Glenn Circulation #4: The Glenn Paradox

After a bidirectional Glenn or superior cavopulmonary connection, pulmonary blood flow is no longer generated by a subpulmonary ventricle. Instead, the superior vena cava drains directly into the pulmonary arteries, creating a passive venous pathway in which SVC return becomes Glenn flow. Therefore, systemic oxygenation depends not only on pulmonary vascular resistance, but also on cerebral blood flow, upper-body venous return, intrathoracic pressure, ventricular filling pressure, and the transpulmonary gradient.

This physiology creates a counterintuitive phenomenon known as the Glenn paradox: hyperventilation may lower pulmonary vascular resistance, yet systemic oxygenation can deteriorate because hypocapnia reduces cerebral blood flow and therefore reduces SVC-to-pulmonary artery flow [1].

1. The Core Physiology of Glenn Flow

In the Glenn circulation:

SVC return → pulmonary arteries → pulmonary blood flow → pulmonary venous return → systemic ventricle

Because there is no pumping chamber between the SVC and the pulmonary arteries, pulmonary blood flow is determined by a balance between:

1. Upstream flow source
• Cerebral blood flow
• Upper-body venous return
• SVC pressure and patency
2. Downstream resistance
• Pulmonary vascular resistance
• Pulmonary artery anatomy
• Pulmonary venous pressure
• Ventricular end-diastolic pressure
3. Respiratory mechanics
• Intrathoracic pressure
• Mean airway pressure
• Lung recruitment
• Spontaneous versus positive-pressure ventilation

A simple but important relationship is:

↑ Cerebral blood flow → ↑ SVC return → ↑ Glenn flow → ↑ pulmonary blood flow → ↑ SpO₂

Conversely:

↓ Cerebral blood flow → ↓ SVC return → ↓ Glenn flow → ↓ pulmonary blood flow → ↓ SpO₂

Thus, in Glenn physiology, the brain is not merely an end-organ receiving blood flow; it is also a major determinant of pulmonary blood flow.

2. Why PaCO₂ Has Competing Effects

PaCO₂ influences Glenn circulation through two vascular beds with opposite clinical implications.

A. Pulmonary vascular bed

Lower PaCO₂ tends to reduce pulmonary vascular resistance through respiratory alkalosis. This is why hyperventilation may initially appear attractive:

↓ PaCO₂ → ↓ PVR → lower downstream resistance to Glenn flow

In a standard postoperative setting, this concept often leads clinicians to ventilate more aggressively when oxygen saturation is low.

B. Cerebral vascular bed

However, PaCO₂ is also a powerful regulator of cerebral vascular tone. Hypercapnia causes cerebral vasodilation, whereas hypocapnia causes cerebral vasoconstriction. In a Glenn circulation, this matters because cerebral venous return drains into the SVC and directly contributes to pulmonary blood flow.

Therefore:

↑ PaCO₂ → cerebral vasodilation → ↑ cerebral blood flow → ↑ SVC return → ↑ Glenn flow → ↑ SpO₂

Whereas:

↓ PaCO₂ → cerebral vasoconstriction → ↓ cerebral blood flow → ↓ SVC return → ↓ Glenn flow → ↓ SpO₂

The paradox occurs when the reduction in cerebral blood flow outweighs the benefit of lower pulmonary vascular resistance.

3. The Glenn Paradox

The Glenn paradox can be summarized as follows:

Hyperventilation may lower PVR, but excessive hypocapnia can reduce cerebral blood flow so much that total Glenn flow decreases.

Bradley and colleagues demonstrated that hyperventilation after bidirectional superior cavopulmonary connection significantly impaired systemic oxygenation, despite a decrease in transpulmonary gradient [1]. This finding is physiologically important because it shows that Glenn oxygenation is not determined by PVR alone.

The mechanism is:

1. Hyperventilation lowers PaCO₂.
2. Low PaCO₂ causes cerebral vasoconstriction.
3. Cerebral blood flow decreases.
4. SVC return decreases.
5. Glenn flow decreases.
6. Pulmonary blood flow decreases.
7. Systemic oxygen saturation falls.

