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Management of Cerebral Edema

Article  in  Pediatrics in Review · January 1983

DOI: 10.1542/pir.4-7-217

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Derek A Bruce
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 Management of Cerebral Edema
Derek A. Bruce, MB, ChB*

Cerebral edema is an increase in ter. Thus, neurophysiologic dys-

the water content of the brain. It is function is almost always present
EDUCATIONAL OBJECTIVES
usually associated with an increase when there is intracellular edema.
in sodium content and a decrease in Extracellular edema is the corn- 49. Appropriate knowledge of re-
potassium content in the brain. Cer- mon type of brain edema that the cent advances in monitoring of
ebral edema must not be simply clinician is faced with treating. It re- cerebral edema and in its manage-
equated with increased intracranial suIts from a primary disturbance of ment (82/83).
pressure (ICP). Although the dele- the blood-brain barrier with leakage
6. Appropriate evaluation of the
terious effects of brain edema may of plasma ultrafiltrate containing al-
child with head trauma, with the
be produced by increased ICP, other bumin and other proteins out of the
ability to differentiate among con-
pathologic lesions can elevate the small intraparenchymal blood yes-
cussion, skull fracture, simple he-
cranial pressure with little or no cer- sels into the brain extracellular
matoma of scalp, subdural hema-
ebral edema (eg, acute hydroceph- space. The fluid can spread widely
toma, acute epidural hematoma,
alus, large hematoma, brain tumor, through the brain and is maximally
Intracerebral hemorrhage, child
or marked increase in cerebral blood present in the white matter with rel-
volume [CBV]). This discussion re- ative sparing of the gray matter (Fig abuse or neglect, laceration of the
scalp, contusion, and seizure die-
fers to the problems of brain edema 1).
order, and to determine by tele-
specifically, although many of the
phone consultation with the
therapeutic measures discussed STAGES OF EDEMA FORMATION
are, in fact, those for elevated ICP in mother whether the child needs to
AND REABSORPTION
general. be seen immediately for more cx-
It is important to think of brain tensive examination, with ability to
edema as a dynamic process. There Initiate appropriate management
TYPES OF BRAIN EDEMA
is a formation phase during which (Topics 82/83).
There are three types of brain the edema is forming and spreading.
7. Appropriate evaluation of the
edema: intracellular (cytotoxic), ex- In the case of intracellular edema,
comatose adolescent, with the
tracellular (vasogenic), and intersti- this will depend upon the metabolic
S tial (around the ventricles in associ- disturbance, whether it is focal or
ability to differentiate
trauma, seizure disorder,
among head
cerebral
ation with acute hydrocephalus). diffuse, its duration, and whether
accident, drug or alcohol inges-
The pathology of the latter is spread- neuronal cell death has occurred. tion, suicide attempt, heat exhaus-
ing of CSF through the ependymal The formation phase for extracellu-
tion, cardiac dysfunction, conver-
lining of the ventricles, as a result of lar edema and the extent and spread
sion reaction, metabolic disorders
hydrostatic pressure, into the brain of the edema fluid will be dependent
such as diabetes mellitus or hy-
interstitial space. The excess fluid is upon the area of blood-brain barrier
poglycemia, and meningococ-
CSF, the blood-brain barrier (BBB) disruption, the arterial pressure
cemia, and the ability to manage
is intact, and there appears to be no head, and the time course of the
each appropriately (Topics 82/
acute physiologic effect of the in- barrier opening. The next phase of
83).
creased water content. If the high edema is one of relative equilibrium
hydrostatic pressure is unrelieved, in which the edema is present, but
however, demyelination and even- the amount being added to the brain
tually axonal destruction occur in the is being counterbalanced by the gray matter, in which the cell bodies
periventricular region. The treatment amount being removed. Finally, and dendrites are found. Dependent
of this type of edema is clearly relief there is a phase of resolution during upon the insult, the intracellular ac-
of the hydrocephalus, and this will which additional edema formation cumulation of sodium and water will
not be discussed here. ceases and the excess water and occur in the neurons, glia, or both.
Intracellular edema is a secondary other products .are slowly removed Occasionally, intramyelinic swelling
event. The primary abnormality in all from the brain. Both the signs and
cases of intracellular edema is a dis- symptoms and appropriate therapy
turbance of cellular metabolism. will depend upon where in the proc-
This leads to inhibition of membrane ess of edema formation and resolu- Abbreviations
pumping and secondary accumula- tion the patient is. Therapy that is
tion of intracellular sodium and wa- appropriate at one stage may not be ICP Intracranial pressure
appropriate at another. CBF Cerebral blood flow
CBV Cerebral blood volume
Associate
#{176} Neurosurgeon, Children ‘s Hos-
PATHOPHYSIOLOGY SAP Systemic arterial pres-
pital of Philadelphia, 34th and Civic Center

S Boulevard,
ate Professor
Philadelphia,
Neurosurgery
PA 19104, Associ-
and Pediatrics, Intracellular Edema BBB
sure
Blood-brain barrier
University of Pennsylvania School of Medi-
cine. Intracellular edema occurs in the

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Cerebral Edema

ical pediatrics is hexachlorophene

poisoning. A final clinical situation in
which intracellular brain edema oc-
curs quite
that of water
frequently
intoxication
in children
or the syn-
is S
drome of inappropriate antidiuretic
hormone secretion. In this circum-
stance, there is a marked decrease
in blood and extracellular fluid os-
molality; water moves into the cell to
equilibrate the osmotic differences
and the result is cell swelling and
neuronal dysfunction.

