Emergency Neurological Life Support: Airway,

Ventilation, and Sedation

Christopher P. Robinson, DO, MS1*†, Thomas L. Delmas, MD2‡ and
A.M. Iqbal O’Meara, MD3§
1Departments of Neurology and Neurosurgery, Division of Neurocritical Care.
University of Florida College of Medicine.
2Department of Pulmonary and Critical Care, Baylor Scott and White Memorial

Hospital
3Department of Pediatrics, Division of Pediatric Intensive Care Medicine, Virginia

Commonwealth University

Abstract
Neurocritically ill patients often have evolving processes that threaten the airway, com-
promising oxygenation and 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
(ENLS) topics discussed here include acute airway management, indications for intu-
bation 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 neurologic injury.
Key words: Airway, Ventilation, Sedation, Neurocritical Care, Emergency

*Corresponding author.
†E-mail: [email protected]
‡E-mail: [email protected]
§E-mail: [email protected]

1
 2

1 Introduction
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 progres-
sive neurological decline may result in respiratory arrest, acidosis, secondary brain injury
from hypoxemia, elevated intracranial pressure, cerebral edema from hypercapnia, acute
respiratory distress syndrome, and cardiac arrest. Conversely, the process of induction
and intubation itself can result in physiologic changes that decrease cerebral perfusion
pressure (CPP), increase intracranial pressure (ICP), 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 ventilation, optimize cerebral physiology, preserve cerebral perfusion,
and prevent aspiration. A rapid neurological assessment prior to the administration of
sedating and paralyzing medications should be performed to provide a functional baseline
whereby neurological and neurosurgical decision making may ensue.
The suggested ENLS algorithm for the initial management of airway, ventilation, and
sedation is shown in Figure 1. Suggested 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 frame-
work for the principles of diagnosis and emergent management of airway, ventilation, and
sedation, which can be adapted to reflect global and regional variations based on the local
availability of diagnostic tools and treatments.

TABLE 1
Airway, ventilation, and sedation checklist within the first hour

Checklist
 Assess the need for intubation or non-invasive
positive pressure ventilation
 Perform and document a focused neurological
assessment prior to intubation
 Assess difficulty for bag mask ventilation and
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
 3

2 Assessing the Need for Intubation

Patients in severe respiratory distress or impending respiratory or cardiac arrest should
be intubated without delay. Additionally, patients with acute brain injury or neurologic
decline who suffer abrupt loss of airway reflexes may need to be intubated to avoid aspi-
ration. Intubation in such settings should not be delayed, however, a rapid but thorough
risk-benefit assessment should be conducted to assess potential hemodynamic complica-
tions associated with intubation. The decision to intubate is influenced by factors specific
to patient physiology, clinical environment, and the anticipated course of care. With these
considerations in mind, there are four commonly accepted indications to intubate:
 4

FIGURE 1
ENLS Airway, Ventilation, and Sedation protocol

2.1 Failure to oxygenate

The assessment of hypoxemia includes visual inspection for respiratory distress or
cyanosis and objective findings of hypoxia on pulse oximetry or arterial blood gas (ABG)
analysis.

2.2 Failure to ventilate

The assessment of hypercapnia includes visual inspection of respiratory effort and acces-
sory muscle use, elevated carbon dioxide (CO2) on capnography, and hypercapnia with
acidosis on ABG.
 5

2.3 Loss of airway reflexes

The assessment of airway reflexes incorporates numerous variables including bulbar func-
tion, airway anatomy, secretion burden, strength of cough reflex, and ability to swallow
after suctioning.1,2 The presence of a gag reflex is an inadequate method of assessing
airway protection.3

2.4 Elective peri-procedural intubation

Anticipation of peri-procedural intubation need can allow for appropriate preparation for
the procedure as opposed to rushed or emergent intubations.

3 Prehospital Management
First responders assessing patients with impaired breathing in the setting of possible un-
derlying neurologic injury should rapidly assess the scene and provide support for airway
and breathing in a safe and expeditious manner. Those with an inability to protect the air-
way should be managed immediately with an airway-opening maneuver. Of the accepted
maneuvers the jaw-thrust maneuver is preferred in the setting of trauma to limit cervi-
cal spine injury. When spontaneous breathing is absent or seriously impaired, bag-mask
ventilation (BMV) should be performed. Airway adjuncts such as a nasal or oropha-
ryngeal airway may be used. The decision to perform endotracheal intubation in the
prehospital setting can be challenging. Prehospital intubation has been best studied in
severe traumatic brain injury (TBI). Observational studies have been inconsistent,4 with
some demonstrating possible harm from prehospital intubation, while others demonstrate
improved outcomes.56 In a randomized trial of TBI patients with Glasgow Coma Scale
(GCS) <9 and >10 minutes of ground-transport time, prehospital intubation improved 6-
month outcomes.7 Given conflicting results, prehospital patients with acute neurological
injury should be assessed for intubation and the procedure performed by trained person-
nel within the scope of their practice. When personnel with appropriate training and
experience are not present, 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 circumstances as an alternative. Once an endotracheal
tube or SGA has been placed, the use of quantitative capnography should be used when
available, to avoid both hypoventilation and hyperventilation.8

3.1 Decision Made to Intubate: Perform Neurological Assessment

When circumstances permit, urgent management of the airway should coincide with a fo-
cused neurological assessment. The examination can typically be conducted in 3 minutes
or less. The pre-intubation neurologic exam establishes a baseline that is used to assess
future therapeutic interventions or may identify injuries that are at risk of progressing.
Findings should be documented and communicated directly to the team that assumes care
 6

of the patient. The pre-intubation neurological examination should include an evaluation

of:

• Level of arousal, interaction, orientation, eye opening, and cortical functions such
as vision, attention, speech, and comprehension
• Limited cranial nerve evaluation: pupil assessment, eye movements, and gaze

• Motor function of each individual extremity

• Tone & reflexes

• Recognition of involuntary movements consistent with tremor or epileptic activity.

• Cervical tenderness or spinal abnormality

• Sensory examination in patients with suspected spinal cord injury to identify a sen-
sory level

3.2 Airway Assessment

Difficult airways are defined as an endotracheal intubation attempt in which a provider
who is appropriately trained in airway management experiences difficulty with BMV, tra-
cheal intubation, or both9. Using this definition, up to 30% of emergency department (ED)
intubations may involve “difficult airways”10. Patients with acute neurological injury may
be at higher risk for a difficult airway due to cervical spine immobilization or loss of air-
way reflexes in neurological emergencies. It is essential that all healthcare providers who
manage critically ill neurological patients be able to identify common factors that may
increase the complexity of airway management. Identification of the difficult airway is
essential for selection of the appropriate intubation techniques and tools. Failure to iden-
tify a difficult airway prior to induction is one of the most important factors predicting a
subsequent failed airway during the intubation attempt11,12.
Described below, the “MACOCHA” and “MOANS” mnemonics have been shown to
successfully predict difficult tracheal intubation and difficult BVM respectively13:

M-A-C-O-C-H-A
M = Mallampati Score III or IV (5 points)
(Figure 2)
A = Apnea Syndrome (obstructive) (2 points)
C = Cervical spine limitation (1 point)
O = Opening mouth < 3cm (1 point)
C = Coma (1 point)
H = Hypoxia (<80%) (1 point)
A = Anesthesiologist non-trained (1 point)
Score > 3 suggests a difficult airway
M-O-A-N-S
M = Mask seal, may be compromised by abnormal facies, facial hair and body fluids
O = Obesity/obstruction
 7

A = Age > 55
N = No teeth
S = Stiff lungs

When a difficult airway is identified, the most important next step is to ensure the
provider with the most experience in airway management is present at the bedside, as
well as a provider capable of rapidly establishing a surgical airway in the event of a failed
intubation. Availability and operational status of all necessary tools at the bedside, such
as a video laryngoscope, supraglottic airway, endotracheal tube introducer (bougie), and
cricothyroidotomy tray should be confirmed. Finally, it is important to remember that
prediction of a difficult airway is imperfect and that an unanticipated difficult airway may
be encountered at any time15. 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 airway16.
 8

FIGURE 2
The Mallampati score assesses the extent of mouth opening inrelation to tongue size.

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

Adapted from Allen B., Ganti L.,Desai B. (2013) Intubation, Airway, and Mechanical
Ventilation. In: Quick Hitsin Emergency Medicine. Springer, New York, NY.
 9

4 Endotracheal Intubation of the Critically Ill Neuro-

logical Patient
Several societies have published guidelines for the management of the difficult
airway9,17−20. Intubation of the critically ill patient is a fundamentally different clinical
situation than intubation in the relatively stable environment of the operating room19,20.
20%-25% of critically ill patients will develop severe hypoxemia during intubation,
10%-25% will develop severe hypotension, and about 2% will suffer cardiac
arrest12,21,22. More so than other critically ill patients, patients with acute brain injury
are unlikely to tolerate significant periods of hypoxemia or hypotension due to the risk of
secondary brain injury23−25.
The ENLS intubation algorithm (Figure 3) emphasizes evidence-based practices for
maintenance of adequate oxygenation and perfusion during intubation, as well as the most
direct and dependable pathway to a definitive airway in neurocritically ill patients.

FIGURE 3
Algorithm for tracheal intubation of the critically ill neurological patient

5 Pre-Oxygenation and Apneic Oxygenation

Maintaining adequate oxygenation before and during intubation is critical for the pa-
tient with acute neurological illness. Any significant period of hypoxemia may result
 10

in secondary injury to the vulnerable brain and exacerbate ICP24,26. Pre-oxygenation

should be performed prior to every intubation via noninvasive positive pressure venti-
lation (NIPPV)27, or high-flow nasal cannula (HFNC). Pre-oxygenation should be per-
formed with the head of bed elevated to 30 degrees.
Apneic oxygenation consists of the administration of high-flow oxygen via HFNC at
or a regular nasal cannula at 15 L/minute after induction and during laryngoscopy. While
randomized trials have failed to consistently demonstrate an improvement in outcomes,
four recent meta-analyses suggest that apneic oxygenation increases time to desaturation
and first-pass success without hypoxemia28−32. As apneic oxygenation is easy to per-
form, inexpensive, and without serious adverse effects, its use is recommended during
intubation of the critically ill neurological patient.

