How do you diagnose an intrapulmonary shunt?

Diagnosis of Intrapulmonary Shunt

The diagnosis of intrapulmonary shunt is established through contrast echocardiography with agitated saline (bubble study), where microbubbles appearing in the left atrium within 3-6 cardiac cycles after injection confirms the diagnosis, and this should be quantified using a 99mTechnetium-macroaggregated albumin (MAA) perfusion lung scan when precise measurement is needed. 1

Initial Screening Approach

Clinical Suspicion

Begin evaluation when patients present with:

• Unexplained hypoxemia with pulse oximetry <97% on room air in the upright position 1
• Digital clubbing, facial telangiectasia, dyspnea, wheezing, or syncope in patients with liver disease or portal hypertension 1
• Platypnea-orthodeoxia (worsening hypoxemia when upright) 1

Pulse Oximetry Screening

• Perform transcutaneous oxygen saturation measurement with the patient in the upright position as the first-line screening tool 1
• SpO2 <96% has 100% sensitivity and 88% specificity for detecting intrapulmonary shunt in adults with hepatopulmonary syndrome 1
• If SpO2 <96%, proceed to arterial blood gas analysis 1

Arterial Blood Gas Analysis

• PaO2 <80 mmHg or alveolar-arterial oxygen gradient (P[A-a]O2) ≥15 mmHg (≥20 mmHg in patients ≥65 years) indicates need for further investigation 1
• The hypoxemia in intrapulmonary shunt is relatively refractory to supplemental oxygen, distinguishing it from V/Q mismatch 1

Definitive Diagnostic Testing

Contrast Echocardiography (Bubble Study)

This is the primary diagnostic modality for confirming intrapulmonary shunt. 1, 2

Technique and Interpretation

• Inject agitated saline containing microbubbles intravenously during two-dimensional echocardiography 1, 2
• Microbubbles appearing in the left atrium within 3-6 cardiac cycles confirm intrapulmonary shunt (hepatopulmonary syndrome pattern) 1
• Immediate appearance (<3 cardiac cycles) indicates intracardiac shunt (patent foramen ovale or atrial septal defect), not intrapulmonary shunt 1, 2
• Transthoracic echocardiography has 98-99% sensitivity for detecting intrapulmonary shunt 2

Grading the Shunt

• Grade the degree of left ventricular opacification (1+ to 4+) to semi-quantitatively assess shunt severity 3, 4
• Patients with ≥2+ left ventricular opacification have significantly lower PaO2 values (mean 66 mmHg vs 82 mmHg) 3

Transesophageal Echocardiography (TEE)

• TEE provides higher sensitivity (51% vs 32%) compared to transthoracic echocardiography for detecting shunts 1, 2
• Use TEE to definitively exclude intracardiac shunts when transthoracic imaging is equivocal 1, 2
• TEE allows direct visualization of bubbles entering the left atrium from pulmonary veins rather than crossing the interatrial septum 1

Quantitative Assessment with MAA Scan

When precise quantification is needed:

• 99mTechnetium-macroaggregated albumin (MAA) perfusion lung scan quantifies the degree of intrapulmonary shunting 1
• MAA shunt fraction of 27.8% is highly specific for intrapulmonary shunting associated with hypoxia 1
• Perform MAA scan in patients with severe hypoxemia (PaO2 <50 mmHg) and coexistent intrinsic lung disease to differentiate causes 1
• Use MAA scan to assess prognosis in patients with very severe hypoxemia 1

Distinguishing Intrapulmonary from Intracardiac Shunt

Key Timing Differences

• Intrapulmonary shunt: bubbles appear 3-6 cardiac cycles after injection (time for blood to traverse pulmonary circulation) 1
• Intracardiac shunt: bubbles appear immediately or within 1-3 cardiac cycles 1, 2

Additional Differentiation

• Perform Valsalva maneuver during bubble study: increased right atrial pressure enhances detection of patent foramen ovale 2
• TEE can definitively differentiate by visualizing the anatomic location of bubble passage 1

Invasive Measurement (Reference Standard)

Shunt Calculation

The reference standard for quantifying shunt is invasive oximetry with measurement of oxygen saturations in pulmonary and systemic arterial and venous systems. 1

Shunt Equation Components

• Measure oxygen content in central venous blood (before gas exchange) 5
• Calculate oxygen content in pulmonary capillaries (after gas exchange, assuming complete equilibration with alveolar gas) 5
• Measure oxygen content in arterial blood (after mixing of shunted and non-shunted blood) 5

Limitations of Invasive Measurement

• Requires multiple sampling sites during steady state, leading to significant error propagation 1
• Cannot measure shunt distal to extracardiac lesions (e.g., systemic-pulmonary arterial collaterals) 1
• Invasive nature with associated morbidity and high cost 1

Phase-Contrast Cardiac MRI

For congenital heart disease with suspected shunt lesions:

• Phase-contrast cardiac MRI is the non-invasive reference standard for measuring Qp/Qs ratio (pulmonary to systemic blood flow) 1
• Qp/Qs >1 indicates left-to-right shunt; Qp/Qs <1 indicates right-to-left shunt 1
• PC-CMR allows highly accurate and reproducible quantification without assumptions, validated against direct flow measurement 1

Clinical Context-Specific Considerations

Hepatopulmonary Syndrome

• Prevalence of intrapulmonary shunt is 17-47% in patients with end-stage liver disease 1, 3, 4
• Significant correlation exists between degree of intrapulmonary shunt and Child-Pugh classification score 4
• Screen all liver transplant candidates with pulse oximetry in upright position 1

Pulmonary Hypertension Evaluation

• Screen for intrapulmonary shunt when evaluating patients with elevated RVSP >45 mmHg 2
• Bubble study helps identify intracardiac shunts that may contribute to or complicate pulmonary hypertension 1, 2

ARDS and Sepsis

• Intrapulmonary shunt in ARDS is due to persistent perfusion of atelectatic and fluid-filled alveoli 1
• Normal intrapulmonary shunt is <5% of cardiac output; in ARDS it may exceed 25% 1
• Shunt calculation becomes important in ECMO patients, as arterial oxygen levels may not reflect native lung gas exchange 5

Common Pitfalls to Avoid

• Do not rely solely on PaO2 to diagnose intrapulmonary shunt: patients with significant shunt may have near-normal PaO2 at rest 3
• Do not perform bubble study in supine position only: orthodeoxia may be missed without upright positioning 1
• Do not confuse timing of bubble appearance: late appearance (3-6 cycles) is intrapulmonary, not intracardiac 1
• Do not use CT or MRI to exclude intrapulmonary shunt: these modalities lack sensitivity for functional shunt assessment 1
• Do not assume 100% oxygen will worsen shunt: studies show shunt does not increase with 100% oxygen ventilation in acute respiratory failure 6