Paediatric Respiratory Reviews 20 (2016) 39

Contents lists available at ScienceDirect

Paediatric Respiratory Reviews

Mini-Symposium: Ventilation Strategies in the Paediatric Intensive Care Unit

Ventilation strategies in paediatric inhalation injury

Chong Tien Goh 1,*, Stephen Jacobe 2
1
Advanced Trainee in Intensive Care Medicine, Paediatric Intensive Care Unit, The Childrens Hospital at Westmead, Sydney
2
Senior Staff Specialist, Paediatric Intensive Care Unit, The Childrens Hospital at Westmead, Sydney, and Clinical Associate Professor, Sydney Medical School,
University of Sydney, NSW, Australia

EDUCATIONAL AIMS

After reading this article the reader will be able to recognise:

 the signicance of inhalation injuries in children

 ventilatory management strategies suitable for children with inhalation injuries
 the potential role of additional pharmacological adjuncts that are sometimes used in inhalation injury

A R T I C L E I N F O S U M M A R Y

Keywords: Inhalation injury increases morbidity and mortality in burns victims. While the diagnosis remains
Inhalation injury
largely clinical, bronchoscopy is also helpful to diagnose and grade the severity of any injury. Inhalation
Treatment
injury results from direct thermal injury or chemical irritation of the respiratory tract, systemic toxicity
Children
from inhaled substances, or a combination of these factors. While endotracheal intubation is essential in
cases where upper airway obstruction may occur, it has its own risks and should not be performed
prophylactically in all cases of inhalation injury. The evidence-base informing the selection of optimal
ventilation strategy in inhalation injury is sparse, and most recommendations are based on extrapolation
from (largely adult) studies in acute respiratory distress syndrome (ARDS). Conventional ventilation
using a lung-protective approach (i.e. low tidal volume, limited plateau pressure, and permissive
hypercarbia) is recommended as the initial approach if invasive ventilation is required; various rescue
strategies may become necessary if there is a poor response. The efcacy of many widely used
pharmacologic adjuncts in inhalation injury remains uncertain. Further research is urgently required to
address these gaps in our knowledge.
Crown Copyright 2015 Published by Elsevier Ltd. All rights reserved.

INTRODUCTION
Approximately 10-30% of patients hospitalised with burn
injury have a concomitant inhalation injury, and inhalation
injury is a signicant risk factor for increased mortality and
morbidity in adult and paediatric burns patients [18]. A recent
large series of 850 children with inhalation injury admitted to a
Shriners Childrens Hospital in the U.S.A. over a 10-year
period found these children required mechanical ventilation
* Corresponding author. Paediatric Intensive Care Unit, The Childrens Hospital at
Westmead, Locked Bag 4001, Westmead NSW 2145 Australia.
E-mail address: chongtien.goh@health.nsw.gov.au (C.T. Goh).
for a mean of 15.2 days and the overall mortality rate was
approximately 16%, with most deaths due to pulmonary
dysfunction [9]. Mortality was signicantly related to the size
and depth of the burn.
Inhalation injury increases the risk for pneumonia, and the
contributions of inhalation injury and pneumonia to mortality are
independent and additive [6]. A recent meta-analysis found the
risk of death doubled with inhalational injury (13.9% vs 27.6%)
[5]. While inhalation injury is associated with increased morbidity
in the acute phase, a study of paediatric burn survivors found it did
not affect long-term quality of life [10].
Unfortunately, a universally recognised denition of inhalation
injury is currently lacking, and specic evidence-based treatment
options are largely lacking.

