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J Thorac Cardiovasc Surg 1999;118:740-745
© 1999 Mosby, Inc.

CARDIOPULMONARY SUPPORT AND PHYSIOLOGY

DECREASED CEREBRAL EMBOLI DURING DISTAL AORTIC ARCH CANNULATION: A RANDOMIZED CLINICAL TRIAL

From the Divisions of Cardiovascular Surgery and Cardiac Anesthesia, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada.

Supported in part by the Heart and Stroke Foundation of Ontario. M.A.B. is a Research Fellow of the HSFO. R.D.W. is a Career Investigator of the HSFO.

Address for reprints: Christopher M. Feindel, MD, The Toronto Hospital, EN 14-222, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4.

	Abstract

Top Abstract Introduction Methods Results Discussion Study limitations Conclusions References

 
Background: Cerebral emboli occur during cardiopulmonary bypass and are a principal cause of postoperative neurologic dysfunction. We hypothesized that arterial cannulation of the distal aortic arch, with placement of the cannula tip beyond the left subclavian artery, will result in fewer cerebral microemboli than conventional cannulation of the ascending aorta.
Methods: Patients undergoing coronary bypass surgery with a single crossclamp technique were randomized to receive cannulation of the distal aortic arch (n = 17) or standard cannulation of the ascending aorta (control group, n = 17). Trendelenburg positioning was used whenever possible. Cerebral emboli were quantified by continuous transcranial Doppler monitoring of the middle cerebral artery.
Results: Baseline demographics were similar for the 2 groups of patients, including cardiopulmonary bypass and crossclamp times. Cerebral microemboli were detected during cardiopulmonary bypass in all patients, with a range of 17 to 627 emboli. The total number of detected emboli was lower in the arch cannulation group (152 ± 33, mean ± standard error of the mean) than in the conventional cannulation group (249 ± 35, P = .04). Embolization rates were lower in distal arch patients than in control patients during cardiopulmonary bypass (2.0 ± 0.3 vs 4.2 ± 0.9 per minute, respectively, P = .03). Reduction in cerebral emboli by distal arch cannulation was most pronounced during perfusionist interventions.
Conclusions: Cannulation of the distal aortic arch results in less cerebral microembolism than conventional cannulation of the ascending aorta. Provided it is performed safely, distal arch cannulation may be an important surgical option for patients with severe atherosclerosis of the ascending aorta.

	Introduction

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Despite continuous improvements in cardiac morbidity and mortality after coronary bypass surgery (CABG), neurologic complications remain an important problem. ¹ Neurologic injury ranges from neuropsychologic impairment, which is very common but difficult to detect, to stroke, which is infrequent but devastating. Several investigators have demonstrated that neuropsychologic impairment occurs in 50% to 70% of patients undergoing CABG within 1 week after the operation, ^2,3 with 30% to 40% of patients having long-term cognitive deficits. ^4,5

The introduction of transcranial Doppler ultrasonography in the cardiac operating room has revealed that cerebral microemboli occur in virtually all patients during cardiopulmonary bypass (CPB), ^6,7 a finding that has been verified by retinal fluorescein angiography ⁸ and postmortem histologic analysis. ⁹ These emboli are thought to be the principal reason for the development of postoperative neuropsychologic impairment. ^10,11 However, few published clinical trials have investigated methods of reducing cerebral embolization during CPB. ^12-15

We have previously demonstrated that the majority of cerebral emboli during CPB consist of air. ¹⁶ Since air bubbles ascend in blood, we hypothesized that CPB arterial inflow distal to the carotid arteries, combined with Trendelenburg positioning, will result in delivery of an increased proportion of emboli to the distal circulation and decreased embolization to the cerebral circulation. We therefore conducted a randomized, controlled clinical trial comparing rates of cerebral embolism after cannulation of the distal aortic arch, with positioning of the cannula tip beyond the left subclavian artery, to embolic rates after conventional cannulation of the ascending aorta.