6 Intubating the Patient with Acute Elevations in ICP

RSI consists of the simultaneous administration of fast-acting sedatives and a
neuromuscular-blocking agent to achieve rapid and optimal intubating conditions.
RSI specifically limits the ICP elevations often associated with the physiologic responses
to laryngoscopy and is the preferred method for intubation in such setting33,34. Of note,
acute comatose states should not justify proceeding without pharmacological agents, or
administration of only a neuromuscular blocking agent without appropriate pretreatment
induction agents, as laryngoscopy and intubation often provoke reflexes that elevate the
ICP.35
Functional outcomes in acute brain injury rely on maintenance of both brain perfusion
and oxygenation. It is recommended that the ICP be maintained below 22 mmHg, systolic
blood pressure (SBP) >100-110 mmHg, and cerebral perfusion pressure (CPP=MAP-ICP)
> 60 mmHg during intubation.36
When the airway is manipulated, two specific responses may exacerbate intracranial
hypertension. The reflex sympathetic response (RSR) results in increased heart rate, in-
creased blood pressure, and in brain injured patients, increased ICP due to the loss of
normal autoregulation. The direct laryngeal reflex stimulates an increase in ICP indepen-
dent of the RSR13. As ICP is not always known at the time of intubation, clinicians should
anticipate elevated ICP in patients with acute brain injury and choose an appropriate blood
pressure target accordingly. Elevations in ICP should be mitigated by minimizing airway
manipulation and use of pre-medication.
Pre-medicating the patient to prevent increased ICP during intubation is discussed
below:

6.1 Lidocaine
Administered intravenously at a dose of 1.5 mg/kg 60–90 seconds before intubation, li-
docaine attenuates the direct laryngeal reflex. There is poor evidence that it mitigates the
RSR 37,38. Given the paucity of strong evidence and potential for worsening hypotension
after administration, it cannot be universally given and its use must be approached on a
case-by-case basis.
 11

6.2 Fentanyl
Administered intravenously at doses of 2–3 micrograms/kg 30-60 seconds before intuba-
tion, fentanyl attenuates the RSR and reduces chances of apnea or hypoventilation prior to
induction and paralysis 39. It is generally not recommended in patients who are dependent
on sympathetic drive to maintain adequate blood pressure for cerebral perfusion.
ICP during intubation also rises due to body positioning and hypoventilation.
Hypoventilation immediately increases the arterial partial pressure of carbon dioxide
(PaCO2), a potent acute cerebral vasodilator. When ICP is known or suspected to be
elevated, the following approach is suggested (Figure 4):

FIGURE 4
Intubation with Elevated ICP 40
 12

7 Intubating the Patient with Acute Brain Ischemia

In suspected or proven ischemic stroke, careful attention should be taken to avoid hypoten-
sion during induction and intubation. In the healthy state, the cerebrovascular circulation
is well collateralized. During acute ischemia, many patients possess an infarct core sur-
rounded by a greater region of ischemic penumbra, consisting of regional blood vessels
receiving maximal shunting from the cardiovascular circulation. Hypertension and tachy-
cardia often reflect a compensatory response to this ischemia and may be necessary to
maintain perfusion of the ischemic territory. Importantly, certain vasoactive agents during
intubation may cause hypotension and reverse regional blood flow, leading to an increase
in infarct size.
Brain ischemia is not simply limited to ischemic stroke and is present in patients
with vasospasm, TBI, intracranial and extracranial cerebrovascular stenosis, and hypoxic-
ischemic injury. Strong correlations between episodic hypotension and poor neurological
outcome have been noted in the critical hours following resuscitation from TBI and car-
diac arrest25,41−43. Even transient reductions in cerebral blood flow (CBF) may be harm-
ful, and every effort should be made to maintain CBF and systemic vascular tone during
airway management. A fluid bolus should be administered prior to intubation in any pa-
tient with possible volume depletion. Ketamine or etomidate are the preferred induction
agents due to their favorable hemodynamic profiles. Vasopressors should be adminis-
tered to prevent hypotension as needed during or following RSI. Brain ischemia can also
be worsened with hypercapnia and dilation of cerebral vessels. Normocapnia should be
maintained during intubation, and early correlation of PaCO2 is recommended8.
Conflicting evidence exists regarding the risks of routine intubation and general anes-
thesia for acute ischemic stroke patients who require endovascular intervention.44−46
Randomized trials of conscious sedation vs. intubation in patients undergoing urgent en-
dovascular thrombectomy showed no difference in outcomes; as such, patients should not
be intubated simply because they are undergoing urgent thrombectomy.47,48 Intubation
should be considered, however, for patients with bulbar dysfunction, inability to protect
the airway or control secretions, hypoxemia, hypercapnia, or significant agitation.46

8 Intubating the Patient with an Unsecured Vascular

Malformation or Expanding Hematoma
Laryngoscopy may result in severe hypertension as a consequence of the RSR. Severe
hypertension may increase the risk of rebleeding from a ruptured aneurysm or other in-
tracranial vascular malformation.49 Severe hypertension may also result in hematoma ex-
pansion following intracerebral hemorrhage.50 Lidocaine or 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 hypertension from discomfort caused by the presence of the endotracheal tube.
 13

9 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 un-
dergo a trial of non-invasive ventilation combined with airway clearance techniques51.
Any patient with neuromuscular weakness that complains of dyspnea should un-
dergo an assessment of respiratory 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 in-
ability to manage airway 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 non-invasive ventilation51.
The choice of neuromuscular blockade should be carefully considered in patients with
acute neuromuscular weakness. The use of paralytics in patients with myasthenia gravis
must be done with cautious consideration of the pathophysiology of the condition. De-
polarizing agents such as succinylcholine are safe but require higher doses for the same
effect while non-depolarizing agents such as rocuronium may benefit from lowered doses
as they will have a prolonged duration of action52. In conditions such as Guillain-Barré,
succinylcholine can precipitate life-threatening hyperkalemia, and only non-depolarizing
agents should be used.

10 Intubating the Patient with Acute Cervical Spine In-

jury
Cervical spine injury should be suspected following direct neck or blunt head trauma re-
sulting in loss of consciousness. During the care of these patients, measures must be
taken to protect the spinal cord during any movements or procedures, including intuba-
tion. Certain airway maneuvers including head-tilt/ chin lift, BMV, cricoid pressure, and
direct laryngoscopy can result in displacement of the cervical spine and should be avoided
in this patient population53−55. Blade elevation results in the greatest displacement of the
spine during laryngoscopy53. Awake fiberoptic intubation should therefore be considered
the best option in patients with significant cervical spine injury if patients are clinically
stable56,57. Patients with acute hypoxemic or hypercapnic respiratory failure and rapid
clinical decline may not be suitable candidates. As such, patients may require RSI with
manual in-line stabilization (MILS). When RSI is performed, every precaution should be
taken to minimize displacement of the cervical spine, although some movement may be
 14

inevitable53−55. Prior to intubation, the anterior part of the cervical collar should be re-
moved to permit greater mouth opening during laryngoscopy. The head should then be
maintained in the neutral position using MILS (Figure 5), in which an assistant stands by
the patient with a hand on either side of the head between the mastoid process and the oc-
ciput, holding the head steady and gently opposing the pressures of manual intubation.54

FIGURE 5
Manualin-line stabilization during intubation of the patient who requiresim-
mobilization of the cervical spine.

When a basic maneuver is necessary to open the airway, a jaw-thrust, should be per-
formed rather than a head-tilt/ chin lift. The use of cricoid pressure is no longer recom-
mended during intubation, as it may cause posterior displacement of the cervical spine58.
MILS adversely impacts visualization of the glottis, with only the epiglottis visible in
22% of patients using direct laryngoscopy (DL).59 Video laryngoscopy (VL) to improve
glottic visualization has therefore become the standard when MILS is necessary.60 While
VL consistently results in a better view of the glottis than DL,61−63 manipulation of the
ETT into the glottis can be challenging. When using VL, the hyper-angulated rigid stylet
should be used. The anterior part of the semi-rigid collar should be promptly re-applied
following intubation.

11 Rapid Sequence Intubation

Prior to intubation, consider the use of a pre-intubation checklist (Figure 6).12,20
 15

F IGURE 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 adults2018.12,20

12 Induction Agents
Hypotension is common following induction. 12,21,22,64 Due to the risk of secondary
brain injury with hypotension, 23−26,41,65 the use of a hemodynamically neutral agents
such as etomidate or ketamine is recommended. Table 2 lists the properties of some
medications commonly used for RSI in patients with acute neurological illness.

12.1 Etomidate
Etomidate is a short-acting agent that provides sedation and muscle relaxation with mini-
mal hemodynamic effect. Despite concerns about adrenal suppression, it is considered to
be one of the most hemodynamically neutral of all commonly used induction agents and
a drug of choice for patients with elevated ICP or compromised cerebral perfusion66.

12.2 Ketamine
Ketamine is a dissociative agent that targets NMDA receptors. Ketamine causes sympa-
thetic stimulation and is the most favorable of all available induction agents for patients
with shock or compromised cerebral perfusion67,68. Historically, the use of ketamine was
 16

CHART 1
Medicationscommonly used in rapid sequence intubation

avoided in patients with elevated ICP, however data shows that ketamine is in fact safe
and effectively reduces ICP.69,70 In view of the significant sympathetic stimulation that
accompanies its use, an alternative to ketamine should be considered in patients with un-
secured vascular malformations, acute intracerebral hemorrhage, or significant ischemic
heart disease.

12.3 Propofol
Propofol is a short acting GABA agonist that can be considered as an alternative induc-
tion agent. However, it is a potent vasodilator that may cause hypotension and may not
be appropriate for patients with threatened cerebral perfusion.71 Propofol may therefore
be most useful in patients with severe hypertension, particularly in the context of acute
subarachnoid or spontaneous intraparenchymal hemorrhage.

13 Neuromuscular blockade
13.1 Succinylcholine
Succinylcholine is a depolarizing neuromuscular blocker with a rapid onset (30-60 sec-
onds) and short duration of action (5-15 minutes). Although it has been associated with
transient increases in ICP, the effect is not considered clinically significant72. Immobile
 17

and chronically ill neurologic patients such as those with neuromuscular weakness are
at risk for succinylcholine-induced hyperkalemia due to upregulation in extra-junctional
acetylcholine receptors73. It is therefore critical that providers screen for contraindica-
tions to succinylcholine to avoid precipitating a life-threatening bradyarrhythmia, ven-
tricular arrhythmia or cardiac arrest. Succinylcholine should be avoided in these patients,
and a non-depolarizing agent used74.

13.2 Non-depolarizing agents

Non-depolarizing agents have a longer duration of action than succinylcholine. A non-
depolarizing agent such as rocuronium or vecuronium with rapid onset and relatively short
duration of action should be used. Rocuronium produces optimal intubating conditions al-
most as quickly (45-60 seconds) as succinylcholine but has a significantly longer duration
of action (45-70 minutes). The novel agent, Sugammadex, can reverse neuromuscular
blockade and restore muscle function faster than with the use of succinylcholine, and
should be readily available when utilizing non-depolarizing agents75,76.

14 Bag Mask Ventilation and Basic Airway Manage-

ment
Following induction and paralysis, the use of BMV prior to laryngoscopy may improve
oxygenation during intubation. While there has been concern about an increased risk of
aspiration with routine BMV, trials have shown that routine BMV following induction
decreases the incidence of severe hypoxemia with no increase in aspiration.77 The use of
proper BMV technique is critical. Two-provider BMV is preferable, with one provider
entirely focused on attaining an effective mask seal and basic airway-opening maneuvers,
(Figure 7), while a second individual performs bag-ventilation. A breath should be ad-
ministered approximately every 6 seconds, 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.77 The routine use of an adjuvant such as an oral or nasal airway may
greatly facilitate effective BMV. Apneic oxygenation with a HFNC or a regular nasal can-
nula at 15 L/ minute should be performed following induction and continued during BMV
and laryngoscopy.

