Methylene Blue in Hepatopulmonary Syndrome
Abstract & Commentary
Synopsis: Intravenous methylene blue improved hypoxemia and hyperdynamic circulation without apparent adverse effects in patients with end-stage liver disease and the hepatopulmonary syndrome.
Source: Schenk P, et al. Ann Intern Med. 2000; 133(9):701-706.
Schenk and associates at the University of Vienna administered methylene blue intravenously to 7 patients with the hepatopulmonary syndrome. They postulated that methylene blue, an oxidizing agent that blocks the stimulation of soluble guanylate cyclase by nitric oxide (NO), would inhibit NO-induced pulmonary vasodilation and, thus, improve arterial oxygenation and decrease the hyperdynamic state in these patients. The patients all met the following criteria for the hepatopulmonary syndrome: advanced hepatic cirrhosis, absence of intrinsic pulmonary disease, increased P(A-a)O2, and positive contrast-enhanced echocardiogram suggesting intrapulmonary vascular dilation. In each patient, pulmonary artery and systemic arterial catheters were inserted, and methylene blue, 3 mg/kg body weight, was infused intravenously over 15 minutes.
Mean P(A-a)O2 in these patients was 49 mm Hg breathing air before the intervention, with a mean right-to-left shunt fraction of 41%. After methylene blue administration, PaO2 on room air increased in every patient, from a baseline of 58 ± 2.5 mm Hg to 74 ± 11.5 mm Hg after 5 hours (P = .006). Mean P(A-a)O2 and right-to-left shunt decreased by approximately 20 mm Hg and 16%, respectively, with a maximum effect of 5 hours after infusion. Mean pulmonary arterial pressure increased from 20 to 23 mm Hg (P = .028), and cardiac output decreased from 10.6 to 8.6 L/min (P = .008); pulmonary artery wedge pressure and systemic blood pressure did not change. The effect on arterial oxygenation remained significant even after 10 hours. The only detectable side effect was a blue-green discoloration of the urine lasting 1-2 days.
Comment by David J. Pierson, MD, FACP, FCCP
As many as one-fourth of patients with end-stage liver disease (ESLD) develop hypoxemia due to the hepatopulmonary syndrome, defined by the triad of chronic liver disease, hypoxemia, and intrapulmonary vascular dilation in the absence of intrinsic pulmonary disease.1 This syndrome is important in the ICU because of the frequency with which patients with ESLD are admitted for upper gastrointestinal bleeding and other problems, and because hypoxemia caused by the hepatopulmonary syndrome is notoriously difficult to correct.
Hypoxemia in this setting also may confound usual management for acute respiratory failure, as when a patient with ESLD develops pneumonia or another acute pulmonary process. In circumstances such as this, arterial oxygenation as assessed by the PaO2/FIO2 ratio may remain sufficiently impaired in the presence of the hepatopulmonary syndrome that usual thresholds for decreasing positive end-expiratory pressure or ventilator weaning may not be reached, prolonging mechanical ventilation and ICU stays.
Mainly this is a problem of recognition in that once the diagnosis of hepatopulmonary syndrome is made, clinicians can modify their usual criteria for oxygenation and usually wean patients successfully (although they may remain hypoxemic) once the acute pulmonary problem has improved. However, it would be good to have more effective therapy for the gas exchange impairment of the hepatopulmonary syndrome itself. This preliminary study suggests that methylene blue, a readily available and apparently nontoxic agent, may prove helpful in this regard.
Reference
1. Rodriguez-Roisin R, et al. Thorax. 1992;47:897-902.
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