Buffered Crystalloids: Indications and Dosing
Buffered (balanced) crystalloid solutions should be used as the first-line intravenous fluid for critically ill adults, including those with sepsis, septic shock, hemorrhagic shock, and perioperative patients, to reduce mortality and adverse renal events compared to 0.9% saline. 1, 2
Primary Indications
Sepsis and Septic Shock
Use balanced crystalloids preferentially over 0.9% saline for fluid resuscitation in sepsis and septic shock. 1 The SMART study demonstrated that balanced crystalloids reduced major adverse kidney events (MAKE30: composite of death, new renal replacement therapy, or persistent doubling of baseline creatinine) with an odds ratio of 0.80 (95% CI 0.67-0.94) in 2,336 sepsis patients 1. In-hospital mortality showed a trend toward reduction (OR 0.80,95% CI 0.67-0.97) 1. The benefit was most pronounced when balanced crystalloids were initiated in the emergency department rather than after ICU admission 1.
Hemorrhagic Shock
Balanced crystalloids are recommended over 0.9% saline as first-line fluid therapy in hemorrhagic shock, particularly when high volumes (>5000 mL) are anticipated. 1 While no randomized trials have specifically studied hemorrhagic shock, large observational studies demonstrate increased mortality with high-volume chloride-rich solutions 1. Balanced solutions consistently maintain better acid-base balance and may reduce perioperative blood transfusion requirements 1.
Perioperative Setting
Buffered crystalloid solutions are strongly recommended over 0.9% saline for perioperative fluid management. 2 The evidence is particularly compelling when moderate to large fluid volumes are administered. Two recent large trials showed no difference in outcomes, but patients received only small volumes (median 1,900 mL), limiting their applicability 2.
Kidney Transplantation
Balanced crystalloids are strongly recommended over 0.9% saline in kidney transplantation. 2, 3 The BEST-Fluids trial demonstrated that balanced crystalloids reduced delayed graft function from 40% to 30% (adjusted relative risk 0.74,95% CI 0.66-0.84, p<0.0001) 3. This represents an absolute risk reduction of 10.1% 3.
Specific Balanced Solutions
The following solutions are appropriate:
- Lactated Ringer's solution
- Plasma-Lyte A/148
- Ringer's acetate
No outcome-based preference exists between different buffer types (lactate, acetate, malate) 4. The key distinction is the lower chloride content (approximately 98-110 mEq/L) compared to saline's 154 mEq/L.
Dosing Considerations
Volume Administration
- No specific volume limits distinguish balanced crystalloids from saline in terms of safety
- The benefit of balanced crystalloids appears dose-dependent: greater advantages emerge with larger volumes (>5000 mL) 1
- In the SMART trial, median volumes were only 1,000 mL in trauma patients, which may have underestimated the benefit 1
Timing
- Administer from initial resuscitation through 48 hours post-intervention (as demonstrated in kidney transplant studies) 3
- Earlier initiation (emergency department vs. ICU) provides greater mortality benefit 1
Clinical Outcomes
Mortality
A 2022 systematic review of critically ill adults showed balanced crystalloids reduced mortality with a risk ratio of 0.96 (95% CI 0.91-1.01), with an 89.5% posterior probability of mortality reduction 5. The effect ranges from a 9% relative reduction to a 1% relative increase in death risk 5.
Renal Outcomes
- Reduced acute kidney injury in adult ICU patients 6
- Lower MAKE30 composite outcomes in critically ill adults 7
- No consistent difference in new renal replacement therapy requirements across all populations 5
Metabolic Effects
Balanced crystalloids consistently prevent hyperchloremic metabolic acidosis compared to saline 2, 8. This effect occurs even with relatively small volumes in healthy volunteers 8.
Common Pitfalls
- Assuming small volumes don't matter: Even modest volumes (1-2 L) can cause measurable metabolic acidosis with saline 8
- Delaying the switch: Benefits are greatest when balanced crystalloids are used from initial resuscitation 1
- Using saline "by default": The evidence now supports balanced crystalloids as the default choice, with saline requiring justification 1, 2
Contraindications and Cautions
- Traumatic brain injury: The evidence base is less robust; some clinicians prefer saline due to theoretical concerns about lactate metabolism, though this is not definitively established
- Severe hyperkalemia: Balanced solutions contain 4-5 mEq/L potassium; use saline if serum potassium is critically elevated
- Severe metabolic alkalosis: The buffering capacity may worsen alkalosis in rare cases