Venous air embolism (VAE), a subset of gas embolism, is an entity with the potential for severe morbidity and mortality. It is a predominantly iatrogenic complication[1, 2] that occurs when atmospheric gas is introduced into the systemic venous system.[3]
In the past, VAE was mostly associated with neurosurgical procedures conducted in the sitting position.[4, 5] Subsequently, it has been associated with central venous catheterization,[3, 6, 7] scalp incision,[8] cervical spine fusion,[9] penetrating and blunt chest trauma,[10, 11, 12] high-pressure mechanical ventilation,[3] thoracocentesis,[1] hemodialysis,[3, 7, 13] and several other invasive vascular procedures.
VAE has also been observed during diagnostic studies, such as during radiocontrast injection for computed tomography (CT).[14, 15] The use of gases such as carbon dioxide and nitrous oxide during medical procedures and exposure to nitrogen during diving accidents can also result in VAE.[2] In addition, apparent cases of VAE resulting from pressurized, intravenous infusion of normal saline have been reported in professional football players.[16]
Many cases of VAE are subclinical with no adverse outcome and thus go unreported. Usually, when symptoms are present, they are nonspecific, and a high index of clinical suspicion for possible VAE is required to prompt investigations and initiate appropriate therapy.
The following two preconditions must exist for VAE to occur[4, 17] :
The key factors determining the degree of morbidity and mortality in venous air emboli are related to the volume of gas entrainment, the rate of accumulation, and the patient’s position at the time of the event.[1, 6, 15]
Generally, small amounts of air are broken up in the capillary bed and absorbed from the circulation without producing symptoms. Traditionally, it has been estimated that more than 5 mL/kg of air displaced into the intravenous space is required for significant injury (shock or cardiac arrest) to occur.[1] However, complications have been reported with as little as 20 mL of air[7] (the length of an unprimed IV infusion tubing) that was injected intravenously.
Injection of 2 or 3 mL of air into the cerebral circulation can be fatal.[18] Furthermore, as little as 0.5 mL of air in the left anterior descending coronary artery has been shown to cause ventricular fibrillation.[11, 18] Basically, the closer the vein of entrainment is to the right heart, the smaller the lethal volume is.[1]
Rapid entry or large volumes of air entering the systemic venous circulation puts a substantial strain on the right ventricle, especially if this results in a significant rise in pulmonary artery (PA) pressures. This increase in PA pressure can lead to right ventricular outflow obstruction and further compromise pulmonary venous return to the left heart. The diminished pulmonary venous return will lead to decreased left ventricular preload with resultant decreased cardiac output and eventual systemic cardiovascular collapse.[1, 4, 6]
With VAE, resultant tachyarrhythmias are frequent, but bradyarrhythmias can also occur.[2, 4]
The rapid ingress of large volumes of air (>0.30 mL/kg/min) into the venous circulatory system can overwhelm the air-filtering capacity of the pulmonary vessels, resulting in a myriad of cellular changes.[3] The air embolism effects on the pulmonary vasculature can lead to serious inflammatory changes in the pulmonary vessels; these include direct endothelial damage and accumulation of platelets, fibrin, neutrophils, and lipid droplets.[1]
Secondary injury as a result of the activation of complement and the release of mediators and free radicals can lead to capillary leakage and eventual noncardiogenic pulmonary edema.[1, 3, 7]
Alteration in the resistance of the lung vessels and ventilation-perfusion mismatching can lead to intra-pulmonary right-to-left shunting and increased alveolar dead space with subsequent arterial hypoxia and hypercapnia.[1, 4, 15]
Arterial embolism as a complication of VAE can occur through direct passage of air into the arterial system via anomalous structures such as an atrial or ventricular septal defect, a patent foramen ovale, or pulmonary arteriovenous malformations. This can cause paradoxic embolization into the arterial tree.[1, 2, 3, 4, 11] The risk for a paradoxical embolus seems to be increased during procedures performed in the sitting position.[1, 5]
Air embolism has also been described as a potential cause of the systemic inflammatory response syndrome (case report), triggered by the release of endothelium-derived cytokines.[17]
In order for VAE to occur, the following two physical preconditions for the entry of gas into the venous system must be met[2, 4] :
Classically, VAE has been recognized as occurring in the context of decompression illness in divers, aviators, and astronauts. Barotrauma and air emboli complicate an estimated 7 of every 100,000 dives.[19, 20] However, the most common cause of VAE is iatrogenic.
