THE INFLUENCE OF ANAESTHESIA AND OF ARTERIAL HYPOCAPNIA ON REGIONAL BLOOD FLOW IN THE NORMAL HUMAN CEREBRAL HEMISPHERE

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1 Brit. J. Anaesth, (1970), 42, 472 THE INFLUENCE OF ANAESTHESIA AND OF ARTERIAL HYPOCAPNIA ON REGIONAL BLOOD FLOW IN THE NORMAL HUMAN CEREBRAL HEMISPHERE BY I. M. S. WILKINSON AND DOREEN R. G. BROWNE SUMMARY Grey matter perfusion is not homogeneous throughout the "normal" cerebral hemisphere in patients anaesthetized by nitrous oxide and oxygen supplemented by neuroleptanalgesia (droperidol and phenoperidine). The regional pattern under these conditions is significantly different from the pattern found in conscious patients. Grey matter perfusion is relatively homogeneous throughout the "normal" cerebral hemisphere in patients anaesthetized by the same technique but studied during conditions of arterial hypocapnia. At the low levels of perfusion induced in this way the regional differences throughout the hemisphere are reduced. White matter perfusion is not homogeneous throughout the "normal" cerebral hemisphere. The region of the internal capsule is more highly perfused than elsewhere. The same basic regional pattern is found in conscious normocapnic patients, anaesthetized normocapnic patients, and in anaesthetized hypocapnic patients. Using a single mean value to express the rate of perfusion of grey matter throughout the "normal" cerebral hemisphere, there was a slight, but statistically ^significant, reduction in grey matter perfusion in patients anaesthetized by nitrous oxide and oxygen, supplemented by neuroleptanalgesia (droperidol and phenoperidine), compared with a well-matched group of conscious patients. White matter perfusion, expressed in the same way, was very similar in the anaesthetized and conscious groups of patients. In a previous study (Wilkinson et al., 1969) the results for regional cerebral perfusion in the "normal" cerebral hemisphere in ten conscious subjects were reported. Significant regional differences in the perfusion of grey and white matter were found, grey matter perfusion being high in the precentral region and low in the temporal region, and white matter perfusion being high in the region of the internal capsule. It was decided to investigate a group of similar patients, anaesthetized by a specific technique, with the following aims in mind: (i) to observe the regional patterns of cerebral perfusion during the unconscious state produced by this anaesthetic regime;,._,,. r MATERIALS AND METHODS Patients studied. -T^ patients were all in-patients at the National Hospital, Queen Square, London. The blood flow stu(jy was carried out immediately prior to carotid arteriography under general anaesthesia which had be en requested on clinical grounds. The nature and significance of the investigation was explained to all the patients and their consent obtained N one o f the patients was strictly normal since all were undergoing diagnostic arteriography for a suspect Jntracranial lesion. The criteria for "normality" were that there were no abnormal physical signs referable to the cerebral hemisphere, an( * t^al tne carotid arteriogram subsequently (11) to study the regional pattern of cerebral perfusion at low arterial carbon dioxide.,, _,,.,.,.. I. M. S. WILKINSON, B.SC., M.B., CH.B., MJI.CP.; DOREEN tensions during this anaesthetic regime; R G BROWOT,* M.B, B.S., F.F.A.R.C.S.; The Institute (iii) to determine the gross quantitative effect of g S & S i SSo^S? *" * this; particular anaesthetic regime on cere-, prcsem address: Depamnem of A bra Diced How. Massachusetts General Hospital, Boston, U.S.A.

