Acute Respiratory Distress Syndrome

RESPIRATORY FAILURE
• Type I: Acute Hypoxemic Respiratory Failure (AHRF,
ARDS)
• Type II: A consequence of alveolar hypoventilation
by impaired central nervous system (CNS) drive to
breathe, impaired strength with failure of
neuromuscular function in the respiratory system,
and increased load(s) on the respiratory system.
• Type III: Results from lung atelectasis.
• Type IV: Results from hypoperfusion of respiratory
muscles in patients in shock.
 Type I: Acute Hypoxemic Respiratory Failure (AHRF, ARDS)

• Acute hypoxemic respiratory failure is severe

arterial hypoxemia that is refractory to
supplemental oxygen.
• It is caused by intrapulmonary shunting of blood
resulting from airspace filling or collapse.
• Findings include dyspnea and tachypnea.
• Diagnosis is by ABGs and chest x-ray.
• Treatment usually requires mechanical
ventilation.
 TYPE I: ACUTE HYPOXEMIC RESPIRATORY FAILURE

• This type of respiratory failure occurs with

alveolar flooding and subsequent
intrapulmonary shunt physiology.
• Alveolar flooding may be a consequence of
pulmonary edema, lung injury, pneumonia,
or alveolar hemorrhage.
• Pulmonary edema can be further categorized
as occurring due to elevated pulmonary
microvascular pressures, as seen in heart
failure and intravascular volume overload or
ARDS.
 TYPE I: ACUTE HYPOXEMIC RESPIRATORY FAILURE

• This syndrome is defined by acute onset (≤1

week) of bilateral opacities on chest imaging
that are not fully explained by cardiac failure
or fluid overload and of shunt physiology
requiring positive end-expiratory pressure
(PEEP).
• Type I respiratory failure occurs in clinical
settings such as sepsis, gastric aspiration,
pneumonia, near-drowning, multiple blood
transfusions, and pancreatitis.
 TYPE I: ACUTE HYPOXEMIC RESPIRATORY FAILURE

• It is well established that mechanical ventilation of

patients with ARDS may propagate lung injury. As
seen in Fig. 293-5, the pressure-volume
relationship of the lung in ARDS is not linear.
Alveoli may collapse at very low lung volumes.
• There is growing interest in avoiding intubation in
patients with ARDS by the use of a variety of
devices, such as masks, high flow oxygen delivery
systems, and helmets for respiratory support;
however, this is tempered by concern that higher
tidal volumes during spontaneous breathing with
these devices could result in progression of
preexisting lung injury.
 Pathophysiology

• ARDS
• In ARDS, pulmonary or systemic inflammation leads to
release of cytokines and other proinflammatory molecules.
• The cytokines activate alveolar macrophages and recruit
neutrophils to the lungs, which in turn release leukotrienes,
oxidants, platelet-activating factor, and proteases.
• These substances damage capillary endothelium and
alveolar epithelium, disrupting the barriers between
capillaries and airspaces.
• Edema fluid, protein, and cellular debris flood the airspaces
and interstitium, causing disruption of surfactant, airspace
collapse, ventilation-perfusion mismatch, shunting, and
pulmonary hypertension.
• The airspace collapse more commonly occurs in dependent
lung zones.
 Pathophysiology

• Causes of ARDS may involve:

• Direct lung injury (eg, pneumonia, acid
aspiration)
• Indirect lung injury (eg, sepsis, pancreatitis,
massive blood transfusion, nonthoracic
trauma)
• Sepsis and pneumonia account for about 60%
of cases.
 Pathophysiology

• ARDS is divided into 3 categories of severity:

mild, moderate, and severe based on
oxygenation defects and clinical criteria.
• The mild category corresponds to the
previous category termed acute lung injury
(ALI).
• The natural history of ARDS is marked by three
phases—exudative, proliferative, and fibrotic
—that each have characteristic clinical and
pathologic features.
 Exudative Phase

• In this phase, alveolar capillary endothelial

cells and type I pneumocytes (alveolar
epithelial cells) are injured, with consequent
loss of the normally tight alveolar barrier to
fluid and macromolecules.
• Edema fluid that is rich in protein accumulates
in the interstitial and alveolar spaces.
 Exudative Phase

• Pro-inflammatory cytokines (e.g., interleukin 1,

interleukin 8, and tumor necrosis factor a [TNF-a]) and
lipid mediators (e.g., leukotriene B) are increased in
this acute phase, leading to the recruitment of
leukocytes (especially neutrophils) into the pulmonary
interstitium and alveoli.
• In addition, condensed plasma proteins aggregate in
the air spaces with cellular debris and dysfunctional
pulmonary surfactant to form hyaline membrane
whorls.
• Pulmonary vascular injury also occurs early in ARDS,
with vascular obliteration by microthrombi and
fibrocellular proliferation
 Exudative Phase

