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ur battant : risque de lésions cérébrales ischémiques en présence d’une aorte thoracique athéromateuse]
* From the Department of Anesthesia and Pain Medicine, the
Division of Cardiac Surgery, and
Neuroradiology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Address correspondence to: Dr. George Djaiani, Department of Anesthesia and Pain Medicine, Eaton North 3-410, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada. Phone: 416-340-4800, ext.6205; Fax: 416-340-3698; E-mail: george.djaiani{at}uhn.on.ca
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Abstract |
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Methods: Patients who underwent ONCAB surgery (n = 13) and who had aortic atheroma > 2 mm were compared to a risk-adjusted prospective cohort of patients (n = 13) undergoing OPCAB surgery. Transesophageal echocardiography and epiaortic scanning were performed to assess the proximal thoracic aorta. Patients were evaluated for new ischemic brain lesions utilizing DW-MRI three to seven days after surgery. The NEECHAM confusion scale was used to evaluate patient consciousness.
Results: The groups were comparable with respect to demographic data, and prevalence of preoperative risk factors. The extent and severity of aortic atheroma was similar in the two groups. The average maximum height of atheroma was 5.0 ± 2.0 mm in the OPCAB and 4.8 ± 1.9 in the ONCAB groups, respectively. The prevalence of new ischemic brain lesions on DW-MRI was 0% in the OPCAB group and 61% in the ONCAB group (P = 0.001). Patients in the OPCAB group were less confused during the first two postoperative days.
Conclusion: Patients with aortic atheroma > 2 mm may have a lower risk of new ischemic brain lesions as identified by DWMRI after OPCAB surgery. Patient stratification based upon aortic atheroma burden should be addressed in future trials designed to tailor treatment strategies to improve short- and long-term neurological outcomes in patients undergoing cardiac surgery.
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Introduction |
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Recently, we reported that patients with atheromatous disease of the proximal thoracic aorta (ascending aorta and aortic arch) undergoing coronary artery bypass (CAB) surgery with cardiopulmonary bypass (CPB) were exposed to a high risk of ischemic brain injury as identified by diffusion-weighted magnetic resonance imaging (DW-MRI). These patients had a threefold increase in cerebral embolic load during CPB, and a change in postoperative mental status when compared to patients with a normal aorta.9
The purpose of this study was to determine whether or not there is an association between proximal thoracic aortic atheroma and ischemic brain lesions on DW-MRI after on-pump (ONCAB) compared to off-pump (OPCAB) CAB surgery.
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Methods |
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Patients with aortic atheroma > 2 mm who underwent ONCAB surgery (n = 13)9 were compared to a risk-adjusted prospective cohort of patients (n = 13) undergoing OPCAB surgery. All patients were evaluated for new ischemic brain lesions utilizing DW-MRI three to seven days after surgery.
Echocardiographic assessment
All patients underwent transesophageal echocardiography (TEE) and epiaortic scanning of the proximal thoracic aorta. Echocardiographic data was acquired using a Hewlett-Packard Sonos 5500TM (Agilent Technologies, Andover, MA, USA) ultrasound system equipped with multiplane 4–7 MHz transesophageal and 6–15 MHz epiaortic probes. The TEE examination was performed after induction of anesthesia. After median sternotomy, the epiaortic probe was used by the surgeon to scan the ascending aorta from the aortic valve to the proximal arch in transverse and longitudinal planes.
Grading of the aorta was determined according to intimal aortic thickness: 
2 mm (grade 0); 2–4 mm (grade 1); > 4 mm (grade 2); and presence of mobile atheroma (grade 3).5,10 The same weighting criteria were applied to the presence of atheroma in the ascending aorta, and the aortic arch. Only patients with grade 1 or grade 2 atheroma were included in this study.
