Journal of
Neurology
J. Neurol. 218, 157--169 (1978)
© by Springer-Verlag 1978
Doppler Flow Velocity Measurements in Patients with Intracranial Hypertension E. J. Jonkman*, J . T . J . Tans, and P. C. M. Mosmans Werkgroep TNO voor Klinische Neurofysiologie, St. Ursula Kliniek, Eikenlaan 3, NL-Wassenaar, The Netherlands Summary. In patients with severe brain lesions monitoring of the intracranial pressure as well as monitoring of cerebral blood flow can be of clinical value. While at the m o m e n t there is no atraumatic method for measuring cerebral blood flow in man, it is recommended to measure blood flow velocity with the ultrasound Doppler technic in the c o m m o n carotid artery. On theoretical grounds a positive correlation between cerebral blood flow and blood flow velocity can be expected and the observations presented show that such a correlation exists in normal controls and in neurological patients. In m a n y neurological patients the flow velocity in the c o m m o n carotid artery decreases with increasing intracranial pressure. This suggests that the autoregulation is disturbed. The demonstration of such a disturbance can have clinical implications. Key words: Intracranial hypertension - Cerebral blood flow - Doppler flow velocity measurements.
Zusammenfassung. Bei Patienten mit ernsten L~isionen im Gehirn kann ,,Monitoring" von sowohl intercraniellem Druck als auch der zerebralen Blutdurchstr6mung ftir die Klinik von Bedeutung sein. Da im Moment keine atraumatische Methode for die Messung der zerebralen Blutdurchstr6mung besteht, wird anempfohlen, die Durchstr6mungsgeschwindigkeit mit der Ultraschall-Doppler-Technik in der Arteria carotis communis zu messen. Theoretisch kann eine positive Korrelation zwischen der zerebralen Blutdurchstr6mung und der Str6mflngsgeschwindigkeit erwartet werden. Die beschriebenen Ergebnisse zeigen, dab tats~ichlich ein solcher Zusammenhang besteht, sowohl bei gesunden Versuchspersonen als auch bei neurologischen Patienten. * Corresponding author
0340-5354/78/0218/0157/$02.60
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E.J. Jonkman et al. Bei vielen dieser Patienten nimmt die Durchstr6mungsgeschwindigkeit in der Arteria carotis communis ab bei einer Zunahme des intracraniellen Druckes. Dies suggeriert eine gest6rte Autoregulation. Das Aufzeigen einer solchen St6rung kann klinische Bedeutung haben.
Introduction in recent years the monitoring of intracranial pressure (ICP) has proved useful in the treatment of traumatic and non-traumatic neurological disorders. However, a direct relationship between the clinical course and ICP is not always present. There is e.g. no constant relationship between ICP and the level of coma (Bruce et al., 1972). The mortality and severe morbidity rates are very high in patients with a severe intracranial hypertension after head injury, but in one third of patients dying of head injuries an increased ICP cannot be demonstrated (Langfitt, 1976). The cells in the central nervous system are probably quite well equipped to tolerate increased pressure if only their energy needs are met. In brain injured patients the available data seem to indicate that prognosis is more directly related to the effect of increased pressure on the blood supply to the brain cells than to the direct effect on the brain cells themselves. In other words the link between increased ICP and impaired brain function may be the cerebral blood flow (CBF) (Brock and Jennet, 1975). This would explain the inconsistent relationship between raised ICP and the clinical course, because the relation between ICP and CBF is extremely complex as demonstrated by several authors. Cronqvist and Lundberg (1968) had the opportunity to study ICP and CBF in seven patients with intracranial hypertension. Lowering of ICP by removing CSF resulted in a decrease of mean CBF but an increase of fast (= cortical?) flow. The reverse effect could more or less be demonstrated by Baldy-Moulinier and Frhrebeau (1968): increased CSF pressure in cats decreased cortical flow directly and more rapidly than the total cerebral flow. Fieschi et al. (1972) thought that in head injured patients a linear although quite scattered relationship existed between CBF and ICP. Such a relationship was explicitly denied by Bruce et al. (1972). The I C P / C B F relationship may vary with the cause of the increased ICP (intracranial mass, edema, increased CSF volume). This was demonstrated in rhesus monkeys by Lewis. and McLaurin (1972). In man autoregulation may be impaired with intracranial hypertension. Gobiet et al. (1975) found that in head injured patients increasing ICP or decreasing mean arterial blood pressure led to a fall in CBF. In a comparable group Kelly et al. (1975) failed to demonstrate a clear relationship between ICP and CBF. The lack of correlation between ICP and CBF was also demonstrated by Enevoldsen and Jensen (1976). They thought that intracranial hypertension did not limit CBF, at least not if ICP was kept below 4 5 m m H g . On the contrary, high intraventricular pressure (IVP) was often accompanied by increased CBF. In patients with brainstem symptoms but without signs of cortical lesions, a positive correlation between IVP and CBF was found. These clinical data are relevant in connection with the results of Johnston
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159
and Rowan (1975), who induced intermittent waves of intracranial pressure in baboons. Relatively adequate cerebral blood flow levels were maintained during episodic increases of ICP, despite quite marked changes in cerebral perfusion pressure. Summarizing the available data we must realize that both ICP and CBF are important parameters for prognosis and clinical management. As there is no obvious relationship between both parameters, it would appear to be valuable if both parameters could be monitored, because signaling a critical fall in CBF or a critical rise in ICP and knowledge of the I C P / C B F relationshi p (present, part i a l - - o r total abolished autoregulation, false autoregulation) m a y influence therapeutic decisions. Although measuring the ICP is a noxious procedure, once the neurosurgical details of inserting the intraventricular catheter or placing the epidural device are accomplished, the measurements can be continued for several days without severe discomfort for the patient. Continuous monitoring of the CBF, however, is not possible in humans. Even repeated CBF measurements with intraarterially injected xenon-133 are in most cases impossible, because of the discomfort and small but unavoidable risk resulting from repeated catheterization of the carotid artery. The xenon inhalation technic (Mallet and Veall, 1965; Obrist et al., 1975) is a quantitative innocuous technic. However, even the inhalation technic has severe limitations because it requires a certain amount of patient cooperation. The complexity of the apparatus and the relatively high amount of radioactivity make this technic unsuitable for bedside use and it is difficult to study rapid changes of CBF because of the length of the washout curves, necessary for computer analysis. This implies that a simple innocuous technic, that could give an indication of changes in mean CBF would still be a very welcome diagnostic tool, even if the results of such a technic have to be considered only as semiquantitative. We think that an addition to the xenon measurements may be found in the use of Doppler technics. As already pointed out by Miyazaki and Kato in 1965, it is possible by means of the Doppler shift to measure the blood flow velocity in the neck vessels continuously and without trauma. The necessary equipment is simple and can be used at the bedside. The procedure requires only a gentle stable hand of the investigator but almost no patient cooperation. We thought it worthwhile to study the theoretical relationship between blood flow velocity (BFV) and CBF in man. If such a relationship could be expected to exist it ought to be established in combined studies and thereafter the I C P / B F V relation could be examined in neurological patients.
The Theoretical Relationship between CBF and BFV in the Common Carotid Artery According to Mol (1973) the velocity/time curve of the common carotid artery (CCA) consists of a systolic and diastolic phase. The mean velocity during the systolic phase is determined by the perfusion pressure, the diameter of the common carotid artery and the vascular resistance in the bed of the internal and external carotid arteries. However, during the mid-diastolic period there is practically no flow through the external carotid artery and in this period the flow through the common carotid artery is determined by the flow through the internal carotid artery only (Fig. 1).
