Trends in Anaesthesia and Critical Care 48 (2023) 101212

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Trends in Anaesthesia and Critical Care

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Review

Physiologically difficult airway: How to approach the difficulty beyond

anatomy
lder Pereira a, b, *
^s Graça a, Carolina Salgueirinho a, He
Diana Fonseca a, Maria Ine
a rio Sa
Centro Hospitalar Universita ~o Joa
~o, Porto, Portugal
b
Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Portugal

a r t i c l e i n f o a b s t r a c t

Article history: Physiologically Difficult Airway is a recent concept of difficult airway that accounts for difficulties
Received 10 November 2022 associated with patients' underlying physiologic derangements independent of their anatomical char-
Received in revised form acteristics and situational aspects. A higher risk of cardiovascular collapse and arrest, during or imme-
1 January 2023
diately after airway approach, is present in these cases, which can include hypoxemia, hypotension/
Accepted 11 January 2023
shock, severe metabolic acidosis and right ventricular failure. Recently, recommendations on Physio-
Handling Editor: Robert Greif logically Difficult Airway evaluation and management have emerged. In this literature review, we
summarize existing evidence on assessment tools and general strategies for airway approach in Physi-
Keywords: ologically Difficult Airway, as well as the optimization targets in airway management for each scenario.
Physiologically difficult airway © 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
Airway approach license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Physiological derangements

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Physiologically difficult airway approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
3. Physiologically difficult airway types and their specificities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.1. Hypoxemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.2. Cardiovascular impairment, hypotension, or shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3.3. Right ventricular dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3.4. Metabolic acidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
4. Specific populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
4.1. The critically ill . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
4.2. The neurocritical patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
4.3. Other populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4.3.1. High aspiration risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4.3.2. The bleeding upper airway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4.3.3. Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4.3.4. Obstructive sleep apnoea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4.3.5. Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
4.3.6. Paediatric patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
CRediT authorship contribution statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Declaration of competing interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

* Corresponding author. Anesthesiology Department, Centro Hospitalar Uni-

rio S~
versita ~o, Alameda Prof. Hern^
ao Joa ani Monteiro, 4200-319, Porto, Portugal.
E-mail address: hdrpereira@med.up.pt (H. Pereira).

