Neurocrit Care

https://doi.org/10.1007/s12028-019-00812-6

AIRWAY, VENTILATION, AND SEDATION

Emergency Neurological Life Support:

Airway, Ventilation, and Sedation
Asma Moheet1*, Marlina Lovett2, Stephanie Qualls3 and Venkatakrishna Rajajee4*

© 2019 Neurocritical Care Society

Abstract
Neurocritically ill patients often have evolving processes that threaten the airway and adequate ventilation; as such,
airway and respiratory management are of utmost importance. Airway management, intubation, ventilation, and
sedative choices directly affect brain physiology and perfusion. Emergency Neurological Life Support topics discussed
here include acute airway management, indications for intubation with special attention to hemodynamics and
preservation of cerebral blood flow, initiation of mechanical ventilation, and the use of sedative agents based on the
patient’s neurological status in the setting of acute neurological injury.
Keywords: Airway, Ventilation, Sedation, Neurocritical care, Emergency

Introduction paralyzing medications should be performed to provide

Airway management and respiratory support of the
acutely brain-injured patient can be a matter of life or
death. Failure to establish an airway in a patient with
rapidly progressive neurological decline may result in
respiratory arrest, acidosis, secondary brain injury from
hypoxemia, elevated intracranial pressure, severe aspira-
tion pneumonitis, acute respiratory distress syndrome
(ARDS), and cardiac arrest. Conversely, the process of
induction and intubation itself can result in physiologic
changes which increase intracranial pressure (ICP) in
brain-injured patients, worsen cerebral perfusion in
patients with an ischemic penumbra, and result in loss
of the neurological examination at a time when it is
required for urgent decision-making.
The goals of airway management in neurological
patients are to maintain adequate oxygenation and ven-
tilation, optimize cerebral physiology, preserve cerebral
perfusion, and prevent aspiration. A rapid neurological
assessment prior to the administration of sedating and
*Correspondence: Asma.Moheet@ohiohealth.com; vrajajee@yahoo.com
1
Neurocritical Care, OhioHealth - Riverside Methodist Hospital,
Columbus, OH, USA
4
Departments of Neurosurgery and Neurology, University of Michigan,
Ann Arbor, MI, USA
Full list of author information is available at the end of the article
a functional baseline whereby neurological and neurosur-
gical decision-making may ensue.
The Emergency Neurological Life Support (ENLS)-
suggested algorithm for the initial management of
airway, ventilation, and sedation is shown in Fig. 1. Sug-
gested items to complete within the first hour of evalu-
ating a patient are shown in Table 1. These suggestions
are meant to give a broad framework for the principles of
diagnosis and emergent management of airway, ventila-
tion, and sedation, which can be adapted to reflect global
and regional variations based on the local availability of
diagnostic tools and treatments.
Assessing the Need for Intubation
Patients in severe respiratory distress or impending res-
piratory or cardiac arrest should be intubated without
delay. Additionally, a patient who cannot “protect their
airway” because of progressive neurological decline or
concern for aspiration may need tracheal intubation.
Intubation should not be delayed, but due to the potential
for complications such as significant hemodynamic dis-
turbances, a rapid but thorough risk–benefit assessment
should be conducted. The decision to intubate is influ-
enced by factors specific to patient physiology, clinical
environment, and the anticipated course of care.
 Fig. 1 ENLS airway, ventilation, and sedation protocol

A stuporous, deteriorating, or comatose patient requir- With these considerations in mind, there are four com-
ing extended transport, transfer, imaging, or invasive monly accepted indications to intubate:
procedures may be most appropriately managed with a
secure endotracheal airway.
Table 1 Airway, ventilation, and sedation checklist within the first hour
Checklist
□ Assess the need for intubation or noninvasive positive pressure ventilation
□ Perform and document a focused neurological assessment prior to intubation
□ Verify the endotracheal tube position
□ Determine ventilation and oxygenation targets, and verify with ABG/SpO2/ETCO2
□ Assess the need for analgesia and/or sedation in mechanically ventilated patients
ABG arterial blood gas, ETCO2 end-tidal C
­ O2, SpO2 peripheral oxygen saturation
1. Failure to oxygenate
This finding may be determined by visual inspection
such as evidence of respiratory distress or cyanosis, vital
signs data such as low oxygen saturation on pulse oxime-
try, or laboratory data such as arterial blood gas analysis.
2. Failure to ventilate
Ventilation is assessed by visual inspection including
observation of respiratory effort exerted, capnometry
through nasal cannula or transcutaneous monitoring [1],
and/or arterial blood gas analysis.
3. Failure to protect the airway
Airway protection is the result of numerous variables
including bulbar function, airway anatomy, quantity and
quality of secretions, strength of cough reflex, and ability to
swallow after suctioning [2, 3]. The presence of a gag reflex
is an inadequate method of assessing airway protection [4].
4. Anticipated neurological or cardiopulmonary decline
requiring transport or immediate treatment
Anticipation of the trajectory of the patient’s condition
can allow for appropriate preparation for the procedure
as opposed to rushed or emergent intubations.
Prehospital Management
First responders assessing patients with impaired breath-
ing in the setting of possible underlying neurological
injury should rapidly assess the scene and provide support
for airway and breathing in a safe and expeditious man-
ner. Patients who suffer acute neurological injury may
demonstrate one of the above criteria for intubation at the
time of assessment. Those with an inability to protect the
airway should be managed immediately with an airway-
opening maneuver: the jaw-thrust maneuver is preferred
when the cause of the patient’s neurological impairment
is not readily apparent and cervical spine immobilization
is indicated. When spontaneous breathing is absent or
seriously impaired, bag mask ventilation (BMV) should
be performed. Airway adjuvants such as a nasal airway or
oropharyngeal airway may be used. The decision to per-
form endotracheal intubation in the prehospital setting,
however, can be challenging. Prehospital intubation has
been best studied in severe traumatic brain injury (TBI).
Observational studies in the setting of TBI have been
inconsistent [5], with some studies demonstrating pos-
sible harm from prehospital intubation [6]. In one study,
prehospital intubation performed by aeromedical crews
with specialized training was associated with improved
outcomes [7]. An Australian randomized clinical trial of
patients with TBI with Glasgow Coma Scale (GCS) ≤ 9
and > 10 min of ground transport time to a designated
trauma center demonstrated improved 6-month out-
comes in patients who underwent prehospital intubation
[8]. Given these conflicting results, and extrapolating
from studies performed in TBI, prehospital intubation
in patients with acute neurological injury should be per-
formed by personnel with appropriate training and expe-
rience in Rapid Sequence Intubation (RSI) patients with
GCS < 9, an inability to protect the airway or hypoxemia
despite the use of supplemental oxygen. When person-
nel with appropriate training and experience are not pre-
sent, or an attempted intubation is unsuccessful, BMV
should be performed in conjunction with basic airway-
opening maneuvers or airway adjuncts while the patient
is transported to the hospital. Of note, supraglottic airway
(SGA) devices may be especially useful under these cir-
cumstances, as an alternative to endotracheal intubation
in the prehospital setting, or by persons trained in these
devices, but not intubation. Once an endotracheal tube or
SGA has been placed, the use of quantitative capnography
should be used when available, to avoid both hypoventila-
tion and hyperventilation [1].
Decision Made to Intubate: Perform Neurological
Assessment
When circumstances permit, urgent management of
the airway should coincide with a focused neurological
assessment. The examination can typically be conducted
in 3 min or less, as many components of the examination
rely simply on careful observation of the patient while
they are being stabilized. The pre-sedation/pre-intuba-
tion neurological examination establishes a baseline that
is used to assess therapeutic interventions (e.g., patients
with stroke, seizures, hydrocephalus, or other disorders)
or may identify injuries that are at risk of progressing
(e.g., unstable cervical spine fractures). The assessment
identifies the type of testing required and may help to
limit unnecessary interventions, such as radiological cer-
vical spine clearance. Findings should be documented
and communicated directly to the team that assumes care
of the patient. The pre-intubation neurological examina-
tion should include an evaluation of:
••  Level of arousal, interaction, and orientation, as well
as assessment of simple cortical functions such as
vision, attention, and speech, and comprehension
••  Limited cranial nerve evaluation: pupil assessment,
eye movements
••  Motor function of each individual extremity
••  Tone and reflexes
••  Recognition of involuntary movement consistent
with tremor or epileptic activity
••  Cervical tenderness or spinal abnormality
••  Sensory examination in patients with suspected spi-
nal cord injury to identify a sensory level
Airway Assessment
A difficult airway may be broadly defined as an endotra-
cheal intubation attempt in which a provider who is
appropriately trained in airway management experi-
ences difficulty with BMV, tracheal intubation, or both
[9]. Using this broad definition, up to 30% of emergency
department (ED) intubations may involve “difficult air-
ways” [10]. Patients with acute neurological injury may
be at higher risk for a difficult airway because of the need
to immobilize the cervical spine in patients who suffer
trauma or are “found down” following neurological emer-
gencies such as strokes or seizures. It is essential that all
healthcare providers who manage critically ill neurologi-
cal patients be able to identify common factors that may
increase the complexity of airway management. Iden-
tification of the difficult airway is essential for selection
of the appropriate technique (awake fiberoptic vs. rapid
sequence induction) and tools [video vs. direct laryngo-
scopy (DL)]. Failure to identify a difficult airway prior to
induction is one of the most important factors predicting
a subsequent failed airway during the intubation attempt
[11, 12].
The “LEMON” pneumonic has been shown to success-
fully predict difficult tracheal intubation in the ED [13]:
L = Look externally, for features such as abnormal
facies, oro-maxillo-facial trauma, and abnormal body
habitus
E = Evaluate with the 3-3-2 rule:
• Will 3 of the patient’s fingers fit between the inci-
sors of the open mouth? If not, mouth opening may
be too limited to permit adequate DL or manipula-
tion of the endotracheal tube.
•  Will 3 of the patient’s fingers fit between the chin
(mentum) and the hyoid bone? If not, the airway
may be too anterior for easy visualization with DL.
•  Will 2 of the patient’s fingers fit between the hyoid
bone and the superior thyroid notch? If not, the
airway may be too high in the neck to permit easy
visualization.
M = Mallampati score assesses the extent of mouth
opening in relation to tongue size [14] (Fig. 2).
Grade I—Soft palate, entire uvula, faucial pillars visible
Grade II—Soft palate, entire uvula visible
Grade III—Soft palate, base of uvula visible
Grade IV—Only hard palate visible
Grades I and II predict easy visualization, Grade III
predicts difficulty, and Grade IV extreme difficulty. Mal-
lampati grading ideally requires some patient coopera-
tion and may be difficult to assess in patients with acute
brain injury.
O = Obstruction/Obesity. The presence of redundant
soft tissue (obesity), a supraglottic mass, or trauma/
hematoma within the oropharynx may obscure the view
of the glottis.
N = Neck mobility. Inability to attain the sniffing posi-
tion because of immobilization of the cervical spine in
the trauma patient, ankylosing spondylitis, rheumatoid
arthritis, or age-related degenerative disease.
The “MOANS” pneumonic predicts difficulty of bag
mask ventilation [13]:
M = Mask seal may be compromised by abnormal
facies, facial hair, and body fluids
O = Obesity/obstruction
A = Age > 55
N = No teeth
S = Stiff lungs
When a difficult airway is identified, the most impor-
tant next step is to ensure the provider with the most
experience in airway management is present at the bed-
side, as well as a provider capable of rapidly establish-
ing a surgical (or percutaneous) airway in the event of a
failed intubation. Availability and functional status of all

