SYMPOSIUM: INTENSIVE CARE
Paediatric acute
respiratory distress
syndrome (PARDS)
Catarina Silvestre
Harish Vyas
Abstract
Acute respiratory distress syndrome (ARDS) is a syndrome with acute,
diffuse, inflammatory lung injury associated with non-haemodynamic
lung oedema. It is responsible for almost a quarter of the ventilated pa-
tients in intensive care. The causes of ARDS are variable. They include
primary pulmonary diseases such as pneumonia, drowning and aspi-
ration and extra-pulmonary conditions including sepsis, trauma or
burns. Although ARDS is well recognized in children, it is, in our expe-
rience, underdiagnosed in the paediatric intensive care units. This
short article describes the diagnostic criteria, the causes and the man-
agement of ARDS in children.
Keywords ARDS; management; paediatric; ventilation
Introduction
Acute respiratory distress syndrome (ARDS) was first described
by Ashbaugh and colleagues in 1967. They reported a cohort of
12 patients that presented with tachypnoea, hypoxaemia and loss
of lung compliance who did not respond to the usual respiratory
treatment. This presentation of patients with ARDS is the result
of acute inflammation that occurs in the lungs after an insult that
can be pulmonary or extra-pulmonary. This inflammation results
in alteration of the alveolar-capillary permeability and is associ-
ated with lung oedema and hypoxia. Chest imaging typically
demonstrates the presence of bilateral infiltrates.
Over the last fifty years huge amount of research into has gone
into understanding the mechanisms of injury and pathophysi-
ology as well as optimising treatment to improve prognosis of
this entity.
ARDS is one of the most challenging pathologies to manage in
critical care medicine. There is no specific treatment, the man-
agement is primarily based on supportive care. The goal is to try
and protect the lungs from any further injury.
In paediatric practice the challenges are even greater due to
the overlap of diseases especially chronic lung disease, congen-
ital heart defects and bronchiolitis. The recent PARDIE (paedi-
atric acute respiratory distress syndrome incidence and
epidemiology) study, reported an incidence of 3.2% of paediatric
Catarina Silvestre MD, Consultant Paediatric Intensivist, Paediatric
Critical Care Unit, Nottingham Children’s Hospital, Nottingham, UK.
Conflicts of interest: none declared.
Harish Vyas DM FRCP FRCPCH, Honorary Consultant Paediatric
Intensivist, Paediatric Critical Care Unit, Nottingham Children’s
Hospital, Nottingham, UK. Conflicts of interest: none declared.
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Please cite this article as: Silvestre C, Vyas H, Paediatric acute respiratory distress syndrome (PARDS), Paediatrics and Child Health, https://
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ARDS (PARDS) admitted to PICU and 6.1% among those on
mechanical ventilation. The mortality is still high and varies
between 17% and 32%. Early recognition and intervention may
help improve the outcome of children with PARDS.
Definition
Adult ARDS
Since the original description by Ashbaugh et al., there have been
several task forces collaborating to arrive at a diagnostic criterion
for ARDS in adults. The first consensus was published in 1994 by
the AmericaneEuropean Consensus Conference; this classifica-
tion stratified the degree of hypoxia based on the PaO2/FiO2
correlation; the chest imaging changes (bilateral infiltrates; see
Figure 1) in the absence of pulmonary oedema that can be
explained by cardiac disease (Table 1).
The definition subsequently evolved, and in 2011 the same
task force revised the definition and the Berlin criteria for ARDS
were published for the adult population. The main difference was
in the stratification of the severity of the disease according to the
degree of hypoxia (Table 2). The changes incorporated from the
1994 definition were elimination of the term acute lung injury.
PaO2/FiO2 ratio was evaluated with a minimum amount of
positive end expiratory pressure (PEEP) and three categories of
ARDS, mild, moderate and severe were classified based on the
PaO2/FiO2 ratio.
Paediatric ARDS
The anatomic and physiological differences in children’s respi-
ratory system, such as chest wall compliance, respiratory muscle
reserve, alveolar maturation and metabolic demands, made it
necessary for specific paediatric definitions. In 2015, a group of
27 experts from different countries (PALICC, the Paediatric Acute
Lung Injury Consensus Conference) published criteria for PARDS
(Table 3).
This definition excluded causes of acute hypoxia unique in the
neonatal period. The differences between adult and paediatric
definitions are summarized in Box 1. The goal of these paediatric
criteria is to promote an earlier diagnosis and earlier intervention
for those with significant lung injury.
Summary of differences between adult ARDS and PALLIC
definitions
Radiological changes: in children x-ray changes can be unilateral.
This change is controversial from the pathophysiological point of
view; the inflammation is a diffuse process of both lungs.
It incorporates pulse oximetry and oxygen saturation when arterial
blood gases and PaO2 are not available.
Oxygenation index (OI) and/or oxygenation saturation index (OSI) are
used to stratify severity instead of PaO2/FiO2.
Specific criteria exist for children receiving non-invasive and invasive
ventilation.
Paediatric specific pathologies like chronic lung disease and cyanotic
heart disease have particular criteria.
Box 1
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 SYMPOSIUM: INTENSIVE CARE