https://doi.org/10.1016/j.tacc.2023.101212
2210-8440/© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
D. Fonseca, M.I. Graça, C. Salgueirinho et al.
1. Introduction
Physiologically Difficult Airway was first described in 2015. It
accounts for patients' underlying physiologic derangements that
place them at higher risk of cardiovascular collapse and arrest
during or immediately after airway approach and conversion to
positive pressure ventilation. It presents itself independently of
anatomical characteristics usually associated with difficult airway
and despite first attempt success [1e5]. Moreover, iatrogenic al-
terations provoked by induction agents and resuscitation strategies
could deteriorate the patient's pre-induction status [1e6].
Anaesthesiologists are frequently involved with emergency
airway management in the operating room and other locations
(pre-hospital care, emergency department, intensive care units,
and reanimation teams). The airway approach in these non-
operating room locations confers unique challenges related to in-
frastructures, equipment, and human factors. These are situation-
ally difficult airways associated with increased morbidity and
mortality [6].
Common Physiologically Difficult Airways include physiological
alterations mainly related to hypoxemia (desaturation or increased
oxygen consumption), hypotension/shock, severe metabolic
acidosis and right ventricular failure. Multifactorial contributors are
often present, particularly in critically ill patients with a minimal
physiological reserve and high aspiration risk [2,6].
Recently, recommendations on Physiologically Difficult Airway
evaluation and management have emerged. Evidence suggests that
anatomically and physiologically difficult airways similarly
decrease first-pass success and present an additive risk effect.
Therefore, difficult airway evaluation and management plans
should anticipate potential physiologic and situational challenges,
even if an anatomic difficulty is not predicted [1,3,4,6].
2. Physiologically difficult airway approach
When approaching an airway, the first step should be to
recognize all aspects of a potentially difficult airway, evaluating the
patient for anatomical, physiological, and situational factors.
A Cochrane systematic review found a poor screening test per-
formance of commonly used bedside tests for predicting an
anatomically difficult airway in patients with no apparent airway
abnormalities (Mallampati test, modified Mallampati test, Wilson
risk score, thyromental distance, sternomental distance, mouth
opening and the upper lip bite test), despite being recommended in
airway management guidelines [7]. MACOCHA system and HEAVEN
criteria have been used for Physiologically Difficult Airway evalu-
ation. However, evidence of their reliability is conflicting, and more
validation studies are needed to evaluate their use as predictor
tools for difficult airway [8e11]. The MACOCHA score system has a
maximum of 12 points (the higher the score, the greater the ex-
pected difficulty), and, despite not predicting first-attempt success,
it has a sensitivity of 73% for direct laryngoscopy (not validated for
video laryngoscopy) [8,10,12]. It includes the following anatomical,
physiological and operator aspects: Mallampati score III-IV,
obstructive sleep apnoea, decreased cervical mobility, mouth
opening <3 cm, Glasgow Coma Score <8, severe hypoxemia, and
non-anesthesiologist. The acronym of HEAVEN criteria stands for
Hypoxemia (oxygen saturation 93% at the time of initial laryn-
goscopy), Extremes of size (paediatric patient 8 years of age or
clinical obesity), Anatomic abnormalities (trauma, mass, swelling,
foreign body, or other structural abnormality limiting laryngo-
scopic view), Vomit/blood/fluid (clinically significant fluid present
in the pharynx/hypopharynx at the time of laryngoscopy), Exsan-
guination (suspected anaemia that could potentially accelerate
desaturation during rapid-sequence intubation associated apnoea),
2
Trends in Anaesthesia and Critical Care 48 (2023) 101212
and Neck mobility issues (limited cervical range of motion due to
immobilization or arthritis) [12]. The presence of at least one of
these was associated with lower first-pass success, except for
hypoxemia and exsanguination [10].
All team members should be aware of predicted difficulties,
airway management plans, and a backup plan. Equipment for both
plans should be readily available as well as a clear assignment of
roles for each team member. If feasible, the presence of two airway
operators is preferred. Moreover, a multidisciplinary approach
should be considered, particularly in critically ill patients.
Before the airway approach is initiated, patients should be
prepared and optimized whenever possible. The target of action to
optimize the patient's medical state is variable and depends on the
Physiologically Difficult Airway. Correct patient positioning and
concerns with anatomical DA must be taken into account.
Furthermore, situational factors should be minimized.
General strategies to optimize the Physiologically Difficult
Airway approach are summarized in Table 1. Specificities of the
approach according to the scenario are detailed below.
Special consideration must be given to preoxygenation strate-
gies since desaturation is the most significant risk factor for car-
diopulmonary arrest [3]. Preoxygenation is essential in every
airway approach to prolong desaturation, maximizing oxygen
arterial partial pressure and haemoglobin saturation [4]. Indeed, it
is associated with a higher first-pass success rate and lower desa-
turation risk [11]. However, its efficacy is variable, depending
mainly on the patient's functional residual capacity (FRC), the
presence of an increased rate of oxygen consumption or shunt/
ventilation-perfusion mismatch scenarios (atelectasis, alveolar
filling, shunt, increased dead space …) [3,4]. Positioning patients
head-up during preoxygenation increases FRC, which improves
efficacy, and reduces aspiration risk [3,8,13]. Reverse-
Trendelenburg positioning can be an option when optimal align-
ment is contraindicated (e.g. cervical spine injury) [13].
Traditionally, pre-oxygenation is accomplished with tight-
fitting facemasks (bag-valve-mask or a closed anaesthetic circuit)
or a non-rebreathing mask over 3e5 min. Nevertheless, in the
latter, air entrainment due to improper mask seal leads to a
decreased effective fraction of inspired oxygen, especially in criti-
cally ill patients with very high minute ventilation [3,11]. In past
years other methods have been described - Table 2 - and the choice
between them should be based on patient characteristics and
Physiologically Difficult Airway type scenarios once an optimal
method is not clear. Assisted spontaneous respirations with a bag-
valve-mask with a PEEP valve and one-way exhalation valve can be
used when tight-fitting non-rebreathing masks or noninvasive
positive pressure ventilation facemasks are unavailable [3,10].
Non-respiratory depressant sedatives like ketamine or dexme-
detomidine could be used in agitated or delirious patients to help
accomplish adequate preoxygenation [3]. Moreover, a protocol for
maximizing preoxygenation in agitated patients, termed delayed
sequence intubation, has been described in a recent observational
study and relies on inducing a dissociated state with ketamine in
small doses during preoxygenation with the non-rebreathing mask
or noninvasive positive pressure ventilation before neuromuscular
block [4,11]. Because this state can be unreliable, one should be
prepared for emergent intubation when using delayed sequence
intubation.
Apnoeic oxygenation prolongs safe apnoea time by continuously
replenishing consumed oxygen from the FRC during apnoea and
should be considered in some Physiologically Difficult Airway
scenarios. It can be performed with a standard nasal cannula at 15 L
per minute or high-flow nasal oxygen (HFNO) systems at 40e70 L
per minute. Methods like Transnasal Humidified Rapid-Insufflation
Ventilatory Exchange (THRIVE) possibly have the potential to
D. Fonseca, M.I. Graça, C. Salgueirinho et al. Trends in Anaesthesia and Critical Care 48 (2023) 101212

