treatments. massive brain swelling after cranioplasty decompressive craniectomy is frequently performed in cases of resistant intracranial hypertension secondary to several neurological conditions and is commonly followed by cranioplasty. complications, such as infection and hematomas after cranioplasty occur in roughly about a third of cases. massive brain swelling after cranioplasty (msbc) is a rare and potentially fatal complication of an uneventful cranioplasty that has recently been elucidated. preoperative sinking skin flap (ssf) and intracranial hypotension were factors associated with the development of msbc after cranioplasty. data suggests that pathologic changes are triggered immediately following the procedure, especially an acute increase in intracranial pressure. radiation-induced brain edema with the rise of sophisticated treatment modalities such as gamma knife, cyberknife, and intensity-modulated radiotherapy, a large number of individuals with brain tumors are treated with radiosurgery and radiotherapy. radiation-induced brain edema (ribe) is a potentially life threatening complication of brain tissue radiation and is characterized radiation necrosis, endothelial cell dysfunction, increased capillary permeability, and breakdown of the blood–brain barrier. symptoms include headache, seizure, psychomotor slowing, irritability, and focal neurological deficits. options for management of ribe are limited and include corticosteroids, antiplatelet drugs, anticoagulants, hyperbaric oxygen therapy, multivitamins, and bevacizumab. brain tumor-associated cerebral edema this kind of cerebral edema is a significant cause of morbidity and mortality in patients with brain tumors and characterized by a disruption of the blood brain barrier and vasogenic edema. the exact mechanism is unclear but hypothesized that cancerous glial cells (glioma) of the brain can increase secretion of vascular endothelial growth factor (vegf), which weakens the tight junctions of the blood–brain barrier. historically, corticosteroids such as dexamethasone were used to reduce brain tumor-associated vascular permeability through poorly understood mechanisms and was associated with systemic side effects. agents that target the vegf signaling pathways, such as cediranib, have been promising in prolonging survival in rat models but associated with local and systemic side effects as well. diagnosis cerebral edema is commonly present in a variety of neurological injuries. thus, determining a definitive contribution of cerebral edema to the neurological status of an affected person can be challenging. close bedside monitoring of a person's level of consciousness and awareness of any new or worsening focal neurological deficits is imperative but demanding, frequently requiring admission into the intensive care unit (icu). cerebral edema with sustained increased intracranial hypertension and brain herniation can signify impending catastrophic neurological events which require immediate recognition and treatment to prevent injury and even death. therefore, diagnosis of cerebral edema earlier with rapid intervention can improve clinical outcomes and can mortality, or risk of death. diagnosis of cerebral edema relies on the following: imaging serial neuroimaging (ct scans and magnetic resonance imaging) can be useful in diagnosing or excluding intracranial hemorrhage, large masses, acute hydrocephalus, or brain herniation as well as providing information on the type of edema present and the extent of affected area. ct scan is the imaging modality of choice as it is widely available, quick, and with minimal risks. however, ct scan can be limited in determining the exact cause of cerebral edema in which cases, ct angiography (cta), mri, or digital subtraction angiography (dsa) may be necessary. mri is particularly useful as it can differentiate between cytotoxic and vasogenic edema, guiding future treatment decisions. intracranial pressure monitoring intracranial pressure (icp) and its management is a fundamental concept in traumatic brain injury (tbi). the brain trauma foundation guidelines recommend icp monitoring in individuals with tbi that have decreased glasgow coma scale (gcs) scores, abnormal ct scans, or additional risk factors such as older age and elevated blood pressure. however, no such guidelines exist for icp monitoring in other brain injuries such as ischemic stroke, intracerebral hemorrhage, cerebral neoplasm. clinical researches have recommended icp and cerebral perfusion pressure (cpp) monitoring in any persons with cerebral injury who are at risk of elevated intracranial pressure based on clinical and neuroimaging features. early monitoring can be used to guide medical and surgical decision