Why is normal saline (0.9% sodium chloride) recommended for the treatment of diabetic ketoacidosis (DKA)?

Why Normal Saline is Recommended for DKA

Normal saline (0.9% NaCl) is recommended as the initial fluid for DKA treatment because it rapidly expands intravascular volume and restores renal perfusion in severely dehydrated patients, though emerging evidence suggests balanced crystalloid solutions may lead to faster DKA resolution. 1, 2

Initial Fluid Resuscitation Rationale

The American Diabetes Association guidelines recommend isotonic saline at 15-20 ml/kg/h (approximately 1-1.5 liters in the first hour for average adults) as the initial fluid therapy because: 1

• DKA causes profound volume depletion with typical total body water deficits of 6 liters (100 ml/kg body weight), requiring aggressive initial volume expansion 1, 2
• Isotonic saline matches plasma tonicity, preventing rapid osmotic shifts that could precipitate cerebral edema during initial resuscitation 1
• Restoration of renal perfusion is critical before initiating potassium replacement and insulin therapy, which normal saline accomplishes effectively 1, 3

Physiologic Considerations

Normal saline serves multiple therapeutic goals in DKA management: 1

• Corrects severe dehydration from osmotic diuresis caused by hyperglycemia 1
• Improves tissue perfusion and glomerular filtration rate, essential for clearing ketones 1
• Allows safe potassium replacement once adequate urine output confirms renal function (20-30 mEq/L potassium should be added after initial resuscitation) 1, 3

Transition to Hypotonic Fluids

After initial hemodynamic stabilization with normal saline, the American Diabetes Association recommends transitioning to 0.45% NaCl at 4-14 ml/kg/h if corrected serum sodium is normal or elevated, continuing 0.9% NaCl only if corrected sodium remains low. 1, 2 This prevents hypernatremia as glucose levels decline and free water deficits become more apparent.

Emerging Evidence on Balanced Crystalloids

Recent high-quality research challenges the traditional normal saline approach, showing balanced crystalloid solutions may be superior: 4, 5, 6

• A 2025 retrospective cohort study found balanced fluids resulted in faster DKA resolution (13 vs 17 hours, P=0.02) compared to normal saline 4
• A 2024 meta-analysis of 1,006 patients demonstrated balanced electrolyte solutions resolved DKA 5.36 hours faster than normal saline (95% CI: -10.46 to -0.26 hours) 5
• The SALT-ED/SMART trials subgroup analysis (172 DKA patients) showed balanced crystalloids achieved faster DKA resolution (median 13.0 vs 16.9 hours, aHR=1.68, P=0.004) and shorter insulin infusion duration (9.8 vs 13.4 hours, aHR=1.45, P=0.03) 6

Mechanism of Balanced Crystalloid Advantage

Balanced solutions avoid the hyperchloremic metabolic acidosis caused by large-volume normal saline administration: 7, 5, 6

• Post-resuscitation chloride levels were 4.26 mmol/L lower with balanced solutions 5
• Post-resuscitation bicarbonate levels were 1.82 mmol/L higher with balanced solutions 5
• Normal saline's acidic properties may delay resolution of the underlying ketoacidosis 7

Critical Safety Considerations

Common pitfalls to avoid during fluid resuscitation: 1, 2

• Never use hypotonic fluids initially in severely dehydrated patients—this risks cerebral edema from rapid osmotic shifts 1
• Correct serum sodium for hyperglycemia before selecting subsequent fluids (add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose above 100 mg/dL) 1
• Limit osmolality change to <3 mOsm/kg/h to prevent neurological complications 2, 8
• Delay insulin until potassium ≥3.3 mEq/L to avoid life-threatening arrhythmias, as insulin drives potassium intracellularly 3
• Exercise caution in cardiac or renal compromise—slower fluid rates may be necessary to prevent volume overload 2

Practical Algorithm

For adult DKA patients without cardiac compromise: 1, 2

1. Hour 1: Isotonic saline (0.9% NaCl) at 15-20 ml/kg/h 1
2. After initial resuscitation: Calculate corrected sodium 1
   • If corrected sodium normal/elevated: Switch to 0.45% NaCl at 4-14 ml/kg/h 1
   • If corrected sodium low: Continue 0.9% NaCl at 4-14 ml/kg/h 1
3. Once urine output established: Add 20-30 mEq/L potassium (2/3 KCl, 1/3 KPO4) to fluids 1, 3
4. Consider balanced crystalloids (Ringer's lactate or Plasma-Lyte) instead of normal saline for initial resuscitation based on recent evidence showing faster DKA resolution 4, 5, 6

Pediatric Modifications

In patients under 20 years, initial isotonic saline should be 10-20 ml/kg/h for the first hour, with total reexpansion not exceeding 50 ml/kg over the first 4 hours to reduce cerebral edema risk. 2