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Cardio-Pulmonary Pathophysiology and Disease
Management
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PULMONARY EDEMA & ACUTE RESPIRATORY
DISTRESS SYNDROME (ARDS)
Overview :
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Acute Hypoxemic Respiratory Failure may develop
in many clinical settings and is common for
admission to the intensive care unit (ICU).
Hypoxemia occurs when oxygen is unable to reach
the blood in enough quantity to allow function.
Several causes of acute hypoxemia includes:
 Abnormalities involving the airway (tumor,
mucus plugging)
 Pulmonary vasculature (pulmonary embolus)
 Abnormal leakage of fluid from the vascular
space into the alveoli (pulmonary edema)←
most common cause
One of the most common cause of Pulmonary Edema
is ARDS.
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The lung lymphatic drainage system is the primary
system for removing the filtered fluid and protein
from the lungs.
 Drainage is assisted by the presence of a
modest pressure gradient within the
interstitium:
 HIGH pressure near the alveolus
 LOW pressure near the nonalveolar interstitium
and terminal lymphatic vessels
 + changes in intrathoracic pressure during
inspiration
Once the capacity of the interstitium to capture fluid
is surpassed and the rate of fluid accumulation
exceeds the rate of lymphatic drainage, Pulmonary
Edema occurs.
The accumulation of intra-alveolar fluid typically
results in a far more serious impairment of
oxygenation and ventilation.
Hydrostatic vs. Nonhydrostatic Edema
PULMONARY EDEMA
Pathophysiology :
The walls of the alveolus are separated from the capillary walls
by a very thin lung interstitium which minimizes the distance
for gases to diffuse between the airspace and blood.
 There is a balance between a normal physiologic
amount of fluid that leaks into the alveoli and a
mechanism that clears it. If the balance is broken,
pulmonary edema results.
 The surface area of the capillary network provides a
low-hydrostatic pressure (5-12 mm Hg) for the blood
to come into close contact with the alveolar gas.
 The interstitial space (Interstitium) between the
alveolus and capillary is very thin (<0.5 μm) and is
separated into two compartments :
1) The relative stiff alveolar side between the capillaries
and alveolar epithelium
2) The more compliant nonalveolar side around the
capillary wall
 The physical properties of the interstitium allow
absorption of water and solutes.
 Interstitial Fluid leads to a Hydrostatic Pressure (aka.
Interstitial Pressure) - similar to but opposes the
hydrostatic pressure in the vascular space.
 The nonalveolar component of the interstitium is
highly compliant and is able to accommodate
relatively large increase in fluid volume in the
interstitium without significant change In interstitial
hydrostatic pressure or leaking of fluid into the
alveolar space.
 The net exchange of fluids between the capillaries
and the interstitium of the lungs is determined by
the combined influences of hydrostatic and osmotic
forces within each compartment.
The intact dam (A) represents the normal condition in which
oncotic and hydrostatic forces (Starling forces) are balanced,
keeping the town dry (where the town represents the alveolar
space). (B) The dam remains intact but the water level has risen,
overwhelming the dam (i.e., exceeding the forces that resist
alveolar flooding) and flooding the town representing the
alveoli. This condition resembles hydrostatic pulmonary
edema. (C) A crack in the dam (simulating the alveolar-capillary
interface) allows water through the dam, flooding the town.
Note that the water flooding the town is darker because it
contains more sediment and mud from the lake. The condition
in (C) simulates the damage to the alveolar-capillary interface
that accompanies inflammation in acute respiratory distress
syndrome, causing nonhydrostatic pulmonary edema. The
muddier water flooding the town (representing the alveolar
space) in (C) than in (B) represents the more proteinaceous,
inflammatory nature of the fluid that floods the alveoli in
nonhydrostatic pulmonary edema.
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HYDROSTATIC PULMONARY EDEMA
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Aka. Cardiogenic Pulmonary Edema or Congestive
Heart Failure (CHF) - because of its close association
with cardiac abnormalities in intravascular
hydrostatic pressures that cause edema.
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Increased hydrostatic pressure in the pulmonary veins
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Increased hydrostatic pressure in the alveolar capillaries
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Increase fluid leakage out of the capillary
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In most patients, elevation of pulmonary venous
pressures is caused by increased pressures in the
left-sided heart pressures (left atrial or left
ventricular end-diastolic pressures), which are key
characteristics of left-sided heart failure (CHF), both
diastolic and systolic.
In the setting of increased hydrostatic pressure, the
endothelial and epithelial barriers remain INTACT
and IMPERMEABLE to large proteins and molecules,
thus, the fluid that accumulates in the alveoli
(measured using BAL), has characteristics identical to
those of normal interstitial fluid, which typically
contain minimal cells and low protein levels － can
also be referred as transudative fluid collections or
transudate.
Causes of Hydrostatic Pulmonary Edema
Cardiac
Volume Overload
 Left ventricular Failure
 Excessive fluid
- Systolic (MI,
administration
myocarditis)
 Renal failure
- Diastolic (left
 Hepatic failure
ventricular
 Hypoalbuminemia
hypertrophy)
(malnutrition)
 Valvular heart disease
(aortic, mitral)
NONHYDROSTATIC PULMONARY EDEMA
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Aka. Noncardiogenic Pulmonary Edema
Results from injury to the vascular endothelium
and/or alveolar epithelium which creates a loss if
integrity in the barrier between the vascular and
alveolar spaces.
