Can high-flow oxygen (O2) be used as a pulmonary vasodilator in patients with pulmonary embolism (PE)?

High-Flow Oxygen as a Pulmonary Vasodilator in Pulmonary Embolism

High-flow oxygen should be considered as a supportive therapy in PE patients with hypoxemia or right ventricular dysfunction, as it provides pulmonary vasodilation and reduces RV afterload, though it cannot replace definitive reperfusion therapy.

Mechanism and Rationale

Oxygen functions as a pulmonary vasodilator in PE through direct effects on pulmonary vascular resistance. In experimental models, supplemental oxygen reduces pulmonary artery pressure and RV mechanical work with effects comparable to inhaled nitric oxide 1. The mechanism addresses the V/Q mismatch that drives hypoxemia in PE, while simultaneously reducing pulmonary vascular resistance 2, 3.

Evidence for Efficacy

Experimental Data

• Animal studies demonstrate that oxygen therapy (FiO2 40-100%) immediately lowers mean pulmonary arterial pressure and pulmonary vascular resistance in PE models, with maximal hemodynamic benefit achieved at FiO2 40% 1
• Oxygen reduces RV volumes, decreases RV mechanical work, and shows persistent effects over 75 minutes with efficacy similar to inhaled nitric oxide (40 ppm) 1
• These effects occur within minutes of administration 4, 1

Clinical Application

Small clinical studies and case series report that inhaled nitric oxide improves hemodynamic status and gas exchange in PE patients 2. While direct high-flow oxygen studies in humans are limited, an ongoing randomized trial (SO-PE) is investigating supplemental oxygen's mechanisms in acute PE patients with RV dysfunction 5.

Guideline Recommendations

The 2019 ESC Guidelines explicitly recommend considering high-flow oxygen (via high-flow nasal cannula) as an oxygenation technique in PE patients, particularly when conventional oxygen supplementation is insufficient 2. This recommendation applies to:

• Patients with SaO2 <90% (supplemental oxygen is indicated) 2
• Severe hypoxemia refractory to conventional oxygen 2
• Patients requiring respiratory support but not yet requiring intubation 2, 6

Practical Implementation

When to Use High-Flow Oxygen

• Initiate when conventional nasal oxygen fails to maintain SaO2 ≥90% 2, 6
• Consider early in patients with RV dysfunction even if not severely hypoxemic, given the pulmonary vasodilator effects 1
• Prefer high-flow nasal cannula over mechanical ventilation when feasible, as positive pressure ventilation can worsen RV failure 2, 7

Target Oxygen Saturation

• Maintain SaO2 94-98% (or 88-92% if risk of hypercapnic respiratory failure) 6, 7
• Note that SaO2 ≥90% does not exclude hypoxemic respiratory failure; a target of ≥92% is more reliable for excluding significant hypoxemia (PaO2 <60 mmHg) 8

Critical Limitations and Caveats

Not a Replacement for Reperfusion

Correction of hypoxemia ultimately requires pulmonary reperfusion through anticoagulation or thrombolysis, not oxygen supplementation alone 2, 3. Oxygen is supportive therapy that must be combined with:

• Immediate anticoagulation 6, 7
• Thrombolytic therapy in high-risk PE 7
• Definitive reperfusion strategies based on risk stratification 6

Refractory Hypoxemia

Severe hypoxemia that does not improve with high-flow oxygen should raise suspicion for right-to-left shunting through a patent foramen ovale or atrial septal defect 2, 3. In these cases:

• Oxygen will be less effective due to true shunt physiology 3
• Echocardiography should be performed to evaluate for intracardiac shunting 6, 3
• Elevated right atrial pressure exceeding left atrial pressure drives the shunt 2, 3

Mechanical Ventilation Considerations

If intubation becomes necessary despite high-flow oxygen 2:

• Use low tidal volumes (approximately 6 mL/kg lean body weight) 2
• Apply positive end-expiratory pressure cautiously, as it reduces venous return and worsens RV failure 2, 6
• Avoid anesthetic agents prone to causing hypotension 2, 6

Alternative Pulmonary Vasodilators

While high-flow oxygen is readily available and safe, other pulmonary vasodilators have been studied 2:

• Inhaled nitric oxide shows similar efficacy to oxygen in reducing pulmonary vascular resistance 4, 9, 1
• Systemic vasodilators lack pulmonary specificity and risk worsening systemic hypotension 2
• Levosimendan may restore RV-pulmonary arterial coupling but remains investigational 2

Clinical Algorithm

1. Assess oxygenation status immediately upon PE diagnosis 6, 7
2. If SaO2 <90%: initiate supplemental oxygen via nasal cannula or face mask 2, 6, 7
3. If conventional oxygen insufficient: escalate to high-flow nasal cannula 2, 6
4. If hypoxemia refractory to high-flow oxygen: evaluate for intracardiac shunt and consider mechanical ventilation 2, 6, 3
5. Throughout: ensure simultaneous anticoagulation and risk-appropriate reperfusion therapy 6, 7