Acute Respiratory Distress Syndrome
Heba Ismail, M.B.Ch.B
Assistant Clinical Professor
Division Of Pulmonary and Critical Care
Medicine
ARDS
Objectives
 Updated definition of ARDS
 Briefly review Pathophysiology and Pathogenesis
 Etiology/Risk factors
 Clinical Presentation
 Diagnosis, Differential Diagnosis
 Management
ARDS
Case #1
A 70-year-old man was admitted to the ICU
 acute hypoxemic respiratory failure
48 hours earlier
 He underwent a surgical resection of the left lower lobe for stage
IIIB adenocarcinoma of the lung.
Intra-operative course
 He received a total fluid infusion of 5.5 L (including 3 units of
packed red blood cells)
 The cumulative fluid infusion given during the peri-operative
period was 8.0 L with a net negative 0.7L
ARDS
Case#1
Post Operative course
Extubated and transferred to the ward
36 hours later
dyspnea and hypoxemia were noted
 re-intubated
ARDS
Case#1
Past Medical History
 Adenocarcinoma of the lung, stage IIIb, diagnosed 3
months before surgery, treated with preoperative
neo-adjuvant chemotherapy and radiotherapy
 History of moderate COPD
Social History
 80-pack-years of cigarette smoking
 chronic alcohol consumption of approximately 30g of
ethanol per day.
ARDS
Case #1
Pre-operative evaluation
 Complete blood count and blood chemistry were
normal
 Pre-operative evaluation for chronic heart
disease was negative
 Forced Expiratory Volume in 1s (FEV1) was 1.79
L; 58% of the predicted value; calculated postoperative FEV1 was 49% of the predicted value
ICU Admission
 Physical examination
 Vital signs,
 BP 100/70 mmHg, Pulse 120/min, Respirations 33/min, SpO2 of 85% on
100% Non rebreather, Temperature 37.0 C
 Cardiovascular
 S1, S2 normal
 Respiratory
 Decreased breath sounds over the left lower lung field, diffuse endinspiratory crackles over the remaining lobes .
 Laboratory Data
 Normal complete blood count and chemistry
 Blood and bronchoalveolar lavage (BAL) specimens were collected and
sent for microbiologic analysis.
 Blood cultures, done
 Arterial blood gases: (on FiO2 0.6), PaO2 70mmHg,, PaCO2 45mmHg,
HCO3 24, PaO2/ FiO2 117
CXR
ARDS
Case #1
What is your next diagnostic study?
 CT chest/PE Protocol
 Transthoracic Echocardiogram
 Right Cardiac Catheterization
 Repeat Bronchoscopy
CT chest
ARDS
Case #1
Transthoracic echocardiography:
 Ejection fraction 60 %, normal left ventricular systolic
function. Mild right ventricular dilation
Right heart catheterization:
 Cardiac Output (CO): 7.74 L/min (normal 5-7
L/min) Cardiac Index (CI): 4.8 L/min/m2(normal 3-5
L/min/m2) CVP 8 mmHg SVRI: 960 dynes/sec/cm5/m2
(normal 1200-1800) Pulmonary artery systolic pressure
(PASP): 59 mmHg Pulmonary Wedge Pressure: 11
mmHg
ARDS
Case #1
Which of the following statements is true:
The Development of acute respiratory
failure in this patient is due to:
A. Pulmonary edema due to fluid overload
B. Cardiogenic pulmonary edema due to left-sided heart
failure
C. Acute respiratory distress syndrome (ARDS)
D. Pneumonia
E. Massive pulmonary embolism
The American-European Consensus
Conference Definition of Acute Lung Injury
and ARDS, AECC
AECC Criticism
From: Acute Respiratory Distress Syndrome: The Berlin Definition JAMA.
