Cerebral edema

• Cerebral edema represents the accumulation of excess fluid in the

intracellular or extracellular spaces of the brain
The Blood-Brain Barrier
Blood-Brain barrier (BBB) is exceptionally active system
• Endothelial cells can inactivate neuroactive or neurotoxic substances
• Regulate microenvironment of the brain, fluid and ions between
circulation and brain
Interstitial fluid of the brain
• low Ca2+ and K+ and high Mg2+
 Cerebral edema
Four categories
• Cytotoxic edema
• Vasogenic edema
• Interstitial edema
• Osmotic edema
 Clinical presentation
• Headache
• Tinnitus
• Vomiting
• Visual obscuration ,visual loss
• Papilledema
• Diplopia
• Hypertension and Bradycardia
• Herniation syndromes
 Cytotoxic edema
Cause of cytotoxic edema
• Cerebral infarction or ischemia
• Meningitis
• Reye’s syndrome
• Trauma
• Seizure
• Water intoxication
 Mechanisms
• cytotoxic edema associated with cerebral ischemia - direct role for excess
glutamate
• dysfunction of the Na+K+-ATPase pump, which permits sodium influx, and
activation of the Na+/H+ and Cl–/HCO3– exchangers and the Na+/K+/2Cl–
cotransporter contribute to combined neuronal and astrocytic swelling
• Loss of ATP and excess glutamate after cerebral ischemia or TBI cause influx
of calcium into cell then apoptosis and sodium exchange (3 Na+ per Ca3+)
occur
• Nitric oxide (NO) from nitric oxide synthase (NOS)
• Neuronal NOS produces toxic free radical (early after cytotoxic
injury)
• Endothelial NOS cause vasodilatation and increase blood flow
• Inducible NOS produce NO and free radical at 24-48 hr after
injury
• Diffuse-weighted MRI signal
change within minute after
events occur (very early)
• In first 12 hour, loss of visible
gray-white matter junction and
gyral edema occur
• 12-24 hour , increase signal in T2-
weighted MRI
• acute infarcts have a lower ADC
than normal brain does, and
these ADC maps sensitively
indicate early cytotoxic edema
 Vasogenic edema
Cause of vasogenic edema
• Primary or secondary brain tumour
• Brain abscess and encephalitis
• Trauma
• Lead poisoning
• Late stage of cerebral infarction
 Mechanisms
• Blood-tumor barrier has abnormal micro vessels that lacks of tight
junctions cause plasma leakage into brain’s extracellular space
• Macromolecular protein produced by tumor has been identified as
vascular permeability factor (VPF) / vascular endothelial growth factor
(VEGF)
• induces capillary permeability, endothelial proliferation, and
migration and organization of new capillaries that lack tight junctions.
• Glucocorticoids can block permeability-enhancing effects of
VPF/VEGF and inhibit tumor cell production of VEGF
• High VPF/VEGF gene expression found in glioblastomas, meningiomas
and metastases
 Interstitial edema
• Cause of interstitial edema
• Hydrocephalus
• Mechanism
Transependymal flow of water and solute into periventricular
extracellular space
• Hypodensity area around periventricular white matter in CT scan
• Increased signal in FLAIR MRI at interstitial brain surrounding
ependyma
 Osmotic edema
• Cause of osmotic edema
• Hemodialysis
• SIADH
• Hypertensive crisis
• Water intoxication
• Rapid reduction of blood glucose in hyperglycaemic crisis
• Mechanism
• Hyperosmolarity in brain relatively to circulatory then water move into brain
along osmotic gradient
• Pathological increase in the water content of the brain
• Increased intracranial pressure
• Neurological deterioration
• Herniation
• Death
 General Measures for
Managing Cerebral Edema
1. Optimizing Head and Neck Positions
2. Ventilation and Oxygenation
3. Maintain Intravascular Volume and Cerebral Perfusion
4. Seizure Prophylaxis
5. Management of Fever and Hyperglycemia
6. Nutritional Support
 Optimizing Head and Neck Positions
• 30 ̊elevation of the head in patients is essential for
–decreasing CSF hydrostatic pressure.
– avoiding jugular compression and impedance of venous outflow from the
cranium
• to avoid the use of restricting devices and garments around the neck
(such as devices used to secure endotracheal tubes), which may impair
cerebral venous outflow via compression of the internal jugular veins.
• Head position elevation may be detrimental in ischemic stroke,
because it may compromise perfusion to ischemic tissue at risk.