Extracellular Edema

Extracellular edema is the result

of leakage of the blood-brain barrier
and occurs predominantly in the
white matter of the brain, spreading
along the fiber tracts, even though
the area of barrier damage may be
in the cortex (Fig 2). The reason for
the relative sparing of the cortex is
iss ‘sparing of cortex and finger-like projections of edema
probably the cytoarchitecture. In the
through external capsule. gray matter, the cells have a cell fuzz
layer of glycoproteins and sialic acid
residues that project into the extra-
limited, the final step of the electron cellular space and probably act to
TABLE 1. Etiology and transport chain cannot be com- maintain the integrity of the cortex.
Location of Cerebral Edema: pleted, and ATP cannot be manufac- Thus, the gray matter acts like a
Intracellular(I), Extracellular
and Periventricular (P)
(E), tured by aerobic
ond major cause
glycolysis. The sec-
is ischemia, in
piece of porous
can be driven
porcelain
through
(ie, fluid
the extracel-
S
I E P which not only is 02 delivery limited, lular channels by bulk flow) but it is
but also delivery of glucose and re- very difficult to produce expansion
Ischemia + + +
I moval of waste products. Because of the extracellular space. Thus,
Hypoxia ++ -

Reyesyn- ++ +
of the interference with sodium po- fluid that leaks into the gray matter
drome tassium ATPase activity, extracellu- passes into the underlying white
Herpes enceph- + + I lar fluid enters the cell with an in- matter where it can accumulate and
alitis crease in cell volume and a decrease expand the extracellular space. The
Hexachloro- + - in the gray matter extracellular fluid is then free to move through the
phene space. As this process continues, if white matter along the fiber tracts
Water intoxi- + + -
there is blood flow present, fluid is (Fig 2). The fluid is a protein filtrate
cation continually absorbed from the blood containing albumin and other pro-
Peritumor - + +
through the extracellular space into teins. The site of origin of the edema
Periabscess - + +
the cells until cell rupture and cell is the vascular space and, thus, the
Cerebritis + +
death occur. If the insult is reversed term vasogenic edema. The gener-
Contusion - + +
Hydrocephalus - - ++ (eg, blood flow is reestablished) be- ation and spread of vasogenic
fore the stage of cell death, recon- edema has been likened to a broken
stitution of ATP may occur and the pipe in the ground with fluid seeping
is seen and, in this case, the edema intracellular swelling may be re- from the pipe and spreading through
appears to be between the myelin versed and function reestablished. the soil. The triggering event ap-
lamellae and, therefore, not truly in- Viral infections (eg, herpes simplex) pears to be a disruption of the blood-
tracellular. The common clinical produce a combination of intra- and brain barrier and occurs with such
causes of intracellular edema are extracellular edema. This is also true lesions as tumors, intracerebral he-
events that limit adenosine triphos- in Reye syndrome. Lead intoxication matomas, postsurgical resection of
phate (ATP)availability and, there- is a primary intracellular edema. brain, in association with brain con-
fore, sodium potassium ATPase ac- Certain chemical toxins have been tusion from trauma, around brain ab-
tivity. There are a number of major found which produce cellular scess and cerebritis and around
causes of intracellular edema in clin- edema. However, these are of areas of infarction. The rate of
ical pediatrics
hypoxemia,
(Table
in which
1). The first is
02 delivery is
mainly experimental
only one of major importance
interest and the
in din-
edema
spread
formation
depend upon
and the extent
the areas
of
of
S
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 NEUROLOGY

