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MCC 280202

REVIEW

CURRENT
OPINION Optimizing oxygen delivery to the injured brain
Shaurya Taran a, Paolo Pelosi b,c, and Chiara Robba b,c

Purpose of review
The principle of optimizing oxygen delivery to the injured brain rests on the premise that both hypoxia and
hyperoxia are important mediators of secondary brain injury and should be avoided. This rationale has
prompted a move towards incorporating oxygenation endpoints into the management of neurocritical care
patients, particularly those with traumatic brain injury. The present review will seek to describe clinical
strategies to optimize oxygenation in the acutely brain-injured patient, drawing upon relevant physiologic
principles and clinical data, where it exists.
Recent findings
A phase II randomized trial found that a protocolized approach to improving oxygen delivery resulted in
less duration of brain hypoxia and a trend towards lower mortality among patients with severe traumatic
brain injury. Recent clinical protocols have been published to guide oxygen delivery based on core
physiologic principles: increasing oxygen supply via modulation of mean arterial pressure and intracranial
pressure, blood oxygen carrying capacity, and cerebral vasoreactivity; and decreasing oxygen demand
via sedation, pharmacologic coma, and hypothermia.
Summary
Although there is growing interest in the use of brain tissue oxygenation as a resuscitative endpoint, many
of these therapies are based on physiologic principles with little robust clinical evidence to guide their
application. Clinicians must be mindful of this and balance the putative benefits of improving oxygenation
against the risks associated with the use of such therapies.
Keywords
acute brain injury, brain tissue oxygenation, hyperoxia, neurocritical care, oxygen delivery

INTRODUCTION Traditionally, the primary focus of intervention

Optimizing oxygen delivery is an important prior-
ity in patients with acute brain injury (ABI),
defined here as patients with subarachnoid hem-
orrhage (SAH), intracranial hemorrhage (ICH),
acute ischemic stroke (AIS), and traumatic brain
injury (TBI). Devastating ABI activates a wide array
after ABI has been intracranial pressure (ICP), but
strategies to control ICP do not always guarantee
optimal oxygen delivery, and moreover, may some-
times worsen global or regional oxygen supply–
demand mismatch. Recent clinical algorithms have
thus sought to combine strategies to optimize oxy-
&&

of maladaptive processes within neurons that
result in excitatory neurotransmitter release, pro-
tease activation, lipid peroxidation, free radical
production, and – ultimately – cellular apoptosis
and necrosis [1]. These cascades underpin the clin-
ical phenomenon of secondary brain injury and
are a major driver of worse neurologic outcomes in
brain-injured patients [1]. In particular, oxygen
derangements (i.e. excess or insufficient oxygen
supply relative to demand) may contribute to sec-
ondary brain injury through a variety of mecha-
nisms and are clinically associated with worse
outcomes across the full spectrum of ABI [2 –6].
This knowledge has prompted a move towards
incorporating oxygen-based targets into the care
of patients with ABI.
gen delivery with those targeting ICP [7 ]. As this is
a rapidly evolving research area, this Current Opin-
ion piece will provide a topical overview of strategies
to optimize oxygen delivery in the acutely brain-
a
Interdepartmental Division of Critical Care, University of Toronto, Tor-
onto, Ontario, Canada, bAnesthesia and Intensive Care, San Martino
Policlinico Hospital, IRCCS for Oncology and Neurosciences and
c
Department of Surgical Sciences and Integrated Diagnostics, University
of Genoa, Genoa, Italy
Correspondence to Chiara Robba, Anaesthesia and Intensive Care, San
Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences,
Largo Rosanna Benzi, 15, 16100 University of Genoa, Genoa, Italy.
Tel: +39 3473912338; e-mail: kiarobba@gmail.com
Curr Opin Crit Care 2022, 28:000–000
DOI:10.1097/MCC.0000000000000913

