Ventilatory strategies for patients with acute brain injury

Neil Younga, Jonathan K.J. Rhodesa, Luciana Masciab and Peter J.D. Andrewsa
a
Department of Anaesthesia, Critical Care and Pain
Medicine, University of Edinburgh, Edinburgh, UK and
b
Dipartimento di Anestesiologia e Rianimazione,
Università di Torino, Ospedale S. Giovanni Battista,
Torino, Italy
Correspondence to Professor Peter J.D. Andrews,
Western General Hospital, Crewe Road South,
Edinburgh EH4 2XU, UK
Tel: +44 131 5371666; fax: +44 131 5371021;
e-mail: p.andrews@ed.ac.uk
Current Opinion in Critical Care 2010,
16:45–52
Purpose of review
The ventilation of patients with acute brain injuries can present significant challenges.
Frequently, guidelines recommending management strategies for patients with
traumatic brain injuries come into conflict with what is now considered best ventilatory
practice. In this review, we will explore many of these areas of conflict.
Recent findings
The use of ventilatory strategies to control partial pressure of carbon dioxide in patients
with traumatic brain injury is associated with the development of acute lung injury.
Analysis of the International Mission for Prognosis And Clinical Trial (IMPACT) database
has confirmed the association between hypoxia and poor neurological outcome.
Although a recent meta-analysis has suggested a survival benefit for steroids in acute
lung injury, the use of steroids has been associated with a worsening of outcome in
patients with traumatic brain injuries and their effects on the brain have not been fully
elucidated.
Summary
There are unlikely to be randomized controlled trials advising how best to ventilate
patients with acute brain injuries because of the heterogeneous nature of such injuries.
Hypoxia should be avoided. The more widespread use of multimodal brain monitoring,
including brain tissue oxygen and cerebral blood flow monitoring, may allow clinicians to
tolerate a higher arterial partial pressure of carbon dioxide than has been traditional,
allowing a less injurious ventilatory strategy. Modest positive end-expiratory pressure
can be used. In severe respiratory failure, most ‘rescue’ strategies have been attempted
in patients with acute brain injuries. Choice of rescue therapy at present is best decided
on a case-by-case basis in conjunction with local expertise.

Keywords
acute brain injury, acute lung injury, acute respiratory distress syndrome, traumatic
brain injury

Curr Opin Crit Care 16:45–52

ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
1070-5295

monary contusions, neurogenic pulmonary oedema and

Introduction
In the absence of a pharmaceutical agent with proven
neuroresuscitative efficacy, the central goal in the man-
agement of a patient with traumatic brain injury (TBI)
becomes the prevention of hypoxic secondary insults
through the maintenance of an adequate cerebral per-
fusion pressure (CPP) and cerebral oxygen delivery. A
number of evidence-based recommendations have been
published by the Brain Trauma Foundation [1], which
include the treatment and prevention of hypoxic hypoxia,
maintenance of CPP above 60 mmHg and avoidance of
intracranial pressure (ICP) above 20 mmHg wherever
possible. Standard practice is tracheal intubation and
mechanical ventilation of all coma-inducing head inju-
ries, and of many patients with TBI who cannot obey
commands. The achievement of good oxygenation and
low normal PaCO significantly contributes to ICP control,
2
and these are considered ‘first-stage’ therapies. However,
achieving these goals in a patient with aspiration, pul-
1070-5295 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
developing an acute lung injury (ALI) can often be in
conflict with lung protective ventilatory strategies that
are now considered best practice for mechanical venti-
lation in the critically ill.
Maintenance of adequate CPP (>60 mmHg), jugular
bulb saturations (>50%) or brain tissue oxygen tension
(>15 mmHg), in order to optimize cerebral oxygen deliv-
ery, frequently requires support of arterial blood pressure
(BP). However, in patients with TBI, such support with
crystalloid loading and vasopressors is associated with an
increased incidence of the acute respiratory distress syn-
drome (ARDS) [2,3]. It is again clear that a conflict exists
between maintaining cerebral oxygenation and lung
protection.
In this review, we will explore what we consider standard
best practice in the ventilatory management of patients
with TBI, concentrating on those areas in which a conflict
DOI:10.1097/MCC.0b013e32833546fa

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 46 Respiratory system
exists. We will also explore the evidence for techniques,
which at present are used for ‘rescue’ in ARDS, with
regard to patients with TBI. Owing to the heterogeneity
of patients with TBI and ALI/ARDS, it is very unlikely
that double-blind randomized control trials will be
possible that can conclusively demonstrate how best to
manage ARDS in patients with TBI. Clinicians will have
to base care decisions on expert opinion, experience and
the best compromise we can achieve.
