What is the role of hypertonic saline (HS) in managing elevated intracranial pressure (ICP) in head injury patients?

Hypertonic Saline in Head Injury

Hypertonic saline (HS) is recommended as an effective osmotic agent for treating elevated intracranial pressure (ICP) in head injury patients, administered as either 7.5% solution at 250 mL bolus over 15-20 minutes or as continuous 3% infusion targeting serum sodium 145-155 mmol/L, though it does not improve neurological outcomes or survival. 1, 2

Primary Indication and Mechanism

• HS should be used specifically for documented intracranial hypertension (ICP >20 mmHg) or signs of brain herniation (mydriasis, anisocoria) after controlling secondary brain insults—prophylactic administration to patients without evidence of elevated ICP provides no benefit over standard crystalloids 1, 2

• The mechanism involves creating an osmotic pressure gradient across the blood-brain barrier, displacing water from brain tissue to the hypertonic extracellular environment, with maximum ICP reduction occurring at 10-15 minutes and lasting 2-4 hours 1, 2

Dosing Strategies

For acute ICP elevation:

• Administer 7.5% hypertonic saline at 250 mL (approximately 250 mOsm) as a bolus over 15-20 minutes 1, 2
• Alternative: 23.4% hypertonic saline at 30 mL over 15 minutes for severe refractory cases 3
• Re-administration may be considered if ICP remains elevated, but only after confirming serum sodium <155 mmol/L 2, 4

For sustained ICP management:

• Use continuous infusion of 3% hypertonic saline targeting serum sodium concentration of 145-155 mmol/L 2, 4
• This strategy is particularly validated in pediatric TBI with mean treatment duration of 7.6 days 2

Comparison with Mannitol

When to choose hypertonic saline over mannitol:

• Presence of hypovolemia or hypotension—mannitol causes significant osmotic diuresis requiring volume compensation, while HS provides volume expansion 1, 5
• Need for longer duration of effect—HS demonstrates reduced cumulative and daily ICP burdens compared to mannitol (15.52% vs 36.5% cumulative burden, p=0.003) 6
• Shorter ICU stays—patients receiving HS had significantly fewer ICU days (8.5 vs 9.8 days, p=0.004) 6

When to choose mannitol:

• Hypernatremia is already present (sodium >150 mmol/L) 1, 5
• Improved cerebral oxygenation is the priority—mannitol is the only ICP-lowering therapy associated with improved cerebral oxygenation 1, 5

Equiosmotic equivalence:

• At equiosmotic doses (approximately 250 mOsm), both agents demonstrate comparable efficacy for ICP reduction 1, 5

Monitoring Requirements

Serum sodium surveillance:

• Measure serum sodium within 6 hours of bolus administration 2, 4
• Target range: 145-155 mmol/L for both bolus and continuous infusion strategies 2, 4
• Do not exceed 155-160 mmol/L to prevent complications including osmotic demyelination syndrome, seizures, and hemorrhagic encephalopathy 2
• Do not re-administer bolus therapy until serum sodium falls below 155 mmol/L 2, 4

Additional monitoring:

• Check serum sodium every 6 hours initially during continuous infusion 2
• Monitor fluid balance, chloride levels (risk of hyperchloremia), and renal function 1, 2
• Sustained sodium >170 mEq/L for >72 hours significantly increases risk of thrombocytopenia, renal failure, neutropenia, and acute respiratory distress syndrome 2

Clinical Efficacy Data

ICP reduction:

• 23.4% HS decreased ICP from 33±9 mmHg to 19±6 mmHg within 1 hour, with maximum effect at 98 minutes post-bolus 7
• 23.4% HS reduced ICP by mean of 8.3 mmHg (p<0.0001) with greater reduction (14.2 mmHg) when baseline ICP >31 mmHg 3
• Cerebral perfusion pressure improved from 68±11 mmHg to 79±11 mmHg at 1 hour 7

Brain tissue oxygenation:

• PbtO2 improved by 3.1 mmHg (p<0.01) following 23.4% HS administration 3
• Patients with lower baseline CPP (<70 mmHg) responded more significantly, with CPP increasing by mean of 6 mmHg (p<0.0001) 3

Critical Limitations and Caveats

No mortality or outcome benefit:

• Despite effectiveness in reducing ICP, there is no evidence that HS improves neurological outcomes (Grade B evidence) or survival (Grade A evidence) in patients with raised ICP 2, 4
• A 2016 systematic review of 11 RCTs (1,820 patients) found no mortality benefit (RR 0.96,95% CI 0.83-1.11) or improvement in ICP control compared to other solutions 8

Contraindications:

• HS is not recommended for volume resuscitation in hemorrhagic shock unless combined with severe head trauma and focal neurological signs 2, 4
• Avoid in patients with baseline sodium >150 mmol/L 7

Safety profile:

• No evidence of osmotic demyelination syndrome has been reported with proper monitoring, even with bolus doses of 23.4% HS or sustained hypernatremia 2, 4
• Avoid rapid sodium correction exceeding 10 mmol/L per 24 hours 2
• One study monitoring adverse events found no significant differences between HS and comparison groups 8

Refractory Intracranial Hypertension

• For therapy-resistant ICP elevation (>25 mmHg) not responding to standard management and with plasma sodium <150 mmol/L, repeated bolus applications of 7.5% HS (2 mL/kg body weight) at 163±54 minute intervals effectively decrease ICP 7
• HS/HHES (7.5% saline with 6% hydroxyethyl starch) reduced ICP by 44% and improved CPP by 38% to >70 mmHg at 30 minutes in patients with therapy-resistant intracranial hypertension 9

Clinical Context

• HS represents a temporizing measure before definitive treatment such as decompressive craniectomy—despite intensive medical management, mortality in patients with increased ICP remains 50-70% 5
• Both HS and mannitol require monitoring of fluid, sodium, and chloride balances to prevent complications 1, 5
• The choice between continuous infusion versus bolus therapy depends on whether ICP elevation is sustained versus episodic 2, 4