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A c u t e R e s p i r a t o r y D i s t res s
S y n d ro m e , M e c h a n i c a l
Ven t i l a t i o n , a n d In h a l a t i o n I n j u r y
in Bur n Patients
a,b c,
Edward Bittner, MD , Robert Sheridan, MD *

KEYWORDS
 ARDS  Burn injury  Inhalation injury  Mechanical ventilation
 Protective ventilation  Ventilator-induced lung injury

KEY POINTS
 Acute respiratory distress syndrome (ARDS) is common in seriously burned patients,
driven by a combination of inflammatory and infection factors.
 Inhalation injury contributes to respiratory failure in some burn patients.
 In burn patients, ARDS with or without inhalation injury is effectively managed using prin-
ciples evolved for non–burn patients.

ACUTE RESPIRATORY DISTRESS SYNDROME

Epidemiology and Pathophysiology
Burn patients are at risk of developing acute respiratory distress syndrome (ARDS) as
a result of systemic inflammation, fluid resuscitation, protein loss, prolonged mechan-
ical ventilation (MV), and multiorgan dysfunction (MODS) (Fig. 1). Inhalation injury—via
direct cellular damage, disruption of mucociliary clearance, airway obstruction, and
proinflammatory cytokines—further increases the risk.1 Between 20% and 50% of
mechanically ventilated burn patients will develop ARDS. Onset is most commonly
during the first week postburn, although it may be delayed.2,3 Pathologically, ARDS
is acutely characterized by inflammation-mediated injury resulting in increased
alveolar-capillary permeability, edema, alveolar collapse/derecruitment, reduced
lung compliance, increased pulmonary vascular resistance, ventilation-perfusion
(VQ) mismatch and shunting, and impaired gas exchange.4 Chronic changes are

a
Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital
and Shriners Hospital for Children, 51 Blossom Street, Boston, MA 02114, USA; b Department of
Anesthesia, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA;
c
Department of Surgery, Massachusetts General Hospital and Shriners Hospital for Children, 51
Blossom Street, Boston, MA 02114, USA
* Corresponding author.
E-mail address: rsheridan@mgh.harvard.edu

Surg Clin N Am 103 (2023) 439–451

https://doi.org/10.1016/j.suc.2023.01.006 surgical.theclinics.com
0039-6109/23/ª 2023 Elsevier Inc. All rights reserved.
440 Bittner & Sheridan

Fig. 1. Postburn ARDS are often nonspecific, showing inhomogeneous consolidation and
perihilar fullness.

characterized by fibrosis, vascular smooth muscle hypertrophy, and capillary obliter-

ation.4 ARDS contributes to mortality and morbidity in burn patients.5 Mortality in
ARDS is caused primarily by the development of MODS.6
The management of ARDS is largely supportive, and most approaches in burn pa-
tients have been translated from the non–burn population. Although MV is often
essential, the process itself can inflict further damage to the lungs, referred to as
ventilator-induced lung injury (VILI).7 Mechanisms of VILI include high inspiratory pres-
sures (barotrauma), high tidal volumes (TV; volutrauma), repeated opening and closing
of alveoli (atelectrauma), oxygen toxicity, and inflammatory cytokine release (bio-
trauma).8,9 Recently, additional mechanisms of injury have been implicated, including
high mechanical power (ergotrauma), stress frequency, respiratory muscle overuse/
underuse (myotrauma), and pulmonary capillary stress failure.10–12

Protective Ventilation
The standard approach to protective mechanical ventilation (PMV) includes small TVs
to limit volutrauma, setting positive end-expiratory pressure (PEEP) to minimize ate-
lectrauma, and recruitment maneuvers (RMs) to open collapsed regions of the lung.
An individualized approach to MV based on lung pathophysiology and morphology,
ARDS cause, and lung imaging and monitoring has been suggested to improve venti-
lation practice and outcome.13 In addition, PMV has been expanded beyond the lung
itself to include right-heart-protective ventilation, diaphragmatic-protective ventila-
tion, minimization of repetitive-stress injury, capillary-stress reduction, and consider-
ation of patient self-inflicted lung injury (P-SILI).11

