Cerebral Dysfunction Following Extracorporeal Circulation for Aortocoronary Bypass Surgery: No Differences in Neuropsychological Outcome After Pulsatile Versus Nonpulsatile Flow Th. Henz el. H. Stephan", and Il. So nnuut' Departmen ts of ' Ne urology an d 2Anaesthesiology, Univers ity Ilosp ital Gouin gen. FHG

Nonpulsa tile perfus ion techn iques with extraco rporeal circu lalion for open-heart surge ry and aortoco ronary bypass grafting are wide ly used ; this treatment is often followed by temporary or perman en t ne uro logical deficits. Experi mental stud ies sug gest that pulsatile now may be of greater benefit because of its ab ility to am eliorate cere bra l microcirculation . We therefore investigated 22 men who unde rwent aortocoronar y bypass grafting. Patients we re ra nd omly divide d into eithe r a group und ergoing nonpu lsa tile (0 = 14) or pulsa tile now (0 = 8). Neurological exam ina tions were done pr ior to the operation an d on the 7lh posto perative day. EEG. cere bra l blood Dow (CBF), and the meta bolic rates of 0, (CMB O2 ) and glucose (CM H Glucose) were meas ure d before a naes thes ia and 30 minutes after the start of ext racorporeal circ ulation. when venous blood te mperature was 26 0(, Postopera tive neurological symp to ms consisted of cra nial nerve palsies . dysfunctions of the visual cortex. cere bellar sympto ms. an d slight ar m par esis. hut no difTe rences between the two trea tment groups were detected. Moreover. cha nges in EEG. CB1". and CM H rates du ring a naesthes ia did not difTer between the two grou ps. Our dat a suggest that pulsat ile flow is not su per ior to the nonpulsatile perfusion techniq ue. but to confirm this la rger patien t sam ples a re requ ired . Keywords Extracorporeal circulation - Pulsa tile flow - Nonpulsatile flow Neurologica l dysfunction - Aortocorona ry bypass

Zereb ra le Dysfunkti on na ch extrakorpo ralcr Zir ku lalion : Vcrgl eic h zwisc hen pulsatiler und nnnpul sa file r Teeh nik Nonpulsat ile Technikcn bel extra kcrporalcrn Kreislau f wa hrend ofTene r lIerzch irurgie und ao rto koronarem Vene nbypass (ACVB) sind Sta nda rdmet hoden. gehen jed och hfiuflg mit vor iibergeh enden oder dau erh aften ne urolog isc hen Srdrungen einhe r. Aufgrund der Ergebniss e tierexper imen teller Studie n ist anz une hmen . da B das pulsatile Verfahre n die se StOrungcn durch Ver besse ru ng de r zere bralen Mikrozirkulati on verhi ndern kann. Wir haben da he r in einer prospektiven ra ndomisie rte n Studie 22 Patienten (..pulsatil e" Gruppe 8 Pat .: ..no npulsatile" Gru ppe 14 Pat .). die sich einer ACVB- Operation unterziuhcn mu llten . pr aoperativ und am 7. posto pera tiven Tag neu rologisch untersuch t. Dauer -EltG. lli rn durchblut un g ICBF), und die zerebralen StofTwechs elra te n filr Sa uerstofT (CMHOz) und Glucose (CM Hc;lurosr) wurden vor Na rkose und 30 Minu ten nach Beginn dcr extra kor poralen Zirkulation bei e ine r Ilypoth ermie von 26 °Ca ufgczeichnet hzw. gemessen. Bei der postoper ativen neurologischen Untersuc hung bestan den Hirnn er ven au sfalle, Stdru nge n des visuellen Kortex. zere bella rc Sympto mc sow ie cinmalig cine ze ntrule Arm pa rese . Beide unt ersu cht en Gruppen wa re n hier von jedoch glcich erm aBen betroffen. Ents prec he nd difTerierten die intraoperativen Vera nderungen des EEG. des CBF, de r CMHO? sow ie CM HG1u"u"" in den heiden Grup pen nicht . Unse re Ergeb nisse logon na he, daB das pulsatil e gege niiberdem nonpu lsa tilen Vcrfahren keine Vorteile hi nsichtli ch posto perativer neurologischer Symptome a ufweist. Es ist jedoch eine grofscrc Za hl von Untersuchun gen erfo rder llch. urn eine sichere Aussage zu ennogllchen.