In other words, less resistance does not help if there is not enough upstream venous flow to pass through the circuit.

4. Evidence Supporting the Paradox

The clinical evidence is consistent across several physiologic studies.

Bradley et al. first showed that hyperventilation worsened oxygenation after bidirectional superior cavopulmonary connection, even though transpulmonary gradient decreased [1]. In a subsequent study, the same group showed the opposite effect: controlled hypoventilation increased PaCO₂, improved arterial oxygen tension and systemic saturation, and increased cerebral blood flow velocity [2].

Hoskote et al. further demonstrated that PaCO₂ levels of approximately 45–55 mmHg increased systemic oxygenation, pulmonary blood flow, systemic blood flow, and cerebral blood flow compared with a PaCO₂ of 35 mmHg after bidirectional cavopulmonary anastomosis [3]. Li et al. similarly reported that moderate hypercapnia improved systemic oxygenation and was associated with lower oxygen consumption and blood lactate levels after bidirectional superior cavopulmonary anastomosis [4].

Fogel et al. provided a particularly elegant mechanistic explanation using flow analysis in single-ventricle patients with superior cavopulmonary connection. Their study showed that when the pulmonary and cerebral CO₂ feedback loops compete, the cerebral feedback loop predominates [5]. This supports the central concept that, in Glenn physiology, cerebral blood flow regulation may dominate over the pulmonary vascular response to CO₂.

5. Practical Clinical Interpretation

When a Glenn patient becomes desaturated, the reflex response should not be automatic hyperventilation. The critical question is:

Is the patient desaturated because PVR is high, or because Glenn inflow is insufficient?

Potential contributors include:

• Excessive hypocapnia causing cerebral vasoconstriction
• Elevated PVR from atelectasis, hypoxia, acidosis, pain, agitation, or lung disease
• Excessive positive-pressure ventilation or high mean airway pressure
• Elevated ventricular end-diastolic pressure or atrial pressure
• Pulmonary artery stenosis, distortion, thrombosis, or uneven branch PA flow
• SVC obstruction or Glenn anastomotic narrowing
• Low systemic cardiac output with increased oxygen extraction
• Anemia or reduced oxygen-carrying capacity

The key point is that SpO₂ is a downstream signal, not a diagnosis. In Glenn physiology, desaturation may reflect pulmonary vascular resistance, impaired venous return, reduced cerebral perfusion, ventricular dysfunction, or an anatomic obstruction.

6. Ventilation Strategy After Glenn

The goal of ventilation is not simply to minimize PaCO₂ or PVR. The goal is to optimize the entire passive-flow circuit.

A balanced strategy includes:

1. Avoid marked hypocapnia

Excessive hyperventilation can reduce cerebral blood flow and worsen oxygenation.

2. Maintain adequate lung recruitment

Atelectasis increases PVR and may impair Glenn flow.

3. Avoid excessive intrathoracic pressure

High mean airway pressure, excessive PEEP, or large tidal volumes may impede systemic venous return and reduce pulmonary blood flow.

4. Prevent hypoxia and acidosis

Both can increase PVR and destabilize Glenn physiology.

5. Consider the benefit of spontaneous breathing when appropriate

Negative intrathoracic pressure may augment venous return and improve pulmonary blood flow compared with positive-pressure ventilation [6].

6. Use PaCO₂ as a physiologic lever, not an isolated target

Mild hypercapnia may improve oxygenation in selected patients, but excessive hypercapnia can cause acidosis, increase PVR, and impair myocardial performance.

7. Monitoring the Glenn Patient

Because the Glenn circulation is sensitive to multiple interacting variables, assessment should integrate several parameters:

• SpO₂ trend
• PaCO₂ and pH
• Lactate
• Cerebral and somatic NIRS
• SVC or central venous pressure
• Common atrial pressure, when available
• Ventricular function and AV valve regurgitation
• Pulmonary artery anatomy and Glenn pathway patency
• Chest radiograph for lung recruitment, effusion, or atelectasis

Mott et al. showed that changes in mechanical ventilation can alter cerebral oxygenation in infants with bidirectional superior cavopulmonary connection, supporting the clinical value of cerebral monitoring during ventilatory adjustments [7]. Bertolizio et al. also demonstrated that conversion from shunt-dependent circulation to bidirectional Glenn circulation changes cerebral oxygenation and perfusion, emphasizing that cerebral hemodynamics are central to Glenn physiology [8].

