Venous air embolism (VAE) is a dangerous perioperative complication that occurs insidiously but can be very dangerous. VAE has been known for a long time, but in recent years it has been reported from time to time, and it can occur in almost all kinds of surgeries and anesthesia operations, which makes people unable to prevent it. There are few studies and reports on VAE in China, and only 6 reports were found in the Chinese Biomedical Abstracts Database (CBM) using the keywords “air embolism” or “gas embolism”. Therefore, it is necessary to introduce the pathophysiology and preventive treatment of VAE in order to improve clinical awareness and vigilance. Etiology VAE mainly refers to the entry of air into the venous system and its subsequent entry into the right atrium, right ventricle, and pulmonary artery through the central vein. There are two basic conditions that need to be met: first, there is a passageway for air to enter the blood; second, there needs to be a certain pressure difference, i.e., the venous pressure is relatively lower than atmospheric pressure, or there is a direct or indirect external pressure to push the air into the blood. VAE often occurs in the midst of a number of surgical procedures, the most familiar being seated neurosurgery. Mainly due to the sitting position, the surgical incision is higher than the right atrium, the pressure in the vein is negative relative to the right heart, and the venous sinus on the skull and dura mater belongs to the noncollapsing veins, once cut, the air can be sucked into the vein from the rupture to cause embolism. The incidence of VAE during surgery of the posterior cranial fossa in the sitting position is reported to be 7-50% in adults and 26-69% in children. The reason for the wide variation in reports may be related to the different means of determining or monitoring VAE, or to the method of study, either prospective or retrospective. The incidence of VAE in seated cervical spine surgery is slightly lower, around 10%. Gas embolism is common among some surgeries using medical gases. For example, gas embolism in laparoscopic surgery is due to a perforation of the vein, and during pneumoperitoneum, the gas enters the circulation directly under pressure. A case of severe VAE during ophthalmic surgery using air-fluid exchange was reported in Anesth Analg ’05 and Can J Anesth ’07 in an adult and a pediatric case, respectively. Gas embolisms caused by wound irrigation with hydrogen peroxide (H2O2) have also been reported. Khan et al. reported a case of pulmonary gas embolism in a child with a tibial cyst irrigated with H2O2. Similar reports have been reported in cervical and lumbar spine surgeries in which wounds were flushed with H2O2. Gas embolism is most likely to occur when H2O2 is used to flush unopened and semi-open wounds (e.g., sinus tracts). This is mainly because the oxygen released by H2O2 is not sufficiently connected to the outside world, and a certain pressure is formed locally, forcing the oxygen to enter the bloodstream, resulting in embolism. Some anesthesia operations, such as deep vein puncture, floating catheter placement, etc., are also prone to VAE. Vesely investigated 11,583 patients with central venous catheterization and found that VAE occurred in 15 cases, and VAE was also reported in patients who had deep venous catheter removal. Deceuninck et al. reported a patient with persistent cough, decreased respiration, and hypoxemia after removal of a left internal jugular vein catheter, and a cardiac ultrasound suggesting massive air embolism in the right heart. Thus many procedures or operations have the potential for VAE, but the mechanisms are no more than access and pressure differentials. Common causes of VAE are listed in Table 1. Table 1 Clinical operations prone to VAE Possible causes of gas embolism Possible mechanisms of gas embolism All medical operations Accidental entry of gas through a peripheral vein All surgical operations Application of hydrogen peroxide, resulting in oxygen embolism in a vein or artery Anesthesia operations Passage of gas through an unattached venous catheter or artificially accidental push of air Cardiac operations Air intake in the extracorporeal circulation, or resumption of a beat Cardiac catheterization Air enters through cardiac catheter during operations such as angiography Lumpectomy Accidental entry of gas into arteries or veins during intracorporeal insufflation Neurosurgery Sitting craniotomy, entry through dura mater and cranial venous sinuses Orthopedic surgery Total hip replacement, spinal surgery in prone or sitting position Obstetrics and gynecology Rupture of uterus, laparoscopy, cesarean section Urology Entry of air into venous sinuses during transurethral electrocautery of the prostate. (From Muth CM, Shank ES. Gas embolism. N Engl J Med, 2000;342:477) Pathophysiology The prognostic impact of VAE on a patient’s prognosis is primarily related to the amount and rate of air entry into the circulation and the patient’s position at the time of gas entry. Rapid entry of air into the circulation can cause severe hemodynamic fluctuations. Opinions on the lethal dose of gas entering the body have not been unanimous, and it is generally believed that the lethal dose is about 300-500 ml of air entering at a rate of 100 ml/s. It is also believed that a volume of gas of about 100 ml rapidly entering the circulation can lead to heart failure in adults. In some critically ill or circulatory unstable patients, even a small amount of air can lead to serious accidents. Once a large amount of air enters the vein quickly, it reaches the right atrium and right ventricle and can obstruct the right ventricular