REVIEW

C URRENT
OPINION Ventilatory targets following brain injury
Shaurya Taran a,b, Sarah Wahlster c,d,e and Chiara Robba f,g

Purpose of review
Recent studies have focused on identifying optimal targets and strategies of mechanical ventilation in
patients with acute brain injury (ABI). The present review will summarize these findings and provide
practical guidance to titrate ventilatory settings at the bedside, with a focus on managing potential brain-
lung conflicts.
Recent findings
Physiologic studies have elucidated the impact of low tidal volume ventilation and varying levels of positive
end expiratory pressure on intracranial pressure and cerebral perfusion. Epidemiologic studies have
reported the association of different thresholds of tidal volume, plateau pressure, driving pressure,
mechanical power, and arterial oxygen and carbon dioxide concentrations with mortality and neurologic
outcomes in patients with ABI. The data collectively make clear that injurious ventilation in this population is
associated with worse outcomes; however, optimal ventilatory targets remain poorly defined.
Summary
Although direct data to guide mechanical ventilation in brain-injured patients is accumulating, the current
evidence base remains limited. Ventilatory considerations in this population should be extrapolated from
high-quality evidence in patients without brain injury -- keeping in mind relevant effects on intracranial
pressure and cerebral perfusion in patients with ABI and individualizing the chosen strategy to manage
brain-lung conflicts where necessary.
Keywords
acute brain injury, acute respiratory distress syndrome, lung protective ventilation, mechanical ventilation

INTRODUCTION summarize recent clinical updates in the literature,

Patients with acute brain injury (ABI) account for up
to 20% of individuals receiving mechanical venti-
lation worldwide [1,2], yet little data currently exists
to inform the selection of optimal ventilatory tar-
gets and strategies in this population (ABI is defined
here as patients with traumatic brain injury, subar-
achnoid hemorrhage, intracranial hemorrhage,
acute ischemic stroke, and postanoxic encephalop-
athy) [3]. Moreover, whereas targets of mechanical
ventilation are well defined in patients with acute
respiratory distress syndrome (ARDS) without ABI
[4,5], brain-injured patients were largely excluded
from landmark ARDS trials [6–9]. Extrapolation of
these targets to the ABI population may cause con-
flicts between brain- and lung-specific ventilatory
priorities [10–15]. A recent consensus guideline
emphasized the lack of direct evidence to help
clinicians manage ventilatory conflicts in patients
with ABI, including in those with elevated intra-
cranial pressure (ICP) [3]. Notwithstanding, there
has been a push to update the current evidentiary
&& &
basis in this domain [16 ,17 ,18]. The present
review will provide a rationale for the importance
of safe ventilation in brain-injured patients,
and identify appropriate ventilatory targets for
application at the bedside. Practical advice for rec-
ognizing and managing brain-lung conflicts will
also be reviewed.
BRAIN-LUNG INTERACTIONS AND THEIR
RELEVANCE TO MECHANICAL
VENTILATION
Neuro-pulmonary interactions following ABI are
conceptually summarized by the paradigm of
a
Department of Neurology, Massachusetts General Hospital, Harvard
University, Boston, MA, USA, bInterdepartmental Division of Critical
Care Medicine, University of Toronto, Toronto, Ontario, Canada,
c
Department of Neurology, dDepartment of Neurological Surgery,
e
Department of Anesthesiology and Pain Medicine, University of
Washington, Seattle, Washington, USA, fIRCCS, Policlinico San
Martino and gDepartment of Surgical Sciences and Diagnostic
Integrated, University of Genoa, Genoa, Italy
Correspondence to Chiara Robba, Ospedale Policlinico San Martino,
Genova, Italy.
E-mail: kiarobba@gmail.com
Curr Opin Crit Care 2023, 29:41–49
DOI:10.1097/MCC.0000000000001018

