Role of transcranial Doppler in neurocritical care

Maher Saqqur, MD, FRCPC; David Zygun, MD, MSc, FRCPC; Andrew Demchuk, MD, FRCPC

T ranscranial Doppler (TCD) isincreasingly utilized in pa-tients with life-threateningneurologic injury. The pur-

pose of this review is to provide an ac-count of the common indications for TCDin the neurocritical care unit. The mostwidespread application of TCD is for thedetection of vasospasm in patients withsubarachnoid hemorrhage (SAH). In ad-dition, TCD is being studied as a nonin-vasive estimator of intracranial pressure(ICP) and cerebral perfusion pressure(CPP) in patients with severe traumaticbrain injury. TCD-based assessment ofcerebral pressure autoregulation and CO2

reactivity has been shown to have prog-nostic implications and holds the poten-tial to allow for individualization of ther-apy. Finally, TCD has been extensivelystudied in the setting of clinical braindeath.

Subarachnoid Hemorrhage:Detection of Vasospasm

Cerebral vasospasm is a delayed con-traction of the cerebral vessels that isinduced by blood products that remain incontact with the cerebral vessel wall after

SAH (1). Vasospasm usually begins aboutday 3 after SAH onset and is maximal byday 6 to day 8. It is often responsible forthe delayed ischemic neurologic defectsseen in SAH patients (2). In addition,patients with severe vasospasm have sig-nificantly higher mortality than thosewithout vasospasm. The most commoncause of SAH is the spontaneous ruptureof a cerebral aneurysm (3). Other causesinclude head injury and neurosurgicalprocedures. Vasospasm resulting fromaneurysmal SAH is a well-known compli-cation, occurring in up to 40% of patientsafter an aneurysmal SAH, and carries a15% to 20% risk of stroke or death (4).

This vasospasm was first demon-strated angiographically by Ecker andRiemenschneider (5) as cerebral arterialnarrowing followed SAH course. Cerebralangiography of the brain is consideredthe gold-standard diagnostic test for de-tection of vasospasm. However, this pro-cedure is invasive and not without risk ofcomplication, such as stroke due to cere-bral embolus, dissection, or rupture ofcerebral arteries (6). Almost 20 yrs ago,TCD was proposed for the diagnosis ofcerebral vasospasm (7). The diagnosis ofspasm with a TCD device is based on thehemodynamic principle that the velocityof blood flow in an artery is inverselyrelated to the area of the lumen of thatartery. In theory, TCD may serve as arelatively simple screening method of ce-rebral vasospasm, and some investigatorshave advocated the replacement of an-giography by TCD (8–11).

Technical Aspects of TCD. TCD is anoninvasive, bedside, transcranial ultra-sound method of determining the flow

velocities in the basal cerebral arteries.Placement of the probe of a range-gatedultrasound Doppler instrument in thetemporal area just above the zygomaticarch allowed the velocities in the middlecerebral artery (MCA) to be determinedfrom the Doppler signals (Fig. 1). Theflow velocities in the proximal anteriorcerebral artery (ACA), terminal internalcarotid artery (ICA), and posterior cere-bral artery were also recorded at steadystate and during test compression of thecommon carotid arteries. TCD had one ofits first applications in the identificationof cerebral vasospasm after SAH (7, 10).

TCD begins with obtaining a baselineTCD study on day 2 or 3 after SAH onsetafter a comprehensive insonation proto-col that examines all proximal intracra-nial arteries. TCD studies are then con-tinued daily or every other day from day 4to day 14 after SAH onset. The TCD ex-amination begins with temporal windowinsonation of the proximal MCA on theaffected side, usually 50–60 mm, andthen distal MCA, at a depth of 40–50 mm(Fig. 1). The examination then returnsproximally to the MCA/ACA bifurcation,where a bidirectional flow signal is lo-cated at a depth of 60–80 mm. The tem-poral window insonation continues withmore caudal angulation of the probe toevaluate the terminal ICA at a depth of 60to 70 mm. The temporal window in-sonation is completed by posterior an-gulation to evaluate the posterior cere-bral artery at a depth of 55–75 mm. Theprotocol is then repeated for the oppo-site hemisphere. The ICA siphon canalso be insonated via the transorbitalwindow at depths of 60 –70 mm (Fig. 2).

From the Departments of Critical Care Medicine(DZ), Clinical Neurosciences (DZ, AD), and CommunityHealth Sciences (DZ), University of Calgary, Calgary,Alberta, Canada; and the Department of Medicine,Division of Neurology, University of Alberta, Edmonton,Alberta, Canada (MS).

For information regarding this article, E-mail:ademchuk@ucalgary.ca.

