Vascular air embolism (VAE) is a life-threatening event that occurs when air enters the circulatory system.
Paradoxical air embolism (PAE) is a form of VAE in which air that has entered the venous circulation bypasses the pulmonary circulation through a right-to-left shunt such as a patent foramen ovale (PFO) and moves into the arterial circulation.
When the posterior cerebral artery is occluded, it can cause acute visual impairment.
PFO is reported to be present in 25–30% of the general population1), with some reports indicating 15–35%2). The incidence of PAE varies depending on the causative procedure; air embolism in CT-guided transthoracic needle biopsy (TNB) is approximately 0.23%3), and cerebral artery air embolism due to bronchoscopic procedures is reported to be less than 0.02%4).
QDoes the presence of a patent foramen ovale (PFO) always lead to paradoxical embolism?
A
PFO is present in 25–30% of the general population, but most cases are asymptomatic. For paradoxical embolism to occur, conditions are required in which right atrial pressure exceeds left atrial pressure, opening a right-to-left shunt through the PFO; invasive procedures or pulmonary hypertension can act as triggers.
End-tidal CO2 (EtCO2) decrease: The earliest indicator of VAE. Reflects increased dead space ventilation.
Arterial blood gas analysis: Hypoxemia. Arterial embolism may not show immediate EtCO2 decrease.
Brain CT findings: Air bubbles in the subarachnoid space or brain parenchyma. Sensitivity is time-dependent and highest within 1.5 hours of onset. 6)
Brain MRI findings: Restricted diffusion on diffusion-weighted imaging (DWI), FLAIR hyperintensity, and a mixed pattern of cytotoxic and vasogenic edema. 6)
Central venous catheter manipulation: Air enters due to the negative pressure gradient at the tip of the superior vena cava.
Vitrectomy: Improper placement of the infusion line allows pressurized air to enter the suprachoroidal space → vortex veins → systemic veins.
Transthoracic needle biopsy (TNB): Caused by misplacement of the needle tip into the pulmonary vein or formation of a bronchial-pulmonary venous fistula. 3)
Bronchoscopic ablation: Formation of a bronchovascular fistula and positive pressure ventilation are triggers. 4)
Removal of hemodialysis catheter: Retrograde venous air embolism may occur. 6)
Causes of right-to-left shunt
Patent foramen ovale (PFO): Most common. Present in 25–30% of the general population. 1)
Atrial septal defect (ASD): A major shunt cause alongside PFO.
Pulmonary arteriovenous malformation: This creates a pathway that bypasses the pulmonary circulation. 8)
Persistent left superior vena cava (PLSVC): Present in 0.2–3% of the general population, it forms a right-to-left shunt via the unroofed coronary sinus. 5)
Risk factors:
Central venous line manipulation in the sitting or standing position: Increased negative intrathoracic pressure enhances the air inflow gradient.
Decreased intrathoracic pressure during inspiration: Increases air inflow into the venous system.
Pulmonary hypertension / massive pulmonary embolism: Elevated right atrial pressure induces right-to-left shunt via PFO. 8)
Valsalva maneuver, tricuspid regurgitation, right ventricular failure: Transiently increase right atrial pressure. 8)
QIs there a risk of air embolism even in ophthalmic surgery (vitrectomy)?
A
In vitrectomy, if the infusion line is improperly positioned, pressurized air can enter the systemic venous circulation from the suprachoroidal space via the vortex veins. A preoperative timeout to confirm the position of the infusion cannula before fluid-air exchange is recommended as a preventive measure.
Sudden deterioration during or immediately after an invasive procedure is the most important diagnostic clue. A history of right-to-left shunt and procedural history are essential.
The characteristics of each test are shown below.
Test
Characteristic
Main purpose
Brain CT
Optimal within 1.5 hours 6)
Detection of air bubbles and hypodense areas
Brain MRI (DWI)
Detects infarction even after air bubble absorption 6)
Confirmation of ischemic areas
Transesophageal echocardiography (TEE)
Gold standard for PFO detection5)
Confirmation of right-to-left shunt
Key points in imaging diagnosis:
Brain CT has time-dependent sensitivity for detecting air, and air bubbles may disappear after 16 hours. 6)
Air is not detected on CT in 25% of cases, and MRI is useful as a complementary tool. 6)
Detection on CT may be difficult when air bubbles are smaller than 1.3 cm. 4)
Echocardiography:
Transesophageal echocardiography (TEE): Combining agitated saline contrast (bubble study) with the Valsalva maneuver maximizes PFO detection sensitivity. 5)
Transthoracic echocardiography (TTE): PFO sensitivity is lower than with TEE. 8)
Supplementary indicators:
EtCO2 decrease: The earliest indicator of VAE (due to increased dead space ventilation).