Ventilatory goals
In this section of the review, we will discuss what we
consider to be best practice in terms of oxygenation goals,
and targets for the arterial partial pressure of carbon
dioxide in the patient with TBI and an emerging ALI.
We will also discuss what we consider to be best use of
positive end-expiratory pressure (PEEP) in the brain-
injured patient.
Oxygenation
Hypoxaemia has long been identified as a significant
secondary insult following TBI, associated with poor
outcome [4–6]. This has been confirmed more recently
by the analysis of the IMPACT study database, a merged
cohort of more than 9000 patients with TBI recruited to
randomized controlled trials and series dating back to the
1980s [7]. Arterial hypoxaemia will result in a double
effect: as well as decreased cerebral oxygen delivery,
cerebral vasodilatation will occur, resulting in an increase
in ICP and reduction in CPP. Although the inflection
point for cerebral vasodilatation is classically taught as
50 mmHg, these data are based on animal research. A
transcranial Doppler study [8] in healthy human volun-
teers found the inflection point to be 58 mmHg or an S pO
2
of 90%. Cognitive impairment following ARDS has been
shown to correlate with worsening hypoxia [9]. The
ARDSnet ventilation protocol [10] suggests a target
PaO of 55–80 mmHg or S pO of 88–95%. The Brain
2 2
Trauma Foundation guidelines [1] recommend avoid-
ance of hypoxia (PaO < 60 mmHg), Addenbrooke’s
2
neurocritical care unit protocol [11] recommends a
PaO more than 11 kPa (82.5 mmHg) and the UK Transfer
2
guidelines [12] for patients with TBI recommend a PaO
2
more than 13 kPa (97.5 mmHg). We would recommend
that normoxia should be maintained wherever possible in
patients with TBI, and hypoxia be avoided at all costs.
The ARDSnet target PaO2 of 55–80 mmHg would
seem to be too low to be safely applied to patients
with TBI.
Tidal volume and PaCO
2
In 2000, the ARDSnet trial [13] found a decreased
mortality and increased number of days without venti-
lator use in patients with ALI or ARDS, who were
mechanically ventilated with a lower tidal volume
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
(6 ml/kg) than was traditional. The patients in the low
tidal volume group had a higher mean PaCO (44 mmHg at
2
day 7) than those in the traditional group (40 mmHg at
day 7). Grubb et al. [14] demonstrated that cerebral blood
volume is linearly related to PaCO . In patients with TBI,
2
who have low intracranial compliance, it is standard
practice to ventilate to low normocapnia (e.g. 31–
34 mmHg). If ICP control is not achieved then hyper-
ventilation to a PaCO below 31 mmHg may be instituted.
2
This reduction in PaCO will cause cerebral vasoconstric-
2
tion, reducing cerebral blood volume and ICP. This may
have a deleterious effect on cerebral blood flow (CBF)
and should not be instituted without monitoring of the
jugular venous bulb oxygen saturation, partial pressure of
brain tissue oxygen or CBF. Although most patients
with TBI will be managed with a PaCO in the low normal
2
range rather than hyperventilation, even this may be a
challenge in the patient with ALI or ARDS. When ARDS
and severe TBI coexist, a balance will have to be struck
between CO2 control and lung protection on a case-
by-case basis. Multimodal brain monitoring such as
the parenchymal oxygen electrode or microdialysis
may allow clinicians to tolerate a higher PaCO than has
2
been traditional if cerebral metabolism appears to remain
intact. Alternatively rescue therapies for improving both
gas exchange and intracranial compliance may have to be
considered at a relatively early stage.
Aside from the difficulties of controlling PaCO with lung
2
protective ventilation, it should be noted that high tidal
volume ventilation in patients with TBI has been associ-
ated with the development of ARDS [15]. What this
observation cannot tell us is whether patients receiving
high tidal volumes to achieve PaCO control develop
2
ARDS as a consequence of this strategy, or whether they
required higher tidal volumes to control their PaCO2
because they were already developing an ALI.
Positive end-expiratory pressure
The use of PEEP has been considered controversial in
the management of patients with TBI. A raised mean
intrathoracic pressure might reduce cerebral venous
return and so increase ICP. However, McGuire et al.