	Methods

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Patient population.
From November 1997 to August 1998, 40 patients undergoing isolated CABG by one surgeon (C.M.F.) consented to participate in this trial. A total of 198 patients underwent CABG by C.M.F. over this same time period. The predominant determinant of whether or not patients were approached to participate was the availability of the transcranial Doppler ultrasonograph and appropriate personnel. Patients were excluded if they had a history of carotid stenosis or carotid bruit (n = 18), if they had previous CABG (n = 20), or if concomitant surgical procedures were planned (n = 51). Patients who consented to participate in the trial were excluded in the operating room if they had evidence of atherosclerosis of the ascending or transverse aorta as determined by digital palpation (n = 2). Four patients who consented were also excluded because of an inability to obtain an adequate transcranial Doppler signal of the middle cerebral artery. After these exclusions, 34 randomized patients formed the focus of the remainder of this article. Patients were randomized within the operating room, via an opaque sealed envelope, to one of two aortic cannulation techniques: group I, cannulation of the distal aortic arch (n = 17), and group II, standard cannulation of the ascending aorta (control patients, n = 17). On the basis of previous data, ¹⁶ we determined that a sample size of 17 patients per group would give us an 80% chance of detecting a 25% relative risk reduction in our primary outcome, mean cerebral emboli per minute, with a corresponding -level of .05.

The experimental protocol was approved by the Human Experimentation Committee of The Toronto Hospital and all participating patients gave informed written consent.

Operative management.
Anesthetic management consisted of induction with midazolam, fentanyl, and sodium thiopental, followed by maintenance with isoflurane and propofol. All patients received a Swan-Ganz catheter (Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif) placed through the right internal jugular vein.

Patients were randomized within the operating room to conventional cannulation of the ascending aorta with a 24F standard arterial cannula (model 6672, Sarns/3M Health Care, Ann Arbor, Mich) or to cannulation of the distal aortic arch with a 24F flexible aortic arch cannula (model 4335, Sarns). The aortotomy was located just proximal to the innominate artery in the conventional cannulation group and on the inferolateral aspect of the arch, just proximal to the origin of the left subclavian artery, in the arch cannulation group. The aortic arch cannula was inserted approximately 8 cm and directed into the descending aorta, thus ensuring that the tip was distal to the left subclavian artery. Both cannulas had a single distal aperture for the exit of blood. Trendelenburg positioning of the patient (approximately 20°) was used whenever possible.

Myocardial protection consisted of intermittent cold antegrade blood cardioplegia. All patients received a left internal thoracic artery graft to the left anterior descending coronary artery, plus additional saphenous vein grafts as required. All anastomoses were performed during a single period of aortic crossclamping.

CPB was established with the appropriate randomized arterial cannula and a single 2-stage right atrial cannula. The CPB circuit consisted of a softshell venous reservoir, a hollow-fiber membrane oxygenator, and nonpulsatile roller pumps. A 32-µm filter was used in the arterial perfusion line. The hematocrit value was maintained between 20% and 25% during CPB, pump flow rates between 2.0 and 2.5 L · min^–1 ·m ^–2, and mean arterial pressure between 50 and 70 mm Hg by use of phenylephrine as required. Systemic body temperature was allowed to drift to a minimum of 34°C, with active rewarming to 37.5°C at the end of CPB.

Transcranial Doppler monitoring.
A transcranial Doppler ultrasonograph (MultiDop X4, DWL, Sipplingen, Germany) was used to continuously monitor the middle cerebral artery during the operation. We attempted to monitor both middle cerebral arteries in all patients but were unable to obtain a satisfactory signal from 1 artery in 8 patients. The Doppler sound was turned off during monitoring to keep the operative team blinded to the number and timing of microemboli. A 2-MHz pulsed-wave transducer (diameter = 1.7 cm) was used to simultaneously monitor 2 depths spaced 4.97 mm apart. The mean (± standard deviation) insonation depths were 48.9 ± 1.1 mm and 53.8 ± 1.1 mm. A 64-point fast Fourier transform was used. In addition, a high-pass filter set at 100 Hz and a low-pass filter at 80 kHz were used.

