EudraCT 2008-004153-15 andNCT00847977The work in this trial was performed at Nantes University Hospital in Nantes, France.IntroductionBrain injuries remain a 17-AAG major concern for public health services, particularly because of the high mortality rate and long-term disabilities that result [1]. In the early stages of caring for brain-injured patients, therapies are focused on minimising secondary brain injuries that are centrally involved in determining outcomes [2]. Intracranial hypertension (ICH) is the most frequent cause of death and secondary brain insults after brain injury [3]. The maintenance of adequate cerebral perfusion pressure (CPP), which is associated with control of intracranial pressure (ICP), is the cornerstone of treating the ion deficit associated with brain ischaemia in brain-injured patients.

Infusion of hypo-osmotic solutions, which increases cerebral swelling, should be avoided after brain injury [4,5]. Current recommendations are to use isotonic solutions in patients with severe brain injury [6,7], with isotonic sodium chloride (0.9% saline solution) being the mainstay of therapy. Isotonic sodium chloride solutions induce hyperchloraemic metabolic acidosis and have side effects including haemostatic alterations, cognitive dysfunction and ileus [8].Hyperchloraemia is relatively common in critically ill patients, and it is now commonly accepted that chloride-rich fluids are the primary cause of hyperchloraemic acidosis in critically ill patients [9].

In a before-after study, a chloride-restrictive strategy was associated with a significant decrease in renal failure in critically patients and significantly affected electrolyte and acid-base status [10]. In a post hoc analysis of a retrospective study in TBI patients receiving isotonic sodium chloride solutions for basal infusion [11], 65% of the patients experienced hyperchloraemia. Chloride channels regulate cell oedema [12], and it could be hypothesised that dyschloraemia contributes Drug_discovery to brain swelling.Isotonic balanced solutions are now available and include crystalloids as well as hydroxyethyl starch (HES) solutions. In these isotonic solutions, the use of malate and acetate allows the reduction of chloride concentration while ensuring isotonicity. Balanced solutions could thus reduce the incidence of hyperchloraemic metabolic acidosis. Balanced solutions decrease the rate of hyperchloraemic acidosis in healthy volunteers [13,14] and during perioperative care compared with saline solutions [15-17].