Thorax (1974), 29, 633.

Cerebral blood flow and metabolism duringopen-heart surgery

M. A. BRANTHWAITE

Brompton Hospital, London SW3

Branthwaite, M. A. (1974). Thorax, 29, 633-638. Cerebral blood flow and metabolismduring open-heart surgery. Changes in cerebral blood flow and metabolism were investi-gated in 30 patients during the first five minutes of cardiopulmonary bypass. The ratioof blood flow to oxygen uptake (the cerebral blood flow equivalent or CBFE) rose by54% and this change could not be attributed to simultaneous variations in arterialcarbon dioxide tension, haematocrit or temperature.A modified thermovelocity technique was used to assess changes in blood flow in the

internal jugular vein in 12 of the 30 subjects. The method suffers from a number ofserious limitations, but the evidence suggests that there was a reduction in cerebralblood flow at the onset of bypass in more than 50% of the patients studied. The fallwas associated with a particularly marked reduction in systemic blood pressure andoccurred in spite of high overall flow rates from the oxygenator.

It is argued that the findings indicate considerable depression of cerebral metabolism,which may be due to the decreased oxygen availability consequent upon haemodilutionand hypotension and which may contribute to neurological damage in some patients.

Previous work on the aetiology of neurologicaldamage related to open-heart surgery (Branth-waite, 1973a) identified the onset of cardio-pulmonary bypass as a period of hazard andsuggested that systemic hypotension resulting ininadequate cerebral blood flow may be a contri-butory factor. Monitoring jugular venous oxygensaturation has been advocated as a means ofdetecting cerebral ischaemia during cerebro-vascular surgery (Lyons, Clark, McDowell, andMcArthur, 1964), and although the method haslimitations (Larson, Ehrenfeld, Wade, andWylie, 1967) a study was undertaken to examinechanges in jugular venous oxygenation at theonset of cardiopulmonary bypass. Changes in bothblood flow and metabolic rate influence venousoxygen saturation, and, in some of the patientsstudied, an attempt was made therefore to com-bine the measurement of changes in jugularvenous oxygenation with an assessment ofchanges in cerebral blood flow.

MATERIAL AND METHODS

Studies were made on 30 unselected adult patients(average age 45 years) undergoing surgery for a

variety of congenital or acquired defects. Informedconsent was obtained at the preoperative visit.

Following premedication with papaveretum andscopolamine, anaesthesia was induced with thiopen-tone (3-4 mg/kg) and pancuronium bromide andmaintained with nitrous oxide (60-67%) and oxygen(40-33 %) with additional supplements of papaveretumif necessary. Perfusion was established with a rotatingdisc oxygenator, and some degree of haemodilutionwas employed in all cases. A flow of at least 80 ml/kgwas reached in less than five minutes in all cases, andin all but three, artificial ventilation had been dis-continued and the aorta cross-clamped within thisperiod.The radial artery and internal jugular vein are

cannulated routinely and, for this study, a secondjugular catheter was introduced percutaneously andthreaded in a retrograde direction to the base of theskull. In 12 patients, this jugular catheter consisted ofa specially constructed thermovelocity probe.

Arterial and jugular venous blood samples werecollected immediately before and at one-minute in-tervals for the first five minutes after the onset ofperfusion, and were analysed for oxygen contentusing either a Lex-02-Con (Albury Instruments Ltd.)or the electrode method of Linden, Ledsome, andNorman (1965). The haematocrit (PCV) was measuredon each arterial sample using a Hawkesley micro-

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haematocrit centrifuge. The arterial blood gastensions were measured both before and five minutesafter the onset of perfusion and these results werecorrected for temperature when necessary. Changesin arterial and jugular venous oxygen content wereexpressed as the cerebral blood flow equivalent(CBFE), which represents blood flow per unit oxygenconsumption and is derived as the reciprocal of thearteriovenous oxygen content difference (A-V)02(Cotev, Lee, and Severinghaus, 1968).

