Retrospective versus Prospective Neurologic Assessment

The detection of central nervous system (CNS) injury depends critically on the methodology used, and retrospective studies have been deemed insensitive by different authors. A retrospective chart review is inadequate as an assessment of the overall incidence of postoperative neurologic dysfunction. The reasons for the inability of retrospective chart audit to detect the majority of patients with neurologic dysfunction are readily apparent and include incompleteness of records, a reluctance to document apparently minor complications, and, most important, an insensitivity to subtle neurologic dysfunction. The timing, thoroughness, and reproducibility (single examiner) of the neurologic examinations, as well as the incorporation of a preoperative assessment for comparison, all determine the sensitivity and accuracy with which postoperative CNS injury can be detected.

Valvular versus Coronary Artery Bypass Graft Surgery

Increasing the complexity or undertaking open chamber-type procedures increases the risk of CNS injury. Ebert and coworkers prospectively studied 42 patients who underwent valve replacement surgery and 42 patients for CABG, with both groups matched post hoc for age, sex, and preoperative cognitive status.⁵ Patients were investigated preoperatively as well as 2 and 7 days postoperatively with a comprehensive neuropsychological and neuropsychiatric assessment. Valve replacement surgery patients exhibited more severe neuropsychological deficits and showed a slower recovery than patients who underwent CABG. In a study of 64,467 patients who underwent CABG alone and 3297 patients who underwent CABG in conjunction with aortic valve replacement (CABG/AVR) or CABG in conjunction with mitral valve repair or replacement (CABG/MVR), the incidence of type I cerebral injury in patients younger than 80 years of age was 4.2% for CABG, 9.1% for CABG/AVR, and 11.2% for CABG/MVR.² It should be noted that the total CPB time was 96 minutes for CABG, 148 minutes for CABG/AVR, and 161 minutes for CABG/MVR.

The incidence of subtle neurologic dysfunction and cognitive abnormalities is similar in all adult patients undergoing surgical coronary artery revascularization. Increasing age has been repeatedly shown to be one of the major risk factors for stroke after CABG, likely related to the greater prevalence of severe aortic atherosclerosis in the elderly. This suggests that there may be different factors operative in the production of gross neurologic damage than in the genesis of cognitive dysfunction. Although calcific or atheromatous macroembolic debris from the ascending aorta or aortic arch appears to be a prime factor in the production of clinical stroke syndromes and it was formerly thought that microembolic elements, either gaseous or particulate, produced cognitive dysfunction, studies from beating-heart surgery in which CPB is avoided, despite a much lower incidence of embolic events, appear to have a relatively similar incidence of cognitive dysfunction to CABG using conventional CPB.⁶

Aortic Atherosclerosis

Atheroembolism from an atheromatous ascending aorta and aortic arch is recognized as a major risk factor in the patient undergoing cardiac surgery and is a widespread problem.⁷

Atheroembolism in cardiac surgery has a broad spectrum of clinical presentations, including devastating injuries and death; yet its true incidence is probably underestimated. Thoracic aorta atheromatosis is associated with coronary artery disease and stroke in the general population. Yahia and associates prospectively studied patients with diagnoses of TIA or stroke using TEE for assessment of aortic atheromatosis.⁷ Thoracic aortic atheromas were present in 141 of 237 patients (59%); mild plaque (<2 mm) was present in 5%, moderate plaque (2 to 4 mm) in 21%, severe plaque (≥4 mm) in 33%, and complex plaque in 27%. Plaques were more frequently present in the descending aorta and the arch of the aorta than in the ascending aorta. Overall, atherosclerosis of the ascending aorta is present in 20% to 40% of cardiac surgical patients, with the percentage increasing with age, and it is an independent risk factor for type I cerebral injury.

