Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies

Iatrogenic vascular air embolism is an infrequent but potentially lethal complication of medical procedures. While historically associated with major surgeries, it is increasingly linked to minimally invasive interventions such as endoscopy, hemodialysis, thoracentesis, and central venous access. The clinical presentation varies widely based on whether the air enters the venous or arterial circulation and the volume of gas involved. Because many cases are asymptomatic or misdiagnosed, the true incidence is likely higher than reported.

The core of the injury caused by air emboli is not merely mechanical obstruction, but a complex thromboinflammatory response. When air bubbles enter the vasculature, they act as foreign surfaces that trigger the alternative complement pathway, specifically activating C3. This activation, combined with direct contact between the bubble and the endothelium, promotes platelet aggregation, leukocyte recruitment, and the release of proinflammatory cytokines.

Crucially, air emboli differ from blood clots due to the formation of a thin, lubricating film between the bubble and the vessel wall. This film allows for some residual microperfusion and explains why cerebral air embolism can sometimes be reversed with hyperbaric oxygen therapy (HBOT) even many hours after the initial event, a window significantly longer than that for thrombotic strokes. However, the bubble-endothelial interface also triggers mechanotransduction pathways, where stretching of the endothelial glycocalyx leads to calcium influx and subsequent cell damage.

Immediate management focuses on preventing further air entry and mitigating the effects of existing emboli. For venous air embolism, the Durant maneuver—placing the patient in the left lateral decubitus and Trendelenburg position—is used to trap air in the right ventricle and prevent it from reaching the pulmonary outflow tract or the brain. However, this maneuver is contraindicated for arterial air embolism, where it could increase intracranial pressure.

Hyperbaric oxygen therapy (HBOT) remains the gold standard treatment. It works by reducing bubble volume (Boyle’s Law) and increasing the diffusion gradient for nitrogen washout. Emerging research is investigating adjunctive therapies, including surfactants to reduce bubble-endothelial adhesion, C3 inhibitors to dampen the thromboinflammatory response, and aggressive pulmonary recruitment maneuvers to improve hemodynamics in patients who do not respond to standard care.