Transcript Acute Respiratory Distress Syndrome

ACUTE RESPIRATORY
DISTRESS SYNDROME
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BACKGROUND
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Since World War I, it has been recognized that
some patients with non-thoracic injuries, severe
pancreatitis, massive transfusion, sepsis, and other
conditions develop respiratory distress, diffuse lung
infiltrates, and respiratory failure, sometimes after a
delay of hours to days.
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Ashbaugh et al described 12 such patients in 1967,
using the term “adult respiratory distress syndrome”
to describe this condition.
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Before research into the pathogenesis and treatment of
this syndrome could proceed, it was necessary to
formulate a clear definition of the syndrome.
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Such a definition was developed in 1994 by the AmericanEuropean Consensus Conference (AECC) on acute
respiratory distress syndrome (ARDS).
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The term “acute respiratory distress syndrome” was used
instead of “adult respiratory distress syndrome” because
the syndrome occurs in both adults and children.
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ARDS was recognized as the most severe form of acute lung injury
(ALI), a form of diffuse alveolar injury.
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The AECC defined ARDS as an acute condition characterized by
bilateral pulmonary infiltrates and severe hypoxemia in the absence
of evidence for cardiogenic pulmonary edema.
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The severity of hypoxemia necessary to make the diagnosis of ARDS
was defined by the ratio of the partial pressure of oxygen in the
patient’s arterial blood (PaO2) to the fraction of oxygen in the inspired
air (FiO2).
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ARDS was defined by a PaO2/FiO2 ratio of less than 200, and in ALI,
less than 300.
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This definition was further refined in 2011 by a panel of experts
and is termed the Berlin definition of ARDS.
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ARDS is defined by timing (within 1 wk of clinical insult or onset of
respiratory symptoms); radiographic changes (bilateral opacities
not fully explained by effusions, consolidation, or atelectasis);
origin of edema (not fully explained by cardiac failure or fluid
overload); and severity based on the PaO2/FiO2 ratio on 5 cm of
continuous positive airway pressure (CPAP).
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The 3 categories are mild (PaO2/FiO2 200-300), moderate
(PaO2/FiO2 100-200), and severe (PaO2/FiO2 ≤100).
PATHOPHYSIO
LOGY
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ARDS is associated with diffuse alveolar damage
(DAD) and lung capillary endothelial injury.
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The early phase is described as being exudative,
whereas the later phase is fibroproliferative in
character.
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Early ARDS is characterized by an increase in the
permeability of the alveolar-capillary barrier, leading to
an influx of fluid into the alveoli.
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The alveolar-capillary barrier is formed by the
microvascular endothelium and the epithelial lining of
the alveoli.
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Hence, a variety of insults resulting in damage either to
the vascular endothelium or to the alveolar epithelium
could result in ARDS.
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The main site of injury may be focused on either the
vascular endothelium (eg, sepsis) or the alveolar
epithelium (eg, aspiration of gastric contents).
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Injury to the endothelium results in increased
capillary permeability and the influx of protein-rich
fluid into the alveolar space.
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Injury to the alveolar lining cells also promotes
pulmonary edema formation.
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Two types of alveolar epithelial cells exist.
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Type I cells, which make up 90% of the alveolar
epithelium, are injured easily.
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Damage to type I cells allows both increased entry of
fluid into the alveoli and decreased clearance of fluid
from the alveolar space.
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Type II alveolar epithelial cells are relatively more resistant to
injury.
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However, type II cells have several important functions, including
the production of surfactant, ion transport, and proliferation and
differentiation into type l cells after cellular injury.
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Damage to type II cells results in decreased production of
surfactant with resultant decreased compliance and alveolar
collapse.
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Interference with the normal repair processes in the lung may lead
to the development of fibrosis.
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Neutrophils are thought to play a key role in the pathogenesis of
ARDS, as suggested by studies of bronchoalveolar lavage (BAL)
and lung biopsy specimens in early ARDS.
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Despite the apparent importance of neutrophils in this syndrome,
ARDS may develop in profoundly neutropenic patients, and
infusion of granulocyte colony-stimulating factor (G-CSF) in
patients with ventilator-associated pneumonia (VAP) does not
promote its development.
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This and other evidence suggests that the neutrophils observed
in ARDS may be reactive rather than causative.
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Cytokines (tumor necrosis factor [TNF], leukotrienes, macrophage
inhibitory factor, and numerous others), along with platelet
sequestration and activation, are also important in the
development of ARDS.
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An imbalance of pro-inflammatory and anti-inflammatory cytokines
is thought to occur after an inciting event, such as sepsis.
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Evidence from animal studies suggests that the development of
ARDS may be promoted by the positive airway pressure delivered
to the lung by mechanical ventilation. This is termed ventilatorassociated lung injury (VALI).
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ARDS expresses itself as an inhomogeneous process.
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Relatively normal alveoli, which are more compliant than
affected alveoli, may become over-distended by the
delivered tidal volume, resulting in barotrauma
(pneumothorax and interstitial air).
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Alveoli already damaged by ARDS may experience further
injury from the shear forces exerted by the cycle of collapse
at end-expiration and re-expansion by positive pressure at
the next inspiration (so-called volutrauma).
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In addition to the mechanical effects on alveoli,
these forces promote the secretion of proinflammatory cytokines with resultant worsening
inflammation and pulmonary edema.
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The use of positive end-expiratory pressure (PEEP)
to diminish alveolar collapse and the use of low tidal
volumes and limited levels of inspiratory filling
pressures appear to be beneficial in diminishing the
observed VALI.
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ARDS causes a marked increase in intrapulmonary shunting, leading
to severe hypoxemia.
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Although a high FiO2 is required to maintain adequate tissue
oxygenation and life, additional measures, like lung recruitment with
PEEP, are often required.
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Theoretically, high FiO2 levels may cause DAD via oxygen free
radical and related oxidative stresses, collectively called oxygen
toxicity.
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Generally, oxygen concentrations higher than 65% for prolonged
periods (days) can result in DAD, hyaline membrane formation, and,
eventually, fibrosis.
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ARDS is uniformly associated with pulmonary
hypertension.
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Pulmonary artery vasoconstriction likely contributes to
ventilation-perfusion mismatch and is one of the
mechanisms of hypoxemia in ARDS.
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Normalization of pulmonary artery pressures occurs as the
syndrome resolves.
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The development of progressive pulmonary hypertension
is associated with a poor prognosis.
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The acute phase of ARDS usually resolves completely.
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Less commonly, residual pulmonary fibrosis occurs, in which the
alveolar spaces are filled with mesenchymal cells and new blood
vessels.
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This process seems to be facilitated by interleukin (IL)-1.
