Methylene blue improves the hepatopulmonary syndrome.

The hypoxemia of the hepatopulmonary syndrome, seen in patients with severe chronic liver dysfunction, results from widespread pulmonary vasodilation. No established drug therapy is available for this condition. To study the effect of methylene blue, a potent inhibitor of guanylate cyclase, in patients with severe hepatopulmonary syndrome. Open, uncontrolled trial. Medical intensive care unit at the university hospital in Vienna, Austria. 7 patients with advanced cirrhosis and severe hepatopulmonary syndrome with PaO(2) of 60 mm Hg or less. Insertion of a pulmonary artery catheter and an arterial indwelling catheter; intravenous administration of methylene blue, 3 mg/kg of body weight, over a 15-minute period. Serial measurements of gas exchange and hemodynamic variables. After methylene blue administration, PaO(2) increased in all patients (from a baseline mean +/- SD of 58 +/- 2.5 mm Hg to 74 +/- 11.5 mm Hg 5 hours after infusion; P = 0.006) and the alveolar-arterial difference for partial pressure of oxygen (PAO(2) - PaO(2) ) decreased in all patients, with a maximum effect achieved after 5 hours (from 49 +/- 3.3 mm Hg to 30 +/- 10.4 mm Hg; P = 0.003); even after 10 hours, PAO(2) - PaO(2) was still significantly reduced compared with baseline (P = 0.041). Oxygenation improved because of reduction in shunt fraction (from 41% +/- 3.1% to 25% +/- 4.5%; P < 0.001). Mean pulmonary artery pressure increased (from 20 +/- 5.2 mm Hg to 23 +/- 3.6 mm Hg; P = 0. 028), as did pulmonary vascular resistance (from 58 +/- 23 dyne/sec. cm(-5) to 115 +/- 56 dyne/sec. cm(-5); P = 0.012). Arterial blood pressure did not change significantly. Cardiac output decreased (from 10.6 +/- 2.2 L/min to 8.6 +/- 2.7 L/min; P = 0.008) and systemic vascular resistance increased (from 527 +/- 144 dyne/sec. cm(-5) to 729 +/- 222 dyne/sec. cm(-5); P = 0.037). Heart rate, central venous pressure, and pulmonary capillary wedge pressure remained unchanged. Intravenous methylene blue improved hypoxemia and hyperdynamic circulation in patients with liver cirrhosis and severe hepatopulmonary syndrome.