Fluid therapy after brain injury: the pendulum swings again

Arthur Beck/Science Photo Library

Fluid management in critical care medicine has gone through several phases since the 1960s. These changes in clinical practice have substantially affected the management of patients with severe traumatic brain injury. In The Lancet Neurology, Eveline Wiegers and colleagues¹ now report findings from the CENTER-TBI and OzENTER-TBI studies that provide evidence in support of yet another change, this time towards more precise fluid management.

Until the early 1980s, management of severe traumatic brain injury involved fluid restriction. This practice, accompanied by use of hyperosmolar therapy to treat cerebral oedema, often produced dehydration, which could be severe. Subsequent work identified special concerns with dehydration in patients with traumatic brain injury (ie, a reduction in cerebral perfusion pressure by hypotension produces cerebral vasodilation, exacerbating intracranial hypertension).² Dehydration also increases the risk of acute renal failure, a complication that adds serious challenges to the management of patients with traumatic brain injury. These concerns with hypovolaemia and dehydration ushered in an era in which the production of a euvolaemic hyperosmolar state became the target in severe traumatic brain injury.³

Over the past decade, the deleterious consequences of fluid overload have been highlighted in studies of acute lung injury and sepsis, including worsened lung function and prolonged duration of mechanical ventilation and intensive care unit (ICU) stay.^4,5 An early prospective study of patients with traumatic brain injury suggested similar effects from fluid overload. Robertson and colleagues⁶ compared targeting two thresholds for cerebral perfusion pressure (60 mm Hg vs 70 mm Hg) in patients with severe traumatic brain injury, and reported that when the higher target was applied, acute lung injury was worsened by the larger fluid volumes required, and overall outcome was not improved. Given the constraints of the cranial vault, the impact of fluid overload on brain oedema is another reason to avoid this strategy in patients with traumatic brain injury. There have, however, been few contemporary reports on fluid overload in traumatic brain injury that have addressed either cerebral or extracerebral complications.

Wiegers and colleagues¹ present a valuable report by investigators from more than 50 centres in Europe and Australia, examining the impact of fluid balance on outcome in 2125 critically ill patients with traumatic brain injury. Cranial surgery was done in 877 (42%) of 2111 patients and extracranial surgery done in 651 (31%) of 2110. Hyperosmolar therapy was used in 582 (27%) of 2125 patients, vasopressors in 1145 (57%) of 2002, and colloids in 338 (16%) of 2107. The median of the mean daily fluid balance was 0.37 L (ranging from −0.85 L to 1.13 L across centres), and the median of the mean daily fluid input was 2.91 L (range 2.15 to 3.60). After 6 months, 853 (46%) patients had an unfavourable outcome, assessed by the Glasgow Outcome Scale Extended (GOSE). A mean daily positive fluid balance was associated with higher ICU mortality (odds ratio 1.10 [95% CI 1.07–1.12] for each 0.1 L increase) and with a similar unfavourable impact on GOSE. Similar results were seen across multiple sensitivity analyses, including adjustments for cerebral perfusion pressure and serum sodium. In an instrumental variable analysis, higher fluid balance was again associated with mortality and unfavourable outcome, unlike higher fluid input.

By contrast, in 2002, Clifton and colleagues⁷ examined the variability and impact of fluid balance on outcome in the first multicentre randomised controlled trial of hypothermia in patients with severe traumatic brain injury. Variability in management was huge: fluid balances ranged from −10 L to 20 L. Remarkably, a total fluid balance at 96 h that was more negative than −0.594 L (equivalent to around −0.15 L per day) was associated with poor outcome, with a similar association with poor outcome to that of Glasgow Coma Scale score at admission. This effect of negative fluid balance on outcome suggested that over-aggressive dehydration was deleterious. The contrasting findings between Clifton and colleagues⁷ versus Wiegers and colleagues¹ merit careful consideration. Although fluid overload is an important concern in management of patients with traumatic brain injury, caution is advised to avoid overshooting, given the goal of euvolaemia. Notably, the difference between a fluid balance of 0.1 L and −0.15 L each day is small. Perfect euvolaemia seems an impractical goal, yet it might warrant closer daily attention than previously appreciated.

The types of fluids used might also influence patient outcome. The use of hyperosmolar therapy in the study by Wiegers and colleagues¹ was low and there might be differences between a hypervolaemic hyperosmolar state and the normo-osmolar or hypo-osmolar fluid overloaded states seen in critically ill patients outside of neurocritical care. Unique relationships between fluid composition and patient outcome were seen when comparing the neuro-ICU setting with other ICU settings.⁸ Nevertheless, the report of Wiegers and colleagues¹ was long overdue, and although the findings are based on observational studies, they suggest the need to meticulously titrate fluid use in patients with severe traumatic brain injury, while avoiding dehydration.

Often, patients with severe traumatic brain injury experience polytrauma and present with hypotension; 305 (15%) of 2010 patients in this study were hypotensive on admission and 1202 (57%) of 2125 had a major extracranial injury. The need for a large initial fluid resuscitation superimposes challenges in the management of these patients. In sepsis, use of aggressive resuscitation followed by de-resuscitation is an area of investigation.⁹ Such an approach, along with the need to identify novel therapies to prevent the development of brain oedema, merits exploration in patients with severe traumatic brain injury.¹⁰

In critical care, the most beneficial therapies keep coming back into favour. We rediscover them and optimise them within contemporary care. Wiegers and colleagues¹ echo that message. The pendulum has swung, suggesting the need for more precise fluid management, along with prospective studies on fluid management, in patients with severe traumatic brain injury.