Copyright © 2007 by the Society of Critical CareMedicine and Lippincott Williams & Wilkins

DOI: 10.1097/01.CCM.0000260633.66384.FB

Transcranial Doppler has several practical applications in neu-rocritical care. It has its main application in the diagnosis andmonitoring of vasospasm in patients with subarachnoid hemor-rhage. In addition, it holds promise for the detection of criticalelevations of intracranial pressure. Its ability to measure CO2

reactivity and autoregulation may ultimately allow intensivists tooptimize cerebral perfusion pressure and ventilatory therapy for

the individual patient. Transcranial Doppler findings of braindeath are well described and can be useful as a screening tool.(Crit Care Med 2007; 35[Suppl.]:S216–S223)

KEY WORDS: transcranial Doppler; neurocritical care; vaso-spasm; subarachnoid hemorrhage; intracranial pressure; cerebralperfusion pressure; ventilatory therapy

S216 Crit Care Med 2007 Vol. 35, No. 5 (Suppl.)

This is preferable if no terminal ICAsignal can be obtained through thetemporal window.

The transforaminal window in-sonation occurs via the foramen magnumand is first performed at a depth of 75mm to locate the terminal vertebral ar-tery (VA) and proximal basilar artery(BA). Insonation of the BA is performednext along its course (range of depth,80–100 mm), followed by assessment ofthe more proximal left and right VAs atdepths of 50–80 mm by lateral probe

positioning (Fig. 3). Finally, submandib-ular window insonation is performed toobtain reference velocities from the cer-vical ICA for calculating the Lindegaardratio (Fig. 4). The Lindegaard ratio orhemispheric index compares the highestvelocity recorded in an intracranial vesselas the numerator with the highest veloc-ity recorded in the ipsilateral extracranialICA as the denominator.

TCD technology called power M-modeTCD (PMD/TCD) is now available, whichsimplifies operator dependence on TCD

by providing multi-gate flow informationsimultaneously in the power M-modeTCD display (12). Power M-mode TCDcould be rapid bedside technology be-cause power M-mode TCD facilitates tem-poral window location and alignment ofthe US beam to view blood flow frommultiple vessels simultaneously, withoutsound or spectral clues. The presence ofsignal drop-off with power M-mode TCDfrom excess turbulence can indicate flowdisturbance that may represent vaso-spasm (Fig. 5) (13).

Figure 1. Transtemporal window. Middle cerebral artery (MCA) signature is obtained by aiming the probe anterior between the ear and frontal process ofzygomatic bone using 100% ultrasound power at a depth of 30–60 mm. PMD, power M-mode.

Figure 2. Orbital window. Internal carotid artery (ICA) siphon signature is obtained by placing the transducer over the eye globe in the horizontal planeand slightly tilted medially with 10% ultrasound power.

S217Crit Care Med 2007 Vol. 35, No. 5 (Suppl.)

The degree of vasospasm in the basalvessels is correlated with the amount ofacceleration of blood flow velocitiesthrough the vessels as they become nar-rowed (10). The best work on correlationbetween TCD mean flow velocities(MFVs) and with vessel narrowing using

cerebral angiography was performed inthe MCA. Lindegaard et al. (10) showed intheir work that vasospastic MCAs usuallydemonstrate velocities of �120 cm/secon TCD, with the velocities being in-versely related to arterial diameter. Inaddition, velocities of �200 cm/sec are

predictive of a residual MCA lumen diam-eter of �1 mm (normal MCA diameter isapproximately 3 mm).

Unfortunately, TCD MFVs do not allowcalculation of cerebral blood flow volumeand cannot be substituted for cerebralblood flow measurements (14–16). What

Figure 3. Transforaminal window. The patient will either bend at the neck or be put into lateral decubitus position and head tilt to chest to open the spacebetween the atlas and skull base.

Figure 4. Submandibular window. In the submandibular areas, the transducer will be directed slightly medially and posterior to the longitudinal axis ofthe body to obtain the cervical internal carotid artery (ICA) signature at a depth of 40–60 mm.

S218 Crit Care Med 2007 Vol. 35, No. 5 (Suppl.)

the TCD MFV information provides us isprediction of the degree of vessel narrow-ing, spasm progression or regression, andcompensatory vasodilatation.

TCD has been used as a monitoringtool for the development of cerebral va-sospasm in different drug trials (17, 18).It has also monitored the efficacy of in-terventional angioplasty treatment (19)and detected the recurrence of arterialnarrowing (20).

TCD MFVs can give an indication forcerebral vasospasm. However, the veloci-ties alone cannot determine whether apatient has symptomatic cerebral vaso-spasm (21). In addition, different intra-cranial vessels have different velocitiescriteria for diagnosing vasospasm. In thenext few sections, we will review the lit-erature for TCD criteria based on differ-ent intracranial vessels.

Middle Cerebral Artery Vasospasm.TCD is well studied and of establishedvalue in detecting MCA vasospasm (22–28). The TCD sensitivity varies from 38%to 91% and the specificity varies from94% to 100%, based mainly on the cutoffor threshold selected for moderate and

severe vasospasm. Figure 5 provides anexample of a patient with severe proximalMCA and moderate ACA vasospasm.