Transesophageal Echocardiography versus Epiaortic Scanning

The detection of ascending aorta atheromatosis is a cornerstone of strategies to decrease cerebral injury in cardiac surgery. Despite its widespread utilization, manual palpation of the aorta has a very low sensitivity for this purpose. The association of severe thoracic aortic plaques (defined as 5-mm-thick focal hyperechogenic zones of the aortic intima and/or lumen irregularities with mobile structures or ulcerations) and coronary artery disease is well established. Identifying severe aortic disease has important clinical implications because surgical technique, including surgical procedure and siting of cannulation and anastomotic sites for proximal grafts, may be altered to avoid producing emboli and stroke. Intraoperative epiaortic ultrasound scanning (EAS) has emerged as a most helpful tool for the diagnosis of ascending aortic atherosclerosis and has revealed major insights into the nature and distribution of this disease.

Djaiani and colleagues performed TEE and EAS to assess the severity of aortic atherosclerosis in the ascending aorta and the aortic arch.⁸ Patients were allocated to either low-risk or high-risk groups according to thickness of the intima of the aorta. Transcranial Doppler imaging was used to monitor the middle cerebral artery. Diffusion-weighted magnetic resonance imaging (MRI) was performed 3 to 7 days after surgery. The NEECHAM Confusion Scale was used for assessment and monitoring patient consciousness level. In the high-risk group (intimal thickness > 2 mm), confusion was present in six (16%) patients versus five (7%) patients in the low-risk group, and there was a threefold increase in median embolic count, 223.5 versus 70.0 (P = .0003). Diffusion-weighted MRI–detected brain lesions were only present in patients from the high-risk group, 61.5% versus 0% (P < .0001). There was significant correlation between the NEECHAM scores and embolic count in the high-risk group. Multiple studies have documented that most of the significant atherosclerotic lesions in the ascending aorta are missed by intraoperative palpation by the surgeon, and intraoperative echocardiographic studies of the aorta have been recommended (Fig. 29-1). However, the ability of TEE to reliably detect all ascending aorta and aortic arch lesions is limited.

Figure 29-1 Transverse ultrasonic image of the ascending aorta and the corresponding segment of aorta in a patient with severe atherosclerosis. Note the calcification (arrowhead) and the projection of atheroma (arrow) into the lumen.

(From Wareing TH, Davila-Roman VG, Barzilai B, et al: Management of the severely atherosclerotic ascending aorta during cardiac operations: A strategy for detection and treatment. J Thorac Cardiovasc Surg 103:453, 1992.)

The high acoustic reflectance attributable to the air-tissue interface resulting from overlying right main bronchus and trachea limits TEE assessment of the upper ascending aorta where cannulation is generally undertaken. Intraoperative EAS has emerged as a most helpful tool for the diagnosis of ascending aortic atherosclerosis and has revealed major insights into the nature and distribution of this disease. Konstadt and colleagues investigated 81 patients (57 male and 24 female; aged 32 to 88 years, mean age 64 years) scheduled for elective cardiac surgery.⁹ A comprehensive examination of the entire thoracic aorta in both the longitudinal and transverse planes was performed by biplane TEE. After pericardiotomy, a sterile-draped 7-MHz probe was used to scan the entire ascending aorta in both long- and short-axis views. In both echocardiographic examinations, the presence and location of protruding plaques and intimal thickening greater than 3 mm were recorded. Fourteen (17%) of the 81 patients had significant atherosclerotic disease of the ascending aorta as diagnosed by EAS echocardiography. The sensitivity of TEE was 100%, the specificity was 60%, the positive predictive value was 34%, and the negative predictive value was 100%. According to the authors, if the complete biplane TEE examination is negative for plaque, it is highly unlikely that there is significant plaque in the ascending aorta. If the TEE examination is positive for plaque, there is a 34% chance that there is significant disease of the ascending aorta, and EAS should be considered. TEE is a very sensitive but only mildly specific method of determining whether ascending aortic atherosclerosis is present.

Identification of ascending aorta atheromatous disease would prompt the surgical team for strategies to either modify, decrease, or avoid aortic manipulation. Management strategies for the diseased ascending aorta range from minimally invasive aortic “no-touch” techniques to maximally invasive procedures, including ascending aorta replacement with application of deep hypothermic circulatory arrest. Operative modifications in CABG include avoidance of aortic cross-clamping, alternative methods of aortic cross-clamping, and placement of all arterial in situ bypass conduits, Y-grafts, or extra-anatomic bypass grafts.

