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Traumatic
Brain Injury
Science, Practice, Evidence
and Ethics
Stephen Honeybul
Angelos G. Kolias
Editors

123
Traumatic Brain Injury
Stephen Honeybul • Angelos G. Kolias
Editors

Traumatic Brain Injury

Science, Practice, Evidence
and Ethics
Editors
Stephen Honeybul Angelos G. Kolias
Department of Neurosurgery Division of Neurosurgery
Sir Charles Gairdner and Department of Clinical Neurosciences
Royal Perth Hospitals University of Cambridge and
Perth Addenbrooke’s Hospital
WA Cambridge
Australia UK

ISBN 978-3-030-78074-6    ISBN 978-3-030-78075-3 (eBook)

https://doi.org/10.1007/978-3-030-78075-3

© Springer Nature Switzerland AG 2021

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This Springer imprint is published by the registered company Springer Nature Switzerland AG
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To Louise and Robert (SH)
To Jenny and Johnny (AK)
Preface

It is often stated in the literature that traumatic brain injury TBI is a silent
epidemic with an estimated 64–74 million new cases presenting each year. It
is called silent because the long-term impairments suffered by many TBI
patients, such as memory loss, cognitive dysfunction or behavioural distur-
bance, are often not visible. However, there is a growing realization that
robust pre-hospital, acute in-hospital, and post-acute/long-term care deliv-
ered by various disciplines with specific areas of expertise is paramount to
optimize patient outcomes. As healthcare systems are implementing path-
ways for managing TBI patients from the scene of the injury and beyond
discharge from the acute setting, we can be optimistic that the silence will
eventually be broken.
At the same time, the involvement of several disciplines, each approaching
the TBI patient from slightly different angles, poses a challenge. Different
disciplines often use “different languages” and may approach the same issue
in a different way. An appreciation of the key concepts underpinning TBI
management by all disciplines involved is essential if we are to develop a
common “TBI language”.
The present book aims to facilitate the development of a common “TBI
language” by covering key concepts. We have organized it into four distinct
but interrelated parts:

I. Scientific background
II. Current clinical practice
III. Evidence
IV. Ethical considerations

The first part covers topics that TBI books traditionally cover (i.e. epide-
miology, pathophysiology) but we also wanted to touch upon novel insights
generated by new disciplines (e.g. brain mechanics). The second part covers
current clinical practice from the scene of the injury to long-term rehabilita-
tion. We decided to have separate chapters discussing the management of TBI
in resource-limited settings, as there is a growing appreciation that when the
resources are vastly different, a “one size fits all” approach (or guideline) for
high-income countries (HICs) and low- and middle-income countries
(LMICs) is inappropriate. The third part is discussing evidence. We are pro-
ponents of evidence-based medicine, but we also appreciate its limitations.
Hence, this part provides a critical appraisal of the evidence underpinning key

vii
viii Preface

interventions (e.g. hypothermia, decompressive craniectomy) and key aspects

of TBI (e.g. long-term neurological consequences). The fourth and final part
is covering ethical considerations. Perhaps there is no other medical field
with so many ethical issues, which is a reflection of two parameters in the
definition of TBI: sudden trauma due to an external force that causes an alter-
ation of brain functioning.
We would like to thank the authors of all chapters, as without their time
and effort, you would not be holding this book in your hands. We sincerely
hope that this book will contribute to the development of a common “TBI
language” for all disciplines striving to optimize the outcomes of patients
who have been unfortunate to suffer a TBI.
Financial Support No financial support has been required for this research.
Conflict of Interest None declared.

Perth, WA, Australia Stephen Honeybul

Cambridge, UK  Angelos G. Kolias
Acknowledgements

We would like to thank the authors of all chapters for their efforts in preparing
some excellent content despite the Covid-19 pandemic, which has been a
huge challenge for everyone. We also thank the Springer staff for their sup-
port in completing this book. We hope that you will enjoy reading it and that
you will suggest it to your colleagues. If you would like to get in touch with
comments or suggestions, please feel free to email us at Stephen.honeybul@
health.wa.gov.au and [email protected].

ix
Contents

Part I Scientific Background

1 Epidemiology of Traumatic Brain Injury��������������������������������������   3

Corrado Iaccarino, A. Gerosa, and E. Viaroli
2 Pathophysiology of Traumatic Brain Injury �������������������������������� 13
Katherine R. Giordano and Jonathan Lifshitz
3 Mechanics of Brain Tissue Deformation and Damage
Following Trauma���������������������������������������������������������������������������� 19
Michael Sutcliffe and Shijia Pan
4 Evidence Pyramid, Comparative Effectiveness Research,
and Randomised Trials�������������������������������������������������������������������� 29
Kwok M. Ho
5 Big Data Collection and Traumatic Brain Injury ������������������������ 35
Rianne G. F. Dolmans, Brittany M. Stopa, and
Marike L. D. Broekman

