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PULMONARY GRAND ROUNDS Acute Respiratory Distress Syndrome 20 April 2006, AVR
PULMONARY GRAND ROUNDS
Acute Respiratory Distress Syndrome
20 April 2006, AVR

OBJECTIVES

 To review the criteria for the diagnosis of ARDS/ALI  To review the epidemiology and
 To review the criteria for the diagnosis
of ARDS/ALI
 To review the epidemiology and
pathogenesis of ALI/ARDS
 To discuss the issues on the
management of ALI/ ARDS among
patients with sepsis
Acute Respiratory Distress Syndrome

What is Acute Respiratory Distress Syndrome?

NEJM, May 2000 Acute Respiratory Distress Syndrome
NEJM, May 2000
Acute Respiratory Distress Syndrome
What is Acute Respiratory Distress Syndrome? NEJM, May 2000 Acute Respiratory Distress Syndrome

What is Acute Respiratory Distress Syndrome?

American European Consensus Conference on ARDS, 1994 Acute Respiratory Distress Syndrome
American European Consensus Conference on ARDS, 1994
Acute Respiratory Distress Syndrome
What is Acute Respiratory Distress Syndrome? American European Consensus Conference on ARDS, 1994 Acute Respiratory Distress

Epidemiology

 1972 NIH Estimate annual incidence of 75 per 100,000 population  accurate estimation hindered by
 1972 NIH Estimate annual incidence of
75 per 100,000 population
 accurate estimation hindered by
differences in definition, heterogeneity
of causes
 Variable accounts of epidemiologic
studies across
Acute Respiratory Distress Syndrome

Epidemiology

Author Publication Patient (per Incidence Mortality Year 100,000 rate population Fowler 1983 88 5.2 65 Webster
Author
Publication
Patient (per
Incidence
Mortality
Year
100,000
rate
population
Fowler
1983
88
5.2
65
Webster
1988
139 4.5
38
Evans
1988
62
25
60
Thomsen
1995
110/ 89
8.8/ 4.8
Lewandowski
1995
17
3
58.8
Acute Respiratory Distress Syndrome

Review of Pathogenesis:

Acute Phase

Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome
Review of Pathogenesis: Acute Phase Acute Respiratory Distress Syndrome

Radiologic Correlation:

Acute Phase

 Diffuse bilateral alveolar opacities consistent with pulmonary edema Acute Respiratory Distress Syndrome
 Diffuse bilateral
alveolar opacities
consistent with
pulmonary edema
Acute Respiratory Distress Syndrome
Radiologic Correlation: Acute Phase  Diffuse bilateral alveolar opacities consistent with pulmonary edema Acute Respiratory Distress

Radiographic Correlation: Acute Phase

Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome

Histologic Correlation:

Acute Phase

Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome

Pathogenesis:

Fibrosing Alveolitis

Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome

Radiographic Correlation: Fibrosing Alveolitis Phase

Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome

Radiographic Correlation

Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome

Pathogenesis: Resolution

Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome

Who are at risk for ARDS?

 Ability to identify who are at risk is important if therapies are to be developed
 Ability to identify who are at risk is
important if therapies are to be
developed to prevent the disorder
Acute Respiratory Distress Syndrome

Who are at Risk for ARDS?

NEJM, May 2000 Acute Respiratory Distress Syndrome
NEJM, May 2000
Acute Respiratory Distress Syndrome

SEPSIS AND ARDS

prospectively identified 695 patients admitted to intensive care units from 1983 - 1985 ARDS: 179 of
prospectively identified 695 patients admitted
to intensive care units from 1983 - 1985
ARDS: 179 of the 695 patients (26%).
Highest incidence:
sepsis syndrome (75 of 176; 43%)
multiple emergency transfusions (>
or = 15 units in 24 h) (46 of 115; 40%)
Hudson et. al., Am Jour of Respir Crit Care Med, 1998
Acute Respiratory Distress Syndrome
Mechanical Ventilation in sepsis induced acute lung injury/ acute respiratory distress syndrome: An evidence based review
Mechanical Ventilation in sepsis
induced acute lung injury/ acute
respiratory distress syndrome: An
evidence based review
Critical Care Med 2004
Acute Respiratory Distress Syndrome