Watershed Infarctions

Watershed, or boundary zone, infarcts are ischemic lesions that are situated along border zones between the territories of two major cerebral arteries (e.g., the middle and posterior, or the anterior and middle cerebral arteries) where terminal arteriolar anastomoses exist.

A profound reduction in systemic blood pressure is the most frequent cause of watershed infarcts. These areas are thought to be more susceptible to ischemia resulting from hypotension because of their critical dependence on a single blood supply.

These areas are also highly susceptible to ischemia due to end-artery embolization, and it is also recognized that although severe hypotension is the most common cause, showers of microemboli may lodge preferentially in these areas and cause infarcts in the underlying brain.¹² As such, although they are commonly due to profoundly hypotensive episodes, watershed lesions are not pathognomonic of a hypotensive episode and may be the result of cerebral emboli. Embolization and hypoperfusion acting together play a synergistic role and either cause or magnify the brain damage of cardiac surgical patients.

Cerebral Perfusion Pressure

Using radioisotope techniques for measurement of cerebral blood flow (CBF), and incorporating a jugular venous catheter for calculation of the cerebral metabolic rate of oxygen, it was determined that there is a profound reduction in the cerebral metabolic rate of oxygen during hypothermic CPB and that CBF is decreased proportionately and will autoregulate down to a cerebral perfusion pressure (CPP) of 20 mm Hg in the presence of α-stat pH management. Low arterial pressure during the hypothermic phase of CPB is, thus, unlikely to result in cerebral ischemia in the absence of cerebrovascular disease.

It should also be appreciated that during CPB cerebral venous hypertension can result from partial obstruction of the superior vena cava (SVC), particularly in the presence of a single two-stage venous cannula, and may give rise to cerebral edema, as well as producing a disproportionate lowering of CPP relative to arterial pressure. This strongly suggests that cerebral venous hypertension, as can occur during CPB with myocardial dislocation and impaired drainage of SVC, may result in cerebral ischemia and necrosis if unrecognized and untreated. It is feasible that such unrecognized cerebral venous hypertension has resulted in some of the postoperative neurologic syndromes that have been reported.

Although the association between hypotension during CPB and cerebral dysfunction remains contentious, there is some evidence that certain subsets of patients may be at particular risk. Although mean arterial pressure (MAP) and rewarming are not primary determinants of cognitive decline, hypotension and rapid rewarming contribute significantly to cognitive dysfunction in the elderly. Again, because elderly patients comprise an increasing segment of the cardiac surgical population, these aspects are becoming increasingly important clinical management issues.

The interaction of emboli, perfusion pressure, and the particular conditions of the regional cerebral circulation (e.g., preexisting cerebral intravascular lesions) will determine the final expression of brain damage in the cardiac surgical patient. Combinations of hemodynamic events from apparently normal CPB procedures are related to the development of postoperative neurologic complications and affect the impact of common clinical risk factors. A multivariate statistical procedure (cluster analysis) was applied to a dataset of automatically recorded perfusions from 1395 patients who underwent CABG.¹³ The following five parameters emerged for cluster analysis: MAP, dispersion of MAP, dispersion of systemic vascular resistance, dispersion of arterial pulse pressure, and the maximum value of mixed venous saturation. Patients who underwent CPB procedures with large fluctuations in hemodynamic parameters particularly showed an increased risk for the development of postoperative neurologic complications.

Cerebral Emboli and Outcome

Two different types of cerebral emboli appear to occur during CPB and are composed of solid or gaseous matter, such as macroemboli (e.g., atherosclerotic debris) and microemboli (e.g., micro-gaseous bubbles, microparticulate matter). Overt and focal neurologic damage likely reflects the occurrence of cerebral macroemboli (e.g., calcific and atheromatous debris generated during valve tissue removal or instrumentation of an atheromatous aorta), whereas less focal neurologic dysfunction has been ascribed to cerebral microemboli. Microemboli appear to have some role in diffuse, subtle neurologic and cognitive disturbances, whereas macroemboli likely produce clinically apparent catastrophic strokes. Whatever the nature of the cerebral insult, however, it seems that coexistent inflammatory processes can exacerbate the magnitude of injury.

