3. Mechanism and risk factors of neurologic injury
The spectrum of post-operative neurologic injury can be schematically outlined as:
Coronary artery bypass performed on an arrested heart relies on aortic cannulation and cross-clamping; both steps represent considerable aortic manipulation associated with significant atheroembolic risk. The mechanisms for this to occur include detachment of atherosclerotic material from the aortic intima as a result of external manipulation (cannulation, aortic cross-clamping and partial occlusion); or internal disruption caused by the ”sandblasting” effect of the high-velocity jet of blood exiting the aortic cannula and impacting on the atherosclerotic intima or pedunculated atheroma.
The role of the “porcelain aorta” (43) (Figure 1) in the pathogenesis of adverse neurologic outcome after isolated CABGs has been postulated for almost four decades (3-6).
Multiple cadaveric studies have documented a high embolic burden to the brain during CPB and aortic manipulation in the presence of ascending aortic atherosclerosis (7,8). This is manifested by specific cerebral microvascular alterations in the form of small capillary and arteriolar dilatation (7). In an autopsy study by Blauth (8) 21.7% of patients who died after cardiac surgery on CPB had evidence of atheroemboli (or abnormalities consistent with atheroemboli) in the brain; severe aortic atherosclerosis and coronary surgery were significantly associated with higher risk of neurologic embolization.
In a multicenter prospective study that enrolled 2,108 patients undergoing elective CABG in 24 U.S. medical institutions, Roach (9) reported an overall incidence of type I cerebral events (coma, stroke or TIA) of 3.1%; moderate to severe aortic atherosclerosis assessed by manual palpation of the ascending aorta was the main risk factor, increasing the rate of postoperative stroke four-fold. Similar findings were reported by Stamou (10) on a series of 16,528 patients who underwent isolated on-pump CABG with an overall stroke rate of 2.0%; atherosclerosis of the ascending aorta and prolonged bypass and cross-clamp time were significantly more frequent in patients with postoperative neurologic complications. Data from Tarakji (1) showed an overall stroke rate of 1.6% in a large series of consecutive isolated CABG performed over a period of 30 years. The main risk factors were older age and variables representing higher atherosclerotic burden like PVD and carotid stenosis. Minimization of aortic manipulation with off-pump or on-pump beating heart techniques provided the lowest risk.
In a review of 6,682 consecutive patients undergoing isolated on-pump CABG performed with single aortic clamp technique and without epiaortic scanning, Borger (11) reported a prevalence of postoperative stroke of 1.5%, associated with a significant increase of in-hospital mortality (p<0.001). The atheroembolic etiology of those strokes was supported by radiological and pathological evidence of ischemic lesions in the territory distribution of major cerebral vessels; surgical manipulation (cannulation, cross-clamping, proximal anastomosis) of an atherosclerotic ascending aorta was the most common embolic source.
Aortic calcifications were once again found to increase threefold the risk of post-operative stroke (overall rate 1.4%) in a review of 19,224 patients undergoing isolated on-pump CABG in 31 hospitals in the State of New York by John (12). As for other studies, stroke patients experienced a significantly increased in-hospital mortality (24.8% vs 2.0%, p<0.001). Likewise, Rao (14) reported a stroke rate of 1.4% among a series of 3,910 consecutive isolated on-pump CABGs (single clamp technique). Severe coronary artery disease was found to be the most important predictor of stroke, followed by older age, previous TIA/stroke, PVD and diabetes: all those factors clearly represent a surrogate for aortic atherosclerosis. A higher stroke rate of 4.3% was reported by Lynn (15) in a series of 1,000 consecutive on-pump CABGs; extensive aortic calcifications noted by the surgeon was a highly significant risk factor for permanent neurologic deficit (11 strokes in 57 patients with aortic calcification, 19%; p<0.0001). Finally, the investigators of the Multicenter Study of Perioperative Ischemia (13) developed a preoperative stroke risk index used to estimate the individual risk of postoperative stroke. Advanced age, PVD and diabetes were strong predictors of atherosclerotic disease of the aorta and cerebral vessels, hence the authors implicated embolization as the likely primary aetiology of major neurologic deficits after CABG.
Early postoperative strokes are more often right-sided compared with delayed strokes that are more uniformly distributed. Data from Boivie and Hedberg (44-46) showed clinical and radiological evidence that right-sided perioperative events were largely preponderant compared to contralateral strokes. Manipulation of a calcified ascending aorta explains the embolic nature of particles tangentially expelled into the brachiocephalic artery.
Grooters (47) looked at the effect of perfusion jets and “sandblasting” from CPB aortic cannulae into the aortic arch. Using transesophageal echo (TEE) they demonstrated that both end-hole and side-holes cannulae generated high velocity jets directed against the aortic wall, potentially responsible for the disruption of friable atherosclerotic plaques. On the other hand, the Dispersion cannula showed a broad wedge-like perfusion pattern with significantly lower exit velocities.
The effect of aortic clamping has also been extensively investigated. In a cadaveric study from Boivie (48), ten calcified ascending aortas were mounted on a perfusion model, clamped multiple times and finally washed out. The investigators found that a significant amount of particular matter had been released, comprised of both calcified and cellular material (average diameter of 0.63 ± 0.03 mm). Although the majority of the embolic load occurred following the first clamping, subsequent clamps still continued to release particulate matter and therefore this questions multiple-clamp surgical techniques (Figure 2). Barbut (49) looked at the embolic burden detected by transcranial doppler (TCD) during on-pump CABG using a double-clamping technique. The largest number of embolic signals (58%) were noted at aortic cross-clamp or partial-occlusion clamp removal (seven-fold and five-fold higher rates respectively) especially when higher grade of aortic atheroma were present (p<0.05).
Watters (50) detected a significant decrease in TCD embolic signals in patients undergoing off-pump CABG (OPCAB) with partial occlusion clamp, compared to on-pump CABG with double clamping (median embolic signals 79vs 3 respectively). Although this study was non-randomized, the two groups were similar in terms of Parsonnet risk score, number of grafts performed and overall presence of aortic calcification. Finally, in another study involving TCD monitoring during CABG, Taylor (51) showed that a relevant number of embolic events while on CPB were recorded during perfusionist interventions (drugs administration and blood sampling) in the form of small air bubbles.