2 INFLUENCE OF ANAESTHESIA ON REGIONAL BLOOD FLOW 473 proved to be normal. Frequently other investigations, including gamma scan of the brain and airencephalography, were performed in these patients, with normal results. The definitive diagnoses at the time of discharge from hospital in these patients were ipsilateral orbital pain, ipsilateral 3rd nerve palsy, pituitary adenoma, migraine (between attacks) and epilepsy. No patient with the diagnosis of epilepsy was on treatment and none had suffered more than two attacks. A group of six anaesthetized patients was studied at an arterial Pco 3 level of 45 mm Hg, which will be referred to as the normocapnic group, and a group of six anaesthetized patients was studied at an arterial Pco 2 level near to 30 mm Hg, referred to subsequently as the hypocapnic group. Choice of anaesthetic regime. An anaesthetic regime which, in the light of present knowledge, seemed likely to have little effect on cerebral blood flow was chosen. Wollman and associates (1965) showed that induction of anaesthesia with a short-acting barbiturate followed by unsupplemented nitrous oxide-oxygen anaesthesia had minimal effects on cerebral blood flow. Such an unsupplemented regime, however, only produces light anaesthesia during which some patients may become aware of their environment. Maintenance of anaesthesia by means of barbiturates was not considered suitable as McDowall (1965) showed that barbiturates in anaesthetic doses reduced cerebral blood flow in proportion to depth of anaesthesia. Halothane, trichloroethylene and methoxyflurane were not used because they have all been shown to increase cerebral flow (McDowall, 1965, 1967; McDowall, Barker and Jennett, 1966; Jennett et al., 1969). Neuroleptanalgesia in the form of droperidol and phenoperidine has been shown to have no effect on cerebral blood flow or intracranial pressure in man by Barker and associates (1968) and Fitch and associates (1969). For these reasons it was decided to use a shortacting barbiturate for induction and intubation, followed by maintenance with nitrous oxideoxygen anaesthesia supplemented by neuroleptanalgesia. Technique. All the patients were premedicated with droperidol 5 mg and phenoperidine 0.5 mg, given intramuscularly 1 hour before induction of anaesthesia. Sleep was induced with methohexitone (0.88 mg/kg body weight) and relaxation for intubation was obtained using suxamethonium 75 mg to ensure rapid intubation while under the influence of the short-acting barbiturate. Droperidol 5 mg and phenoperidine mg were then given intravenously, and after spontaneous respiration had returned tubocurarine mg was given to enable ventilation to be controlled using a Beaver ventilator with a constant gas flow of 15 l./min. This was composed of nitrous oxide and oxygen (2:1), with the addition of a small amount of carbon dioxide to give the required level of arterial Pco.. Incremental doses of phenoperidine 0.5 mg were given at 30-minute intervals throughout the procedure, and at the end atropine 12 mg and prostigmine 2.5 mg were used to reverse the effects of tubocurarine. Great care was taken to ensure that no rebreathing occurred by having a Beaver one-way exhaust valve situated on the inspiratory tubing a few inches from the mouth. This was important to avoid any interference with the elimination of xenon 133 from the body via the expired air during cerebral clearance. Regional cerebral blood flow was estimated from the rate of clearance of xenon 133 from the cerebral hemisphere after injection of this radio - isotope into the internal carotid artery in the neck (H0edt-Rasmussen, 1965, 1967; Ingvar et al., 1965; Paulson et al., 1969). Clearance was monitored by fifteen highly regionalized small detectors as described in detail in a previous communication (Wilkinson et al., 1969). By this method relatively discrete estimates of regional cerebral perfusion throughout the hemisphere were obtained. Twocompartmental analysis of the clearance curves was performed to yield an estimate of the following two variables in each region of the hemisphere: Fg = the perfusion rate in grey matter measured in ml/100 g/min; Fw=the perfusion rate in white matter also measured in ml/100 g/min. The estimation of regional cerebral blood flow was carried out (mean 62) minutes after induction of anaesthesia, by which time steady

