1 Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710, USA 2 Present address: Klinik für Anaesthesiologie, Technische Universität München, München, Germany
Corresponding author. E-mail: h.grocott@duke.edu The members of the Neurologic Outcome Research Group of the Duke Heart Center are listed in the Appendix.
Accepted for publication: July 10, 2003
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods. Transoesophageal echocardiographic images of the ascending, arch and descending aorta were evaluated in 128 patients to determine the aortic atheroma burden. Transcranial Doppler (TCD) of the right middle cerebral artery was performed in order to measure cerebral embolic load during surgery. Using multivariate linear regression, the numbers of emboli were compared with the atheroma burden.
Results. After controlling for age, cardiopulmonary bypass time and the number of bypass grafts, cerebral emboli were significantly associated with atheroma in the ascending aorta (R2=0.11, P=0.02) and aortic arch (P=0.013). However, there was no association between emboli and descending aortic atheroma burden (R2=0.05, P=0.20).
Conclusions. We demonstrate a positive relationship between TCD-detected cerebral emboli and the atheromatous burden of the ascending aorta and aortic arch. Previously demonstrated associations between TCD-detectable cerebral emboli and adverse cerebral outcome may be related to the presence of significant aortic atheromatous disease.
Br J Anaesth 2003; 91: 65661
Keywords: brain, embolism; complications, atherosclerosis; heart, cardiopulmonary bypass; measurement techniques, transcranial Doppler; measurement techniques, transoesophageal echocardiography
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In a similar fashion, emboli (both macro and micro) have been associated with adverse cerebral outcome and overall length of hospital stay.5 6 An independent link between atheroma and transcranial Doppler ultrasonography (TCD)-detectable emboli, however, has not been demonstrated previously, possibly because of methodological limitations. Previous investigations have been limited by their use of semiquantitative atheroma measurement methods, which reduce a three-dimensional structure, such as the aorta, to a one-dimensional (height) ordinal variable by using a somewhat arbitrary grading system to categorize the height of the atheroma.7 8 Categorical assessments of atheroma severity may have had limited sensitivity in detecting relationships between emboli and atheroma that might well be uncovered by using more sensitive linear regression methods to analyse continuous (as opposed to ordinal) data.
The purpose of our investigation was to determine the relationship between TCD emboli and a more quantitative two-dimensional aortic atheroma severity assessment9 in patients undergoing CABG.
![]() |
Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Induction and maintenance of anaesthesia were achieved with bolus and continuous infusions of midazolam and fentanyl, with supplementary isoflurane (0.51.0%) to maintain heart rate and mean blood pressure within 25% of the preinduction values. Pancuronium was given as needed for neuromuscular paralysis. The cardiopulmonary bypass apparatus included a membrane oxygenator (Cobe Laboratories, Lakewood, CO, USA), Sarns roller pump (3M, Ann Arbor, MI, USA) and a 40 µm arterial line filter (Pall Biomedical Products, Glencove, NY, USA) that allowed non-pulsatile cardiopulmonary bypass with flows of 22.4 litre min1 m2 to be carried out. A haematocrit of 0.18 was maintained throughout cardiopulmonary bypass by the addition of packed red blood cells as necessary. Arterial PCO2 during cardiopulmonary bypass was 3540 mm Hg (uncorrected for temperature) and the PaO2 was maintained at 150250 mm Hg. Mean arterial pressure between 50 and 90 mmHg during cardiopulmonary bypass was achieved using i.v. phenylephrine and/or nitroprusside as required. During cardiopulmonary bypass, hypothermia (3234° C) was induced and the patient was rewarmed when the last distal coronary anastomosis was being placed. Separation from cardiopulmonary bypass was accomplished when bladder and nasopharyngeal temperatures were both >36° C.