http://dx.doi.org/10.1016/j.prrv.2015.10.005
1526-0542/Crown Copyright 2015 Published by Elsevier Ltd. All rights reserved.
4 C.T. Goh, S. Jacobe / Paediatric Respiratory Reviews 20 (2016) 39
The lung injury seen following inhalation associated with burns
results from direct thermal injury to the airways, local chemical
irritation to the respiratory tract, or systemic toxicity due to
inhalation of carbon monoxide, cyanide, or other toxins [11]. In
addition, the systemic inammatory response to burns, sepsis,
pneumonia, and ventilator-induced lung injury (VILI) may
contribute to additional lung injury.
Inhalation injury may often be associated with pneumonia and
ARDS, however burn victims without inhalation injury can also
develop these, and it should not be assumed that the presence of
pulmonary complications signies that an inhalation injury has
been sustained.
While some studies found patients with inhalation injury
required increased uid volume for resuscitation compared to
those without [12,13], others have not conrmed this [14].
Unlike damaged skin that can be dressed and grafted, the
management of inhalation injury is mainly supportive, with care
taken to protect the lung from secondary injury. This review will
focus on the respiratory support strategies, and in particular,
ventilation strategies, for children with inhalation injuries.
PATHOPHYSIOLOGY
Inhalation injury can cause damage by a combination of: 1) direct
thermal damage to the upper airways; 2) local chemical irritation of
the respiratory tract, and; 3) systemic toxicity due to inhalation of
toxic substances. Lee et al. [15] recently reviewed this topic.
Direct thermal damage to upper airways
Air temperature in an enclosed re can reach in excess of 600 8C.
Due to a combination of efcient heat dissipation of the upper
airway, reex closure of the larynx and low heat capacity of air,
direct thermal injury is usually conned to airway structures above
the carina [16]. Thermal injuries to upper airway structures can,
however, lead to massive swelling and partial or even total airway
obstruction [16]. Airway swelling develops rapidly over a few
hours, particularly as uid resuscitation is ongoing, and may not
peak until 24 hours post injury. Therefore evaluation immedi-
ately following the injury may be an unreliable indicator of the
severity of obstruction that may develop, and it is essential that all
patients suspected of having signicant upper airway burns are
carefully assessed by an experienced senior clinician for consid-
eration of early elective intubation for airway protection.
Endotracheal intubation has potential complications including
the need for heavy sedation and even neuromuscular blockade;
hypotension and uid creep; and tube misplacement, dislodge-
ment, or blockage. Prophylactic intubation of all patients with
inhalation injury should be avoided where safe to do so [17].
Chemical irritation of the respiratory tract
Lower airway injury is usually caused by chemical irritation
rather than thermal injury, and the nature and severity depends on
the type of materials burnt, the temperature of combustion, and
the duration of exposure or dose [15]. Burnt rubber and plastics
produce sulphur dioxide, nitrogen dioxide, ammonia and chlorine,
which form corrosive acids and alkalis when combined with water
in the alveoli. Hydrocarbons, aldehydes, ketones and acids form
from polyethylene, while burning cotton or wool produce toxic
aldehydes. Carbon monoxide and cyanide are generated from
combustion of wood and polyurethane respectively.
Studies using Multiple Inert Gas Elimination Technique
(MIGET) suggest that the hypoxia associated with smoke-inhala-
tion-induced small airways injury is predominantly due to V/Q
mismatch [18].
The tragic Dellwood re [19] shed some light on the histological
process following smoke inhalation. Autopsy ndings of infants
who died revealed a combination of bronchial necrosis, alveolar
congestion and atelectasis, with vascular engorgement and
formation of dense membranes or casts obstructing the lower
airways. Bronchiolitis and bronchopneumonia were observed in
some.
Pulmonary oedema due to increased vascular permeability
plays an important role in the pathophysiological processes
leading to lung injury. This is thought to be mediated in part by
increased nitric oxide (NO) production, which forms a potent
oxidant peroxynitrite (ONOO-), causing cellular injury and lipid
peroxidation [20]. Chemicals in smoke promote the formation of
neutrophil-generated oxygen radicals and inammatory radicals
which cause bronchial constriction, and exudate and airway cast
formation. Impaired chemotactic and phagocytic function of the
alveolar macrophage increases the risk of infection. Destruction
and damage to the airways ciliary transport function leads to the
accumulation of casts, airway plugging and impaired clearance of
bacteria. The end result is progressive respiratory failure over the
course of 48 hours due to decreased lung compliance, V/Q
mismatch, and increased dead space ventilation.
Systemic toxicity due to inhaled substances
Carbon monoxide (CO) and cyanide inhalation can lead to major
morbidity following inhalation injury. Carbon monoxide is an
odourless, colourless gas with an afnity 200 times greater
than oxygen for haemoglobin [11]. CO shifts the oxyhaemoglo-
bin dissociation curve to the left, and, following prolonged
exposure, binds to cytochrome oxidase, impairing mitochondri-
al function and reducing adenosine triphosphate production.
Carbon monoxide thus reduces both the oxygen-carrying
capacity of blood and oxygen dissociation at a tissue level, as
well as disrupting cellular respiration. Standard pulse oximetry
cannot reliably distinguish between oxyhaemoglobin and
carboxyhaemoglobin (COHb), and patients may appear cherry
pink rather than cyanosed. Co-oximetry is required to make the
diagnosis.
Hydrogen cyanide is produced by combustion of various
household materials. Cyanide inhibits the cytochrome oxidase
system and may have a synergistic effect with carbon monoxide in
producing tissue hypoxia, lactic acidosis and decreased cerebral
oxygen consumption [21]. One study of smoke inhalation victims
(with burns <15%) found a signicant correlation between a
lactate level of >10 mmol/L and an elevated blood cyanide level
[22]. A lactic acidosis in burn victims may, however, be due to
several causes and is not specic for cyanide toxicity. The in vitro
half-life of cyanide is approximately 1 hour [22]. Although a
number of potential antidotes for cyanide toxicity are available, a
rapid diagnostic test for cyanide poisoning is not widely available,
and as a result the accurate evaluation of the efcacy of these
therapies remains difcult.
DIAGNOSIS OF INHALATION INJURY
The diagnosis of inhalation injury is suggested by a history of
exposure to smoke, ames or super-heated air in an enclosed
space, and duration of exposure (trapped or unconscious at the
scene), together with physical ndings of facial burns, upper
airway injury (redness and swelling of the oropharynx, hoarseness,
stridor, carbonaceous sputum) and lower airway involvement
(tachypnoea, dyspnoea, crackles or wheeze, decreased breath
sounds, decreased O2 saturations) [16,23]. The diagnosis can be
conrmed and graded by beroptic bronchoscopy (Table 1)
[9,24,25].
 C.T. Goh, S. Jacobe / Paediatric Respiratory Reviews 20 (2016) 39 5