making and to detect potentially life-threatening brain herniation. there was however, conflicting evidence on the threshold values of icp that indicated the need for intervention. researches also recommend that medical decisions should be tailored to the specific diagnosis (e.g. subarachnoid hemorrhage, tbi, encephalitis) and that icp elevation should be used in conjunction with clinical and neuroimaging and not as an isolated prognostic marker. treatment the primary goal in cerebral edema is to optimize and regulate cerebral perfusion, oxygenation, and venous drainage, decrease cerebral metabolic demands, and to stabilize the osmolality pressure gradient between the brain and the surrounding vasculature. as cerebral edema is linked to increased intracranial pressure (icp), many of the therapies will focus on icp. positioning finding the optimal head position in persons with cerebral edema is necessary to avoid compression of the jugular vein and obstruction of venous outflow from the skull, and for decreasing cerebrospinal fluid hydrostatic pressure. the current recommendation is to elevate the head of the bed to 30 degrees to optimize cerebral perfusion pressure and control the increase in intracranial pressure. it is also worth noting that measures should be taken to reduce restrictive neck dressings or garments as these may lead to compression of the internal jugular veins and reduce venous outflow. ventilation and oxygenation decreased oxygen concentration in the blood, hypoxia, and increase in the carbon dioxide concentration in the blood, hypercapnia, are potent vasodilators in the cerebral vasculature, and should be avoided in those with cerebral edema. it is recommended that persons with decreased levels of consciousness be intubated for airway protection and maintenance of oxygen and carbon dioxide levels. however, the laryngeal instrumentation involved in the intubation process is associated with an acute, brief rise in intracranial pressure. pretreatment with a sedative agent and neuromuscular blocking agent to induce unconsciousness and motor paralysis has been recommended as part of standard rapid sequence intubation (rsi). intravenous lidocaine prior to rsi has been suggested to reduce the rise in icp but there is no supporting data at this time. additionally, ventilation with use of positive pressure (peep) can improve oxygenation with the negative effect of decreasing cerebral venous drainage and increasing intracranial pressure (icp), and thus, must be used with caution. fluid management and cerebral perfusion maintenance of cerebral perfusion pressure using appropriate fluid management is essential in patients with brain injury. dehydration, or intravascular volume loss, and the use of hypotonic fluids, such as d5w or half normal saline, should be avoided. blood serum ion concentration, or osmolality, should be maintained in the normo to hyperosmolar range. judicial use of hypertonic saline can be used to increase serum osmolality and decrease cerebral edema, as discussed below. blood pressure should be sufficient so as to sustain cerebral perfusion pressures greater than 60 mm hg for optimal blood blow to the brain. vasopressors may be used to achieve adequate blood pressures with minimal risk of increasing intracranial pressures. however, sharp rises in blood pressure should be avoided. maximum blood pressures tolerated are variable and controversial depending on the clinical situation. seizure prophylaxis seizures, including subclinical seizure activity, can complicate clinical courses and increase progression of brain herniation in persons with cerebral edema and increased intracranial pressure. anticonvulsants can be used to treat seizures caused by acute brain injuries from a variety of origins. however, there are no clear guidelines on the use of anticonvulsants for prophylactic use. their use may be warranted on depending on the clinical scenario and studies have shown that anticonvulsants such as phenytoin can be given prophylactically without a significant increase in drug-related side effects. fever fever has been demonstrated to increase metabolism and oxygen demand in the brain. the increased metabolic demand results in an increase in cerebral blood flow and can increase the intracranial pressure within the skull. therefore, maintaining a stable body temperature within the normal range is strongly recommended. this can be achieved through the use of antipyretics such as acetaminophen (paracetamol) and cooling the body, as described below. hyperglycemia elevated blood glucose levels, known as hyperglycemia, can exacerbate brain injury and cerebral edema and has been associated with worse clinical outcomes in persons affected by traumatic