blood-brain barrier disruption, the

height of the systemic arterial pres-

S sure (SAP)
flow (CBF).
and the cerebral
Since the driving
blood
force
for edema formation and spread is
the hydrostatic force in the capillar-
ies, the higher the blood pressure,
the more rapidly edema will form and
the greater the distance it will spread
through the brain. The higher the
cerebral blood flow, the greater the
rate of delivery of plasma to the dam-
aged barrier and the greater the
amount of fluid that will leak in any
given time. It is important to realize
that the blood-brain barrier is dis-
rupted only at the site of generation
of the edema and is intact in the
areas of edema spread (Fig 2). One
of the mechanisms limiting the
amount of edema that will accumu-
late in the tissue is reabsorption of
edema fluid across the normal cap-
illary bed. A second compensatory
clearance mechanism appears to be Fig 2. Cat brain four hours after liquid nitrogen induced lesion of cortex (dark area). Evan ‘s
drainage of the edema fluid from the Blue was injected intravenously at time lesion was induced to demonstrate spread of edema
extracellular space into the ventric- (vasogenic). Arrow indicates edema fluid spreading into ventricle; solid arrowhead indicates
ular system (Fig 2), across the epen- sparing of gray matter; open arrowhead indicates margin of edema spread and normal white
matter.
dymal lining. This mechanism, how-
ever, is active only when there is a
pressure gradient being generated need for therapy, and to measure
S from the site of the BBB leakage to
tive
ciently
pathology
advanced
are
that
usually
the
suffi-
spatial the effects of that therapy.
the ventricles. As the barrier damage compensation inside the cranium
is repaired, then clearance into the MONITORING SYSTEMS
has been exhausted (ie, compensa-
CSF pathways becomes minimal be- tory mechanisms such as displace- Outside the neonatal age group,
cause of lack of driving force. The ment of CSF out of the cranium, ICP monitoring is performed by pres-
further clearance of the edema fluid displacement of blood volume out of sure measuring devices placed in
is across a normal cerebral capillary. the cranium, and brain compression the epidural, subdural, or subarach-
Pinocytosis, the vesicular transport have already occurred) and, there- noid spaces or in the lateral ventri-
of matter across cell membranes, fore, any further increase in intracra- des. Ideally, the measuring system
may play a role in this clearance nial volume is likely to produce a should be simple, reliable, easily in-
mechanism. large increase in ICP and acute de- serted, and have minimal complica-
terioration. Thus, headache associ- tions. The standard for ICP monitor-
ated with papilledema; transient ep- ing is still the intraventricular cathe-
EFFECTS OF EDEMA
isodes of visual loss or diffuse pos- ter. This is inserted through a twist
There is little evidence that cere- tural stiffening with or without loss of drill hole, usually in the frontal re-
bral vasogenic edema primarily pro- consciousness; focal neurologic gion. The catheter is passed into one
duces interference with electrophys- findings plus papilledema; or third frontal horn and frequently through
iologic function. The deleterious ef- cranial nerve palsy suggesting early the foramen of Monro into the third
fects appear to be related to brain herniation all signify that the patient ventricle. The tube is then usually
distortion and/or herniation. The is in the decompensated state. Epi- tunneled under the skin for a short
herniation may occur below the falx sodes of bradycardia in the younger distance in an effort to avoid infec-
cerebri, at the tentorial notch, or at child should trigger similar alarm tion. The monitoring is done through
the foramen magnum. The deleteri- systems. These patients are at real a fluid column connected to a strain-
ous effects are also produced by risk for rapid deterioration, and di- gauge transducer. This is the
generally elevated levels of ICP and agnosis and therapy should be un- method of choice in children with
a reduction in cerebral blood flow to dertaken immediately. Patients who large ventricles because it is the only
ischemic levels. The signs of brain are stuperous or comatose (ie, do monitoring system that can be used
edema then are those of focal neu- not make purposeful pain responses for therapy (ie, CSF withdrawal). The
S rologic
creased
deficit or of generalized
ICP. By the time symptoms
in- or open their eyes) require
ing of at least ICP and SAP to estab-
monitor- drawbacks
bleeding
of
or increased
this method
brain swelling
are:

present, the edema and the causa- lish what the ICP is, to define the as a result of passage of the catheter