Table 1
Strategies to optimize airway approach in Physiologically Difficult Airway.

Strategies to optimize airway approach in Physiologically Difficult Airway

Preoxygenation Head-up, ramped or reverse-Trendelenburg positioning to improve oxygenation and decrease aspiration risk
Methods of preoxygenation are listed in Table 2
Apnoeic oxygenation and minimization of apnoea time
Rapid sequence Should be considered in all patients with high risk of pulmonary aspiration
intubation
Delayed sequence May be considered to maximize preoxygenation in agitated patients
intubation
Drugs Consider the use of etomidate or ketamine in patients with hemodynamic instability (hypotension, shock, right ventricular dysfunction …)
If propofol is used in critically ill patients, the induction dose should be reduced and carefully titrated
The use of neuromuscular blocking agents improves first attempt success
Type of laryngoscopy Video laryngoscopy increases first-pass success and should be the device of first choice
Awake fiberoptic intubation with topical anaesthesia in the spontaneously breathing patient should be considered in the presence of high risk of
anatomically difficult airway or high risk of clinical deterioration, including patients with refractory hypoxemia or metabolic acidosis
Hemodynamic Hemodynamic assessment with bedside ultrasound
optimization Fluid resuscitation in hypovolemic patients
Administration of vasopressor perfusion if unresponsive to fluids or at risk of fluid overload
Consider diluted ephedrine, phenylephrine, or epinephrine boluses administered peripherally to attenuate the decrease in vascular tone
induced by anaesthetic agents
In patients with right ventricular dysfunction, pulmonary vasodilators may decrease pulmonary pressures and afterload
Extracorporeal membrane oxygenation (ECMO) cannulation should be considered if the patient is in shock

Table 2
Advantages and Disadvantages of different preoxygenation dispositives.