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MCC 280202
Acute neurological problems
KEY POINTS
 Following acute brain injury, both hyperoxia and
hypoxia are important mediators of secondary brain
injury and represent extremes to be avoided.
 Oxygen delivery can be monitored according to
systemic targets (e.g. PaO2 and SaO2/SpO2) and
brain-specific targets (e.g. brain tissue oxygen, jugular
venous oximetry, cerebral microdialysis, and near
infrared spectroscopy).
 Optimizing oxygenation to the injured brain entails
matching O2 supply (e.g. by manipulating arterial
oxygen content, cerebral perfusion pressure, and
cerebral vasoreactivity) to O2 demand (e.g. by
manipulating cerebral metabolic rate).
 Recent protocols have focused on optimizing brain-
tissue oxygenation in tandem with intracranial pressure.
 This paradigm, however, remains largely unstudied for
conditions apart from severe traumatic brain injury, and
therefore, an ‘optimal’ oxygenation strategy remains as
yet undefined.
injured patient, with emphasis on basic physiologic
principles and the most recent evidence to guide
clinical care.
OXYGEN DELIVERY TO THE INJURED
BRAIN: WHY IT MATTERS AND HOW (AND
WHERE) TO MEASURE IT
Despite accounting for only 2% of total body weight,
the healthy brain receives approximately 15% of over-
all cardiac output (CO), which translates into 700 ml/
min (or 50–60 ml/100 g) of blood flow to brain tissue
per minute [8]. With minimal energy stores, neurons
rely on a constant supply of oxygen for energy genera-
tion via aerobic metabolism. This exquisite depen-
dence is perhaps best highlighted by the clinical
observation that loss of consciousness can result
within 10 s of complete cessation of cerebral blood
flow (CBF) [9]. Under sustained conditions of reduced
CBF, neuronal oxygen extraction increases to main-
tain steady oxygen supply; however, this process is
exhausted below a CBF of 25–30 ml/100 g/min, at
which point neurons convert to anaerobic metabo-
lism with consequent production of lactate and
hydrogen ions [10]. At flow rates of 10–12 ml/100 g/
min, sodium–potassium pumps fail and neurotrans-
mission ceases [10]. Further reductions in CBF beyond
this range are untenable and lead to cell death.
Oxygen optimization thus seeks to preserve the
dynamic equilibrium between brain O2 supply and
demand. In clinical practice, this matching can be
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guided by both systemic and brain-specific oxygen
targets. Oxygen can be measured systemically via
arterial blood gas analysis as the partial pressure of
oxygen (PaO2) or percentage saturation of hemoglo-
bin (SaO2), which indicate the body’s overall oxy-
genation status but are not direct markers of oxygen
delivery to the brain. Oxygen can also be measured
at the cerebral level via the brain tissue oxygen
(PbO2) monitor, which provides a measure of free,
dissolved oxygen within a 1 mm3 region of the
&
sampling site [11 ]. Various catheters are available
for PbO2 monitoring, including the Licox and Neu-
rovent. These are inserted directly into the brain
parenchyma by means of a burr hole and are gener-
ally quite well tolerated and accurate [12]. In
patients with severe TBI, a PbO2 threshold less than
20 mmHg is a common threshold to implement
&
interventions to improve oxygenation [11 ]. Addi-
tional strategies to guide brain oxygenation include
the jugular venous oxygen saturation (SjO2), which
provides a global ratio of oxygen delivery to con-
sumption from a probe placed in the jugular bulb;
and cerebral microdialysis, which measures lactate,
pyruvate and other metabolites in brain tissue and
can suggest insufficient oxygen delivery via an ele-
vated lactate : pyruvate ratio [13]. Finally, oxygen
can be measured noninvasively at the forehead
using near-infrared spectroscopy (NIRS), which
measures cerebral oxygen saturation to a depth of
about 2 cm from the skin surface. Table 1 reviews the
relevant technical aspects, advantages, and limita-
tions of each of these modalities in further detail.
For each of the above sampling methods, oxygen
targets are available to guide provision of treatments.
Table 2 provides an overview of studies examining
outcomes for various neurologic conditions accord-
ing to targets obtained by PaO2, PbO2, jugular bulb
oximetry, microdialysis, and NIRS [2,6,14–34].
STRATEGIES TO OPTIMIZE OXYGEN
DELIVERY IN ACUTE BRAIN INJURY
Oxygen delivery can be optimized by manipulating
each of the determinants of brain oxygen supply
and consumption. Brain oxygen supply depends on
arterial blood oxygen content (CaO2), cerebral perfu-
sion pressure (CPP), and cerebral vasoreactivity,
whereas consumption depends primarily on the cere-
bral metabolic rate of oxygen (CMRO2). An addi-
tional factor to consider is diffusion impairment,
which limits neuronal utilization of delivered oxygen
via microvascular collapse, perivascular edema, and
endothelial swelling; this phenomenon has been
shown in patients with traumatic brain injury [35]
and also more recently in patients following cardiac
arrest [36,37].
Volume 28  Number 00  Month 2022
 Table 1. Overview of oxygen measurement methods
Modality Sampling method
Systemic
PaO2 monitoring Achieved via arterial blood gas
analysis (e.g. by serial blood
samples or indwelling arterial
line)
SaO2/SpO2 Achieved via arterial blood gas
monitoring analysis or (in the case of
SpO2) noninvasively via
placement of a pulse oximeter
over the nail bed or forehead
PbO2 monitor Thin, metallic electrode that
samples the partial pressure of
dissolved oxygen within a
local, 1 mm region of the brain
white matter
Can be inserted via the same burr
hole as an ICP monitor or
independently placed
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Brain-specific
Jugular venous bulb Blood is sampled from the jugular
oximetry venous bulb via a catheter
inserted retrograde through the
internal jugular vein
Sampling can be intermittent or
continuous
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Principle behind measurement
Represents the partial pressure of
oxygen dissolved in arterial
blood
Represents the proportion of
hemoglobin molecules saturated
with oxygen
Offers a surrogate of oxygenation
that reflects oxygen delivery
(via blood oxygen content and
perfusion) and consumption
Reduction of brain tissue oxygen
can be seen with reduced
delivery (e.g. hypotension,
anemia), or increased
consumption (e.g. fever)
Provides a global, indirect
measure of the brain’s supply,
utilization, and extraction of
oxygen
Reduction of jugular venous
oxygen saturation can be seen
with reduced oxygen delivery,
increased demand (e.g.
because of fever or seizures), or
increased extraction
Advantages
Easy and inexpensive to obtain
Simple to interpret
Well studied parameter with
reasonable evidence to guide
oxygen provision to specific
thresholds
Easy and inexpensive to obtain
Simple to interpret
Can be acquired noninvasively in
the case of SpO2
Growing evidence base to inform
treatment thresholds,
particularly for severe TBI
Insertion of probe into a focal
area of injury can allow
provision of treatments to
improve oxygenation in the
worst affected area
Changes in oxygen delivery and
consumption are reflected in
real time
Offers a ‘wide-angle’ view of
oxygen balance across the
brain
Changes in oxygen delivery and
consumption are reflected in
real time
Limitations
Not specific to brain oxygenation
Not specific to brain oxygenation
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SpO2 is inaccurate under
conditions of severe
hypoxemia,
methemoglobinemia, and
carbon monoxide poisoning
Expensive
Samples oxygen within a small
area, with the result that values
are critically dependent on
insertion site and not
representative of global
cerebral oxygenation status
MCC 280202
Requires technical and
troubleshooting expertise not
available at many centers
Small risk of hematoma and
infection
Catheter misplacement can result
in inaccurate sampling of blood
from extra-cranial vessels
Provides only a global measure of
oxygenation and cannot
identify regional disturbances in
oxygen use or delivery (oxygen
values may be normal with
focal injury)
Requires technical and
troubleshooting expertise not
available at many centers
Small risk of hematoma and
infection
Optimizing oxygen delivery to the injured brain Taran et al.
 4
Table 1 (Continued)
Modality Sampling method
Cerebral Dual-lumen probe that is inserted
microdialysis into the brain tissue via a burr
hole (can also be independently
placed)
Metabolites from the brain mix
with perfusate delivered via one