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Cerebral Edema

through the cerebral substance, the used of these systems has been the and extracellular cerebral edema. In
difficulty of correct positioning when Ladd Fiberoptic System. This device pediatrics, the main pathologic
the ventricles are small or displaced, is usually inserted into the epidural states in which this occurs are
and the risk of infection.
fection is uncommon
Active in-
if the catheter
space through a burr hole. Despite
the need for a burr hole, the device
herpes encephalitis,
Reye syndrome.
infection,
A combination
and
also
S
is left in place for less than five days. can be inserted in the emergency occurs in cerebral infarction. When
Thereafter, the rate of positive cul- room or intensive care unit. The in- an encephalopathic process is
tures from the catheter system and cidence of infection in a reported present, the amount of brain edema
true ventriculitis rises rapidly. series is low, approximately 2% to and the intracranial pressure will not
The next most commonly used de- 3%. Some of the other drawbacks of necessarily correlate well with the
vice in children is the subarachnoid this system are its slow response level of consciousness. Nonethe-
bolt. This is a hollow metal bolt that time so that a pulsatile ICP wave is less, secondary deterioration and
is screwed into a twist drill hole, not recorded with each heart beat death can occur as a result of in-
again usually in the frontal region. and, therefore, changes in the shape creased ICP and cerebral herniation
The tip of the hollow metal device of the pulse wave cannot be identi- and it is to avoid this complication
lies in the subarachnoid space and fied. All solid state systems have the that ICP monitoring and therapy to
is connected through a fluid column potential disadvantage of not being maintain the ICP in the normal range
to a strain-gauge transducer. This amenable to calibration in vivo and is directed. A normal level of ICP is
device is simple to insert, and no of having drift of the base line with up to 1 5 mm Hg. Current intensive
intracranial infections have been temperature and time. Although the care management endeavors to
seen with the use of this device in Ladd System has these drawbacks, keep the ICP level below 20 mm Hg,
some 300 children. Potential com- reports of its use in children are most ifpossible.
plications include subdural, sub- encouraging. Newer devices are
arachnoid, or intracerebral hemor- being created to overcome some of
Intracellular Edema
rhage. There has been one signifi- the problems of the solid state sys-
cant subdural hemorrhage in a child tems. The major therapy for intracellular
with a severe clotting abnormality, In the newborn and premature in- edema is to establish normal cell
and no other significant intracranial fant the problem of ICP monitoring metabolism. Thus, the primary goal
hemorrhages. The commonest com- has not been solved. Many efforts of therapy is to reverse the patho-
plication has been local scalp infec- have been made to develop a fon- logic or physiologic aberrations as
tion requiring only local therapy. The tanel transducer, but none has been early as possible (Table 2). In anoxia
advantages of this method are: it can
be used no matter how small the
sufficiently
achieved
successful
routine usage
to have
at present.
or ischemia,
Unfortunately,
this is often possible.
if the period of limited S
ventricles; the brain is not violated Intraventricular catheters are clearly 02 and glucose delivery exceeds
and, therefore, the risk of increasing capable of being used, particularly five to ten minutes, it is unlikely that
swelling or bleeding is minimized; when the ventricles are large or in- total reversibility will occur despite
intracranial infection is exceedingly traventricular hemorrhage has oc- restitution of normal physiologic
uncommon; the bolt can be inserted curred. The problem with these cath- conditions. This will be less true the
with ease in the emergency room or eters is that, because of the prema- colder the child is, since the cerebral
intensive care unit. The disadvan- ture brain, porencephalic dilation metabolic rate decreases with de-
tages of the system are: it cannot be occurs along the tract in the brain creasing temperature and, at least
used for CSF withdrawal, when the and there is a risk of secondary in- theoretically the brain can tolerate
ICP is very high and the brain soft fection. A modified subarachnoid longer periods without cerebral
(impending brain death), the bolt bolt for use in the neonate and pre- blood flow and oxygen delivery. If
may become plugged with brain and mature child that has functioned the insult has been so severe that
register fairly low values despite quite successfully has recently been irreversible cellular disruption has
having good oscillations; ifthe dura developed. Finally, the application of occurred, the reestablishment of
is not open, false values may be the Ladd system to the fontanel is normal flow and oxygenation will not
recorded. currently performed in a number of save those cells that are already too
Another similar fluid-connecting institutions. The problems are co- damaged to survive. The outcome
device is the subdural/subarach- planar application and the fact that will depend upon the recovery of the
noid cup catheter. This is a soft Si- it really does not lend itself to contin- less damaged cells. Because the
lastic tube which is placed in the uous monitoring. There is a real edema is a secondary phenomenon,
subarachnoid space at the time of need for a simple, reliable, and safe control of the ICP following anoxic
craniotomy. Its disadvantages are system of intracranial pressure mon- ischemic injury does not seem to
clearly that it is restricted to an op- itoring for this age group. Hopefully, result in any improvement in out-
erating room setting and, therefore, there will be one within the next few come. Indeed, experience at the
it is rarely used simply as a monitor- years. Children’s Hospital of Philadelphia
ing technique. has been that if the level of ICP rises
A variety of solid state transducers THERAPY significantly (above 25 torr) after se-
appear and disappear
ket place yearly.
from the mar-
The most widely
In many pathologic
a combination (Table
states, there is
1) of both intra-
vere ischemic
by severe irreversible
injury, this is followed
cortical dam-
S
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 NEUROLOGY

age. It has proved possible to main-

tam the ICP level in a normal range,
S but the outcome for these patients
TABLE 2. Treatment
Therapy
of Intracellular Brain Edema
Physiologic Effect
has either been death or a persistent
vegetative state. They show both Restitution of normal parameters CBF, substrate delivery
EEG and CT scan evidence of cor- General measures PA02, PAco2, pH, electrolytes, SAP, os-
molality
tical necrosis. Thus, ICP is no longer
Antiseizure agents Dilantin, phenobarbital
monitored in postischemic anoxic
Specific therapy Herpes simplex, cerebritis
encephalopathy because it has not Brain resuscitation Dilantin, barbiturates, Naloxone, calcium
altered the outcome. blockers, ethacrynic acid
Much interest has been generated General decrease of ICP PAco2, osmotic diuretics, tubular diuret-
by the concept of cerebral resusci- ics, corticosteroids
tation. This is a therapeutic regimen
designed to minimize the cerebral
effects of systemic insults (eg, hy-
poxia or ischemia) by maximizing the tients, there has been no evidence is little clinical or experimental evi-
postinsult state of the brain (ie, ad- that the use of barbiturates alters the dence to suggest that the use of
equate CBF, adequate supply of outcome following ischemia. At Chil- these agents is of any particular
metabolic substrate and removal of dren’s Hospital of Philadelphia, as benefit. They may be used at the
byproducts of metabolism, control of noted above, elevated levels of ICP discretion of the attending physi-
ICP, and maintenance of ventilatory have been controlled with the use of cian. See ‘ ‘Typical Approach to
status). In the early 1 970s, there barbiturates in large doses but neu- Therapy’ below.
‘