via high-flow nasal cannula (HFNC) has been proposed as an

alternative of NIV. However, the use of non-invasive techniques
in patients with hypoxic respiratory failure is controversial.
Children and young people who require NIV or HFNC to treat
mild ARDS must be very closely monitored.
Whilst invasive mechanical ventilation is associated with
several complications; neuro-myopathy, diaphragmatic
dysfunction and drug associated withdrawal and delirium, there
is a need to balance the risk of these with the possible harm of
maintaining spontaneous breathing in a patient with hypoxic
respiratory failure.
Patient self-inflicted lung injury (P-SILI) is a new concept,
which must be considered in children with worsening respiratory
failure and respiratory distress. Spontaneously breathing chil-
dren and young people with damaged lungs and high respiratory
drive are at risk for P-SILI. In respiratory failure, volume and
Figure 1 Chest X-ray shows diffuse bilateral infiltrates with air bron-
chogram in a 2-year-old girl, with a background of trisomy 21 and pressure changes in the lungs may aggravate the initial injury.
severe PARDS due to adenovirus pneumonia. X-ray taken while prone. Large swings of trans-pulmonary pressure triggered by strong
inspiratory effort can result in further damage to damaged lungs.
High tidal volumes and high vascular transmural pressure in-
crease vessels permeability leading to formation of alveolar
ARDS criteria from AECC (AmericaneEuropean
oedema (negative pressure pulmonary oedema) further perpet-
Consensus Conference)
uating the cycle of lung injury. The diaphragm can also be
Time PaO2/ Chest X-ray Pcwp injured by the high inspiratory effort due to high mechanical
FiO2 forces.
The control which can be exerted over ventilation with
ALI Acute <300 Bilateral interstitial <15e18 mmHg. invasive mechanical ventilation, paralysis and ventilation pro-
or alveolar infiltrates No hypertension in tective strategies can be beneficial and may help to prevent the P-
left atrium SILI.
ARDS Acute <200 Same Same
Moderate to severe RDS
ALI, acute lung injury; ARDS, acute respiratory distress syndrome; PaO2/FiO2,
PaO2 arterial oxygen pressure in mmHg/fraction of inspired O2; Pcwp, pulmo- The goal of mechanical ventilation in ARDS is lung protection
nary capillary wedge pressure. and the prevention of ventilation-induced lung injury (VILI). VILI
results from excessive forces applied to the lung parenchyma
Table 1 leading to stretching and over-distention. The prevention of VILI
is the cornerstone to the management of PARDS; most of the
Causes of ARDS evidence is extrapolated from adult population with very few
The triggers for paediatric ARDS are summarized in Table 4. In paediatric studies.
children processes like pneumonia, bronchiolitis and sepsis are
Determining the optimal tidal volume to reduce lung
the major risk factors. Children with pre-existing lung disease, a
injury
history of prematurity, those on long term ventilation and/or
Lower tidal volume will reduce lung over-distention, decreasing
with congenital heart disease are at a greater risk PARDS.
alveolar cellular damage, interstitial oedema, and release of pro-
inflammatory cytokines. The recommended tidal volume in the
Management of ARDS
adult population from the ARDS network group is 6 ml/kg and
Mild ARDS this number is normally extrapolated to PARDS. Studies in pae-
Non-invasive ventilation (NIV) is frequently used in hypoxic diatric patients show an inverse relationship between tidal vol-
patients with mild to moderate ARDS. Recently the use of oxygen umes and mortality.

Berlin criteria for ARDS

Time Chest X-ray Oedema Oxygenation (with PEEP/CPAP >5 cmH2O)

Acute onset, <1 week Bilateral opacities (exclude pleural effusions, Exclude cardiac failure/ Mild: PaO2/FiO2 200e300
before insult lung collapse, nodules) fluid overload Moderate: PaO2/FiO2 100e200
Severe: PaO2/FiO2 <100

PaO2, PaO2 arterial oxygen in mmHg; FiO2, fraction of inspired O2; PEEP, positive end expiratory pressure; CPAP, continuous positive airway pressure.

