Acute Treatment of Cerebral Edema in Neurocritical Care Patients: NCS guidelines

• In patients with SAH, does sodium target-based dosing with hypertonic sodium solutions (sodium chloride, lactate, or bicarbonate) improve ICP/cerebral edema compared to intermittent, symptom-based bolus doses of hypertonic sodium solutions?
• In patients with SAH, does sodium target-based dosing with hypertonic sodium solutions (sodium chloride, lactate, or bicarbonate) improve neurological outcomes at discharge compared to intermittent, symptom-based bolus doses of hypertonic sodium solutions?

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).

• In patients with TBI, does the use of hypertonic sodium solutions improve cerebral edema compared to mannitol?
• In patients with TBI, does the use of hypertonic sodium solutions for cerebral edema improve neurological outcomes compared to mannitol?

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).

2.We suggest that the use of mannitol is an effective alternative in patients with TBI unable to receive hypertonic sodium solutions (conditional recommendation, low-quality evidence).

3.We recommend against the use of hypertonic sodium solutions in the pre-hospital setting to specifically improve neurological outcomes for patients with TBI (strong recommendation, moderate-quality evidence).

4.We suggest against the use of mannitol in the pre-hospital setting to improve neurological outcomes for patients with TBI (conditional recommendation, very low-quality evidence).

• In patients with ischemic stroke, does the use of hypertonic sodium solutions improve cerebral edema compared to mannitol?
• In patients with ischemic stroke, does the use of hypertonic sodium solutions for cerebral edema improve neurological outcomes compared to mannitol?

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). There is insufficient evidence to recommend either hypertonic saline or mannitol for improving neurological outcomes in patients with acute ischemic stroke.

• In patients with ICH, does the use of hypertonic sodium solutions improve cerebral edema compared to mannitol?
• In patients with ICH, does the use of corticosteroid therapy improve neurological outcomes compared to placebo/control?

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).
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).

• In patients with bacterial meningitis, does the use of hypertonic sodium solutions for cerebral edema improve CE compared to mannitol?
• In patients with bacterial meningitis, does the use of corticosteroid therapy improve neurological outcomes compared to placebo/control?

1. We recommend dexamethasone 10 mg intravenous every 6 h for 4 days to reduce neurological sequelae (primarily hearing loss) in patients with community-acquired bacterial meningitis (strong recommendation, moderate-quality evidence).
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 effects (good practice statement).
3. We recommend administering dexamethasone before or with the first dose of antibiotic in patients with bacterial meningitis (strong recommendation, moderate-quality evidence).
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 specific corticosteroid or dose in patients with TB meningitis due to the inconsistency of agents and doses evaluated in the literature.
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).
6. There is insufficient evidence to determine whether hypertonic sodium solutions or mannitol is more effective to reduce ICP or cerebral edema in patients with community-acquired bacterial meningitis.

• In patients with hepatic encephalopathy, does the use of hypertonic sodium solutions improve cerebral edema compared to mannitol?
• In patients with hepatic encephalopathy, does the use of hyperosmolar therapy improve neurological outcomes at discharge compared to ammonia-lowering agents?

• In patients receiving mannitol, does osmolarity or osmolar gap best predict the likelihood for AKI?
• In patients receiving hypertonic sodium solutions, does the serum sodium concentration best predict toxicity [AKI, unwanted acidosis] compared to the serum chloride concentration?

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).
2. There is insufficient evidence to recommend a cutoff value for osmolar gap when evaluating for the risk of acute kidney injury.
3. Renal function measures should be monitored closely in patients receiving mannitol due to the risk of AKI with hyperosmolar therapy (good practice statement)

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).
2. Clinicians should routinely monitor both sodium and chloride serum concentrations to assess risk of AKI related to elevated concentrations (good practice statement).
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).

• In patients with cerebral edema, how does continuous infusion of hypertonic sodium solutions compare to bolus infusion of hypertonic sodium solutions in improving neurological outcomes?

1. There is insufficient evidence to support use of a continuous infusion of HTS targeting a serum sodium goal for the purpose of improving neurological outcomes.
2. Due to insufficient evidence, we cannot recommend a specific dosing strategy for HTS to improve neurological outcomes in patients with cerebral edema.
3. Clinicians should avoid hyponatremia in patients with severe neurological injury due to the risk of exacerbating cerebral edema (good practice statement).

• In patients with cerebral edema, how do non-pharmacological interventions compare to pharmacological interventions for reduction of cerebral edema?

The pharmacologic treatment of cerebral edema should be guided whenever possible by the underlying pathology. The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected.