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13 TRANSCRANIAL DOPPLER

Peter J. Kirkpatrick and Kwan-Hon Chan

13.1 Introduction

The study of large numbers of head-injured patientshas identified clinical and radiological features whichindicate the severity of the initial cerebral trauma.(Born et al., 1985; Jennett et al., 1979; Marshall et al.,1991; Miller, 1985; Miller, 1992). In some individuals,secondary neuronal injury follows the primary injury(Chan et al., 1992a; Gopinath et al., 1994; Kirkpatrick etal., 1995; Miller, 1986; Robertson et al., 1989). Thesesecondary insults may, in part, account for the poorpredictive value of early clinical findings. Untilrecently, the nature of secondary neuronal injuryfollowing severe head trauma has remained elusive.However, modern methods for monitoring variousphysical and biochemical parameters indicate thatpotentially adverse episodes can be detected (Boumaet al., 1992; Chan, Dearden and Miller, 1992; Chan,Miller and Dearden, 1992; Chan, Miller and Piper,1992; Chan et al., 1992a, b; 1993; Cruz et al., 1991; Cruz,1993; Czosnyka et al., 1994a; Jones et al., 1993;Kirkpatrick et al., 1994a, 1995, 1996; Kirkpatrick,Czosnyka and Pickard, 1996) and that some areimportant in terms of prognosis. Low cerebral bloodflow (CBF) values in the first few hours after injury,and profound cerebral hypoxia are events whichpredict a poor outcome (Bouma and Muizelaar, 1990;Chan et al., 1992a; Gopinath et al., 1994). Episodes ofhypoxia, hypotension and reduced cerebral perfusiondue to high levels of intracranial pressure (ICP) areimportant factors that reduce cerebral blood flow andoxygen delivery (Siesjo, 1992). Cerebral ischemiaensues if compensation by increased oxygen extrac-tion is incomplete. Since histological ischemic changesare found in the brains of up to 80% of patients dyingfrom head injuries, the provision for monitoringcerebral ischemic episodes appears important, and hasreceived wide attention (Kirkpatrick, Czosnyka andPickard., 1996). The reliable detection and quantifica-tion of such episodes has, however, proven difficult.

The depth and duration of secondary cerebralischemic episode varies, and recent evidence indicates

that such episodes may last only a few minutes (Cruz,1993; Kirkpatrick, Czosnyka and Pickard, 1996;Robertson et al., 1989). The need for real-time meas-urements is therefore apparent. The imaging methodsfor estimations of CBF and oxygenation using contrastagents and isotopes (xenon-enhanced CT, SPECT andPET) are invasive, and may require transfer of criticalpatients to specialized facilities (Bouma and Muize-laar, 1990; Choksey et al., 1991; Gonalaves et al., 1994;Marion, Darby and Yonas, 1991; Meixensberger, 1993;Obrist and Wilkinson, 1990). Most importantly, theyonly allow isolated estimations which will misstransient secondary episodes. Their routine use in theintensive care of head-injured patients is clearlyinappropriate. In response, monitors that allow thereal-time estimation of cerebral pathophysiologicalparameters have evolved and include the continuousmeasurement of ICP, arterial blood pressure (BP),cerebral perfusion pressure (CPP = BP – ICP), and theindirect estimation of global cerebral oxygenation bymeasuring jugular venous oxygen saturation (SjO2)using jugular venous oximetry. Episodes of low CPPand SjO2 are now recognized as being detrimental(Chan et al., 1992a; Czosnyka et al., 1994a; Gopinath etal., 1994) although the exact values at which cerebralischemia occurs probably varies with time andbetween individuals (Chan, Miller and Dearden,1992). The continuous measurement of CBF for clinicalapplication remains a goal shared by many.

Transcranial Doppler (TCD) provides a means ofmeasuring relative changes in CBF by observing bloodflow velocity (FV) in basal cerebral arteries (Aaslid,Markwalder and Nornes, 1982). The method doesrequire a certain degree of technical expertise, but isnon-invasive, relatively inexpensive and provides real-time information with high temporal resolution. TCDcan be used for measuring flow velocities from severalvessels of the circle of Willis (Aaslid, 1986; Figure 13.1),but most published data refer to the middle cerebralartery (MCA). This vessel has a favorable orientation(see below), is readily accessible to TCD insonation andprovides the most reliable flow velocity signal with a

Head Injury. Edited by Peter Reilly and Ross Bullock. Published in 1997 by Chapman & Hall, London. ISBN 0 412 58540 5


high signal-to-noise ratio. Further, the MCA deliversapproximately 70–80% of the ipsilateral carotid arteryblood flow and can therefore be considered to reflectblood flow to the majority of the ipsilateral cerebralhemisphere. Bilateral real-time estimations are nowavailable using a dual-channel facility. Most commer-cial machines provide analog signals with provision fordigital logging, making on-line analysis of the FVsignal possible and the collection of data on bedsidecomputers convenient.

Before discussing the application of TCD in thehead-injured patient, attention to the theoretical lim-itations of the technique and their relevance inpractical terms is necessary.

For a detailed description of TCD theory, the readeris referred to the excellent descriptions provided byrespected workers in the field (Newell and Aaslid,1992a, b).

13.2 The theory of TCD sonography

13.2.1 PHYSICAL PRINCIPLES

The shift in frequency of a wave when either thetransmitter or the receiver are moving with respect tothe wave propagating medium was described byDoppler in 1843 and is accordingly known as theDoppler effect. The difference in frequency is knownas the Doppler shift.