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Progression to fibrosis may be predicted early in the course by the
finding of increased levels of procollagen peptide III (PCP-III) in the
fluid obtained by BAL.
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This and the finding of fibrosis on biopsy correlate with an
increased mortality rate.
ETIOLOGY
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Multiple risk factors exist for ARDS.
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Approximately 20% of patients with ARDS have no
identified risk factor.
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ARDS risk factors include direct lung injury (most
commonly, aspiration of gastric contents), systemic
illnesses, and injuries.
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The most common risk factor for ARDS is sepsis.
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Given the number of adult studies, major risk factors
associated with the development of ARDS include
the following:
Bacteremia
Sepsis
Trauma, with or without
pulmonary contusion
Fractures, particularly
multiple fractures and long
bone fractures
Burns
Massive transfusion
Pneumonia
Aspiration
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Drug overdose
Near drowning
Postperfusion injury after
cardiopulmonary bypass
Pancreatitis
Fat embolism
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General risk factors for ARDS have not been
prospectively studied using the 1994 EACC criteria.
However, several factors appear to increase the risk of
ARDS after an inciting event, including advanced age,
female sex (noted only in trauma cases), cigarette
smoking, [4] and alcohol use. For any underlying cause,
increasingly severe illness as predicted by a severity
scoring system such as the Acute Physiology And
Chronic Health Evaluation (APACHE) increases the risk
of development of ARDS.
GENETIC FACTORS
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A study by Glavan et al examined the association
between genetic variations in the FAS gene and ALI
susceptibility.
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The study identified associations between four
single nucleotide polymorphisms and increased ALI
susceptibility.
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Further studies are needed to examine the role of
FAS in ALI.
EPIDEMIOLOG
Y
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The incidence of ARDS varies widely, partly because
studies have used different definitions of the disease.
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Moreover, to determine an accurate estimate of its
incidence, all cases of ARDS in a given population
must be found and included.
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Although this may be problematic, recent data are
available from the United States and international
studies that may clarify the true incidence of this
condition.
UNITED STATES STATISTICS
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In the 1970s, when a National Institutes of Health
(NIH) study of ARDS was being planned, the
estimated annual frequency was 75 cases per
100,000 population.
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Subsequent studies, before the development of the
AECC definitions, reported much lower figures. For
example, a study from Utah showed an estimated
incidence of 4.8-8.3 cases per 100,000 population.
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A prospective study using the 1994 AECC definition
was performed in King County, Washington, from
April 1999 through July 2000 and found that the
age-adjusted incidence of ALI was 86.2 per 100,000
person-years.
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Incidence increased with age, reaching 306 per
100,000 person-years for people in aged 75-84
years.
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On the basis of these statistics, it is estimated that
190,600 cases exist in the United States annually
and that these cases are associated with 74,500
deaths.
INTERNATIONAL STATISTICS
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The first study to use the 1994 AECC definitions
was performed in Scandinavia, which reported
annual rates of 17.9 cases per 100,000 population
for ALI and 13.5 cases per 100,000 population for
ARDS.
AGE-RELATED DIFFERENCES IN
INCIDENCE
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ARDS may occur in people of any age.
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Its incidence increases with advancing age, ranging
from 16 cases per 100,000 person-years in those
aged 15-19 years to 306 cases per 100,000 personyears in those between the ages of 75 and 84 years.
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The age distribution reflects the incidence of the
underlying causes.
SEX-RELATED DIFFERENCES IN
INCIDENCE
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For ARDS associated with sepsis and most other
causes, no differences in the incidence between
males and females appear to exist.
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However, in trauma patients only, the incidence of
the disease may be slightly higher among females.
PROGNOSIS
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Until the 1990s, most studies reported a 40-70% mortality
rate for ARDS.
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However, 2 reports in the 1990s, one from a large county
hospital in Seattle and one from the United Kingdom,
suggested much lower mortality rates, in the range of 3040%.
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Possible explanations for the improved survival rates may be
better understanding and treatment of sepsis, recent
changes in the application of mechanical ventilation, and
better overall supportive care of critically ill patients.
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Note that most deaths in ARDS patients are
attributable to sepsis (a poor prognostic factor) or
multi-organ failure rather than to a primary
pulmonary cause, although the recent success of
mechanical ventilation using smaller tidal volumes
may suggest a role of lung injury as a direct cause
of death.
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Mortality in ARDS increases with advancing age.
The study performed in King County, Washington,
found mortality rates of 24% in patients between
ages 15 and 19 years and 60% in patients aged 85
years and older.
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The adverse effect of age may be related to
underlying health status.
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Indices of oxygenation and ventilation, including the
PaO2/FiO2 ratio, do not predict the outcome or risk
of death.
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The severity of hypoxemia at the time of diagnosis
does not correlate well with survival rates.
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However, the failure of pulmonary function to
improve in the first week of treatment is a poor
prognostic factor.
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Peripheral blood levels of decoy receptor 3 (DcR3), a
soluble protein with immunomodulatory effects,
independently predict 28-day mortality in ARDS
patients.
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In a study comparing DcR3, soluble triggering receptor
expressed on myeloid cells (sTREM)-1, TNF-alpha,
and IL-6 in ARDS patients, plasma DcR3 levels were
the only biomarker to distinguish survivors from nonsurvivors at all time points in week 1 of ARDS.
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Non-survivors had higher DcR3 levels than
survivors, regardless of APACHE II scores, and
mortality was higher in patients with higher DcR3
levels.
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Morbidity is considerable.
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Patients with ARDS are likely to have prolonged
hospital courses, and they frequently develop
nosocomial infections, especially ventilator-associated
pneumonia (VAP).
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In addition, patients often have significant weight loss
and muscle weakness, and functional impairment may
persist for months after hospital discharge.
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Severe disease and prolonged duration of
mechanical ventilation are predictors of persistent
abnormalities in pulmonary function.
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Survivors of ARDS have significant functional
impairment for years following recovery.
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In a study of 109 survivors of ARDS, 12 patients
died in the first year.
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In 83 evaluable survivors, spirometry and lung
volumes were normal at 6 months, but diffusing
capacity remained mildly diminished (72%) at 1
year.
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ARDS survivors had abnormal 6-minute walking
distances at 1 year, and only 49% had returned to work.
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Their health-related quality of life was significantly below
normal.
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However, no patient remained oxygen dependent at 12
months.
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Radiographic abnormalities had also completely
resolved.
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A study of this same group of patients 5 years after
recovery from ARDS (9 additional patients had died
and 64 were evaluated) was recently published and
demonstrated continued exercise impairment and
decreased quality of life related to both physical and
neuropsychological factors.
