Beruflich Dokumente
Kultur Dokumente
By
M. Brock, K. Schiirmann, and A. Hadjidimos
With r Figures
The well known clinical picture of "coma depassd" ao, ~1 which follows
lethal post-anoxic cerebral oedema (e.g. in cases of severe head trauma
or prolonged cardiac arrest with isoelectrie EEG) is sometimes accom-
panied by the angiographic phenomenon of non-filling of cerebral
v e s s e l s 4, 12-14, 21, 22, 26-29, 35, 39, 43, 44
I t is accepted--but has not been p r o v e n - - t h a t this non-filling phenom-
enon represents an arrest of cerebral circulation, supposed to be due to
an increase in intracranial pressure to levels above systolic 1, 27, 29 or
diastolic 22 blood pressure. However, "minimal residual carotid blood flow
when intracranial pressure had been elevated far above the systolic pres-
sure" has been observed 26, 27. Further, the fact that apparently no anglo-
graphic contrast has penetrated into the cranium by the carotid arteries
is no proof that there is no cerebral blood flow (CI3F) because the amount
of contrast medium able to enter the cerebral vessels may be too little to be
visualized. [Further attention will be directed to this point in the discussion.
The isoelectricity of the E E G often observed in such cases, and which
seems to precede the non-filling phenomenon 14, has been invoked by some
as a proof of cerebral (and total) death. (For an extensive discussion on
this subject see the work of Spann et a/.47). Since there are several clinical
conditions compatible with life which m a y also be associated with an
isoelectric EEG, even for long periods of time2, a, 7, ~, 82-34, 56, recovery
having been recorded even after four and five days of isoeleetrieity 51,
and since, on the other hand, in patients with isoeleetric E E G and
lethal outcome evoked potentials or central reflexes may still be ob-
tained 2, 3, 40 and others, the E E G cannot be considered a reliable criterion
of so-called cerebral death--even if the basal ganglia are also silent 25.
lYiodern resuscitative and intensive care techniques have allowed such
irreversibly comatose patients to be maintained in a state of vegetative
life for longer periods of time. However, the outcome has not been altered
196 M. Brock, K. Schfirmann, and A. Hadjidimos:
Fig. 1. Bilateral percutaneous common carotid arteriogram showing ~he non-filling phenomenon on
both sides.
1 4
B
t t
lmkt
t
1
t
100.
9 10 12
10-
100 84
15 16
10.
Fig. 2. Position of the 16 channels as well as the corresponding tracings after selective injection of
l~aXe-solution into the su~'gically e x p o s e d interna! carotid artery. Notice ~he small amoun~ of traoer
r e a c h i n g the brain a n d the absence of clearance. The h i g h b a c k g r o u n d is due to a previous injection
(80 m i n u t e s before),
200 M. Brock, K. Schiirmann, and A. Hadjidimos:
1-3
@
3-13
13- 5
5-7
4-14
14-6
lO01N l ! w..
6-8
1-3
3-13 @
13-5
5-7
2-4
"14.p . . . . . .
1-3
3"13
9
13-5 5 0 i N IT 1 ser
5-7
A
clapping
24 I
4-14
6-8
:Fig. 3. E E G (needle electrodes) a t the time of the CBF study. (For discussion see text.)
Cerebral Blood Flow and Cerebral Death 201
interval to 0.63 see (the normal for this frequency being 0.38 to 0.46 see) as
commonly seen in hypothermia *.
Artificial ventilation was continued until the next morning, when cardiac
arrest ensued, some 90 hours after the accident. Body temperature at this
time was below 340 C.
Necropsy ** revealed maeroscopieal signs of increased intraeranial pressure
with marked flattening of the convolutions and signs of tentorial and cerebellar
herniation. Multiple punetate haemorrhagie feel were sparsely distributed
throughout both the grey and white matter. However there were no gross
focal lesions. Microscopic sections revealed generalized brain oedema, poor in
protein substance, with widening of the pericellular spaces and swelling of
macroglial elements. The white matter displayed a pronounced imbibition
and cribiform changes in the sense of a status lacunaris. The blood vessels to
the brain and within it were permeable.