Dispositive Advantages Disadvantages

Standard or wide-bore nasal
prongs Oxygen: 10e15 L per Low-cost
minute
High-flow nasal oxygen
(HFNO)
Oxygen: 40e70 L per minute
Noninvasive positive pressure Delivers high oxygen concentration
ventilation
Extraglottic devices
Well tolerated Capnography cannulas only allow oxygen flow rates
of 0e6 L per minute
Low risk
Delivers heated and humidified oxygen Variable PEEP-like effect (produces varying amounts
Allows flushing of dead space, reducing carbon dioxide [1, 10, 11] of continuous positive pressure depending on flow
Decreases respiratory rate and improves thoracoabdominal synchrony, reducing rate) [1]
the work of breathing [1]
Effective alternative to noninvasive positive pressure ventilation for patients with
shunt who cannot achieve peripheral arterial oxygen saturation SpO2 > 93% on
non-rebreathing mask at flush rate [1, 10]
Useful for awake intubation and for patients who cannot tolerate a tight-fitting
non-rebreathing mask or a noninvasive positive pressure ventilation mask [1]
Possible derecruitment when continuous positive
pressure is removed
Allows to unload respiratory muscle work Hemodynamic changes related to positive pressure
Promotes alveolar recruitment of atelectatic areas Anxiolysis and sedation may be needed
Improves oxygenation, particularly in patients with obesity and shunt physiology
[2, 10]
Preoxygenation by noninvasive positive pressure ventilation with PEEP is
preferred over bag-valve-mask with a PEEP valve in patients with significant
shunt physiology or reduced FRC [1, 5]
Better method for preoxygenation when compared to conventional bag-mask and
HFNO in patients with moderate-to-severe hypoxemia [10, 11, 15]
Useful if the patient requires higher airway pressures or cannot tolerate the Possible derecruitment when continuous positive
noninvasive positive pressure ventilation mask Should be considered if high PEEP pressure is removed
is necessary Hemodynamic changes related to positive pressure
Anxiolysis and sedation needed [2]

FRC, functional residual capacity; PEEP, positive end-expiratory pressure.

reduce the rate of carbon dioxide increase by gaseous mixing and
flushing of dead space, thus decreasing hypercapnia and conse-
quent pH alterations that can lead to ventricular arrhythmias,
neurologic compromise and even death [3,4,6].
3. Physiologically difficult airway types and their specificities
3.1. Hypoxemia
In hypoxemic respiratory failure, arterial oxygenation is
impaired, placing the patient at higher risk of desaturation during
airway approach, which may result in hemodynamic instability,
hypoxic brain injury or cardiopulmonary arrest. In addition to
hypoxemia, concerns due to potential major carbon dioxide
retention should be considered in hypercapnic respiratory failure
[4].
Shunt and ventilation/perfusion (V/Q) mismatch are the most
common involved mechanisms [4,9,11]. When a significant shunt is
present (high alveolar-arterial gradient), increasing the FiO2 may
not result in improvement of oxygenation and pre-oxygenation
efficacy with or without apnoeic oxygenation is reduced, thereby
increasing the risk of rapid desaturation during attempts at tracheal
intubation [3,9,10]. Also, when using FiO2 100%, hypoxemia could
be worsened in some of these patients, likely through absorption
atelectasis [8].
Airway approach strategies should prioritize reducing shunt and
improving V/Q mismatch, which is best accomplished with positive
pressure alveolar recruitment [3,4,9,11]. Adequate preoxygenation,