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l
kH
t
~
Fig. 1. Blood flow velocity in a normal common carotid artery as a function of time. The BFV is indicated by the Doppler shift in kH (emitter frequency 5 MH). Systolic and mid-diastolic values are indicated
The blood flow velocity (BFV) can be calculated from the measured Doppler shift (A F), the emitter frequency (F), the angle of the probe (a) and the velocity of sound in tissue (C). C.AF 1) B F V - - 2F • cos a The blood flow through the internal carotid artery (BFC) or through the common carotid artery in the mid-diastolic period is the product of the diameter surface (1/4n d 2) and the mean flow velocity (BFV) 2) B F C -
7r • d -~• BFV 4
or
3) BFV
4 • BFC ~T
Combining of 1) and 3) leads to:
: l. Fd .COS The angle a between probe and vessel is intraindividually rather constant (interindividuaUy cos a can change maximally 8%). If we also acknowledge the fact that the diameter of the common carotid artery seems to vary little with changes in mean arterial blood pressure and intracranial pressure, we can write for 4): 5) A F = K 2 . B F C
(K 2 =
KldCOSa
)
This means that a linear relationship can be expected between changes in blood flow and the accompanying changes in measured Doppler shift, as long as we take only intraindividual changes in A F (mid-diastolic) and BFC into consideration.
Relation between BFV and CBF in Man The blood flow velocity in the common carotid artery was measured in the following experiments with a Parks 806 bidirectional Doppler device (for details see Jonkman and Mosmans, 1977). The hypothetical relationship between BFV and CBF in humans was tested in two ways: i) If such a relationship exists there must also be a linear relationship between changes in ApCO2 and BFV, because the relationship between ApCO2 and CBF is a linear one (Hoedt-
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161
AF %1 120 110 100 90
80 70 60 50 40
A
3O
-2I
-1I
0I
+11
+12
+13 %
CO 2
Fig. 2. Relation between mid-diastolic flow velocity (resting value 100%) and changes in endexpiratory CO2 (indicated in mm Hg; 0 = normal resting value). Mean of 19 controls
%
~CB~I 150-
iHo ~o) Fig. 3. The effect of papaverine injected in the common carotid artery on mean rCBF and BFV (indicated as AF) in 4 patients (100% = resting value for both parameters)
Rasmussen, 1967). This was tested in 19 young healthy adults by measuring BFV in the common carotid artery and the end-expiratory, CO2 simultaneously. The ApCO2 was changed by hyperventilation or breathing air with 5% CO2. The mean velocity during the mid-diastolic period showed a rather good correlation with changes in the CO2 (Fig. 2) as measured in the end-expiratory samples, the parameters of the resulting regression line (y = p x + q) between A CO2 and A F in per cent being as follows: P = I 1.3; q = 87%. A remarkable fact is the finding that the regression line is steeper than the one originally indicated by Hoedt-Rasmussen (1967): P = 2.5; q = 100 for the CBF/ApCO2 relationship. One of the reasons for this may be that changes induced in ApCO2 were greater than the recorded changes in pCO2 in the end-expiratory samples. 2) The following test was to relate changes in mean velocity and changes in the mean rCBF as measured with xenon-133 injected intra-arterially. This is rather difficult for technical reasons. We managed to do this in 4 patients. Changes in rCBF were induced by injection of papaverine into the internal carotid artery. An induced increase to 150% of the resting value in mean rCBF resulted in a mean increase of 154% in mid-diastolic flow velocity (Fig. 3).
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Table 1. Increase of mean rCBF and mean BFV after intraarterial injection of papaverine (resting value = 100%) Patient No.
Increase CBF %
Increase BFV % (systolic)
Increase BFV % (diastolic)
Increase CBF %/BFV % (systolic)
Increase CBF %/increase BFV % (diastolic)
80
178
131
180
1.35
1.00
82
167
129
136
1.36
1.23
83
168
109
160
1.54
1.05
86
164
115
182
1.42
0.90
The complete data are given in Table 1. It appears that the relationship between increases in CBF and BFV is poor if the BFV is calculated from the Doppler shift during the systolic period, but is rather good when the BFV is measured during diastole. Unexpected differences (patients 82 and 86) can have several reasons, the most obvious being: a) turbulence caused by the indwelling catheter disturbing the Doppler shift measurements; b) changes in the angle a during the measurements. In our opinion these experiments confirm the hypothesis that Doppler shift measurements can be used as a simple technic for monitoring changes in mean rCBF.
Relation between ICP and BFV in Neurological Patients Simultaneous registration of ICP and BFV was accomplished in 13 patients. The ICP was measured with a special intraventricular catheter (11 patients) or with a needle in a previously placed Rickham reservoir (2 patients). One patient developed signs of ventriculitis after the procedure, reacting well to antibiotic therapy; otherwise there were no complications. In one patient the BFV curves were of poor quality due to extreme restlesness of the patient; in another patient severe intracranial hypertension existed which did not change very much during the procedure. In 11 patients the BFV could be measured at various levels of ICP (3 patients with subarachnoidal hemorrhage, 2 patients with an intracranial tumor and 6 patients with hydrocephalus of diverse origin). In all cases the BFV was registered during increase of the ICP and during lowering of the ICP (in the figures only the relationship ICP/BFV is given during the increase of the ICP). Sometimes the BFV was higher at the normal ICP value after a short lasting ICP increase (probably caused by the acidosis induced by the increased ICP). The ICP increase was accomplished by injecting saline into the ventricle or by closing the artificial drainage which was used in two patients with subarachnoid hemorrhage. In all patients the BFV was not influenced by small increases of ICP but between values of 16 and 40mm Hg the mean changes in BFV showed an almost linear change with the mean increase in ICP. At intraventricular pressures of 36--40mm Hg a mean decrease of 35% of the resting BFV was found (Fig. 4). There were large interindividual differences in the ICP/BFV relationship. In only one patient (Fig. 5) was there no decrease of BFV with increasing ICP. (A 21 year old female patient had internal hydrocephalus due to aqueduct stenosis. She had headache as an only complaint and slightly blurred discs were the only neurological signs.) Apparently there was an undisturbed autoregulatory function up to 50 mm Hg. All other patients, however, showed a decrease of BFV (and probably of CBF) with an increase of ICP. None of the patients showed a reaction of the mean arterial blood pressure to ICP increases during the tests, which is in accordance with the observations that in animals, and probably in
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163
%,',Fl/ 110 |I 100 I 90
i
,
T
8O 7O 6O J.
5O i
i
i
6-10 111-15 16-20 2;-25 26-30 311"3s 361"40~mmHg Fig. 4. Mean decrease of BFV (indicated as % AF) in 11 patients under increasing ICP
20-3-77 %LXF 100
I
I
20
I
I
40
I
I
60 MM HG
Fig. 5. Patient with intact autoregulation
man also, the Cushing response is only activated at an ICP level of more than 50 mm Hg. As mentioned above the I C P / B F V relationship varied a great deal. Roughly three types of curves could be distinguished in patients without normal autoregulation: a) There is a horizontal curve up to a certain ICP level after which the BFV decreases with a further increasing ICP (Fig. 6). Such a curve was found in a 10 year old hydrocephalic child with an occluded Spitz-Holter drain. Apparently there was some autoregulation but with a shift of the lower margin of the autoregulation towards higher perfusion pressures (~- lower ICP).
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13-5 -76 %,~F 100
5O
I
I
20
l
i
40
!
60 MM HG
Fig. 6. Patient with partial loss of autoregulation
5-5-77 °~o~F 100
SO
i
i
20
i
I
40
60 MM HG
Fig. 7. Patient with total loss of autoregulation
b) A 69 year old lady with hydrocephalus and dementia (the ICP measurements gave no indication of a normal pressure hydrocephalus syndrome) showed a very simple relationship of ICP and BFV (Fig. 7). Even increases at low levels of ICP resulted in a tremendous decrease in BFV. Apparently there was no autoregulation left at all. At high levels of ICP the BFV (and CBF?) was diminished to about 40%. This means that the arterial hypertension in this patient (170/110) should not be treated because a decrease in the mean arterial blood pressure has the
Doppler Flow Velocity Measurements
165 18 - 1 0 - 7 6
%ZF 100
50
I
I
20
I
I
40
i
i
60 MM HG
Fig. 8. Patient with increase of BFV after small increase of ICP
same effect on the perfusion pressure as the increase of ICP and may lead to the same disastrous result for the cerebral circulation. c) The most remarkable relationship ICP/BEV was found in two patients, one with hydrocephalus based on aqueduct stenosis, and one patient with subarachnoid hemorrhage (for the last patient see Fig. 8). In these patients a short lasting increase of BFV was found when there was a mild increase in ICP. After this increase of BFV a decrease occurred when the ICP was raised further. Enevoldsen (1976) also found in patients with brain stem symptoms, but without cortical lesions a positive correlation between ICP and rCBF, while Johnston (1975) found the same phenomenon in baboons with artificially introduced intracranial hypertension.
