Moderate and severe traumatic brain injury in adults

Article (PDF Available)inThe Lancet Neurology 7(8):728-41 · August 2008with1,111 Reads
DOI: 10.1016/S1474-4422(08)70164-9 · Source: PubMed
Abstract
Traumatic brain injury (TBI) is a major health and socioeconomic problem that affects all societies. In recent years, patterns of injury have been changing, with more injuries, particularly contusions, occurring in older patients. Blast injuries have been identified as a novel entity with specific characteristics. Traditional approaches to the classification of clinical severity are the subject of debate owing to the widespread policy of early sedation and ventilation in more severely injured patients, and are being supplemented with structural and functional neuroimaging. Basic science research has greatly advanced our knowledge of the mechanisms involved in secondary damage, creating opportunities for medical intervention and targeted therapies; however, translating this research into patient benefit remains a challenge. Clinical management has become much more structured and evidence based since the publication of guidelines covering many aspects of care. In this Review, we summarise new developments and current knowledge and controversies, focusing on moderate and severe TBI in adults. Suggestions are provided for the way forward, with an emphasis on epidemiological monitoring, trauma organisation, and approaches to management.
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www.thelancet.com/neurology Vol 7 August 2008
Review
Moderate and severe traumatic brain injury in adults
Andrew I R Maas, Nino Stocchetti, Ross Bullock
Traumatic brain injury (TBI) is a major health and socioeconomic problem that aff ects all societies. In recent
years, patterns of injury have been changing, with more injuries, particularly contusions, occurring in older
patients. Blast injuries have been identifi ed as a novel entity with specifi c characteristics. Traditional approaches to
the classifi cation of clinical severity are the subject of debate owing to the widespread policy of early sedation and
ventilation in more severely injured patients, and are being supplemented with structural and functional
neuroimaging. Basic science research has greatly advanced our knowledge of the mechanisms involved in
secondary damage, creating opportunities for medical intervention and targeted therapies; however, translating
this research into patient benefi t remains a challenge. Clinical management has become much more structured
and evidence based since the publication of guidelines covering many aspects of care. In this Review, we summarise
new developments and current knowledge and controversies, focusing on moderate and severe TBI in adults.
Suggestions are provided for the way forward, with an emphasis on epidemiological monitoring, trauma
organisation, and approaches to management.
Introduction
Traumatic brain injury (TBI) constitutes a major health
and socioeconomic problem throughout the world.
1,2
It
is the leading cause of mortality and disability among
young individuals in high-income countries, and
globally the incidence of TBI is rising sharply, mainly
due to increasing motor-vehicle use in low-income and
middle-income countries. WHO has projected that, by
2020, traffi c accidents will be the third greatest cause of
the global burden of disease and injury.
3
In higher
income countries, traffi c safety laws and preventive
measures have reduced the incidence of TBI due to
traffi c accidents,
4
whereas the incidence of TBI caused
by falls is increasing as the population ages, leading to
a rise in the median age of TBI populations (table 1).
This has consequences for the type of brain damage
currently seen, and contusions (falls in older patients)
are becoming more frequent than diff use injuries
(high-velocity traffi c accidents in younger patients).
Violence is now reported as the cause of closed head
injury in approximately 7–10% of cases,
9,10
a substantial
increase from earlier studies. The incidence of
penetrating brain injury is also increasing, particularly
in the USA, due to the use of fi rearms in violence-
related injuries. Worldwide, armed confl icts and
terrorist activities are causing more brain injuries, often
due to improvised explosive devices, to the extent that
blast injuries of the brain are now recognised as a
specifi c entity. The changing patterns of injury and
treatment approaches have challenged current concepts
of classifi cation. Moreover, basic research has greatly
advanced our knowledge of what happens in the brain
after TBI, off ering opportunities to limit processes
involved in secondary brain damage. However,
translating advances from basic research into clinical
benefi t has proven complex. Here, we discuss current
knowledge and novel insights and controversies in the
study of adults with moderate and severe TBI, with the
aim of integrating basic science and clinical research to
provide guidelines on the epidemiological monitoring
of TBI, trauma organisation, and management at the
acute stage.
Epidemiology and cost
In the USA, monitoring by the Centers for Disease
Control and Prevention shows the annual incidence of
emergency department visits and hospital admissions
for TBI to be 403 per 100 000 and 85 per 100 000,
respectively.
11
Epidemiological data on TBI from the
European Union are scarce, but do indicate an annual
aggregate incidence of hospitalised and fatal TBI of
approximately 235 per 100 000,
12
similar to that found
in Australia,
13
although substantial variation exists
between European countries. Most patients with TBI
have milder injuries, but residual defi cits in these
patients are not infrequent.
14
Approximately 10–15% of
patients with TBI have more serious injuries, requiring
specialist care.
TBI is more common in young adults, particularly
men (75%), which causes high costs to society because
of life years lost due to death and disability. In Europe,
TBI accounts for the greatest number of total years
lived with disability resulting from trauma, and is
among the top three causes of injury-related medical
Lancet Neurol 2008; 7: 728–41
Department of Neurosurgery,
University Hospital Antwerp,
Antwerp, Belgium
(A I R Maas MD); Neuroscience
Intensive Care Unit, Ospedale
Maggiore Policlinico, Milan
University, Milan, Italy
(N Stocchetti MD); and
Department of Neurosurgery,
University of Miami, Miller
School of Medicine, Miami, FL,
USA (R Bullock MD)
Correspondence to:
Andrew I R Maas, Department of
Neurosurgery, University
Hospital Antwerp, Wilrijkstraat
10, 2650 Edegem, Belgium
andrew.maas@uza.be
Year of
study
n Median
age (years)
Proportion
aged >50 years
Traumatic Coma
Data Bank
5
1984–1987 746 25 15%
UK four centre study
6
1986–1988 988 29 27%
European Brain
Injury Consortium
Core Data Survey
7
1995 847 38 33%
Rotterdam cohort
study*
1999–2003 774 42 39%
Austrian Severe TBI
study
8
1999–2004 415 48 45%
*Unpublished (Maas, AIR).
Table 1: Increasing age in TBI studies
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costs.
15,16
In the USA, the fi nancial burden has been
estimated at over US$60 billion per year.
17
These
numbers stand in stark contrast to the amount of
funding for TBI research, which has one of the highest
unmet needs within the already severely underfunded
eld of brain research.
18
Classifi cation
TBI can be isolated, but is associated with extracranial
injuries (limb fractures, thoracic or abdominal injuries)
in about 35% of cases,
19
which increases the risk of
secondary brain damage due to hypoxia, hypotension,
pyrexia, and coagulopathy. The recording of the severity
of extracranial injuries should therefore form an
integral part of TBI classifi cation (panel).
