Cardiopulmonary Bypass: Principles and Practice

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CHAPTER 16: EMBOLIC EVENTS

BRUCE D. BUTLER

MARK KURUSZ

Quick Links to Sections in this Chapter

–TYPES OF EMBOLI

–DETECTION

–PATHOPHYSIOLOGY

–PREVENTION

–TREATMENT

–CONCLUSIONS AND FUTURE TRENDS

–KEY POINTS

–References

B. D. Butler: Department of Anesthesiology, Hermann Center for Environmental, Aerospace and Industrial Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.

M. Kurusz: Department of Surgery, Division of Cardiothoracic Surgery, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-0528.

The word embolus is derived from the two Greek words en (in) and ballein (to throw); the combination embolos originally was used to describe a wedge-shaped object or stopper. The modern standard medical definition of embolism is "a sudden blocking of an artery by a clot or foreign material which has been brought to its site of lodgment by the blood current" (1).

Embolic events associated with cardiopulmonary bypass (CPB) have been a concern from the earliest clinical applications to the present time. Gross air embolism was one of the first identified risks of open heart surgery, but in the 1960s emboli composed of blood-derived material became increasingly recognized as etiologic factors in adverse postoperative sequelae. Improved techniques for anticoagulation management in the 1970s and a growing acceptance of blood filtration in the 1980s probably contributed to a decrease in morbidity and mortality during CPB procedures. Although current technologies, such as microporous membrane oxygenation, improved arterial line filters, and blood surface coatings, have decreased the incidence of microemboli even further, subtle embolic events still occur whenever CPB is used.

The production of emboli during CPB, whether gross or microscopic, has been causally linked to numerous perioperative and postoperative complications, patient characteristics such as age, technical features relating to the type of oxygenator, pump, reservoir, or CPB circuit, and the surgical procedure (2). Emboli fall into three general categories: biologic, foreign material, and gaseous. By definition, each type has the propensity to distribute into and ultimately obstruct microvessels (3 to 500 m in diameter) of any number of tissues. Because of their small size, vast quantities (namely, hundreds of thousands to hundreds of millions) are required to cause detectable organ injury (3,4).

Each of the three categories of emboli has been addressed to some degree by device design changes, adaptation of specific surgical or therapeutic procedures, or enhanced removal and preventive efforts by surgeons and perfusionists. These efforts have likely contributed to an appreciable decline in morbidity associated with CPB. In spite of this, emboli continue to be a topic of concern with all medical uses of extracorporeal circulation and open heart surgery. Of particular concern is the susceptibility of the brain to embolic damage. This condition is the subject of numerous reports demonstrating varying degrees of neurologic dysfunction after CPB (5–8).

The purpose of this chapter is to review the various types of emboli associated with CPB, their detection and pathophysiology, preventive measures and treatment, and future trends.

TYPES OF EMBOLI

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Bloodborne

Bloodborne microemboli associated with CPB consist primarily of autologous cellular products or aggregates of various cell types (9,10). Cellular products include microthrombi containing fibrin/fibrinogen, lipid material, protein (denatured or not), bone or muscle fragments, and so forth. Platelet, neutrophil, and red cell aggregates also are commonly observed during and after bypass. Bloodborne emboli can derive from homologous transfused blood that accumulate proportionately with storage time (11,12). Fibrin formation occurs when inadequately anticoagulated blood contacts a foreign surface, thereby activating factor XII to factor XIIa and thus initiating the coagulation cascade. Heparin blocks coagulation within the cascade at multiple points, mainly by potentiating antithrombin III (13). An initial rapid adsorption of protein material, predominantly fibrinogen, occurs on foreign surfaces (14,15). Fibrin deposits likely form in areas of stagnant blood flow or where turbulence or cavitation phenomena exist and on roughened surfaces (14,16). Specific sites include intraluminal projections (17), oxygenator connectors (18), within bubble oxygenators (19), or within arterial line filters (20).

Anticoagulation therapy with heparin is usually assessed by measurement of the activated coagulation time, which, if greater than 300 to 400 seconds, is considered adequate for prevention of fibrin formation within circuits (21,22). Activated coagulation time measurement is necessary because the rate of heparin metabolism may vary with different patients (23); thus, dosage or plasma levels may not accurately predict the degree of anticoagulation (24).

Macroembolic and microembolic particles of fat are generated during CPB and are found in capillaries of the kidneys, lungs, heart, brain, liver, spleen (25), and in pericardial blood (26). These emboli are released as a result of trauma to the fat cells in the epicardium and surgical wound (27,28) and can occur without CPB after median sternotomy or thoracotomy (27). Fat emboli may be observed directly using microscopy or possibly inferred from increases in serum levels of total lipids, free fatty acids, triglycerides, or lipases. It has been estimated that two thirds of the fat emboli developed within a CPB circuit enter via cardiotomy suction (28). Fat emboli are commonly observed with bubble oxygenators (26,28,29) and to a lesser degree with membrane-type oxygenators (28), although this claim is not without challenge (30).

Fat emboli are typically formed with denaturation of plasma lipoproteins and lipids. The fat molecules that come out of solution consist of chylomicron aggregates (29) or free fat-containing triglycerides and cholesterol (28). Fat emboli may vary from 4 to 200 m in diameter (26). A number of fatty acids and other lipid molecules have been linked with postperfusion lung parenchymal damage or alterations in surface properties (31,32). Generation of immiscible fat, however, is reduced by hemodilution (27).

As plasma proteins come into contact with foreign surfaces within the extracorporeal circuit, denaturation can occur (29). This process results in alterations in immunologic and complement proteins (33,34). Blood contact with foreign surfaces also activates platelets, which leads to aggregate formation and subsequent thrombocytopenia as platelets are consumed in this process (35–38). Membrane oxygenators reportedly produce fewer aggregates than bubble oxygenators (35). Platelet aggregates also are commonly observed in stored whole blood, packed red cells, and stored platelet concentrates (12). Although many aggregates are likely to disperse within the circulation (38), their embolic potential has been manifested in various organs, including the brain.

Significant decreases (30% to 50%) from preoperative platelet counts are usually observed early in the procedure as the platelets adhere to the surfaces within the circuit (39) or to the gas–blood interface of gaseous microemboli (40). Functional changes and decreased platelet counts have been associated with postoperative bleeding, whereas the circulating aggregates may provide a causative link with postoperative neurologic dysfunction (41). Preservation of platelet numbers has been reported with prostacyclin use and a reduction in aggregate formation (42,43). Reducing platelet sensitivity to aggregation with heparin (44) may be assisted with prostacyclin therapy, thus reducing the microembolic risk associated with bypass (45,46).

