Effect of haemodilution on experimental cerebral oedema in cats

Resuscitation 6, 197-206

Effect of h a e m o d i l u t i o n on experimental cerebral o e d e m a in cats J. JURKIEWICZ

Department of Neurosurgery, Medical Research Centre, Polish Academy of Sciences, 3 Dworkowa Street, 00784, Warsaw,Poland

Summary The effect of haemodilution with Dextran 60 on experimental cerebral oedema produced by the modified method of Ishii, Hayner, Kelly & Evans (1959) is described. The intracranial pressure was measured from the cistema magna or epidurally in the parietooccipital region. In the group of cats subjected to haemodilution, with a haematocrit of 27.20 -+ 1.48%, the intracranial pressure first increased by 500% and, after 1.5 h, began to fall gradually so that at the end of the experiment it was only 160% of initial value. In the other experimental group in which haemodilution with a haematocrit of 27.40 + 1.14% was started after 6 h of the experiment, the intracranial pressure gradually fell for the next 6 h from 350% of initial value to 200% of initial value after 12 h. It was concluded that haemodilution slows down the development of cerebral oedema, and can be employed in the treatment of fully developed oedema.

Introduction

The search for an effective method of controlling cerebral oedema has evoked increased interest in haemodilution. The numerous advantages, aims and indications, and the technique of haemodilution, were extensively discussed at the Rottach-Egern Symposium in 1971 and the Symposium at Frankfurt-on-Main in 1975 (Messmer, 1972; 1976). Numerous authorS have observed that haemodilution decreasing haemoglobin content to 25-35% of normal increases cerebral blood flow by up to 25%, while still maintaining a satisfactory level of oxygen transport; this would make the technique particularly useful in neurosurgical practice (Gottstein, Held & Sedlmeyer, 1972; Haggendal & Norback, 1966; Pilchmayr, Sippel, Coburg & Grosse, 1975; Sunder-Plassmann, Koverkorn & Messmer, 1976). However, publications dealing with neurosurgical applications of haemodilution have been fairly rare. McMurtry, Pool & Nova (1967) reported the beneficial effect of Rheomacrodex administered during surgery of intracranial aneurysms. Luboifiski (1976) stressed the smooth course of anaesthesia and the early postoperative period in patients subjected to haemodilution during neurosurgical procedures. The effect of haemodilution on cerebral oedema has been dealt with in only a few papers. Mead, Moody, Ruamsuke & Mullan (1970) described the beneficial effect of haemodilution on cerebral blood flow 197

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and brain oedema produced by epidural balloon compression and subsequent sudden decompression. The aim of this work was to investigate the effect of haemodilution on developing and fully developed Cerebral oedema.

Materials and Methods The studies were carried out on 20 cats weighing from 3500 to 4000 g, divided into four groups of five cats each. Cerebral oedema was produced by epidural balloon compression, by the modified method of Ishii, Hayner, Kelly & Evans (1959). The animals were anaesthetized with intraperitoneal Nembutal (Abbot Ltd) in a dose of 40 mg/kg body weight; they were tracheostomized and ventilated artificially. The minute volume of the respirator was adjusted according to the results of gas measurements. Arterial and central venous blood pressures were measured continuously. Intracranial pressure was measured either from the cisterna magna, for 6 h from the start of the experiment, or epidurally, for 12 h, each in groups of five animals. Such a measurement procedure was employed to avoid possible errors in measurement of intracranial pressure due to the cisterna magna being cut off from the remaining cerebrospinal fluid spaces, which can sometimes happen at the high pressures attained during the experiment, because of the particular anatomy of the cat, which has a calcified cerebellar tentorium. A burr hole was made in the parieto-occipital region (the ectosylvian gyrus), and a latex balloon was placed epidurally. The balloon was filled with 0.9% NaC1 solution in steps, 0.2 ml every 10 min, up to a total volume of 1 ml. Initial haematocrit and osmotic

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pressure values were determined. Then 35--40 ml of blood was withdrawn from the femoral artery with simultaneous administration into the femoral vein of 50 ml of Dextran 60 solution (Polfa Ltd). Five cats were subjected to haemodilution just before the start of balloon compression, and five other cats were subjected to this procedure 6 h after the start of compression. At 90 rain before the end of the experiment the animals were injected intravenously with Evans Blue solution (2 ml/kg body weight).