Tidal Volumes
A TV of 4 to 6 mL/kg predicted body weight is commonly used to maintain a plateau
pressure (Pplat) < 30 cm H2O.14 Minimizing airway driving pressure (DP), calculated as
Pplat minus PEEP, is another suggested strategy for selecting TV.15 Importantly, Pplat
and DP are indirect measures for peak lung stress. When functional residual capacity
is markedly reduced in severe ARDS, overdistention can occur in nondependent re-
gions despite achieving target levels. Real-time bedside monitoring with pressure
and imaging techniques, such as esophageal manometry, electrical impedance
 Inhalation Injury in Burn Patients 441

tomography, and lung ultrasound, are increasingly used to select TV to minimize

overdistention.16–18
Unique characteristics of burn patients may affect the successful application of a
low-TV approach. For example, low TV in a burn patient with poor chest compliance
and/or inhalation injury with obstruction of the conducting airways can result in lung
underinflation. A retrospective study in pediatric burn patients with inhalation injury
found that a low-TV approach was associated with more atelectasis, longer duration
of MV, and a higher incidence of ARDS than a higher-TV approach.19 A recent inter-
national cohort study found that low-TV ventilation was used in most burn patients,
but was not associated with a reduction in days ventilator-free and alive at day
28.20 Strict application of low-TV ventilation in the setting of increased CO2 production
from burn-associated hypermetabolism can result in “air hunger,” patient-ventilator
dyssynchrony, and hypercapnia. Although hypercapnia may be tolerated to an extent
(“permissive hypercapnia”), adjustments to the ventilator mode and increases in seda-
tion are often needed.

POSITIVE END-EXPIRATORY PRESSURE

PEEP is used in ARDS to minimize atelectasis and reduce lung heterogeneity, thereby
increasing the amount of aerated lung available for ventilation. PEEP may also shift
edema fluid from the flooded alveoli into the interstitial space, decreasing shunt frac-
tion and promoting more uniform alveolar mechanics.8 However, PEEP will only have
benefit when alveolar recruitment surpasses overexpansion of patent alveoli. There is
no simple method to assess the risk-to-benefit ratio of different PEEP levels. In ARDS,
derecruitment is a continuous process in which the rate of collapse increases as PEEP
decreases. With decreasing levels of PEEP, derecruitment ceases in the sternal lung
zones at PEEP of 10 cm H2O, whereas it continues in dorsal regions down to
0 cm H2O.21 Consequently, a minimum PEEP of 10 to 12 cm H2O might reduce dere-
cruitment during the acute phase of ARDS, and higher levels may be necessary in se-
vere cases. Approaches to select an optimal PEEP level in ARDS include the use of
tables that assign PEEP based on FiO2, use of the highest PEEP that optimizes
oxygenation while allowing an acceptable TV and Pplat, and bedside PEEP titration
based on lung compliance and recruitability.22

Recruitment Maneuvers
Computed tomographic (CT) scans have indicated that tissue consolidation can ac-
count for up to 50% of the lung in ARDS.23 RMs apply a higher-than-normal inflation
pressure (usually 35 cm H2O) to the lungs for 20 to 40 seconds to “open the lung” by
recruiting atelectatic regions.24 Evidence to support their routine use in ARDS is lack-
ing.25 However, RMs may be beneficial for improving oxygenation in patients with hyp-
oxemia.25 The improvement in oxygenation from an RM is often greatest when
followed by an increase in the level of PEEP.25 Repeated RMs during lung-
protective ventilation can improve pulmonary compliance and oxygenation and do
not appear to worsen lung injury in severe ARDS.26 Most alveolar recruitment occurs
during the first 10 seconds of an RM; extended durations (eg, minutes) may be asso-
ciated with worse outcomes.27 RMs appear to be most effective in improving oxygen-
ation during early ARDS rather than during the fibroproliferative phase.28

