What is the recommended treatment for reducing intracranial pressure in patients with traumatic brain injuries based on the Sahara trial?

Hypertonic Saline in Traumatic Brain Injury: Evidence from the SAHARA Trial and Related Studies

Based on the most recent high-quality evidence, hypertonic saline does NOT improve survival or neurological outcomes in patients with traumatic brain injury, despite its effectiveness in reducing intracranial pressure. The SAHARA trial (referenced as studies by Bulger and colleagues) demonstrated no advantage of pre-hospital hypertonic saline administration compared to normal 0.9% saline among 2,184 patients with severe TBI and traumatic hypovolemic shock 1.

Key Findings on Mortality and Neurological Outcomes

The evidence conclusively shows that hypertonic saline solutions are safe but will neither improve survival nor improve neurological outcome after TBI (Grade A evidence). 1

• Cooper et al. found almost no difference in neurological function six months after TBI in patients who received pre-hospital hypertonic saline resuscitation compared to conventional fluid 1

• Meta-analysis by Perel and Roberts comparing dextran in hypertonic crystalloid with isotonic crystalloid demonstrated a pooled relative risk of 1.24 (95% CI 0.94 to 1.65), showing no beneficial effects 1

• A 2016 systematic review and meta-analysis of 11 randomized controlled trials (1,820 patients) confirmed that hypertonic saline did not decrease mortality (risk ratio 0.96,95% CI 0.83 to 1.11) or improve intracranial pressure control compared to other solutions 2

Effect on Intracranial Pressure Reduction

While hypertonic saline effectively reduces ICP, this does not translate to improved clinical outcomes:

• Hypertonic saline reduces intracranial pressure more effectively than mannitol at equimolar dosing (approximately 250 mOsm) 1

• A 2020 study demonstrated that HTS bolus therapy appears superior to mannitol in reducing the combined burden of intracranial hypertension (ICP >25 mm Hg) and cerebral hypoperfusion (CPP <60 mm Hg), with significantly fewer days with elevated ICP (0.6 ± 0.8 vs 2.4 ± 2.3 days, P < 0.01) 3

• The mechanism involves creating an osmotic pressure gradient across the blood-brain barrier, with maximum effect observed after 10-15 minutes and lasting 2-4 hours 4

Clinical Recommendations Based on Current Evidence

If hypertonic saline is used for ICP management (recognizing it does not improve survival), the recommended approach is:

• Administer 7.5% hypertonic saline at 250 mL per bolus over 15-20 minutes for acute ICP elevation 4

• Target serum sodium concentration of 145-155 mmol/L 4

• Measure serum sodium within 6 hours of bolus administration 4

• Do not re-administer until serum sodium is <155 mmol/L to avoid hypernatremia 4

• Avoid sodium levels exceeding 155-160 mmol/L to prevent complications including osmotic demyelination syndrome 4

Important Clinical Caveats

Hypertonic saline should NOT be used as a volume resuscitation solution in hemorrhagic shock 4, despite earlier promising results in specific subgroups:

• A 2008 RCT showed improved ARDS-free survival only in the subset requiring ≥10 units of packed RBCs (19% of the population), but no overall benefit 1

• One study showed improved survival with hypertonic saline dextran in penetrating torso injuries requiring surgery, but this has not been replicated in broader populations 1

Comparison with Mannitol

Use hypertonic saline instead of, not in conjunction with, mannitol for ICP reduction 4:

• Hypertonic saline may be preferred in patients with hypovolemia, as mannitol can cause dehydration over time 5

• Both agents have comparable efficacy at equiosmotic doses 4

• Mannitol remains FDA-approved for ICP reduction at doses of 0.25 to 2 g/kg body weight as a 15-25% solution over 30-60 minutes 6

Special Populations

In pediatric TBI patients, continuous infusions of 3% hypertonic saline are commonly used, targeted at achieving elevated sodium levels or osmolality 4:

• Pediatric dosing for bolus therapy: 1-2 g/kg body weight or 30-60 g/m² body surface area over 30-60 minutes 6

Avoid 4% albumin solution in patients with brain injury, as it may increase mortality 4

Monitoring Requirements

• Continuous ICP monitoring is recommended when using hypertonic saline 4

• Monitor fluid, sodium, and chloride balances to prevent complications 4

• Discontinue if renal, cardiac, or pulmonary status worsens, or CNS toxicity develops 6

• Be aware that hypertonic saline may increase cerebral blood flow and risk of postoperative bleeding in neurosurgical patients 6