15 Laryngoscopy and Intubation

When BMV is effective, up to three attempts at laryngoscopy and intubation are permis-
sible, so 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) and/ or technique (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
 18

F IGURE 7
Technique of two-provider bag mask ventilation, with a third provider per- forming
MILS. The first provider grasps the mask with the thumb and index finger in a “C” hold
and uses the other three fingers to grasp the mandible in an “E” hold, while si-
multaneously performing either jaw thrust, as shown in this patient, ora head-tilt/ chin-lift.
The second provider supports ventilation, while a third provider provides MILS.

considered for this “single, best attempt” for optimal glottis visualization. The use of VL
consistently results in higher rates of glottis visualization,61−63 and may be particularly
valuable for less experienced operators with difficult airways61,78. Although randomized
trials have not consistently demonstrated superiority in outcomes with the use of VL,78−80
a recent meta-analysis suggests the use of VL improves glottic visualization and decreases
the number of failed intubations.78
The Cormack-Lehane system is used to grade the direct laryngoscopic view of the
glottis81. (Figure 8)
 19

FIGURE 8
Cormack-Lehane Laryngoscopic Grade.

TABLE 2
Cormack-LehaneLaryngoscopic Grade
Grade 1- Entire glottis visible
Grade 2a- Partial view of the glottis
Grade 2b- Only the posterior extremity of the glottis (or only arytenoids) visible
Grade 3- Only epiglottis visible, no view of glottis inlet
Grade 4- Neither epiglottis nor glottis visible
Adapted from Chakravarthy B., Seipp W. (2016) Direct Laryngoscopy. In: Ganti L.
(eds) Atlas of Emergency Medicine Procedures. Springer, New York, NY.

Documentation of the direct laryngoscopic grade in the medical record is critical to

inform future airway management decisions.
 20

16 The Failed Airway

A failed airway is considered to exist in one of two situations:
1) The “cannot intubate, cannot ventilate” scenario, when BMV is ineffective at
achieving gas exchange and a “single, best attempt” at intubation by an experienced
operator is unsuccessful.
2) The “cannot intubate, can ventilate” scenario, when three attempts at intubation
have been unsuccessful, but BMV remains effective.
As both scenarios may result in death or devastating anoxic injury,11,12 each provider
who participates in airway management 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 intubation algorithm recommends an attempt at placement of a supra-
glottic airway (SGA), such as a laryngeal mask airway, in the event of a failed airway.
SGAs have a high success rate with inexperienced providers and typically require
limited training to use82,83. Second generation SGAs that include features such as a bite-
blocks, esophageal/ gastric channels, or those that serve as conduits for guided passage
of an ETT, are preferable84. Up to two attempts, with different operators and/ or tech-
niques, are permissible as long as the SpO2 remains >94%. Apneic oxygenation should
be continued 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 desaturation occurs at any time, immediate
cricothyroidotomy should be performed using a surgical or percutaneous technique. De-
lays in performing a cricothyroidotomy in patients with a failed airway are an important
cause of death and morbidity in the ICU11,12.

17 Post-Intubation Management
Following intubation, consider the use of a post-intubation checklist (Table 3).85
TABLE 3
Post-intubation checklist

Post-intubation checklist
 Secure endotracheal tube
 Confirm tube position, listen for breath sounds, 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

17.1 Basic Ventilator Settings

Immediately following intubation, respiratory and hemodynamic homeostasis should be
restored. With the special exception of acute brain herniation, the goals of mechanical
 21

ventilation are:

• Normalization of oxygenation utilizing the lowest FiO2 that will maintain oxygen
saturation > 94%.
• Normalization of ventilation to achieve a systemic pH of 7.35–7.45, and PaCO2 of
35–45 mmHg (4.7 – 6.0 kPa).
• Normalization of the work of breathing.

17.2 Prevention of ventilator induced lung injury

In most circumstances, clinicians should default to volume-cycled ventilation at 6-8 cc/kg
of ideal body weight and a respiratory rate of 12–14 per minute. Normal PaCO2 range
is an appropriate target unless there is chronic hypercapnia (i.e., severe COPD or sleep-
disordered breathing). In situations of chronic hypercapnia, the admission bicarbonate
level should be used to estimate the baseline PaCO2. When metabolic acidosis is present,
ventilation should target a normal serum pH.

17.3 Ventilator modes and settings

Mechanical ventilators deliver breaths defined by volume control (VC) (flow targeted,
volume cycled) in which tidal volume is assured but airway pressures are variable, or by
pressure control (PC) (pressure targeted, time cycled) in which maximum airway pressure
is assured but tidal volume depends on airway resistance and patient effort. VC ventila-
tion is most commonly utilized, given the importance of avoiding excessive tidal vol-
umes, particularly in the setting of the Acute Respiratory Distress Syndrome (ARDS).86
The initial ventilator mode should provide a set respiratory rate, while permitting pa-
tient initiation of respiration (triggered breaths). Assist control (AC) ventilation, synchro-
nized intermittent mandatory ventilation (SIMV), and pressure regulated volume control
(PRVC) are the most widely used modes in patients who require ventilatory support. AC
results in stereotypical breaths generated regardless of initiation by machine or patient.
With SIMV, breaths delivered within the set rate reflect the ventilator 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. The set rate is adjusted to achieve the goal PaCO2,
while maintaining the goal ratio of inspiratory to expiratory time (I:E ratio) to avoid gas-
trapping. PRVC is another volume-controlled mode of ventilation that allows for patient-
initiated breaths and provides minimally needed pressure to maintain a set tidal volume.
With VC ventilation, a peak inspiratory flow rate (about 60L/ minute, titrated to goal
I:E ratio and airway pressure), flow pattern (typically a square waveform) and tidal volume
(typically 6-8cc/kg) are specified. Using lower tidal volumes (4-8cc/kg) is particularly
important for patients with ARDS.86 With (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. In all cases of VC and PC ventilation,
FiO2 and positive end-expiratory pressure (PEEP) are specified. The FiO2 is usually set
at 100% following intubation then titrated to an oxygenation goal. The PEEP is most
 22

commonly set at 5cmH2O and is also titrated to an oxygenation 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.

17.4 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 ICP.
Most studies of applied PEEP up to 15-20 cm H2O, in the setting of acute brain injury have
demonstrated modest or no impact on ICP. 87,88 In the setting of ARDS, applied PEEP
appears to improve brain tissue oxygenation.89 A PEEP-induced drop in cardiac output
may, however, compromise cerebral perfusion.88 Higher levels of PEEP (>10cm H2O)
can therefore be used in the setting of acute brain injury, in conjunction with continuous
monitoring of ICP and CPP, as well as brain tissue oxygenation where available.

18 Titration Of Ventilation
18.1 Ventilation and Carbon Dioxide Tension
Hyperventilation causes cerebral vasoconstriction and decreased CBF, while hypoventi-
lation causes cerebral vasodilation and increased ICP90. Dysventilation (and especially
hyperventilation) is associated with poor outcomes in TBI91−93. However, the relation-
ship between arterial pH, central nervous system (CNS) pH, and PaCO2 is complex and
incompletely understood. During metabolic acidosis, CNS pH and CBF are often pre-
served despite severe systemic acidosis due to the blood brain barrier’s CNS buffering
capacity94. Alternatively, in chronic respiratory acidosis, the set-point of cerebral CO2
reactivity changes. It is therefore recommended that in patients with normal ventilation, a
PaCO2 of 35-45 mm Hg be targeted, whereas in patients with chronic acidosis ventilation
targets should be adjusted to correct pH and not PaCO2. (Table 4)

TABLE 4
Chronic respiratory acidosis: estimated pre-morbid PaCO2based on admission HCO3
level

Chronic Respiratory Acidosis:

Estimated pre-morbid pCO2 based on admission HCO3 level

Admission 45 42 39 36 33 30 27 24
Bicarbonate
(mEq/ L)
Predicted 92.5 85 77.5 70 (9.3) 62.5 55 (7.3) 47.5 40 (5.3)
“usual” PaCO2 (12.3) (11.3) (10.3) (8.3) (6.3)
in mmHg
(kPa)
 23

19 Brain Herniation: Intentional Hyperventilation to

Treat Brain Herniation and Increased ICP
When a patient develops brain herniation with elevated intracranial pressure, hyperven-
tilation is an appropriate temporizing intervention designed to acutely decrease ICP and
prevent subsequent neuronal injury and death95,96. Maximal cerebral vasoconstriction
is achieved at a PaCO2 near 20 mmHg (2.7 kPa). Hyperventilation below this level re-
sults in no further therapeutic advantage and may impede venous return to the heart, de-
crease blood pressure, and exacerbate cerebral hypoperfusion. During hyperventilation,
ETCO2 monitoring (quantitative capnography) is suggested. As soon as other treatments
to control ICP are in place (e.g., blood pressure support, osmotherapy, surgical decom-
pression, hypothermia, metabolic therapy), hyperventilation should be weaned to restore
brain perfusion97. Hyperventilation severely reduces CBF, increases the volume of is-
chemic tissue and may result in rebound elevation of ICP during weaning98,99. Prolonged
hyperventilation (beyond a few hours) should therefore not be used.

20 Acidemic and Alkalemic Hypocapnia: Potential for

Supression of Spontaneous Hyperventilation
There are two circumstances that should be considered in patients with spontaneous
hypocapnia: those whose response to metabolic acidosis accounts for high ventilatory
demand, and those (alkalotic) in whom ventilation exceeds systemic metabolic needs.
In patients whose ventilation is driven by metabolic acidosis, suppression of the res-
piratory drive with sedation or neuromuscular blockade is not recommended, unless di-
rect 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 out-
comes than their normocapnic peers. However, non-intubated TBI patients presenting
with hypocapnia do not have worse outcomes, suggesting that hypocapnia, in this setting,
may be a physiologic response and should not be suppressed.92 Despite decades of ob-
servation 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 compensatory mechanisms can catch up
• Inadequately treated pain, anxiety, fear, or agitation

• Fever

• Auto-regulation of elevated ICP

 24

• Heme breakdown products or a lactic acid load in the ventricular system

• Direct pressure on chemoreceptors present in the floor of the 4th ventricle

• Physiologic dysregulation of the medullary respiratory rhythm generator, which has

afferent inputs from the pons, mesencephalon, and higher cortical centers

A trial of patients with severe brain injury monitored for brain tissue oxygen showed
brain tissue hypoxia worsened when ETCO2 values were reduced by spontaneous alka-
lemic hyperventilation, suggesting possible harm100. 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.

21 Oxygenation and Outcomes

Hypoxemia is a major source of secondary brain injury.101 Similarly, supra-physiologic
levels of oxygen provided to acutely ill patients have the potential to worsen reperfu-
sion injury and outcomes102,103. Hyperoxia specifically drives the formation of reactive
oxygen species that overwhelm antioxidants at sites of injury, directly injures respiratory
epithelium and alveoli, drives hypercapnia, and leads to absorption atelectasis in the lung.
Hyperoxia (PaO2 > 300 mmHg or 40 kPa) immediately following resuscitation is indepen-
dently associated with poor outcomes in TBI and cardiac arrest.103,104 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 a saturation of 95-100%.