Part II Current Clinical Practice

6 Prehospital and Emergency Department Management

of TBI������������������������������������������������������������������������������������������������ 47
David J. Barton and Francis X. Guyette
7 Monitoring the Injured Brain�������������������������������������������������������� 53
Enza La Monaca, Orazio Mandraffino, Deepak Gupta, and
Anna Teresa Mazzeo
8 Contemporary Medical Management of Traumatic
Brain Injury: High-Income Countries ������������������������������������������ 69
Marcel Aries and Gerrit Schubert
9 Contemporary Management of Traumatic Brain Injury:
Low and Middle-Income Countries ���������������������������������������������� 79
Andrés M. Rubiano and Jeffrey V. Rosenfeld

xi
xii Contents

10 Contemporary Surgical Management of Traumatic

Brain Injury�������������������������������������������������������������������������������������� 93
Wellingson Silva Paiva, Davi J. Fontoura Solla, and
Stephen Honeybul
11 Military Management of Traumatic Brain Injury������������������������ 111
Brian P. Curry, Michael Cirivello, Melissa Meister,
Jeffrey V. Rosenfeld, and Randy S. Bell
12 Contemporary Management of Paediatric Head Injuries ���������� 123
Snigdha Saha and Stephen Honeybul
13 Sports-Related Traumatic Brain Injury���������������������������������������� 137
Niklas Marklund
14 Rehabilitation After Traumatic Brain Injury������������������������������� 147
H. Mee, L. M. Li, and F. Anwar

Part III Evidence

15 Predicting Outcome Following Traumatic Brain Injury�������������� 161

Kwok M. Ho
16 Biomarkers in Traumatic Brain Injury ���������������������������������������� 169
Jussi P. Posti and Olli Tenovuo
17 Erythropoietin, Progesterone, and Amantadine in the
Management of Traumatic Brain Injury: Current Evidence������ 179
Davi Jorge Fontoura Solla and Wellingson Silva Paiva
18 Tranexamic Acid in the Management of Traumatic
Brain Injury�������������������������������������������������������������������������������������� 187
Omar K. Bangash, Kwok M. Ho, and Stephen Honeybul
19 Hypothermia in the Management of Traumatic
Brain Injury�������������������������������������������������������������������������������������� 197
Stephen Honeybul
20 Decompressive Craniectomy in the Management of
Traumatic Brain Injury������������������������������������������������������������������ 205
Sara Venturini, Peter Hutchinson, and Angelos G. Kolias
21 Cranioplasty Following Traumatic Brain Injury�������������������������� 215
Stephen Honeybul
22 Thromboembolic Prophylaxis in Traumatic Brain Injury���������� 229
Kwok M. Ho and Stephen Honeybul
23 Long-Term Neurological Consequences of Traumatic
Brain Injury�������������������������������������������������������������������������������������� 237
Stephen Honeybul
Contents xiii

24 Post-Traumatic Epilepsy ���������������������������������������������������������������� 247

L. G. Viswanathan, Harsh Deora, Ajay Asranna, and
Andrés M. Rubiano
25 Brain Death: Current Evidence and Guidelines �������������������������� 259
Anna Teresa Mazzeo and Deepak Gupta

Part IV Ethical Considerations

26 Introduction to Bioethics ���������������������������������������������������������������� 269

Ahmed Ammar and Stephen Honeybul
27 Consent for Neurosurgery in Cases of Traumatic
Brain Injury�������������������������������������������������������������������������������������� 277
Camilla Louise Scanlan, Cameron Stewart, and Ian Kerridge
28 Team-Based Decision-Making in Traumatic Brain Injury���������� 285
Timothy R. Smith, Brittany M. Stopa,
Caroline M. W. Goedmakers, and Aakanksha Rana
29 Traumatic Brain Injury and Resource Allocation������������������������ 295
Allan Taylor, Solomon Benatar, and Bettina Taylor
30 Research Ethics in Clinical Trials�������������������������������������������������� 301
Stephen Honeybul and Kwok M. Ho
31 Artificial Intelligence and Healthcare Ethics�������������������������������� 315
Aakanksha Rana, Caroline M. W. Goedmakers, and
Timothy R. Smith
32 Ethical Issues in Paediatric Traumatic Brain Injury�������������������� 327
Ahmed Ammar and Stephen Honeybul
33 Withholding and Withdrawing Treatment������������������������������������ 335
Tamra-Lee McCleary and Stephen Honeybul
34 Long-Term Outcome Following Traumatic Brain Injury������������ 345
Stephen Honeybul
 Part I
Scientific Background
 Epidemiology of Traumatic Brain
Injury 1
Corrado Iaccarino, A. Gerosa, and E. Viaroli