In a pulsed ultrasound Doppler instrument, thesame transducer is used for both transmitting andreceiving wave energy. The moving blood acts as areflector, first receiving the transmitted ultrasoundwave from the transducer and then reflecting theultrasound wave back toward the transducer.

The simplified formula for the Doppler shift ( f)from the moving blood with a velocity v is:

f = 2 f0v/c

where f0 and c are the frequency and velocity of theemitted ultrasound wave respectively.

Insonation of the basal vessels of the circle of Williswas made possible by the development of a highfrequency pulsed Doppler technique designed topenetrate skull bone. (Aaslid, Markwalder and Nornes,1982). The frequency necessary for transcranial Dop-pler (TCD) applications is in the order of 2 MHz.

It is seldom that blood within a vessel is movingdirectly toward or away from the transducer. Moregenerally, it will be moving in a direction at an angleof insonation to the ultrasound beam. The blood flowvelocity measured using TCD is thus dependent onthe angle of insonation, and can vary according totechnique. For the middle cerebral artery (MCA) theerror is small and of the order ± 3%, since the directionof proximal segment of the MCA is such that, ifextrapolated, it would meet the pterional bone at anear right angle (Figure 13.1).

Figure 13.1 Diagram showing the different anatomical locations of the basal cerebral arteries from which Doppler signalsare obtained. Flow detected from the middle cerebral artery (middle trace) is towards the probe and is shown as a positive(above zero baseline) waveform. This is in contrast to the normal flow direction in the anterior cerebral artery, which is awayfrom the probe (negative flow – upper trace). The posterior cerebral artery also produces a positive waveform.

TRANSCRANIAL DOPPLER MEASUREMENTS 245

The TCD recorded velocity varies with the realblood velocity according to the cosine of the angle ofinsonation. For angles of insonation between 0 and30°, the observed velocity varies between 0.87 and 1.0of the true velocity. The anatomical limitations fortranstemporal insonation of the MCA are such thatsignal capture is only possible at narrow angles. Thusthe observed velocity is a close approximation of truevelocity at a typical depth of insonation of 5–6 cmfrom the scalp surface (1 cm less for children). Otheranterior circulation basal vessels have a less favorableorientation, hence variation in FV derived from themis much more dependent on the technique of insona-tion (Figure 13.1).

13.2.2 RELATIONSHIP BETWEEN INTRACRANIALMCA BLOOD FLOW VELOCITY AND CBF

TCD measures the velocity of red blood cell movingwithin a vessel. It has a single dimension per unit oftime (usually quoted in cm/s). In contrast, CBF is athree-dimensional measure of volume of blooddelivered per unit of cerebral tissue per unit of time(usually quoted in ml/100 g/min). The two para-meters are quantitatively different; hence the correla-tion between absolute values of FV and CBF is poor.However, provided the cross-sectional area of theinsonated blood vessel remains constant, the CBF andFV should vary directly with one another. The MCAdiameter appears to be relatively constant underchanging conditions of BP and carbon dioxide tensionin the normal brain, as demonstrated in healthyvolunteers (Aaslid et al., 1989; Dahl et al., 1989; Newellet al., 1994) thus good correlations between relativechanges in FV and CBF have been reported experi-mentally (Barzo et al., 1991; Czosnyka et al., 1994c;Richards et al., 1995) and in clinically stable patients(Bishop et al., 1986; Romner et al., 1991). However inunstable patients with acute brain injury, the MCAdiameter may be altered by changes in ICP and theeffects of vasospasm, reducing the reliability of therelationship between relative CBF and FV (Kontos,1989).

Some workers have indicated that the relationshipbetween FV and CBF varies according to the level ofCBF, with a stronger correlation occurring when CBFwas low (less than 20 ml/100 g/min; Halsey, McDowelland Gelmon, 1986). These observations may reflectdifferent states of autoregulation and a changing MCAdiameter, although pressure autoregulation is believedto primarily involve the microcirculation rather thanmedium sized vessels. Alternatively, the flow charac-teristic of the formed elements may change at differentflow rates, and become non-laminar at extreme valuesfor CBF thus varying the relationship between flow andvelocity. The variable relationship between absolute

FV and absolute CBF is a clear disadvantage, reflectedby the normal variation in MCA FV of between 35 and90 cm/s in the awake resting state. Thus TCD demandscaution in interpretation when attempting to estimateCBF from FV data in isolation of other parameters inhead-injured patients.

13.3 TCD measurements

Three main pathways to access the intracranial arter-ies can be employed. They comprise the transtemporalapproach through the thin bone above the zygomaticarch to the anterior, middle and posterior cerebralarteries and circle of Willis, the transorbital approachto the carotid siphon, and the suboccipital route to thebasilar and vertebral arteries. The transtemporalapproach is usually employed in critically ill patients.In expert hands, about 5% of the individuals will yieldan unsatisfactory image employing the temporalwindow (Aaslid, 1986; Harders and Gilsbach, 1985;Harders, 1986).