was a great deal of concern about rologic recovery has not improved. Many of the pathologic causes of
the no-reflow
‘ ‘ phenomenon. This
‘ ‘ In children who have sustained near intracellular brain edema are asso-
was the failure of blood to recirculate drowning in cold water, reports have ciated with seizures. It is desirable
through the cerebral vessels after a suggested an improved outcome to prevent recurrent seizures, since
period of cessation of flow. It was with the early use of phenobarbital, the focal increases in flow and me-
found that agents such as mannitol but these benefits may not be the tabolism may lead to further cell
or induced systemic hypertension result of barbiturate therapy, and its death, increased edema formation,
appeared to decrease the amount of role here remains unproven. At the and focal mass effect with hernia-
S no reflow. Later experimental
ies have demonstrated that
stud-
the no-
present time, the major resuscitative
efforts are put into reestablishment
tion.
because
Dilantin is the
it does not interfere with
drug of choice

reflow phenomenon was most fre- of a normal physiologic systemic the patient’s level of consciousness.
quently an artifact of perfusion and state, control of other organ sys- There is experimental evidence sug-
does not appear to be a significant tems, and general body hemostasis. gesting that Dilantin has a specific
clinical phenomenon. Further, the An adequate Pao2 and slightly re- beneficial effect in global or focal
induction of systemic hypertension duced Paco2 in the range of 30 torr ischemia, but there has been no din-
can produce severe brain swelling with a normal or slightly alkaline ical support for this hypothesis. The
as a result of vascular distension if blood pH are the goals of therapy. myoclonic jerks seen two or three
pressure autoregulation is dis- As there is evidence to suggest that days after anoxia are difficult to con-
turbed, or it can result in hydrostatic high serum glucose may extend the trol, but the drug of choice appears
brain edema. Thus, the routine use size of focal ischemic lesions and to be phenobarbital.
of systemic hypertension following worsen recovery after diffuse is- Experimental work with etha-
anoxia or ischemia in children is not chemia, the blood glucose should be crynic acid and nonrenal effect de-
suggested; it is felt to be potentially maintained around 1 00 mg/i 00 ml. rivatives suggests that these com-
dangerous. Mannitol, in doses of 0.5 Serum osmolality around 300 pounds have a direct effect on glial
to 1 gm/kg, may have some value mOsm/liter with normal sodium val- cell swelling with a reduction of the
after normal blood pressure and ox- ues will help prevent further water intracellular swelling seen following
ygenation have been reestablished shifts into the brain. A normal to trauma and hypoxia. A clinical study
in an effort to remove excess water slightly increased systemic arterial suggests an improved outcome for
that may have accumulated in the pressure is recommended. adults with head injuries after treat-
brain during the insult. The use of steroids, dexametha- ment with ethacrynic acid. These
Barbiturates have also been pro- sone, or methyl prednisolone, has data are encouraging enough to
posed for use during cerebral resus- been suggested in patients with in- suggest that when a diuretic is re-
citation. Several different barbitu- tracellular brain edema. The theo- quired ethacrynic acid may well be
rates have been used: sodium thio- retical value is preservation of lyso- the drug of choice. Other drugs that
pental, pentobarbital, and pheno- somal membranes and potentially are being considered as potential
barbital. Experimental evidence the mopping up of free radical oxy- therapy in the postischemic hypoxic
showing that the addition of barbi- gen molecules with prevention of
5 turates
outcome
significantly
in animals
improves
subjected
the
to
membrane lipid peroxidation. Thio-
brain are the new calcium blocking
agents and Naloxone. All of these
pental has been shown to be a free agents have been experimentally
global ischemia is lacking. In pa- radical scavenger. At present, there demonstrated to be of some poten-

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Cerebral Edema

vasoconstriction, thereby, lowering

TABLE 3. Extracellular Edema Therapy the end-capillary pressure and fur-
ther reducing the rate of edema for-
Therapy