Platelet aggregation is associated with release of biogenic amines such as serotonin and other bioactive mediators such as thromboxane, which not only produce vasoconstriction but also may further promote adhesiveness and aggregate formation. Release of histamine from platelets and mast cells may promote changes in microvascular membrane permeability to plasma proteins, promoting interstitial edema formation (47).

Neutrophil aggregation during CPB may lead to complement activation (34). Hicks et al. (38) and Ratliff et al. (48) found aggregated leukocytes in the lungs of dogs undergoing bypass, and their presence was difficult to prevent clinically, although damage to other organs was not reported. Complement-mediated neutrophil aggregation appears to depend on the nature of the foreign material that the neutrophils contact (49). After aggregation, lysosomal enzyme release increases microvascular endothelial permeability to protein, especially in the lungs, contributing to the postperfusion lung syndrome (50). Upregulation of adhesion molecules and the subsequent adherence and activation of neutrophils with CPB is reviewed by Hall et al. (51).

Patients who possess cold-reacting antibodies, usually of the IgM class, may be at risk for red cell aggregate microembolization with cold cardioplegia or other hypothermic techniques used during open heart surgery (52–54).

Foreign material

Foreign material emboli may consist of cotton fibers, plastic or metal particles from connectors or housings of disposable devices, filter material, tubing, talc, or surgical thread. Pulmonary embolism from bone wax used as a hemostatic agent with sternotomy incisions in experimental studies has been suggested as a potential contributor to pulmonary complications after open heart surgery (55). Obviously, some of the material described above may be present on artificial surfaces that come into contact with blood during CPB or result from inadvertent inclusion within the circulating blood (56). Braun et al. (57) reported elevated serum aluminum levels postoperatively in patients who had undergone CPB. Such aluminum contamination was associated with use of specific manufacturers' aluminum heat exchangers. When a stainless steel heat exchanger was used, there was no elevation in plasma aluminum levels. More recently, Challa et al . (58) elevated levels of aluminum and silicone in the brains of patients who died after CPB.

Microemboli that are usually relatively large in diameter (greater than 300 m) may be released into the circuit from tubing (e.g., by spallation). These emboli are more common with silicone-based rubber tubing than with tubing of polyvinyl chloride or polyurethane base (59–62). Another known foreign material is microfibrillar collagen used for surgical hemostasis. Used topically, this material has been shown to pass through autotransfusion devices and oxygenators, and although effectively removed by filtration, the ability of platelets to aggregate seems to persist. This effect has resulted in the recommendation that blood from treated patients should not be returned to the extracorporeal circuit (63).

Microparticles (10 m and greater) of silicone antifoam A (Dow Corning Corp., Midland, MI) have been observed after bypass in the adrenal gland and pancreas (64). Antifoam is composed of a liquid polymer (dimethylpolysiloxane) and particulate silica. The polymer material is the defoaming agent, whereas the silica provides for blood dispersion.

In the early 1960s, a number of studies demonstrated antifoam emboli in experimental animals and patients undergoing bypass. The amount of defoamer material and methods of incorporation were less understood during that period. Orenstein et al. (64) reported particle-droplet complexes incorporating antifoam in patients up to 8 months after open heart surgery. The ultimate fate of antifoam in the body is not clear. Some reports have described particles in the phagocytic cells of the spleen or lymph nodes, whereas others have reported continuous recirculation for prolonged periods (65). Tissue reaction to silicone or antifoam has not been reported to any significant degree. Wells et al. (66), however, reported that the antifoam polymethylsiloxane magnified the hemolytic phenomena attributed to oxygenators primarily by decreasing the resistance of red cells to mechanical stress. In earlier experimental studies on dogs, antifoam emboli were found in the brain, kidneys, and occasionally in the spleen and liver (67–69).

Gupta et al. (70) reported a significant yet transient rise in pulmonary artery pressure with antifoam injections in dogs, demonstrating the capacity of these microparticles to obstruct pulmonary microvascular blood flow. Washoff of antifoam material from the oxygenator and cardiotomy reservoir has been shown to decrease the surface tension of the pre-CPB prime solution, which has important implications for gaseous microembolus stability or removal by arterial line filters (71). Further reductions in post-CPB plasma surface tension were not observed, and the values did not correlate with the duration of bypass or plasma-free hemoglobin (72). Design changes and a better understanding of the amounts and methods of applications of antifoam material and the use of membrane oxygenators have enabled significant reductions in the occurrence of embolic risk from these particles. Table 16.1 summarizes the reported types of nongaseous emboli associated with CPB.

Gaseous

Gaseous microemboli originate from a number of sources during bypass; however, oxygen microbubbles generated by bubble oxygenators have historically been the most commonly reported source. Gaseous microemboli produced in these devices are usually 400 m or less in diameter and consist primarily of oxygen, although other gases, including carbon dioxide, nitrogen, or nitrous oxide, may exchange with the bubbles once they are formed and perfused into the patient (73–80). Gaseous microemboli size may be quite variable, with most in the 10- to 100-m range. Bubbles with diameters greater than 35 to 40 m are reportedly associated with CPB morbidity, unlike those of smaller diameters (3,81). Table 16.2 compares bubble diameters with volume and surface area. By the mid-1980s, bubble oxygenators had been designed to minimize gaseous microemboli production while maintaining oxygen transfer characteristics at lower gas-to-blood flow ratios (82–85). These design changes, along with chemical defoaming agents and arterial line filtration, significantly reduced the numbers and sizes of gaseous microemboli produced by bubble oxygenators. Gaseous microemboli with diameters below 40 m are still reported, however, even with arterial line filtration (86,87).

Production of gaseous microemboli depends in part on the methods of operation of the bubble oxygenator. Maintaining a low gas-to-blood flow ratio will reduce the number of microbubbles released into the arterial line (88,89). Current oxygenators operate efficiently at ratios approximating 1:1. This represents a significant advance over earlier models requiring ratios 10-fold greater (4). The enhanced efficiency is largely because of the production of smaller oxygen bubbles. The smaller size increases the total area of the contact surface of the oxygen bubble and the blood (82). These smaller microbubbles are more difficult to remove, however, and often require arterial line filtration. Arterial and venous blood reservoir levels have been shown to be inversely related to gaseous microemboli production (74,90–93). With increased fluid levels, the time available for gas dissipation and defoamer action increases. Persistent gaseous microemboli often adhere to the artificial surfaces in quiescent areas of the oxygenator and reservoir, and any unnecessary jarring or abrupt shock releases these bubbles into the arterial line (75).