Fig. 2 Mallampati score assesses the extent of mouth opening in
relation to tongue size. From Allen et al. [15]
necessary tools at the bedside, such as a SGA, endotra-
cheal tube introducer (bougie), cricothyroidotomy tray,
and a video laryngoscope, should be confirmed. Finally,
it is important to remember that prediction of a diffi-
cult airway is imperfect and that an unanticipated diffi-
cult airway may be encountered at any time [16]. Ready
availability of the necessary expertise and equipment in
the form of an institutional airway team may increase
survival to hospital discharge and decrease the need for a
surgical airway [17].
Endotracheal Intubation of the Critically Ill
Neurological Patient
Several societies have published guidelines for the man-
agement of the difficult airway, particularly in the setting
of anesthesia for elective procedures [9, 18–21]. Intu-
bation of the critically ill patient is a fundamentally dif-
ferent clinical situation than intubation in the relatively
stable environment of the operating room [20, 21]. While
over 90% will be technically successful, about 20–25%
of critically ill patients will develop severe hypoxemia
during intubation, 10–25% will develop severe hypoten-
sion, and about 2% will suffer cardiac arrest [12, 22, 23].
More so than other critically ill patients, the patient with
an acute brain injury is unlikely to tolerate significant
periods of hypoxemia or hypotension due to the risk of
secondary brain injury [24–26]. The ENLS intubation
algorithm (Fig. 3) therefore emphasizes evidence-based
best practice for maintenance of adequate oxygenation
and perfusion during intubation, as well as the most
direct and dependable pathway to a definitive airway.
As a first step, at least two providers, including at least
one provider experienced in airway management, should
be present at the bedside. Two-provider presence may
decrease complications associated with intubation of the
critically ill [22, 27].
Awake Intubation
The provider may be “forced to act” in the patient with
acute neurological illness who has a compromised airway
and rapid progression to cardiovascular or respiratory
collapse, necessitating an urgent attempt at laryngoscopy
and intubation. When the provider is not “forced to act,”
however, and the patient is spontaneously breathing and
oxygenating adequately on supplemental oxygen, consid-
eration should be given first to an awake intubation. An
awake fiberoptic intubation will avoid possible displace-
ment of the cervical spine due to use of the laryngoscope
[28] and may be the intubation technique of choice in the
presence of significant cervical spine injury. An awake
intubation may also be the procedure of choice when
an anticipated difficult airway or BMV makes cessation
of spontaneous respiratory effort RSI hazardous. Awake
intubation is typically performed using moderate seda-
tion in conjunction with topical anesthesia, most com-
monly with a flexible endoscope that is navigated into the
trachea via an oral or nasal route [29]. An endotracheal
tube fitted onto the flexible endoscope is then advanced
over the endoscope into the trachea. An awake intuba-
tion is not appropriate in patients with elevated intrac-
ranial pressure, as stimuli are often avoided and deep
sedatives may be required in this setting. A fiberoptic
intubation requires considerable expertise and should
be performed only with a highly experienced provider at
the bedside. Should awake intubation be unsuccessful,
the experienced provider must decide on an alternative
technique with the greatest likelihood of success and may
consider video laryngoscopy (VL), a SGA, or a surgical
airway.
Pre‑oxygenation and Apneic Oxygenation
Maintaining adequate oxygen saturation before and
during intubation is critical for the patient with acute
 Fig. 3 Algorithm for tracheal intubation of the critically ill neurological patient
neurological illness. Any significant period of hypoxemia
may result in secondary injury to the vulnerable brain
and exacerbate ICP elevation [25, 30]. When feasible,
pre-oxygenation should be performed prior to intuba-
tion. Three minutes of pre-oxygenation with noninvasive
positive pressure ventilation (NIPPV) [31] or a heated
high-flow nasal cannula (HHFNC) at 60–70 L/min that
is continued following induction may be more effective
at preserving oxygenation during the intubation attempt
than pre-oxygenation with a high-flow (non-rebreather)
face mask. Pre-oxygenation should be performed with
the head of bed (HOB) elevated to 30°.
Apneic oxygenation consists of the administration of
high-flow oxygen via HHFNC at 60–70 L/min or a regu-
lar nasal cannula at 15 L/min after RSI, during laryngos-
copy. While randomized trials have failed to consistently
demonstrate an improvement in outcomes, the prepon-
derance of evidence, including four recent meta-analyses,
suggests that apneic oxygenation increases time to
desaturation and first-pass success without hypoxemia
[32–35]. Since apneic oxygenation is easy to perform,
inexpensive, and without serious adverse effects, its use is
recommended during intubation of the critically ill neu-
rological patient.
Intubating the Patient with Intracranial Pathology
RSI consists of the simultaneous administration of a fast-
active sedative to induce immediate unresponsiveness
and a neuromuscular-blocking agent to achieve optimal
intubating conditions, with the goal of attaining control
of the airway in the critically ill patient at risk of aspira-
tion of stomach contents. RSI limits the elevation of ICP
often associated with the physiologic responses to laryn-
goscopy and is the preferred method for intubation of the
patient with elevated ICP [36, 37]. The presence of coma
should not justify proceeding without pharmacological
agents, or administration of only a neuromuscular-block-
ing agent without appropriate pre-treatment induction
agents. Although the patient may seem unresponsive,
laryngoscopy and intubation often provoke reflexes that
elevate the ICP unless appropriate pre-treatment induc-
tion agents are used [38].
Outcomes in brain-injured patients are related to
the maintenance of both brain perfusion and oxy-
genation. It is generally recommended that the ICP be
maintained below 23 mmHg, systolic blood pressure
(SBP) > 100–110 mmHg, and cerebral perfusion pressure
(CPP = MAP–ICP) at a minimum of 60 mmHg during
intubation [39]. When the airway is manipulated, two
responses may exacerbate intracranial hypertension. The
reflex sympathetic response (RSR) results in increased
heart rate, increased blood pressure, and in brain-injured
patients, increased ICP due to the loss of normal autoreg-
ulation. The direct laryngeal reflex stimulates an increase
in ICP independent of the RSR [13]. Because the ICP may
not be known at the time of urgent intubation, clinicians
should anticipate elevated ICP in patients with conditions
such as mass lesions, hydrocephalus, or extensive cerebral
edema and choose an appropriate BP target accordingly.
Elevations in ICP should be mitigated by minimizing air-
way manipulation by having the most experienced person
perform the intubation and administer medications.
Two common pre-medications used to prevent
increased ICP during intubation are discussed in more Fig. 4 Intubation with elevated ICP [43]
detail below.

••  Perform intubation with HOB ≥ 30°. Reverse Tren-

Lidocaine
Administered intravenously at a dose of 1.5 mg/kg
60–90 s before intubation, lidocaine attenuates the direct
laryngeal reflex. There is mixed evidence that it mitigates
the RSR [40, 41]. It is not associated with drop in mean
arterial pressure (MAP).
Fentanyl
At doses of 2–3 μg/kg, fentanyl attenuates the RSR asso-
ciated with intubation and is administered as a single pre-
treatment dose over 30–60 s in order to reduce chances
of apnea or hypoventilation prior to induction and paral-
ysis [42]. It is generally not used in patients with incipient
or actual hypotension, or those who are dependent on
sympathetic drive to maintain an adequate blood pres-
sure for cerebral perfusion.
ICP during intubation also rises due to body position-
ing and hypoventilation. Hypoventilation immediately
increases the arterial partial pressure of carbon diox-
ide ­(PaCO2), a potent acute cerebral vasodilator. When
ICP is known or suspected to be elevated, the following
approach is suggested (Fig. 4):
delenburg positioning during intubation may be con-
sidered instead for patients who continue to require
immobilization of the thoraco-lumbar spine.
••  MAP must be preserved throughout the procedure,
with a goal of 80–110 mmHg, but not lower than the
pre-intubation blood pressure. If ICP is monitored,
keep CPP > 60 mmHg.
••  Pain, discomfort, agitation, and fear must be con-
trolled with adequate analgesia and sedation.
••  Hypoventilation must be avoided, and quantitative
end-tidal capnography monitoring is recommended.
••  Adequate oxygen saturation should be maintained
at all times during intubation. In addition to the use
of effective pre-oxygenation and apneic oxygenation,
BMV should be used between intubation attempts
and at any time that the peripheral oxygen saturation
­(SpO2) is lower than 94%.
Intubating the Patient with Brain Ischemia
In suspected or proven ischemic stroke, careful atten-
tion should be taken to avoid hypotension during
induction and post-intubation. In the healthy state, the
cerebrovascular circulation is well collateralized. During
an ischemic stroke, many patients possess an infarct core
surrounded by a greater region of ischemic penumbra.
Under these circumstances, the ischemic penumbra con-
sists of a region of vasodilated vessels, receiving maximal
compensatory shunting from the adjacent cerebrovas-
cular circulation. Hypertension and tachycardia often
reflect a compensatory, not pathophysiologic, response
to this ischemia and may be necessary to maintain perfu-
sion of the ischemic territory.
Certain vasoactive agents may reverse regional vaso-
constriction in normal areas of the brain that is neces-
sary to maintain physiologic shunting of blood to the
region of ischemia, even if they do not drop the systemic
blood pressure or alter the global CPP. An episode of
relative or actual hypotension can dramatically increase
brain infarct size by “stealing” blood flow from the maxi-
mally dilated watershed territories between vascular
distributions.
Brain ischemia is not limited to ischemic stroke but is
also variably present in patients with vasospasm, TBI,
intracranial and extracranial cerebrovascular stenosis,
and hypoxic–ischemic encephalopathy following resus-
citation from cardiac arrest. Strong correlations between
episodic hypotension and poor neurological outcome
have been noted in the critical hours following resus-
citation from TBI and cardiac arrest [26, 44–46]. Even
transient reductions in cerebral blood flow (CBF) may
be harmful, and every effort should be made to main-
tain CBF and systemic vascular tone during airway man-
agement. A fluid bolus should be administered prior to
intubation in any patient with possible volume depletion.
Ketamine or etomidate is the preferred induction agents
in patients with compromised cerebral perfusion. Vaso-
pressors should be administered to prevent hypotension
as needed during or following RSI. Brain ischemia is
worsened by the effect of hyperventilation upon vascular
tone. Normocapnia should be maintained during intuba-
tion, and early correlation of ­PaCO2 with end-tidal ­CO2
­(ETCO2) is suggested to enable noninvasive tracking of
ventilation [1].
Conflicting evidence exists regarding the risks of rou-
tine intubation and general anesthesia for acute ischemic
stroke patients who require endovascular intervention
[47–49]. Two randomized trials of conscious sedation
versus intubation in patients undergoing urgent endo-
vascular thrombectomy for acute ischemic stroke did not
show a difference in outcomes; as such, patients should
not be intubated simply because they are undergoing
urgent thrombectomy with no other indications [50, 51].
Since there is some evidence to suggest harm from rou-
tine use of general anesthesia [47–49], moderate seda-
tion without intubation may be the technique of choice
for most ischemic stroke patients requiring endovascu-
lar therapy. Intubation should be considered, however,
for patients with bulbar dysfunction, an inability to pro-
tect the airway or control secretions, hypoxemia, hyper-
capnia, a high risk of aspiration (including patients with
emesis), or significant agitation [49].
Intubating the Patient with an Unsecured Vascular
Malformation or Expanding Hematoma
Laryngoscopy may result in severe hypertension as a con-
sequence of the RSR. Severe hypertension may increase
the risk of rebleeding from a ruptured aneurysm or other
intracranial vascular malformation [52]. Severe hyper-
tension may also result in hematoma expansion following
intracerebral hemorrhage [53]. Fentanyl should therefore
be considered for pre-treatment prior to RSI, to blunt the
RSR. In addition, ketamine, which causes sympathetic
stimulation, should likely be avoided for RSI. Appropriate
analgesia and sedation should be initiated immediately
following intubation, to avoid dyssynchrony and hyper-
tension from discomfort caused by the presence of the
endotracheal tube.
Intubating the Patient with Neuromuscular
Weakness
Although some patients with neuromuscular disease
require immediate intubation, those with preserved
bulbar function and reasonable functional ventilatory
reserves may undergo a trial of noninvasive ventilation
combined with airway clearance by the frequent use of
chest physiotherapy and a cough-assist device [54].
Any patient with neuromuscular weakness that com-
plains of dyspnea should undergo an assessment of res-
piratory function that includes (see also the ENLS Acute
Non-Traumatic Weakness protocol):
••  Arterial blood gas measurement
••  Serial respiratory function assessments including
negative inspiratory force (NIF), forced vital capacity
(FVC), and/or maximum expiratory force (MEF)
••  Assessment of bulbar function, neck strength, and
cough
Candidates for intubation include patients with bulbar
dysfunction and a demonstrated inability to manage air-
way secretions or maintain a patent airway, those who
have a rapidly progressive course, and those who do not
rapidly stabilize gas exchange and work of breathing with
noninvasive ventilation [54].
Choice of neuromuscular blockade should be carefully
considered in neurocritically ill patients. In myasthenia
gravis, succinylcholine is safe but requires approximately
2.5 times the dose for the same effect [55]. Non-depo-
larizing agents such as rocuronium are also safe but
will have a prolonged duration [55]. In conditions such
as Guillain–Barré, succinylcholine can precipitate life-
threatening hyperkalemia, and only non-depolarizing
agents should be used.
Intubating the Patient with Cervical Spine Injury
Cervical spine injury should be suspected following
direct neck trauma or blunt head trauma resulting in loss
of consciousness. During care of these patients, meas-
ures must be taken to protect the spinal cord during any
movements or procedures, including intubation. Certain
airway maneuvers can result in displacement of the cervi-
cal spine and injury to the spinal cord in the setting of
cervical instability. These include head tilt/chin lift, BMV,
cricoid pressure, and DL and should be avoided in this
patient population [28, 56, 57]. Blade elevation results in
the greatest displacement of the spine during laryngos-
copy [28]. Awake fiberoptic intubation should, therefore,
be considered the best option in patients with signifi-
cant cervical spine injury who are awake, spontaneously
breathing, and have stable oxygenation on supplemental
oxygen [58, 59]. Patients with acute hypoxemic or hyper-
capnic respiratory failure and rapid clinical decline may
not be suitable candidates for an awake fiberoptic intuba-
tion; such patients may require RSI with manual in-line
stabilization (MILS). Similarly, patients who may have
raised ICP and those with impending or established car-
diovascular collapse should not undergo awake fiberop-
tic intubation. When RSI is performed, every precaution
should be taken to minimize displacement of the cervical
spine, although some movement may be inevitable [28,
56, 57]. Prior to intubation, the anterior part of the semi-
rigid collar should be removed to permit greater mouth
opening during laryngoscopy. The head should then be
maintained in the neutral position using MILS (dem-
onstrated in Fig. 5), in which an assistant stands by the
patient with a hand on either side of the head between
the mastoid process and the occiput [56]. The assistant
must then hold the head steady while gently opposing the
applied forces of airway manipulation.
When a basic maneuver is necessary to open the air-
way, a jaw thrust should be performed rather than a head
tilt/chin lift. The use of cricoid pressure is no longer rec-
ommended during intubation. It definitely should not be
implemented in patients with cervical spine injury, as it
may cause posterior displacement of the cervical spine
[60]. MILS adversely impacts visualization of the glottis,
with only the epiglottis visible in about 22% of patients
intubated using DL [61]. The use of VL to improve glot-
tic visualization has therefore become common practice
when MILS is necessary [62]. While VL consistently
Fig. 5 Manual in-line stabilization during intubation of the patient
who requires immobilization of the cervical spine. Image depicts use
of video laryngoscopy
results in a better view of the glottis than DL [63–65],
­ lidescope® (Verathon Medical Inc,
manipulation of the ETT into the glottis can be challeng-
ing. When using the G
Bothell, WA) VL, the hyperangulated rigid stylet should
be used. The anterior part of the semirigid collar should
be promptly re-applied following intubation.
Rapid Sequence Intubation
Prior to intubation, consider the use of a pre-intubation
checklist (Fig. 6) [12, 21].
Induction Agents
Since hypotension is common following sedation [12, 22,
23, 66] and may exacerbate secondary injury in patients
with acute brain injury [24–26, 30, 44, 67], the use of a
hemodynamically neutral agent such as etomidate or
a sympathetic stimulant such as ketamine is recom-
mended. Table 2 lists the properties of some medications
commonly used for RSI in patients with acute neurologi-
cal illness.
Etomidate
Etomidate is a short-acting agent that provides sedation
and muscle relaxation with minimal hemodynamic effect,
administered at a dose of 0.3 mg/kg intravenous (IV)
push. Despite concerns about adrenal suppression, it is
considered to be one of the most hemodynamically neu-
tral of all commonly used induction agents and a drug of
choice for patients with elevated ICP or compromised
cerebral perfusion [68].
Ketamine
Ketamine is a dissociative agent administered at a dose
of 2 mg/kg IV push. Ketamine causes sympathetic stimu-
lation and is therefore the most favorable of all available
 PATIENT EQUIPMENT TEAM PLAN FOR DIFFICULTY

