What is the indication for 3% (three percent) saline in patients with intracranial hemorrhage (ICH)?

Hypertonic Saline (3%) for Intracerebral Hemorrhage

Primary Indication

Administer 3% hypertonic saline as a continuous infusion when patients with intracerebral hemorrhage develop elevated intracranial pressure, targeting serum sodium of 145-155 mmol/L. 1, 2

The specific clinical triggers that warrant initiating therapy include:

• Glasgow Coma Scale ≤8 with evidence of elevated ICP 2
• Clinical signs of transtentorial herniation (pupillary changes, posturing, deteriorating consciousness) 2
• Significant intraventricular hemorrhage with hydrocephalus 2
• Radiological evidence of mass effect or midline shift 1

Administration Strategy

For Acute ICP Crisis

• Give 2 mL/kg of 3% saline as a bolus over 15-20 minutes for immediate ICP reduction 2
• Maximum effect occurs at 10-15 minutes and lasts 2-4 hours 1, 2
• Do not re-administer bolus until serum sodium is <155 mmol/L 1, 2

For Sustained ICP Control

• Initiate continuous infusion of 3% hypertonic saline targeting serum sodium 145-155 mmol/L 1, 2
• Continuous infusion is superior to repeated boluses as it provides sustained control over days and reduces frequency of ICP spikes at 6,12,24,48, and 72 hours 1
• This approach avoids repeated bolus administration and associated sodium fluctuations 1

Critical Monitoring Requirements

Measure serum sodium within 6 hours of initiating therapy and every 6 hours thereafter 1, 2

Key safety thresholds:

• Target range: 145-155 mmol/L 1, 2
• Never exceed 155-160 mmol/L to prevent complications including osmotic demyelination syndrome, seizures, and hemorrhagic encephalopathy 1
• Sustained sodium >170 mEq/L for >72 hours significantly increases risk of thrombocytopenia, renal failure, neutropenia, and acute respiratory distress syndrome 1
• Avoid rapid sodium correction exceeding 10 mmol/L per 24 hours 1

Evidence Supporting Use in ICH

The evidence base for 3% saline in ICH is more limited than in traumatic brain injury, but demonstrates clear physiological benefits:

• Early continuous 3% saline infusion reduced perihematomal edema evolution and ICP crises, with a trend toward reduced mortality in a retrospective study of 26 patients with severe ICH 3
• In this study, absolute edema volume was significantly smaller between days 8-14 (P=0.04), and relative edema volume was significantly smaller between days 2-14 (P=0.02) 3
• ICP crises occurred less frequently in the treatment group (12 versus 56 episodes, P=0.048) 3
• In-hospital mortality was 11.5% in the hypertonic saline group versus 25% in controls (P=0.078) 3

In experimental ICH models, 3% NaCl produced significantly higher cerebral perfusion pressure and lower water content in lesioned white matter compared to mannitol 4

The European Stroke Organisation notes that one nonrandomized feasibility study showed 3% hypertonic saline led to less perihematomal edema and a mortality trend favoring treatment compared to historical controls 5

Superiority Over Mannitol

Prefer hypertonic saline over mannitol in ICH patients for the following reasons:

• More rapid ICP reduction and greater increases in cerebral perfusion pressure at equiosmolar doses 1, 2
• Longer duration of action, particularly with 3% solution 4
• Preferred in patients with hypovolemia (common in ICH) as it avoids the osmotic diuresis associated with mannitol 2
• Avoids potential for acute kidney injury associated with mannitol, particularly relevant in patients with chronic kidney disease 2
• Meta-analysis showed hypertonic saline has relative risk of 1.16 (95% CI, 1.00-1.33) for successful ICP control compared to mannitol 2

In the experimental ICH model, only 3% NaCl maintained significantly lower ICP at 120 minutes compared to pretreatment values (P=0.02), while mannitol did not (P=0.08) 4

Essential Adjunctive Measures

Always combine hypertonic saline with:

• Elevate head of bed 20-30 degrees to assist venous drainage 1, 2
• Adequate sedation and analgesia to control pain and agitation 1
• Maintain cerebral perfusion pressure >70 mmHg 1
• Avoid hypotonic fluids (Hartmann's, Ringer's lactate, 5% dextrose, 0.45% saline) as they worsen cerebral edema 1
• Use 0.9% saline for maintenance fluids, reserving hypertonic saline specifically for ICP management 1

Critical Limitations and Caveats

Despite proven efficacy in reducing ICP (Grade A evidence), hypertonic saline does not improve neurological outcomes (Grade B evidence) or survival (Grade A evidence) in patients with raised intracranial pressure 1, 2

This is a crucial distinction: while 3% saline effectively treats the physiological derangement of elevated ICP and reduces perihematomal edema, it has not been shown to translate into improved functional outcomes or mortality reduction in randomized controlled trials. The European Stroke Organisation explicitly states there is insufficient evidence from RCTs to make strong recommendations on measures to lower ICP for adults with acute ICH 5

Contraindications

• Do not use for volume resuscitation in hemorrhagic shock unless combined with severe head trauma and focal neurological signs 1
• Avoid in patients with baseline sodium >155 mmol/L 2

Potential Complications

• Pulmonary edema (led to treatment termination in some patients) 6
• Diabetes insipidus (led to treatment termination in some patients) 6
• No evidence of osmotic demyelination syndrome has been reported with proper monitoring, even with bolus doses of 23.4% hypertonic saline or sustained hypernatremia 1

Clinical Context

The evidence for 3% saline in ICH comes primarily from observational studies and experimental models rather than randomized controlled trials. The strongest clinical evidence is from a retrospective study showing reduced perihematomal edema evolution and fewer ICP crises 3, and experimental data demonstrating superior cerebral perfusion and reduced brain water content compared to mannitol 4.

Given the lack of RCT evidence but clear physiological benefits and safety profile, 3% hypertonic saline represents a reasonable first-line osmotic agent for managing elevated ICP in ICH patients who meet clinical criteria 5, 1, 2, with the understanding that it treats the immediate life-threatening complication of elevated ICP rather than improving ultimate neurological recovery.