3 474 BRITISH JOURNAL OF ANAESTHESIA state conditions of anaesthesia, arterial blood pressure, heart rate and arterial Pco 2 were established. Since xenon 133 clearance from the hemisphere was much slower at the low perfusion rates incurred by hypocapnia, clearance was recorded for 20 minutes in the six patients studied at low arterial Pco s levels, compared with the usual 15 minutes at normal arterial Pco, levels. Two specimens of carotid arterial blood were taken for Paooj estimation during the period of xenon 133 clearance. One specimen was taken shortly after the onset of clearance and the other was taken towards the end of the period of clearance. Pacoj was estimated in these specimens immediately after their removal from the body. The estimation was carried out at body temperature by micro-astrup equipment (Radiometer). The results of the first and second estimations were within 1-2 mm Hg of each other in all cases, and the mean of the two estimations was used to represent the patient's Pa<x>. during the period of clearance. The mean blood pressure in the internal carotid artery was recorded at 3-minute intervals during the period of clearance by means of a transducer (Bell and Howell Type 4-327). The mode of presentation of the results. For each of the two variables, Le. Fg and Fw, fifteen regional values were obtained in each patient, and from these a mean value for the hemisphere was calculated for the patient (the arithmetic mean of the fifteen values). The fifteen regional values were then expressed as percentages of the mean value for the hemisphere. For each patient, therefore, there were four aspects to consider, first the mean values for the hemisphere of Fg and Fw, and secondly the regional patterns of Fg and Fw expressed in percentage terms. The results obtained in the two groups of anaesthetized patients, i.e. the normocapnic group and the hypocapnic group, were handled separately. The mean values for the hemisphere were tabulated (table I), to yield overall mean values for Fg and Fw in the two groups of patients. The regional values, expressed in percentage terms, were accumulated into four composite diagrams (figs. 1-4), showing the regional patterns of perfusion of grey and white matter in the two groups of patients. The composite diagrams were prepared in the way already described by Wilkinson and associates (1969), in which the regional patterns were shown at two levels of statistical significance: (i) at the P<0.001 level, at which any regions appearing significantly di&erent from 100 were almost certainly not due to chance, but represented definite regional variation in the cerebral hemisphere; (ii) at the P<0.05 level, at which one region would be expected to appear significantly different from 100 purely by chance, since 1 in 20 and 1 in 15 are similar levels of probability. TABLE I Individual and overall mtan results in the two groups of patients in this investigation. 6 anaesthetized normocapnic patients (average age yr) Overall mean + SD 6 anaesthetized hypocapnic patients (average age yr) Overall mean ± SD Arterial Pco, (mm Hg) ^ Mean arterial blood pressure (mm HfO Fg mean value for hemisphere (ml/100 R/min) Fw mean value for hemisphere (ml/100 e/min)

4 INFLUENCE OF ANAESTHESIA ON REGIONAL BLOOD FLOW 475 To facilitate the description of the regional patterns, the fifteen regions were enumerated as in figures 5D and 6D. RESULTS The most convenient way to present the flow results in the two groups of patients is in two sections. In the first section the blood flow results are reported as mean values for the hemisphere. The second section consists of a description of the regional patterns of the flow variables. 