3
D. Fonseca, M.I. Graça, C. Salgueirinho et al.
apnoeic oxygenation and anaemia correction can help improve the
airway approach in these scenarios. Nevertheless, awake intubation
should be strongly considered for patients with refractory hypox-
emia by allowing them to maintain spontaneous respiration [3].
3.2. Cardiovascular impairment, hypotension, or shock
Hypotension may be caused or exacerbated during induction by
a combination of pharmacologically induced sympatholytic action
and transition to positive-pressure ventilation [4,6], conferring an
increased risk of complications, including bradycardia, cardiopul-
monary arrest, prolonged hospital stay and death [2,10,11,14].
Hemodynamic optimization before intubation should be pref-
erentially guided by bedside ultrasound assessment when possible
[10]. It should include fluid resuscitation in hypovolemic patients
and early administration of vasopressors in patients unresponsive
to fluids or at risk of fluid overload [2,6,9,11,15]. In case of
impending cardiopulmonary arrest, diluted ephedrine, phenyl-
ephrine, or epinephrine boluses administered peripherally can be
useful to attenuate the decrease in vascular tone induced by
anaesthetic agents and maintain systemic vascular resistance dur-
ing intubation [2e4].
Furthermore, hemodynamically stable induction agents such as
etomidate should be considered in hemodynamically compromised
patients since propofol may cause hypotension and myocardial
depression. Despite its cardio-stable profile, etomidate does not
suppress airway reflexes and cannot blunt the sympathetic
response to intubation, contributing to increased myocardial oxy-
gen demand [6,11]. Moreover, its use in patients with septic shock is
controversial, as it leads to adrenocortical suppression. If propofol
is used, the induction dose in patients presenting with shock
should be reduced and carefully titrated [2,11,14e16]. Ketamine has
sympathomimetic properties that contribute to increasing blood
pressure and decreasing airway resistance, which is particularly
useful in these patients [11,14]. Additionally, ketamine exhibits both
amnestic and analgesic properties and allows for the maintenance
of spontaneous ventilation. However, concerns regarding its use
include airway secretions and potential hemodynamic collapse in
patients with depleted catecholamine stores [6,11].
3.3. Right ventricular dysfunction
Patients in shock should be screened for right ventricular
dysfunction (RVD), considering the significant risk of peri-
intubation cardiovascular collapse associated with the transition
to mechanical ventilation. In addition to reducing preload by
decreasing venous return to the right atria, positive pressure
ventilation increases pulmonary pressures, resulting in increased
afterload, which is exacerbated by hypoxia and hypercarbia. So,
adequate preoxygenation and a short apnoea period in these pa-
tients are essential [3,11].
Patients should be resuscitated according to their fluid and
vasopressor responsiveness to maintain coronary perfusion pres-
sure, as empiric fluid loading may be deleterious. Pulmonary va-
sodilators such as epoprostenol and inhaled nitric oxide may
decrease the right ventricle afterload [11].
Echocardiography can be used not only to assess right heart
function but also to guide the management of mechanical venti-
lation, fluid therapy and vasoactive drug choice [17,18].
Moreover, pre-intubation extracorporeal membrane oxygena-
tion (ECMO) cannulation should be considered in patients with
shock. After intubation, ventilation goals should include the pre-
vention of hypoxia, hypercarbia, and atelectasis [3,4,11].
4
Trends in Anaesthesia and Critical Care 48 (2023) 101212
3.4. Metabolic acidosis
Compensatory hyperventilation is a crucial physiologic response
in metabolic acidosis. Intubating patients with severe metabolic
acidosis can be challenging since brief periods of apnoea can cause
a marked increase in CO2, worsening the acid-base imbalance and
triggering cardiac arrest. If tracheal intubation is required, preox-
ygenation with noninvasive positive pressure ventilation may be
given to reduce the work of breathing, and an awake approach with
preservation of spontaneous respiration during intubation should
be considered [2,3,11]. The aim should be to address the minimal
apnoea time and to treat the underlying cause of acidosis. After
intubation, the selected ventilator mode should allow the patient to
maintain their respiratory compensation by elevated minute
ventilation, so pressure control and pressure support modes are
