Mechanism of Action of Hypertonic Saline in Lowering Intracranial Pressure
Hypertonic saline lowers intracranial pressure primarily through a marked osmotic shift of fluid from the intracellular space of brain tissue into the intravascular compartment, creating an osmotic gradient across the blood-brain barrier that draws water out of edematous neurons. 1
Primary Osmotic Mechanism
The fundamental mechanism relies on the osmotic properties of sodium at the cellular level:
The reflection coefficient of the cell membrane for sodium is 1.0 (compared to 0.9 for mannitol), meaning sodium is completely excluded from crossing neuronal membranes and creates a maximal osmotic gradient. 1
This high reflection coefficient is maintained by the persistent action of sodium/potassium ATPase pumps in cell membranes. 1
The reflection coefficient of the endothelial membrane is only 0.1, which means most fluid mobilization occurs from the intracellular space (brain parenchyma) rather than the interstitial space. 1
Hypertonic saline causes a transient increase in osmolarity of the extracellular space, creating an osmotic pressure gradient across the blood-brain barrier that results in water displacement from brain tissue to the hypertonic intravascular environment, reducing cerebral edema. 2
Immediate Volume Expansion Effects
The osmotic action produces rapid intravascular volume expansion:
An infusion of 7.5% hypertonic saline can increase intravascular volume by as much as four times the infused volume within minutes of administration. 1
Osmotic equilibrium is reached within approximately 4 hours of a bolus dose. 1
The net effect of 7.5% saline dextran is to increase plasma volume by 750 mL for every liter administered, substantially better than the 300 mL achieved with crystalloid. 1
Cerebrovascular and Hemodynamic Effects
Beyond simple osmosis, hypertonic saline produces beneficial vascular changes:
Hypertonicity has a direct relaxant effect on vascular smooth muscle, resulting in arteriolar vasodilation and improved regional blood flow throughout the microcirculation. 1
Endothelial cell volume normalizes as osmotic fluid shift reverses the water accumulation that occurs during shock and ischemic states, increasing capillary diameter and reducing resistance to flow. 1
Plasma viscosity decreases due to increased plasma water content, further improving microcirculatory flow. 1
Administration results in increased cardiac output through increased preload (volume expansion) and decreased afterload (reduced pulmonary and systemic vascular resistance). 1
Brain Tissue Dehydration
Direct experimental evidence demonstrates the tissue-level effect:
The ICP-lowering effect is primarily due to dehydration of brain tissue, with cerebral blood volume remaining largely unaffected. 3
Hypertonic saline extracts water from neurons into arterial vessels, producing cerebral vasoconstriction and a reduction in cerebrovascular volume. 4
A significant positive correlation exists between changes in serum osmolality and ICP reduction, supporting the osmotic mechanism. 5
Time Course and Duration
The therapeutic effect follows a predictable temporal pattern:
Maximum effect is observed 10-15 minutes after administration and lasts for 2-4 hours. 2
ICP decreases to approximately 30% of baseline during the study period following administration. 5
Mean ICP reduction of 8.3 mm Hg has been demonstrated, with greater reductions (14.2 mm Hg) in patients with baseline ICP >31 mm Hg. 6
Secondary Beneficial Effects
Additional mechanisms contribute to the therapeutic benefit:
Immune-modulator effects include blunting of neutrophil activation and altered cytokine production, with reduced TNF-alpha and increased anti-inflammatory IL-ra and IL-10. 1
Myocardial performance may improve through reduction in myocyte edema or increased myocardial calcium uptake with restoration of transmembrane potential. 1
Improved regional blood flow may prevent ischemia-induced complications in multiple organ systems. 1
Critical Limitation
Despite robust Grade A evidence for ICP reduction, hypertonic saline does NOT improve neurological outcomes (Grade B evidence) or survival (Grade A evidence) in patients with raised intracranial pressure. 1, 2