Traditionally, TBI has been classifi ed by mechanism
(closed vs penetrating), by clinical severity (Glasgow
coma scale [GCS]
20
), and by assessment of structural
damage (neuroimaging;
21
panel). The GCS has evolved
into a universal classifi cation system for the severity of
TBI, and consists of the sum score (range 3–15) of the
three components (eye, motor, and verbal scales). For
assessment of severity in individual patients, the three
components should be reported separately. A
standardised approach to assessment is advocated. If
painful stimuli are required to elicit a response, nail-
bed pressure and supraorbital pressure (to test for
localising) are recommended. Increasingly, in modern
practice, classifi cation of TBI by clinical severity is
limited. The level of consciousness might be obscured
in the acute setting by confounders such as medical
sedation, paralysis, or intoxication.
22,23
Assessment of structural damage by neuroimaging is
not infl uenced by these confounders. Marshall and
colleagues
21
proposed a descriptive system of CT
classifi cation, which focuses on the presence or absence
of a mass lesion, and diff erentiates diff use injuries by
signs of increased intracranial pressure (ICP; ie,
compression of basal cisterns, midline shift). However,
the Marshall classifi cation has limitations, such as the
broad diff erentiation between diff use injuries and mass
lesions, and the lack of specifi cation of the type of mass
lesion (eg, epidural vs subdural). Thus, this classifi cation
system might mask patients who have diff use axonal
injury (DAI) or signs of raised ICP in addition to a mass
lesion, and does not fully use the prognostic information
contained in the individual CT characteristics scored.
24
Furthermore, CT can only capture momentary
snapshots of the dynamically evolving process of TBI,
and important lesions that occur at the microscopic
level, such as DAI and ischaemic damage, cannot be
visualised. Therefore, new surrogate markers for these
processes are needed. Such markers have revolutionised
cardiology (eg, troponin) and AIDS therapy, but have
not yet been established for TBI.
An alternative approach is to classify patients by
prognostic risk. Although not new, this is an approach
under development. Recent, well validated models,
developed on large patient samples, have become
available to facilitate this approach.
25,26
Prognostic
classifi cation can serve as an objective basis for
comparison of diff erent TBI series, form the basis for
quality assessment of the delivery of health care, and
aid the analysis of clinical trials.
27,28
Types of brain damage
Primary damage
TBI is a heterogeneous disorder with diff erent forms of
presentation. The unifying factor is that brain damage
results from external forces, as a consequence of direct
impact, rapid acceleration or deceleration, a penetrating
object (eg, gunshot), or blast waves from an explosion.
The nature, intensity, direction, and duration of these
forces determine the pattern and extent of damage.
On the macroscopic level, damage includes shearing
of white-matter tracts, focal contusions, haematomas
Panel: Approaches to classifi cation of TBI
Mechanistic
Closed; penetrating; crash; blast.
Clinical severity: level of consciousness (Glasgow coma scale)
The GCS score comprises the values from three component tests (eye, motor, and verbal
scales). Injuries are classifi ed as severe (GCS 3–8), moderate (GCS 9–13), or mild (GCS 14–15).
Eyes: 1=no response; 2=open in response to pain; 3=open in response to speech;
4=spontaneous
Motor: 1=no response; 2=extension to painful stimuli; 3=abnormal fl exion to painful
stimuli; 4=fl exion/withdrawal to painful stimuli; 5=localises painful stimuli; 6=obeys
commands
Verbal: 1=no response; 2=incomprehensible sounds; 3=inappropriate utterances;
4=disoriented, confused; 5=oriented, converses normally
Clinical severity (injury severity score)
An abbreviated injury scale (range 0–6) is obtained for six body regions. The injury
severity score (range 0–75) is the sum of quadratic scores for each of the six body regions.
Body regions: external (skin); head/neck (includes brain); thorax; abdomen/pelvis;
spine; extremities
Scores: 0=none; 1=minor; 2=moderate; 3=serious; 4=severe; 5=critical; 6=virtually
unsurvivable
Structural damage (CT)
• Diff use injury I: no visible pathology
• Diff use injury II: cisterns present, midline shift 0–5 mm and/or lesion densities present
or no mass lesion >25 mL
• Diff use injury III (swelling): cisterns compressed or absent with midline shift 0–5 mm
or no mass lesion >25 mL
• Diff use injury IV (shift): midline shift >5 mm, no mass lesion >25 mL
Evacuated mass lesion: any lesion surgically evacuated
Non-evacuated mass lesion: High or mixed-density lesion >25 mL, not surgically
evacuated
Prognosis
Classifi cation by expected outcome as calculated from prognostic models. Examples of
prognostic models can be found at the CRASH and IMPACT websites.
For more on the CRASH study
see http://www.crash2.lshtm.
ac.uk/
For more on the IMPACT study
see http://www.tbi-impact.org/
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(intracerebral and extracerebral), and diff use swelling
(fi gure 1). At the cellular level, early neurotrauma events
(which can occur minutes to hours after initial injury)
include microporation of membranes, leaky ion
channels, and stearic conformational changes in
proteins. At higher shear rates, blood vessels can be
torn, causing (micro)haemorrhages.
DAI is characterised by multiple small lesions in
white-matter tracts. Patients with DAI are usually in
profound coma as a result of the injury, do not manifest
high ICP, and often have a poor outcome. Focal cerebral
contusions are the most common traumatic lesion, are
more frequent in older patients, and usually arise from
contact impact. Traumatic intracranial haematomas
occur in 25–35% of patients with severe TBI and in
5–10% of moderate injuries.
In static crush injuries and focal blows, much of the
energy is absorbed by the skull; thus, brain damage
might remain superfi cial, often with a depressed skull
fracture. Blast injuries have been identifi ed as a novel
entity within TBI.
30,31
The pathological mechanism is
much less understood, but the injuries are characterised
by severe early brain swelling, subarachnoid
haemorrhage, and often prominent vasospasm.
32,33
Outcome of severe blast injuries, even with aggressive
management, is still unknown, but has been encouraging
after debridement of wounds and aggressive control of
ICP, including decompressive surgery.
Ischaemic brain damage is often superimposed on
the primary damage (fi gure 1), and can be widespread
or, more commonly, perilesional. Impaired cerebral
perfusion and oxygenation, excitotoxic injury, and focal
microvascular occlusion can be contributing factors.
34,35
Secondary damage
Each type of head injury might initiate diff erent
pathophysiological mechanisms, with variable extent
and duration (fi gure 1). These mechanisms (acting
concurrently and often with synergising eff ects) and
the intensity of systemic insults determine the extent of
secondary brain damage. Secondary processes develop
over hours and days, and include neurotransmitter
release, free-radical generation, calcium-mediated
damage, gene activation, mitochondrial dysfunction,
and infl ammatory responses.