lumen and are returned for
analysis by the second lumen
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Near infrared Consists of a series of light
spectroscopy transmitter and detector
electrodes arranged across the
scalp
ICP, intracranial pressure; PaO2, partial pressure of arterial oxygen; PbO2, brain tissue oxygen; SaO2/SpO2, percentage saturation of hemoglobin; TBI, traumatic brain injury.
Volume 28  Number 00  Month 2022
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Principle behind measurement
Samples metabolites from the
extracellular space, including
lactate, pyruvate, glucose,
glutamate, and glycerol
Cerebral ischemia may be
predicted by an elevated
lactate:pyruvate ratio or
increased glycerol and
glutamate
Measures the relative absorption
of oxy- and deoxy-hemoglobin
at different near-infrared
wavelengths of light
Proportion used to estimate the
cerebral tissue oxygenation
status
Advantages
Placement of the probe into a
focal, high-risk area for
ischemia can allow targeted
delivery of treatments
Can sample multiple metabolites
at once
Noninvasive measurement
modality
Good temporal resolution
Limitations
Small sampling area provides
only a local measure of brain
metabolism and oxygenation
status
Requires technical and
troubleshooting expertise not
available at many centers
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Acute neurological problems
Limited time resolution to detect
acute changes in oxygen
delivery or consumption
Small risk of hematoma and
infection
Limited spatial resolution; only
allows detection of superficial
brain oxygen saturation
Unreliable with increasing skull
thickness, scalp hematomas,
intracerebral hematomas,
patient movement, and excess
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Table 2. Studies examining outcomes according to oxygen measurement modality and disease condition
Modality Author/year/n
Traumatic brain injury
PaO2 monitoring Brenner et al. [2]/2012/
n ¼ 1547
Briain et al. [14]/2018/
n ¼ 24 148
PbO2 monitoring Martini et al. [15]/2009/
n ¼ 629
Spiotta et al. [16]/2010/
n ¼ 123
Okonkwo et al. [17]/
2017/n ¼ 119
Jugular venous bulb Robertson [18]/1993/
oximetry n ¼ 116
Cormio et al. [19]/1999/
n ¼ 450
Struchen et al. [20]/
2001/n ¼ 184
Cerebral microdialysis Timofeev et al. [21]/
2011/n ¼ 97
Near infrared Kirkpatrick et al. [22]/
spectroscopy 1995/n ¼ 14
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Optimizing oxygen delivery to the injured brain Taran et al.
Study objective and outcomes
To investigate the relationship
between PaO2 within 24 h after
admission and mortality and
discharge GCS
To determine the association between
worst recorded PaO2 in the first
24 h and in-hospital mortality
To compare PbO2 þ ICP vs. ICP
management alone on resource
utilization and hospital mortality
To assess mortality and GCS at
3 months following PbO2 þ ICP
management vs. ICP management
alone
To compare a protocol of PbO2 þ
ICP management vs. ICP
management alone
To examine the effect of jugular
venous desaturation on mortality
and GOS at 3 months post injury
To investigate the effects of elevated
SjO2 on GOS at 3 and 6 months
To determine the effects of multiple
cerebral hemodynamic variables
on GOS and DRS at 1, 3, and
6 months post injury
To examine the effect of CPP
perturbation on various indices
including the L : P ratio
To examine the change in NIRS
signal compared with SjO2, ICP,
and systemic oxygenation with
hemodynamic changes
Results
Patients with average high PaO2
(>200 mmHg) in the first 24 h had
higher mortality and lower GCS at
discharge than patients with lower
PaO2 (<100 mmHg)
Profound hypoxemia
(PaO2 < 40 mmHg) was associated
with increased in-hospital mortality
whereas there was no association
with mortality for hyperoxemia
(PaO2 > 300 mmHg)
PbO2 þ ICP treatment resulted in no
difference in mortality but higher
hospital costs and lower functional
independence compared with ICP
management alone
PbO2 þ ICP treatment resulted in a
19.6% absolute mortality
difference compared to ICP
management alone. GOS was
improved in the former group
(64.3% with good outcome
compared with 39.6%,
respectively)
A PbO2 þ ICP management protocol
reduced the duration of brain tissue
hypoxia by 66% and the depth of
hypoxia by 72%. GOS-E and DRS
trended towards improvement in
the PbO2 þ ICP group compared
with the ICP group
Mortality at 3 months was 18, 46,
and 71% when there were no
episodes of desaturation (defined
as SjO2 < 50%), one episode, and
multiple episodes, respectively
Patients with SjO2 > 75% had
significantly increased CBF and
worse outcomes compared with
those with an SjO2 between 56
and 74%
Greater number and duration of
episodes of SjO2 less than 50%
were independently associated
with worse GOS at 1, 3, and
6 months and worse DRS at 3 and
6 months
Higher L : P ratios were observed in
the setting of impaired
autoregulation, decreased CPP,
and higher ICP
Changes in CPP correlated in 97% of
occasions with a change in the
NIRS signal, vs. in 53% of
occasions with SjO2, 26% with
intracranial pressure, and 21%
with peripheral oxygen
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Acute neurological problems
Table 2 (Continued)
Modality Author/year/n
Subarachnoid hemorrhage
PaO2 monitoring Rincon et al. [6]/2014/
n ¼ 2894; n ¼ 936 for
SAH)
Yokoyama et al. [23]/
2019/n ¼ 196
PbO2 monitoring Bogossian et al. [24]/
2021/n ¼ 163
Chen et al. [25]/2011/
n ¼ 19
Jugular venous bulb Heran et al. [26]/2004/
oximetry n ¼ 10
Cerebral microdialysis Sarrafzadeh et al. [27]/
2002/n ¼ 97
Near infrared Ekelund et al. [28]/1998/
spectroscopy n ¼ 14
Stroke (acute ischemic or hemorrhagic)
PaO2 monitoring Rincon et al. [6]/2014/
n ¼ 2894 (n ¼ 1404 for
ICH, n ¼ 554 for AIS)
Fallenius et al. [29]/
2016/n ¼ 3033
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Study objective and outcomes
To examine the association between
oxygen level and in-hospital
mortality in patients with SAH,
ICH, and AIS
To assess the association between
early hyperoxemia within 24 h of
ICU admission and neurologic
outcome
To determine the effect of PbO2-
guided therapy on neurologic
outcome in patients with
nontraumatic SAH
To examine the prevalence of brain
hypoxia in the presence of normal
and abnormal ICP and CPP in
patients with high-grade SAH
To determine if preclinical vasospasm
could be detected by an increase
in the SjO2
To examine the time course of
changes in cerebral metabolic
parameters in patients with SAH
To assess the correlation between
TCD velocity and NIRS signal in
patients with vasospasm following
SAH
To examine the association between
oxygen level and mortality in
patients with SAH, ICH, and AIS
To determine the association between
early high oxygen tension and 6-
month mortality among patients
with ICH
Volume 28  Number 00  Month 2022
Results
In the subgroup of patients with SAH
(32% of overall cohort), PaO2
greater than 300 mmHg was
associated with a higher odds of
in-hospital mortality vs. PaO2 60–
300 mmHg (OR 2.5; 95% CI 1.7–
3.3) and PaO2 greater than
60 mmHg (OR 2.0; 95% CI 1.3–
2.5)
Hyperoxemia (defined as
PaO2 > 120 mmHg) occurred in
93.4% of patients but was not
associated with increased mortality
in the overall patient cohort
Patients receiving PbO2-guided
therapy had improved neurologic
outcomes at 6 months compared
with those managed according to
ICP alone. There was no
improvement in hospital mortality
with PbO2 monitoring
A total of 145 samples (80.6%) had
mild brain hypoxia (defined as
PbO2 11–20 mmHg) and 118
samples had severe brain hypoxia
(defined as PbO2 < 10 mmHg) in
samples where the ICP was normal
In 4/10 patients who had clinical
vasospasm, cerebral oxygen
extraction ratio increased greater
than 24 h before onset of clinical
deficits; oxygen extraction did not
change in patients without
vasospasm
In 83% of patients with delayed
ischemic neurologic deficits, changes
in the metabolic profile indicative of
cerebral ischemia preceded the
onset of clinical ischemia
Overall correlation between TCD
mean flow velocity and NIRS was
significant (r ¼ 0.62; P < 0.01).
All patients with mean flow velocity
greater than 120 cm/s had a NIRS
less than 60%
Among patients with ICH (49% of
overall cohort), PaO2 greater than
300mmHg was associated with a
higher odds of in-hospital mortality
vs. PaO2 60–300mmHg (OR
1.3; 95% CI 1.03–1.7)
There was no independent
association between high oxygen
tension (defined as
PaO2 > 150mmHg in the first
24h of ICU admission) and 6-
month mortality
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Optimizing oxygen delivery to the injured brain Taran et al.