Gaseous emboli are not innocuous. It has been demonstrated that the effects of air emboli on the cerebral vasculature not only are due to bubble entrapment with direct blockage of cerebral vessels but also represent the effects that such bubbles have on vascular endothelial cells.¹⁴ Ultrastructural examinations of pial vessels exposed to cerebral air emboli demonstrated severe injury to endothelial plasmalemma, leading to loss of cellular integrity and endothelial cell swelling. Such endothelial damage produces disruptions of vasoreactivity. Air embolism also produces changes in blood elements, leading to formation of a proteinaceous capsule around the bubbles, marked dilation of pial vessels, platelet sequestration, and damage to endothelial cells. Air-induced mechanical trauma to the endothelium causes basement membrane disruption, thrombin production, release of P-selectin from intracellular vesicles, synthesis of platelet-activating factor, and a reperfusion-like injury with perturbations in inflammation and thrombotic processes. These phenomena likely impair nitric oxide production, giving rise to alterations in cerebral microvascular regulation.

Cardiopulmonary Bypass Equipment

Early studies demonstrated increased microemboli in patients undergoing CPB using bubble oxygenators, with a reduction in cerebral embolization with the use of membrane oxygenators and arterial line filtration¹⁵ (Boxes 29-4 and 29-5). It is apparent that emboli may be generated continuously during CPB and that equipment modification (e.g., arterial line microfiltration and preferential usage of membrane oxygenators) can decrease the generation of such emboli. Membrane oxygenators are currently recommended for CPB. It is equally evident that such equipment modifications, while decreasing the embolic load, cannot completely eliminate it.

In an attempt to decrease emboli originating from the surgical field, cell savers have been used for processing cardiotomy suction blood before returning it to the CPB circuit. Jewell and coworkers¹⁶ reported on 20 patients prospectively randomized to either cell saver or cardiotomy suction and demonstrated that compared with cardiotomy suction, cell saver removed significantly more fat from shed blood, such that the percentage reduction in fat weight achieved by cell saver or cardiotomy suction was 87% compared with 45%.

Applied Neuromonitoring

Intraoperative neurophysiologic monitoring may be of benefit to decrease CNS injury.¹⁷ Brain oximetry studies using noninvasive near-infrared spectrophotometry (NIRS) have shown promising results.

Intraoperative transcranial Doppler imaging has been demonstrated to detect embolic events in real time and allows modification of perfusion and surgical techniques. It has been shown that the numbers of emboli generated by perfusionist interventions (e.g., drug injection, blood return), as well as episodes of entrainment of air from the surgical field, are rapidly identified and corrected by transcranial Doppler detection of intraoperative emboli. Even during beating-heart procedures, compromised cerebral perfusion can occur relatively frequently, and, if unrecognized, may account for the relative lack of difference in CNS outcomes between CABG and off-pump CABG.¹⁸ Combined EEG and cerebral oximetry identified episodes of cerebral ischemia in 15% of a series of 550 beating-heart patients; all were treated successfully by a combination of pharmacologically improved cardiac output, increased perfusion pressure, and cardiac repositioning.

Pharmacologic Cerebral Protection

In general, pharmacologic protection from cerebral ischemia remains an elusive goal. While results suggest that there is as yet no pharmacologic “magic bullet” that can be used to reduce neurologic injury in patients undergoing cardiac surgery, there is a combination of technical and pharmacologic measures currently available that might positively affect the outcome of these patients. In patients identified as being at risk for perioperative cerebral injury, preventive measures as outlined in Box 29-6 should be instituted with organ-targeted management to guide the whole intraoperative and postoperative period. As the age and incidence of comorbid disease in the cardiac surgical population continue to rise, the importance of these issues becomes ever more acute because primary prevention continues to be the only effective measure to decrease cerebral injury in cardiac surgical patients.