Correspondence
Methylene Blue in the Hepatopulmonary Syndrome
N Engl J Med 1994; 331:1098October 20, 1994
- Article
To the Editor:
The hepatopulmonary syndrome, which is characterized by hypoxemia due to intrapulmonary shunting or a ventilation-perfusion mismatch (or both), develops in some patients with liver cirrhosis. Patients with this syndrome have no apparent parenchymal lung disease but may have orthodeoxia, the unusual finding of increased hypoxemia with the change from a supine to a standing position.1
Increased endogenous production of nitric oxide may play a part in the hyperdynamic circulation that is typical of patients with the hepatopulmonary syndrome. An increased concentration of exhaled nitric oxide has recently been reported in one such patient; hypoxemia resolved and the level of exhaled nitric oxide returned to normal after liver transplantation.2
We wondered whether inhibition of the effect of nitric oxide with methylene blue would improve hypoxemia associated with the hepatopulmonary syndrome. Methylene blue is an oxidizing agent that blocks the stimulation of soluble guanylate cyclase by nitric oxide3 and therefore its vasodilative effect. The inhibitory action of methylene blue has been ascribed to its direct effect on guanylate cyclase or the generation of superoxide (or both).3 A bolus dose of intravenous methylene blue (3 mg per kilogram of body weight) was reported to increase blood pressure in a patient with cirrhosis and severe hypotension who had not had a response to high-dose norepinephrine.4
A 45-year-old woman with alcoholic cirrhosis and esophageal varices (total protein, 51 g per liter; albumin, 26 g per liter; bilirubin, 3.1 mg per deciliter; prothrombin time, 54 percent of the control value; hemoglobin, 8.5 g per deciliter; platelet count, 114,000 per cubic millimeter; and white-cell count, 3500 per cubic millimeter) had moderate hypoxemia; her partial pressure of arterial oxygen decreased from 62 mm Hg in a supine position to 56 mm Hg in a standing position. The woman did not smoke. The stability of the measurements of the partial pressure of arterial oxygen was not formally tested immediately before the experiment, although almost identical values in the supine and standing positions had been obtained twice on previous days.
A chest x-ray film and the results of pulmonary-function tests were normal, with the exception of a moderate decrease in lung diffusion of carbon monoxide (72 percent of the predicted value, after correction for hemoglobin). After the patient had been breathing 100 percent oxygen, the partial pressure of arterial oxygen was 325 mm Hg (normal value, > 500 mm Hg) while she was in the supine position, and it decreased to 115 mm Hg while she was standing. These data are consistent with substantial intrapulmonary shunting as the cause of hypoxemia.5 Contrast-enhanced echocardiography showed delayed opacification in the left atrium, a finding that confirms the presence of dilated pulmonary vessels at the precapillary level.
Twenty minutes after the intravenous administration of methylene blue (3 mg per kilogram), the partial pressure of arterial oxygen was 70 mm Hg while the patient was supine and 68 mm Hg while she was standing. After she breathed 100 percent oxygen, the partial pressure of arterial oxygen was 480 mm Hg in the supine position and 390 mm Hg in the standing position. The following day, the supine and standing values for the partial pressure of arterial oxygen were 60 and 53 mm Hg, respectively. The patient refused to undergo repeated measurements while breathing 100 percent oxygen.
Our findings indicate a marked decrease in pulmonary shunting after the administration of methylene blue. Although limited to one patient, our observation suggests that the increased production of nitric oxide in the lungs may contribute to the hepatopulmonary syndrome.
5 ReferencesGiovanni Rolla, M.D.
Caterina Bucca, M.D.
Luisa Brussino, M.D.
University of Torino, 10126 Torino, Italy1
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- Citing Articles (28)
Citing Articles
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Rajan Kochar, Michael B. Fallon. 2011. Pulmonary Manifestations of Liver Disease. , 381-392.
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Mortada H.F. El-Shabrawi, Naglaa M. Kamal. (2011) Medical Management of Chronic Liver Diseases (CLD) in Children (Part II). Pediatric Drugs 13:6, 371-383
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Akiko Miyamoto, Yasumi Katsuta, Xue-Jun Zhang, Hong-Li Li, Masaru Ohsuga, Hirokazu Komeichi, Shuji Shimizu, Toshio Akimoto, Kyoichi Mizuno. (2010) Effect of chronic methylene blue administration on hypoxemia in rats with common bile duct ligation. Hepatology Research 40:6, 622-632
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E. Schiffer, M. Beaussier, C. Pastor. 2010. Syndrome hépatopulmonaire. , 165-177.
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Catherine M Pastor, Eduardo Schiffer. (2007) Therapy Insight: hepatopulmonary syndrome and orthotopic liver transplantation. Nature Clinical Practice Gastroenterology & Hepatology 4:11, 614-621
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