[16] found that provided the PEEP was less than the
ICP then the associated rise in intrathoracic pressure did
not result in an increase in ICP. Observational studies in
patients with acute stroke [17] and subarachnoid haemor-
rhage [18] have found that higher levels of PEEP were
associated with a decrease in CPP, and when autoregula-
tion was impaired, a decrease in CBF. However, the
reduction in CPP occurred with the PEEP-dependent
decrease in mean arterial BP (MAP) rather than an
increase in ICP. When the MAP was restored, the
CPP and CBF returned to baseline [18]. Thus, like
the study by McGuire et al. [16], ICP was not affected
in a clinically important manner by the application of

increased PEEP [17,18]. Furthermore, following TBI,
Huynh et al. [19] found that increasing PEEP from 0–5 to
11–15 cmH2O resulted in a decrease in ICP and an
increase in CPP. It has also been postulated that by
increasing venous pressure it might be possible to re-
recruit collapsed cerebrovasculature; however, at present,
this is conjecture and has not been studied clinically or in
the laboratory [20].
Mascia et al. [21] found that when increased PEEP was
applied to brain-injured patients with ALI, there was a
difference in the effects on ICP, depending on whether
the application of PEEP caused alveolar hyperinflation or
alveolar recruitment. If PEEP induces alveolar recruit-
ment, we may expect a reduction in PaCO , with a
2
decrease in ICP. In those patients in whom alveolar
hyperinflation occurred, there was an increase in PaCO ,
2
with a concurrent increase in ICP. In contrast, in those
patients in whom alveolar recruitment occurred, while
the predominant effect was an improvement in oxygen-
ation, there was a decrease in PaCO due to reduction in
2
dead space and no significant change in ICP occurred.
Uncertainty as to the optimal level of PEEP for the
management of ARDS is long standing. An ARDSnet
study [22] in 2004 found no benefit of an increased PEEP
strategy when compared with the standard ARDSnet
ventilation protocol [10]. Therefore, at present, it seems
that the use of PEEP to treat ARDS may be appropriate
in the patient with TBI, provided that MAP is maintained
and close attention given to ICP and CPP as changes are
made. In the absence of evidence for increasing PEEP
above the levels used in the ARDSnet study, it would also
seem wise to recommend that the minimum PEEP
necessary for an individual patient should be determined.
Adjuvant therapies and rescue strategies
We will now discuss the options for adjuvant therapies
and rescue strategies for the patient with TBI and an ALI.
There is little in terms of evidence from randomized
control trials as to how these strategies are best applied to
patients with TBI.
Steroids
The use of steroids in ARDS remains controversial and is
by no means universal. In 1998, Meduri et al. [23] pub-
lished a report describing a large reduction in mortality
when methylprednisolone was used to treat unresolving
ARDS. More recently, the same group [24] reported that
the early use of steroid was associated with significant
improvement in lung function and decreased ICU
mortality. In a post-hoc analysis of data from Annane
et al.’s [25] study of the use of steroids to treat septic
shock, it was suggested that the reduction in mortality
with steroid treatment was actually in the subgroup of
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ventilatory strategies for acute brain injury Young et al. 47
patients with septic shock and ARDS [26]. However, an
ARDSnet randomized control trial [27] in 2006 was less
supportive of the use of steroids to treat persistent ARDS.
There was no overall change in mortality in patients
receiving methylprednisolone for ARDS, although a tre-
nd towards decreased mortality in those patients who had
steroid commenced on days 7–13, contrasting with those
commencing steroid from day 14 onwards, when there
was a significant increase in mortality. However, over the
7 years of this study, low tidal volume ventilation was
introduced which by modulating the inflammatory
response in the lung may have confounded the outcome
of this study by reducing the potential for benefit in the
steroid treated group. Meta-analyses of corticosteroids
in the treatment of ARDS have produced conflicting
results, with the most recent meta-analysis finding a
survival benefit [28], in contrast to previous meta-
analyses [29,30] that did not find a benefit in terms
of long-term survival. Although much expert opinion
remains in their favour [31,32], the use of corticosteroids
for ARDS is not likely to be adopted by all critical care
physicians until an adequately powered randomized trial
is conducted.