22 Oxygenation and Ventilation Monitoring

Oxygenation should be monitored by pulse oximetry or by arterial blood gas analysis
when oximetry is suspected to be inaccurate. Decreased perfusion to the extremities,
acidosis, vasopressor use, anemia, hypoxia, and carboxyhemoglobinemia and methe-
moglobinemia, all have the potential to compromise the accuracy of pulse oximetry
measurements105.
Ventilation is traditionally monitored by serial arterial blood gas analysis, though ve-
nous blood gas analysis may provide an adequate surrogate when arterial samples cannot
be obtained. End tidal quantitative capnography of exhaled gases also provides a contin-
uous measurement of ventilation and is extremely useful to monitor trends in ventilation.
Because ETCO2 measurements reflect not only ventilation but also systemic perfu- sion,
the correlation between ETCO2 and PaCO2 in the blood is variable, especially when
severe physiologic derangements are present106. In an inpatient environment, ETCO2
measurements should always be correlated with an arterial PaCO2 sample. ETCO2 and
PaCO2 may vary significantly when lung disease and ventilation-perfusion mismatch are
present107.
 25

23 Sedation
23.1 Necessity of Sedation
The use of sedation in the critically ill neurological patient has both benefits and draw-
backs. Sedation may be needed to alleviate fear and anxiety, reduce ICP and cerebral
oxygen consumption, facilitate tolerance of the endotracheal tube and mechanical ven-
tilation, or to reduce sympathetic hyperactivity. Complications associated with under-
sedation include lung injury, patient injury, agitation, anxiety, device removal, and ele-
vated ICP. Adequate sedation is paramount in all therapeutic algorithms for the treatment
of increased ICP.108,109 Conversely, sedation makes accurate neurological examination,
the cornerstone of clinical assessment, difficult or impossible. Therapeutic and procedural
decision-making are often contingent upon an accurate neurological assessment. Acute
changes in brain physiology become difficult to detect, and the accuracy of neuroprog-
nostication is decreased110,111. Sedation may also cause vasodilation, reducing cerebral
perfusion due to hypotension. Despite each of the competing interests, adequate consid-
eration must be made for patient comfort and safety.

23.2 Depth of sedation

In a general intensive care unit (ICU) population, the use of excessive sedation and anal-
gesia contributes to increased duration of mechanical ventilation and longer length of
stay.112,113 Therefore, when appropriate, most patients should be lightly sedated, to limit
secondary brain injury and permit neurological evaluation. Sedation should be titrated to
a validated sedation score such as the Richmond Agitation Sedation Scale (RASS), or the
Riker Sedation Agitation Scale (SAS) (Table 5)114−116. A recent review of sedation as-
sessment tools in the neurocritical care setting concluded that the SAS and RASS are valid
and useful for patients with acute brain injury.117 A goal of light sedation (RASS 0 to -2)
is recommended for most patients without a specific indication for deep sedation.118 Seda-
tion should be titrated to an electrophysiological endpoint when neuromuscular blockade
is employed or burst suppression on electroencephalography (EEG) is desired.

23.3 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 conversely, most
sedative medications provide no analgesia. Sedation without pain control may be an im-
portant cause of delirium. Infusion of short acting-analgesics allows for interruption and
neurological assessment at intervals. Recent studies have demonstrated that analgoseda-
tion, a strategy that focuses on using a short-acting opioid infusion alone to manage pain
and discomfort, without a sedative, may result in a reduction in duration of mechanical
ventilation and ICU length of stay119−121. The use of analgosedation should therefore be
considered first in all mechanically ventilated patients who do not have a specific indica-
tion for a sedative infusion.118
 26

TABLE 5
The Richmond Agitation-Sedation Scale (RASS) and TheRiker Sedation Assessment
Scale (SAS)
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 ag-
gressive or vigorous
0 Alert and calm
-1 Drowsy Not fully alert, but has sustained (more than 10
seconds) awakening, with eye contact, to voice
-2 Light sedation Briefly (less than 10 seconds) 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 phys-
ical stimulation
-5 Unarousable No response to voice or physical stimulation

23.4 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 benzodiazepine
infusions to propofol and dexmedetomidine. A meta-analysis of these studies suggests
that both propofol and dexmedetomidine are associated with shorter ICU length of stay
and duration of mechanical ventilation compared to benzodiazepine infusions.118 This is
important because the agent that is initiated in the early hours for sedation is typically
continued in the ICU. Either dexmedetomidine or propofol should be utilized as a first-
line agent for continuous sedation, rather than a benzodiazepine.118

24 Common Sedatives In Neurological Intensive Care

24.1 Propofol
Propofol is among the best studied sedative agents used in neurological critical care. Phar-
macologically, 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 depres-
sant effects on cerebral electrical and metabolic activity, and it does not require renal or
hepatic metabolism for elimination. Disadvantages include robust vasodilating and hy-
potensive effects, considerable IV lipid load, and the potential for the rare, but frequently
fatal, propofol infusion syndrome. This syndrome is characterized by acidosis, hepatic
failure, hypertriglyceridemia, and elevated creatine kinase level. Propofol infusion syn-
drome may be fatal and is more common in children and adults when used at higher doses
 27

122.Caution must be utilized with this medication when concerns for brain ischemia are
present.

24.2 Fentanyl
Fentanyl is an opioid agonist exhibiting analgesic effects with a rapid onset and a short du-
ration of action. It is an agent which can be used as part of a combined sedative analgesic
approach.

24.3 Benzodiazepines
Midazolam is an appealing sedative option given the rapid onset of action and short du-
ration of effect with bolus administration, making it an ideal agent for procedural seda-
tion. Conversely, midazolam infusion has been associated with prolonged mechanical
ventilation 123-124. Though most studies suggest the impact of midazolam on hemody-
namics is similar compared to dexmedetomidine or propofol, a recent report suggests less
instability compared to dexmedetomidine 124.

24.4 Dexmedetomidine
Dexmedetomidine is a centrally acting alpha agonist similar to clonidine, but more spe-
cific for the alpha-2 receptor. It is increasingly utilized for ICU sedation. Desirable prop-
erties include rapid onset and termination of activity, mild to moderate sedation with-
out significant respiratory depressant action, analgesic effects, and less delirium than the
benzodiazepines124,125. Undesirable properties include a high incidence of bradycardia
and hypotension124,125.

25 Pediatric Considerations
Anatomical and physiological differences alter the approach to endotracheal intubation of
children with neurological injury. While isolated cervical spinal injury is uncommon in
children, approximately half of all cervical spinal injuries are associated with concomi-
tant TBI126. Therefore, cervical spine precautions should be taken when intubating a
child with suspected traumatic mechanism. Criteria for endotracheal intubation of chil-
dren with acute brain injury include hypoxemia unresponsive to supplemental oxygen,
apnea, hypercapnia (PaCO2>45mmHg or 6 kPa), GCS score ≤8 (a pediatric version is
recommended for children 2 years of age and younger), rapid decrease in GCS, aniso-
coria >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.127
Anatomical differences between the pediatric and adult airway that should be consid-
ered prior to intubation 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) children have a prominent occiput.
The narrowest portion of the child’s upper airway is subglottic, at the level of the cricoid
 28

ring128. The infant’s larynx is more anterior and cephalad (C3-4 vs. C5-6 in adults), so po-
sitioning may be improved by placing a small shoulder roll or padding beneath the infant’s
torso to promote neutral positioning for intubation. Optimal positioning results in neck
extension with the external auditory meatus and suprasternal notch aligned in a horizon-
tal plane. Providers should be aware that infants and young children have higher oxygen
consumption and are therefore susceptible to hypoxia, have less physiologic reserve than
adults, are more likely to have oxygen desaturation earlier, and have an enhanced vagal
response. Pediatric Advanced Life Support Guidelines advise that oral intubation, follow-
ing pre-oxygenation, should be performed while maintaining spine immobilization using
a cuffed endotracheal tube in children with TBI 129,130. Pre-oxygenation extends the
time to apneic desaturation, and apneic oxygenation using a nasal cannula throughout
intuba- tion is used in many pediatric centers as it is in adults. Length-based
resuscitation tapes such as the Broselow 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 appropriately sized un-cuffed
endotracheal tube (if cuffed is not available) for a child can be calculated using the age-
based formula: 4 + (age in years/4)131−133. When using a regular cuffed endotracheal
tube, select one full size smaller than deter- mined by the age-based formula116. When
using a micro-cuffed endotracheal tube, select a tube one half size smaller than the age-
based calculation for un-cuffed tubes131−133. During intubation endotracheal tubes a half
size larger and smaller should be readily avail- able. Endotracheal tube cuffs should be
inflated only when necessary, and to “minimal leak” which is the point at which air
leaks from around the tube during a positive pres- sure breath just disappears. Cuff
pressures should be monitored and limited according to manufacturer’s
recommendations (usually less than 20 cm H2O). While previous teach- ings held that
the subglottic narrowing of the pediatric airway precludes the use of cuffed endotracheal
tubes in children, a multi-center, randomized control trial demonstrated no increase in
post-extubation stridor or long-term complications when using cuffed tubes
appropriately134. Neurocritically ill children requiring invasive mechanical ventilation
are prone to the same changes in respiratory compliance throughout the course of their
illness as adults, and uncuffed endotracheal tubes frequently require exchanging for cuffed
tubes in order to provide adequate ventilation and oxygenation.
When intubating the trachea of a child less than two years old, a straight laryngo-
scope blade directly lifting the epiglottis 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. Video laryngoscopy is an
option for infants and young children and may be used in the setting of a difficult airway or
associated facial trauma. In addition to obvious facial trauma, difficult intubation should
be anticipated in children with Pierre Robin sequence, retrognathia or micrognathia, or
children with glycogen storage diseases that cause muscular deposition of sugars in con-
nective tissues and muscles, including the tongue. For the child with an anticipated diffi-
cult airway, a contingency plan involving an advanced airway expert should be available
for back-up. If an appropriately sized endotracheal tube is placed, the ideal depth can be
 29