preferred once the patient determines the tidal volume and res-
piratory rate [2,11].
4. Specific populations
4.1. The critically ill
Critically ill patients frequently present with a minimal physi-
ological reserve and are at high risk for aspiration due to full
stomach and gastroparesis of critical illness [2,6]. Thus, their airway
approach is potentially more complex and more likely to be asso-
ciated with cardiovascular collapse, described in nearly 30% of
critically ill patients [4,16]. Additionally, a higher rate of airway-
related complications, namely death or brain injury, was reported
in the NAP4 report during tracheal intubation in critically ill in the
intensive care unit (ICU) when compared to patients presenting at
the operating room for surgery (61% vs 14%) [11].
Physiologically Difficult Airway in these cases is frequently
multifactorial, resulting from reduced FRC, shunt and V/Q
mismatch, metabolic acidosis, right ventricular failure, intracranial
hypertension, high aspiration risk, also, situational factors as there
may be a reduced time for preparation owing to illness rapid pro-
gression that demands an emergent intervention [3,5,16]. Emer-
gent intubation is the intervention where risk is highest [10].
Pre-oxygenation is crucial but is often ineffective in critically ill
patients who are hypoxemic before the airway approach. However,
noninvasive positive pressure ventilation is associated with a
reduced incidence of severe hypoxemia [13]. The risk of fatal
complications associated with desaturation and cardiovascular
collapse usually overweight the risk of aspiration [8].
The operator should perform a pre-intubation global assess-
ment and optimize the patient to mitigate potential difficulties
[5,8]. When desaturation (oxygen saturation 90%) occurs, rescue
manoeuvres include optimization of mask ventilation with an
oropharyngeal airway and, if needed, the call of a second operator
to ensure an adequate mask seal. Supraglottic devices can also
provide rescue oxygenation, and emergency cricothyrotomy is
indicated when a situation “can't intubate, can't ventilate” develops
[5].
4.2. The neurocritical patient
The neurocritical patient presents a higher risk of Physiologi-
cally Difficult Airway due to the imperative need to avoid hypoxia,
maintain normocapnia and stable hemodynamic in order to allow
adequate cerebral perfusion in a patient with a disrupted capacity
to maintain cerebral autoregulation and at risk for secondary
neurological injury at this stage. Cerebral perfusion pressure de-
pends on mean arterial and intracranial pressure (ICP), and cerebral
blood flow is very sensitive to changes in pCO2, highlighting the
D. Fonseca, M.I. Graça, C. Salgueirinho et al.
need for minimizing laryngoscopy's duration until tracheal intu-
bation [3,11]. Topical or intravenous lidocaine, esmolol and opiates
are useful to blunt sympathetic stimulation in response to airway
approach [3]. Also, induction agents can lead to hypotension that
may compromise cerebral perfusion and drugs with the least he-
modynamic effects should be preferred.
4.3. Other populations
Physiological Difficult Airway is commonly encountered in
critically ill patients. However, other non-critically ill populations
with unique physiological characteristics that can be associated
with difficulties during airway approach independently of their
anatomical characteristics (namely by decreasing time to desatu-
ration) may be included in this concept in its broadest sense.
Therefore, the concepts mentioned above could also be helpful to
the clinician when applied to the following scenarios, expanding
this emerging and comprehensive concept in airway management
to a variety of other populations [9,11].
4.3.1. High aspiration risk
Pulmonary aspiration was identified as the most significant
cause of airway-related mortality in the Fourth National Audit
Project (NAP4) report, responsible for 50% of anaesthetic deaths.
Patients with increased risk of peri-intubation regurgitation and
pulmonary aspiration include those with inadequate fasting status,
delayed gastric emptying (pregnant patients, trauma patients and
patients with gastroparesis of critical illness or diabetes), incom-
petent lower oesophageal sphincter and intestinal obstruction
[9,11]. In these patients, rapid sequence intubation (RSI) with rapid
onset neuromuscular blocking agents minimizes the time between
loss of protective airway reflexes and a secure airway. RSI is asso-
ciated with increased first-attempt success, fewer intubation-
related complications, and fewer laryngeal injuries [5]. Neverthe-
