Elsevier

The Lancet

Volume 380, Issue 9847, 22–28 September 2012, Pages 1088-1098
The Lancet

Series
Early management of severe traumatic brain injury

https://doi.org/10.1016/S0140-6736(12)60864-2Get rights and content

Summary

Severe traumatic brain injury remains a major health-care problem worldwide. Although major progress has been made in understanding of the pathophysiology of this injury, this has not yet led to substantial improvements in outcome. In this report, we address present knowledge and its limitations, research innovations, and clinical implications. Improved outcomes for patients with severe traumatic brain injury could result from progress in pharmacological and other treatments, neural repair and regeneration, optimisation of surgical indications and techniques, and combination and individually targeted treatments. Expanded classification of traumatic brain injury and innovations in research design will underpin these advances. We are optimistic that further gains in outcome for patients with severe traumatic brain injury will be achieved in the next decade.

Introduction

Traumatic brain injury is a major global health problem. Country-based estimates of incidence range from 108 to 332 new cases admitted to hospital per 100 000 population per year.1 On average, 39% of patients with severe traumatic brain injury die from their injury, and 60% have an unfavourable outcome on the Glasgow Outcome Scale (appendix p 2). The incidence of traumatic brain injury is rising in low-income and middle-income countries because of increased transport-related injuries,2 and young men (who are over-represented in transport, work, and recreational injuries) are particularly affected. In most countries, ageing populations have given rise to a new cohort—elderly people—who sustain substantial traumatic brain injuries from fairly low-impact falls.1 Furthermore, blast injury to the brain, which has distinctive pathological changes, treatment, and prognosis, is common in civilians and military personnel who are exposed to improvised explosive devices and suicide terrorist attacks.3

Key messages

  • Incidence of traumatic brain injury is increasing worldwide and overall mortality rates have only slightly improved since 1990. The weighted average mortality for severe traumatic brain injury is 39%, and for unfavourable outcome on the Glasgow Outcome Scale is 60%.

  • The randomised trial of early decompressive craniectomy for diffuse brain injury noted worse outcomes after surgery than with medical treatment. Further trials are needed. Steroids are not indicated after traumatic brain injury, except in cases of anterior pituitary insufficiency. Induced hypothermia and hyperoxia need further assessment in clinical trials.

  • Promising drug candidates are erythropoietin, statins, ciclosporin-A, tranexamic acid, and progesterone.

  • Multimodal monitoring, including cerebral oximetry and microdialysis, needs further assessment to determine if it leads to improved outcomes.

  • The IMPACT and MRC-CRASH online prediction models are valuable for clinical practice and research. Promising new biomarkers are glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1.

Survivors of severe traumatic brain injury have a low life expectancy, dying 3·2 times faster than the general population.4 Furthermore, survivors face prolonged care and rehabilitation, and have consequent long-term physical, cognitive, and psychological disorders that affect their independence, relationships, and employment. In 2007, a conservative estimate of lifetime costs per case of severe traumatic brain injury was US$396 331, with costs for disability and lost productivity ($330 827) outweighing those for medical care and rehabilitation ($65 504).5

Mortality and functional outcomes, and resulting long-term dependence and disability, are determined by the initial injury and subsequent treatment. However, an audit6 of 774 patients treated at an urban, level 1 trauma centre between 2006 and 2008 showed only 17% compliance with Brain Trauma Foundation guidelines for craniotomy, intracranial pressure monitoring, and reversal of coagulopathy. Adherence to clinical practice guidelines for traumatic brain injury, such as those of the Brain Trauma Foundation, are likely to reduce mortality, optimise clinical outcomes, and create substantial economic savings by reducing costs of medical care, rehabilitation, and lost productivity.5 Survival after severe traumatic brain injury was three times higher in a regionalised trauma system in which patients with serious head injury were transferred to neurosurgical centres, than in a less organised system in which fewer patients were treated in specialist centres.7

In this report, which is aimed especially at surgeons and other clinicians who care for patients with acute traumatic brain injury, we summarise advances in the understanding of severe traumatic brain injury and recovery, and give an update of clinical interventions in the crucial early stages of care.

