Higher Fluid Balance is Associated With Worse Outcome in Critically Ill Traumatic Brain Injury Patients

Background:  Fluid therapy is a ubiquitous part of management of critically ill patients with traumatic brain injury (TBI) and may impact on outcome. Our aim was to quantify variability in current fluid therapy in patients with TBI admitted at European and Australian Intensive Care Units (ICUs) and to study the association between fluid therapy and outcome after TBI.  Methods: We analyzed data from patients admitted to the ICU with TBI and aged 16 and older included in the observational European CENTER-TBI and Australian OzENTER-TBI studies. The association of net daily fluid balance and -input with outcome (ICU mortality and functional outcome at 6 months) was analyzed at patient level with mixed effects logistic and ordinal regression with a random intercept for centre and adjustment for patient characteristics, and at centre level with centre as instrumental variable. Findings: In total, 2125 patients were included (1005 patients with isolated TBI). Mean daily fluid input ranged from 1·5 to 4·2L per centre. More positive daily mean fluid balance and fluid input were associated with worse outcome in patient-level analyses (fluid balance: ORs per 0·1L increase 1·10 [95%CI:1·07–1·13] and 1·03 [95%CI:1·02–1·05] for ICU mortality and functional outcome respectively; fluid input: ORs 1·05 [95%CI:1·03–1·06] and 1·03 [95%CI:1·02–1·04]). Centre-level analysis showed similar associations for fluid balance (ORs 1·15 [95%CI:1·02-1·29]; and 1·07 [95%CI:1·01-1·12], but not for fluid input (ORs: 0·95 [95%CI: 0·90-1·00]; and 1·01 [95%CI:0·99–1·03]). Interpretation: In critically ill patients with TBI, there is significant variability in fluid management with more positive fluid balances being associated with worse outcomes. Further research is needed to establish whether mitigation of positive fluid balance by less liberal fluid administration contributes to improved outcome. Funding: This research was funded by the European Commission 7th Framework program (602150) and the Australian Health and Medical Research Council (NHMRC 1074181). Declaration of Interests: DJC is an Australian NHMRC Practitioner Fellow and reports grants from the NHMRC and consulting fees to Monash University from PresSura Neuro. AIM declares consulting fees from PresSura Neuro, Integra Life Sciences, and NeuroTrauma Sciences. DKM reports grants from the UK National Institute for Health Research, during the conduct of the study; grants, personal fees, and non-financial support from GlaxoSmithKline; personal fees from Neurotrauma Sciences, Lantmaanen AB, Pressura, and Pfizer, outside of the submitted work. ES reports personal fees from Springer, during the conduct of the study. All other authors declare no competing interests. Ethics Approval Statement: In each recruiting site ethical approval was given.