(Table 1) occurs in at least 5% of opera ted pati ents (l l, Complication rates up to 6 1%bave been reported (2). On the

delay of dischar ge from hospi tal an d a longer rehabilit ation peri od. Unfortunately a minorit y of patients will suffer from perm anent disability. A long bypass time (5. 61. advanced age (5), preexisting cere br ovascular illness (7), and intrao pera tive hypotension (8. 9) are gene ra lly considered to favour cerebra l dysfun c-

first po st op e r ati ve da y n ew n eurologic al s ig ns we r e d ete ct e d in even 64% of p atients (3) . Using di sti n ct neu ro -

and platelet aggregates are oth er causes 11 . 10,11) . Despit e

Introd uction Cereb ra l dysfunct ion following extraco rporeal circulation for ope n- he a rt s u rge ry a n d ao rtocoro na ry byp as s graft ing

psychological detection methods an impairment ra te of 70 % may be found (4). In most patients cereb ral dysfunction is not disabling or even life-threatening, but may lea d to a

Thorae. cardiovasc. Surgn 38 (1990) 65-68 © GeorgThieme VerlagStuttgart - New York

tio n . In a d d itio n . a ir e m bo lis m . parti cu late m atte r . thromb i, th e in troducti on of filter systems w ith in th e ext r a c or p or e a l ci rc ula tio n the p ercenta ge of ce reb ra l co m plicatio ns h a d

hardly decr eased.

Received for Publication : Novem ber 9. 1989

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Summary

Thome. eard iovasc. Surgn 38 (99 0) Table 1 Neurological and neuropsychological symptoms which can occur afterextracorporeal circulation foropenheart surgery and aortocoronary bypass grafting II,4, 25,26, 27) Hemiparesis, hemiplegia, tetraparesis. tetraplegia, abnormal tendon reflexes, positive Babinski's sign Diminished sensory function Cortical blindness, visual field defects, conjugate pa ralysis of gaze, retinal infarction, retinal embolus, ischemic opticneuropathy Pareses ofcranial nerves other than optic nerve Horner'ssyndrome Aphasia, agraphia. acalculia, apraxia Cerebellar dysfunction Seizures Disturbance of consciousness and orientation, delirium, paranoid psychosis. depression

It is still a matter of controversial discuss ion if a pulsatile perfusion technique - in contras t to the widely used non pulsatile flow method - could lower the incidence of postoperative neuro logical dysfunction. It is well known that in anim al studies pulsatile flow am eliorates renal and ca rdiac function (12, 13); however changes of cere bral function have been studied to a less intensive degr ee. Pulsatile fl ow may result in a lower amount of sludges and ede ma format ion (14), in an elevated oxygen tension of cerebrospinal fluid, and in decreased lactate concentrations of cerebral venou s blood (15), when compared to nonpulsatile flow techniques . Tranmer and co-workers reported that in the ischem ic normothermi c dog brain cerebral blood flow (CBF) increas es to 155 'Yo, when non pulsat ile flow is followed by the pulsatile techniqu e (16). So far no studies have been published comp aring nonpulsatile flow to pulsatile techniqu es by quantifying the frequency of subsequent cerebral dysfunction using neur ological examination, CBF and cerebr ai metabo lic ra te (CMR) measu rements. We therefore studied pro spectively the influence of the two different method s on cere bra l blood flow and metaboiism as well as on neuropsychological out come.

