REVIEW

URRENT
C
OPINION

Whats new in the management of traumatic brain

injury on neuro ICU?
Dhuleep S. Wijayatilake a,b and Stephen J. Shepherd c

Purpose of review
In recent years, we have begun to better understand how to monitor the injured brain, look for less
common complications and importantly, reduce unnecessary and potentially harmful intervention. However,
the lack of consensus regarding triggers for intervention, best neuromonitoring techniques and
standardization of therapeutic approach is in need of more careful study. This review covers the most
recent evidence within this exciting and dynamic field.
Recent findings
The role of intracranial pressure monitoring has been challenged; however, it still remains a cornerstone in
the management of the severely brain-injured patient and should be used to compliment other techniques,
such as clinical examination and serial imaging.
The use of multimodal monitoring continues to be refined and it may be possible to use them to guide novel
brain resuscitation techniques, such as the use of exogenous lactate supplementation in the future.
Summary
Neurocritical care management of traumatic brain injury continues to evolve. However, it is important not
to use a one-treatment-fits-all approach, and perhaps look to use targeted therapies to individualize
treatment.
Keywords
brain injury, intracranial pressure, neuromonitoring, traumatic brain injury

INTRODUCTION

TRAUMATIC BRAIN INJURY

The timely transfer of patients to a neurosurgical

center with a dedicated neuro-intensive care unit
(NICU) in the management of brain injury is vital, a
process highlighted by high-profile cases, such as
racing driver Michael Schumacher and actress
Natasha Richardson. The role of dedicated neurointensivists in improving functional outcomes is
evolving; this review highlights key or interesting
publications over the past 2 years.

The epidemiology of traumatic brain injury (TBI) is

changing. Once primarily a disease of the young,
there is a growing representation of older victims
with additional medical problems. The incidence in
low-income and medium-income countries is
increasing with the adoption of motor vehicles
[1]. In the USA, older patients have higher outpatient costs, longer inpatient stays and significantly
higher rates of rehospitalization, particularly for
those aged 7584 years [2], but there is a general

METHODS
The OVID database and Google Scholar were used to
search for all publications with the term intensive
care, neurointensive care, neurocritical care,
NICU, NITU, brain injury or brain trauma
from January 2012 to March 2014. Searches were
limited to human adults in the English language.
After exclusion of articles not meeting these
initials, predominantly age criteria, a selection of
the most interesting or pertinent are presented
below.

a
Clinical Lead Neuro Intensive Care, Queens Hospital, Barking Havering
and Redbridge NHS Trust, London, bHonorary Senior Clinical Lecturer,
Queen Marys, University of London and cSpecialist Registrar, Anesthesia and Intensive Care Medicine, Barts and The London School of
Anesthesia, London, UK

Correspondence to Dhuleep S. Wijayatilake, Neurointensive Care Unit,

Queens Hospital, Rom Valley Way, Romford, Essex, RM7 0AG, UK.
Tel: +44 1708 503727; fax: +44 1708 503763; e-mail: sanjay.wijaya
tilake@bhrhospitals.nhs.uk
Curr Opin Anesthesiol 2014, 27:459464
DOI:10.1097/ACO.0000000000000105

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Neuroanesthesia

KEY POINTS
 Specialized neurocritical care can and does improve
patient outcomes.
 More advanced neuromonitoring techniques are
developing which allow us to better understand the
dynamics of the injured brain.
 Consensus guidelines are needed about which
intracranial pressure targets to treat and how best to
individualize therapy, thereby avoiding dangerous
overtreatment.
 Albumin appears harmful in the setting of TBI, most
likely due to deleterious effects upon intracranial
pressure.
 Early tracheostomy for non-neurological reasons does
not appear beneficial but is a well tolerated option for
those patients in whom level of consciousness is likely
to need ongoing airway protection.

trend toward better outcome across all ages in TBI.

Indeed, although mortality remains higher for elderly patients, the proportion with severe disability is
not increased, perhaps reflecting successful neurorehabilitation [3].
The role of intracranial pressure (ICP) monitoring in the assessment of TBI remains controversial.
Average ICP within the first 48 h of injury predicts
both mortality and neuropsychiatric outcome [4].
The complexity of this issue was highlighted in the
recent multicenter, randomized controlled trial
BEST-TRIP [5]. Conducted in South America, this
study compared monitoring to maintain an ICP up
to 20 mmHg with serial neurological examination
and imaging. No difference was found in survival,
consciousness, functional status or neuropsychological status at 6 months.
Although a relatively innovative design, this
study has a number of limitations. First, BEST-TRIP
was inadequately powered to detect small improvements in the minority with raised ICP. Second,
the generalizability to other developed countries
is limited. Third, mortality across the board was
high. Fourth, prehospital care was poorly developed
in these localities. Fifth, rehabilitation after discharge was not routinely available. However, the
authors did not question the value of knowing the
ICP, or its value as a guide to therapy, prognostic
indicator or research tool. Management without a
bolt has been shown to worsen outcomes [6], and
poor response to treatment predicts mortality [7].
ICP monitors are just that, not a treatment. This
study highlights how the relatively simplified model
through which we manipulate this single variable
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may not improve recovery in the wider population