2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
AECC Criticism, Hypoxemia

Factors that affect PaO2/FiO2 vs FiO2
 Cardiac output
 A-V O2 Difference
 Distribution of blood flow to different V/Q regions
 Low V/Q
 Shunt
 Oxygen consumption
 Hemoglobin concentration
Effect of Intrapulmonary Shunt (S) and
arterio-venous O2 Difference (AVD) on
PaO2/FiO2
AECC Criticism, Hypoxemia
AECC Criticism, Hypoxemia
AECC Criticism, hypoxemia
AECC Criticism, CXR
AECC Criticism, CXR
AECC Criticism, PCWP
ARDS
New Definition
ARDS, New Definition
ESICM convened an international panel of
experts, with representation of ATS and
SCCM
The objectives were to update the ARDS
definition using a systematic analysis of:
current epidemiologic evidence
 physiological concepts
results of clinical trials
ARDS, New Definition
All modifications were based on the
principle that syndrome definitions must
fulfill three criteria:
 Feasibility
 Reliability
 Validity
Acute Respiratory Distress Syndrome
The Berlin definition
JAMA. 2012;307(23):2526-2533.
doi:10.1001/jama.2012.5669
ARDS
The Berlin Definition
JAMA. 2012;307(23):2526-2533.
doi:10.1001/jama.2012.5669
ARDS
The Berlin Definition
 No change in the underlying conceptual understanding of
ARDS
 “acute diffuse, inflammatory lung injury, leading to increased
pulmonary vascular permeability, increased lung weight, and loss
of aerated lung tissue…[with] hypoxemia and bilateral
radiographic opacities, associated with increased venous
admixture, increased physiological dead space, and decreased
lung compliance.”
 Although the authors emphasize the increased power of the
new Berlin definition to predict mortality compared to the
AECC definition, in truth it’s still poor, with an area under the
curve of only 0.577, (95% CI, 0.561-0.593) compared to
0.536, (95% CI, 0.520-0.553;P < 001 ) for the old definition.
ARDS
Pathophysiology
ARDS
Pathological Stages
 Initial "exudative" stage-diffuse alveolar damage
within the first week
 “Proliferative" stage-resolution of pulmonary
edema, proliferation of type II alveolar cells,
squamous metaplasia, interstitial infiltration by
myofibroblasts, and early deposition of collagen.
 Some patients progress to a third "fibrotic" stage,
characterized by obliteration of normal lung
architecture, diffuse fibrosis, and cyst formation
ARDS
Pathophysiology
Risk Factors
 Sepsis
 Severe trauma
 Surface burns
 Multiple blood
transfusions
 Drug overdose
 Following bone
marrow transplantation
 Multiple fractures
 Aspiration
 Pneumonia
 Pulmonary contusion
 Pulmonary embolism
 Inhalational injury
 Near drowning
Negative Pressure Pulmonary Edema
Type of Non-Cardiogenic Pulmonary
Edema
Mechanism
Rapid resolution of large levels of
negative intra-thoracic pressures by
removal of airways obstruction ------leads
to alveolar and capillary damage -----leads to increased vascular permeability
ARDS
Clinical Presentation
Dyspnea, Tachypnea
Persistent hypoxemia, despite the
administration of high concentrations of
inspired oxygen
Increase in the shunt fraction
Decrease in pulmonary compliance
Increase in the dead space ventilation
Management of ARDS
Basic Management Strategies for Patients
with ALI/ARDS
 Identify and treat underlying causes
 Ventilatory support
 Lung protective ventilatory support strategy
 Application of PEEP
 Restore and maintain hemodynamic function
 Conservative fluid replacement strategy
 Vasopressors and inotropics support
 Prevent complications of critical illness
 Ensure adequate nutrition
 Avoid oversedation
 Using weaning protocol with spontaneous breathing trials
 Continous use of steroids for fibroproliferative phase
?questionable
Fluid management and vasoactive
support
SAFE trial
Resuscitation with saline is as beneficial as
resuscitation with albumin in critically ill
patients with shock
FACTT trial
 Prospective, Randomized, Multi-Center Trial
 Utility and safety of using a pulmonary artery
catheter versus central venous catheter to guide
the volume replacement
 Liberal versus conservative fluid replacement
ARDS
FACTT
Patients were treated with the specific fluid
management strategy (to which they were
randomized) for 7 days or until unassisted
ventilation, whichever occurs first.
