Methylene blue improves the hepatopulmonary syndrome

Background: 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. Objective: To study the effect of methylene blue, a potent inhibitor of guanylate cyclase, in patients with severe hepatopulmonary syndrome, Design: Open, uncontrolled trial, Setting: Medical intensive care unit at the university hospital in Vienna, Austria. Patients: 7 patients with advanced cirrhosis and severe hepatopulmonary syndrome with Pao(2) of 60 mm Hg br less, Intervention: 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. Measurements: Serial measurements of gas exchange and hemodynamic variables, Results: 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 <plus/minus> 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. Conclusion: Intravenous methylene blue improved hypoxemia and hyperdynamic circulation in patients with liver cirrhosis and severe hepatopulmonary syndrome.