Aortic atheroma assessment
A comprehensive transoesophageal echocardiography examination was performed before cardiopulmonary bypass according to recommended guidelines.10 The ascending aorta was visualized by pulling up slightly on the transoesophageal echocardiography probe from a 120° mid-oesophageal view at the level of the aortic valve, to display the ascending aorta longitudinally. The descending aorta was visualized by withdrawing the transoesophageal echocardiography probe from the gastro-oesophageal junction until the left subclavian artery was seen. Withdrawing and rotating the transoesophageal echocardiography probe from the descending aorta visualized the longitudinal segment of the aortic arch. The entire transoesophageal echocardiography study was recorded on videotape for subsequent off-line analysis. The videotaped transoesophageal echocardiography examination of each segment of the aorta was reviewed frame by frame.
After the frame that displayed the most diseased area in each aortic segment (ascending, arch, descending) had been selected, the frame was digitized and analysed using image analysis software (NIH Image 1.6.2; National Institutes of Health, Bethesda, MD, USA). The area of the visualized aorta in the descending aorta was measured by estimating the angle () subtended by the vessel wall, and calculated as a portion of a circular or complete vessel (
r2
/360°) (Fig. 1).9 Atheroma burden in each segment was calculated as the percentage of the area of the visualized aorta containing atheroma (atheroma burden (% atheroma)=area of plaque/area of visualized aorta). Mobile or pedunculated lesions were measured in exactly the same manner. All measurements were made by consensus between two investigators accredited in transoesophageal echocardiography by the National Board of Echocardiography (LKT, GBM). These investigators were blinded to the TCD emboli information from the patients.
|
Statistics
The details of the patients are presented as mean (SD). Atheroma data and embolus counts are presented as median (interquartile range (IQR)). Emboli counts were log- transformed before analysis in order to produce a normally distributed variable. Multivariate linear regression, to control for potential confounding factors that may affect the number of emboli or the severity of aortic atheroma (including age, cardiopulmonary bypass time and numbers of bypass grafts), was used to compare the number of TCD-detected emboli with the percentage atheroma in each aortic segment. A P value <0.05 was considered significant.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Patients undergoing cardiopulmonary bypass experience considerable numbers of cerebral (as well as systemic) macroemboli (e.g. atherosclerotic debris or fat particles) or as many as thousands of microemboli (e.g. gaseous bubbles or other smaller particulate matter) during a typical cardiac surgical procedure. Convincing evidence for embolization of material to the brain during cardiopulmonary bypass procedures is based on investigations using retinal angiography, TCD techniques, histological examinations and magnetic resonance imaging.1113 The precise composition and the source of these emboli are not clear; however, it is likely that a combination of gaseous emboli and particulate matter can be detected by TCD equipment. Both particulate and gaseous emboli can cause distal obstruction of end-arterial flow in small cerebral arteries, resulting in cerebral ischaemia and neuronal failure. In addition, it has been shown that cerebral embolization can cause a local inflammatory response.14 These processes are probably responsible for some, if not all, of the functional deficits that can be detected in cardiac surgery patients. These data suggest that some of the cerebral emboli may indeed be derived from atheromatous disease in the thoracic aorta.
Numerous reports in the literature have described a strong association between the degree of aortic atherosclerosis and neurological injury in non-surgical populations.15 16 The severity of aortic atherosclerosis also has particularly important ramifications for the neurological outcome of patients undergoing cardiopulmonary bypass. Roach and colleagues1 reported that moderate to severe proximal aortic atherosclerosis was associated with an incidence of cerebral injury (focal injury, or stupor or coma at discharge) at least four times that seen in patients without significant plaques. Atherosclerosis of the aortic arch has also been correlated with an increased risk of stroke after cardiac surgery; the greater incidence of left-hemispheric (representing a destination for arch-generated emboli to move in the direction of blood flow to the downstream carotid vessel) strokes is indirect evidence of the importance of aortic arch atherosclerosis.17
The mechanism by which aortic atherosclerosis causes an adverse neurological outcome after cardiac surgery is believed to be cerebral embolization of atheromatous debris. This embolization occurs primarily as a result of aortic manipulation during palpation, cannulation, cross-clamping, proximal coronary anastomosis and decannulation, and possibly as a result of a sandblasting effect from the high-velocity jet exiting the aortic cannula.1820 The results of the present study further support the potential causal role of atheroma burden in the ascending aorta and the arch in the genesis of cerebral embolization and consequent neurological injury.
