Central Nervous System Dysfunction After Cardiopulmonary Bypass

Early, Delayed, and Late Stroke

In considering the incidence of perioperative stroke it is apparent that distinguishing stroke as early (ie, neurologic deficit apparent on emergence from anesthesia), delayed (ie, neurologic deficit developing more than 24 hours postoperatively), or late (ie, stroke developing more than 30 days postoperatively) is important to better discriminate causative factors and potential risk reduction strategies. Such an analysis facilitates identification of potentially causal intraoperative events (eg, hypotension, atherosclerotic aorta) from perioperative occurrences (eg, atrial fibrillation) and later progression of underlying disease (eg, cerebrovascular atherosclerosis).

Studies strongly indicate that patient comorbidities, particularly aortic atherosclerosis, in concert with intraoperative factors, whether associated with CABG, OPCAB, or PCI, fundamentally impact the incidence of early stroke and are thus potentially modifiable, whereas late stroke reflects progression of comorbid disease and atrial arrhythmias.

Age-Associated Risk for Central Nervous System Injury

In a review of 67,764 cardiac surgical patients, of whom 4743 were octogenarians, and who underwent cardiac surgery at 22 centers in the National Cardiovascular Network, the incidence of type I cerebral injury was 10.2% in patients older than 80 years versus 4.2% in patients younger than 80. Although global mortality for cardiac surgery in octogenarians was greater than in younger patients, the researchers reported that, when octogenarians without significant comorbidities were considered, their mortality rates were similar to those of younger patients.

In addition to the age-related factor, reports from Europe and North America consistently describe previous cerebrovascular disease, diabetes mellitus, hypertension, peripheral vascular disease (including carotid disease), aortic atherosclerosis, renal dysfunction, infarction or unstable angina within 24 hours before surgery, and intraoperative and postoperative complications as being additional factors increasing the incidence of cerebral injury in cardiac surgical patients ( Box 31.1 ). Determining the impact of age-associated cerebral injury in cardiac surgery is becoming more relevant because of the progressive increase in the average age of the general population and, in particular, of the cardiac surgical population. The presence of preoperative comorbidities is increasingly recognized as the primary determinant of the age-associated risk for CNS complications. As overall survival and quality of life after cardiac surgery continue to improve in older patients, advanced age alone is no longer considered a deterrent when evaluating a patient for cardiac surgery. The presence and extent of comorbidities should be considered as being of equal or greater importance than age itself as a risk factor for cerebral injury in cardiac surgical patients.

Box 31.1

Factors Related to Cerebral Injury in Cardiac Surgery

• Age

• Aorta atheromatosis

• Carotid disease

• Diabetes mellitus

• Hypertension

• Peripheral vascular disease

• Renal dysfunction

• Stroke or cerebrovascular disease

• Recent unstable angina or acute myocardial infarction

• Preoperative low output/low ejection fraction

• Combined/complex procedures

• Redo surgery

• Prolonged cardiopulmonary bypass time

• Intraoperative hemodynamic instability

• Postoperative atrial fibrillation

Risk factors consistently reported for perioperative cerebral injury in cardiac surgery patients; see discussion in the text.

Retrospective Versus Prospective Neurologic Assessment

The detection of CNS injury depends critically on the methodology used, and retrospective studies have been demonstrated as insensitive in various studies. 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. Many of the types of neurologic impairment now being documented are subclinical and not readily detectable by a standard “foot-of-the-bed” assessment and have currently unknown implications for longer-term patient outcomes.

Watershed Infarctions

Watershed, or boundary zone, infarcts are ischemic lesions that are situated along border zones between the territories of two major cerebral arteries (eg, the middle and posterior, or the anterior and middle cerebral arteries) where terminal arteriolar anastomoses exist ( Fig. 31.1 ).

By the same rationale, however, these areas are also highly susceptible to ischemia because of 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. As such, although they commonly arise from 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 Emboli and Outcome

Cerebral emboli during CPB can be arbitrarily differentiated into macroemboli (eg, calcific or atherosclerotic debris) and microemboli (eg, microgaseous bubbles, microparticulate matter). Overt and focal neurologic damage likely reflects the occurrence of cerebral macroemboli (eg, 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. 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, causing alterations in cerebral microvascular regulation. Whether heparin anticoagulation during CPB mitigates the impact of cerebral gas embolization as demonstrated during cerebral angiography remains speculative.