Right-Heart-Protective Ventilation
Pulmonary hypertension (PH) in ARDS results from pulmonary vasoconstriction
(caused by hypoxia or hypercarbia), microthrombosis, and ventilation with high
442 Bittner & Sheridan

DPs.29 Right-ventricular (RV) dysfunction develops with sustained elevations in PH, as

the RV has no adaptive mechanism other than dilatation when its afterload is
increased.30 In ARDS, RV dysfunction can lead to RV failure (acute cor pulmonale),
and if left untreated, cardiogenic shock can develop. Elevated right-heart pressure
can also worsen hypoxemia by right-to-left intracardiac shunting of deoxygenated
blood through a patent foramen ovale. RV PMV has been suggested to reduce RV
afterload to include the following: (1) minimizing lung stress by limiting Pplat and
DP, (2) reducing pulmonary vasoconstriction by improving oxygenation and control
of CO2, and (3) prone positioning (PP) to unload the RV.31 Optimization of RV-
protective PEEP must balance alveolar recruitment and overdistention. If RV-
protective measures are insufficient (or unfeasible), ancillary therapies, such as
inhaled vasodilators or extracorporeal membrane oxygenation (ECMO), may be
required.

Diaphragm
Respiratory-muscle weakness rapidly develops in critically ill, mechanically ventilated
patients and carries a poorer prognosis.32,33 Exposure to excessive workloads even
for brief periods can result in diaphragmatic inflammation referred to as use atrophy.11
Failing to allow full rest following the onset of acute respiratory failure or after a failed
weaning trial can induce this injury and prolong MV.11 Furthermore, sepsis can incite
and exacerbate diaphragmatic injury, through the effects of proinflammatory cyto-
kines.34 Disuse atrophy can result from prolonged periods of MV and loss of electro-
myographic stimulation.35 Diaphragmatic PMV uses the following dual approach12: (1)
early after the onset of acute respiratory failure, avoiding prolonged periods of high
work of breathing (WOB) by providing adequate ventilatory support and sedation;
(2) during recovery, limiting passive ventilation and targeting an inspiratory effort level
similar to that of healthy subjects at rest to accelerate liberation from ventilation.33

Self-Induced Lung Injury

Increased respiratory drive and vigorous inspiratory efforts are often attempts to
compensate for impairments in respiratory mechanics and gas exchange. These
vigorous spontaneous breathing efforts may have injurious physiologic effects medi-
ated by swings in transpulmonary pressure (TPP), increases in transvascular pressure
resulting in edema, intratidal shift of gas between different lung zones (pendelluft), and
diaphragmatic injury. This is referred to as P-SILI.36 In patients receiving MV, vigorous
respiratory efforts may also result in patient-ventilator dyssynchrony and increased
mechanical lung injury owing to high TPPs and/or cyclic atelectasis.37,38 Preventing
P-SILI in clinical practice requires assessment of a patient’s inspiratory effort and
the detection of potentially harmful patient-ventilator interactions. For some patients
with vigorous spontaneous breathing and/or patient-ventilator dyssynchrony, seda-
tion or paralysis may be protective treatment.

Stress Frequency and Permissive Hypercapnia

Higher ventilatory frequencies are often used with low-TV ventilation to reduce hyper-
capnia, but this may have detrimental effects on respiratory mechanics, gas ex-
change, and cumulative lung trauma.39,40 Higher ventilatory frequencies shorten
inspiratory time, resulting in the need for higher peak-flow rates, which may augment
parenchymal shear stress, worsen oxygenation, and contribute to greater pressure-
related cyclic lung stress and strain. Shortened expiration times may have detrimental
effects, including dynamic hyperinflation, reduced compliance, increased TPP, and
diaphragmatic dysfunction. A reduction of the frequency of ventilation with resulting
 Inhalation Injury in Burn Patients 443