The production of gaseous microemboli by membrane-type blood oxygenators is significantly reduced or, by some accounts, nonexistent (74,84,94). Physical damage to the membrane material may allow release of gas bubbles into the blood, or areas with elevated transmembrane pressure ratios may cause bubble formation on the blood side. Graves et al. (95) described a counter-diffusion phenomenon whereby bubbles would be formed at the membrane surface.

Regardless of oxygenator type, the solubility characteristics of gases are such that the colder the solution, the greater the number of molecules dissolved within the liquid phase. The solubility of oxygen, for example, is 2.6 volume percent in water at 30°C and 4.9 volume percent at 0°C. While warming from hypothermia, gaseous microemboli will form in the blood if the warming gradient exceeds a certain critical threshold (96). This relationship is most evident when the subsequent rewarming gradient is in excess of 10 to 17°C (3,94,97,98), which can cause gaseous microemboli to be released in the heat exchanger. Another condition could also occur whereby gaseous microemboli are released into the blood during the cooling phase when the saturated cold arterial blood exiting the heat exchanger is warmed upon mixture with the patient's warm blood (99). The opposite situation also has been described, whereby the warm arterial blood coming from the heat exchanger is circulated into a hypothermic patient and the increased solubility of the gases in the cold blood prevents the evolution of bubbles (100). Any existent bubbles likewise would be expected to dissolve under these conditions.

Based on these principles, Edmunds and Williams (3) concluded that the greatest chance of gaseous microemboli production as a result of temperature changes most likely occurs during the cooling phase, where bubbles are released directly into the patient's circulation. Almond et al. (101) reported ischemic cerebral injury in dogs with cooling gradients of 13 to 15°C. However, their studies did not involve the search for or detection of circulating bubbles. Circumstantial evidence lending support to these phenomena has been reported clinically with rapid induction of hypothermia in patients undergoing CPB (102–104). Geissler et al. (105) studied cooling gradients and gaseous microemboli formation in dogs undergoing CPB using membrane oxygenators. With transesophageal echocardiography and Doppler ultrasound sensors located on the CPB circuit and carotid arteries, they reported that rapid cooling did not result in gaseous microemboli formation when the cooled perfusate entered the subject, even when temperature gradients between the water bath and core (esophageal) temperatures exceeded 20°C. It was observed, however, that the actual determinative gradient site for the formation of gaseous microemboli was in the aortic arch where the blood and perfusate first mix. Gaseous microemboli were detected in small quantities when the temperature gradient was preestablished and exceeded 10°C. The incidence of gaseous microemboli was directly correlated with the extent of the temperature gradient, and in no cases were bubbles detected in the carotid arteries. Although currently available bubble oxygenators incorporate the heat exchanger directly into the oxygenating column, thereby enabling the defoamer action to minimize gaseous microemboli production, standard operating procedures should continue to require that heating or cooling gradients not exceed 10°C (4,98).

Gaseous and particulate emboli are commonly reported with cardiotomy suction (36,106). Inherent to all suctioning procedures is the mixing of air with the blood, forming relatively large bubbles, often in a foamlike matrix. These bubbles are not only larger than the gaseous microemboli produced by the oxygenator but consist of air (mostly nitrogen) and hence are more stable and often associated with other blood products or aggregate material (107). The increased stability is due not only to the larger volume of gas in the bubbles that must be reabsorbed, but also to the differences in solubility of nitrogen in blood as compared with oxygen or carbon dioxide. Because of their greater stability, these bubbles present a significant risk to the patient if filtration techniques are inadequate. Previously, it has been demonstrated that bubbles can pass through a cardiotomy reservoir (108,109); however, newer design changes incorporating improved defoamer material, unique flow patterns, and integral filters have significantly reduced the incidence of this phenomenon.

The process of suctioning also results in significant blood trauma, which causes cellular aggregation and gas foam formation. Efforts to reduce the amount of air aspirated with operative field blood and care in monitoring suction pump speed will reduce blood cell trauma and decrease the likelihood of embolization.

Gaseous emboli also can be produced by processes known as gaseous or vaporous cavitation (110,111). Cavitation involves hydrodynamic phenomena that consist of bubble nucleation, growth in volume, and then ultimate collapse (112). The bubbles or cavities contain gas or vapor. True vaporous cavitation is an extremely transient phenomenon. Gaseous cavitation, similar to effervescence, is more common in gas-nucleated fluids, including blood, that are subjected to tensile, ultrasonic, or supersaturating pressures (113). In these conditions, bubble growth is achieved by mass transfer of gas molecules by diffusive mechanisms and occurs with lesser pressure reductions. Vaporous cavitation occurs when a vacuous space is created in blood, for example, within the negative pressure regions that develop behind the roller pump heads, and the sudden pressure reduction creates a drop to below liquid vapor pressure (114,115). Early model centrifugal pumps reportedly produce fewer gaseous microemboli than roller pump heads (116).

Similar cavitating phenomena can occur at arterial injection sites or at stenotic regions in the circuit where vortices are created with turbulent flow and negative pressures spontaneously develop (117–119). In their review of cavitation phenomena during CPB, Kuntz and Maurer (120) evaluated a number of factors involved with gaseous microemboli production at the arterial cannula site. Such factors include Reynolds' number, kinetic energy, hydrostatic and line pressure, temperature, PO2 levels, cannula size, and fluid flow rate. The authors concluded that excess blood gas tensions should be avoided and that larger bore arterial cannulas were less likely to be associated with gaseous microemboli production at cavitating velocities. In addition to the formation of gaseous microemboli, cavitating phenomena are extremely traumatic to red cells and can cause platelet activation, granule release, and cell lysis (112). Vapor bubbles are also reported with transmyocardial laser revascularization, as detected with transesophageal echo and transcranial Doppler (121,122). Although both studies detected cerebral vascular emboli, neither reported adverse gross neurologic deficits or decreases in mean cerebral blood flow velocity or jugular bulb oxygen saturation.

Air emboli can be introduced into the patient's arterial blood when the cardiac chambers are opened to the atmosphere for valvular, atrial septal, or ventricular septal repair. Pearson (79) characterized "surgical air" as that entering the arterial circulation from cannulation of the heart and aorta, after removal of the aortic clamp, air entrainment at the site of venous cannulation, after restoration of cardiac function, and during left atrial catherization. Air may be introduced with insertion of the aortic, caval, or right atrial cannulas. In the presence of an atrial septal defect or with placement of a left atrial or left ventricular vent cannula, air may be introduced directly into the systemic circulation (123).

