Last updated March 14, 2022

Acute Treatment of Cerebral Edema in Neurocritical Care Patients

Recommendations

Treatment of Cerebral Edema in Patients with Subarachnoid Hemorrhage

1. We suggest using symptom-based bolus dosing of hypertonic sodium solutions rather than sodium target-based dosing for the management of ICP or cerebral edema in patients with SAH (conditional recommendation, very low-quality evidence)
Rationale: In making this recommendation, the panel felt that while the quality of evidence was very low, the consistency of the literature justifed symptom-based bolus dosing of HTS as an efective means of reducing ICP and cerebral edema in patients with SAH. Te data on sodium target-based HTS dosing regimens for ICP control were extremely limited and provided only indirect evidence and thus could not be recommended.
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2. Due to insufficient evidence, we cannot recommend a specifc dosing strategy for HTS to improve neurological outcomes in patients with SAH.
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Treatment of Cerebral Edema in Patients with Traumatic Brain Injury

1. We suggest using hypertonic sodium solutions over mannitol for the initial management of elevated ICP or cerebral edema in patients with TBI (conditional recommendation, low-quality evidence). We suggest that neither HTS nor mannitol be used with the expectation for improving neurological outcomes in patients with TBI (conditional recommendation, low-quality evidence).
Rationale: In making this recommendation, the panel felt that while the quality of evidence was low, the consistency of the literature suggested HTS was at least as safe and efective as mannitol. In addition, the panel agreed that the putative advantages of HTS over mannitol for fuid resuscitation and cerebral perfusion justifed the suggestion to use HTS over mannitol. Although treatment efect of these agents on elevated ICP or cerebral edema may be expected based on the literature, neither agent has been demonstrated to improve neurological outcomes.
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2. We suggest that the use of mannitol is an efective alternative in patients with TBI unable to receive hypertonic sodium solutions (conditional recommendation, low-quality evidence).
Rationale: Although HTS was recommended over mannitol, the quality of evidence was low and the literature consistently suggests that mannitol is also a safe and efective option for the initial management of elevated ICP or cerebral edema in patients with TBI, particularly those with concomitant severe hypernatremia or volume overload.
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3. We recommend against the use of hypertonic sodium solutions in the pre-hospital setting to specifcally improve neurological outcomes for patients with TBI (strong recommendation, moderate-quality evidence)
Rationale: Acute treatment of cerebral edema and herniation syndromes is often necessary in the pre-hospital setting. However, well-designed clinical trials did not suggest any beneft from the use of HTS in the pre-hospital setting on long-term outcomes in patients with TBI.
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4. We suggest against the use of mannitol in the prehospital setting to improve neurological outcomes for patients with TBI (conditional recommendation, very low-quality evidence).
Rationale: In making this recommendation, the panel felt that the quality of evidence was very low and did not suggest any potential beneft in the pre-hospital setting on long-term outcomes in patients with TBI.
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Treatment of Cerebral Edema in Patients with Acute Ischemic Stroke

1. We suggest using either hypertonic sodium solutions or mannitol for the initial management of ICP or cerebral edema in patients with acute ischemic stroke (conditional recommendation, low-quality evidence). Tere is insufcient evidence to recommend either hypertonic saline or mannitol for improving neurological outcomes in patients with acute ischemic stroke.
Rationale: In making this recommendation, the panel felt that the quality of evidence was low and the literature in patients with AIS was not compelling to recommend one agent over the other for initial management of elevated ICP or cerebral edema. Patient-specifc factors may be employed to aid clinicians in selecting the appropriate initial agent in patients with either measured elevated ICP or symptoms of cerebral edema.
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2. We suggest that clinicians consider administration of hypertonic sodium solutions for management of ICP or cerebral edema in patients with acute ischemic stroke who do not have an adequate response to mannitol (conditional recommendation, low-quality evidence).
Rationale: In making this recommendation, the panel felt that the quality of evidence was low, but the literature in patients with AIS suggested that patients who do not have an adequate treatment response to mannitol may still respond to HTS.
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3. We suggest against the use of prophylactic scheduled mannitol in acute ischemic stroke due to the potential for harm (conditional recommendation, low-quality evidence).
Rationale: In making this recommendation, the panel felt that while the quality of evidence was low, the lack of beneft and the potential association with worse neurological outcomes justifed avoiding prophylactic mannitol in patients with acute ischemic stroke.
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Treatment of Cerebral Edema in Patients with Intracerebral Hemorrhage