Associated with increased total lung water despite
normal microvascular hydrostatic pressure.
All causes of ARDS feature disruption of endothelial
and epithelial barriers and typically occur under
conditions associated with widespread microvascular
injury to the lungs.
Vascular endothelial injury in the lungs causes
increased permeability and allows fluid to pass from
the capillaries to the interstitial space.
As protein-rich fluid enters the alveolar interstitium
from the vasculature, the osmotic gradient is
drastically changed and no longer opposes fluid
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movement from the capillary into the lung. This
process s likely aided both by:
1. Damage to the normally impermeable alveolar
epithelial barrier － key feature of ARDS, and;
2. Impaired alveolar fluid clearance
Regardless of cause, ARDS is typically associated with
an influx of polymorphonuclear neutrophils, which
release inflammatory bi-products such as proteases,
phospolipases, and oxygen radicals into the lung.
 These processes lead to degradation of the
endothelial and epithelial barriers and recruit
additional neutrophils to continue the
inflammatory cascade.
The alveolar fluid that accumulates in ARDS typically
demonstrates very high levels of protein, neutrophils,
and total cells －comparable to and consistent with
exudative fluid collection or exudates.
Neutrophils play a central role in the development of
ARDS.
Other causes of inflammatory cascade that damages
the alveolar membrane integrity and contribute to
the hemodynamic and inflammatory events in ARDS:
a. Chemical insults (gastric aspiration)
b. Inhalation injury of noxious gas such (chlorine)
c. Immunologic pathway (tumor necrosis factor
[TNF] or interleukin-8 [IL-8])
Sepsis － one of the most common cause of ARDS;
features activation of inflammatory pathways.
Acute illnesses associated with the development of
ARDS also can lead to widespread systemic organ
injury (e.g., renal failure, encephalopathy), which is
caused by the same inflammatory pathways leading
to vascular injury, local tissue injury, and fluid leak in
those organs, as seen in the lungs.
Multiple Organ Dysfunction Syndrome (MODS) －
syndrome of diffuse organ impairment.
 ARDS is the pulmonary manifestation of MODS.
Gas Exchange and Lung Mechanics in Pulmonary
Edema
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Pulmonary edema is characterized by reduced lung
and chest wall compliance (restrictive physiology)
and refractory hypoxemia.
The stiff lung and chest wall lead to increased work
of breathing.
Patients with pulmonary edema of any cause use a
higher fraction (25%-50%) of their total metabolic
output to support their increased WOB. If the insult
is not reversed, the combination of hypoxemia and
increased WOB leads to respiratory failure and the
need for ventilatory assistance.
NOTE : In most cases, the severity of lung
dysfunction and hypoxemia is MORE SEVERE and
MORE PROLONGED in the the nonhydrostatic
pulmonary edema compared with the hydrostatic
pulmonary edema caused by CHF.
In addition to the replacement of air with fluid, the
problems with gas exchange and increased WOB
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seen in ARDS are also caused by the inflammatory
nature of the intra-alveolar fluid causing impaired
surfactant synthesis, secretion and function.
The resulting surfactant abnormalities lead to
increased alveolar collapse (atelectasis), due to the
loss of surfactant’s natural effects on lowering
surface tension at the air-liquid interface in the
alveolus.
The negative effects of alveolar consolidation and
atelectasis on pulmonary gas exchange are worsened
by a loss of the normal vascular response to alveolar
hypoxemia. Normally, pulmonary arteries in areas of
alveolar hypoxia will CONSTRICT as a physiologic
response to preserve ventilation/perfusion V̇/Ȯ
matching. However, in ARDS, this normal
vasoconstrictive response is impaired in hypoxic
areas; thus nonaerated alveoli receive higher blood
flow than needed, which contributes to severe V̇/Ȯ
mismatching and an intrapulmonary right-to-left
shunting of blood flow (leading to hypoxemia.
The principal mechanism for the respiratory distress
syndrome (RDS) in neonates was identified as a
deficiency of surfactant.
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
Overview :
AMERICAN-EUROPEAN CONSENSUS CONFERENCE (AECC)
 Was created in 1994 with the collective input of
established experts from EU and USA.
 AECC definition included all patients beyond
newborns and discontinued use of the term adult in
ARDS.
 Five Central Components:
1. Reduced lung compliance
2. Hypoxemia (ratio of PaO2/FiO2 <300)
3. An acute illness associated with the
development of ARDS that can trigger the
onset of ARDS.
4. No evidence of CHF (typically based on direct
measurements from an invasive pulmonary
catheter of vascular filling pressures on the left
side of the heart)
 Acute Lung Injury － shares all characteristics of
ARDS except the severity of hypoxemia in ALI is LESS
SEVERE (P/F ratio of <300) as compared with ARDS
(P/F ratio of <200).
