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Emboli and renal dysfunction in CABG patients

      IN THIS ISSUE, Sreeram et al
      • Sreeram G.M.
      • Grocott H.P.
      • White W.D.
      • et al.
      Transcranial Doppler emboli count predicts rise in creatinine following coronary artery bypass graft surgery.
      describe an association between ultrasonically detected cerebral microemboli and evidence of renal dysfunction in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Previous studies have established the presence of microemboli and implicated them in cognitive decline and other manifestations of brain injury accompanying surgery involving CPB. Brown et al
      • Brown W.R.
      • Moody D.M.
      • Challa V.
      • et al.
      Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli.
      identified the presence of thousands of microemboli in postmortem brain tissue obtained from patients dying after CPB. Their appearance was dependent on the use of CPB, and their number was directly related to CPB duration. For CABG surgery, the emboli number was seen to double with each successive hour of CPB. Barbut et al
      • Barbut D.
      • Yao F.S.
      • Hager D.N.
      • et al.
      Comparison of transcranial Doppler ultrasonography and transesophageal echocardiography to monitor emboli during coronary artery bypass surgery.
      showed good concordance between the number of echogenic particles imaged with transesophageal echocardiography and those detected with transcranial Doppler (TCD) ultrasound. More recently, Harringer
      • Harringer W.
      International council of emboli management study group
      Capture of particulate emboli during cardiac procedures in which aortic cross-clamp is used.
      directly visualized embolic material trapped by a filter basket placed around the arterial cannula tip; of 243 filters examined, more than half contained fibrous atheroma, platelet aggregates, or fibrin strands, while nearly one quarter contained thrombus. Stump et al
      • Stump D.A.
      • Rogers A.T.
      • Hammon J.W.
      • et al.
      Cerebral emboli and cognitive outcome after cardiac surgery.
      showed an association between ultrasonically detected emboliform signals and neurocognitive decline, whereas Schmitz et al
      • Schmitz C.
      • Weinreich S.
      • White J.
      • et al.
      Can particulate extraction from the ascending aorta reduce neurologic injury in cardiac surgery?.
      showed that intra-aortic filtering resulted in a significantly lower incidence (4.3% v unfiltered 11.9%, p < 0.001) of adverse neurologic events (ie, transient ischemic attack, stroke, delirium, coma, or new memory deficit). Because both the presence of microemboli during CPB and their capacity for organ injury are now apparent, the proposed emboli-renal dysfunction link is a reasonable extension of current knowledge.
      The present study is important, in part, because it broadens perspective on the potential clinical consequences of microembolization. The presence, severity, and socioeconomic costs of cognitive decline and subtle neurologic injury are difficult to quantify. As a result, there appears to be an underappreciation of their impact on health care delivery. However, renal injury is a different story. Sreeram et al
      • Sreeram G.M.
      • Grocott H.P.
      • White W.D.
      • et al.
      Transcranial Doppler emboli count predicts rise in creatinine following coronary artery bypass graft surgery.
      succinctly summarize the widely recognized major influence that renal injury has on the cost of care and hospital profitability. Thus, should the emboli-renal injury link be definitively established, there are clear and powerful economic incentives for its correction.
      Sreeram et al
      • Sreeram G.M.
      • Grocott H.P.
      • White W.D.
      • et al.
      Transcranial Doppler emboli count predicts rise in creatinine following coronary artery bypass graft surgery.
      used TCD ultrasound to quantify cerebral microemboli. Because this technology has not yet become commonplace in cardiac surgery, its application in this study deserves comment. The investigators relied on a pulse-wave single-gate spectral Doppler ultrasonograph to detect and quantify emboli. Devices of this design measure ultrasonic echoes arising from a single intracranial locus. Fourier spectral analysis, like that used with a quantitative electroencephalogram, maps the family of Doppler-shifted echoes as a function of time. Signal intensity at each frequency shift-time intersection is used to identify emboli. Both gaseous and particulate emboli are more sound reflective than erythrocytes and produce echoes of higher intensity.
      Most TCD devices designed for intraoperative monitoring automatically detect and count high-intensity transients as emboli. Such transients also may arise from nonembolic sources such as electrocautery and acoustic artifacts. Therefore, reliable quantification of true microembolic signals (MES) with single-gate spectral TCD requires visual and acoustic confirmation of their embolic ultrasonic signature using established criteria.
      • Ringelstein E.G.
      • Droste D.W.
      • Babikian V.L.
      • et al.
      Consensus on microembolus detection by TCD.
      To assure that their MES counts were of uniformly high quality, one of the investigators experienced in TCD measurement and blinded to the renal injury data made these tedious but necessary measurements for each patient.
      Despite the care used by the investigators during MES quantification, there is reason to suspect that the actual number of emboli may have been even larger. Recent innovations in TCD technology now permit simultaneous measurement at several loci along the vessel axis with multigate spectral
      • Devuyst G.
      • Darbellay G.A.
      • Vesin J.-M.
      • et al.
      Automatic classification of HITS into artifacts or solid or gaseous emboli by a wavelet representation combined with dual-gate TCD.
      or power M-mode Doppler (PMD).
      • Moehring M.A.
      • Spencer M.P.
      Power M-mode Doppler (PMD) for observing cerebral blood flow and tracking emboli.
      For example, Saqqur et al
      • Saqqur M.
      • Dean N.
