Background

Pada tahun 1967, Ashbaugh pertama kali menyebutkan istilah

adult respiratory distress syndrome, dikenal juga sbg acute
respiratory distress syndrome (ARDS).
Tahun 1994, Konfrensi EuropeanNorth American mnyetujui
standar definisi ARDS dan acute lung injury (ALI). Definisi
didasarkan pd (1) chest radiographic, (2) rasio tekanan parsial
oxygen darah arteri sampai prosentase konsentrasi inhalasi
oksigen (PaO2/FiO2 ratio), dan (3) pengkajian tekanan
pengisian atrium kiri
ARDS ditunjukan dgn adanya infiltrat pada kedua paru
berdasarkan rontgen dada, PaO2/FiO2 <200, dan tekanan
pengisian atrium kiri <18 mm Hg atau tidak ada tanda klinik atau
radiologi yang menunjukan peningkatan tekanan atrium kiri.
ALI didefinisikan hampir sama dgn ARDS, dengan perbedaan
pada PaO2/FiO2 <300.

What is ARDS?
Acute respiratory distress syndrome (ARDS), merupakan
penyakit berat sistem pernapasan yang memerlukan
perawatan kritis. Pada ARDS, cairan mengisi kantong
alveli pada kedua paru, shg menyebabkan paru inflamasi.
ARDS menyebabkan napas menjadi berat.
Acute lung injury (ALI) serupa dgn ARDS tetapi tidak
seberat ARDS. ALI & ARDS dapat terjadi pd:

Pneumonia
injuri, spt kecelakaan lalulintas & luka bakar berat
infeksi sistemik sepsis
Shock
komplikasi pembedahan
dsb

Merokok, alkohol, dan beb penyakit lain spt asma dpt

menyebabkan ARDS & ALI menjadi lebih buruk.

Causes
Banyak faktor resiko ARDS. Kira-kira 20% pasien ARDS tdk teridentifikasi
faktor resikonya. Berikut ini beberpa faktor resiko ARDS berdasarkan studi:
Bakteremia
Sepsis
Trauma, dgn atau tanpa kontusio paru
Fraktur, terutama pd multiple fractures & fraktur tl. panjang
Luka bakar
Tranfusi masif
Pneumonia
Aspirasi
Overdosis obat
Kelebihan cairan (tenggelam)
Cidera postperfusi setelah tindakan bypass cardiopulmonary
Pankreatitis
Emboli lemak
dsb

Cidera Langsung

Trauma dada kontusio paru

Tenggelam
Hypervolemia edema paru
Menghirup gas dan uap beracun
Emboli paru
Pneumonia (virus, bakteri atau jamur)

Cidera tidak langsung

Sepsis
Shock atau
hipotensi yg lama
Trauma Multisystem, terutama
multiple fractures
Luka bakar

DIC
Pankreatitis akut
Cidera kepala
Trauma abdomen
Multiple blood
transfusions

Pathophysiology

Patofisiologi ARDS kompleks & mulifaktor, dengan mempertimbangkan 3 komponen:

1) sifat dasar stimulus penyebab ARDS, 2) Respon host terhadap stimulus, and 3)
peran kerusakan iatrogenic dlm kemajuan dan outcome kondisi. Ada 3 tahap
patofisiologi ARDS.
Stimulus menimbulkan efek peningkatan permiabelitas alveolar dan kapiler pulmonalis.
Alveolus terisi cairan yang kaya protein, diikuti dengan aktivitas neutrophils &
macrophages, dan terjadi proses inflamasi. Termasuk di dalamnya terjadi pengeluaran
interleukins (ILs), faktor nekrosis tumor, dan mediator kimia lainnya. Neutrophils
melepaskan oxidants, leukotrienes, & macam-macam protease. Efeknya pada tingkat
sel adalah kerusakan sel masif, pengikisan alveolar, dan pengelupasan sel-sel debris
ke dalam lumen alveolus. Selanjutnya , surfactant menjadi tidak aktif.
Sementara itu dalam kapiler pulmonalis, sel endothelial bengkak, terjadi agregasi
platelets & peningkatan prokoagulan, yang dpt menyebabkan trombosis pembuluh
darah kecil.
Penurunan surfactant, alveolar yg tergenang, cellular debris di dalam alveoli, &
meningkatkan tahanan jalan napas yang menyebabkan peningkatan kerja pernapasan.
Kehilangan surfaktan menyebabkan alveolus menjadi kolaps karena terjadi
peningkatan tekanan permukaan, situasi ini sering terjadi pada bayi prematur yang
mengalami infant RDS (IRDS). Akibat alveolus kolaps terjadi penurunan volume paru
di bawah kapasitas residual fungsional (FRC), selanjutnya akan meningkatkan kerja
pernapasan. Ditandai dengan penurunan compliance.