Th. Henz e. H. S tephan. and II. Sonntag tained at 4 0mmllg by addition of exoge nous CO2 during hypothermic cardiopulmonary bypass. Nonpulsat ile flow was performed using a roller pump and a mem brane oxyge nator. Pulsatile now was achieve d with a Pulsatile Ass ist Device in combination with a n intraaortal balloon pump (systolic-diasto lic gradient of at least 40 mmllg). Blood temperature was maintained at 26 °C du ring operat ion. Neurological examination. The neurological examinatio n (cranial nerves, tendon reflexes, functions of visual, se nso rimotor, extrapyramidal and ce rebellar systems) was performed on the preoperative and the 7th postoperative day and always by the sa me physician. In addition, level of consci ousness. psychotic symptoms and sig ns of desor ientation, aphasia. acalcu lia, and apraxia were recorded. The neurologist was unaware of th e extracorporea l circulation method use d in the individual patient. CBF- and CMR-measurements, EHG recordings. Cerebral blood flow (CSF) was measured usi ng the Argon inert gas techn ique (17) . a modification of the Kety-Schmid t method (18 ). Cerebral metabolic rate (CMRJ was ca lculated as the product of ar terial ce rebral venous oxyge n (0 2) or glucose difference (AVI) 0 2' AVD Glucose) and CSF. For AVD O2 and AVD Glucose blood samp les we re collected simultaneo usly from a radial artery and the interna l jugular bulb. respectively. Cerebral perfusion pressure lepp) was calculated as the difference between mean arterial pressure and jugula r veno us bulb pressure. EEG activity was recorded with a frequen cy ana lysis system Il.ifescan TrL Neurometrics Inc.I. Measure me nts we re performed before anaest hes ia (1' 11 and 30 minutes after the start of extraco rporeal circulation when venous and arte rial blood and nasopharyngeal temperatures were all 26 °C (T 2).

Results No intra- or postoperative complications occurred in either group. Mean arterial blood pr essure and CI'I' never dropped to critical levels. All patients could leave the Intensive Care Unit on the second postop erative day at the iate s!. Posto p erative neurological symptoms. Postoperative neuro logical dysfunctions are iisted in Tab le 2.

Table 2 grafting

Neurological symptoms in 22 patients after aortocoronary bypass

Flow

Materials a nd Metbods Patien ts . In this prospective study 22 men (age 38-59 years, mea n 52 y) undergoi ng elective aortocoronary bypass grafting we re studied. The study was approved by the G6ttingen Human Subject Review Committee. Written informed consen t was obtained from eac h patient at the time of the preoperative visit. The patients were randomly divided into either a group undergoing non pulsat ile (group A, n = 14) or pulsatile flow (group S, n = 8) during cardiopulmonary bypass . All patients suffered from coronary heart disease with stable angina pectoris. Those with cardiac failure, leftventricular end-diastolic pressure greater than 15 mmll g, or an ejection fraction less than 0.4 were excluded . None of the patients suffered from a forme r central nervous sys tem diso rder and all of them had a normal neuro logical exa mination on the preoperative day. Doppler ultraso und measurem ents showed the ce rebral vesse ls normal in all patients . No differences in mean age , bodyweight, medical treatment before operation, and cardiopulmonary diseas es were found between the two groups. Ana esthesia and byp ass techniques . Patien ts we re anaesthetized with fentanyl (7 JLg x kg"! b. w. ] and midazo lam (20 0 ILg x kg'" b. w.l. For muscle relaxation patients received pancuronium 6-8 mg. Anaes thes ia was maintained with fentanyl (0.15 ILg x kg'" b. w.I and midazolam (3 ILg x kg" b. w.). Patie nts were ventilated with an al r/ O, mixture. Arterial pC0 2 was main-

Ptosis Diplopia Macropsia, altered colour perception Nystagmus Xllth nerve paresis Dysdiadochokinesia Arm paresis

nonpulsatile In ~ 14)

pulsatile In ~ 8)