• Alveolar edema predominantly involves dependent portions

of the lung with diminished aeration.
• Collapse of large sections of dependent lung can contribute
to decreased lung compliance. Consequently,
intrapulmonary shunting and hypoxemia develop and the
work of breathing increases, leading to dyspnea.
• The pathophysiologic alterations in alveolar spaces are
exacerbated by microvascular occlusion that results in
reductions in pulmonary arterial blood flow to ventilated
portions of the lung (and thus in increased dead space) and
in pulmonary hypertension.
• Thus, in addition to severe hypoxemia, hypercapnia
secondary to an increase in pulmonary dead space can be
prominent in early ARDS.
 Exudative Phase

• The exudative phase encompasses the first 7 days of

illness after exposure to a precipitating ARDS risk factor,
with the patient experiencing the onset of respiratory
symptoms.
• Although usually presenting within 12–36 h after the
initial insult, symptoms can be delayed by 5–7 days.
• Dyspnea develops, with a sensation of rapid shallow
breathing and an inability to get enough air. Tachypnea
and increased work of breathing result frequently in
respiratory fatigue and ultimately in respiratory failure.
• Chest computed tomography (CT) in ARDS also reveals the
presence of bilateral pulmonary infiltrates and
demonstrates extensive heterogeneity of lung
involvement.
 Proliferative Phase

• This phase of ARDS usually lasts from day 7 to day 21. Most
patients recover rapidly and are liberated from mechanical
ventilation during this phase.
• Despite this improvement, many patients still experience
dyspnea, tachypnea, and hypoxemia.
• Some patients develop progressive lung injury and early
changes of pulmonary fibrosis during the proliferative phase.
• Histologically, the first signs of resolution are often evident in
this phase, with the initiation of lung repair, the organization
of alveolar exudates, and a shift from neutrophil- to
lymphocyte-predominant pulmonary infiltrates.
• As part of the reparative process, type II pneumocytes
proliferate along alveolar basement membranes. These
specialized epithelial cells synthesize new pulmonary
surfactant and differentiate into type I pneumocytes.
 Fibrotic Phase

• While many patients with ARDS recover lung function 3–4 weeks
after the initial pulmonary injury, some enter a fibrotic phase that
may require long-term support on mechanical ventilators and/or
supplemental oxygen. Histologically, the alveolar edema and
inflammatory exudates of earlier phases convert to extensive
alveolar-duct and interstitial fibrosis.
• Marked disruption of acinar architecture leads to emphysema-like
changes, with large bullae. Intimal fibroproliferation in the
pulmonary microcirculation causes progressive vascular occlusion
and pulmonary hypertension.
• The physiologic consequences include an increased risk of
pneumothorax, reductions in lung compliance, and increased
pulmonary dead space.
• Patients in this late phase experience a substantial burden of excess
morbidity.
• Lung biopsy evidence for pulmonary fibrosis in any phase of ARDS is
associated with increased mortality risk.
 Refractory hypoxemia
• In both types of AHRF, flooded or collapsed airspaces
allow no inspired gas to enter, so the blood perfusing
those alveoli remains at the mixed venous oxygen
content no matter how high the fractional inspired
O2 (FIO2).
• This effect ensures constant admixture of
deoxygenated blood into the pulmonary vein and
hence arterial hypoxemia.
• In contrast, hypoxemia that results from ventilating
alveoli that have less ventilation than perfusion (ie,
low ventilation-to-perfusion ratios as occurs in
asthma or COPD and, to some extent, in ARDS) is
readily corrected by supplemental oxygen.
 Symptoms and Signs
• Acute hypoxemia (see also Oxygen Desaturation) may cause
dyspnea, restlessness, and anxiety.
• Signs include confusion or alteration of consciousness,
cyanosis, tachypnea, tachycardia, and diaphoresis.
• Cardiac arrhythmia and coma can result.
• Inspiratory opening of closed airways causes crackles,
detected during chest auscultation; the crackles are
typically diffuse but sometimes worse at the lung bases,
particularly in the left lower lobe.
• Jugular venous distention occurs with high levels of positive
end-expiratory pressure (PEEP) or right ventricular failure.
 Hypoxia
• Low (inadequate) O₂ delivery to tissues
• Early signs
• R-Restlessness
• A- Anxiety
• T- Tachycardia
• T-Tachypnea
• Late signs
• B-bradycardia
• E- Extreme Restlessness
• D- Dyspnea
• C-Cyanosis
 Diagnosis