Through the temporal window, the middle (MCA),anterior (ACA) and posterior (PCA) cerebral arteriescan be readily examined (Figure 13.1). In each patient,the same insonation window should be used through-out the entire study period. This could be accomplishedby putting a small marker at the patient’s temporalregion. The Doppler examination begins with theidentification of the bifurcation of the intracranialportion of the internal carotid artery into the MCA andACA according to the method described by Aaslid(1986). This bifurcation can usually be identified at adepth of 60–65 mm. The typical Doppler signal fromthe carotid bifurcation is shown in Figure 13.2, whichconsists of images above and below the xero line ofreference representing the flow directions towards andaway from the ultrasound probe of the MCA and ACArespectively. The depth of insonation is then reduced tofollow the upward deflection image of the MCA flowvelocity as the vessel runs towards the skull. The MCAcan usually be traced up to a depth of 30 mm, which isbeyond the bifurcation of the MCA into the peripheralbranches. The proximal portion of the main trunk of theMCA (the M1 segment) can be located at a depth ofaround 45–55 mm. The depth which gives the highestvelocity is usually chosen for measurement. In chil-dren, the depth which gives the highest MCA velocityis usually 10 mm less than that of adults, but the sameprinciples apply. This method of obtaining the MCAsignal eliminates the possibility of mistaking the PCAfor the MCA because the PCA signal cannot beobtained at a depth less than 55 mm for anatomicalreasons (Aaslid, 1982; Lindegaard, 1989). Mistaking thePCA for the MCA would introduce a major error intovelocity measurement due to the lower velocity of theformer vessel.


After the MCA signal is obtained, the depth ofinsonation is increased so that the image of the carotidbifurcation can be seen again; the depth is increasedfurther with the probe directed slightly anteriorly sothat the ACA image can be found. The first part of theACA (the A1 segment) is recognized by a direction offlow that is away from the probe. With the identifica-tion of the ACA, the depth of insonation is decreaseduntil the carotid bifurcation signal is obtained. Theprobe is then angled slightly posteriorly until thesignal of the PCA is seen. The PCA can be dis-tinguished from the MCA signal by a lower flowvelocity and failure to obtain the PCA signal when thedepth of insonation is decreased much below 55 mm.The velocity parameters measured included the peaksystolic velocity (S), end-diastolic velocity (D), thetime-averaged mean velocity (M) and the pulsatilityindex (PI). The latter is defined as S-D/M. The timedmean velocity and PI are calculated by the Dopplermachine by averaging the signals from a number ofcardiac cycles by fast Fourier transformation, whicheliminates error as a result of beat-to-beat and respira-tory variations. Beat-to-beat variation in adults sug-gests that about five heart beats are adequate formeasurement (Burns, 1987).

13.3.1 LONG-TERM TCD MEASUREMENT ON THEINTENSIVE CARE UNIT – PRACTICALCONSIDERATIONS

Fixation of the probe for continuous monitoring ismost conveniently achieved in the pterional region.Both solid and elasticized devices are available for

probe fixation. None provide a universally acceptedmeans of keeping the probe fixed in an identicalorientation in the hostile environment of the intensivecare unit. With an elasticized band we have achievedan approximately 60% signal reliability for MCAinsonation in patients monitored over several days(Kirkpatrick et al., 1995). Nursing education is anessential part of this process, and it is vital to inspectthe band and probe regularly to check for pressuresore development. The latter complication usuallyresults from placement across injured scalp and bonyprominences. Elasticized bands should only beapplied across such areas with extreme care, since therisk of scalp swelling and necrosis is increased. Thesolid frame variety provides the advantage thatprobes can still be applied to those patients withsignificant scalp trauma and/or postoperative scalpflaps. However, they are bulky and cumbersome, andprobe displacement is more likely during nursingmaneuvers. It is clear that there is room for consider-able improvement in the design of attachment devicesfor the purpose of long-term TCD monitoring.

The advantage of continuous monitoring is theestablishment of stable baseline conditions of vari-ables that may affect FV over intermediate periods oftime. These variables include the insonation angle,arterial oxygen and CO2 tension, blood pressure,different anesthetic agents and hemoglobin levels(Newell and Aaslid, 1992b). These concerns may beoverstated, since the basal cerebral arteries, do notappear to dilate or constrict significantly with vascularresistance and/or anesthetic changes (Matta and Lam,1995; Schregel et al., 1992, 1994). Blood pressure and

Figure 13.2 Doppler tracing showing the carotid bifurcation.

SIGNAL PROCESSING AND DATA COLLECTION 247

carbon dioxide tension, important determinants ofcerebrovascular resistance, have little effect on thediameter of the basal arteries (Huber and Handa,1967). Some potent vasoactive agents (e.g. sodiumnitroprusside) have only a small effects on thediameter of basal cerebral vessels (Giller et al., 1993),whereas others (e.g. nitroglycerin) demonstrate sig-nificant vasodilatation (Dahl et al., 1989). While mostreport the diameter of the proximal MCA to beresistant to cerebrovascular variables, it would seemprudent to maintain stability during acquisition ofTCD-related data. Under such stable conditions, FVchanges are likely to reflect changes in CBF ratherthan changes in MCA diameter or technicalvariation.

13.4 Signal processing and datacollection

13.4.1 COMPUTERS

A computer-based system is essential for logging,collating and processing the large volume of dataacquired by TCD. Recognizing the changing cer-ebrovascular hemodynamics demands reliable mon-itoring techniques and sophisticated signal analysiswhich can only be provided by dedicated computersupport.(Czosnyka et al., 1994f; Kirkpatrick, Czosnykaand Pickard, 1996). Contemporary systems includesophisticated multichannel digital recorders withoptions for complex signal processing. The consider-able flexibility of such systems permits signal analysisand presentation of information that is comprehen-sible to medical and nursing staff. The importance ofmonitoring multiple variables to increase the power ofdata interpretation is increasingly recognized.