The above findings are similar to those reported in other pathological
studies of cases of longer artificial prolongation of "life" 6, sl
Discussion
I n the case reported here the evoked potentials obtainable over both
temporal areas, m a i n l y on the right side, after clapping hands near to
the right ear are difficult to interpret. As demonstrated by Ar/el2, however,
such potentials bear no prognostic significance.
2. The lack of penetration of angiographic contrast medium into the
cranium t h r o u g h one more of its afferent arteries also does not prove
t h a t there is no brain circulation. Reversibility of the non-filling phenom-
enon (case 3 of Gros et al.la; case 11 of Pribram as) and even recovery from
it (ease 5 of Riishede and Ethelberg89; ease 6 of Pribram 3s) have been
reported. I n addition, to the objections already made to this criterion at
the beginning of this paper, we should like to add the diagnostic problem
which can be posed b y cases of t r a u m a t i c thrombosis of the internal
carotid artery. Although in such cases coma is not the ruleS, 18, 42 ann
others, it can occur 87, a2. Deep coma with unilateral non-filling m a y even
follow spontaneous carotid thrombosis (ease 2 of Horwitz and Dunsmore 21)
or a t h c r o m a t o u s occlusion (ease 8 of Pribram~S).
If, on the other hand, an inert diffusible tracer "'deposed" within the
brain is not washed out, this quite obviously means that. there is no blood
flowing through this organ s . The question is: " H o w can the tracer be
deposed w i t h i n the b r a i n i n cases of non-filling ?" The m a n u a l injection
seems sufficient to " p u l l " some tracer into the c r a n i u m i n such cases,
provided re/lux /roqn the internal into the external carotid arteries is pre-
vented. This was certainly so i n the present case, as already described.
Fig. 4. Anteropostcrior scan about 10 hours after the injection of labelled (131I) albumin macro-aggregates
into the right common carotid artery of another patient of this series.
and from 105/80 to 140/85) was induced without causing any significant
change in the clearance slopes. I n one of these patients 131I-labelled
albumin macro-aggregates injected into the common carotid artery
immediately following angiography* failed to penetrate into the cranial
cavities, remaining trapped in the capillaries of the neck and the base of
the cranium (Fig. 4). I n no case was the average CBF higher than 5 ml/
100 g rain.
Although, b y preventing the reflux of tracer, it is possible to force the
indicator into the brain, its amount will not be very large (unless large
volumes are injected) since, under such circumstances, some injected
material will always remain in the extracranial portion of the internal
carotid for very long periods of time e~ and diffuse into the surrounding
tissues of the neck. In the examination of the case here reported only 3 ml
were injected. This explains (a) the very low height of the recorded plateaus
and (b) that practically only the basal brain regions have been attained
b y the tracer.
At the present stage of our researches we do not know if the demon-
stration of a practically complete unilateral flow arrest (even if undoubted)
is sufficient to demonstrate cerebral death. I t should be surprising if it
were not so, although, of course, bilateral studies will provide greater
safety. For a better understanding of the problems involved vertebral
flow studies will also have to be performed in some borderline cases.
However, it is difficult to conceive t h a t the maintainance of blood flow
to the brain s t e m - - e v e n if sufficient to allow the functioning of its centres
---is compatible with the condition of h u m a n life in the absence of blood
supply to the cerebral hemispheres.
Summary
Cerebral Blood Flow and Cerebral Death
Preliminary Report
At present the diagnosis of cerebral death is based on the absence of
manifestations of cerebral function (deep coma, wide pupils, absence of
reflexes and spontaneous respiration, isoelectric EEG, etc.) during a
variable period of time. However, the absence of vital signs of an organ,
even for prolonged periods, is no proof of its death. The death of an organ
can only be considered as proved b y the demonstration t h a t this organ
has remained completely deprived of its blood flow during a period of
time that surpasses its ability to survive circulatory arrest. I n the case
of the brain, the permanent absence of clearance of a radioactive tracer
deposed within the brain is considered to demonstrate total absence of
flow through it and, thus, to prove cerebral death. As discussed in the
text, previous attempts at angiographic "demonstration" of the arrest
of cerebral blood flow cannot be accepted uncritically.
