Lay summary
Fluid resuscitation is a fundamental component of the management of critically ill patients and the choice of fluid is a longstanding issue of debate. While 0.9% saline is the most commonly used crystalloid worldwide, recent data suggest that the high chloride content in 0.9% saline might have clinically important adverse consequences and that resuscitation with so-called ‘balanced crystalloids’ might achieve better patient outcomes. Despite this, the safety and efficacy of using any crystalloid over any other has not been tested in a high quality, large-scale randomised controlled trial. We propose an 8800-participant, multicentre, double-blind, randomised controlled trial to determine whether fluid resuscitation and therapy with a ‘balanced’ crystalloid solution (Plasma-Lyte 148® [PL148]) compared to saline decreases 90 day mortality in critically ill patients.