In all cases the arterial and superior vena cavalpressures, nasopharyngeal temperature, and thecerebral function monitor signal (a modified EEG)were recorded on an ultraviolet recorder (S.E.Laboratories Ltd.). In 12 patients changes in jugularblood flow were assessed using a modification of thethermovelocity technique (Meyer, Gotoh, Tomita,and Akiyama, 1966). Two thermistors (StandardTelephones and Cables, type U23US) were mountedin the tip of a Portex 30 cm nylon cannula (IDP2 mm). The distal thermistor was heated threetimes each minute by a battery-operated constantcurrent source while the change in temperature sensedby the proximal thermistor was amplified and re-corded using the temperature-sensing circuit of aDevices thermal dilution cardiac output monitor.The integral of the temperature change detected bythe sensing thermistor is inversely proportional to thevelocity of blood flow past the tip of the cannulaand was recorded on the same tracing as the variablesenumerated above.

RESULTS

The changes which occurred during the first fiveminutes of perfusion are shown in Table I. The

CBFE increased from 15-2 to 23-4 ml blood/ml 02

uptake and, at the same time, the mean arterialblood pressure,.superior vena caval pressure, andPCV decreased. There was a small but significantincrease in the arterial carbon dioxide tension(Paco2) together with a small, but highly signifi-cant fall in nasopharyngeal temperature.Four patients were found postoperatively to

have sustained neurological damage which was ahemiplegia of varying severity in three and amid-brain lesion in one. The changes recorded inthese four patients were compared with thosein 24 undamaged patients who survived the opera-tion (Table II); two patients died on the tableand were excluded from this comparison. Al-though none of the differences reached statisticalsignificance, there was a tendency for the increasein CBFE during the first five minutes to be greaterin patients who suffered neurological injury. Thecerebral function monitor record was unsatis-factory in one of these patients for technicalreasons, but in the other three, there was a suddenchange at the onset of bypass which could notbe attributed to any other variable known toinfluence this signal (Branthwaite, 1973b),and the remainder of these three records wasunremarkable.

In the 12 patients in whom changes in cerebralblood flow were assessed, the thermovelocityintegral height was measured for the first 15cycles (5 minutes) following the onset of bypassand compared with the last six cycles (2 minutes)

TABLE IMEAN AND STANDARD ERROR OF MEAN FOR VALUES RECORDED BEFORE AND 5 MINUTES AFTER ONSET OF

CARDIOPULMONARY BYPASS

Before 5 min. Mean Diff. Significance

Cvo, (vol9)1 89±0-6 5240 5 - 3-66+0-56 <0-001(A-V) 0, (vol 7'3)73±0-4 5-1±0-4 - 2-27±0-54 <0-001CBFE (ml blood/ml O.) 15-2±1-0 23-4±2-2 8-3 ±2-0 <0-001BP (mmHg)' 79-0±2-1 44-0±2-3 -35-7 ±3-17 < 0-001SVC (mmHg) 114±0 9 1 9±0 7 - 95 ±0 9 <0-001Temperature(°C) 36-3±0-1 35 8±0-2 - 0-5 ±01S <0-01PCV % 41 3±0 9 28-1±0 9 -13-1 ±0-6 < 0-001Paco,(mmHg) 33-0±1-1 35-2+1-1 2-2 ±0-8 <0-05Pao,(mmHg) 104-4±4-4 100-0±6-9 - 4-4 ±6-92 >0-1

"Pulsatile pressures were adjusted to a calculated mean by taking diastolic pressure + (1/3 x pulse pressure).

TABLE IICOMPARISON OF CHANGES OCCURRING DURING FIRST 5 MINUTES OF CARDIOPULMONARY BYPASS IN FOUR

PATIENTS WITH NEUROLOGICAL DAMAGE AND 24 UNDAMAGED SURVIVORS

4 Patients with 24 Undamaged Mean Diff. SignificanceCNS Damage Survivors ± SEM

Age (yr) 53 8 42-3 11-5 ±7-4 NSA4 (A-V)0, (vol ) _ 3-83 - 2 18 - 1-65±1-63 NSJ CBFE (ml blood/mlO) 18-2 7-3 10-9 ±5-74 0-1 > p > 0-054 BP (mmHg) -32-5 -36-2 3-7 ±9 4 NSJ Paco, (mmHg) 2-4 1-8 0-6 ±2-2 NS4T('C) - 0 25 - 0-62 0 37±0-42 NS