For patients with TBI, there has been a similar long
interest in the use of steroids to modulate the disease
process. As anti-inflammatory agents, they offer the
potential to modulate early inflammatory events occur-
ring after central nervous system injury [33], and early
administration in models of brain trauma has shown some
benefit in the experimental setting [34,35]. However, in
clinical practice, benefit has not been demonstrated. The
corticosteroid randomization after significant head injury
trial [36] studied over 10 000 patients with TBI and was
the largest trial of steroid use in TBI to date. Rather than
a benefit, it found an excess of mortality in those patients
treated with methylprednisolone. The treatment regime
with methylprednisolone was based on that used in
studies of spinal cord trauma [37,38], which demonstrated
benefit by subgroup analysis and multiple comparisons of
secondary endpoints. Doubt has, therefore, been cast on
the validity of these results [39]. Furthermore, the dose of
steroid approximated to 10 g/patient/day, which is orders
of magnitude greater than that used in ARDS treatment
paradigms. The actions of steroids on the brain are very
specific. Certain populations of neurones can be harmed
by elevated steroid levels [40], potentially protective
neurotrophic factors may be reduced [41] and the vulner-
ability of neurones to concurrent insults such as hypoxia
increased [42]. Furthermore, the inhibitory effect of
steroids on inflammatory mediator expression may not
be universal [43]. Finally, the timing of this inhibition
may also be crucial as, for example, the acute antagonism
of tumour necrosis factor alpha (TNFa) following experi-
mental TBI can reduce the injury severity [44], but
in animals chronically deficient in TNF, there is less
 48 Respiratory system
recovery of function over weeks following injury [45].
This would imply a dual role for TNFa, not only acute
expression being harmful but also a possible role in
resolution of inflammation or repair. These observations
made in experimental animals have not been completely
verified in the clinical setting. It is, therefore, unlikely
that sufficient understandings of the optimal timing,
dose, duration or therapeutic endpoints of steroid treat-
ment are known. It is, therefore, reasonable that as the
Brain Trauma Foundation [1] surmised: ‘there is little
enthusiasm for re-examining the use of existing formu-
lations of steroids for treatment of patients with TBI’. At
present, when the evidence for steroid use in ARDS
remains controversial, they have been associated with
increased mortality in TBI, and pharmacological under-
standing is incomplete, it would seem prudent to avoid
steroid use in patients with TBI when possible.
Prone positioning
Prone ventilation is known to improve the PaO2 /FiO ratio
2
[46] in ARDS but not to improve mortality, although a
recent study [47] that proned patients for a more pro-
longed period (mean of 17 h for 10 days) demonstrated a
nonstatistically significant decrease in mortality from 58
to 43%. It may be that future larger studies demonstrate a
survival benefit. Despite the unproven survival benefit,
few critical care physicians would allow a patient with
ARDS to die of hypoxaemia without attempting a trial of
prone ventilation.
In the patient with TBI, there are concerns over effects of
prone position on ICP, and practicalities, such as risk of
displacement of ICP bolt, intracranial drains and diffi-
culty of EEG monitoring to consider. Thelandersson et al.
[48] showed no adverse effect on ICP of prone position-
ing in neuro-ICU patients in contrast to Beuret et al. [49]
who found that prone positioning caused a significant
increase in ICP. In both groups, there was an improve-
ment in respiratory mechanics with prone positioning.
There is no clear evidence to aid the physician when
deciding whether or not to prone a patient when ARDS
and TBI coexist. It does not seem unreasonable to
attempt prone ventilation in patients with severe ARDS
and TBI when hypoxaemia is a concern. The effects of
this intervention on ICP should then be observed in real
time, with additional treatments for raised ICP or alterna-
tive ventilatory strategies sought if ICP control becomes
problematic. Increasing local pressure may compromise
the vulnerable pericontusional perumbra, we would not
advocate this strategy in patients with significant frontal
injuries.
Nitric oxide
In numerous studies [50–53], nitric oxide has been shown
to improve oxygenation, but there have never been any
convincing data that patient outcome and mortality are
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
improved. These findings are supported by a meta-
analysis [54]. Recent work [55] has demonstrated anti-
inflammatory effects of inhaled nitric oxide beyond the
respiratory system, and it has been hypothesized that
inhaled nitric oxide may be of benefit when TBI and
ARDS coexist. However, like the duplicity of TNFa
function after TBI, the role of nitric oxide after cerebral
injury appears to be complex. Acutely, nitric oxide
released from infiltrating leucocytes or the activation of
inducible nitric oxide synthase has been regarded as
important secondary injury mechanisms, contributing,
for example, to the accumulation of free radicals. Later
nitric oxide appears to be protective and has been associ-
ated with reduced neuronal loss and improved cognitive
functioning. This may be due to improving CBF [56].