outflow tract, resulting in acute right heart failure and immediate death. If air enters slowly, obstruction occurs only at the level of the pulmonary circulation, resulting in pulmonary vasoconstriction and pulmonary hypertension, increased right ventricular afterload, decreased pulmonary blood flow, decreased left ventricular preload, decreased cardiac output, and severe circulatory failure. Increased pulmonary vascular resistance and dysfunctional ventilation/blood flow ratios lead to right-to-left shunting in the lungs and increased alveolar dead space, resulting in hypoxia and hypercapnia. The body can tolerate small amounts of air by circulatory absorption. The body is relatively tolerant to more soluble gases such as CO2, but if more gas is injected in a short period of time, it can still cause serious damage. Therefore, CO2 gas should not be used lightly in hysteroscopy, laparoscopy, and other examinations or surgeries that use CO2 gas to avoid accidents. Microthrombus formed in VAE is also harmful to the body, Schlimp et al. found that microthrombus can travel backwards to the brain through the veins against the direction of blood flow, causing cerebrovascular gas embolism, and whether the thrombus can reach the brain depends on the size of the thrombus, the diameter of the central vein and the cardiac output. Microemboli can cause endothelial rupture, disrupt the blood-brain barrier, increase intracranial pressure, and cause cerebral dysfunction if the embolus is large. A large air embolus can cause cerebral dysfunction. Microemboli are also endothelial irritants that can disrupt the normal function of the vascular endothelium. Paradoxical embolism, on the other hand, is the passage of air from the right heart into the left heart through a potentially unclosed patent foramen ovale or atrial septal defect, resulting in an air embolism in the body circulation, which is prone to embolization of coronary arteries or intracranial vessels, with corresponding manifestations. Symptoms and manifestations For awake patients, there are often uncomfortable symptoms such as chest pain and dizziness. They can be categorized into two main groups, i.e. circulatory and respiratory manifestations. Cardiac manifestations: A “mill-wheel murmur” can be detected by transesophageal or anterior chest auscultation, but it occurs later. The electrocardiogram is characterized by nonspecific ST-T changes and right ventricular strain. Tachycardia and bradycardia and even cardiac arrest can be seen in VAE. Pulmonary artery pressure (PAP) is decreased during massive air embolization but increased during slow air-induced embolization. Central venous pressure (CVP) is usually elevated due to right heart dysfunction. RESPIRATORY MANIFESTATIONS: Awake patients present primarily with dyspnea and tachypnea. There is a rapid fall in end-expiratory CO2 partial pressure, accompanied by an increase in arterial CO2 partial pressure and a fall in oxygen partial pressure. Air embolism can lead to the release of inflammatory factors from neutrophils in the lungs, increase pulmonary vascular permeability, and pulmonary injury manifestations similar to ARDS. Patients have decreased lung compliance and impaired lung function. Monitoring There are various means of clinical monitoring to determine VAE, with transesophageal ultrasound (TOE) being the most sensitive and intuitive, detecting air as small as 0.02 mL/kg or air bubbles of 5-10 micrometers, and is currently considered the gold standard for determining VAE. The second is precordial Doppler, which is noninvasive, easy to use, and very sensitive to intracardiac air embolism, which can be perceived by a small amount of air (about 0.25 ml) entering, and appears as a change in sound. It is generally used routinely during surgery in the seated position abroad and is placed in the 3rd and 6th interstices on the right side of the sternum. Carbon dioxide tracings are the most widely used, but are only moderately sensitive. It complements the function of precordial Doppler, which can differentiate whether an air embolus detected by ultrasound has a hemodynamic impact. If an air embolus is detected by ultrasound but there is no decrease in PETCO2, this indicates that the amount of air entering has not yet had an effect on the circulation. The pulmonary artery catheter reflects VAE with a slight lag; it is suggestive mainly after an air embolus has caused a secondary increase in pulmonary artery pressure, but it has the advantage of being therapeutic in the event of VAE. The 4th edition of Clinical Anesthesia (Barash et al., eds.) recommends that pulmonary artery cannulation should be routinely performed in seated neurosurgery. End-expiratory N2 is specific for the monitoring of VAE, but is less sensitive than end-expiratory CO2. Diagnosis The diagnosis of VAE is based on three main clinical criteria: a “mill-wheel murmur” on esophageal or chest auscultation, a decrease in the partial pressure of end-expiratory CO2 (PETCO2), and the detection of an intracardiac air embolus on ultrasound. detection of an intracardiac air embolus. Other diagnostic aids include risk factors for VAE (e.g., craniotomy in the sitting position, laparoscopic surgery, etc.), sudden onset of hypotension, hypoxia, bradycardia, and aspiration of air bubbles through a central venous catheter. Prevention Sitting neurosurgery must be performed under general anesthesia with tracheal intubation and controlled breathing. This is because negative intrathoracic pressure during voluntary respiration may increase the risk of VAE.Suarez et al. reported two patients with Parkinson’s disease who underwent stereotactic pallidotomy with preservation