 The AECC definition served as “gold standard” for
identifying and enrolling patients with ARDS into
clinical trial for almost 20 years.
BERLIN CRITERIA
 In 2012, the definition of ARDS was revised and
updated by a new international consensus group that
met in Berlin, Germany, in 2011.
 The updates were made in response to the
limitations of AECC criteria that had been identified.
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Key Features:
1. Discontinuation of the us the term “acute lung
injury” (ALI), which had proven to be nothing
more than redundant terminology without
adding meaningful value.
2. Creation of three categories for ARDS disease
severity (mild, moderate, severe) based on
ranges of PaO2/FiO2 (P/F) ratio and levels of
positive end-expiratory pressure (PEEP).
3. Inclusion and acceptance of noninvasive
techniques to estimate left heart pressures
including echocardiography.
4. Enhanced specificity for interpretation of chest
radiographs when determining the presence of
bilateral infiltrates or opacities most
characteristic of nonhydrostatic pulmonary
edema.
5. Greater specificity regarding the time frame by
which the development of the disease may still
be considered “acute” (<1 wk of the triggering
condition).
ARDS Severity
PaO2/FiO2 (P/F) Ratio
201-300 ---------------------- Mild ARDS
101-200 ---------------------- Moderate ARDS
<100
---------------------- Severe ARDS
NOTE : the P/F ratio is calculated using the PaO2 obtained
from an arterial blood gas (ABG) analysis and FiO2 at the
time ABG value was obtained.
Example: A PaO2 value of 90 mm Hg was obtained through
ABG analysis from a px who is receiving 50% supplemental
O2.
90/.50 = 180 (the px has Moderate ARDS)
Distinguishing ARDS from Nonhydrostatic Pulmonary
Edema in Clinical Practice
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Patients presenting with hydrostatic pulmonary
edema are much more common than ARDS and
should be considered whenever the history or
physical examination findings suggest on the of the
causes of CHF.
A clinical history of infection, recent trauma, or risk
factors for aspiration may be present in either groups,
but the presence of these risk factors (triggers)
favors a diagnosis of ARDS.
Pulmonary Artery Catheter (aka. Right Heart
Catheter or Swan-Ganz Catheter) used to measure
invasively the hemodynamic variables and can
differentiate hydrostatic and nonhydrostatic edema.
 NOTE: Shown not to be essential in the
diagnosis of ARDS or beneficial in the
management.
Echocardiography when combined with other
physical examination features (capillary refill and
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mottling), can provide reliable information that can
effectively guide clinical decision making.
Bronchoalveolar Lavage (BAL) can be used to obtain
the composition of alveolar edema fluid and
differentiate CHF from ARDS.
 Increased inflammatory cells and serum
proteins (exudative fluid) are seen on ARDS.
Clinical Signs and Symptoms of ARDS
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Anatomic Alterations in ARDS
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The lungs of patients affected by ARDS undergo
similar anatomic changes, regardless of the cause of
the disease.
In response to injury, the pulmonary capillaries
become engorged and the permeability of the
alveolar-capillary membrane INCREASES.
Interstitial and intraalveolar edema and hemorrhage
ensue, as well as scattered areas of hemorrhagic
alveolar consolidation. These processes result in a
decrease in alveolar surfactant and in alveolar
collapse, or atelectasis.
As the disease progresses, the intraalveolar walls
become lined with a thick, rippled hyaline
membrane identical to the hyaline membrane seen
in newborns with respiratory distress syndrome
(hyaline membrane disease).
 The membrane contains fibrin and cellular
debris. In prolonged cases there is hyperplasia
and swelling of the type II cells. Fibrin and
exudate develop and lead to intraalveolar
fibrosis.
In gross appearance the lungs of patients with ARDS
are heavy and “red,” “beefy,” or “liverlike.” The
anatomic alterations that develop in ARDS create a
restrictive lung disorder.
Major Pathologic/Structural Changes Associated with
ARDS :
― Interstitial and intraalveolar edema and
hemorrhage
― Alveolar consolidation
― Intraalveolar hyaline membrane formation
― Pulmonary surfactant deficiency or abnormality
― Atelectasis
The illustration compares a normal alveolus (A) and an alveolus with acute respiratory distress syndrome
(ARDS) (B). The normal alveolus includes intact type I and II pneumocytes along with a layer of surfactant
at the air-liquid interface over the epithelium. In ARDS, there is injury and loss of type I cells through
apoptosis and necrosis, some preservation of typically dysfunctional type II cells and depletion and
inactivation of surfactant. The alveolar lumen becomes filled with protein-rich fluid from leak of serum,
activated neutrophils releasing mediators like matrix metalloproteinases (MMP) and neutrophil elastases
(NE), and leak of serum coagulation factors that form fibrin-rich hyaline membranes lining the alveolar
wall.
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The clinical manifestations associated with ARDS
usually appear within 6 to 72 hours of an inciting
event, and worsen rapidly.
Patient typically presents with:
 Dyspnea
 Cyanosis
 Bilateral crackles
 Tachypnea, tachycardia
 Diaphoresis
 Use of accessory muscles
 Cough and chest pain may also be present
The general clinical course is characterized by several
days of hypoxemia that requires moderate to high
concentrations of inspired oxygen.
