What is the difference between isotonic, hypertonic, and hypotonic intravenous (IV) fluids?

Differences Between Isotonic, Hypertonic, and Hypotonic IV Fluids

Definitions Based on Sodium Concentration and Osmolarity

Isotonic fluids have sodium concentrations similar to plasma (135-154 mEq/L) and osmolarity around 308 mOsm/L, hypotonic fluids contain lower sodium concentrations (30-100 mEq/L), and hypertonic fluids contain higher sodium concentrations than plasma. 1

Isotonic Solutions

• Sodium concentration: 135-154 mEq/L, matching the aqueous phase of plasma (154 mEq/L) 1
• Osmolarity: Approximately 308 mOsm/L (similar to 0.9% sodium chloride) 1
• Common examples: 0.9% sodium chloride (normal saline), Plasma-Lyte (140 mEq/L sodium), Hartmann solution (131 mEq/L sodium) 1, 2
• Mechanism: Remains primarily in the extracellular space, providing effective volume expansion without significant fluid shifts across cell membranes 1

Hypotonic Solutions

• Sodium concentration: 30-100 mEq/L, significantly lower than plasma 1
• Common examples: 0.45% saline, 0.3% saline, 0.18% saline 3
• Mechanism: Distributes across both intracellular and extracellular compartments, with water moving into cells due to osmotic gradient 1
• Key risk: Associated with development of hyponatremia (serum sodium <135 mEq/L) 1

Hypertonic Solutions

• Sodium concentration: Higher than plasma (>154 mEq/L) 4
• Common example: 3% saline, 7.5% saline 4
• Mechanism: Draws fluid from intracellular to extracellular space, providing small-volume resuscitation 4
• Key risk: Can cause hypernatremia (serum sodium >145 mEq/L) 4

Clinical Outcomes and Safety Profile

Isotonic Fluids: The Preferred Standard

The American Academy of Pediatrics strongly recommends isotonic solutions with appropriate potassium chloride and dextrose for maintenance IV fluids in hospitalized children aged 28 days to 18 years, based on Level A evidence showing significant reduction in hyponatremia risk. 1, 3

• Number needed to treat: Only 7.5 patients need isotonic fluids (versus hypotonic) to prevent one case of hyponatremia 1, 3
• Evidence base: 16 of 17 randomized controlled trials (2,455 patients total) demonstrated superiority of isotonic over hypotonic fluids in preventing hyponatremia 1
• Hypernatremia risk: No evidence of increased hypernatremia risk with isotonic fluids (RR 1.24,95% CI 0.65-2.38) 1

Hypotonic Fluids: Significant Harm Risk

• Hyponatremia incidence: 20-22% with hypotonic solutions versus 1.9% with isotonic solutions 5
• Relative risk: Greater than 2-fold increased risk for mild hyponatremia and greater than 5-fold for moderate hyponatremia 1
• Clinical consequences: Hyponatremia is an independent risk factor for mortality, increased length of hospitalization, and increased costs 1
• Contraindicated: Should not be used for maintenance therapy in hospitalized children 3

Hypertonic Fluids: Limited Specific Indications

• Primary use: Small-volume resuscitation in hypovolemic shock and mannitol-refractory intracranial hypertension 4
• Disadvantage: Risk of hypernatremia limits routine use 4
• Evidence limitation: Insufficient data to determine mortality benefit in trauma, burns, or surgical patients (RR 0.84,95% CI 0.69-1.04) 6

Clinical Application Algorithm

For Maintenance IV Fluids (Hospitalized Patients)

1. Use isotonic solutions (0.9% saline, Plasma-Lyte, or balanced crystalloids) with 2.5-5% dextrose and appropriate potassium 1, 3
2. Avoid hypotonic solutions (0.45% saline, 0.3% saline) for routine maintenance 3
3. Monitor serum sodium at least daily during IV fluid administration 3

For Resuscitation from Hypovolemia/Shock

1. Administer isotonic crystalloids immediately for severe dehydration, shock, or altered mental status 2
2. Continue until pulse, perfusion, and mental status normalize 2
3. Consider hypertonic saline only for specific indications like refractory intracranial hypertension 4

Common Pitfalls to Avoid

• Do not use hypotonic solutions based on outdated teaching about "free water" requirements—this significantly increases iatrogenic hyponatremia risk 3
• Do not assume isotonic fluids cause hypernatremia—this concern is not supported by evidence 1
• Do not fail to account for all fluid sources when calculating maintenance volume, as this leads to fluid overload 3
• Do not use these recommendations in excluded populations: neonates <28 days, patients with neurosurgical disorders, cardiac disease, hepatic disease, renal dysfunction, diabetes insipidus, or severe burns 1, 3

Special Exceptions Requiring Alternative Approaches

Hypotonic fluids may be required in specific conditions including nephrogenic diabetes insipidus, voluminous diarrhea, or severe burns 2. Hypertonic solutions are indicated for mannitol-refractory intracranial hypertension 4.