Surgical procedures are the primary cause of VAE. Neurosurgical procedures, especially those performed in the Fowler (sitting) position, and otolaryngologic interventions are the two most common surgeries complicated by VAE.[5] Note the following:
Obstetric/gynecologic procedures, laparoscopy
Obstetric/gynecologic procedures (cesarean delivery) and laparoscopic surgeries each carry their own risk for VAE. Although this risk is commonly not considered, they each have a reported associated incidence risk of VAE greater than 50%.[1] The risk of VAE during cesarean deliveries may be highest when the uterus is exteriorized. The risk of VAE in laparoscopic surgery may require an inadvertent opening of vascular channels through surgical manipulation rather than simply resulting from a complication of insufflation.
Both of these surgical procedures have been associated with intraoperative mortality as a direct sequelae of air emboli.[1, 26, 27, 28] Despite this, the potential for venous air embolism is often ignored in laparoscopic surgery and cesarean delivery.
VAE may also result from the iatrogenic creation of a pressure gradient for air entry. Procedures causing such a pressure gradient include lumbar puncture (case report),[1, 23] peripheral intravenous lines,[1] and central venous catheters.[2, 3, 22, 29]
Central venous catheterization
VAE is a potentially life-threatening and under-recognized complication of central venous catheterization (CVC), including central lines, pulmonary catheters, hemodialysis catheters[7, 13] and Hickman (long-term) catheters. As mentioned earlier, the frequency of VAE associated with CVC use ranges from 1 in 47 to 1 in 3000. The emboli may occur at any point during line insertion, maintenance, and/or removal.[3] A pressure gradient of 5 cm H2O between air and venous blood across a 14-gauge needle allows entry of air into the venous system at a rate of 100 mL/s.[1, 2, 11, 15, 21, 30] Ingress of 300-500 mL of air at this rate can cause lethal effects.[15, 29]
A number of factors increase the risk of catheter-related VAE, including the following:
Mechanical insufflation or infusion
Mechanical insufflation or infusion is another cause of venous air emboli. Several different procedures involve the use of insufflation, including arthroscopic procedures, CO2 hysteroscopy, laparoscopy, urethral procedures, and orogenital sexual activity during pregnancy (by entering veins of the myometrium during pregnancy and/or after delivery).[1, 22]
Inadvertent infusion of air can also occur during the injection of IV contrast agents for CT,[14, 15, 31] angiography,[2] and cardiac catheterization, as well as during cardiac ablation procedures.[22, 32] Little information exists on the incidence and the complication rate associated with iatrogenic air embolization caused by injections of contrast medium during CT examinations; however, this is a potentially serious complication, which could be catastrophic. Few case reports exist, and all agree that the actual number of such cases is probably higher than reported.
Positive-pressure ventilation
Positive-pressure ventilation during mechanical ventilation places patients at risk for barotrauma and, subsequently, arterial and/or venous air emboli.[1, 3] Entry of gas into the circulation may result if violation of pulmonary vascular integrity occurs at the same time alveoli rupture from overdistention of the airspaces. This complication can occur in the setting of various diagnoses; however, it is most frequently reported in patients with acute respiratory distress syndrome and in premature neonates with hyaline membrane disease. For these same reasons, SCUBA divers can also have VAE from alveolar distention.
VAE has also been described in the setting of blunt and penetrating chest and abdominal trauma, as well as in neck and craniofacial injuries.
Because of the nonspecific nature of the signs and symptoms of VAE, as well as the difficulty of documenting the diagnosis, the true incidence of VAE is not known. Interventional radiology literature reports an incidence of 0.13% during the insertion and removal of central venous catheters despite optimal positioning and techniques.[33] The frequency of VAE with central venous catheters based on a reported case series has also ranged from 1 in 47 to 1 in 3000.[2, 30] The neurosurgical procedure-related complications of VAE have been estimated to be between 10-80%.[2, 21, 22] Reports of VAE in the setting of severe lung trauma have been estimated between 4-14%.[10, 11, 18, 22, 34]
No racial, sex, or specific age predilection exists for VAE.
The presence of gyriform air on CT scans of the brain appears to be a negative prognostic indicator in venous catheter-related cerebral air embolism.[35] Other potential predictors of unfavorable outcomes in patients with catheter-related VAE include older age of onset, an initial disturbance in consciousness, and the presence of hemparesis.