The bilateral alveolar infiltrates and diffuse crackles
are persistent during this period, and the patient’s
overall health status is often fragile as a result of
severe hypoxemia.
Arterial Blood Gases in ARDS
Mild to Moderate ARDS
Acute Alveolar Hyperventilation with Hypoxemia
(Acute Respiratory Alkalosis)
↑pH ↓PaCO2 ↓HCO3* ↓ PaO2 ↓ SaO2 / SpO2
Severe ARDS
Acute Ventilatory Failure with Hypoxemia
(Acute Respiratory Acidosis)
↓pH ↑PaCO2 ↑HCO3* ↓PaO2 ↓SaO2 / SpO2
*Decreased but NORMAL
Clinical Features of CHF and ARDS
Features Common to Both
 Symptoms of anxiety, dyspnea, tachypnea
 Decreased compliance and reduced lung volumes
 Hypoxemia (mild to severe), often requiring ventilator
assistance
 CXR shows diffuse alveolar and interstitial infiltrates
Features Favoring CHF
 Suggestive clinical history (see causes of hydrostatic pulmonary edema)
 Symmetric pulmonary infiltrates, cardiomegaly, or pleural
effusions on CXR
 Elevated pulmonary artery catheter wedge pressure (1830 mm Hg)
 Bronchoalveolar lavage fluid: LOW protein and minimally
increased cellularity
 Prompt (<12-24 h) and lasting response to diuretics and
CHF therapy
Features Favoring ARDS
 Clinical history of a risk factor for ARDS
 Asymmetric, peripheral infiltrates on chest radiograph
 Bronchoalveolar lavage fluid: VERY HIGH protein level and
marked cellular influx
 Transient improvement with CHF therapy, but uncommon
to significantly improve during initial trial 12-36 h.
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Histologic Findings in ARDS
The changes in the lung tissue in ARDS are typically separated
into two phases based on the overall duration of the disease
process:
(1) Acute Exudative Phase (1-7 days)
 Exudative phase is characterized by diffuse damage
to alveoli and blood vessels and the influx of
proteinaceous fluid and inflammatory cells into the
interstitium and alveolar spaces.
 There is capillary congestion, intra-alveolar edema,
and injury/death of pneumocytes that form the
alveolar wall which includes type I pneumocytes (the
predominant structure cells lining the alveoli) and
type II pneumocytes (makes and secretes surfactant).
 Cellular injury to the lining (endothelium) of the
pulmonary capillaries.
 The alveolar spaces are lined with hyaline
membranes － composed of cellular debris and
condensed plasma proteins.
 Thus, the early name for ARDS is “Hyaline
Membrane Disease”
 The exudative phase is typically short, lasting only a
few days, and is fully reversible.
(2) Fibroproliferative Phase aka. Organizing Phase (3 days
to weeks)
 After the cause of lung injury is controlled, a process
of lung repair begins.
 This appears as an overabundance of alveolar type II
pneumocytes and infiltration or proliferation by
fibroblasts within the alveolar basement membrane
and intra-alveolar spaces.
 Fibroblasts drive intra-alveolar and interstitial
fibrosis.
 The extent of fibrosis determines the degree of
pulmonary disability in patients who survive ARDS.
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patients
have
nearly
complete
normalization of lung compliance and oxygenation 612 months after the illness.
 However, a small percentage (5-10%) of
patients do not fully return to normal and can
experience chronic respiratory disability related
to pulmonary fibrosis and obliteration of
pulmonary vasculature.
 Secondary forms of lung injury include nosocomial
infection, O2 toxicity, and forms of ventilatorinduced lung injury (VILI).
Risk Factors (Triggers) and Host Susceptibility
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Risk Factors / Triggers － refers to acute illnesses
that stimulates an acute inflammatory response that
leads to lung injury.
Direct Injury － occurs as the result of triggers that
begin in the lung (e.g., pneumonia and aspiration)
and create an acute inflammatory reaction, within
the lung, that initially leads to injury of the alveolar
epithelium and subsequent damage to the
interstitium and capillary endothelium injury.
― Pneumonia (viral, bacterial, fungal)
― Gastric aspiration
― Toxic inhalation (phosgene, cocaine, smoke,
high O2 concentration)
― Near drowning
― Lung contusion
Indirect Injury －caused by acute illnesses that begin
outside of the lung (e.g., pyelonephritis, trauma or
massive hemorrhage) and trigger and acute
inflammatory reaction that initially injures that
capillary endothelium via circulating inflammatory
mediators, which leads to subsequent injury of the
interstitium and alveolar epithelium.
― Sepsis and prolonged shock
― Burn injury (chemical or heat induced)
― Multiple trauma
― Transfusions (TRALI)
― Pancreatitis
― Gynecologic causes (abruptio placentae,
amniotic embolism, eclampsia)
― Drug effect (trans-retinoic acid for acute
leukemia)
― Sickle cell crisis
The key factor that determine which patients will
develop ARDS are the severity and duration of the
risk factors, and variables that lead some patients to
be more susceptible.