Table 2

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Please cite this article as: Silvestre C, Vyas H, Paediatric acute respiratory distress syndrome (PARDS), Paediatrics and Child Health, https://
doi.org/10.1016/j.paed.2021.03.001
 SYMPOSIUM: INTENSIVE CARE

PALICC criteria for PARDS

Age Exclude children with perinatal lung disease
Timing Within 7 days of a known clinical insult
Origin of oedema Not explained by cardiac disease
Chest X-ray Lung infiltrates consistent with parenchymal
disease
Oxygenation Non-invasive ventilation Invasive ventilation
Full face mask with bilevel ventilation Mild Moderate Severe
or CPAP
5 cmH2O 4  OI < 8 8  OI < 16 OI > 16
P/F ratio 300 5  OSI < 7.5 7.5  OSI < 12.3 OSI > 12.3
SF ratio 264
Cyanotic heart disease Standard criteria as above and a chest x-ray and hypoxia that cannot be explained by cardiac disease
Chronic lung disease Standard criteria as above and a chest imaging consistent with new infiltrate and acute deterioration in
oxygenation from baseline
Left ventricular dysfunction Standard criteria as above with new infiltrate on the chest x-ray and acute deterioration in oxygenation not
explain by left ventricular dysfunction

CPAP, continuous positive airway pressure; PaO2/FiO2 (P/F), arterial oxygen pressure in mmHg/fraction of inspired O2; OI, oxygenation index (FiO2  mean airway pressure
 100)/PaO2; OSI, oxygen saturation index ¼ (FiO2  mean airway pressure  100)/SaO2. Use PaO2 when available; if PaO2 is not available, wean FiO2 to maintain SpO2
97% to calculate SF (SpO2/FiO2) ratio or OSI. SF and OSI should not be applied to children on long term ventilation or children with cyanotic heart disease.

Table 3

not show difference on mortality when compared against

Mechanisms of injury of ARDS clinician-guided PEEP.
Direct lung injury Indirect lung injury
Higher peak inspiratory pressure (PIP) and driving
Pneumonia Severe sepsis pressure (DP) are associated with poorer outcomes
Aspiration of gastric contents Major trauma The ground-breaking ARDS network study showed an associa-
Pulmonary contusion Hyper transfusion tion between mortality, tidal volume and PIP. Since this study
Toxic gas inhalation Acute pancreatitis most ARDS protocols have recommended limiting the plateau
Near drowning Drug overdose pressure to 28e30 mmH2O.
Diffuse pulmonary infection Reperfusion injury Recent studies in adult have addressed the importance of
Post cardiac bypass driving pressure (DP) in ARDS. DP is the difference between
Lung transplant plateau pressure and PEEP. The DP seems to be one of the most
important parameters related to VILI in ARDS.
Table 4 Amato et al. enrolled 3562 patients and they observed a sig-
nificant association between DP and mortality. DP higher than 15
cmH2O was associated with increase mortality rate in ARDS
PALICC recommended that tidal volume should be between 5
patients.
and 8 ml/kg of predicted body weight and adjusted to the lung
pathology and respiratory compliance: children with severe lung Permissive hypercapnia
injury and poor compliance will benefit from tidal volume of 3e6 Permissive hypercapnia is a consequence of lung protective
ml/kg while children with a better compliance, tidal volume of 5 strategies based on a high PEEP, low tidal volume and low DP
e8 ml/kg are recommended. strategy. Permissive hypercapnia is associated with better out-
comes in ARDS and it is accepted to maintain the patient’s pH
What is the ideal PEEP and how can we set it up?
between 7.15 and 7.3. There are exceptions on using permissive
PEEP prevents repetitive opening and collapse of the alveoli
hypercapnia and those include children with pulmonary hyper-
during the inspiratory phase, and maintains the alveoli open
tension, raised intracranial pressure, haemodynamic instability
during the expiratory phase. By preventing lung collapse and
and select congenital heart defects.
maintaining alveolar recruitment during expiration, PEEP can
promote more homogeneous ventilation. PEEP also improves
Adjuvant therapies
oxygenation due to alveolar recruitment, but there are also
adverse effects of excessive PEEP that can contribute to VILI. Corticosteroids
Increase pressure and volume at the end of expiration can lead to The role of corticosteroids in ARDS is controversial. Adult studies
over-distention and excessive stress of the lung tissue. show no difference in mortality; the only steroid protocol that
The optimal PEEP should be the one that improves arterial had positive outcomes was the Meduri protocol that uses low
oxygenation; the ARDS network generated PEEP/FiO2 tables, doses of methylprednisolone (1e2 mg/kg/day) begun early in
where the PEEP was adjust according to the FiO2, but studies did the course of the ARDS. Currently, the evidence in paediatrics is