of voluntary respiration in the sitting position, both of whom developed VAE.It is essential that the lower extremities be wrapped in an elastic bandage prior to changing the position to the sitting position, and that sufficient volume be replaced as early as possible to raise the central venous pressure; the use of N2O should be avoided during anesthesia. Intermittent jugular vein compression with positive end-expiratory pressure (PEEP) and anti-gravity suit have been recommended as effective in preventing air embolism. Currently, PEEP is used in most medical institutions for respiratory control in seated surgery, and according to a questionnaire survey in Germany, 78% of hospitals use PEEP in seated neurosurgery.Traditionally, it has been believed that PEEP can increase PCWP and CVP, which in turn can increase the intracranial venous pressure and prevent and alleviate VAE.However, there are some studies that have shown that even 250pxH2O of PEEP cannot increase the intracranial venous pressure, and PEEP is not effective in preventing air embolism. However, some studies showed that even 250pxH2O PEEP could not increase intracranial venous pressure, and PEEP did not significantly reduce the incidence of VAE. On the contrary, PEEP could reduce cardiac output, which could easily lead to circulatory instability, and could easily lead to paradoxical air embolism in patients with potentially unenclosed patent foramen ovale. Therefore, some scholars recommend abandoning PEEP.Schmitt et al. also studied the occurrence of VAE at the end of a seated neurosurgical procedure when PEEP was discontinued and when the seated position was subsequently changed to the prone position, and found that both maneuvers could lead to the occurrence of VAE. The prevention of VAE during other maneuvers requires a case-by-case approach. For example, during central venous puncture, care should be taken to keep the patient in the head-down position (Trendelenburg position), and the catheter should always be filled with saline. If the central venous catheter is to be removed, it should be done in the Trendelenburg position and after the patient has held his/her breath at the end of a deep inspiration. For high-risk procedures, precordial Doppler monitoring and, if necessary, TOE should be routinely used for early detection and prevention. Therapeutic measures In the event of a suspected VAE, immediate measures need to be taken to prevent further air entry. The key is to discover the entrance of air. The surgical area needs to be covered with saline immediately, and the central venous access should be checked for the possibility of loose connectors or accidental air entry. Pure oxygen (FIO2 100%) ventilation to improve arterial oxygen saturation and oxygenation of peripheral tissues Another effect of 100% oxygen is to reduce the volume of the air embolus by decreasing the nitrogen content and thus the volume of the air embolus. Rapid volume expansion increases venous system pressure and reduces further air entry. Keep cardiovascular active medications on hand to manage possible circulatory abnormalities such as hypotension, severe bradycardia, etc., and perform cardiopulmonary resuscitation (CPR) if necessary. CPR not only assists in maintaining cardiac output (CO), but also helps to break up the large air embolus into smaller bubbles that can enter the pulmonary circulation, avoiding obstruction of the right ventricular outflow tract, and thus increasing CO. Gas can be returned through a central venous catheter or pulmonary artery catheter. A central venous catheter or pulmonary artery catheter can be used to pump back the gas. However, it has been suggested that fewer than 6% of bubbles are actually extracted. This is mainly related to the position of the catheter, and it has been suggested that the tip of the central venous catheter should be placed 50 px below the junction of the superior vena cava and the right atrium. It has also been suggested that the use of a multiport catheter (multiportifice catheter) may be more effective. If the catheter is properly positioned, it is claimed that 50% of the air in the chambers of the heart can be evacuated. Hyperbaric oxygen is not a first-line treatment and is only used as an adjunct in some critical cases. The position of the patient during rescue is also important. The patient should be placed in a semirecumbent position on the left side with the head tilted down so that the right ventricular outflow tract is at the lowest part of the right ventricle, allowing gas to leave the right ventricular outflow tract. However, if CPR is required, the patient should also be placed in the supine position with the head down. Of course, there are studies that suggest that position does not have much of an effect, and Geissler, after injecting air intravenously into an anesthetized dog, changed the dog from supine to left lateral recumbency and left lateral head-down, and found by esophageal ultrasonography that there was no hemodynamic improvement or alteration of right heart function, despite the redistribution of the air embolus. In anesthesia, if N2O is used, VAE needs to be discontinued when it occurs, as it can diffuse into the air bubble to increase its volume. After successful rescue, some tiny bubbles can remain in the circulation for 10-30 minutes but are eventually absorbed. In conclusion, VAEs are actually a common class of clinical complications that sometimes just don’t show up. We should be more aware of it and always be on the lookout for prevention. Once serious VAE occurs, effective treatment measures are extremely limited, so the idea of prevention over cure should always be implemented.