Pathophysiology

Terjadi pelebaran jarak interstitial space antara alveolus & the vascular endothelium decreases
oxygen-diffusing capacity. Hypoxia arises as a result of the change described above. Collapsed
alveoli result in either low ventilation-perfusion (V/Q) units or a right-to-left pulmonary shunt. The
end result is marked venous admixture, the process whereby deoxygenated blood passing
through the lungs does not absorb sufficient oxygen and causes a relative desaturation of arterial
blood when it mixes with blood that is oxygenated adequately. Hence, relatively deoxygenated
arterial blood attempts to supply respiratory muscles that are working harder than usual. These
muscles become fatigued; the body is unable to maintain such sustained work of breathing, and
respiratory failure ensues.
In addition, hypoxia, hypercarbia, and small-vessel thrombosis combine to elevate pulmonary
artery pressures, leading to increased right ventricular work, increased right ventricular filling,
and, ultimately, a septal shift toward the left ventricle. These changes, in turn, may decrease
cardiac output, further reducing oxygen delivery to the tissues.
Iatrogenic problems may further complicate the patient's clinical picture. High-inspired oxygen
concentration (FiO2 >95%) may cause absorption atelectasis, further reducing the number of
patent alveoli. Oxygen toxicity can be seen with FiO2 >60% over time, leading to additional
inflammation secondary to free radical damage.
High mean airway pressures during attempts to maintain adequate oxygenation and ventilation
may decrease cardiac output. In addition, high peak airway pressures may cause air leaks (eg,
pneumothoraces), which may acutely compromise cardiac and respiratory function. Ventilatorinduced lung injury (VILI), discussed in detail below, may further complicate and accelerate
disease progression.
Finally, fluid resuscitation may lead to further alveolar and pulmonary interstitial flooding, with
worsening compliance and oxygenation.

 Onset of symptoms is usually 12 48

hours after time from acute injury
Has acute and chronic phases

Acute phase
Acute lung injury
Reduces normal perfusion to the lungs
Causes platelet aggregation and stimulation of the inflammatoryimmune system
Release of mediators of the
inflammatory process
Mediators activate neutrophils, macrophages and other cells to release
toxic substances that cause microvascular injury

Acute and diffuse injury to endothelium and epithelium surface of lung

occur
Damage to pulmonary capillary membrane and increase in capillary
permeability occurs
Capillary leak allows proteins and fluids to spill into the interstitium and
alveolar spaces
Pulmonary lymphatic drainage capacity is overwhelmed and alveolar
flooding occurs

Pulmonary edema results and causes interference with oxygen

diffusion and inactivation of surfactant
Alveolar collapse and massive atelectasis occur and decrease
functional residual capacity and lung compliance
Profound hypoxemia related to
extensive shunting (V/Q mismatch)
Vasoconstrictive mediators cause increased pulmonary
vasoconstriction and
pulmonary hypertension

Chronic phase
Type I pneumocytes are destroyed and replaced
by type II pneumocytes which proliferate
Interstitial space expands by edema fluid, fibers
and proliferating cells
Hyaline membranes are formed which increase the
thickness of the alveolar-capillary membrane
Pulmonary fibrosis may occur

History
The history is generally remarkable for evidence of the
precipitating event. The presence of comorbid
pathologies, iatrogenic complications, and multiorgansystem failure may complicate the clinical pictures.
Cough may be present, reflecting a primary lung injury,
such as pneumonia or aspiration. Absence of a cough or
gag reflex in a patient with symptoms and signs
consistent with ARDS who had a witnessed episode of
vomiting suggests that aspiration may have been the
primary risk factor for ARDS.
Dyspnea usually develops shortly after the initiating
stimulus, and it becomes progressively severe, reflecting
the increasing alveolar flooding and decreasing
pulmonary compliance.

Physical

The evident physical signs primarily reflect lung pathology and other organ injury
associated with ARDS.
Tachypnea is an early sign as pulmonary edema develops, as pulmonary compliance
decreases, as tidal volume decreases toward the FRC, and, therefore, as the work of
breathing increases.
Cyanosis may become apparent with increasing hypoxemia. Remembering that
clinically evident cyanosis requires a certain minimum hemoglobin concentration is
important, particularly in the patient with trauma.
Fever may reflect the underlying process causing ARDS (eg, pneumonia, sepsis) or
may reflect massive cytokine release.
Crackles may be audible throughout the lung fields, signifying pulmonary edema.
Physical signs of air leak syndromes may manifest in the late stages of ARDS. These
include pneumothoraces, pneumomediastinum, pneumopericardium, and
subcutaneous emphysema.

Features of a pneumothorax include decreased air entry on the side of the air leak, an
increased percussion note on the same side, and tracheal deviation toward the side of
collapse in a simple pneumothorax or toward the contralateral side in a tension
pneumothorax.
Heart sounds may be muffled, and signs of decreased cardiac output may be observed with
a tension pneumothorax

Lab Studies

General testing

CBC analysis

No definitive laboratory tests aid in the diagnosis of ARDS.

Because ARDS often develops concomitantly with severe acute illness, major derangement of laboratory
indices may be present, including thrombocytopenia and abnormal liver function, renal function, electrolyte
levels, blood glucose concentrations, lactate values, and coagulation parameters.
Hypoproteinemia is predictive of ARDS, weight gain, and death in patients with severe sepsis.
Leucocytosis may be evident, reflecting either the initiating stimulus or a nonspecific inflammatory response.
Anemia secondary to acute illness, underlying chronic disease, acute blood loss, or hemodilution secondary
to massive fluid resuscitation may be evident.
Thrombocytopenia may be present.