achieved by inserting the tube until the centimeter marking at the lip is three times the
endotracheal tube size135.
It is prudent to assume a full stomach and a cervical spinal injury when intubat-
ing the trachea of a child presenting with neurologic injury. Endotracheal intubation
should utilize a cerebral-protective rapid sequence induction with pre-oxygenation. The
time to desaturation following pre-oxygenation is shorter in apneic infants compared
to older children (less than 100 seconds), and a modified RSI technique with gentle
pressure-limited mask ventilation (10-12cm H2O) and 100% oxygen may be used to avoid
hypoxemia136,137. This technique may also limit hypercapnia and keeps small airways
open without the risk of gastric inflation and related morbidity138−140. Cricoid pres-
sure is routinely applied despite questionable evidence that it improves clinical outcomes,
however, it should be abandoned if it interferes with intubation or ventilation139,141,142.
Pretreatment with lidocaine (1.5 mg/kg IV with max dose 100 mg) may be used, but
its administration should not delay emergent intubation143. Atropine (0.02 mg/kg IV with
a single max dose 0.5mg) is recommended in children ≤ 1 year old or children < 5 years
receiving succinylcholine144. For hemodynamically unstable children, the combination
of etomidate (0.2-0.6 mg/kg) and neuromuscular blockade with rocuronium (1mg/kg) or
vecuronium (0.3 mg/kg) IV is often used. The association between etomidate and clini-
cally significant adrenal insufficiency should be considered when selecting optimal med-
ications for intubation. Succinylcholine is often avoided because of the risk of malignant
hyperthermia, possible ICP elevation, hyperkalemia in the setting of crush injury, and
life-threatening complications associated with unknown occult metabolic or neuromus-
cular disease145,146. Fentanyl (2-4 micrograms/kg IV) or ketamine (1-2 mg/kg IV) are
alternative sedatives. Recent pediatric studies show that ketamine does not increase ICP
and may be neuroprotective68,147,148. If hemodynamically 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 PaO2
of 90-100 mmHg (12-13.3 kPa) and a PaCO2 of 35-45 mmHg (4.7-6 kPa).127 Unless the
child has signs of herniation, hyperventilation (PaCO2<35mmHg or 4.7 kPa) should be
avoided149. Adequate blood pressure must always be maintained when administering
sedatives to assure adequate cerebral perfusion pressure. A CPP between 40-50 mmHg
is recommended for children with severe TBI, with infants at the lower end of this range
and adolescents at the upper end150. Many studies have demonstrated that a CPP ≤ 40
mmHg is associated with higher mortality and morbidity151,152. However, optimal age
appropriate CPP thresholds have not been established for TBI and other acute neurolog-
ical diagnoses. Furthermore, abnormal cerebrovascular autoregulation, which is more
common in children less than 4 years old153, makes establishing such thresholds difficult
in the absence of advanced neuromonitoring.
Sedative regimens following intubation of the child with acute neurologic illness are
variable, but typically utilize shorter acting agents due to the need for neurologic assess-
ments. In children, propofol infusions are often avoided due to the concern for propofol
infusion syndrome but may be preferable in certain situations in consultation with a pedi-
atric neurocritical care provider, as long as CPP can be assured. For a child who requires
frequent neurologic exams, a remifentanil infusion may also be useful, at a starting infu-
 30

sion rate of 0.1 micrograms/kg/minute.154 Remifentanil is a short-acting synthetic opioid

that is metabolized via the plasma esterase system, resulting in a very short half-life (3-4
minutes) and a high rate of tachyphylaxis that may restrict its role to short-term admin-
istration. A recent study of children with severe TBI noted that once remifentanil was
paused, the examiner was able to perform a neurologic exam within a median time of 9
minutes.154
If continuous sedation is needed after placement of an ICP monitor, options for
appropriate sedation include: 1) an opioid infusion (fentanyl 1-4 micrograms/kg/hr)
with intermittent dosing of benzodiazepines or 2) an opioid infusion (fentanyl 1-4
micrograms/kg/hr) with a benzodiazepine infusion (midazolam 0.05-0.3 mg/kg/hr).
A dexmedetomidine infusion at 0.2-1.2 mg/kg/hr 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 brain injury, though there are some potential
pharmacological benefits such as increased production of brain-derived neurotrophic
factor and cholinergic anti-inflammatory effects reported in animal models162. Whether
dexmedetomidine is of benefit in children and the timing of administration has yet to be
determined. Finally, while information is currently limited, concern exists regarding the
potential neurotoxicity of sedatives on the developing brain155. The strongest evidence
for this comes from animal models, with limited evidence in clinical studies 156−162.

26 Pregnancy
Pregnant patients with neurological illness or injury present additional considerations for
airway management, ventilation and sedation. Normal physiology of pregnancy causes
changes to the airway including rhinitis, airway edema, and obstructive sleep apnea due
to vasodilation induced by progesterone; neck circumference and Mallampati scores in-
crease throughout the progression of pregnancy. Both result in more difficult intubation
associated with a pregnant patient. Functional residual capacity decreases with upward
displacement of the diaphragm from the gravid uterus. Hyperventilation of pregnancy re-
duces baseline pCO2 to 27-34 with metabolic compensation increasing renal secretion of
bicarbonate. Partial pressure of oxygen is increased during pregnancy, as is oxygen con-
sumption. Anticipation of more rapid onset of hypoxemia should be expected during the
apneic phase of intubation for these patients, and ventilator settings should compensate
for normal pregnancy physiology163.
When providing sedation for pregnant patients, consider the effects on the fetus and
mother. Dexmedetomidine is thought to be the safest sedating medication and is widely
used in pregnancy164. Propofol carries an FDA warning for the third trimester of preg-
nancy if used for greater than 3 hours due to neurotoxic effects on the fetus but is used
when it is the least harmful option for sedation165,166. Dexmedetomidine has been shown
to be neuroprotective for effects of propofol when used together167. Opiates may be used
as needed for pain control. Benzodiazepines are known to cause harm to the fetus as they
easily cross the placenta and have been associated with spontaneous abortions and low
birth weight infants. Lorazepam, which is more lipophilic than other benzodiazepines,
 31

does not cross the placenta as readily and may be considered, if necessary, as in the setting
of status epilepticus168. Ketamine has shown delirious effects on neuronal development
in animal models, and therefore is not recommended in pregnancy169−171.

27 Communication
When communicating patient information to an accepting or referring physician, consider
including specific key elements. (Table 6).

TABLE 6
Airway, ventilation, and sedation communication regarding assessment and referral

Communication

 Mental status and neurological examination immediately pre-intubation

 Intracerebral hemorrhage (ICH) score, if appropriate

 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 5mm and sluggish and left pupil was 3mm and briskly reactive. Following
intubation, his pupils are 3mm and reactive bilaterally.”
“His vitals prior to intubation were BP 220/110, HR 66/mt, SpO2 97% on 2L/mt nasal
cannula. Following intubation, his BP is 130/60, HR 55/mt, SpO2 99% on FiO2 100%
and ETCO2 is 32.”
“We treated with him with Lidocaine, Fentanyl and 30cc 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 6cc/kg,
respiratory rate of 24/mt, PEEP 5 and FiO2 100%. Our goal ETCO2 is 30-35 and goal
SpO2 is >94%.”
 32

“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 counselled about his condition”
 33

28 Transport Considerations
Consider the use of checklists prior to transport of the critically ill. The pre-transport
checklist includes considerations specific to airway, ventilation and sedation. (Table 7)

TABLE 7
Critical Care Pre-Transportation Checklist - Airway, Ventilation and Sedation

Critical Care Pre-Transportation Checklist

 Confirm adequate pulse oximetry and end-tidal CO2; continue SpO2 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

29 Nursing Considerations
In the initial stages of a neurologic emergency, the patient’s status may change rapidly.
Frequent assessment of the patient’s neurologic status should include assessment of the
patient’s airway and respiratory status. Alert the care team immediately about changes in
the patient’s ability to oxygenate, ventilate, protect their airway, and anticipate the need
for an advanced airway. It is the astute assessment that will yield the best patient outcome.
Topics that may be of particular significance to nursing are listed in Table 8.

30 Case Senario
30.1 Case Scenario #1
You are called to the bedside of a 57-year-old male with a known large right hemispheric
arterial venous malformation due to acute oxygen desaturations. Prior to his desaturation,
the patient was alert and oriented without neurologic deficits. Upon your initial evaluation,
 34

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.
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 MACHOCA
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.
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.
Secure endotracheal tube (ETT) using tape or commercial tube holder. Note the depth
of insertion of ETT at teeth or lip.
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, hyper-oxygenate prior to suctioning. Suctioning should be
limited to two to three passes as this can increase intracranial pressure.

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 neurologic exam 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).
If respiratory effort is dyssynchronous with the ventilator, alert respiratory therapist
and provider to change ventilator settings as required. If Nursing considerations:
Airway, Ventilation and Sedationthis does not control dyssynchrony, increased
sedation may be necessary.
Recognize common complications of sedative medications such as hypotension and
bradycardia; notify provider and treat immediately using fluid bolus and/or
vasopressor agents.
 35

Clinical Pearls
• Use the MOANS mnemonic to predict difficulty with bag-mask ventilation.
• Use the MACOCHA mnemonic to identify a difficult airway.
• Identify patients who might benefit from an awake fiberoptic intubation- 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 and/or 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 population.
• Consider differences in pediatric and pregnant patients.
• 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 reserved for patients with acute cerebral herniation or
acute life-threatening intracranial pressure elevation.
• 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.

you find the patient with non-rebreather in place, snoring respirations, and hypoxia into
the high 80’s on Sp02. You decide to intubate the patient to protect his airway and correct
his hypoxemia. While instructing your team to obtain the necessary tools/medications
to proceed with the intubation, what two examinations will be key prior to induction for
intubation?

The patient will need a detailed neurologic exam including the following:

• Level of arousal, interaction, orientation, eye opening, and cortical functions such
as vision, attention, speech, and comprehension
• Limited cranial nerve evaluation: pupil assessment, eye movements, and gaze

• Motor function of each individual extremity

• Tone & reflexes

• Recognition of involuntary movements consistent with tremor or epileptic activity.

• Cervical tenderness or spinal abnormality

This should be done in order to establish an accurate baseline that can be used to assess
future therapeutic interventions and identify potential injuries that could be at risk of
progressing.
Additionally, performing a focused examination of the patient’s risk factors of a dif-
ficult airway will provide you with early identification of troublesome airways and allow
 36

you to prepare appropriately. Using the MACOHA score will appropriately identify these
patients within the ICU setting.

M-A-C-O-C-H-A
M = Mallampati Score III or IV (5 points)
A = Apnea Syndrome (obstructive) (2 points)
C = Cervical spine limitation (1 point)
O = Opening mouth < 3cm (1 point)
C = Coma (1 point)
H = Hypoxia (<80%) (1 point)
A = Anaesthesiologist non-trained (1 point)
Score > 3 suggests a difficult airway

30.2 Case Scenario #2

Based upon your assessment of the patients MACHOHA score you determine he is at risk
for having a difficult airway (MACHOCA score of 7). What personnel and equipment
should you have available prior to proceeding with intubation?
If time and the patient’s clinical stability permits, having the provider with the most
airway experience and ability to perform a surgical airway if needed is the most important
next step. Airway tools that should be readily available include direct laryngoscope with
a variety of blades, video laryngoscope with rigid stylet, endotracheal tube inducer, supra-
glottic airway, and surgical/percutaneous airway kit. 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 airway16.

30.3 Case Scenario #3

You have appropriately contacted the on-call Anesthesiologist/Pulmonary Critical Care
Provider and they are on their way to assist you with the intubation. The patient remains
mildly hypoxic, though hemodynamically stable. What pre-induction intervention can
you provide to prevent secondary brain injury due to hypoxia?
Pre-oxygenation should be performed prior to every intubation via noninvasive pos-
itive pressure ventilation (NIPPV), or high-flow nasal cannula (HFNC)27. Apneic oxy-
genation consists of the administration of high-flow oxygen via HFNC at or a regular
nasal cannula at 15 L/ minute after induction and during laryngoscopy. As apneic oxy-
genation is easy to perform, inexpensive, and without serious adverse effects, its use is
recommended during intubation of the critically ill neurological patient.

30.4 Case Scenario #4

After appropriately preparing for the suspected difficult airway and obtaining all the
needed tools and personnel to bedside, you decide to proceed with induction and intuba-
tion. You appropriately select the induction agents given the clinical scenario and proceed
with induction. What objective targets will you monitor during induction and intubation
 37

that are unique to the critically ill neurologic patient and what will your goals be for these
values?
In general, if you have the ability to monitor ICPs it is recommended that the ICP be
maintained below 22 mmHg. Systolic blood pressure (SBP) should be >100-110 mmHg
and cerebral perfusion pressure (CPP=MAP-ICP) > 60 mmHg during intubation36. Ad-
ditional parameters should be considered depending on the clinical scenario as well (i.e.,
avoidance of severe hypertension in patients with intracerebral hemorrhage or unsecured
vascular abnormalities).