1. RELIABLE IV/ IO ACCESS 1. MONITORING 1. ASSIGN ROLES 1. CANNOT INTUBATE CAN

2. OPTIMAL POSITION
o Head of bed- consider 30-45o
elevaon
o Bed height
o Access to airway
o Sniffing/ neutral/ ramped
3. PRE-OXYGENATION
o Heated high flow nasal
cannula 60-70 L/mt
o Noninvasive posive
Pressure venlaon
o Reservoir-bag mask
o Bag-valve mask
4. APNEIC OXYGENATION IN
PLACE
5. Heated high flow nasal
cannula 60-70 L/mt
o Nasal cannula 15L/mt
6. OPTIMIZE PATIENT STATE
o Pre-treat with fentanyl and
lidocaine
o Raised intracranial pressure-
23.4% NaCL or mannitol
o Hypotension/ hypovolemia-
fluid bolus, vasopressors
infusing
o Le/ right ventricular failure-
vasopressor available/
infusing
o SpO2 with volume turned o First intubator VENTILATE
up o Backup intubator o 2-3 aempts by
o Quantave waveform o Bag-mask venlaon experienced operator with
capnography (ETCO2) o Manual in-line stabilizaon apneic oxygenaon as long
o Electrocardiogram o Drugs as SpO2>95%
o Blood pressure- cuff to cycle o Monitoring o Supragloc airway
every 2 minutes or arterial o Documentaon o Invasive airway
line. Cuff not on side of o Invasive airway
SpO2 probe. 2. CANNOT INTUBATE
2. Who will be called for CANNOT VENTILATE
2. EQUIPMENT backup? o Supragloc airway
o Laryngoscope handle and o Emergent
blades, test bulb Cricothyroidotomy
o Video laryngoscope, blade
and rigid stylet
o Endotracheal tube x2 with
stylet- selected size and
smaller opon
o Bougie
o Oral/ nasal airway
o Sucon
o CO2 detector
o Supragloc airway
o Kit for invasive airway
3. MEDICATIONS
o Sedave
o Neuromuscular blocking
agent
o Vasopressor
o Sedaon/ analgesia
following intubaon

Fig. 6 Pre-intubation checklist. Adapted from 4th National Audit Project of the Royal College of Anaesthetists and Difficult Airway Society (NAP4)
and Difficult Airway Society Guidelines for the management of tracheal intubation in critically ill adults 2018 [12, 21]

induction agents from a hemodynamic standpoint [69,
70]. It is the induction agent of choice for patients with
shock or compromised cerebral perfusion. Historically,
use of ketamine was avoided in patients with elevated
ICP. Some evidence suggests, however, that when con-
current sedation is provided, it is safe in patients with
elevated ICP [71]. In view of the significant sympathetic
stimulation that accompanies its use, an alternative to
ketamine should be considered in patients with unse-
cured vascular malformations, acute intracerebral hem-
orrhage, or significant ischemic heart disease.
Propofol
At a dose of 1.5–2 mg/kg IV push, propofol is an alter-
native induction agent. However, it is also a potent vas-
odilator that may cause hypotension and may not be
appropriate for patients with threatened cerebral perfu-
sion unless concurrently administered with a vasopres-
sor agent [72]. Propofol may therefore be most useful
in patients with severe hypertension, particularly in the
context of acute subarachnoid or spontaneous intra-
parenchymal hemorrhage.
Neuromuscular Blockade
Succinylcholine
Succinylcholine is a depolarizing neuromuscular blocker
with a rapid onset (30–60 s) and short duration of action
(5–15 min), making it an ideal agent for RSI. The RSI
dose is 1.5–2 mg/kg IV. Although it has been associated
with transient increases in ICP, the effect is not consid-
ered clinically significant [73]. Immobile and chronically
ill neurological patients are at risk for succinylcholine-
induced hyperkalemia because of an upregulation in
extra-junctional acetylcholine receptors. This includes
patients with chronic neurological/neuromuscular dis-
ease such as amyotrophic lateral sclerosis, multiple
sclerosis and chronic myopathies, as well as those with
as little as 24–72 h of immobility following acute brain
Table 2 Medications commonly used in Rapid Sequence Intubation
Drug Dose Onset of action Duration of effect Indications Precautions

Fentanyl 2–3 μ/kg IV over 1–2 min Within 2–3 min 30–60 min Pre-induction, blunts ICP rise Respiratory depression,
hypotension, rare chest wall
rigidity
Lidocaine 1.5 mg/kg IV 2–3 min before 45–90 s 10–20 min Pre-induction, blunts ICP rise Avoid if allergic or high-grade
intubation heart block if no pacemaker
Esmolol 1–2 mg/kg IV 2–10 min 10–30 min Pre-induction, blunts ICP rise Bradycardia, hypotension,
increased airway reactivity
Etomidate 0.3 mg/kg IV 30–60 s 3–5 min Induction, sedation; good Decreases seizure threshold,
in hypotension. Decreases decreases cortisol synthesis;
CBF, ICP, preserves CPP avoid in sepsis
Propofol 2 mg/kg IV 9–50 s 3–10 min Induction, sedation, reduces Hypotension, myocardial
ICP and airway resistance, depression
anticonvulsive effects
Ketamine 1.5–2 mg/kg IV 1–2 min 5–15 min Induction, analgesia, seda- Catecholamine surge, possible
tion, amnesia, broncho- increase in ICP, “re-emer-
dilatory effects; good in gence” phenomenon if not
hypotension pretreated with benzos
Succinylcholine 1.5–2 mg/kg IV 30–60 s 5–15 min Preferred paralytic unless Avoid in hyperkalemia, myo-
contraindicated pathy, neuropathy/denerva-
tion, history of malignant
hyperthermia
Rocuronium 1.2 mg/kg 45–60 s 45–70 min Paralysis when succinylcho- Caution in difficult mask venti-
line contraindicated lation and difficult intubation
Vecuronium 0.2 mg/kg Within 3 min 35 min Least preferred paralytic This dose speeds onset during
for RSI RSI.
Caution in difficult mask venti-
lation and difficult intubation
CBF cerebral blood flow, CPP cerebral perfusion pressure, ICP increase intracranial pressure, RSI Rapid Sequence Intubation

or spinal cord injury [74]. It is critical, therefore, that
the provider performing RSI always screens for con-
traindications to succinylcholine in patients with acute
neurological illness, to avoid precipitating a life-threat-
ening bradyarrhythmia, ventricular arrhythmia, or car-
diac arrest. Succinylcholine should be avoided in these
patients and a non-depolarizing agent used [75].
Non‑depolarizing Agents
Non-depolarizing agents have a longer duration of action
than succinylcholine. A non-depolarizing agent with
rapid onset and relatively short duration of action should
be used, such as rocuronium (at 1.2–1.4 mg/kg IV push)
or vecuronium (at 0.1–0.2 mg/kg IV push). Rocuronium
produces optimal intubating conditions almost as quickly
(45–60 s) as succinylcholine but has a significantly longer
duration of action (45–70 min). The novel agent sugam-
madex, administered at a dose of 16 mg/kg 3 min fol-
lowing rocuronium dosing, can reverse neuromuscular
blockade and restore muscle function faster than with
the use of succinylcholine [76, 77]. Sugammadex should
therefore be available at locations where the use of steroi-
dal neuromuscular-blocking agents such as rocuronium
is common and can be utilized in clinical situations
where a rapid return of muscle function is desirable.
Bag Ventilation and Basic Airway Management
Following induction and paralysis, the use of BMV prior
to laryngoscopy may improve oxygenation during intuba-
tion. While there has been concern about an increased
risk of aspiration with routine BMV, the recent PreVent
randomized clinical trial of 401 critically ill patients
demonstrated that routine BMV following induction
decreased the incidence of severe hypoxemia with no
increase in aspiration [78]. The use of proper BMV tech-
nique is critical. Two-provider BMV is preferable, with
one provider entirely focused on attaining an effective
mask seal while simultaneously performing a basic air-
way-opening maneuver, such as the head tilt/chin lift, or,
when cervical spine immobilization is necessary, a jaw
thrust (Fig. 7). A second individual performs bag ventila-
tion, and a third provides MILS when necessary. A breath
should be administered approximately every 6 s, using
the minimum volume required to attain chest rise, along
with an expiratory–port valve that provides 5–10 cmH2O
of positive end-expiratory pressure (PEEP) [78]. The rou-
tine use of an adjuvant such as an oral or nasal airway
may greatly facilitate effective BMV. Apneic oxygenation
 Fig. 7 Technique of two-provider bag mask ventilation, with a third
provider performing MILS. A first provider grasps the mask with the
thumb and index finger in a “C” hold while the other three fingers
grasp the mandible in an “E” hold, while performing either jaw thrust,
as shown in this patient, or a head tilt/chin lift. A third provider
provides MILS

