Emergency Topic

Normal saline isn't normal.

0.9% saline was set by an 1890s hemolysis experiment, not matched to plasma. Its chloride load, what SMART, BaSICS, and PLUS actually showed, and when saline still beats balanced.

Reviewed June 2026 · verify against current guidelines

Where It Came From

Never based on plasma.

The 1890s accident

Often credited to the 1830s cholera wards, but those fluids were hypotonic, nothing like saline. The 0.9% number came later: Hamburger fixed it by watching when red cells burst in a dish, matched to hemolysis, not to the chemistry of human plasma.

Composition (per litre)

0.9% NaClLactated Ringer'sPlasma
Sodium (mmol)154130136-145
Chloride (mmol)15410994-106
BufferNoneLactate 28Bicarb 24
Osmolarity (mOsm)308273280-295
Chloride 154 vs plasma ~100. That 50% excess is the whole problem.
The Physiology

Why chloride matters.

Hyperchloremic metabolic acidosis

Strong ion difference (mEq/L)

0.9% NaClLactated Ringer'sPlasma
SID0~28~40

SID = strong cations (mainly Na) minus strong anions (mainly Cl); the lower it is, the more acidifying the fluid.

The hypothesis

More chloride drives acidosis and renal hypoperfusion, the proposed path to acute kidney injury.

Mechanism predicts harm. The hard outcome data is softer than the physiology suggests.
SID strong ion differenceGFR glomerular filtration rateAKI acute kidney injury
What The Trials Showed

Signal, not slam dunk.

The big trials

SMART (2018)ICU, single-center, unblinded. Kidney events (MAKE-30) 14.3% vs 15.4%. OR 0.91. Small win.
SALT-ED (2018)Non-ICU ER. Fewer kidney events (secondary outcome). Same direction.
BaSICS (2021)Blinded, ~11k. 90-day mortality 26.4% vs 27.2%. No difference.
PLUS (2022)Blinded, ~5k ICU. 90-day mortality 21.8% vs 22.0%. No difference.

The honest read

Both blinded mega-trials found no mortality benefit. Balanced fluid is a reasonable default, not a proven life-saver.

Pooled patient-level meta-analyses lean slightly toward balanced, but no mortality threshold is firmly crossed.

Sepsis is the exception. SMART subgroup OR 0.80 (0.67-0.94); SSC 2026 suggests balanced (moderate certainty).
MAKE-30 major adverse kidney events at 30 daysOR odds ratioSSC Surviving Sepsis Campaign
When It Still Matters

Pick by patient.

Reach for saline

Hypochloremic alkalosisVomiting, NG suction. Saline replaces the lost chloride.
Brain injury or edemaIn TBI, balanced fluid (not saline) was tied to higher mortality in BaSICS. SSC 2026 picks saline in sepsis plus TBI.
HyponatremiaAvoid relatively hypotonic balanced fluids. Saline's higher sodium is safer.

Reach for balanced

SepsisSSC 2026 suggests balanced over saline. SMART subgroup OR 0.80.
Large-volume resusDKA, pancreatitis, burns. Avoids the chloride load.

LR carries calcium: do not co-infuse with ceftriaxone or with citrated blood in the same line.

Myth: "LR is dangerous in hyperkalemia." SMART secondary analysis says no.
NG nasogastricTBI traumatic brain injuryLR lactated Ringer'sDKA diabetic ketoacidosis

Sources

Verify against current guidelines and local protocol before acting.

  1. Semler MW et al. Balanced Crystalloids versus Saline in Critically Ill Adults (SMART). NEJM 2018;378:829-839.
  2. Self WH et al. Balanced Crystalloids versus Saline in Noncritically Ill Adults (SALT-ED). NEJM 2018;378:819-828.
  3. Zampieri FG et al. Effect of a Balanced Solution vs 0.9% Saline on Mortality (BaSICS). JAMA 2021;326:818-829.
  4. Finfer S et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults (PLUS). NEJM 2022;386:815-826.
  5. Prescott H et al. Surviving Sepsis Campaign 2026. Crit Care Med 2026 (suggests balanced over saline; saline if concurrent TBI).
  6. Zampieri FG et al. Balanced Crystalloids versus Saline (BEST-Living): individual patient data meta-analysis. Lancet Respir Med 2023.

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Normal saline isn't normal.
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