Table 1
Bronchoscopic criteria used to grade inhalation injury {derived from reference [14]}
Grade 0 - no injury: absence of carbonaceous deposits, erythema, edema,
bronchorrhea, or obstruction
Grade 1 - mild injury: minor or patchy areas of erythema, carbonaceous
deposits in proximal or distal bronchi (any or combination)
Grade 2 - moderate injury: moderate degree of erythema, carbonaceous
deposits, bronchorrhea, with or without compromise of the bronchi
(any or combination)
Grade 3 - severe injury: severe inammation with friability, copious
carbonaceous deposits, bronchorrhea, bronchial obstruction (any or
combination)
Grade 4 (massive injury): evidence of mucosal sloughing, necrosis,
endoluminal obliteration (any or combination)

Advances in the management of inhalational injury have been

hampered by the lack of uniform criteria for diagnosis and severity
grading [23]. Inhalation injury in children can largely be
determined by clinical ndings, with or without bronchoscopy
[9]. A number of scoring systems have been developed in an effort
to grade the severity of inhalation injury [26,27]; however, due to
the heterogeneous presentation of burns patients, predicting
which patients are vulnerable to increased pulmonary dysfunction,
respiratory failure, and mortality has proved difcult [11]. Some
authors, for instance, demonstrated a signicant correlation
between the severity of inhalation injury graded by bronchoscopy
and uid resuscitation volume [12,13], while others have not
[14]. Liffner failed to demonstrate a relationship between their
scoring system and the development of Acute Respiratory Distress
Syndrome (ARDS) [27].
Figure 1. Simplied pressure-time waveform depicting the various forms of
ventilation used in inhalation injury (see text for explanation).
VENTILATORY STRATEGIES

