In CAAE, air enters the arterial circulation either directly through a breach in an arterial wall or indirectly through an intracardiac or pulmonary shunt from the venous circulation. When this happens, the air follows the blood flow and occludes one of the major intracranial arteries and/or blocks terminal arterioles as the smaller bubbles cannot continue past the decreasing diameter of the lumen. Ultimately, the result of this process is brain tissue ischemia in the affected vascular territories.

Venous emboli can cause CAAE through paradoxical embolization, most commonly via a patent foramen ovale, which is present in about 24.2% of the general population (1). In critical care patients, barotrauma can occur as a complication of mechanical ventilation and may manifest as pulmonary interstitial emphysema, pneumothorax, and pneumomediastinum (2). Systemic air embolism has been recognized to occur as a complication of mechanical ventilation, during which air has been detected in the cerebral arterial circulations (3, 4).

The pathophysiology of CVAE is more complicated. Air can enter intracranial veins or venous sinuses when they are directly compromised, for example during a neurosurgical procedure. Sometimes, no clear cause of the CVAE is identified (5). The most common etiology of CVAE, however, is a central venous catheter placement, removal, or malfunction (6). As the blood in the venous system flows away from the brain toward the heart, one could expect the air bubbles to follow this flow and end up lodged in the pulmonary circulation, which does happen to some extent in every case of venous air embolism. However, it has been experimentally demonstrated that air bubbles can, under the right conditions, travel retrogradely toward the intracranial veins due to their low specific weight (7). The main factors enabling this retrograde flow in CVAE are insufficiency of the jugular vein valves, hypovolemia leading to low venous pressure, upright position (>45°) causing a lower pressure gradient for the gas bubbles, and, increased intrathoracic pressure, such as during mechanical ventilation.

Depending on the amount of air that enters the cerebral venous system, CVAE can cause various degrees of blood stasis and ultimately venous brain infarction. Additionally, air bubbles trigger an inflammatory reaction of the endothelium that can lead to activation of the coagulation system further exacerbating the venous congestion (8). In some cases, when the amount of air is not significant, CVAE can be asymptomatic.

The rate of air embolism resorption depends on air volume, bubble shape (with an elongated linear bubble taking longer to resorb compared to a spherical one), and blood flow velocity. CAE should resorb completely in minutes to hours given that no more air is entering the circulation (9).

Specific causes of CAAE and CVAE are summarized in Table 2. Most common etiology of CAE in our patients was central venous catheter related (either disconnection, malfunction or during extraction) which occurred in three cases. Two patients had a CAE following mechanical thrombectomy. In these patients, no clear reason for an air embolism was recognized during the procedure. To decrease the chance of CAE during mechanical thrombectomy, it is important to use an air filter during the contrast injection, which should be done slowly, as well as priming the catheter to eliminate all air in the circuit.

Other causes, including a lung tumor resection, percutaneous lung biopsy, pineal cyst surgery, peripheral intravenous catheter placement, and contrast agent injection admixed with air, were observed a single time each. All CAEs were iatrogenic.

Cerebral air embolism can cause a broad spectrum of neurological symptoms, which include encephalopathy with a varying degree of mental status alteration and impairment of consciousness (5, 10, 21, 23), large vessel occlusion stroke (29), focal neurological deficits (e.g., aphasia, hemiparesis, facial droop, and hemianopsia) (10), symptomatic epileptic seizures (23) or, headache (31). This rather general list of symptoms means that CAE can mimic many other neurological conditions, such as stroke from other causes, intracranial hemorrhage, epilepsy, etc. The main distinguishing factor is the temporal relationship of the onset of symptoms to the causative event allowing air to enter the circulation. In addition to neurological symptoms, CAE can also cause cardiovascular and respiratory manifestations due to coinciding air embolisms in the pulmonary and/or cardiac circulation.

In some cases, the event can be self-limiting, though a lasting neurological deficit is often present, particularly in larger infarctions and in patients significantly disabled at the time of presentation. A fatal course is also not unusual (11, 21, 32).

An accurate diagnosis of cerebral air embolism requires a high index of suspicion based on clinical history and presentation. A history of recent trauma, surgery, medical procedures, or risks that expose the patient to air suggests the possibility of cerebral air embolism. All of our included patients had a presumed iatrogenic cause.

A “mill-wheel” murmur can be appreciated on heart auscultation with large intracardiac air emboli (33). Signs of acute respiratory failure, pulmonary edema, and shock can also be apparent during the physical examination. Often, however, the physical examination is unrevealing.

Transthoracic and transesophageal echocardiography (TEE) have been used to document the presence of air in cardiac chambers as well as air in the great veins. They may also show evidence of acute right ventricular dilation and pulmonary artery hypertension (34). TEE and transcranial Doppler ultrasonography are useful adjunct tests that can detect intracardiac shunts and air bubbles in intracranial vessels, respectively.

Imaging studies play a key role in establishing the diagnosis. Computed tomography (CT) is highly sensitive for the detection of gas in the vessels which appears as highly hypodense areas (the radiodensity of air is defined as −1,000 Hounsfield units). However, as the gas can be resorbed rather rapidly, the initial CT may not show evidence of air directly but only the consequences of CAE, such as cerebral infarction or brain edema. Minimum intensity projection (MinIP) is a visualization method that selectively detects the most hypodense structures in a given volume. In CAE, this can be employed to highlight air bubbles in the cerebral circulation (Figure 1B).

Magnetic resonance imaging (MRI) can also be helpful in the diagnosis of CAE, but it is usually reserved for assessment of consequences of CAE or differential diagnosis, not for directly proving the presence of air, as the CT is usually the more readily available and faster to perform the diagnostic method. In our cohort, CT was used in all patients. The most important MRI sequence in CAE diagnosis is diffusion-weighted imaging (DWI), which shows areas of brain infarction with very high sensitivity.

The primary strategy in CAE management is prevention, which involves strict adherence to procedural guidelines, especially during invasive medical procedures. In case a CAE is suspected, the first step is to prevent further air from entering the circulation, e.g., by putting pressure on the open wound.

A patient with venous air embolization including CVAE should be immediately placed into the left lateral decubitus position (Durant’s maneuver), Trendelenburg position, or left lateral decubitus head-down position (35). Trendelenburg position should avoid additional bubbles from migrating into the brain vasculature by directing air bubbles upwards. In the case of a massive venous air embolism, obstruction of the right ventricle outflow tract by air can lead to shock or cardiac arrest. The left lateral decubitus position is supposed to prevent air from obstructing the right ventricular outflow tract by moving the bubbles into the right atrium (36). However, there are some controversies surrounding these positional maneuvers (especially in the case of the head-down position) due to their potential for exacerbating cerebral edema and increasing intracranial pressure.

For CAAE, the right lateral decubitus position could in theory prevent air bubbles from entering the left ventricular outflow tract by trapping them in the upper portion of the left ventricle (37). Trendelenburg position worsens cerebral edema and intracranial hypertension and therefore should not be used in these cases. The most common recommendation is that a patient with arterial air embolism should be placed in the supine position (35).

High-flow 100% oxygen therapy should be started immediately. The supplemental oxygen increases the partial pressure of oxygen and decreases the partial pressure of nitrogen in the blood. This causes the diffusion of nitrogen from inside the air bubble into the blood, which reduces bubble size and accelerates air resorption. Simultaneously, additional steps to stabilize the patient should be taken as necessary, including airway (tracheal intubation), breathing (mechanical ventilation), and circulation (intravenous fluid resuscitation, vasopressor therapy) management. In comatose patients or those with symptoms of convulsive or non-convulsive status epilepticus, electroencephalography monitoring and treatment with antiseizure medication is indicated.

The definitive treatment for cerebral air embolism is hyperbaric oxygen therapy (HBOT). When available, HBOT should be administered to patients with evidence of hemodynamic or cardiopulmonary compromise, as well as to those with neurologic deficits or other evidence of end-organ damage (38, 39). HBOT should be administered as soon as possible (within the first 4–6 h after symptom onset) as its efficacy diminishes with time (6). HBOT provides oxygen at pressures greater than atmospheric pressure and at 100% concentration so that very high levels of systemic hyperoxia can be achieved. This degree of hyperoxia allows enormous gradients for nitrogen to be displaced from inside the air bubble, which in turn, reduces air bubble size and the degree of arterial blood flow obstruction. Moreover, by increasing the pressure, the volume of the air bubbles is decreased as per Boyle’s law (volume of gas has an inverse relationship with pressure at a constant temperature) and the concentration of dissolved oxygen in plasma is increased which can enhance oxygen supply to ischemic tissues. The benefits of HBOT therapy should be weighed against the risk of death during transfer (40). In our cohort, four patients (36%) in critical state were considered to be too high risk for a transfer to an HBOT facility.

Adjunct treatment with lidocaine infusion is suggested by the European Consensus Conference on Hyperbaric Medicine (41). Lidocaine might confer some neuroprotective effects, although robust data on this treatment are not available (42).

The use of anticoagulation and antiplatelet agents in cerebral air embolism is controversial. In theory, these medications may prevent further thrombosis on the surface of the air bubble. However, there is no robust evidence to suggest a significant improvement in outcomes and the air emboli should resorb rapidly. As such, the decision to use these therapies should be individualized, taking into account the risk of hemorrhage, especially in cases of trauma-related embolism.