Management strategies
Anesthetic techniques were similar between the two groups. Premedication consisted of lorazepam 2–4 mg sl one-hour before surgery. Anesthesia was induced with fentanyl 10–15 µg·kg–1 iv and propofol 1–1.5 mg·kg–1 iv Pancuronium 0.1 mg·kg–1 iv was administered to facilitate tracheal intubation. Anesthesia was maintained with propofol infusion at 1–4 mg·kg–1·hr–1 and isoflurane. Only patients in the ONCAB group received tranexamic acid 50 mg·kg–1 iv prior to sternotomy. Heparin 2–3 mg·kg–1 iv was used in the OPCAB group to maintain activated clotting time (ACT) > 300 sec, and 3–4 mg·kg–1 iv in the ONCAB group to maintain ACT > 450 sec.
All patients underwent median sternotomy. Management of CPB included systemic temperature drift to 33–34°C, alpha-stat pH management, mean perfusion pressure between 50 and 70 mmHg, nonpulsatile pump flow rates of 2.0–2.4 L·min–1·m–2, and hematocrit > 20%. A 32-µm filter (Avecor Affinity, Minneapolis, MN, USA) was used in the arterial perfusion line. The aortic cannulation, cross-clamp application, and placement of proximal grafts were performed under a single cross-clamp application in the disease free area of the ascending aorta (grade 0 aorta, confirmed by epiaortic scanning). Prior to separation from CPB, patients were re-warmed to nasopharyngeal temperature 36–37°C. During rewarming the maximal inflow temperature was limited to 37°C. Protamine 1 mg·100 U–1 of heparin was used to fully reverse heparin in both groups.
In the OPCAB group, after performing epiaortic scanning, a partial aortic clamp was used in the atheroma free area of the ascending aorta (grade 0 aorta) to assist with construction of proximal coronary anastomoses. The mean arterial blood pressure was maintained above 60 mmHg.
After surgery, all patients were transferred to the intensive care unit for postoperative ventilation. Sedation was achieved with propofol infusion 0.5–4 mg·kg–1·hr–1 and morphine boluses. Patients were extubated according to the following criteria: patient responsive and cooperative, SaO2 
94% with FIO2 60%, complete reversal of neuromuscular blockade, PaCO2 35–55 mmHg, stable hemodynamics, absence of uncontrolled arrhythmia, and nasopharyngeal temperature > 36°C.
Magnetic resonance imaging assessment
Patients were evaluated for new ischemic brain lesions utilizing DW-MRI three to seven days after surgery. The MRI protocol consisted of sagittal T1, axial diffusion (5 mm thick no inter-slice gap whole brain diffusion images), axial echo-planar imaging gradient echo, echo-planar imaging fluid-attenuated inversion recovery, and phase contrast magnetic resonance angiography sequences. Voxel size for the diffusion sequences was 1.6 x 1.6 x 5 mm.
The MRI data were analyzed for overall incidence of new ischemic lesions which were visible as high signal areas on diffusion-weighted image and low signal areas on the apparent diffusion coefficient (ADC) maps. New ischemic lesions were identified as regions of signal hyperintensity on DW imaging (three orthogonal gradient directions, b = 1000 sec·mm2) and signal hypointensity on the apparent diffusion coefficient maps. Diffusion-weighted and ADC images were analyzed for the number, location, and size of each lesion. Magnetic resonance imaging results were reviewed by a single neuro-radiologist who was blinded to patient group assignment.
Assessment of consciousness
Patient consciousness assessment was conducted utilizing the NEECHAM confusion scale11 at six discrete time periods: preoperatively (baseline), and postoperatively daily (days one to five). The NEECHAM confusion scale was divided into three subscales pertinent to patient cognitive function, behaviour, and physiologic/autonomic stability. Total score indicated the different degrees of confusion and was weighted as follows: 0–19, moderate to severe confusion; 20–24, mild or early development of confusion; 25–26, ‘not confused’ but at high risk; 27–30, normal function.