Increase removal
Category and Treatment Effect
mation.
creases
Hyperventilation
CBF, thereby,
also
limiting
de-
the
S
Ventricular drainage Extracellular fluid into ventricle
Hyperventilation venous capillary pressure amount of edema formation by de-
Osmotherapy Removal of edema fluid across intact creasing blood flow.
BBB Therapy to Increase Removal of
Decrease formation Edema. Therapy to facilitate or in-
Surgery Tumor, abscess, hematoma crease the rate of removal of edema
Corticosteroids Area of barrier disruption fluid is limited. Drainage of ventric-
Decreased SAP capillary hydrostatic pressure ular fluid has been suggested to
Hyperventilation end capillary pressure, CBF maintain the ventricular fluid pres-
Barbiturates CBF sure below the cerebral tissue pres-
General measures to reduce ICP
sure, thereby, encouraging clear-
Position
ance of the brain edema fluid into
Head up 30#{176} ICP by sinus pressure, CSF absorp-
tion the ventricular system. Practically,
Head in midline Avoid constriction of internal jugular vein this has not proven to be successful
Controlled SAP I brain compliance because the ventrLles are usually
Hyperventilation CBF, CBV compressed in th#{128}
presence of brain
Corticosteroids CSF formation . edema and, if the fluid is drained,
Barbiturates CBV, metabolism the cannula becomes occluded and
Hypothermia CBV no further CSF drainage is possible.
Tubular diuretics CSF formation, ? brain water
Osmotic diuretics extracellular fluid : Hyperventilation by lowering end-
capillary venous pressure will en-
Removal of CSF CSF volume
Surgical decompression courage passage of water from brain
Internal Removal of brain volume tissue to the venous blood (based on
External Increased volume of cranial space the Starling hypothesis) and, there-
fore, is of some value. Theoretically,
the use of osmotic diuretics by rais-
ing serum osmolality will encourage
tial benefit
As yet, there
following
has been
brain ischemia.
no clinical
complish
nial volume
a generally lower
and diffusely
intracra-
elevated
fluid
blood.
movement
Experimentally,
from the brain
however, the
to
S
information on these drugs. ICP (Table 3). maximal effect of osmotherapy is on
Surgery has a minor role in the Reduction of Edema Formation. the normal brain and not on the area
treatment of diffuse intracellular Inasmuch as extracellular edema of edema.
edema. However, both in Reye syn- spreads from areas of disturbed General Therapy to Lower ICP.
drome and lead encephalopathy, de- blood-brain barrier, it follows that if Other measures used in the treat-
compressive craniotomy has been the area of damaged barrier can be ment of cerebral edema have their
reported in the past to result in a removed the focus for edema for- effect through a general reduction of
good outcome in a few children. It mation would be gone. Thus, when intracranial volume. These treat-
makes little sense to decompress a brain tumor, brain abscess, or fo- ments effectively decrease CBV,
the brain since the brain is simply cal contusion (temporal tip) is pre- CSF volume, or brain volume. The
permitted to swell further once the sent, surgical resection of the lesion simplest method of decreasing cer-
tissue pressure is reduced by cran- may be the treatment of choice. ebral blood volume is to place the
iotomy and dural opening. The value When there are multiple areas of patient in the head-up, 30-degree
of this technique is probably that it disruption of the barrier or when no position. This will decrease cerebral
prevents herniation at the tentorial surgical resectable lesion is the venous sinus pressure, decrease in-
notch and, thus, may be life-saving cause, corticosteroids (dexametha- tracranial venous pressure, and re-
in a few patients. There is little rea- sone or methyl prednisolone) appear suIt in a decrease in intracranial
son to believe that it will decrease to be valuable therapy. The cortico- blood volume. The beneficial effect
the brain damage from the cyotoxic steroids appear to have a nonspe- is augmented by assuring that the
edematous process. cific effect in tightening up the leak- head is in the midline so that neither
ing BBB and, thereby, decreasing jugular vein is compressed. This
edema formation. Because the SAP head-up position also facilitates CSF
Extracellular Edema
constitutes the driving force for removal across the arachnoid villi by
This is the form of edema that edema formation, this is controlled increasing the gradient between the
clinicians are most frequently called to normal or slightly decreased ICP and the sagittal sinus. At ele-
upon to treat. Therapy can be con- mean values. In the unconscious pa- vated levels of SAP the brain stiffens
sidered
reduce
under
edema
three categories:
formation, to accel-
to tient, it is only safe to lower the SAP
when the ICP is monitored. Hyper-
and the volume/pressure
displaced to the left with a reduction
curve is
S
erate removal of edema fluid, to ad- ventilation produces intracerebral of intracranial compliance, such that

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 NEUROLOGY

small increases in intracranial vol- blood volume. Finally, surgical de- therapy to control ICP have been
compression may be effective in hypotension, severe pulmonary in-