Vora et al. (27) studied the correlationbetween proximal MCA MFV and angio-graphic vasospasm after SAH. Theylooked at different variables: MCA’s high-est MFV at three depths (5, 5.5, 6 cm), thelargest MFV increase in 1 day before dig-ital subtraction cerebral angiography,and ipsilateral MCA/contralateral MCAMFV difference. For MCA MFVs of �120cm/sec, the sensitivity of TCD for detect-ing moderate or severe MCA vasospasm is88% and the specificity is 72%; whereas,for MCA MFVs of �200 cm/sec, the sen-sitivity of TCD for detecting moderate orsevere MCA vasospasm was 27% and thespecificity is 98%. So, for individual pa-tients, only low or very high MCA flowvelocities (i.e., �120 or �200 cm/sec)reliably predicted the absence or presenceof clinically significant angiographic va-sospasm (moderate or severe vasospasm).Intermediate velocities, which were ob-served for approximately one half of thepatients, were not dependable and shouldbe interpreted with caution. Interest-

ingly, all patients with MCA MFVs of160–199 cm/sec and right-to-left MFVdifferences of �40 cm/sec had significantvasospasm.

Burch et al. (22) found TCD had lowsensitivity (43%) and good specificity(93.7%) for detecting moderate or severevasospasm (�50%) when MCA MFV of120 cm/sec was used as the cutoff. Whenthe diagnostic criterion was changed to�130 cm/sec, specificities were 100%(intracranial ICA) and 96% (MCA) andpositive predictive values were 100% (in-tracranial ICA) and 87% (MCA). The au-thors concluded that TCD accurately de-tects terminal ICA and MCA vasospasmwhen flow velocities are �130 cm/sec.However, its sensitivity may be underes-timated and the importance of operatorerror overestimated.

Increased blood flow velocities maynot necessarily imply arterial narrowing.Indeed, both increasing flow and reducedvessel diameter may lead to high flowvelocities. Consequently, cerebral vaso-spasm may not be safely and definitelydifferentiated from cerebral hyperemia bythe mere assessment of flow velocities in

Figure 5. An example of a patient with severe left middle cerebral artery (MCA) and moderate anterior cerebral artery (ACA) vasospasm. The highest meanflow velocities (MFVs) were obtained at the drop-off signals in both MCA and ACA vessels. Left ACA MFV � 127 cm/sec, indicative of moderate vasospasm;left MCA MFV � 212 cm/sec, indicative of severe vasospasm. PMD, Power M-mode Doppler.

S219Crit Care Med 2007 Vol. 35, No. 5 (Suppl.)

the basal arteries (26, 27). To cope withthis diagnostic shortcoming of TCD,Lindegaard et al. (9) suggested defineduse of ratios of flow velocities betweenintracranial arteries and cervical ICAs.The normal value for this ratio is 1.7 �0.4 (29). It is advisable to use an individ-ual’s own ratio as control before spasm asa reference because there are anatomicdifferences among individuals. The pres-ence of an MCA/cervical ICA MFV ratio of�3 is indicative of moderate proximalMCA vasospasm., whereas a ratio of �6 isindicative of severe vasospasm.

MCA vasospasm detection is limited bydifferent factors: improper vessel identi-fication (terminal ICA, posterior cerebralartery), increased collateral flow, hyper-emia/hyperperfusion, proximal hemody-namic lesion (cervical ICA stenosis or oc-clusion), operator inexperience, andaberrant vessel course.

Anterior Cerebral Artery Vasospasm.The ability of TCD in detecting ACA va-sospasm was examined in different stud-ies (7, 23, 25, 30, 31). In general, TCD haslow sensitivity (13–83%) and moderatespecificity (65–100%) for detecting ACAvasospasm. Wozniak et al. (31) found thatTCD has very low sensitivity (18%) andmarginal specificity (65%) for detectingany degree of ACA vasospasm. They usedthe ACA MFV of �120 cm/sec as the cri-terion for vasospasm. For moderate andsevere vasospasm (�50% stenosis), thesensitivity increased to 35%. Grolimundet al. (30), using the flow velocity crite-rion of a 50% increase in ACA flow veloc-ity, successfully detected 10 of 14 (sensi-tivity, 71%). ACA vasospasm could not bedetected when it was presented in themore distal pericallosal portion of theACA. In contrast, Lennihan et al. (25)used a flow velocity criterion of �140cm/sec and detected vasospasm in onlytwo of 15 ACAs (sensitivity, 13%). Vaso-spasm was present in a portion of fiveACAs not insonated by TCD. In addition,Doppler signals could not be obtained fromnine ACAs (false-positive occlusion), in-cluding three ACAs with angiographic va-sospasm. Aaslid et al. (29) found that flowvelocities in ACAs correlated poorly withresidual lumen diameter.