1.1 Introduction (LMICs) has led to a marked increase in motor-

ized transportation, for both two- and four-­
It is often stated in the literature that traumatic wheeled vehicles. This has often not been
brain injury (TBI) is a silent epidemic with an accompanied by concomitant improvements in
estimated 64–74 million new cases presenting safety legislation, and this has led to a significant
each year [1]. It is called silent because the increase in the incidence of motor vehicle-related
impairments suffered by many TBI patients, such TBI, so much so that TBI is becoming one of the
as memory loss, cognitive dysfunction, or behav- major causes of death and disability in many of
ioral disturbance, are often not visible. However, these countries.
the silence is gradually being broken as the global In high-income countries (HICs), improve-
healthcare implications for the management of ments in healthcare have led to considerably
TBI patients become increasingly visible. The extended life expectancy, which has increased the
issues that need to be considered will vary risk of fall-related TBI. In addition, in high-­
depending on the evolving patterns of injury and income countries (HICs), vast amounts of money
the local healthcare resources available [2, 3]. For are involved in organized sports such as American
example, the rapidly increasing industrialization football, where players from a young age are
of some low- and middle-income countries encouraged to target the head in repetitive, high-­
impact collisions. It is now recognized that the
C. Iaccarino (*) long-term effects of these repetitive minor TBIs
Department of Biomedical, Metabolic and Neural are not insignificant, and this may present sub-
Sciences, University of Modena and Reggio Emilia, stantial governance issues for some of the major
Modena, Italy
sporting authorities. Finally, it is becoming
Neurosurgery Division, University Hospital of apparent that military personnel returning from
Modena, Modena, Italy
e-mail: [email protected]
conflict zones such as Iraq and Afghanistan are
suffering from the long-term consequences of
A. Gerosa
Neurosurgery Division, Department of Clinical
their trauma-related brain injuries.
Surgical Diagnostic and Pediatric Sciences, Some of the most robust data on the epidemi-
University of Pavia, Pavia, Italy ology can be obtained from the Centers for
E. Viaroli Disease Control and Prevention in the USA. They
Division of Neurosurgery, Department of Clinical report that 52,000 people die every year from
Neurosciences, Addenbrooke’s Hospital, Cambridge TBI, 275,000 people are hospitalized, and
Biomedical Campus, University of Cambridge,
Cambridge, UK

© Springer Nature Switzerland AG 2021 3

S. Honeybul, A. G. Kolias (eds.), Traumatic Brain Injury,
https://doi.org/10.1007/978-3-030-78075-3_1
4 C. Iaccarino et al.

roughly 1.4 million people are seen and dis- “an alteration of brain functioning or the emer-
charged from an emergency room for TBI. gence of evidence of brain pathology caused by an
external force” [5].
TBI is a contributing factor in 30.5% of all
injury-related deaths that occur in the USA and is This definition will cover most situations,
the leading cause of death for people under the especially in circumstances where a patient seeks
age of 45 in the Western world [4]. The economic medical attention or where they require hospital
and social impact is considerable, with an esti- admission. However, there are many instances
mate of direct medical expenditures and indirect where there has been a minor impact to the head
costs (e.g., loss of productivity) attributable to and there is no alteration in function or evidence
TBI exceeding $60 billion in 2000 in the USA. of pathology. Currently, this is an area of intense
However, notwithstanding the economic interest because it remains to be determined
impact, the World Health Organization (WHO) when a (presumably) insignificant strike to the
estimates that almost 90% of deaths due to inju- head, as occurs on a regular basis when heading a
ries occur in LMICs, where the 85% of the global ball in a soccer game, becomes significant, as
population live. This situation will continue to occurs in high velocity head-to-head collisions in
represent an important global healthcare problem an American football game. The cumulative
in the upcoming years, and in light of these find- effects of the latter type of injuries are currently
ings, there is a strong need to study the epidemi- under intense investigation, and there is also a
ology of TBI in order to plan preventive measures, growing interest in the cumulative impact of the
allocate resources effectively to manage acute former types of injury. These issues and the
injuries and long-term rehabilitation services, implications for sports-related injuries are dis-
and assess the short- and long-term outcomes in cussed in more detail in Chaps. 13 and 23.
order to assess treatment efficacy.
Despite these requirements, the reality is that
the global epidemiological literature on TBI has 1.3 Classifying Traumatic Brain
significant limitations because: Injury