2 1 1 4

These sympt oms occurred in 5 of 14 patients after nonpu lsatiie flow bypass and in 2 of 8 patients undergoing pulsati le flow. Macropsia and altered coiour perception were report ed by 2 patients to have appea red after tran sfer from the Intensive Care Unit, iasting 2 and 4 hours only. In 2 furthe r pat ients a slight arm paresis had already begun to resolve at the time of postop erative exa minat ion. Due to the small patient sample estimation of statistical significances was not attempted in our study. CEF- and CMR-measurements. The mean dur ation of bypass was 91 min (range 65- 156min) in the patients with out postoperative cerebral dysfunction , and 111 min (range 62-223 min) in thos e who developed neuro iogical

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Thora e. ca rdiolJuse. .)·urgIl38 (1 990)

Cerebral DYsfuflction Following Extracorpo rea i Circulat ion

symptoms. Mean bypass ti me with non -p ulsatile flow was 96 min . and 103 m in in the pu lsa tile flow group. In eac h of the A2- a nd th e Ill -gro up (for ex planations see Ta ble 3)

CBF- and CMR-measurements

Group

C8r {ml x min -I x 100 g-'l CMRO, (ml x min -I x 100 g-I) CMR Glucose (mg x min-I x lOO g-l)

T1 T2 T1 T2 TI

Al

A2

8 I

82

56 81 3.45 0.66 4.94

55 109 3.21 0.98 4.31

56 101 J 08 0.66 4.35

60 96 3.30 0.74 3.98

Groups:

AI: A2: B 1: B2:

T 1: T 2:

differe nt surgical and ana esthetic procedu res as well as differen t degrees of hypothe rmia : deta ils of operation incomplete or lacking - differ ent su rg ica l con ditions : ope n a nd closed heart surgery not dist inguished .

nonpulsatile flow, no postoperative neurological dysfunction nonpulsatileflow. postoperative neurological symptoms pulsatile flow. no postoperative neurological dysfunction pulsatile flow. postoperative neurological symptoms Time before anaesthesia Time after 30 min. of bypass

there was one patient with a much longer bypass time than Ihe gro up 's m ean duratio n. Exclud ing these 2 patients. mean bypass time cor respond ed well in a ll grou ps . Resul ts of CIlF. CMIl a,. and CMIl Glucos e measu rem ents a re listed in Tab le 3. CIlF increased fro m 55-60 ml x m tn" x 100 gO' be fore ex traco rporea l circ ulation (T 1) to 81- 109 m l x min " x 100 g- ' afler 30 mi n of bypass (T 2). In th e nonpulsatil e group the increase of CBF was more pronounced in the patients with postoperative cerebral dysfunction than in th ose wit ho ut. In the pulsatil e flow gro up results were qu ite th e contrary. Preoperative CMIl 0 , was betwee n 3.08 a nd 3.4 5 ml x min " x 100 g" (T1) a nd decreased st rongly at T 2 according to a QIll va lue of 2.6 . CMIl Glucos e also de cr eased in nea rly all patients . with the exceptio n of two individuals . in whom CMIl Glucos e incr eased slightly - : T2 . possibly du e to an onl y small glucos e uptak e combine d with th e e rro r of th e glucos e estima tio n m ethod . Th e refore th e resu lts of CMIl Glucose measurem ents a t T2 are left out in Ta ble :l. EEG recordings. Continuous EEG recording reveal ed alpha - a nd beta-pa tterns (8-12 Hertz a nd 13- 30 He rtz, respectively) pr eoper ati vely. After ind uction of hypot he rmia alpha patterns decreas ed a nd th en va nishe d as did th e theta - a nd delta-ba nd s . During hypothermia a nd anaes thesi a most patients had a burst-suppression EEG or an isoelectric band . EEG cha nges were th e sa me in a ll four groups . Lat erali za tion of EEG depression as an indi cator of localized deficits of CIlF or ce rebra l functio n never occurred.