Fig. 8 Cormack–Lehane laryngoscopic grade. From Chakravarthy

with a HHFNC or a regular nasal cannula at 15 L/min
should be performed following induction and continued
during BMV and laryngoscopy.
Laryngoscopy and Intubation
When BMV is effective, up to three attempts at laryn-
goscopy and intubation are permissible, as long as
the ­SpO2 remains > 94%. BMV should be performed
between attempts, and apneic oxygenation continued
at all times. With every subsequent attempt, a change
in operator (more experienced operator steps in) and/
or technique (such as a change from DL to VL, or use
of a bougie) should occur. When BMV using optimal
technique is ineffective, an experienced operator may
make a single attempt at laryngoscopy and intubation.
Use of VL should be considered for this “single, best
attempt” for optimal glottis visualization. The use of
VL consistently results in higher rates of glottis visu-
alization [63–65] and may be particularly valuable for
less experienced operators and for difficult airways [63,
79]. Although randomized trials have not consistently
demonstrated superiority in outcomes with the use of
VL in the critically ill [79–81], a recent Cochrane meta-
analysis of 64 clinical trials suggested that the use of VL
improves glottic visualization and decreases the num-
ber of failed intubations, particularly in patients with
with the ­Glidescope® (Verathon Medical Inc, Bothell,
difficult airways [79]. When intubation is performed
WA) VL, use of the hyperangulated rigid ­Glidescope®
stylet is recommended, to facilitate navigation of the
and Seipp [84]
ETT past the sharp curve of the VL blade to the glottis
[82].
The Cormack–Lehane system is used to grade the
direct laryngoscopic view of the glottis [83] (Fig. 8).
Grade I—Entire glottis visible
Grade IIa—Partial view of the glottis
Grade IIb—Only the posterior extremity of the glottis
(or only arytenoids) visible
Grade III—Only epiglottis visible, no view of glottis
inlet
Grade IV—Neither epiglottis nor glottis visible
Documentation of the direct laryngoscopic grade in the
medical record is critical, to inform future airway man-
agement decisions.
The Failed Airway
A failed airway is considered to exist in one of the two
situations: (1) the “cannot intubate, cannot ventilate” sce-
nario, when BMV is ineffective at achieving gas exchange
and a “single, best attempt” at intubation by an expe-
rienced operator is unsuccessful, and (2) the “cannot
intubate, CAN ventilate” scenario, when three attempts
at intubation (at least one by an experienced operator)
using best equipment (including VL) and technique have
been unsuccessful, but BMV remains effective. Since
both these scenarios may result in death or devastating
anoxic injury [11, 12], every provider who participates
in airway management of the critically ill neurological
patient must have a basic knowledge of the approach to
a failed airway. In order to provide the most direct and
dependable path to a definitive airway, the ENLS intuba-
tion algorithm recommends an attempt at placement of
a SGA, such as a laryngeal mask airway, in the event of
a failed airway. SGAs have a high success rate with inex-
perienced providers and typically require limited training
to use [85, 86]. The second-generation SGAs that include
features such as a bite block and an esophageal/gastric
channel, or SGAs that can serve as conduits for subse-
quent blind or fiberoptic-guided passage of an ETT, are
preferable [87]. Up to two attempts, with different opera-
tors and/or techniques, are permissible as long as the
­SpO2 remains > 94%. Apneic oxygenation should be con-
tinued and BMV performed between attempts. If SGA
placement is successful and gas exchange established,
insertion of an ETT through the SGA may be attempted.
When SGA insertion is unsuccessful, or oxygen desatu-
ration occurs at any time, immediate cricothyroidotomy
should be performed using a surgical or percutaneous
technique. Delays in performing a cricothyroidotomy in
patients with a failed airway are an important cause of
death and severe morbidity [11, 12].
Post‑intubation Management
Following intubation, consider the use of a post-intuba-
tion checklist (Table 3) [88].
Basic Ventilator Settings
Immediately following intubation, respiratory and hemo-
dynamic homeostasis should be restored. Except in situ-
ations of acute brain herniation, the goals of mechanical
ventilation are:
••  Normalization of oxygenation utilizing the lowest
fraction of inspired oxygen ­(FiO2) that will maintain
oxygen saturation of hemoglobin > 94%
Table 3 Post-intubation checklist
Post-intubation checklist
□ Secure endotracheal tube
□ Confirm tube position, order chest x-ray
□ Set cuff pressure to 20–30 cmH2O
□ Pulse oximetry and quantitative waveform capnography
□ Arterial blood gas measurement
□ Deep sedation while neuromuscular blockade in effect
□ Counsel next of kin on change in patient status
••  Normalization of ventilation to achieve a systemic
pH of 7.35–7.45, and ­PaCO2 to 35–45 mmHg (4.7–
6.0 kPa) or E
­ TCO2 that corresponds to ­PaCO2 target
••  Normalization of the work of breathing
••  Prevention of ventilator-induced lung injury
In most circumstances, clinicians should default to vol-
ume-cycled ventilation at 6–8 cc/kg of ideal body weight
and a respiratory rate of 12–14 per minute. However,
these settings must take into account the patient’s min-
ute ventilation prior to intubation. Normal ­PaCO2 range
is an appropriate target unless there is chronic hypercap-
nia (i.e., severe chronic obstructive pulmonary disease
or sleep-disordered breathing). In situations of chronic
hypercapnia, the admission bicarbonate level should
be used to estimate the “baseline” ­PaCO2, and that level
should subsequently be used as the target. When meta-
bolic acidosis is present, ventilation should target a nor-
mal serum pH.
Ventilator Modes and Settings
The initial ventilator mode should provide a set respira-
tory rate, while permitting patient initiation of respira-
tion (triggered breaths). Assist-control (AC) ventilation
and synchronized intermittent mandatory ventilation
(SIMV) are the most widely used modes in patients who
require substantial ventilator support. AC results in ste-
reotypical breaths generated regardless of initiation
by machine or patient. With SIMV, breaths delivered
within the set rate reflect the defined parameters, while
patient-initiated breaths above the set rate reflect either
patient effort alone, or a level of pressure support that
is added to SIMV (typically about 10 cmH2O). The set
rate is adjusted to achieve the goal P­ aCO2, while main-
taining the goal ratio of inspiratory to expiratory time
(I:E ratio) to avoid gas trapping. Most commonly, a flow
trigger is used to detect patient inspiratory effort, set at
about 2 L/min. Regardless of mode, breaths delivered
may be defined by volume (flow targeted, volume cycled)
in which tidal volume is assured, but airway pressures are
variable, or by pressure (pressure targeted, time cycled)
in which maximum airway pressure is assured, but tidal
volume depends on airway resistance and patient effort.
Volume-control (VC) ventilation is most commonly uti-
lized, given the importance of avoiding excessive tidal
volumes, particularly in the setting of the ARDS [89].
With VC ventilation, a peak inspiratory flow rate (about
60 L/min, titrated to goal I:E ratio and airway pressure),
flow pattern (typically a square waveform although
ramp and sinusoidal waveforms may also be used), and
tidal volume (typically 6–8 cc/kg) are specified. Using
lower tidal volumes (4–8 cc/kg) is particularly impor-
tant for patients with ARDS [89]. With pressure control
(PC) ventilation, an inspiratory pressure (Pi, starting at
8–10 cmH2O and titrated to the goal tidal volume) and
inspiratory time (Ti, titrated to the desired I:E ratio) are
specified. A specific mode of PC ventilation that permits
constant auto-titration of Pi by the ventilator to achieve
a set tidal volume is frequently used and combines bene-
fits of PC and VC ventilation. This mode may be referred
to as “Pressure-Regulated Volume Control” (Siemens),
“VC+” (Puritan Bennett), or “Auto-flow” (Drager),
among others. In all cases, ­FiO2 and PEEP are specified.
The ­FiO2 is usually set at 100% following intubation and
then titrated to an oxygenation goal. The PEEP is most
commonly set at 5 cmH2O and is also titrated to an oxy-
genation goal to permit reduction of the ­FiO2 to < 60%. A
higher initial PEEP may be set in patients with hypoxemia
prior to intubation (particularly those with ARDS) as well
as patients with morbid obesity. Airway pressure release
ventilation (APRV) is a form of extreme inverse ratio PC
ventilation used in patients with severe acute hypoxic
respiratory failure and ARDS. In APRV, the presence of
a dynamic expiratory valve in the circuit allows sponta-
neous breathing at high lung volumes, thereby improv-
ing patient comfort while achieving high mean airway
pressures to maintain an “open lung.” Pressure support
ventilation (PSV) is a weaning mode without a set rate,
in which all breaths are spontaneous and supported by a
defined level of pressure (often starting at 10–15cmH2O).
PSV is used when the patient is on minimal sedation, and
ventilatory requirements have substantially decreased.
Unlike PC, breaths in PSV are pressure targeted but flow
cycled (with breaths cycled off most commonly at 25% of
peak inspiratory flow), which makes this the most com-
fortable ventilator mode for most patients. Patients with
neurological injury intubated for airway protection alone,
with low requirements of sedation and ventilatory sup-
port, may therefore benefit from PSV. While peak airway
pressures are generally maintained < 30–40 cmH2O, the
pressure parameter that best reflects the risk of baro-
trauma at the alveolar level is the plateau pressure, meas-
ured using an inspiratory hold. The plateau pressure must
be maintained < 30 cmH2O. Gas trapping (auto-PEEP)
is measured with an expiratory hold, which is used to
determine a total PEEP. Intrinsic (auto-) PEEP is then cal-
culated by subtracting the applied PEEP. While typically
minimal or no spontaneous respiratory effort should be
Table 4 Chronic respiratory acidosis: estimated pre-morbid ­PaCO2 based on admission ­HCO3 level
Chronic respiratory acidosis:
Estimated pre-morbid ­pCO2 based on admission H
­ CO3 level
Admission bicarbonate (mEq/L) 45
Predicted “usual” ­PaCO2 in mmHg (kPa) 92.5 (12.3)
HCO3 bicarbonate, PaCO2 partial pressure of carbon dioxide
present when performing an inspiratory or expiratory
hold, measurement of plateau and driving pressure in
spontaneously breathing patients may be feasible [90].
PEEP and Brain Injury
A theoretical concern in patients with acute brain injury
is that higher levels of PEEP will increase intrathoracic
pressure, impair venous return from the brain, and
worsen elevated ICP. Most studies of applied PEEP up
to 15–20 cmH2O [91, 92], as well as ventilator modes
such as APRV [93], in the setting of acute brain injury
have demonstrated modest or no impact on ICP. In
the setting of ARDS, applied PEEP appears to improve
brain tissue oxygenation [94]. A PEEP-induced drop in
cardiac output may, however, compromise cerebral per-
fusion [92]. Higher levels of PEEP (> 10 cmH2O) and
APRV can, therefore, be used as otherwise appropriate
in the setting of acute brain injury, in conjunction with
continuous monitoring of ICP and CPP, as well as brain
tissue oxygenation where available.
Titrate Ventilation
Induced Hyperventilation: Ventilation, Carbon Dioxide
Tension, and Clinical Outcome
Hyperventilation causes cerebral vasoconstriction and
decreased CBF, while hypoventilation causes cerebral
vasodilation and increased ICP [95]. Dysventilation
(and especially hyperventilation) is associated with poor
outcomes in TBI [96–98]. However, the relationship
between arterial and central pH and P ­ aCO2 is complex
and incompletely understood. During concomitant meta-
bolic acidosis and TBI, central nervous system (CNS) pH
and CBF are often preserved despite severe systemic aci-
dosis due to the blood brain barrier and the CNS buffer-
ing capacity [99]. Alternatively, in patients with chronic
respiratory acidosis, the set point of cerebral ­CO2 reactiv-
ity changes. It is therefore recommended that mechani-
cal ventilation be adjusted to correct the pH and not the
­PaCO2 or that the estimated “pre-morbid” ­PaCO2 target
be used (see Table 4 below). This is a practical goal since
ventilating these patients to “normal” ­PaCO2 targets may
be extremely difficult or impossible when obstructive
lung disease is present.
42 39 36 33 30 27 24
85 (11.3) 77.5 (10.3) 70 (9.3) 62.5 (8.3) 55 (7.3) 47.5 (6.3) 40 (5.3)
Herniation: Intentional Hyperventilation to Treat Brain
Herniation and Increased ICP
When a patient develops brain herniation with elevated
intracranial pressure, hyperventilation is an appropriate
temporizing intervention designed to acutely decrease
ICP and prevent subsequent neuronal injury and death
[100, 101]. Maximal cerebral vasoconstriction is achieved
at a P
­ aCO2 near 20 mmHg (2.7 kPa). Therefore, hyper-
ventilation below this level results in no further therapeu-
tic advantage and even less profound ­PaCO2 reductions
may impede venous return to the heart, decrease blood
pressure, and exacerbate cerebral hypoperfusion. Dur-
ing hyperventilation, E ­TCO2 monitoring (quantitative
capnography) is suggested. As soon as other treatments
to control ICP are in place (e.g., blood pressure support,
osmotherapy, surgical decompression, hypothermia,
metabolic therapy), hyperventilation should be weaned
to restore brain perfusion [102]. Hyperventilation
severely reduces CBF, increases the volume of ischemic
tissue, and may result in rebound elevation of ICP during
weaning [103, 104]. Prolonged hyperventilation (beyond
a few hours) should therefore not be used.
Acidemic and Alkalemic Hypocapnia: Potential
for Suppression of Spontaneous Hyperventilation
There are two circumstances that should be considered
in patients with spontaneous hypocapnia: those whose
response to systemic metabolic acidosis accounts for
their high ventilatory demand, and those (alkalotic)
patients in whom ventilation exceeds systemic metabolic
needs.
In patients whose ventilation is driven by metabolic
acidosis, suppression of the respiratory drive with seda-
tion or neuromuscular blockade is not recommended,
unless direct measurement of brain chemistry suggests
that hyperventilation is driving cerebral metabolic crisis.
Under these circumstances, clinicians must find another
means to buffer pH.
Mechanically ventilated TBI patients presenting with
hypocapnia have worse outcomes than their normocap-
nic peers. However, non-intubated patients presenting
with hypocapnia do not exhibit similar findings, suggest-
ing that hypocapnia, in this setting, may be a physiologic
response and should not be suppressed [97]. Despite
decades of observation and consideration, little is known
about alkalemic hypocapnia in patients with an acute
brain injury. Alkalemic hypocapnia following brain injury
may be theoretically explained by a variety of physiologic
and pathophysiologic mechanisms, more than one of
which may be present in an individual patient:
••  Brain tissue acidosis requiring acute hyperventilation
as a buffer until CNS bicarbonate-generating com-
pensatory mechanisms can catch up
••  Inadequately treated pain, anxiety, fear, or agitation
••  Fever
••  Autoregulation of elevated ICP
••  Heme breakdown products or a lactic acid load in the
ventricular system
••  Direct pressure on chemoreceptors present in the
floor of the fourth ventricle
••  Physiologic dysregulation of the medullary respira-
tory rhythm generator, which has afferent inputs
from the pons, mesencephalon, and higher cortical
centers
A recent trial of patients with severe brain injury
monitored for brain tissue oxygen showed brain tissue
hypoxia worsened when E ­ TCO2 values were reduced by
spontaneous alkalemic hyperventilation, suggesting pos-
sible harm [105]. It is rarely known whether alkalemic
hypocapnia is a physiologic or pathophysiologic process,
suppression of this respiratory activity is recommended
only in response to evidence that hyperventilation is
causing direct harm, either by inducing cerebral ischemia
or indirectly by increased systemic metabolic demands
and work of breathing.
Oxygenation and Outcomes
Hypoxemia is a major source of secondary brain injury
[106], and the injured and ischemic brain is particularly
vulnerable to low oxygen levels. Similarly, supra-physio-
logic levels of oxygen provided to acutely ill patients have
the potential to worsen reperfusion injury and outcomes
[107, 108]. Hyperoxemia drives the formation of reactive
oxygen species, overwhelming antioxidants at sites of
tissue injury; directly injures respiratory epithelium and
alveoli inducing inflammation; drives hypercapnia; and
leads to absorption atelectasis in the lung. Hyperoxemia
­(PaO2 > 300 mmHg or 40 kPa) immediately following
resuscitation is independently associated with poor out-
comes in TBI and cardiac arrest [108, 109], though not all
published data are concordant [110–112].
It is recommended that 100% oxygen be provided for
pre-oxygenation immediately prior to intubation, but
that oxygen be immediately weaned following intubation
to 50%, or the lowest ­FiO2 that will support an oxyhemo-
globin saturation of 95–100%.
Oxygenation and Ventilation Monitoring
Oxygenation should be monitored by pulse oximetry
or by arterial blood gas analysis when oximetry is sus-
pected to be inaccurate. Conditions of poor perfusion
to the extremities, acidosis, vasopressor use, anemia,
carboxyhemoglobinemia and methemoglobinemia, and
hypoxia all have the potential to compromise the accu-
racy of pulse oximetry measurements [113].
Ventilation is traditionally monitored by serial arte-
rial blood gas analysis, though venous blood gas analysis
may provide an adequate surrogate when arterial samples
cannot be obtained. End-tidal quantitative capnography
of exhaled gases provides an appealing continuous meas-
urement and is extremely useful to monitor trends in ven-
tilation. One study showed that severely hyperventilated
head trauma patients ­(PaCO2 < 25 mmHg or 3.3 kPa) in
the prehospital environment had higher mortality and
that use of quantitative capnography by paramedics sig-
nificantly decreased the incidence of hyperventilation
[114]. A similar study in patients with major trauma
showed a much higher incidence of normocapnia on hos-
pital arrival when ­ETCO2 was monitored by medics.
Because ­ETCO2 measurements reflect not only ventila-
tion but also systemic perfusion, the correlation between
­ETCO2 and ­PaCO2 in the blood is variable, especially
when severe physiologic derangements are present [115].
In an inpatient environment, E ­TCO2 measurements
should always be correlated with an arterial P­ aCO2 sam-
ple. ­ETCO2 and P­ aCO2 may also vary significantly when
lung disease and ventilation–perfusion mismatch are
present [116].
Sedation
Necessity of Sedation
The use of sedation in the critically ill neurological
patient has both benefits and drawbacks. Sedation may
be needed to alleviate fear and anxiety, reduce ICP and
cerebral oxygen consumption, facilitate tolerance of the
endotracheal tube and mechanical ventilation, or reduce
sympathetic hyperactivity. Complications associated with
under-sedation include ventilator, patient injury, agita-
tion, anxiety, device removal, and elevated ICP. Adequate
sedation is paramount in all therapeutic algorithms for
the treatment of increased ICP [117, 118], since psy-
chomotor restlessness, pain, and autonomic stress all
adversely affect ICP, CBF, CPP, and the cerebral meta-
bolic rate for oxygen metabolism (­CMRO2). Conversely,
sedation makes accurate neurological examination, the
cornerstone of clinical assessment, difficult or impos-
sible. Therapeutic and procedural decision-making are
often contingent upon an accurate neurological assess-
ment. Acute changes in brain physiology become diffi-
cult to detect, and the accuracy of neuroprognostication
is decreased [119, 120]. Sedation may cause vasodila-
tion, reducing cerebral perfusion due to hypotension and
also reversing physiologically advantageous shunting of
blood into areas of ischemia. Even short-acting sedatives
are known to accumulate in fatty tissues, causing effects
beyond their intended duration. Despite each of the com-
peting interests, adequate consideration must be made
for patient comfort and safety.
Depth of Sedation
In a general intensive care unit (ICU) population, the
use of excessive sedation and analgesia contributes to
increased duration of mechanical ventilation and longer
length of stay in the ICU and hospital [121, 122]. There-
fore, while some patients with acute neurological illness
will require deep sedation for the control of ICP or the
management of status epilepticus, most patients should
be lightly sedated, so they are easily arousable and attend
to voice, to the extent their neurological injury permits.
Sedation should be titrated to a validated sedation score
(Table 5), such as the Richmond Agitation–Sedation
Scale (RASS) [123, 124], or the Riker Sedation–Agitation
Scale (SAS) [125]. A recent review of sedation assess-
ment tools in the neurocritical care setting concluded
that the SAS and RASS are valid and useful for patients in
the neurocritical care unit (NCCU) [126]. A goal of light
sedation (approximately a RASS score of 0 to − 2) is rec-
ommended for most patients without a specific indica-
tion for deep sedation [127]. Sedation should be titrated
to an electrophysiologic endpoint when neuromuscular
blockade is employed or burst suppression on electroen-
cephalography (EEG) is desired.
Role of Analgesics
Unless deep sedation or general anesthesia is desired,
analgesia should precede sedation. Many patients with
adequate pain control do not require sedation, and con-
versely, most sedative medications provide no analgesia.
Sedation without pain control may be an important cause
of delirium. Infusion of short-acting analgesics allows for
interruption and neurological assessment at intervals.
Recent studies have demonstrated that analgosedation, a
strategy that focuses on using a short-acting opioid infu-
sion (remifentanil or fentanyl) alone to manage pain and
discomfort, without a sedative, may result in a reduction
in duration of mechanical ventilation and ICU length of
stay [128–130]. The use of analgosedation should there-
fore be considered first in all mechanically ventilated
patients who do not have a specific indication for a seda-
tive infusion, such as raised ICP, seizures, or ongoing use
of neuromuscular blockade [127].
Choice of Sedative
Patients may require sedation despite the effective use
of analgesia within the first hours following intubation.
Several randomized trials have compared the use of ben-
zodiazepine infusions, mostly midazolam, to propofol
and dexmedetomidine. A meta-analysis of these studies,
Table 5 Richmond Agitation–Sedation Scale (RASS) the Riker Sedation–Agitation Scale (SAS)
Richmond Agitation–Sedation Scale (RASS)
Score Term Description