Study design and statistical analysis
One of the purposes of this pilot study was to address sample size requirements for a large randomized controlled trial comparing ONCAB and OPCAB techniques in patients with atheromatous aorta. The design of the current study was to compare 13 ONCAB patients who had documented aortic atheroma > 2 mm to a risk-adjusted prospective cohort of 13 patients undergoing OPCAB surgery. We hypothesized that OPCAB surgery would be associated with lower risk of new DW-MRI lesions.
Comparability of both groups was tested with the use of Chi-square statistics or Fisher’s exact t test on qualitative variables as appropriate and the t test and ANOVA on quantitative variables. The association between atheroma and MRI brain infarcts was assessed using a 2 x 2 contingency table. One-way ANOVA was used to compare the NEECHAM scores. A P value < 0.05 was considered significant. Statistical analysis was conducted with the MINITAB computer software (Minitab Inc., University of Wales, Cardiff, UK).
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There was no significant difference with respect to the maximal height of atheroma (the worst lesion) between the two groups; OPCAB, 5.0 ± 2.0 mm vs ONCAB, 4.8 ± 1.9 (data shown as mean ± SD). The location and severity of atheroma were similar between the ONCAB and OPCAB groups (Table II). In the ONCAB group; three patients had atheroma limited to the ascending aorta, eight patients had atheroma restricted to the aortic arch, and two patients had atheroma present in both ascending aorta and aortic arch. In the OPCAB group; two patients had atheroma limited to the ascending aorta, seven patients had atheroma restricted to the aortic arch, and four patients had atheroma present in both ascending aorta and aortic arch.
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). Atheroma was restricted to aortic arch in four of these patients. The prevalence of preexisting lacunar infarcts on T2 imaging was similar between the two groups. An example of new DW-MRI lesions is reflected in Figure 1.
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). None of the patients had any clinically significant metabolic changes that would justify this altered level of consciousness. One patient in the ONCAB group had a clinical stroke with a lesion in the motor cortex of the left hemisphere.
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).
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Discussion |
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Although new DW-MRI brain infarcts have been reported to occur in 21–45% of patients after CAB surgery with CPB,12–16 none of these series stratified patients on the basis of aortic atheroma. Interestingly, patient ages were comparable in previous reports, suggesting a possible frequency and distribution of atheroma in the proximal thoracic aorta similar to our cohort of patients. Therefore, had these patients been stratified according to the severity of aortic atheroma, the prevalence of new ischemic brain lesions may have been considerably higher. These findings become important with respect to patient risk stratification based on the aortic atheromatic burden that may reduce the risk of perioperative neurological injury.
Contrary to ONCAB surgery, OPCAB surgery is associated with reduced cerebral embolic load.17–21 Nevertheless, a recent meta-analysis of randomized controlled trials (RCTs) by Cheng et al.22 failed to show any benefit in neurological and neurocognitive outcomes with OPCAB surgery. With respect to perioperative stroke, we reached similar conclusions to Cheng et al.,22 in our meta-analysis of 37 RCTs comparing ONCAB and OPCAB treatment modalities. However, the OPCAB technique was associated with significant reduction in stroke in a meta-analysis of 22 risk-adjusted observational studies evaluating patients at high risk for neurological injury.23 It was likely that lower stroke rates after OPCAB surgery were secondary to less aortic manipulation and reduced cerebral embolic load in patients with atheromatous aorta.24–26 The discrepancies between the RCTs and risk-adjusted observational studies may be attributed to different patient populations being studied, i.e., the RCTs are usually associated with recruitment of low-risk patients whilst the observational studies better reflect patient diversity similar to that of clinical practice.
Similarly to our findings, a small RCT conducted by Baker et al.27 found that new DW-MRI lesions were present in three (33%) patients in the ONCAB (n = 9) group and one (7.7%) patient in the OPCAB (n = 13) group.27 Contrary to our findings, Friday et al.28 reported that new DW-MRI lesions were present in five (31%) of 16 patients after OPCAB surgery. Unfortunately, the authors did not report on the extent and severity of aortic atheroma. These reports further emphasize the controversy between ONCAB and OPCAB treatment strategies with respect to neurological outcomes. Likely resolution to this debate may arrive from an adequately powered RCT including patients at high risk from neurological injury. In order to prevent a possible under-powering of such a study we have lowered the potential frequency of new ischemic brain infarcts in the ONCAB group from 60% to 45%. As a result, to see a one-third reduction (from 45% to 30%) in new brain infarcts in patients undergoing OPCAB surgery, with 
= 0.05 and power 1-ß = 0.8, a group of 175 patients in each arm of the study would be required.