1. We suggest using hypertonic sodium solutions over mannitol for the management of ICP or cerebral edema in patients with intracerebral hemorrhage (conditional recommendation, very low-quality evidence).
Rationale: In making this recommendation, the panel felt that while the quality of evidence was very low, the consistency of the literature suggested HTS was at least as safe and efective as mannitol. In addition, the panel agreed that the putative advantages of HTS over mannitol for fuid resuscitation and cerebral perfusion justifed the suggestion to use HTS over mannitol.
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2. We suggest that either symptom-based bolus dosing or using a targeted sodium concentration is appropriate hypertonic sodium solution administration strategy for the management of elevated ICP or cerebral edema in patients with intracerebral hemorrhage (conditional recommendation, very low-quality evidence).
Rationale: In making this recommendation, the panel felt that the quality of evidence was very low and the literature in patients with ICH was not compelling to recommend one method of administration of HTS over the other for initial management of elevated ICP or cerebral edema. Patient-specifc factors may be employed to aid clinicians in selecting the appropriate initial agent.
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Treatment of Cerebral Edema in Patients with Bacterial Meningitis

1. We recommend dexamethasone 10  mg intravenous every 6 h for 4 days to reduce neurological sequelae (primarily hearing loss) in patients with communityacquired bacterial meningitis (strong recommendation, moderate-quality evidence).
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2. We suggest dexamethasone 0.15  mg/kg intravenous every 6 h for 4 days as an alternative dose for patients with low body weight or high risk of corticosteroid adverse efects (good practice statement).
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3. We recommend administering dexamethasone before or with the frst dose of antibiotic in patients with bacterial meningitis (strong recommendation, moderate-quality evidence).
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4. We recommend use of corticosteroids to reduce mortality in patients with tuberculosis meningitis (strong recommendation, moderate quality of evidence). We cannot make a recommendation for one specifc corticosteroid or dose in patients with TB meningitis due to the inconsistency of agents and doses evaluated in the literature.
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5. We suggest that treatment with corticosteroids should be continued for two or more weeks in patients with tuberculosis meningitis (conditional recommendation, low quality of evidence).
Rationale: In making this recommendation, the panel felt that the quality of evidence was low and considerable variability exists within and across studies regarding the duration of corticosteroid treatment. Clinicians should use patient-specifc response and clinical factors to optimize the duration of corticosteroid treatment in this setting.
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6. Tere is insufcient evidence to determine whether hypertonic sodium solutions or mannitol is more efective to reduce ICP or cerebral edema in patients with community-acquired bacterial meningitis.
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Treatment of Cerebral Edema in Patients with Hepatic Encephalopathy

1. We suggest using either hypertonic sodium solutions or mannitol for the management of ICP or cerebral edema in patients with hepatic encephalopathy (conditional recommendation, very low-quality evidence).
Rationale: In making this recommendation, the panel felt that the quality of evidence was very low and the literature in patients with hepatic encephalopathy was not compelling to recommend one form hyperosmolar therapy over the other. Tus, either agent could be used and patient-specifc factors may be employed to aid clinicians in selecting the appropriate initial agent.
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2. Tere is insufcient evidence to determine whether either hyperosmolar therapy or ammonia-lowering therapy improves neurological outcomes in patients with hepatic encephalopathy.
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Hyperosmolar Therapy Safety and Infusion Considerations

Recommendations for Assessing the Risk of Renal Injury After Mannitol Administration

1. We suggest using osmolar gap over serum osmolarity thresholds during treatment with mannitol to monitor for the risk of AKI (conditional recommendation, very low-quality evidence).
Rationale: In making this recommendation, the panel felt that the quality of evidence was very low. While osmolar gap has not been defnitively shown to predict AKI during mannitol treatment, the osmolar gap appears to correlate best with mannitol concentration and elevated mannitol concentration is best associated with toxicity. Tus, the physiological rationale for the use of osmolar gap is stronger than using an empiric osmolarity threshold.
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2. There is insufcient evidence to recommend a cutof value for osmolar gap when evaluating for the risk of acute kidney injury.
Rationale: In making this recommendation, the panel felt that the quality of evidence was too low to make a defnitive recommendation. While the panel recognizes that an osmolar gap of 20 mOsm/kg has been used in clinical practice, we were unable to identify evidence to support this threshold. Research suggests that serum mannitol concentrations are the most efective method to assess but AKI risk, but this laboratory measurement is not commonly available. We did identify one study that demonstrated an osmolar gap of 55  mOsm/kg or higher being most correlated with serum mannitol concentration.
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3. Renal function measures should be monitored closely in patients receiving mannitol due to the risk of AKI with hyperosmolar therapy (good practice statement).
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Recommendations for Assessing the Risk of Toxicity (Acute Kidney Injury or Unwanted Acidosis) After Hypertonic Sodium Solution Administration

