Buffered Crystalloid Fluid versus Saline in the ICU: What It means for AKI Risk

Among patients in the intensive care unit (ICU) receiving crystalloid fluid therapy, there was no association between use of a buffered crystalloid compared with saline and risk of acute kidney injury (AKI). That was the primary finding of a double-blind, cluster randomized, double-crossover trial conducted recently by Paul Young, FCICM, and colleagues. The researchers reported results online in JAMA [doi:10.1001/jama.2015.12334].

Administering fluid to increase intravascular volume or maintain hydration to patients in the ICU is a frequent intervention used in that setting. However, according to the researchers, the choice of fluid remains controversial. The most commonly used resuscitation fluid worldwide is 0.9% sodium chloride (saline), but emerging data suggest question the safety of saline in critically ill patients.

Much of the concern regarding saline safety centers on the hypothesis that the high chloride content of saline may contribute to the risk of AKI. A possible alternative has been use of a buffered crystalloid solution with an electrolyte composition more closely resembling plasma.

There have been observational data suggesting that, compared with saline, there may be an association between the use of buffered crystalloids and reductions in the risk of AKI and of death. However, to date, there have been no randomized trials assessing that association in a broad range of patients. The current study was designed to identify the comparative effectiveness of a buffered crystalloid and saline for crystalloid-based fluid therapy in a heterogeneous population of patients treated in the ICU. The researchers sought to determine the effect of specific fluid type on the development of AKI in this patient population.

The study was conducted in four ICUs (three general medical and one surgical) in New Zealand from April 2014 through October 2014. One of the study ICUs had a predominance of cardiothoracic and vascular surgical patients. All patients admitted to the study ICUs were eligible for inclusion. Exclusion criteria included established AKI requiring renal replacement therapy (RRT).

All eligible 2278 patients were enrolled in the study. Of those, 1152 of 1162 (99.1%) who received buffered crystalloid and 1110 of 1116 (99.5%) who received saline were included in the analysis. The study participants were assigned a masked study fluid (either saline or a buffered crystalloid) for alternating 7-week treatment blocks. Two of the ICUs began using one fluid and the others began using the alternative. Two crossovers occurred during the study period, so that each ICU used each fluid twice over the 28-week study period. The treating clinician determined the rate and frequency of fluid administration.

The primary study outcome was the proportion of patients with AKI. The researchers defined AKI as a rise in serum creatinine level of at least 2-fold or a serum creatinine level of ≥3.96 mg/dL with an increase of ≥0.5 mg/dL. Secondary outcomes included incidence of RRT use and in-hospital mortality.

Baseline characteristics were similar in the two groups. Mean age of participants was 60 years and approximately 66% were men. Most were admitted to the ICU following elective surgery (most commonly cardiovascular surgery) and “relatively few” had comorbidities. The mean APACHE II (Acute Physiology and Chronic Health Evaluation) illness severity scores were 14.1 in the buffered crystalloid group and 14.1 in the saline group. The two groups received similar volumes of study fluid (median 2000 mL for buffered crystalloid vs 2000 mL for saline). Most fluid was administered in the first day in the ICU.

In the buffered crystalloid group, 9.6% (n=102/1067) developed AKI within 90 days after enrollment compared with 9.2% (n=94/1025) in the saline group, for an absolute difference of 0.4% (95% confidence interval [CI], -2.1% to 2.9%), and a relative risk of 1.04 (95% CI, 0.80 to 1.36).

There was no significant difference in the probability of requiring RRT between the two groups 90 days after enrollment. However, there was a significant interaction between the effect of treatment on AKI and study site. There was no significant heterogeneity in the effect of treatment on AKI or failure in any of the predefined subgroups.

RRT was required in 38 of 1152 patients (3.3%) in the buffered crystalloid group versus in 38 of 1110 patients (3.4%) in the saline group, for an absolute difference of -0.1% (95% CI, -1.6% to 1.4%) and relative risk of 0.96 (95% CI, 0.62 to 1.50). The indications for RRT initiation were similar between the groups and there was no significant between-group difference in the rates of death in the ICU or in the hospital or in the cause-specific mortality within the 90-day follow-up period.

Overall, 7.6% (n=82/1152) of the patients in the buffered crystalloid group and 8.6% (n=95/1110) of those in the saline group died in the hospital, for an absolute difference of -1.0% (95% CI, -3.3% to 1.2%, and relative risk of 0.88 (95% CI, 0.67 to 1.17). There was no significant difference in the probability of survival between the two groups.

Not performing sample size calculations was cited by the authors as the most important study limitation. Other limitations cited were more than 90% of patients were exposed to intravenous fluids prior to enrollment and the majority of pre-enrollment fluid was buffered crystalloid, and due to studying a heterogeneous population with an overall low incidence of AKI, the findings do not preclude the possibility of significant benefits to using buffered crystalloids in groups with higher risk.

“Among patients receiving crystalloid fluid therapy in the ICU, use of a buffered crystalloid compared with saline did not reduce the risk of AKI. Further large randomized clinical trials are needed to assess efficacy in higher-risk populations and to measure clinical outcomes such as mortality,” the researchers said.

Takeaway Points

  1. Saline is commonly administered in the intensive care unit (ICU), but observational studies have suggested an association between saline use and acute kidney injury and increased risk for death.
  2. Researchers conducted a study at four centers to compare the effect of a buffered crystalloid with saline on renal complications in patients admitted to the ICU.
  3. Compared with saline, the use of a buffered crystalloid fluid did not reduce the risk of AKI and there was no significant difference in requiring renal replacement therapy or in the rates of death between the two groups.