With open heart procedures, air often is entrained on the luminal surfaces of the heart or trapped within the muscular trabeculae. Cardiac ejection should be avoided until complete blood filling occurs. Residual air has been reported for 30 to 45 minutes using transesophageal echocardiography even with careful deairing attempts (124,125), and upon resumption of cardiac contractions cerebral vascular gas was detected with transcranial Doppler (124). Prevention of systemic air embolism can be accomplished by insertion of a vent into the left ventricle (126) or needle aspiration of the pulmonary veins and cardiac chambers (127). Another technique reported to reduce air embolism at the operative site is flooding the surgical field with carbon dioxide (128–130). Recent reports on cardiac valve operations have demonstrated with transesophageal echocardiography that carbon dioxide field flooding caused residual gas, remaining after careful deairing maneuvers, to disappear within 1 minute in 86% of cases and within 1 to 24 minutes in the remaining cases (125). Other maneuvers include closure of the left atrium under blood, lung expansion to clear pulmonary venous blood, and placement of the patient in the Trendelenburg position or allowing the right lung to collapse (131), thus preventing air from entering pulmonary veins on the right side. Details of ventricular venting have been described by Utley and Stephens (132) and are discussed more fully in Chapter 6. Both advantages and disadvantages of venting and explicit procedures have been described by these authors for operative ways to prevent or remove surgical air.

As previously mentioned, gaseous microemboli produced by bubble oxygenators usually consist of oxygen, and because of the solubility/diffusibility of this gas, their longevity and pathophysiology are limited to some degree. Experimentally, animals embolized intravascularly with gases of high solubility, such as carbon dioxide or oxygen, tolerate the insult better than those embolized with air or nitrogen bubbles (133–135). Bubbles will pass into the systemic vasculature, causing blood flow obstruction, until the volume decreases by mass diffusion across the gas–blood interface and further movement within the microcirculation ensues. In the case of oxygen bubbles, the diffused gas will combine with unsaturated hemoglobin while carbon dioxide may be absorbed within the plasma. Yang et al. (136,137) studied stationary and moving bubbles in whole blood and plasma and found that dissolution rates were proportional to the fluid flow rate. The outward diffusion of the gas was largely assisted by the convective effects of the flowing blood and subsequent thinning of the boundary layer (138). A small microbubble has an increased degree of curvature that accelerates the dissolution rates as surface tension increases and pressure within the bubble rises (Fig. 16.1).

FIG 16.1. Bubble in blood showing the effects of gas diffusion on size. Oxygen diffuses out and nitrogen, carbon dioxide, and nitrous oxide diffuse in, according to partial pressure gradients. (From Butler BD. Biophysical aspects of gas bubbles in blood. Med Instrum 1985;19:59–62, with permission.)


Because gaseous microemboli are likely to occur with bypass, it has been shown that ventilation with highly soluble gases more soluble than nitrogen, such as nitrous oxide, may cause existing bubbles to grow. Some therefore recommend that nitrous oxide should be discontinued at least 10 minutes before establishing CPB (139–141). Wells et al. (142) confirmed the benefit of this practice by measuring cerebrospinal fluid markers of ischemia in 20 patients, 10 of whom received 50% to 60% nitrous oxide until CPB was begun. Lactate levels were significantly elevated in these 10 patients. Several extensive reviews cover the behavior of gas bubbles in fluids (143–149).

Free microbubbles in blood provide a foreign surface that initiates microthrombus formation (150), activates platelets and leukocytes, and alters erythrocyte count (150–152). These gas–liquid interfaces also cause the adsorption and denaturation of plasma proteins (150,151,153) subsequent to formation of a lipoprotein layer (154). This lipoprotein coat has been described as a layer 40 to 100 Å thick, within which physical forces exist that cause disruption of the secondary and tertiary protein configurations. Release of bound lipids is likely to occur as well (155). This includes phospholipids, which may have a polar attraction to the gas–liquid interface. Activation of the Hageman factor and acceleration of coagulation also are reported with intravascular bubbles (153).

Adherence of platelets to bubble interfaces has been observed microscopically, which apparently forms a thin outer layer that contains fibrinogen (40,150,156). Figure 16.2 is a photomicrograph of cellular adhesion to a gas bubble. As the first protein layered onto a bubble surface, fibrinogen has nonpolar hydrophilic groups that are exposed as possible binding sites for other bloodborne products, including fatty acids (153) and large lipid particles that may further promote platelet adhesion and spreading (157). Ultrastructural changes of microbubble-activated platelets resemble those following activation with thrombin, adenosine diphosphate, or collagen (158). Accumulation of platelets within the interstices between bubbles may also play a role in foam stabilization where excess bubbling occurs.

FIG 16.2. Air embolism in sheep blood. A: Single air embolism (AE) 4 hours after pulmonary artery (PA) embolization. Note dark cells (neutrophils) aggregated around the AE. B: Clumps of neutrophils believed to be remnants of the air bubble–blood interface after the air bubble was resorbed. C: Transmission electron micrograph of an AE nearly completely surrounded by neutrophils at the AE–blood interface.  (From Albertine KH, Weiner-Kronish JP, Koike K, et al. Quantitation of damage by air emboli to lung microvessels in anesthetized sheep. J Appl Physiol 1984;57:1360–1368, with permission.)


Microbubble-activated platelet density is greater when bubbles are 40 m or more in diameter, suggesting a dependency on size rather than on total bubble count (157). This may be partly because of the lesser degree of curvature with larger bubbles, which could facilitate platelet adhesion and spreading (158), thereby initiating aggregate formation (153). Table 16.3 summarizes the reported causes of gaseous microemboli during CPB. Direct action of gaseous emboli on the vascular endothelium reportedly includes functional changes, denudation and herniation of the cells, and leukocyte and platelet aggregation and activation (40,149,159–162). Release of inflammatory mediators from activated cells, including leukotrienes, thromboxanes, and prostaglandins, is also reported with gas embolism and causally linked to changes in microvascular permeability (163–166). Because the endothelial cells are also responsible for release of other vasoactive mediators such as nitric oxide, the degree of injury caused by the gas emboli can affect vessel diameter and flow (161,167–169). Table 16.4 lists mediators that are released during bubble–blood interactions. Contrasting evidence indicating no adverse effect of gaseous microemboli on cerebral blood flow or metabolism or arterial vasospasm was partially explained by differences in size and total amount of emboli involved (161,170). Table 16.5 summarizes both direct and indirect bubble–blood interactions.