Sepsis is the most common cause ; among all
patients with sepsis, fewer than 20% will develop
ARDS ; as the severity of sepsis increases, the
likelihood of ARDS developing also increases (up to
50%).
Pneumonia is the most common direct insult cause
of ARDS
Important host factor susceptibility:
 Increased age (age >50 yrs)
 Liver disease
 Alcoholism
 Genetic polymorphisms related to inflammatory
mediators (e.g., IL-1, TNF, surfactant)
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Treatment and Management
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The hallmark of treatment of ARDS is supportive care
with mechanical ventilation with disease specific
treatment.
Identifying and treating the cause of ARDS is an
important step to stop progression of the lung injury.
Positive End-Expiratory Pressure (PEEP)
Goals and Priorities for Mechanical Ventilation in
ARDS
1. Lung Protective Strategy
a) Low Tidal Volume - using predicted body weight
b) Low plateau or driving pressure
c) PEEP titration - minimize derecruitment
2. Goals for Gas Exchange
a) Permissive hypercapnia
b) Avoidance of hyperoxia and hyperoxemia
MECHANICAL VENTILATION
 MV is the cornerstone of supportive care for patients
with ARDS.
 Goals of Mechanical Ventilation:
1. Safety － encompasses two main clinical
objective: a) ensuring gas exchange;
b)preventing further lung injury or VILI.
2. Comfort － focuses on ensuring synchrony
with the VR and balancing the WOB distribution.
3. Liberation
NOTE: Safety is main goal during early exudative
phase while comfort and liberation are the main
goals as the disease processes.
Setting Tidal Volume
 Barotrauma － is the rupture of alveolar structures,
presumably due to excessive airway pressure, that
results in gross leakage of air outside of the lung
parenchyma
into
adjacent
tissue
spaces
(pneumothorax and pneumomediastinum).
 Volutruama － is a form of injury to the alveolar
structure; there is a microscopic cellular injury to the
alveolar and capillary walls causing them to become
leaky. This becomes the trigger for an inflammatory
cascade that may trigger or worsen ARDS.
 Lung Protective Ventilation (LPV) － aka. Low Tidal
Volume Ventilation (LTVV) a strategy of using a tidal
volume (VT) that avoids volutrauma.
 Made by a landmark trial known as the ARMA
trial (2000).
 Use of VT = 6 mL/kg PBW
Formula:
PBWMEN = 50.0 + 0.905 x (Height in cm - 152.4)
PBWWOMEN = 45.5 + 0.905 X (Height in cm - 152.4)
Pressure-Volume (P-V) Curve
 Has an S or Sigmoid Shape
 Can be established by measuring lung volume during
step increases in airway pressure.
 Can help us understand the rationale for using PEEP.
 Initial Limb － has large changes in pressure that are
associated with only small increase in volume;
inspiratory pressure increases faster than lung
volume; have high surface tension.
 Middle Limb － has the best change in pressure per
volume; represents the most compliant portion of
the curve.
 Compliance = ΔV/ΔP
 Final Limb － similar with Initial Limb; large changes
in pressure with small increase in volume.
 Lower Inflection Point (LIP) － the point where the
lower limb shifts to middle limb.
 Represents at which the recruitment (opening)
of the alveoli units begin and point below
where the units close (collapse, atelectasis) if
the airway pressure at end expiratory drops
below.
 Upper Inflection Point (UIP)－point which expansion
of the alveoli units becomes more difficult and may
cause injury from overdistention.
PEEP
 Reduces lung collapse thereby increasing the amount
of aerated lung, a phenomenon known as
recruitment.
 During mechanical ventilation, the goals for titration
of PEEP are staying above the LIP to avoid repeated
cycles of alveolar collapse.
 In ARDS, the P-V curves are flatter and more
deviated to the right thus making it challenging to
determine the best PEEP.
 The P-V relationships in ARDS are highly dynamic and
and depends on the px’s overall condition, can
change rapidly due to fluctuations in the patient’s
lung compliance (pneumonia, pulmonary edema),
synchrony with the vr, and many more.
 NOTE: the use of PEEP is further complicated by the
potential adverse hemodynamic effect of PEEP to
decrease venous return to the right heart.
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Higher levels of PEEP in more severe disease (P/F
ratio <150) may lead to decreased mortality and less
use of rescue strategies.
NOTE: when decreasing PEEP, the changes in
physiology become evident usually within 5 minutes;
when increasing PEEP, the changes in physiology
usually take at least 60 minutes.
Recruitment Maneuver － use of transient large
increases in PEEP to generate greater recruitment
that may be sustained even after return of PEEP to
their prior levels.
 Discontinued due to lack of evidence (ARDS
Network ALVEOLI Trial).
In most patients with ARDS, PEEP levels less than 20
cm H20 are generally preferred.
 Use of PEEP >20 cm H2O should not the
routinely used.
Managing Airway Pressures
 Plateau Airway Pressure (Pplat) － the goal is to
maintain a Pplat of <30 cm H2O.