+4 Combative Overtly combative or violent; immediate danger to staff

+3 Very agitated Pulls on or removes tube(s) or catheter(s) or has aggressive behavior toward staff
+2 Agitated Frequent, non-purposeful movement or patient–ventilator dyssynchrony
+1 Restless Anxious or apprehensive but movements not aggressive or vigorous
0 Alert and calm
−1 Drowsy Not fully alert, but has sustained (more than 10 s) awakening, with eye contact, to voice
−2 Light sedation Briefly (less than 10 s) awakens with eye contact to voice
−3 Moderate sedation Any movement (but no eye contact) to voice
−4 Deep sedation No response to voice, but any movement to physical stimulation
−5 Unarousable No response to voice or physical stimulation
Riker Sedation–Agitation Scale (SAS)
Score Term Description

7 Dangerous agitation
6 Very agitated
5 Agitated
4 Calm and cooperative
3 Sedated
2 Very sedated
1 Unarousable
Pulling at endotracheal tube (ETT), trying to remove catheters, climbing over bedrail, striking at staff,
thrashing side to side
Does not calm down despite frequent verbal reminding of limits, requires physical restraints, biting ETT
Anxious or mildly agitated, attempting to sit up, calms down to verbal instructions
Calm, awakens easily, follows commands
Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple com-
mands
Arouses to physical stimuli but does not communicate or follow commands, may move spontaneously
Minimal or no response to noxious stimuli, does not communicate or follow commands

mostly conducted in general ICU patients, suggests that
both propofol and dexmedetomidine are associated with
shorter ICU length of stay and duration of mechanical
ventilation compared to benzodiazepine infusions [127].
This is relevant because the agent that is initiated in the
early hours for the management of intubation-related dis-
comfort is typically continued in the ICU. Either dexme-
detomidine or propofol should be utilized as a first-line
agent for continuous sedation, rather than a benzodiaz-
epine [127].
syndrome. This syndrome is characterized by acidosis,
hepatic failure, hypertriglyceridemia, and elevated cre-
atine kinase level. Propofol infusion syndrome may be
fatal and is more common in children and adults when
used at higher doses [131]. A recent study, comparing
propofol to dexmedetomidine sedation in critically ill
neurological patients, found high (30%) incidences of
hypotension in both groups [132]. Caution must be uti-
lized with these medications when concerns for brain
ischemia are present.

Common Sedatives in Neurological Intensive Care

Propofol
Propofol is among the best studied sedative agents used
in neurological critical care. Pharmacologically, its lipid
formulation allows for rapid penetration of the blood
brain barrier, resulting in rapid onset and cessation of
action. It has potent and immediate depressant effects
on cerebral electrical and metabolic activity, and it does
not require renal or hepatic metabolism for elimination.
Disadvantages include robust vasodilating and hypoten-
sive effects, considerable IV lipid load, and the poten-
tial for the rare, but frequently fatal, propofol infusion
Fentanyl
Fentanyl is an opioid agonist exhibiting analgesic effects
with a rapid onset and a short duration of action. It is an
agent which can be used as part of a combined sedative
analgesic approach.
Benzodiazepines
Midazolam is an appealing sedative option given the
rapid onset of action and short duration of effect with
bolus administration, making it an ideal agent for proce-
dural sedation.
 Bolus-dose midazolam is a good choice for intermittent
agitation in a NCCU population. Conversely, midazolam
infusion has been associated with prolonged mechanical
ventilation [132, 133]. Though most studies suggest the
impact of midazolam on hemodynamics is similar com-
pared to dexmedetomidine or propofol, a recent report
suggests less instability compared to dexmedetomidine
[132].
Dexmedetomidine
Dexmedetomidine is a centrally acting alpha agonist
similar to clonidine, but more specific for the alpha-2
receptor. It is increasingly utilized for ICU sedation.
Desirable properties include rapid onset and termination
of activity, mild to moderate sedation without significant
respiratory depressant action, analgesic effects, and less
delirium than the benzodiazepines [132, 134]. Undesir-
able properties include a high incidence of bradycardia
and hypotension [132, 134].
Pediatric Considerations
Anatomical and physiologic differences alter the
approach to endotracheal intubation and mechanical
ventilation of children with neurological injury. While
isolated cervical spinal injury is uncommon in chil-
dren, approximately half of all cervical spinal injuries
are associated with concomitant TBI [135]. Therefore,
cervical spine precautions should be taken when intu-
bating the trachea of a child with suspected TBI. Crite-
ria for endotracheal intubation of children with TBI and
other forms of acute brain injury include hypoxemia
unresponsive to supplemental oxygen, apnea, hyper-
capnia ­(PaCO2 > 45 mmHg or 6 kPa), GCS score ≤ 8 (a
pediatric version is recommended for children younger
than 4 years of age), rapid decrease in GCS, anisocoria
> 1 mm in the context of altered mental status, cervical
spinal injury compromising ventilation, abnormal airway
reflexes, and any clinical signs of herniation or impending
herniation [136].
Anatomical differences between the pediatric and adult
airways that should be considered prior to intubation
of the trachea include the following: (1) children have a
proportionally larger tongue, (2) upper airway tissues are
more compliant, (3) the epiglottis is longer, narrower, and
floppier, (4) the tracheal distance is shorter, and (5) chil-
dren have a prominent occiput. The narrowest portion
of the child’s upper airway is subglottic, at the level of
the cricoid ring. Historically, the child’s airway has been
described as conical in appearance, in contrast to the
adult’s cylindrical airway. However, recent imaging and
direct visualization studies have questioned this descrip-
tion and have suggested more of an elliptical appearance,
with uncertain clinical significance [137]. The infant’s
larynx is more anterior and cephalad (C3-4 vs. C5-6 in
adults), so positioning may be optimized by placing a
small shoulder roll or padding beneath the infant’s torso
to promote neutral positioning prior to intubation. Pro-
viders should be aware that infants and young children
have higher oxygen consumption and are therefore sus-
ceptible to hypoxia, have less physiologic reserve than
adults, are more likely to have oxygen desaturation
earlier, and have an enhanced vagal response. Pediat-
ric Advanced Life Support Guidelines advise that oral
intubation, following pre-oxygenation, should be per-
formed while maintaining spine immobilization using
a cuffed endotracheal tube in children with TBI [138,
139]. Length-based resuscitation tapes are helpful when
choosing appropriate intubation equipment for the child,
including blade and endotracheal tube sizes. If a length-
based resuscitation tape is unavailable, the appropriate
sized un-cuffed endotracheal tube (if cuffed is not avail-
able) for a child can be calculated using the age-based
formula: 4 + (age in years/4) [140–142]. When using
a regular cuffed endotracheal tube, select one full size
smaller than determined by the age-based formula [119].
When using a micro-cuffed endotracheal tube, select
a tube one half size smaller than the age-based calcula-
tion for un-cuffed tubes [140–142]. Cuff pressures should
be monitored and limited according to manufacturer’s
recommendations (usually less than 20–25 cmH2O). A
multicenter, randomized control trial demonstrated no
increase in post-extubation stridor or long-term compli-
cations when using cuffed tubes [143].
When intubating the trachea of a child less than 2 years
old, a straight laryngoscope blade directly lifting the epi-
glottis may be preferable because of the infant’s large and
acutely angled epiglottis. A straight size 00 laryngoscope
blade is appropriate for extremely premature infants,
size 0 for average-sized newborns, size 1 for most infants
beyond the immediate newborn period, and size 2 for
children over the age of two. For older children, either a
curved or straight blade may be used. VL is an option for
infants and young children and may be used in the set-
ting of a difficult airway or associated facial trauma. For
the child with an anticipated difficult airway, a contin-
gency plan involving an advanced airway expert should
be available for backup. If an appropriately sized endotra-
cheal tube is placed, the ideal depth can be achieved by
inserting the tube until the centimeter marking at the lip
is three times the endotracheal tube size [144].
 It is prudent to assume a full stomach and a cervical
spinal injury when intubating the trachea of a child with
TBI. Endotracheal intubation should utilize a cerebral-
protective rapid sequence induction with pre-oxygena-
tion. The time to desaturation following pre-oxygenation
is shorter in apneic infants compared to older children
(less than 100 s), and a modified RSI technique with gen-
tle pressure-limited mask ventilation (10–12 cmH2O)
and 100% oxygen may be used to avoid hypoxemia [145,
146]. This technique may also limit hypercapnia and
keeps small airways open without the risk of gastric infla-
tion and related morbidity [147–149]. Cricoid pressure
is routinely applied despite questionable evidence that it
improves clinical outcomes; however, it should be aban-
doned if it interferes with intubation or ventilation [148,
150, 151].
Pre-treatment with lidocaine (1.5 mg/kg IV with max
dose 100 mg) may be used, but its administration should
not delay emergent intubation [152]. Atropine (0.02 mg/
kg IV with a single max dose 0.5 mg) is recommended
in children ≤ 1 year old or children < 5 years receiving
succinylcholine [153]. For hemodynamically unstable
children, the combination of etomidate (0.2–0.6 mg/kg)
and neuromuscular blockade with rocuronium (1 mg/
kg) or vecuronium (0.3 mg/kg) IV is often used. The
association between etomidate and clinically significant
adrenal insufficiency should be considered when select-
ing optimal medications for intubation. Succinylcholine
is sometimes avoided because of the risk of malignant
hyperthermia, possible ICP elevation, hyperkalemia in
the setting of crush injury, and life-threatening complica-
tions associated with unknown occult metabolic or neu-
romuscular disease [154, 155]. Fentanyl (2–4 μg/kg IV) or
ketamine (1–2 mg/kg IV) is alternative sedatives. Recent
pediatric studies show that ketamine does not increase
ICP and may be neuroprotective [70, 156, 157]. If hemo-
dynamically stable, midazolam (0.1–0.2 mg/kg) may be
added to any of the above combinations.
After successful intubation, an arterial blood gas
should be obtained to confirm a P ­ aO2 of 90–100 mmHg
(12–13.3 kPa) and a P ­ aCO2 of 35–45 mmHg (4.7–6 kPa)
[136]. Unless the child has signs of herniation, hyperven-
tilation ­(PaCO2 < 35 mmHg or 4.7 kPa) should be avoided
[158]. Adequate blood pressure must always be main-
tained when administering sedatives to assure adequate
CPP. A CPP between 40 and 50 mmHg is recommended
for children with severe TBI, with infants at the lower
end of this range and adolescents at the upper end [159].
Many studies have demonstrated that a CPP ≤ 40 mmHg
is associated with higher mortality and morbidity [160,
Table 6 Airway, ventilation, and sedation communication
regarding assessment and referral
Communication
□ Mental status and neurological examination immediately pre-intuba-
□ Intracerebral hemorrhage (ICH) score, if appropriate
tion
□ Vitals, hemodynamics, and gas exchange pre- and post-intubation
□ Relevant drugs used around intubation
□ Technique of intubation, confirmation of tube position
□ Ease of bag mask ventilation, intubation, and tube passage
□ Cormack–Lehane grade, if appropriate
□ Ventilator settings, ventilation, and ­ETCO2 targets
□ Analgesia and sedation strategy
□ Pending investigations
Sample communication:
“Mr. Smith the 52-year-old gentleman with intracerebral hemorrhage
required urgent intubation.”
“His GCS was 6 prior to intubation—would not open eyes to pain, was
mute, and would only withdraw to pain on the right; he appeared to be
left hemiplegic. His right pupil was 5 mm and sluggish, and left pupil
was 3 mm and briskly reactive. Following intubation, his pupils are
3 mm and reactive bilaterally.”
“His vitals prior to intubation were BP 220/110, HR 66/m, ­SpO2 97% on
2 L/m nasal cannula. Following intubation, his BP is 130/60, HR 55/m,
­SpO2 99% on F­ iO2 100% and ­ETCO2 is 32.”
“We treated with him with lidocaine, fentanyl, and 30 cc of 23.4% NaCL
prior to intubation. We used etomidate and rocuronium for RSI.”
“We intubated him with direct laryngoscopy using a Mac 4 blade. Tube
position was confirmed with a ­CO2 detector and auscultation.”
“Bag mask ventilation was easy, although I did use an oral airway. I had a
Grade 2a view without cricoid pressure, and tube passage was easy.”
“We have him on assist control, volume control, with a tidal volume
of 6 cc/kg, respiratory rate of 24/m, PEEP 5, and ­FiO2 100%. Our goal
­ETCO2 is 30–35, and goal S­ pO2 is > 94%.”
“We started a propofol infusion, titrated to deep sedation because of the
herniation syndrome.”
“He will be transported to CT now, and the neurosurgeons will likely
take him straight to the operating room. We did not have time to get
a chest X-ray, but he has equal breath sounds and is ventilating and
oxygenating well.”
“His wife is with him and has been counseled about his condition”
CT computed tomography, ETCO2 end-tidal ­CO2, FiO2 fraction of inspired oxygen,
GCS Glasgow Coma Scale, PEEP positive end-expiratory pressure, RSI Rapid
Sequence Intubation
161]. However, optimal age-appropriate CPP thresh-
olds have not been established for TBI and other acute
neurological diagnoses. Furthermore, abnormal cer-
ebrovascular autoregulation, which is more common
in children less than 4 years old [162], makes establish-
ing such thresholds difficult in the absence of advanced
neuromonitoring.
Sedative regimens following intubation of the child
with acute neurological illness are variable. In chil-
dren, propofol infusions are often avoided due to the
concern for propofol infusion syndrome (a potentially
Table 7 Critical care pre-transportation checklist—airway, ventilation and sedation
Checklist