Detection and analysis of microemboli.
We have previously described our method of microembolus detection. ¹⁶ In brief, automated software (TCD-8 for MultiDop x4, version 8.00q) was used to discriminate between emboli and artifact according to the bigate method. ¹⁷ Simultaneous monitoring of 2 different depths of the middle cerebral artery was used. High-intensity signals were considered artifact if they occurred in both depths simultaneously. They were considered emboli if they appeared sequentially in a manner that was consistent with flow velocity and distance between the 2 sample volumes. In addition, manual off-line analysis of all high-intensity signals was performed by an observer blinded to patient group assignment. A detection threshold of 12 dB was used to improve reproducibility while maximizing sensitivity, in accordance with recommendations of an international consensus group. ¹⁸

Cerebral embolization rates were calculated as the number of emboli detected per minute. For those patients who had both middle cerebral arteries monitored, we evaluated the artery with the highest quality signal.

Statistical analysis.
Data are expressed as mean ± standard deviation for continuous variables and as percentages for categoric variables. Baseline patient demographics were compared by means of the Student t test, ², or Fisher’s exact test where appropriate. Embolic rates between the 2 treatment groups were compared by means of the Student t test. The effect of perfusionist interventions and treatment group, as well as their interaction, were simultaneously assessed with a 2-way analysis of variance. Analysis of covariance was used to assess for possible confounding variables. All analyses were performed with SAS software (SAS Institute, Inc, Cary, NC).

	Results

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Baseline and intraoperative demographics for the 2 groups of patients are displayed in Table I. There were no significant differences between the 2 groups for any variable.

View larger version (14K): [in this window] [in a new window]   Fig. 1. Comparison of cerebral embolization rates during CPB (mean ± standard error of the mean) between aortic arch cannulation and conventional ascending aorta cannulation groups. There were significantly fewer cerebral emboli per minute in the distal arch group.

View larger version (17K): [in this window] [in a new window]   Fig. 2. Cerebral embolization rates during perfusionist interventions, surgical interventions, and during baseline (see text for definitions). The decrease in cerebral embolization by distal arch cannulation was most pronounced during perfusionist interventions.

	Discussion

Top Abstract Introduction Methods Results Discussion Study limitations Conclusions References

 
Neurologic morbidity after CABG has received increasing attention in the literature. ¹ Stroke is the most thoroughly studied complication but occurs in only a small percentage of patients. ^20,21 Postoperative neuropsychologic impairment, in contrast, is very common. This complication is important because approximately half of patients are aware of their cognitive deficits ²² and one third of patients display long-standing impairment. ^4,5

Cerebral microemboli have been established as the principal cause of postoperative neuropsychologic impairment. ^10,11 Several investigators have documented that cerebral embolization occurs in virtually all patients undergoing CPB and that a reduction in the number of emboli is associated with less cognitive impairment. ^{8,11,13,23-25} Hammon and associates ¹¹ assessed neuropsychologic impairment in 395 patients undergoing CABG and demonstrated that 100 or more cerebral emboli, as quantified by transcranial Doppler sonography, is an independent predictor of cognitive dysfunction. Pugsley and coworkers ²³ found 43% of patients with more than 1000 emboli had neuropsychologic impairment 8 weeks after the operation, compared with only 9% of patients with fewer than 200 emboli. Similarly, Blauth and associates ⁸ used retinal fluorescein angiography to demonstrate increased emboli in patients with cognitive deficits compared with those without deficits. Sylivris and coworkers ²⁴ recently demonstrated a lower mean embolic rate (number of cerebral emboli per minute of CPB) in patients with neuropsychologic impairment compared with those without impairment.

The precise composition of cerebral microemboli during CPB is not known. ⁶ We ¹⁶ have previously demonstrated that the vast majority of emboli occur immediately after the injection of drugs, as well as small amounts of air contained within the syringe, into the venous reservoir by the perfusionists. We recorded cerebral embolic rates during CABG and found a 7-fold increase in emboli detection after perfusionist events when compared with other time periods. In addition, we found that careful deairing of the syringe before injection into the CPB circuit resulted in less embolization. These findings would strongly suggest that the majority of cerebral emboli during CPB consist of microbubbles. Further evidence for this conclusion can be found in a randomized trial by Padayachee and associates. ¹⁵ These investigators demonstrated that bubble oxygenators result in significantly more cerebral emboli than membrane oxygenators. Because air emboli would be expected to ascend in blood, we hypothesized that cannulation of the distal aortic arch, with placement of the cannula tip into the descending aorta and Trendelenburg positioning, would result in less cerebral embolization than conventional cannulation of the ascending aorta.