13.4.2 DERIVATIVES OF FV

Signal analysis can produce large volumes of informa-tion, leading to a state of data chaos. The recording ofuser-defined targeted variables is therefore mostdesirable. Various TCD signals recorded from flow offormed elements within the MCA generate a spectrumof flow velocities that are presented as a waveform(Czosnyka et al., 1994d). The mean FV of the spectrumtheoretically varies with CBF and is therefore usuallypresented. Since MCA flow is laminar, the maximumFV (FVmax) varies in proportion with the mean FV. Thuscommercial machines take advantage of the superiorsignal-to-noise ratio with FVmax and calculate FVmeanfrom the area under the curve. The FVmax signal isfrequently displayed as a FV envelope which can beresolving into FVmax during diastole (FVd) and FVmaxduring systole (FVs). It is these two components thatdefine the pulsatility of the waveform (Figure 13.3).

13.4.3 PULSATILITY INDICES

The MCA FV waveform observed using TCD isdependent on the arterial blood pressure waveformand the viscoelastic properties of the cerebrovascularbed provided the blood rheology remains constant.Thus, if variables such as MCA diameter and BPremain constant, the pulsatility of blood flow throughthe conductance vessel reflects distal cerebrovascularresistance (Czosnyka et al., 1994b; Gosling and King,1974; Lindgaard, 1992). Common determinants ofchanging MCA pulsatility include CO2 tension andCCP. Several indices describing the pulsatility of bloodhave been formulated, the most commonly adopted isthe pulsatility index (PI) of Gosling:

Gosling PI = (FVs – FVd)/FVmean = FVamp/FVmean.

The key advantage of the Gosling PI is that it isdimensionless and therefore independent of samplingtechniques, provided the signal-to-noise ratio is goodand the gain setting of the instrument is constant.Most TCD software packages calculate the PI index asaveraged from several cardiac cycles. However, takenalone the PI cannot distinguish the cause of the flowpattern change (that is, an increase in PI can be due tocerebral vasoconstriction or to high ICP), and it needsto be interpreted in the light of other data.

Figure 13.3 Relationship between the components of FV(FVs and FVd) with changing CPP during a plateau wave ofraised ICP and low CPP. As CPP falls, FVd is proportionallyaffected to a greater extent than FVs resulting in thedivergence of these parameters, hence an increase in the pulseamplitude (FVs minus FVd) of the waveform is seen. ICP =intracranial pressure (mmHg); CPP = cerebral perfusionpressure (mmHg); FV = middle cerebral artery flow velocity(cm/s); FVs = FV during systole; FVs = FV during diastole.(Source: redrawn from Czosnyka et al., 1994b.)


(a)

(b)

Figure 13.4 (a) Continuous recordings of ICP, CPP and LDF signals during waves of raised ICP in a patient with a diffusehead injury. Variations in relative CBF, estimated from FV, were closely coupled to changes in CPP indicating a state of non-autoregulation. (b) Regression analysis of the FV and LDF signal data from the period of recording shown in (a). The closecorrelation indicates coupling between medium vessel flow and capillary perfusion. ICP = intracranial pressure (mmHg);CPP = cerebral perfusion pressure (mmHg), FV = right middle cerebral artery flow velocity (cm/s); LDF = laser Doppler fluxfrom the right frontal region; AU = arbitrary units. (Source: reproduced from Kirkpatrick et al., 1994a, with permission.)

ANALYSIS USING TCD IN HEAD-INJURED PATIENTS 249

Thus TCD provides a basis for cerebrovascularinvestigations in head-injured patients. These includethe non-quantified monitoring of changing CBF, cer-ebrovascular autoregulatory reserve, cerebrovascularreactivity, cerebral perfusion pressure, cerebral hyper-emia, post-traumatic spasm and the estimation ofcerebral tamponade.

13.5 Results of analysis using TCD inhead-injured patients

13.5.1 MEASUREMENT OF RAW BASELINE FV DATA

Collection of intermittent mean FV data from head-injured patients is of limited use (Chan, Miller andDearden, 1992; Weber, Grolimund and Seiler, 1990).Chan, Miller and Dearden (1992) report that inseverely head-injured patients (GCS < 8), the mean FVat admission was lower than in those with less severehead injuries. Further, the mean FV remaineddepressed in those same patients. However, thedispersal of data points was so wide that rawadmission FV data was not a useful predictor ofoutcome for individuals except where very low FV

was encountered (less than 28 cm/s = 80% death rate).These findings are not surprising, bearing in mind thevariables that affect FV measurements in these unsta-ble patients.

