Shock Syndromes I

iii.

A large, double-blind, cluster randomized, double-crossover trial, the SPLIT trial, allocated

four ICUs in New Zealand to either 0.9% sodium chloride (n=1025) or a balanced crystalloid

solution (Plasma-Lyte; n=1067) for all patients requiring crystalloid fluid therapy. Two

crossovers occurred with 7-week intervals such that each ICU used each fluid twice during

the 28-week study. A total of 2278 patients were enrolled, with 2092 patients having data

available for analysis of the primary outcome of the incidence of acute kidney injury within

90 days. The balanced crystalloid solution group had no lower risk of acute kidney injury than

did the 0.9% sodium chloride group (9.6% vs. 9.2%, relative risk [RR] 1.04; 95% CI, 0.80–1.36;

p=0.77). There was also no difference between groups in the use of renal replacement therapy

(relative risk [RR] 0.96; 95% CI, 0.62–1.50; p=0.91) or hospital mortality (RR 0.88; 95% CI,

0.67–1.17; p=0.40). Of note, this study included all fluid use (not just resuscitation fluids) as

well as a primarily surgical population with a relatively low severity of patient illness and

patients who received relatively low volumes of fluid overall (2 L in each group).

iv.

The Isotonic Solutions and Major Adverse Renal Events Trial (SMART) was a large, cluster-

randomized, multiple-crossover, single-center trial, in which balanced crystalloids (lactated

Ringer’s solution or Plasma-Lyte A; n=7942) were compared with 0.9% sodium chloride

(n=7860). The median volume of fluid received in the balanced crystalloid group was 1000

mL (interquartile range [IQR] 0–3210) and 1020 mL in the 0.9% sodium chloride group (IQR

0–3500). Patients in the balanced crystalloids group had a significantly lower incidence of

a major adverse kidney event (14.3% vs. 15.4%; OR 0.90; 95% CI, 0.82–0.99; p=0.04). In-

hospital mortality was not significantly different between groups (10.3% vs. 11.1%, p=0.06). Of

note, in a prespecified subgroup analysis, there was a greater difference in the primary outcome

favoring patients who received smaller volumes of intravenous fluids; thus, the differences

between fluid types are likely magnified and more significant in patients who receive larger

volumes of intravenous fluids.

The BaSICS study was a double-blind, randomized controlled trial that compared Plasma-Lyte

148 with 0.9% sodium chloride in ICU patients requiring fluid expansion. The intervention

included all fluids over 100 mL administered for fluid challenges, maintenance fluids, and

drug infusions. Over 10,000 patients were included in this study. There was no difference in

the primary outcome of 90-day survival (26.4% balanced solution vs. 27.2% saline; HR 0.97;

95% CI, 0.90–1.05). Of note, this study did not evaluate fluids specifically for resuscitation;

rather, it evaluated any fluid volume over 100 mL.

vi.

The Plasma-Lyte 148 versus Saline (PLUS) Study randomized 2037 critically ill patients from

centers cross Australia and New Zealand to receipt of either Plasma-Lyte 148 or 0.9% sodium

chloride as primary fluid therapy in the ICU for 90 days. No difference was detected in the

primary outcome of death from any cause within 90 days (21.8% vs. 22.0%, absolute difference

−0.15; 95% CI, −3.60 to 3.30). Additionally, no difference in acute kidney development or new

renal replacement therapy need was detected. Similar to the aforementioned trials, the PLUS

study included all fluid use, and the intervention was not limited to resuscitation fluids.

vii.

A meta-analysis of 13 randomized controlled trials (n=35,884) compared the use of balanced

crystalloids with 0.9% sodium chloride and found no difference in the primary outcome of

90-day mortality (RR 0.96; 95% CI, 0.91−1.01). The Bayesian analysis determined an 89.5%

probability that balanced crystalloid solutions were associated with lower mortality compared

with 0.9% sodium chloride.