Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial

Abstract

Rationale: Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown.Objectives: To pilot a cluster-randomized, multiple-crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids.Methods: This was a cluster-randomized, multiple-crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringer's solution or PlasmaLyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction.Measurements and Main Results: Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500-3,377] vs. 1,617 ml [500-3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P , 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98).Conclusions: An electronic health record-embedded, clusterrandomized, multiple-crossover trial comparing saline with balanced crystalloids can produce well-balanced study groups and separation in crystalloid receipt.Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).

Fluid management in acute kidney injury

“…As a result, it is plausible that the dose of 0.9% saline administered in these studies was insufficient to cause clinically evident renal toxicity even if the potential for such toxicity exists. In the SALT study, among patients who received the largest volumes of crystalloid, there appeared to be more AKI in patients who received 0.9% saline [51]. However, systematic differences between patients that received high volumes of 0.9% saline compared with patients that received high volumes of buffered crystalloids cannot be excluded.…”

“…In the Saline vs. Plasma-Lyte 148 ® (a gluconate/acetate-buffered crystalloid) for ICU fluid Therapy (SPLIT) trial there were no significant between-group differences in serum creatinine levels, rates of AKI, or requirements for RRT [50]. Similarly, in the recent Balanced Crystalloids vs. Saline in the ICU trial [51] (the SALT trial) there were no between-group difference in serum urea or creatinine measures, major adverse kidney events (in-hospital mortality, receipt of new RRT or final inpatient serum creatinine of at least 200% of baseline) recorded up until 30 days post enrolment.…”

“…In the SPLIT trial [50] and the SALT trial [51] the volumes of crystalloid delivered to patients were small (median of 2 L and 1.5 L, respectively) and both study populations were dominated by low acuity patients. As a result, it is plausible that the dose of 0.9% saline administered in these studies was insufficient to cause clinically evident renal toxicity even if the potential for such toxicity exists.…”

“…Low-quality data raise the possibility that buffered crystalloids may be associated with a lower AKI risk than 0.9% saline in some settings, and preliminary data suggest that the buffered crystalloids lactated Ringer's and Plasma-Lyte 148 ® can be used safely in the critically ill [50,51]. There are no data comparing different buffered crystalloids in patients with AKI or evaluating whether or not the choice of buffered crystalloid affects the risk of AKI developing.…”

Prävention der akuten Nierenschädigung beim kritisch kranken Patienten

“…Bei der Verabreichung einer isotonen Kochsalzlösung (NaCl 0,9 %) besteht das Risiko einer hyperchlorämischen Acidose sowie einer renalen Vasokonstriktion mit Abfall der glomerulären Filtrationsrate (GFR). Bei Verabreichung größerer Mengen von NaCl (>2000-2500 ml) steigt das Risiko für die Induktion einer AKI [72]. "Balancierte" Lösungen zeigen diesbezüglich ein deutlich geringeres Risikoprofil und sollten daher bei größeren Infusionsmengen bevorzugt werden [34].…”