Continuous monitoring of mean FV is potentially ofvalue when used purely as a non-quantified trendrecorder, where dynamic changes from a variablebaseline are considered (Kirkpatrick et al., 1994a;Kirkpatrick et al., 1995; Newell et al., 1992). Ourexperience in Cambridge of continuous multimodalitymonitoring systems, indicates that the TDC is able todetect transient changes in relative CBF with highresolution (Kirkpatrick et al., 1994a; Kirkpatrick,Czosnyka and Pickard, 1996). Thus, episodes lastingbetween 12 and 70 minutes were seen which corre-sponded to cortical cerebral perfusion changes asassessed using laser Doppler flowmetry (Figure13.4(a)). The correlation between relative changes washigh (Figure 13.4(b)) and could help to distinguishbetween rises in ICP associated with low CPP andthose associated with hyperemia (Figure 13.5). Instan-ces where there was significant uncoupling betweenFV and cortical perfusion were rare (Figure 13.6). It isthe high dynamic resolution provided by TCD and the

(a) (b)

Figure 13.5 (a) Recording of an event characterized by intracranial hypertension with an increase in ICP. A relative dropin CBF is predicted from the fall in FV which is associated with cerebral desaturation (SjO2 and HbO2 signal changes).(b) Recording suggesting cerebral hyperemia. In this event synchronous increases in all recorded parameters occurredduring the rise in ICP. ICP = intracranial pressure (mmHg), CPP = cerebral perfusion pressure (mmHg), Fv = right middlecerebral artery flow velocity (cm/s) HbO2 = oxygenated hemoglobin (�mol/l); tHb = total hemoglobin concentration(�mol/l), SjO2 = right jugular venous oxygen saturation (%). (Source: reproduced from Kirkpatrick et al., 1995, withpermission.)


correlation with other hemodynamic modalities thatare proving encouraging to neurointensivists employ-ing the technique as a real-time monitor.

13.5.2 AUTOREGULATION IN HEAD INJURY

Cerebral autoregulation describes the cerebrovascularreflexes that maintain CBF during changing CPP(Paulson, Olesen and Edvinsson, 1990). Failure ofautoregulation, which is frequent after severe headinjury, may aggravate cerebral ischemia during peri-ods of relative poor perfusion.(Miller, 1985; Siesjo,

1992). Thus the autoregulatory status of the cerebralvasculature may provide an index of injury severity,help define the cerebrovascular reserve and indicatethe susceptibility of individuals to secondary ischemiaduring low cerebral perfusion (Marmarou et al., 1991).Assessment of autoregulation using TCD depends onthe assumption that relative changes in FV correlatewith relative changes in CBF. Thus, if autoregulationis intact, FV should remain constant with a changingCPP. Conversely, if autoregulation has failed, then therelation between CPP and FV becomes linear (Figures13.3, 13.7) The value of CPP at which autoregulation

Figure 13.6 An abrupt rise in ICP and fall in CPP recorded during attempted withdrawal of dopamine inotropic support.Simultaneous falls in FV and LDF occurred. On recovery of CPP a transient hyperemia was registered by LDF, but not byFV, indicating uncoupling of flow in different sized vessels. ICP = intracranial pressure (mmHg); CPP = cerebral perfusionpressure (mmHg), FV = right middle cerebral artery flow velocity (cm/s); LDF = laser Doppler flux from the right frontalregion; AU = arbitrary units. (Source: reproduced from Kirkpatrick et al., 1994a, with permission.)

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fails and FV begins to fall is called the autoregulatory‘threshold’ or ‘break point’. Since the autoregulatorythreshold is dependent on PCO2 levels – in states ofhypercapnia the threshold is exceeded at lower levelsof CPP (Markwalder et al., 1984; Paulson, Olesen andEdvinsson, 1990) – this variable has to be keptconstant for repeated evaluations.

The autoregulatory status can be assessed usingTCD in a variety of ways. Formal lowering of bloodpressure is no longer considered ethical in the head-injured. Observing the responses to spontaneouschanges in BP is an alternative (Czosnyka et al., 1994b),but such transients are infrequent, often of lowmagnitude, and assessments cannot be made atdesignated times. This is especially so in the presentera of promoting a high CPP with fluid replacementsand inotropes (Rosner, Rosner and Johnson, 1991).However, transient falls in CPP can be safely inducedby a three second carotid compression, or for longerperiods (20–30s) by inflating and releasing large bloodpressure cuffs applied to the legs (Czosnyka, Pickardand Whitehouse, 1992; Giller, 1991; Smielewski et al.,1996). These indirect methods have been employed forbedside assessments, but the results are technique-dependent. Although such methods have confirmedthat autoregulation is more frequently absent in themost severe head-injured patient (Chan, Miller andDearden, 1992; Czosnyka et al., 1994e; Steiger et al.,1994; Wong, Piper and Miller, 1994), further evaluationis required.

The continuous assessment of the TCD wave profileis potentially a sophisticated way of estimatingcerebral autoregulation. Thus with falling CPP, FVdwill reach the autoregulatory threshold before FVs,resulting in divergence of these parameters and anincrease in pulse amplitude and PI (Figure 13.3). Thus adecline in FVd, and an increase in PI gives an earlierwarning of impending autoregulatory failure than doesFVmean. If FVs also falls with a drop in CPP, then allcomponents of the FV waveform have reached theautoregulatory threshold, indicating a severelydepleted cerebrovascular reserve. An evaluation of thegradient of linear regression between the two maincomponents of the FV waveform (FVs and FVd) and theCPP show that patients with failure of autoregulationin both components are most likely to have anunfavorable outcome when compared to those patientswho have intact autoregulation or failed autoregula-tion in FVd alone (Figure 13.7; Czosnyka et al., 1995).