 Driving Pressure － (ΔP) represents the airway
pressure during inspiration (above PEEP) that is not
influenced by airway resistance (which affects the
peak inspiratory pressure but not Pplat).
 Driving Pressure = Pplat - PEEP
 Ideally should be ≤15 cm H2O
 NOTE: Increasing the PEEP may improve lung
recruitment and oxygenation but may also increase
the Pplat, which may indicate the UIP of the P/V
curve is being reached or exceeded and creating risk
for VILI from overdistention.
Selecting the Mode of Ventilation
 The mode of ventilation should principally serve the
goals of safety (avoiding VILI) while also ensuring
adequate ventilation and oxygenation to maintain
the patient’s frequently evolving cardiorespiratory
and metabolic needs.
 The mode that most directly achieves the goal of
controlling the Vt is Volume Control Mode. In this
mode, the clinician sets the VT (6 mL/kg of PPBW)
and the ventilator delivers the target VT on every
breath, whether the patient-initiated or not.
 Cons : patient-ventilator dyssynchrony->patient
discomfort, increased WOB, increased O2
consumption, and delivery of large (unsafe) VT.
 As an alternative to volume control, patients may be
placed on Pressure Control Mode, the VT depends
on the set inspiratory pressure above the PEEP and a
set inspiratory time.
 To resolve dyssynchrony, sedation, analgesia and or
neuromuscular blockade (NMD) are used to blunt
patient respiratory effort.
Respiratory Rate and Inspiratory Time
 ARDS is associated with alveolar consolidation, V/Q
mismatching, increased physiologic shunt, and
deadspace ventilation.
 Critically ill patients typically have elevated rates of
metabolism and CO2 production, thus, requiring
higher minute ventilation to maintain PaCO2 in the
normal range.
 Conventionally, respiratory frequency is kept <35
breaths/min.
 NOTE: Faster respiratory rates will not allow
adequate time for exhalation, leading to air-trapping
(auto-PEEP) and overdistention which can worsen
oxygenation and reduce cardiac output.
 Permissive Hypercapnia is allowed in the absence of
contraindication (elevated intracranial pressure); the
goal is to maintain the arterial pH at no less than
7.15 - 7.20.
 Correction of pH can also be achieved either
pharmacologic supplementation (IV or oral) of
bicarbonate or physiologic retention of
bicarbonate by the kidneys.
 In rate instances, extracorporeal removal of
CO2 is considered.
 Closely related to the ventilator rate is the
Inspiratory Time (Ti), which is the means by which
clinicians and RTs adjust the Inspiratory-toExpiratory Ratio (I:E) Ratio.
 Intubated patients with COPD require LONGER
expiratory time.
 Intubated patients with ARDS use an I:E ratio of
1:1 due to their stiffer lungs and required less
time for exhalation and are achieved decreasing
inspiratory flow rates which results in desirable
reductions of Pplat and driving pressures to
maintain targets of LPV.
 NOTE: As RR is increased and Ti is prolonged, risk for
air trapping and auto-PEEP will naturally increase.
 Diligent monitoring of auto-PEEP during the
management of mechanical ventilation in patients
with ARDS is ESSENTIAL.
Oxygen Titration
 Administering high levels of supplemental O2 (FiO2)
can cause direct lung injury as a result of O2 Toxicity.
 O2 toxicity is time and dose dependent.
 Continuously titrate and minimize the FiO2 and PEEP
while targeting SpO2 between the range of 88%-96%.
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LEZZGO Batch TRES! RTRP ✨Cutie✨ | @venceoy
Adjunctive Strategies to Improve Lung Function
a. Prone Positioning
 The distribution of lung injury in patients with ARDS
is heterogeneous and changing the position of the
patient can result in improved V/Q mismatching
within the lungs.
 Alveolar consolidation is ARDS tends to be more
pronounced in the dependent lung zones (posterior
regions when then patient is lying supine), where
blood flow is greatest.
 Proning (placing chest and face down) - “put the
good lung down”.
 Mechanism include: improved V/Q matching,
increased FRC, increased CO, more effective drainage
of upper and lower airway secretions, and improved
diaphragmatic excursion.
 Ventilation in the supine position causes compressive
forces on dorsal airspaces, resulting in
“derecruitment” of lung units, and the phenomenon
is reversed by ventilation in the prone position.
 Some patients may not tolerate prone ventilation or
may have relative contraindication such as open
surgical wounds or late-trimester pregnancy.
Three Theoretical Benefits of Prone Positioning:
1. The posterior lung has a larger surface area for gas
exchange which reduces V/Q mismatch
2. Shifting the heart anterior offloads its weight from
the surrounding lung tissue
3. The large airways move to a gravitationally
dependent position that better facilitates drainage of
posterior and lower-lobe secretions.
b. Neuromuscular Blockade
 Used to enhance compliance and synchrony with
mechanical ventilation in patients with ARDS.
 Patients who continue to be hypoxemic despite
optimizing ventilator settings and adequate
ventilation, a trial of NMB by bolus or continuous IV
infusion is frequently performed.
 Similar to prone positioning, the benefit of NMD was
most evident in patients with severe ARDS (P/F ratio
<120).
