What are the recent trials supporting the use of balanced crystalloids, such as Ringer's (lactated Ringer's solution), for fluid resuscitation in adult patients with diabetic ketoacidosis (DKA)?

Balanced Crystalloids for Diabetic Ketoacidosis: Recent Trial Evidence

Balanced crystalloids (lactated Ringer's or Plasma-Lyte) should replace normal saline as the first-line fluid for DKA resuscitation, as they resolve DKA approximately 5 hours faster and reduce insulin infusion duration without safety concerns.

Landmark Randomized Trial Evidence

The strongest evidence comes from a 2020 subgroup analysis of two large cluster-randomized trials (SALT-ED and SMART) that directly compared balanced crystalloids versus saline in 172 adults with DKA 1. This analysis demonstrated:

• Time to DKA resolution was significantly shorter with balanced crystalloids (median 13.0 hours) versus saline (median 16.9 hours), with an adjusted hazard ratio of 1.68 (95% CI: 1.18-2.38, P=0.004) 1
• Insulin infusion duration was reduced in the balanced crystalloids group (median 9.8 hours) compared to saline (median 13.4 hours), with adjusted HR 1.45 (95% CI: 1.03-2.03, P=0.03) 1
• Patients received substantial fluid volumes (median 4,478 mL), making these findings clinically relevant for typical DKA management 1

Supporting Real-World Implementation Studies

Multiple recent observational studies confirm these trial findings in routine clinical practice:

• A 2024 protocol change study (246 patients) showed time to DKA resolution decreased from 20.6 hours with NS to 17.1 hours with lactated Ringer's (P=0.02), with insulin drip duration reduced from 21.4 to 16.0 hours (P<0.001) 2
• A 2025 retrospective cohort (110 patients) demonstrated faster DKA resolution with balanced fluids (13 hours) versus NS (17 hours, P=0.02), with NS independently associated with longer resolution time even after adjusting for baseline bicarbonate and AKI 3

Meta-Analysis Confirmation

A 2024 systematic review and meta-analysis of 10 studies (1,006 participants) provides the most comprehensive evidence synthesis 4:

• Mean difference in time to DKA resolution: -5.36 hours (95% CI: -10.46 to -0.26) favoring balanced crystalloids 4
• Post-resuscitation chloride levels were 4.26 mmol/L lower and bicarbonate levels were 1.82 mmol/L higher with balanced solutions 4
• No significant difference in mortality (OR: 0.67,95% CI: 0.12-3.68) or insulin infusion duration, though individual studies showed benefits 4

Mechanistic Rationale from Guidelines

The physiological superiority of balanced crystalloids is well-established in current guidelines:

• Normal saline causes hyperchloremic metabolic acidosis due to supraphysiologic chloride concentration (154 mmol/L), which worsens the existing acidosis in DKA and delays resolution 5
• Balanced crystalloids avoid chloride-induced renal vasoconstriction and reduce major adverse kidney events compared to saline in critically ill patients 5
• Large volume saline administration (typical in DKA) is associated with increased mortality and renal complications across multiple clinical contexts 5

Critical Contraindication to Remember

• Avoid lactated Ringer's in patients with severe traumatic brain injury or head trauma due to its slightly hypotonic nature (osmolarity 273-277 mOsm/L), which can worsen cerebral edema 6, 7
• In DKA patients with concurrent severe TBI, use 0.9% saline as the isotonic crystalloid of choice 6

Practical Implementation Algorithm

For adult DKA patients presenting to the emergency department:

• First-line fluid choice: Lactated Ringer's or Plasma-Lyte for initial resuscitation and maintenance 1, 3
• Avoid normal saline unless lactated Ringer's is contraindicated (severe TBI, rhabdomyolysis/crush syndrome) 6, 5
• Expected benefit: Approximately 4-5 hours faster DKA resolution and 3-5 hours shorter insulin infusion duration 1, 2, 4
• The potassium content in lactated Ringer's (4 mmol/L) should not be considered a contraindication even in patients with mild-to-moderate hyperkalemia, as it approximates normal plasma concentration 6

Common Pitfalls to Avoid

• Do not default to normal saline based on outdated guidelines that predate the 2018-2020 trial evidence demonstrating balanced crystalloid superiority 5, 1
• Do not limit balanced crystalloid use due to concerns about potassium content in typical DKA patients, as large trials involving 30,000 patients showed comparable plasma potassium between groups 6
• Do not assume adding potassium to normal saline eliminates its disadvantages, as the hyperchloremic acidosis from high chloride load remains problematic 5