8. Key Concept

The Glenn paradox is not a contradiction. It reflects the unique arrangement of the Glenn circulation.

In a biventricular circulation, pulmonary blood flow is primarily pump-driven.

In a Glenn circulation, pulmonary blood flow is venous-return-driven.

Therefore:

Low PVR is necessary, but not sufficient.

The patient also needs adequate SVC inflow.

The essential sequence is:

Excessive hyperventilation → ↓ PaCO₂ → cerebral vasoconstriction → ↓ cerebral blood flow → ↓ SVC return → ↓ Glenn flow → ↓ pulmonary blood flow → ↓ SpO₂

This is the Glenn paradox.

Take-Home Message

After a bidirectional Glenn, oxygenation depends on passive SVC-to-pulmonary artery flow. Although hyperventilation may reduce pulmonary vascular resistance, excessive hypocapnia can reduce cerebral blood flow, decrease SVC return, and ultimately reduce Glenn flow. The optimal ventilatory strategy is therefore not aggressive hyperventilation, but balanced management: preserve lung recruitment, avoid excessive intrathoracic pressure, prevent hypoxia and acidosis, and avoid hypocapnia-induced reduction in cerebral and SVC flow.

References

[1] Bradley SM, Simsic JM, Mulvihill DM. Hyperventilation impairs oxygenation after bidirectional superior cavopulmonary connection. Circulation. 1998;98(19 Suppl):II372-II376; discussion II376-II377. (PubMed)

[2] Bradley SM, Simsic JM, Mulvihill DM. Hypoventilation improves oxygenation after bidirectional superior cavopulmonary connection. J Thorac Cardiovasc Surg. 2003;126(4):1033-1039. (PubMed)

[3] Hoskote A, Li J, Hickey C, Erickson S, Van Arsdell G, Stephens D, Holtby H, Bohn D, Adatia I. The effects of carbon dioxide on oxygenation and systemic, cerebral, and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis. J Am Coll Cardiol. 2004;44(7):1501-1509. (PubMed)

[4] Li J, Hoskote A, Hickey C, Stephens D, Bohn D, Holtby H, Van Arsdell G, Redington AN, Adatia I. Effect of carbon dioxide on systemic oxygenation, oxygen consumption, and blood lactate levels after bidirectional superior cavopulmonary anastomosis. Crit Care Med. 2005;33(5):984-989. (PubMed)

[5] Fogel MA, Durning S, Wernovsky G, Pollock AN, Gaynor JW, Nicolson S. Brain versus lung: hierarchy of feedback loops in single-ventricle patients with superior cavopulmonary connection. Circulation. 2004;110(11 Suppl 1):II147-II152. (PubMed)

[6] Al-Eyadhy A. Mechanical ventilation strategy following Glenn and Fontan surgeries: On going challenge! J Saudi Heart Assoc. 2009;21(3):153-157. (PubMed)

[7] Mott AR, Alomrani A, Tortoriello TA, Perles Z, East DL, Stayer SA. Changes in cerebral saturation profile in response to mechanical ventilation alterations in infants with bidirectional superior cavopulmonary connection. Pediatr Crit Care Med. 2006;7(4):346-350. (PubMed)

[8] Bertolizio G, Dinardo J, Laussen P, Polito A, Pigula F, Zurakowski D, Kussman B. Evaluation of cerebral oxygenation and perfusion with conversion from an arterial-to-systemic shunt circulation to the bidirectional Glenn circulation in patients with univentricular cardiac abnormalities. J Cardiothorac Vasc Anesth. 2015;29(1):95-100. (PubMed)