1. Mean Values for the Hemisphere. Table I shows the mean values for the hemisphere for Fg and Fw in the two groups of patients, together with the average age of the two groups, and the mean blood pressure and arterial Pco 3 levels of the individual patients at the time of the blood flow study. In the normocapnic group, in which the mean arterial Pco 2 was 45 mm Hg, the overall mean value for Fg was 77.3 ± 16.9 ml/100 g/min, and for Fw was 20.8 ±2.6 ml/100 g/min. The considerable variation in the mean hemisphere values for Fg from patient to patient was reflected by the large SD on the overall mean value. In the hypocapnic group the mean arterial Pco, was 29 mm Hg, and the overall mean value for Fg was 45.6±6.5 ml/100 g/min, and for Fw was 15.1 ±2.1 ml/100 g/min. The difference between these results and those obtained in the normocapnic anaesthetized patients was highly significant (P<0.005 in the case of Fg and Fw). It may be noted that the mean value for Fg at an arterial Pco 5 level of 29 mm Hg (45.6 ml/100 g/min) was 59 per cent of the corresponding value at?n arterial Pco, level of 45 mm Hg (77.3 ml/100 g/min). For Fw, the low Pco, value (15.1 ml/100 g/min) was 72 per cent of the normal PcOj value for Fw (20.8 ml/100 g/min). Fg thus appeared to be more responsive to the change in arterial Pco, than Fw. 2. Regional Patterns throughout the Hemisphere. (a) Perfusion of grey matter. In die six anaesthetized patients studied at normal arterial Pco, levels (fig. 1), perfusion of grey matter in the temporal region was per cent below the mean value for the hemisphere. There was an area of high perfusion in the frontoparietal region, per cent higher than in the rest of the hemisphere. These high and low flow areas were each represented by more than one detector region respectively, and both were significandy different from 100 at the P<0.001 level. IO5 IO6 MF IO5 IT7 IO2 91 P=0.05 IO FIG. 1 The pattern of perfusion of grey matter in six normocapnic anaesthetized subjects. At the P<0.05 level, the fronto-parietal high flow area was found to extend downwards over the insular region, and the low flow area extended backwards and upwards over the parieto-occipital region. In the hypocapnic group of patients (fig. 2), Fg was relatively homogeneous throughout the cere-

5 476 BRITISH JOURNAL OF ANAESTHESIA bral hemisphere. All the mean regional values were within the range between 92 and 111 per cent, and none of them was significantly different from 100 at the P<0.001 level. The temporal region was 5-8 per cent less well perfused than the rest of the hemisphere (region 15 being significantly different from 100 at the P<0.05 level). Values over the convexity of the hemisphere were 6-11 per cent higher than the mean hemisphere value in the fronto-parietal region (regions 1 and 3 being significant at the P<0.05 level). Region 4 was 8 per cent below the mean hemisphere value, which change was significant at the P<0.05 level. In summary it may be said that during general anaesthesia produced by nitrous oxide and oxygen supplemented by neuroleptanalgesia, grey matter perfusion was not homogeneous throughout the hemisphere at normal arterial Pco, levels. The temporal region formed a low flow area, whilst an area of high perfusion existed in the frontoparietal region. At low levels of arterial Pco 2, during the same anaesthetic regime, perfusion of grey matter was more homogeneous throughout the hemisphere with no evidence of significant regional variation at the P<0.001 level. (b) Perfusion of white matter. In the normocapnic group of patients (fig. 3) a high value for Fw was found in the region of the internal capsule (region 11), where perfusion was 20 per cent above the mean value for the hemisphere, which was significantly high at the P=0.05 FIG. 2 FIG. 3 The pattern of perfusion of grey matter in six hypocapnic anaesthetized subjects. The pattern of perfusion of white matter in six normo- capnic anaesthetized subjects.

6 INFLUENCE OF ANAESTHESIA ON REGIONAL BLOOD FLOW 477 P<0.001 level. The adjacent and posteriorly lying region 12 also showed a high value for Fw, 11 per cent above the mean value for the hemisphere, which was only significantly high at the P<0.05 level. Low Fw values were found in the frontal region (regions 1, 5 and 10), where perfusion was 8-11 per cent below the mean for the hemisphere. These three regions were significantly below the mean value of 100 at the P<0.05 level. In the hypocapnic group (fig. 4) Fw was again significantly high (P<0.001), 19 per cent above the mean value for the hemisphere, in the region of the internal capsule (region 11). A low value for Fw (P<0.001) was found in region 7 where white matter perfusion was 15 per cent below the hemisphere mean value. Low values were also found in P=0.05 FIG. 4 The pattern of perfusion