Cerebral Blood Flow in Acute Head Injury: The Regulation of Cerebral Blood Flow and Metabolism During the Acute Phase of Head Injury, and Its Significance for Therapy

73 Pages·1990·3.56 MB·English

by  Georg Emil Cold M.D. (auth.)

Cerebral Blood Flow
in Acute Head ItyUry
of
The Regulation Cerebral Blood Flow and Metabolism
of
During the Acute Phase Head Injury)
and Its Significance for Therapy
Georg Emil Cold
Acta Neurochirurgica
Supplementum 49
Springer-Verlag Wien New York
Georg Emil Cold, M.D.
Department of Neuroanesthesiology, Arhus Kommunehospital, Arhus, Denmark
With 16 Figures
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Softcover reprmt of the hardcover 1s t edition 1990
Printed on acid-free paper
Library of Congress Cataloging-in-Publication Data. Cold, G. E. (Georg Emil), 1938- . Cerebral blood flow in acute head injury: the regulation of cerebral
blood flow and metabolism during the acute phase of head injury, and its significance for therapy j Georg Emil Cold. p. cm. - (Acta neurochirurgica. Supplementum,
ISSN 0065-1419; 49). Includes bibliographical references. ISBN-13:978-3-7091-9103-3 1. Brain damage. 2. Cerebral circulation. 3.
Brain - Metabolism. I. Title. II. Series. [DNLM: 1. Brain - blood supply. 2. Cerebrovascular Circulation. 3. Head Injuries - metabolism. 4. Head Inju
ries-physiopathology. WI AC8661 no. 49 j WL 302 C688c]. RC387.5.C64 1990. 61 7.4'8 1044-dc20. 90-10379.
ISSN 0065-1419
ISBN-13 :978-3-7091-91 03-3 e-ISBN-13:978-3-7091-9101-9
DOl: 10.1007/978-3-7091-9101-9
Preface
The present studies were carried out at the Department of Neurosurgery G, Arhus University Hospital 1970-
1973; at the Department of Anesthesiology, Hvidovre University Hospital, Copenhagen, 1976-1977; and finally
at the Department of Neurosurgery GS, Arhus University Hospital, 1986-1987. Accordingly, I want to thank
the chiefs of these departments, Professor Richard Malmros, Professor Peter Rasmussen, and Jens Buhl in Arhus,
and Professor Henning Ruben in Copenhagen.
I am deeply indebted to my collaborators in these clinical studies. For help during the first studies, lowe
special thanks to Hans Hvid Hansen M.D., Head of the Department of Nuclear Medicine, Finn Hlgeh0j Jensen
B.Sc., and Erna Enevoldsen M.D. Regarding the studies performed in Copenhagen, I am indebted to Mogens
Stig Christensen M.D. and Kare Schmidt M.D. Dr. E. Spencer provided valuable assistance with regard to the
linguistic formulation of the review.
Furthermore, I am indebted to my colleagues anaesthesiologists Erland Hansen M.D. and J0rgen Kaalund
Jensen, who encouraged me to continue the clinical studies. Finally, I want to express my gratitude to my wife
Ida Cold and my sons Jakob and Christian for their patience and understanding during two decades.
Georg Emil Cold
This review is based on the following previously published papers:
I Cold GE, Jensen FT, Malmros R (1977) The cerebrovascular CO reactivity during the acute phase of
2
brain injury. Acta Anaesthesiol Scand 21: 222-231.
II Cold GE, Jensen FT, Malmros R (1977) The effects of PaC0 reduction on regional cerebral blood flow
2
in the acute phase of brain injury. Acta Anaesthesiol Scand 21: 359-367.
III Cold GE (1978) Cerebral metabolic rate of oxygen (CMR02) in the acute phase of brain injury. Acta
Anaesthesiol Scand 22: 249-256.
IV Cold GE, Jensen FT (1978) Cerebral autoregulation in unconscious patients with brain injury. Acta
Anaesthesiol Scand 22: 270-280.
