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Methylene Blue Improves the Hepatopulmonary Syndrome

Peter Schenk, MD; Christian Madl, MD; Shahrzad Rezaie-Majd, MD; Stephan Lehr; and Christian Müller, MD
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Copyright ©2004 by the American College of Physicians

Ann Intern Med. 2000;133(9):701-706. doi:10.7326/0003-4819-133-9-200011070-00012
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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.


Grahic Jump Location
Effect of methylene blue infusion in each patient.

Shown are baseline values (timepoint 0) and serial measurements after methylene blue infusion, 3 mg/kg of body weight injected over a period of 15 minutes, of Pa , alveolar–arterial difference for the partial pressure of oxygen, and pulmonary shunt fraction. Black circles represent patient 1, black squares represent patient 2, black triangles represent patient 3, black diamonds represent patient 4, asterisks represent patient 5, white circles represent patient 6, and white squares represent patient 7.

Grahic Jump Location




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Summary for Patients

Methylene Blue To Treat Hepatopulmonary Syndrome

Copyright ©2004 by the American College of Physicians


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