Glutamate and other excitatory neurotransmitters
exacerbate ion-channel leakage, worsen astrocytic
swelling, and contribute to brain swelling and raised
ICP. Neurotransmitter release continues for many days
after TBI in human beings, paralleling the course of
high ICP, and, with free-radical and calcium-mediated
damage, is a major cause of early necrotic cell death.
Early gene activation and release of proapoptotic
molecules (eg, caspases) induce apoptotic neuronal
loss. A third potential cause of cell death, autophagy,
might also play an important part.
36,37
Infl ammatory response is an important component
of TBI, particularly around contusions and
(micro)haemorrhages. The maximum response occurs
within a few days, but cytokines are released from
microglia, astrocytes, and polymorphonuclear cells
within hours after TBI, leading to opening of the blood–
brain barrier, complement-mediated activation of cell
death, and the triggering of apoptosis. Although the
infl ammatory response can be deleterious in excess, it
is necessary in order to clean up cellular debris after
injury, and infl ammatory signals might also trigger
Inflammation
Receptor-mediated damage
Oxidative damage
Calcium-mediated damage
0
Diffuse axonal
injury
Contribution to secondary damage (%)
90
80
70
60
50
40
30
20
10
100
SDH DAIContusion
Systemic insults
Swelling
Haematoma
Contusion
Hypoxia/ischemia
ICP ↑
CPP ↓
B
A
Figure 1: Components of TBI and importance of diff erent pathophysiological mechanisms
(A) The diff erent components of TBI with ischaemic damage are superimposed on the primary types of injury (haematoma, contusion, and diff use axonal injury).
Systemic insults and brain swelling contribute to ischaemic damage, which might in turn cause more swelling. (B) The relative importance of diff erent
pathophysiological mechanisms in various types of TBI. CPP=cerebral perfusion pressure. ICP=intracranial perssure. SDH=acute subdural haematoma. DAI=diff use
axonal injury. Adapted from Graham et al,
29
with permission from Hodder Arnold.
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731
Review
regeneration. Hence, infl ammation in TBI can be
thought of as both helpful and harmful.
38
Recent research has raised new insights that challenge
existing concepts of pathophysiology. Mitochondrial
dysfunction can cause energy failure after TBI, with a
decrease in production of ATP and consumption of
oxygen by 40–50%. This can trigger opening of the
mitochondrial transition pore, setting off an autodestruct
phenomenon that induces both apoptosis and necrosis.
39
Mitochondrial dysfunction might also lead to axonal
disruption. The classical concept that DAI is due to
mechanical rupture of axons, incompatible with
regeneration or repair, has now been abandoned.
Neurons can at least partially regenerate their axonal
anatomy. This accords with clinical observations that
patients with the hallmark features on CT of DAI can
recover with modern neurocritical care. Furthermore,
laboratory studies have shown that DAI can take up to
48 hours to become fully established and is thus
amenable to therapeutic interventions.
40
Whether decreased cerebral blood fl ow (CBF) after
trauma is indicative of ischaemia or is secondary to
metabolic depression remains the subject of debate.
PET studies have attempted to clarify the eff ects of
hyperventilation, which lowers ICP by reducing CBF.
Some investigators have found that oxygen metabolism
is preserved,
41
whereas others are more concerned that
ischaemia could be induced.
42
A combined PET and
microdialysis study showed an increase in the oxygen
extraction fraction in only 1% of cases, whereas lactate
increases were seen in 25% of cases.
43
These observations
are not consistent with the classical concept of
ischaemia, and indicate that other mechanisms
contribute to derangements of fl ow and metabolism.
Energy failure due to mitochondrial dysfunction and
diff usion barriers to oxygen delivery resulting from
cytotoxic oedema are likely to be involved. The role of
vasospasm is unclear. Although transcranial doppler
studies report fl ow velocity values suggestive of
vasospasm in up to 35% of patients,
44
the correlation
with CBF is relatively poor.
45
Diagnosis
Head injury does not always implicate TBI. A diagnosis
of TBI is established on the basis of clinical symptoms:
for example, the presence of any documented loss of
consciousness and/or amnesia (retrograde or post-
traumatic). Additional clinical investigations can be
driven by the patient’s level of awareness, presence of
risk factors, and mechanisms of injury (fi gure 2).
CT is the preferred method of assessment on
admission to determine structural damage and to detect
(developing) intracranial haematomas. Traumatic
intracranial lesions occur frequently in severe and
moderate injuries, but are also reported in 14% of
patients with a GCS of 14.
46
The risk of intracranial
lesions in patients with a GCS of 15 is generally low,
unless risk factors are present. Therefore, current
guidelines advocate CT examinations in all TBI patients
with a GCS of 14 or lower and in patients with a GCS of
15 in the presence of risk factors.
47–49
Some studies have
successfully identifi ed risk factors for intracranial
lesions, such as vomiting, age, duration of amnesia,
injury mechanism, neurological defi cit, and
anticoagulant therapy.
46,50,51
In the past, much attention
was focused on conventional radiographs of the skull to
triage indications for CT, but these are no longer
thought to be required. Fractures of the skull can be
Closed Penetrating
Head injury
No Yes
MRI Treatment
CT
Findings consistent with
neurological status
GCS ≤14
Present Absent
CT Discharge with
instructions
GCS=15
Risk factors
CT
Abnormal Normal
Suspect
wooden object
ICH; major vessel
trajectory involved
Consider CT
angiography
MRI
Figure 2: Diagnostic approaches in TBI
GCS=Glasgow coma scale. ICH=intracerebral haematoma.
732
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seen adequately on CT in the bone-window setting, and
three-dimensional reconstructions with volume
rendering techniques provide a far superior insight into
complex fractures.
MRI studies are seldom done in the acute phase of
TBI because they are logistically complex and more
time consuming, and do not necessarily provide any
further information for clinical decisions. However,
MRI can be more informative if a penetrating injury
with a wooden object is suspected.
52
In the subacute
and chronic phases of TBI, MRI is more informative
than CT, off ering better detection of white-matter
lesions in patients with DAI.
53
Neuroimaging techniques
are rapidly progressing from purely structural
assessments to more functional imaging, off ering a
potentially better understanding of TBI.
54
Because TBI is a dynamic process and pathology
evolves, follow-up CT is advisable if lesions were present
on the initial CT or if indicated by clinical deterioration.
New lesions develop in approximately 16% of patients
with diff use injuries,
55
and 25–45% of cerebral
contusions will enlarge signifi cantly.
55,56
Higher
occurrences are reported if the initial CT scan is done
within 2 hours of injury.
57
Many clinics will usually follow up the patient on the
day after admission, but recent studies indicate that CT
progression will generally occur within 6–9 hours after
injury.
58
Follow-up CT is always indicated if larger
lesions are present or if there is clinical deterioration or
increasing ICP.