Section snippets

Classification

Although modern approaches to disease classification use anatomical, physiological, metabolic, immunological, and genetic attributes, traumatic brain injury remains largely classified on the basis of clinical signs. With the Glasgow Coma Scale, patients are divided into crude categories of mild, moderate, and severe injury. These categories not only fail to identify the heterogeneity and complexity of severe injuries, but also minimise the real burden of mild traumatic brain injury. This issue

Pathophysiology

Traumatic brain injury has a dynamic pathophysiology that evolves in time (figure). The mechanism consists of the primary injury, followed by a combination of systemic derangements (hypoxia, hypotension, hypercarbia) and local events, which together cause secondary brain injury. Changes to the cerebral environment involve a complex interplay between cellular and molecular processes, in which glutamate-driven excitotoxic effects, oxidative stress, inflammation, ion imbalance, and metabolic

Pre-hospital

Despite the potential benefits of early intervention, few pre-hospital treatment options have proved effective. In nine randomised controlled trials and one cohort study of pre-hospital fluid treatment in patients with traumatic brain injury,15 hypertonic crystalloids and colloid solutions were not more effective than was isotonic saline. Results from observational studies16 of pre-hospital endotracheal intubation have been conflicting. Poor outcomes in intubated patients were probably due to

Monitoring of the injured brain

Continuous intensive-care monitoring of patients with severe traumatic brain injury provides information to help prevent and treat secondary cerebral ischaemia. Monitoring of intracranial pressure is standard practice for severe traumatic brain injury in most neurosurgical centres. Guidelines66 from the Brain Trauma Foundation detail indications for such monitoring alongside supporting evidence. However, the first randomised trial67 to test the effectiveness of treatment based on intracranial

Outcomes and their prediction

Comparison and prediction of outcomes in traumatic brain injury is challenging because of heterogeneity within the patient population, substantial differences in baseline prognostic risk, and the complexity of outcomes. Seemingly, mortality after traumatic brain injury has decreased and outcome has improved. Mortality rates of 10–15% noted in selected trials are compared with historial cohorts, such as the US Traumatic Coma Databank, which reported a mortality rate of 39% in 1984–87 (appendix p

Implications for research

Disappointingly, discoveries in the laboratory have translated into few new treatments for traumatic brain injury in human beings. Strategies for addressing this failure have been identified,108 including more research in larger animals, such as pigs and sheep with gyriform brains, rather than in rodents, whose brains are small and lissencephalic.108 CNS drugs take about 18 years to go from the laboratory bench to the patient, and spend on average 8·1 years in human testing.109 The cost of

Conclusion

The outcome of severe traumatic brain injury is dependent on delivery of high-quality care by a well-integrated multidisciplinary team of health professionals. Further improvements will probably result from precise classification, innovations in trial design, implementation of comparative effectiveness research, selection of patients who are likely to benefit from particular interventions, and individualised treatment in intensive-care units based on multimodal monitoring. Preclinical

Search strategy and selection criteria

We searched Medline, evidence-based medicine reviews, Cochrane Central Register of Controlled Trials, CENTRAL, and Embase from Jan 1, 2006, to Nov 28, 2011, using the core terms “brain injuries”, “craniocerebral trauma” and “traumatic brain injury” and keywords for the following topics: monitoring, decompressive craniectomy, haematoma evacuation, steroids, antifibrinolytics, therapeutic hypothermia, hyperoxia, stem cells, outcomes, predictors of outcome, and novel predictors of outcome. All

References (112)

  • AP Sen et al.

    Use of magnesium in traumatic brain injury

    Neurotherapeutics

    (2010)
  • NR Temkin et al.

    Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial

    Lancet Neurol

    (2007)
  • EF Wible et al.

    Statins in traumatic brain injury

    Neurotherapeutics

    (2010)
  • M Cekic et al.

    Traumatic brain injury and aging: is a combination of progesterone and vitamin D hormone a simple solution to a complex problem?

    Neurotherapeutics

    (2010)
  • AT Mazzeo et al.

    The role of mitochondrial transition pore, and its modulation, in traumatic brain injury and delayed neurodegeneration after TBI

    Exp Neurol

    (2009)
  • AL Siren et al.

    Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system

    Neurotherapeutics

    (2009)
  • ZX Zhang et al.

    A combined procedure to deliver autologous mesenchymal stromal cells to patients with traumatic brain injury

    Cytotherapy

    (2008)
  • WL Wright

    Multimodal monitoring in the ICU: when could it be useful?

    J Neurol Sci

    (2007)
  • JA Hartings et al.

    Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study

    Lancet Neurol

    (2011)
  • HF Lingsma et al.