Although our current study is not a randomized trial, we attempted to compare two risk-adjusted (atheroma burden) groups of patients exposed to two treatment modalities. The decision regarding scheduling patients for ONCAB or OPCAB surgery was made by the operating surgeon taking into account patient preferences. It is likely that patients with significant atheromatous disease of the ascending aorta (particularly mobile atheroma) may benefit from OPCAB surgery, and if the surgeon suspects that the patient is at high risk from perioperative stroke, the OPCAB technique may become the technique of choice. Although this approach clearly introduces bias, the risk factors for perioperative stroke (history of stroke, atrial fibrillation, symptomatic carotid artery disease, ‘porcelain aorta’, or mobile plaques) were part of the exclusion criteria in this study i.e., minimizing this very bias. Furthermore, patients who were scheduled for OPCAB surgery and were converted to ONCAB intraoperatively were also excluded due to higher morbidity and mortality in this particular subgroup.
The findings of our current study are limited to patients with grade 1 and grade 2 atheroma. The reason for not including patients with normal aorta (grade 0) was based on our previous observation where the lack of new DW-MRI brain lesions was demonstrated in a subgroup of 37 patients with normal aorta. In contrast, eight of 13 patients with grade 1 or grade 2 atheroma had new DW-MRI lesions. Moreover, half of these patients had normal ascending aorta and atheroma restricted to the aortic arch.9 Consequently, the same weight was given to the location of atheroma in the ascending aorta or the aortic arch in both study groups.
The current study design did not merit formal neuropsychological assessment of cognitive function. However, our results support the findings of a recent meta-analysis of risk adjusted observational studies23 favouring the OPCAB technique for stroke reduction. To assess patient consciousness status we utilized the NEECHAM confusion scale which has been shown to reflect clinical impact of cerebral embolic load and new DW-MRI lesions after ONCAB surgery.9 Current DW-MRI technology permits detection of the embolic ischemic lesions 3 mm with unprecedented accuracy. The reported sensitivity and specificity of DW-MRI exceeds 90%, specifically, for acute subcortical infarction it is 94.9% and 94.1% respectively.29 Diffusion-weighted magnetic resonance imaging is rapidly becoming a gold standard on which both early diagnosis and early treatment strategies of stroke are currently predicted.30
In conclusion, our study demonstrates that patients with aortic atheroma > 2 mm may have a low risk of new DW-MRI ischemic brain lesions after OPCAB surgery when compared to ONCAB surgery. Patient stratification based on the aortic atheromatic burden should be addressed in future trials designed to tailor treatment strategies to improve short- and long-term outcomes of patients with coronary artery disease.
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Footnotes |
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Competing interests: None declared.
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2 Newman MF, Kirchner JL, Phillips-Bute B, et al.; Neurological Outcome Research Group; Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med 2001; 344: 395–402.
3 Borger MA, Ivanov J, Weisel RD, Rao V, Peniston CM. Stroke during coronary bypass surgery: principal role of cerebral macroemboli. Eur J Cardiothorac Surg 2001; 19: 627–32.
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21 Watters MP, Cohen AM, Monk CR, Angelini GD, Ryder IG. Reduced cerebral embolic signals in beating heart coronary surgery detected by transcranial Doppler ultrasound. Br J Anaesth 2000; 84: 629–31.
22 Cheng DC, Bainbridge D, Martin JE, Novick RJ; Evidence-Based Perioperative Clinical Outcomes Research Group. Does off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials. Anesthesiology 2005; 102: 188–203.[Medline]
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