What is the difference between 0.9% Normal Saline, Plain Normal Saline Solution (NSS), and Lactated Ringer's (LR) solution for intravenous fluid resuscitation?

Intravenous Fluid Selection: Normal Saline vs Lactated Ringer's Solution

Direct Answer

For most critically ill patients requiring IV fluid resuscitation, use balanced crystalloids (Lactated Ringer's or Plasma-Lyte) as first-line therapy rather than 0.9% normal saline, as they reduce mortality and major adverse kidney events. 1, 2

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Key Compositional Differences

0.9% Normal Saline (NS)

• Sodium: 154 mEq/L
• Chloride: 154 mEq/L (supraphysiologic concentration)
• pH: ~5.5 (acidic)
• Osmolality: 308 mOsm/L
• No buffer or potassium 2

Lactated Ringer's Solution (LR)

• Sodium: 130 mEq/L
• Chloride: 109 mEq/L (near-physiologic)
• Potassium: 4 mEq/L
• Calcium: 3 mEq/L
• Lactate: 28 mEq/L (metabolized to bicarbonate as buffer)
• pH: ~6.5
• Osmolality: 273 mOsm/L (slightly hypotonic) 2, 3

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Clinical Decision Algorithm

Use Lactated Ringer's (or balanced crystalloid) for:

• Sepsis and septic shock - Reduces 30-day mortality (adjusted HR 0.71,95% CI 0.51-0.99) and increases hospital-free days by 1.6 days compared to saline 4
• Hemorrhagic shock without traumatic brain injury - Preferred as initial crystalloid to reduce renal complications 5, 1
• Emergency surgery/laparotomy - Reduces major adverse kidney events (MAKE 30) 1
• Hyperchloremia or metabolic acidosis - LR helps correct rather than worsen these conditions 2
• Large volume resuscitation (>5L) - High chloride loads from saline increase mortality risk 1, 2

Use 0.9% Normal Saline for:

• Traumatic brain injury - LR is slightly hypotonic and can worsen cerebral edema; NS is mandatory 2, 3
• Severe hyponatremia - NS helps correct sodium deficits without further dilution 3
• Metabolic alkalosis - The acidifying effect of NS helps correct the alkalosis 3
• Limit to maximum 1-1.5L when used to minimize hyperchloremic complications 2, 3

Avoid Lactated Ringer's in:

• Severe traumatic brain injury - Risk of cerebral edema from hypotonic solution 2, 3
• Severe liver dysfunction - Impaired lactate metabolism 3
• Severe hyperkalemia - LR contains 4 mEq/L potassium 3

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Evidence Quality and Nuances

Mortality and Renal Outcomes

The evidence shows divergent findings that require careful interpretation:

• The SMART trial (15,802 ICU patients) demonstrated balanced crystalloids reduced major adverse kidney events (death, persistent renal dysfunction, or dialysis) compared to saline 1, 2

• The CLOVERS secondary analysis (2025) showed lactated Ringer's reduced mortality by 29% (HR 0.71) in sepsis-induced hypotension compared to saline 4

• However, the BaSICS trial (2021,10,520 patients) found no significant mortality difference between balanced solution and saline (26.4% vs 27.2%, HR 0.97,95% CI 0.90-1.05) 6

• The SOLAR trial (2020,8,616 surgical patients) found no clinically meaningful difference in complications between LR and saline in elective orthopedic/colorectal surgery 7

Resolution of contradictions: The benefit of balanced crystalloids appears most pronounced in sepsis 4 and when large volumes are required 1. In stable surgical patients receiving moderate volumes (~2L), the difference is negligible 7. Guidelines favor balanced crystalloids based on the totality of evidence showing reduced renal complications 5, 1.

Hyperchloremic Acidosis Risk

• Normal saline's supraphysiologic chloride (154 mEq/L) causes hyperchloremic metabolic acidosis, especially with volumes >5L 1, 2
• Hyperchloremia causes renal vasoconstriction, worsening kidney perfusion and increasing acute kidney injury risk 2
• Observational studies link postoperative hyperchloremia with increased 30-day mortality 5, 2
• LR's lactate component (28 mEq/L) is metabolized to bicarbonate, helping correct concurrent acidosis 2

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Common Pitfalls to Avoid

Pitfall #1: Using LR in traumatic brain injury

• Never use LR in TBI patients - its hypotonic nature (273 mOsm/L) can worsen cerebral edema 2, 3
• Use 0.9% saline despite hyperchloremia risk, as preventing cerebral edema takes priority 2

Pitfall #2: Excessive normal saline administration

• Limit saline to 1-1.5L maximum when used 2, 3
• Monitor chloride levels every 4-6 hours during resuscitation 2
• Chloride >110 mEq/L indicates established hyperchloremia that will worsen with continued saline 2

Pitfall #3: Assuming LR worsens lactic acidosis

• LR does not worsen lactic acidosis despite containing lactate 3
• The lactate in LR is metabolized to bicarbonate by the liver, providing buffering capacity 2

Pitfall #4: Using colloids in hemorrhagic shock

• Crystalloids should be preferred over colloids (hydroxyethyl starch, gelatins) 5
• Colloids show no mortality benefit and increase renal failure and hemorrhagic complications 5
• Albumin is not recommended in hemorrhagic shock due to lack of benefit and higher cost 5

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Volume Considerations in Hemorrhagic Shock

• Hemorrhagic shock often requires 5-10L of fluid in the first 24 hours 5
• Permissive hypotension strategy: Target systolic BP 80-90 mmHg until bleeding is controlled 3
• With such high volumes, balanced crystalloids become critical to avoid massive chloride loads 5, 1
• The trauma subgroup in SMART (3,328 patients) received only median 1L, limiting applicability to major hemorrhage 5

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Guideline Consensus

European Society of Anaesthesiology (2022): Balanced crystalloids should be used rather than 0.9% NaCl as first-line therapy in hemorrhagic shock to reduce mortality and adverse renal events (GRADE 2+) 5

American College of Emergency Physicians: Balanced crystalloids are strongly recommended as first-line fluid therapy, particularly in sepsis 1

American College of Critical Care Medicine: Use balanced crystalloids like LR or Plasma-Lyte for most patients; reserve saline for TBI, severe hyponatremia, or metabolic alkalosis 3