V Cold GE, Jensen FT (1980) Cerebral blood flow in the acute phase after head injury. Part I: Correlation
to age of the patients, clinical outcome and localization of the injured region. Acta Anaesthesiol Scand
24: 245-251.
VI Cold GE, Christensen MS, Schmidt K (1981) Effect of two levels of induced hypocapnia on cerebral
autoregulation in the acute phase of head injury coma. Acta Anaesthesiol Scand 25: 397-401.
VII Cold GE (1986) The relationship between cerebral metabolic rate of oxygen and cerebral blood flow in
the acute phase of head injury. Acta Anaesthesiol Scand 30: 453-457.
VIII Cold GE (1989) Does acute hyperventilation provoke cerebral oligaemia in comatose patients after acute
head injury? Acta Neurochir (Wien) 96: 100-106.
IX Cold GE (1989) Measurements of CO reactivity and barbiturate reactivity in patients with severe head
2
injury. Acta Neurochir (Wien) 98: 153-163.
Contents
Abbreviations VIII
Introduction ................................................................................................. .
1. Measurement and Cerebral Blood Flow (CBF) and Oxygen Consumption, and the Regulation of
Cerebral Circulation ...................................................................................... 2
Experimental Studies of Cerebral Blood Flow .......................................................... 2
Measurement of Cerebral Blood Flow (Human Studies) ................................................ 3
Human Studies of Cerebral Metabolic Rate of Oxygen (CMR02) .......•..................•.........• 5
Hypothermia .............................................................................................. 6
CO Reactivity and Adaptation to Prolonged Hyperventilation ........................................ 7
2
The Use of Prolonged Continuous Hyperventilation. Pro et contra .................................... 9
Cerebral Autoregulation (CA) ........................................................................... 11
2. Ischaemic Thresholds and Development of Ischaemia .................................................. 14
3. The Effect of Barbiturate and Mannitol on CBF and Metabolism..................................... 16
Barbiturate: Experimental Studies ....................................................................... 16
Human Investigations .................................................................................... 18
Mannitol .................................................................................................. 18
Mannitol and Blood-Brain Barrier (BBB) ............................................................... 19
4. Experimental Studies of Head Injury .................................................................... 21
5. Human Studies of Head Injury .......................................................................... 24
ICP Recordings in Patients with Head Injury ........................................................... 24
Biochemical Studies of CSF .............................................................................. 25
6. The Author's Own Studies ............................................................................... 27
CBF and CMR0 in the Acute Phase of Head Injury (Own Studies) .................................. 27
2
Presentation of the Study and the Investigational Methods Used ...................................... 27
Repeated Studies of CBF ................................................................................ 28
Studies of CMR02 ............•............•.....................•...........•.....••...........••....•.• 29
Studies of Relationship Between CMR02 and CBF .................................................... 30
Repeated Studies of Cerebral Autoregulation ........................................................... 30
Studies of Cerebral Autoregulation During Two Levels of PaC0 31
2 ••••••••••••••••••••••.•••••.••••••••
Studies of CO Reactivity ................................................................................ 32
2
Studies of Barbiturate- and CO Reactivities ............................................................ 35
2
Summary of the Nine Studies ............................................................................ 36
Discussion of the Results................................................................................. 37
Summary Concerning Dynamic Changes in Cerebral Circulation and Metabolism.................... 41
Therapeutic Considerations .............................................................................. 42
Future Studies of Cerebral Circulation and Metabolism in the Acute Phase of Head Injury. . . . . . . . . . 43
Summary..... .... ..... .......... ... ........... .... ..... ............. ... ...... .... .......... .......... ........ 44
References .................................................................................................... 48
Listed in Current Contents
Abbreviations
AVD0 Arterio-venous difference of oxygen
2
BBB Blood-brain barrier
BI Brain injury
CA Cerebral autoregulation
CBF Cerebral blood flow
CBV Cerebral blood volume
CMR0 Cerebral metabolic rate of oxygen
2
CPP Cerebral perfusion pressure
CVP Central venous pressure
CVR Cerebral vascular resistance
CPH Controlled prolonged hyperventilation
CSF Cerebrospinal fluid
GCS Glasgow coma score
HI Head injury
ICP Intracranial pressure
IH Intracranial hypertension
MABP Mean arterial blood pressure
MCAO Middle cerebral artery occlusion
MR Magnetic resonance
Introduction
Understanding of the dynamic changes in cerebral ter 2 reviews present knowledge ofischaemic threshold.
