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Eur J Cardiothorac Surg 2001;20:1163-1167
© 2001 Elsevier Science NL

Cerebral embolisation during modern cardiopulmonary bypass

S.J. Fearn, R. Pole, M. Burgess, S.G. Ray, T.L. Hooper, C.N. McCollum

University Hospital of South Manchester, West Didsbury, Manchester M20 2LR, UK

Received 31 March 2001; received in revised form 21 August 2001; accepted 31 August 2001.

Corresponding author. Tel.: +44-161-291-3840; fax: +44-161-291-3946
e-mail: cnmcc{at}fs1.with.man.ac.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Objectives: Cerebral microembolisation still occurs during cardiopulmonary bypass and may cause both stroke and postoperative cognitive impairment. We investigated the frequency of cerebral embolisation during coronary artery bypass surgery with modern cardiopulmonary bypass and related these to ascending aortic atherosclerosis. Methods: Transcranial Doppler monitoring for cerebral embolisation to both middle cerebral arteries was performed in 65 patients undergoing coronary artery surgery with non-pulsatile alpha-stat hypothermic bypass. Epicardial ultrasound imaging of ascending aortic atherosclerosis was performed in 14 patients. Results: Thirty patients (56.9%) had more than 200 emboli entering the middle cerebral artery territories during surgery; most at the start of bypass and during defibrillation. Readjustment of aortic clamps and aortic cannulation also caused a large number of emboli which were probably particulate. Aortic disease was mild (mean plaque thickness 1 mm, interquartile range 0.9–1.2 mm) and did not relate to the number of cerebral emboli produced by aortic manipulation. Conclusions: Cerebral embolisation remains common during coronary surgery despite advances in filter and bypass pump technology. Aortic manipulation and clamping was associated with emboli but epicardial ultrasound imaging was of little help in its prediction.

Key Words: Embolisation • Cardiopulmonary bypass • Epicardial aortic scanning


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Cerebral embolisation has been widely recognised during cardiac surgery and is associated with postoperative cognitive deficits and prolonged hospital stays [1,2]. Advances in bypass technology and the use of 40 micron arterial filtration and membrane oxygenation are believed to have reduced the number of emboli [2–4]. The ascending aorta remains an important source of emboli that may be displaced during the application and removal of aortic clamps [5–7].

We investigated the frequency of cerebral embolisation at different stages during modern cardiopulmonary bypass in patients undergoing coronary artery bypass graft surgery (CABG), using transcranial Doppler (TCD) to insonate both middle cerebral arteries. The severity of ascending aortic atherosclerosis was assessed in a sample of the patients using epicardial ultrasound imaging; the method of choice for investigating the severity of aortic arch atherosclerosis [8].


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
Sixty five consecutive patients admitted for CABG underwent intraoperative TCD monitoring of both middle cerebral arteries throughout surgery. Ethical committee approval and informed consent were obtained in writing.

Anaesthesia and bypass were standardised utilising alpha-stat management, non-pulsatile perfusion, membrane oxygenation, 40 µm arterial filtration, and hypothermia to 32°C. The bypass circuit was primed with a standardised crystalloid-colloid prime at 37°C and circulated at a flow of five litres per minute for a minimum of 15 min through a 0.2 micron screen filter (Pall Biomedical). During priming all connectors were manipulated to remove bubbles from the circuit. Priming volume was 2000 ml to maintain a high enough level in the venous reservoir to prevent vortexing at the outlet. This volume was reduced to 1500 ml after priming.

CABG was carried out by two surgeons using the same surgical techniques; proximal graft anastomoses were fashioned using an aortic side-clamp. An aortic root vent was used for de-airing throughout cardiopulmonary bypass and defibrillation.

Two 2 MHz transcranial Doppler probes were applied to insonate both middle cerebral arteries through the temporal windows and held in place by a headband (Neuroguard CDS, USA). High intensity transient signals were distinguished from artefact because they fulfilled the criteria for emboli defined by the International Consensus Group on Microembolus Detection [9]:

  1. The strength of the embolic signal was higher than the Doppler signal and background noise.
  2. Embolic signals appeared only in one direction because they were travelling in the blood stream.
  3. The time duration of an embolic signal was short compared to the normal Doppler signal.

TCD is not currently able to differentiate particulate signals from gaseous signals although research has suggested that signals limited to the Doppler waveform produced in control conditions in models, are more likely to be particulate whereas gaseous signals tend to extend beyond the Doppler waveform [10,11].

Embolic signals were recorded manually by a trained observer throughout surgery and related to the following operative events:

  1. Placement of aortic purse-string sutures.
  2. Aortic cannulation for bypass.
  3. Aortic cannulation by cardioplegia delivery system.
  4. Application, adjustment and removal of aortic cross- and side-clamps.
  5. Start and end of bypass.
  6. Manipulation of heart at any point during surgery.
  7. Defibrillation.

