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LETTERS
Cognitive Outcomes FollowingCardiopulmonary Bypass
To the Editor:
Dr Van Dijk and colleagues
1
found no differ-ence in 12-month cognitive outcomes between patients whounderwent either on-pump or off-pump coronary artery by-pass grafting (CABG). Although the authors alluded to a pos-sibleroleofmicroemboli,theydidnotprovideanexplanationfor the disturbing frequency and permanency of memory lossand dementia following CABG.It is possible that patients with extremely low hemoglobinlevelsmaybeathigherriskforcognitivedeficitsfollowingCABG.The current practice of performing cardiac surgery on pa-tientswithhematocritsaslowas18%hasnotbeenadequatelyevaluated.
2
Preoperativetransfusionstohematocritsashighas33%mayincreasesurvival.
3
Valerietal
4
estimatedthatasmanyas 40000 myocardial infarctions per million surgical proce-dures were caused by undertransfusion.Patients who have coronary atherosclerosis are more likelyto have similar lesions throughout the body, including in thecarotid and cerebral vasculature. Oxygen delivery to tissue isdirectly related to the amount of red blood cells as a functionof time. A patient with both anemia and stenosis has evenhigher risk of ischemia. It is not surprising that patients whoundergo surgery with severe anemia and stenosed vessels aremore likely to experience irreversible cell loss due to tissueanoxia.Thereisaneedforstudiestoassesswhetherthecurrentprac-tice of hemodilution in arteriosclerotic patients is a major fac-tor in postoperative cerebral dysfunction. Other options, in-cluding use of erythropoietin, frozen blood storage, andhemoglobinsubstitutes,alsorequirefurtherstudy.Itwouldbeinteresting to determine if the use of these substitutes, whichwould enable a normal perioperative hemoglobin level to beachieved, has a protective benefit.
Fetnat M. Fouad-Tarazi, MDDepartment of Cardiovascular MedicineCleveland Clinic FoundationCleveland, Ohio Joseph Feldschuh, MDDAXOR CorporationNew York, NY
DAXOR manufactures blood volume kits and instruments for the measurementof blood volume.—E
D
.
1.
Van Dijk D, Jansen EWL, Hijman R, et al. Cognitive outcome after off-pumpandon-pumpcoronaryarterybypassgraftsurgery:arandomizedtrial.
JAMA.
2002;287:1405-1412.
2.
Wu WC, Rathore SS, Wang Y, et al. Blood transfusion in elderly patients withacute myocardial infarction.
N Engl J Med.
2001;345:1230-1236.
3.
NewmanMF,KirchnerJL,Phillips-ButeB,etal.Longitudinalassessmentofneu-rocognitive function after coronary-artery bypass surgery.
N Engl J Med.
2001;344:395-402.
4.
Valeri CR, Crowley JP, Loscalzo J. The red cell transfusion trigger: has a sin ofcommission now become a sin of omission?
Transfusion.
1998;36:602-610.
To the Editor:
Dr Van Dijk and colleagues
1
demonstrated thatpatients who received their first CABG without cardiopulmo-narybypass(CPB)hadasmallimprovementinthecognitiveout-come 3 months after the procedure, but the effects did not per-sist at 12 months. Cerebral microembolism and hypoperfusion,whichareassociatedwithCPB,arethemainmechanismsofbraininjury in patients undergoing CABG. Microembolic signals de-tected by transcranial Doppler ultrasound and echocardiogra-phymonitoringduringCPBcanbedirectlyassociatedwithaor-ticmanipulations,butalargeproportionofthemarethoughttorepresentairbubblesormicroparticulateemboligeneratedfromthe pump circuit and not completely eliminated by the arteriallinefilters.
2
Off-pumpCABGisassociatedwithamarkedreduc-tion of the microembolic load during surgery and, therefore, isbelieved to reduce cognitive impairment in those patients.OurcenterhasbeenperformingroutineCABGwithoutCPBforthepast2decades.
3
In1995,wereported
4
aprospectivestudycomparing48patientsundergoingCABGwithCPBand33pa-tients operated without CPB. At that time, we did not find sig-nificant differences in early neurologic and neuropsychologicexaminationsbetweenthe2groups.Inaddition,wecouldnotobserve differences in early neurologic outcome in a small se-ries of patients with similar risk factors randomized to CABGwithandwithoutCPB.
