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Ann Thorac Surg 1995;59:1187-1191
© 1995 The Society of Thoracic Surgeons

Cerebral Microemboli During Coronary Artery Bypass Using Different Cardioplegia Techniques

Andrew J. Baker, MD, Basem Naser, MBBS, Mark Benaroia, C. David Mazer, MD

Department of Anaesthesia, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada

Accepted for publication February 2, 1995.


    Abstract
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Larger numbers of microemboli detected by transcranial Doppler echocardiography have been linked to adverse neuropsychological outcome after coronary artery bypass grafting. Differences in neurologic outcome have been attributed to different cardioplegia techniques. Transcranial Doppler-detected microembolic events were recorded during coronary artery bypass grafting using different cardioplegia techniques. Patients received cold antegrade (n = 20), warm antegrade (n = 17), or warm retrograde (n = 20) cardioplegia. Continuous monitoring was divided into stages: aortic cannulation, initiation of cardiopulmonary bypass, aortic cross-clamping, aortic declamping and decannulation until chest closure. Rate of embolic events and number of total and immediate embolic events were tabulated. Total embolic events ranged from 22 to 2,072 per patient and were similar among groups. The rate and total at each stage were similar. Total embolic events were highest during aortic clamping; the rate was highest at initiation of bypass. The immediate embolic events were higher in the warm retrograde group than both antegrade groups at aortic declamping. In summary, a high total and rate of embolic events were detected and differences between cardioplegia techniques were detected.


    Introduction
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Despite improvements in cardiovascular surgery techniques over the years, the incidence of neurologic sequelae has not changed. Stroke rate after coronary artery bypass grafting (CABG) is reported between 1% and 5% [15]. However, neurophysiological dysfunction has been identified in up to 80% of patients [68]. Mechanisms of neurologic injury during CABG need to be studied further and advances in CABG should be evaluated, at least in part, with respect to their impact on neurologic sequelae. Microemboli have been implicated in the etiology of neuropsychological deficits after CABG. Multiple types of microemboli have been associated with cardiopulmonary bypass (CPB) including fat [9, 10], calcific and atheromatous debris [1013], thromboembolic debris (platelet aggregates and fibrin meshwork) [14], and gas. The importance of microemboli observed via transcranial Doppler echography (TCD) studies is shown by the association of higher number of TCD-detected microembolic events linked to worse neuropsychological deficits after CABG [15, 16].

There is controversy regarding cardioplegia technique and its relationship to neurologic deficits. Continuous warm retrograde cardioplegia and normothermic systemic perfusion has been reported [17] to have a significantly higher incidence of total neurologic events and acute perioperative cerebrovascular accidents than the hypothermic intermittent cold antegrade cardioplegia. It is suggested that the neurologic deficits may be due to particulate and gaseous microemboli. In contrast, other investigators [1820] have found no differences in stroke rate or postoperative neuropsychological test scores in patients receiving either warm antegrade or cold antegrade cardioplegia combined with normothermic systemic perfusion. Because there is an association between number of emboli and neuropsychological deficits and because there is a difference in neurologic outcome attributed to different cardioplegia techniques, this study was undertaken to determine the frequency and timing of TCD-detected microembolic events in the middle cerebral artery during CABG using different cardioplegia techniques.


    Material and Methods
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Fifty-seven patients scheduled for elective CABG who were free of neurologic dysfunction or peripheral vascular disease were included in the study. Patients who had other concurrent cardiac operations or who were in cardiogenic shock were excluded. Three different cardioplegia techniques were employed: cold antegrade (n = 20), warm antegrade (n = 17), and warm retrograde (n = 20).