ACA vasospasm detection is limited bythe presence of collateral flow (patientwith one ACA vasospasm might not havea high MFV in that affected vessel becauseflow will be diverted to the contralateralACA through the anterior communicat-ing artery), difficulty insonating the moredistal A2 portion (pericallosal artery), and

the poor angle of insonation the temporalwindow provides for ACA flow detection.

Internal Carotid Artery Vasospasm.There are few studies that have examinedthe role of TCD in detecting ICA vaso-spasm (22, 32). Burch et al. (22) foundthat when a MFV of �90 cm/sec was usedto indicate terminal ICA vasospasm, thesensitivity was 25% and specificity was93%. When the diagnostic criterion waschanged to �130 cm/sec, specificitieswere 100% (intracranial ICA) and 96%(MCA), and positive predictive valueswere 100% (intracranial ICA) and 87%(MCA). The authors conclude that TCDaccurately detects terminal ICA and MCAvasospasm when flow velocities are �130cm/sec. However, its sensitivity may beunderestimated and the importance ofoperator error overestimated.

ICA vasospasm detection is limited bydifferent factors: increased collateralflow, hyperemia/hyperperfusion, and an-atomic factors (angle of insonation be-tween the trajectories of ophthalmic ar-tery and vasospasm ICA of �30 degrees).

Vertebral and Basilar Arteries Vaso-spasm. The ability of TCD in detectingvertebral and basilar artery vasospasmwas examined in different studies (33–35). Sloan et al. (34) found that a MFV of�60 cm/sec was indicative of both VA andBA vasospasm. For the VA, the sensitivitywas 44% and specificity was 87.5%. Forthe BA, the sensitivity was 76.9% andspecificity was 79.3%. When the diagnos-tic criterion was changed to �80 cm/sec(VA) and �95 cm/sec (BA), all false-positive results were eliminated (specific-ity and positive predictive value, 100%).They concluded that TCD has good spec-ificity for the detection of VA vasospasmand good sensitivity and specificity forthe detection of BA vasospasm. TCD ishighly specific (100%) for VA and BA va-sospasm when flow velocities are �80and �95 cm/sec, respectively.

Soustiel et al. (35) found that the BA/extracranial VA ratio may contribute toan improved discrimination between BAvasospasm and vertebrobasilar hyperemiaand enhance the accuracy and reliabilityof TCD in the diagnosis of BA vasospasm.A BA/extracranial VA threshold value of 3would accurately delineate patients withhigh-grade BA vasospasm (�50% reduc-tion in diameter). As such, the BA/extracranial VA ratio may therefore con-tribute to the differential diagnosisbetween hemodynamically significantBA vasospasm and nonsymptomatic BAnarrowing.

The difficulty in detecting vertebraland basilar artery vasospasm can becaused by different factors, which in-clude: severe bilateral posterior cerebralartery vasospasm, increased collateralflow, hyperperfusion, and anatomic fac-tors (horizontal course of VA, tortuouscourse of BA).

Complete TCD Examination withLindegaard Ratio Determination. Al-though TCD diagnosis of MCA vasospasmis more accurate than with other vessels,the complete TCD insonation protocol(MCA, ICA, ACA) carries more diagnosticeffect than insonating the MCA alone, asshown by Creissard and Proust (32). Navalet al. (36) performed a two-part study tocompare the reliability of relative in-creases in flow velocities with conven-tionally used absolute flow velocity indi-ces and to correct for hyperemia-inducedflow velocity change. Relative changes inflow velocities in patients with aneurys-mal SAH correlated better with clinicallysignificant vasospasm than absolute flowvelocity indices. Correction for hyper-emia (Lindegaard ratio) improved predic-tive value of TCD in vasospasm. All tenpatients who developed symptomatic va-sospasm exhibited a two-fold increase inflow velocities before developing symp-tomatic vasospasm, and five patients hada three-fold increase.

Distal Vasospasm Detection by TCD.Vasospasm can be limited to distal vascu-lar distribution in a small percentage ofcases and is quite often missed on TCD(37). This can be predicted based on thedistal distribution of blood on head com-puted tomography after SAH. TCD is notthat sensitive for the detection of distalvasospasm, but an abnormality of flow inM2 MCA might be picked up on TCD, in-dicative for distal narrowing. Fortunately,isolated distal vasospasm is a rare entity(37) and cerebral blood flow methods suchas xenon computed tomography or single-photon emission computed tomographyare useful to confirm the diagnosis. Newercomputed tomography bolus techniques inthe form of computed tomographic angiog-raphy also provide better delineation of thedistal vasculature.

TCD has its advantage as a monitoringtool for cerebral vasospasm in neuro-intensive care because it is portable, in-expensive, easily repeatable, and noninva-sive. However, there is some limitation ofbeing operator dependent and insensitivefor detecting distal vasospasm. TCDseems to have greatest value in detectingMCA vasospasm, although a complete in-

S220 Crit Care Med 2007 Vol. 35, No. 5 (Suppl.)

tracranial artery evaluation should beperformed with use of the Lindegaard ra-tio to correct for hyperemia-induced flowvelocity change.