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Acute neurological problems
KEY POINTS
 Despite limited direct evidence, establishing safe
mechanical ventilation is an important priority in brain-
injured patients, with the potential to significantly
improve outcomes.
 Clinically, it is prudent to target tidal volume close to
6 ml/kg predicted body weight, plateau pressure
<30 cm H2O, and driving pressure <15 cm H2O,
keeping in mind the potential for hypercapnia,
cerebrovascular dilatation, and attendant intracranial
pressure (ICP) elevation which may necessitate
individualization of ventilatory targets and
consideration of invasive ICP monitoring in some
clinical contexts.
 Careful application of positive end expiratory pressure
(PEEP) prevents cyclic de-recruitment of alveoli,
potentially improving systemic and brain tissue
oxygenation, although care must be taken to ensure
that PEEP does not compromise mean arterial pressure
and cerebral perfusion pressure, or increase ICP.
 Recent data suggest that higher driving pressure and
higher mechanical power are independently associated
with increased mortality and worse neurocognitive
outcomes in brain-injured patients, although safe
thresholds for these targets remain unknown.
 Until additional direct evidence becomes available,
careful extrapolation of established ventilatory targets
from patients without neurologic injury is suggested,
keeping in mind additional relevant intracranial effects
in the brain-injured population.
‘brain-lung crosstalk’ [15]. Brain injury increases
susceptibility to pulmonary complications via
increased sympathetic activation, local and sys-
temic inflammation, elevated ICP, autonomic dys-
function, and immune suppression (Fig. 1) [19–21].
Consequently, high rates of ventilator-associated
pneumonia (20–23%) [22,23] and ARDS (19–38%)
have been reported across ABI subtypes [24,25].
Development of lung injury, in turn, may cause
further brain injury via systemic release of inflam-
matory cytokines crossing the blood-brain barrier,
or via hypoxia and hypercapnia – lending support
to the concept that brain-lung crosstalk is bi-direc-
tional [15,26].
Mechanical ventilation itself can promote
adverse brain–lung crosstalk, and emerging preclin-
ical data highlight the significant potential for even
short durations of mechanical ventilation to cause
neurologic injury [27,28]. In a porcine study, hippo-
campal apoptosis and infiltration by pro-inflamma-
tory microglia was significantly higher in animals
ventilated for 50 h compared to animals that
were never ventilated [27]. In rats undergoing
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mechanical ventilation for 90 min, cognitive per-
formance was lower among animals receiving
higher tidal volumes (VT) compared to those with
lower VT; concentrations of pro-inflammatory cyto-
kines in the hippocampus were also higher in the
high VT group [28]. Clinical data in human subjects
further suggests the association of injurious venti-
lation with higher VT, higher driving pressure (DP),
and higher mechanical power (MP) with worse clin-
ical outcomes across multiple subtypes of ABI
&
[17 ,29,30,31]. In this context, establishing safe
ventilatory targets becomes a major clinical priority,
and each ventilatory parameter deserves thoughtful
consideration (Fig. 2).
VENTILATORY TARGETS IN BRAIN INJURY
Tidal volume
In the landmark ARDS Network trial, patients receiv-
ing low tidal volume ventilation (LTVV) with 6.2 ml

0.8 ml/kg predicted body weight (PBW) had an
8.8% absolute reduction in hospital mortality com-
pared to patients receiving VT of 11.8
0.8 ml/kg
PBW [6]. Current ARDS guidelines recommend use
of LTVV with 4–8 ml/kg PBW, or close to 6 ml/kg
PBW [4,5]. LTVV is also associated with clinical
benefits in patients without ARDS, including
improved postsurgical outcomes among patients
undergoing intra-abdominal surgery [32], increased
rates of successfully transplanted lungs among neu-
rologically deceased organ donors [33], and reduced
progression to ARDS among individuals without
initial lung injury [34]. Ventilatory care bundles
incorporating LTVV have been associated with
shorter duration of mechanical ventilation [35,36]
and reduced mortality when all aspects of the care
bundle were followed [35].
An important concern with LTVV in brain-
injured patients is the potential for hypercapnia,
which may lead to ICP elevation via cerebral acidosis
and cerebrovascular dilatation. Notwithstanding, a
meta-analysis of 2822 patients comparing a LTVV
strategy (with the majority of studies using a thresh-
old of <6 ml/kg PBW) to ventilation with higher
tidal volumes found a relatively modest absolute
increase of 3.15 mmHg in the partial pressure of
arterial carbon dioxide (PaCO2) and a decrease of
0.03 units pH in the LTVV group [34]. In the neuro-
logic population, a single-center intraoperative
randomized controlled trial (RCT) of 40 patients
without lung injury undergoing supratentorial neu-
rosurgery found that PaCO2 and ICP were similar
among patients randomized to receive 7 ml/kg PBW
vs. 9 ml/kg PBW [37]. However, in patients with loss
of cerebral autoregulation (e.g., due to severe ABI),
Volume 29  Number 2  April 2023
 Ventilatory targets following brain injury Taran et al.

