Why is phenoxybenzamine preferred over norepinephrine (noradrenaline) in patients with Fontan circulation experiencing hypotension?

Phenoxybenzamine in Fontan Resuscitation: Rationale and Benefits

Phenoxybenzamine is preferred over norepinephrine in Fontan circulation hypotension because it reduces systemic vascular resistance, improving pulmonary blood flow and cardiac output, while norepinephrine would increase systemic vascular resistance and worsen the already compromised hemodynamics.

Understanding Fontan Circulation Physiology

The Fontan circulation represents a unique hemodynamic state characterized by:

• Direct connection of systemic venous return to pulmonary arteries without a subpulmonary ventricle
• Passive pulmonary blood flow dependent on central venous pressure
• Chronically elevated central venous pressure (>10 mmHg) 1
• Relatively low cardiac output (approximately 80% of normal at rest) 1
• Preload-limited single ventricle physiology 1

Key Hemodynamic Principles

In Fontan circulation, three driving forces enable blood flow from systemic veins to the systemic atrium:

1. "Suction effect" from left atrial emptying
2. Lung and muscle pump effects
3. Low pulmonary vascular resistance 1

Why Phenoxybenzamine is Preferred

Mechanism of Action Benefits

Phenoxybenzamine, an α-adrenergic antagonist, provides several critical benefits in Fontan circulation:

• Reduces systemic vascular resistance (SVR): This improves systemic oxygen delivery and reduces the likelihood of cardiac arrest in patients with Fontan physiology 1
• Improves balance between systemic and pulmonary circulation: By reducing SVR, it helps optimize the Qp:Qs ratio (pulmonary to systemic flow ratio) 2
• Addresses underlying pathophysiology: Fontan patients have increased sympathetic activity and altered endothelial function contributing to their elevated SVR 3

The 2015 American Heart Association guidelines specifically recommend: "Neonates in a low cardiac output state following stage I repair may benefit from systemic vasodilators such as α-adrenergic antagonists (eg, phenoxybenzamine) to treat or ameliorate increased systemic vascular resistance, improve systemic oxygen delivery, and reduce the likelihood of cardiac arrest (Class IIa, LOE B)" 1.

Problems with Norepinephrine

Norepinephrine would be counterproductive in Fontan circulation because:

1. Increases systemic vascular resistance: This would worsen the already compromised hemodynamics by further limiting cardiac output 1
2. Impairs pulmonary blood flow: By increasing SVR, it reduces passive flow through the pulmonary circulation 1
3. Worsens ventricular preload: Increased afterload further compromises the already preload-limited single ventricle 1

Clinical Management Algorithm

1. Identify Fontan circulation in hypotensive patient

   • Check for surgical history, elevated CVP, single ventricle anatomy
   • Assess for signs of low cardiac output: decreased urine output, cool extremities

2. Initial management steps:

   • Ensure adequate oxygenation
   • Consider hypoventilation to improve oxygen delivery in pre-arrest state 1
   • Consider negative pressure ventilation to improve cardiac output 1

3. Pharmacological intervention:

   • First-line: Phenoxybenzamine to reduce systemic vascular resistance
   • Alternative options: Other systemic vasodilators (e.g., milrinone) may be considered for patients with excessive Qp:Qs 1
   • Avoid: Norepinephrine, other pure vasoconstrictors that increase SVR

4. Refractory cases:

   • Consider extracorporeal membrane oxygenation (ECMO) for patients with Fontan physiology during cardiopulmonary arrest 1

Important Considerations and Pitfalls

• Fluid management: Excessive fluid loading may worsen hemodynamics in patients with Fontan circulation 1
• Monitoring: Continuous assessment of central venous pressure, systemic venous oxygen saturation, and cardiac output is essential
• Long-term management: Consider PDE-5 inhibitors (sildenafil) for chronic management of elevated pulmonary vascular resistance 1, 4

Evidence Quality Assessment

The recommendation for phenoxybenzamine is based on Class IIa, Level of Evidence B guidelines from the American Heart Association 1, supported by clinical studies showing improved systemic oxygen delivery after its administration 2. While the evidence is not from large randomized controlled trials, the physiological principles and available clinical data strongly support this approach.