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A study examining health-related quality of life
(HRQL) after ARDS determined that ARDS
survivors had poorer overall HRQL than the general
population at 6 months after recovery.
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This included lower scores in mobility, energy, and
social isolation.
ACUTE RESPIRATORY DISTRESS SYNDROME CLINICAL
PRESENTATION
HISTORY
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Acute respiratory distress syndrome (ARDS) is
characterized by the development of acute dyspnea
and hypoxemia within hours to days of an inciting
event, such as trauma, sepsis, drug overdose,
massive transfusion, acute pancreatitis, or
aspiration. In many cases, the inciting event is
obvious, but, in others (eg, drug overdose), it may
be harder to identify.
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Patients developing ARDS are critically ill, often with
multi-system organ failure, and they may not be
capable of providing historical information.
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Typically, the illness develops within 12-48 hours
after the inciting event, although, in rare instances, it
may take up to a few days.
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With the onset of lung injury, patients initially note
dyspnea with exertion.
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This rapidly progresses to severe dyspnea at rest,
tachypnea, anxiety, agitation, and the need for
increasingly high concentrations of inspired oxygen.
PHYSICAL
EXAMINATION
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Physical findings often are nonspecific and include
tachypnea, tachycardia, and the need for a high fraction of
inspired oxygen (FiO2) to maintain oxygen saturation.
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The patient may be febrile or hypothermic.
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Because ARDS often occurs in the context of sepsis,
associated hypotension and peripheral vasoconstriction
with cold extremities may be present.
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Cyanosis of the lips and nail beds may occur.
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Examination of the lungs may reveal bilateral rales.
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Rales may not be present despite widespread
involvement.
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Because the patient is often intubated and
mechanically ventilated, decreased breath sounds
over 1 lung may indicate a pneumothorax or
endotracheal tube down the right main bronchus.
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Manifestations of the underlying cause (eg, acute
abdominal findings in the case of ARDS caused by
pancreatitis) are present.
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In a septic patient without an obvious source, pay careful
attention during the physical examination to identify potential
causes of sepsis, including signs of lung consolidation or
findings consistent with an acute abdomen.
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Carefully examine sites of intravascular lines, surgical
wounds, drain sites, and decubitus ulcers for evidence of
infection.
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Check for subcutaneous air, a manifestation of infection or
barotrauma.
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Because cardiogenic pulmonary edema must be
distinguished from ARDS, carefully look for signs of
congestive heart failure or intravascular volume
overload, including jugular venous distention,
cardiac murmurs and gallops, hepatomegaly, and
edema.
COMPLICATIO
NS
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Patients with ARDS often require high-intensity mechanical
ventilation, including high levels of positive end-expiratory
pressure (PEEP) or continuous positive airway pressure
(CPAP) and, possibly, high mean airway pressures; thus,
barotrauma may occur.
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Patients present with pneumomediastinum, pneumothorax,
or both.
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Other potential complications that may occur in these
mechanically ventilated patients include accidental
extubation and right mainstem intubation.
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If prolonged mechanical ventilation is needed,
patients may eventually require tracheostomy.
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With prolonged intubation and tracheostomy, upper
airway complications may occur, most notably postextubation laryngeal edema and subglottic stenosis.
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Because patients with ARDS often require prolonged
mechanical ventilation and invasive hemodynamic monitoring,
they are at risk for serious nosocomial infections, including
ventilator-associated pneumonia (VAP) and line sepsis.
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The incidence of VAP in ARDS patients may be as high as 55%
and appears to be higher than that in other populations requiring
mechanical ventilation.
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Preventive strategies including elevation of head of the bed, use
of subglottic suction endotracheal tubes, and oral
decontamination.
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Other potential infections include urinary tract infection (UTI)
related to the use of urinary catheters and sinusitis related to
the use of nasal feeding and drainage tubes.
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Patients may also develop Clostridium difficile colitis as a
complication of broad-spectrum antibiotic therapy.
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Patients with ARDS, because of the extended intensive care
unit (ICU) stay and treatment with multiple antibiotics, may
also develop infections with drug-resistant organisms such
as methicillin-resistant Staphylococcus aureus (MRSA) and
vancomycin-resistant Enterococcus (VRE).
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In a study of survivors of ARDS, significant
functional impairment was noted at 1 year, primarily
related to muscle wasting and weakness.
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Corticosteroid treatment and use of neuromuscular
blockade are risk factors for muscle weakness and
poor functional recovery.
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Patients may have difficulty weaning from
mechanical ventilation.
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Strategies to facilitate weaning, such as daily
interruption of sedation, early institution of physical
therapy, attention to maintaining nutrition, and use of
weaning protocols, may decrease the duration of
mechanical ventilation and facilitate recovery.
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Renal failure is a frequent complication of ARDS,
particularly in the context of sepsis.
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Renal failure may be related to hypotension,
nephrotoxic drugs, or underlying illness.
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Fluid management is complicated in this context,
especially if the patient is oliguric.
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Multisystem organ failure, rather than respiratory
failure alone, is usually the cause of death in ARDS.
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Other potential complications include ileus, stress
gastritis, and anemia.
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Stress ulcer prophylaxis is indicated for these
patients.
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Anemia may be prevented by the use of growth
factors (erythropoietin).
ACUTE RESPIRATORY DISTRESS SYNDROME
DIFFERENTIAL DIAGNOSES
DIAGNOSTIC
CONSIDERATI
ONS
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Other conditions to be considered
include the following:
pneumonitis
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Transfusion-related acute lung
injury (TRALI)
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Pulmonary hemorrhage
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Near drowning
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Acute eosinophilic pneumonia
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Drug reaction
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Reperfusion injury
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Noncardiogenic pulmonary
edema
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Leukemic infiltration
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Fat embolism syndrome
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Hamman-Rich syndrome
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Retinoic acid syndrome
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Acute hypersensitivity
DIFFERENTIA
L DIAGNOSES
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Aspiration Pneumonitis
and Pneumonia
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Noninvasive Ventilation
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Toxic Shock Syndrome
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Hospital-Acquired
Pneumonia (Nosocomial
Pneumonia) and
Ventilator-Associated
Pneumonia
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Transfusion Reactions
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Tumor Lysis Syndrome
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Ventilator-Associated
Pneumonia
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Viral Pneumonia
Bacterial Pneumonia
Bacterial Sepsis
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Goodpasture Syndrome
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Hemorrhagic Shock
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Heroin Toxicity
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Hypersensitivity
Pneumonitis
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Mechanical Ventilation
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Multiple Organ
Dysfunction Syndrome in
Sepsis
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Perioperative Pulmonary
Management
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Pneumocystis jiroveci
Pneumonia
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Pulmonary Eosinophilia
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Respiratory Failure
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Salicylate Toxicity
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Septic Shock
ACUTE RESPIRATORY DISTRESS SYNDROME
WORKUP
APPROACH
CONSIDERATI
ONS
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Acute respiratory distress syndrome (ARDS) is defined by
the acute onset of bilateral pulmonary infiltrates and
severe hypoxemia in the absence of evidence of
cardiogenic pulmonary edema.