The location of the atheromas within the aorta and their relationship to the emboli that were detected is significant. Unlike the ascending aorta and aortic arch, the descending aorta showed no association of atheroma with TCD emboli counts. A possible explanation for this is that the descending atheroma seems an unlikely source for cerebral embolization, as antegrade flow from the ascending aortic cannula would cause any atheroma-generated emboli to flow distal to the aortic arch and to be undetectable in the middle cerebral artery. However, some studies have shown a relationship between descending aortic atherosclerosis and postoperative stroke,4 but it is likely that this association simply reflects a greater severity of ascending aortic or arch atherosclerosis in patients with high degrees of descending aortic disease.
There are several limitations to our study. The atheroma assessment technique we used, although potentially an improvement over previously published one-dimensional categorical measurement techniques, involves a two-dimensional image of a specific segment of the aorta. Ideally, a true reflection of atheroma burden should be based on a three-dimensional image of the entire length of a given aortic segment. When technological improvements permit routine three-dimensional ultrasound imaging, additional valuable data may be obtained. Given the current technological limitations of transoesophageal echocardiography imaging, the percentage atheroma method that we used does at least account for the total plaque area that can be visualized. Other methods assume that the area of the aorta that is not able to be imaged is not diseased. Furthermore, our assessment technique does not account for any plaques that contain mobile components, apart from including these mobile plaques in the area of the plaque itself with no special notation of mobility. Katz and colleagues7 showed that atheromatous disease with mobile components conferred a significant risk of perioperative stroke in a population of elderly cardiac surgical patients.
A further limitation relates to the ability of transoesophageal echocardiography to give an adequate image of the distal portion of the ascending aorta, which, because of the interposition of the trachea and the left main-stem bronchus between the aorta and the oesophagus, is difficult to image adequately with transoesophageal echocardiography.21 Epiaortic imaging is a more sensitive means of assessing plaque in the ascending aorta and it is likely that a greater degree of atherosclerosis might have been detected had epiaortic scanning been used. With respect to the TCD, we may have underestimated the total cerebral embolic load, as we were insonating only a single cerebral vessel (right middle cerebral artery). We make the assumption that the embolic load as measured in the right middle cerebral artery reflects the total cerebral embolic load. This could potentially lead to a somewhat inaccurate assessment of the association between emboli and atheromatous burden. Limitations also exist in the TCD technology that we used; it is unable to discriminate between gaseous emboli and particulate emboli (such as those originating from atheroma). The emboliatheroma relationship could potentially be better defined if the atheroma burden were compared only with the particulate emboli.
A final limitation relates to the fact that the significance of these findings must be considered in the context of their implications for neurological outcome. No neurological outcomes are available for these patients, yet a valuable piece of information would be to understand whether the relationship between cognitive outcome, for example, which is known to be related to cerebral emboli,5 12 could be made stronger by taking into account the atheroma burden of individual patients.
This finding of a relationship between aortic atheroma and cerebral emboli elucidates the likely mechanism behind the previously described relationship between TCD-detected emboli and cerebral outcome. These findings also complete an evidence gap, thereby closing the loop that relates atheroma to emboli, the relationship of which to major adverse cerebral outcomes after cardiac surgery has already been defined.
![]() |
Acknowledgements |
---|
![]() |
Appendix |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Behavioral medicine: M. A. Babyak, J. A. Blumenthal and K. A. Welsh-Bohmer.
Cardiology: D. B. Mark and M. H. Sketch,
Neurology: C. Graffagnino, D. T. Laskowitz, J. R. Lynch, A. M. Saunders and W. J. Strittmatter.
Pathology: E. Bennett.
Perfusion services: G. Smigla and I. Shearer.