of white matter in six hypocapnic anaesthstized subjects. the frontal region (regions 5 and 10) but these were not significantly different from the mean value for the hemisphere in this group of patients. In region 12 perfusion was only 4 per cent above the hemisphere mean value, which was not as high as it had been in the normocapnic group. In summary the regional pattern for perfusion of white matter throughout the hemisphere showed one constant feature, which was the high perfusion of the white matter in the region of the internal capsule represented by region 11. This region was per cent more highly perfused than the rest of the hemisphere in both groups of patients. There was also a tendency for low values to be found in the frontal region. DISCUSSION The regional pattern of perfusion of grey matter. This investigation showed that the rate of perfusion of grey matter throughout the "normal" cerebral hemisphere was not homogeneous in a group of normocapnic anaesthetized patients. Furthermore the pattern of Fg in this group was not the same as that observed in a group of normocapnic conscious patients studied previously by the same method (Wilkinson et al., 1969). Figure 5A, B shows the pattern of Fg in these two groups of "normal" patients. In both groups the grey matter in the temporal region (regions 14 and 15) was perfused at a significantly lower rate than the grey matter throughout the rest of the hemisphere. In the conscious group, however, high flow values were observed in the precentral region (regions 2 and 6), whereas during anaesthesia an area of high flow was found over the region of the central sulcus (regions 3 and 7). Figure 5E is a diagrammatic representation of a statistical comparison of these two patterns by means of the two-sample Student t test. (The value in one region in one group of patients was compared with the corresponding regional value in the other group of patients, using their respective standard deviations.) It was found (fig. 5E) that the increase in perfusion in regions 3, 7 and 11 that occurred in the anaesthetized patients compared with the conscious ones, was not significant in region 3 but was significant in region 7 (P<0.01) and in region 11 (P<0.005). This was accompanied by a fall in perfusion in regions 2

7 IO CONSCIOUS PATIENTS Pa CM -45 REGIONS NUMBERED AND OUTLINE OF HEMISPHERE AND MAJOR SULCI MARKED B 6 ANAESTHETIZED PATIENTS Pa COT -45 SIGNIFICANCE OF THE DIFFERENCE IN THE REGIONAL PATTERN Of FQ IN B COMPARED WITH A 6ANAMTHETIZED PATIENTS Pa cm -29 SIGNIFICANCE OF THE DIFFERENCE IN THC AtOtOMAL PATTERN OF F Q IN C COMPARED WITH B FIG. 5 Statistical comparison of the regional pattern of perfusion of grey matter in the three groups of patients. In A, B and C the regional patterns are expressed in percentage terms, and the Par Ol is measured in mm Hg. The values in E and F are P values for the significance of the difference between corresponding regional values.

8 INFLUENCE OF ANAESTHESIA ON REGIONAL BLOOD FLOW 479 and 6 which was not significant, and by a fall which was significant (P<0.02) in region 13. Thus these two regional patterns for grey matter perfusion were significantly different from each other, and regions 7, 11 and 13 were identified as the areas of brain in which significant changes in perfusion had occurred. The most rational explanation of the differing regional patterns of grey matter perfusion observed in these two groups of patients is that they represent corresponding regional patterns of functional and metabolic activity in the cerebral cortex throughout the hemisphere. There is, however, no direct evidence to support such a conclusion at the moment. The influence of the particular anaesthetic agents which were used in this study must not be forgotten, for they may have been responsible for the particular pattern found in this group of anaesthetized patients. The pattern of grey matter perfusion might be different in patients anaesthetized by other anaesthetic agents. During the cerebral vasoconstrictive influence of arterial hypocapnia, the perfusion of grey matter became more homogeneous throughout the hemisphere. Figure 5c shows the pattern obtained in the group of hypocapnic anaesthetized patients, and figure 5F shows the same method of statistical