Discussion A u t o r e g u l a t i o n o f the cerebral b l o o d flow is a m e c h a n i s m often d e m o n s t r a t e d in l a b o r a t o r y a n i m a l s a n d is generally t h o u g h t to be present in h u m a n s , b u t m e a s u r e m e n t s in n o r m a l c o n t r o l s are relatively scarce ( S t r a n d g a a r d et al., 1975). A t first we were a s t o n i s h e d b y the o b s e r v a t i o n t h a t in 10 o f 11 patients a n increase o f I C P led to a d i m i n i s h e d B F V ( a n d p r o b a b l y also a d i m i n i s h e d C B F ) even at relatively low I C P values. H o w e v e r , f r o m the d a t a in the l i t e r a t u r e it b e c a m e o b v i o u s t h a t a u t o r e g u l a t i o n in a n i m a l s a n d h u m a n s can be easily a b o l i s h e d b y m a n y factors ( Z w e t n o w , 1968). Studies in hypertensive patients revealed a n a b o l i s h e d o r n a r r o w e d range in a u t o r e g u l a t i o n ( A g n o l i et al., 1975; S t r a n d g a a r d et al., 1975; Pistolese et al., 1975). H g g g e n d a l (1968) a n d F r e e m a n (1968) f o u n d a d i s t u r b a n c e o f a u t o r e g u l a t i o n u n d e r h y p o x i a in dogs a n d cats. A c c o r d i n g to Raichle a n d Stone (1972) a u t o r e g u l a t o r y responses in m o n k e y s c o u l d be shifted to high b l o o d pressure ranges, a n d u l t i m a t e l y a b o l i s h e d b y increasing arterial c a r b o n d i o x i d e tension. Bentsen et al. (1975) d e m o n s t r a t e d in 4 o u t o f 16 p a t i e n t s
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with long term diabetes mellitus a significant degree of pressure passiveness of the cerebral circulation at levels of mean arterial blood pressure above the lower limit of normal autoregulation. Paulson et al. (1975) found a global loss of autoregulation in 6 of 10 patients with meningitis and global or focal loss in 5 of 6 patients with encephalitis. Observations concerning the focal or global loss of autoregulation with ischemic lesions were made by Lassen and Paulson (1969), Skinh~j (1969), Paulson (1969), Fieschi (1975). Confirmation of these studies in humans is found in the experimental studies in baboons by Branston et al. (1977). Fieschi et al. (1972) made the interesting observation that autoregulation can be present shortly after cerebral trauma, but can disappear in the following days. In hydrocephalus Mathew et al. (1975) found an increase of CBF after lumbar puncture, a finding confirmed by G r u b b et al. (1977) and in accordance with the observation of Schoonderwalt et al. that the BFV increases in patients with normal pressure hydrocephalus after lowering the CSF pressure (Lying-Tunnell et al., 1977). To our knowledge Pfilv61gyi (1968) was the first to demonstrate an impairment of autoregulation in a patient with a glioma, while Brock et al. (1969) pointed to the fact that in only one of 19 patients with a cerebral tumor was there no disturbance of autoregulation. Heilbrun and Olesen (1972) found global loss of autoregulation in 50% of patients with subarachnoid hemorrhage (preoperatively) while a focal disturbance was found in almost all patients (Hartmann et al., 1977). Disturbance of autoregulation was demonstrated in patients with a Shy-Drager syndrom by G o t o h et al. (1972) and Depresseux et al. (1977). In dogs (Brennan and Plum, 1970) seizures caused a short depression of autoregulation. Taking into account these data, it seems probable that in almost all our patients (most of whom were in a serious condition due to hydrocephalus, tumor or subarachnoid bleeding) autoregulation was completely or partially lost. This knowledge helped us to take the appropriate therapeutic measures in some patients, e.g. it became obvious that in two patients with subarachnoid hemorrhage the pressure without continuous drainage was not extremely high, but high enough to diminish the BFV by 30%. This was reason to continue the drainage until normal levels of ICP were reached spontaneously. The knowledge that a normal autoregulatory mechanism is lost may also be important for the treatment of an increased blood pressure. In patients without normal autoregulation lowering of t h e w f o r the patient a d e q u a t e - - m e a n arterial pressure may have a direct adverse effect on the cerebral perfusion. As long as no better methods are available, we think that the measurement of the blood flow velocity may be a valuable tool in the handling of patients with a severe brain lesion. From the data in the literature and the small series of patients described in this study, we think that every patient with a severe brain lesion should be treated as having lost autoregulation until proved otherwise. References Agnoli, A., Pistolese, G. R., Prencipe, M., Faraglia, V., Pastore, E., Fiorani, P.: rCBF study as a test in the management of arterial hypertension. In: Cerebral circulation and metabolism, W. Langfitt, et al., eds. Berlin-Heidelberg-New York: Springer 1975
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Baldy-Moulinier, M., Fr~rebeau, P.: Blood flow of the cerebral cortex in intracranial hypertension. Scand. J. clin. Lab. Invest. Suppl. 102, p.V: G (1968) Bentsen, N., Larsen, B., Strandgaard, S.: Chronic impairment of CBF autoregulation in man. Observations in hypertensive and diabetic patients. In: Blood flow and metabolism in the brain, A. M. Harper et al., eds. London: Churchill Livingstone 1975 Branston, N. M., Symon, L., Strong, A. J." Measurements of autoregulation impairment and low-reflow related to cortical rCBF in acute experimental ischaemia in baboons. Acta neurol. scand. 56, Suppl. 64, p. 20.10--11 (1977) Brennan, R. W., Plum, F.: Dissociation of autoregulation and chemical regulation in cerebral circulation following seizures. In: Brain and blood flow, E. W. Ross Russell, ed. Pitman 1970 Brock, M., Hadjidimos, A. A., Schiirmann, K., Ellger, M., Fischer, F.: Regional cerebral blood flow in cases of brain tumor. In: Cerebral blood flow, M. Brock et al., eds. Berlin-Heidelberg-New York: Springer 1969 Brock, M., Jennett, W. B.: Summary of Session 8. In: Cerebral circulation and metabolism, W. Langfitt et al., eds. Berlin-Heidelberg-New York: Springer 1975 Bruce, D. A., Miller, J. D., Langfitt, T. W., Goldberg, H. I., Stanek, A. E., Vapalahti, M.: rCBF and intracranialpressure in comat/gsepatients. In: Cerebral blood flow and intracranial pressure. Proc. 5th Int. Symp., Rome-Sienna 1971, part II. Europ. Neurol. 8, 200--206 (1972) Cronqvist, S., Lundberg, N.: Regional cerebral blood flow in intracranial tumors with special regard to cases with intracranial hypertension. Scand. J. clin. Lab. Invest. Suppl. 102, p. XV:A (1968) Depresseux, J. C., Rousseau, J. J., Franck, G.: Cerebrovascular autoregulation and reactivity in primary neuropathic orthostatic hypotension. Acta neurol, scand. 56, Suppl. 64, p.22.8--9 (1977) Enevoldsen, E. M., Jensen, F. T.: The relation between intracranial pressure and regional cerebral blood flow in the acute phase of severe head injury. In: Intracranial pressure III, J. W. F. Beks et al., eds. Berlin-Heidelberg-New York: Springer 1976 Fieschi, C., Beduschi, A., Agnoli, A., Battistini, N., Collice, M., Prencipe, M., Risso, M., with the technical assistance of Passero, S.: Regional cerebral blood flow and intraventricular pressure in acute brain injuries. In: Cerebral blood flow and intracranial pressure. Proc. 5th Int. Symp., Rome-Sienna 1971, part II. Europ. Neurol. 