2
Themuchlowernumberofmicroem-bolic signals detected by intraoperative transcranial Dopplerultrasound monitoring in the patients operated without CPBsuggeststhattheconstitutionandthenatureoftheemboli,ratherthan their number, could be associated with neurologic out-come. Moreover, the changes in flow velocity and pulsatilityindex might be another potential mechanism of brain injuryin patients who do not undergo CPB.
2
Despite the methodological limitations, these studies sug-gestamultifactorialgenesisofcerebralinjuryinCABGandre-
GUIDELINES FOR LETTERS.
Letters discussing a recent
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article shouldbe received within 4 weeks of the article’s publication and should not exceed 400words of text and 5 references. Letters reporting original research should not ex-ceed 500 words and 6 references. All letters should include a word count. Lettersmust not duplicate other material published or submitted for publication. Letterswill be published at the discretion of the editors as space permits and are subjecttoeditingandabridgment.Asignedstatementforauthorshipcriteriaandrespon-sibility, financial disclosure, copyright transfer, and acknowledgment is requiredfor publication. Letters not meeting these specifications are generally not consid-ered. Letters will not be returned unless specifically requested. Also see Instruc-tions for Authors (January 2, 2002). Letters may be submitted by surface mail:LettersEditor,
JAMA
,515NStateSt,Chicago,IL60610;e-mail:JAMA-letters@ama-assn.org;or fax (please also send a hard copy via surface mail):(312) 464-5225.
Letters Section Editor:
Stephen J. Lurie, MD, PhD, Senior Editor.
©2002 American Medical Association. All rights reserved.
(Reprinted) JAMA,
June 19, 2002—Vol 287, No. 23
3077
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emphasize the need for large randomized trials to further elu-cidate these complex interactions.
Suzana M. F. Malheiros, MDAyrton R. Massaro, MDEnio Buffolo, MDDepartments of Neurology and Cardiovascular SurgeryUniversidade Federal de Sa˜o PauloSa˜o Paulo, Brazil
1.
Van Dijk D, Jansen EWL, Hijman R, et al. Cognitive outcome after off-pumpandon-pumpcoronaryarterybypassgraftsurgery:arandomizedtrial.
JAMA
.2002;287:1405-1412.
2.
Malheiros SMF, Massaro AR, Gabbai AA, et al. Is the number of microembolicsignals related to neurologic outcome in coronary bypass surgery?
Arq Neurop- siquiatr
. 2001;59:1-5.
3.
Buffolo E, de Andrade CS, Branco JN, et al. Coronary artery bypass graftingwithout cardiopulmonary bypass.
Ann Thorac Surg
. 1996;61:63-66.
4.
Malheiros SMF, Brucki SMD, Gabbai AA, et al. Neurological outcome in coro-naryarterysurgerywithandwithoutcardiopulmonarybypass.
ActaNeurolScand
.1995;92:256-260.
TotheEditor:
DrVanDijkandcolleagues
1
reportedlittledif-ference in the cognitive function of patients 12 months aftereither off-pump or on-pump CABG. This outcome was unex-pectedsinceon-pumpproceduresareassociatedwithaorticcan-nulationandprolongedextracorporealperfusion,bothofwhichmay shower the brain with emboli. One explanation for thisfinding, which the authors did not discuss, might be that pa-tients in need of CABG have a high baseline rate of 12-monthcognitivedeclinewithorwithoutsurgery.Thisisatestablehy-pothesis:controlgroupsofpatientswhoaremanagedwithoutsurgery (eg, with drugs only or with drugs and angioplasty)could be assembled and followed up for a year and subjectedtothesametestsofcognitivefunctionastheinterventiongroupsinthisstudy.ThenwemightbetterlearnifCABGorsomeotheraspect of these patients’ illness is responsible for their cogni-tive decline over time.
Donald Venes, MDPortland, Ore
1.
Van Dijk D, Jansen EWL, Hijman R, et al. Cognitive outcome after off-pumpandon-pumpcoronaryarterybypassgraftsurgery:arandomizedtrial.
JAMA.
2002;287:1405-1412.
To the Editor:
The results of Dr Van Dijk and colleagues
1
donot appear to have resolved the conflicting conclusions drawnfrom the 2 prior randomized trials that have found that off-pump CABG reduced the postoperative cognitive dysfunc-tion.