hypercapnia may be beneficial in ARDS by facilitating a reduction of the cumulative

intensity of cyclic stress and strain. Hypercapnia itself may also have beneficial phys-
iologic benefits, including improved VQ matching from pulmonary vasoconstriction,
increased local alveolar ventilation from inhibition of airway tone, increased oxygen
delivery from an increase in cardiac output, increased unloading of oxygen in the tis-
sues, microvascular vasodilation, and anti-inflammatory effects.41 Some studies have
reported benefit from permissive hypercapnia in ARDS, although they are confounded
by the inability to dissect the effects of permissive hypercapnia from the effects of low
TV.42 Because hypercapnia increases respiratory drive, deep sedation or neuromus-
cular blockade may be required.

Fluid Overload and Capillary Stress Reduction

Fluid-conservative approaches have been associated with improved outcomes in
non–burn ARDS, but have the potential to compromise burn resuscitation.43 Conse-
quently, application of a fluid-conservative approach in a burn patient with ARDS
should be considered carefully, with close attention to administering the least amount
of fluid that still achieves adequate organ perfusion.

Unconventional Mechanical Ventilation

A variety of unconventional modes of MV, including high-frequency percussive venti-
lation (HFPV), high-frequency oscillatory ventilation (HFOV), or airway-pressure-
release ventilation (APRV), are used in some burn centers for patients with ARDS.44
HFPV delivers very small, high-frequency tidal breaths superimposed on a conven-
tional pressure-controlled breath.45 HFPV improves oxygenation, improves ventila-
tion, and lowers airway pressures compared with other modes of MV. HFPV also
produces intrabronchial percussion, airway turbulence, and higher airflow, all of which
enhance mobilization and clearance of airway debris and secretions. HFPV, although
shown not to be superior to conventional ventilation in the general ARDS population,
has a suggested role in inhalation injuries and burn-related ARDS.46 HFPV is routinely
used in some burn centers, particularly in patients with inhalation injury or in those who
fail conventional MV.
HFOV delivers small, sub-dead-space TVs at high frequency to maximize lung
recruitment and avoid cyclic alveolar collapse.47 HFOV in burn-related ARDS has
not been extensively studied. HFOV is sometimes used as a rescue approach for
burn patients with refractory hypoxemia but is generally unsuccessful in improving
oxygenation in inhalation injury, probably because effective lung recruitment is
impaired by obstruction of the conducting airways.48
APRV is a mode of pressure-controlled ventilation that allows spontaneous breath-
ing at regularly fluctuating high and low levels of continuous positive airway pres-
sure.49 Proposed benefits include alveolar recruitment and stabilization, improved
VQ matching, increased mean airway pressure, and minimization peak and Pplats.50
Spontaneous breathing in APRV reduces sedation requirements, thereby preserving
airway reflexes and facilitating cough and pulmonary toilet. There is limited literature
supporting the benefit of APRV for ARDS. Specific evidence in the burn population
is lacking.

Noninvasive Ventilation
For patients with mild ARDS, noninvasive ventilation (NIV) may be beneficial, as it al-
lows patients to communicate more easily, requires less sedation, allows more effec-
tive cough and expectoration of secretions, and avoids intubation-related
complications. NIV appears safe and effective in mild to moderate hypoxemia, but it
444 Bittner & Sheridan

may delay intubation and increase mortality in more severe hypoxemia.51 In patients
with inhalation injury or that have received large-volume fluid resuscitation, NIV may
mask evidence of progressive airway obstruction.52 There is currently limited literature
examining the impact of NIV in the burn population.53
High-Flow Nasal Cannula
High-flow nasal cannula (HFNC) is increasingly used in the management of respiratory
failure, including mild ARDS.54 HFNC is capable of delivering up to 100% heated and
humidified oxygen at flow rates of up to 60 L per minute. The benefits include a reduc-
tion in WOB, reduction of the anatomic dead space, generation of a small amount of
PEEP, and improvement of mucociliary clearance.55 There are limited reports of HFNC
use in patients with burns and/or inhalation injury.56