• The definition of TBI can be variable. Traditionally, the severity of injury in TBI is clas-
• Classification can be inconsistent across sified as mild, moderate, or severe. This is based
studies. on clinical indicators, the most common of which
• There are limited systems in most LMICs that are as follows:
can prospectively and accurately track the
incidence of TBI. • Post-resuscitation level of consciousness
• The incidence of TBI is highest in LMICs • Episode and length of time of loss of
where resources are limited. consciousness
• Duration of posttraumatic amnesia (PTA)
The aim of this chapter is to assess these limi-
tations, outline the global healthcare burden of The most commonly used tool for assessing
TBI, and explore some preventive strategies. conscious level is the post-resuscitation Glasgow
Coma Scale (GCS), which was initially described
nearly half a century ago, and there is no doubt
1.2 Defining Traumatic Brain that it is a robust assessment tool that has stood
Injury the test of time. It has also been shown to be
highly effective when predicting outcome, espe-
Any definition of TBI will have limitations, given cially in the context of severe TBI. A score of
that it is such a diverse and heterogeneous disease 13–15 is considered mild, 9–12 is considered
process. However, one definition that encom- moderate, and 3–8 is considered a severe injury.
passes most aspects is However, notwithstanding its usefulness as a
1 Epidemiology of Traumatic Brain Injury 5

v­alidated and reliable assessment tool, it does Most studies describe the incidence as cases
have a number of limitations, especially when per 100,000 of a population, and a systematic
considering epidemiological studies. For severe review of European epidemiological studies
injuries, especially in HICs, the modern-day found a very wide range reported [6]. One study
emphasis placed on aggressive resuscitation and from a Spanish province estimated the annual
early endotracheal intubation can make it diffi- average to be 91 cases per 100,000, whereas a
cult to make a reliable assessment because a study from Sweden estimated the annual average
patient may already be under the influence of to be 546 per 100,000. In the USA, data from the
sedative agents prior to hospital admission. This Centers for Disease Control and Prevention
is in no way a criticism of the accuracy of the (CDC) estimates the average incidence between
paramedical staff assessment or indeed that of the the years 2002 and 2006 to be 576.8 per 100,00,
emergency physician because in the acute setting and while the number of emergency department
of a severe TBI, they will understandably con- visits and subsequent hospitalizations has
centrate on the time-dependent issue of securing increased, the mortality rate has decreased [7].
a patent airway and maintaining tissue perfusion. Overall, there is little doubt that these studies
However, in these circumstances, an initial GCS underestimate the true incidence of TBI, and the
may be recorded as severe when the patient has wide variation in reported incidence serves to
actually sustained a more moderate injury. In highlight the difficulty in assessing the true inci-
these circumstances, further confounders to mak- dence even in HICs.
ing a reliable assessment include the following: One of the most robust epidemiological stud-
ies comes from a prospective population-based
• Alcohol intoxication study conducted in the city of Hamilton in New
• Recreational (or in some circumstances pre- Zealand [8]. The investigators enrolled all health-
scription) drug usage care providers from primary healthcare to hospi-
• Multiple injuries requiring prolonged tal and ambulance services as well as the local
resuscitation schools and prisons. During the period of the
study, 1369 TBIs were recorded, which placed
In the context of minor TBI, the prognostic the annual incidence rate at 790 per 100,000.
value of the GCS is useful from an epidemiologi- There is no reason to suspect that New Zealanders
cal basis, but from an individual clinical perspec- are more prone to TBI than any other HIC, so this
tive, it may be more useful to consider other data goes some way to underscore the issue of
indicators when considering prognosis, such as underreporting.
the length of time a patient was unconscious or
the length of time a patient has been in PTA.
1.5  he Severity of Traumatic
T
Brain Injury
1.4  he Incidence of Traumatic
T
Brain Injury Despite the inconsistencies regarding injury clas-
sification, it is generally estimated that by far, the
The true incidence of TBI and its global distribu- most common TBIs are mild, and it has been esti-
tion is unknown, although it has been estimated mated that this may represent between 70% and
using a mathematical model [1]. There are many 90% of all TBIs. However, given the aforemen-
reasons for this, not the least of which are the tioned confounder of underreporting, the figure
issues with heterogeneous study methodology of 95%, which was reported in the New Zealand
and underreporting of minor TBI; however, the study, may be nearer the true incidence. When
overriding limitation is the lack of robust trauma considering the incidence of moderate and severe
registries in LMICs where up to 80% of the TBI, the previously mentioned confounders make
global burden of TBI are located. a clear distinction difficult, and this is
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