• Chest x-ray and ABGs

• Clinical definition
• Hypoxemia is usually first recognized using
pulse oximetry. Patients with low oxygen
saturation should have a chest x-ray and ABGs
and be treated with supplemental oxygen
while awaiting test results.
 Diagnosis
• If supplemental oxygen does not improve the oxygen saturation to > 90%,
right-to-left shunting of blood should be suspected.
• An obvious alveolar infiltrate on chest x-ray implicates alveolar flooding as
the cause, rather than an intracardiac shunt. However, at the onset of
illness, hypoxemia can occur before changes are seen on x-ray.
• Once AHRF is diagnosed, the cause must be determined, considering both
pulmonary and extrapulmonary causes.
• Sometimes a known ongoing disorder (eg, acute MI, pancreatitis, sepsis) is
an obvious cause.
• In other cases, history is suggestive; pneumonia should be suspected in an
immunocompromised patient, and alveolar hemorrhage is suspected after
bone marrow transplantation or in a patient with a connective tissue
disease.
• Frequently, however, critically ill patients have received a large volume of IV
fluids for resuscitation, and high-pressure AHRF (eg, caused by ventricular
failure or fluid overload) resulting from treatment must be distinguished
from an underlying low-pressure AHRF (eg, caused by sepsis or pneumonia).
 Diagnosis
• High-pressure pulmonary edema is suggested by a 3rd
heart sound, jugular venous distention, and peripheral
edema on examination and by the presence of diffuse
central infiltrates, cardiomegaly, and an abnormally
wide vascular pedicle on chest x-ray.
• The diffuse, bilateral infiltrates of ARDS are generally
more peripheral.
• Focal infiltrates are typically caused by lobar
pneumonia, atelectasis, or lung contusion.
• Although echocardiography may show left ventricular
dysfunction, implying a cardiac origin, this finding is not
specific because sepsis can also reduce myocardial
contractility.
 Diagnosis
• When ARDS is diagnosed but the cause is not obvious
(eg, trauma, sepsis, severe pulmonary infection,
pancreatitis), a review of drugs and recent diagnostic
tests, procedures, and treatments may suggest an
unrecognized cause, such as use of a radiographic
contrast agent, air embolism, or transfusion.
• When no predisposing cause can be uncovered, some
experts recommend doing bronchoscopy with
bronchoalveolar lavage to exclude alveolar
hemorrhage and eosinophilic pneumonia and, if this
procedure is not revealing, a lung biopsy to exclude
other disorders (eg, extrinsic allergic alveolitis, acute
interstitial pneumonitis).
 Diagnosis
• Because the early features of ARDS are nonspecific,
alternative diagnoses must be considered.
• In the differential diagnosis of ARDS, the most
common disorders are cardiogenic pulmonary
edema, bilateral pneumonia, and alveolar
hemorrhage.
• Less common diagnoses to consider include acute
interstitial lung diseases (e.g., acute interstitial
pneumonitis); acute immunologic injury (e.g.,
hypersensitivity pneumonitis); toxin injury (e.g.,
radiation pneumonitis); and neurogenic pulmonary
edema.
 Treatment

• Mechanical ventilation if saturation is < 90%

on high-flow oxygen
• Underlying conditions must be addressed as
discussed elsewhere on the site.
• AHRF is initially treated with high flows of 70
to 100% oxygen by a nonrebreather face
mask.
• If oxygen saturation > 90% is not obtained,
mechanical ventilation probably should be
instituted.
• Specific management varies by condition.
 Mechanical ventilation in ARDS

• Nearly all patients require mechanical

ventilation, which, in addition to improving
oxygenation, reduces oxygen demand by
resting respiratory muscles. Targets include:
• Plateau alveolar pressures< 30 cm H2O (factors
that potentially decrease chest wall and
abdominal compliance considered)
• Tidal volume 6 mL/kg predicted body weight
to minimize further lung injury
• FIO2 as low as is allowed to maintain adequate
SaO2 to minimize possible oxygen toxicity
 Mechanical ventilation in ARDS

• PEEP should be high enough to maintain open alveoli and minimize

FIO2 until a plateau pressure of 28 to 30 cm H2O is reached. Patients with
moderate to severe ARDS are the most likely to have mortality reduced
by use of higher PEEP.
• NIPPV is occasionally useful with ARDS. However, compared with
treatment of cardiogenic pulmonary edema, higher levels of support for
a longer duration are often required, and EPAP of 8 to 12 cm H2O is often
necessary to maintain adequate oxygenation.
• Achieving this expiratory pressure requires inspiratory pressures > 18 to
20 cm H2O, which are poorly tolerated; maintaining an adequate seal
becomes difficult, the mask becomes more uncomfortable, and skin
necrosis and gastric insufflation may occur.
• Also, NIPPV-treated patients who subsequently need intubation have
generally progressed to a more advanced condition than if they had
been intubated earlier; thus, critical desaturation is possible at the time
of intubation.
• Intensive monitoring and careful selection of patients for NIPPV are
required.
 Mechanical ventilation in ARDS