STRATEGIES FOR REFRACTORY HYPOXEMIA

Prone Positioning
When a patient with ARDS is turned from supine to prone, the atelectatic dorsal lung
regions are freed from the weight of the more ventral lung, the heart, and the medias-
tinum, favoring expansion of dorsal regions. The net effect is more homogeneous
aeration with a more uniform strain distribution leading to an improvement of gas ex-
change and a decreased risk of VILI.57 A systematic review of 9 randomized controlled
trials (RCTs) concluded that patients with ARDS most likely to derive a survival benefit
from PP were those with severe hypoxemia and in whom it was used more than
16 hours per day.58 Data on PP of burn patients are limited; it presents logistical
and safety challenges.59 A case series reports improvements in oxygenation and a
low rate of complications in patients with burn-related ARDS undergoing PP.60 PMV
should continue to be used during PP, and reassessment of ventilatory parameters
should be performed, as respiratory mechanics may change with proning.61,62
Increased sedation and neuromuscular blockade may be required.
Neuromuscular Blockade
Neuromuscular blocking agents (NMBAs) are sometimes used in patients with severe
ARDS to enhance gas exchange and reduce Pplats, ventilator dyssynchrony, and VILI.
A meta-analysis of 5 RCTs in moderate to severe ARDS concluded that early initiation
(within 36–48 hours of ARDS diagnosis) of a 48-hour infusion of cisatracurium
improved oxygenation and lowered barotrauma risk without increasing intensive
care unit weakness.63 There is no specific evidence to guide the use of NMBAs in
burn-injured patients with ARDS. It is reasonable to consider them in burn patients
with severe ARDS.64
Inhaled Pulmonary Vasodilators
Inhaled pulmonary vasodilators, including nitric oxide (NO) and epoprostenol, selec-
tively increase blood flow to ventilated lung regions, thereby improving VQ matching
and improving oxygenation.65 They can also benefit ARDS patients with right-heart
failure. A meta-analysis of 14 RCTs in adults with ARDS found that inhaled NO
increased oxygenation but did not affect duration of MV or survival.66 Improvement
in oxygenation with inhaled NO has been demonstrated in burn-injured patients with
ARDS.67 Inhaled epoprostenol is a less-expensive agent that has similar effects.68
Extracorporeal Life Support
If other rescue strategies used in ARDS management fail to improve oxygenation,
ECMO may be beneficial. A recent report concluded that mortality for burn-injured
 Inhalation Injury in Burn Patients 445

patients receiving ECMO was comparable that for non–burn ECMO patients.69 Con-
siderations include the risks of anticoagulation, need for further operative care, and
consideration of the goals or futility of care.70 Patients most likely to benefit from
ECMO are those with severe ARDS within the first week of MV and without multiple
organ failure.71 ECMO for burn patients should be provided only in centers experi-
enced in both burn care and in the use of extracorporeal support for ARDS.

INHALATION INJURY

Usually sustained in structural or vehicular fires, inhalation injury occurs in about 5% of

burn-unit admissions.72,73 Survival has improved with the evolution of supportive res-
piratory care, but inhalation injury remains a significant source of morbidity and mor-
tality in burn patients. It increases mortality in patients with large cutaneous burns.74