DETECTION

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Detection of microemboli associated with bypass has been described using histologic techniques (18,79), direct visual or optical methods (171–173), radiography (127), computed tomography (174), particle sizing using resistance or laser devices (12,175), screen filtration pressure (176), screen sampling (35), bulk compressibility (177), fluorescein angiography (178,179), and ultrasound (180). Each of the above techniques has afforded some degree of precision in its ability to size or count microemboli; however, more often than not, one parameter is gained at the expense of another. Optical detection devices, including particle-size analyzers and screen sampling, usually require a small sample volume obtained through a sidestream suitably narrow for light and optical through-transmission. Such techniques may be reliable for sizing, but not counting, the microemboli (181). Sequential sampling of aliquots of blood can be used with settling or rising chambers (in the case of gaseous microemboli) to determine bulk volume or total gas phase using dilatometry but are less reliable for size determination (182,183). This same analogy applies to screen filtration techniques. Bulk compressibility takes advantage of the compressible nature of gas bubbles dispersed within a fluid to determine total volume but not size or count of total numbers. More recently described techniques for detecting microembolism during or resulting from CPB surgery are magnetic resonance imaging (184) and the potential for combined use of single-photon emission computed tomography with transcranial Doppler to evaluate subclinical effects (185).

Of all emboli detection techniques, ultrasonic devices are the most commonly used today. These devices include transcranial, transesophageal, and Doppler flow devices (pulsed and continuous wave) and echo machines using both M- and B-modes. The enthusiasm for using ultrasound to detect microemboli is based in part on the ability to discriminate the circulating particles from the background blood flow using usually noninvasive techniques. Ultrasound devices work by emitting a sound signal from a piezoelectric crystal that is reflected from the moving blood cells. The frequency of the reflected signals differs from that of the transmitted signal in proportion to the blood velocity. With Doppler devices, these frequency shifts typically occur within the audible range (0 to 10 kHz). The audio signal contains both amplitude and frequency information, and the degree of reflection of the sound waves is a function of the difference in acoustic properties of the reflecting particles.

Microemboli, whether solid or gaseous, are more effective in scattering sound because of the difference in density between the particle and the surrounding blood or tissue. Gas bubbles are much more efficient at scattering ultrasound than more rigid particles, such as red cell aggregates or microthrombi, especially at the smaller diameters (150). This difference is due to the acoustic properties of nongaseous emboli being similar to those of blood. Additionally, gas bubbles have the propensity to resonate as the ultrasonic wave causes pressure oscillations and hence vibration of the gas inside the bubble. At the resonance frequency of a bubble of a particular size, the scattering of sound is maximal (186). The reflection of sound waves also is influenced by the frequency of the ultrasonic wave as it passes through the tissue and fluid and by the diameter of the microembolus itself (108). Gaseous microemboli as small as 1 m have been detected with ultrasound (186) in tissues, whereas other authors have detected circulating microbubbles of 20 to 50 m (186–188).

Ultrasonic Doppler devices used for detection of microemboli used pulsed or continuous-wave transmission. With pulsed systems, short energy bursts (about 2 s) are emitted at rates on the order of 1,000 pulses per second. Particles along the beam path are then set in motion, reflecting the sound waves, whereas the regions in front of or behind it are not affected. This technique enables the operator to focus the beam to a specified depth. Using pulsed Doppler systems for microemboli detection highly depends on the particle diameter (189,190), angulation of the ultrasonic transducer (75,108,191), and incident pulse length (189,190). Blood flow rate also has an important influence on pulsed Doppler systems in that the pulse echoes usually represent the product of the pulse frequency and the time that the bubble resides within the sampling field (190). Some devices take this feature into consideration by making the pulse-repetition frequency proportional to the blood flow (192). With continuous-wave ultrasound, the emitted beam is continuous, and the particles are sonified along the entire length of beam penetration. Continuous-wave Doppler devices are currently used in a number of clinical diagnostic devices and are commonly used for microemboli detection.

Echo imaging systems have gained widespread support in recent years in detecting circulating microemboli. Transthoracic, transesophageal, and transcranial ultrasound devices enable localization of microemboli within each of the respective acoustic fields. The B-mode enables the operator to view the emboli within the heart chambers, although some degree of quantitation may be obtained by M-mode, because the x-axis represents the time scale and relative counts are possible (193). Transesophageal echocardiography has been shown to be particularly effective in detecting gaseous microemboli during and after CPB and is useful in determining the adequacy of deairing maneuvers (194–198). The closeness of the esophagus to the myocardium and aorta enable transesophagal echo to obtain an acoustic window without interference from the chest wall, ribs, and lungs and does not interfere with the surgical field (199,200). It also represents one of the most sensitive modalities for gas embolus detection of volumes as small as 0.0001 mL/kg within the left ventricle (196) or of individual bubbles ranging in size from 25 to 225 m (mean, 70 ± 49) in diameter (201).

Transcranial Doppler has been used for detection of perioperative cerebral microemboli, for evaluation of arterial line filtration (202), for valve replacement monitoring (124), and for its original application during carotid endarterectomy (203,204). These devices not only enable the detection and visualization of bubbles or particulate matter in the cranial arteries but also determine blood flow characteristics (124,202–205).

Yao et al. (206) compared the efficacy of simultaneous embolic monitoring using transcranial Doppler of the middle cerebral artery and transesophageal echocardiography of the aortic arch in 20 patients undergoing CPB. Emboli signals were obtained from all patients, with the mean total signal counts of the aorta being 77% greater than the cerebral emboli. Overall, 83% of the emboli signals were detected during the aortic cross-clamp and partial occlusion clamp placement. Both techniques were recommended as effective emboli monitors. Because fewer emboli circulate into the cerebral vessels, Droste et al. (207) suggested that monitoring times last at least 1 hour when using transcranial Doppler to allow greater specificity.

Clark et al. (208) combined data on stroke with coma and inappropriate behavior to validate these effects against total microembolic counts measured with transcranial Doppler in patients undergoing CPB. The Doppler device was used to evaluate the various surgical maneuvers and their role in emboli generation. Seventy percent of the patients that demonstrated cerebral dysfunction had embolic counts greater than 60. Those patients with the highest incidence of surgical air had the highest incidence of cerebral dysfunction, whereas those with the higher counts of CPB-generated emboli had greater decrements in cognitive function compared with those with fewer. Overall, the CPB-generated emboli were relatively well tolerated.

Quantitation of microemboli is difficult with any ultrasonic device because of certain limitations inherent to their proper operation (192,209,210). These limitations involve characteristics such as the frequency requirements, transducer angulation, and electrical circuitry used for signal analysis and sampling area (85,88,181,192,209). Calibration of the devices, although often overlooked, is very important. Use of solid artificial microparticles of plastic or glass is common for calibration; however, their acoustic properties are usually different than those of bloodborne or gaseous microemboli (75,148,211), and clumping or settling may further complicate any sort of accurate calibration. For accurate gaseous microemboli quantification, calibrated microbubbles are more reliable because of their similarities in acoustic properties (150,175,190,209,211–213).