• Conventional mechanical ventilation in ARDS previously focused on

normalizing ABG values. It is now clear that ventilating with lower tidal
volumes reduces mortality. Accordingly, in most patients, tidal volume
should be set at 6 mL/kg ideal body weight. This setting necessitates an
increase in respiratory rate, even up to 35/min, to produce sufficient
alveolar ventilation to allow for adequate carbon dioxide removal.
• On occasion, however, respiratory acidosis develops, some degree of
which is accepted for the greater good of limiting ventilator-associated
lung injury and is generally well tolerated, particularly when pH is ≥ 7.15.
If pH drops below 7.15, bicarbonate infusion or tromethamine may be
helpful.
• Because hypercapnia may cause dyspnea and cause the patient to
breathe in a fashion that is not coordinated with the ventilator,
analgesics (fentanyl or morphine) and sedatives (eg, propofol initiated
at 5 mcg/kg/min and increasing to effect up to 50 mcg/kg/min; because
of the risk of hypertriglyceridemia, triglyceride levels should be checked
every 48 h) may be needed. Sedation is preferred to neuromuscular
blockade because blockade still requires sedation and may cause residual
weakness.
 Mechanical ventilation in ARDS

• PEEP improves oxygenation in ARDS by increasing the volume

of aerated lung through alveolar recruitment, permitting the
use of a lower FIO2.
• The optimal level of PEEP and the way to identify it have been
debated. Recently, routine use of recruitment maneuvers (eg,
titration of PEEP to maximal pressure of 35 to 40 cm H2O and
held for 1 min) followed by decremental PEEP titration was
found to be associated with an increased 28-day mortality.
Therefore, many clinicians simply use the least amount of PEEP
that results in an adequate arterial oxygen saturation on a
nontoxic FIO2.
• In most patients, this level is a PEEP of 8 to 15 cm H2O,
although, occasionally, patients with severe ARDS require
levels > 20 cm H2O. In these cases, close attention must be paid
to other means of optimizing oxygen delivery and minimizing
oxygen consumption.
 Mechanical ventilation in ARDS

• The best indicator of alveolar overdistention is measurement

of a plateau pressure through an end-inspiratory hold
maneuver; it should be checked every 4 h and after each
change in PEEP or tidal volume.
• The target plateau pressure is < 30 cm H2O.
• If the plateau pressure exceeds this value and there is no
problem with the chest wall that could be contributing (eg,
ascites, pleural effusion, acute abdomen, chest trauma), the
physician should reduce the tidal volume in 0.5- to 1.0-mL/kg
increments as tolerated to a minimum of 4 mL/kg, raising the
respiratory rate to compensate for the reduction in minute
ventilation and inspecting the ventilator waveform display to
ensure that full exhalation occurs.
• The respiratory rate may often be raised as high as 35/min
before overt gas trapping due to incomplete exhalation results.
 Mechanical ventilation in ARDS

• If plateau pressure is < 25 cm H2O and tidal volume is < 6

mL/kg, tidal volume may be increased to 6 mL/kg or until
plateau pressure is > 25 cm H2O. Some investigators believe
pressure control ventilation protects the lungs better, but
supportive data are lacking, and it is the peak pressure
rather than the plateau pressure that is being controlled.
• With pressure control ventilation, because the tidal volume
will vary as the patient's lung compliance evolves, it is
necessary to continually monitor the tidal volume and
adjust the inspiratory pressure to ensure that the patient is
not receiving too high or too low a tidal volume.
• Prone positioning improves oxygenation in some patients
by allowing recruitment of nonventilating lung regions. A
recent study suggests this positioning may improve
survival.
 Mechanical ventilation in ARDS

• Optimal fluid management of patients with ARDS balances

the requirement for an adequate circulating volume to
preserve end-organ perfusion with the goal of lowering
preload and thereby limiting transudation of fluid in the lungs.
• A large multicenter trial has shown that a conservative
approach to fluid management, in which less fluid is given,
shortens the duration of mechanical ventilation and ICU
length of stay when compared with a more liberal strategy.
• However, there was no difference in survival between the 2
approaches, and use of a pulmonary artery catheter also did
not improve outcome.
• Patients not in shock are candidates for such an approach but
should be monitored closely for evidence of decreased end-
organ perfusion, such as hypotension, oliguria, thready pulses,
or cool extremities.
 Mechanical ventilation in ARDS

• A definitive pharmacologic treatment for ARDS that

reduces morbidity and mortality remains elusive.
• Inhaled nitric oxide, surfactant replacement,
activated protein C (drotrecogin alfa), and many
other agents directed at modulating the
inflammatory response have been studied and
found not to reduce morbidity or mortality.
• Some small studies suggest that systemic
corticosteroids may be beneficial in late-stage ARDS,
but a larger, prospective, randomized trial found no
reduction in mortality.
• Corticosteroids may be deleterious when given early
in the course of the condition.