High-frequency ventilation
High-frequency ventilation utilizes very high respiratory
rates in combination with tidal volumes, which are below
that of the anatomical dead space. It has been postulated
that this may reduce ventilator-associated lung injury and
barotrauma in patients with ARDS. High-frequency
ventilation has been shown to improve oxygenation in
adult patients with ARDS [57,58], but the use of this
modality in adults is still relatively new. There is more
than 20 years of experience of high-frequency ventilation
in neonatal and paediatric intensive care. Early trials of
high-frequency ventilation in adults utilized settings
which were tried and tested in children; it seems that,
at present, we are still in a position of finding the optimal
‘dose’ for high-frequency ventilation in adults [59,60].
Until a randomized controlled trial compares high-fre-
quency ventilation with conventional low-volume venti-
lation, as used in the ARDSnet trials, high-frequency
ventilation will remain a rescue strategy.
Although experience with high-frequency ventilation in
TBI is limited, retrospective studies [61,62] to date have
found an improvement in oxygenation, without unma-
nageable changes in ICP. One retrospective study [63],
which looked at high-frequency percussive ventilation,
found a decrease in ICP when this was instituted,
possibly as a result of improved gas exchange. Although
the numbers studied to date are small, it would seem that
high-frequency ventilation should be considered as a
rescue strategy in patients with TBI and ARDS. High-
frequency ventilation has been shown to decrease cardiac
output and increase central venous pressure [58], and a
concurrent increase in ICP or decrease in MAP or CPP
would have to be closely monitored and rectified as
necessary. PaCO2 should be frequently or continuously
monitored at the institution of high-frequency venti-
lation. As end-tidal CO2 measurement is not compatible
with high-frequency ventilation modes, transcutaneous
CO2 measurement might have a useful role in the min-
ute-to-minute monitoring of CO2 trends [64].

Arteriovenous extracorporeal membrane CO2 removal
Using arteriovenous extracorporeal membrane CO2
removal (AV-ECCO2R) has the attraction in the treat-
ment of ARDS of allowing CO2 removal without having
to increase the minute volume. This would allow a given
CO2 level to be reached with a less injurious ventilatory
strategy. Evidence from randomized controlled trials is
lacking. The largest case series published to date [65], of
90 patients, demonstrated improvement in oxygenation
and reduction in PaCO , allowing less aggressive venti-
2
lation, with the use of AV-ECCO2R. There has been a
small case series [66] published describing the use of AV-
ECCO2R in five patients with TBI. In all patients, PaO /
2
FiO ratios improved and PaCO decreased; in some, there
2 2
was a concurrent decrease in ICP. The authors reported
no bleeding complications, although one patient devel-
oped an ischaemic leg after removal of the arterial canula,
which resolved with stenting. At present, great caution is
advised if considering embarking upon AV-ECCO2R in a
patient with TBI; while the doses of anticoagulant are
lower than would be used for extracorporeal membrane
oxygenation (ECMO), for example, 200–600 IU heparin
per hour to achieve activated partial thromboplastin time
of 50–60 s, this is not insignificant. Concern must be
expressed regarding the risk of intracranial bleeding. In
the case series of patients with TBI, the authors used a
lower dose of heparin (100–300 IU/h) to achieve an
activated clotting time (ACT) of 130–150 s [66]. This
system can be run without additional heparin, as the
components are heparin bonded, although the CO2
exchanger will need to be replaced more frequently
(personal communication, Inspiration-Healthcare for
Novalung). An alternative, pumped, veno-veno system
is in development, although heparin is still required [67].
Extracorporeal membrane oxygenation
The first international presentation of the results of the
Conventional ventilation or ECMO for Severe Adult
Respiratory failure trial occurred in February 2008 [68].
Fifty-seven of 90 patients in the ECMO group met the
primary endpoint of survival and absence of severe dis-
ability at 6 months as compared with 41 of 87 evaluable
patients in the conventional ventilation group, giving a
relative risk in favour of the ECMO group of 0.69 (95%
confidence interval 0.05–0.97). However, it is of note that
22 patients in the ECMO group did not receive ECMO
because they improved without it, and that it took 5 years
to recruit 180 patients. There are case reports of ECMO
being used in patients with TBI who have undergone
concurrent [69] and recent [70] craniotomy, with sub-
sequent good neurological outcome. In the latter of these
case reports, the patient did not undergo systemic hepar-
inization at institution of ECMO, and heparin-bonded
circuitry was utilized. At present, ECMO is only available
in a limited number of centres and experience of its use in
patients with TBI is very small. For patients with TBI,
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Ventilatory strategies for acute brain injury Young et al. 49
ECMO is likely to remain a rescue strategy, used in the
direst of clinical situations by those experienced in its use.