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Please cite this article as: Silvestre C, Vyas H, Paediatric acute respiratory distress syndrome (PARDS), Paediatrics and Child Health, https://
doi.org/10.1016/j.paed.2021.03.001
 SYMPOSIUM: INTENSIVE CARE
very poor and the use of steroids is not recommended by
PALICC.
Inhaled nitric oxide (iNO)
iNO is a selective pulmonary vasodilator with a short half-life
and its action in ARDS has been postulated as beneficial by
reducing the ventilation/perfusion mismatch. Although the
mechanism is logical, in randomized controlled trials in children
and adults demonstrated that iNO does not change the outcome
of ARDS, despite the initial short-term benefit.
Potential clinical indications of iNO are children with docu-
mented pulmonary hypertension and as a bridge to extracorpo-
real life support (ECLS).
Prone position
Prone position has been used and effective in adults with mod-
erate to severe ARDS in the PROVESA trial. The benefits of the
prone position are better distribution of the gas from the
dependent to non-dependent areas of the lungs, opening
collapsed alveolar units, better distribution of the gas exchange
and a decrease the overall chest compliance and diaphragmatic
pressure. Current recommendations are to prone the patients
early in the disease and for long periods of at least 16 hours a
day.
Neuromuscular blockade
The value of neuromuscular agents in adults with ARDS is
increasingly debated. Neuromuscular blockage can have benefits
in preventing VILI, optimizing the patient- ventilator synchrony,
preventing over-distention and de-recruitment, decreasing oxy-
gen consumption and minimize the high respiratory efforts and
therefore P-SILI. However, it will increase muscle weakness as
well as the need of more deep sedation increasing the risk of
delirium.
The use of paralysis in the first 48 hours, together with lung
protective ventilation has been shown to improve oxygenation,
reduce ventilator free days and lower mortality in severe ARDS.
High-frequency oscillation ventilation (HFOV)
HFOV is a mode of ventilation that theoretically provides lung
protective ventilation, by using an ‘open lung strategy’ which
prevents lung de-recruitment due to a high constant applied
airway pressure.
It is a mode of ventilation commonly used in the neonatal
intensive care and is popular amongst the paediatric intensivists.
The studies in adults with ARDS are, however, very disap-
pointing and show increase mortality when compared to con-
ventional modes of ventilation. HFOV is not recommended and
not used in adult intensive care medicine. Paediatric studies are
small, retrospective and non-randomized. They do not show any
benefit.
Extracorporeal life support
The use of ECMO for refractory ARDS is becoming more popular
in all age groups. The risk/benefit needs to be carefully balanced
and discussed with the ECMO team. A
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FURTHER READING
Amato MB, Meade MO, Slutsky AS, et al. Brower RG Driving pressure
and survival in the acute respiratory distress syndrome. N Engl J
Med 2015 Feb 19; 372: 747e55.
Cheifetz IM. Pediatric ARDS. Respir Care 2017; 62: 718e31.
Gattinoni L, Marini JJ, Collino F, et al. The future of mechanical
ventilation: lessons from the present and the past. Crit Care 2017;
21.
Grieco DL, Menga LS, Eleuteri D, Antonelli M. Patient self-inflicted lung
injury: implications for acute hypoxemic respiratory failure and
ARDS patients on non-invasive support. Minerva Anestesiol 2019;
85: 1014e23.
rin C, Albert RK, Beitler J, et al. Prone position in ARDS patients:
Gue
why, when, how and for whom. Intensive Care Med 2020; 46:
2385e96.
Hraiech S, Yoshida T, Annane D, et al. Myorelaxants in ARDS patients.
Intensive Care Med 2020; 46: 2357e72.
Khemani RG, Smith L, Lopez-Fernandez YM, et al. Paediatric acute
respiratory distress syndrome incidence and epidemiology
(PARDIE): an international, observational study. Lancet Respir Med
2019; 7: 115e28.
Khemani RG, Parvathaneni K, Yehya N, et al. Positive end-expiratory
pressure lower than the ARDS network protocol is associated with
higher pediatric acute respiratory distress syndrome mortality. Am
J Respir Crit Care Med 2018; 198: 77e89.
Loring SH, Malhotra A. Driving pressure and respiratory mechanics in
ARDS. N Engl J Med 2015; 372: 776e7.
Practice points
C PARDS classification is different from adult ARDS: recogni-
tion is important and respiratory support should be
commenced early in the disease
C The causes of ARDS can be related to direct and indirect
lung injury
C Optimal ventilation support is based on lung protective
strategies and permissive hypercapnia
C Prone position and neuromuscular blockage reduce mor-
tality in severe ARDS; iNO and HFOV do not improve the
outcome
C The PEEP for lung protective ventilation is still undeter-
mined. Methods to assess optimal PEEP using electrical
impedance tomography show promise
C In children with mild ARDS the use of non-invasive tech-
niques can be effective but not in patients with moderate to
severe ARDS. Patients need close monitoring and, if dete-
riorating, early intubation is recommended.
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