blood flow (CBF), cerebral metabolic rate of oxygen On the basis of experimental and clinical studies con
(CMROz), and intracranial pressure (lCP) is of utmost cerning the effects of barbiturates and mannitol on
importance in the clinical care of patients with severe cerebral circulation and metabolism, studies concern
head injury (HI). Thus, four principles of treatment in ing barbiturate treatment and the use of mannitol in
common use in the management of patients with HI patients with head injury are reviewed in chapter 3.
(i.e. prolonged artifical hyperventilation, barbiturate Chapter 4 considers experimental and clinical studies
sedation, hypothermia and mannitol treatment) are of ICP, CBF and metabolism after acute head injury.
based on the principles for regulation ofCBF, CMROz, In chapter 5 human studies of ICP and, biochemical
and ICP. During the last decade a multitude of studies studies of CSF are summarized. Chapter 6 includes a
concerning the dynamic changes in CBF, CMROz, and presentation of the author's studies of CBF and me
ICP have been published. These studies have been sup tabolism in the acute phase of head injury and the
plemented with studies of cerebral autoregulation (CA) chapter is concluded with a general discussion. A sum
and studies of the chemical regulation of CBF, espe mary concerning the dynamic changes in cerebral cir
cially COz reactivity. Recently the topic has been re culation and metabolism is elaborated and followed by
viewed (Enevoldsen 1980, Jennett and Teasdale 1981, theoretical considerations concerning the therapeutic
Enevoldsen 1986, Sundbarg 1988); however, the ther effect of prolonged hyperventilation, barbiturate treat
apeutical implications of clinical CBF studies have only ment, and treatment with mannitol.
rarely been discussed. In this review experimental and This review is primary addressed to neurosurgeons
clinical studies of cerebral circulation and metabolism and neuroanaesthesiologists concerned with the man
in severe head injury have been supplemented with agement of patients with severe head injury. Studies of
studies of intracranial pressure (ICP), biochemical subarachnoid haemorrhage, cerebral tumours and in
studies of brain tissue and cerebrospinal fluid, and the tracerebral haematoma have not been reviewed, unless
theoretical implications for therapy are discussed. Elec these investigations were relevant to other aspects in
troencephalographic investigations, studies with trans the text. New principles of treatment including Ca + +
cranial doppler technique, studies of magnetic reso blocking agents and indomethacin have not been re
nance and CT scanning have only been considered if viewed. Nevertheless, the aim is, that the text presented
they elucidated the dynamic changes in CBF, ICP or might offer some help in the understanding of the dy
metabolism. namic changes in cerebral circulation and metabolism
The review consists of five chapters. Chapter 1 con in neurosurgical and neuroanaesthesiological practice
siders experimental and human methodology of CBF and inspire even deeper exploration into this interesting
studies, metabolism and the regulation of CBF. Chap- field.
1. Measurement and Cerebral Blood Flow and Oxygen Consumption, and the
Regulation of Cerebral Circulation
Experimental Studies of Cerebral Blood Flow Microsphere cerebral blood flow determination was
introduced by Roth et al. (1970). A number of condi
Measurements of cerebral blood blow (CBF) is
tions must be fulfilled for the accurate reflection of
based on the use of freely diffusible indicators, which
CBF by microspheres. The microspheres must be well
reach the brain tissue by the arterial system and give
mixed at the injection site, the distribution in the blood
rise to a fast and complete equilibration in concentra
stream must be proportionally to the actual blood flow,
tion between blood and tissue. The principle of cal
the micro spheres must be trapped completely on first
culation of CBF is based on the measurement of mean
passage and not disturb the regional or general cir
transit time. The technique has been developed during
culation, and they must be stabely lodged until counted.