59
Indiscriminate and too frequent use
of CT follow-up are thought to be inappropriate. There
is growing concern about the cancer risk connected to
CT radiation exposure, which is held responsible for
2% of all cancer cases in the USA,
60–62
where more than
62 million CT scans, including 4 million in children,
are done each year. The need for CT follow-up should
thus be balanced against awareness of the cancer risk.
Specifi c injury mechanisms might cause vascular
lesions. Arterial dissections (extracranial and
intracranial) have been recognised in up to 17% of
patients with cervical spine injuries, and in those with
skull-base fractures involving the carotid canal.
Traumatic aneurysms are seen in about 15% of patients
with penetrating TBI.
63
Consequently, in penetrating
brain injury, CT angiography is indicated in the
presence of an intracranial haematoma, or when a
missile tract, for example, crosses a major vessel
trajectory.
Guidelines and individualised management
Over the past 10 years, much of the treatment of TBI
has evolved towards standardised approaches that
follow international and national guidelines (table 2).
International guidelines for severe head injury are
mostly evidence based, and address specifi c aspects of
management. National guidelines focus more on
organisational issues, such as admission and referral
policy; however, these remain limited to the constraints
of existing trauma systems, and clear statements on the
best trauma organisation are often avoided.
Patel and colleagues
71
unequivocally showed a 2·15
times increase in the odds of death (adjusted for case
Year of publication Description Type Topics (n) Recommendations (n)
Class I Class II Class III
Maas and co-workers
59
1997 European Brain Injury Consortium guidelines on management
of severe head injury in adults
Consensus/expert opinion .. .. .. ..
Bullock and co-workers
64
* 1996 Management of severe TBI (fi rst edition) Evidence based 13 1 10 14
Bullock and co-workers
65
2000 Management and prognosis of severe TBI Evidence based 13 3 10 16
Brain Trauma Foundation* 2000 Prehospital management Evidence based 7 0 5 12
Aarabi and co-workers
63
2001 Penetrating brain injury Evidence based 7 0 0 12
Vos and co-workers
47
2002 European Federation of Neurological Societies guidelines on
mild traumatic brain injury
Evidence based/consensus .. .. .. ..
Adelson and co-workers
66
* 2003 Paediatric guidelines Evidence based 17 0 6 40
Brain Trauma Foundation* 2005 Field management of combat-related head trauma Evidence based 5 0 3 15
Bullock and co-workers
67
* 2006 Surgical management of TBI Evidence based 5 0 0 26
Brain Trauma Foundation
68
* 2007 Revised guidelines for management of severe TBI Evidence based 15 1 14 17
Italian Society of Neurology
46
1996 Italian guidelines for management of patients with minor
head injuries
Consensus/expert opinion .. .. .. ..
Bartlett and co-workers
69
1998 UK guidelines for the initial management of head injuries Expert opinion .. .. .. ..
Newcombe and Merry
70
1999 Management of acute neurotrauma in rural and remote
locations of Australia
.. .. .. .. ..
UK National Institute for Health
and Clinical Excellence
48
2003 UK guidelines for triage, assessment, investigation, and
management of TBI
Evidence based 27 3 16 107
*http://www.braintrauma.org/. †http://www.efns.org/. ‡In the NICE guidelines (http://www.nice.org/), the grading scheme for level of recommendations was adapted from the Oxford Centre for Evidence Based
Medicine levels of evidence as level A–D; for consistency, we considered grade A as class I, grade B as class II, and grades C and D as class III.
Table 2: Overview of international and national guidelines
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mix) for patients with severe head injury treated in non-
neurosurgical centres versus neurosurgical centres.
Their report makes a strong case for transferring and
treating all patients with severe head injury in a setting
with 24-hour neurosurgical facilities. Most neurosurgical
centres in the UK are not equipped to receive all patients
with TBI because of shortages in human and technical
resources,
72
and patients with TBI are referred only for
selected surgical indications. In light of these data, we
suggest that all treatable patients with TBI should be
centralised in large neurotrauma centres that off er
surgical therapy and access to specialised neurocritical
care.
73–75
However, this cannot be achieved without
profound re-design of national health systems and re-
allocation of resources.
76
A similar case has been made
in the USA: for example, in the state of Florida, which
has 20 million inhabitants, fi ve neurotrauma centres
have been designated to receive patients with severe
TBI and spinal-cord injuries. The concept here is that
greater volume (and hence experience) will lead to
higher quality services and better outcome.
77–79
The evidence-based guidelines show that the strength
of supporting data is relatively weak, underscoring the
need for more rigorous evidence (table 2). However, for
various aspects of care in TBI, such as surgery for
epidural haematomas in patients with deteriorating
consciousness, randomised controlled trials are unlikely
to be considered ethical. Notwithstanding the great
benefi ts of evidence-based approaches, guidelines and
practice recommendations should not be made on the
basis of the conclusions of literature reviews alone.
Furthermore, we should recognise that no single
treatment can be uniformly appropriate across the wide
range of conditions within TBI, and this vision would
support the search for more individualised treatment
approaches (ie, determined by monitoring, biomarkers,
and possibly genotype).
80
Approaches to management
Pre-hospital emergency care
The main goals of prehospital management are to
prevent hypoxia and hypotension, because these
systemic insults lead to secondary brain damage.
68,81
When assessed before hospital admission (by
ambulance or helicopter crews), oxygen saturation
below 90% is found in 44–55% of cases and hypotension
in 20–30%.
81–83
Trauma renders the brain more
vulnerable to these insults,
84
and hypoxia and
hypotension are strongly associated with poor outcome
(hypoxia: odds ratio [OR] 2·1, 95% CI 1·7–2·6;
hypotension: OR 2·7, 95% CI 2·1–3·4).
81
In various settings, the introduction of a pre-hospital
system capable of normalising oxygenation and blood
pressure has been associated with improved outcome.
85,86
However, ensuring adequate training of paramedics is
vital because intubation by poorly trained paramedics
has been associated with worse outcome.
87
Arterial
hypotension is best prevented by early and adequate
uid resuscitation with normotonic crystalloids and
colloids. No benefi ts have yet been shown for hypertonic
solutions,
88
or for albumin, which has been associated
with worse outcome.
89
Admission care
The primary aims of admission care are stabilisation
and diagnostic assessment with prioritisation according
to US Advanced Trauma Life Support standards. From
a neurosurgical perspective, the immediate priority is
rapid detection and treatment of operable lesions.
Indications for emergency surgery in closed severe TBI
are summarised in the evidence-based surgical
guidelines.