8, 192--199 (1972) Fieschi, C., Battistini, N., Ciacci, G., Nardini, M., Volante, F., Antonini, F. M., Bertini, G., Fumagalli, C.: CSF pressure, rCBF and its autoregulation in cerebral infarction before and after glycerol treatment. In: Blood flow and metabolism in the brain, A. M. Harper et al., eds. London: Churchill Livingstone 1975 Freeman, J.: Elimination of brain cortical blood flow autoregulation following hypoxia. Scand. J. clin. Lab. Invest., Suppl. 102, p.V:E (1968) Gobiet, W., Bock, W. J., Grote, W., Bettag, M.: Cerebral blood flow in patients with traumatic cerebral edema. In: Intracranial pressure II, N. Lundberg et al., eds. Berlin-HeidelbergNew York: Springer 1975 Gotoh, F., Ebihara, S.-I., Toyoda, M., Shinohara, Y.: Role of autonomic nervous system in autoregulation of human cerebral circulation. In: Cerebral blood flow and intracranial pressure. Proc. 5th int. Symp., Rome-Sienna 1971, part I. Europ. Neurol. 6, 203--207 (1971/72) Grubb, R. L., Jr., Raichle, M. E., Gado, M. H., Eichling, J. O., Hughes, C. P.: Cerebral blood flow, oxygen utilization, and blood volume in dementia. Neurology (Minneap.) 27, 905--910 (1977) H~iggendal, E.: Elimination of autoregulation during arterial and cerebral hypoxia. Scand. J. clin. Lab. Invest., Suppl. 102, p.V:D (1968) Hartmann, A., Alberti, E., Lange, D.: Effects of CSF-drainage on CBF and CBV in subarachnoid hemorrhage and communicating hydrocephalus. Acta Neurol. Scand. 56, Suppl. 64, 18.10--11 (1977)
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Heilbrun, M. P., Olesen, J." Regional cerebral blood flow studies in subarachnoid hemorrhage. In: Cerebral blood flow and intracranial pressure. Proc. 5th int. Symp., Rome-Sienna 1971, part II. Europ. Neurol. 8, 1--7 (1972) Hoedt-Rasmussen, K.: Regional Cerebral Blood Flow. Med. Diss. Copenhagen 1967 Jonkman, E. J., Mosmans, P. C. M.: Doppler haematotachography: Problems in interpretation and new applications. Clin. Neurol. Neurosurg. 80, 33--45 (1977) Johnston, I., Rowan, J. O.: The effect of intermittent waves of raised intracranial pressure on cerebral blood flow: an experimental study in primates. In: Intracranial pressure II, N. Lundberg et al., eds. Berlin-Heidelberg-New York: Springer 1975 Kelly, P. J., Iwata, K., McGraw, C. P., Tindall, G. T.: Intracranial pressure, cerebral blood flow, and prognosis in patients with severe head injuries. In: Cerebral circulation and metabolism, W. Langfitt et al., eds. Berlin-Heidelberg-New York: Springer 1975 Langfitt, T. W.: The incidence and importance of intracranial hypertension in head-injured patients. In: Intracranial pressure III, J. W. F. Beks et al., eds. Berlin-Heidelberg-New York: Springer 1976 Lassen, N. A., Paulson, O. B.: Partial cerebral vasoparalysis in patients with apoplexy: Dissociation between carbon dioxide responsiveness and autoregulation. In: Cerebral blood flow, M. Brock et al., eds. Berlin-Heidelberg-New York: Springer 1969 Lewis, H. P., McLaurin, R. L.: Regional cerebral blood flow in increased intracranial pressure produced by increased cerebrospinal fluid volume, intracranial mass on cerebral edema. In: Intracranial pressure I, M. Brock et al., eds. Berlin-Heidelberg-New York: Springer 1972 Lying-Tunell, U., Lindblad, B. S., Malmlund, H. O., Persson, B.: Cerebral blood flow and metabolic rate of oxygen, glucose, lactate, pyruvate, ketone bodies and amino acids in patients with normal pressure hydrocephalus before and after shunting and in normal subjects. Acta Neurol. Scand. 56, Suppl. 64, 18.12--13 (1977) Mallet, B. L., Veall, N.: The measurement of regional cerebral clearance rates in man using xenon inhalation and extracranial recording. Clin. Sci. 29, 179--191 (1965) Mathew, N. T., Hartmann, A., Stirling Meyer, J., Ott, E. O.: The importance of "CSF pressureregional cerebral blood flow dysautoregulation" in the pathogenesis of normal pressure hydrocephalus. In: Intracranial pressure III, N. Lundberg et al., eds. Berlin-HeidelbergNew York: Springer 1975 Miyazaki, M., Kato, K.: Measurement of cerebral blood flow by ultrasonic Doppler technique. Jap. Circul. J. 29, 375--382 (1965) Mol, J. M. F. A.: Doppler haematotachografisch onderzoek bij cerebrale circulatiestoornissen. Thesis University of Utrecht (Netherlands) Pecasse - - Maastricht 1973 Obrist, W. B.: Regional cerebral blood flow estimated by "xenon inhalation". Stroke 6, 245--256 (1975) P~tlv61gyi, R.: Regional cerebral blood flow in tumour patients. Scand. J. clin. Lab. Invest. Suppl. 102, p. XV:B (1968) Paulson, O. B.: Regional cerebral blood flow at rest and during functional tests in occlusive and non-occlusive cerebrovascular disease. In: Cerebral blood flow, M. Brock et al., eds. BerlinHeidelberg-New York: Springer 1969 Paulson, O. B., Brodersen, P. B., Kristensen, H. S.: Regional cerebral blood flow, cerebral metabolic rate of oxygen, and cerebrospinal fluid acid-base findings in patients with acute pyogenic meningitis and with acute encephalitis. In: Cerebral circulation and metabolism, W. Langfitt et al., eds. Berlin-Heidelberg-New York: Springer 1975 Pistolese, G. R., Agnoli, A., Prencipe, M., Massa, R., Faraglia, V.: CBF studies during controlled hypotension in hypertensive patients: Pathophysiological and clinical correlations. In: Blood flow and metabolism in the brain, A. M. Harper et al., eds. London: Churchill Livingstone 1975 Raichle, M. E., Stone, H. L.: Cerebral blood flow autoregulation and graded hypercapnia. In: Cerebral blood flow and intracranial pressure. Proc. 5th. int. Symp., Rome-Sienna 1971, part I. Europ. Neurol. 6, 1--5 (1971/72) Skinhoj, E.: rCBF at rest and during functional tests in transient ischemic attacks. In: Cerebral blood flow, M. Brock et al., eds. Berlin-Heidelberg-New York: Springer 1969
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Schoonderwaldt, H. C., Colon, E., Hommes, O. R., Schijns, W. A. C.: Changes in carotid flow velocity induced by lowering cerebrospinal fluid pressure in normal pressure hydrocephalus. (in press, 1978) Strandgaard, S., Sengupta, D., Mackenzie, E. T., Rowan, J. O., Olesen, J., Skinhoj, E., Lassen, N. A., Harper, A, M.: The lower and upper limits for autoregulation of cerebral blood flow. In: Cerebral circulation and metabolism, W. Langfitt et al., eds. Berlin-Heidelberg-New York: Springer 1975 Zwetnow, N.: CBF autoregulation to blood pressure and intracranial pressure variations. Scand. J. clin. Lab. Invest. Suppl. 102, p.V:A (1968)
Received February 6, 1978
Neurology
J. Neurol. 218, 157--169 (1978)
© by Springer-Verlag 1978
Doppler Flow Velocity Measurements in Patients with Intracranial Hypertension E. J. Jonkman*, J . T . J . Tans, and P. C. M. Mosmans Werkgroep TNO voor Klinische Neurofysiologie, St. Ursula Kliniek, Eikenlaan 3, NL-Wassenaar, The Netherlands Summary. In patients with severe brain lesions monitoring of the intracranial pressure as well as monitoring of cerebral blood flow can be of clinical value. While at the m o m e n t there is no atraumatic method for measuring cerebral blood flow in man, it is recommended to measure blood flow velocity with the ultrasound Doppler technic in the c o m m o n carotid artery. On theoretical grounds a positive correlation between cerebral blood flow and blood flow velocity can be expected and the observations presented show that such a correlation exists in normal controls and in neurological patients. In m a n y neurological patients the flow velocity in the c o m m o n carotid artery decreases with increasing intracranial pressure. This suggests that the autoregulation is disturbed. The demonstration of such a disturbance can have clinical implications. Key words: Intracranial hypertension - Cerebral blood flow - Doppler flow velocity measurements.
