Background and objective: Despite multiple interventions, mortality due to severe traumatic brain injury (sTBI) within mature Trauma Systems has remained unchanged over the last decade. During this time, the use of vasoactive infusions (commonly norepinephrine) to achieve a target blood pressure and cerebral perfusion pressure (CPP) has been a mainstay of sTBI management. However, evidence suggests that norepinephrine, whilst raising blood pressure, may reduce cerebral oxygenation. This study aimed to review the available evidence that links norepinephrine augmented CPP to clinical outcomes for these patients. Methods: A systematic review examining the evidence for norepinephrine augmented CPP in TBI patients was undertaken. Strict inclusion and exclusion criteria were developed for a dedicated literature search of multiple scientific databases. Two dedicated reviewers screened articles, whilst a third dedicated reviewer resolved conflicts. Results: The systematic review yielded 4,809 articles, of which 1,197 duplicate articles were removed. After abstract/title screening, 45 articles underwent full text review, resulting in the identification of two articles that investigated the effect of norepinephrine administration on clinical outcomes in patients following TBI when compared to other vasopressors. Neither study found a difference in neurological outcome between the vasopressor groups. No articles measured the effect of norepinephrine compared to no vasopressor use on the clinical outcome of patients with sTBI. Conclusions: Despite being a mainstay of pharmacological management for hypotension in patients following sTBI, there is minimal clinical evidence supporting the use of norepinephrine in targeting a CPP for either improving neurological outcomes or reducing mortality. Outcomes-based clinical trials exploring the role of brain tissue perfusion and oxygenation monitoring are required to validate any benefit.

Memantine at a 20-mg daily dose is a well tolerated drug that can improve BPD symptomatology and may be a promising novel therapeutic for its treatment. Further studies are needed to explore the efficacy of memantine versus placebo, as well as in comparison with other potential treatments for BPD. ClinicalTrials.gov identifier: NCT02097706.