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Cerebral blood flow and metabolism during open-heart surgery

preceding the onset. Although the circuit wasarranged to compensate for minor changes inbackground temperature, this could not eliminatethe effects of rapid changes, and there were someminor, transitory temperature changes whichresulted in obviously artefactual signals (Fig. 4)which were discounted.For the group as a whole, there was no signifi-

cant change in integral height following the onsetof perfusion, but there was considerable variationbetween patients, in five of whom there was a

significant fall, whereas in seven there was eitherno change or an increase. There was a greaterincrease in Paco2 and a tendency towards a smallerfall in mean arterial blood pressure in the fivepatients in whom the integral height fell, thanin the seven patients in whom the integralheight either increased or remained unchanged(Table III).

DISCUSSION

A number of the physiological variables whichchange acutely at the onset of cardiopulmonarybypass could influence either cerebral blood flowor cerebral metabolic rate and so lead to theincrease in CBFE which has been documentedhere.

In normal circumstances Paco2 is the mostimportant determinant of cerebral blood flowwhich rises approximately 1 ml/100 g per minutefor each increment of 1 mm in Paco2 (Smith andWollman, 1972). The behaviour of the cerebralvessels when subjected to an alteration in Paco2during perfusion is a matter of dispute (Halley,Reemtsma, and Creech, 1958; Wollman, Stephen,Clement, and Danielson, 1966), but even if theresponse is normal, the predicted increase inCBFE due to the increase in Paco2 in the presentstudy would only be of the order of 6%.The effect of dilutional anaemia on cerebral

blood flow and metabolism was studied in dogsby Michenfelder and Theye (1969), who foundthat a fall in haemoglobin concentration from12 4 to 7'8 g/100 ml (a decrease of 37 1%) resultedin an increase in CBFE from 16-1 to 19-4 mlblood/ml 02 uptake. This was achieved by anincrease in cerebral blood flow, while the cerebralmetabolic rate remained unchanged. In thepresent study a fall in haematocrit from 41-3 to281% (a reduction by 32% of the initial value)was associated with an increase in CBFE from'Thermal conductivity of blood: 506 mW m-1 K-Thermal conductivity of saline: 625 mW m1 K-1(Personal communication, National Engineering Laboratory, EastKilbride)

15 2 to 23-4 ml blood/ml 02 uptake (+54%),which is more than twice the change recorded byMichenfelder and Theye (1969) for a comparabledegree of haemodilution in dogs. Even if the samemechanism applies in man, the increase in CBFEin the present study was out of proportion to thechange in haematocrit.Both cerebral blood flow and metabolic rate

can be influenced by changes in body temperature(Michenfelder and Theye, 1968), but the reductionof only 0-5°C which was recorded in the presentseries could not be expected to change the CBFEby more than approximately 3%.The mean arterial blood pressure fell at the

onset of perfusion to 44 mmHg, which is belowthe value at which, in normal circumstances,autoregulation can preserve a normal cerebralblood flow (Harper, 1965). It is possible, however,that the reduction in cerebral blood flow whichwould be expected to result from this hypotensiondid not occur because the overall flow rate fromthe oxygenator was high (80 ml/kg per minute).This emphasized the need to make some assess-ment of changes in cerebral blood flow at theonset of cardiopulmonary bypass, but many of theconventional measurement techniques are inap-plicable in these circumstances. It is a time whena number of variables change acutely, the lungsare excluded from the circulation, the headvessels are not exposed, and the patient is fullyheparinized so that intra-arterial injection orcannulation is more hazardous than usual. Thethermovelocity technique was selected in spite ofits disadvantages (Ingvar and Lassen, 1965)because it enables small, rapid changes in venousflow to be detected.The height of the integrated signal derived from

the thermovelocity system is inversely propor-tional to the velocity of blood flow past the tip ofthe probe, but velocity and volume flow are onlyrelated consistently if the diameter of the vesselremains constant. A typical calibration curve ofintegral height plotted against volume flow intubing of comparable diameter to the normalinternal jugular vein is shown (Fig. 1). A decreasein the diameter of the vein probably results fromthe abrupt reduction in superior vena caval pres-sure which occurs at the onset of bypass (Table I).Even if the cerebral blood flow did not alter,reduction in the diameter of the vein wouldincrease the velocity of blood flow and so decreasethe height of the integrated thermovelocity signal.In addition, the slight increase in thermal conduc-tivity caused by haemodilution1 would enhancethermal dissipation and so accentuate the pre-