Zusammenfassung. Bei Patienten mit ernsten L~isionen im Gehirn kann ,,Monitoring" von sowohl intercraniellem Druck als auch der zerebralen Blutdurchstr6mung ftir die Klinik von Bedeutung sein. Da im Moment keine atraumatische Methode for die Messung der zerebralen Blutdurchstr6mung besteht, wird anempfohlen, die Durchstr6mungsgeschwindigkeit mit der Ultraschall-Doppler-Technik in der Arteria carotis communis zu messen. Theoretisch kann eine positive Korrelation zwischen der zerebralen Blutdurchstr6mung und der Str6mflngsgeschwindigkeit erwartet werden. Die beschriebenen Ergebnisse zeigen, dab tats~ichlich ein solcher Zusammenhang besteht, sowohl bei gesunden Versuchspersonen als auch bei neurologischen Patienten. * Corresponding author
0340-5354/78/0218/0157/$02.60
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E.J. Jonkman et al. Bei vielen dieser Patienten nimmt die Durchstr6mungsgeschwindigkeit in der Arteria carotis communis ab bei einer Zunahme des intracraniellen Druckes. Dies suggeriert eine gest6rte Autoregulation. Das Aufzeigen einer solchen St6rung kann klinische Bedeutung haben.
Introduction in recent years the monitoring of intracranial pressure (ICP) has proved useful in the treatment of traumatic and non-traumatic neurological disorders. However, a direct relationship between the clinical course and ICP is not always present. There is e.g. no constant relationship between ICP and the level of coma (Bruce et al., 1972). The mortality and severe morbidity rates are very high in patients with a severe intracranial hypertension after head injury, but in one third of patients dying of head injuries an increased ICP cannot be demonstrated (Langfitt, 1976). The cells in the central nervous system are probably quite well equipped to tolerate increased pressure if only their energy needs are met. In brain injured patients the available data seem to indicate that prognosis is more directly related to the effect of increased pressure on the blood supply to the brain cells than to the direct effect on the brain cells themselves. In other words the link between increased ICP and impaired brain function may be the cerebral blood flow (CBF) (Brock and Jennet, 1975). This would explain the inconsistent relationship between raised ICP and the clinical course, because the relation between ICP and CBF is extremely complex as demonstrated by several authors. Cronqvist and Lundberg (1968) had the opportunity to study ICP and CBF in seven patients with intracranial hypertension. Lowering of ICP by removing CSF resulted in a decrease of mean CBF but an increase of fast (= cortical?) flow. The reverse effect could more or less be demonstrated by Baldy-Moulinier and Frhrebeau (1968): increased CSF pressure in cats decreased cortical flow directly and more rapidly than the total cerebral flow. Fieschi et al. (1972) thought that in head injured patients a linear although quite scattered relationship existed between CBF and ICP. Such a relationship was explicitly denied by Bruce et al. (1972). The I C P / C B F relationship may vary with the cause of the increased ICP (intracranial mass, edema, increased CSF volume). This was demonstrated in rhesus monkeys by Lewis. and McLaurin (1972). In man autoregulation may be impaired with intracranial hypertension. Gobiet et al. (1975) found that in head injured patients increasing ICP or decreasing mean arterial blood pressure led to a fall in CBF. In a comparable group Kelly et al. (1975) failed to demonstrate a clear relationship between ICP and CBF. The lack of correlation between ICP and CBF was also demonstrated by Enevoldsen and Jensen (1976). They thought that intracranial hypertension did not limit CBF, at least not if ICP was kept below 4 5 m m H g . On the contrary, high intraventricular pressure (IVP) was often accompanied by increased CBF. In patients with brainstem symptoms but without signs of cortical lesions, a positive correlation between IVP and CBF was found. These clinical data are relevant in connection with the results of Johnston
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and Rowan (1975), who induced intermittent waves of intracranial pressure in baboons. Relatively adequate cerebral blood flow levels were maintained during episodic increases of ICP, despite quite marked changes in cerebral perfusion pressure. Summarizing the available data we must realize that both ICP and CBF are important parameters for prognosis and clinical management. As there is no obvious relationship between both parameters, it would appear to be valuable if both parameters could be monitored, because signaling a critical fall in CBF or a critical rise in ICP and knowledge of the I C P / C B F relationshi p (present, part i a l - - o r total abolished autoregulation, false autoregulation) m a y influence therapeutic decisions. Although measuring the ICP is a noxious procedure, once the neurosurgical details of inserting the intraventricular catheter or placing the epidural device are accomplished, the measurements can be continued for several days without severe discomfort for the patient. Continuous monitoring of the CBF, however, is not possible in humans. Even repeated CBF measurements with intraarterially injected xenon-133 are in most cases impossible, because of the discomfort and small but unavoidable risk resulting from repeated catheterization of the carotid artery. The xenon inhalation technic (Mallet and Veall, 1965; Obrist et al., 1975) is a quantitative innocuous technic. However, even the inhalation technic has severe limitations because it requires a certain amount of patient cooperation. The complexity of the apparatus and the relatively high amount of radioactivity make this technic unsuitable for bedside use and it is difficult to study rapid changes of CBF because of the length of the washout curves, necessary for computer analysis. This implies that a simple innocuous technic, that could give an indication of changes in mean CBF would still be a very welcome diagnostic tool, even if the results of such a technic have to be considered only as semiquantitative. We think that an addition to the xenon measurements may be found in the use of Doppler technics. As already pointed out by Miyazaki and Kato in 1965, it is possible by means of the Doppler shift to measure the blood flow velocity in the neck vessels continuously and without trauma. The necessary equipment is simple and can be used at the bedside. The procedure requires only a gentle stable hand of the investigator but almost no patient cooperation. We thought it worthwhile to study the theoretical relationship between blood flow velocity (BFV) and CBF in man. If such a relationship could be expected to exist it ought to be established in combined studies and thereafter the I C P / B F V relation could be examined in neurological patients.
The Theoretical Relationship between CBF and BFV in the Common Carotid Artery According to Mol (1973) the velocity/time curve of the common carotid artery (CCA) consists of a systolic and diastolic phase. The mean velocity during the systolic phase is determined by the perfusion pressure, the diameter of the common carotid artery and the vascular resistance in the bed of the internal and external carotid arteries. However, during the mid-diastolic period there is practically no flow through the external carotid artery and in this period the flow through the common carotid artery is determined by the flow through the internal carotid artery only (Fig. 1).