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Workup includes selected laboratory tests, diagnostic
imaging, hemodynamic monitoring, and bronchoscopy.
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ARDS is a clinical diagnosis, and no specific laboratory
abnormalities are noted beyond the expected disturbances
in gas exchange and radiographic findings.
LABORATORY
TESTS
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In ARDS, if the partial pressure of oxygen in the
patient’s arterial blood (PaO2) is divided by the
fraction of oxygen in the inspired air (FiO2), the
result is 300 or less.
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For patients breathing 100% oxygen, this means
that the PaO2 is less than 300.
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In addition to hypoxemia, arterial blood gases often
initially show a respiratory alkalosis.
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However, in ARDS occurring in the context of
sepsis, a metabolic acidosis with or without
respiratory compensation may be present.
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As the condition progresses and the work of breathing
increases, the partial pressure of carbon dioxide
(PCO2) begins to rise and respiratory alkalosis gives
way to respiratory acidosis.
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Patients on mechanical ventilation for ARDS may be
allowed to remain hypercapnic (permissive
hypercapnia) to achieve the goals of low tidal volume
and limited plateau pressure ventilator strategies aimed
at limiting ventilator-associated lung injury.
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To exclude cardiogenic pulmonary edema, it may be
helpful to obtain a plasma B-type natriuretic peptide
(BNP) value and echocardiogram. A BNP level of less
than 100 pg/mL in a patient with bilateral infiltrates and
hypoxemia favors the diagnosis of ARDS/acute lung
injury (ALI) rather than cardiogenic pulmonary edema.
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The echocardiogram provides information about left
ventricular ejection fraction, wall motion, and valvular
abnormalities.
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Other abnormalities observed in ARDS depend on
the underlying cause or associated complications
and may include the following:
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Hematologic:
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In septic patients, leukopenia or leukocytosis may be
noted.
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Thrombocytopenia may be observed in septic patients in
the presence of disseminated intravascular coagulation
(DIC).
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Von Willebrand factor (VWF) may be elevated in patients
at risk for ARDS and may be a marker of endothelial
injury.
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Renal:
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Acute tubular necrosis (ATN) often ensues in the
course of ARDS, probably from ischemia to the
kidneys.
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Renal function should be closely monitored.
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Hepatic:
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Liver function abnormalities may be noted in either a
pattern of hepatocellular injury or cholestasis.
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Cytokines:
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Multiple cytokines, such as interleukin (IL)–1, IL-6,
and IL-8, are elevated in the serum of patients at
risk for ARDS.
RADIOGRAPH
Y
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ARDS is defined by the presence of bilateral
pulmonary infiltrates.
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The infiltrates may be diffuse and symmetric or
asymmetric, especially if superimposed upon
preexisting lung disease or if the insult causing
ARDS was a pulmonary process, such as aspiration
or lung contusion.
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The pulmonary infiltrates usually evolve rapidly, with
maximal severity within the first 3 days.
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Infiltrates can be noted on chest radiographs almost
immediately after the onset of gas exchange
abnormalities.
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They may be interstitial, characterized by alveolar
filling, or both.
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Initially, the infiltrates may have a patchy peripheral
distribution, but soon they progress to diffuse
bilateral involvement with ground glass changes or
frank alveolar infiltrates (see the image below).
Anteroposterior portable chest radiograph in patient who had been in respiratory
failure for 1 week with diagnosis of acute respiratory distress syndrome. Image shows
endotracheal tube, left subclavian central venous catheter in superior vena cava, and
bilateral patchy opacities in mostly middle and lower lung zones.
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The correlation between radiographic findings and
severity of hypoxemia is highly variable.
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In addition, diuresis tends to improve infiltrates and
volume overload tends to worsen them, irrespective
of improvement or worsening in underlying ARDS.
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For patients who begin to improve and show signs
of resolution, improvement in radiographic
abnormalities generally occurs over 10-14 days;
however, more protracted courses are common.
COMPUTED
TOMOGRAPHY
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In general, clinical evaluation and routine chest radiography are
sufficient in patients with ARDS.
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However, computed tomography (CT) scanning may be indicated in
some situations.
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CT scanning is more sensitive than plain chest radiography in
detecting pulmonary interstitial emphysema, pneumothoraces and
pneumomediastinum, pleural effusions, cavitation, and mediastinal
lymphadenopathy.
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The heterogeneity of alveolar involvement is often apparent on CT
scan even in the presence of diffuse homogeneous infiltrates on
routine chest radiograph.
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In some instances, the discovery of unexpected
pulmonary pathology, such as a pneumothorax, may
be lifesaving.
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However, this potential benefit must be weighed
against the risk associated with transporting a
critically ill patient on high-intensity mechanical
ventilation out of the intensive care unit (ICU) to the
CT scan equipment.
ECHOCARDIO
GRAPHY
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As part of the workup, patients with ARDS should
undergo 2-dimensional echocardiography for the
purpose of screening.
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If findings are suggestive of patent foramen ovale
shunting, 2-dimensional echocardiography should
be followed up with transesophageal
echocardiography.
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Because patients with severe ARDS often require
prolonged prone positioning due to refractory
hypoxemia, a study assessed the use of
transesophageal echocardiography (TEE) in
patients in the prone position.
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The study determined that TEE can be safely and
efficiently performed in patients with severe ARDS in
the prone position.
INVASIVE
HEMODYNAMI
C
MONITORING
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Because avoiding fluid-overload may be beneficial in
the management of ARDS, the use of a central
venous catheter or pulmonary artery catheter may
facilitate appropriate fluid management in these
patients in whom judging intravascular volume
status on clinical grounds may be difficult or
impossible.
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This may be especially helpful in patients who are
hypotensive or those with associated renal failure.
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Use of the generic pulmonary artery catheter past
the time of initial resuscitation confers no survival
benefit and possibly has an adverse effect on
survival.
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In addition, accurate measurement of hemodynamic
parameters with the pulmonary artery catheter
requires skill and care.
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This is especially difficult in patients either on
mechanical ventilation or with forced spontaneous
inspirations because the pressure tracing is affected
by intrathoracic pressure. PCWP should be measured
at end-expiration and from the tracing rather than from
digital displays on the bedside monitor.
BRONCHOSCO
PY
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Bronchoscopy may be considered to evaluate the possibility
of infection, alveolar hemorrhage, or acute eosinophilic
pneumonia in patients acutely ill with bilateral pulmonary
infiltrates.
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Culture material may be obtained by wedging the
bronchoscope in a sub-segmental bronchus and collecting
the fluid suctioned after instilling large volumes of nonbacteriostatic saline (bronchoalveolar lavage; BAL).
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The fluid is analyzed for cell differential, cytology, silver
stain, and Gram stain and is quantitatively cultured.
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Ten thousand organisms per milliliter is generally
considered significant in a patient not previously
treated with antibiotics.
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As noted, early ARDS is characterized by the
presence of neutrophils in the BAL fluid, so the
presence of intracellular organisms and the use of
quantitative culture are important in establishing
infection.
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An alternative means of obtaining a culture is by
means of a protected specimen brush, which is
passed through the bronchoscope into a segmental
bronchus.
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Subsequently, the brush is cut off into 1 mL of sterile
non-bacteriostatic saline. Culture of 1000 organisms
is considered significant.
•
Analysis of the types of cells present in the BAL fluid
may be helpful in the differential diagnosis of
patients with ARDS.
•
For example, the finding of a high percentage of
eosinophils (>20%) in the BAL fluid is consistent
with the diagnosis of acute eosinophilic pneumonia.
The use of high-dose corticosteroids in these
patients may be lifesaving.
•
A high proportion of lymphocytes may be observed
in acute hypersensitivity pneumonitis, sarcoidosis, or
bronchiolitis obliterans-organizing pneumonia
(BOOP).
•
Red cells and hemosiderin-laden macrophages may
be observed in pulmonary hemorrhage. Lipid laden
macrophages are suggestive of aspiration or lipoid
pneumonia.
•
Cytologic evaluation of the BAL fluid may also be
helpful in the differential diagnosis of ARDS.
•
This may reveal viral cytopathic changes, for
example.
•
Silver stain may be helpful in diagnosing an
infection, such as Pneumocystis.
•
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.
•
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
•
The histologic changes in ARDS are those of diffuse
alveolar damage.
•
An exudative phase occurs in the first several days and
is characterized by interstitial edema, alveolar
hemorrhage and edema, alveolar collapse, pulmonary
capillary congestion, and hyaline membrane formation.
•
These histologic changes are nonspecific and do not
provide information that would allow the pathologist to
determine the cause of the ARDS.
Photomicrograph from patient with acute respiratory distress syndrome
(ARDS). Image shows ARDS in exudative stage. Note hyaline
membranes and loss of alveolar epithelium in this early stage of ARDS.
•
A biopsy performed after several days shows the
beginning of organization of the intra-alveolar
exudate and repair, the proliferative phase of ARDS,
which is characterized by the growth of type 2
pneumocytes in the alveolar walls and the
appearance of fibroblasts, myofibroblasts, and
collagen deposition in the interstitium.
•
The final phase of ARDS is fibrotic. Alveolar walls
are thickened by connective tissue rather than
edema or cellular infiltrate.
ACUTE RESPIRATORY DISTRESS SYNDROME
TREATMENT & MANAGEMENT
APPROACH
CONSIDERATI
ONS
•
No drug has proved beneficial in the prevention or
management of acute respiratory distress syndrome
(ARDS).
•
Early administration of corticosteroids to septic
patients does not prevent the development of
ARDS.
•
Numerous pharmacologic therapies, including the
use of inhaled synthetic surfactant, intravenous (IV)
antibody to endotoxin, ketoconazole, simvastatin,
and ibuprofen, have been tried and are not effective.
•
A study that examined the use and outcomes
associated with rescue therapies in patients with
ARDS determined that these therapies offered no
survival benefit.
•
The study also determined that rescue therapies are
most often used in younger patients with more
severe oxygenation deficits.
•
Inhaled nitric oxide (NO), a potent pulmonary
vasodilator, seemed promising in early trials, but in
larger controlled trials, it did not change mortality
rates in adults with ARDS.
•
A systematic review, meta-analysis, and trial
sequential analysis of 14 randomized controlled
trials, including 1303 patients, found that inhaled
nitric oxide did not reduce mortality and results in
only a transient improvement in oxygenation.
•
Although no specific therapy exists for ARDS,
treatment of the underlying condition is essential,
along with supportive care, noninvasive ventilation
or mechanical ventilation using low tidal volumes,
and conservative fluid management.
•
Because infection is often the underlying cause of ARDS,
early administration of appropriate antibiotic therapy broad
enough to cover suspected pathogens is essential, along
with careful assessment of the patient to determine potential
infection sources.
•
In some instances, removal of intravascular lines, drainage
of infected fluid collections, or surgical debridement or
resection of an infected site (eg, the ischemic bowel) may
be necessary because sepsis-associated ARDS does not
resolve without such management.
•
In addition, preventing complications associated with
prolonged mechanical ventilation and ICU stay can
include deep venous thrombosis (DVT) prophylaxis,
stress ulcer prophylaxis, early mobilization,
minimizing sedation, turning and skin care, and
strategies to prevent ventilator-induced pneumonia,
such as elevation of the head of the bed and use of
a subglottic suction device.
•
The only treatment found to improve survival in
ARDS is a mechanical ventilation strategy using low
tidal volumes (6 mL/kg based upon ideal body
weight).
•
The main concerns are missing a potentially treatable
underlying cause or complication of ARDS.
•
In these critically ill patients, pay careful attention to early
recognition of potential complications in the intensive care
unit (ICU), including pneumothorax, IV line infections, skin
breakdown, inadequate nutrition, arterial occlusion at the site
of intra-arterial monitoring devices, DVT and pulmonary
embolism (PE), retroperitoneal hemorrhage, gastrointestinal
(GI) hemorrhage, erroneous placement of lines and tubes,
and the development of muscle weakness.
•
In situations where the patient requires the use of
paralyzing agents to allow certain modes of
mechanical ventilation, take meticulous care to
ensure that an adequate alarm system is in place to
alert staff to mechanical ventilator disconnection or
malfunction.
•
In addition, adequate sedation is important in most
patients on ventilators and is essential when
paralytic agents are in use.
•
As in all situations in which patients are critically ill, family and friends
are under stress and likely have many questions and concerns.
•
Keep them informed and allow them to be at the bedside as much as
possible.
•
Caretakers should assume that even though sedated, the patient may
be capable of hearing and understanding all conversations in the
room and may experience pain.
•
Keeping this in mind, all conversation at the bedside should be
appropriate and all procedures should be performed with local
anesthesia and pain medication.
FLUID
MANAGEMENT
•
Distinguishing between initial fluid resuscitation, as
used for therapy of septic shock, and maintenance
fluid therapy is important.