FIGURE 1. Pathophysiology of brain-lung cross-talk. BBB, blood--brain barrier; CNS, central nervous system; ICP, intracranial
pressure; LOC, level of consciousness; O2, oxygen.

Use LTVV (close to 6 ml/kg PBW)

FIGURE 2. Summary of ventilatory targets after brain injury. ARDS, acute respiratory distress syndrome; CBF, cerebral blood
flow; CPP, cerebral perfusion pressure; HOB, head of bed; ICP, intracranial pressure; JVO, jugular venous outflow; LTVV, low
tidal volume ventilation; MAP, mean arterial pressure; PaCO2, partial pressure of carbon dioxide; PaO2, partial pressure of
oxygen; PbtO2, partial pressure of brain tissue oxygen; PBW, predicted body weight.

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Acute neurological problems
even modest hypercapnia and acidosis can lead to
ICP elevation, and the putative benefits of LTVV
must be balanced against this important risk.
Recent data indicate that clinicians feel increas-
ingly comfortable applying LTVV in the brain-
&
injured population [38 ,39]. A secondary analysis
of three cohort studies including 4152 patients
with heterogenous ABI subtypes found that the
proportion of days patients spent receiving VT
<8 ml/kg PBW increased from 30% in 2004, to
&
49% in 2010, to 56% in 2016 [38 ]. An international
survey of 687 clinicians found that 53% of respond-
ents would manage patients with traumatic brain
injury with VT of 4–6 ml/kg PBW if they also had
moderate to severe hypoxemic respiratory failure
[39]. A consensus guideline indicated that LTVV
should be used in brain-injured patients with ARDS
and without elevated ICP (strong recommenda-
tion), and should be considered in patients without
ARDS and without elevated ICP (weak recommen-
dation) [3]. The guideline made no recommenda-
tion on the use of LTVV in patients with ARDS and
high ICP [3].
Clinically, most patients with ABI (including
those with and without ARDS) and without concern
for high ICP should receive VT close to 6 ml/kg PBW.
In patients with suspected or confirmed increased
ICP and concomitant ARDS, an invasive ICP mon-
itor should be considered to individualize VT and
PaCO2 goals based on ICP and cerebral perfusion
pressure (CPP). Although data are limited, carefully
lowering VT to a level that yields a minimal change
(or clinically tolerable increase) in ICP may be pru-
dent. ICP increases in response to LTVV may be
proactively mitigated by administering osmother-
apy, deepening sedation, or performing cerebrospi-
nal fluid diversion if a ventricular drain is present. In
addition, removal of excess dead space from the
ventilatory circuit may permit reduction of VT by
as much as 1.8 ml/kg PBW, without concomitant
increase in ICP or PaCO2 [40]. Further considera-
tions for managing brain-lung conflicts as they
relate to LTVV are reviewed in Fig. 2.
Plateau pressure
Pplat refers to the pressure within small airways
and alveoli during end-inspiration. In the ARDS
Network trial, patients receiving Pplat 25–30 cm
H2O (achieved by provision of LTVV and, where