Discussion Cere bral dysfun ction following ao rto coro nary bypass grafting has been a matter of investiga tion for m any neurologists. anaesthesists , and surgeo ns . A lot of mec hanisms were considered to be ca usally re lated to those dysfun ctions. as mentioned above. For several reasons it is not possible to compare the res ults of the stud ies published so far : - differ en t met hods a nd tests for th e detection of cerebral dysfun ction :

According to the technical advances in performing aortocoronary bypass grafting fewer severe or even fatal neurological com plica tions occurre d durin g th e last yea rs (19) . Ilut despite shorter bypass tim es a nd a voida nce of hyp otensive states and em bolisms the re is still a co nside ra ble a mo unt of postoperative neurological dysfu nction . After elimina tio n of th e mo st obvious tech nical defects th ese co mplica tions ma y be related to disturbances ofi ntrao pe ra tive cerebral microcirculation due to gene ralized athero scleros is which has to be assumed present in most of the ope ra ted patients. In previous inves tigations most often no npul satil e flow was us ed . With the exce ption of one study (20) non puls atil e flow and pulsatile flow were never compared in terms of th eir effect on int raope ra tive brain metabolism and post operative cerebral dysfunction . Nea rly all neu ro logica l sympto ms see n postoperati vely in our pati en ts cou ld be related to dysfu nct ions with in the basila r a rt ery territo ry. Th is is in contrast with oth er studi es in wh ich stro kes in a ll ce re bra l regions ha ve heen do cum en ted . Only in the neurop ath ologic series of Brierleu (21) wa s th ere a high er in ciden ce of neu rological sym pto ms that cou ld be rel at ed to ve rtebro- basilar territory dys function . On th e oth er hand. the fre que ncy of tho se sym plo ms reported from others. i. e. visual impairment and cranial nerve palsies , indicates that this cerebral territory is particu larly expos ed to microemb oliza tion a nd hypoperfusion . With respect to the am ount an d density of ne ur on al fun ctions and efferentiafTerent nerve tracts located here it seems likely that microembolization a nd hypoperfusioo in this territory are followed by neurological impairment more often than in other cortical region s . In our se ries no serious neurological complica tions occ urre d poss ibly du e to advanced operation techniques . In th e present study CRF. CMIl a,. a nd CMIl Glucose were co m pa ra ble in a ll groups before op er ati on . Cll F values corresponded well with those given from previous inves tigat ors (18. 22) . CMR a, a nd CMIl Glucose va lues wer e lower than ex pected from th e liter ature. probabl y du e to influences of premedication at the time of measurement. During extracorporeal circulation CBF increased because of the lower cerebral vascular resistance in hypothermia ca used by th e addition of CO, to maintain a tempera turecorrected pa CO, of 40mmHg. CMIl a, a nd CMIl Glucos e decreased as a result of the influence of anaes thetic agents a nd hyp oth ermia. Reduction ofC MIl 0 , du rin g hypoth ermia sho we d a QlO va lue that corresponded well with th e findings of othe rs 123. 24). No obvious difTerences we re detected in the two treatment grou ps . Lookin g at ea ch sing le pa tie nt with post op erative ce re bral dysfun ction Cll F a nd CMIl values were with in the respective group's range. Thus. patients suffering from po sto perative neurologica l symptoms could not be identified by m ea ns of intr aop er ative CllF a nd CMIl measurements. EEG recordings di d not contri bute to an int raoperative difTerentiation between the two groups either. In conclusion, neurological symptoms occurred in the pul satil e flow group as well as in th e non pul satil e flow