ABG analysis

In the early stages of ARDS, ABG values may be in the reference ranges.
Respiratory alkalosis reflecting a relative hyperventilation and hypocarbia is an early sign of respiratory
distress.
Hypercarbia develops with worsening disease, reflecting an increasing shunt fraction and an increased
dead space.
Hypoxemia may also be evident. The degree of oxygen supplementation may determine the severity.
Because of the uncertainty imposed by the measurement of the partial pressure of oxygen in arterial blood
and the necessity of a standard definition of ARDS, the PaO2/FiO2 ratio is often used as a measure of
disease severity.
Depending on coexisting pathologies, a metabolic acidosis may also be present.

Imaging Studies:

Chest radiography

Chest radiography is essential for diagnosing ARDS or ALI. In the early stages of ARDS, findings on chest radiography may be
normal. Early changes reflect increased pulmonary alveolar and endothelial permeability. As the alveoli fill with a protein-rich
exudate, patchy alveolar infiltrates develop.
As the disease progresses, the lung fields become diffusely and homogeneously opaque. However, this homogeneous
appearance is misleading, as chest CT scanning demonstrates. Although the radiographic appearance may initially be
indistinguishable from that observed in cardiac failure, a number of characteristic differences are present.
ARDS-related edema and edema secondary to heart failure may be difficult to distinguish on radiographs. Cardiomegaly is not a
feature of ARDS; it is usually present with marked cardiac failure. Kerley B lines, which indicate interstitial edema or lymphatic
swelling, are rarely observed in ARDS.
Other radiologic differential diagnoses of the infiltrates observed in ARDS include aspiration, hemorrhage, pneumonia, and
atelectasis. Distinguishing these entities on the basis of chest radiographic appearances is often difficult. As opacification of the
lung fields increases, air bronchograms may become apparent. Radiologic worsening is often associated with clinical deterioration
and death.
Air-leak syndromes are commonly observed on plain chest radiographs of patients with ARDS. These include pneumothoraces,
pneumomediastinum, pneumopericardium, subcutaneous emphysema, pneumoperitoneum, and pneumoretroperitoneum (free air
in the retroperitoneal space). In intubated patients, free air rises to the high caudal areas overlying the diaphragm because of their
supine position. Early and subtle signs suggestive of free air include the deep sulcus sign, which is increased radiolucency in the
costophrenic angle of the affected side and increased acuteness of the costophrenic angle on the same side. The doublediaphragm sign is also reported in association with air leaks; subpulmonic air produces the impression of a second diaphragm
formed by the basal border of the lower lobe. Air below the diaphragm, which does not cross the midline, suggests
pneumoretroperitoneum.
Characteristic radiologic changes of late ARDS corresponding to histopathologic changes are well described. After a variable
period (ie, usually days to weeks), patchy areas of increased lucency appear. Associated with clinical resolution of illness,
radiologic improvement follows slowly. Although radiologic changes completely resolve in most children, chronic changes are
apparent in a small subset. Whether the persisting changes (often ascribed to fibrosis) are the result of the primary illness or VILI
is often unclear. Iatrogenic features visible on a chest radiograph in a patient with ARDS may include an endotracheal tube, central
venous lines, and chest tubes.

CT scanning

CT scanning of the chest was first reported almost 2 decades ago. Since then, the utility of chest CT in understanding the pathophysiologic
mechanisms underlying ARDS and the response of the ARDS lung to ventilator maneuvers have been reported many times.
Gattinoni et al have been at the forefront of this research. Before the introduction of CT imaging, clinicians assumed that ARDS was a
homogeneous lung process. The use of chest CT scanning demonstrated that, though pulmonary involvement in ARDS was diffuse, it also was
heterogeneous. In 1994, Gattinoni et al reported that, in adults with ARDS, areas of normal lung were interspersed with poorly aerated lung
parenchyma.
Researchers have shown a marked spatial distribution of parenchymal collapse in the lungs of patients with ARDS. In patients ventilated in a
supine position, collapse was most pronounced in the more dorsal regions. A combination of edematous lung, the weight of the chest wall and
mediastinal structures (ie, specifically the heart), and supine positioning are postulated to play a part in the development of dorsal atelectasis.
These findings provide an intellectual basis for the role of prone positioning in severe ARDS.
CT findings support the baby lung hypothesis. Simply stated, the lungs of patients with ARDS are functionally smaller than normal lungs.
Indeed, some authors suggest that the volume reduction may be on the order of 75% of total lung volume. Hence, ventilation with normal
physiologic tidal volume may lead to iatrogenic lung damage. Recent data, which show improved outcomes in patients with ARDS ventilated
with small tidal volumes, lend credence to this theory.
In 1994, Gattinoni proposed that 2 types of ARDS exist: ARDS due to primary pulmonary disease (eg, aspiration, pneumonia) and ARDS arising
secondary to extrapulmonary disease (eg, sepsis, trauma). In support of this hypothesis, Goodman et al (1999) described CT findings in adults
with ARDS due to pulmonary and extrapulmonary disease. Marked differences existed between the populations; the group with pulmonaryrelated ARDS had ground-glass opacification or consolidation, which tended to be asymmetric. The group with extrapulmonary ARDS generally
had symmetric ground-glass opacification. In both groups, pleural effusions and air bronchograms were common, whereas Kerley B lines and
pneumatoceles were uncommon. Mortality tended to increase in the group with extensive consolidation versus those with extensive groundglass opacification, but this difference was not statistically significant.
In the present clinical setting, the main usefulness of chest CT scanning is to determine the presence of coexisting illness, specifically thoracic
abscess formation, barotrauma undefined on plain radiography, or other unsuspected pathology. CT is not routinely required to diagnose or
manage ARDS.