30.5 Case Scenario #5

The patient undergoes induction with appropriate medications. BMV is initiated by Res-
piratory Therapist (RT) while you provide the correct mask seal with airway opening
technique. The RT reports that the patient is difficult to bag, and an oral pharyngeal air-
way is placed. The patient continues to be difficult to ventilate via BVM and the oxygen
saturations begin to fall into the 70s on Sp02. What is the most appropriate next step?
In this “cannot ventilate” scenario, the most experienced provider should provide the
“single, best attempt” and intubation. This is usually accomplished with video laryn-
goscopy and the possible use of an ETT introducer. Although randomized trials have
not consistently demonstrated superiority in outcomes with the use of VL,78−80 a recent
meta-analysis suggests the use of VL improves glottic visualization and decreases the
number of failed intubations.78

30.6 Case Scenario #6

Despite the “single, best attempt” the patient is unable to be intubated and oxygenation
continues to fall. What “scenario” would this be considered and what is the best next
step?
This is considered a “cannot intubate, cannot ventilate” scenario at this point. The
placement of a supraglottic airway (SGA) is indicated at this time. SGAs have a high suc-
cess rate with inexperienced providers and typically require limited training to use 82,83.
Second generation SGAs that include features such as a bite-blocks, esophageal/ gastric
channels, or those that serve as conduits for guided passage of an ETT, are preferable84 If
SGA placement is unsuccessful then 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 morbidity in the
ICU 11,12.

30.7 Case Scenario #7

The patient undergoes successful placement of a supraglottic airway (intubating laryngeal
mask airway in this scenario) and subsequently intubated using the device. With the
airway secure, the oxygen saturations are improved, and the patient is hemodynamically
stable. The patient is connected to the ventilator and the RT inquires as to what ventilator
mode/settings you would prefer. You are concerned the patient may be developing acute
 38

respiratory distress syndrome (ARDs) and set the ventilator’s initial settings accordingly.
What mode/settings would you request?
Volume Control (VC) ventilation is most utilized, given the importance of avoiding
excessive tidal volumes, particularly in the setting of the ARDS86. Using lower tidal
volumes (6-8cc/kg) is particularly important for patients with ARDS86. FiO2 is usually
set at 100% following intubation then titrated to an oxygenation goal. The PEEP is most
commonly set at 5cmH2O and is also titrated to an oxygenation 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. An
ABG shortly after intubation will assist with providing the correct ventilator adjustments
to correct any oxygenation/ventilatory abnormalities present.

30.8 Case Scenario #8

With a secure airway and proper ventilator settings the patient’s nurse inquires as to what
sedation strategy will you be employing on this patient. In general, what strategy should
you consider utilizing and if needed what types of sedatives would you prefer to use based
on the current evidence?
Unless deep sedation or general anesthesia is required (i.e. elevated intracranial pres-
sures, seizure activity, ventilatory desynchrony, etc.), analgesia should precede sedation.
Studies have demonstrated that analgosedation, a strategy that focuses on using a short-
acting opioid infusion alone to manage pain and discomfort, without a sedative, may result
in a reduction in duration of mechanical ventilation and ICU length of stay119−121. The
use of analgosedation should therefore be considered first in all mechanically ventilated
patients who do not have a specific indication for a sedative infusion118.
In regard to sedation, a meta-analysis suggests that both propofol and dexmedeto-
midine are associated with shorter ICU length of stay and duration of mechanical ven-
tilation compared to benzodiazepine infusions118. Given this, either dexmedetomidine
or propofol should be utilized as a first-line agent for continuous sedation, rather than a
benzodiazepine118.

31 Starred References
Reference #9- Apfelbaum JL, Hagberg CA, Caplan RA, Blitt CD, Connis RT, Nicki-
novich DG, Hagberg CA, Caplan RA, Benumof JL, Berry FA, Blitt CD, Bode RH, Ch-
eney FW, Connis RT, Guidry OF, Nickinovich DG, Ovassapian A, American Society of
Anesthesiologists Task Force on Management of the Difficult A (2013) Practice guide-
lines for management of the difficult airway: an updated report by the American Society
of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology
118 (2):251-270. doi:10.1097/ALN.0b013e31827773b2
This is the standard for the management of the difficult airway.
Reference #20- Higgs A, McGrath BA, Goddard C, Rangasami J, Suntharalingam
G, Gale R, Cook TM, Difficult Airway S, Intensive Care S, Faculty of Intensive Care
 39

M, Royal College of A (2018) Guidelines for the management of tracheal intubation in

critically ill adults. Br J Anaesth 120 (2):323-352. doi:10.1016/j.bja.2017.10.021
Widely accepted guidelines for the management of the difficult airway, specific to the
critically ill.

Reference #102- Muizelaar JP, Marmarou A, Ward JD, Kontos HA, Choi SC, Becker
DP, Gruemer H, Young HF (1991) Adverse effects of prolonged hyperventilation in pa-
tients with severe head injury: a randomized clinical trial. J Neurosurg 75 (5):731-739.
doi:10.3171/jns.1991.75.5.0731
Randomized clinical trial that demonstrated that the use of prolonged hyperventilation
may worsen outcomes.
Reference #124- Delvin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pand-
haripande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den
Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL,
Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani
MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM,
Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K,
Alhazzani W (2018) 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 46 (9):e825-e873. doi:10.1097/CCM.0000000000003299
Current standard for the use of sedation and analgesia in the critically ill.

32 References
1. Coplin WM, Pierson DJ, Cooley KD, Newell DW, Rubenfeld GD. Implications of
extubation delay in brain-injured patients meeting standard weaning criteria. Am J Respir
Crit Care Med 2000;161:1530-6.
2. 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;14:85-93.
3. 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;16:444-5.
4. 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;60:732-6.
5. 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;58:933-9.
6. 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;46:115-22.
7. Bernard SA, Nguyen V, Cameron P, et al. Prehospital rapid sequence intubation im-
proves functional outcome for patients with severe traumatic brain injury: a randomized
controlled trial. Ann Surg 2010;252:959-65.
 40

8. 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;56:808-14.
9. Apfelbaum JL, Hagberg CA, Caplan RA, et al. Practice guidelines for management
of the difficult airway: an updated report by the American Society of Anesthesiologists
Task Force on Management of the Difficult Airway. Anesthesiology 2013;118:251-70.
10. Orebaugh SL. Difficult airway management in the emergency department. J
Emerg Med 2002;22:31-48.
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;106:617-31.
12. Cook TM, Woodall N, Harper J, Benger J, Fourth National Audit P. Major com-
plications 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 departments. Br J Anaesth 2011;106:632-42.
13. Walls RM MM. 3 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;32:429-34.
15. 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;115:827-48.
16. Sample G MP, Vandruff T. Code critical airway teams improves patient safety.
Critical Care 2010;14:231.
17. Cooper RM, O’Sullivan E, Popat M, Behringer E, Hagberg CA. Difficult Airway
Society guidelines for the management of tracheal extubation. Anaesthesia 2013;68:217.
18. Law JA, Broemling N, Cooper RM, et al. The difficult airway with recom-
mendations for management–part 1–difficult tracheal intubation encountered in an un-
conscious/induced patient. Can J Anaesth 2013;60:1089-118.
19. Myatra SN, Ahmed SM, Kundra P, et al. The All India Difficult Airway Associa-
tion 2016 guidelines for tracheal intubation in the Intensive Care Unit. Indian J Anaesth
2016;60:922-30.
20. Higgs A, McGrath BA, Goddard C, et al. Guidelines for the management of
tracheal intubation in critically ill adults. Br J Anaesth 2018;120:323-52.
21. Jaber S, Amraoui J, Lefrant JY, et al. Clinical practice and risk factors for imme-
diate complications of endotracheal intubation in the intensive care unit: a prospective,
multiple-center study. Crit Care Med 2006;34:2355-61.
22. Simpson GD, Ross MJ, McKeown DW, Ray DC. Tracheal intubation in the crit-
ically ill: a multi-centre national study of practice and complications. Br J Anaesth
2012;108:792-9.
23. 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;35:1027-31.
 41

24. Stocchetti N, Furlan A, Volta F. Hypoxemia and arterial hypotension at the acci-
dent scene in head injury. J Trauma 1996;40:764-7.
25. Trzeciak S, Jones AE, Kilgannon JH, et al. Significance of arterial hypotension
after resuscitation from cardiac arrest. Crit Care Med 2009;37:2895-903; quiz 904.
26. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury
in determining outcome from severe head injury. J Trauma 1993;34:216-22.
27. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves preoxy-
genation before intubation of hypoxic patients. Am J Respir Crit Care Med 2006;174:171-
7.
28. Pavlov I, Medrano S, Weingart S. Apneic oxygenation reduces the incidence of
hypoxemia during emergency intubation: A systematic review and meta-analysis. Am J
Emerg Med 2017;35:1184-9.
29. Binks MJ, Holyoak RS, Melhuish TM, et al. Apnoeic oxygenation during in-
tubation in the intensive care unit: A systematic review and meta-analysis. Heart Lung
2017;46:452-7.
30. Oliveira JESL, Cabrera D, Barrionuevo P, et al. Effectiveness of Apneic Oxy-
genation During Intubation: A Systematic Review and Meta-Analysis. Ann Emerg Med
2017;70:483-94 e11.
31. Tan E, Loubani O, Kureshi N, Green RS. Does apneic oxygenation prevent desat-
uration during emergency airway management? A systematic review and meta-analysis.
Can J Anaesth 2018;65:936-49.
32. Frat JP, Ricard JD, Quenot JP, et al. Non-invasive ventilation versus high-flow
nasal cannula oxygen therapy with apnoeic oxygenation for preoxygenation before intu-
bation of patients with acute hypoxaemic respiratory failure: a randomised, multicentre,
open-label trial. Lancet Respir Med 2019;7:303-12.
33. Li J, Murphy-Lavoie H, Bugas C, Martinez J, Preston C. Complications of emer-
gency intubation with and without paralysis. Am J Emerg Med 1999;17:141-3.
34. Walls RM. Rapid-sequence intubation in head trauma. Ann Emerg Med
1993;22:1008-13.
35. Bedford RF, Persing JA, Pobereskin L, Butler A. Lidocaine or thiopental for rapid
control of intracranial hypertension? Anesth Analg 1980;59:435-7.
36. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the Management of Severe
Traumatic Brain Injury, Fourth Edition. Neurosurgery 2017;80:6-15.
37. Donegan MF, Bedford RF. Intravenously administered lidocaine prevents intracra-
nial hypertension during endotracheal suctioning. Anesthesiology 1980;52:516-8.
38. Salhi B, Stettner E. In defense of the use of lidocaine in rapid sequence intubation.
Ann Emerg Med 2007;49:84-6.
39. Reynolds SF, Heffner J. Airway management of the critically ill patient: rapid-
sequence intubation. Chest 2005;127:1397-412.
40. Seder DB, Mayer SA. Critical care management of subarachnoid hemorrhage and
ischemic stroke. Clin Chest Med 2009;30:103-22, viii-ix.
41. 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;79:410-6.
 42