67
CT criteria, including volume, thickness,
and signs of mass eff ect (midline shift), are as relevant
as signs of neurological deterioration. A shift of
emphasis is continuing from the conventional approach
of surgery after neurological deterioration to a more
pre-emptive approach in which the aim of surgery is to
prevent deterioration. In penetrating TBI, a superfi cial
debridement and dural closure is recommended as
general standard of care,
63
but in patients with small
entry wounds, simple wound closure may be
considered. This approach is much more conservative
than earlier policies of extensive debridement and
repeated surgery for removal of bone fragments with
the aim of preventing infection. There is no evidence
to support such aggressive approaches, and routine
antibiotic treatment is usually eff ective for infection
prevention.
Intensive care management
A major focus for neurointensive care is to prevent and
limit ongoing brain damage and to provide the best
conditions for natural brain recovery by reducing brain
swelling and raised ICP. Optimum oxygenation,
perfusion, nutrition, glycaemic control, and temperature
homoeostasis are indicated, as in general intensive
care. However, the concern that the injured brain
cannot tolerate hypoglycaemia, which might result as
an adverse event from over-enthusiastic glycaemic
control, is specifi c to neurointensive care.
90
Furthermore,
the brain must be protected from overt or silent
seizures. The benefi ts of prophylactic antiseizure
activity should be balanced against the potential risks.
Opinions vary greatly about routine antiseizure
prophylaxis, but recommended indications include
penetrating brain injury and the presence of a depressed
skull fracture in patients with post-traumatic amnesia
for more than 24 hours in whom a dural lesion is
suspected.
Sedation and artifi cial ventilation are used to reduce
brain swelling and raised ICP in patients with severe
head injuries. In the 1990s, hyperventilation was
commonly used, which, although eff ective in reducing
ICP, has the risk of enhancing ischaemia.
91
Arterial
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Review
carbon dioxide lower than 30 mm Hg should be
avoided, unless facilities exist for more advanced
monitoring; osmotherapy is currently preferred as the
rst agent in the medical management of raised ICP,
and interest in early and extensive decompressive
craniotomies is increasing.
Osmotherapy
Rapid infusion of mannitol, which creates an osmolar
gradient, mobilises water across an intact blood–brain
barrier,
92
but also improves focal CBF.
93
Hypertonic
saline infusion creates an analogous, sometimes
stronger, osmolar gradient with corresponding
improvement in ICP.
94–96
When used for medical
management of raised ICP, hyperosmolar agents should
be administered repeatedly (at least every 4–6 hours) or
even continuously, because a rebound phenomenon
might otherwise occur after reversal of the osmotic
gradients by passing into the extracellular space of the
brain. Few studies have compared mannitol with
hypertonic saline.
68,97
In one study in which short-term
administration of equimolar amounts of mannitol and
hypertonic saline were compared, hypertonic saline was
associated with a larger and more lasting ICP
reduction.
98
However, use of osmotherapy, particularly for long
periods, is associated with electrolyte abnormalities,
especially hypernatraemia, cardiac failure, bleeding
diathesis, and phlebitis. No benefi ts of small-volume
resuscitation with hypertonic saline have been shown
in patients with TBI.
88
Consequently, in adults, there is
insuffi cient evidence to support the use of hypertonic
saline over mannitol for osmotherapy. We caution
against the use of hypertonic saline because of the risks
of severe hypernatraemia, and advise particular caution
with the combined use of mannitol and hypertonic
saline. Careful control of fl uid balance, electrolyte
status, and serum osmolarity (<320 mMol/L) is
mandatory in the use of hypertonic agents.
Decompressive craniectomy
Decompressive craniectomy has been used for more
than a century to treat brain swelling and reduce ICP,
and a resurgence of interest has recently been seen in
this practice, with 240 papers published between 1996
and 2006.
99
Despite this renewed enthusiasm, the
technique remains controversial. It does not produce
improved outcome in all series,
100
and has many side-
eff ects, some severe.
101
The evidence is also confounded
by ambiguous defi nitions and a lack of focus. A clear
distinction should be made between true decompressive
craniectomy versus simple removal of a small bone
ap, and between procedures done in combination with
the evacuation of a mass lesion versus an isolated
decompressive craniectomy in diff use injuries.
However, there is consensus that the craniectomy
should be large enough (approximately 15 cm×15 cm)
and should be done early and with duraplasty.
102
Two
trials are currently ongoing: the RESCUEicp
(Randomised Evaluation of Surgery in Craniectomy for
Uncontrollable Elevation of Intracranial Pressure)
Study in Europe and the DECRA (Decompressive
Craniectomy) Study in Australia.
103
Monitoring of the severely injured brain
Many patients develop progressive damage without
clear clinical signs; in others, damage develops at an
alarming pace, exemplifi ed by the so-called “talk and
die” syndrome.
104,105
Neuroworsening, defi ned as a
deterioration of the GCS motor score, development of
pupillary abnormalities, or development of progressive
CT lesions, has been reported in 29–44% of patients.
106–108
Clinical monitoring (level of consciousness and
pupillary reactivity) remains essential. However, more
severely injured patients are universally treated with
sedation and artifi cial ventilation, and advanced
monitoring of cerebral variables is required. Besides
standard systemic monitoring, ICP and cerebral
perfusion pressure monitoring are important. The
eff ectiveness of ICP monitoring in TBI has been
questioned;
109,110
no monitoring technique can improve
outcome unless it can drive an appropriate intervention.
Intracranial hypertension develops in up to 77% of
cases, and raised ICP is related to poorer outcome.
68
ICP monitoring carries a 0·5% risk of haemorrhage
and a 2% risk of infection. Intraventricular catheters
are preferable, because they are accurate, can be re-
calibrated, and allow drainage of CSF. Intraparenchymal
probes are user friendly and accurate.
64
Less accurate
data are provided by subdural catheters,
64,111
and epidural
probes are unreliable.
112,113
The accuracy of ICP
monitoring can be enhanced by use of computer-
supported systems.
114
Attempts to monitor ICP non-
invasively have been unsatisfactory.
115,116
More advanced techniques include the monitoring of
cerebral oxygenation, CBF measurements,
microdialysis, and electrophysiological monitoring.
Cerebral oxygenation can be measured focally (brain
tissue oxygen tension) or, more globally, by measuring
the oxygen content in the cerebral venous outfl ow.
Brain tissue oxygen tension indicates the balance
between oxygen delivered to the tissue and its
consumption in a specifi c area, and can indicate
regional hypoxia if it falls below 15–20 mm Hg.
117,118
The
diameter of microvascular vessels and diff usion barriers
might also infl uence recorded values.
119,120
Venous
oxygen saturation is a more global approach to
monitoring oxygenation. Values below 55% indicate an
increased oxygen extraction relative to perfusion, and
suggest the presence of ischaemia.
121,122
Non-randomised
studies have indicated benefi t of an oxygen-directed
therapy protocol.