Pathophysiology
The smoke generated during structural fires contains many incomplete combustion
products, chemicals, and fine debris with varied particle size and weight. Gas temper-
atures can rise above floor level to several hundred degrees Fahrenheit. Exposure to
such temperatures in inhaled gas can cause direct thermal damage to the supraglottic
airway. Rarely, particularly with steam inhalation injury in enclosed spaces, thermal
injury below the glottis can occur. Aerosolized irritants can cause inflammation, bron-
chospasm, increased bronchial blood flow, surfactant depletion, and mucosal slough.
The local response to inhaled irritants attracts inflammatory cells, generates reactive
oxygen species, and causes local release of proinflammatory molecules.75 These
can induce variable degrees of alveolar flooding and bronchial exudate with second-
ary VQ mismatching. These inflammatory changes are thought to explain the signifi-
cant resuscitation fluid volume required by burn patients with inhalation injury.76–78
Inhalation injury may be accompanied and complicated by carbon monoxide and/or
cyanide poisoning.
Inhalation injury carries a strong risk of ARDS, and of pneumonia secondary to
sloughing of the respiratory epithelium with resulting loss of ciliary clearance and
accrual of obstructive endobronchial debris. This results in small-airway occlusion,
atelectasis, and infection. Deaths owing to inhalation injury are often related to sec-
ondary ARDS and infection, with a classic report suggesting up to a 60% increase
in expected burn mortality in the setting of coincident inhalation injury and
pneumonia.79

Diagnosis
Tools to evaluate the presence and severity of inhalation injury include clinical evalu-
ation, bronchoscopy, and radiography. Unfortunately, none of these tools reliably pre-
dict clinical course.80 Severity grading schemes have been proposed,81 but have not
proven to be reliably useful for clinical care. History and clinical presentation are the
most reliable methods of evaluation. Burns occurring in a closed space, burns around
the nose and mouth, singed nasal hair, soot in the airway, carbonaceous sputum,
hoarseness, wheezing, and stridor all suggest inhalation injury. Bronchoscopic exam-
ination will often reveal carbonaceous debris, ulceration, pallor, and mucosal slough,
although patients inhaling fine-particle smoke or burning hydrocarbons may have
deceptively unremarkable bronchoscopy. Those with overt bronchoscopic signs on
initial evaluation seem to have more challenging clinical courses.82 Serial bronchos-
copy for pulmonary toilet may have value later in the hospital course, but there is no
demonstrated role for early bronchoscopic removal of visible soot. Early chest
446 Bittner & Sheridan

radiographs are usually normal. Radionuclide ventilation scanning with xenon-133,

technetium-99 DTPA, or macroaggregated albumin may show inhomogeneous tracer
clearance suggestive of small airway obstruction.83 CT scanning has been proposed
for early diagnosis.84–88
Management
During initial evaluation, intubation is indicated for usual reasons of obtunded mental
state or respiratory distress. Inhalation injury alone does not mandate intubation un-
less airway patency is threatened, particularly if cutaneous burns are small. In patients
with severe facial edema or stridor, rapid assessment is critical, and intubation is often
required. Evolving upper airway edema may complicate reintubation, so tube security
is essential. Routine use of prophylactic antibiotics or empiric steroids is not
supported.
Inhalation injury is associated with mucosal slough and loss of ciliary clearance with
compromised pulmonary toilet. Chest physiotherapy and suctioning or stimulated
cough is front-line therapy. Uncommonly, repeated bronchoscopy for pulmonary toilet
may be needed.89 Tracheobronchitis and pneumonia may occur and are addressed
with targeted antibiotics and pulmonary toilet. Additional proposed therapies have
included HFPV,90 high-volume ventilation,91 and nebulized heparin and N-acetylcys-
teine.92 Tracheostomy, weaning, and extubation follow standard critical-care indica-
tions. Rarely, patients will suffer tracheal injury requiring reconstruction93; most
survivors have no long-term pulmonary sequalae.94

SUMMARY

ARDS is common in patients with burn injury, and the need for large-volume fluid
resuscitation, frequent surgery, presence of inhalation injury, superimposed sepsis,
and burn-associated hypermetabolism all contribute to ventilation challenges.

CLINICS CARE POINTS

 Respiratory distress and failure are common occurences in burn patients driven by direct
respiratory system injury, pulmonary and systemic infection, and systemic inflammation
 Inhalalation injury is caused by inhaled irritants and can result in multi-level iinvolvement of
the respiratory system

DISCLOSURE

The authors have nothing to disclose.

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