necessary, reduction of VT from 6 ml/kg PBW to
4 ml/kg PBW), had lower mortality and spent fewer
days receiving mechanical ventilation compared
to patients receiving Pplat 45–50 cm H2O [6].
In brain-injured patients, the optimal Pplat cur-
rently remains unknown [3]. Until further evidence
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becomes available, it is prudent to limit Pplat <30 cm
H2O in patients without concern for high ICP. In
cases where Pplat >30 cm H2O, lowering VT usually
leads to a corresponding reduction in Pplat, but the
effect on PaCO2 and ICP needs to be carefully moni-
tored. Patients with concomitant ARDS and high
ICP should receive an individualized ventilatory
strategy, where Pplat is carefully lowered (e.g., by
lowering VT and titrating PEEP to promote alveolar
recruitment) while observing ICP effects and treat-
ing ICP as needed. Deep sedation and occasionally
neuromuscular blockade may be necessary to facil-
itate ICP control and LTVV in this context [41].
Finally, Pplat may also be elevated independently
of VT in patients with alveolar overdistension,
migration of the endotracheal tube into a mainstem
bronchus, pulmonary congestion, or pneumo-
thorax. Addressing these underlying factors may
often enable reduction of Pplat.
Positive end expiratory pressure
Positive end expiratory pressure (PEEP) is defined as
the alveolar pressure above atmospheric pressure at
end-expiration. Careful selection of PEEP promotes
alveolar patency throughout the respiratory cycle,
improves pulmonary compliance, and enables
more homogeneous distribution of the forces of
mechanical ventilation [42]. A meta-analysis of
three RCTs in patients with ARDS without ABI
demonstrated a 5% absolute reduction in hospital
mortality with a higher PEEP strategy [43], and
current guidelines recommend higher PEEP in
patients with moderate to severe ARDS [4,5]. How-
ever, excessive PEEP may also reduce venous pre-
load and cardiac output, attenuate jugular venous
drainage, and promote alveolar overdistension. In
brain-injured patients, these changes may lead to
intracranial hypertension and cerebral ischemia via
a reduction in CPP [10,12].
Current data on PEEP thresholds in ABI come
from small, monocentric studies that rarely evaluate
higher levels of PEEP and include patients with
heterogeneous ABI subtypes. In a single-center phys-
iologic study, increases in PEEP from 5 to 15 cm H2O
in brain-injured patients led to a significant increase
in ICP and reduction in CPP, but only when accom-
panied by lung overdistension and significant
hypercapnia [44]. A study of 12 patients receiving
PEEP of 5 and 10 cm H2O found that when PEEP led
to alveolar recruitment, ICP did not increase,
whereas the partial pressure of oxygen (PaO2) mark-
edly improved [45]. Although there is legitimate
concern that excess PEEP may impair CPP, a phys-
iologic study of 20 patients with acute stroke found
that PEEP-related attenuation of CPP was primarily
Volume 29  Number 2  April 2023