Table 2 (Continued)

Modality Author/year/n Study objective and outcomes Results

López et al. [30]/2019/ To examine the effects of Hyperoxemia (defined as

n ¼ 333 hyperoxemia on mRS at 90 days PaO2 > 120mmHg) was
among patients with AIS following associated with higher odds of a
thrombectomy poor functional outcome at 90
days, as defined by mRS > 3 (OR
2.27; 95% CI 1.22–4.23)
PbO2 monitoring Allen et al. [31]/2011/ To evaluate the safety and utility of Multiple hypoxic episodes as defined
n¼2 PbO2 monitoring in pediatric by a PbO2 less than 20 mmHg
patients with ischemic stroke were observed, independent of
simultaneous abnormalities in other
measured parameters
Jugular venous bulb Keller et al. [32]/2002/ To assess if jugular venous oximetry Among a total of 101 recordings of
oximetry n ¼ 10 has clinical value as a prognostic ICP and SjO2, only two SjO2
tool in patients with severe values were recorded below the
hemispheric infarction critical threshold for ischemia
(SjO2 < 50%), suggesting that
ischemic thresholds identified in TBI
may not carry over to ischemic
stroke
Cerebral microdialysis Pinczolits et al. [33]/ To assess for correlation between A greater number of spreading
2017/n ¼ 18 neuronal metabolite concentrations depolarizations and clustered
and spreading depolarizations depolarizations were seen with
following malignant hemispheric elevations in glutamate
stroke concentration
Near infrared Giacalone et al. [34]/ To determine whether oxygen Compared with controls, patients with
spectroscopy 2019/n ¼ 47 saturation as determined by NIRS large vessel occlusion had a higher
varies between patients with large concentration of deoxy-
vessel occlusion, recanalized hemoglobin. Among patients with
patients, and controls recanalization, the ischemic area
had a persistently increased deoxy-
hemoglobin concentration

AIS, acute ischemic stroke; CBF, cerebral blood flow; CI, confidence interval; CPP, cerebral perfusion pressure; DRS, disability rating scale; GCS, Glasgow coma
scale; GOS, Glasgow outcome scale; GOS-E, Glasgow outcome scale extended; ICH, intracranial hemorrhage; ICP, intracranial pressure; L : P, lactate to
pyruvate ratio; mRS, modified Rankin scale; NIRS, near infrared spectroscopy; OR, odds ratio; PaO2, partial pressure of arterial oxygen; PbO2, brain tissue
oxygen; SAH, subarachnoid hemorrhage; SjO2, jugular venous oxygen saturation; TBI, traumatic brain injury; TCD, transcranial Doppler.

Arterial blood oxygen content (CaO2) depends
on the hemoglobin level (Hb), percentage hemoglo-
bin saturation (SaO2), and to a small extent on the
partial pressure of oxygen in arterial blood (PaO2), as
summarized by the following equation:
CaCO2 ðml=100 ml bloodÞ
¼ ð1:34  Hb  SaO2 Þ þ ðPaO2  0:003Þ
Meanwhile, the CPP depends on the systemic
mean arterial pressure (MAP) and ICP and is derived
from the difference between these two values:
CPP ðmmHgÞ ¼ MAP  ICP
Cerebral vasoreactivity depends on the blood
partial pressure of carbon dioxide (PaCO2), such that
increasing PaCO2 leads to cerebral vasodilation and
decreasing PaCO2 leads to cerebral vasoconstriction
[38]. This potent relationship exists over a PaCO2
range of 20–80 mmHg, with each 1 mmHg increase
in PaCO2 resulting in an approximately 3% increase
in CBF [38,39]. Cerebral vasoreactivity is also deter-
mined by hypoxemia, which causes a potent, linear
increase in CBF as PaO2 declines below 50–
60 mmHg [40] (there is little change in CBF across
physiologic levels of PaO2).
CMRO2 depends on cellular activity and can be
increased by factors such as fevers, seizures, or sym-
pathomimetics and decreased by factors such as
sedation or hypothermia. Figure 1 discusses each
of the factors related to oxygen supply and con-
sumption along with a brief rationale for their
importance. This is followed by a discussion of
strategies to optimize oxygen delivery by leveraging
the above relationships.
Arterial blood oxygen content
Increasing arterial oxygen content via higher hemo-
globin levels can theoretically improve oxygen
delivery to the injured brain, although there is
presently little robust evidence to guide the