Arterial blood gas: Confirms hypoxemia but has low sensitivity.
Durant’s maneuver: Before the procedure, place the patient in left lateral decubitus or Trendelenburg position. This keeps air bubbles in the right atrium, preventing migration to the brain and coronary arteries.
Avoid central venous line manipulation in sitting or standing positions: Prevents air entry due to negative intrathoracic pressure.
Intraoperative timeout: Confirm proper placement of infusion cannula before fluid-air exchange during vitrectomy.
PFO screening before neurosurgery in semi-sitting position: Preoperative evaluation with TEE + bubble study + Valsalva maneuver is recommended. 5)
Position management during hemodialysis catheter removal: Supine position, removal at end-expiration, and correction of circulating blood volume are important. 6)
Hyperbaric oxygen therapy (HBO2): First-line treatment. Administration of 100% oxygen increases blood PO2, promoting nitrogen diffusion and reducing bubble size (Boyle’s law). 3) Mortality without HBO2 is 93%, whereas with HBO2 it improves significantly to 7%. 4) Ideally initiated within 5–7 hours of onset, but delayed initiation after 30–60 hours may still be effective. 6)
Position management:
If arterial embolism is suspected, immediately place the patient in the supine position (Trendelenburg position may worsen cerebral edema).
For venous air embolism, use the Durant maneuver (left lateral decubitus and Trendelenburg position).
Hemodynamic support: Administer fluids and vasopressors for hypotension and cardiovascular collapse.
If HBO2 is unavailable: Administer normobaric oxygen (NBO2) at FiO2 100% via a high-flow mask. 4)
Transcatheter PFO closure: Considered for symptomatic PFO. The absolute risk reduction of recurrent stroke compared to medical therapy is reported as 3.3% (RD −0.033, 95% CI −0.062 to −0.004). 1)
Surgical thrombectomy + PFO closure: In impending paradoxical embolism (IPDE), the 30-day mortality rate is 10.8%, which is significantly lower compared to thrombolysis (26.3%) and anticoagulation (25.6%). 9)
For incidental PFO with a single embolic event, closure may not be necessary. 8)
QWhat should be done if hyperbaric oxygen therapy is not available?
A
If HBO2 is not available, normobaric oxygen therapy (NBO2) with FiO2 100% via a high-flow mask is the next best option. Position management (supine or left lateral decubitus) and hemodynamic support (fluids and vasopressors) should be performed concurrently. HBO2 may still be effective even when started late (after 30–60 hours), so transfer to a hyperbaric oxygen treatment facility should be considered if transport is possible.
6. Pathophysiology and Detailed Mechanism of Onset
Route of venous air embolism: Air → internal jugular vein → brachiocephalic vein → superior vena cava → right atrium → stagnation in pulmonary vasculature → increased pulmonary artery pressure and right ventricular pressure → impaired left ventricular diastolic filling.
Conversion to paradoxical embolism: Air bubbles in the right atrium bypass the pulmonary circulation via PFO/ASD → left atrium → left ventricle → aorta → brachiocephalic artery → vertebral artery → basilar artery → circle of Willis.
Role of pressure gradient: The venous system has lower pressure than the arterial system, and in 40% of patients, central venous pressure is below atmospheric pressure. Sitting position and inspiration further decrease intrathoracic pressure, increasing air inflow.
Effects of air bubbles: Small bubbles are absorbed in the capillary bed, but large bubbles cause ischemia in peripheral organs. As little as 2 mL in the cerebral circulation or 0.5 mL in the coronary artery (LAD) can be fatal. 6)
Inflammatory response: Neutrophil activation, endothelial adhesion via β2 integrins, reduced blood flow, and blood-brain barrier disruption occur. 6)
Retrograde venous air embolism: A mechanism in which air ascends retrograde against venous flow, contributed by low cardiac output and low circulating blood volume. 6)
Bronchovascular fistula formation: During bronchoscopic cauterization, inflammation, thermal coagulation, and mechanical disruption lead to fistula formation, allowing air to enter the circulation when internal pressure rises. 4)
QIs even a small amount of air dangerous?