42. Oddo M, Bosel J, Participants in the International Multidisciplinary Consensus

Conference on Multimodality M. Monitoring of brain and systemic oxygenation in neur-
ocritical care patients. Neurocrit Care 2014;21 Suppl 2:S103-20.
43. Prough DS, Lang J. Therapy of patients with head injuries: key parameters for
management. J Trauma 1997;42:S10-8.
44. Brinjikji W, Murad MH, Rabinstein AA, Cloft HJ, Lanzino G, Kallmes DF. Con-
scious sedation versus general anesthesia during endovascular acute ischemic stroke treat-
ment: a systematic review and meta-analysis. AJNR Am J Neuroradiol 2015;36:525-9.
45. 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;41:1175-9.
46. Dhakal LP, Diaz-Gomez JL, Freeman WD. Role of anesthesia for endovascu-
lar treatment of ischemic stroke: do we need neurophysiological monitoring? Stroke
2015;46:1748-54.
47. Lowhagen Henden P, Rentzos A, Karlsson JE, et al. General Anesthesia Versus
Conscious Sedation for Endovascular Treatment of Acute Ischemic Stroke: The AnStroke
Trial (Anesthesia During Stroke). Stroke 2017;48:1601-7.
48. Schonenberger S, Uhlmann L, Hacke W, et al. Effect of Conscious Sedation vs
General Anesthesia on Early Neurological Improvement Among Patients With Ischemic
Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial. JAMA
2016;316:1986-96.
49. Connolly ES, Jr., Rabinstein AA, Carhuapoma JR, et al. Guidelines for the
management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare pro-
fessionals from the American Heart Association/american Stroke Association. Stroke
2012;43:1711-37.
50. Rodriguez-Luna D, Pineiro S, Rubiera M, et al. Impact of blood pressure
changes and course on hematoma growth in acute intracerebral hemorrhage. Eur J Neurol
2013;20:1277-83.
51. Seneviratne J, Mandrekar J, Wijdicks EF, Rabinstein AA. Noninvasive ventilation
in myasthenic crisis. Arch Neurol 2008;65:54-8.
52. Abel M, Eisenkraft JB. Anesthetic implications of myasthenia gravis. Mt Sinai J
Med 2002;69:31-7.
53. Sawin PD, Todd MM, Traynelis VC, et al. Cervical spine motion with direct
laryngoscopy and orotracheal intubation. An in vivo cinefluoroscopic study of subjects
without cervical abnormality. Anesthesiology 1996;85:26-36.
54. Austin N, Krishnamoorthy V, Dagal A. Airway management in cervical spine
injury. Int J Crit Illn Inj Sci 2014;4:50-6.
55. Hauswald M, Sklar DP, Tandberg D, Garcia JF. Cervical spine movement during
airway management: cinefluoroscopic appraisal in human cadavers. Am J Emerg Med
1991;9:535-8.
56. Rosenblatt WH, Wagner PJ, Ovassapian A, Kain ZN. Practice patterns in
managing the difficult airway by anesthesiologists in the United States. Anesth Analg
1998;87:153-7.
 43

57. 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;24:217-21.
58. Ellis DY, Harris T, Zideman D. Cricoid pressure in emergency department rapid
sequence tracheal intubations: a risk-benefit analysis. Ann Emerg Med 2007;50:653-65.
59. Nolan JP, Wilson ME. Orotracheal intubation in patients with potential cervical
spine injuries. An indication for the gum elastic bougie. Anaesthesia 1993;48:630-3.
60. Kill C, Risse J, Wallot P, Seidl P, Steinfeldt T, Wulf H. Videolaryngoscopy with
glidescope reduces cervical spine movement in patients with unsecured cervical spine. J
Emerg Med 2013;44:750-6.
61. Griesdale DE, Liu D, McKinney J, Choi PT. Glidescope(R) video-laryngoscopy
versus direct laryngoscopy for endotracheal intubation: a systematic review and meta-
analysis. Can J Anaesth 2012;59:41-52.
62. Su YC, Chen CC, Lee YK, Lee JY, Lin KJ. Comparison of video laryngoscopes
with direct laryngoscopy for tracheal intubation: a meta-analysis of randomised trials.
Eur J Anaesthesiol 2011;28:788-95.
63. 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;40:629-39.
64. Jaber S, Jung B, Corne P, et al. An intervention to decrease complications related
to endotracheal intubation in the intensive care unit: a prospective, multiple-center study.
Intensive Care Med 2010;36:248-55.
65. Chesnut RM, Marshall SB, Piek J, Blunt BA, Klauber MR, Marshall LF. Early
and late systemic hypotension 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.
66. Moss E, Powell D, Gibson RM, McDowall DG. Effect of etomidate on intracranial
pressure and cerebral perfusion pressure. Br J Anaesth 1979;51:347-52.
67. Langsjo JW, Maksimow A, Salmi E, et al. S-ketamine anesthesia increases
cerebral blood flow in excess of the metabolic needs in humans. Anesthesiology
2005;103:258-68.
68. Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Effectiveness of ketamine in
decreasing intracranial pressure in children with intracranial hypertension. J Neurosurg
Pediatr 2009;4:40-6.
69. Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on ICP in
traumatic brain injury. Neurocrit Care 2014;21:163-73.
70. Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on intracranial
pressure in nontraumatic neurological illness. J Crit Care 2014;29:1096-106.
71. Hug CC, Jr., McLeskey CH, Nahrwold ML, et al. Hemodynamic effects of propo-
fol: data from over 25,000 patients. Anesth Analg 1993;77:S21-9.
72. Kovarik WD, Mayberg TS, Lam AM, Mathisen TL, Winn HR. Succinylcholine
does not change intracranial pressure, cerebral blood flow velocity, or the electroen-
cephalogram in patients with neurologic injury. Anesth Analg 1994;78:469-73.
 44

73. Martyn JA, Richtsfeld M. Succinylcholine-induced hyperkalemia in acquired

pathologic states: etiologic factors and molecular mechanisms. Anesthesiology
2006;104:158-69.
74. 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. Pharmacotherapy 2016;36:57-63.
75. Lee C, Jahr JS, Candiotti KA, Warriner B, Zornow MH, Naguib M. Reversal of
profound neuromuscular block by sugammadex administered three minutes after rocuro-
nium: a comparison with spontaneous recovery from succinylcholine. Anesthesiology
2009;110:1020-5.
76. Sorensen MK, Bretlau C, Gatke MR, Sorensen AM, Rasmussen LS. Rapid se-
quence induction and intubation with rocuronium-sugammadex compared with succinyl-
choline: a randomized trial. Br J Anaesth 2012;108:682-9.
77. Casey JD, Janz DR, Russell DW, et al. Bag-Mask Ventilation during Tracheal
Intubation of Critically Ill Adults. N Engl J Med 2019;380:811-21.
78. Lewis SR, Butler AR, Parker J, Cook TM, Smith AF. Videolaryngoscopy versus
direct laryngoscopy for adult patients requiring tracheal intubation. Cochrane Database
Syst Rev 2016;11:CD011136.
79. Griesdale DE, Chau A, Isac G, et al. Video-laryngoscopy versus direct laryn-
goscopy in critically ill patients: a pilot randomized trial. Can J Anaesth 2012;59:1032-9.
80. Lascarrou JB, Boisrame-Helms J, Bailly A, et al. Video Laryngoscopy vs Direct
Laryngoscopy on Successful First-Pass Orotracheal Intubation Among ICU Patients: A
Randomized Clinical Trial. JAMA 2017;317:483-93.
81. Cormack RS, Lehane J. Difficult tracheal intubation in obstetrics. Anaesthesia
1984;39:1105-11.
82. Murray MJ, Vermeulen MJ, Morrison LJ, Waite T. Evaluation of prehospital in-
sertion of the laryngeal mask airway by primary care paramedics with only classroom
mannequin training. CJEM 2002;4:338-43.
83. 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;31:750-3.
84. 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;115:497-9.
85. McConnell RA, Kerlin MP, Schweickert WD, Ahmad F, Patel MS, Fuchs BD.
Using a Post-Intubation Checklist and Time Out to Expedite Mechanical Ventilation
Monitoring: Observational Study of a Quality Improvement Intervention. Respir Care
2016;61:902-12.
86. 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;342:1301-8.
87. Boone MD, Jinadasa SP, Mueller A, et al. The Effect of Positive End-
Expiratory Pressure on Intracranial Pressure and Cerebral Hemodynamics. Neurocrit
Care 2017;26:174-81.
 45

88. 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;33:2367-72.
89. Nemer SN, Caldeira JB, Santos RG, et al. Effects of positive end-expiratory
pressure on brain tissue oxygen pressure of severe traumatic brain injury patients with
acute respiratory distress syndrome: A pilot study. J Crit Care 2015;30:1263-6.
90. Dumont TM, Visioni AJ, Rughani AI, Tranmer BI, Crookes B. Inappropriate
prehospital ventilation in severe traumatic brain injury increases in-hospital mortality. J
Neurotrauma 2010;27:1233-41.
91. 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;34:1202-8.
92. Davis DP, Stern J, Sise MJ, Hoyt DB. A follow-up analysis of factors associ-
ated with head-injury mortality after paramedic rapid sequence intubation. J Trauma
2005;59:486-90.
93. Rangel-Castilla L, Lara LR, Gopinath S, Swank PR, Valadka A, Robertson C.
Cerebral hemodynamic effects of acute hyperoxia and hyperventilation after severe trau-
matic brain injury. J Neurotrauma 2010;27:1853-63.
94. Koenig MA, Bryan M, Lewin JL, 3rd, Mirski MA, Geocadin RG, Stevens RD.
Reversal of transtentorial herniation with hypertonic saline. Neurology 2008;70:1023-9.
95. 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;28:1556-64.
96. Oertel M, Kelly DF, Lee JH, et al. Efficacy of hyperventilation, blood pressure el-
evation, and metabolic suppression therapy in controlling intracranial pressure after head
injury. J Neurosurg 2002;97:1045-53.
97. Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged hyper-
ventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg
1991;75:731-9.
98. Stocchetti N, Maas AI, Chieregato A, van der Plas AA. Hyperventilation in head
injury: a review. Chest 2005;127:1812-27.
99. Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head
injury: effect on ischemic burden and cerebral oxidative metabolism. Crit Care Med
2007;35:568-78.
100. Kilgannon JH, Jones AE, Shapiro NI, et al. Association between arterial hy-
peroxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA
2010;303:2165-71.
101. Balan IS, Fiskum G, Hazelton J, Cotto-Cumba C, Rosenthal RE. Oximetry-
guided reoxygenation improves neurological outcome after experimental cardiac arrest.
Stroke 2006;37:3008-13.
102. Brucken A, Kaab AB, Kottmann K, et al. Reducing the duration of 100% oxygen
ventilation in the early reperfusion period after cardiopulmonary resuscitation decreases
striatal brain damage. Resuscitation 2010;81:1698-703.
103. Kilgannon JH, Jones AE, Parrillo JE, et al. Relationship between supranor-
mal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation
 46