Surgery: R. W. Anderson, T. A. DAmico, R. D. Davis, D. D. Glower, R. D. Harpole, J. Jaggers, R. H. Jones, K. Landolfo, J. E. Lowe, R. H. Messier, C. Milano, P. K. Smith, E. M. Toloza and W. G. Wolfe.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Blauth CI, Cosgrove DM, Webb BW, et al. Atheroembolism from the ascending aorta. An emerging problem in cardiac surgery. J Thorac Cardiovasc Surg 1992; 103: 110411[Abstract]
3 Wareing TH, Davila-Roman VG, Daily BB, et al. Strategy for the reduction of stroke incidence in cardiac surgical patients. Ann Thorac Surg 1993; 55: 14007[Abstract]
4 Hartman GS, Yao FS, Bruefach M 3rd, et al. Severity of aortic atheromatous disease diagnosed by transesophageal echocardiography predicts stroke and other outcomes associated with coronary artery surgery: a prospective study. Anesth Analg 1996; 83: 7018[Abstract]
5 Pugsley W, Klinger L, Paschalis C, Treasure T, Harrison M, Newman S. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 1994; 25: 13939[Abstract]
6 Barbut D, Lo YW, Hartman GS, et al. Aortic atheroma is related to outcome but not numbers of emboli during coronary bypass. Ann Thorac Surg 1997; 64: 4549
7 Katz ES, Tunick PA, Rusinek H, Ribakove G, Spencer FC, Kronzon I. Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography. J Am Coll Cardiol 1992; 20: 707[ISI][Medline]
8 Barbut D, Yao F, Hager D, Kavanaugh P, Trifiletti R, Gold J. Comparison of transcranial Doppler ultrasonography and transesophageal echocardiography to monitor emboli during coronary artery bypass surgery. Stroke 1996; 1: 8790
9 Ti LK, Mackensen GB, Grocott HP, et al. Apolipoprotein E4 increases aortic atheroma burden in cardiac surgical patients. J Thorac Cardiovasc Surg 2003; 125: 2113
10 Shanewise JS, Cheung AT, Aronson S, et al. ASE/SCA guidelines for performing a comprehensive intraoperative multiplane transesophageal echocardiography examination: recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography. Anesth Analg 1999; 89: 87084
11 Blauth C, Arnold J, Kohner EM, Taylor KM. Retinal microembolism during cardiopulmonary bypass demonstrated by fluorescein angiography. Lancet 1986; 2: 8379[ISI][Medline]
12 Stump D, Rogers A, Hammon J, Newman S. Cerebral emboli and cognitive outcome after cardiac surgery. J Cardiothorac Vasc Anesth 1996; 10: 1139[ISI][Medline]
13 Moody DM, Brown WR, Challa VR, Stump DA, Reboussin DM, Legault C. Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study. Ann Thorac Surg 1995; 59: 13047
14 Muth CM, Shank ES. Gas embolism. N Engl J Med 2000; 342: 47682
15 Mitusch R, Doherty C, Wucherpfennig H, et al. Vascular events during follow-up in patients with aortic arch atherosclerosis. Stroke 1997; 28: 369
16 Amarenco P, Cohen A, Hommel M, Moulin T, Leys D, Bousser M-G. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. N Engl J Med 1996; 334: 121621
17 Marschall K, Kanchuger M, Kessler K, et al. Superiority of transesophageal echocardiography in detecting aortic arch atheromatous disease: identification of patients at increased risk of stroke during cardiac surgery. J Cardiothorac Vasc Anesth 1994; 8: 513[Medline]
18 Barbut D, Hinton RB, Szatrowski TP, et al. Cerebral emboli detected during bypass surgery are associated with clamp removal. Stroke 1994; 25: 2398402[Abstract]
19 Reichenspurner H, Navia JA, Berry G, et al. Particulate emboli capture by an intra-aortic filter device during cardiac surgery. J Thorac Cardiovasc Surg 2000; 119: 23341
20 Stump DA, Rogers AT, Hammon JW. Neurobehavioral tests are monitoring tools used to improve cardiac surgery outcome. Ann Thorac Surg 1996; 61: 12956
21 Konstadt S, Reich D, Quintana C, Levy M. The ascending aorta: how much does transesophageal echocardiography see? Anesth Analg 1994; 78: 2404[Abstract]