and the need to adopt a more holistic, multimodal
monitoring approach.
ICP-based therapies remain the cornerstone
of the Brain Trauma Foundation guidelines for
the management of severe TBI [8]. Although well
established and evidence-based, adherence remains
nonuniform [9]. In an 8-year retrospective analysis
from the New York State there was a steady decrease
in case-fatality rate from 22 to 13% (P < 0.0001) as
guideline utilization increased [9]. ICP monitoring and adherence to cerebral perfusion pressure
treatment thresholds improved in particular and
nutritional targets were more likely to be met. The
observation that guidelines-led treatment is beneficial is not new [10].
Similarly, significant heterogeneity exists
regarding optimal surgical management. Evacuation of mass lesions may be life-saving, but timing,
technique and need for decompressive craniotomy
are not fully defined. Authors compared postsurgical course and long-term outcome of differing neurosurgical approaches at two academic centers [11 ].
This UKUSA trial found that the UK patients were
typically older but otherwise patients had similar
prognoses, lesion types and preoperative ICP. Earlier
surgery, larger craniotomy and removal of bone flap
improved outcomes. Those requiring evacuation of
subdural hematomas and contusions seemed to
benefit from decompression even when elevated
ICP was not a factor in the decision to perform a
surgery [11 ], a finding echoed elsewhere [12].
&

&

NEUROMONITORING
Despite its perceived limitations, ICP remains the
most commonly measured intracranial parameter
[13 ]. Definitive class 1 evidence is lacking but
benefit is suggested when used to guide treatment.
The US trauma centers with higher rates of ICP
monitoring demonstrated superior patient outcomes than those less likely to use it [14]. A German
study found that ICP bolts were placed in only 85%
of cases of severe TBI [15]. Technological and interpretative limitations also persist with a fundamental
lack of consensus in how to interpret this information. Although intraventricular catheters remain
the gold standard [16 ], a large North American
survey demonstrated variation in preference of
determining ICP as maximum, mode or mean and
even the transducer reference point [17]. Such a lack
of clarity is worrisome and may have contributed to
problematic data validity in multicenter trials; this
must be urgently addressed. The one-size-fits-all
approach to ICP triggers is also blunt. It is entirely
plausible that the apparently disappointing results
&&

&

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Neuro ICU management of TBI: whats new? Wijayatilake and Shepherd

from Decompressive Craniectomy Trial reflect a

distinctly nonphysiologic clinical provocation
[18]. Recent Scandinavian evidence suggested for
patients with only mildly elevated ICP outcome
was not worse [19]. Indeed, overtreatment is not
trivial and a functional or perfusion-guided paradigm may shift us from overreliance on pressure.
Intraparenchymal monitors are well tolerated
than intraventricular but can in certain conditions
be imprecise through zero drift, and still require an
invasive procedure. The incidence of baseline errors
is not insignificant: in a study within subarachnoid
hemorrhage, two separate but identical-type straingauge sensors were placed in the same burr hole [20].
Baseline errors were detected in over 50% of
patients, being 25 mmHg in a median of 34% of
observations. Major differences in mean ICP
between the sensors were observed in 44% [20].
The potential clinical consequences of this are significant. Even between invasive modalities, correlation is lacking even in the same patient [21]. When
extra-ventricular drains are used, we are unclear
whether constant opening to allow continuous cerebrospinal fluid (CSF) drainage or intermittent only
in response to increased ICP is the best. The latter
allows continuous ICP measurement and the former
may allow tighter ICP control. This was ratified by a
cohort study with a significant (average 5.6 mmHg)
difference in mean ICP for the open group but
similar survival and 6-month Glasgow Outcome
score [22 ].
Cortical spreading depolarizations are waves
of sustained neuronal activity originating spontaneously and propagating across the cortex in
response to structural or ischemic injury [23]. They
are characterized on electrocorticography by large,
negative and slow potential change followed by
silencing of electrical activity and are associated
with poor outcome in TBI [24]. Spreading depolarizations have been directly measured in brain parenchyma using cortical and depth electrode arrays
inserted at craniotomy [25 ]. In the future, it may
be possible to introduce an electrode array via a
burr hole.
Invasiveness is a flaw of many neuromonitoring
modalities and an accurate, noninvasive method
is desirable. Computed tomography (CT) and MRI
can provide some assessment, but the utility of
transcranial Doppler, power electrocorticography
analysis and ophthalmological-based methods is
increasing [16 ] with issues of interobserver variability reduced by using the same technician. Combination neuromonitoring may yield the most
benefits. A recent systematic review suggested that
the addition of brain tissue oxygen (PbtO2)-guided
therapy to ICP may provide better functional
&

