Breathless, Blue, and Better Lying Flat
A 54-year-old man with alcohol-related cirrhosis (Child-Pugh B, MELD 14, no ascites, platelets 78 ×10⁹/L) is referred with six months of progressive breathlessness. He reports that breathlessness is worse standing and improves lying flat, and he has noticed his fingertips are blue. He has no cough, no orthopnoea and no chest pain. Examination: spider naevi, no jaundice, no ascites, chest clear, no raised JVP, no peripheral oedema, no clubbing. Sitting SpO2 88% on room air, rising to 94% after lying supine for five minutes. Room-air arterial blood gas (sitting): pH 7.46, PaO2 52 mmHg, PaCO2 32 mmHg, bicarbonate 22 mmol/L. Chest radiograph is clear. Echocardiogram shows normal left ventricular size and function, mild right ventricular dilatation, tricuspid regurgitant jet 2.4 m/s, no pericardial effusion. Haemoglobin 116 g/L.
1. Calculate the alveolar–arterial oxygen gradient on room air and interpret it. What response to 100% oxygen would you predict, and why?
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Calculation (sea level, Patm 760 mmHg).
- Alveolar oxygen: PAO2 = FiO2 × (Patm − 47) − PaCO2/0.8 = 0.21 × 713 − 32/0.8 = 149.7 − 40 ≈ 110 mmHg.
- Arterial oxygen: PaO2 = 52 mmHg.
- A–a gradient ≈ 58 mmHg, against an expected value for his age of about 54/4 + 4 ≈ 17 mmHg. The gradient is grossly elevated.
Interpretation of the components.
- A PaO2 of 52 with a PaCO2 of 32 means hypoxaemia with hyperventilation (respiratory alkalosis, bicarbonate 22). The low PaCO2 excludes alveolar hypoventilation as the cause - he is blowing off CO2 and still hypoxic.
- A wide A–a gradient with a clear chest radiograph and no airflow obstruction places the defect in the pulmonary parenchyma or vasculature: ventilation–perfusion mismatch, shunt, or diffusion limitation.
- The normal left ventricle and a tricuspid jet of only 2.4 m/s argue against left heart failure and against portopulmonary hypertension. The haemoglobin is only mildly low, so anaemia does not explain a PaO2 of 52.
Predicted response to 100% oxygen. In a true right-to-left shunt, mixed venous blood passes through non-ventilating (or here, grossly dilated, over-perfused) capillaries and never equilibrates with alveolar gas. Raising FiO2 to 1.0 drives the PaO2 of ventilated lung very high, but the shunted fraction stays low in oxygen, so arterial PaO2 typically remains far below the ~500 mmHg expected - often under 150–200 mmHg. By contrast, hypoxaemia from V/Q mismatch or diffusion limitation corrects readily with modest increases in FiO2. A PaO2 that remains below about 200 mmHg on 100% oxygen therefore indicates a genuine shunt, which is the pattern here. In practice, give 100% oxygen for 20 minutes via a tight-fitting mask and measure the arterial PaO2 to document it.
2. Explain the mechanisms of platypnoea and orthodeoxia in this patient and name the investigations that would confirm your diagnosis.
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Mechanism. In cirrhosis with portal hypertension, nitric-oxide-mediated intrapulmonary vascular dilatations develop, predominantly in the basal and mid lung zones. These capillaries are too wide for red cells at their centre to be fully oxygenated, and they receive a disproportionate share of pulmonary blood flow - a functional right-to-left shunt (the 'diffusion–perfusion defect' of hepatopulmonary syndrome).
Orthodeoxia and platypnoea. In the upright position, gravity directs the greatest perfusion to the lung bases, exactly where the dilatations are most numerous. The shunt fraction therefore increases on standing, PaO2 falls (orthodeoxia), and breathlessness worsens (platypnoea). Lying flat redistributes perfusion more evenly towards less affected upper zones, the shunt falls, and saturation improves from 88% to 94% with symptoms easing. This is the opposite of the orthopnoea of left heart failure, where lying flat worsens breathlessness.
Confirmatory tests.
- Contrast (agitated saline) transthoracic echocardiography. Bubbles appearing in the left atrium 3–6 cardiac cycles after right-heart opacification indicate an intrapulmonary shunt; appearance within one cycle suggests an intracardiac shunt such as a patent foramen ovale.
- ⁹⁹mTc macroaggregated albumin lung perfusion scan. Lung–brain uptake above 6% quantifies the shunt fraction, supports the diagnosis and has prognostic value.
- Arterial blood gas on room air and on 100% oxygen to demonstrate the shunt physiology, with measurement of the A–a gradient in both postures.
- Supportive work-up: severity of liver disease (MELD, Child-Pugh), hepatitis and alcohol history, and exclusion of other causes of hypoxaemia - chest imaging for parenchymal disease, echocardiography for pulmonary hypertension, and iron studies for anaemia.
3. Outline the management options and what you would tell the patient about prognosis and transplantation.
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No drug reverses hepatopulmonary syndrome. Management consists of not making it worse and getting him assessed for transplantation early.
Supportive care.
- Supplemental oxygen when PaO2 <60 mmHg. The shunt limits the benefit, but oxygen improves exercise tolerance and is often required to qualify for transplant listing; titrate to a saturation of roughly 90%.
- Avoid over-diuresis and volume overload, both of which worsen oxygenation. Treat infection and sepsis promptly. Avoid sedatives that blunt the hypoxic drive.
- Manage the cirrhosis: variceal surveillance, ascites prophylaxis where relevant, nutrition, and abstinence from alcohol - also relevant to transplant eligibility.
- Options that do not work: TIPS (may worsen shunting), somatostatin analogues, pentoxifylline, methylprednisolone.
Prognosis. HPS is progressive and roughly doubles mortality for a given MELD score; median survival without transplantation is around 2–3 years from diagnosis. He should be told this plainly, with an honest statement that the trajectory is downhill and that breathlessness will increase.
Transplantation. Liver transplantation is the only definitive treatment and reverses HPS in the majority, although improvement in oxygenation can take weeks to months and some patients remain hypoxaemic for up to a year. Refer now, not when he deteriorates: severe pre-operative hypoxaemia (PaO2 persistently <50–60 mmHg) is often considered a contraindication because perioperative mortality becomes prohibitive. Many programmes grant standard MELD exception points for HPS because MELD underestimates its mortality - make sure that pathway is explored with the transplant centre.
Also discuss ceilings of care and advance care planning, the involvement of his family, and the interaction of ongoing alcohol use with transplant eligibility criteria.