Background: Intravenous almitrine, which augments hypoxic pulmonary vasoconstriction, is used for short-term improvement of arterial oxygenation. However, recent research has suggested a potentially harmful effect on lactate metabolism and hepatic function.
Methods: Arterial oxygenation, hemodynamic parameters, plasma lactate, and hepatic function were monitored prospectively in 25 patients with acute lung injury (defined as a ratio of arterial oxygen pressure to inspiratory oxygen fraction < or = 150 mmHg) who where treated with intravenous almitrine. In 21 of 25 patients, acute lung injury was related to primary lung lesions, including pneumonia, postcardiosurgical atelectasis, and lung contusions.
Results: Intravenous almitrine increased the ratio of arterial oxygen pressure to inspiratory oxygen fraction from 93 +/- 33 mmHg to 207 +/- 107 mmHg (mean +/- SD). In eight patients (three men), the plasma lactate concentration increased by an average of +3.5 +/- 1.8 mM, and the pH and bicarbonate concentration both decreased during the first 24 h of treatment. In this group of patients, the total bilirubin concentration was elevated before almitrine administration, and the results of other hepatic function tests, such as aspartate aminotransferase, alanine aminotransferase, and prothrombin time, were altered by almitrine administration. Therefore, intravenous almitrine was discontinued. Lactic acidosis and hepatic dysfunction improved. In the other 17 patients (14 men), the plasma lactate concentration and the hepatic function tests remained unaltered during intravenous almitrine therapy for > 60 h. Univariate and multivariate analyses revealed that an abnormal plasma concentration of total bilirubin before almitrine administration and female gender were the two factors significantly linked with lactic acidosis during almitrine infusion.
Conclusions: This study confirms that intravenous almitrine greatly improves arterial oxygenation in patients with acute lung injury but may also induce lactic acidosis and hepatic dysfunction. The coexistence of lactic acidosis and hepatic dysfunction in the same patients strongly suggests that the liver is the primary source of intravenous almitrine-induced lactic acidosis.