&&

&

outcomes [26]. Individualization of ICP targets

has theoretical benefits but has not yet been subject
to a true randomized trial. Cerebrovascular pressure
reactivity index technology examines for cerebral
autoregulation in just this way, and a recent small
study showed a strong link with the brains ability to
control for its extracellular oxygen content [27].
This technology may identify those who would
benefit from hyperoxia treatment.

OSMOTHERAPY
Administration of osmotic agents to reduce ICP is
frequently used yet hard evidence is lacking. Physician and institutional variation in therapeutic
practice and a lack of standardized protocols and
indications mean that most data are derived from
retrospective and case series [28]. Traditionally,
mannitol has been used. It is well tolerated and
effective, but its mechanism of action remains
unclear; it may reduce blood volume, brain water
or both. This former theory has been disproved by a
small PET CT study in which a single bolus of 1 g/kg
20% mannitol did not alter cerebral blood volume
significantly [29]. A single bolus dose of 14.6 or
23.4% hypertonic saline is an alternative, but many
centers lack experience and few published studies
have evaluated the safety of repeated bolusing. A
retrospective review demonstrated repeated administration to be safe without increased incidence
of demyelination, although there was a marked
increase in serum sodium concentration [30]. The
optimal dose, method of administration and superiority to mannitol remains unclear [28,31,32].
Indeed, the efficacy of routine osmotherapy is questionable [31]. Rebound intracranial hypertension is
a significant concern with all agents [33] and their
role undoubtedly is as a rescue measure pending
definitive (usually surgical) treatment.

INTRACEREBRAL BLEEDING
Both primary and traumatic intracerebral bleeds
remain a common indication for intensive care
admission, although outside aneurysm-associated
etiologies therapeutic option was perhaps until
relatively recently more limited. Traditionally,
standard practice for isolated traumatic subarachnoid hemorrhage includes neurosurgical consultation which may involve tertiary trauma center
transfer. However, a cross-sectional study of patients
with isolated traumatic subarachnoid hemorrhage
demonstrated a low risk of deterioration [34].
Although traditionally associated with aneurysmal
subarachnoid hemorrhage, cerebral vasospasm
may be a significant contributor to mortality in

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Neuroanesthesia

traumatic disease, with an incidence proportional to

the severity of TBI [35]. However other researchers
argue that the association of angiographic vasospasm
which is sometimes seen in patients with traumatic
sub arachnoid haemorhage and neurological deficits
is poorly understood and may be associative rather
than causative [36]. Cerebral ischemia often involves
more than one arterial territory with both microthrombosis and impaired autoregulation contributing to the clinical picture [37].
Magnesium may be protective in vasospasm by
modulating vascular reactivity and inhibiting Nmethyl-D-aspartate-glutamate receptors and voltage-dependent calcium channels. Trials of magnesium in aneurysmal subarachnoid hemorrhage have
failed to affect mortality or neurological outcome
[38]. However, the neuroprotective effects of magnesium rely on adequate CSF concentration which is
limited by systemic toxicity before these levels are
reached. Intracisternal administration offers an
alternative [39,40]. Supplementation may also be
significantly delayed after the initial ictus by up
to 3040 h in most trials; more rapid administration
may be beneficial.

BRAIN RESUSCITATION
Goal-directed resuscitation is an emerging field [41].
Post-hoc analysis of the 2004 Saline versus Albumin
Fluid Evaluation study previously demonstrated an
increased mortality for TBI patients resuscitated
with albumin rather than 0.9% saline [42]. The
mechanism behind this was unclear, but a significant increase in mean ICP and subsequent deaths in
patients who received albumin coupled with higher
sedative and vasopressor requirements, presumably
suggest that this effect is due to increasing ICP [43].
PbtO2 or lactate-guided resuscitation is increasingly popular, but again targets remain controversial [44]. Exogenous lactate supplementation may
offer a potential therapeutic option. Preferential
aerobic utilization of this substrate is seen in injured
brain tissue; in a small pilot study, hypertonic
sodium lactate was administered to increase arterial
lactate to supraphysiological levels subsequently
improved PbtO2 with a reduction in ICP [45 ].
Adopting this approach may provide positive effects
on brain energy metabolism although avoiding the
complications of commonly used fluids, such as
0.9% sodium chloride [46].
&

