What is the comparison between 3% normal saline (NS) and mannitol in the management of traumatic brain injury (TBI) with elevated intracranial pressure (ICP)?

3% Hypertonic Saline vs Mannitol in Traumatic Brain Injury

Both 3% hypertonic saline and mannitol are equally effective at reducing intracranial pressure at equiosmotic doses (approximately 250 mOsm), but hypertonic saline offers practical advantages including longer duration of effect, shorter ICU stays, and better maintenance of cerebral perfusion without causing hypovolemia. 1

Comparative Efficacy for ICP Reduction

At equiosmotic doses, mannitol and hypertonic saline demonstrate comparable efficacy in treating intracranial hypertension. 1 However, the evidence reveals important nuances:

• Hypertonic saline produces significantly greater ICP reduction with mean reductions of 9.3 mm Hg versus 6.4 mm Hg for mannitol, and a higher response rate (92.6% vs 74%) 2
• Duration of effect is longer with hypertonic saline (mean difference of 0.67 hours longer) 3
• Cumulative and daily ICP burdens are significantly lower with hypertonic saline (15.52% vs 36.5% cumulative burden; 0.3 vs 1.3 hours/day daily burden) 4

Clinical Outcomes

ICU Length of Stay

• Hypertonic saline is associated with significantly shorter ICU stays (mean difference of 1.18 days shorter) 3
• Patients receiving HTS had 8.5 ± 2.1 ICU days versus 9.8 ± 0.6 days for mannitol 4

Mortality and Neurological Outcomes

• No statistically significant difference in mortality rates between the two agents (RR = 1.55; 95% CI = 0.98-2.47, p = 0.06) 3
• Favorable neurological outcomes are similar between both agents (RR = 0.92,95% CI = 0.11-7.96) 3
• Mannitol is the only therapy among ICP-lowering treatments associated with improved cerebral oxygenation 1

Dosing Recommendations

Hypertonic Saline

• 7.5% hypertonic saline at 250 mL per bolus administered over 15-20 minutes is the recommended concentration and dose 5
• Target serum sodium concentration of 145-155 mmol/L 5
• 3% hypertonic saline as continuous infusion is commonly used in pediatric populations 5
• Re-administration should not occur until serum sodium is <155 mmol/L 5

Mannitol

• 20% mannitol at 0.25-0.5 g/kg IV over 20 minutes, repeated every 6 hours as needed 6
• Equiosmotic dose is approximately 250 mOsm 1
• Maximum daily dose of 2 g/kg to avoid adverse effects 6

Side Effect Profiles and Monitoring

Mannitol Considerations

• Induces significant osmotic diuresis requiring volume compensation 1
• Can cause dehydration and hypovolemia over time 7
• May lead to hypotension 6
• Serum osmolality must remain below 320 mOsm/L 6

Hypertonic Saline Considerations

• Exposes patients to hypernatremia and hyperchloremia 1
• Helps maintain normovolemia and cerebral perfusion 7
• Serum sodium should be measured within 6 hours of bolus administration 5
• Avoid sodium levels exceeding 155-160 mmol/L 5

Clinical Decision Algorithm

Choose hypertonic saline when:

• Hypovolemia or hypotension is present or a concern 6
• Longer duration of ICP control is desired 3
• Maintaining cerebral perfusion pressure is critical 7

Choose mannitol when:

• Hypernatremia is already present 6
• Improved cerebral oxygenation is the priority 1
• Improved cerebral blood flow rheology is desired 6

Both agents require:

• Monitoring of fluid, sodium, and chloride balances 1
• Use only for documented intracranial hypertension, not prophylactically 1
• Administration in conjunction with other ICP control measures including head-of-bed elevation, sedation, analgesia, and CSF drainage 6

Critical Caveats

• Prophylactic administration of hypertonic saline to patients without evidence of intracranial hypertension is not superior to crystalloids 1
• Neither agent has proven benefit for improving neurological outcomes or survival despite effectiveness in reducing ICP 5
• Hypertonic saline is not recommended for volume resuscitation in hemorrhagic shock 5
• Both agents are temporizing measures before definitive treatment such as decompressive craniectomy 6
• Despite intensive medical management with either agent, mortality in patients with increased ICP remains high (50-70%) 6