Critical Care Research Area, Southampton, NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton, SO16 6YD, UK.