P Schenk1, C Madl, S Rezaie-Majd, S Lehr, C Müller. 1. Department of Internal Medicine 4, Intensive Care, University of Vienna, Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna, Austria. peter.schenk@akh-wien.ac.at
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 PaO(2) 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, 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. CONCLUSION: Intravenous methylene blue improved hypoxemia and hyperdynamic circulation in patients with liver cirrhosis and severe 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 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, 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. CONCLUSION: Intravenous methylene blue improved hypoxemia and hyperdynamic circulation in patients with liver cirrhosis and severe hepatopulmonary syndrome.
Authors: Kari E Roberts; Steven M Kawut; Michael J Krowka; Robert S Brown; James F Trotter; Vijay Shah; Inga Peter; Hocine Tighiouart; Nandita Mitra; Elizabeth Handorf; James A Knowles; Steven Zacks; Michael B Fallon Journal: Gastroenterology Date: 2010-03-24 Impact factor: 22.682