•
Early aggressive resuscitation for associated
circulatory shock and its associated remote organ
injury are central aspects of initial management.
•
However, several small trials have demonstrated improved
outcome for ARDS in patients treated with diuretics or
dialysis to promote a negative fluid balance in the first few
days.
•
Thus, distinction between primary ARDS due to aspiration,
pneumonia, or inhalational injury, which usually can be
treated with fluid restriction, from secondary ARDS due to
remote infection or inflammation that requires initial fluid and
potential vasoactive drug therapy is central in directing initial
treatments to stabilize the patient.
•
The use of a conservative fluid management approach
has been called into question by the long-term followup of
a subset of survivors of the Fluid and Catheter Treatment
Trial (FACTT). Although mortality in the survivors was
similar regardless of fluid management strategy, and the
conservative fluid management group required about 18
hours less mechanical ventilatory support, cognitive
function was markedly impaired in the conservative fluid
group compared with the liberal fluid group, with an
adjusted odds ratio of 3.35.
•
Cognitive impairment was defined as impairment in
memory, verbal fluency, or executive function.
Although all those were more common in the
conservative fluid management group, only the
decrement in executive function reached statistical
significance (p=0.001).
•
Lower partial pressure of arterial oxygen during the
trial was also independently associated with
cognitive impairment.
•
Maintaining a low-normal intravascular volume may be
facilitated by hemodynamic monitoring with a central venous or
pulmonary artery (Swan-Ganz) catheter, aimed at achieving a
central venous pressure (CVP) or pulmonary capillary wedge
pressure (PCWP) at the lower end of normal.
•
The ARDS clinical trials network of pulmonary artery catheter
versus CVP to guide fluid management in ARDS showed no
difference in mortality or ventilator-free days, regardless of
whether fluid status was monitored by pulmonary artery
catheter or CVP.
•
Closely monitor urine output and administer diuretics
to facilitate a negative fluid balance.
•
In oliguric patients, hemodialysis with ultrafiltration
or continuous veno-venous hemofiltration/dialysis
(CVVHD) may be required.
•
A study by Lakhal et al determined that respiratory
pulse pressure variation fails to predict fluid
responsiveness in patients with ARDS.
•
Careful fluid challenges may be a safer alternative.
NONINVASIVE
VENTILATION
AND HIGHFLOW NASAL
CANNULA
•
Because intubation and mechanical ventilation may
be associated with an increased incidence of
complications, such as barotrauma and nosocomial
pneumonia, alternatives to mechanical ventilation
such as a high-flow nasal cannula or noninvasive
positive-pressure ventilation (NIPPV) may be
beneficial in patients with ARDS.
•
High-flow nasal cannula uses a system of heated
humidification and large-bore nasal prongs to deliver
oxygen at flows of up to 50 L/min.
•
This is usually used in conjunction with an oxygen blender,
allowing delivery of precise inspired oxygen
concentrations.
•
High-flow nasal cannula is usually well tolerated and
allows the patient to talk, eat, and move around.
•
NIPPV is usually given by full face-mask.
•
Sometimes, continuous positive airway pressure
(CPAP) alone may be sufficient to improve
oxygenation.
•
In a 2015 study on hypoxemic, non-hypercapnic
patients comparing standard oxygen, high-flow
nasal cannula, and NIPPV, all three modes had the
same incidence of need for intubation/mechanical
ventilation, but high-flow nasal cannula resulted in
improved 90-day mortality.
•
Noninvasive ventilation has been studied best in
patients with hypercapnic respiratory failure caused
by chronic obstructive pulmonary disease (COPD)
or neuromuscular weakness.
•
Patients who have a diminished level of
consciousness, vomiting, upper GI bleeding, or
other conditions that increase aspiration risk are not
candidates for NIPPV.
•
Other relative contraindications include
hemodynamic instability, agitation, and inability to
obtain good mask fit.
MECHANICAL
VENTILATION
•
The goals of mechanical ventilation in ARDS are to maintain
oxygenation while avoiding oxygen toxicity and the
complications of mechanical ventilation.
•
Generally, this involves maintaining oxygen saturation in the
range of 85-90%, with the aim of reducing the fraction of
inspired oxygen (FiO2) to less than 65% within the first 2448 hours.
•
Achieving this aim almost always necessitates the use of
moderate-to-high levels of positive end-expiratory pressure
(PEEP).
•
Experimental studies have shown that mechanical
ventilation may promote a type of acute lung injury
termed ventilator-associated lung injury.
•
A protective ventilation strategy using low tidal
volumes and limited plateau pressures improves
survival when compared with conventional tidal
volumes and pressures.
•
In an ARDS Network study, patients with ALI and
ARDS were randomized to mechanical ventilation
either at a tidal volume of 12 mL/kg of predicted body
weight and an inspiratory pressure of 50 cm water or
less or at a tidal volume of 6 mL/kg and an inspiratory
pressure of 30 cm water or less; the study was
stopped early after interim analysis of 861 patients
demonstrated that subjects in the low-tidal-volume
group had a significantly lower mortality rate (31%
versus 39.8%).
•
Whereas previous studies employing low tidal volumes
allowed patients to be hypercapnic (permissive
hypercapnia) and acidotic to achieve the protective
ventilation goals of low tidal volume and low inspiratory
airway pressure, the ARDS Network study allowed
increases in respiratory rate and administration of
bicarbonate to correct acidosis.
•
This may account for the positive outcome in this study
as compared with earlier studies that had failed to
demonstrate a benefit.
•
Thus, mechanical ventilation with a tidal volume of 6
mL/kg predicted body weight is recommended, with
adjustment of the tidal volume to as low as 4 mL/kg
if needed to limit the inspiratory plateau pressure to
30 cm water or less.
•
Increase the ventilator rate and administer
bicarbonate as needed to maintain the pH at a near
normal level (7.3).
•
In the ARDS Network study, patients ventilated with lower
tidal volumes required higher levels of PEEP (9.4 vs 8.6 cm
water) to maintain oxygen saturation at 85% or more.
•
Some authors have speculated that the higher levels of
PEEP may also have contributed to the improved survival
rates.
•
However, a subsequent ARDS Network trial of higher versus
lower PEEP levels in patients with ARDS showed no benefit
from higher PEEP levels in terms of either survival or
duration of mechanical ventilation.
•
Patients with severe ARDS receiving mechanical
ventilation responded more favorably to early
administration of a neuromuscular blocking agent (ie,
cisatracurium) than to placebo.
•
Compared with the placebo group, the cisatracurium
group showed improvement in 90-day survival and
increased time off the ventilator.
•
No significant difference in ICU-acquired paresis was
observed.