Chest ultrasonography: The only role for chest ultrasonography in patients with ARDS is to define the presence of pleural effusions and to
determine whether loculation of the pleural fluid is present if drainage of the effusion is being considered.
MRI: To the authors' knowledge, no data are available concerning the role of MRI in patients with ARDS.
Echocardiography

The primary role of echocardiography in ARDS is to detect congenital or acquired heart disease as a cause of respiratory distress and
pulmonary edema.
Echocardiography may provide evidence of pulmonary hypertension; however, the practical implications of this finding are unclear because little
evidence supports the clinical benefit of pulmonary vasodilators in ARDS.

Other Tests

Pulmonary mechanics: Many authorities debate the utility of determining pulmonary mechanics as a means of
defining optimal ventilatory strategies. As of yet, no clear consensus exists on their use.
Procedures:
Bronchoalveolar lavage (BAL) is not required to diagnose ARDS. BAL may be useful in determining the underlying
etiology in patients with primary pulmonary ARDS in whom pneumonia or an infective pneumonitis is thought to
be the cause. This is especially true for immunocompromised patients.
Many investigators are interested in the use of BAL as a research tool.
Cytokine levels in BAL fluid have been determined in patients with ARDS.
Much has been learned regarding the complex interplay of the inflammatory response in ARDS. In a small series
of patients, elevated levels of IL-8 in BAL fluid was predictive of ARDS in at-risk patients and predictive of
mortality in patients with ARDS (Meduri, 1995).
The use of bronchoscopy as an adjunct to surfactant therapy has been reported. In 10 adults with ARDS,
sequential bronchopulmonary segmental lavage with a dilute synthetic was safe, well tolerated, and associated
with a decrease in oxygen requirements (Walmrath, 1996). To the authors' knowledge, no study has been
performed to compare the use of surfactant with or without bronchoscopy in the setting of ARDS.
Histologic Findings: Three classic histopathologic phases of ARDS are described. These correspond to the time
course of the disease. The earliest or exudative phase occurs during days 1-7 of the initial injury. Typical
histologic appearances include diffuse hemorrhage, edema, leukocyte infiltration, and cellular necrosis or
apoptosis. Evidence of the initiating illness may also be apparent, such as pneumonia or aspiration.
The proliferative phase begins at about day 7 of the illness. The main features of this period include fibroblast
proliferation, hyperplasia of type II pneumocytes, and ongoing evidence of inflammation.
The fibrotic phase begins approximately 3 weeks after the onset of illness, of which the main features are fibrosis,
honeycombing, and bronchiectasis.

Signs and symptoms of ARDS

It is very hard for oxygen to get into the
bloodstream when the lungs are filled with fluid.
Air sacs filled with fluid may collapse. This can
lead to the following signs and symptoms:

difficult and fast breathing

shortness of breath
low blood pressure
fast heart beat
changes in awareness or difficulty concentratin

 Usually, symptoms of ARDS or ALI begin within

2 days of the original illness or injury to the body.
ARDS often happens at the same time other
organs fail. When a doctor thinks a patient has
ARDS, he or she may use these tests:
chest x-rays to look for a pattern that is typical with
ARDS
measure blood gases in arteries to check oxygen
and carbon dioxide levels
blood tests to find out the condition of other organs
samples of blood and saliva (sputum) to look for
possible infections

Clinical Presentation
Presence of a predisposing condition
Severe oxygenation defect hypoxemia is
the hallmark of ARDS
PaO2 < 60 mmHg on FiO2 > 50%
PaO2/FiO2 ratio < or = to 200
CXR: diffuse bilateral parenchymal infiltrates
PAOP: < 18 mm Hg.

Clinical Presentation
Elevated PAP with normal PAOP (cardiac
pulmonary edema causes elevated PAP
and PAOP)
Pulmonary vascular resistance (PVR) is
increased because of hypoxemic
pulmonary vasoconstriction
ABG: Refractory hypoxemia

Pulmonary function studies

Lung volumes decreased:
Tidal volume /vital capacity
Functional residual capacity decreased
Static and dynamic compliance decreased

Chest x-ray findings

Bilateral diffuse interstitial and alveolar
infiltrates
Ground glass appearance
White-out due to massive atelectasis
Heart size is normal (unusual in cardiac
pulmonary edema)

Ventilatory management
Modes: pressure control / inverse ratio
ventilation or high-frequency jet ventilation
may be used
Tidal volume: limitation of peak inspiratory
pressure and reduction of regional lung
overdistension by the use of low tidal
volumes with permissive hypercapnia.

