By Kathryn Radigan, MD
Attending Physician, Division of Pulmonary and Critical Care, Stroger Hospital of Cook County, Chicago; Assistant
Professor of Medicine, Rush University Medical Center
Dr. Radigan reports no financial relationships relevant to this field of study.
SYNOPSIS: The use of a buffered crystalloid compared with saline did not reduce the risk of acute kidney injury (AKI) in patients receiving crystalloid fluid therapy in the ICU.
SOURCE: Young P et al. Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit. JAMA 2015;314:1701-1710.
The use of saline (0.9% sodium chloride) in critically ill patients is a common intervention to increase intravascular volume or maintain hydration. Although the use of saline in the critically ill is widespread, there is concern that the high chloride content of saline contributes to the development of acute kidney injury (AKI), and its use may be associated with an increased risk of mortality. It is unclear whether a buffered crystalloid solution with an electrolyte composition that more closely resembles plasma would lead to better outcomes.
Since the relationship between the use of saline in critically ill patients and renal failure is unclear, Young et al pursued a double-blind, cluster randomized, double-crossover trial from April 2014 through October 2014 to determine the effect of a buffered crystalloid compared with saline on renal complications in ICU patients. The trial took place in four New Zealand ICUs and included all patients admitted to the ICU who required crystalloid fluid therapy. The trial excluded patients with established AKI requiring renal replacement therapy (RRT) or expected to require RRT within 6 hours. Most patients were admitted to the ICU following elective surgery, most commonly cardiovascular surgery, and few had comorbidities. Of the 2278 eligible patients enrolled in the study, researchers analyzed 1152 of the 1162 patients (99.1%) receiving buffered crystalloid and 1110 of the 1116 patients (99.5%) receiving saline. Researchers randomized two of four ICUs to saline intervention and the other two to buffered crystalloid for alternating treatment blocks of 7 weeks. Two crossovers occurred so that each ICU used one of two study fluids twice over the 28-week period. The treating physician determined the rate and frequency of fluid administration. The primary outcome was proportion of patients with AKI (defined as a rise in serum creatinine level of at least two-fold or a serum creatinine level of ≥ 3.96 mg/dL with an increase of ≥ 0.5 mg/dL). The incidence of RRT and in-hospital mortality were the main secondary outcomes.
For the patients who received buffered crystalloid, 102 developed AKI compared with 94 in the saline group (absolute difference [AD], 0.4%; 95% confidence interval [CI], -2.1% to 2.9%; relative risk [RR], 1.04; 95% CI, 0.80-1.36; P = 0.77). Similarly, for patients who received buffered crystalloid, RRT was required in 38 (3.3%) compared with 38 (3.4%) in the saline group (AD, -0.1%; 95% CI, -1.6% to 1.4%; RR, 0.96; 95% CI, 0.62-1.50; P = 0.91). Additionally, there was no difference in mortality between the buffered crystalloid and saline groups (7.6% vs 8.6%; AD, -1.0%; 95% CI, -3.3% to 1.2%; RR, 0.88; 95% CI, 0.67-1.17; P = 0.40). In summary, for patients who received crystalloid fluid therapy in the ICU, the use of a buffered crystalloid compared with saline did not reduce the risk of AKI, RRT, or in-hospital mortality.
The administration of IV fluids for hydration and resuscitation is common in critically ill patients. Many different types of IV fluid, including normal saline, contain supraphysiological concentrations of chloride. Excessive chloride administration is associated with hyperchloremic metabolic acidosis and may lead to renal vasoconstriction along with a reduced GFR.1
Since renal failure in the ICU is associated with increased hospital mortality,2 there has been substantial interest in examining the relationship between the high chloride content of saline and the development of AKI. In a single-center, open-label study of chloride-rich (n = 760) vs chloride-restrictive (n = 773) fluids in the ICU, Yunos et al found that implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT. Unfortunately, physicians should interpret cautiously the outcomes of this trial, as one of the alternative IV fluids used was a synthetic gelatin-based colloid that has been associated with increased risk of AKI in patients with sepsis.1 Other recently conducted studies, including a retrospective study and a meta-analysis, favored balanced fluids, but results were tempered in light of the innate design of the trials.3,4 In light of the remaining question, it was expected that this double-blind, cluster randomized, double-crossover trial might finally achieve some clarity on the subject.
Unfortunately, the trial revealed that there was no difference in AKI and mortality between patients who received 0.9% saline vs buffered crystalloid. Although results of the trial appeared to be definitive, there were aspects of the trial design worth noting. First, 90% of patients received fluids prior to admission to the ICU; the majority of this IV fluid was buffered crystalloid with 1.2 L administered to the buffered crystalloid group and 1 L of buffered crystalloid administered to the saline group. Although 1 L of fluid does not appear to be significant, the average fluid administration between groups over the entire study period was only 2 L. This low volume of fluid may be insufficient to demonstrate a hazard, especially in study groups that are lower risk and may not be representative of a typical ICU patient population since the majority of patients were surgical. Second, the design of the trial may require more consideration. Although this trial anticipated examining the effect of IV fluids on AKI, RRT, and mortality, the design of the study was not based on this particular intervention. For instance, the treating physician determined the rate and frequency of fluid administration, but the reason for the fluid administration was unknown. Therefore, the effectiveness of the fluid provided for each indication could not be measured, and researchers measured the overall adverse events instead.
Although this study fails to reveal an ideal fluid management strategy for our high-risk, severely septic patients who will need aggressive fluid administration, it does emphasize that neither 0.9% saline nor a low-chloride electrolyte IV fluid is particularly hazardous in a lower-risk patient population receiving on average 2 L of fluid. Until further studies examine a higher-risk patient population, there is insufficient evidence to support the use of one type of IV crystalloid fluid vs another. Therefore, it is our responsibility to continue to be thoughtful regarding the administration of fluids in our patients on a case-by-case basis.
- Yunos NM, et al. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 2012;308:1566-1572.
- Hoste EA, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Crit Care 2006;10:R73.
- Raghunathan K, et al. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med 2014;42:1585-1591.
- Krajewski ML, et al. Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation. Br J Surg 2015;102:24-36.