TCD in Traumatic Brain Injury:Intracranial Pressure andCerebral Perfusion Pressure

The measurement and management ofICP, in conjunction with CPP, is recom-mended in patients after severe traumaticbrain injury (38, 39). Conventionally, ICPmeasurement has required placement ofan invasive monitor. Inherent in the ap-plication of these monitors is the risk ofinfection, hemorrhage, malfunction, ob-struction, or malposition. Consequently,TCD has been suggested as a potentialnoninvasive assessment of ICP and CPP.

A number of different approaches havebeen employed to describe the relation-ship between TCD variables, CPP, andICP. Chan et al. (40) studied 41 patientswith severe traumatic brain injury. AsICP increased and CPP decreased, flowvelocity decreased. This decrease prefer-entially affected diastolic values initially.Below a CPP threshold of 70 mm Hg,they found a progressive increase in theTCD pulsatility index (pulsatility index �[peak systolic velocity � end-diastolic ve-locity]/timed mean velocity) (r � �.942,p � .0001). This occurred whether theCPP decrease was due to an increase inICP or a decrease in arterial blood pres-sure. Klingelhofer et al. (41) showed thatincreasing ICPs are reflected in changesin the Pourcelot index (peak systolic ve-locity � end-diastolic velocity/peak sys-tolic velocity) and MFV. In a subsequentstudy, the same group demonstrated a goodcorrelation between ICP and the productmean systemic arterial pressure � Pourcelotindex/MFV in a select group of 13 patientswith cerebral disease (r � .873; p � .001)(42). Homburg et al. (43) found pulsatilityindex changes of 2.4% per 1 mm Hg of ICP.

Although the aforementioned evi-dence suggests TCD variables are corre-lated with ICP and CPP in certain in-stances, acceptance into clinical practicerequires analysis of agreement of nonin-vasive estimation methods with mea-sured values. Initial proposed formulasfor the prediction of absolute CPP haveproved disappointing, with large 95%confidence intervals for predictors (44,45). More recent work by Schmidt et al.(46) using a prototype bilateral TCD ma-chine with a built-in algorithm to assessCPP and externally measured values for ar-

terial blood pressure has improved agree-ment. They used the formula: CPP � meanarterial blood pressure � diastolic flow ve-locity/MFV � 14 mm Hg. They found thatthe absolute difference between measuredCPP and estimated CPP was �10 mm Hgin 89% of measurements and �13 mm Hgin 92% of measurements. The 95% confi-dence range for predictors was �12 mmHg for the CPP, varying from 70 to 95 mmHg. Attempts at estimation of ICP havedemonstrated similar confidence intervals(47). Unfortunately, these values are stillunacceptable for clinical purposes. How-ever, using the pulsatility index, Bellner etal. (48) have demonstrated that ICP of �20mm Hg can be determined with a sensitiv-ity of 0.89 and specificity of 0.92. Theyconcluded that the pulsatility index mayprovide guidance in those patients withsuspected intracranial hypertension andthat repeated measurements may be of usein the neurocritical care unit.

Assessment of CO2 Reactivityand Pressure Autoregulation

TCD has been utilized for the assess-ment of cerebral CO2 reactivity and pres-sure autoregulation (49, 50), givenchanges in MCA velocity reliably corre-late with changes in cerebral blood flow(51). Impairment of CO2 reactivity andpressure autoregulation has been associ-ated with poor neurologic outcome afterhead injury (52–56). In addition to thevaluable prognostic information providedby these examinations, it has been sug-gested that TCD-identified disturbancesof pressure autoregulation and CO2 reac-tivity may be used for optimization ofcerebral hemodynamics after brain injury(50, 57). However, the utility of such anapproach has yet to be tested with respectto effect on neurologic outcome in clini-cal trials.

Brain Death

TCD findings compatible with the di-agnosis of brain death include: 1) briefsystolic forward flow or systolic spikesand diastolic reversed flow, 2) brief sys-tolic forward flow or systolic spikes andno diastolic flow, or 3) no demonstrableflow in a patient in whom flow had beenclearly documented on a previous TCDexamination. Recently, de Freitas andAndre (58) performed a systematic reviewof 16 previous studies examining the useof TCD in patients with the clinical diag-nosis of brain death. The overall sensitiv-

ity was 88%, with the cause of false neg-atives a lack of signal in 7% andpersistence of flow in 5%. The overallspecificity was 98%. Importantly, the cri-teria for brain death were variable, withonly seven groups assessing the vertebro-basilar artery and some authors acceptingthe absence of flow in only one artery.The same authors performed the largeststudy to date in 206 patients with theclinical diagnosis of brain death in Brazil.TCD had a sensitivity of 75% for confirm-ing brain death. Multivariable analysis re-vealed absence of sympathomimetic druguse and female sex were associated withfalse-negative results. The validity ofTCD-diagnosed brain death depends onthe time lapse between brain death andthe performance of TCD (59), as somepatients require repeated examinationsbefore TCD criteria are met (60).