13.5.3 NON-INVASIVE ASSESSMENT OF CPP

From the above considerations, it can be seen that thedifferent FV parameters may be used to indicatefailing autoregulation. If this occurs at a consistentvalue of CPP between individuals, then changes in FV

may provide a non-invasive estimation of CPP. Themost sensitive index of falling CPP is the increase inFV amplitude due to divergence of FVs and FVd(Figures 13.3, 13.7). By calculating the PI from FVamplitude and FVmean, an index of falling CPP isprovided which is independent of the angle of insona-tion (Figure 13.8). Clinical experience has demon-strated a close correlation between CPP and PI. Chanet al. (1992a) demonstrated a better correlationbetween CPP and PI than between FVmean and CPP,and this relationship was independent of the mecha-nism of reduced CPP (hypotension or raised ICP).Two breakpoints were identified on the CPP/PI curveusing sequential linear regressions: PI was independ-ent of CPP when the latter was above 70 mmHg;between 70 and 20 mmHg the PI increased (r = 0.767,p < 0.0001, n = 41); and below 20 mmHg PI roserapidly. Thus at a CPP of between 20 and 70 mmHgautoregulation is impaired but not completelyexhausted. Other groups have confirmed the existenceof a relationship between CPP and PI (Aaslid et al.,1986; Czosnyka et al., 1994e; Newell et al., 1993),although different breakpoints are quoted that prob-ably reflect methodological variation (anestheticagents and differences in the preferred level of CO2maintenance). Since the PI is dependent on BP, astandardized pulsatility index (SPI) can be calculated(SPI = PI/BP), which promises to improve the con-vergence of data describing the relationship between

Figure 13.8 Relationship between the pulsatility index ofthe FV waveform (PI) and CPP. At high CPP values PIremains constant. At low CPP values PI increases rapidly.The exact threshold for CPP at which PI starts to increasediffers among patients, and can vary in the same patient atdifferent times. However, pooled data from different sourcesindicates that the threshold lies between 55 and 75 mmHg.(Source: redrawn from Czosnyka et al., 1994e.)

ANALYSIS USING TCD IN HEAD-INJURED PATIENTS 253

CPP and pulsatility (Kirkpatrick et al., 1993). Thiswork raises the concept of a therapeutic windowexisting between the completely intact autoregulatorystate and the completely exhausted autoregulatorystate, the equivalent of the ‘transient’ zone describedin experimental animals using TCD and laser Dopplermethods (Czosnyka et al., 1994c; Nelson et al., 1992;Richards et al., 1995).

Mathematical models can be generated that attemptto predict the CPP and cerebral autoregulatory statusof the cerebral circulation from TCD FV waveformanalysis. Aaslid and colleagues (1986) and Czosnyka etal. (1994b) have suggested different formulae relatingCPP with flow velocity amplitude, flow velocity meanand BP amplitude. The difficulty encountered by thesegroups is that the convergence of data points frompooled patient groups is relatively low, makingprediction of CPP for individuals imprecise. Further,the various thresholds described for CPP, FV and PImay vary for any patient with time (Chan, Miller andDearden, 1992).

13.5.4 RELATIONSHIP BETWEEN TCD CHANGESAND OTHER CEREBRO-HEMODYNAMIC VARIABLES

Cerebral tissues can tolerate limited changes in CBFbefore metabolic requirements fail and neuronal func-tion becomes compromised. (Wong, Piper and Miller,1994). Thus a fall in CPP below certain thresholdsresults in loss of cerebral electrical activity and, onfurther reduction, loss of membrane stability resultingin neuronal death. Failure of pressure autoregulationdoes not necessarily indicate impending cell death,since the CPP threshold for pressure autoregulatoryfailure and metabolic failure may be different. By

employing continuous multimodality monitoringtechniques, the response of both CBF and cerebralmetabolic variables to changing CPP can be observedin individual cases (Chan et al., 1992a; Kirkpatrick etal., 1995). Transient episodes of cerebral hypoperfu-sion due to hypotension or ICP plateau wave activityusually result in relative falls in CBF, and cerebraloxygenation (Figure 13.5(a)). A delay in the fall intissue oxygenation (read with near-infrared spectro-scopy and jugular venous oximetry) of approximately2 minutes is seen after the fall in CPP, suggesting thatparenchymal desaturation is secondary to the changein tissue perfusion.

By pooling intermittent data from patients in whomCPP and SjO2 measurements were recorded, a thresh-old of 71 mmHg was found below which SjO2 fell (r =0.78, p < 0.0001, n = 22; Chan et al., 1992a). This isalmost identical to the CPP threshold defined by PI(see above; Figure 13.8), suggesting that pressureautoregulatory failure defined by TCD does imply theonset of cerebral desaturation and the need forincreased oxygen extraction (Figure 13.9). The precisethreshold at which neuronal injury ensues has yet tobe defined and awaits the identification and monitor-ing of products of neuronal damage in the venouseffluent. Despite this, some reputable centers nowadvocate the maintenance of CPP above 70 mmHg,with very impressive results (Miller, 1992; Rosner,Rosner and Johnson, 1991).

13.5.5 CEREBROVASCULAR REACTIVITY IN HEADINJURY

Cerebrovascular reactivity describes the near linearrelationship between cerebral artery CO2 levels and

Figure 13.9 Composite plot of cerebral perfusion pressure (CPP) versus jugular venous oxygen saturation (SjO2) anddoppler pulsatility index (PI) showing the CPP breakpoint of 70 mmHg.