2011;123:2717-22.
104. Bellomo R, Bailey M, Eastwood GM, et al. Arterial hyperoxia and in-hospital
mortality after resuscitation from cardiac arrest. Crit Care 2011;15:R90.
105. Pulse oximetry in adults. (Accessed March 13, 2017, at www.uptodate.com.)
106. Helm M, Schuster R, Hauke J, Lampl L. Tight control of prehospital ventilation
by capnography in major trauma victims. Br J Anaesth 2003;90:327-32.
107. Hardman JG, Aitkenhead AR. Estimating alveolar dead space from the arterial
to end-tidal CO(2) gradient: a modeling analysis. Anesth Analg 2003;97:1846-51.
108. Brain Trauma F, American Association of Neurological S, Congress of Neu-
rological S, et al. Guidelines for the management of severe traumatic brain injury. VI.
Indications for intracranial pressure monitoring. J Neurotrauma 2007;24 Suppl 1:S37-44.
109. Citerio G, Cormio M. Sedation in neurointensive care: advances in understand-
ing and practice. Curr Opin Crit Care 2003;9:120-6.
110. Riker RR, Fugate JE, Participants in the International Multi-disciplinary Con-
sensus 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.
111. Samaniego EA, Mlynash M, Caulfield AF, Eyngorn I, Wijman CA. Sedation
confounds outcome prediction in cardiac arrest survivors treated with hypothermia. Neu-
rocrit Care 2011;15:113-9.
112. 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;27:2609-15.
113. 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;37:2527-34.
114. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation
Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care
Med 2002;166:1338-44.
115. 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;289:2983-91.
116. Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation
Scale for adult critically ill patients. Crit Care Med 1999;27:1325-9.
117. Deogaonkar A, Gupta R, DeGeorgia M, et al. Bispectral Index monitoring cor-
relates with sedation scales in brain-injured patients. Crit Care Med 2004;32:2403-6.
118. 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:e825-e73.
119. 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;37:469-76.
120. Devabhakthuni S, Armahizer MJ, Dasta JF, Kane-Gill SL. Analgosedation: a
paradigm shift in intensive care unit sedation practice. Ann Pharmacother 2012;46:530-
40.
 47

121. Karabinis A, Mandragos K, Stergiopoulos S, et al. Safety and efficacy 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:R268-80.
122. Iyer VN, Hoel R, Rabinstein AA. Propofol infusion syndrome in patients with re-
fractory status epilepticus: an 11-year clinical experience. Crit Care Med 2009;37:3024-
30.
123. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the manage-
ment of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care
Med 2013;41:263-306.
124. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam
or propofol for sedation during prolonged mechanical ventilation: two randomized con-
trolled trials. JAMA 2012;307:1151-60.
125. Grof TM, Bledsoe KA. Evaluating the use of dexmedetomidine in neurocritical
care patients. Neurocrit Care 2010;12:356-61.
126. 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;36:1107-14.
127. Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the Management
of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma
Foundation Guidelines, Executive Summary. Pediatr Crit Care Med 2019;20:280-9.
128. Wani TM, Bissonnette B, Engelhardt T, et al. The pediatric airway: Historical
concepts, new findings, and what matters. Int J Pediatr Otorhinolaryngol 2019;121:29-33.
129. Kleinman ME, Chameides L, Schexnayder SM, et al. Part 14: pediatric ad-
vanced life support: 2010 American Heart Association Guidelines for Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S876-908.
130. 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 Associa-
tion Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Circulation 2018;138:e731-e9.
131. Khine HH, Corddry DH, Kettrick RG, et al. Comparison of cuffed and un-
cuffed endotracheal tubes in young children during general anesthesia. Anesthesiology
1997;86:627-31; discussion 27A.
132. King BR, Baker MD, Braitman LE, Seidl-Friedman J, Schreiner MS. Endo-
tracheal tube selection in children: a comparison of four methods. Ann Emerg Med
1993;22:530-4.
133. Wheeler M CC, Todres ID. The pediatric airway. In: Cote´C LJ, Todres ID, ed.
A practice of anesthesia for infants and children. 4 ed. Philadelphia: Saunders-Elsevier;
2009:237.
134. Weiss M, Dullenkopf A, Fischer JE, Keller C, Gerber AC, European Paediatric
Endotracheal Intubation Study G. Prospective randomized controlled multi-centre trial of
cuffed or uncuffed endotracheal tubes in small children. Br J Anaesth 2009;103:867-73.
135. Phipps LM, Thomas NJ, Gilmore RK, et al. Prospective assessment of guidelines
for determining appropriate depth of endotracheal tube placement in children. Pediatr Crit
 48

Care Med 2005;6:519-22.

136. Patel R, Lenczyk M, Hannallah RS, McGill WA. Age and the onset of desatura-
tion in apnoeic children. Can J Anaesth 1994;41:771-4.
137. Weiss M, Gerber AC. Rapid sequence induction in children – it’s not a matter of
time! Paediatr Anaesth 2008;18:97-9.
138. Lawes EG, Campbell I, Mercer D. Inflation pressure, gastric insufflation and
rapid sequence induction. Br J Anaesth 1987;59:315-8.
139. 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;78:652-6.
140. Weiler N, Heinrichs W, Dick W. Assessment of pulmonary mechanics and gastric
inflation pressure during mask ventilation. Prehosp Disaster Med 1995;10:101-5.
141. Brock-Utne JG. Is cricoid pressure necessary? Paediatr Anaesth 2002;12:1-4.
142. Landsman I. Cricoid pressure: indications and complications. Paediatr Anaesth
2004;14:43-7.
143. Lev R, Rosen P. Prophylactic lidocaine use preintubation: a review. J Emerg
Med 1994;12:499-506.
144. Sagarin MJ, Chiang V, Sakles JC, et al. Rapid sequence intubation for pediatric
emergency airway management. Pediatr Emerg Care 2002;18:417-23.
145. Gronert GA. Cardiac arrest after succinylcholine: mortality greater with rhab-
domyolysis than receptor upregulation. Anesthesiology 2001;94:523-9.
146. Larach MG, Rosenberg H, Gronert GA, Allen GC. Hyperkalemic cardiac arrest
during anesthesia in infants and children with occult myopathies. Clin Pediatr (Phila)
1997;36:9-16.
147. Filanovsky Y, Miller P, Kao J. Myth: Ketamine should not be used as an induc-
tion agent for intubation in patients with head injury. CJEM 2010;12:154-7.
148. Sehdev RS, Symmons DA, Kindl K. Ketamine for rapid sequence induction
in patients with head injury in the emergency department. Emerg Med Australas
2006;18:37-44.
149. Skippen P, Seear M, Poskitt K, et al. Effect of hyperventilation on regional
cerebral blood flow in head-injured children. Crit Care Med 1997;25:1402-9.
150. 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.
151. Downard C, Hulka F, Mullins RJ, et al. Relationship of cerebral perfusion pres-
sure and survival in pediatric brain-injured patients. J Trauma 2000;49:654-8; discussion
8-9.
152. 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;67:1430-5.
153. 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;108:588-95.
154. Hungerford JL, O’Brien N, Moore-Clingenpeel M, et al. Remifentanil for Seda-
tion of Children With Traumatic Brain Injury. J Intensive Care Med 2019;34:557-62.
 49

155. Nemergut ME, Aganga D, Flick RP. Anesthetic neurotoxicity: what to tell the
parents? Paediatr Anaesth 2014;24:120-6.
156. Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic neu-
rodegeneration in the developing brain. Proc Natl Acad Sci U S A 2002;99:15089-94.
157. 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;23:876-82.
158. Loepke AW, Soriano SG. An assessment of the effects of general anesthetics on
developing brain structure and neurocognitive function. Anesth Analg 2008;106:1681-
707.
159. 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;33:220-30.
160. 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
U S A 1999;96:2508-13.
161. V Degos, T Charpentier, V Chhor, O Brissaud, S Lebon, L Schwendimann, N
Bednareck, S Passemard, J Mantz, P Gressens. “Neuroprotective effects of dexmedetomi-
dine against glutamate agonist-induced neuronal cell death are related to increased astro-
cyte brain-derived neurotrophic factor expression”. Anesthesiology 2013; 118(5):1123-
1132.
162. Y Zhu, K Peng, XW Ji. “Attenuation of neuroinflammation by dexmedetomidine
is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial
fracture model”. Brain Research 2016; 1644: 1-8.
163. Hegewald MJ, Crapo RO. Respiratory physiology in pregnancy. Clin Chest Med
2011;32(1):1-13. (In eng). DOI: 10.1016/j.ccm.2010.11.001.
164. Kitsiripant C, Kamata K, Kanamori R, Yamaguchi K, Ozaki M, Nomura M. Post-
operative management with dexmedetomidine in a pregnant patient who underwent AVM
nidus removal: a case report. JA Clin Rep 2017;3(1):17. (In eng). DOI: 10.1186/s40981-
017-0085-6.
165. Olutoye OA, Baker BW, Belfort MA, Olutoye OO. Food and Drug Ad-
ministration warning on anesthesia and brain development: implications for obstet-
ric and fetal surgery. Am J Obstet Gynecol 2018;218(1):98-102. (In eng). DOI:
10.1016/j.ajog.2017.08.107.
166. Xia Y, Ma X, Griffiths BB, Luo Y. Neurosurgical anesthesia for a pregnant
woman with macroprolactinoma: A case report. Medicine (Baltimore) 2018;97(37):e12360.
(In eng). DOI: 10.1097/md.0000000000012360.
167. Li J, Xiong M, Nadavaluru PR, et al. Dexmedetomidine Attenuates Neurotoxi-
city Induced by Prenatal Propofol Exposure. J Neurosurg Anesthesiol 2016;28(1):51-64.
(In eng). DOI: 10.1097/ana.0000000000000181.
168. Bulloch MN, Carroll DG. When one drug affects 2 patients: a review of medica-
tion for the management of nonlabor-related pain, sedation, infection, and hypertension
in the hospitalized pregnant patient. J Pharm Pract 2012;25(3):352-67. (In eng). DOI:
10.1177/0897190012442070.
 50

169. Zhang X, Zhao J, Chang T, Wang Q, Liu W, Gao L. Ketamine exerts neurotoxic
effects on the offspring of pregnant rats via the Wnt/β-catenin pathway. Environ Sci Pollut
Res Int 2020;27(1):305-314. (In eng). DOI: 10.1007/s11356-019-06753-z.
170. Li X, Li Y, Zhao J, et al. Administration of Ketamine Causes Autophagy
and Apoptosis in the Rat Fetal Hippocampus and in PC12 Cells. Front Cell Neurosci
2018;12:21. (In eng). DOI: 10.3389/fncel.2018.00021.
171. Li Y, Li X, Guo C, et al. Long-term neurocognitive dysfunction in offspring
via NGF/ ERK/CREB signaling pathway caused by ketamine exposure during the second
trimester of pregnancy in rats. Oncotarget 2017;8(19):30956-30970. (In eng). DOI:
10.18632/oncotarget.16042.

Acknowledgements
The authors are grateful for the contributions and insight provided by the following
reviewers: Scott Thomas May, PharmD, BCPS, BCCCP, Aaron Raleigh, BA, EMT-P,
Ebonye Green, AM Iqbal O’Meara, MD, Pedro Kurtz, MD, PhD