Conclusion

TCD is an established monitoring mo-dality in the neurocritical care unit. It isa validated screening test for the diagno-sis of vasospasm in patients with SAH andmay be used to follow therapy. Recentevidence suggests TCD holds promise forthe detection of critical elevations of ICPand decreases in CPP. Its use to describeCO2 reactivity and pressure autoregula-tion may ultimately allow intensivists tooptimize CPP and ventilatory therapy forthe individual patient. Finally, the TCDfindings of brain death are well described,and its use may allow for the most favor-able timing of a confirmatory test such asangiography.

ACKNOWLEDGMENT

We thank Dr. Vadim Beletsky for pro-viding us with some of the figures.

REFERENCES

1. Weir B, Grace M, Hansen J, et al: Timecourse of vasospasm in man. J Neurosurg1978; 48:173–178

2. Sloan M: Cerebral vasoconstriction: Physiol-ogy, patho-physiology and occurrence in se-lected cerebrovascular disorder. In: Brain Isch-emia: Basic Concepts and Their ClinicalRelevance. Caplan LR (Ed). London, Springer-Verlag, 1994, pp 151–172

3. Reynolds AF, Shaw CM: Bleeding patternsfrom ruptured intracranial aneurysms: Anautopsy series of 205 patients. Surg Neurol1981; 15:232–235

4. Bleck TP: Rebleeding and vasospasm afterSAH: New strategies for improving outcome.J Crit Illn 1997; 12:572–582

S221Crit Care Med 2007 Vol. 35, No. 5 (Suppl.)

5. Ecker A, Riemenschneider PA: Arteriographicdemonstration of spasm of the intracranial ar-teries, with special reference to saccular arte-rial aneurysms. J Neurosurg 1951; 8:660–667

6. Cloft HJ, Joseph GJ, Dion JE: Risk of cerebralangiography in patients with subarachnoidhemorrhage, cerebral aneurysm, and arterio-venous malformation: A meta-analysis.Stroke 1999; 30:317–320

7. Aaslid R, Huber P, Nornes H: Evaluation ofcerebrovascular spasm with transcranialDoppler ultrasound. J Neurosurg 1984; 60:37–41

8. Seiler R, Grolimund P, Huber P: Transcra-nial Doppler sonography: An alternative toangiography in the evaluation of vasospasmafter subarachnoid hemorrhage. Acta RadiolSuppl 1986; 369:99–102

9. Lindegaard KF, Nornes H, Bakke SJ, et al:Cerebral vasospasm diagnosis by means ofangiography and blood velocity measure-ments. Acta Neurochir (Wien) 1989; 100:12–24

10. Lindegaard KF, Nornes H, Bakke SJ, et al:Cerebral vasospasm after subarachnoidhaemorrhage investigated by means of trans-cranial Doppler ultrasound. Acta NeurochirSuppl (Wien) 1988; 42:81–84

11. Grosset DG, Straiton J, McDonald I, et al:Angiographic and Doppler diagnosis of cere-bral artery vasospasm following subarach-noid haemorrhage. Br J Neurosurg 1993;7:291–298

12. Moehring MA, Spencer MP: Power M-modeDoppler (PMD) for observing cerebral bloodflow and tracking emboli. Ultrasound MedBiol 2002; 28:49–57

13. Akhtar N, Saqqur M, Roy J, et al: Developingcriteria on power M Mode transcranial Dopp-ler ultrasound for angiographic proven cere-bral vasospasm in aneurysmal subarachnoidhemorrhage patients. Abstr. World StrokeCongress, Vancouver, British Columbia,June 2004

14. Yonas H, Sekhar L, Johnson DW, et al: De-termination of irreversible ischemia by xe-non-enhanced computed tomographic mon-itoring of cerebral blood flow in patients withsymptomatic vasospasm. Neurosurgery1989; 24:368–372

15. Clyde BL, Resnick DK, Yonas H, et al: Therelationship of blood velocity as measured bytranscranial Doppler ultrasonography to ce-rebral blood flow as determined by stablexenon computed tomographic studies afteraneurysmal subarachnoid hemorrhage. Neu-rosurgery 1996; 38:896–904

16. Romner B, Brandt L, Berntman L, et al:Simultaneous transcranial Doppler sonogra-phy and cerebral blood flow measurements ofcerebrovascular CO2-reactivity in patientswith aneurysmal subarachnoid haemor-rhage. Br J Neurosurg 1991; 5:31–37