Despite these calibration procedures, certain limitations exist with any attempt to quantitate the size or number of microemboli present in vessels or the bypass circuit (180,208,213,214). Figure 16.3 depicts potential causes for signal differences from bubbles detected by Doppler ultrasound. Current trends are to develop techniques to both discriminate between gaseous and solid microemboli and to quantitate them in terms of size and/or numbers. Using multifrequency devices or sophisticated signal analysis of spectral patterns, some investigators have undertaken efforts to accomplish these goals (215–219). Other efforts have been made to determine the nature and size of the emboli using the intensity of the reflected signals (220–221); however, features relevant to the composition of the embolus may be more difficult to characterize (222). Dual frequency, multifrequency, second harmonic, pattern recognition, and artificial neural network using ultrasound devices have also recently been tested for further refinement of the embolus characteristics (223–229).

FIG 16.3. Potential causes for signal differences from bubbles detected by Doppler ultrasound: (A) encapsulated bubble; (B) ideal condition with signal reflected back from discrete bubble; (C) multiple bubbles with scattered signals (D) different location of bubbles within sample beam (E) bubbles of different sizes blocking sound waves of others (F) probe operated at different frequencies (G) artifact due to gross movement of skin/surface probe interface; and (H) refraction of beam due to density differences at tissue interfaces.  (Modified from Butler BD. Biophysical aspects of gas bubbles in blood. Med Instrum 1985;19:59–62, with permission.)


PATHOPHYSIOLOGY

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It is generally accepted that postoperative diffuse cerebral dysfunction after the use of CPB is largely attributable to microembolism and/or compromise of cerebral blood flow (223). Individual differences in patient tolerance to bypass make it difficult to universally define safe thresholds for flow, pressure, and pulsatility (170,230,231). The brain has been the focus of most studies evaluating negative surgical outcome after CPB, principally because of the variety of sensitive tests capable of implicating cerebral damage (232,233). Histologic studies have also shown embolic material in the kidneys, heart, liver, lungs, and spleen after CPB (25,26). Histology of the brains of patients who died after open heart surgery has demonstrated fibrin, fat, muscle fragments, calcium, and platelet aggregate microemboli in the vasculature (30). In these studies, fat emboli were detected in 80% of the cases and their presence was independent of perfusion variables, whereas nonfat emboli were related to the length of perfusion time. Thus, the period of greatest risk of cerebral injury is likely to be at the beginning of CPB when the patient is susceptible to both hypotension and microemboli initially released from the perfusion circuit (234,235).

Postoperative cerebral dysfunction after bypass, as demonstrated with psychomotor tests, may persist from a few hours to days or weeks (236–239). Some misinterpretation of the etiology of the injury may occur because similar changes in cerebral function are reported not only after microembolization but also with anxiety, sleep deprivation, drugs, cerebral edema, or hypoxemia (7,210,240,241).

Additional reasons for the wide range of reported incidences of neurologic dysfunction after CPB include the variability commonly observed when comparing prospective and retrospective studies, the time lapse between pre- and postsurgical evaluation, and the thoroughness of the tests conducted (6,242). In their retrospective evaluation of postoperative neurologic dysfunction, Bojar et al. (243) and Coffey et al. (244) reported incidence rates of 1% to 5%. This is in contrast to reported incidence rates in prospective studies as high as 30% to 61% (245–247). Incidence of stroke has been reported in approximately 5% of coronary artery bypass procedures in two prospective studies. Shaw (6), Newman (7), Smith (248), and Campbell and Raskin (249) have published excellent reviews on the subject of neurologic and neuropsychologic morbidity and its prevention during cardiac surgery. Johnston et al. (170) reported increases in gaseous microemboli during hypothermia with a bubble oxygenator in dogs; however, global cerebral blood flow and regional brain perfusion were not affected.

Adverse neurologic outcome after bypass also has been correlated with arterial line microemboli (250). Earlier, Lee et al. (241) found postoperative deficits in 23% of their patients after open heart surgery, 14% of whom had psychiatric findings. Carlson et al. (236) found a greater percentage of patients with decreased Bender-Gestalt visual motor test scores when a bubble oxygenator was used instead of a membrane-type or without use of an arterial line filter. These results correlated with ultrasonic detection of circulating microemboli. Levels of the brain-specific enzymes of creatine phosphokinase were significantly elevated in patients undergoing open heart surgery (251–253), and this effect was preventable in dogs with use of an arterial filter (254). Other cerebrospinal fluid and serum enzymatic protein markers of brain injury have been reported in 6% to 50% of cardiac surgery patients (253,255,256). Moody et al. (258) detected focal small cerebral capillary and arteriolar dilations in dogs and patients after bypass that they attributed to microemboli, the identity of which was suggested as either silicone antifoam (258) or air (259). In earlier studies, cardiotomy suction was implicated as an important source of lipid emboli (36) that can lead to formation of small capillary and arterial dilatations (260) found in brain and other organs (257,261). They suggested that these focal dilations could be the equivalent of an anatomic correlate to neurologic deficits.

In the case of gas emboli, the topic of pathophysiology has been studied for more than three centuries (262). A number of reports and reviews have described the outcome of arterial air embolism with cardiac surgery involving gaseous microemboli and gross air (3,4,79,209,210,214,263–265). Cerebral gas embolism can cause transient changes in the electroencephalogram that may persist from seconds to hours, in addition to the neurologic dysfunction described for nongaseous microemboli. Coronary air is associated with impaired left and right ventricular function and with numerous electrocardiographic changes, including ventricular dysrhythmias, atrioventricular dissociation, QRS complex widening, and ST segment and T wave changes (264,266). Clearance of coronary air while on CPB can be accomplished with the use of certain drugs, surface-active chemicals (267,268), aortic clamping with ventricular or aortic compression, or retrograde cerebral perfusion (269,270). Figure 16.4 illustrates the major mechanisms of CPB air embolism as reported in 1986 (271). More recent surveys (272,273) have indicated that iatrogenic air embolism continues to occur during CPB, but the incidence of patient injury is greatly reduced from the earlier survey data (271).

FIG 16.4. Major mechanisms of gas embolism. Survey respondents who observed 284 incidents of air embolism during clinical cardiopulmonary bypass reported these etiologies. CPS, cardioplegic solution; LV, left ventricular. (From Kurusz M, Wheeldon DR. Risk containment during cardiopulmonary bypass. Semin Thorac Cardiovasc Surg 1990;2:400–409, with permission.)