mediated by a reduction in systemic mean arterial
pressure (MAP), and that when MAP was main-
tained, CPP also remained stable [46].
Guidelines suggest that brain-injured patients
should receive the same level of PEEP as patients
without ABI, as long as ICP is judged to be PEEP-
insensitive [3]. In clinical practice, PEEP titration in
brain-injured patients should be deliberate and
individualized, with the goal of maintaining
MAP and avoiding alveolar overdistension; the
latter may be suspected with worsening hypercap-
nia, hypoxemia, or increasing Pplat. Practical strat-
egies to mitigate hemodynamic and intracranial
effects of PEEP include maintaining head-of-bed
elevation, determining the indication for an inva-
sive ICP monitor or utilizing noninvasive methods
to gauge ICP response during PEEP titration [47],
augmenting MAP with fluids or vasopressors before
PEEP augmentation, setting PEEP below the level of
ICP [48], and using lung ultrasound to predict
potential ICP response to PEEP [49]. Furthermore,
PEEP should be titrated to maintain a PaO2 of 80–
120 mmHg [3], or a brain tissue oxygen (PbtO2)
>20 mmHg [50].
Driving pressure
In a secondary analysis of nine RCTs of patients with
ARDS, DP (derived as the difference between Pplat
and PEEP) was the ventilatory variable most strongly
associated with increased mortality (relative risk
[RR] 1.41, per each standard deviation increase in
DP; 95% confidence interval [CI] 1.31–1.51) [51].
Ventilatory strategies aimed at limiting exposure to
higher DP are increasingly gaining traction in
patients with ARDS without ABI [52,53]. In the
neurologic population, an observational study of
986 brain-injured found that a higher DP was asso-
ciated with increased risk of ARDS (odds ratio [OR]
1.12, per 1 cm H2O increase in DP; 95% CI 1.01–
1.23), whereas no association with ARDS was
observed with VT or PEEP [29]. In a secondary anal-
ysis of 1848 patients with postanoxic encephalop-
athy from the recent Targeted Temperature
Management 2 (TTM2) trial, a higher DP was asso-
ciated with increased mortality and worse neuro-
&
logic outcome at 6 months [17 ].
Current evidence remains strongest for ventila-
tion with LTVV and appropriate use of PEEP, and
the initial ventilatory approach in brain-injured
patients should be established with these targets
in mind [52]. Additional modifications in select
patients may then be attempted to maintain DP
<15 cm H2O [51]. Clinically, DP may be minimized
by carefully lowering VT and adjusting PEEP to pro-
mote alveolar recruitment without overdistension.
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Ventilatory targets following brain injury Taran et al.
Ideal brain-injured candidates for DP-related venti-
latory adjustments include patients without cor-
responding ICP elevation in whom there is
established or impending concern for lung injury
[13].
Mechanical power
Mechanical power (MP) is defined as the energy
transferred by the ventilator to the respiratory sys-
tem per unit time. This composite variable is
derived from the PEEP, DP, respiratory rate, peak
inspiratory pressure, Pplat and VT, although formu-
lae incorporating fewer variables have also been
suggested [54,55]. A secondary analysis of eight
RCTs including 5159 patients with ARDS found
that MP normalized to PBW was significantly better
at predicting mortality than VT, Pplat, or DP [56].
Lower MP (<17 J/min) was also associated with
reduced mortality in an observational study
of patients without ARDS [57]. In the neurologic
population, a single-center study including 529
patients with mixed subtypes of ABI found that
higher MP was associated with increased ICU mor-
tality in the overall cohort and in subgroups strati-
fied by high vs. low body mass index and presence
vs. absence of ARDS [58]. Finally, a secondary anal-
ysis of 1848 patients after cardiac arrest found that
MP was independently associated with increased 6-
month mortality (omnibus P-value for nonlinear
trajectory ¼ 0.026), but not worse neurologic out-
come (OR 1.01, per 1-unit increase in MP; 95% CI
0.99–1.03).
Given the limited existing evidence, ventilatory
approaches designed to limit MP in brain-injured
patients should be viewed as exploratory, and cur-
rent guidelines in this population do not address
this variable [3]. Moreover, the impact of individual
components of mechanical power on outcomes
warrants further investigation.
PaO2 and PaCO2
Evidence consistently points to the association of
hypoxemia with worse clinical outcomes in patients
with ABI. In cardiac arrest patients, a sub-analysis of
the TTM2 trial found that the best hypoxemia
threshold for predicting 6-month mortality was
PaO2 <69 mmHg [59 ]. Hyperoxemia has also been
&
associated with worse outcomes [60,61], putatively
via free radical production and nitric oxygen scav-
enging [62]. In a recent international survey, the
most common PaO2 range adopted by clinicians
managing patients with severe traumatic brain
injury (regardless of respiratory failure) was 81–
100 mmHg [39]. Current guidelines suggest, in
www.co-criticalcare.com 45
Acute neurological problems

