There are substantial practice variations in fluid management in patients with traumatic brain injury in the intensive care unit (ICU), with a new study published in Lancet Neurology suggesting that positive fluid balances are associated with worse outcomes.

While most patients with traumatic brain injury receive intravenous fluids to maintain adequate organ tissue perfusion and oxygenation, the recommended fluid management in these patients is controversial. The objective of the current study was to quantify the variability in fluid management policies in patients with traumatic brain injury across ICUs in Europe and Australia and to determine the association between different strategies for fluid therapy and outcomes.

The study used data on patients of at least 16 years with traumatic brain injury requiring a head CT, and admitted to the ICU from 2 observational cohorts: CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury), an ongoing multicenter, prospective observational cohort study done in 18 countries across Europe, and OzENTER-TBI (Australia-Europe NeuroTrauma Effectiveness Research in Traumatic Brain Injury), a study that included data from patients admitted to the ICUs of 2 major trauma centers in Australia.

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Study researchers collected detailed information about demographics, injury characteristics, clinical characteristics, laboratory values, monitoring, treatment intensity level, and outcomes. They recorded the mean daily fluid intake and calculated mean fluid balance, defined as the difference between fluid input and loss, to determine the association between fluid management with ICU mortality and functional outcome at 6 months.

A total of 2125 patients (median age, 50 years; 74% men) from 55 hospitals in 18 countries were eligible for the data analysis, including 1928 patients from the CENTER-TBI study and 197 patients from the OzENTER-TBI study.

Across centers, the median of the mean daily fluid balance ranged from -0.85 L to 1.13 L and the median of the mean daily fluid input ranged from 1.48 L to 4.23 L.

In the adjusted analysis, a mean daily positive fluid balance was associated with higher ICU mortality (odds ratio [OR], 1.10 [95% CI, 1.07-1.12] per 0.1 L increase) and worse functional outcome (OR, 1.04 [95% CI, 1.02-1.05]). On the other hand, a there was no association between a negative mean daily fluid balance with ICU mortality or functional outcome.

Higher mean daily input was associated with higher ICU mortality, with a 5% increased mortality risk per 0.1 L increase (OR, 1.05 [95% CI, 1.03-1.06]), and with worse functional outcome (OR, 1.04 [95% CI, 1.03-1.04] per 1-point decrease of the Glasgow Outcome Scale Extended per 0.1 L increase).

Due to the potential residual confounding by indication, an instrumental variable analysis, which is less sensitive to confounding by indication, was also completed. This analysis confirmed the association between higher fluid balance with increased ICU mortality (OR, 1.17 [95% CI, 1.05-1.29]) and worse functional outcome (OR, 1.07 [95% CI, 1.02-1.13]).  However, higher fluid input was not associated with ICU mortality or worse functional outcome.

The study had several limitations, including the observational design, missing data on important variables, potential over-estimation of fluid balance as insensible fluid losses were not accounted for.

“Our findings, in combination with previous evidence, argue for a more rigorous policy of normovolaemia, carefully avoiding both hypervolaemia and hypovolaemia as indicated by mean neutral fluid balances, given the harm associated with both mean negative and positive fluid balances”, concluded the study researchers.


Wiegers EJA, Lingsma HF, Huijben JA, et al. Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI): a prospective, multicentre, comparative effectiveness study. Lancet Neurol. 2021;20(8):627-638. doi:10.1016/S1474-4422(21)00162-9