Ventilatory management
Baby-lung treatment: TV should be 4-8 ml/kg.
- excessive volume forced into a small aerated
lung can cause volutrauma
PaCO2 is allowed to gradually increase as
minute ventilation is reduced bicarbonate may
be used in pH is less than 7.15
Hypercapnia contraindicated with
concurrent head injury

Ventilator management
CPAP or PEEP
Decreases surface tension: keeps alveoli
open
Aids in reopening collapsed alveoli
Reduces intrapulmonary shunt and
increases functional residual volume
Obtain higher PaO2 with same or lower
FIO2
Usual level 5-15 cm H2O may be higher

Ventilator management
FIO2 should be maintained as low as possible to
prevent oxygen toxicity
Need nitrogen to keep alveoli inflated
CPAP may be administered via mask prior to
intubation
Patients very PEEP dependent and will quickly
desaturate when temporarily discontinued
Utilize transport ventilator when moving patient
May require sedation and/or paralysis to maintain
PEEP

Intraalveolar fluid
CPAP or PEEP increases intraalveolar
pressure prevents further fluid
sequestration into the alveoli
Diuretics may be considered - maintain
PAOP at ~ 12 mmHg
Colloids leak across the alveolar-capillary
membrane as readily as crystalloids

Hemodynamics
Inotropes as indicated by cardiac
index/output
Dobutamine is usually the first choice
Best PEEP =
in PaO2 and SaO2 but
does not cardiac output

Other therapies
Nitric oxide:
Synthesized by vascular endothelium and
acts as a natural local vasodilator when
inhaled it dilates vessels only to ventilated
areas and acts as a potent bronchdilator
More effective when used during early stages

Other therapies
Corticosteriods: May be helpful during the
fibroprofilerative phase
Nutritional support: To prevent respiratory
muscle atrophy and translocation of
bacteria from GI tract

Medical Care

No treatment for ARDS is definitive. The cornerstone of management is

impeccable intensive care. Early anticipatory management may avoid late
complications and poor outcome. Treat the primary cause (eg, sepsis,
pneumonia) if possible. As much as possible, minimizing the risk of multiple
organ failure and VILI is essential.
Critical aspects are maintaining nutrition and being cognizant of the risk of
numerous complications in critically ill children, including sepsis, fluid
overload, inappropriate levels of sedation, and neuromuscular blocking
agents. Many of the therapies and strategies proposed for ARDS are
founded on rational physiologic and pathologic principles, but they have not
been shown to have unequivocal benefits. Reasons include an incomplete
understanding of the pathophysiology of ARDS, the lack of a standardized
diagnostic test, and the heterogeneity of the illness and the patient
population. Furthermore, an inability to adequately control for other
therapies, specifically ventilation modalities, and the fact that most patients
die from multiple organ failure or their precipitating illness confound the
analysis and interpretation of data from many trials.

Ventilation

Ventilation is the cornerstone of treating the patient with ARDS. Striking a balance between the level of
ventilator support necessary to provide a reasonable ventilation and oxygenation while minimizing VILI is
one of the most active areas of research in critical care.
Noninvasive ventilation has been used early in ALI and ARDS to avoid endotracheal intubation. Published
experience has largely been limited to the adults, and most patients with ARDS require endotracheal
intubation for airway control and invasive mechanical ventilation.
Traditional ventilatory strategies are aimed at maintaining normal tidal volumes and normal blood gas
values; however, this was associated with a high morbidity and mortality rate. Therefore, many clinicians
attempted to use high partial pressures of carbon dioxide (PaCO2), ie, the permissive hypercapnic strategy.
Associated with this was the increasing recognition that repetitive opening and closing of alveoli
exacerbated lung injury. Hence, a strategy of maintaining an open lung evolved.
The twin goals of permissive hypercapnia and open lung maintenance are achieved, in simple terms, by
optimizing PEEP and minimizing delivered tidal volumes.

Hickling et al (1990) gave one of the original descriptions of permissive hypercapnia, reporting an almost 80% reduction in
mortality rates. Although subsequent trials showed no benefit in reducing tidal volumes.
Amato et al (1998) reported that their strategy of ventilating at a low tidal volume with an elevated carbon dioxide level and
preventing alveolar closure by optimizing PEEP decreased the mortality rate (38% versus 71%, P < .001).
The study by Amato et al was criticized for the high mortality rate in the control arm. However, a multicenter study
sponsored by the National Institutes of Health (NIH) confirmed these results. The control group was ventilated with a tidal
volume of 12 mL/kg adjusted to maintain a plateau pressure of 45-50 cm H2O. In the study group, tidal volume was
reduced to 6 mL/kg and then as low as 4 mL/kg to maintain a plateau pressure <30 cm H2O. The trial was terminated
prematurely when an interim analysis showed a markedly reduced mortality rate in the group receiving low tidal volume
(31% vs 39.8%, P = .007).