    Early prognosis in traumatic brain injury: from prophecies to predictions

    Lancet Neurol

    (2010)
  • N Abelson-Mitchell

    Epidemiology and prevention of head injuries: literature review

    J Clin Nurs

    (2008)
  • G Ling et al.

    Explosive blast neurotrauma

    J Neurotrauma

    (2009)
  • IJ Baguley et al.

    Late mortality after severe traumatic brain injury in New South Wales: a multicentre study

    Med J Aust

    (2012)
  • M Faul et al.

    Using a cost-benefit analysis to estimate outcomes of a clinical treatment guideline: testing the Brain Trauma Foundation guidelines for the treatment of severe traumatic brain injury

    J Trauma

    (2007)
  • N Rayan et al.

    Barriers to compliance with evidence-based care in trauma

    J Trauma Acute Care Surg

    (2012)
  • BJ Gabbe et al.

    Comparison of mortality following hospitalisation for isolated head injury in England and Wales, and Victoria, Australia

    PLoS One

    (2011)
  • KE Saatman et al.

    Classification of traumatic brain injury for targeted therapies

    J Neurotrauma

    (2008)
  • NINDS common data elements: traumatic brain injury

  • PG Tan et al.

    Review article: Prehospital fluid management in traumatic brain injury

    Emerg Med Australas

    (2011)
  • SA Bernard et al.

    Prehospital rapid sequence intubation improves functional outcome for patients with severe traumatic brain injury: a randomized controlled trial

    Ann Surg

    (2010)
  • OP Ryynanen et al.

    Is advanced life support better than basic life support in prehospital care? A systematic review

    Scand J Trauma Resusc Emerg Med

    (2010)
  • MR Bullock

    Hyperoxia

    J Neurosurg

    (2008)
  • MN Diringer et al.

    Effect of hyperoxia on cerebral metabolic rate for oxygen measured using positron emission tomography in patients with acute severe head injury

    J Neurosurg

    (2007)
  • R Hlatky et al.

    Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain

    J Neurosurg

    (2008)
  • SB Rockswold et al.

    Hyperbaric oxygen in traumatic brain injury

    Neurol Res

    (2007)
  • CS De Deyne

    Therapeutic hypothermia and traumatic brain injury

    Curr Opin Anaesthesiol

    (2010)
  • HL Sinclair et al.

    Bench-to-bedside review: hypothermia in traumatic brain injury

    Crit Care

    (2010)
  • E Sydenham et al.

    Hypothermia for traumatic head injury

    Cochrane Database Syst Rev

    (2009)
  • RA Finkelstein et al.

    Induced hypothermia for trauma: current research and practice

    J Intensive Care Med

    (2010)
  • E Christian et al.

    A review of selective hypothermia in the management of traumatic brain injury

    Neurosurgical Focus

    (2008)
  • P Edwards et al.

    Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury—outcomes at 6 months

    Lancet

    (2005)
  • E Ghigo et al.

    Consensus guidelines on screening for hypopituitarism following traumatic brain injury

    Brain Inj

    (2005)
  • M Klose et al.

    Acute and long-term pituitary insufficiency in traumatic brain injury: a prospective single-centre study

    Clin Endocrinol

    (2007)
  • D Lu et al.

    Statins increase neurogenesis in the dentate gyrus, reduce delayed neuronal death in the hippocampal CA3 region, and improve spatial learning in rat after traumatic brain injury

    J Neurotrauma

    (2007)
  • B Li et al.

    Simvastatin attenuates microglial cells and astrocyte activation and decreases interleukin-1beta level after traumatic brain injury

    Neurosurgery

    (2009)
  • JH Tapia-Perez et al.

    Effect of rosuvastatin on amnesia and disorientation after traumatic brain injury (NCT003229758)

    J Neurotrauma

    (2008)
  • EB Schneider et al.

    Premorbid statin use is associated with improved survival and functional outcomes in older head-injured individuals

    J Trauma

    (2011)
  • M Schumacher et al.

    Novel perspectives for progesterone in hormone replacement therapy, with special reference to the nervous system

    Endocr Rev

    (2007)
  • LH Mbye et al.

    Comparative neuroprotective effects of cyclosporin A and NIM811, a nonimmunosuppressive cyclosporin A analog, following traumatic brain injury

    J Cereb Blood Flow Metab

    (2009)
  • A Buki et al.

    Postinjury cyclosporin A administration limits axonal damage and disconnection in traumatic brain injury

    J Neurotrauma

    (1999)
  • Cited by (0)

    View full text