Balanced Crystalloids versus Saline in Critically Ill Adults

Abstract

BACKGROUND Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. METHODS In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P = 0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P = 0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P = 0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P = 0.60). CONCLUSIONS Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779.)

Balanced Crystalloid Solution Versus Normal Saline on Biochemical Outcomes in Acute Medical and Surgical Patients

“…Nevertheless, our results strengthen the suspicion that there is no discernible difference in the use of NS compared to CSL infusions in outcomes relevant to kidney function, in non-critically ill patients. It is also worthy to note that our study represents the first Australian based cohort study in this field, extending the generalisability of the large-scale trial results demonstrated in the United States [8,10].…”

“…NS infusions have been associated with greater chloride administration and high rates of resultant renal dysfunction in some cases [1,11]. On the contrary, recent evidences in both the critical and noncritical care setting (with both small and large volume infusions), have suggested that there is no significant difference in severe AKI rates when comparing NS to a balanced crystalloid solution [2,7,8,10]. Our data add to the literature investigating the effects of intravenous infusions on AKI incidence.…”

Surviving sepsis campaign: research priorities for sepsis and septic shock

“…While balanced crystalloids did not change the primary outcome of hospital free days in non-critically ill patients, they were associated with a statistically significant 0.9% decrease in the composite outcomes of major adverse kidney events seen in critically ill patients. Although a subgroup analysis showed a larger decrease (5.1%) in composite outcome in septic patients given balanced crystalloids, it is important to note that patients with sepsis or septic shock represented less than 15% of the ICU patients in this study [70]. Further, the percent of septic patients was not reported in the study on non-critically ill patients [71].…”

“…As such, the relevance of this study to septic patients is unclear. Recently, two large randomized controlled trials compared balanced crystalloids to 0.9% normal saline in 15,802 critically ill patients from 5 ICUs and 13,347 non-critically ill emergency department patients who were subsequently hospitalized outside of the ICU [70,71]. In critically ill patients, balanced crystalloids resulted in a statistically significant 1.1% decrease in the composite outcome of death from any cause, new renal-replacement therapy or persistent renal dysfunction.…”

Endpoints for Clinical Trials of Acute Kidney Injury

“…1b). These major adverse kidney events (MAKE), assessed at 30, 60, 90, or even 180 days have been utilized as primary endpoints in several recent clinical trials [14][15][16]. However, some caution must be employed when using the MAKE endpoint.…”