brain injuries, subarachnoid hemorrhages, and ischemic strokes. sedation pain and agitation can worsen cerebral edema, acutely increase intracranial pressure (icp), and should be controlled. careful use of pain medication such as morphine or fentanyl can be used for analgesia. for those persons with decreased levels of consciousness, sedation is necessary for endotracheal intubation and maintenance of a secure airway. sedative medication used in the intubation process, specifically propofol, have been shown to control icp, decrease cerebral metabolic demand, and have antiseizure properties. due to a short half-life, propofol, is a quick-acting medication whose administration and removal is well tolerated, with hypotension being the limiting factor in its continued use. additionally, the use of nondepolarizing neuromusclar blocking agents (nmba), such as doxacurium or atracurium, have been indicated to facilitate ventilation and manage brain injuries but there are no controlled studies on the use of nmbas in the management of increased intracranial pressure. depolarizing neuromuscular blocking agents, most notably succinylcholine, can worsen increased icp due to induction of muscle contraction within the body. nutrition nutritional support is necessary in all patients with acute brain injury. enteral feeding, or through mouth via tube, is the preferred method, unless contraindicated. additional attention must be placed on the solute concentration of the formulations to avoid free water intake, decreased serum osmolality, and worsening of the cerebral edema. elevated blood glucose, or hyperglycemia, is associated with increased edema in patients with cerebral ischemia and increases the risk of a hemorrhagic transformation of ischemic stroke. maintaining a normal blood glucose level of less than 180 mg/dl is suggested. however, tight glycemic control of blood glucose under 126 mg/dl is associated with worsening of stroke size. specific measures although cerebral edema is closely related to increased intracranial pressure (icp) and cerebral herniation and the general treatment strategies above are useful, the treatment should ultimately be tailored to the primary cause of the symptoms. the management of individual diseases are discussed separately. the following interventions are more specific treatments for managing cerebral edema and increased icp: osmotic therapy the goal of osmotic therapy is to create a higher concentration of ions within the vasculature at the blood–brain barrier. this will create an osmotic pressure gradient and will cause the flow of water out of the brain and into the vasculature for drainage elsewhere. an ideal osmotic agent produces a favorable osmotic pressure gradient, is nontoxic, and is not filtered out by the blood–brain barrier. hypertonic saline and mannitol are the main osmotic agents in use, while loop diuretics can aid in the removal of the excess fluid pulled out of the brain. hypertonic saline is a highly concentrated solution of sodium chloride in water and is administered intravenously. it has a rapid-onset, with reduction of pressures within 5 minutes of infusion, lasting up to 12 hours in some cases, and with negligible rebound pressure. the exact volume and concentration of the hypertonic saline varies between clinical studies. bolus doses, particularly at higher concentrations, for example 23.4%, are effective at reducing icp and improving cerebral perfusion pressure. in traumatic brain injuries, a responsiveness to hypertonic saline lasting greater than 2 hours was associated with decreased chance of death and improved neurologic outcomes. the effects of hypertonic saline can be prolonged with combination to agents such as dextran or hydroxyethyl starch, although their use is currently controversial. when compared to mannitol, hypertonic saline has been shown to be as effective as mannitol in decreased icp in neurocritical care and is more effective in many cases. hypertonic saline may be preferable to mannitol in persons with hypovolemia or hyponatremia. mannitol is an alcohol derivative of simple sugar mannose, and is historically the most commonly used osmotic diuretic. mannitol acts as an inert solute in the blood, decreasing icp through osmosis as discussed above. additionally, mannitol decreases icp and increased cerebral perfusion pressure by increasing reabsorption of cerebrospinal fluid, dilutes and decreased the viscosity of the blood, and can cause cerebral vasoconstriction. furthermore, mannitol acts in a dose-dependent manner and will not lower icp if it is not elevated. however, the common limitation of the use of mannitol is its tendency to cause low blood pressure hypotension. compared to hypertonic saline, mannitol