The cardioplegia solution was composed of oxygenated blood and crystalloid (4:1 blood:Fremes' solution). High-potassium blood cardioplegia was administered into the aortic root at 200 to 300 mL/min to achieve antegrade cardiac arrest. The temperature of cardioplegia was 37°C in the warm group and 5° to 8°C in the cold group. Warm cardioplegia was given continuously in the retrograde group and intermittently (<10 minutes of interruption) in the antegrade group. In the cold antegrade group, intermittent infusions of cardioplegia were given every 15 to 20 minutes after completion of each distal anastomosis. No filter was used in the cardioplegic delivery system. After initiation of continuous warm blood cardioplegia, the aorta was vented via the cardioplegic needle in the ascending aorta by applying gentle (10 cm H2O) suction. This was a totally closed system.

The body temperature for cardioplegia groups was kept at approximately 36.5° to 37.0°C, and mild hypothermia of 32°C was achieved in 10 patients in the cold antegrade group. Target hematocrits during CPB were 20% to 25%. All extracorporeal circuits included a membrane oxygenator, an inline arterial filter (44 µm), and a priming stage where lactated Ringer's solution was used while closed circuit flushing took place for 15 minutes before the air trap filter was removed.

All patients received similar anesthesia management: moderate dose fentanyl supplemented with benzodiazepines, inhalation agents, or both. Nitrous oxide was not used in any patient. During CPB systemic flows were 2.2 to 2.5 L • m-2 min-1, and mean arterial pressure was kept between 50 and 90 mm Hg using either phenylephrine or isofluorane as necessary. Blood sugar was monitored every 30 minutes, and if it exceeded 20 mmol/L insulin was given. Before aortic cannulation the systolic blood pressure was between 90 and 110 mm Hg. The aortic cross-clamp was applied gently. At the time of cross-clamp release the pump flow was not decreased; however, the cross-clamp was removed slowly.

The right middle cerebral artery (MCA) was monitored for evidence of cerebral microembolization using TCD (Cerebral Diagnostic System; Medasonics, Freemont, CA). When this was not possible the left MCA was used. A low profile 2-MHz pulsed wave TCD probe was placed on the posterior or anterior middle transtemporal window just above the zygomatic arch. The MCA was identified by locating the bifurcation between the anterior and middle cerebral artery (bidirectional flow) and decreasing the Doppler focal point until only forward blood flow of good quality was identified. In situations where the bifurcation could not be located, identification of the MCA was confirmed using probe position by increasing or decreasing the focal point to determine whether the MCA was identified throughout a range of depths. The MCA was located at a depth of 41 to 64 mm, the probe was fixed using waterproof adhesive tape, and the ultrasound power was kept to a minimal level to give a clear blood velocity tracing. Microembolic events were counted prospectively by a trained observer who remained in the operating room throughout the surgical procedure. Microembolic events were identified on line by their characteristic sound (chirps and whistles), and behavior [21]; care was taken to eliminate artifact. Doppler signals and TCD processing were recorded on S-VHS tapes for storage.

For comparison, the data collection was divided into the following stages: aortic cannulation, initiation of cardiopulmonary bypass, aortic cross-clamping, aortic declamping, and aortic decannulation. For each stage, three variables were measured or calculated: the number of immediate embolic events (embolic events within 60 seconds of the onset of a stage), total embolic events, and rate of embolic events. The total embolic load-total number of embolic events detected throughout the whole procedure-also was tabulated for each patient.

Data were analysed using a two-way analysis of variance with post hoc test (Tukey's test), or a Student's t test when applicable. A p value less than 0.05 is considered statistically significant. Values are reported as mean ± standard error of the mean.


    Results
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
There was no demographic difference between patients in the cardioplegia groups (Table 1Go). The total embolic load for all patients ranged from 22 to 2,072, with a mean of 326 ± 47 (for distribution see Table 2Go). The total embolic load was similar in the three cardioplegia groups. There were no differences in total embolic events or rate of events between cardioplegia groups at the various stages. Total events was highest at the aortic cross-clamping stage (p < 0.00001) for all patients (Fig 1Go), and rate of events was highest at the initiation of CPB stage (p < 0.005) for all patients (see Fig 2Go). The number of immediate events was significantly higher in the warm retrograde group than the cold antegrade (p < 0.01) and warm antegrade (p < 0.001) groups (Fig 3Go).