EARLY TRACHEOSTOMY
Many ICU patients require tracheostomy for reasons
not least of which is to facilitate ventilatory weaning. Patients admitted to NICU are more likely to
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undergo tracheostomy than general ICU patients

[47]. The TracMan trial suggested no benefit to early
rather than late tracheostomy [48]. However,
patients with chronic neurological conditions were
excluded and although no difference was demonstrated in the duration of mechanical ventilation or
mortality, of those randomized to late tracheostomy
only 45% still required the procedure at 10 days.
Although those with acute intracranial lesions or
peripheral neuromuscular disorders were included,
they were the minority. Most patients underwent
tracheostomy for pulmonary reasons which may
show more rapid reversal.
The SETPOINT study examined this in more
detail. Sixty patients with severe stroke predicted
to require ventilation for more than 2 weeks underwent tracheostomy within 13 days rather than
standard practice of 714 days [49]. Both ICU and
6-month mortality were lower in the early group
alongside the requirement for sedatives which was
postulated to account for much of this effect. A
larger retrospective analysis of TBI patients similarly
suggested that tracheostomy within 7 days reduced
length of stay and increased the likelihood of functional independence [50]. These factors involved a
Rey complex, not least including predicted survival
but this database is large, covering a 15-year period.

PROGNOSTICATION
Predicting survival from cerebral injury remains
challenging yet a frequently sought after role for
the neurointensivist.

Biomarkers
A number of biomarkers, including S110B, neuronspecific enolase and myelin basic protein, have been
proposed as potentially prognostic but proven disappointing with only ubiquitin carboxyl-terminal
hydroxylase L1 deemed worthy of further study
[51]. Nitric oxide may have both protective and
damaging effects in the injured brain and its metabolites have shown promising early results as prognostic indicators [52,53]. Glucose management also
remains of relevance, whereas hyperglycemia is
associated with poor outcomes, tight glycemic
control offers little benefit [54,55]. Microdialysis
studies have corroborated the attendant risk of hypoglycemia with intensive insulin therapy [56,57]. A
brain: serum glucose ratio less than 0.12 predicts
cerebral metabolic distress and mortality after severe
TBI [58].

Imaging
No single-imaging technique ideally suits the role of
prognostication. In a Dutch study of 605 patients,
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Neuro ICU management of TBI: whats new? Wijayatilake and Shepherd

the aspect of the ambient cisterns on CT predicted

death in TBI but disability in survivors [59]. The
utility of MRI is improved with more advanced
diffusion tensor techniques [60] and identification
of brainstem lesions strongly predicts poor outcome
[61].

Genetic predisposition
ATP-binding cassette transporters are important
mediators of bloodbrain barrier solute transport.
A variety of polymorphisms (ABCB1, ABCC1 and
ABCC2) exist which impact the bioavailability of
both drugs and endogenous substrates in the brain
[62]. Patients homozygous for the T allele of ABCB1
or the G allele of ABCC1 appear to have better
outcomes after severe TBI [63]. Further work is
required to move this outside the experiment.

Ethical considerations
Policies on withdrawal of care vary greatly. In an
extremely thought-provoking study, factors contributing to variability in outcome prognostication in
moderate to severe TBI were examined [64 ]. Treatment withdrawal was the major determinant of inhospital mortality, negating all other predictors.
Patients in whom withdrawal was more likely
included those with included coagulopathy on
admission, cardiac arrest on NICU, brain herniation
and ICP crisis. Significant interhospital and interspecialty variation was seen; clinical nihilism is an
important entity and the role of the multidisciplinary team in discussions of withdrawal remains
paramount.
&&

CONCLUSION
Excellence in NICU improves life after neurological
injury, perhaps more relevant than crude mortality.
Our patients are older with increasingly complex
requirements yet outcomes are improving. We still
suffer from a lack of consensus in which monitors to
use, how to standardize their interpretation, when
to intervene upon the information they provide
and when not to. Translation of what we are coming
to know as a good practice on paper into good
practice at the bedside is essential if we are to continue to gain good outcomes for those who can
benefit.
Acknowledgements
None.
Conflicts of interest
There are no conflicts of interest.

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&
of special interest
&& of outstanding interest
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&&

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&&
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Excellent article examining the potentially inbuilt nihilism seen within NICU.
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Volume 27  Number 5  October 2014

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