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l
kH
t
~
Fig. 1. Blood flow velocity in a normal common carotid artery as a function of time. The BFV is indicated by the Doppler shift in kH (emitter frequency 5 MH). Systolic and mid-diastolic values are indicated
The blood flow velocity (BFV) can be calculated from the measured Doppler shift (A F), the emitter frequency (F), the angle of the probe (a) and the velocity of sound in tissue (C). C.AF 1) B F V - - 2F • cos a The blood flow through the internal carotid artery (BFC) or through the common carotid artery in the mid-diastolic period is the product of the diameter surface (1/4n d 2) and the mean flow velocity (BFV) 2) B F C -
7r • d -~• BFV 4
or
3) BFV
4 • BFC ~T
Combining of 1) and 3) leads to:
: l. Fd .COS The angle a between probe and vessel is intraindividually rather constant (interindividuaUy cos a can change maximally 8%). If we also acknowledge the fact that the diameter of the common carotid artery seems to vary little with changes in mean arterial blood pressure and intracranial pressure, we can write for 4): 5) A F = K 2 . B F C
(K 2 =
KldCOSa
)
This means that a linear relationship can be expected between changes in blood flow and the accompanying changes in measured Doppler shift, as long as we take only intraindividual changes in A F (mid-diastolic) and BFC into consideration.
Relation between BFV and CBF in Man The blood flow velocity in the common carotid artery was measured in the following experiments with a Parks 806 bidirectional Doppler device (for details see Jonkman and Mosmans, 1977). The hypothetical relationship between BFV and CBF in humans was tested in two ways: i) If such a relationship exists there must also be a linear relationship between changes in ApCO2 and BFV, because the relationship between ApCO2 and CBF is a linear one (Hoedt-
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AF %1 120 110 100 90
80 70 60 50 40
A
3O
-2I
-1I
0I
+11
+12
+13 %
CO 2
Fig. 2. Relation between mid-diastolic flow velocity (resting value 100%) and changes in endexpiratory CO2 (indicated in mm Hg; 0 = normal resting value). Mean of 19 controls
%
~CB~I 150-
iHo ~o) Fig. 3. The effect of papaverine injected in the common carotid artery on mean rCBF and BFV (indicated as AF) in 4 patients (100% = resting value for both parameters)
Rasmussen, 1967). This was tested in 19 young healthy adults by measuring BFV in the common carotid artery and the end-expiratory, CO2 simultaneously. The ApCO2 was changed by hyperventilation or breathing air with 5% CO2. The mean velocity during the mid-diastolic period showed a rather good correlation with changes in the CO2 (Fig. 2) as measured in the end-expiratory samples, the parameters of the resulting regression line (y = p x + q) between A CO2 and A F in per cent being as follows: P = I 1.3; q = 87%. A remarkable fact is the finding that the regression line is steeper than the one originally indicated by Hoedt-Rasmussen (1967): P = 2.5; q = 100 for the CBF/ApCO2 relationship. One of the reasons for this may be that changes induced in ApCO2 were greater than the recorded changes in pCO2 in the end-expiratory samples. 2) The following test was to relate changes in mean velocity and changes in the mean rCBF as measured with xenon-133 injected intra-arterially. This is rather difficult for technical reasons. We managed to do this in 4 patients. Changes in rCBF were induced by injection of papaverine into the internal carotid artery. An induced increase to 150% of the resting value in mean rCBF resulted in a mean increase of 154% in mid-diastolic flow velocity (Fig. 3).
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Table 1. Increase of mean rCBF and mean BFV after intraarterial injection of papaverine (resting value = 100%) Patient No.
Increase CBF %
Increase BFV % (systolic)
Increase BFV % (diastolic)
Increase CBF %/BFV % (systolic)
Increase CBF %/increase BFV % (diastolic)
80
178
131
180
1.35
1.00
82
167
129
136
1.36
1.23
83
168
109
160
1.54
1.05
86
164
115
182
1.42
0.90
The complete data are given in Table 1. It appears that the relationship between increases in CBF and BFV is poor if the BFV is calculated from the Doppler shift during the systolic period, but is rather good when the BFV is measured during diastole. Unexpected differences (patients 82 and 86) can have several reasons, the most obvious being: a) turbulence caused by the indwelling catheter disturbing the Doppler shift measurements; b) changes in the angle a during the measurements. In our opinion these experiments confirm the hypothesis that Doppler shift measurements can be used as a simple technic for monitoring changes in mean rCBF.
Relation between ICP and BFV in Neurological Patients Simultaneous registration of ICP and BFV was accomplished in 13 patients. The ICP was measured with a special intraventricular catheter (11 patients) or with a needle in a previously placed Rickham reservoir (2 patients). One patient developed signs of ventriculitis after the procedure, reacting well to antibiotic therapy; otherwise there were no complications. In one patient the BFV curves were of poor quality due to extreme restlesness of the patient; in another patient severe intracranial hypertension existed which did not change very much during the procedure. In 11 patients the BFV could be measured at various levels of ICP (3 patients with subarachnoidal hemorrhage, 2 patients with an intracranial tumor and 6 patients with hydrocephalus of diverse origin). In all cases the BFV was registered during increase of the ICP and during lowering of the ICP (in the figures only the relationship ICP/BFV is given during the increase of the ICP). Sometimes the BFV was higher at the normal ICP value after a short lasting ICP increase (probably caused by the acidosis induced by the increased ICP). The ICP increase was accomplished by injecting saline into the ventricle or by closing the artificial drainage which was used in two patients with subarachnoid hemorrhage. In all patients the BFV was not influenced by small increases of ICP but between values of 16 and 40mm Hg the mean changes in BFV showed an almost linear change with the mean increase in ICP. At intraventricular pressures of 36--40mm Hg a mean decrease of 35% of the resting BFV was found (Fig. 4). There were large interindividual differences in the ICP/BFV relationship. In only one patient (Fig. 5) was there no decrease of BFV with increasing ICP. (A 21 year old female patient had internal hydrocephalus due to aqueduct stenosis. She had headache as an only complaint and slightly blurred discs were the only neurological signs.) Apparently there was an undisturbed autoregulatory function up to 50 mm Hg. All other patients, however, showed a decrease of BFV (and probably of CBF) with an increase of ICP. None of the patients showed a reaction of the mean arterial blood pressure to ICP increases during the tests, which is in accordance with the observations that in animals, and probably in
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%,',Fl/ 110 |I 100 I 90
i
,
T
8O 7O 6O J.
5O i
i
i
6-10 111-15 16-20 2;-25 26-30 311"3s 361"40~mmHg Fig. 4. Mean decrease of BFV (indicated as % AF) in 11 patients under increasing ICP
20-3-77 %LXF 100
I
I
20
I
I
40
I
I
60 MM HG
Fig. 5. Patient with intact autoregulation
man also, the Cushing response is only activated at an ICP level of more than 50 mm Hg. As mentioned above the I C P / B F V relationship varied a great deal. Roughly three types of curves could be distinguished in patients without normal autoregulation: a) There is a horizontal curve up to a certain ICP level after which the BFV decreases with a further increasing ICP (Fig. 6). Such a curve was found in a 10 year old hydrocephalic child with an occluded Spitz-Holter drain. Apparently there was some autoregulation but with a shift of the lower margin of the autoregulation towards higher perfusion pressures (~- lower ICP).
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13-5 -76 %,~F 100
5O
I
I
20
l
i
40
!
60 MM HG
Fig. 6. Patient with partial loss of autoregulation
5-5-77 °~o~F 100
SO
i
i
20
i
I
40
60 MM HG
Fig. 7. Patient with total loss of autoregulation
b) A 69 year old lady with hydrocephalus and dementia (the ICP measurements gave no indication of a normal pressure hydrocephalus syndrome) showed a very simple relationship of ICP and BFV (Fig. 7). Even increases at low levels of ICP resulted in a tremendous decrease in BFV. Apparently there was no autoregulation left at all. At high levels of ICP the BFV (and CBF?) was diminished to about 40%. This means that the arterial hypertension in this patient (170/110) should not be treated because a decrease in the mean arterial blood pressure has the
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165 18 - 1 0 - 7 6
%ZF 100
50
I
I
20
I
I
40
i
i
60 MM HG
Fig. 8. Patient with increase of BFV after small increase of ICP
same effect on the perfusion pressure as the increase of ICP and may lead to the same disastrous result for the cerebral circulation. c) The most remarkable relationship ICP/BEV was found in two patients, one with hydrocephalus based on aqueduct stenosis, and one patient with subarachnoid hemorrhage (for the last patient see Fig. 8). In these patients a short lasting increase of BFV was found when there was a mild increase in ICP. After this increase of BFV a decrease occurred when the ICP was raised further. Enevoldsen (1976) also found in patients with brain stem symptoms, but without cortical lesions a positive correlation between ICP and rCBF, while Johnston (1975) found the same phenomenon in baboons with artificially introduced intracranial hypertension.