Results

The_effect of cerebral compression with the epidural balloon on the intracranial pressure is shown in Fig. 1 and Fig. 2. In the five cats during the first hour the mean intracranial pressure rose rapidly from 4.40 --- 1.71 mmHg to 14.50 -+ 4.56 mmHg, i.e. to 330% of its initial value. During the subsequent half-hour it fell to 12.60 -+ 3.71 mmHg, i.e. to 280% of initial value. From then on the pressure rose gradually and by 6 h it reached 21.30 -+ 5.47 mmHg, i.e. 500% of initial value. Fig. 2 shows a part of a recording obtained in one cat of this group. The effects of haemodilution introduced just before the start of balloon compression are shown in Figs. 3 - 6 . The intracranial pressure was measured in the cisterna magna for 6 h (Fig. 3). There was a rapid increase during the first hour, from 6.60 + 2.07 mmHg to 17.60 + 5.54 mmHg, i.e. to 266% of the initial value. During the subsequent half-hour, as in the previous group, the pressure fell gradually to 11.90 -+ 5.72 mmHg, i.e. 180% of

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Fig. 6. Osmotic pressure in five cats (Fig. 3)before and after haemodilution (H) during epidural balloon compression for 6 h. its initial value. Unlike the first group, after 1.5 h the pressure continued to fall and by 6 h reached 10.50 + 4.50 mmHg, values only one-third of those in the group Without haemodilution. Fig. 4 shows a part of the recording of intracranial pressure from one cat of this group. The Haematocrit fell after haemodilution, from an initial value of 40.20 -+ 5.63% to 25.20 -+ 3_46% after 1.5 h (Fig. 5) and 27.20 -+ 1.48% in hour 6 o f the experiment. The osmotic pressure decreased after haemodilution, from an initial value o f 320.2 -+ 7.89 mosmol/1 to 304 -+ 4.84 mosmol/1 after 1 h and 312.0 -+ 6.04 mosmol/1 after 6 h.

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These differences were less than 12% and were not significant. The effect of epidural balloon compression lasting for 12 h on the intracranial pressure is illustrated in Fig. 7 and Fig. 8. The curve of mean epidural pressure was similar to that of Fig. 1, with the exception that the final pressure after 12 h was higher: 48.4 -+ 16.40 mmHg, i.e. 681% of initial value (Fig. 7). A recording of epidural pressure in one cat of this group is shown in Fig. 8. Initiation of haemodilution after 6 h had a considerable effect on the intracranial pressure for the next 6 h, as compared with the previous group (Fig. 9 and Fig. 10).

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After 6 h of balloon compression, the former pressure increased from 6.00 + 2.57 mmHg to 20.96 + 9.33 rnmHg, i.e. to 350% of initial value. The effect ofhaemodilution initiated at that time, in contrast with the group presented in Fig. 7, was that the intracranial pressure began to fall, so that by 12 h (atthe end of the experiment) it was only 11.94 -+ 8.95 mmHg, i.e. only about 200% of the initial value. A recording of the intracranial pressure in one cat of this group is shown in Fig. 10. The haematocrit in this group fell from 43.80 + 3.83% just before haemodilution to 27.40 -+ 1.14% after 12 h (Fig. 11). The osmotic pressure in this group did not change significantly: from 311.2 -+ 6.53 mosmol/1 to 306.4 + 2.27 mosmol/1 (Fig. 12). In all the animals studied the central venous pressure during the whole experiment was between 4 and 6 mmHg. The animals were bled and Dextran was given throughout the experiments to avoid excessive fluctuations in central venous pressures.

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Discussion The method of producing cerebraloedema by epidural balloon compression has a number o f advantageS: it is technically easy and reproducible; cerebral oedema occurs in a reasonably short time, and the model constitutes a good representation of the pathological mechanisms Characteristic o f certain human diseases, such as intracranial haematoma. The rise in intracranial pressure during the first hour o f compression was a result o f the rapid increase, by 1 m l , o f the intracranial contents produced by inflating the balloon; this volume represented one-thirtieth of the total intracranial volume. Subsequently,

HAEMODILUTIONIN OEDEMA 205 compensating mechanisms, such as partial displacement of cerebrospinal fluid from the cranium or partial displacement of venous blood by compression of veins, resulted in a decrease of intracranial pressure during the period from 1 to 1.5 h of the experiment; however, the pressure did not fall to that observed at the start of the experiment. During this period the first biochemical and morphological signs of imminent cerebral oedema appeared (Gromek, Czajkowska, Czernicki, Jurkiewicz & Kunicki, 1973; Jurkiewicz & Borowicz, 1973). The gradual rise in intracranial pressure starting after 2 h is a result of the intensification of the disturbances of the biochemistry, morphology and blood-brain barrier characteristic of ischaemic cerebral oedema, which after 6 h involves the whole of the compressed hemisphere and later also the contralateral one (Zehnan, Szewczykowski, Czernicki & Jurkiewicz, 1974). Haemodilution introduced just before the start of cerebral compression resulted in a considerable change in the rate of rise of intracranial pressure compared with the previous group. After 6 h of compression it was only 160% of the initial value in the presence of a mean haematocrit of 27.20 + 1.48% and at an insignificantly reduced osmotic pressure. Haemodilution with a haematocrit of 27.40 + 1.14% was introduced after 6 h of cerebral compression and resulted in a slower rate of rise of intracranial pressure and then a fall to below that at the beginning of the procedure. It should be stressed that this tendency to fall was maintained throughout the experiment. If it is borne in mind that in the present experimental model the measured intracranial pressure corresponds well to the magnitude and spread of the oedema produced, then one can conclude that haemoditution with Dextran 60 with a haematocrit of 27 +- 1.5% delays the development of oedema considerably, and therefore could be effective as a treatment for oedema, even when the cerebral oedema was widespread. This conclusion is fully supported by the results of studies on the blood-brain barrier with Evans Blue (unpublished work). It was found that the area of disturbances of the blood-brain barrier was considerably smaller and the disturbances themselves appeared later than in the control group without haemoditution. In agreement with other workers, we believe that the beneficial effect of haemodilution on brain oedema was due to the fact that haemodilution caused a considerable improvement of the microcirculation, which had previously been disturbed by the oedema, and that it increased the cerebral blood flow with the maintenance of sufficient oxygen transport (Cyrus, Close, Foster, Brown & Ellison, 1962; McMurtry, Pool & Nova, 1967; Sundt, Waltz & Sayre, 1967; Gottstein et al., 1971). The results presented in this work have induced us to apply the technique of haemodilution in clinical practice. We have obtained excellent results in the treatment of severe cranio-cerebral trauma by decreasing the haematocrit to approximately 30 g/100 ml by means of Dextran and human albumin in the ratio of 1 : 1 (unpublished work). Furthermore, cerebral oedema did not occur in patients operated on for cerebral tumours, who had been subjected to haemodilution (Jurkiewicz, Luboifiski, Czernicki & Dziduszko, 1977).