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Table 1. . Patient Demographics
 

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Table 2. . Distribution of Embolic Events Among 57 Patients
 


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Fig 1. . Total embolic events as detected by transcranial Doppler echography at each stage of operation: aortic cannulation (ACann), initiation of cardiopulmonary bypass (iCPB), application of cross-clamp (X on), removal of cross-clamp (X off), and aortic decannulation (ADecann).

 


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Fig 2. . Rate of embolic events as detected by transcranial Doppler echography at each stage of operation: aortic cannulation (ACann), initiation of cardiopulmonary bypass (iCPB), application of cross-clamp (X on), removal of cross-clamp (X off), and aortic decannulation (ADecann).

 


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Fig 3. . Number of embolic events as detected by transcranial Doppler echography during the cross-clamp removal stage in each of the three cardioplegia groups: cold antegrade (CA), warm antegrade (WA), and warm retrograde (WR).

 
Major neurologic complications (cerebrovascular accident) developed in 2 patients, 1 patient each from the cold antegrade and warm retrograde groups. Their total number of detected microembolic events were 371 and 934, respectively. These 2 patients suffered prolonged hypotension and required inotropic support, and 1 required an intraaortic balloon pump.


    Comment
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
A high number of TCD-detected embolic events during CABG is documented in this study. A mean total embolic load of 326 ± 47 was observed in 57 patients. Higher total numbers of embolic events as detected by TCD have been associated with increased neuropsychological deficits after CABG [15, 16]. Thus methods to identify the sources of such emboli have been employed with a view to their minimization and improvement of neuropsychological outcome. Stump and associates [15] reported a mean embolic load of 114 in 54 patients, a somewhat smaller number than our study; however, Pugsley and colleagues [16] reported high-intensity transcranial signals among 94 patients that were similar in number and distribution to our study. Pugsley and colleagues' series included nonfiltered CPB circuits, however, which would tend to increase their numbers. Although our reported rate of embolic events is similar to other reports, it may be higher because of the method of detection and definition of embolic events. We used a trained observer to monitor continuously the audio and processed visual TCD signal and identify embolic events. Others have detected emboli by automated analysis of wave form velocities and setting threshold velocities over which an embolic event is counted [15, 16, 2224]. We were able to identify embolic events that fell within the velocity spectrum and thus would have been missed by the automated methods.

Different sensitivity also may arise from different technology or Doppler echographic settings. Presumably the lower limit of sensitivity could be pushed so low with ``improved'' technology as to make the detection of smaller and smaller emboli possible but likely not meaningful. The objectives of our study were to compare embolic load between different stages of CABG and different cardioplegia techniques using a consistent detection technique and sensitivity. Thus although sensitivities may vary depending on technique, definition, or technology, the use of one consistent method to make comparisons is valid.

Different types of microemboli have been described during CPB and include fat, particulate, and gas. Although methods are being developed to distinguish between types of emboli using TCD [25, 26], there remains uncertainty. We did not attempt to make that distinction in our study. Comparisons of bubble to membrane oxygenators also imply that many of the emboli detected are gas [27, 28]. There may be different neurologic implications of various types of microemboli or a threshold volume for neurologic impact [25, 28].

In this study the finding that embolic events were detected during aortic cannulation implies either the entrainment of air at the site or more likely the dislodgement of atheromatous material. These effects were obviously independent of the CPB machine. Techniques for site selection of aortic cannulation were not used or evaluated in this study. The use of TCD may be helpful in evaluating the efficacy of such techniques.

Initiation of CPB resulted in the highest rate of embolic events and a large total number of embolic events. At the initiation of CPB sources of emboli may include the effect of mixing warm blood with cooler prime on removing gas from dissolved phase [23]. As well, there may be the effect of turbulent and jet streams within the aorta generated from flow through the cannula causing release of atheromatous material. Additionally, the CPB circuit may have been a source of gas emboli or platelet/fibrin aggregates. These effects persisted beyond the initiation phase into and throughout the cross-clamping period. The relatively high number detected during CPB during aortic cross-clamping was unexpected. Linden and Casimir-Ahn [24] described this phase as relatively quiescent for TCD-detected microemboli. Arterial filters (44 µm), membrane oxygenators, and prime precirculation for deairing were employed for all patients in this study.