Discussion A u t o r e g u l a t i o n o f the cerebral b l o o d flow is a m e c h a n i s m often d e m o n s t r a t e d in l a b o r a t o r y a n i m a l s a n d is generally t h o u g h t to be present in h u m a n s , b u t m e a s u r e m e n t s in n o r m a l c o n t r o l s are relatively scarce ( S t r a n d g a a r d et al., 1975). A t first we were a s t o n i s h e d b y the o b s e r v a t i o n t h a t in 10 o f 11 patients a n increase o f I C P led to a d i m i n i s h e d B F V ( a n d p r o b a b l y also a d i m i n i s h e d C B F ) even at relatively low I C P values. H o w e v e r , f r o m the d a t a in the l i t e r a t u r e it b e c a m e o b v i o u s t h a t a u t o r e g u l a t i o n in a n i m a l s a n d h u m a n s can be easily a b o l i s h e d b y m a n y factors ( Z w e t n o w , 1968). Studies in hypertensive patients revealed a n a b o l i s h e d o r n a r r o w e d range in a u t o r e g u l a t i o n ( A g n o l i et al., 1975; S t r a n d g a a r d et al., 1975; Pistolese et al., 1975). H g g g e n d a l (1968) a n d F r e e m a n (1968) f o u n d a d i s t u r b a n c e o f a u t o r e g u l a t i o n u n d e r h y p o x i a in dogs a n d cats. A c c o r d i n g to Raichle a n d Stone (1972) a u t o r e g u l a t o r y responses in m o n k e y s c o u l d be shifted to high b l o o d pressure ranges, a n d u l t i m a t e l y a b o l i s h e d b y increasing arterial c a r b o n d i o x i d e tension. Bentsen et al. (1975) d e m o n s t r a t e d in 4 o u t o f 16 p a t i e n t s
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with long term diabetes mellitus a significant degree of pressure passiveness of the cerebral circulation at levels of mean arterial blood pressure above the lower limit of normal autoregulation. Paulson et al. (1975) found a global loss of autoregulation in 6 of 10 patients with meningitis and global or focal loss in 5 of 6 patients with encephalitis. Observations concerning the focal or global loss of autoregulation with ischemic lesions were made by Lassen and Paulson (1969), Skinh~j (1969), Paulson (1969), Fieschi (1975). Confirmation of these studies in humans is found in the experimental studies in baboons by Branston et al. (1977). Fieschi et al. (1972) made the interesting observation that autoregulation can be present shortly after cerebral trauma, but can disappear in the following days. In hydrocephalus Mathew et al. (1975) found an increase of CBF after lumbar puncture, a finding confirmed by G r u b b et al. (1977) and in accordance with the observation of Schoonderwalt et al. that the BFV increases in patients with normal pressure hydrocephalus after lowering the CSF pressure (Lying-Tunnell et al., 1977). To our knowledge Pfilv61gyi (1968) was the first to demonstrate an impairment of autoregulation in a patient with a glioma, while Brock et al. (1969) pointed to the fact that in only one of 19 patients with a cerebral tumor was there no disturbance of autoregulation. Heilbrun and Olesen (1972) found global loss of autoregulation in 50% of patients with subarachnoid hemorrhage (preoperatively) while a focal disturbance was found in almost all patients (Hartmann et al., 1977). Disturbance of autoregulation was demonstrated in patients with a Shy-Drager syndrom by G o t o h et al. (1972) and Depresseux et al. (1977). In dogs (Brennan and Plum, 1970) seizures caused a short depression of autoregulation. Taking into account these data, it seems probable that in almost all our patients (most of whom were in a serious condition due to hydrocephalus, tumor or subarachnoid bleeding) autoregulation was completely or partially lost. This knowledge helped us to take the appropriate therapeutic measures in some patients, e.g. it became obvious that in two patients with subarachnoid hemorrhage the pressure without continuous drainage was not extremely high, but high enough to diminish the BFV by 30%. This was reason to continue the drainage until normal levels of ICP were reached spontaneously. The knowledge that a normal autoregulatory mechanism is lost may also be important for the treatment of an increased blood pressure. In patients without normal autoregulation lowering of t h e w f o r the patient a d e q u a t e - - m e a n arterial pressure may have a direct adverse effect on the cerebral perfusion. As long as no better methods are available, we think that the measurement of the blood flow velocity may be a valuable tool in the handling of patients with a severe brain lesion. From the data in the literature and the small series of patients described in this study, we think that every patient with a severe brain lesion should be treated as having lost autoregulation until proved otherwise. References Agnoli, A., Pistolese, G. R., Prencipe, M., Faraglia, V., Pastore, E., Fiorani, P.: rCBF study as a test in the management of arterial hypertension. In: Cerebral circulation and metabolism, W. Langfitt, et al., eds. Berlin-Heidelberg-New York: Springer 1975
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Baldy-Moulinier, M., Fr~rebeau, P.: Blood flow of the cerebral cortex in intracranial hypertension. Scand. J. clin. Lab. Invest. Suppl. 102, p.V: G (1968) Bentsen, N., Larsen, B., Strandgaard, S.: Chronic impairment of CBF autoregulation in man. Observations in hypertensive and diabetic patients. In: Blood flow and metabolism in the brain, A. M. Harper et al., eds. London: Churchill Livingstone 1975 Branston, N. M., Symon, L., Strong, A. J." Measurements of autoregulation impairment and low-reflow related to cortical rCBF in acute experimental ischaemia in baboons. Acta neurol. scand. 56, Suppl. 64, p. 20.10--11 (1977) Brennan, R. W., Plum, F.: Dissociation of autoregulation and chemical regulation in cerebral circulation following seizures. In: Brain and blood flow, E. W. Ross Russell, ed. Pitman 1970 Brock, M., Hadjidimos, A. A., Schiirmann, K., Ellger, M., Fischer, F.: Regional cerebral blood flow in cases of brain tumor. In: Cerebral blood flow, M. Brock et al., eds. Berlin-Heidelberg-New York: Springer 1969 Brock, M., Jennett, W. B.: Summary of Session 8. In: Cerebral circulation and metabolism, W. Langfitt et al., eds. Berlin-Heidelberg-New York: Springer 1975 Bruce, D. A., Miller, J. D., Langfitt, T. W., Goldberg, H. I., Stanek, A. E., Vapalahti, M.: rCBF and intracranialpressure in comat/gsepatients. In: Cerebral blood flow and intracranial pressure. Proc. 5th Int. Symp., Rome-Sienna 1971, part II. Europ. Neurol. 8, 200--206 (1972) Cronqvist, S., Lundberg, N.: Regional cerebral blood flow in intracranial tumors with special regard to cases with intracranial hypertension. Scand. J. clin. Lab. Invest. Suppl. 102, p. XV:A (1968) Depresseux, J. C., Rousseau, J. J., Franck, G.: Cerebrovascular autoregulation and reactivity in primary neuropathic orthostatic hypotension. Acta neurol, scand. 56, Suppl. 64, p.22.8--9 (1977) Enevoldsen, E. M., Jensen, F. T.: The relation between intracranial pressure and regional cerebral blood flow in the acute phase of severe head injury. In: Intracranial pressure III, J. W. F. Beks et al., eds. Berlin-Heidelberg-New York: Springer 1976 Fieschi, C., Beduschi, A., Agnoli, A., Battistini, N., Collice, M., Prencipe, M., Risso, M., with the technical assistance of Passero, S.: Regional cerebral blood flow and intraventricular pressure in acute brain injuries. In: Cerebral blood flow and intracranial pressure. Proc. 5th Int. Symp., Rome-Sienna 1971, part II. Europ. Neurol. 8, 192--199 (1972) Fieschi, C., Battistini, N., Ciacci, G., Nardini, M., Volante, F., Antonini, F. M., Bertini, G., Fumagalli, C.: CSF pressure, rCBF and its autoregulation in cerebral infarction before and after glycerol treatment. In: Blood flow and metabolism in the brain, A. M. Harper et al., eds. London: Churchill Livingstone 1975 Freeman, J.: Elimination of brain cortical blood flow autoregulation following hypoxia. Scand. J. clin. Lab. Invest., Suppl. 102, p.V:E (1968) Gobiet, W., Bock, W. J., Grote, W., Bettag, M.: Cerebral blood flow in patients with traumatic cerebral edema. In: Intracranial pressure II, N. Lundberg et al., eds. Berlin-HeidelbergNew York: Springer 1975 Gotoh, F., Ebihara, S.-I., Toyoda, M., Shinohara, Y.: Role of autonomic nervous system in autoregulation of human cerebral circulation. In: Cerebral blood flow and intracranial pressure. Proc. 5th int. Symp., Rome-Sienna 1971, part I. Europ. Neurol. 6, 203--207 (1971/72) Grubb, R. L., Jr., Raichle, M. E., Gado, M. H., Eichling, J. O., Hughes, C. P.: Cerebral blood flow, oxygen utilization, and blood volume in dementia. Neurology (Minneap.) 27, 905--910 (1977) H~iggendal, E.: Elimination of autoregulation during arterial and cerebral hypoxia. Scand. J. clin. Lab. Invest., Suppl. 102, p.V:D (1968) Hartmann, A., Alberti, E., Lange, D.: Effects of CSF-drainage on CBF and CBV in subarachnoid hemorrhage and communicating hydrocephalus. Acta Neurol. Scand. 56, Suppl. 64, 18.10--11 (1977)
168
E.J. Jonkman et al.