17. Yahia AM, Kirmani JF, Qureshi AI, et al: Thesafety and feasibility of continuous intrave-nous magnesium sulfate for prevention ofcerebral vasospasm in aneurysmal subarach-

noid hemorrhage. Neurocrit Care 2005;3:16–23

18. Pachl J, Haninec P, Tencer T, et al: The effectof subarachnoid sodium nitroprusside on theprevention of vasospasm in subarachnoidhaemorrhage. Acta Neurochir Suppl 2005;95:141–145

19. Newell DW, Eskridge JM, Mayberg MR, et al:Angioplasty for the treatment of symptom-atic vasospasm following subarachnoid hem-orrhage. J Neurosurg 1989; 71:654–660

20. Hurst RW, Schnee C, Raps EC, et al: Role oftranscranial Doppler in neuroradiologicaltreatment of intracranial vasospasm. Stroke1993; 24:299–303

21. Torbey MT, Hauser TK, Bhardwaj A, et al:Effect of age on cerebral blood flow velocityand incidence of vasospasm after aneurysmalsubarachnoid hemorrhage. Stroke 2001; 32:2005–2011

22. Burch CM, Wozniak MA, Sloan MA, et al:Detection of intracranial internal carotid ar-tery and middle cerebral artery vasospasmfollowing subarachnoid hemorrhage. J Neu-roimaging 1996; 6:8–15

23. Kyoi K, Hashimoto H, Tokunaga H, et al:[Time course of blood velocity changes andclinical symptoms related to cerebral vaso-spasm and prognosis after aneurysmal sur-gery]. No Shinkei Geka 1989; 17:21–30

24. Langlois O, Rabehenoina C, Proust F, et al:[Diagnosis of vasospasm: Comparison be-tween arteriography and transcranial Dopp-ler. A series of 112 comparative tests]. Neu-rochirurgie 1992; 38:138–140

25. Lennihan L, Petty GW, Fink ME, et al: Trans-cranial Doppler detection of anterior cerebralartery vasospasm. J Neurol Neurosurg Psy-chiatry 1993; 56:906–909

26. Sloan MA, Haley EC Jr, Kassell NF, et al:Sensitivity and specificity of transcranialDoppler ultrasonography in the diagnosis ofvasospasm following subarachnoid hemor-rhage. Neurology 1989; 39:1514–1518

27. Vora YY, Suarez-Almazor M, Steinke DE, etal: Role of transcranial Doppler monitoringin the diagnosis of cerebral vasospasm aftersubarachnoid hemorrhage. Neurosurgery1999; 44:1237–1247

28. Hutchison K, Weir B: Transcranial Dopplerstudies in aneurysm patients. Can J NeurolSci 1989; 16:411–416

29. Aaslid R, Markwalder TM, Nornes H: Nonin-vasive transcranial Doppler ultrasound re-cording of flow velocity in basal cerebral ar-teries. J Neurosurg 1982; 57:769–774

30. Grolimund P, Seiler RW, Aaslid R, et al: Eval-uation of cerebrovascular disease by com-bined extracranial and transcranial Dopplersonography: Experience in 1,039 patients.Stroke 1987; 18:1018–1024

31. Wozniak MA, Sloan MA, Rothman MI, et al:Detection of vasospasm by transcranialDoppler sonography: The challenges of theanterior and posterior cerebral arteries.J Neuroimaging 1996; 6:87–93

32. Creissard P, Proust F: Vasospasm diagnosis:Theoretical sensitivity of transcranial Dopp-

ler evaluated using 135 angiograms demon-strating vasospasm: Practical consequences.Acta Neurochir (Wien) 1994; 131:12–18

33. Soustiel JF, Bruk B, Shik B, et al: Transcra-nial Doppler in vertebrobasilar vasospasm af-ter subarachnoid hemorrhage. Neurosurgery1998; 43:282–291

34. Sloan MA, Burch CM, Wozniak MA, et al:Transcranial Doppler detection of vertebro-basilar vasospasm following subarachnoidhemorrhage. Stroke 1994; 25:2187–2197

35. Soustiel JF, Shik V, Shreiber R, et al: Basilarvasospasm diagnosis: Investigation of a mod-ified “Lindegaard Index” based on imagingstudies and blood velocity measurements ofthe basilar artery. Stroke 2002; 33:72–77

36. Naval NS, Thomas CE, Urrutia VC: Relativechanges in flow velocities in vasospasm aftersubarachnoid hemorrhage: A transcranialDoppler study. Neurocrit Care 2005;2:133–140

37. Newell DW, Grady MS, Eskridge JM, et al: Dis-tribution of angiographic vasospasm after sub-arachnoid hemorrhage: Implications for diag-nosis by transcranial Doppler ultrasonography.Neurosurgery 1990; 27:574–577

38. The Brain Trauma Foundation, The Ameri-can Association of Neurological Surgeons,The Joint Section on Neurotrauma and Crit-ical Care: Indications for intracranial pres-sure monitoring. J Neurotrauma 2000; 17:479–491