the last 40 years and was originally introduced by Kety
Currently, 10 isotopes for labelling micro spheres are
and Schmidt (1945) with the use of nitrous oxide as
available. Each isotop is characterized by specific
tracer. Later, the technique was elaborated to include
gamma energy peak, thereby allowing detection by dif
diffusible indicators including Krypton-85 and Xenon-
ferential spectrometry. Organ blood flow in relative
133. The Kety-Schmidt and the intraarterial 133-Xenon
terms is calculated as the percentage of spheres in the
methods have been used in several animal experiments.
area of interest in relation to the total number of spheres
By surgical removal of soft tissue over the calvaria and
13 3-Xenon injection in the lingual artery, it is possible injected. In absolute terms, blood flow can be calcu
to avoid extracerebral contamination in monkeys and lated by measuring cardiac output by a separate tech
rats (Harper and Jennett 1968, Hertz et al. 1977). nique (Nuetze et al. 1968, Mendell and Hollenberg
The Hydrogen clearance technique introduced by 1971), or by determining a reference organ blood flow
Aukland et al. (1964) has some advantages in experi by withdrawing blood at a constant rate during mi
mental studies, because of its ability to obtain multiple crosphere injection (Makowski et al. 1968, Domenech
flow measurements over long periods of time (up to et al. 1969). Under normal physiological conditions a
10 hours), the ability to measure flow in a small tissue good correlations between CBF determined by mi
volume, and the stability of the partition coefficient, crosphere technique and that obtained with 133-Xe
especially in damaged tissue. The measurement of non, iodoantipyrine, and hydrogen clearance have been
rCBF is based on a linear function between electrode found (Fan et al. 1979, Horton et al. 1980, Marcus et al.
current and tissue hydrogen concentration, provided 1981, Heiss and Traupe 1981). Under pathologic con
that the thickness of the diffusion layer is constant. ditions a good correlation was found with the 133-
Comparisons with other methodologies (venous out Xenon technique at flow rates below 120 mil 100 glmin,
flow, 133-Xe, radioactive microspheres and 14-C an but not above this flow rate (Marcus et al. 1981). Dur
tipyrine) have shown fairly good correlations (Rowan ing middle cerebral artery occlusion, flow determined
et al. 1975, LaMorgese et al. 1975, Heiss and Traupe by the microsphere method consistently showed higher
1981). On the other hand, the technique is traumatic, flow values than those obtained with the hydrogen
giving rise to tissue injury due to electrode implantation clearance method (Heiss and Traupe 1981). In anaes
and resulting in loss of autoregulation, hyperaemia and thetized and awake animals the microsphere technique
oedema (Tuor and Farrar 1984). Moreover, zero base works excellently. Both regional and whole brain blood
line stability can be difficult to obtain; arterial recir flow are easily obtained, and the calculation of flow is
culation of hydrogen and intercompartmental diffusion not dependent on a diffusion coefficient. Shunting of
might be causes of error as well (for review see Farrar micro spheres might occur, especially under patholog
1987). ical conditions and during anaesthesia. It must be
Experimental Studies of Cerebral Blood Flow 3
stressed that the use of micro spheres in various patho mate local CBF even in small animals (Pulsinelli et aZ.
logic models has not been fully evaluated. 1982).