CBF, and can be tested by observing the change in FVin response to changes in CO2 (Dahl, 1992; Klingelho-fer and Sander, 1992; Markwalder et al., 1984; Mar-marou et al., 1991; Romner et al., 1991; Schalen,Messeter and Nordstrom, 1991; Smielewski et al., 1994,1995; Strebel et al., 1994). In normal individuals, a1kPa increase in CO2 causes (on average) a 22%increase in MCA FV, and thus TCD has been used toassess CO2 reactivity in many clinical situations.Reduced or absent CO2 reactivity indicates that theability of the cerebrovascular bed to vasodilate isdepleted hence indicating loss of cerebrovascularreserve. Thus CO2 reactivity may provide predictiveinformation in patients with severe head injuries.Klingelhofer and Sander reported on patients withraised ICP due to cerebral hemorrhage, indicating thatthe long term outcome was worse in those withimpaired CO2 reactivity (Klingelhofer and Sander,1992). The same appears true of head-injured patients(Grosset et al., 1993; Schalen, Messeter and Nordstrom,1991). The use of acetazolamide, a potent cerebralvasodilator, cannot assess vasoconstriction and hasnot been employed in head-injured patients.

13.5.6 ABNORMALLY HIGH FV IN HEAD INJURY

Elevated levels of FV can either indicate a narrowedMCA (vasospasm or stenosis) or high CBF (hyper-emia). Both vasospasm and hyperemia are wellrecognized following head injury (Chan, Dearden andMiller, 1992; Chan et al., 1992b; Compton and Teddy,1987; Muttaqin et al., 1993) and since they demand adifferent therapeutic response their distinction ispotentially important (Pickard and Czosnyka, 1993).If vasospasm is suspected, one can insonate theextracranial internal carotid FV and calculate theLindegaard ratio (FVmca/FVica; Lindegaard et al.,1988). Vasospasm is likely when this ratio exceeds 3(Aaslid et al., 1986). Cerebral vasospasm after severehead injury has long been recognized (Macphersonand Graham, 1973) and is frequently associated withtraumatic subarachnoid blood. The flow velocitiesrecorded in such cases are usually between 100 and150 cm/s, hence lower than those found after aneur-ysmal subarachnoid hemorrhage, and the time courseis also shorter, occurring within the first 2–5 days.Nevertheless, CBF can be significantly impaired withischemic consequences (Chan et al., 1992b). Earlyevidence from randomized trials suggests that suchpatients may benefit from cerebral calcium antago-nists (European Study Group, 1994).

Protracted cerebral hyperemia is also recognizedfollowing head injury, especially in children (Bruce etal., 1981; Muizelaar et al., 1989). Transient elevationsin FV due to hyperemia may also occur, and can becaptured with multimodality monitoring using near-

infrared spectroscopy. Such episodes are accompaniedby highly correlated elevations in ICP, FV, SjO2 andtotal blood volume (Figure 13.5(b)). Chan et al. (1993)described a waveform notch in diastole in non-hyperemic patients with increased Fv (Figure 13.10).The importance of recognizing hyperemia as a causeof pathologically raised ICP is that conventionalmethods for treating elevated ICP (such as mannitol,and inotropes/colloid to elevate CPP) will increaseCBF and worsen the intracranial hypertension.

13.6 Role of TCD in monitoring therapy

TCD allows the opportunity to observe the responseof the MCA FV to different therapies (Chan et al., 1993;Eng et al., 1992; Schregel et al., 1992; Thiel et al., 1992).When therapy was instigated to improve CPP (n = 22),a linear relationship with PI (r = 0.941, p < 0.0001) andSjO2 (r = 0.837, p < 0.0001) was seen with a CPPthreshold at 70 and 68 mmHg respectively, abovewhich the correlations disappeared (Chan et al., 1993;Figure 13.11). These thresholds are virtually identicalto those seen during spontaneous changes in CPP (seeabove). In the same group of patients, treatment withhypnotics frequently caused falls in CPP, SjO2 and PIby virtue of arterial hypotension.

The real-time facility offered with a secured TCDprobe can also be used to monitor the dynamicresponse to therapy (Eng et al., 1992; Kirkpatrick et al.,1994b; Kirkpatrick, Czosnyka and Pickard, 1996; May-berg et al., 1993; Schregel et al., 1992; Thiel et al., 1992).The response to an infusion (n = 23) of a 200 ml bolusof mannitol has been compared with that of apreceding bolus of 200 ml saline, both given over 20minutes in 14 severely head-injured patients withraised ICP (Figure 13.12(a)). After mannitol only, a fall

(a)

(b)

Figure 13.10 Doppler tracing showing waveforms of(a) non-hyperemic and (b) hyperemic increase in Dopplerflow velocity.

SUMMARY 255

in ICP (–21%) was accompanied by an increase in FV(+13%, p < 0.001) and fall in cerebrovascular resistance(Figure 13.12(b)). The effect of mannitol on FVdecayed exponentially with a time constant of 34.0minutes (Figure 13.12(c)) and was independent of thepressure autoregulatory status of the patient (Kirkpa-trick et al., 1994b; Kirkpatrick, Czosnyka and Pickard,1996).