Although the rate was highest at the onset of CPB, the total number was highest during the aortic cross-clamped stage because it was so much longer. The implication is that a significant source of microembolic events detected by TCD in this study originated from CPB circulation. The effect of CPB was greater than cannulation and decannulation, or deairing problems common in open heart procedures. Thus although we are unable to evaluate the relative impact of emboli occurring during the different stages, potentially of different quality (solid versus gas), efforts to isolate sources of emboli during aortic cross-clamped CPB circulation would be most productive numerically in reducing total embolic load. Pugsley and associates [29] described the high-risk period for microemboli as ``aortic cannulation, inception of bypass and nonfiltered bypass, the latter being by far the most significant.'' In this study filtered bypass was the high-risk period.

For the purpose of comparing the difference between cardioplegia groups the period of aortic declamping was analyzed. Although Linden and Casimir-Ahn [24] found this period, and in particular weaning from CPB, to generate the highest number of emboli, that study examined open heart procedures where inadequate deairing would be expected to be the source of emboli. We hypothesized that the use of different cardioplegia techniques may result in different numbers of microembolic events detected immediately after aortic declamping. Specifically, the patients were divided into three groups: those receiving cold antegrade, warm antegrade, and warm retrograde cardioplegia. No differing effect would be expected at cannulation, initiation, or cross-clamped stages. It was found that there were higher numbers of embolic events detected immediately upon aortic declamping in the warm retrograde group compared with either the warm or cold antegrade group. Retrograde flow through diseased coronary arteries may have resulted in the deposit of atheromatous material (or air) in the proximal aorta, which was released (both down the coronary arteries or up the aorta) when the aorta was declamped. Antegrade flow, however, would result in the deposit of all such material in the capillary bed of the myocardium before aortic declamping. No difference was detected in the total embolic event count for the entire aortic declamping period between cardioplegia groups or in the total embolic load for all stages combined. The difference between groups for the immediate minute after cross-clamp removal was small compared with the total numbers detected. However, no distinction was made in this study regarding the quality of emboli. Although many of the embolic events detected in this study may represent gas emboli, which may be of little significance [28], the increased but small number of embolic events after cross-clamp removal in the retrograde group may represent more detrimental solid emboli. Thus the implications of this finding on neurologic sequelae (and, by inference, myocardial sequelae) may be important.

Recent studies have addressed the impact of cardioplegia technique on neurologic outcome comparing warm antegrade with cold antegrade cardioplegia. There were no differences detected in the neuropsychologic deficit [19, 20] or stroke rate [18] between groups. Another study compared cold antegrade with warm retrograde cardioplegia and reported a similar incidence of myocardial infarctions but a higher neurologic event rate in the retrograde group [17]. These data are consistent with the notion that important emboli from diseased coronary arteries may cause myocardial or neurologic injury depending on the direction of flow of cardioplegia. They are consistent with the finding in this study of a greater number of embolic events detected in the MCA immediately after aortic declamping after retrograde cardioplegia.

In summary, we herein report a high number of microembolic events that were detected in the MCA using TCD during CABG. Microembolic events were detected throughout the procedure, but the greatest rate was at the initiation of CPB and the highest number were detected during the aortic cross-clamped period. A greater number of microembolic events were detected immediately after the release of the aortic cross-clamp in patients receiving warm retrograde cardioplegia than in those receiving warm and cold antegrade cardioplegia.


    Acknowledgments
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
We acknowledge Dr Tomas A. Salerno for his help in reviewing the manuscript.


    Footnotes
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Address reprint requests to Dr Baker, Department of Anaesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.


    References
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

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