Arteriolar obstruction by gaseous emboli may be associated with vascular spasm followed by hyperemia (266) and perivascular hemorrhage (274). Immediately after occlusion, vasodilation occurs in the arteries and venules, followed by congestion and stasis. These responses represent a direct action or injury to the vascular endothelium (265). Cerebral pathology may include many features of infarction or ischemia such as hemorrhage, edema, astrocyte and neuronal swelling, vacuolation, and necrosis (40,275–280).

Visual abnormalities manifested as occult visual field defects after cardiac surgery may be explained by ocular embolization with subsequent microvessel obstruction of the retina (179,281).

PREVENTION

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It is unlikely today that even with the most current bypass devices, all embolic events can be totally eliminated. However, an awareness of those factors responsible for their production and interaction with the blood (282), as previously described, may allow perfusion teams to minimize the numbers generated and consequences during clinical bypass. Undoubtedly, filtration has been the single most important technique used to reduce all types of emboli, whereas the current near-universal acceptance of membrane oxygenators has led to dramatic decreases in gaseous microemboli production.

The technique of blood filtration began with the development of modern blood banking and blood transfusion practices in the 1930s (283,284). An early blood collection/transfusion apparatus incorporating a 250-m reusable stainless steel filter was reported by Cooksey (285) and was later modified and used successfully on more than 11,000 transfusions.

Early laboratory experience with extracorporeal circulation confirmed the superior filtration characteristics of the pulmonary bed, and blood was often precirculated through the animal's lungs before beginning perfusion. Bjork (286) and Miller et al. (287) used filters with pores 300 x 300 m in the arterial line during early clinical applications. The original Lillehei-DeWall bubble oxygenator incorporated four standard infusion set screen filters on the outflow side of the arterial settling reservoir (288). The early CPB experience of Kolff et al. (289) and Gross et al. (290) also relied on arterial filters for particulate trapping and air removal.

The seminal work of Swank et al. (291,292) in the mid-1960s led to the use in 1970 by Hill et al. (293) and others of the Swank depth filter for filtration of cardiotomy blood first (292) and later arterial blood (294). The hospital mortality for patients decreased significantly in those on whom filters were used. Also, in the early 1970s, Patterson and Twichell (295) described a 40-m pleated polyester mesh filter that functioned with low pressure drop at clinical flow rates.

Solis et al. (36) evaluated the effectiveness of both types of filters using a microparticle counter and concluded that microaggregates in the cardiotomy-suctioned blood comprised a tremendously greater volume than those found in arterial or venous blood. Figure 16.5 compares the volume of particulates detected in venous, arterial, and cardiotomy return blood during CPB. Further, such microaggregates found in the cardiotomy-return blood were more resistant to deaggregation and thus posed the greatest risk to the patient. Page et al. (296) confirmed the benefit of depth filtration of cardiotomy-suctioned blood during clinical perfusion to reduce embolus transmission to patients.

FIG 16.5. Largest volume of particulates detected in cardiotomy blood and a small gradient between venous and arterial blood that disappears by 30 minutes on cardiopulmonary bypass. (From Solis RT, Noon GP, Beall AC, et al. Particulate microembolism during cardiac operation. Ann Thorac Surg 1974;17:332–344, with permission.)


The extent of filter use by cardiac surgical teams nationwide was reported in 1983 (297). Ninety-four percent reported the practice of filtering bank blood added to the CPB circuit. Ninety-seven percent filtered cardiotomy-suctioned blood, and 78% filtered blood in the arterial line during both adult and pediatric perfusion. Because of the potential for filter occlusion with inadequate anticoagulation, several questions on this survey were posed regarding its management. Blood coagulation status was measured by greater than 95% of the respondents, who most often performed the activated coagulation time at least every 30 minutes during CPB. Forty percent also reported filtration of the cardioplegic solution after earlier reports of particulate emboli contained in these solutions (298–301). The importance of rinsing and filtering the circuit with crystalloid solution before establishing bypass was emphasized by Reed et al. (56) in 1974 and was performed by most perfusionists in 1982 (297). Subsequent surveys (273,302) have shown the near universal use of arterial line filtration during CPB.

The benefit of arterial line filtration, in conjunction with either bubble or membrane oxygenation, has been confirmed in several reports using Doppler or transesophageal echocardiographic detection of decreased quantities of microemboli (303–306) or improved patient scores on neuropsychologic tests after CPB (307). Figure 16.6 is a scanning electron photomicrograph of a heparin-coated screen arterial filter after clinical bypass.

FIG 16.6. Scanning electron micrograph (original magnification, x300) of mesh of 40-m heparin-coated screen arterial line filter after approximately 90 minutes of cardiopulmonary bypass. Note relatively clean surfaces with sparse depositions of amorphous debris and absence of occluded filter pores or platelet/neutrophil adhesion. (From Borowiec JW, Bylock A, Van der Linden J, Thelin SHeparin coating reduces blood cell adhesion to arterial filters during coronary bypass: a clinical study. Ann Thorac Surg 1993;55:1540–1545, with permission.)


Pharmacologic interventions to minimize emboli during bypass consist primarily of ensuring adequate heparin anticoagulation (22,24,308,309). Close monitoring of the activated coagulation time during CPB, as previously described, is now nearly universally practiced. Although controversial, administration of isoflurane has been shown by some to afford better tolerance for cerebral ischemia and would therefore appear potentially useful in minimizing the effects of cerebral emboli (310–312). Barbiturates also have been used by some (313) to improve the cerebral outcome after open heart surgery, but their use as prophylaxis against emboli appears less clearly defined. Royston (314) reviewed pharmacologic interventions aimed at reducing platelet and neutrophil emboli during CPB.

Acid-base management using alpha-stat was popularized in the early 1980s (315–317), and more recent survey results (318) indicate its use in most CPB cases. Alpha-stat management more closely maintains cerebral autoregulation in contrast to pH-stat management, during which enhanced cerebral blood flow occurs. Decreased transmission of microemboli per unit volume of blood flow, therefore, favors the alpha-stat approach to minimize the embolic "load" in perfused tissue beds (319). In a recent study on swine, Plochl and Cook (281) introduced the physiologic intervention of PaCO2 manipulation to control cerebral blood flow during periods of high embolic risk.

Prevention of gross air embolism from either the bypass circuit or operative field has been the subject of numerous reports (270,320,321). A variety of safety devices with proven efficacy is available for the circuit and includes arterial line filters, bubble traps, air bubble detectors, low-level alarms, and one-way valves for the vent or arterial filter purge line. The arterial line filter and air bubble detector have been reported to be highly effective in prevention of air embolism originating in the extracorporeal arterial line (271). Equally important in prevention of air embolism are clear lines of communication and use of protocols during CPB (322). Prebypass checklists have gained wide acceptance by teams and are effective in uncovering unsafe conditions before initiating bypass (323) (see Chapter 27 for a more detailed discussion).

