In adult patients with severe traumatic brain injury, does the use of norepinephrine for augmenting cerebral perfusion pressure improve neurological outcome? A systematic review

Patryck Lloyd-Donald; William Spencer; Jacinta Cheng; Lorena Romero; Ron Jithoo; Andrew Udy; Mark C Fitzgerald

doi:10.1016/j.injury.2020.07.054

In adult patients with severe traumatic brain injury, does the use of norepinephrine for augmenting cerebral perfusion pressure improve neurological outcome? A systematic review

Injury. 2020 Oct;51(10):2129-2134. doi: 10.1016/j.injury.2020.07.054. Epub 2020 Jul 25.

Authors

Patryck Lloyd-Donald¹, William Spencer², Jacinta Cheng³, Lorena Romero⁴, Ron Jithoo⁵, Andrew Udy⁶, Mark C Fitzgerald⁷

Affiliations

¹ Trauma Services, The Alfred Hospital, 89 Commercial Rd, Melbourne VIC, Australia; National Trauma Research Institute, Level 4, 89 Commercial Rd, Melbourne 3004, VIC, Australia.
² Trauma Services, The Alfred Hospital, 89 Commercial Rd, Melbourne VIC, Australia; National Trauma Research Institute, Level 4, 89 Commercial Rd, Melbourne 3004, VIC, Australia. Electronic address: w.spencer@alfred.org.au.
³ Trauma Services, The Alfred Hospital, 89 Commercial Rd, Melbourne VIC, Australia; National Trauma Research Institute, Level 4, 89 Commercial Rd, Melbourne 3004, VIC, Australia. Electronic address: jacinta.cheng@alfred.org.au.
⁴ Library Services, The Alfred Hospital, 89 Commercial Rd, Melbourne VIC, Australia. Electronic address: l.romero@alfred.org.au.
⁵ National Trauma Research Institute, Level 4, 89 Commercial Rd, Melbourne 3004, VIC, Australia; Department of Neurosurgery, The Alfred Hospital, 89 Commercial Rd, Melbourne VIC, Australia. Electronic address: r.jithoo@alfred.org.au.
⁶ Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, 89 Commercial Rd, Melbourne VIC, Australia; Australian and New Zealand Intensive Care Research Centre, School of Public and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne VIC, Australia. Electronic address: a.udy@alfred.org.au.
⁷ Trauma Services, The Alfred Hospital, 89 Commercial Rd, Melbourne VIC, Australia; National Trauma Research Institute, Level 4, 89 Commercial Rd, Melbourne 3004, VIC, Australia. Electronic address: m.fitzgerald@alfred.org.au.

PMID: 32739152
DOI: 10.1016/j.injury.2020.07.054

Abstract

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.

Keywords: Cerebral perfusion; Neurological outcomes; Norepinephrine; Traumatic brain injury; Vasopressor.

Publication types

Review
Systematic Review

MeSH terms

Adult
Brain Injuries*
Brain Injuries, Traumatic* / drug therapy
Cerebrovascular Circulation
Humans
Intracranial Pressure
Norepinephrine / therapeutic use
Perfusion

Substances

Norepinephrine