S ICP.
ume
sure By
at acontrolling
will produce
normal the
orlarge arterial
increases
slightly pres-in
reduced
controlling
gressive
the elevated
herniation
ICP and pro-
produced by
fection,
change.
and decreased
Because
gas
of these
ex-
factors,
level, the intracranial compliance is brain edema. The decompression such therapy should be carefully
increased and small volume may be internal, in which case, chosen, should not be given in a
changes will not have such a dele- brain, usually frontal or temporal shotgun fashion, and should be re-
terious effect on ICP. Hyperventila- lobe is resected. This is rarely, if stricted to the least amount of treat-
tion produces a general decrease in ever, indicated in children because ment necessary to maintain a normal
CBF and, more importantly, in CBV, of the danger of removing poten- level of ICP (below 20 torr). Changes
thus generally lowering the ICP. Bar- tially functional brain. External de- in therapy may be necessary as time
biturates, which decrease cerebral compression consists of expanding goes by to account for the changing
metabolism and decrease CBF, the size of the intracranial space by phases of edema.
probably have an ICP lowering effect removing a large area of bone and
by decreased CBV. The use of bar- opening the dura mater. This pro- SUMMARY
biturates to control elevated ICP and cedure also has very limited indica-
Although no new drugs have be-
brain edema in children is usually tions in childhood; the benefits, if
come available for improved treat-
reserved as a last measure when all any, remain to be clearly estab-
ment of cerebral edema, the in-
other methods seem to have failed. lished.
Corticosteroids lower the level of creased understanding of the
ICP and increase intracranial com- pathophysiology of the edematous
SELECTION OF THERAPY process has led to more rational ap-
pliance, probably by reduction of
proaches to therapy, both in patients
CSF formation. This is also accom- The choice of therapy for brain
with cytotoxic intracellular brain
plished by tubular diuretics. Another edema will depend upon the pa-
method of generally lowering ICP is edema and those with extracellular
tient’s neurologic state, the under-
vasogenic brain edema. In the un-
to withdraw CSF. This may be done lying etiology of the edema, and the
via ventricular cannula or occasion- presence or absence of brain shifts
conscious patient, the addition of
ICP monitoring is invaluable in help-
ally by lumbar puncture when there and elevated levels of ICP. In pa-
ing in the selection of therapy and in
is no evidence of mass effect or ten- tients who are awake, significant in-
tonal herniation. Pseudotumor cer- measuring the results of therapy.
S ebri, in which diffusely elevated
tracellular
present
edema
and so therapy
is unlikely to be
for this con-
levels of ICP present with papille- dition is not in question. Treatment
dema, headache, and sometimes of extracellular edema will usually
sixth nerve palsy is well treated in be with corticosteroids plus any spe- Typical Approach to Therapy
children by repeated lumbar punc- cific therapy for the causative lesion History
ture and corticosteroids. Lumbar (eg, surgery for tumor or antibiotics A 6-year-old child has head-
puncture is, of course, dangerous for infection). A decreasing level of ache, progressive left hemi-
when there is any question of tento- consciousness, progressive focal paresis, papilledema, and known
rial herniation or focal mass effect. neurologic deficit, or signs of cere- congenital heart disease. CT scan
Finally, there are those therapies bral herniation all suggest the need shows small area of enhancing
that either decrease the brain dis- for increasing therapy preceded by cyst plus edema. Diagnosis is
brain abscess with mass effect.
placement or decrease the brain monitoring of ICP and SAP. In the
bulk itself. The prime therapy in this unconscious patient, therapy will be Treatment
category is an osmotic diuretic: selected on the basis of the etiology, 1. Steroids.
either mannitol, glycerol, or urea. the likely location of the brain 2. Surgery to drain abscess, ob-
The treatment of choice continues to edema, the presence or absence of tam cultures, and decompress
be mannitol in doses of 0.5 to 1 gm/ brain displacement and measured mass.
3. Antibiotics.
kg. In an effort to minimize the os- ICP. Although the treatment modali-
4. If progressive obtundation and
motic changes and avoid severe hy- ties are limited, an understanding of
edema:
perosmolality the smallest dose of the effects of the various agents will
(a) Repeat CT scan; if more
mannitol that effectively lowers the permit the physician to select the edema but no abscess, use
ICP should be used. To some extent, most appropriate therapy. In severe ICP monitoring.
this must be determined by trial and cases, a combination of multiple (b) Mannitol. If worsening of
error; a beginning dose is usually therapies may be necessary, indlud- clinical state or failure of
approximately 0.5 gm/kg. The ac- ing the head-up position, hyperven- ICP to respond, use endo-
tion of the osmotic diuretics appears tilation, steroids, mannitol, barbitu- tracheal tube, hyperventi-
to remove water from the brain; the rates, and occasionally the addition lation to Paco2 20 to 25
maximum effect is on the normal torr. If critical increase in
of hypothermia. As the number and
level of ICP, consider bar-
level of therapies are escalated, the
biturates, assuming still no
S rather than on the
Hypothermia
bulk, probably
also edematous
reduces
by decreasing
brain.
brain
metab-
risk of complications
major problems
increases.
encountered
The
in
surgical mass.