Although this data is of greater scientific interestthan clinical relevance, the short-term manipulation ofcerebrovascular hemodynamics is gaining in impor-tance. Bearing in mind the short duration of manysecondary events, continuous TCD is of use in theirrapid detection and in monitoring the subsequentresponse to chosen therapy. This is especially impor-tant if potentially dangerous maneuvers, such ashyperventilation in states of cerebral oligemia, are tobe avoided (Gold, 1989).

13.7 TCD in the diagnosis of brain death

From Figure 13.3 it can be seen that, as CPP falls, FVdapproaches zero and forward movement of blood onlyoccurs during systole. When CPP falls further, a stateof reverberant flow can be seen, where reverse flowoccurs during diastole. It is at this point that a veryhigh PI is seen. Once backflow during diastole equalsforward flow during systole (oscillating flow pat-tern), no net flow of blood occurs and cerebraltamponade in the territory of the insonated vessel iscomplete (Feri et al., 1994; Hassler, Steinmetz andGawlowski, 1988; Hassler, Steinmetz and Pirschel,1989; Newell, Grady and Sirotta, 1989; Perry et al.,1990; Werner et al., 1990). Multimodality monitoringusing laser Doppler flowmetry and TCD during

cerebral tamponade has shown that positive flowthrough the basal arteries can be seen after the patienthas coned with no net flow through the capillary bed(Figure 13.13; Kirkpatrick et al., 1994a). Such real-timeobservations concur with the reports using angio-graphic techniques, showing that the basal cerebralarteries remain patent during early stages of circu-latory arrest (Hassler, Steinmetz and Gawlowski,1986). One explanation for this phenomenon would bethe presence of internal cerebrovascular shunts thatbypass the parenchymal small vessel networks, rein-forcing the concept that initial blood flow obstructionoccurs at the level of the capillary.

Although high specificity and sensitivity have beenreported using various TCD criteria for brain death(Perry et al., 1990), false positives have been reported,more commonly in children. Consequently, TCDmeasurements have not been included in the formaltesting for brain death. At present TCD can beconsidered as a useful diagnostic aid in patients whoare progressing towards brain tamponade.

13.8 Summary

Although measurement of basal vessel FV using TCDhas restrictions in terms of quantification and spatialresolution, monitoring of the MCA FV in head-injuredpatients has produced data that have improved ourunderstanding of cerebral hemodynamic changes fol-lowing cerebral injury. The most important contribu-tion has been derived from observing the FV changeswith falling CPP and the evolution of the concept thatCPP should be maintained above a certain thresholdlevel. That threshold is different between patients, butan ‘average’ value of between 60 and 70 mmHg would

(a) (b)

Figure 13.11 (a) Plot of cerebral perfusion pressure (CPP) versus jugular venous oxygen saturation (SjO2), showing CPPbreakpoint after intracranial pressure (ICP) reduction therapy. (b) Plot of CPP versus Doppler pulsatility index (PI), showingCPP breakpoint after ICP reduction therapy.


(a)

(b)

(c)Figure 13.12 (a) A graphical display of multiple parameters measured during a 200 ml infusion of mannitol (20%), which waspreceded by an identical infusion of normal saline (arrowheads). Mannitol caused a rapid increase in FV and LDF signals,which was associated with a fall in ICP. These changes were not seen after saline. BP remained unchanged throughout therecording period. (b) Mean changes in FV (± s.e. of mean) recorded over approximately 60 minutes during and after a singlemannitol infusion from patients with diffuse head injuries (number of infusions = 23). The first point for each recordingrepresents the start of infusion, which was complete at t = 0 min. In all patients a rise in FV was seen, which decayed soon aftercompletion of infusion. Mean change in FV for all mannitol infusions shown. (t = 0: time of completion of infusion ofmannitol; t = 15: 15 minutes after completion of mannitol.) (c) The decay of the effect of mannitol on FV after completion ofmannitol infusion (time = 0 minutes). The FV has been normalized to a relative baseline of 1 and maximum effect of 2. The fallof FV fits an exponential model with a decay time constant of 34 minutes. ICP = intracranial pressure (mmHg); BP = meanarterial blood pressure (mmHg), FV = right middle cerebral artery flow velocity (cm/s); LDF laser Doppler flux from the rightfrontal region; AU = arbitrary units. (Source: reproduced from Kirkpatrick et al., 1996, with permission.)

SUMMARY 257

Figure 13.13 Progressive fall in CPP during cerebral coning in a head-injured patient who did not respond to treatment.The progressive failure of microcirculatory flow is seen in the decline in the LDF signal. FV remained positive and laterbecame reverberant. ICP = intracranial pressure (mmHg), CPP = cerebral perfusion pressure (mmHg), FV = right middlecerebral artery flow velocity (cm/s); LDF laser Doppler flux from the right frontal region; AU = arbitrary units. (Source:reproduced from Kirkpatrick et al., 1994a, with permission.)

seem appropriate for most individuals. Other con-tributions include the facility to discriminate betweendifferent causes of raised ICP in real time, allowing anearlier, more targeted hence more appropriate,approach to therapy. Thus TCD can be used to

distinguish between raised ICP due to cerebral hypo-perfusion, and that due to hyperemia.

Future development of TCD in head injury appearsto lie in its incorporation into multimodality monitor-ing systems, allowing identification of thresholds for


neuronal injury. Dynamic monitoring is also likely tobe of considerable use in the evaluation of compoundsthat aim to assist the injured brain by mechanisms thatimprove CPP or affect the cerebral vasculature.

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