The study enrolled 1000 patients and
showed no benefit with PAC guided fluid
therapy over the less invasive CVC guided
therapy.
ARDS
FACTT
The Use of Conservative fluid management
strategy was associated with
Significant improvement in oxygenation
index
 Significant improvement in Lung Injury
score
 increase in the number of ventilator- free
days
ARDS
Mechanical Ventilation
Ventilator associated lung injury
Volutrauma
Atelectotrauma
Biotrauma
Barotrauma
Air embolism/translocation
NHLBI ARDS Network
Compared low tidal volumes (6ml/kg of
ideal body weight ) against conventional
tidal volumes (12ml/kg ideal body weight )
Significant decrease in mortality
associated with the use of low tidal
volumes (39.8% versus 31%, P= 0.007)
NHLBI ARDS Network
Improved Survival with Low VT
NHLBI ARDS Network
Main Outcome Variables
NHLBI ARDS Network
Main Organ Failure Free Days
ARDS
Mechanical Ventilation
 Initial tidal volumes of 8 mL/kg predicted body weight in kg,
calculated by:
 [2.3 *(height in inches - 60) + 45.5 for women or + 50 for men].
 Respiratory rate up to 35 breaths/min
 expected minute ventilation requirement (generally, 7-9 L /min)
 Set positive end-expiratory pressure (PEEP) to at least 5 cm
H2O (but much higher is probably better)
 FiO2 to maintain an arterial oxygen saturation (SaO2) of 8895% (paO2 55-80 mm Hg).
 Titrate FiO2 to below 70% when feasible.
 Over a period of less than 4 hours, reduce tidal volumes to 7
mL/kg, and then to 6 mL/kg.
ARDS
Mechanical Ventilation
ARDS
Mechanical Ventilation
 Plateau pressure (measured during an inspiratory hold of
0.5 sec) less than 30 cm H2O,
 High plateau pressures vastly elevate the risk for harmful alveolar
distension ( volutrauma).
If plateau pressures remain elevated after
following the above protocol, further strategies
should be tried:
 Reduce tidal volume, to as low as 4 mL/kg by 1 mL/kg stepwise
increments.
 Sedate the patient to minimize ventilator-patient dyssynchrony.
 Consider other mechanisms for the increased plateau pressure
Potential benefits of hypercapnia in
patients with ARDS
Decrease in TNF-alpha release by alveolar
macrophages
Decrease in PMNL-endothelial cell
adhesion
Decrease in Xanthine oxiedase activity
Decrease in NOS activity
Reduction of IL-8
ARDS
High versus Low PEEP
Higher PEEP along with low tidal volume
ventilation should be considered for
patients receiving mechanical ventilation for
ARDS. This suggestion is based on a
 2010 meta-analysis of 3 randomized trials
(n=2,229) testing higher vs. lower PEEP in
patients with acute lung injury or ARDS, in which
ARDS patients receiving higher PEEP had a
strong trend toward improved survival.
ARDS
High versus Low PEEP
 However, patients with milder acute lung injury
(paO2/FiO2 ratio > 200) receiving higher PEEP had
a strong trend toward harm in that same metaanalysis.
 Higher PEEP can conceivably cause ventilatorinduced lung injury by increasing plateau pressures,
or cause pneumothorax or decreased cardiac
output. These adverse effects were not noted in the
largest ARDSNet trial (2004) testing high vs. low
PEEP.
ARDS
Mechanical Ventilation
ARDS
Mechanical Ventilation
ARDS
Mechanical Ventilation

Neuromuscular blockers in early acute
respiratory distress syndrome.
N Engl J Med, 2010;363:1107-16.