In a sample of patients, the aortic root was imaged prior to cannulation, using echocardiography with a 7.5 MHz ultrasound probe (HP 2500 Sonos Echo, Massachusetts, USA). The ascending aorta (aortic valve to innominate artery) was divided into three equal segments; proximal, mid and distal. Transverse and longitudinal views of each of the three segments were obtained by placing the probe into a sterile sheath for direct application to the exposed aorta. Ultrasound gel (Kitecko, 3M, France) was used within the sterile sheath between the probe and aorta to enable adequate resolution of the anterior aortic wall. A video recording of each image was made so that aortic root atherosclerosis could be measured later by two blinded sonographers as follows:

Each transverse view was divided into quadrants; posterior, anterior, right lateral and left lateral and scored according to criteria described by Wareing et al. [12]:

Each quadrant was assessed for:

  1. Intimal thickness. This was measured in two places per quadrant and a mean taken. A further mean was calculated from all four quadrants for each level.
  2. Presence of confluent calcification.
  3. Presence of ulceration.
  4. Presence of thrombus.

Variability of intimal thickness was calculated using the overall means for each level of the aortic root; those patients whose intimal thickness did not vary more than 0.04 mm from the proximal to the distal segment were graded 1 and those with more variation were graded 2.

The number of embolic signals on TCD in those patients with calcification was compared to the number in those without.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Patients
One patient was excluded from this analysis as he underwent simultaneous carotid endarterectomy and CABG. The mean age was 60 years (range 43–77) and 53 (81.5%) were men (Table 1). Two patients had redo surgery for recurrent vein graft or coronary disease.


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  		Table 1. Patients

 
3.2. Surgery and bypass
The mean number of grafts performed was 3.2 (range 1–7) and in 51 patients (78.5%) the internal mammary artery was used as a graft. The median duration of CPB was 73 min (58–93 IQR) and cross-clamp time was 43 min (33.5–56 IQR). The ideal flow during bypass was calculated using a height/weight nomogram to calculate the patient's surface area, and maintained at 2.4 l/min/m2 throughout surgery.

3.3. Intraoperative embolisation
Emboli detected in each middle cerebral artery were counted manually from the TCD screen (Table 2). Thirty patients (56.9%) had more than 200 emboli entering both middle cerebral arteries. Most embolic signals occurred at the time bypass was started and may well have been microbubbles of air. A second flush of emboli occurred when the heart was defibrillated at the end of bypass.


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  		Table 2. The number of emboli produced by operative event, median (IQR) for all CABG patientsa

 
Although current TCD technology cannot distinguish particulate from gaseous emboli reliably, we can assume that most of those signals occurring during placement of aortic purse-strings, aortic cannulation, cardioplegia cannulation, application, adjustment and removal of aortic cross- and side- clamps and defibrillation are more likely to be particulate in nature because plaque can be dislodged from the aortic wall or microthrombi from the ventricles on defibrillation. Most particulate emboli signals were produced after defibrillation, but readjustment of aortic clamps and aortic cannulation also produced substantial numbers. Thirty-nine (60%) patients had more than 50 emboli thought to be particulate entering their middle cerebral circulation.

Eighteen had showers of emboli which may have been underestimated by manual counting from the TCD screen. These showers occurred in relation to events described in Table 3.


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  		Table 3. Embolic showers

 
3.4. Aortic root disease
Epicardial scanning of the aortic root was performed in a sample of 14 patients (21.5%). Median intimal thickness of the aortic root is shown in Table 4 and all aortas were graded mild according to Wareing [12].


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  		Table 4. Measurement of aortic plaque using epicardial ultrasound

 
The patients that were imaged had surprisingly little aortic disease with median plaque thickness less than 2 mm at all aortic levels and no ulceration or thrombus. Calcification was present in eight patients and this was almost evenly distributed from proximal to distal involving the proximal root in three patients, mid in four and distal root in four patients. No thrombus or ulceration was seen.

The number of emboli produced on aortic manipulation in these patients was highly variable considering the lack of severe aortic atherosclerosis and the similarity of aortic disease between patients: median number of emboli to the right middle cerebral artery was 18 (IQR 4–55), and 36 (IQR 6–55) to the left side. There was no correlation between intimal thickness or presence of calcification and the number of emboli produced on aortic manipulation. Neither did those patients with intimal thickness which varied throughout the length of the aortic root produce significantly more emboli than those in whom intimal thickness was relatively constant; within 0.04 cm throughout the aortic root. As this approach was not proving productive, aortic root imaging was then abandoned.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
Our data suggest that emboli are still common during modern cardiopulmonary bypass despite 40 micron arterial filtration and membrane oxygenation. A comparison with the frequency of embolisation in other studies is meaningless as emboli characteristics are not standardised between monitoring systems. The Consensus on microembolus detection by TCD has been a major step towards standardisation [9].

Current TCD technology cannot distinguish particulate from gaseous embolic signals, however, embolic signals limited to the Doppler spectrum are more likely to be particulate whereas those signals extending beyond the spectrum are more likely to be gaseous [10,11]. We could not record TCD data for off-line analysis in this study although this would have been useful to compare subsequently with the operative event producing the signals. However, it is reasonable to assume that emboli appearing in the cerebral circulation after aortic cannulation, cardioplegia cannulation, application, adjustment and removal of aortic clamps were more likely to be particulate rather than gaseous and possibly originated from atherosclerotic disease in the aorta.