      • Schebel M.
      • et al.
      Improved detection of microbubble signals using power M-mode Doppler.
      recently showed that MES counts obtained with PMD technology were double those seen with the single-gate spectral TCD approach used by Sreeram et al.
      • Sreeram G.M.
      • Grocott H.P.
      • White W.D.
      • et al.
      Transcranial Doppler emboli count predicts rise in creatinine following coronary artery bypass graft surgery.
      Presumably, the higher counts reflected PMD capacity to simultaneously detect MES along the entire linear portion of the middle and adjacent anterior cerebral arteries.
      Retrospective analysis cannot prove cause and effect because of the possibility of unrecognized sources of bias. Nevertheless, Sreeram et al
      • Sreeram G.M.
      • Grocott H.P.
      • White W.D.
      • et al.
      Transcranial Doppler emboli count predicts rise in creatinine following coronary artery bypass graft surgery.
      attempted to limit bias through the use of multivariate statistical techniques, which removed the influence of many potentially confounding covariates. Furthermore, they used nonparametric statistics appropriate for the non-Gaussian distributions of aggregate MES and postoperative creatinine change. Thus, their results provide a sound justification for the initiation of carefully designed prospective studies to determine the clinical and economic impact of embolization resulting from extracorporeal circulation.
      Of course, if emboli were an unavoidable consequence of CPB, this knowledge would be of little practical use. Fortunately, growing evidence suggests that embolization is a multifactorial process that is subject to modification. The following is a partial list of these correctable sources:
      • 1.
        Atheromatous emboli may be dislodged from the aorta during its instrumentation and manipulation. Ultrasonic epiaortic echocardiography can quickly identify optimal sites for cannulation and clamping as well as those patients in whom a “no-touch” surgical technique may be indicated.
        • Katz E.S.
        • Tunick P.A.
        • Rusinek H.
        • et al.
        Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass Experience with intraoperative transesophageal echocardiography.
        Use of this approach has been associated with a reduction in stroke incidence.
        • Borger M.A.
        • Taylor R.L.
        • Weisel R.D.
        • et al.
        Decreased cerebral emboli during distal aortic arch cannulation A randomized clinical trial.
        TCD has also been used to identify the optimal aortic cannulation site with similar results.
        • Katz E.S.
        • Tunick P.A.
        • Rusinek H.
        • et al.
        Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass Experience with intraoperative transesophageal echocardiography.
        ,
        • Mullges W.
        • Franke D.
        • Reents W.
        • et al.
        Brain microembolic counts during extracorporeal circulation depend on aortic cannula position.
      • 2.
        The aggregate MES detectable by TCD may be heavily influenced by the specific performance characteristics of disposable perfusion circuit components, particularly the design of the venous reservoir.
        • Jones T.J.
        • Deal D.D.
        • Vernon J.C.
        • et al.
        How effective are cardiopulmonary bypass circuits at removing gaseous microemboli?.
        Poorly designed venous reservoirs may create a powerful vortex at high pump-flow rates, which trap air bubbles in blood. Once these bubbles pass into the systemic circulation, they may stimulate the formation of microthrombi, activate platelets, denature and aggregate plasma proteins, and result in free-radical attack of the vascular endothelium via released phospholipids.
        • Butler B.D.
        Gaseous microemboli A review.
      • 3.
        Many of the microemboli detected by postmortem examination appear to be lipid in nature. An extracorporeal source for these lipid emboli was suggested by the presence of aluminum silicate in the lipid material.
        • Challa V.R.
        • Lovell M.A.
        • Moody D.M.
        • et al.
        Laser microprobe mass spectrometric study of aluminum and silicon in brain emboli related to cardiac surgery.
        Subsequently, the primary lipid source was identified as the reinfusion of unwashed cardiotomy suction. Avoidance of the suction effluent resulted in a 10-fold reduction in the number of lipid microemboli.
        • Brooker R.F.
        • Brown W.R.
        • Moody D.M.
        • et al.
        Cardiotomy suction a major source of brain lipid emboli during cardiopulmonary bypass.
      Adoption of epiaortic echocardiography and optimal circuit components, avoidance of unwashed cardiotomy suction, and the routine use of TCD to guide surgical and perfusion technique may result in a dramatic reduction of cerebral microembolization. For example, the aggregate (median and interquartile range) MES/CABG surgery at one of the author’s affiliated hospitals declined from 203 (58–512, n = 71) in 1994 to 10 (0–25, n = 81) in 2003. There were no MES-free cases observed in 1993, whereas 31% of the 2003 cases resulted in no ultrasonically detectable emboliform signals.
      The findings of Sreeram et al
      • Sreeram G.M.
      • Grocott H.P.
      • White W.D.
      • et al.
      Transcranial Doppler emboli count predicts rise in creatinine following coronary artery bypass graft surgery.
      suggest that steps like those mentioned previously may prevent injury not only to the brain but also the kidney. However, the routine use of TCD monitoring has been hampered by technical limitations. Transcranial insonation through the temporal ultrasonic window is technically challenging and not possible in all patients. Fortunately, these limitations can be easily overcome by fixation of the standard 2-MHz TCD probe at a submandibular site. Bilateral insonation of the common and/or internal carotid arteries is easily achieved in all patients. Thus, there is compelling evidence supporting the integration of cranial vascular ultrasonic monitoring into the management of cardiac surgical patients.

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