•
Managing physicians should not use paralytics in all
cases; rather, they should use them only in those
where length of ventilation is expected to exceed a
few hours.
•
Patients should not remain ventilated for longer than
it takes for the paralytics to have their effect.
•
The duration of paralysis will depend upon the
condition.
•
A study by Jaber et al examined diaphragmatic weakness
during mechanical ventilation along with the relationship
between mechanical ventilation duration and diaphragmatic
injury or atrophy.
•
The study determined that longer periods of mechanical
ventilation were associated with significantly greater
ultrastructural fiber injury, increased ubiquitinated proteins,
higher expression of p65 nuclear factor-kB, greater levels of
calcium-activated proteases, and decreased cross-sectional
area of muscle fibers in the diaphragm.
•
The conclusion was that weakness, injury, and
atrophy can occur rapidly in the diaphragms of
patients on mechanical ventilation and are
significantly correlated with the duration of ventilator
support.
POSITIVE ENDEXPIRATORY
PRESSURE AND
CONTINUOUS
POSITIVE
AIRWAY
PRESSURE
•
ARDS is characterized by severe hypoxemia.
•
When oxygenation cannot be maintained despite
high inspired oxygen concentrations, the use of
CPAP or PEEP usually promotes improved
oxygenation, allowing the FiO2 to be tapered.
•
With PEEP, positive pressure is maintained throughout
expiration, but when the patient inhales spontaneously, airway
pressure decreases to below zero to trigger airflow.
•
With CPAP, a low-resistance demand valve is used to allow
positive pressure to be maintained continuously.
•
Positive-pressure ventilation increases intrathoracic pressure and
thus may decrease cardiac output and blood pressure.
•
Because mean airway pressure is greater with CPAP than
PEEP, CPAP may have a more profound effect on blood
pressure.
•
In general, patients tolerate CPAP well, and CPAP
is usually used rather than PEEP.
•
The use of appropriate levels of CPAP is thought to
improve the outcome in ARDS.
•
By maintaining the alveoli in an expanded state
throughout the respiratory cycle, CPAP may
decrease shear forces that promote ventilatorassociated lung injury.
•
The best method for finding the optimal level of
CPAP in patients with ARDS is controversial.
•
Some favor the use of just enough CPAP to allow
reduction of the FiO2 below 65%.
•
Another approach, favored by Amato et al, is the socalled open lung approach, in which the appropriate
level is determined by the construction of a static
pressure volume curve.
•
This is an S-shaped curve, and the optimal level of
PEEP is just above the lower inflection point.
•
Using this approach, the average PEEP level
required is 15 cm water.
•
However, as noted above, an ARDS Network study of
higher versus lower PEEP levels in ARDS patients did not
find higher PEEP levels advantageous.
•
In this study, PEEP level was determined by how much
inspired oxygen was required to achieve a goal oxygen
saturation of 88-95% or a target partial pressure of oxygen
(PO2) of 55-80 mm Hg. The PEEP level averaged 8 in the
lower PEEP group and 13 in the higher PEEP group. No
difference was shown in duration of mechanical ventilation
or survival to hospital discharge.
PRESSURECONTROLLED
VENTILATION
AND HIGHFREQUENCY
VENTILATION
•
If high inspiratory airway pressures are required to deliver even
low tidal volumes, pressure-controlled ventilation (PCV) may be
initiated.
•
In this mode of mechanical ventilation, the physician sets the
level of pressure above CPAP (delta P) and the inspiratory time
(I-time) or inspiratory/expiratory (I:E) ratio.
•
The resultant tidal volume depends on lung compliance and
increases as ARDS improves.
•
PCV may also result in improved oxygenation in some patients
not doing well on volume-controlled ventilation (VCV).
•
If oxygenation is a problem, longer I-times, such that
inspiration is longer than expiration (inverse I:E ratio
ventilation) may be beneficial; ratios as high as 7:1
have been used.
•
PCV, using lower peak pressures, may also be
beneficial in patients with bronchopleural fistulae,
facilitating closure of the fistula.
•
Evidence indicates that PCV may be beneficial in
ARDS, even without the special circumstances
noted.
•
In a multicenter controlled trial comparing VCV with
PCV in ARDS patients, Esteban found that PCV
resulted in fewer organ system failures and lower
mortality rates than VCV, despite use of the same
tidal volumes and peak inspiratory pressures.
•
High-frequency ventilation (jet or oscillatory) is a ventilator mode that
uses low tidal volumes and high respiratory rates.
•
Given that distention of alveoli is known to one of the mechanisms
promoting ventilator-associated lung injury, high-frequency
ventilation would be expected to be beneficial in ARDS.
•
Results of clinical trials comparing this approach with conventional
ventilation in adults have generally demonstrated early improvement
in oxygenation but no improvement in survival.
•
HFOV may be the most useful for patients with bronchopleural
fistulae.
•
Partial liquid ventilation has also been tried in
ARDS.
•
A randomized controlled trial that compared it with
conventional mechanical ventilation determined that
partial liquid ventilation resulted in increased
morbidity (pneumothoraces, hypotension, and
hypoxemic episodes), and a trend toward higher
mortality.
PRONE
POSITIONING
•
Some 60-75% of patients with ARDS have significantly improved
oxygenation when turned from the supine to the prone position.
•
The improvement in oxygenation is rapid and often substantial
enough to allow reductions in FIO2 or level of CPAP.
•
The prone position is safe, with appropriate precautions to secure
all tubes and lines, and does not require special equipment.
•
The improvement in oxygenation may persist after the patient is
returned to the supine position and may occur on repeat trials in
patients who did not respond initially.
•
Possible mechanisms for the improvement noted
are recruitment of dependent lung zones, increased
functional residual capacity (FRC), improved
diaphragmatic excursion, increased cardiac output,
and improved ventilation-perfusion matching.
•
Despite improved oxygenation with the prone position,
randomized controlled trials of the prone position in
ARDS have not demonstrated improved survival.
•
However, a subsequent French study, in which patients
were in the prone position for at least 8 hours per day,
did not document a benefit from the prone position in
terms of 28-day or 90-day mortality, duration of
mechanical ventilation, or development of ventilatorassociated pneumonia (VAP).
TRACHEOSTO
MY
•
In patients requiring prolonged mechanical ventilation,
tracheostomy allows the establishment of a more stable
airway, which may allow for mobilization of the patient and,
in some instances, may facilitate weaning from mechanical
ventilation.
•
Tracheostomy, may be performed in the operating room or
percutaneously at the bedside.
•
Timing of the procedure should be individualized, but it is
generally performed after about 2 weeks of mechanical
ventilation.