* The authors are indebted to the Dept. of Radiology, Univ. of Mainz,
for this scan.
Cerebral Blood Flow a~nd Cerebral Death 5)05
Th e v al u e of t h e p r e s e n t findings in d e t e r m i n i n g t h e d e a t h of ~ p a t i e n t
w i t h reference to organ t r a n s p l a n t a t i o n has been discussed.
The authors are indebted to M. Ellger, 3{.D. and to G. Busch, M.D. for their
help in the study of the cases herein reported.
We t h an k Mrs. B. MiZller for her assistance in preparing the manuscript
and Mrs. R. A d a m for the photogTaphic work.
Zusammenfassung
Hirndurchblutung und Hgrntod
Vorldiufiye Mitteilung
Zur Zeit st6tzt sich die Diagnose des zerebralen Todes auf das Fehlen yon
Zeichen zerebraler Funktion (tiefes Korea, w e r e Pupillen, Fehlen yon Reflexen
und Spontanatmung, isoelektrisches E E G usw.) w~ihrend eines versehieden
langen Zeitabschnittes. Indessen ist das Fehlen yon Lebenszeichen eines
Organes, selbst fiber ]/ingere Zeit, kein Beweis ftir dessen Ted. Der Ted eines
Organes kann nut dann als gesichert gelten, wenn nachgewiesen ist, dab dieses
Organ fiir eine Zeitspanne vollstgndig seiner Blutversorgung beraubt war, die
seine Fghigkeit iiherschreitet, einen zirkulatorischen Stitlstand zu iiberleben.
I m Falle des Gehirns wird die Ansicht vertreBen, dab ein dauerhaftes Fehlen
einer Clearance eines radioaktiven Indikators, der in das Hirn eingebraeht
worden ist, das vollst/~ndige Fehlen einer Durchblutung und damit den tIirn-
ted beweist. Wie im Text diskutiert, k6nnen frfihere Versuehe des angio-
graphiachen Beweises eines Stillstandes der Hirndurehblutung nicht0 unkritiseh
akzeptiert werden.
Die Bewertung der dargestellten Befunde bezfig]ieh der Festste]Iung des
Todes eines Patienter~ in Hinbliek auf Organtransptantationen wird diskutiert.
R6sum6
Circulation c~r~br'ale et mort du cerveau
Communication prdliminaire
Le diagnostic de mort du eerveau est bas6 jusqu' g pr6sent sur l'absence
de manifestations des fonetions cdrdbrales (coma profond, mydriase bitat6rale,
abolition des rgflexes, arr~t respiratoire, tracds E.E.G. plats ere . . . . ) pendant
un laps de temps variable. Cependant l'absence de signes fonctionnels d'un
organe, m6me pendant un laps de temps prolongd, n'est pas la preuve formelle
de sa mort. La mort d'organe ne pent ~tre prouv6e sue par la ddmonstration
que oct organe est rest6 compldtement priv6 de circulation sanguine
pendant un laps de temps qui d@asse sa eapacit6 de survie s un arr~t
eireulatoire.
Dana le eas du cerveau, l'absenee de clearance d'un produit radioactif
d6pos6 dana cet organe, est la preuve de Farr~t total de la circulation
sanguine et ainsi de la mort du cerveau. La d6monstration de l'arrgt
circulatoire par l'angiographie dans les tr a v a ux ant6rieurs, ne pent 6tre
aeeept6e sans rgserves.
La valeur des d6couverfies r6sentes pour diagnostiquer la mort d'un patient,
en cas de transplantation d'organe, a 6t6 diseut6e.
