Methylene Blue Improves the Hepatopulmonary Syndrome

  1. Peter Schenk, MD;
  2. Christian Madl, MD;
  3. Shahrzad Rezaie-Majd, MD;
  4. Stephan Lehr; and
  5. Christian Müller, MD
  1. From the University of Vienna, Vienna, Austria.

    Abstract

    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.

    Article and Author Information

    • Acknowledgments: The authors thank Gabriele Wölfl of the Department of Medical Statistics at the University of Vienna for help with statistical analysis.

    • Requests for Single Reprints: Peter Schenk, MD, Department of Internal Medicine 4, Intensive Care, University of Vienna, Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna, Austria; e-mail, peter.schenk{at}akh-wien.ac.at.

    • Current Author Addresses: Drs. Schenk and Madl: Department of Internal Medicine 4, Intensive Care, University of Vienna, Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

    • Dr. Rezaie-Majd: Department of Internal Medicine 2, Division of Cardiology, University of Vienna, Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

    • Mr. Lehr: Department of Medical Statistics, University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.

    • Dr. Müller: Department of Internal Medicine 4, Division of Gastroenterology, University of Vienna, Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

    • Author Contributions: Conception and design: P. Schenk, C. Madl, S. Lehr, C. Müller.

    • Analysis and interpretation of the data: P. Schenk, C. Madl, S. Rezaie-Majd, S. Lehr, C. Müller.

    • Drafting of the article: P. Schenk, C. Madl, S. Rezaie-Majd, C. Müller.

    • Critical revision of the article for important intellectual content: P. Schenk, C. Madl, S. Lehr, C. Müller.

    • Final approval of the article: P. Schenk, C. Madl, S. Rezaie-Majd, S. Lehr, C. Müller.

    • Provision of study materials or patients: P. Schenk, C. Madl, S. Rezaie-Majd, C. Müller.

    • Statistical expertise: P. Schenk, S. Lehr, C. Müller.

    • Administrative, technical, or logistic support: C. Madl, C. Müller.

    • Collection and assembly of data: P. Schenk, S. Rezaie-Majd, C. Müller.

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    1. Ann Intern Med November 7, 2000 vol. 133 no. 9 701-706
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