Background: The hypoxemia of the hepatopulmonary syndrome, seen in patients
with severe chronic liver dysfunction, results from widespread pulmonary v
asodilation. No established drug therapy is available for this condition.
Objective: To study the effect of methylene blue, a potent inhibitor of gua
nylate 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 syn
drome with Pao(2) of 60 mm Hg br less,
Intervention: Insertion of a pulmonary artery catheter and an arterial indw
elling catheter; intravenous administration of methylene blue, 3 mg/kg of b
ody 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 patie
nts (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 signific
antly reduced compared with baseline (P = 0.041), Oxygenation improved beca
use of reduction in shunt fraction (from 41% +/- 3.1% to 25% +/- 4.5%; P <
0.001). Mean pulmonary artery pressure increased (from 20 <plus/minus> 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 decre
ased (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 syn
drome.