References Cyrus, A. E., Close, A. St, Foster, L. L., Brown, D. H. & Ellison, E. M. (1962) Effect of low molecular weight dextran on infarction after experimental occlusion of middle cerebral artery. Surgery 52, 25-31. Gottstein, U., Held, K. & Sedlmeyer, I. (1972) Cerebral and peripheral blood flow as affected by induced haemodilution. In: Haemodilution, Theoretical Basis and Clinical Application. Int. Symp. Rottach-Egern, 1971, pp. 247-263. Karger, Basel.

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Gromek, A., Czajkowska, D., Czernicki, Z., Jurkiewicz, J. & Kunicki, A. (1973). Biochemical disturbances in experimental brain edema. In: Brain Edema. Cerebello pontine angle tumors, pp. 28-33. Ed. Schurman, K., Brockl M., Reulen, K. J. & Voth, D. Springer Verlag, BerlinHeidelberg-New York. Haggendal, E. & Norback, B. (1966). Effect of viscosity on cerebral blood flow. Acta Chit. Setmd. 364, 13-21. Ishii, S. R., Hayner, R., Kelly, W. A. & Evans, J. P. (1959) Studies on cerebral swelling. II Experimental cerebral swelling produced by supratentorial extradural compression. Jo Neurosurg. 16, 152-166. Jurkiewicz, J. & Borowicz, J. W. (1973) Electron microscopic studies of experimental brain oedema. Folia Histocherr~ Cytochem. 11, 3-4. Jurkiewiez, J., Luboi~ski, P., Czernicki, Z. & Dziduszko, J. (1977) Niezamierzona kra~tcowa haemodilucja w przebiegu operacji oponiaka m6zgu. (Unintended extremal haemodilufion during surgery of meningioma.) Anest. Reanim. lnten. Terap. In press. Luboinski, P. ( 1976) Haemodilution bei neurochirurgischen Eingriffen- Anaesthetist 25, 167-169. McMurtry, J. G., Pool, J. L. & Nova, H. R. (1967) The use of Rheomacrodex in the surgery of intracranial aneurism. J. Neurosurg. 26, 218-222. Mead, C. O., Moody, R. A., Ruamsuke, S. & MuUan,S. (1970) Effect of isovolemic haemodilution on cerebral blood flow following experimental head injury. J. Neurosurg. 32, 40-50. Messemer, K. (1972) Haemodilution. Theoretical basis and clinical application, lnt. Syrup. RottachEgern 1971. Karger, Basel. Messmer, K. (1976) Zussamenfassung des Round Table Gespraches uber praeoperative Hamodilufion. Anaesthetist 25, 181-188. Pilchmayr, J., Sippel, R., Coburg, A. J. & Grosse, H. (1975) Hamodilution und Gehirndurblutung. Anaesthetist 24, 440-444. Sunder-Plassmann, L., Klovekorn, W. P. & Messmer, K. (1976) Praoperative Hamodilution: Grundlagen, Adaptationmechanismen und Grenzen klinischer Anwendung. Anaesthetist 25, 124-130. Sundt, Th. M., Waltz, A. G. & Sayr, G. P. (1967) Experimental cerebral infarction. Modification by treatment with hemodiluting, hemocontracting and dehydrating agents. J. Neurosurg. 26, 46-56. Zelman, J. B., Szewczykowski, J., Czernicki, Z. & Jurkiewicz, J. (1974) Pathomorphology in experimental brain oedema produced by compression of the cat brain. Neuropat. PoL 12, 427 -436.