2,3
One potential limitation of all these studies is the ad-equacy of management of the patient during CPB. Relevantvariableswouldincludemaintaininganappropriatehematocrit,highflowrate,andmeanperfusionpressurewhileonbypass,andhavingabloodfilteronthearteriallimbofthebypasscircuit.Thesedifferences could greatly influence cerebral morbidity.In addition to psychometric evaluation of the cerebral in- jury in patients with CPB procedures, a high incidence of ab-normalities was found on magnetic resonance imaging (MRI)obtainedbeforeandaftertheCPBprocedure.Theischemicle-sions demonstrated by MRI typically are localized at the gray/ white junction and the watershed area suggesting that em-bolic phenomena and hypoperfusion, respectively, are likelythe underlying causes of the cerebral injury. Based on our ex-perience with preoperative and postoperative (3-7 days) MRIimaging, the CPB procedures performed with strict in-line fil-trationandrelativelyhighperfusionratedemonstratednoMRIor neurological evidence of ischemic injury in any of our pa-tients.
4
Suchfindingsfurthersupportthenotionthatthevaria-tion in CPB procedure can influence the neurological out-comeinpatientsundergoinganytypeofsurgeryrequiringCPBprocedure. Therefore, the efficacy of off-pump CABG surgerycannot be adequately assessed without standardized CPB pro-cedure and quality control.
William T. C. Yuh, MD, MSEEChristopher J. Knott-Craig, MDMonala D. Tilak, MDDepartment of Radiological SciencesOklahoma University Health Science CenterOklahoma City
1.
Van Dijk D, Jansen EWL, Hijman R, et al. Cognitive outcome after off-pumpandon-pumpcoronalarterybypassgraftsurgery:arandomizedtrial.
JAMA.
2002;287:1405-1412.
2.
Diegeler A, Hirsch R, Schneider F, et al. Neuromonitoring and neurocognitiveoutcome in off-pump versus conventional coronary bypass operation.
Ann Tho-rac Surg
. 2000;69:1162-1166.
3.
Lloyd CT, Ascione R, Underwood MJ, et al. Serum S-100 protein release andneuropsychologicoutcomeduringcoronaryrevascularizationonthebeatingheart:a prospective randomized study.
J Thorac Cardiovasc Surg.
2000;119:148-154.
4.
SimonsonTM,YuhTCY,HindmanJ,etal.ContrastMRofthebrainafterhigh-perfusion cardiopulmonary bypass.
AJNR Am J Neuroradiol.
1994;15:3-7.
InReply:
WeagreewithDrsFouad-TaraziandFeldschuhthatwhilemoderatehemodilutionmayimproverheologyandmain-tainoxygendelivery,severehemodilutioncombinedwithste-nosis of cerebral arteries may contribute to negative cerebraloutcomes.However,thishypothesisneedstobeformallyevalu-ated. This could be accomplished in a retrospective study in-vestigating the relationship between perioperative hematocritandstroke,inadesigncomparablewiththestudyofWuetal,
1
which assessed the association between hematocrit and mor-tality in patients with myocardial infarction. If a negative im-pact of severe hemodilution during CABG were confirmed, aformal trial of a more aggressive transfusion regimen wouldbe warranted, in which the effect on subtle cognitive declinecould be evaluated.Dr Malheiros and colleagues have a large experience in off-pump surgery and were one of the first groups to describe alargeseriesofoff-pumpprocedures.
2
Theresultsoftheirstud-iesareinaccordancewithours;avoidingCPBdoesnotleadtoa large or easily detectable improvement of cognitive or neu-rologic outcome.
2,3
The shower of microemboli to the brain isonlyoneofthepostulatedmechanismsofcognitivedeclinefol-lowing CABG. A subsample of the patients in our study alsounderwentintraoperativetranscranialDopplerultrasoundex-amination. Like Malheiros et al, we found more emboli in on-pumppatientsthaninoff-pumppatients(unpublishedresults). We agree that the composition rather than the number of theemboliprobablydeterminestheclinicaleffect.Atriallargerwithmorestatisticalpowerthanoursmayhelptoestablishwhether
LETTERS
3078
JAMA,
June 19, 2002
—
Vol 287, No. 23
(Reprinted)
©2002 American Medical Association. All rights reserved.
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