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11 N Y2 tubingT 35°C

10

100 200 300 400 mVmin

FIG. 1. Calibration curve showing change in heightof integrated thermovelocity signal against volumeflow rate.

dicted reduction in integral height. An increase incerebral blood flow would accentuate this reduc-tion in integral height still further, whereas a fallin cerebral blood flow would tend to offset it. Ifthe fall in cerebral blood flow was profound, itwould be sufficient ultimately to obliterate thecombined effect of a decrease in vessel diameterand haemodilution, and the integral height wouldtherefore remain unchanged or even increase(Figs 2-4).

In five out of 12 patients, a significant fall inintegral height was recorded; in the remainingseven instances the integral height either rose orremained unchanged, which, for the reasons out-lined above, implies that the cerebral blood flowhad fallen in these patients. The tendency towardsa greater reduction in arterial blood pressure anda smaller increase in Paco, in this group has beennoted already (Table III).

Unequivocal conclusions cannot be drawn fromthis study because of the limitations of thethermovelocity method, in particular its limitedresolution, the inconsistent relationship betweenvolume and velocity of flow, and the influence ofother factors such as haemodilution. However, the

findings favour the hypothesis that in at least 50O/%of patients, cerebral blood flow falls at the onsetof cardiopulmonary bypass in association withsudden systemic hypotension. This fall occurs inspite of high overall flow rates but may be offsetto some extent by an increase in arterial carbondioxide tension.The combination of hypotension and a fall

in cerebral blood flow, together with a reductionin haematocrit due to haemodilution, mustseriously impair oxygen availability at tissue level(Nunn and Freeman, 1964), and it is of particularinterest that the CBFE rose consistently; thismust indicate a very considerable fall in cerebralmetabolic rate.The increase in CBFE at the onset of perfusion

tended to be greater in patients who sufferedcerebral injury, and arterialization of jugularvenous blood has been recorded previously inpatients suffering from cerebral damage (Shalitet al., 1970; Alexander and Lassen, 1970). Itwould appear that profound cerebral depressionprobably occurs at the onset of cardiopulmonarybypass and that the most likely mechanism is awidespread reduction in oxygen availability,although redistribution of cerebral blood flow,perhaps related to loss of the pulsatile componentof the pressure waveform, may also be important(Sanderson, Wright, and Sims, 1972). High flowrates from the oxygenator confer no protection,and the extent to which the individual patient cantolerate these conditions cannot be predicted. Asudden change in cerebral electrical activity,which is generally detectable with the cerebralfunction monitor, is a valuable warning sign, andprompt treatment of hypotension and the avoid-ance of hypocapnia are useful prophylacticmeasures.

I am grateful to Mr. S. C. Lennox, F.R.C.S., forpermission to study patients under his care. The workhas been supported by a grant from the MedicalResearch Council, and the results will be included

TABLE IIICOMPARISON OF CHANGES DURING FIRST 5 MINUTES OF BYPASS

Group A' Group B' Mean Diff./SEM Significance

CVo2 (vol %) -422 - 507 - 0-85 ±2-28 > 0-14 (A-V)O (vol %) - 2-36 - 1-77 0-59±2-33 > 0-14 CBFE (ml blood/ml O) 6-34 8-50 2-16±6-96 > 0-1A BP (mmHg) -28-8 -490 -20-2 +979 0-1 > p > 005BP at S min (mmHg) 45-0 33-3 -1 1-7 5-7 0-1 > p > 0 05I PatCOi(mmHg) 5-8 1-53 - 4-27+1-76 < 0P05J T(°C) - 0-04 - 0-64 - 0-60+0-44 > 0-1

'Patients in whom height of integral thermovelocity signal fell.'Patients in whom height of integrated thermovelocity signal increased or remained unchanged.

