Isotonic Sodium Bicarbonate Preparation in the Bicarb ICU 2 Trial
Standard Preparation Method
The Bicarb ICU 2 trial used 1.4% sodium bicarbonate solution, which was prepared by diluting standard 8.4% sodium bicarbonate injection to achieve an isotonic formulation suitable for intravenous hydration. 1
The specific preparation involved:
- Starting material: 8.4% (1 mEq/mL) sodium bicarbonate injection from standard 50 mL vials 2
- Final concentration: 1.4% sodium bicarbonate solution 1
- Dilution ratio: This represents a 1:6 dilution of the 8.4% stock solution (8.4% ÷ 6 = 1.4%)
Administration Protocol in the Trial
The isotonic bicarbonate solution was administered using the following protocol 1:
- Pre-contrast bolus: 3 mL/kg over 1 hour before contrast medium exposure
- Post-contrast maintenance: 1 mL/kg/hr for 6 hours after contrast exposure
- Route: Intravenous infusion
Verification of Isotonicity
The trial confirmed successful urinary alkalinization, with patients in the bicarbonate group achieving a significantly higher urinary pH (6.7 ± 2.1) compared to the saline group (6.2 ± 1.8, p < 0.0001), demonstrating that the bicarbonate was bioavailable and physiologically active 1.
Critical Preparation Considerations
Why Isotonic Formulation Matters
No commercially available isotonic bicarbonate solutions exist in the United States, requiring pharmacy compounding and creating substantial risk for preparation errors, including inadvertent administration of hypertonic solutions. 3
The KDIGO guidelines specifically warn about compounding errors with sodium bicarbonate administration because standard stock solutions (8.4%, 7.5%, and 4.2%) are all hypertonic 4, 2. The 8.4% solution has an osmolality of 2 mOsmol/mL, making it extremely hypertonic 2.
Alternative Isotonic Preparations
Other studies have used different dilution strategies 3:
- 4.2% concentration: Created by diluting 8.4% sodium bicarbonate 1:1 with sterile water or normal saline, commonly used for contrast-induced AKI prevention 3, 5
- 150 mEq/L solution: Prepared by adding 150 mEq of sodium bicarbonate to 1 liter of 5% dextrose, used for maintenance infusions in sodium channel blocker toxicity 3
Stability Data
When preparing isotonic bicarbonate solutions in advance 6:
- Refrigerated storage (2-4°C): Solutions of 50,100, and 150 mEq in sterile water or 5% dextrose remain stable for up to 7 days
- Room temperature (21-24°C): 50 mEq solutions stable for 48 hours; 100-150 mEq solutions stable for 30 hours
Blinding Capability
The 1.4% bicarbonate solution used in Bicarb ICU 2 allowed for successful double-blinding 1. Research demonstrates that when 100 mL of 8.4% sodium bicarbonate is diluted in 150 mL of 5% dextrose within a 250 mL polyolefin bag, clinicians cannot visually distinguish it from dextrose alone (60% correct identification, κ = 0.20, P = 0.12), confirming that isotonic bicarbonate preparations can be effectively blinded 7.
Clinical Context
The Bicarb ICU 2 trial specifically tested whether isotonic bicarbonate was superior to isotonic saline (0.9% sodium chloride) for preventing contrast-associated acute kidney injury in critically ill patients 1. The trial found no significant difference in outcomes between the two solutions, with contrast-associated AKI occurring in 35.1% of bicarbonate patients versus 33.3% of saline patients (p = 0.81) 1.