Table 1. Ongoing studies of mechanical ventilation in brain-injured patients

Population
Studya Design (participants) Objectives Outcomes

NCT04459884 Multicenter TBI, ICH, AIS, SAH To describe ventilator settings in -Mortality and neurologic
prospective (3000) neurocritically ill patients, describe outcome at 6 months
observational ventilator settings in the presence/ -Pulmonary complications
absence of high ICP, and report the -In-hospital and ICU mortality
association of ventilator settings with -Hospital LOS in patients
clinical outcomes discharged alive
-Duration of mechanical
ventilation and ventilator-
free days at ICU discharge
NCT03114033 Multicenter, parallel Resuscitated To compare outcomes between -Favorable neurologic
assignment, postcardiac arrest patients receiving mild hypercapnia outcome at 6 months
assessor-blinded (1700) (PaCO2 50--55 mmHg for the first -In-hospital mortality, ICU
RCT 24 h following randomization) vs. mortality, and 6-month
standard ventilation (PaCO2 35--45 mortality
mmHg) -mRS at 6 months
-Health-related quality of life
at 6 months
NCT03754114 Multicenter, parallel Severe TBI (1094) To compare clinical outcomes among -Neurologic outcome at 6
assignment, patients receiving ICP and PbtO2- months
outcome assessor- guided management, vs. ICP-only -Survival at hospital
blinded RCT management (ventilatory discharge
optimization constitutes a core -Cognitive and emotional
management feature of both groups) health outcomes at 6
months
-Total brain tissue hypoxia
exposure (PbtO2 < 20
mmHg) up to 5 days
NCT03243539 Single-center, single TBI, ICH, AIS, anoxic To measure physiologic and clinical -Proportion of time at target
group assignment, brain injury, endpoints associated with tidal volume and target
open label cerebral edema implementation of a lung protective PaCO2 (35--45 mmHg)
interventional trial (728) ventilation protocol, targeting 6--8 -Hospital and ICU LOS
ml/kg PBW -In-hospital, 28-day, and 90-
day mortality
NCT01690819 Multicenter, parallel TBI, ICH, AIS, SAH To compare clinical outcomes -Survival without ventilator
assignment, open- (524) associated with a protective dependency or ARDS at
label RCT ventilatory strategy targeting 6 mL/ 28 days
kg PBW and PEEP 8 cm H2O, vs. -Ventilator-free days, ICU-free
ventilation with higher tidal volumes days, cumulative SOFA
(lower limit 8 mL/kg PBW) and score, and ICU mortality at
PEEP 4 cm H2O 28 days
-ICU LOS and hospital LOS
NCT02754063 Multicenter, parallel Severe TBI (320) To compare clinical outcomes among -Neurologic outcome at 6
assignment, patients receiving ICP and PbtO2 months
outcome assessor- guided management, vs. ICP-only -Quality of life outcomes at 6
blinded RCT management (ventilatory and 12 months
optimization constitutes a core -Mortality at 28 days
management feature of both groups)
NCT02574169 Single-center, TBI, ICH, AIS, SAH To compare effects on oxygen and -Brain tissue oxygen 60 min
crossover with concomitant intracranial hemodynamics after recruitment maneuver
assignment, open ARDS [62] associated with 2 different methods -Plateau pressure and static
label RCT of performing alveolar recruitment lung compliance
(extended sigh with PEEP at 10 cm -Mean arterial pressure, heart
H2O, targeting a plateau pressure rate, cardiac output,
of 40 cm H2O, vs. CPAP with PEEP PaO2, and PaCO2
at 40 cm H2O for 40 s) -ICP, CPP, and transcranial
Doppler velocities (mean,
systolic, diastolic)
NCT05464277 Multicenter, parallel Severe TBI [50] -To compare time at target oxygen -Mean area-under-the-curve
assignment, double- levels and clinical outcomes in for SpO2 and FiO2
blinded RCT patients receiving intermediate -Development of nosocomial
normal oxygen (SpO2 95--97%) vs. pneumonia and acute
high-normal oxygen (SpO2 99-- respiratory distress
100%) for the first 6 h of syndrome within 7 days of
mechanical ventilation enrolment
-ICU mortality