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Acute neurological problems

O2 Supply O2 Demand

Hemoglobin: Increasing hemoglobin increases

O2 carrying capacity and therefore O2 content Primary determinant

Arterial SaO2 : Increasing the percent saturation of

1 oxygen hemoglobin increases O2 content Cerebral metabolic rate: Increasing cerebral metabolic
content
rate increases O2 demand and can lead to tissue ischemia
PaO2 : Increasing the partial pressure of
if not properly matched by O2 delivery. Various factors can
dissolved oxygen in the blood provides a small
increase cerebral metabolic rate, as shown below.
increase in overall arterial O2 content
Reduction of metabolic rate is achieved by controlling the
underlying stimulus for its increase and generally also by
Mean arterial pressure: increasing mean administering sedation.
arterial pressure increases cerebral perfusion
Cerebral
pressure when intracranial pressure is held
2 perfusion
constant
pressure
Intracranial pressure: Decreasing intracranial
pressure increases cerebral perfusion pressure
when mean arterial pressure is held constant

PaCO2 : Each 1 mmHg increase in PaCO2 leads

to an ~3% increase in cerebral blood flow, with a
Cerebral strong potential to increase O2 delivery provided
3 vaso- there is no increase in intracranial pressure
reactivity PaO2 : At normal physiologic levels of PaO2
there is no major affect on cerebral blood flow.
However, at PaO2 < 50-60 mmHg, there is a
near-linear inverse relationship between PaO2
and blood flow in an effort to preserve oxygen Fever Seizures Drugs
delivery

FIGURE 1. Determinants of cerebral oxygen supply and demand.

selection of a specific hemoglobin target. Two inter-
national surveys of critical care practitioners found
that hemoglobin thresholds for blood transfusion in
ABI were highly variable: in one survey, more than
50% of practitioners considered transfusions at
hemoglobin levels above 80 g/l in patients with
TBI, SAH, and stroke [41]. The second survey found
that transfusion thresholds varied between 70 and
100 g/l by acuity of presentation, and over 50% of
participants ranked low PbO2, CPP, and CBF as the
most important physiologic factors driving their
decision to transfuse [42].
Among patients with TBI, a randomized clinical
trial (RCT) examining erythropoietin administration
and two hemoglobin transfusion thresholds of 70 vs.
100 g/l found no difference between groups in neu-
rologic outcomes at 6 months postinjury, whereas
thromboembolic complications were increased in
the higher threshold group [43]. A large, ongoing
RCT is aiming to compare neurologic outcomes in
patients with moderate or severe TBI according to
restrictive (<70 g/l) versus liberal (<100 g/l) transfu-
sion targets (NCT03260478). A separate RCT exam-
ining transfusion thresholds of less than 80 g/l vs. less
than 100 g/l in patients with SAH is also ongoing
(NCT03309597). No RCT to date has evaluated trans-
fusion thresholds among patients with ICH or AIS.
Balancing the limited available evidence, a recent
consensus guideline suggested to consider blood
transfusion in patients with severe TBI for hemoglo-
bin less than 90 g/l with concomitant evidence of
brain tissue hypoxia (i.e. PbO2 < 20 mmHg) as a final-
&&
tier measure to improve oxygenation [7 ]. Whether
this recommendation should be applied more gener-
ally to other ABI states is unknown, and until further
evidence becomes available, a sensible clinical strat-
egy is to transfuse at hemoglobin less than 70 g/l
while carefully considering the benefits of transfu-
sion for hemoglobin levels between 70 and 100 g/l in
the presence of a low PbO2.

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Arterial oxygen content can also be increased by
augmenting the PaO2, for example, via hyperbaric
oxygenation. In a phase II clinical trial among
patients with severe TBI, patients who received a
combination of hyperbaric oxygen treatments at
1.5 atmospheres followed by normobaric hyperoxia
had lower ICP, improved markers of oxidative
metabolism, and better neurologic outcomes at
6 months, compared with usual care [44]. Hyper-
baric oxygenation has also been studied in patients
with SAH [45], AIS [46], and preclinical models of
ICH [47], with benefits seen in various outcomes
across each condition (and likely explained by fac-
tors beyond just PaO2 augmentation). However,
notwithstanding these results, current evidence
for hyperbaric oxygenation is weak, and this
approach should still be regarded as experimental
among patients with ABI.
Cerebral perfusion pressure
CPP can be manipulated by controlling either the
mean arterial pressure (MAP), ICP, or both. As MAP
is the product of heart rate, stroke volume, and
systemic vascular resistance, each of these compo-
nents can be further manipulated with the goal of
optimizing CPP and, in turn, PbO2. Current guide-
lines for severe TBI suggest maintaining CPP within
60–70 mmHg [38]. With this general target in mind,
stroke volume can be improved in the fluid-respon-
sive patient by administered intravenous fluids. Sys-
temic vascular resistance can be increased with
judicious vasopressor administration, keeping in
mind that higher vasopressor doses might attenuate
oxygenation via an increase in cerebrovascular resis-
tance [48]. Bradycardia should prompt corrective
strategies (e.g. providing chronotropic agents or
increasing pacemaker rate in patients with a perma-
nent pacemaker) if it is felt to be contributing to
reduced MAP. These strategies should be mindful of
preexisting comorbidities (e.g. heart failure) or com-
plications of devastating ABI (e.g. neurogenic pul-
monary edema, stress cardiomyopathy) that may
limit their consideration [49].
In patients who are receiving mechanical venti-
lation, careful attention must also be paid to opti-
mize the ventilatory approach to minimize
&&
untoward effects on CPP, ICP, and PbO2 [50 ].
Excessive positive end expiratory pressure (PEEP)
may attenuate preload and stroke volume, with a
downstream reduction of MAP and CPP. These
effects are exaggerated when high PEEP is applied
in the hypovolemic patient, which might prompt
volume loading in the appropriate context before
increasing PEEP [51]. PEEP also exerts complex and
variable effects on ICP via a Starling resistor
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Optimizing oxygen delivery to the injured brain Taran et al.
mechanism [52]; however, a general strategy to
minimize the effects of PEEP on ICP are to maintain
head elevation and set PEEP lower than the ICP [51].
Although it might be tempting to minimize PEEP in
order to obviate the above hemodynamic and intra-
cranial effects, this is not advisable: PEEP improves
alveolar recruitment and V/Q matching, leading to
improved systemic oxygenation and PbO2 [53]. As a
practical starting point, among patients with ABI
and no concern for elevated ICP, PEEP should be set
at the same level as patients without ABI; whereas in
patients with ABI and high ICP, PEEP can be care-
fully adjusted to strike a balance between ICP and
optimization of relevant parameters (e.g. MAP, CPP,
&&
PbO2) [50 ].
Strategies to control ICP include keeping the
head of the bed at 308, ensuring adequate jugular
venous drainage, removing cerebrospinal fluid via
ventricular drains, and administering osmotherapy
[38]. Decompressive craniectomy can be considered
&
as a final resort [54 ]. For a given MAP, reduction of
ICP through the above measures can improve CPP
and often also PbO2. A recent consensus guideline
on ICP management in patients with severe TBI
offers recommendations about the sequence in
&
which to consider these therapies [54 ].
Cerebral vasoreactivity
The principle of PaCO2-mediated cerebral vasoreac-
tivity can be leveraged to optimize cerebral blood flow
and PbO2. In patients receiving mechanical ventila-
tion, careful adjustments to the respiratory rate and
tidal volume can be applied to manipulate PaCO2
&&
while being cognizant of ICP effects [50 ]. In the
BOOST-II pilot trial, patients with a PbO2 less than
20 mmHg and ICP less than 20 mmHg were allowed to
have their PaCO2 increased to greater than 45 mmHg
in order to improve PbO2 [17]. A recent guideline for
PbO2 and ICP management in patients with severe TBI
permitted PaCO2 to rise to 45–50 mmHg as a final-tier
option to improve PbO2 under conditions of normal
&&
ICP [7 ]. In patients with poor grade SAH and delayed
cerebral ischemia, brief and controlled periods of
PaCO2 elevation have been shown to improve CBF
and PbO2 [55]. However, PaCO2-guided PbO2 optimi-
zation remains an experimental strategy and may
have dramatic effects on ICP; it should also generally
not be attempted without direct PbO2 and ICP mon-
itors (without which titration to endpoints and detec-
tion of harm can be difficult).
Cerebral metabolism
Cerebral metabolism is the primary determinant of
brain oxygen consumption. CMRO2 is normally
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MCC 280202