123
Measurements of CBF have shown widespread zones
of brain ischaemia in a third of patients with severe
For more on the
RESCUEicp study see http://
www.rescuicp.com/
www.thelancet.com/neurology Vol 7 August 2008
735
Review
TBI, especially if done within 8 hours of TBI.
124
Microsensor technology has recently been devised to
allow continuous blood fl ow monitoring within the
brain by use of thermal diff usion and laser doppler
probes.
125
Clinical microdialysis allows metabolic exploration of
the cerebral cortex in vivo. Within the fi rst few hours,
most patients with severe TBI have a high lactate:pyruvate
ratio, indicating ischaemia or hyperglycolysis.
126–128
More
recently, microdialysis has been used to measure brain
penetration of drugs.
129
Microdialysis, oxygen tension
catheters, and CBF probes can be used to assess events
in a small region, but possibly fail to detect harmful
events in other parts of the brain. Conversely, more
global approaches (venous oxygen saturation) fail to
detect regional abnormalities.
41,130
Continuous electroencephalographic monitoring can
be used to identify occult seizure activity, which can
occur in 15–18% of patients with moderate and severe
TBI.
131
In the research setting, interest exists in
monitoring cortical spreading depression.
Traumatically
damaged neurons decrease their fi ring rates
substantially in the early post-injury period. Waves of
depolarisation result in ionic fl ux and loss of resting
membrane potential, which worsens neurochemical
dysregulation, and places extra metabolic demands on
damaged tissue.
132–134
Outcome and prognosis
Outcome after head injury is generally assessed at
6 months after injury, representing a compromise
between true fi nal outcome and logistic limitations.
Experience shows that about 85% of recovery occurs
within this time period, but further recovery can occur
later. Accurate and consistent outcome determination
at a fi xed timepoint is a prerequisite for any TBI study.
The most frequently used global outcome measure in
TBI is the Glasgow outcome scale. More specifi c tools
are required for detailed examination, such as for
functional and neuropsychological assessment. These
are particularly relevant in the rehabilitation setting.
Early and intensive rehabilitation is recommended to
achieve the best possible functional outcome and social
re-integration. However, the optimum timing and
approach to rehabilitation of patients with TBI remains
to be determined.
In severe closed head injury, the outcome distribution
represents a U-shaped curve, with most patients either
dying or recovering to an independent lifestyle. This
has promoted dichotomisation of outcomes into
unfavourable (death, vegetative state, or severe
disability) versus favourable outcome (moderate
disability or good recovery). Recent studies using the
more detailed 8-point Glasgow outcome scale (extended
version), and a structured interview for its assessment,
135
did not fi nd the typical U-shaped outcome
distribution.
88,108
In non-military penetrating head
injury, mortality is consistently over 95% in patients
with a GCS of 3–5, raising ethical questions of whether
active treatment should be initiated, particularly if the
cause of injury was a suicide attempt.
The widespread belief that all patients in a vegetative
state are awake but not aware has been challenged.
Incidental reports on functional MRI studies show that
external stimuli can be processed in the human cortex
of some vegetative patients, and that even spoken
commands might elicit appropriate cortical responses
that are indistinguishable from normal human
responses.
136
The implications are that caretakers should
be aware that the patient might hear, see, and realise a
lot more than is commonly thought, and the concept
that a vegetative state might be a worse outcome than
death has become uncertain.
Few TBI studies have used health-related quality of
life measures. Comprehensive disease-specifi c
instruments for such assessment in people after TBI
are needed, such as the new disease-specifi c scale,
quality of life in brain injury (QOLIBRI).
137
Many studies have reported on the univariate
association between predictors and outcome after TBI,
but few have used multivariate analyses, which adjust
for associations between predictors. Extensive work by
the IMPACT study group, which analysed individual
patient data from over 9000 patients with severe or
moderate TBI merged from 11 studies, confi rmed age,
GCS motor score, pupillary response, and CT
n Odds ratio (95% CI)
Unadjusted Adjusted
Age 8719 2·14 (2·00–2·28) ..
Motor score 8199
None 5·30 (3·49–8·04) ..
Extensor 7·48 (3·60–9·95) ..
Abnormal fl exion 3·58 (2·71–4·73) ..
Flexion 1·74 (1·44–2·11) ..
Pupils 7310
Non-reactive 7·31 (5·35–9·99) ..
One reactive 2·71 (2·36–3·12) ..
Hypoxia 5661 2·08 (1·69–2·56) 1·65 (1·37–2·00)
Hypotension 6629 2·67 (2·09–3·41) 2·06 (1·64–2·69)
CT classifi cation 5209
Class I 0·45 (0·31–0·67) 0·47 (0·32–0·70)
Class III 2·50 (2·09–3·00) 2·20 (1·54–2·63)
Class IV 3·03 (2·12–4·35) 2·22 (1·44–3·42)
Class V/VI 2·18 (1·83–2·61) 1·48 (1·27–1·71)
Traumatic subarachnoid haemorrhage 7407 2·64 (2·42–2·89) 2·01 (1·83–2·21)
Laboratory testing
Glucose 4831 1·68 (1·54–1·83) 1·45 (1·36–1·55)
Haemoglobin 3872 0·69 (0·60–0·78) 0·76 (0·66–0·88)
Data from Murray et al.
138
Table 3: Predictors of outcome in TBI
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Review
characteristics as the most powerful independent
prognostic variables (table 3).
138
Other important
prognostic factors include hypotension, hypoxia, eye
and verbal components of the GCS, and laboratory
variables (glucose, platelets, and haemoglobin). Other
studies have shown an association between coagulopathy
and poorer outcome,
35
indicating that more careful
attention to correcting these disturbances might be
appropriate.
For clinical application and research, the predictive
value of variables can be combined into prognostic
models. Many previously developed models had
shortcomings in development (in particular, a lack of
external validation),
139,140
but more recently published
models have greater validity and generalisability.
25,26
These models can provide a scientifi c basis for
informing relatives about the likely long-term outcome,
facilitate prognostic classifi cation and valid comparisons
of outcome between diff erent patient series, and enable
the setting of baselines for clinical audits. Furthermore,
prognostic models will have an important role in
randomised controlled trials for stratifi cation and
statistical analyses that explicitly consider prognostic
information, such as covariate adjustment.
141
Neuroprotection and clinical trials
The original concept of neuroprotection involved the
initiation of treatment before the onset of the event,
and was aimed at minimising the intensity of an insult
or its immediate eff ects on the brain by interrupting the
harmful cascades of biochemical events. A major new
focus of neurobiology now revolves around cell
replacement, aimed at promoting neuroplasticity, and
regeneration or replacement of lost neuronal and glial
cells and neuronal circuits. Over the past 25 years, over
20 agents have been studied in phase III clinical trials
of severe TBI (table 4). Other strategies have focused on
the use of hypothermia and evaluation of a CBF-targeted
approach versus an ICP-directed approach.