206 M. B r o c k , K . S c h t i r m a n n , a n d A. H a d j i d i m o s :
Riassunto
Circolazione cerebrale e morte cerebrale
t~apporto preliminare
A1 m o m e n t o a t t u a l e la d i a g n o s i di m o r t e c e r e b r a l e si b a s a s u l l ' a s s e n z a di
m a n i f e s t a z i o n i della f u n z i o n e c e r e b r a l e ( c o m a p r o f o n d o , d i l a t a z i o n e p u p i l l a r e ,
a s s e n z a di riflessi e di r e s p i r a z i o n e s p o n t a n e a , E E G isolelettrico ecc.) d u r a n t e
u n p e r i o d o di t e m p o v a r i a b i l e . T u t t a v i a l ' a s s e n z a di segni v i t a l i d a u n o r g a n o
a n c h e p e r u n p r o l u n g a t o periodo, n o n e' p r o v a della s u a m o r t e .
L a m o r t e di u n o r g a n o p u o ' essere c o n s i d e r a t a c o m e p r o v a t a solo c o n la
d i m o s t r a z i o n e che q u e s t o o r g a n o e' r i m a s t o p r i v a t o della s u a cireolazione p e r
u n p e r i o d o t e m p o che s o r p a s s a la s u a e a p a c i t a ' di s o p r a v v i v e r e a d u n a r r e s t o
circolatorio.
Nel caso del cervello la a s s e n z a p e r m a n e n t e della c l e a r a n c e di u n m a r c a n t e
r a d i o a t t i v o d e p o s i t a t o d e n t r o il cervello e' c o n s i d e r a t a c o m e d i m o s t r a z i o n e
d e l l ' a s s e n z a t o t a l e della circolazione i n esso e q u i n d i c o m e p r o v a di m o r t e
cerebrale.
Come discusso n e l t e s t o , p r e c e d e n t i t e n t a t i v i di u n a ~(d i m o s t r a z i o n e ~)angio-
g r a f i c a d e l l ' a r r e s t o della eireolazione c e r e b r a l e n o n p u o ' essere a e e e t t a t a s e n z a
eritiche.
I1 significato delle p r e s e n t i r i c e r c h e p e r la d e t e r m i n a z i o n e d e l l a m o r t e di u n
p a z i e n t e e' discusso a n c h e i n r a p p o r t o ai t r a p i a n t i di o r g a n o .
Resumen
Circulacidn cerebral y muerte cerebral
Communicacidn provisional
Actualmente el diagndstico de muerte cerebral se funda en la falta de
sefiales de funcidn cerebral (coma profundo, pupilas dilatadas, falta de
reflejos y respiraci6n espontdnea, EEG isoel~ctrico, etc.) durante un espa-
cio de tiempo de distinta duraci6n. La falta de signos de vida de un 6r-
gano, afin durante largo tiempo, no es una prueba de su muerte. La mu-
erte de un 6rgano solo puede asegurarse cuando se ha demostrado que
para ese 6rgano su irrigaci6n de sangre fu~ suprimida totalmente durante
u n espacio de t i e m p o , el eual s o b r e p a s a s u c a p a c i d a d de s o b r e v i v i r u n
p a r e circulatorio. E n case del c e r e b r o se d e f i e n d e ]a o p i n i d n , de que l a
f a l t a d u r a d e r a de a c l a r a m i e n t o (Clearance) de u n i n d i e a d o r r a d i o a c t i v e ,
t r a n s p o r t a d o al eerebro, d e m u e s t r a la f a l t a c o m p l e t a de c i r c u l a c i 6 n y c o n
ello la m u e r t e c e r e b r a l . C o m e se d i s c u t e e n el t e x t o , n o loueden ser acep-
f a d e s sin crltica, p r u e b a s a n t e r i o r e s de la d e m o s t r a c i d n a n g i o g r s de u n
p a r e de la c i r c u l a c i d n cerebral.
Se d i s c u t e la v a l o r a c i 6 n de los h a l l a z g o s e n r e l a e i d n a la d e m o s t r a c i 6 n
de m u e r t e de u n p a c i e n t e , e n v i s t a de u n a t r a n s p l a n t a c i 6 n de 6rganos.
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Cerebral Blood Flow and Cerebral Death 207
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Cerebral Blood Flow and Cerebral Death 209