Acute neurological problems

tightly coupled to CBF, such that reducing CMRO2
decreases the CBF and also the ICP [8,56]. Provided
that systemic MAP is maintained, this may
improve CPP and thus oxygen delivery. In clinical
practice, reduction of CMRO2 is most commonly
achieved through administration of sedation, with
common agents including propofol, benzodiaze-
pines, and barbiturates [56]. CMRO2 can also be
decreased with temperature reduction. Each 1 8C
drop in temperature leads to a 7% reduction in
CMRO2 and CBF, with CBF nearly halved at a
temperature of 27 8C [8]. In the ongoing BOOST-
III trial, protocolized reductions in temperature
to 35–36 or 32 –35 8C, will be targeted as higher
tier measures in patients who have elevated ICP
and low PbO2 despite conservative treatment
(NCT03754114). Controlled temperature reduc-
tion might, therefore, be considered in clinical
practice to improve PbO2 when ICP is also high,
recognizing that this approach is not yet widely
validated.
OPTIMIZING OXYGEN DELIVERY WITH
SIMULTANEOUS CONTROL OF
INTRACRANIAL PRESSURE
In clinical practice, PbO2 optimization is rarely an
isolated end goal but rather part of a comprehensive
care plan in which other clinical targets are also
simultaneously addressed. The most important
additional target of focus is the ICP, and currently,
three major RCTs are investigating whether the
combination of PbO2 and ICP-guided care improves
outcomes compared with ICP-guided management
alone in patients with severe TBI (NCT03754114,
NCT02754063, CTG1718-05). Until these results
become available, however, a practical algorithm
to optimize PbO2 and ICP simultaneously has been
&&
proposed [7 ]. This algorithm provides a stepwise
approach to implementing various treatments con-
sidering various levels of PbO2 and ICP. Practical
recommendations based on this algorithm and
other relevant physiologic principles are summa-
rized in Fig. 2, with the caveat that these are specific

FIGURE 2. Oxygen consumption or delivery can be optimized through a variety of respiratory, neurologic, cardiac, and
general critical care interventions, as outlined here. ABI, acute brain injury; CPP, cerebral perfusion pressure; ICP, intracranial
pressure; MAP, mean arterial pressure; PaCO2, partial pressure of arterial carbon dioxide; PaO2, partial pressure of arterial
oxygen; PbO2, brain tissue oxygen; PEEP, positive end expiratory pressure; TBI, traumatic brain injury.