Another less appreciated source of emboli during cardiac surgery relates to the status of the patient's ascending aorta, which usually must be cannulated, cross-clamped, and manipulated during the procedure. Atheromatous plaques that are present may be dislodged during these maneuvers (324,325). The recent multicenter study investigating adverse cerebral outcomes after coronary bypass surgery (8) found the presence of proximal aortic atherosclerosis to be a strong predictor of stroke. Alternative cannulation (326–328) or venting sites have been proposed, as well as the so-called no-touch technique (329). Intraoperative epiaortic echocardiography is becoming increasingly popular to define the extent of disease in the aorta. (See Chapter 28 for further discussion of management of the atherosclerotic aorta.)

TREATMENT

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There is no specific treatment for microemboli per se; instead, prevention, as discussed previously, has received the most attention and appears to be the most rational approach in decreasing the risk. However, when gross air embolism occurs, definite treatment protocols have been proposed (330,331) and used with remarkable success (332–335). The importance of having a plan for this rare event has been emphasized and can often make the difference between severe injury or death and an uneventful recovery (322,330,336). Hyperbaric oxygenation is considered the most effective treatment of gross air embolism (337–344), although access to such a treatment facility may be limited (271). Detection of cerebral air embolism by computed tomography often indicates that a large volume of gas remains. Dexter and Hindman (345) modeled the absorption rates of cerebral gas emboli and determined that volumes in excess of 1.0 x 10–3 will remain for periods from 1.6 to 4.9 hours depending on the breathing gases, oxygen or air. Larger volumes remain proportionately longer, indicating that postsurgical hyperbaric oxygenation treatment may remain effective even hours or days after the initial insult (346).

A treatment modality for gas embolism studied in animals but not yet tested in humans is hemodilution with perfluorocarbon emulsions, which aids in the absorption of the vascular bubbles (347). Another treatment modality is systemic heparinization, especially with air embolism to reduce thrombi and other blood–bubble interactions, although it may be deleterious if cerebral infarction has already occurred (348). If the air embolization occurs during open chest procedures, direct aspiration of the cardiac chambers or great vessels is possible, as well as venting, direct cardiac massage to mobilize the emboli, induction of hypothermia for cerebral protection, or retrograde coronary sinus or cerebral perfusion (270,331,349–355). If air is suspected as the embolizing gas, 100% oxygen ventilation should be implemented to achieve favorable bubble resolution conditions and to limit cerebral ischemia and use of nitrous oxide should be discontinued to avoid bubble growth (356,357). Use of the Trendelenburg position or other patient repositioning techniques have been previously advocated to aid in the removal or prevention of arterial bubbles entering the brain. These techniques, however, have been shown experimentally using in vivo and in vitro techniques to offer little or no protection (358,359). Recently, Dexter et al. (360) verified this finding using maximum gas bubble absorption rates to indicate no benefit in absorption of air bubbles. Reviews of this topic describe various effective treatment modalities (223,274,330).

The use of transesophageal echocardiography and transcranial Doppler has been reported to aid in the identification of intraventricular or intravascular bubbles, primarily during valvular procedures or when the heart chambers have been opened (361). Rigorous deairing techniques may be assessed in this manner to decrease the persistence of entrapped surgical air emboli (195,350,362–365).

CONCLUSIONS AND FUTURE TRENDS

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The subject of cerebral reactions to open heart surgery continues to receive much attention (366–369), and further improvements in CPB techniques (370) and patients' neurologic outcomes appear likely to emerge in the coming years. Although controversy sometimes continues regarding what are the optimal specific devices, a consensus now clearly favors incorporating membrane oxygenation and filtration of blood and all fluids during bypass. The chemical modification of blood-contacting surfaces used in extracorporeal devices may further decrease blood-derived microemboli from blood–foreign surface interaction. The current predominance of membrane oxygenation over that of bubble oxygenation has undoubtedly reduced gaseous microembolic phenomena in patients during bypass. Finally, ongoing research and continuing education will increase our understanding of the problems of embolic events and CPB and should further reduce levels of patient morbidity and mortality.

KEY POINTS

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  • The three categories of emboli are biologic, foreign material, and gaseous.

  • Bloodborne emboli consist of cellular and noncellular products or aggregates.

  • Most fat emboli are derived from cardiotomy-suctioned blood.

  • Platelet aggregates are present in bank blood and are generated by CPB foreign surface contact.

  • Platelet and neutrophil activation releases biogenic amines and other bioactive mediators that promote adhesion, further aggregation, and changes in microvascular endothelial permeability.

  • Foreign material emboli are derived from the CPB circuit and from materials and debris in the operative field.

  • Antifoam emboli were more prevalent with bubble oxygenators but are still present in smaller quantities in most circuits using membrane oxygenators.

  • Generation of gaseous microemboli is greatly reduced when using membrane oxygenators.

  • Gaseous microemboli production is minimized by adherence to cooling and warming gradients that do not exceed 10°C.

  • Gaseous microemboli may be produced by rapid injection of drugs or blood into the CPB circuit.

  • Cardiotomy-suctioned blood contains the greatest volume of both gaseous and particulate emboli.

  • Cavitation refers to transient hydrodynamic phenomena that consists of bubble nucleation, growth, and collapse and is produced by extreme (positive and negative) pressure changes within blood.

  • Surgical air refers to gas bubbles that enter the bloodstream when native vessels or chambers are opened during cannulation for CPB or application of vascular clamps.

  • Depending on gas composition and bubble volume, bubbles will persist in the blood for long periods or resolve quickly, with air (composed mostly of nitrogen) resolving slowest and carbon dioxide resolving most quickly.

  • Free microbubbles in blood are a foreign surface that promote cellular and protein activation at the bubble–blood interface.

  • Bubble contact with vascular walls alters endothelial cells that further promotes release of vasoactive mediators and platelet and neutrophil adhesion.

  • Ultrasonic detection (including transcranial, transesophageal, and Doppler) of microemboli is the most frequently used clinical modality.

  • Ultrasonic detection devices are limited in their ability to quantitate sizes or emboli count.

  • The most common manifestation of emboli after CPB is cerebral injury or dysfunction.

  • The pathophysiology of arterial and venous gas embolism has been well studied in the laboratory.

  • Filtration of bank, cardiotomy, and arterial blood is the most important technique to reduce emboli during CPB.

  • Maintenance of adequate anticoagulation can decrease CPB-generated microemboli.

  • Hyperbaric oxygenation is considered the most effective treatment for gross air embolism.

  • Transesophageal echocardiography is an effective tool to assess thoroughness of cardiac deairing techniques.

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