While intubation and ventilation must be considered early in

cases of inhalational injury, it shouldnt be performed without a
careful consideration of the potential morbidity outlined above.
Reasons for intubation include: protection against anticipated
airway swelling; treatment of impaired oxygenation and/or
ventilation due to lung injury; and to ensure airway protection
and optimal oxygenation in cases of hypoxia or carbon monoxide
poisoning with neurological impairment. In all cases, the goal of
mechanical ventilation should be to optimise oxygenation and
ventilation while minimising potential ventilator-induced lung
injury (VILI).
The mechanisms leading to VILI include: high airway pressure
causing barotrauma; over-distension leading to volutrauma;
repetitive opening and closing of alveoli causing atelectrauma;
and lung inammation secondary to the release of pro-inamma-
tory cytokines producing biotrauma. These have been extensively
reviewed elsewhere [28,29].
As mentioned above, the pathophysiology of inhalation injury
may involve airway oedema and secretions as well as uid leak
causing alveolar and interstitial oedema. If the former predomi-
nates, signs of airway obstruction with increased resistance will be
present, whereas in the latter situation there will be decreased gas
exchange and decreased lung compliance. Alveolar collapse is
likely in both situations, and of course, most patients with
inhalation injury will have a mixture of these pathologies, which
will often change over time.
Optimal conventional mechanical ventilation aims to ventilate
the lung at the steepest point of its compliance curve by setting the
level of peak end-expiratory pressure (PEEP) just above the lower
inection point of the inspiratory pressure-volume curve.
A number of ventilator modalities have been used in the setting
of inhalation injury, and Figure 1 is a simplied diagram depicting
the different pressure waveforms generated by these.
Conventional lung protective ventilation
Amato [30] rst described the benet of a low tidal volume
ventilator strategy in cases of Acute Lung Injury (ALI)/ARDS,
ndings subsequently replicated by the ARDSNet trial [31] and
Villar [32]. Since then, the open-lung ventilation strategy using
low-tidal volume ventilation and sufcient PEEP to maintain
alveolar and airway patency has been widely advocated in cases of
ALI/ARDS irrespective of underlying aetiology.
Caution is required in extrapolating the ARDSNet strategy to
paediatric patients generally [33] - and those with inhalational
injury specically - as none of the three studies above included
paediatric patients, and the ARDSNet trial excluded patients with
burns exceeding 30% body surface area. Whether a low tidal
volume strategy of 6 ml/kg predicted body weight (PBW) is as
benecial in children as in adults remains unproven. A prospective
observational study of paediatric ARDS in Australia and New
Zealand found higher maximum and median tidal volumes were
associated with reduced mortality, even after correction for
severity of lung disease [34]. Another study found that ventilating
children with ALI/ARDS with tidal volumes between 6-10 ml/kg
was not associated with increased mortality [35].
A study from the Shriners Hospital for Children [36] found that
children with inhalational injury ventilated with high tidal
volumes had a decreased incidence of ARDS and reduced ventilator
days. This study included 932 children treated from 1986 to
2014 with bronchoscopically-conrmed inhalational injury, 691 of
whom were ventilated with either a high tidal volume (HTV, 15 +/
3 ml/kg) or a low tidal volume (LTV, 9 +/ 3 ml/kg) strategy. In
spite of signicantly higher ventilator pressures and a higher
incidence of pneumothoraces, patients in the HTV group had a
signicant reduction in ventilator days when compared to the LTV
6 C.T. Goh, S. Jacobe / Paediatric Respiratory Reviews 20 (2016) 39
group. The mortality observed in the LTV group was almost a third
lower (15%) than the HTV group (22%), however, this did not reach
statistical signicance. It should be noted that the groups
compared were from two different eras over 29 years (HTV:
1986-1996, LTV: 1997-2014), and changes in patient demo-
graphics over this period raised questions regarding the generali-
sability of the ndings.
Inhalation injury involving secretions and debris in the airways
as well as airway oedema and bronchoconstriction may have
pronounced airway obstruction, and inasmuch as the pathology is
similar to other obstructive airway conditions like severe asthma,