Ranieri et al provided additional information to suggest that low tidal volume may be beneficial. They
reported lowered levels of cytokines in BAL fluid and plasma in patients treated with low tidal volume. The
authors postulated that decreased levels of cytokines reflect reduced inflammation in organs other than the
lungs, leading to a possible survival benefit. Numerous ventilator modes are available; however, little if any
data demonstrate the superiority of 1 mode versus another.
Two modes of high-frequency ventilation are high-frequency oscillatory ventilation (HFOV) and highfrequency jet ventilation (HFJV).

HFJV is rarely used in pediatric practice, and it is not discussed any further.
HFOV may be thought of as the ultimate in high-PEEP low-tidal-volume strategy. Because of the extremely small tidal
volumes used, HFOV minimizes repetitive opening and closing and possibly reduces VILI, if the lung is recruited sufficiently.
Because of the extremely high respiratory rates, carbon dioxide can be maintained at satisfactory levels. Randomized
controlled trials have been done to compare HFOV with conventional mechanical ventilation in pediatric and neonatal
practice, with generally encouraging results. Although initial studies in neonates show no benefit, the strategy was less than
optimal. Recruiting (or opening) the atelectatic areas of the lung is critical to maintaining lung volume at the FRC. Optimal
lung volume is gauged with clinical assessment, monitoring of arterial oxygen saturation, ABGs, and lung inflation on chest
radiography.

Airway pressurerelease ventilation (APRV) is a relatively new mode of ventilation that allows for
spontaneous ventilation with mean airway pressures similar to that achieved with HFOV. Case studies
report the successful use of APRV in ARDS; however, data are insufficient to compare it with conventional
or HFOV.
As an adjunct to ventilator management, prone positioning has been advanced as a means to improve
oxygenation in patients with severe ARDS. By turning patients prone, V/Q matching is thought to be
optimized by reducing atelectasis in dependent areas of the lung. Many trials have shown improved
oxygenation with prone positioning, however, a recent multicenter trial of 102 patients demonstrated no
significant difference in clinical outcomes, including ventilator-free days. The study population had a
mortality rate of only 8%, suggesting that prone positioning may still have a role in extremely ill patients with
ARDS. Although no consensus exists regarding how to incorporate prone positioning into the care of a child
with ARDS, it should still be attempted in a patient with profound hypoxemia.

Steroid therapy
The use of steroids is reported as a therapy for ARDS. A number of reported trials demonstrated
no benefit with large doses of steroids administered as a short course in the early phases of
ARDS. However, many investigators contend that on-going or late-stage ARDS is partly an
inflammatory condition. Hence, by virtue of their anti-inflammatory properties, steroids may be
beneficial when used in the fibroproliferative phase.
In 1998, Meduri et al reported their randomized double-blind placebo-controlled trial in adults with
ARDS who were not improving, as defined by lack of improvement in lung injury score by day 7 of
respiratory failure. Patients received methylprednisolone or placebo for 32 days. Those with no
response were given the alternative treatment on day 10. Those receiving steroids had reduced
lung injury and multiorgan dysfunction scores, and they were extubated more frequently than
those given placebo. The hospital mortality rate significantly decreased (12% vs 62%). Rates of
infection did not differ between the groups. Similar data in the pediatric population are not
available. Many centers begin steroid therapy on days 7-10 of mechanical ventilation. Use of
steroids for the fibroproliferative phase of ARDS in the pediatric population is extrapolated from
this study.
To the authors' knowledge, no study has been performed to examine the potential role of inhaled
steroids in ARDS.
Steroids may be indicated as part of the treatment for the underlying etiology of ARDS, eg, ARDS
secondary to Pneumocystis jiroveci infection.
A subgroup of patients with ARDS with marked eosinophilia in their peripheral blood or
bronchoalveolar fluid may benefit from steroid therapy.
Steroid use may contribute to prolonged weakness after ARDS. Care should be taken to
minimize concomitant neuromuscular blockade.

Surfactant treatment

One of the key events in the progression of ARDS is a reduction in both volume and function of surfactant. In
addition, surfactant inhibitors may be present in the alveolus. Based on positive results of many clinical trials of
IRDS, a number of studies have been conducted to examine the role of surfactant in ARDS.
Administration of exogenous surfactant has many theoretical benefits, as demonstrated in vitro. These include the
prevention of alveolar collapse, maintenance of pulmonary compliance, optimization of oxygenation,
enhancement of ciliary function, enhancement of bacterial killing, and downregulation of the inflammatory
response.
Studies of various surfactants and different modes of delivery in adults have not yielded a consensus regarding
the efficacy of surfactant in ARDS. In vitro data and extrapolated data from neonatal in vivo studies suggest that
animal-derived surfactant may be superior to synthetic surfactant. In addition, inhalation may be inefficient as a
means of delivery.
A growing body of literature supports the use of surfactant for severe pediatric ARDS. A retrospective chart review
of 19 patients showed improvement in oxygenation index and hypoxemia score but no change in other outcome
measures. Prospective studies from the late 1990s to early 2000 involving porcine or bovine surfactant showed
variable outcomes ranging from improvement in only oxygenation to shortened ventilation and PICU stay.
A recent multicenter randomized double-blind placebo-controlled trial (Wilson, 2005) of Calfactant demonstrated a
significant reduction in mortality, with an absolute risk reduction of 17%. This reduction was most pronounced in
patients younger than 12 months, who had a corresponding absolute risk reduction of 33%. Significant
improvement was also demonstrated in the oxygenation index, in ventilator-free days, and in rates of failure with
conventional mechanical ventilation. One confounding factor was that the placebo group had more
immunocompromised patients than the treatment group.
Data from a cost-effectiveness study of Infasurf suggested that the use of exogenous surfactant may be costeffective in an American healthcare setting. The expense of the surfactant was offset by early PICU discharge.
Mortality benefits and ventilator-free days were not factored into the model.

