24 (95% CI = 0.10 to 0.59; P = 0.003) (Figure (Figure2A2A).Figure license with Pfizer 2Kaplan-Meier curves for hyperchloraemic acidosis. Hyperchloraemic acidosis was defined as the association of hyperchloraemia (>108 mmol/L) with strong ion difference (SID) (<40 mmol/L). SID = (Na + K + Ca + Mg) - (Cl + lactate). Na; sodium, ...In the FAS analysis, 18 patients (90%) in the saline group and 10 patients (50%) in the balanced group had hyperchloraemic acidosis within the first 48 hours (P = 0.01). The Kaplan-Meier estimators at hour 48 were 90% (range = 73% to 98%) in the saline group and 50% (range = 31% to 72%) in the balanced group, with a HR for hyperchloraemic acidosis in the balanced group of 0.28 (95% CI = 0.11 to 0.70; P = 0.006) (Figure (Figure2B).2B). Two sensitivity analyses did not change the results.

The HR for hyperchloraemic acidosis in the balanced group was 0.18 (95% CI = 0.06 to 0.55; P = 0.002) when the patients with acidosis prior to inclusion were excluded, and it was 0.25 (95% CI = 0.09 to 0.69; P = 0.008) with a censorship of the biological values (SID, chloraemia) prior to inclusion. In the subgroup of TBI patients, the HR for hyperchloraemic acidosis in the balanced group was 0.30 (95% CI = 0.12 to 0.80; P = 0.015) (Figure (Figure2C2C).Secondary efficacy outcomesThe pH was lower in the saline group than in the balanced group (mean difference = -0.03 (-0.05 to -0.01); P = 0.004) (Figure (Figure3A).3A). Patients in the saline group had a lower SID than the balanced group (mean difference = -1.55 mEq/L (-3.09 to -0.02); P = 0.047) (Figure (Figure3B).3B).

Chloraemia was higher in the saline group than in the balanced group (mean difference = 4.8 mmol/L (1.9 to 7.6); P = 0.002) (Figure (Figure3C).3C). Compared with the balanced group, patients in the saline group had lower phosphataemia (mean difference = -0.12 mmol/L [-0.21 to -0.04); P = 0.008) (Figure (Figure3D).3D). From hour 0 to hour 48, albuminaemia and partial pressure of carbon dioxide in arterial blood (PaCO2) were not altered in the saline group compared with the balanced group (Figures (Figures3E3E and and3F).3F). The reported differences in the acid-base status between groups were not significantly modified in the subgroup of TBI patients (Additional file, Figure S1). The results for base excess, effective SID, simplified anion gap and corrected anion gap are provided in the Additional file, Table S2.

The blood osmolarity was higher in the saline group than in the balanced group (mean difference Anacetrapib = 7 mOsmol/L (1 to 14); P = 0.024) (Figure (Figure4A).4A). The natraemia levels were higher in the saline group than in the balanced group (mean difference = 2 mmol/L (0 to 4); P = 0.036) (Figure (Figure4B).4B). ICP was not altered in the study group (mean difference = 4 mmHg (-1 to 8); P = 0.088) (Figure (Figure4C).4C).