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4FIG. 4. Duration of record 27 min; marker 3 on bypass, marker 4-artefact due to flushing probe with cold saline.FIGS 2-4: Onset ofcardiopulmonary bypass associated with moderate, severe, orprofound hypotension. Recordsfrom abovedownwards: arterial blood pressure, superior vena caval pressure, background temperature with superimposed thermo-velocity pulse, and the cerebralfunction monitor signal. The integrated thermovelocity signal appears as an uncalibrated,step-like trace superimposed on the lower half of the record.

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in a thesis to be presented for the degree of M.D.(Cantab.).

REFERENCES

Alexander, S. C. and Lassen, N. A. (1970). Cerebralcirculatory response to acute brain disease:implications for anesthetic practice. A nesthesi-ology, 32, 60.

Branthwaite, M. A. (1973a). Detection of neurologicaldamage during open-heart surgery. Thorax, 28,464.

- (1973b). Factors affecting cerebral activity duringopen-heart surgery. Anaesthesia, 28, 619.

Cotev, S., Lee, J., and Severinghaus, J. W. (1968). Theeffects of acetazolamide on cerebral blood flowand cerebral tissue P02. Anesthesiology, 29, 471.

Halley, M. M., Reemtsma, K., and Creech, 0. Jr.(1958). Cerebral blood flow, metabolism, andbrain volume in extracorporeal circulation. Jour-nal of Thoracic Surgery, 36, 506.

Harper, A. M. (1965). Physiology of cerebral bloodflow. British Journal of Anaesthesia, 37, 225.

Ingvar, D. H. and Lassen, N. A. (1965). Methods forcerebral bloodflow measurements in man. BritishJournal of Anaesthesia, 37, 216.

Larson Jr., C. P., Ehrenfeld, W. K., Wade, J. G., andWylie, E. J. (1967). Jugular venous oxygen satu-ration as an index of adequacy of cerebraloxygenation. Surgery, 62, 31.

Linden, R. J., Ledsome, J. R., and Norman, J. (1965).Simple methods for the determination of theconcentrations of carbon dioxide and oxygen inblood. British Journal of Anaesthesia, 37, 77.

Lyons, C., Clark, Jr., L. C., McDowell, H., andMcArthur K. (1964). Cerebral venous oxygencontent during carotid thrombintimectomy.Annals of Surgery, 160, 561.

Meyer, J. S., Gotoh, F., Tomita, M., and Akiyama, M.(1966). Cerebral blood flow: new technics forrecording cerebral blood flow and metabolism insubjects with cerebrovascular disease. In:Cerebral Vascular Diseases, edited by C. H.Millikan, R. G. Siekert, and J. P. Whisnant,p. 147. Grune and Stratton, New York andHeinmann, London.

Michenfelder, J. D. and Theye, R. A. (1968). Hypo-thermia: effect on canine brain and whole-bodymetabolism. Anesthesiology, 29, 1107.

- and - (1969). The effects of profound hypo-capnia and dilution anemia on canine cerebralmetabolism and blood flow. Anesthesiology, 31,449.

Nunn, J. F. and Freeman, J. (1964). Problems ofoxygenation and oxygen transport during haemor-rhage. Anaesthesia, 19, 206.

Sanderson, J. M., Wright, G., and Sims, F. W. (1972).Brain damage in dogs immediately followingpulsatile and non-pulsatile blood flows in extra-corporeal circulation. Thorax, 27, 275.

Shalit, M. N., Beller, A. J., Feinsod, M., Drapkin,A. J., and Cotev, S. (1970). Blood flow and oxy-gen consumption of the dying brain. Neurology,20, 740.

Smith, A. L. and Wollman, H. (1972). Cerebral bloodflow and metabolism: effects of anesthetic drugsand techniques. Anesthesiology, 36, 378.

Wollman, H., Stephen, G. W., Clement, A. J., andDanielson, G. K. (1966). Cerebral blood flow inman during extracorporeal circulation. Journal ofThoracic and Cardiovascular Surgery, 52, 558.

Requests for reprints to: Dr. M. Branthwaite,Brompton Hospital, Fulham Road, London SW3 6HP.

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