The current study assessed 34 patients undergoing CABG in a prospective, randomized trial. We found significantly lower cerebral embolic rates in patients randomized to distal arch cannulation, with the most pronounced effect during perfusionist interventions. We believe this is an important finding because microembolization is an important cause of postoperative neuropsychologic impairment. Although the majority of emboli in our study probably consisted of microbubbles, which may be less detrimental than atherosclerotic debris because of the ability of air to resorb, we believe that any reduction in cerebral embolic load is clinically significant.

The current study excluded patients with evidence of aortic or carotid atherosclerosis to minimize possible confounding factors. However, we believe that patients with aortic atherosclerosis may also benefit from distal arch cannulation. Although atherosclerosis of the aortic arch is more common than atherosclerosis of the ascending aorta, the disease process is often localized to the superior portion of the arch. ²⁶ It is sometimes possible, therefore, to find a disease-free segment of the inferior aortic arch in patients with diffuse atherosclerosis of the ascending aorta. Indeed, our largest experience for this particular cannulation technique is in this patient population. Furthermore, use of a long, straight arterial cannula, as used in the current study for arch cannulation, is associated with lower peak aortic flow velocities than conventional short, right-angled cannulas. ²⁷ A decrease in flow velocity, as well as positioning of the cannula tip below the left subclavian artery, may result in decreased embolization from an atherosclerotic aortic wall (known as the "sandblast effect"). Distal arch cannulation, therefore, may be the preferred technique for patients with aortic atherosclerosis.

The benefits of distal arch cannulation would be mitigated if any serious complications arose from this procedure. The small number of patients involved in this study limits conclusions on the safety of this procedure. However, we have previously performed distal arch cannulation in well over 200 patients, predominantly for diffuse atherosclerosis of the ascending aorta. There have been no cases of aortic dissection in this group of patients. In addition, there have been no re-explorations for bleeding from the arch cannulation site. We therefore believe that distal aortic arch cannulation is a safe and effective procedure.

	Study limitations

Top Abstract Introduction Methods Results Discussion Study limitations Conclusions References

 
One limitation of this study is that we did not perform neuropsychologic testing in the 2 groups of patients. Because of the small number of patients planned for this study, however, we thought that we would not have the power to comment on neuropsychologic outcomes. Approximately 200 patients per group would be required to detect a 30% relative risk reduction in cognitive impairment. In addition, we thought there was significant evidence in the literature supporting the role of microemboli in the etiology of neuropsychologic impairment.

Another limitation of this study is that we did not use epiaortic ultrasonography or transesophageal echocardiography in the assessment of atherosclerosis of the aorta. The use of digital palpation alone may have resulted in unequal distribution of patients with mild to moderate aortic atherosclerosis to one of the randomized groups. However, we have demonstrated that the majority of cerebral emboli during CPB are associated with perfusionist events and therefore probably consist of air. This finding would suggest that the presence of mild to moderate atherosclerosis would not significantly affect our findings of decreased cerebral emboli with arch cannulation.

	Conclusions

Top Abstract Introduction Methods Results Discussion Study limitations Conclusions References

 
Distal aortic arch cannulation results in less cerebral microembolism than conventional cannulation of the ascending aorta, particularly during perfusionist interventions. Provided it is performed safely, distal arch cannulation may be an important surgical option in the management of patients with severe atherosclerosis of the ascending aorta.

	Acknowledgments

 
We acknowledge the help of The Toronto Hospital cardiovascular surgery staff, in particular the anesthetists and perfusionists, for their cooperation and support. We also thank DWL Electronics Systems for the use of their transcranial Doppler equipment.

	References

Top Abstract Introduction Methods Results Discussion Study limitations Conclusions References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Michael A. Borger Richard D. Weisel Vivek Rao Gideon Cohen Christopher M. Feindel Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Borger, M. A. Articles by Feindel, C. M. Search for Related Content PubMed PubMed Citation Articles by Borger, M. A. Articles by Feindel, C. M.