□ Confirm adequate pulse oximetry and end-tidal ­CO2; continue S­ pO2 and ­ETCO2 monitoring during transport
□ Evaluate hemodynamic status, confirm stability for transport, electrocardiogram and blood pressure monitoring during transport
□ Focused neurological assessment prior to transport
□ Confirm endotracheal tube position and bilateral air entry; confirm depth of insertion of endotracheal tube has not changed
□ Confirm endotracheal tube is secured appropriately
□ Ambu bag present with appropriate size of mask and positive end-expiratory pressure valve
□ Full tank of oxygen (or adequate oxygen for duration of transport)
□ Complete oral and endotracheal suctioning prior to transport
□ Confirm adequate IV access and appropriate length of tubing (extra long for magnetic resonance imaging)
□ If using a transport ventilator: trial ventilator and settings on patient prior to transport
□ Confirm emergency medication box available during transport.
□ Confirm sedation plan if appropriate, and availability of sedative/analgesia medications
□ Designate individuals in charge of bag ventilation, airway, and monitoring of vital signs
ETCO2 end-tidal C
­ O2, SpO2 peripheral oxygen saturation

Table 8 Nursing considerations: airway, ventilation, and sedation

Airway

Vigilantly monitor patients with neurological illness, and alert the provider for respiratory failure based on the four major criteria:
• failure to oxygenate
• failure to ventilate
• failure to protect the airway
• anticipated neurological or cardiopulmonary decline
If concerned that patient obstructing airway due to decreased level of consciousness, consider use of airway adjuncts such as oropharyngeal airway or
nasopharyngeal airway [170]
Identify and alert airway team to special considerations: elevated intracranial pressure, unstable cervical spine, cerebral ischemia, vascular malformation,
neuromuscular weakness
Assist with manual in-line stabilization as required
Alert the airway team to a potential difficult airway, identified using LEMON criteria
Ensure adequate intravenous access, presence of suction set up, and hemodynamic monitoring, and assist with optimal positioning, pre-oxygenation,
and preparation of medications for induction and neuromuscular blockade [170]
Rapid Sequence Intubation: administer medications and monitor hemodynamics during intubation. Anticipate hypotension due to positive pressure
ventilation, PEEP, and sedation, and have vasopressors at the bedside to use if necessary [171]
Secure endotracheal tube (ETT) using tape or commercial tube holder. Note the depth of insertion of ETT at teeth or lip [170]
Perform key functions in the checklist for transportation of the critically ill
Ventilation

Auscultate bilateral breath sounds

Establish an appropriate oxygenation goal with the provider, send arterial blood gas, alert respiratory therapist and providers to values outside the
desired range
Establish an appropriate end-tidal ­CO2 goal with the provider, alert respiratory therapist and providers to values outside the desired range
Suction ETT as needed, hyperoxygenate prior to suctioning [172]. Suctioning should be limited to two to three passes as this can increase intracranial
pressure [173]
Sedation