Nitric oxide (NO) therapy

NO is a potent vasodilator, first described in 1989. Its use as a specific pulmonary vasodilator was first described
almost a decade ago in neonates with persistent pulmonary hypertension. Subsequent trials confirmed the
efficacy of inhaled NO (iNO) in this population, in whom iNO decreased the use of extracorporeal membrane
oxygenation (ECMO).
iNO is a selective pulmonary vasodilator, as it rapidly binds to hemoglobin and is inactivated before reaching the
systemic circulation. It may have a number of attractive properties in patients with ARDS. By reducing hypoxic
pulmonary vasoconstriction (HPV), iNO may reduce right-sided pulmonary pressures. This, in turn, lessens the
degree of leftward septal shift, which improves cardiac output. Oxygenation benefits that occur while iNO diffuses
to only relatively well-aerated parts of the lung lessen any local HPV. Other benefits may include decreased
pulmonary edema while pulmonary pressures are reduced.
Despite the potential benefits, no study has shown lasting advantage associated with iNO. Although many studies
demonstrated improvement in surrogate measures (eg, oxygenation, degree of ventilator support), no differences
are noted in primary outcome measures (eg, mortality, ventilator-free days, time to extubation). Reasons for this
lack of clinical benefit are unclear. The fact that ARDS tends to be a heterogeneous lung disease in contrast to
persistent pulmonary hypertension of the newborn may be part of the explanation. As an alternative, the fact that
most patients with ARDS die from sepsis, multiorgan failure, or their primary illness may imply that no survival
benefit is observed with improved oxygenation and decreased ventilator support. Another confounder is that
patients with ARDS are heterogeneous.
A recent multicenter study of the use of iNO (dose of 10 ppm) in children with acute hypoxic respiratory failure
was reported. Although oxygenation acutely improved in the group treated with iNO, this change did not translate
into a survival benefit. However, data from a post-hoc analysis suggested that patients with severe respiratory
failure (oxygenation index >25) or immunocompromise may have benefited from the use of iNO. However, this
analysis has been criticized.
In summary, although a number of trials have shown an improvement in various physiologic indices, these results
have not translated to tangible benefits, such as decreased mortality rates. A recent review by the Cochrane
database confirmed this assessment. According to this review, iNO has no effect on mortality and only transiently
improves oxygenation in both children and adults.

Liquid ventilation

Perfluorocarbons (PFCs) have a number of attractive properties that facilitate their use in liquid
ventilation. Because PFCs are chemically and biologically inert, with a high vapor pressure that
ensures rapid evaporation when exposed to the atmosphere, both oxygen and carbon dioxide
dissolve easily in PFC liquid.
Perceived advantages of PFCs in ARDS include an ability to maintain open lung, and repetitive
opening and closing of the alveoli are minimized. Authors have called this liquid PEEP or "PEEP
in a bottle."
In addition, a lavage effect may clear the alveoli and small airways of debris and inflammatory
mediators, reducing ongoing inflammation.
PFCs are also thought to have intrinsic anti-inflammatory actions.
By flowing preferentially to dependent areas of the lung where alveolar collapse is maximal, intraalveolar pressure is increased; hence, perfusion to these areas is decreased, which may improve
V/Q matching.
Two types of liquid ventilation have been described: partial liquid ventilation (PLV), in which a
volume of liquid equal to the FRC is instilled and total liquid ventilation (TLV) with a conventional
ventilator. In contrast to PLV, TLV requires that the lung is filled completely with PFC and that the
patient is ventilated with a specially designed liquid ventilator. For logistical reasons and because
no data suggest that TLV is superior to PLV, PLV has been used more widely than TLV.
Little convincing data are available to assess the use of PFC liquid ventilation in ARDS.
Investigators from 2 uncontrolled trials (1 in adults and 1 in pediatric patients) described its use in
conjunction with extracorporeal life support (ECLS) (Hirschl, 1998; Fedora, 1999). A randomized
trial in 1998 did not demonstrate a difference in outcome in a group treated with PLV compared
with a group treated with CMV (Davies, 2004).

Other pharmacologic therapy

Although they have shown promise in
animal and small-scale human studies,
many pharmaceutical agents have not
demonstrated an unequivocal benefit in
large trials. These agents include systemic
pulmonary vasodilators, pentoxifylline,
various antioxidants, ketoconazole,
anticytokines, and antiproteases. Their use
is not discussed further.