comparison applied to the two groups of anaesthetized patients studied at different levels of arterial Pco 2. The difference in values in region 7 was significant (P<0.02) but was not significant in region 14 and only assumed possible significance in region 15 (P<0.05). There was evidence, therefore, that these two regional patterns were different from each other though this evidence was rather meagre from the statistical point of view. Nevertheless areas which were significantly (P<0.001) above or below the mean value for the hemisphere during normocapnia were no longer significandy (P<0.001) different from the mean value for the hemisphere during hypocapnia. This can only have occurred as a result of differential lowering of grey matter perfusion in different regions of the hemisphere during arterial hypocapnia; for example, the temporal region underwent less reduction than elsewhere in the hemisphere. No satisfactory explanation is offered for the tendency for grey matter perfusion to become more homogeneous during arterial hypocapnia, but the observation again demonstrates the flexibility of the pattern of perfusion of grey matter throughout the hemisphere. In a third set of circumstances (i.e. anaesthesia plus arterial hypocapnia) die pattern was different from that observed in either of die odier two groups of patients. The regional pattern of perfusion of white matter. The predominant finding in the regional pattern of white matter perfusion in bodi groups of anaesthetized patients was die high value obtained in the region of die internal capsule. The same observation was also reported in ±e previously studied group of conscious patients (Wilkinson et al., 1969). Statistical comparison of die diree regional patterns is shown in figure 6. Figure 6A, B, C show the patterns in die three groups of "normal" patients. The conscious group of patients were compared widi die anaesthetized group studied at normal arterial Pco 5 levels (fig. 6E) and no significant difference was found. Comparison of the two groups of anaesdietized patients studied at different arterial Pco 2 levels (fig. 6F) likewise revealed no significant difference. This reaffirmed die fact that die same basic pattern of Fw was found in all three groups of patients. The stability of the pattern for white matter was in sharp contrast to the flexibility of grey matter perfusion diroughout the hemisphere under different conditions. This may be a reflection of die more direct correlation of cortical activity widi die circumstances of the patient. A possible anatomical reason for die occurrence of high values of Fw in the region of die internal capsule was put forward in a previous paper (Wilkinson et al., 1969). The fact diat this feature was found in all three groups of patients would seem to be compatible with diis anatomical explanation. There was a tendency for low values for Fw to be found in the frontal regions, but this was considered to be wholly or in part due to artefact. (Arterial recirculation of xenon 133 has been found to be most marked in die frontal regions, and distribution of die isotope in the branches of the ophdialmic artery is an inevitable consequence of internal carotid administration. Both these factors combine to reduce the gradient of the latter half of die clearance curves obtained in die frontal

9 480 BRITISH JOURNAL OF ANAESTHESIA IO CONSCIOUS PATIENTS Pa COT -45 REGIONS NUMBERED AND OUTLINE OF HEMISPHERE AND MAJOR SULCI MARKED B 9OU98M98 99UO2 6 ANAESTHETIZED PATIENTS Pa CO2.45 SIGNIFICANCE OF THE DIFFERENCE IN THE REGIONAL PATTERN OF F w IN B COMPARED WITH A b ANAESTHETIZED PATIENTS MONIFKAMCI OF THE DIFFERENCE IN THE Pa C(» «29 moional PATTERN OF F W IN C COMPARED WITH B FIG. 6 Statistical comparison of the regional pattern of perfusion of white matter in the three groups of patients. In A, B and C the regional patterns are expressed in percentage terms, and the Paco, is measured in mm Hg. The values in E and F are P values for the significance of the difference: between corresponding regional values.