EXTRACORPO
REAL
MEMBRANE
OXYGENATIO
N
•
A large multi-center trial in the 1970s demonstrated that
extracorporeal membrane oxygenation (ECMO) did not improve the
mortality rate in ARDS patients.
•
A later trial using extracorporeal carbon dioxide removal along with
inverse ratio ventilation also did not improve survival in ARDS.
•
However, ECMO is still used as a rescue therapy in selected cases.
•
During the H1N1 epidemic in 2009, ECMO appeared to improve
survival in patients with H1N1-associated ARDS who could not be
oxygenated with conventional mechanical ventilation.
NUTRITIONAL
SUPPORT
•
Institution of nutritional support after 48-72 hours of
mechanical ventilation usually is recommended.
Enteral nutrition via a feeding tube is preferable to IV
hyperalimentation unless it is contraindicated
because of an acute abdomen, ileus, GI bleeding, or
other conditions.
•
A low-carbohydrate high-fat enteral formula including antiinflammatory and vasodilating components (eicosapentaenoic
acid and linoleic acid) along with antioxidants has been
demonstrated in some studies to improve outcome in ARDS.
•
In a prospective, randomized study of ARDS patients in Brazil
given an enteral formula containing antioxidants,
eicosapentaenoic acid, and gamma-linoleic acid compared
with a standard isocaloric formula, Pontes-Arruda
demonstrated improved survival and oxygenation with the
specialized diet.
•
The ARDSNet completed a trial of feeding in ARDS
(the EDEN-OMEGA study), in which patients were
randomized to supplements containing omega-3
fatty acid and antioxidants versus placebo. This
study was terminated early for futility, but the full
results have not yet been published.
•
An open-label, multicenter trial (the EDEN study)
randomized 1000 adult patients who required
mechanical ventilation within 48 hours of developing
acute lung injury to receive either trophic or full
enteral feeding for the first 6 days. Initial lowervolume trophic enteral feeding did not improve
ventilator-free days, 60-day mortality, or infectious
complications compared with initial full enteral
feeding, but it was associated with less
gastrointestinal intolerance.
ACTIVITY
RESTRICTION
•
Patients with ARDS are on bed rest. Frequent position changes
should be started immediately, as should passive—and, if
possible, active—range-of-motion activities of all muscle groups.
Elevation of the head of the bed to a 45° angle is recommended to
diminish the development of VAP.
•
Recently, increased interest in minimizing sedation and earlier
ambulation has been proposed. Such approaches are associated
with less posttraumatic stress disorder in survivors and was the
preferred approach by patients’ families. If at all possible, use of
minimal sedation, sedation holidays, and more ambulation appear
to be the goals of management once severe cardiovascular
insufficiency, if present, has resolved.
TRANSFER
CONSIDERATI
ONS
•
Once the acute phase of ARDS resolves, patients
may require a prolonged period to be weaned from
mechanical ventilation and to regain muscle strength
lost after prolonged inactivity. This may necessitate
transfer to a rehabilitation facility once the acute
phase of the illness is resolved.
•
Transfer of the ARDS patient to a tertiary care
facility may be indicated in some situations, provided
that safe transport can be arranged. Transfer may
be indicated if the FIO2 cannot be lowered to less
than 0.65 within 48 hours.
•
Other patients who may potentially benefit from
transfer include those who have experienced
pneumothorax and have persistent air leaks,
patients who cannot be weaned from mechanical
ventilation, patients who have upper airway
obstruction after prolonged intubation, or those with
a progressive course in which an underlying cause
cannot be identified.
•
If ARDS develops in a patient who previously has
undergone organ or bone marrow transplantation,
transfer to an experienced transplant center is
essential for appropriate management.
PREVENTION
•
Although multiple risk factors for ARDS are known, no
successful preventive measures have been identified.
•
Careful fluid management in high-risk patients may be
helpful.
•
Because aspiration pneumonitis is a risk factor for
ARDS, taking appropriate measures to prevent
aspiration (eg, elevating the head of the bed and
evaluating swallowing mechanics before feeding highrisk patients) may also prevent some ARDS cases.
•
In patients without ARDS on mechanical ventilation,
the use of high tidal volumes appears to be a risk
factor for the development of ARDS, and, therefore,
the use of lower tidal volumes in all patients on
mechanical ventilation may prevent some cases on
ARDS.
ACUTE RESPIRATORY DISTRESS SYNDROME
MEDICATION
MEDICATION
SUMMARY
•
No drug has proved beneficial in the prevention or
management of acute respiratory distress syndrome (ARDS).
•
Early administration of corticosteroids to septic patients does
not prevent the development of ARDS. Numerous
pharmacologic therapies, including the use of inhaled or
instilled synthetic surfactant, intravenous (IV) antibody to
endotoxin, ketoconazole, and ibuprofen, have been tried and
are not effective. Statins, which also appeared to have promise
in small studies, also did not show benefit in a recently
published randomized trial in 60 patients with acute lung injury
(ALI).
•
Small sepsis trials suggest a potential role for antibody
to tumor necrosis factor (TNF) and recombinant
interleukin (IL)–1 receptor antagonist.
•
Inhaled nitric oxide (NO), a potent pulmonary
vasodilator, seemed promising in early trials, but in
larger controlled trials, it did not change mortality rates
in adults with ARDS.
•
Inhaled prostacyclin also has not been shown to
improve survival.
•
Because of apparent benefit in small trials, it was thought
that there might be a role for high-dose corticosteroid
therapy in patients with late (fibroproliferative phase) ARDS.
•
However, an ARDS Study Network trial of
methylprednisolone for patients with ARDS persisting for at
least 7 days demonstrated no benefit in terms of 60-day
mortality.
•
Patients treated later in the course of ARDS, 14 days after
onset, had worsened mortality with corticosteroid therapy.
•
Although no survival advantage was shown in
patients treated with methylprednisolone, short-term
clinical benefits included improved oxygenation and
increased ventilator-free and shock-free days.
Patients treated with corticosteroids were more likely
to experience neuromuscular weakness, but the rate
of infectious complications was not increased.
CORTICOSTER
OIDS
•
Development of the late phase of ARDS may
represent continued uncontrolled inflammation, and
corticosteroids may be considered a form of rescue
therapy that may improve oxygenation and
hemodynamics but does not change mortality
(except that corticosteroids increase mortality in
patients who have had ARDS for >14 d).
•
High-dose methylprednisolone has been used in
trials of patients with ARDS who have persistent
pulmonary infiltrates, fever, and high oxygen
requirement despite resolution of pulmonary or
extrapulmonary infection.
•
Pulmonary infection is assessed with bronchoscopy
and bilateral bronchoalveolar lavage (BAL) and
quantitative culture.