Surgical Care
Chest-tube placement: In the event of a pneumothorax,
placement of a chest tube is usually mandatory.
Extracorporeal life support
ECLS has been used since the 1970s to improve oxygenation
and/or ventilation in critically ill patients with severe ARDS.
A number of modalities have been reported, including ECMO,
which may consist of an arterial and venous cannula (AV-ECMO)
or 2 venous cannulae (VV-ECMO).
Extracorporeal carbon dioxide removal (ECCO2R) has been
used, most commonly in Europe.
The rationale of ECCO2R is similar to that for ECMO, which is to
allow the lung to rest while carbon dioxide is removed and
excessive hypercarbia is prevented. Limited data are available
concerning this modality in the pediatric population.

Extracorporeal membrane
oxygenation

A large randomized study of the efficacy of ECMO in adults with severe ARDS was published in 1979. Zapol
et al did not demonstrate a benefit with ECMO, reporting a mortality rate of >90% in both control and ECMO
groups.
Anecdotal reports and case series are numerous. They suggest that ECMO may be of benefit in children
with severe ARDS unresponsive to maximal conventional therapy.
In 1996, Green et al reported data from a pediatric study. Although they concluded that ECMO was
associated with improved survival, their study had a number of limitations. It was not a controlled trial;
instead, it was a retrospective collection of data from a large number of PICUs. Furthermore, conventional
therapy was not uniform. An attempt at a definitive, randomized controlled trial was terminated when the
overall mortality rate in pediatric ARDS decreased to such a degree that sufficient numbers of patients could
not be recruited.
Numerous studies from the United Kingdom showed that the use of ECMO in neonates with respiratory
failure was associated with improved outcomes (Brown, 2004; Petrou, 2004; Bennett, 2001). With pediatric
ECMO, the survival rate is approximately 50%. This is markedly less than the reported survival rate of 80%
in neonates treated with ECMO. Reasons for this disparity may include the heterogeneity of illness leading
to respiratory failure in the pediatric population, relatively limited experience with pediatric versus neonatal
ECMO, or a reluctance to commence ECMO that leads to delays that further exacerbate lung damage.
The question of who should receive ECMO remains uncertain. Candidates should have severe lung disease
that progresses despite maximal conventional medical therapy. The disease process leading to respiratory
failure should have a reasonable potential for reversibility and recovery. Objective indicators include an
alveolar-arterial (A-a) gradient >450 mm Hg or ventilator peak pressures >40 cm H2O. Exclusion criteria
include cerebral hemorrhage, preexisting chronic lung disease, congenital or acquired immunodeficiency,
congenital anomalies, or other organ failure associated with poor outcomes. Ventilation for >10 days before
ECMO is a relative contraindication.
Why ECMO may confer a survival benefit is unclear. Possibilities include the ability to rest the lung by
reducing excess stretch (ie, high pressures) and reducing repetitive opening and closing (ie, high ventilator
rates). Oxygen toxicity may be minimized. Fluid balance can be optimized with aggressive diuresis or with
renal replacement therapy.

Consultations:
Critical care specialist
Infectious diseases specialist
Otolaryngologist (ENT specialist)
Pulmonologist
Diet: The thinking regarding the role of nutrition in patients with ARDS has taken a paradigm shift.
As attention was being given to the role of adequate nutrition in the critically ill patient, bacterial overgrowth in the
GI tract due to antibiotic use and the late introduction of feeds was postulated to contribute to bacterial
translocation across the bowel wall. Hence, the standard practice of introducing early enteral feeds when possible
has expanded.
In situations of feeding intolerance, efforts to optimize enteral nutrition include the placing of a transpyloric tube
(duodenal or jejunal), administering continuous drip feeds, and administering promotility agents (metoclopramide
or erythromycin).
Recent researchers concluded that administration of a formula supplemented with eicosapentaenoic acid,
gamma-linolenic acid, and antioxidants is associated with a reduction in pulmonary neutrophil recruitment,
improved gas exchange, decreased requirement for mechanical ventilation, reduced length of ICU stay, and a
reduction of new organ failures.
In some patients with limited pulmonary reserve, high-energy loads may lead to respiratory failure because of
marked carbon dioxide production.
Intravenous fat emulsions have been associated with worsening pulmonary mechanics in some patients with
ARDS. Published evidence is not currently conclusive and limited to animal data and findings in small case series.
Caution should be used if parenteral nutrition is required during the early stages of ARDS.
Activity: In general, the severity of the precipitating illness (eg, trauma, sepsis) and ARDS limits the patient's
activity. If the patient recovers, no limitation on activity is usually necessary, except in the few patients with
evidence of extensive pulmonary scarring or fibrosis.

Complications
Nosocomial
pneumonia
Sepsis
Shock
Multiple organ
dysfunction syndrome
(MODS)
DIC

Airway trauma
Dysrhythmias
Pulmonary embolism
Pulmonary fibrosis
Barotrauma
GI hemorrhage
Renal failure

ARDS vs. Pulmonary Contusion

Pulmonary contusion is usually localized
and occurs near the site of external trauma
ARDS causes diffuse bilateral changes
CXR with contusions show increased
density reflecting intraalveolar hemorrhage