Malignant Cerebral Edema
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Malignant Cerebral Edema (aka Post-Traumatic Brain Swelling) Malignant edema is a rare (<10%), but often fatal (~100%) complication of TBI. It is diagnosed by a rapid increase in ICP within hours after injury that is refractory to medical management. It likely represents global cytotoxic edema due to activation of apoptotic pathways and failure of energy metabolism.
Post-traumatic edema can be divided into two temporal phases, along with two pathophysiologic mechanisms. There is immediate (early) swelling, within minutes of injury, and delayed (late) swelling, which peaks at 3-5 days post-injury. Furthermore, there is vasogenic edema (i.e. accumulation of extravasated plasma in the interstitium due to derangement of the vascular epithelium), and cytotoxic edema (due to accumulation of intracellular water as energy failure takes place).
Two additional components of cerebral edema are an increase in the cerebral blood volume due to acid-base disturbance (hypercarbia), which results in vasodilation, and interstitial edema due to post-traumatic hydrocephalus. Astrocytes are thought to be the cellular origin of malignant edema, as they are:
- Responsible for maintenance of the interstitial ionic milieu (act as K+ scavengers)
- Capable of swelling to 20 times their normal size
- Have the largest number of ATP dependent ionic exchange pumps (see #1)
- Astrocytes in children have larger numbers of mitochondria compared to adults.
Mitochondrial dysfunction plays a primary role in cytotoxic edema, as demonstrated in animal and pharmacologic knock-out models. More importantly, inhibition of interleukin dependent inflammation, most notably by mitomycin C and FK-506 in rodent models all but abolishes delayed cytotoxic edema in concussion models of TBI.
Two distinct processes
(1) Increased cerebral blood volume (CBV) and (2) possible loss of cerebral vascular autoregulation may contribute to the pathophysiology of malignant cerebral edema.
Malignant cerebral edema can occur within hours of the head injury. It is more common in children and young adults and has a high mortality rate.
Aggressive management is needed to preclude devastating neurological deficit and mortality. Management often includes multi-modality neuromonitoring, osmotic diuretics, cerebral spinal fluid (CSF) drainage thorough an extraventricular drain, and sedation and paralytic agents. Careful attention is paid to laboratory measures particularly to serum sodium levels, avoiding hyponatremia. Carbon dioxide levels from blood gas measurements are titrated to goals of pCO2 35-45 mmHg, aiming for the lower aspect of this range in difficult situations of elevated intracranial pressure (ICP). Significant hyperventilation is not advised, except in critical circumstances as a temporizing measure for ICP control. Patients should not be hyperventilated below a pCO2 of 30 mmHg. Should mild lowering of pCO2 levels (30-35 mmHg) be employed for prolonged durations, ancillary technologies to measure cerebral blood flow (CBF) including CBF and jugular venous saturation monitors are recommended to ensure that vasoconstriction does not lead to cerebral ischemia.
Goals of treatment are to keep ICP < 20 mm Hg and CPP > 60 mmHg.
Additional methods including induced pentobarbital coma, hypothermia, or surgical decompressive craniectomy may also be considered in refractory cases.
It is unclear whether this group of patients may benefit from early surgical decompression. Since this form of TBI related edema represents catastrophic failure of mitochondrial energy exchange,prognosis for meaningful outcome is often guarded and uncertain.