152
None of the phase III trials have convincingly shown
effi cacy in the overall study population (table 4).
153,154
Various factors have contributed to these failures,
including uncertainty about validity and robustness of
preclinical phase II data, problems in translating results
from experimental studies to clinical practice,
uncertainty about whether and when the
pathophysiological mechanisms targeted are indeed
active in individual patients, uncertainty about the
therapeutic window, and inadequacies in clinical trial
design and analysis. Multidisciplinary eff orts are
currently ongoing to implement approaches in trial
design for dealing with challenges posed by the
heterogeneity of TBI populations.
155
Clinical trials in TBI
also pose specifi c ethical dilemmas that are not always
appreciated by policy-making authorities,
156
and current
legislation is often perceived as obstructive
bureaucracy.
Patients with TBI are often acutely incapacitated by
their injury and cannot always provide informed
consent. Proxy consent is generally substituted, but
does not serve to protect the patient’s autonomy, might
induce selection bias,
157
and causes substantial delays
without off ering any real protection to the incapacitated
patient, often only providing some legal protection to
the trial sponsor.
158
The validity of proxy consent in the
emergency situation of TBI is questionable because
many relatives are unlikely to be able to make a balanced
decision at a time of such emotional stress. Various
experts have therefore argued for deferred consent in
TBI trials.
159,160
Future directions
Here, we have illustrated the seriousness and complexity
of the problems posed by TBI to patients, relatives,
doctors, authorities, and society alike. Great
n Year of study Start of treatment Results
Bradykinin inhibition
Bradycor
142
139 1996 ≤12 h 12% improvement in favourable
outcome (p=0·26)
Calcium-mediated damage
HIT I nimodipine
143
351 1987–1989 24 h No signifi cant eff ect
HIT II nimodipine
144
852 1989–1991 12 h of not obeying
commands within
24 h of injury
No signifi cant eff ect in overall
population
HIT III nimodipine
145
123 1994 ≤12 h Signifi cant reduction in
unfavourable outcome
HIT IV nimodipine 592 1997–1999 ≤12 h No signifi cant eff ect
Parke Davis/SNX-111 237 1997–1998 ≤12 h Higher mortality
Glutamate exitotoxicity
Eliprodil 452 1993–1995 ≤12 h No signifi cant eff ect
Selfotel
146
693 1994–1996 ≤8 h and within 4 h
of admission
No signifi cant eff ect
Cerestat/aptiganel 532 1996–1997 ≤8 h No signifi cant eff ect
Saphir/D-CPP-ene 924 1995–1997 ≤12 h No signifi cant eff ect
Pfi zer/CP-101606 356 1997–2000 ≤8 h Better outcome in men
(p=0·057)
Lipid peroxidation/free-radical damage
PEGSOD 1562 1993–1995 ≤8 h No signifi cant eff ect
Tirilazad domestic trial 1155 1991–1994 ≤4 h No signifi cant eff ect
Tirilazad international
trial
147
1120 1992–1994 ≤4 h No signifi cant eff ect
Steroids
Triamcinilone
148
396 1985–1990 ≤4 h No signifi cant eff ect
Ultra high-dose
dexamethasone
149
300 1986–1989 <3 h No signifi cant eff ect
CRASH steroid trial
150
10 008 2000–2004 ≤8 h Higher mortality
Multiple actions
Dexanabinol
108
861 2000–2004 ≤6 h No signifi cant eff ect
Magnesium sulphate
151
499 1998–2004 <8 h Poorer outcome at low dose;
higher mortality at high dose
HIT=Head Injury Trial. PESGOD=polyethylene glycol conjugated superoxide dismutase.
Table 4: Overview of phase III randomised clinical trials in TBI
www.thelancet.com/neurology Vol 7 August 2008
737
Review
advancements have been achieved over the past
10–15 years, but advances in basic science have not yet
led to new treatments of clinically proven benefi t, and
advanced monitoring has not routinely resulted in
individualised management. Current classifi cation
systems are no longer suffi cient and not all patients
have access to the best care. Clinical trials in TBI have
had methodological problems posed by the inherent
heterogeneity of the TBI population, and we note a
disconnection between ethical directives and their
validity and applicability in the emergency situation of
acutely incapacitated patients with TBI. Therefore, a
great deal is still to be accomplished. From the
perspective of clinicians, we would suggest that the
following topics are prioritised.
First, standardised epidemiological monitoring should
be implemented to off er a sound basis for appropriate
targeting of prevention. Second, a specifi c focus should
be directed towards trauma organisation with
concentration of care for more severely injured patients
in specialised centres. The specifi cs of the best structure
might vary with the local setting, but we strongly feel
that there is now suffi cient evidence to prove the benefi ts
of centralisation. This centralisation should form a
continuum from emergency systems through to
rehabilitation care. Third, we suggest that further
dissemination of existing guidelines should form the
basis for standards of care, but recommend an additional
strong focus on more individualised treatment, targeting
the specifi c needs of a given patient. This approach will
require advanced diagnostics and monitoring, thus
allowing identifi cation of pathophysiological alterations.
These diagnostic procedures could include the use of
biomarkers and genotyping. As in the acute phase,
specialised facilities and concentration of care are
necessary in the post-acute setting, off ering appropriate
rehabilitation programmes, and exploring strategies for
promoting recovery and regeneration.
These goals cannot be achieved without more basic
and clinical research. Multiple mechanisms of TBI have
been identifi ed in the experimental setting, but much
more needs to be elucidated. From a research
perspective, attention might focus on the cerebrovascular
interface and mechanisms of energy failure after TBI.
Notwithstanding the importance of basic science,
clinically oriented research with therapeutic trials is
needed, perhaps based more on an integral concept or
combined approaches, rather than focusing on the
possible benefi t of agents that target a single
pathophysiological mechanism among the many other
processes. The methods used in TBI clinical trials
require refi nements, including the implementation of
approaches to deal with the inherent heterogeneity of
TBI populations. Whatever route is taken or priorities
chosen, advancing the fi eld further will require great
multidisciplinary eff orts from researchers and
clinicians, facilitated by appropriate funding.
Contributors
All authors contributed equally to the preparation of this Review.
Confl icts of interest
The authors are members of the European and American Brain Injury
Consortia. AIRM has been a consultant and a member of steering
committees for clinical trials in TBI for Pharmos, Solvay, Vasopharm,
and Novo Nordisk. NS has been a member of steering committees or
safety boards for clinical trials in TBI for Pharmos, Solvay, Vasopharm,
and Xytis.
