INTRAVENOUS ALMITRINE BISMESYLATE REVERSIBLY INDUCES LACTIC-ACIDOSIS AND HEPATIC-DYSFUNCTION IN PATIENTS WITH ACUTE LUNG INJURY

Background: Intravenous almitrine, which augments hypoxic pulmonary va soconstriction, is used for short-term improvement of arterial oxygena tion. However, recent research has suggested a potentially harmful eff ect on lactate metabolism and hepatic function. Methods: Arterial oxyg enation, hemodynamic parameters, plasma lactate, and hepatic function were monitored prospectively in 25 patients with acute lung injury (de fined as a ratio of arterial oxygen pressure to inspiratory oxygen fra ction less than or equal to 150 mmHg) who where treated with intraveno us almitrine. In 21 of 25 patients, acute lung injury was related to p rimary lung lesions, including pneumonia, postcardiosurgical atelectas is, 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 (t hree men), the plasma lactate concentration increased by an average of +3.5 +/- 1.8 mM, and the pH and bicarbonate concentration both decrea sed during the first 24 h of treatment. In this group of patients, the total bilirubin concentration was elevated before almitrine administr ation, and the results of other hepatic function tests, such as aspart ate aminotransferase, alanine aminotransferase, and prothrombin time, were altered by almitrine administration. Therefore, intravenous almit rine was discontinued. Lactic acidosis and hepatic dysfunction improve d. Ln 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 reve aled that an abnormal plasma concentration of total bilirubin before a lmitrine administration and female gender were the two factors signifi cantly Linked with lactic acidosis during almitrine infusion. Conclusi ons: This study confirms that intravenous almitrine greatly improves a rterial oxygenation in patients with acute lung injury but may also in duce lactic acidosis and hepatic dysfunction, The coexistence of lacti c acidosis and hepatic dysfunction in the same patients strongly sugge sts that the Liver is the primary source of intravenous almitrine-indu ced lactic acidosis.