pressure control ventilation (PCV) has at least theoretical
advantages over volume controlled ventilation (VCV) [37]. Due
to variable degrees of obstruction/airways resistance, different
lung units will have a range of time constants. By applying a
constant pressure throughout inspiration, PCV may lead to more
even gas distribution, greater tidal volume for the same inspiratory
pressure, and improved dynamic compliance.
High Frequency Percussive Ventilation (HFPV)
HFPV is a pneumatically driven, pressure-limited, time-cycled
mode of ventilation that delivers high-frequency (450-600/min)
sub-tidal bursts of gas superimposed on a biphasic inspiratory and
expiratory pressure cycle [38,39]. During inspiration, lung volumes
are progressively increased by repetitive diminishing sub-tidal
volume deliveries until an oscillatory plateau is reached. The lung
is then allowed to empty passively until the pre-set expiratory
baseline is reached. The percussive airow delivered by HFPV is
believed to facilitate evacuation of debris resulting from epithelial
sloughing, haemorrhage, and inammation after inhalation injury.
HFPV has been shown to produce better gas exchange at similar
pressures when compared with conventional ventilation [40]. A
study of 15 adults with inhalation injury found HFPV was
associated with a signicant improvement in oxygenation without
increasing biomarkers of lung injury, suggesting that the mode was
lung protective [41].
Initial reports from case series [4245] demonstrated better gas
exchange and lower incidence of pneumonia when HFPV was used
on burns patients with inhalation injury. In a prospective
randomized trial comparing HFPV to conventional ventilation in
burned children with respiratory failure, Carman et al. [46] found
patients ventilated using HFPV required signicantly lower peak
inspiratory pressure and achieved a signicantly higher PaO2/FiO2
ratio compared to those on conventional ventilation, and
concluded that HFPV is a safe and effective method of ventilation
for paediatric burn patients. Repers study [47] revealed similar
ndings in adult patients.
More recently, Chung [48] compared adult burn patients
managed with HFPV or a low-tidal volume conventional ventila-
tion strategy. HFPV resulted in similar clinical outcomes, however,
signicantly more patients on the low-tidal volume ventilation
arm failed to meet ventilation and oxygenation goals and required
rescue therapy with either HFPV or airway pressure release
ventilation (APRV).
These encouraging data on HFPV has led to some burns centres
favouring the use of HFPV as their primary form of ventilation in
inhalational injury.
High Frequency Oscillatory Ventilation (HFOV)
HFOV is a ventilation mode delivering rapid (5-15 Hz) sub-tidal
oscillatory breaths to improve gas exchange while providing lung
protection. In contrast to HFPV, HFOV oscillates the lung around a
constant mean airway pressure higher than that used in
conventional ventilation. The application of a relatively high
constant mean airway pressure recruits collapsed alveoli and
prevents alveolar derecruitment while avoiding high peak
inspiratory pressures.
The results of the OSCAR [49] and OSCILLATE [50] trials have cast
doubt on HFOV use in ARDS. The OSCAR trial reported no mortality
benet with HFOV versus conventional ventilation while the
OSCILLATE trial was stopped early due to an increase in mortality
in the HFOV arm. Increased use of neuromuscular blockade and
vasopressor support in the HFOV arm was noted in both trials. It
should be noted that these studies included a heterogeneous group
of patients with ARDS, and paediatric patients were excluded.
Data for the use of HFOV in burns comes largely from single
centre studies. Cartoto [51,52] reported improved oxygenation in
adult burns patients with ARDS when HFOV was initiated. They
concluded that HFOV should be considered where moderate to
severe oxygenation failure (PaO2/FiO2 ratio <150) persists despite
aggressive and escalating conventional mechanical ventilator
support. Oxygenation failure in this context usually characterised
by a need for either: an FiO2 >0.6 despite a PEEP of >12.5 cm H2O;
the need for inverse ratio ventilation; the use of inhaled nitric
oxide (iNO) to support oxygenation; or an oxygenation index
((FiO2 x mean airway pressure)/paO2 mmHg) >25.
HFOV may be less effective in treating severe hypoxic
respiratory failure associated with ARDS and concomitant inhala-
tion injury than in ARDS and solely a burn injury [53]. The unique
pathophysiologic changes in the lung parenchyma and airway