Acknowledgments
We dedicate this Review to the memory of Bryan Jennett (1926–2008),
who inspired us to devote a large part of our lives and work to TBI. He
was one of the founding leaders of neurotrauma research and a great
inspiration to all around him. Many of the concepts and insights
developed by him in the 1970s are still in use today. We thank our co-
workers and partners in research, both within their own institutes and
within the American and European Brain Injury Consortia. We are
grateful to Beverly Walters for help in editing the manuscript, to Paul
Parizel for advice on neuroradiological items, and to Anne-Claire van
Harderwijk for administrative support. AIRM is a recipient of a NIH
grant (NS-042691) supporting methodological and clinical research in
TBI, and RMB is funded by the US Department of Defense.
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    • "Traumatic brain injury (TBI) is a major cause of death and disability in Western nations [1, 2]. Prognosis is dependent on damage that occurs at the time of the initial trauma, but also over the following days as secondary injury [3]. One potential contributing factor to secondary injury is autonomic dysfunction [4]. "
    [Show abstract] [Hide abstract] ABSTRACT: Myocardial dysfunction has been well described with catastrophic neurological events, such as subarachnoid hemorrhage and brain death. There is very limited data describing myocardial function in the context of traumatic brain injury (TBI), as no prospective study has yet examined this association. The objective of our study was to evaluate cardiac function using echocardiography in patients with clinically important TBI. We conducted a prospective observational study of consecutive TBI patients admitted to the intensive care unit. All patients older than 16 years with moderate to severe TBI according to the Glascow Coma Scale (GCS) were eligible for the study. Only patients with a prior history of heart disease or cardiomyopathy or evidence of brain death on admission were excluded. A complete transthoracic echocardiogram was performed within 4 days of admission. Forty-nine patients (67 % males, median age 34 years) were included in the study. Forty-one patients had severe TBI (84 %) with a median GCS of six, 44 patients (90 %) required mechanical ventilation and 36 (74 %) intracranial pressure monitoring. Hospital mortality was 18 %. No patients had global left ventricular dysfunction as defined by a left ventricular ejection fraction (LVEF) below 50 % (95 % CI, 0–0.07). Average LVEF was 65 +/− 4 %. Four patients (8 %) had regional wall motion abnormalities with preserved LVEF. The main finding of this study is the absence of clinically significant myocardial dysfunction in patients with moderate or severe TBI. Although myocardial dysfunction has been well described in a variety of neurological settings, it is possible that the young age of TBI patients and the absence of cardiovascular risk factors are protective against significant myocardial injury from catecholamine excess. In a group of patients with clinically important TBI, we did not identify any significant cardiac dysfunction.
    Full-text · Article · Dec 2016
    • "In the United States, approximately 1.6–3.8 million persons experience a TBI each year [4, 5]. While short-and long-term sequelae are very likely more frequent and intense in patients with a history of moderate or severe TBI than in patients with a history of mild TBI [6, 7], mild TBIs are probably 10 times more frequent than are moderate or severe TBIs [8]. While most patients seem to recover within days or weeks after the mild trauma [9][10][11][12], there is increasing evidence of persistent cognitive, psychological, physical and social dysfunction, even after mild TBI [6,[12][13][14][15]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Patients with a history of mild TBI (post-mTBI-patients) have an unexplained increase in long-term mortality which might be related to central autonomic dysregulation (CAD). We investigated whether standardized baroreflex-loading, induced by a Valsalva maneuver (VM), unveils CAD in otherwise healthy post-mTBI-patients. Methods In 29 healthy persons (31.3 ± 12.2 years; 9 women) and 25 post-mTBI-patients (35.0 ± 13.2 years, 7 women, 4–98 months post-injury), we monitored respiration (RESP), RR-intervals (RRI) and systolic blood pressure (BP) at rest and during three VMs. At rest, we calculated parameters of total autonomic modulation [RRI-coefficient-of-variation (CV), RRI-standard-deviation (RRI-SD), RRI-total-powers], of sympathetic [RRI-low-frequency-powers (LF), BP-LF-powers] and parasympathetic modulation [square-root-of-mean-squared-differences-of-successive-RRIs (RMSSD), RRI-high-frequency-powers (HF)], the index of sympatho-vagal balance (RRI LF/HF-ratios), and baroreflex sensitivity (BRS). We calculated Valsalva-ratios (VR) and times from lowest to highest RRIs after strain (VR-time) as indices of parasympathetic activation, intervals from highest systolic BP-values after strain-release to the time when systolic BP had fallen by 90 % of the differences between peak-phase-IV-BP and baseline-BP (90 %-BP-normalization-times), and velocities of BP-normalization (90 %-BP-normalization-velocities) as indices of sympathetic withdrawal. We compared patient- and control-parameters before and during VM (Mann-Whitney-U-tests or t-tests; significance: P < 0.05). Results At rest, RRI-CVs, RRI-SDs, RRI-total-powers, RRI-LF-powers, BP-LF-powers, RRI-RMSSDs, RRI-HF-powers, and BRS were lower in patients than controls. During VMs, 90 %-BP-normalization-times were longer, and 90 %-BP-normalization-velocities were lower in patients than controls (P < 0.05). Conclusions Reduced autonomic modulation at rest and delayed BP-decrease after VM-induced baroreflex-loading indicate subtle CAD with altered baroreflex adjustment to challenge. More severe autonomic challenge might trigger more prominent cardiovascular dysregulation and thus contribute to increased mortality risk in post-mTBI-patients.
    Full-text · Article · Dec 2016
    Max J. HilzMax J. HilzMao LiuMao LiuJulia KoehnJulia Koehn+1more author...[...]
    • "Although the majority (80%) of traumatic brain injuries are mild to moderate (Glasgow Coma Scale, 8–15), caution is necessary in the perioperative period for possible neurological deterioration [5,14,62]. Neurological deterioration often occurs from cerebral edema, expansion of cerebral hematoma , seizures, or posttraumatic hydrocephalus, which may lead to various manifestations including vasospasm and subarachnoid haemorrhage (Fig. 2), increased intracranial pressure, or even cerebral circulatory arrest (Fig. 3) [6,41,45]. Therefore, it is obvious that the use of TCD in trauma patients with brain injury may optimize the bedside management of the patients. "
    [Show abstract] [Hide abstract] ABSTRACT: Holistic ultrasound is a total body examination using an ultrasound device aiming to achieve immediate patient care and decision making. In the setting of trauma, it is one of the most fundamental components of care of the injured patients. Ground-breaking imaging software allows physicians to examine various organs thoroughly, recognize imaging signs early, and potentially foresee the onset or the possible outcome of certain types of injuries. Holistic ultrasound can be performed on a routine basis at the bedside of the patients, at admission and during the perioperative period. Trauma care physicians should be aware of the diagnostic and guidance benefits of ultrasound and should receive appropriate training for the optimal management of their patients.
    Article · Jul 2016
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