 Use of NMD in patients with only mild to moderate
ARDS who are stable on conventional ventilation
should be AVOIDED.
c. Inhaled Vasodilators
 The potential benefits of pulmonary vasodilators
delivered via airway is based on deliver of the
vasodilator will be distributed to well-ventilated
portions of the lung, where the vasodilator leads to


local vasodilation. In this way, well-ventilated ares of
the lung receive a greater potion of the total
pulmonary blood flow, which results in improved
oxygenation by reducing shunt factor and V/Q
mismatch.
Nitric oxide (NO) and prostacyclin are naturally
occurring potent vasodilators that play a critical role
regulating blood flow within the normal lungs.
 NO is highly soluble gas that diffuses readily
through various tissues.
 Prostacyclin
is
a
naturally
occurring
prostaglandin and sever analogues have been
pharmacologically developed (epoprostenol
[Flolan]) and are standard of care in pulmonary
arterial hypertension － can be nebulized and
provide effects similar to inhaled NO.
NOTE: It is recommended that the use of inhaled
vasodilators be limited to patients with most severe
forms of ARDS (P/F <80) and used only as abridge to
maintain oxygen while initiating more invasive
adjunctive therapies.
d. Beta-2 Agonists
 In addition to their effects as bronchodilators, high
dose of beta-2 agonists (albuterol, salbutamol) have
been shown to accelerate clearance of alveolar
edema by the epithelium of the alveolar wall in
animal models. However, clinical trial in humans
prove to have no significant effect.
 NOTE: Thus, the use of beta-2 agonist therapy for
improving alveolar fluid clearance in ARDS is NOT
RECOMMENDED.
e. Exogenous Surfactant Administration
 Surfactant dysfunction and deficiency is a wellestablished component of RDS in premature infants,
as well as in children and adults with ARDS.
 Surfactant abnormalities contribute to the
development of ARDS by promoting instability of the
alveolar units (airway shear trauma, atelectasis, and
right-to-left shunt) and by allowing inflammatory
injury to alveoli to continue unchecked.
 Delivery of exogenous surfactants via direct
intratracheal administration has become a
cornerstone of therapy in RDS since the early 1990s.
 Surfactant Preparations
I. Natural surfactant (harvested from lungs of
animals)
II. Synthetic surfactant (created artificially)
 The depletion of surfactant in RDS of prematurity is
secondary to the lack of lung maturation and
surfactant production. In contrast, the surfactant
depletion of ARDS (in adults) is caused
by
inflammation of the alveolus and subsequent
degradation of the endogenous surfactant.
 Clinical trials have demonstrated improvement in
oxygenation
with
intratracheal
surfactant
administration (natural & synthetic). However, it is
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LEZZGO Batch TRES! RTRP ✨Cutie✨ | @venceoy
proven to be short lived (24-72 hours) and have NOT
demonstrated significant impact on clinical outcomes
such as mortality or duration of mechanical
ventilation in survivors.
 These negative results in ARDS (in contrast to
clear benefit in neonatal RDS) are most likely
explained by degradation of the exogenously
administered surfactant via the same
inflammatory mechanisms that depleted the
patient’s native surfactant.
Alternative and Rescue Ventilation Strategies


In those uncommon scenarios, alternative ventilatory
strategies are available and may prove beneficial in
selected patients but are less well-studied or
standardized. These therapies are often referred as
“rescue” and “salvage” therapies.
The thresholds for using alternative approaches
differs across medical institutions but are typically
defined by persistent markers of unsafe ventilation,
such as excessive plateau pressures (e.g., >35 cm
H2O), FiO2 (e.g., >80%), PEEP (e.g., 20 cm H2O), or
hemodynamic instability caused by positive pressure
ventilation.
a. Inverse-Ratio Ventilation (IRV)
 During inverse ratio ventilation (IRV), the inspiratory
time on the ventilator is prolonged so that the I:E
ratio is reversed (i,e., the inspiratory time now
exceeds expiratory time).
 The mechanism for benefit of IRV likely include some
combination of increased percent of time during
each respiratory cycle that alveoli remain patent to
reduce V/Q mismatch and increasing mean airway
pressure to recruit alveolar units.
 NOTE: Increased mean airway pressure results
from incomplete lung emptying (air trapping,
auto-PEEP, intrinsic PEEP).
b. Airway Pressure Release Ventilation (APRV)
 Is a form of pressure control intermittent mandatory
ventilation with IRV (I:E ratio of ≥4:1).
 The aim of APRV is to increase the mean airway
pressure for alveolar recruitment while allowing the
patient to spontaneously breath.
 Two levels of PEEP:
a. HIGH PEEP (25-30 cm H2O for 5-6 s)
b. LOW PEEP (0-5 cm H2O for 0.5-1 s)
 Cons: risk for large tidal volumes, leading to VILI and
high transpulmonary pressures.
 Shown to improve small case series of patients
during H1N1 influenza pandemic.
c. High Frequency (HFV)
 Uses a rapidly moving piston to create movement of
air through a circuit.