olism, blood flow, and cerebral comatose patients receiving multiple

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Cerebral Edema

The various therapies available have Bruce DA, Alavi A, Bilaniuk LT, et al: Diffuse Bourke AS, Nelson LA, et al (eds): Semi-
been reviewed and a logical ap- cerebral swelling following head injuries in nars in Neurological Surgery. Chicago,
children: The syndrome of ‘ ‘ malignant brain Raven Press, 1 979, vol 4, pp 155-171
proach
patients
to treatment
with extracellular
suggested.
edema,
In
it
edema.’ ‘ J Neurosurg 54: 1 70, 1981
Bruce DA, Berman WA, Schut L: Cerebrospi-
Conn AW, Edwards
resuscitation
JF, Barker
in near drowning.
GA: Cerebral
Pediatr C/in
S
is likely that intensive treatment will nal fluid pressure monitoring in children: North Am 26:691 , 1979

result in good recovery. In patients Physiology, pathology and clinical useful- Langfitt TW: Increased intracranial pressure.
ness. Adv Pediatr 24:233, 1977 C/in Neurosurg 1 6:436, 1969
with intracellular edema, the ultimate
Bruce DA, Gennarelli TA, Langfitt TW: Resus- Miller JO: Volume and pressure in the cra-
factor deciding outcome is the etiol- citation from coma due to head injury. Crit niospinal axis. C/in Neurosurg 22:76, 1975
ogy of the metabolic disturbance Care Med 6:254, 1978 Pappius HM, Dayes LA: Hypertonic urea: Its
rather than the cerebral edema it- Bruce DA, Raphaely RA, Swedlow 0, et al: effect on the distribution of water and elec-
self. Until there are drugs that spe- The effectiveness of iatrogenic barbiturate trolysis in normal and edematous brain tis-
coma in controlling increased ICP in 61 sue. Arch Neurol 1 3:395, 1965
cifically reverse the metabolic de- children, in Shulman L, Marmarou A, Miller Raphaely A, Swedlow 0, Downes J, et al:
fects produced by anoxia of is- Jo, et al (eds): Intracranial Pressure IV. Management of severe pediatric head
chemia, it seems unlikely that inten- Berlin, Springer-Verlag, 1 980, pp 630-632 trauma. Pediatr C/in North Am 27:715,
sive care in this group of patients Bruce DA, Sutton LN, Schut L: Acute brain 1980

will result in a dramatically improved swelling and cerebral edema in children, in Sutton LN, Bruce DA, Welsh F: The effects of
de Vlieger M, de Lange SA, Beks JWF cold induced brain edema and white matter
outcome. (eds): Brain Edema. New York, John Wiley ischemia on the somatosensory evoked re-
SUGGESTED READING & Sons, Inc. 1981, pp 125-145 sponse. J Neurosurg 53:180, 1980
Bruce DA: The pathophysiology of increased Bruce DA, ter Weeme C, Kaiser G, et al: Sutton LN, Welsh F, Bruce DA: Bioenergetics
intracranial pressure. Current Concepts. Mechanisms and time course for clearance of acute vasogenic edema. J Neurosurg
Upjohn do, Scope Publication, 1978 of vasogenic cerebral edema, in Popp AJ, 53:470, 1980

Steroids and Cerebral Edema

Steroids in the Treatment of Brain Edema. Fishman RA: N Engi J Med 306:359,
1982.
In an editorial comment, the often indiscriminate use of steroids in the treatment
of brain edema is discussed. It is pointed out that brain edema accompanies a
variety of processes including neoplasms, infectious disorders, vascular disorders,
and trauma. At least three types of cerebral edema are currently recognized.
Vasogenic
evidenced
edema is characterized
by contrast enhancement
by increased
on computed
capillary
tomography
endothelial permeability,
and often having an
S
elevated level of CSF protein. This particular type of edema, which is often seen
surrounding brain tumors, abscesses, and perhaps discrete hematomas, is respon-
sive to steroid medication both clinically and by demonstration on CT scan. The
remaining two types of cerebral edema are cellular (cytotoxic) and interstitial
(hydrocephalic) and have not been shown to be influenced in any way by steroid
medication. Cytotoxic cerebral edema is most commonly seen with asphyxia or
hypoxia and would explain the apparent ineffectiveness of steroids in this situation.
Head trauma probably produces both cytotoxic and vasogenic edema. In recent
years there have been numerous controlled and uncontrolled studies of the use of
steroids in severe head trauma. To date none has convincingly demonstrated a
beneficial effect. Another report found dexamethasone (N Engi J Med 306:313,
1 982) to be deleterious in the treatment of cerebral malaria in a double-blind trial of
1 00 comatose patients.
Comment: To date then, our current knowledge would advise steroid treatment of
only vasogenic cerebral edema as it occurs surrounding brain tumors, abscesses,
and perhaps discrete cerebral hematomas. The treatment with steroids of other
types of cerebral edema has no rationale to support it in either clinical or experi-
mental studies. (L. Epstein, NJ Medical School)

S
PIR 224 pediatrics in review #{149} vol. 4 no. 7 january 1983

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 Management of Cerebral Edema
Derek A. Bruce
Pediatrics in Review 1983;4;217
DOI: 10.1542/pir.4-7-217

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 Management of Cerebral Edema
Derek A. Bruce
Pediatrics in Review 1983;4;217
DOI: 10.1542/pir.4-7-217

The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://pedsinreview.aappublications.org/content/4/7/217

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned, published, and
trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove
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