The potentially life-threatening and catastrophic consequences of VAE) are directly related to its effects on the affected organ system where the embolus lodges. VAE may be fatal and frequently carries high neurologic, respiratory, and cardiovascular morbidity. Catheter-associated VAE mortality is as high as 30%.[2]
In a case series of 61 patients with severe lung trauma, the mortality associated with concomitant VAE was 80% in the blunt trauma group and 48% in the penetrating trauma group.[10, 22, 34] The morbidity and mortality associated with traumatic VAE, as with nontraumatic VAE, depends not only on associated injuries but also on the volume and rate of air entry, underlying cardiac condition, and the patient's position.
In a retrospective study of patients who were placed in a sitting position for neurosurgery, Ganslandt et al found a low rate of severe complications associated with VAE. In the study, 600 individuals underwent surgery for posterior fossa or cervical spinal disorders, with VAE occurring in 19% of these patients. However, only 3.3% of patients suffered severe VAE-associated complications, such as a drop in the partial pressure of oxygen or in blood pressure. Moreover, surgery had to be stopped in only three patients (0.5%) because the VAE could not be eliminated during surgery. No VAE-associated mortality occurred.[36]
Most cases of venous air embolism (VAE) go unrecognized because their presentations are protean and mimic other cardiac, pulmonary, and neurologic dysfunctions, such as the following (in awake patients)[16, 29] :
Because of the lack of specific signs and symptoms of VAE, a high index of suspicion is necessary to establish the diagnosis and institute the appropriate treatment. The number of procedures that place patients at risk for VAE has increased, and these procedures occur across almost all clinical specialties. This must be considered to aid in the confirmation or ruling out of VAE.
If VAE is suspected, obtain the following key historical elements:
Many cases of VAE are subclinical and do not result in untoward outcomes. However, severe cases are characterized by cardiovascular collapse and/or acute vascular insufficiency of several specific organs, including, but not limited to, the brain, spinal cord, heart, and skin. As mentioned earlier, the spectrum of effects is largely dependent on the rate and volume of entrained VAE.[1, 6, 15]
Two additional contributing factors include whether or not the patient is spontaneously breathing (yielding negative thoracic pressure) or is under controlled positive-pressure ventilation.[1] These two factors facilitate the entry of air down a pressure gradient.
The clinical presentation is also dependent on the patient's body position at the time of the event. Generally, if the patient is in a sitting position, gas will travel retrograde via the internal jugular vein to the cerebral circulation, leading to neurologic symptoms secondary to increased intracranial pressure. In a recumbent position, gas proceeds into the right ventricle and pulmonary circulation, subsequently causing pulmonary hypertension and systemic hypotension.[15]
An arterial air embolism can also form if passage of air occurred through a right-to-left shunt, as in the case of a patent foramen ovale.[2, 3] The arterial air emboli can then lodge in the coronary or cerebral circulation, causing myocardial infarction or stroke.
The following hemodynamic, pulmonary, and neurologic complications primarily result from gas gaining entry into the systemic circulation, occluding the microcirculation and causing ischemic damage to these end organs. Animal studies have also suggested the presence of secondary tissue damage resulting from the release of inflammatory mediators and oxygen free radicals that occur in response to air embolism.
Cardiovascular signs include the following
Pulmonary features include the following:
Neurologic findings include the following:
Funduscopic examination may reveal ophthalmologic signs such as air bubbles in the retinal vessels.[18]
Dermatologic evaluation may reveal crepitus over superficial vessels (rarely seen in setting of massive air embolus) and/or livedo reticularis.
Laboratory tests are neither sensitive nor specific for the diagnosis of venous air embolism (VAE). The only indication for obtaining routine laboratory tests is to evaluate the associated end-organ injury resulting from air embolism.
Extravasation of fluid into inflamed tissue may result in laboratory findings consistent with intravascular depletion.
Arterial blood gas samples often show hypoxemia, hypercapnia, and metabolic acidosis secondary to right-to-left pulmonary shunting.
Patients may develop a clinical picture similar to that of classic pulmonary embolism, with hypoxia, decreased PCO2 levels, and respiratory alkalosis.
Transesophageal echocardiography (TEE) has the highest sensitivity for detecting the presence of air in the right ventricular outflow tract or major pulmonary veins. It can detect as little as 0.02 mL/kg of air administered by bolus injection.[1, 2, 5, 11, 15, 18, 22, 23, 38] It also has the added advantage of identifying paradoxical air embolism (PAE), and Doppler allows audible detection of venous air embolism (VAE).
