Hepatopulmonary, syndrome

Different chronic liver diseases with cirrhosis can cause, in some patients, including young children (prevalence: 2-8 %), a modification of the pulmonary vasculature which causes an abnormal respiratory exchange known as hepato-pulmonary syndrome. The pathophysiology of this anomaly combines an anomalous pulmonary vasodilation associated with an impaired distribution of ventilation and perfusion. The problem can also occur in case of portosystemic congenital shunts or following a Fontan procedure due to high venous hepatic pressure.

The diagnosis of hepato-pulmonary syndrome is based on the presence of the following triad:

-         liver failure, sometimes moderate, because there is no correlation between the severity of hypoxemia and liver failure, associated with portal hypertension;

-         moderate to severe hypoxemia (PaO2 at room air < 70 mmHg or SpO2 < 94 %) with orthodeoxia (hypoxemia that worsens in standing position : SpO2 decreases more than 5 % when standing from the supine position); digital clubbing is frequent

-        a pulmonary vasodilation responding weakly to the administration of 100  O2.

In case of hepatic insufficiency and/or portal hypertension, the decrease in the hepatic degradation of vasodilating substances (glucagon, NO...) causes vasodilation at the level of the pulmonary microvascularisation and, consequently, an increase in alveolar-arterial gradient corrected for age (with or without hypoxemia). 

Three physiopathological mechanisms, often combined, are possible:

1) presence of a true shunt, due to intrapulmonary or porto-pulmonary arteriovenous anastomoses: this situation is rare in childhood in the absence of portal atresia; even with administration of 100 % O2, PaO2 does not reach 150 mmHg; it is defined as hepatopulmonary type II syndrome, which can be partially corrected by embolisation of the large anastomoses

2) increase in the physiological intrapulmonary shunt due to a poor distribution of ventilation and perfusion by inhibition of hypoxic vasoconstriction;

3) decrease in the diffusion of O2 at the level of the dilated pulmonary capillaries  (normal diameter 8-15 µm vs 50 - 80 µ in case of hepato-pulmonary syndrome); in case of anomalies 2) and 3), it is defined as hepatopulmonary type I syndrome


In both last situations, the response to the administration of 100 % O2 results in a PaO2 increase > 300 mmHg . Orthodeoxia (decrease of > 5% of SPO2 from the supine to the standing position) is explained by the fact that vasodilation predominates at the lung bases: the shunt is therefore increased in standing position.


Severity:        moderate        if PaO2 60-79 mmHg

       severe        if PaO2 50-59 mmHg

       very severe        if PaO2 ≤ 50 mmHg



Other possible causes of hypoxemia are numerous in case of liver failure: pleural effusion, important ascites, bronchopulmonary infection, alveolar hypoventilation, pulmonary hypertension, combined cyanotic heart disease .

In addition to the response to 100% O2 administration, the following tests may be performed to confirm the presence of hepato-pulmonary syndrome: 

-         if R < 1: absence of shunt

-         if R is between 1 and 2: questionable result or subclinical hepato-pulmonary syndrome,

-         if R is between 4% and 20%: there is a moderate shunt; minor hepatopulmonary syndrome

-         if R is between 21% and 40%: moderate hepatopulmonary syndrome

-         if R > 40%: severe hepatopulmonary syndrome

-         absence of microbubbles in the LA: normal picture, there is no shunt.

-         if microbubbles are spotted in the LA after a very short time (<3 cycles), there is an intrapulmonary shunt;

-         if microbubbles are spotted in the LA 3-6 beats after their appearance in the RA, there is a hepatopulmonary syndrome. 

This test is difficult to perform in tachycardic children  but is more sensitive than nuclear medicine because it detects the hepatopulmonary syndrome at an early stage, before hypoxemia develops. Some teams recommend for these examinations in children with less than 94% SpO2 at room air.

Medical treatment is not very effective: various molecules have been tried such as almitrine bismesylate or octeotride but their effectiveness is limited. A transjugular porto-systemic shunt (TIPS) is sometimes placed temporarily.The only curative treatment is liver transplantation but the pathology restarts in case of graft rejection or portal thrombosis.

N.B.:        a particular form of type II hepatopulmonary syndrome is not linked to an hepatic disease. It is the apparition of pulmonary arteriovenous fistulae after a Glenn's bidirectional cavopulmonary shunt. Those fistulae disappear progressively when thehepatic venous blood flows again through the pulmonary arteries (Fontan's circulation).


Anesthetic implications: 

anesthetic management for a child suffering from a hepatopulmonary syndrome involves:

-         the eviction of the N2O and the titration of FiO2 so as to obtain a SpO2 between 95 and 98%;

-         avoiding ventilation in pure O2 (which promotes atelectasis);

-         maintenance of a slight PEEP (Positive End-Expiratory Pressure);

-         the accurate replacement of fluid losses to prevent hypovolemia and anemia but also any vascular overload  (risk of pulmonary edema).

-         in case of systemic hypotension, titrated norepinepherine is the best option; 'vasodilating' drugs as dobutamine or nitroglycerin are ineffective; 

-         rapid weaning from the ventilator at the end of intervention.

-         traps to avoid:

1)        a refractory hypoxemia may arisein the first hours after a liver transplantation (SpO2 < 85 % even with FIO2 = 1 and use of PEEP).It is probably due to the vasoconstriction of pulmonary vessels in the presence of hepatic mediators.
To be tried successively: Trendelenbourg position, NO or epoprostenol administration, methylene blue, embolization of the still dilated arteries, ECMO. Significant mortality (45 %).

2)        the pulmonary vasodilation may mask mild portopulmonary hypertension (see this term) that will become clinically evident only after the transplantation.


References : 


Updated: July 2022