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Table 3

67

Thora e. eardio uas e. S urgll.18 (/9 90)

grou p. CIlF. CMIl 0 , and CMIl Glucose sh owed correspond109 changes after :l O min of extracorporeal circulation. No results have heen obtained which could dem onstrat e a superiority of pulsatile Row or nonpulsatil e Row. For confirmation of these findin gs a grea ter pa tient sa mple has to be investigated . Refercn ccs Aberg. 1:. G. Ronquist. I/. Tqden. S. Brunnktist. 1. Hultma n. K. lJerg st rom. a nd A Lilja: Adverse effects on the br ai n in ca rdiac opera tions as assess ed by bioche mical. psychometr ic. a nd radi ologic meth ods . J. Thorae. Cardio vasc. Surg. 871 198 4199- 105 2 Bering. E. A : Effect of body tem perat ure cha nge on cereb ra loxygen cons umptio n of the intact monkey. Am. J. Ph vsiol . 200 (196 1) 4 17-4 19 ] ttranthn-ai te. M . A : Prevention of neu rological damage durin g open- hea rt su rge ry. Th or ax 30 (197 5) 258-261 ~ Breu er. A C. A. J. Fur ton . M, R.llanson. R. Ll.ed erman. J.: D.l.oop . /). M. Cosqrore. /l . I.. Greens treet. and F. G. Estafunous: Central ne rvous syste m comp lications of corona ry a rtery bypass gran s urgery: Prospective a na lysis of 42 1 pat ients. Stro ke 14 (19831 682 - 687 IJrier ley . J. IJ.: Cere bra l injury follow ing ca rdiac opera tions . Lancet 1(19641175 b Frate r. R. U'. M.. S. wa kavamo. Y. aka. R. M . Becker. P. Of'.m/, 7: ()y rmlll . a nd M. 11.ttkm f os : Pulsati le ca rdiopulmona ry bypass: Failure to inlluence hem odyna mics or horm on es. Circulation 62, Suppl. 1(1980119- 25 GeIUJ , A. S.. M. 7: Salay me h, T. A be. a nd A. Ii. tt cue. Effect of pulsatile ca rdiop ulmona ry bypass on cerebra l meta bolism . J . Surg . Bes. 12 (19721381- 387 I; ttenriksan. L: Evide nce sugges tive of din'u se brain da mage following ca rdiac opera tions . La ncet I (19H4) 8 16-20 'J Kery. :'j. :.j., a nd C. F. S chm id t: The nitro us oxide metho d for the quan tita tive dete rmination of cere bral blood flow in ma n: Th eory, proced ure a nd normal values. J. Clln. Invcst. 27 0 948 1476- 48:i 10 Kotk ka. tt., a nd M. lttiberman: Neurologic dysfun ction Iollo wtng ca rdiac ope rati on with low-flow, low-p ress ure ca rdiopulmo na ry bypass, J. Thorac. Ca rdiovasc. Surg. 79 (1980 ) 432-4 37 . I I t.arkin.D, I·: P.. A /;". Wood. M. Netiqan. a nd P. Eustace: Ischaem ic optic ne uropathy complicating cardiop ulmona ry bypass. Hr. J. Op hthalm ol. 7 1 (19871344 - 34 7 12 t.ass en. N. A . a nd l\l. S . Chris te nsen: Physiology of cere br al blood flow. Br. J. Anaesth . 48 (197 6171 9 - 734 I l t.erine. F-: lI.. D. M. Philbin. K. Kono. C. I/. Coggins. a nd C. 11'. Emerson: Plas ma vaso pressin levels a nd urin a ry sodium excretio n during ca rdiopulmo nary bypass with a nd without pulsatile flow. Ann . Tho rac . Surg. 32 (1981) 63- 67 14 stat..",mo lo. L C. C. l1'o lferth. a nd M. H. Perlm an: Elfects of pulsatiIe an d non-pu lsati le pe rfusion upon cerebral and conjunctival microci rculat ion in dogs . Am. Surg. 37 (1971)61 - 64 I

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21

22

2]

24

25

21,

27

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Tit. Henz e. AI, D, Depa rtm e nt of Neuro logy Univers ity Hospital Hobert-Koch -Str. 40 [)-34 00 GottingenlFRG

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68