following smoke inhalation, including small airway obstruction,
may limit the ability of HFOV to recruit alveoli. In addition, there
may be difculty in managing secretions, potential worsening of
gas trapping and related hypercapnia. Also HFOV complicates the
intermittent nebulisation of adjunctive therapies for inhalation
injury [54].
Experience from the Riley Hospital for Children [55] suggests
this may be the case in children with burns. While most patients
demonstrated an improvement in oxygenation following initiation
of HFOV, they described a group of slow responders, similar to
Cartoto et al. There was a high incidence of barotrauma (38%) and a
fth of the patients had refractory hypercapnia on HFOV.
Given the current evidence, HFOV should only be considered as
rescue therapy for burn patients failing conventional mechanical
ventilation, and when inhalational injury is present, it should be
anticipated that the response to HFOV might be poor.
Airway Pressure Release Ventilation
APRV is a mode of ventilation where a constant high level of
positive airway pressure is punctuated by brief intermittent releases of
pressure [56]. The prolonged high pressure (Phigh) promotes alveolar
recruitment and maintains lung volume, while the time-cycled release
phase allows the lungs to periodically decompress to a lower set
pressure (Plow) which aids CO2 clearance. The patient is able to breathe
spontaneously and independent of the ventilator cycle, allowing
decreased use of sedation and neuromuscular blockade. Spontaneous
breathing has a positive impact on cardiovascular function, renal
function and splanchnic perfusion [57].
A number of excellent review articles on APRV have been
published [5759], however, there are few studies of APRV in
patients with inhalation injury. Batchinsky et al. [60] compared
APRV to conventional ventilation in pigs with inhalational injury
and found that APRV-treated animals developed ARDS faster than
conventional mechanical ventilation-treated animals, with a lower
PaO2/FiO2 ratio at 12, 18, and 24 hours after injury. They postulated
that the pathophysiologic changes of early smoke inhalation injury
have important clinical implication that may limit the benet of
APRV. Further studies of APRV in the burns population are
required.
 C.T. Goh, S. Jacobe / Paediatric Respiratory Reviews 20 (2016) 39
Non-Invasive Ventilation (NIV)
NIV is dened as any form of ventilatory support applied
without the use of an endotracheal tube, including continuous
positive airway pressure (CPAP) [61]. The potential benets of NIV
are numerous, and stem from the avoidance of the morbidity
associated with endotracheal intubation. Non-intubated patients
can communicate freely, require less sedation, can cough and
expectorate, are able to continue on standard oral intake, and avoid
other potential complications of intubation such as oropharyngeal
trauma, mucosal ulceration and ventilator associated pneumonia.
Key to the success of NIV is an ability of the patient to protect his
own airway, and NIV is contraindicated in unconscious patients
with impaired cough and secretion clearance.
Data regarding the use of NIV in burns patients is limited. Endorf
et al. [62] recently proposed early application of NIV to a high-risk burn
patient who does not require immediate intubation, even before signs
of respiratory insufciency appear, however, this strategy has not been
tested in clinical trials. A retrospective study by Smailes [63] including
30 patients with burns found that for patients with respiratory
insufciency post-extubation, the use of NIV prevented reintubation in
74%. Only eight patients in this study had inhalation injury. Warner
[64] reviewed 200 patients over a 6 year period at the Shriners
Hospital for Children where 6 of 10 patients who received NIV post-
extubation for respiratory insufciency avoided reintubation; none of
the patients had inhalational injury, however.
NIV mask application may be problematic in the setting of facial
burns and the anxious, struggling child. Finally, there are
legitimate concerns that NIV may mask signs of impending airway
obstruction in the setting of an inhalational injury.
Heated Humidied High-Flow Nasal Cannula (HHHFNC)
HHHFNC delivers humidied gas via nasal cannula at ow rates
exceeding minute ventilation. HHHFNC appears to reduce the
work of breathing and improves gas exchange by nasopharyngeal
dead-space washout; decreasing the energy required to humidify
and heat respiratory gases; and by providing a degree of positive
distending pressure [65]. HHHFNC has so far been found to be