10 INFLUENCE OF ANAESTHESIA ON REGIONAL BLOOD FLOW 481 regions, resulting in low values for Fw.) This tendency was found in all three groups of patients. The gross quantitative effect of the anaesthetic regime on cerebral blood flow. When considering the blood flow results as mean values for the hemisphere, the anaesthetic regime of nitrous oxide and oxygen supplemented by neuroleptanalgesia, in the form of droperidol and phenoperidine, had no statistically significant effect on the perfusion rates in grey and white matter (table II). The value for Fg in the anaesthetized group ( ml/100 g/min) was actually lower than the corresponding value in a well-matched group of conscious patients (86.6 ± 17.1 ml/100 g/min). The lack of statistical significance in the difference between these two mean Fg values was in part due to the large standard deviation on each of the two mean values (reflecting the considerable variability in the mean hemisphere values for Fg from one patient to another in each group) and in part due to the small numbers in each group. (The mean age of the conscious group was higher than that of the anaesthetized group, as shown in table II. Comparison of the mean results in the five conscious patients under the age of 50 years, whose mean age was 34 years, with the results obtained in the anaesthetized group, still revealed no significant difference between the two groups.) Fw was very TABLE II Comparison of results obtained in 10 conscious patients and 6 anaesthetized normocapnic patients. Mean age (yr) Mean arterial Pco, (mm Hg) Mean blood pressure (mm Hg) Overall mean Fg (ml/100 g/min) Overall mean Fw (ml/100 g/min) 10 conscious patients (Wilkirson et al., 1969) anaesthetized patients Statistical significance of difference P=0.4 P=0.7 similar in the two groups, 21.7 ±3.7 ml/100 g/ min in the conscious group compared with ml/100 g/min in the anaesthetized group. During this anaesthetic regime the cerebral circulation remained responsive to a reduction in arterial Pco,. Comparison of the overall mean values in the two groups of anaesthetized patients (table I) shows that a reduction in arterial Pco. from 45 to 29 mm Hg, was accompanied by a 41 per cent reduction in Fg and a 28 per cent reduction in Fw. This reduction in perfusion during arterial hypocapnia was of the same order as has been observed by other workers (Harper, 1965; Wollman et al., 1968) in animals and in man. ACKNOWLEDGEMENTS The authors would like to acknowledge the advice and encouragement given by Dr John Marshall in the preparation of this paper. Thanks are also due to Dr G. H. du Boulay and Dr C. Macintosh who performed the carotid catheterization in the patients of this study. The technical assistance of Miss S. M. Bell is gratefully acknowledged. Finally we express our gratitude to the National Fund for Research into Crippling Diseases, by whom this work was financially supported. REFERENCES Barker, J., Harper, A. M., McDowall, D. G., Fitch, W., and Jennett, W. B. (1968). Cerebral blood flow, cerebrospinal fluid pressure and e.e.g. activity during neuroleptanalgesia induced with dehydrobrnzpsridol and phenoperidine. Brit. J. Anaesth., 40, 143. Fitch, W., Barker, J., Jennett, W. B., and McDowall, D. G. (1969). The influence of neuroleptanalgesic drugs on cerebrospinal fluid pressure. Brit. J Anaesth., 41, 800. Harper, A. M. (1965). The inter-relationship between arterial Pco, and blood pressure in the regulation of blood flow through the cerebral cortex. Acta neurol. scand., 41 fsuppl. 14), 94. H0edt-Rasmussen, K. (1965). Regional cerebral blood flow in man measured externally following intraarterial administration of "Kr or "*Xe dissolved in saline. Acta neurol. scand., 41 (Suppl. 14), 65. (1967). Regional cerebral blood flow (M.D. Thesis). Copenhagen: Munksgaard. Ingvar, D. H., Cronqvist, S., Ekberg, R., Risberg, J., and Hpedt-Rasmussen, K. (1965). Normal values of regional cerebral blood flow in man, including flow and weight estimates of grey and white matter. Acta neurol. scand., 41 (Suppl. 14), 72. Jennett, W. B., Barker, J., Fitch, W., and McDowall, D. G. (1969). Effect of anaesthesia on intracranial pressure in patients with space-occupying lesions. Lancet, 1, 61.

