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 end-inspiratory
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 mmHgSVRI: 960 dynes/sec/cm5/m2 (normal 12001800)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 its 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

 Initial tidal volumes of 8 mL/kg predicted body weight in kg,

ARDS
calculated by:

Mechanical
Ventilation
[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, V: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.

Gurin C et al. N Engl J Med 2013;368:2159-2168

Characteristics of the Participants at Inclusion in the Study.

Gurin 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.

Gurin C et al. N Engl J Med 2013;368:2159-2168

KaplanMeier Plot of the Probability of Survival from Randomization to Day 90.

Gurin C et al. N Engl J Med 2013;368:2159-2168

Primary and Secondary Outcomes According to Study Group.

Gurin 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

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

PIP
Elevated PIP suggests need
for switch from volumecycled 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 ventilat

Negative-pressure
ventilators (iron lungs)
Non-invasive ventilation first
used in Boston Childrens
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.