less, gentle mask ventilation should be considered in some cases,
considering the life-threatening complications related to desatu-
ration [5,6].
4.3.2. The bleeding upper airway
The bleeding upper airway is an important cause of airway-
related adverse events whose aetiology can be diverse. Airway
management may be complex because the usual techniques
applied can be ineffective due to the presence of blood, affecting
visualization and potential anatomical and physiological alter-
ations. Hypoxemia, cardiovascular impairment and metabolic
acidosis can all be present in this scenario [19e21].
The site and severity of bleeding, risk of intubation failure by
direct laryngoscopy or difficulties in front-of-neck access, and pa-
tient's general status determine the airway approach plan. Standard
airway management algorithms may be inadequate, and usually,
there is no place for the option of waking the patient up when the
primary airway approach fails. So, whenever difficulties are ex-
pected with conventional techniques or the bleeding is profuse, an
awake approach should be considered, namely by pre-emptive
cricothyroidotomy or tracheotomy [19].
Initial management should include bleeding control and intra-
venous antifibrinolytics such as tranexamic acid in addition to local
measures, coagulopathy correction, metabolic acidosis correction
and maintenance of normothermia [19,21].
Preoxygenation is less efficient due to poor tolerance to face-
masks. The sitting position is usually the most comfortable for
preoxygenation in these patients. Systems such as HFNO and
THRIVE are not recommended due to the risk of forcing blood into
the distal airway with consequent airway obstruction by a blood
clot. To maximize preoxygenation efficacy, if tolerated, a standard
5
Trends in Anaesthesia and Critical Care 48 (2023) 101212
nasal cannula could be used throughout the airway approach and
supplemented with a facemask. Time to desaturation during RSI
could also be reduced due to significant anaemia, and the hazards
of hypoxia are exacerbated when hypovolemia is present. So,
adequate fluid resuscitation and transfusion should be initiated,
and the choice of induction agents should consider the risk of
cardiovascular collapse [19,20].
RSI is indicated due to the risk of aspiration of blood from the
stomach, which should be emptied after securing the airway with
an endotracheal tube. Preparation of 2 rigid large-bore suction
catheters (ideally with different suction sources) and the attribu-
tion of this function to a team member is advised. Moreover, before
starting invasive ventilation, the team should consider aspiration of
the tracheal tube to avoid distal airway obstruction due to blood or
clots [20].
Supraglottic devices may only be used as rescue or as a conduit
for intubation as there is an increased risk of aspiration, and they
restrict access to the bleeding site when it is localized in the hy-
popharynx, glottis, or trachea. When used as a conduit for intu-
bation, the technique should be performed under the visual
guidance of a fiberscope. An Aintree Intubation Catheter could also
help when using supraglottic devices not designed to facilitate
intubation. A retrograde airway technique using a guidewire/
epidural catheter passed by the cricothyroid membrane in a cranial
direction and through the supraglottic device has also been
described to guide the switch to an endotracheal tube. Additionally,
the last attempt before emergency front-of-neck access can include
blind intubation via supraglottic airway devices [20].
Front-of-neck access (cricothyroidotomy or tracheotomy) can be
used pre-emptively in the awake patient or as a rescue airway
management approach after induction. In all cases, to prepare the
approach, correct previous identification of cricothyroid membrane
is recommended (ultrasonography can be used), and a skilled sur-
geon on upper airway surgery should be present and prepared to
actuate. In children less than ten years of age, tracheostomy may be
preferred. Needle cricothyroidotomy only can be used as a tem-
porary oxygenation technique in emergencies. When all other
measures fail, extracorporeal membrane oxygenation should be
considered [19,20].
Of note, extubation should also be carefully planned and
cautiously undertaken as there is a risk of rebleeding and airway
compromise [20].
4.3.3. Obesity
The physiological changes associated with obese patients, such
as the higher resting metabolic demand and oxygen consumption,
the higher cardiac output (100 mL/min for each kilogram increase