 This multicenter RCT of 340 patients with severe ARDS
found early use of 48 hours of neuromuscular blockade
reduced mortality compared to placebo (NNT of 11 to
prevent one death at 90 days in all patients, and a NNT of
7 in a prespecified analysis of patients with a PaO2:FiO2
less than 120).
Basic management Strategies for patients
with ALI/ARDS
 Identify and treat underlying causes
 Ventilatory support
 Lung protective ventilatory support strategy
 Application of PEEP
 Restore and maintain hemodynamic function
 Conservative fluid replacement strategy
 Vasopressors and inotropics support
 Prevent complications of critical illness
 Ensure adequate nutrition
 Avoid oversedation
 Using weaning protocol with spontaneous breathing trials
 Continous use of steroids for fibroproliferative
phase,?questionable
CASE #1
 On admission to the ICU, the patient was sedated and placed
on volume control mechanical ventilation with the follow
settings: FiO2: 0.6, VT: 450 ml, RR:18, PEEP:10 cm H2O,
VΕ:8 L/min.
 Additional supportive therapy included initial, empiric, broadspectrum antibiotics and restrictive fluid management.
 On Day 3, due to further impairment of oxygenation (SaO2
<80%) that did not improve with increases in both PEEP and
FiO2, the patient was placed on high frequency oscillatory
ventilation.
 Although he had an initial improvement in oxygenation, his
overall condition continued to decline and he died on Day 5
due to multiple organ failure.
ARDS
Inhaled NO
Steroids
Prone Position
High Frequency Oscillatory
Ventilation
ECMO
Inhaled Nitric Oxide
It is a bronchial and vascular smooth muscle
dilator
Decreases the Platelets Adherence and
Aggregation
Improves Ventilation –Perfusion ratio
Reduction in Pulmonary Artery Pressure and
pulmonary Vascular Resistance
Inhaled Nitric Oxide
Two Prospective, Randomized, Placebo
Controlled Clinical Trials failed to
demonstrate an improvement in the
survival.
However, there was improvement in the
oxygenation…
ARDS
Steroid
 A protocol for steroids in late ARDS, based on the Meduri
paper*
 The patient must have no demonstrable infection
 broncho-alveolar lavage may be necessary to confirm this. This
includes undrained abscesses, disseminated fungal infection and
septic shock
 Steroids should not be started less than 7 days, or more than
28 days, from admission
 The patient should not have a history of gastric ulceration of
active gastrointestinal bleeding
 Patients with burns requiring skin grafting, pregnant patients,
AIDS, and those in whom life support is expected to be
withdrawn, are unsuitable
*Meduri GU, Kohler G, Headley S, Tolley E, Stentz F, Postlethwaite A. Inflammatory cytokines in the BAL of patients
with ARDS. Persistent elevation over time predicts poor outcome. Chest 1995; 108(5):1303-1314. (2) Meduri GU,
Headley AS, Golden E, Carson SJ, Umberger RA, Kelso T et al. Effect of prolonged methylprednisolone therapy in
unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA 1998; 280(2):159-165.
ARDS
Steroids
 The patient should have evidence of ARDS and
require an FiO2 >/= 50%
 The steroid regimen:
 Loading dose 2mg/kg
 Then 2mg/kg/day from day 1 to 14
 Then 1mg/kg/day from day 15 to 21
 Then 0.5mg/kg/day from day 22 to 28
 Then 0.25mg/kg/day on days 29 and 30
 Finally 0.125mg/kg on days 31 and 32.
Prone Positioning
Relieves the cardiac and abdominal
compression exerted on the lower lobes
Makes regional Ventilation/Perfusion ratios
and chest elastance more uniform
Facilitates drainage of secretions
Potentiates the beneficial effect of
recruitment maneuvers
Study Overview
• Placing patients who require mechanical ventilation in the prone rather
than the supine position improves oxygenation.
• In this trial, the investigators found a benefit with respect to all-cause
mortality with this change in body position in patients with severe
ARDS.
Enrollment, Randomization, and Follow-up of the Study Participants.
Guérin C et al. N Engl J Med 2013;368:2159-2168
Characteristics of the Participants at Inclusion in the Study.