A
Even as little as 2 mL of air reaching the cerebral circulation can be fatal. In the coronary artery (left anterior descending), 0.5 mL can induce ventricular fibrillation. The severity depends on the size and location of the air bubble; large bubbles that exceed the capillary bed can lead to organ ischemia.
7. Latest Research and Future Perspectives (Research Stage Reports)
In 119 cases of venous/arterial gas embolism treated with HBO2, 43% of survivors had neurological sequelae at discharge. The most common complications were visual field defects, motor disorders, cognitive dysfunction, and epileptic seizures. Risk factors for death or persistent neurological sequelae included cardiac arrest at the time of air embolism, SAPS II score ≥33, advanced age, mechanical ventilation for ≥5 days, and acute renal failure.
Henmi et al. (2021) reported an 18.4% 30-day mortality rate in a systematic review of 174 cases of impending paradoxical embolism (IPDE). By treatment type, mortality was 10.8% for surgery, 26.3% for thrombolysis, and 25.6% for anticoagulation, with surgery being significantly better. 9) In an analysis of 88 IPDE cases, 40.9% (36/88) developed systemic embolism before treatment, with cerebral embolism being the most common (26 cases).
A meta-analysis by Aggarwal et al. (2023) showed that PFO closure reduced the absolute risk of recurrent stroke by 3.3% compared to medical therapy (RD −0.033, 95% CI −0.062 to −0.004).1)
Teifurova et al. (2025) systematically described MRI findings of retrograde venous air embolism. Characteristic findings included DWI restriction, FLAIR hyperintensity, a mixed pattern of cytotoxic and vasogenic edema, and leptomeningeal enhancement.6) CT detection of air is optimal within 1.5 hours of onset and may disappear after 16 hours. Air is not detected on CT in 25% of cases, making MRI a useful complementary tool.
Nikolic et al. (2024) discussed the importance of PFO screening using TEE plus bubble study and Valsalva maneuver before semi-sitting neurosurgery. 5) Color Doppler alone is insufficient, and the addition of contrast bubble study is recommended.
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Elzawy G, Petrasek P, Fatehi Hassanabad A. The Unique Case of Acute Limb Ischemia in a Patient With a Patent Foramen Ovale. Vasc Endovascular Surg. 2024;58(8):894-899. doi:10.1177/15385744241276615.
Santos A, Almeida C, Porto LM, Fernandes PD, Silva JP. Cerebral Air Embolism: A Case of a Rare Transthoracic Needle Biopsy Complication. Cureus. 2023;15(2):e35203. doi:10.7759/cureus.35203. PMID:36960241; PMCID:PMC10031384.
He YP, Liu YL, Gao XL, Wang LH. Cerebral arterial air embolism after endobronchial electrocautery: a case report and review of the literature. BMC pulmonary medicine. 2021;21(1):222. doi:10.1186/s12890-021-01580-w. PMID:34247608; PMCID:PMC8274011.
Nikolic M, Eisner C, Neumann JO, Haux D, Krieg SM, Wielpütz MO, et al. Right-to-left-shunts in patients scheduled for neurosurgical intervention in semi-sitting position - a literature review based on two case scenarios. BMC anesthesiology. 2024;24(1):375. doi:10.1186/s12871-024-02757-6. PMID:39415125; PMCID:PMC11481392.
Teifurova S, Rācenis K, Freijs Ģ, Skrastina S, Balodis A. Radiological Findings of Retrograde Venous Cerebral Air Embolism Infarcts: A Case Report and Literature Review. Vascular health and risk management. 2025;21:617-631. doi:10.2147/VHRM.S537865. PMID:40831676; PMCID:PMC12358500.
Cárdenas-Marín PA, Zambrano-Franco JA, Reyes-Cardona MJ, Calderon-Miranda CA, Sanchez-Blanco J, Olaya P, et al. Postpartum ischemic stroke due to persistent left superior vena cava to left atrium after DORV repair: a case report and literature review. BMC cardiovascular disorders. 2025;25(1):463. doi:10.1186/s12872-025-04922-2. PMID:40610942; PMCID:PMC12232136.
Cunha R, Silva M, Henrique A, Maximiano P, Correia M, Vieira I, et al. Paradoxical embolism: a rare cause of acute upper limb ischemia. Journal of surgical case reports. 2023;2023(7):rjad435. doi:10.1093/jscr/rjad435. PMID:37520078; PMCID:PMC10374347.
