adrenoceptor Agonists and Relevant Hyperlactatemia: Systematic Review and Meta-Analysis

Selective ß(2)-agonists have been imputed as potential cause of l-hyperlactatemia since the 1970s. To document the prevalence of hyperlactatemia associated with selective ß(2)-agonists and to investigate the predisposing factors, we searched for published articles until April 2019 pertaining to the interplay of administration of selective ß(2)-agonists and circulating l-lactic acid in the Excerpta Medica, Web of Science, and the U.S. National Library of Medicine databases. Out of the 1834 initially retrieved records, 56 articles were included: 42 papers reporting individual cases, 2 observational studies, and 12 clinical trials. Forty-seven individual patients receiving a selective ß(2)-agonist were found to have l-lactatemia ≥5.0 mmol/L, which decreased by ≥3.0 mmol/L or to ≤2.5 mmol/L after discontinuing (N = 24), reducing (N = 17) or without modifying the dosage of the selective ß(2)-agonist (N = 6). Clinical trials found that l-lactic acid significantly increased in healthy volunteers administered a ß(2)-agonist. l-lactatemia ≥5.0 mmol/L was observed in 103 (24%) out of 426 patients with asthma or preterm labor managed with a selective ß(2)-agonist and was more common in patients with asthma (30%) than in premature labor (5.9%). A significant relationship was also noted between l-lactate level and intravenous albuterol dose or its circulating level. In conclusion, relevant l-hyperlactatemia is common on high dose treatment with a selective ß(2)-agonist.