Guérin C et al. N Engl J Med
2013;368:2159-2168
Ventilator Settings, Respiratory-System Mechanics, and Results of Arterial Blood Gas
Measurements at the Time of Inclusion in the Study.
Guérin C et al. N Engl J Med 2013;368:2159-2168
Kaplan–Meier Plot of the Probability of Survival from Randomization to Day 90.
Guérin C et al. N Engl J Med 2013;368:2159-2168
Primary and Secondary Outcomes According to Study Group.
Guérin C et al. N Engl J Med 2013;368:2159-2168
Conclusions
• In patients with severe ARDS, early application of prolonged pronepositioning sessions significantly decreased 28-day and 90-day
mortality.
Vent settings to improve oxygenation
PEEP and FiO2 are adjusted in tandem
• FIO2
• Simplest maneuver to quickly increase PaO2
• Long-term toxicity at >60%
• Free radical damage
• Inadequate oxygenation despite 100% FiO2
usually due to pulmonary shunting
• Collapse – Atelectasis
• Pus-filled alveoli – Pneumonia
• Water/Protein – ARDS
• Water – CHF
• Blood - Hemorrhage
Vent settings to improve oxygenation
PEEP and FiO2 are adjusted in tandem
• PEEP
• Increases FRC
• Prevents progressive atelectasis and
intrapulmonary shunting
• Prevents repetitive opening/closing (injury)
• Recruits collapsed alveoli and improves
V/Q matching
• Resolves intrapulmonary shunting
• Improves compliance
• Enables maintenance of adequate PaO2
at a safe FiO2 level
• Disadvantages
• Increases intrathoracic pressure (may
require pulmonary a. catheter)
• May lead to ARDS
• Rupture: PTX, pulmonary edema
Oxygen delivery (DO2), not PaO2, should be
used to assess optimal PEEP.
Vent settings to improve ventilation
 Respiratory rate
 Max RR at 35 breaths/min
 Efficiency of ventilation decreases with increasing RR
 Decreased time for alveolar emptying
 TV
 Goal of 10 ml/kg
 Risk of volutrauma
 Other means to decrease PaCO2
 Reduce muscular activity/seizures
 Minimizing exogenous carb load
 Controlling hypermetabolic states
 Permissive hypercapnea
 Preferable to dangerously high RR and TV, as long as
pH > 7.15
Vent settings to improve ventilation
RR and TV are adjusted to maintain VE and PaCO2
• Respiratory rate
• Max RR at 35 breaths/min
• Efficiency of ventilation decreases
with increasing RR
• Decreased time for alveolar emptying
• TV
• Goal of 10 ml/kg
• Risk of volutrauma
• Other means to decrease PaCO2
• Reduce muscular activity/seizures
• Minimizing exogenous carb load
• Controlling hypermetabolic states
• Permissive hypercapnea
• Preferable to dangerously high RR
and TV, as long as pH > 7.15
• PIP
• Elevated PIP suggests need for
switch from volume-cycled to
pressure-cycled mode
• I:E ratio (IRV)
• Increasing inspiration time will
increase TV, but may lead to
auto-PEEP
• Maintained at <45cm H2O to
minimize barotrauma
• Plateau pressures
• Pressure measured at the end
of inspiratory phase
• Maintained at <30-35cm H2O to
minimize barotrauma
Origins of mechanical ventilation
The era of intensive care medicine began with positive-pressure ventilation
• Negative-pressure ventilators
(“iron lungs”)
• Non-invasive ventilation first
used in Boston Children’s
Hospital in 1928
• Used extensively during polio
outbreaks in 1940s – 1950s
• Positive-pressure ventilators
The iron lung created negative pressure in abdomen
as well as the chest, decreasing cardiac output.
• Invasive ventilation first used at
Massachusetts General Hospital
in 1955
• Now the modern standard of
mechanical ventilation
Iron lung polio ward at Rancho Los Amigos Hospital
in 1953.