Establish an appropriate depth of sedation with the provider. Ensure sedation is in place while paralyzed
For patients receiving neuromuscular-blocking agents, perform peripheral nerve stimulator (“train-of-four”) testing. As the neuromuscular-blocking
agent effect dissipates, begin to wean sedation if appropriate, as a neurological examination should be prioritized
Titrate sedation to desired goal, document depth of sedation using the Richmond Agitation–Sedation Scale (RASS) or the Riker Sedation–Agitation
Scale (SAS) [124]
If respiratory effort is dyssynchronous with the ventilator, alert respiratory therapist and provider to change ventilator settings as required. If this does
not control dyssynchrony, increased sedation may be necessary [174]
Recognize common complications of sedative medications such as hypotension and bradycardia; notify provider, and treat immediately using fluid
bolus and/or vasopressor agents
PEEP positive end-expiratory pressure
lethal condition with marked metabolic acidosis). For
a child who requires frequent neurological examina-
tions, a remifentanil infusion may be useful, at a starting
infusion rate of 0.1 μg/kg/min [163]. Remifentanil is a
short-acting synthetic opioid that is metabolized via the
plasma esterase system, resulting in a very short half-life
(3–4 min). A recent study of children with severe TBI
noted that once remifentanil was paused, the examiner
was able to perform a neurological examination within
a median time of 9 min [163]. If continuous sedation is
needed after placement of an ICP monitor, options for
appropriate sedation include: (1) an opioid infusion (fen-
tanyl 1–4 μg/kg/h) with intermittent dosing of benzodi-
azepines or (2) an opioid infusion (fentanyl 1–4 μg/kg/h)
with a benzodiazepine infusion (midazolam 0.05–0.3 mg/
kg/h). A dexmedetomidine infusion at 0.2–1.2 mg/kg/h is
also an option and is frequently combined with an opioid
for the intubated patient. The use of dexmedetomidine is
not well established in children with acute head injury.
Finally, while information is currently limited, concern
exists regarding the potential neurotoxicity of sedatives
on the developing brain [164]. The strongest evidence for
this comes from animal models, with limited evidence in
clinical studies [165–169].
Communication
When communicating patient information to an accept-
ing or referring physician, consider including the key ele-
ments listed in Table 6.
Transport Considerations
Consider the use of checklists prior to transport of
the critically ill. The pre-transport checklist in Table 7
includes considerations specific to airway, ventilation,
and sedation.
Nursing Considerations
In the initial stages of a neurological emergency, the
patient’s status may change rapidly. Frequent assessment
of the patient’s neurological status should include assess-
ment of the patient’s airway and respiratory status. Alert
the care team immediately about changes in the patient’s
ability to oxygenate, ventilate, and protect airway, and
anticipate the need for an advanced airway.
Topics that may be of particular significance to nursing
are listed in Table 8.
Clinical pearls
• Use the LEMON mnemonic to identify a difficult airway
• Use the MOANS mnemonic to predict difficulty with bag mask ventila-
tion
• Identify patients who might benefit from an awake fiberoptic intuba-
tion—unstable cervical spine, anticipated difficult intubation with
relative stability in vital signs
• Always pre-oxygenate prior to intubation and use apneic oxygenation
• Consider pre-treatment with fentanyl, lidocaine, and osmotherapy prior
to intubation of the patient with elevated intracranial pressure
• Avoid hypotension in most patients with acute brain injury. Consider
the use of etomidate or ketamine in these patients
• Patients with neurological illness frequently have contraindications to
succinylcholine. Consider the routine use of rocuronium in this popula-
tion
• Always plan in advance for two different failed airway scenarios—
“cannot intubate can ventilate,” and “cannot intubate cannot ventilate”
• Use pre- and post-intubation checklists
• Identify appropriate ­PaO2 and ­PaCO2 goals
• Induced hyperventilation is generally reserved for patients with acute
cerebral herniation or acute life-threatening intracranial pressure eleva-
tion
• Use analgosedation as a first-line measure in the intubated patient
• When a sedative infusion is necessary, propofol or dexmedetomidine
may be preferable to a benzodiazepine
• Titrate to light sedation
Author details
1
Neurocritical Care, OhioHealth - Riverside Methodist Hospital, Columbus, OH,
USA. 2 Department of Pediatrics, Division of Critical Care Medicine, Nationwide
Children’s Hospital, The Ohio State University, Columbus, OH, USA. 3 Massa-
chusetts General Hospital, Boston, MA, USA. 4 Departments of Neurosurgery
and Neurology, University of Michigan, Ann Arbor, MI, USA.
Acknowledgements
The authors are grateful for the contributions and insight provided by the fol-
lowing reviewers: Aaron Raleigh, BA, EMT-P; Jeffrey Fong, PharmD, BCPS; and
Victoria McCredie, MBChB, PhD, FRCPC, MRCPUK, UNCS.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.
References
* Important papers
** Landmark papers
1. Davis DP, Dunford JV, Ochs M, Park K, Hoyt DB. The use of quantitative
end-tidal capnometry to avoid inadvertent severe hyperventilation in
patients with head injury after paramedic rapid sequence intubation. J
Trauma. 2004;56(4):808–14.
 2. Coplin WM, Pierson DJ, Cooley KD, Newell DW, Rubenfeld GD. Implica-
tions of extubation delay in brain-injured patients meeting standard
weaning criteria. Am J Respir Crit Care Med. 2000;161(5):1530–6.
3. McCredie VA, Ferguson ND, Pinto RL, et al. airway management
strategies for brain-injured patients meeting standard criteria to
consider extubation. A prospective cohort study. Ann Am Thorac Soc.
2017;14(1):85–93.
4. Mackway-Jones K, Moulton C. Towards evidence based emergency
medicine: best BETs from the Manchester Royal Infirmary. Gag reflex
and intubation. J Accid Emerg Med. 1999;16(6):444–5.
5. Gaither JB, Spaite DW, Bobrow BJ, et al. Balancing the potential risks
and benefits of out-of-hospital intubation in traumatic brain injury: the
intubation/hyperventilation effect. Ann Emerg Med. 2012;60(6):732–6.
6. Davis DP, Peay J, Sise MJ, et al. The impact of prehospital endotracheal
intubation on outcome in moderate to severe traumatic brain injury. J
Trauma. 2005;58(5):933–9.
7. Davis DP, Peay J, Serrano JA, et al. The impact of aeromedical response
to patients with moderate to severe traumatic brain injury. Ann Emerg
Med. 2005;46(2):115–22.
8. Bernard SA, Nguyen V, Cameron P, et al. Prehospital rapid sequence
intubation improves functional outcome for patients with severe
traumatic brain injury: a randomized controlled trial. Ann Surg.
2010;252(6):959–65.
9. **Apfelbaum JL, Hagberg CA, Caplan RA, et al. Practice guidelines for
management of the difficult airway: an updated report by the Ameri-
can Society of Anesthesiologists Task Force on Management of the
Difficult Airway. Anesthesiology. 2013;118(2):251–70. This is the standard
for the management of the difficult airway, particularly in the setting of the
operating room.
10. Orebaugh SL. Difficult airway management in the emergency depart-
ment. J Emerg Med. 2002;22(1):31–48.
11. Cook TM, Woodall N, Frerk C, Fourth National Audit P. Major
complications of airway management in the UK: results of the
Fourth National Audit Project of the Royal College of Anaesthetists
and the Difficult Airway Society. Part 1: anaesthesia. Br J Anaesth.
2011;106(5):617–31.
12. Cook TM, Woodall N, Harper J, Benger J, Fourth National Audit P. Major
complications of airway management in the UK: results of the Fourth
National Audit Project of the Royal College of Anaesthetists and the
Difficult Airway Society. Part 2: intensive care and emergency depart-
ments. Br J Anaesth. 2011;106(5):632–42.
13. Walls RM, Murphy M. Manual of emergency airway management. 3rd
ed. Philadelphia: Lippincott Williams & Wilkins; 2008.
14. Mallampati SR, Gatt SP, Gugino LD, et al. A clinical sign to predict
difficult tracheal intubation: a prospective study. Can Anaesth Soc J.
1985;32(4):429–34.
15. Allen B, Ganti L, Desai B Intubation, airway, and mechanical ventilation.
In: Quick hits in emergency medicine. New York: Springer; 2013.
16. Frerk C, Mitchell VS, McNarry AF, et al. Difficult Airway Society 2015
guidelines for management of unanticipated difficult intubation in
adults. Br J Anaesth. 2015;115(6):827–48.
17. Sample G, Mccabe P, Vandruff T. Code critical airway teams improves
patient safety. Crit Care. 2010;14(Suppl 1):231.
18. Cooper RM, O’Sullivan E, Popat M, Behringer E, Hagberg CA. Difficult
Airway Society guidelines for the management of tracheal extubation.
Anaesthesia. 2013;68(2):217.
19. Law JA, Broemling N, Cooper RM, et al. The difficult airway with recom-
mendations for management—part 1—difficult tracheal intubation
encountered in an unconscious/induced patient. Can J Anaesth.
2013;60(11):1089–118.
20. Myatra SN, Ahmed SM, Kundra P, et al. The All India Difficult Airway
Association 2016 guidelines for tracheal intubation in the Intensive
Care Unit. Indian J Anaesth. 2016;60(12):922–30.
21. **Higgs A, McGrath BA, Goddard C, et al. Guidelines for the man-
agement of tracheal intubation in critically ill adults. Br J Anaesth.
2018;120(2):323–52. Widely accepted guidelines for the management of
the difficult airway, specific to the critically ill.
22. Jaber S, Amraoui J, Lefrant JY, et al. Clinical practice and risk factors for
immediate complications of endotracheal intubation in the inten-
sive care unit: a prospective, multiple-center study. Crit Care Med.
2006;34(9):2355–61.
23. Simpson GD, Ross MJ, McKeown DW, Ray DC. Tracheal intubation in the
critically ill: a multi-centre national study of practice and complications.
Br J Anaesth. 2012;108(5):792–9.
24. Henzler D, Cooper DJ, Tremayne AB, Rossaint R, Higgins A. Early
modifiable factors associated with fatal outcome in patients with
severe traumatic brain injury: a case control study. Crit Care Med.
2007;35(4):1027–31.
25. Stocchetti N, Furlan A, Volta F. Hypoxemia and arterial hypotension at
the accident scene in head injury. J Trauma. 1996;40(5):764–7.
26. Trzeciak S, Jones AE, Kilgannon JH, et al. Significance of arterial
hypotension after resuscitation from cardiac arrest. Crit Care Med.
2009;37(11):2895–903 (quiz 904).
27. Schmidt UH, Kumwilaisak K, Bittner E, George E, Hess D. Effects of
supervision by attending anesthesiologists on complications of emer-
gency tracheal intubation. Anesthesiology. 2008;109(6):973–7.
28. Sawin PD, Todd MM, Traynelis VC, et al. Cervical spine motion with
direct laryngoscopy and orotracheal intubation An in vivo cinefluoro-
scopic study of subjects without cervical abnormality. Anesthesiology.
1996;85(1):26–36.
29. Collins SR, Blank RS. Fiberoptic intubation: an overview and update.
Respir Care. 2014;59(6):865–78 (discussion 78–80).
30. 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(2):216–22.
31. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves
preoxygenation before intubation of hypoxic patients. Am J Respir Crit
Care Med. 2006;174(2):171–7.
32. Pavlov I, Medrano S, Weingart S. Apneic oxygenation reduces the inci-
dence of hypoxemia during emergency intubation: a systematic review
and meta-analysis. Am J Emerg Med. 2017;35(8):1184–9.
33. Binks MJ, Holyoak RS, Melhuish TM, et al. Apnoeic oxygenation during
intubation in the intensive care unit: a systematic review and meta-
analysis. Heart Lung. 2017;46(6):452–7.
34. Oliveira JESL, Cabrera D, Barrionuevo P, et al. Effectiveness of apneic
oxygenation during intubation: a systematic review and meta-analysis.
Ann Emerg Med. 2017;70(4):483–494e11.
35. Tan E, Loubani O, Kureshi N, Green RS. Does apneic oxygenation
prevent desaturation during emergency airway management? A
systematic review and meta-analysis. Can J Anaesth. 2018;65(8):936–49.
36. Li J, Murphy-Lavoie H, Bugas C, Martinez J, Preston C. Complications of
emergency intubation with and without paralysis. Am J Emerg Med.
1999;17(2):141–3.
37. Walls RM. Rapid-sequence intubation in head trauma. Ann Emerg Med.
1993;22(6):1008–13.
38. Bedford RF, Persing JA, Pobereskin L, Butler A. Lidocaine or thio-
pental for rapid control of intracranial hypertension? Anesth Analg.
1980;59(6):435–7.
39. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the manage-
ment of severe traumatic brain injury, Fourth Edition. Neurosurgery.
2017;80(1):6–15.
40. Donegan MF, Bedford RF. Intravenously administered lidocaine prevents
intracranial hypertension during endotracheal suctioning. Anesthesiol-
ogy. 1980;52(6):516–8.
41. Salhi B, Stettner E. In defense of the use of lidocaine in rapid sequence
intubation. Ann Emerg Med. 2007;49(1):84–6.
42. Reynolds SF, Heffner J. Airway management of the critically ill patient:
rapid-sequence intubation. Chest. 2005;127(4):1397–412.
43. Seder DB, Mayer SA. Critical care management of subarachnoid hemor-
rhage and ischemic stroke. Clin Chest Med. 2009;30(1):103–22.
44. Kilgannon JH, Roberts BW, Reihl LR, et al. Early arterial hypotension
is common in the post-cardiac arrest syndrome and associated with
increased in-hospital mortality. Resuscitation. 2008;79(3):410–6.
45. Oddo M, Bosel J. Participants in the International Multidisciplinary
Consensus Conference on Multimodality, M. Monitoring of brain and
systemic oxygenation in neurocritical care patients. Neurocrit Care.
2014;21(Suppl 2):S103–20.
46. Prough DS, Lang J. Therapy of patients with head injuries: key param-
eters for management. J Trauma. 1997;42(5 Suppl):S10–8.
47. Brinjikji W, Murad MH, Rabinstein AA, et al. Conscious sedation versus
general anesthesia during endovascular acute ischemic stroke
 treatment: a systematic review and meta-analysis. AJNR Am J Neurora-
diol. 2015;36(3):525–9.
48. Abou-Chebl A, Lin R, Hussain MS, et al. Conscious sedation versus
general anesthesia during endovascular therapy for acute anterior
circulation stroke: preliminary results from a retrospective, multicenter
study. Stroke. 2010;41(6):1175–9.
49. Dhakal LP, Diaz-Gomez JL, Freeman WD. Role of anesthesia for endo-
vascular treatment of ischemic stroke: do we need neurophysiological
monitoring? Stroke. 2015;46(6):1748–54.
50. Lowhagen Henden P, Rentzos A, Karlsson JE, et al. General anesthe-
sia versus conscious sedation for endovascular treatment of acute
ischemic stroke: the anstroke trial (anesthesia during stroke). Stroke.
2017;48(6):1601–7.
51. Schonenberger S, Uhlmann L, Hacke W, et al. Effect of conscious seda-
tion vs general anesthesia on early neurological improvement among
patients with ischemic stroke undergoing endovascular thrombec-
tomy: a randomized clinical trial. JAMA. 2016;316(19):1986–96.
52. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the
management of aneurysmal subarachnoid hemorrhage: a guideline for
healthcare professionals from the American Heart Association/Ameri-
can Stroke Association. Stroke. 2012;43(6):1711–37.
53. Rodriguez-Luna D, Pineiro S, Rubiera M, et al. Impact of blood pressure
changes and course on hematoma growth in acute intracerebral hem-
orrhage. Eur J Neurol. 2013;20(9):1277–83.
54. Seneviratne J, Mandrekar J, Wijdicks EF, Rabinstein AA. Noninvasive
ventilation in myasthenic crisis. Arch Neurol. 2008;65(1):54–8.
55. Abel M, Eisenkraft JB. Anesthetic implications of myasthenia gravis. Mt
Sinai J Med. 2002;69(1–2):31–7.
56. Austin N, Krishnamoorthy V, Dagal A. Airway management in cervical
spine injury. Int J Crit Illn Inj Sci. 2014;4(1):50–6.
57. Hauswald M, Sklar DP, Tandberg D, Garcia JF. Cervical spine movement
during airway management: cinefluoroscopic appraisal in human
cadavers. Am J Emerg Med. 1991;9(6):535–8.
58. Rosenblatt WH, Wagner PJ, Ovassapian A, Kain ZN. Practice patterns in
managing the difficult airway by anesthesiologists in the United States.
Anesth Analg. 1998;87(1):153–7.
59. Malcharek MJ, Rogos B, Watzlawek S, et al. Awake fiberoptic intubation
and self-positioning in patients at risk of secondary cervical injury: a
pilot study. J Neurosurg Anesthesiol. 2012;24(3):217–21.
60. Ellis DY, Harris T, Zideman D. Cricoid pressure in emergency department
rapid sequence tracheal intubations: a risk-benefit analysis. Ann Emerg
Med. 2007;50(6):653–65.
61. Nolan JP, Wilson ME. Orotracheal intubation in patients with potential
cervical spine injuries. An indication for the gum elastic bougie. Anaes-
thesia. 1993;48(7):630–3.
62. Kill C, Risse J, Wallot P, et al. Videolaryngoscopy with glidescope reduces
cervical spine movement in patients with unsecured cervical spine. J
Emerg Med. 2013;44(4):750–6.
63. Griesdale DE, Liu D, McKinney J, Choi PT. Glidescope(R) video-laryn-
goscopy versus direct laryngoscopy for endotracheal intubation: a
systematic review and meta-analysis. Can J Anaesth. 2012;59(1):41–52.
64. Su YC, Chen CC, Lee YK, Lee JY, Lin KJ. Comparison of video laryngo-
scopes with direct laryngoscopy for tracheal intubation: a meta-analysis
of randomised trials. Eur J Anaesthesiol. 2011;28(11):788–95.
65. De Jong A, Molinari N, Conseil M, et al. Video laryngoscopy versus
direct laryngoscopy for orotracheal intubation in the intensive care
unit: a systematic review and meta-analysis. Intensive Care Med.
2014;40(5):629–39.
66. Jaber S, Jung B, Corne P, et al. An intervention to decrease com-
plications related to endotracheal intubation in the intensive care
unit: a prospective, multiple-center study. Intensive Care Med.
2010;36(2):248–55.
67. Chesnut RM, Marshall SB, Piek J, et al. Early and late systemic hypoten-
sion as a frequent and fundamental source of cerebral ischemia
following severe brain injury in the Traumatic Coma Data Bank. Acta
Neurochir Suppl (Wien). 1993;59:121–5.
68. Moss E, Powell D, Gibson RM, McDowall DG. Effect of etomidate on
intracranial pressure and cerebral perfusion pressure. Br J Anaesth.
1979;51(4):347–52.
69. Langsjo JW, Maksimow A, Salmi E, et al. S-ketamine anesthesia increases
cerebral blood flow in excess of the metabolic needs in humans. Anes-
thesiology. 2005;103(2):258–68.
70. Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Effectiveness of keta-
mine in decreasing intracranial pressure in children with intracranial
hypertension. J Neurosurg Pediatr. 2009;4(1):40–6.
71. Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients
with neurological injury? Anesth Analg. 2005;101(2):524–34.
72. Hug CC Jr, McLeskey CH, Nahrwold ML, et al. Hemodynamic effects
of propofol: data from over 25,000 patients. Anesth Analg. 1993;77(4
Suppl):S21–9.
73. Kovarik WD, Mayberg TS, Lam AM, Mathisen TL, Winn HR. Succinylcho-
line does not change intracranial pressure, cerebral blood flow velocity,
or the electroencephalogram in patients with neurologic injury. Anesth
Analg. 1994;78(3):469–73.
74. Martyn JA, Richtsfeld M. Succinylcholine-induced hyperkalemia in