1. We suggest that severe hypernatremia and hyperchloremia during treatment with hypertonic sodium solutions should be avoided due to the association with acute kidney injury (conditional recommendation, low-quality evidence). An upper serum sodium range of 155–160 mEq/L and a serum chloride range of 110–115 mEq/L may be reasonable to decrease the risk of acute kidney injury (conditional recommendation, very low-quality evidence).
Rationale: In making this recommendation, the panel rated the quality of evidence as very low. Te precise serum values associated with acute kidney injury varies across the literature. Clinicians should evaluate the appropriate sodium and chloride concentrations in individual patients based on renal function, acid–base balance, and the need for acute treatment for elevated ICP or cerebral edema.
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2. Clinicians should routinely monitor both sodium and chloride serum concentrations to assess risk of AKI related to elevated concentrations (good practice statement).
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3. Renal function should be monitored closely in patients receiving hypertonic sodium solutions due to the risk of AKI with hyperosmolar therapy (good practice statement).
Rationale: In making these good practice statements on monitoring renal function, serum sodium, and serum chloride, the panel felt that the practice of routine monitoring for acute kidney injury was prudent given the potential risks of both HTS in this setting. Clinicians should use patient-specifc factors to determine the frequency of monitoring with ranging from twice daily to every 2 h based on rapidity of change to interventions.
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Recommendations for the Optimal Administration Method of Hypertonic Sodium Solution

1. There is insufcient evidence to support use of a continuous infusion of HTS targeting a serum sodium goal for the purpose of improving neurological outcomes.
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2. Due to insufcient evidence, we cannot recommend a specifc dosing strategy for HTS to improve neurological outcomes in patients with cerebral edema.
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3. Clinicians should avoid hyponatremia in patients with severe neurological injury due to the risk of exacerbating cerebral edema (good practice statement).
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Non‑pharmacologic Treatment of Cerebral Edema and Elevated Intracranial Pressure

Recommendations for the Non‑pharmacological Treatment of Cerebral Edema

1. We suggest that elevating the head of the bed to 30 degrees (but no greater than 45 degrees) be used as a benefcial adjunct to reduce intracranial pressure (conditional recommendation, very low-quality evidence).
Rationale: In making this recommendation, the panel rated the quality of available evidence as very low. However, this intervention has been used extensively in the clinical setting and the risk of elevating the head of the bed is generally very low and may be benefcial.
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2. We recommend that brief episodes of hyperventilation can be used for patients with acute elevations in intracranial pressure (strong recommendation, very low-quality evidence)
Rationale: In making this recommendation, the panel rated the quality of available evidence was very low. However, a strong recommendation was felt to be appropriate given the extensive amount of practical experience with this therapeutic strategy. Clinicians should be mindful of the limitations of acute hyperventilation related to cerebral blood fow and the extent of PaCO2 reduction. Clinicians should also maintain careful awareness of the duration of therapy to avoid deleterious changes in cerebral perfusion.
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3. We suggest that the use of CSF diversion be considered as a benefcial adjunct to reduce intracranial pressure (conditional recommendation, very lowquality evidence).
Rationale: In making this recommendation, the panel felt that the quality of evidence was very low. Clinicians should assess the risks and benefts of CSF diversion using patient-specifc factors.
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4. While non-pharmacological interventions may be efective for acute elevations in intracranial pressure, there is insufcient evidence that non-pharmacological interventions are efective for the treatment of any specifc physiological changes that produce brain swelling related to cerebral edema.
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Recommendation Grading

Overview

Title

Acute Treatment ofCerebral Edema inNeurocritical Care Patients

Authoring Organization

Publication Month/Year

June 1, 2020

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory, Emergency care, Home health, Long term care

Intended Users

Physician

Scope

Management, Treatment

Diseases/Conditions (MeSH)

D001929 - Brain Edema

Keywords

cerebral edema, elevated intracranial pressure, neurological injury, Clinical guidelines, Neurocritical Care Patients