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CE: Tripti; MCC/280202; Total nos of Pages: 12;
MCC 280202
to TBI and may not carry over in equal measure to
other ABI states.
CONCLUSION
The premise of oxygen monitoring in neurocritical
care is simple: if oxygen delivery can be closely
tracked, it may lead to a minimization of secondary
brain injury via hypoxia or hyperoxia. However, it is
important to recognize the important limitations of
this paradigm. Treatments to improve oxygenation
are not without their risks: CPP augmentation
potentially exposes patients to additional fluids
and vasopressors; blood transfusions carry infec-
tious and inflammatory risks; and invasive oxygen
monitoring devices (e.g. PbO2, jugular venous oxim-
etry) require additional technical and troubleshoot-
ing expertise that may not be available at many
centres. Moreover, enhancing oxygen delivery does
not often address potential co-existing limitations
in oxygen diffusion and utilization that may pre-
vent the injured brain from using this substrate
[36,37]. An additional overarching limitation is that
current oxygen delivery practices in neurocritical
care are informed largely by small physiologic stud-
ies and retrospective observational data with mixed
results. This heterogeneity may reflect important
differences in oxygen metabolism and utilization
between various diseases, such that a ‘one size fits
all’ approach may not be appropriate. Therefore,
until more robust data becomes available, the strat-
egies to improve oxygen delivery discussed herein
should be considered in the context of their limi-
tations and should not abandon higher quality rec-
ommendations, where they exist.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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
1. Hunt K, Bose G. Clinical neuroprotection and secondary neuronal injury
mechanisms. Anaesth Intensive Care Med 2020; 21:293–297.
2. Brenner M, Stein D, Hu P, et al. Association between early hyperoxia and
worse outcomes after traumatic brain injury. Arch Surg 2012; 147:
1042–1046.
1070-5295 Copyright ß 2022 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Optimizing oxygen delivery to the injured brain Taran et al.
3. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury
in determining outcome from severe head injury. J Trauma 1993;
34:216–222.
4. Reynolds R, Amin S, Jonathan SV, et al. Hyperoxia and delayed cerebral
vasospasm in aneurysmal subarachnoid hemorrhage. Neurosurgery 2020;
67(Suppl 1).
5. Bogossian EG, Diaferia D, Djangang NN, et al. Brain tissue oxygenation
guided therapy and outcome in non-traumatic subarachnoid hemorrhage. Sci
Rep 2021; 11:16235.
6. Rincon F, Kang J, Maltenfort M, et al. Association between hyperoxia and
mortality after stroke: a multicenter cohort study. Crit Care Med 2014;
42:387–396.
7. Chesnut R, Aguilera S, Buki A, et al. A management algorithm for adult
&& patients with both brain oxygen and intracranial pressure monitoring: the
Seattle International Severe Traumatic Brain Injury Consensus Conference
(SIBICC). Intensive Care Med 2020; 46:919–929.
This algorithm to manage ICP and PbO2 in tandem in patients with severe TBI was
created using a Delphi process among 42 experts across neurocritical care
disciplines. The algorithm emphasized a tier-based approach to clinical care with
higher tiers representing progressively more aggressive interventions to manage
intracranial hypertenion and brain tissue hypoxia.
8. Tameem A, Krovvidi H. Cerebral physiology. Continuing Educ Anaesth Crit
Care Pain 2013; 13:113–118.
9. Rossen R, Kabat H, Anderson JP. Acute arrest of cerebral circulation in man.
Arch Neurol Psychiatry 1943; 50:510–528.
10. Zhong S, Sun K, Zuo X, Chen A. Monitoring and prognostic analysis of severe
cerebrovascular diseases based on multi-scale dynamic brain imaging. Front
Neurosci 2021; 15:684469.
11. Leach MR, Shutter LA. How much oxygen for the injured brain - can invasive
& parenchymal catheters help? Curr Opin Crit Care 2021; 27:95–102.
This recent Current Opinion article summarized the rationale for PbO2 monitoring
in patients with TBI. The clinical protocols for three international, ongoing RCTs
assessing PbO2 monitoring in TBI are reviewed.
12. Dings J, Meixensberger J, Jäger A, Roosen K. Clinical experience with 118
brain tissue oxygen partial pressure catheter probes. Neurosurgery 1998;
43:1082–1095.
13. Lara LAR, Suarez JI. Multimodality neuromonitoring. In: Nelson SE, Nyquist
PA, editors. Neurointensive care unit: clinical practice and organization.
Cham: Springer International Publishing; 2020. pp. 303–310.
14. Briain DO, Nickson C, Pilcher DV, et al. Early hyperoxia in patients with
traumatic brain injury admitted to intensive care in Australia and New Zealand:
a retrospective multicenter cohort study. Neurocrit Care 2018; 29:443–451.
15. Martini RP, Deem S, Yanez ND, et al. Management guided by brain tissue
oxygen monitoring and outcome following severe traumatic brain injury. J
Neurosurg 2009; 111:644–649.
16. Spiotta AM, Stiefel MF, Gracias VH, et al. Brain tissue oxygen-directed
management and outcome in patients with severe traumatic brain injury. J
Neurosurg 2010; 113:571–580.
17. Okonkwo DO, Shutter LA, Moore C, et al. Brain oxygen optimization in severe
traumatic brain injury phase-ii: a phase ii randomized trial. Crit Care Med
2017; 45:1907–1914.
18. Robertson C. Desaturation episodes after severe head injury: influence on
outcome. Acta Neurochir Suppl (Wien) 1993; 59:98–101.
19. Cormio M, Valadka AB, Robertson CS. Elevated jugular venous oxygen
saturation after severe head injury. J Neurosurg 1999; 90:9–15.
20. Struchen MA, Hannay HJ, Contant CF, Robertson CS. The relation between
acute physiological variables and outcome on the Glasgow Outcome Scale
and Disability Rating Scale following severe traumatic brain injury. J Neuro-
trauma 2001; 18:115–125.
21. Timofeev I, Czosnyka M, Carpenter KL, et al. Interaction between brain
chemistry and physiology after traumatic brain injury: impact of autoregulation
and microdialysis catheter location. J Neurotrauma 2011; 28:849–860.
22. Kirkpatrick PJ, Smielewski P, Czosnyka M, et al. Near-infrared spectroscopy
use in patients with head injury. J Neurosurg 1995; 83:963–970.
23. Yokoyama S, Hifumi T, Kawakita K, et al. Early hyperoxia in the intensive care
unit is significantly associated with unfavorable neurological outcomes in
patients with mild-to-moderate aneurysmal subarachnoid hemorrhage. Shock
2019; 51:593–598.
24. Gouvea Bogossian E, Diaferia D, Ndieugnou Djangang N, et al. Brain tissue
oxygenation guided therapy and outcome in nontraumatic subarachnoid
hemorrhage. Sci Rep 2021; 11:16235.
25. Chen HI, Stiefel MF, Oddo M, et al. Detection of cerebral compromise with
multimodality monitoring in patients with subarachnoid hemorrhage. Neuro-
surgery 2011; 69:53–63.
26. Heran NS, Hentschel SJ, Toyota BD. Jugular bulb oximetry for prediction of