AIS, acute ischemic stroke; ARDS, acute respiratory distress syndrome; CPAP, continuous positive airway pressure; CPP, cerebral perfusion pressure; FiO2, fraction
of inspired oxygen concentration; ICH, intracranial hemorrhage; ICP, intracranial pressure; ICU, intensive care unit; LOS, length of stay; mRS, modified Rankin
score; PaCO2, partial pressure of arterial carbon dioxide; PaO2, partial pressure of arterial oxygen; PbtO2, brain tissue oxygen tension; PBW, predicted body
weight; PEEP, positive end expiratory pressure; RCT, randomized clinical trial; SAH, subarachnoid hemorrhage; SOFA, sequential organ failure assessment; SpO2,
percentage hemoglobin saturation of oxygen; TBI, traumatic brain injury.
a
Clinicaltrials.gov identifier.

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the absence of specific evidence, to maintain PaO2
within 80–120 mmHg in patients with ABI [3].
Furthermore, the value of adjusting hemodynamic
and ventilatory parameters based on PbtO2 in
severe traumatic brain-injured patients is currently
under investigation in three ongoing RCTs
(NCT03754114, NCT02754063, CTG1718-0).
With respect to PaCO2, the general approach to
avoid ‘too much’ or ‘too little’ has been suggested in
guidelines of patients with ABI [3,63], based on the
premise that both extremes are associated with
worse outcomes [64]. Physiologically, carbon diox-
ide is a potent mediator of cerebral vasoreactivity,
with each 1 mmHg increase in PaCO2 over a range of
20–80 mmHg leading to a 3% increase in cerebral
blood flow. Hypocapnia and hypercapnia may thus
precipitate cerebral ischemia and hyperemia, respec-
tively. Guidelines in brain-injured patients support
keeping PaCO2 between 35 and 45 mmHg [3,63],
whereas reduction to 32–35 mmHg may be consid-
ered as an escalating strategy in cases of persistently
elevated ICP (routine PaCO2 reduction below
30 mmHg is not advised) [41]. On the other hand,
mild hypercapnia up to 45–50 mmHg might be
considered in patients with traumatic brain injury
with brain tissue hypoxia (PbtO2 < 20 mmHg) and
normal ICP as a strategy to improve oxygen delivery
via increasing cerebral blood flow [65], although this
approach is not well studied. Finally, in patients
with cardiac arrest, a secondary analysis of the
TTM2 trial found that PaCO2 was not associated
with 6-month mortality or neurologic outcomes
&
[17 ]. Current cardiac arrest guidelines suggest
maintaining PaCO2 within 35–45 mmHg based on
the totality of evidence [66]. However, mild hyper-
capnia is being studied as a potential therapeutic
target in an ongoing clinical trial in this population
(NCT03114033).
Control of PaCO2 is achieved clinically by
manipulating the VT or respiratory rate. Once VT
is set, the respiratory rate should be manipulated
aiming for normocapnia, for the majority of
patients [3,63]. Serial PaCO2 analysis via arterial
blood gases or end tidal CO2 monitoring may be
necessary to ensure that targets are being achieved,
especially under conditions of suspected or con-
firmed intracranial hypertension.
CONCLUSION
High-quality data to guide ventilatory strategies in
patients with ABI is scarce. The majority of current
studies are monocentric, include patients with dif-
ferent ABI subtypes for whom ventilatory strategies
cannot be homogenized and report physiologic
endpoints that may not translate into clinical
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Ventilatory targets following brain injury Taran et al.
benefit. Current ventilatory practices in ABI should
therefore be extrapolated from data on patients
without brain injury, keeping in mind potential
implications to ICP, cerebral blood flow, and CPP
with LTVV and higher PEEP in the ABI population.
In patients with suspected intracranial hyperten-
sion and ARDS, invasive ICP monitoring should be
considered with the goal of monitoring ICP and
CPP responses to VT, Pplat, PEEP, and DP titration.
Identifying optimal targets of mechanical ventila-
tion in patients with ABI remains an area of intense
ongoing research, with numerous observational
studies and RCTs actively enrolling patients world-
wide (see Table 1). These studies will aim to provide
direct data to further inform the selection of ven-
tilatory targets and strategies in the brain-injured
population.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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