Among the entire population, seven patients (35%) in the saline group and eight patients (40%) in the balanced group developed ICH (P = 0.744) (Table (Table4).4). In the subgroup of patients who developed ICH, ICP was not altered by study group (mean difference = -4 mmHg (-11 to 2); P = 0.20). (Additional file, Figure S3).Figure 3Time protein inhibitors course of acid-base status in the saline group and the balanced group. 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) ...Figure 4Time course of (A) blood osmolarity, (B) natraemia and (C) intracranial pressure in the saline group and the balanced group. Results are given as medians (IQR). *P < 0.05 versus saline group (significant group effect).

Table 4Safety assessmentaSafety assessmentSafety outcomes were assessed for the ITT patient population (Table (Table4).4). Decompressive craniectomy was performed before ICU admission in one patient (5%) in the balanced group compared with one patient (5%) in the saline group (P = 0.972) (Table (Table4).4). Three patients (14%) in the saline group died (two with ICH (10%) and one due to care withdrawal (5%)), compared with five patients (25%) in the balanced group (two patients with ICH (10%) and three patients due to care withdrawal (15%)) (P = 0.387). No patients died during the study periodThere is no need to provide this information since it is stated that 3 patients died in the saline group and five in the other group.

DiscussionThe present study shows that balanced solutions, in comparison with isotonic saline solutions, reduced the occurrence of hyperchloraemic acidosis in brain-injured patients. Balanced solutions were not associated with ICP alteration or ICH episodes.According to Stewart et al., hydrogen ion concentration (pH) is independently influenced by three biological variables: (1) PaCO2, (2) total weak acid concentration (labelled Atot) composed of phosphate and albumin and (3) SID corresponding to the difference between strong cations and strong anions [22]. According to Stewart et al.’s concept, sodium chloride solutions are responsible for metabolic acidosis through a decrease in SID [23-25]. Thus, administration of drugs with sodium chloride excipient (such as cloxacillin, midazolam or fentanyl) participate in the decrease in SID, which could partially explain the 50% rate of hyperchloraemic acidosis in the balanced group.

The concentration of chloride in 0.9% saline solutions surpasses the normal ranges for blood chloraemia [26]. A correlation between hyperchloraemia and base excess has been described in patients undergoing major surgery [16]. Balanced solutions reduce the risk Cilengitide of hyperchloraemic acidosis in elderly patients undergoing major surgery [27,28].