vasospasm following subarachnoid hemorrhage. Can J Neurol Sci 2004;
31:80–86.
27. Sarrafzadeh AS, Sakowitz OW, Kiening KL, et al. Bedside microdialysis: a tool
to monitor cerebral metabolism in subarachnoid hemorrhage patients? Crit
Care Med 2002; 30:1062–1070.
28. Ekelund A, Kongstad P, Säveland H, et al. Transcranial cerebral oximetry
related to transcranial Doppler after aneurysmal subarachnoid haemorrhage.
Acta Neurochir (Wien) 1998; 140:1029–1035.
www.co-criticalcare.com 11
CE: Tripti; MCC/280202; Total nos of Pages: 12;
MCC 280202
Acute neurological problems
29. Fallenius M, Raj R, Reinikainen M, et al. Association between high arterial
oxygen tension and long-term survival after spontaneous intracerebral he-
morrhage. Crit Care Med 2016; 44:180–187.
30. López HV, Vivas MF, Ruiz RN, et al. Association between postprocedural
hyperoxia and poor functional outcome after mechanical thrombectomy for
ischemic stroke: an observational study. Ann Intensive Care 2019; 9:59.
31. Allen BB, Hoffman CE, Traube CS, et al. Continuous brain tissue oxygenation
monitoring in the management of pediatric stroke. Neurocrit Care 2011;
15:529–536.
32. Keller E, Steiner T, Fandino J, et al. Jugular venous oxygen saturation thresh-
olds in trauma patients may not extrapolate to ischemic stroke patients:
lessons from a preliminary study. J Neurosurg Anesthesiol 2002;
14:130–136.
33. Pinczolits A, Zdunczyk A, Dengler NF, et al. Standard-sampling microdialysis
and spreading depolarizations in patients with malignant hemispheric stroke. J
Cereb Blood Flow Metab 2017; 37:1896–1905.
34. Giacalone G, Zanoletti M, Re R, et al. Time-domain near-infrared spectro-
scopy in acute ischemic stroke patients. Neurophotonics 2019; 6:015003.
35. Menon DK, Coles JP, Gupta AK, et al. Diffusion limited oxygen delivery
following head injury. Crit Care Med 2004; 32:1384–1390.
36. Hoiland RL, Robba C, Menon DK, Sekhon MS. Differential pathophysiologic
phenotypes of hypoxic ischemic brain injury: considerations for postcardiac
arrest trials. Intensive Care Med 2020; 46:1969–1971.
37. Sekhon MS, Ainslie PN, Menon DK, et al. Brain hypoxia secondary to diffusion
limitation in hypoxic ischemic brain injury postcardiac arrest. Crit Care Med
2020; 48:378–384.
38. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the management of
severe traumatic brain injury, fourth edition. Neurosurgery 2017; 80:6–15.
39. Battisti-Charbonney A, Fisher J, Duffin J. The cerebrovascular response to
carbon dioxide in humans. J Physiol 2011; 589(Pt 12):3039–3048.
40. Gupta AK, Menon DK, Czosnyka M, et al. Thresholds for hypoxic cerebral
vasodilation in volunteers. Anesth Analg 1997; 85:817–820.
41. Badenes R, Oddo M, Suarez JI, et al. Hemoglobin concentrations and RBC
transfusion thresholds in patients with acute brain injury: an international
survey. Crit Care 2017; 21:159.
42. Lessard Bonaventure P, Lauzier F, Zarychanski R, et al., Canadian Critical
Care Trials Group and the Canadian Traumatic Brain Injury Research Con-
sortium. Red blood cell transfusion in critically ill patients with traumatic brain
injury: an international survey of physicians’ attitudes. Can J Anaesth 2019;
66:1038–1048.
43. Robertson CS, Hannay HJ, Yamal J-M, et al. Effect of erythropoietin and
transfusion threshold on neurological recovery after traumatic brain injury: a
randomized clinical trial. JAMA 2014; 312:36–47.
44. Rockswold SB, Rockswold GL, Zaun DA, Liu J. A prospective, randomized
phase II clinical trial to evaluate the effect of combined hyperbaric and
normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen
toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg
2013; 118:1317–1328.
12 www.co-criticalcare.com
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
45. Wang Y, Gao Y, Lu M, Liu Y. Long-term functional prognosis of patients with
aneurysmal subarachnoid hemorrhage treated with rehabilitation combined
with hyperbaric oxygen: case-series study. Medicine (Baltimore) 2020;
99:e18748.
46. Hankey GJ, Bennett MH, Wasiak J, et al. Hyperbaric oxygen therapy for acute
ischemic stroke. Stroke 2006; 37:1953–1954.
47. Cui H-J, He H-Y, Yang AL, et al. Hyperbaric oxygen for experimental intracer-
ebral haemorrhage: systematic review and stratified meta-analysis. Brain Inj
2017; 31:456–465.
48. Brassard P, Seifert T, Secher NH. Is cerebral oxygenation negatively affected
by infusion of norepinephrine in healthy subjects? Br J Anaesth 2009;
102:800–805.
49. Mrozek S, Gobin J, Constantin JM, et al. Crosstalk between brain, lung and
heart in critical care. Anaesth Crit Care Pain Med 2020; 39:519–530.
50. Robba C, Poole D, McNett M, et al. Mechanical ventilation in patients with
&& acute brain injury: recommendations of the European Society of Intensive
Care Medicine consensus. Intensive Care Med 2020; 46:2397–2410.
This international consensus panel highlighted important targets for mechanical
ventilation in patients with ABI, emphasizing indications for endotracheal intuba-
tion, targets for tidal volume ventilation, PaO2 and PaCO2 targets, PEEP selection
strategy, and rescue maneuvers (prone positioning, recruitment maneuvers, neu-
romuscular blockade, and extracorporeal memrane oxygenation) in patients with
severe respiratory failure.
51. Mazzeo AT, Fanelli V, Mascia L. Brain-lung crosstalk in critical care: how
protective mechanical ventilation can affect the brain homeostasis. Minerva
Anestesiol 2013; 79:299–309.
52. Luce JM, Huseby JS, Kirk W, Butler J. A Starling resistor regulates cerebral
venous outflow in dogs. J Appl Physiol Respir Environ Exerc Physiol 1982;
53:1496–1503.
53. Picetti E, Pelosi P, Taccone FS, et al. VENTILatOry strategies in patients with
severe traumatic brain injury: the VENTILO Survey of the European Society of
Intensive Care Medicine (ESICM). Crit Care 2020; 24:158.
54. Hawryluk GWJ, Aguilera S, Buki A, et al. A management algorithm for patients
& with intracranial pressure monitoring: the Seattle International Severe Trau-
matic Brain Injury Consensus Conference (SIBICC). Intensive Care Med
2019; 45:1783–1794.
This Delphin-based consensus approach outlined an algorithm to management of
high ICP in patients with severe TBI. A three tier-based strategy to ICP manage-
ment was provided with each additional tier outlining more aggressive therapies for
ICP control.
55. Stetter C, Weidner F, Lilla N, et al. Therapeutic hypercapnia for prevention of
secondary ischemia after severe subarachnoid hemorrhage: physiological
responses to continuous hypercapnia. Sci Rep 2021; 11:11715.
56. Melin T, Enomoto M. Sedation, analgesia, and neuromuscular blockade in
neurosurgical critical care. In: Brambrink AM, Kirsch JR, editors. Essentials of
neurosurgical anesthesia & critical care: strategies for prevention, early
detection, and successful management of perioperative complications..
Cham: Springer International Publishing; 2020. pp. 557–563.
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