may be more effective at increasing cerebral perfusion pressures and may be preferable in those with hypoperfusion. loop diuretics, commonly furosemide, act within kidney to increase excretion of water and solutes. combination with mannitol produces a profound diuresis and increases the risk of systemic dehydration and hypotension. their use remains controversial. acetazolamide, a carbonic anhydrase inhibitor, acts as a weak diuretic and modulates csf production but has not role in the management of cerebral edema from acute brain injuries. it can be used in the outpatient management of cerebral edema caused by idiopathic intracranial hypertension (pseudotumor cerebri). glucocorticoids glucocorticoids, such as dexamethasone, have been shown to decrease tight-junction permeability and stabilize the blood-brain barrier. their main use has been in the management of vasogenic cerebral edema associated with brain tumors, brain irradiation, and surgical manipulation. glucocorticoids have not been shown to have any benefit in ischemic stroke and have been found to be harmful in traumatic brain injury. due to the negative side effects (such as peptic ulcers, hyperglycemia, and impairment of wound healing), steroid use should be restricted to cases where they are absolutely indicated. hyperventilation as mentioned previously, hypoxia and hypercapnia are potent vasodilators in the cerebral vasculature, leading to increased cerebral blood flow (cbf) and worsening of cerebral edema. conversely, therapeutic hyperventilation can be used to lower the carbon dioxide content in the blood and reduce icp through vasoconstriction. the effects of hyperventilation, although effective, are short-lived and once removed, can often lead to a rebound elevation of icp. furthermore, overaggressive hyperventilation and vasoconstriction and lead to severe reduction in cbf and cause cerebral ischemia, or strokes. as a result, standard practice is to slowly reverse hyperventilation while more definitive treatments aimed at the primary cause are instituted. it is important to note that prolonged hyperventilation in those with traumatic brain injuries has been shown to worsen outcomes. barbiturates induction of a coma via the use of barbiturates, most notably pentobarbital and thiopental, after brain injury is used for secondary treatment of refractory icp. yet their use is not without controversy and it is not clear whether barbiturates are favored over surgical decompression. in patients with traumatic brain injuries, barbiturates are effective in reducing icp but have failed to show benefit to clinical outcomes. evidence is limited for their use in cerebral disease that include tumor, intracranial hypertension, and ischemic stroke. there are several adverse effects of barbiturates that limit their use, such as lowering of systemic blood pressure and cerebral perfusion pressure, cardiodepression, immunosuppression, and systemic hypothermia. hypothermia as discussed previously in the treatment of fever, temperature control has been shown to decrease metabolic demand and reduce further ischemic injury. in traumatic brain injury, induced hypothermia may reduce the risks of mortality, poor neurologic outcome in adults. however, outcomes varied greatly depth and duration of hypothermia as well as rewarming procedures. in children with traumatic brain injury, there was no benefit to therapeutic hypothermia and increased the risk of mortality and arrhythmia. the adverse effects of hypothermia are serious and require clinical monitoring including increased chance of infection, coagulopathy, and electrolyte derangement. the current consensus is that adverse effects outweigh the benefits and its use restricted to clinical trials and refractory increased icp to other therapies. surgery the monroe-kellie doctrine states that the skull is a fixed and inelastic space and the accumulation of edema will compress vital brain tissue and blood vessels. surgical treatment of cerebral edema in the context of cerebellar or cerebral infarction is typically done by removing part of the skull to allow expansion of the dura. this will help to reduce the volume constraints inside of the skull. a decompressive hemicraniectomy is the most commonly used procedure. multiple randomized clinical trials have shown reduced risk of death with hemicraniectomy compared with medical management. however, no individual study has shown an improvement in the percentage of survivors with good functional outcomes. timing of decompressive craniectomy remains controversial, but is generally suggested that the surgery is best performed before there are clinical signs of brainstem compression. postoperative complications include wound dehiscence, hydrocephalus, infection, and a substantial proportion of patients may also require tracheostomy and gastrotomy in the early phase after surgery. outcomes cerebral edema is a severe complication of acute brain injuries, most notably ischemic stroke and traumatic brain injuries, and a significant cause of morbidity and mortality. cerebral edema is the cause of death in 5% of all patients with cerebral infarction and mortality after large ischemic strokes with cerebral edema is roughly 20 to 30% despite medical and surgical interventions. cerebral edema usually occurs between the second and fifth day after onset of symptoms. large territory ischemic strokes can lead to the rapid development of malignant brain edema and increased intracranial pressure. cerebral edema in the context of a malignant middle cerebral artery (mca) infarct has a mortality of 50 to 80% if treated conservatively. individuals with cerebral edema had a worse 3-month functional outcome than those without edema. these effects were more pronounced with increasing extent of cerebral edema and were independent of the size of the infarct. mild traumatic brain injury (tbi) represents 70–90% of all reported head injuries. the presence of brain edema on the initial ct scan of those with traumatic brain injuries is an independent prognostic indicator of in-hospital death. the association of brain edema with increased in hospital risk of death was observed in tbi across all level of severity. edema in the acute and chronic phases were associated with a worse neurologic and clinical outcome. children with tbi and cerebral edema have worse clinical outcomes as well. epidemiology as cerebral edema is present with many common cerebral pathologies, the epidemiology of the disease is not easily defined. the incidence of this disorder should be considered in terms of its potential causes and is present in most cases of traumatic brain injury, central nervous system tumors, brain ischemia, and intracerebral hemorrhage. in one study, cerebral edema was found in 28% of those individuals with thrombolysis-treated ischemic strokes, 10% of which occurred in severe forms. a further study detected cerebral edema in 22.7% of cerebral ischemic strokes. a meta-analysis of current studies showed that 31% of those affected by ischemic strokes developed cerebral edema in 31% of cases. in traumatic brain injuries, cerebral edema occurred in greater than 60% of those with mass lesions, and in 15% of those with initial normal ct scans. research the current understanding of the pathophysiology of cerebral edema after traumatic brain injury or intracerebral hemorrhage is incomplete. current treatment therapies aimed at cerebral edema and increased intracranial pressure are effective at reducing intracranial hypertension but have unclear impacts on functional outcomes. additionally, cerebral and icp treatments have varied effects on individuals based on differing characteristics like age, gender, type of injury, and genetics. there are innumerable molecular pathways that contribute to cerebral edema, many of which have yet to be discovered. researchers argue that the future treatment of cerebral edema will be based on advances in identifying the underlying pathophysiology and molecular characteristics of cerebral edema in a variety of cases. at the same time, improvement of radiographic markers, biomarkers, and analysis of clinical monitoring data is essential in treating cerebral edema. many studies of the mechanical properties of brain edema were conducted in the 2010s, most of them based on finite element analysis (fea), a widely used numerical method in solid mechanics. for example, gao and ang used the finite element method to study changes in intracranial pressure during craniotomy operations. a second line of research on the condition looks at thermal conductivity, which is related to tissue water content.