Whilst we cannot assume that all the other embolic signals were gaseous, it is interesting to examine those that are probably particulate as these are generally regarded as more harmful. Aortic cannulation and clamp readjustments produced substantial numbers of emboli but more were produced after defibrillation with restoration of cardiac output and pulsatile flow. Thrombi may form within the heart, most commonly the left atrial appendage, ischaemic endocardium or left ventricular aneurysm, or within the bypass circuit if anticoagulation is inadequate, and are associated with an increased risk of perioperative neurological deficit during CABG. The main source of cholesterol embolism is probably from manipulation and clamping of large atherosclerotic vessels although denaturation of proteins during bypass may precipitate plasma lipids [13].

Contact activation of platelets by foreign surfaces such as bypass circuit tubing is well documented and may be stimulated by heparin in low flow states [14]. Furthermore, there is evidence to suggest that emboli are produced downstream of blood filters [15]. Platelets contain vasoactive substances that may stimulate further blood cell aggregation and cause endothelial cell injury.

Ultrasound studies on the aortic arch were easy to perform but were only carried out in a proportion of our patients as the severity of aortic disease was uniformly mild in these patients and did not relate significantly to cerebral emboli on aortic root manipulation. There was a clear relationship in post-mortem studies [16,17] but it is difficult to be confident that emboli detected in such studies did not occur prior to or following bypass. It is also possible that epicardial ultrasound was inaccurate or insensitive to the severity of atherosclerosis in the ascending aorta despite the encouraging results published by Barbut et al. [8]. Although more accurate than palpation alone, epicardial scanning needs refining if it is to be useful in the siting of aortic cannulation and clamping.

Embolic showers occurred in 29% of patients saturating the TCD display and total numbers were therefore underestimated. Whilst many of these were likely to have been particulate during aortic cannulation and defibrillation, microbubbles would have been more likely during flushing and filling of vein grafts, air leaks around the venous cannula and injection of drugs into the cardiopulmonary bypass circuit. Despite evidence that they may cause vascular obstruction, stasis, endothelial damage, complement and white cell activation, platelet adhesion and impaired nitric oxide production - all of which may reduce cerebral blood flow during bypass – microbubble emboli do not appear to result in neurological morbidity [18–20]. There is no evidence that gaseous microemboli influence the integrity of the blood-brain barrier, nor do they affect either global or regional brain perfusion or cerebral oxygen metabolism [21].

TCD instruments are very much more sensitive to microbubbles than particulate emboli. Only particles greater than 200 microns can be reliably detected and yet were regularly counted despite the 40 micron arterial line filter. Smaller particulate emboli, still large enough to occlude arterioles and capillaries, may not be detected and the total number of emboli would certainly be many times greater than that we counted. Smaller solid emboli would also cause more damage to the cerebral microcirculation than microbubbles which can be detected below 80 microns.

Cerebral embolisation remains a problem during modern cardiopulmonary bypass despite advances in filtration and bypass pump technology. These emboli were associated with cognitive deficits, particularly memory loss [22]. Aortic imaging with epicardial ultrasound was insensitive to the mild atherosclerosis which remains capable of causing showers of emboli. Perhaps of greater concern was the release of emboli during defibrillation – should we be filling the cardiac chambers with an anticoagulant solution to avoid thrombus formation during cardioplegia? Alternative approaches may be to investigate the value of ultrasonic de-airing of bypass circuits and the left ventricle as well as the role of platelet inhibitory therapy such as prostacyclin infusion.


   Acknowledgments
 
We would like to thank the British Heart Foundation for awarding SJF a research fellowship and Neuroguard CDS for their support. Dr M Patrick, Dr D Greenhalgh anaesthetised these patients and assisted data collection. Mr J Corder and his team of perfusionists were an immense help.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

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  3. Padayachee T.S., Parsons S., Theobol R., Lindley J., Gosling R.G., Deverall P.B. The detection of microemboli in the middle cerebral artery during cardiopulmonary bypass: a transcranial Doppler ultrasound investigation using membrane and bubble oxygenators. Ann Thorac Surg 1987;44:298-302.[Abstract]
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  5. Hosoda Y., Watanabe M., Hirooka Y., Ohse Y., Tanaka A., Watanabe T. Significance of atherosclerotic changes of the ascending aorta during coronary bypass surgery with intraoperative detection by echography. J Cardiovasc Surg 1991;32:301-306.[Medline]
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  7. Barbut D., Gold J.P. Aortic atheromatosis and risks of cerebral embolisation. J Cardiothorac Vasc Anaesth 1996;10:24-30.[Medline]
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  9. Ringelstein E.B., Droste D.W., Babikian V.L., Evans D.H., Grosset D.G., Kaps M., Markus H.S., Russell D., Siebler M. Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection. Stroke 1998;29:725-729.[Abstract/Free Full Text]
  10. Wareing T.H., Davila-Roman V.G., Barzilai B., Murphy S.F., Kouchoukos N.T. Management of the severely atherosclerotic ascending aorta during cardiac operations, a strategy for detection and treatment. J Thorac Cardiovasc Surg 1992;103:453-462.[Abstract]
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