acquired pathologic states: etiologic factors and molecular mecha-
nisms. Anesthesiology. 2006;104(1):158–69.
75. Patanwala AE, Erstad BL, Roe DJ, Sakles JC. Succinylcholine is associated
with increased mortality when used for rapid sequence intubation of
severely brain injured patients in the emergency department. Pharma-
cotherapy. 2016;36(1):57–63.
76. Lee C, Jahr JS, Candiotti KA, et al. Reversal of profound neuromuscular
block by sugammadex administered three minutes after rocuronium: a
comparison with spontaneous recovery from succinylcholine. Anesthe-
siology. 2009;110(5):1020–5.
77. Sorensen MK, Bretlau C, Gatke MR, Sorensen AM, Rasmussen LS. Rapid
sequence induction and intubation with rocuronium-sugammadex
compared with succinylcholine: a randomized trial. Br J Anaesth.
2012;108(4):682–9.
78. Casey JD, Janz DR, Russell DW, et al. Bag-mask ventilation during tra-
cheal intubation of critically ill adults. N Engl J Med. 2019;380(9):811–21.
79. Lewis SR, Butler AR, Parker J, Cook TM, Smith AF. Videolaryngoscopy ver-
sus direct laryngoscopy for adult patients requiring tracheal intubation.
Cochrane Database Syst Rev. 2016;11:CD011136.
80. Griesdale DE, Chau A, Isac G, et al. Video-laryngoscopy versus direct
laryngoscopy in critically ill patients: a pilot randomized trial. Can J
Anaesth. 2012;59(11):1032–9.
81. Lascarrou JB, Boisrame-Helms J, Bailly A, et al. video laryngos-
copy vs direct laryngoscopy on successful first-pass orotracheal
intubation among ICU patients: a randomized clinical trial. JAMA.
2017;317(5):483–93.
82. Sakles JC, Kalin L. The effect of stylet choice on the success rate of
intubation using the GlideScope video laryngoscope in the emer-
gency department. Acad Emerg Med. 2012;19(2):235–8.
83. Cormack RS, Lehane J. Difficult tracheal intubation in obstetrics.
Anaesthesia. 1984;39(11):1105–11.
84. Chakravarthy B, Seipp W. Direct laryngoscopy. In: Ganti L, editor. Atlas
of emergency medicine procedures. New York: Springer; 2016.
85. Murray MJ, Vermeulen MJ, Morrison LJ, Waite T. Evaluation of
prehospital insertion of the laryngeal mask airway by primary
care paramedics with only classroom mannequin training. CJEM.
2002;4(5):338–43.
86. Bosch J, de Nooij J, de Visser M, et al. Prehospital use in emergency
patients of a laryngeal mask airway by ambulance paramedics is a
safe and effective alternative for endotracheal intubation. Emerg
Med J. 2014;31(9):750–3.
87. Cook TM, Kelly FE. Time to abandon the ‘vintage’ laryngeal mask
airway and adopt second-generation supraglottic airway devices as
first choice. Br J Anaesth. 2015;115(4):497–9.
88. McConnell RA, Kerlin MP, Schweickert WD, et al. Using a post-
intubation checklist and time out to expedite mechanical ventilation
monitoring: observational study of a quality improvement interven-
tion. Respir Care. 2016;61(7):902–12.
89. Ventilation with lower tidal volumes as compared with traditional
tidal volumes for acute lung injury and the acute respiratory distress
syndrome. The Acute Respiratory Distress Syndrome Network. N Engl
J Med 2000;342(18):1301–8.
90. Bellani G, Grassi A, Sosio S, Foti G. Plateau and driving pressure
in the presence of spontaneous breathing. Intensive Care Med.
2019;45(1):97–8.
 91. Boone MD, Jinadasa SP, Mueller A, et al. The effect of positive end-
expiratory pressure on intracranial pressure and cerebral hemody-
namics. Neurocrit Care. 2017;26(2):174–81.
92. Muench E, Bauhuf C, Roth H, et al. Effects of positive end-expiratory
pressure on regional cerebral blood flow, intracranial pressure, and
brain tissue oxygenation. Crit Care Med. 2005;33(10):2367–72.
93. Fletcher JJ, Wilson TJ, Rajajee V, Davidson SB, Walsh JC. Changes
in therapeutic intensity level following airway pressure release
ventilation in severe traumatic brain injury. J Intensive Care Med.
2018;33(3):196–202.
94. Nemer SN, Caldeira JB, Santos RG, et al. Effects of positive end-expir-
atory pressure on brain tissue oxygen pressure of severe traumatic
brain injury patients with acute respiratory distress syndrome: a pilot
study. J Crit Care. 2015;30(6):1263–6.
95. Dumont TM, Visioni AJ, Rughani AI, Tranmer BI, Crookes B. Inappropri-
ate prehospital ventilation in severe traumatic brain injury increases
in-hospital mortality. J Neurotrauma. 2010;27(7):1233–41.
96. Davis DP, Idris AH, Sise MJ, et al. Early ventilation and outcome in
patients with moderate to severe traumatic brain injury. Crit Care
Med. 2006;34(4):1202–8.
97. Davis DP, Stern J, Sise MJ, Hoyt DB. A follow-up analysis of fac-
tors associated with head-injury mortality after paramedic rapid
sequence intubation. J Trauma. 2005;59(2):486–90.
98. Rangel-Castilla L, Lara LR, Gopinath S, et al. Cerebral hemodynamic
effects of acute hyperoxia and hyperventilation after severe trau-
matic brain injury. J Neurotrauma. 2010;27(10):1853–63.
99. Koenig MA, Bryan M, Lewin JL 3rd, et al. Reversal of transtentorial
herniation with hypertonic saline. Neurology. 2008;70(13):1023–9.
100. Qureshi AI, Geocadin RG, Suarez JI, Ulatowski JA. Long-term outcome
after medical reversal of transtentorial herniation in patients with
supratentorial mass lesions. Crit Care Med. 2000;28(5):1556–64.
101. Oertel M, Kelly DF, Lee JH, et al. Efficacy of hyperventilation,
blood pressure elevation, and metabolic suppression therapy in
controlling intracranial pressure after head injury. J Neurosurg.
2002;97(5):1045–53.
102. *Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged
hyperventilation in patients with severe head injury: a randomized clini-
cal trial. J Neurosurg. 1991;75(5):731–9. Randomized clinical trial that dem-
onstrated that the use of prolonged hyperventilation may worsen outcomes.
103. Stocchetti N, Maas AI, Chieregato A, van der Plas AA. Hyperventilation
in head injury: a review. Chest. 2005;127(5):1812–27.
104. Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head
injury: effect on ischemic burden and cerebral oxidative metabolism.
Crit Care Med. 2007;35(2):568–78.
105. Kilgannon JH, Jones AE, Shapiro NI, et al. Association between arterial
hyperoxia following resuscitation from cardiac arrest and in-hospital
mortality. JAMA. 2010;303(21):2165–71.
106. Balan IS, Fiskum G, Hazelton J, Cotto-Cumba C, Rosenthal RE. Oximetry-
guided reoxygenation improves neurological outcome after experi-
mental cardiac arrest. Stroke. 2006;37(12):3008–13.
107. Brucken A, Kaab AB, Kottmann K, et al. Reducing the duration of 100%
oxygen ventilation in the early reperfusion period after cardiopul-
monary resuscitation decreases striatal brain damage. Resuscitation.
2010;81(12):1698–703.
108. Kilgannon JH, Jones AE, Parrillo JE, et al. Relationship between
supranormal oxygen tension and outcome after resuscitation from
cardiac arrest. Circulation. 2011;123(23):2717–22.
109. Bellomo R, Bailey M, Eastwood GM, et al. Arterial hyperoxia and
in-hospital mortality after resuscitation from cardiac arrest. Crit Care.
2011;15(2):R90.
110. Wang CH, Chang WT, Huang CH, et al. The effect of hyperoxia on
survival following adult cardiac arrest: a systematic review and meta-
analysis of observational studies. Resuscitation. 2014;85(9):1142–8.
111. Elmer J, Scutella M, Pullalarevu R, et al. The association between
hyperoxia and patient outcomes after cardiac arrest: analysis of a high-
resolution database. Intensive Care Med. 2015;41(1):49–57.
112. Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest
care: 2010 American Heart Association Guidelines for Cardiopulmo-
nary Resuscitation and Emergency Cardiovascular Care. Circulation.
2010;122(18 Suppl 3):S768–86.
113. Mechem CC. Pulse oximetry. In: Finlay G, editors. UpToDate. Waltham,
MA: UpToDate Inc. https​://www.uptod​ate.com/home. Accessed 2 Jan
2019.
114. Dyer BA, White WA Jr, Lee D, Elkins L, Slayton DJ. The relationship
between arterial carbon dioxide tension and end-tidal carbon dioxide
tension in intubated adults with traumatic brain injuries who required
emergency craniotomies. Crit Care Nurs Q. 2013;36(3):310–5.
115. Helm M, Schuster R, Hauke J, Lampl L. Tight control of prehospital
ventilation by capnography in major trauma victims. Br J Anaesth.
2003;90(3):327–32.
116. Hardman JG, Aitkenhead AR. Estimating alveolar dead space from the
arterial to end-tidal CO(2) gradient: a modeling analysis. Anesth Analg.
2003;97(6):1846–51.
117. Brain Trauma F, American Association of Neurological S, Congress of
Neurological S, et al. Guidelines for the management of severe trau-
matic brain injury. VI. Indications for intracranial pressure monitoring. J
Neurotrauma. 2007;24(Suppl 1):S37–44.
118. Citerio G, Cormio M. Sedation in neurointensive care: advances in
understanding and practice. Curr Opin Crit Care. 2003;9(2):120–6.
119. Riker RR, Fugate JE. Participants in the International Multi-disciplinary
Consensus Conference on Multimodality, M. Clinical monitoring scales
in acute brain injury: assessment of coma, pain, agitation, and delirium.
Neurocrit Care. 2014;21(Suppl 2):S27–37.
120. Samaniego EA, Mlynash M, Caulfield AF, Eyngorn I, Wijman CA. Sedation
confounds outcome prediction in cardiac arrest survivors treated with
hypothermia. Neurocrit Care. 2011;15(1):113–9.
121. Brook AD, Ahrens TS, Schaiff R, et al. Effect of a nursing-implemented
sedation protocol on the duration of mechanical ventilation. Crit Care
Med. 1999;27(12):2609–15.
122. Treggiari MM, Romand JA, Yanez ND, et al. Randomized trial of light
versus deep sedation on mental health after critical illness. Crit Care
Med. 2009;37(9):2527–34.
123. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Seda-
tion Scale: validity and reliability in adult intensive care unit patients.
Am J Respir Crit Care Med. 2002;166(10):1338–44.
124. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over
time in ICU patients: reliability and validity of the Richmond Agitation-
Sedation Scale (RASS). JAMA. 2003;289(22):2983–91.
125. Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Seda-
tion-Agitation Scale for adult critically ill patients. Crit Care Med.
1999;27(7):1325–9.
126. Deogaonkar A, Gupta R, DeGeorgia M, et al. Bispectral Index monitoring
correlates with sedation scales in brain-injured patients. Crit Care Med.
2004;32(12):2403–6.
127. *Devlin JW, Skrobik Y, Gelinas C, et al. Clinical practice guidelines for
the prevention and management of pain, agitation/sedation, delirium,
immobility, and sleep disruption in adult patients in the ICU. Crit Care
Med. 2018;46(9):e825–73. Current standard for the use of sedation and
analgesia in the critically ill.
128. Spies C, Macguill M, Heymann A, et al. A prospective, randomized,
double-blind, multicenter study comparing remifentanil with
fentanyl in mechanically ventilated patients. Intensive Care Med.
2011;37(3):469–76.
129. Devabhakthuni S, Armahizer MJ, Dasta JF, Kane-Gill SL. Analgosedation:
a paradigm shift in intensive care unit sedation practice. Ann Pharma-
cother. 2012;46(4):530–40.
130. Karabinis A, Mandragos K, Stergiopoulos S, et al. Safety and effi-
cacy of analgesia-based sedation with remifentanil versus standard
hypnotic-based regimens in intensive care unit patients with brain
injuries: a randomised, controlled trial [ISRCTN50308308]. Crit Care.
2004;8(4):R268–80.
131. Iyer VN, Hoel R, Rabinstein AA. Propofol infusion syndrome in patients
with refractory status epilepticus: an 11-year clinical experience. Crit
Care Med. 2009;37(12):3024–30.
132. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs mida-
zolam or propofol for sedation during prolonged mechanical ventila-
tion: two randomized controlled trials. JAMA. 2012;307(11):1151–60.
133. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the
management of pain, agitation, and delirium in adult patients in the
intensive care unit. Crit Care Med. 2013;41(1):263–306.
134. Grof TM, Bledsoe KA. Evaluating the use of dexmedetomidine in neuro-
critical care patients. Neurocrit Care. 2010;12(3):356–61.
135. Brown RL, Brunn MA, Garcia VF. Cervical spine injuries in children: a
review of 103 patients treated consecutively at a level 1 pediatric
trauma center. J Pediatr Surg. 2001;36(8):1107–14.
136. Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the manage-
ment of pediatric severe traumatic brain injury, third edition: update
of the brain trauma foundation guidelines, executive summary. Pediatr
Crit Care Med. 2019;20(3):280–9.
137. Wani TM, Bissonnette B, Engelhardt T, et al. The pediatric airway: histori-
cal concepts, new findings, and what matters. Int J Pediatr Otorhi-
nolaryngol. 2019;121:29–33.
138. Kleinman ME, Chameides L, Schexnayder SM, et al. Part 14: pediatric
advanced life support: 2010 American Heart Association Guidelines for
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Circulation. 2010;122(18 Suppl 3):S876–908.
139. Duff JP, Topjian A, Berg MD, et al. 2018 American Heart Association
focused update on pediatric advanced life support: an update to
the American Heart Association guidelines for cardiopulmonary
resuscitation and emergency cardiovascular care. Circulation.
2018;138(23):e731–9.
140. Khine HH, Corddry DH, Kettrick RG, et al. Comparison of cuffed and
uncuffed endotracheal tubes in young children during general anes-
thesia. Anesthesiology. 1997;86(3):627–31 (discussion 27A).
141. King BR, Baker MD, Braitman LE, Seidl-Friedman J, Schreiner MS.
Endotracheal tube selection in children: a comparison of four methods.
Ann Emerg Med. 1993;22(3):530–4.
142. Wheeler M, Coté C, Todres ID. The pediatric airway. In: Lerman J, Coté
C, Todres ID, editors. A practice of anesthesia for infants and children.
Philadelphia: Saunders-Elsevier; 2009. p. 237.
143. Weiss M, Dullenkopf A, Fischer JE, et al. Prospective randomized con-
trolled multi-centre trial of cuffed or uncuffed endotracheal tubes in
small children. Br J Anaesth. 2009;103(6):867–73.
144. Phipps LM, Thomas NJ, Gilmore RK, et al. Prospective assessment of
guidelines for determining appropriate depth of endotracheal tube
placement in children. Pediatr Crit Care Med. 2005;6(5):519–22.
145. Patel R, Lenczyk M, Hannallah RS, McGill WA. Age and the onset of
desaturation in apnoeic children. Can J Anaesth. 1994;41(9):771–4.
146. Weiss M, Gerber AC. Rapid sequence induction in children—it’s not a
matter of time! Paediatr Anaesth. 2008;18(2):97–9.
147. Lawes EG, Campbell I, Mercer D. Inflation pressure, gastric insufflation
and rapid sequence induction. Br J Anaesth. 1987;59(3):315–8.
148. Moynihan RJ, Brock-Utne JG, Archer JH, Feld LH, Kreitzman TR. The
effect of cricoid pressure on preventing gastric insufflation in infants
and children. Anesthesiology. 1993;78(4):652–6.
149. Weiler N, Heinrichs W, Dick W. Assessment of pulmonary mechanics
and gastric inflation pressure during mask ventilation. Prehospital
Disaster Med. 1995;10(2):101–5.
150. Brock-Utne JG. Is cricoid pressure necessary? Paediatr Anaesth.
2002;12(1):1–4.
151. Landsman I. Cricoid pressure: indications and complications. Paediatr
Anaesth. 2004;14(1):43–7.
152. Lev R, Rosen P. Prophylactic lidocaine use preintubation: a review. J
Emerg Med. 1994;12(4):499–506.
153. Sagarin MJ, Chiang V, Sakles JC, et al. Rapid sequence intubation
for pediatric emergency airway management. Pediatr Emerg Care.
2002;18(6):417–23.
154. Gronert GA. Cardiac arrest after succinylcholine: mortality greater
with rhabdomyolysis than receptor upregulation. Anesthesiology.
2001;94(3):523–9.
155. Larach MG, Rosenberg H, Gronert GA, Allen GC. Hyperkalemic cardiac
arrest during anesthesia in infants and children with occult myopathies.
Clin Pediatr (Phila). 1997;36(1):9–16.
156. Filanovsky Y, Miller P, Kao J. Myth: Ketamine should not be used as
an induction agent for intubation in patients with head injury. CJEM.
2010;12(2):154–7.
157. Sehdev RS, Symmons DA, Kindl K. Ketamine for rapid sequence induc-
tion in patients with head injury in the emergency department. Emerg
Med Australas. 2006;18(1):37–44.
158. Skippen P, Seear M, Poskitt K, et al. Effect of hyperventilation on
regional cerebral blood flow in head-injured children. Crit Care Med.
1997;25(8):1402–9.
159. Kochanek PM, Carney N, Adelson PD, et al. Guidelines for the acute
medical management of severe traumatic brain injury in infants,
children, and adolescents–second edition. Pediatr Crit Care Med.
2012;13(Suppl 1):S1–82.
160. Downard C, Hulka F, Mullins RJ, et al. Relationship of cerebral perfusion
pressure and survival in pediatric brain-injured patients. J Trauma.
2000;49(4):654–8 (discussion 8–9).
161. Elias-Jones AC, Punt JA, Turnbull AE, Jaspan T. Management and
outcome of severe head injuries in the Trent region 1985-90. Arch Dis
Child. 1992;67(12):1430–5.
162. Freeman SS, Udomphorn Y, Armstead WM, Fisk DM, Vavilala MS.
Young age as a risk factor for impaired cerebral autoregulation after
moderate to severe pediatric traumatic brain injury. Anesthesiology.
2008;108(4):588–95.
163. Hungerford JL, O’Brien N, Moore-Clingenpeel M, et al. Remifentanil for
sedation of children with traumatic brain injury. J Intensive Care Med.
2019;34(7):557–62.
164. Nemergut ME, Aganga D, Flick RP. Anesthetic neurotoxicity: what to tell
the parents? Paediatr Anaesth. 2014;24(1):120–6.
165. Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic
neurodegeneration in the developing brain. Proc Natl Acad Sci USA.
2002;99(23):15089–94.
166. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to
common anesthetic agents causes widespread neurodegeneration
in the developing rat brain and persistent learning deficits. J Neurosci.
2003;23(3):876–82.
167. Loepke AW, Soriano SG. An assessment of the effects of general
anesthetics on developing brain structure and neurocognitive function.
Anesth Analg. 2008;106(6):1681–707.
168. Paule MG, Li M, Allen RR, et al. Ketamine anesthesia during the first
week of life can cause long-lasting cognitive deficits in rhesus monkeys.
Neurotoxicol Teratol. 2011;33(2):220–30.
169. Pohl D, Bittigau P, Ishimaru MJ, et al. N-Methyl-D-aspartate antagonists
and apoptotic cell death triggered by head trauma in developing rat
brain. Proc Natl Acad Sci USA. 1999;96(5):2508–13.
170. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK,
et al. (2015) Adult advanced cardiovascular life support. Circulation.
2015;132(Supp 2):S444–64.
171. Franklin C, Samuel J, Hu TC. Life-threatening hypotension associated
with emergency intubation and the initiation of mechanical ventilation.
Amer J Emer Med. 1994;12(4):425–28.
172. Overend TJ, Anderson CM, Brooks D, Cicutto L, Keim M, McAuslan
D, Nononyama M. Updating the evidence base for suctioning adult
patients: a systematic review. Can Respir J 2009;16(3):e6–17.
173. Gholamzadeh S, Javadi M. Effect of endotracheal suctioning on intrac-
ranial pressure in severe head-injured patients. Crit Care. 2009;13(Suppl
1): 80. https​://doi.org/10.1186/cc724​4.
174. Mellott KG, Grap MJ, Munro, CL, Sessler CN, Wetzel PA. Patient ventilator
dyssynchrony: clinical significance and implications for practice. Crit
Care Nurse 2009;29(6):41–55.