Heilbrun, M. P., Olesen, J." Regional cerebral blood flow studies in subarachnoid hemorrhage. In: Cerebral blood flow and intracranial pressure. Proc. 5th int. Symp., Rome-Sienna 1971, part II. Europ. Neurol. 8, 1--7 (1972) Hoedt-Rasmussen, K.: Regional Cerebral Blood Flow. Med. Diss. Copenhagen 1967 Jonkman, E. J., Mosmans, P. C. M.: Doppler haematotachography: Problems in interpretation and new applications. Clin. Neurol. Neurosurg. 80, 33--45 (1977) Johnston, I., Rowan, J. O.: The effect of intermittent waves of raised intracranial pressure on cerebral blood flow: an experimental study in primates. In: Intracranial pressure II, N. Lundberg et al., eds. Berlin-Heidelberg-New York: Springer 1975 Kelly, P. J., Iwata, K., McGraw, C. P., Tindall, G. T.: Intracranial pressure, cerebral blood flow, and prognosis in patients with severe head injuries. In: Cerebral circulation and metabolism, W. Langfitt et al., eds. Berlin-Heidelberg-New York: Springer 1975 Langfitt, T. W.: The incidence and importance of intracranial hypertension in head-injured patients. In: Intracranial pressure III, J. W. F. Beks et al., eds. Berlin-Heidelberg-New York: Springer 1976 Lassen, N. A., Paulson, O. B.: Partial cerebral vasoparalysis in patients with apoplexy: Dissociation between carbon dioxide responsiveness and autoregulation. In: Cerebral blood flow, M. Brock et al., eds. Berlin-Heidelberg-New York: Springer 1969 Lewis, H. P., McLaurin, R. L.: Regional cerebral blood flow in increased intracranial pressure produced by increased cerebrospinal fluid volume, intracranial mass on cerebral edema. In: Intracranial pressure I, M. Brock et al., eds. Berlin-Heidelberg-New York: Springer 1972 Lying-Tunell, U., Lindblad, B. S., Malmlund, H. O., Persson, B.: Cerebral blood flow and metabolic rate of oxygen, glucose, lactate, pyruvate, ketone bodies and amino acids in patients with normal pressure hydrocephalus before and after shunting and in normal subjects. Acta Neurol. Scand. 56, Suppl. 64, 18.12--13 (1977) Mallet, B. L., Veall, N.: The measurement of regional cerebral clearance rates in man using xenon inhalation and extracranial recording. Clin. Sci. 29, 179--191 (1965) Mathew, N. T., Hartmann, A., Stirling Meyer, J., Ott, E. O.: The importance of "CSF pressureregional cerebral blood flow dysautoregulation" in the pathogenesis of normal pressure hydrocephalus. In: Intracranial pressure III, N. Lundberg et al., eds. Berlin-HeidelbergNew York: Springer 1975 Miyazaki, M., Kato, K.: Measurement of cerebral blood flow by ultrasonic Doppler technique. Jap. Circul. J. 29, 375--382 (1965) Mol, J. M. F. A.: Doppler haematotachografisch onderzoek bij cerebrale circulatiestoornissen. Thesis University of Utrecht (Netherlands) Pecasse - - Maastricht 1973 Obrist, W. B.: Regional cerebral blood flow estimated by "xenon inhalation". Stroke 6, 245--256 (1975) P~tlv61gyi, R.: Regional cerebral blood flow in tumour patients. Scand. J. clin. Lab. Invest. Suppl. 102, p. XV:B (1968) Paulson, O. B.: Regional cerebral blood flow at rest and during functional tests in occlusive and non-occlusive cerebrovascular disease. In: Cerebral blood flow, M. Brock et al., eds. BerlinHeidelberg-New York: Springer 1969 Paulson, O. B., Brodersen, P. B., Kristensen, H. S.: Regional cerebral blood flow, cerebral metabolic rate of oxygen, and cerebrospinal fluid acid-base findings in patients with acute pyogenic meningitis and with acute encephalitis. In: Cerebral circulation and metabolism, W. Langfitt et al., eds. Berlin-Heidelberg-New York: Springer 1975 Pistolese, G. R., Agnoli, A., Prencipe, M., Massa, R., Faraglia, V.: CBF studies during controlled hypotension in hypertensive patients: Pathophysiological and clinical correlations. In: Blood flow and metabolism in the brain, A. M. Harper et al., eds. London: Churchill Livingstone 1975 Raichle, M. E., Stone, H. L.: Cerebral blood flow autoregulation and graded hypercapnia. In: Cerebral blood flow and intracranial pressure. Proc. 5th. int. Symp., Rome-Sienna 1971, part I. Europ. Neurol. 6, 1--5 (1971/72) Skinhoj, E.: rCBF at rest and during functional tests in transient ischemic attacks. In: Cerebral blood flow, M. Brock et al., eds. Berlin-Heidelberg-New York: Springer 1969
Doppler Flow Velocity Measurements
169
Schoonderwaldt, H. C., Colon, E., Hommes, O. R., Schijns, W. A. C.: Changes in carotid flow velocity induced by lowering cerebrospinal fluid pressure in normal pressure hydrocephalus. (in press, 1978) Strandgaard, S., Sengupta, D., Mackenzie, E. T., Rowan, J. O., Olesen, J., Skinhoj, E., Lassen, N. A., Harper, A, M.: The lower and upper limits for autoregulation of cerebral blood flow. In: Cerebral circulation and metabolism, W. Langfitt et al., eds. Berlin-Heidelberg-New York: Springer 1975 Zwetnow, N.: CBF autoregulation to blood pressure and intracranial pressure variations. Scand. J. clin. Lab. Invest. Suppl. 102, p.V:A (1968)
Received February 6, 1978