 Allows setting a mean airway pressure over which
oscillations happen.




Tidal volumes generated by HFV are typically smaller
than the patient’s anatomic dead space and use
higher mean airway pressures to maintain alveolar
patency and theoretically prevent VILI and minimize
hemodynamic compromise caused by larger
inspiratory pressures of conventional modes.
NOTE: HFV was initially devised as a method to
minimize the hemodynamic effects of conventional
mechanical ventilation (i.e., the large inflating
pressures and volume).
Patients on HFV will be exposed to high mean airway
pressures and PEEP, which may reduce CO and
overall O2 delivery despite elevated arterial
oxygenation.
The use of HFV in routine ARDS management is NOT
recommended. Although, HFV as a rescue strategy
for patients with severe refractory ARDS (P/F<80)
remains an option.
d. Extracorporeal Support
 Extracorporeal Membrane Oxygenation (ECMO) and
Extracorporeal Carbon Dioxide Removal (ECCO2R)
involve establishing a circuit for diverting a large
portion of the cardiac output through an artificial
gas-exchange device, or “artificial lung,” to facilitate
the exchange of O2 and CO2.
 For respiratory failure, extracorporeal support is
typically performed using venovenous circuits (versus
venoarterial), which are able to support gas
exchange without need for invasive arterial cannulas
and hemodynamic support and can currently be
offered through single venous cannula.
 In considering ECMO for patients with refractory
severe ARDS (P/F <80), assessment and referral to
ECMO center (if needed) should be made early after
optimization of conventional approaches and time
sufficient is allowed to confirm lack of improvement
or worsening.
Nonventilatory Supportive Care Checklist
Respiratory
Neruologic/
Musculoskeletal
Gastrointestinal
Infection
Prevention
 Fluid conservative management
 Daily spontaneous breathing trial
 Minimize sedation and daily awakening
 Delirium prevention and treatment
 Early mobilization
 Gastric ulcer prophylaxis
 Enteral nutrition
 Avoid excess caloric intake
 Remove indwelling catheters
 Antibiotic deescalation
 Oral chlorhexidine
 Head-of-bed elevation
 Hand hygiene
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LEZZGO Batch TRES! RTRP ✨Cutie✨ | @venceoy
Nonventilatory Supportive Care
a. Conservative Fluid Management
 Critically ill patients receive fluids both IV and oral for
a wide variety of indications:
― To maintain perfusion
― IV medications
― Nutrition
― Hydration
― Correct electrolyte imbalance
 The amount of fluids taken in by critically ill patients
invariably exceeds the amount of fluids that the
patient loses, and patients often gain approximately
1 L of fluid per day.
 The conservative strategy was achieved essentially
by eliminating maintenance IV fluids and earlier
institution of and increased attention toward diuresis.
b. Sedation and Analgesia
 Protocolized sedation and scheduled daily
interruptions of sedation (awakenings) lead to
shorter times on mechanical ventilation and
decreased length of ICU stay.
 Using benzodiazepines (e.g.,lorazepam or midazolam)
carries the greatest risk for these adverse
neurocognitive effects. One of the earliest
neurocognitive warning signs in the ICU is the
development of ICU-associated delirium, which can
be caused by several common environmental
challenges in the ICU, including lack of sleep, noise,
use of restraints, and immobility.
Summary Checklist





The pathologic findings of ARDS are characterized
early by acute alveolar inflammation and injury with
neutrophils and cytokines, which can rapidly reverse.
In severe and/or persistent ARDS, a fibrotic phase
can develop and can lead to a more prolonged
course of recovery.
The clinical definition and diagnosis of ARDS is based
on the presence of a syndrome of characteristics that
include abnormalities on the chest x-ray, hypoxemia,
and a known risk factor or trigger that generates
acute inflammation.
ARDS is a common critical illness with high associated
mortality and morbidity, but close attention to care
protocols for patients with ARDS, in particular lungprotective lung ventilation, has improved survival
and reduced recovery time for survivors.
Ventilatory strategies for patients with ARDS are
designed to minimize VILI by emphasizing low tidal
volumes and driving pressures and sufficient levels of
PEEP.
Multiple modes of mechanical ventilation can be
used to achieve LPV, but providers must prioritize
avoiding VILI and be willing to tolerate reduced gas
exchange, including lower oxygenation and higher
PaCO2.
c. Nutrition
 Malnutrition in the ICU leads to poor outcomes, but
clinicians including RTs should be aware that excess
nutritional supplementation can also lead to adverse
consequences.
 The potential negative impact of overfeeding －
increased CO2 production, increased minute
ventilation, and potentially delayed liberation from
mechanical ventilation.
d. Mobility
 Prolonged period patients spend lying in bed on
mechanical ventilation has an adverse effect on the
mass and function of muscles for patients in the ICU.
 Profound and persistent weakness (≥12 months) is a
commonly reported long-term outcome in ARDS
survivors.
 This adverse consequence is attributable to
inflammatory injury to the muscles and peripheral
nerves, pharmacologic agents (i.g., steroids and
neuromuscular blockers) and most importantly
immobilization.
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