in adipose tissue) and the incidence of heart failure, make them a
group at increased risk of Physiologically Difficult Airway [11].
4.3.4. Obstructive sleep apnoea
Patients with obstructive sleep apnoea share features of an
anatomically difficult airway (related to the increased soft tissue
surrounding the pharyngeal airway and collapsibility) and Physi-
ologically Difficult Airway due to reduced lung volume/FRC,
increased oxygen consumption and also depressed neural
compensation during sleep and anaesthesia. A risk of 3e4 times
higher of a difficult airway has been described in these patients
[22].
Management comprises obviating the need for an airway
approach (regional anaesthesia when possible), maximizing pre-
oxygenation efficacy, using apnoeic oxygenation techniques and
considering an awake intubation approach. Also, minimizing res-
piratory depression and upper airway obstruction post-surgery is
essential. Short-acting drugs with minimal respiratory depression
D. Fonseca, M.I. Graça, C. Salgueirinho et al.
effects and a multimodal analgesia strategy are preferred. Extuba-
tion is as critical as intubation, so an adequate neuromuscular
blockade reversal should be ensured and a semi-upright position
adopted [22].
4.3.5. Pregnancy
The obstetric airway is considered difficult not only because of
the anatomical changes but also due to physiological alterations
related to pregnancy. The reduced FRC and the higher oxygen de-
mand are critical factors in reducing safe apnoea time, resulting in
an increased risk of hypoxemia while securing the airway [11]. In
addition to hypoxemia, other risks such as aspiration, cardiovas-
cular instability and mortality are amplified after attempted intu-
bation. Pre-eclampsia is a specific pregnancy disorder associated
with an increased risk of Physiologically Difficult Airway [9,11]. In
these patients, maximizing pre-oxygenation efficacy and using
apnoeic oxygenation techniques is essential (see Table 1).
4.3.6. Paediatric patients
The paediatric airway differs from the adult anatomically and
physiologically, with significant differences below the age of two
years [9]. Physiologically Difficult Airway in children owes to
increased oxygen consumption (around 6 mL/kg/min compared to
3 mL/kg/min in adults), lower FRC and higher closing capacity,
which makes them more prone to hypoxia [6,11]. Additionally, they
require a greater respiratory rate to clear carbon dioxide adequately
and easily develop gastric distension during bag-mask ventilation
[9]. Airway oedema resulting from repeated intubation attempts is
also more critical [23].
To increase the time until desaturation, passive oxygen flow
rates of 1e2 L/kg/min can be used in small children via a nasal
cannula, modified nasal trumpet or oral RAE tube, potentially
reducing interruptions in tracheal intubation attempts to reox-
ygenate. Systems such as THRIVE are helpful in small children,
doubling the apnoea time compared to no passive oxygen. Never-
theless, the use of high flow nasal oxygen in this population is
limited by reported cases of pneumothorax with flow rates as low
as 6 L/min [23].
5. Conclusion
The airway approach is a crucial moment in the scope of the
anaesthesiologist's practice. In recent years there has been an
increasing awareness of Physiologically Difficult Airway relevance
in its contribution to airway-related adverse events. Indeed, phy-
sicians should assess anatomical, physiological, and situational
difficult airways with the same concern, prepare care, and optimize
the patient to attenuate the risks involved in each setting. Training,
namely with simulation scenarios, application of algorithms or
bundles and the establishment of a detailed plan anticipating dif-
ficulties, can help improve care for patients with various patho-
physiological abnormalities when they require airway
management. Also, multidisciplinary evaluation of the patients,
teamwork and communication play a central role that should be
recognized appropriately and emphasized [6,10,13,15].
CRediT authorship contribution statement
Diana Fonseca: Methodology, Conceptualization, Writing e
^s Graça:
original draft, Writing e review & editing. Maria Ine
Trends in Anaesthesia and Critical Care 48 (2023) 101212
Methodology, Writing e original draft, Writing e review & editing.
Carolina Salgueirinho: Methodology, Writing e original draft,
lder Pereira: Methodology, Writing
Writing e review & editing. He
e review & editing.
Declaration of competing interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
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