Echocardiography, both TEE and transthoracic echocardiography (TTE), not only allows diagnosis of VAE but also aids in the diagnosis of cardiac anomalies, assessment of volume status, pulmonary hypertension, and cardiac contractility, thereby allowing exclusion of other causes of hypotension, dyspnea, and aiding in further patient management. The use of bedside TTE has become more common in emergency medicine. Its use in a case of VAE described by Maddukuri et al aided in the diagnosis and prompt initiation of appropriate therapy.[39]
Precordial Doppler ultrasonography is the most sensitive noninvasive method for detecting venous air emboli. This modality is capable of detecting as little as 0.12 mL of embolized air (0.05 mL/kg).[1, 15, 22, 23, 38]
Transcranial Doppler ultrasonography is another imaging modality commonly used to detect cerebral microemboli.[1]
Chest radiography may be normal or may show gas in the pulmonary arterial system, pulmonary arterial dilatation, focal oligemia (Westermark sign), and/or pulmonary edema.[11, 15, 22]
Computed tomography (CT) can detect air emboli in the central venous system (especially the axillary and subclavian veins), right ventricle, and/or pulmonary artery. Small (< 1 mL) air defects, usually asymptomatic, occur during 10-25% of contrast-enhanced CT scans; thus, the specificity of this modality is best with large filling defects.[1, 11] CT of the head may show intracerebral air, cerebral edema, or infarction. Chest CT in lung trauma may show underlying conditions such as pneumothorax, hemothorax, or emphysematous blebs that may have led to air embolism but is not helpful for initial diagnosis.[40]
MRI of the brain may show increased water concentration in affected tissues, but this finding alone may not be reliable for the detection of gas emboli.
Electrocardiography (ECG) has a low sensitivity for VAE detection. The findings closely resemble those seen with venous thromboembolism and include tachycardia, right ventricular strain pattern, and ST depression. Transient myocardial ischemia may also occur (severe bradycardia, ST elevation in inferior leads and ST depression in L1 and avL, observed 3 minutes post CVC removal (case report).[1, 37]
VAE leads to ventilation/perfusion (V/Q) mismatching and increases in physiologic dead space. This produces a fall in end-tidal CO2 (normal value, < 5). A 2 mm Hg change in end-tidal carbon dioxide (ETCO2) can be an indicator of VAE. However, this finding is nonspecific and may also occur with other disease states, such as pulmonary embolism (PE), massive blood loss, hypotension, circulatory arrest, upper-airway obstruction, mouth breathing, and/or disconnection from monitor. The detector also has a slow response time.[1, 4, 15, 22, 23]
End-tidal nitrogen (ETN2) is the most sensitive gas-sensing VAE detection modality; it measures increases in ETN2 as low as 0.04%. Response time is much faster than ETCO2 (30-90 s earlier). However, it does not detect subclinical VAE or decreases with hypotension and may falsely indicate resolution of VAE too prematurely.[1, 41]
Changes in oxygen saturation are late findings with VAE. Measurement is often skewed secondary to exposure to high fraction of inspired oxygen. Like carbon dioxide measuring, it is on the lower end of sensitive measurements.[1]
A pulmonary artery catheter can detect increases in pulmonary artery pressures, which may be secondary to mechanical obstruction or vasoconstriction from the hypoxemia induced by the VAE. However, it is a relatively insensitive/nonspecific monitor of air entrainment (0.25 mL/kg).[1] The lumen catheter is also too small for air to be removed, thereby limiting its function.
If a central venous catheter is in place, aspiration of air may help to make the diagnosis. It is also helpful in monitoring central venous pressures, which may be increased in VAE.[1]
Any procedure posing a risk for VAE, if in progress, should be aborted immediately once VAE is suspected.
During central venous catheter (CVC) insertion/removal, one attempt at aspirating air back from line may be useful. Prior to aspiration, the tip of the CVC should be optimally placed 2 cm below the junction of the superior vena cava and the right atrium; however, it may have to be advanced to optimize results.
The placement of a CVC (multiorifice) or PA catheter to attempt aspiration of air, if not already done, has been recommended by several authors.[1, 4, 18, 22, 41] When appropriately placed, it may be possible to aspirate approximately 50% of the entrained air with a right atrial catheter.