39. The Brain Trauma Foundation, The Ameri-can Association of Neurological Surgeons,The Joint Section on Neurotrauma and Crit-ical Care: Guidelines for cerebral perfusionpressure. J Neurotrauma 2000; 17:507–511

40. Chan KH, Miller JD, Dearden NM, et al: Theeffect of changes in cerebral perfusion pres-sure upon middle cerebral artery blood flowvelocity and jugular bulb venous oxygen sat-uration after severe brain injury. J Neuro-surg 1992; 77:55–61

41. Klingelhofer J, Conrad B, Benecke R, et al:Intracranial flow patterns at increasing intra-cranial pressure. Klin Wochenschr 1987; 65:542–545

42. Klingelhofer J, Conrad B, Benecke R, et al:Evaluation of intracranial pressure fromtranscranial Doppler studies in cerebral dis-ease. J Neurol 1988; 235:159–162

43. Homburg AM, Jakobsen M, Enevoldsen E:Transcranial Doppler recordings in raised in-tracranial pressure. Acta Neurol Scand 1993;87:488–493

44. Czosnyka M, Matta BF, Smielewski P, et al:Cerebral perfusion pressure in head-injuredpatients: A noninvasive assessment usingtranscranial Doppler ultrasonography.J Neurosurg 1998; 88:802–808

45. Aaslid R, Lundar T, Lindegaard KF: Estima-tion of cerebral perfusion pressure from ar-terial blood pressure and transcranial Dopp-ler recordings. In: Intracranial Pressure VI.Miller JD, Teasdale GM, Rowan JO (Eds).Berlin, Springer-Verlag, 1986, pp 226–229

46. Schmidt EA, Czosnyka M, Gooskens I, et al:Preliminary experience of the estimation of

S222 Crit Care Med 2007 Vol. 35, No. 5 (Suppl.)

cerebral perfusion pressure using transcra-nial Doppler ultrasonography. J Neurol Neu-rosurg Psychiatry 2001; 70:198–204

47. Ragauskas A, Daubaris G, Dziugys A, et al:Innovative non-invasive method for absoluteintracranial pressure measurement withoutcalibration. Acta Neurochir Suppl 2005; 95:357–361

48. Bellner J, Romner B, Reinstrup P, et al:Transcranial Doppler sonography pulsatilityindex (PI) reflects intracranial pressure(ICP). Surg Neurol 2004; 62:45–51

49. Steiner LA, Balestreri M, Johnston AJ, et al:Sustained moderate reductions in arterialCO2 after brain trauma time-course of cere-bral blood flow velocity and intracranial pres-sure. Intensive Care Med 2004; 30:2180–2187

50. Lee JH, Kelly DF, Oertel M, et al: Carbondioxide reactivity, pressure autoregulation,and metabolic suppression reactivity afterhead injury: A transcranial Doppler study.J Neurosurg 2001; 95:222–232

51. Bishop CC, Powell S, Rutt D, et al: Transcra-nial Doppler measurement of middle cere-bral artery blood flow velocity: A validationstudy. Stroke 1986; 17:913–915

52. Obrist WD, Langfitt TW, Jaggi JL, et al: Ce-rebral blood flow and metabolism in coma-tose patients with acute head injury: Rela-tionship to intracranial hypertension.J Neurosurg 1984; 61:241–253

53. Marion DW, Bouma GJ: The use of stablexenon-enhanced computed tomographicstudies of cerebral blood flow to definechanges in cerebral carbon dioxide vasore-sponsivity caused by a severe head injury.Neurosurgery 1991; 29:869–873

54. Klingelhofer J, Sander D: Doppler CO2 test asan indicator of cerebral vasoreactivity andprognosis in severe intracranial hemor-rhages. Stroke 1992; 23:962–966

55. Czosnyka M, Smielewski P, Kirkpatrick P, etal: Monitoring of cerebral autoregulation inhead-injured patients. Stroke 1996; 27:1829–1834

56. Lam JM, Hsiang JN, Poon WS: Monitoring ofautoregulation using laser Doppler flow-metry in patients with head injury. J Neuro-surg 1997; 86:438–445

57. Poon WS, Ng SC, Chan MT, et al: Cerebralblood flow (CBF)-directed management ofventilated head-injured patients. Acta Neuro-chir Suppl 2005; 95:9–11

58. de Freitas GR, Andre C: Sensitivity of trans-cranial Doppler for confirming brain death: Aprospective study of 270 cases. Acta NeurolScand 2006; 113:426–432

59. Kuo JR, Chen CF, Chio CC, et al: Time de-pendent validity in the diagnosis of braindeath using transcranial Doppler sonogra-phy. J Neurol Neurosurg Psychiatry 2006;77:646–649

60. Dosemeci L, Dora B, Yilmaz M, et al: Utilityof transcranial Doppler ultrasonography forconfirmatory diagnosis of brain death: Twosides of the coin. Transplantation 2004; 77:71–75

S223Crit Care Med 2007 Vol. 35, No. 5 (Suppl.)