11 432 BRITISH JOURNAL OF ANAESTHESIA McDowall, D. G. (1965). The effects of general anaesthetics on cerebral bloodflow and cerebral metabolism. Brit. J. Anaesth., 37, 236. (1967). The effects of clinical concentrations of halothane on the blood flow and oxygen uptake of the cerebral cortex. Brit. J. Anaesth., 39, 186. Barker, J., and Jennett, W. B. (1966). Cerebrospinal fluid pressure measurements during anaesthesia. Anaesthesia, 21, 189. Paulson, O. B., Cronqvist, S., Risberg, J., and Jeppesen, F. I. (1969). Regional cerebral blood flow: a comparison of 8-detector and 16-detector instrumentation. J. nucl. Med., 10, 164. Wilkinson, I. M. S., Bull, J. W. D., du Boulay, G. H., Marshall, J., Ross Russell, R. W., and Symon, L. (1969). Regional blood flow in the normal cerebral hemisphere. J. Neurol. Neuroswrg. Psychiat., 32, 367. Wollman, H., Alexander, S. C, Cohen. P. J., Smith, T. C., and Chase, P. E. (1965). Cerebral circulation during general anesthesia and hyperventilation in man. Anesthesiology, 26, 329. Smith, T. C, Stephen, G., Colton, E. T., Gleaton, H. E., and Alexander, S. C (1968). Effects of extremes of respiratory and metabolic alkalosis on cerebral blood flow in man. J. appl. Physiol., 24, 60. L'INFLUENCE DE L'ANESTHESIE ET DE L'HYPOCAPNIE ARTERIELLE SUR LE FLUX SANGUIN REGIONAL DANS L'HEMI SPHERE CEREBRALE NORMALE DE LTOMME SOMMAIRE La perfusion de la matiere grise n'est pas homogene dans tout rhemisphere ofre'bral "normal" de patients, anesthesies au protoxyde d'azote et oxygene, avec neuroleptanalgesie (drope'ridol et phtooperidine) supple'mentaire. II existe des differences regionales significatives, comparativement au patient conscient. La perfusion de la matiere grise est au contraire relativement homogene dans tout l'h misphere diibtal "normal" d:s patients, anesthesies suivant la meme technique mnis e'tudie's durant un 6tat d'hypocapnie artirielle. Les differences rigionales dans rhemisphere sont moins grandes, lorsque la perfusion est rfeluite de cette maniere. La perfusion est plus forte dans la region de la capsule interne qu'autrepart. Une identique situation rigionale fondamentale est observer chez les patients normocapniques conscients, les patients normocapniques anesthesies et les patients hypocapniques anesthesies. Utilisant une seule valeur moyenne pour exprimer le taux de perfusion de la matiere grise dans l'hemisphere c r bral "normal", on nota une reduction 16gere, mais statistiquement significative de la perfusion de la matiere gr.se chez les patients anesthesies au protoxydt d'azote et oxygine, avee neuroleptanalgesie suppkm:ntaire (droperidol et phfoop^ridine), par comparaison a un groupe equivalent de patients conscients. La perfusion de la matiare blanche, exprimes de la meme faoon, fut tres similaire dans les groupes de patients conscients et anesthesies. DER EINFLUSS VON NARKOSE UND ARTERIELLER HYPOKAPNIE AUF DEN REGIONALEN BLUTSTROM IN DER NORMALEN MENSCHLICHEN GROSSHIRN- HEMISPKARE ZUSAMMENFASSUNG Die Perfusion der grauen Substanz ist in der "normalen" Grosshirnhemisphare von Patienten, welche eine Stickoxydul-Sauerstoff-Narkose unter Zusatz von Neuroleptika (Droperidol und Phenopridin) erhalten hatten, nicht homogen. Das Veneilungsmuster ist unter diesen Bedingungen von dem bei wachen Patirnten gefundenen Muster signiflkant verschieden. Die Perfusion der grauen Substanz ist relativ homogen in der "normalen" Grosshirnrinde von Patienten, die mittels der selben Technik narkotisiert, aber unter Bedingungen dir artariellen Hypokapnie untersucht wurden. Bei niedrigen, auf diese Weise hervorgerufenen Perfusionsspiegeln sind die regionalen Unterschiede in der Hem'^phare vermindert. Die Perfusion der weissen Substanz ist innerhalb der "normalen" Grosshirnhemisphare nicht homogen. Die Region der inncren Kapsel ist starker perfundiert als andere Bereiche. Das selbe Grundverteilungsmuster wird bei wachen normokapnischen Patienten, bei narkotisierten normokapnischen Patienten und bei narkotisierten hypokapnischen Patienten gefunden. Verwendet man nur einen Mittelwert, um die Perfusionsgeschwindigkeit der graucn Substanz innerhalb der "normalen" Grosshirnhemisphare auszudrucken, so erhalt man bei Patienten, die mit Stickoxydul und Sauerstoff unter Zusatz von Neuroleptika (Droptridol und Phenopiridin) narkotisiert wurden im Vergleich zu einer entsprechenden Gruppe von wachen Patienten eine geringe, aber statistisch insignifikante Verminderung der Perfusion der grauen Substanz. Die Perfusion der weissen Substanz in gleicher Weise ausgedriickt war bti den Gruppen der narkotisierten und wachen Patienten ahnlich.