Catheter removal should be performed with the patient supine or in a Trendelenburg position while holding his/her breath at the end of inspiration or during a Valsalva maneuver.[2, 14, 22]
In the event of circulatory collapse, cardiopulmonary resuscitation (CPR) should be initiated in order to maintain cardiac output. CPR may also serve to break large air bubbles into smaller ones and force air out of the right ventricle into the pulmonary vessels, thus improving cardiac output.[18]
If an arrest is refractory to CPR, an immediate thoracotomy in the emergency department (ED) may be indicated. An emergency thoracotomy with clamping of the hilum of the injured lung is currently recommended for SAE-associated with unilateral lung injury. This prevents continued passage of air into the coronary, cerebral, and other systemic arteries.[11, 18]
Other measures include cross-clamping the aorta, cardiac massage, and aspirating air from the left ventricle, aortic roots, and pulmonary veins.[11]
If venous air embolism (VAE) is known about before presentation to the emergency department (ED), affected patients should be transported in the left lateral decubitus position.[7]
Management of VAE, once it is suspected, includes identification of the source of air, prevention of further air entry (by clamping or disconnecting the circuit), reduction of the volume of air entrained, and hemodynamic support.
Administer 100% O2 and perform endotracheal intubation for severe respiratory distress or refractory hypoxemia or in a somnolent or comatose patient in order to maintain adequate oxygenation and ventilation. Institution of high-flow (100%) O2 will help reduce the bubble's nitrogen content and therefore size.[1, 4, 7, 10, 11, 15, 23, 30]
Immediately place the patient in the left lateral decubitus (Durant maneuver) and Trendelenburg position. This helps to prevent air from traveling through the right side of the heart into the pulmonary arteries, leading to right ventricular outflow obstruction (air lock). If cardiopulmonary resuscitation (CPR) is required, place the patient in a supine and head-down position.[1, 7, 11, 15, 23]
Direct removal of air from the venous circulation by aspiration from a central venous catheter in the right atrium may be attempted. However, no current data support emergency catheter placement for air aspiration during an acute setting of VAE-induced hemodynamic instability.[1, 4, 11, 15]
If necessary, initiate CPR. Besides maintaining cardiac output, CPR may also serve to break large air bubbles into smaller ones and force air out of the right ventricle into the pulmonary vessels, thus improving cardiac output. Even without the need for CPR, this rationale holds for closed-chest massage. Animal studies have shown that the benefit of cardiac massage equals that of left lateral recumbency, as well as intracardiac aspiration of air.[1, 4, 11, 15]
Admit patients to the intensive care unit (ICU), as they may develop cardiopulmonary distress/failure following VAE.
Consider transfer to a hyperbaric oxygen therapy (HBOT) facility. Indications for HBOT include neurologic manifestations and cardiovascular instability. Potential benefits include compression of existing bubbles, establishing a high diffusion gradient to speed resolution of existing bubbles, improved oxygenation of ischemic tissues, and lowered intracranial pressure.
Immediate HBOT, once VAE is diagnosed, is recommended; however, prognosis may still be good if therapy is initiated beyond 6 hours of event. Prompt transfer to an HBOT center has been reported to decrease mortality in patients with cerebral air embolism. If transfer is necessary, ground transportation is preferred. If air transportation cannot be avoided, the lowest altitude should be sought.[1, 4, 7, 11, 14, 15, 18, 42]
Supportive therapy should include fluid resuscitation (to increase intravascular volume, increase venous pressure and venous return). There is also some evidence that gas emboli may cause a relative hemoconcentration, which increases viscosity and impairs the already compromised circulation. Hypovolemia is less tolerated than relative anemia. In animal studies, moderate hemodilution to a hematocrit of 30% reduces neurologic damage. Crystalloids may cause cerebral edema; therefore, colloids are preferred for hemodilution.[1, 4, 18]
The administration of vasopressors and mechanical ventilation are two other supportive measures that may be necessary.[1, 4, 41] In a case report of a patient undergoing a craniotomy who showed cardiopulmonary findings suggestive of acute VAE, inotropic treatment with ephedrine seemed to rapidly reverse the cardiopulmonary abnormalities. Early inotropic support of the right ventricle has been recommended if venous air embolism is suspected.[41]
In animal studies, the use of perfluorocarbons (FP-43) has been shown to enhance the reabsorption of bubbles and the solubility of gases, thereby decreasing both neurologic and cardiovascular complications of systemic and coronary VAE. These benefits, however, have not been validated in humans.[1]
The optimal management of VAE is prevention. Minimizing the pressure gradient between the site of potential entry and the right atrium is essential in prevention of VAE.
Potential measures to reduce the risk and/or severity of VAE during neurosurgical interventions include the following[38] :
Measures to reduce the risk of air embolism during mechanical ventilation and central line insertion/removal/manipulation should be taken. With regard to these two procedures, the following interventions should be implemented: