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 PaO2 of 60 mm Hg or 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, PaO2 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 (PAO2 − PaO2) 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, PAO2 − PaO2 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.
Conclusion: Intravenous methylene blue improved hypoxemia and hyperdynamic circulation in patients with liver cirrhosis and severe hepatopulmonary syndrome.