Venous outflow from the portion ofthe brain drained After the development of the 2-deoxyglucose
by the sagital and straight sinuses can be drained from method for measurement of regional cerebral glucose
the torcula. If the lateral sinuses and the occipital em utilization (rCMRgl) (Sokoloff et aZ. 1977), matched
issary veins are occluded, the venous outflow represents animal series for studies of rCBF and rCMRgl have
CBF. From the confluence of the sinuses the blood been possible. This double-tracer autoradiographic
passes through a transducer probe or an electromag strategy has recently been developed (Lear et af. 1981,
netic flowmeter. This method was intraduced by Rapela Ginsberg et aZ. 1986), and Lear et aZ. (1984) have de
and Green (1964) and was further elaborated in the veloped a generalized mathematic approach that allows
dog by Michenfelder et aZ. (1968) and Michenfelder and two or more radionuclides with different half-lives to
Theye (1968), who found a good correlation between be used simultaneously to measure multiple aspects of
flow determined by the venous outflow technique and cerebral circulation and metabolism. In the method of
that obtained by the 133-Xenon method. In dogs, the Sokolofffor rCMRgl determination, local2-deoxy glu
venous outflow obtained represents drainage from 43 % cose accumulation is the basis for estimation of local
of the brain. In rats continuous venous outflow can be glucose phosphorylation. However, only in normal tis
measured after cannulation of the retroglenoid vein sue can the rate of 2-deoxyglucose accumulation be
(Meldrum and Nilsson 1976, Nilsson and Siesjo 1983). assumed to be a known fraction of glucose consump
This method has been investigated by Morii et aZ. tion. If the relationship between plasma and brain glu
(1986 a), who found minimal extracerebral contami cose has changed, a correction ratio of 2-deoxcyglucose
nation and a good correlation to flow obtained by the accumulation to glucose consumption (the lumped con
microsphere technique. stant) might be determined separately by 3-0 methyl
The autoradiographic method of measurement of glucose autoradiography. Methods for this triple-tracer
local CBF is based on Kety's study of the kinetics of technique has been developed by Gjedde and Diemer
inert gas exchange. The method was introduced by (1983).
Landau et aZ. (1955) and Freygang and Sokoloff (1958)
using 131-J trifluoroiodomethane as tracer. In 1969
Measurement of Cerebral Blood Flow (Human
Reivich and coworkers introduced antipyrine-14C,
Studies)
whilst Sakurada etaZ. (1978) introduced iodo (14C)
antipyrine, which has a greater blood-brain barrier per Measurement of CBF in humans was introduced by
meability compared with antipyrine-14C. The calcu Kety and Schmidt with nitrous oxide as freely diffusible
lation of local CBF is determined from the concentra indicator (Kety and Schmidt 1945, Kety and Schmidt
tion of the tracer in the region of interest. The values 1948). The method as originally described by Kety,
of the arterial concentration of the tracer apply under presumes catheterization of the internal jugular vein,
the assumptions that the tracer is biologically inert, the either by insertion of a catheter from the lateral or the
tracer in the effluent veins of the tissue is in equilibrium anterior approach of the neck with the tip of the cath
with that of the brain, the CBF remains in a steady eter directed cranially and placed at the base of the
state during the period of measurement, and the value skull. Furthermore, a catheter in a peripheral artery is
of the partition coefficient of the tracer can be deter necessary. During a 15-30 min period of inhalation of
mined. It has been shown that auto radiographic strat the diffusible tracer, or during exhalation of the tracer
egy tends to underestimate flow, especially at increased after establishment of equilibrium between blood and
flow rates (Eklof et al. 1974) and under ischaemic con brain tissue, samples of arterial and jugular venous
ditions. Tomita and Gotoh (1981) have stressed that blood are withdrawn at fixed intervals and the con
the method is inaccurate because of incomplete tracer centration of tracer determined. By the use of the
mixing in ischaemic tissue and altered tracer permea height-over-area formula, CBF is calculated as mil
bility. However, with the use of very short tracer in 100 glmin as a global estimate of blood flow. By si
fusion periods, local CBF can be measured by a mod multaneous determination of arterial and venous blood
ification of the indicator fractionation technique elab oxygen content, the arterio-venous oxygen content dif
orated by Goldman and Sapirstein (1973), and this ference (A VD0 is calculated in vol%, and by simple
2)
technique has been used autoradiographicallyto esti- multiplication the cerebral metabolic rate of oxygen