useful to support infants with bronchiolitis; premature neonates;
and adults with hypoxic respiratory failure [66]. There are no
reports of its use to date in patients with inhalation injury.
Pharmacological Adjuncts
Adjuncts to ventilation seek to tackle the underlying patho-
physiologic processes of inhalation injury. Although some are
promising, there is little to no evidence of improved patient
outcomes and wide variation in the use of many of these therapies.
In an animal model of inhalation injury, those who received iNO
had decreased lung water, decreased pulmonary microvascular
resistance and decreased pulmonary artery pressure when
compared with controls [67]. iNO has been used as rescue therapy
in cases of refractory hypoxic respiratory failure following
inhalation injury. Despite an improvement in PaO2/FiO2 ratio
[6870] no mortality benet was demonstrated.
In inhalation injury, casts formed by a combination of brin,
mucus, inammatory cells, and sloughed epithelial cells may lead
to airway obstruction. Researchers have studied the use of
nebulised anticoagulants to prevent brin formation in an effort
to reduce airway cast formation. Desai [71] demonstrated that
children with inhalation injury who received nebulised heparin
and N-acetylcystine (NAC) had reduced reintubation rates as well
as lower mortality. Miller et al. [72] found this treatment
attenuated lung injury and the progression of ARDS in ventilated
adult patients with ALI following smoke inhalation. El-Sharnouby
7
[73] showed that a higher dose of heparin (10,000U vs 5,000U)
nebulised with NAC led to a reduction in lung injury score and
reduced ventilator days, suggesting a dose-dependent effect. The
higher dose of heparin had no effect on systemic coagulation.
However, a retrospective review by Holt [74] on 150 adult patients
with inhalation injury showed no improvement in clinical
outcome with the use of nebulised heparin/NAC.
The use of nebulised adrenaline [75] and albuterol [76] in
animals have shown promise in improving airway clearance,
decreasing airway pressures and improving PaO2/FiO2 ratio. This is
postulated to be due to beta-receptor induced bronchodilatory and
anti-inammatory effects.
Other potentially useful therapies under investigation include
thromboxane A2 antagonists, free oxygen radical scavengers and
anti-muscarinic agents.
CONCLUSION
Inhalation injury remains a major cause of morbidity and
mortality in children with burns worldwide. The optimal mode and
settings for ventilating children with inhalation injury is currently
unclear, and further studies are required. Until the results of such
studies are known, patients with signicant lung injury should be
conventionally ventilated with a tidal volume of 5-8 mL/kg PBW,
limitation of plateau pressure to 28cmH2O, and application of
sufcient PEEP to maintain alveolar patency and adequate
oxygenation [33]. Permissive hypercapnia should be accepted
unless there is a concomitant neurological injury with suspected
intracranial hypertension.
HFPV has shown promise as an alternative mode of ventilation
in some centres, and it may facilitate the clearance of airway debris
and secretions. APRV and HFOV may be considered as rescue
modes in very severe lung disease, though a benet on outcome
remains unproven.
The efcacy and role of adjunctive pharmacologic therapies on
outcomes in inhalation injury is unclear.
Given the multitude of uncertainties in this important area,
further research is needed to clarify the optimal management -
including ventilation strategy - for children with inhalation injury.
It is important that such research look specically at clinically
important outcome measures such as 28-day mortality, and, given
the heterogeneous patient population and relatively low mortality,
these studies will likely need to be multicentre.
CONFLICTS OF INTEREST
The authors declare that they have no conicts of interest.
FUTURE DIRECTIONS FOR RESEARCH
1. A widely agreed upon denition of inhalation injury is an essential
rst step to establishing multicentre research in this area.
2. Due to small patient numbers in individual centres and
relatively low mortality, large, multi-centred randomised
controlled trials comparing ventilator strategies (e.g. high vs.
low tidal volume, HFPV vs. conventional ventilation) will be
necessary to demonstrate clinically relevant outcome benets
(such as 28-day mortality).
3. The efcacy of pharmacologic adjuncts such as inhaled heparin
and NAC should be subjected to rigorous controlled trials.
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