Hypothermia
Hypothermia has an inherent appeal in both the manage-
ment of TBI and ARDS: being able to reduce oxygen
consumption with a parallel decrease in CO2 production
should allow brain oxygen delivery and PaCO targets to
2
be met with a less injurious ventilatory strategy. There is
some evidence that mild hypothermia can inhibit the
adhesion, activation and accumulation of neutrophils
during the acute phase of acid-induced lung injury in
rats [71]. It could, therefore, be hypothesized that mild
hypothermia may have the potential to reduce inflam-
mation in ARDS. A very small study [72], of 19 patients,
demonstrated improved survival in patients with ARDS
treated with hypothermia.
The largest prospective randomized control trial [73]
published to date in 2001 found no improvement in
outcome or mortality in patients with TBI treated with
therapeutic hypothermia. A large number of studies
have been conducted and several meta-analyses [74–
77] published, which demonstrate improved outcomes
or reduced mortality when hypothermia is used. How-
ever, when studies [75,76] are selected on the basis of
methodological quality, such as baseline compatibility or
allocation concealment, these benefits are lost. It may be
that mortality benefit requires cooling for more than 48 h
[74,77,78]. Furthermore, hypothermia is not without its
concerns, particularly, those of the increased risk of sepsis
or cardiovascular instability. Therefore, seeking evidence
of efficacy is justified. Hopefully the ongoing North
American Brain Injury Study: Hypothermia IIR [79]
and the Eurotherm3235 trial [80] will go some way
towards establishing the role of hypothermia in TBI,
and perhaps ARDS.
Surgical options to improve intracranial compliance
These include evacuation of haematoma, contusionect-
omy and decompressive craniectomy. When ICP cannot
be controlled through medical management or when
medical management might aggravate iatrogenic compli-
cations, such as ARDS, surgical options should be con-
sidered. A recent pooled analysis [81] of decompressive
craniectomy in patients with malignant middle cerebral
artery infarction has shown promising results in decreasing
mortality and poor functional outcome. There are cur-
rently two randomized trials [82,83] assessing the efficacy
of decompressive craniectomy after TBI, which will hope-
fully help further define the indications for this operation.
However, the transfer and care of patients with ARDS
requiring this major surgical procedure is not without its
risks. If of proven benefit, it may be that decompression
should be considered earlier in the patient with TBI
and developing ARDS. Conversely, compared with
 50 Respiratory system
non-ARDS patients, these may be the subgroup in which
the balance of risks is in favour of surgery.
Conclusion
A compromise will frequently be required when attempt-
ing to provide what is considered best ventilatory practice
in the management of patients with TBI; there are
unlikely to be randomized controlled trials to inform
such decisions. At present, we would stress the avoidance
of any hypoxia in patients with TBI. Multimodal brain
monitoring, including brain tissue oxygen tension, CBF
measurement and the further development of intra-
cerebral microdialysis (measuring lactate, pyruvate,
glutamate, glycerol and inflammatory mediators), may
allow clinicians to tolerate a higher PaCO than has been
2 impaired health status in survivors of severe acute respiratory distress
traditional, allowing a less injurious ventilatory strategy.
The use of modest PEEP seems appropriate, as long as it
is less than ICP and any concurrent decrease in MAP is
treated. At present, steroids should be avoided when
possible in patients with TBI.
With regard to rescue therapies, high-frequency venti-
lation can be considered, but with close monitoring of
PaCO and ICP; prone positioning is possible, provided
2
the cervical spine has been ‘cleared’ (as much as this is
possible in an unconscious patient with TBI, but includ-
ing reconstructed thin slice computed tomography), with
constant monitoring of ICP and great care to avoid dis-
placement of any intracerebral device(s). More research
into the effects of prone ventilation and high-frequency
ventilation on ICP and CBF would be helpful. The use of
inhaled nitric oxide may have additional beneficial
effects beyond the respiratory system, making it a useful
drug when ARDS and TBI coexist, more research in this
area would be of benefit. We advise against using any
extracorporeal device requiring systemic anticoagulation
in patients with acute TBI at present, although it is noted
that a very small case series of TBI patients had no
intracranial bleeding complications with ACT in the
range of 130–150 s [65]. Hypothermia could theoretically
be of benefit in TBI and ARDS. The Eurotherm3235 trial
will address the issue of hypothermia in TBI.
At present when TBI and ARDS coexist, we will need to
be guided by expert opinion, clinical acumen and com-
promise.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
 of special interest
 of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 78).
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