 Ventilation and Oxygenation
• Hypoxia and hypercapnia are potent cerebral vasodilator
• Maintain PaCO2 > 30 mmHg to support adequate CBF or CPP to brain
• maintain PaO2 at approximately 100 mmHg
• Pt should be intubated in:
1. GCS scores less than or equal to 8
2. Patients with poor upper airway reflexes be intubated for airway protection.
3. Pulmonary disorder eg: ARDS, aspiration pneumonia
• Avoid high PEEP → # systemic venous return , ↓ COP
• Blunting of upper airway reflexes
 Maintain Intravascular Volume and
Cerebral Perfusion
• Maintain CPP level >60 mmHg
CPP=MAP-ICP
NORMAL CPP= 70 - 90 mm of Hg
• If hypertension avoid use of Potent vasodilators eg. Nitroglycerine,
Nitroprusside as they may exacerbate cerebral edema via accentuated
cerebral hyperemia due to their direct vasodilating effects on cerebral
vessels.
 Seizure Prophylaxis
• Phenytoin are widely used empirically in clinical practice in patients
with acute brain injury
• Early seizures in TBI can be effectively reduced by prophylactic
administration of phenytoin for 1 or 2 weeks.
 Management of Fever
• fever has deleterious effects of on outcome following brain injury,
• increases in oxygen demand,
• normothermia is strongly recommended in patients with cerebral
edema, irrespective of underlying origin.
• Acetaminophen (325–650 mg orally, or rectally every 4–6 hours) is
the most common agent used
• Other surface cooling devices have demonstrated some efficacy
 Hyperglycemia
• Hyperglycemia can also exacerbate brain injury and cerebral edema
• current evidence suggests that rigorous glycemic control may be
beneficial in all patients with brain injury.
 Nutritional Support
• Unless contraindicated, the enteral route of nutrition is preferred.
• Special attention should be given to the osmotic content of
formulations, to avoid free water intake that may result in a
hypoosmolar state and worsen cerebral edema.
 Specific Measures for
Managing Cerebral Edema
1. Controlled Hyperventilation
2. Osmotherapy
3. Corticosteroid Administration
4. Therapeutic Hypothermia
5. Other Adjunct Therapies
 Osmotherapy
• Mannitol is the osmotic agent universally used to treat cerebral edema
• decreases ICPs in two distinct mechanisms
• usual dose is 0.25 g to 1 g/kg at 4- to 6-hour intervals and generally
effective for 48 to 72 hours.
• routine/scheduled use beyond 72 hour can become ineffective
because mannitol’s reflection coefficient is 0.9, meaning that even
with an intact blood-brain barrier it will slowly leak into the interstitial
fluid/brain parenchyma
• serum osmolality to a recommended target value of approximately
320mOsm/L
 HYPERTONIC SALINE
• Thirty-millilitre boluses of 23.4% sodium chloride given through a
central line over 15 minutes have been shown to be at least as
efficacious as mannitol
• reflection coefficient of hypertonic saline is 1.0, meaning that if a
patient’s blood-brain barrier is intact it will not accumulate in the
interstitial space/brain parenchyma
• hypertonic saline produces longer duration of ICP lowering with than
with mannitol.
 Glycerol
• Glycerol is another useful agent given in oral
• Doses:
– 30 ml every 4-6 hour or daily IV 50g in 500 ml of 2.5% saline solution
– its effectiveness appears to decrease after few days.
– It is used in a dose of 0.5-1.0 g/kg body weight.
– In unconscious or uncooperative patients it is given by nasogastric tube
 Therapeutic Basis and Goal of
Osmotherapy
• fundamental goal of osmotherapy is to create an osmotic gradient to
cause egress of water from the brain extracellular (and possibly
intracellular) compartment into the vasculature
• thereby decreasing intracranial volume (normal brain volume 80%,
normal blood volume 10%, and normal CSF volume 10%) and
improving intracranial elastance and compliance.
• In healthy individuals, serum osmolality (285–295mOsm/L) is relatively
constant, and the serum Na+ concentration is an estimate of body water
osmolality.
• Under ideal circumstances,serum osmolality is dependent on the
major cations
– (Na+ and K+)
– plasma glucose
– blood urea nitrogen.
• Because urea is freely diffusible across cell membranes, serum Na+ and
plasma glucose are the major molecules involved in altering serum
osmolality
• The goal of using osmotherapy is to maintain a euvolemic or a slightly
hypervolemic state.
• A serum osmolality in the range of 300 to 320mOsm/L has
traditionally been recommended for patients with acute brain injury
 Corticosteroid
• Used in vasogenic edema associated with brain tumors or
accompanying brain irradiation and surgical manipulation.
• steroids decrease tight-junction permeability and, in turn, stabilize
the disrupted BBB.
• Glucocorticoids, especially dexamethasone, are the preferred
steroidal agents, due to their low mineralocorticoid activity
• Steroids deleterious side effects are peptic ulcers, hyperglycemia,
impairment of wound healing, psychosis, and immunosuppression.
 Surgical management
• Decompressive Hemicraniotomy - Recommended for large
hemispherical infarcts with edema and life threatening brain-shifts.
• Ventricular Drainage
Thank you