MODIFIED DELPHI METHODOLOGY

Grading of Evidence I. Large, randomized trials with clear-cut results; low risk of false-positive (alpha) error
Grading of Evidence
I. Large, randomized trials with clear-cut results; low
risk of false-positive (alpha) error or false-negative
(beta) error
II. Small, randomized trials with uncertain results;
moderate-to-high risk of false-positive (alpha) and/or
false-negative (beta) error
III. Nonrandomized, contemporaneous controls
IV. Nonrandomized, historical controls and expert
opinion
V. Case series, uncontrolled studies, and expert opinion
Acute Respiratory Distress Syndrome

MODIFIED DELPHI METHODOLOGY

Grading of Recommendations A. Supported by at least two level I investigations B. Supported by one
Grading of Recommendations
A. Supported by at least two level I
investigations
B.
Supported by one level I investigation
C.
Supported by level II investigations only
D.
Supported by at least one level III
investigation
E.
Supported by level IV or V evidence
Acute Respiratory Distress Syndrome

MANAGEMENT ISSUE #1: Intubation and Mechanical Ventilation

 Does placement of an ET tube or institution of mechanical ventilation improve outcome in respiratory
 Does placement of an ET tube or
institution of mechanical ventilation
improve outcome in respiratory failure
secondary to sepsis?
Acute Respiratory Distress Syndrome

MANAGEMENT ISSUE #1: Intubation and Mechanical Ventilation

 Mechanical ventilation is the mainstay of supportive care for ALI/ ARDS - Reduces work of
 Mechanical ventilation is the mainstay of
supportive care for ALI/ ARDS
-
Reduces work of breathing
-
Weigh benefit of endotracheal intubation
compared to NIPPV
-
Increased complications in patients with
hypotension on NIPPV favors endotracheal
intubation
Acute Respiratory Distress Syndrome

MANAGEMENT ISSUE #1: Intubation and Mechanical Ventilation

 Does placement of an ET tube /mechanical ventilation improve outcome in respiratory failure secondary to
 Does placement of an ET tube
/mechanical ventilation improve
outcome in respiratory failure
secondary to sepsis?
 ET tube – No, Grade E
 MV
- Yes, Grade E
Acute Respiratory Distress Syndrome

Management Issue #2: NIPPV

 Can non-invasive positive pressure ventilation (NIPPV) be safely used in patients with ALI/ARDS? Acute Respiratory
 Can non-invasive positive pressure
ventilation (NIPPV) be safely used in
patients with ALI/ARDS?
Acute Respiratory Distress Syndrome

Management Issue #2: NIPPV

 NIPPV may be effective for COPD patients and cardiogenic pulmonary edema  It is however
 NIPPV may be effective for COPD
patients and cardiogenic pulmonary
edema
 It is however less likely of help in
hypoxic respiratory failure
Critical Care Medicine 2004
Acute Respiratory Distress Syndrome

Management Issue #2: NIPPV

 Contraindicated among patients with hypotension, altered sensorium, increased secretions  Consider its use in cases
 Contraindicated among patients with
hypotension, altered sensorium, increased
secretions
 Consider its use in cases of ALI/ARDS with
duration of 48-72 hours
 Consider its use in immunosuppressed
patients without hypotension considering the
risk of VAP among this patients if placed on
ET.
Critical Care Medicine 2004
Acute Respiratory Distress Syndrome

Management Issue #2: NIPPV

 Can non-invasive positive pressure ventilation (NIPPV) be safely used in patients with ALI/ARDS?  Uncertain,
 Can non-invasive positive pressure
ventilation (NIPPV) be safely used in
patients with ALI/ARDS?
 Uncertain, Grade B
Acute Respiratory Distress Syndrome

Management Issue #3: LOW TIDAL VOLUMES

 Does the use of small tidal volume ventilation affect outcome in ALI/ARDS related to Sepsis?
 Does the use of small tidal volume
ventilation affect outcome in ALI/ARDS
related to Sepsis?
Acute Respiratory Distress Syndrome

Management Issue #3: LOW TIDAL VOLUMES

ARDS Network Trial, 2000 Acute Respiratory Distress Syndrome
ARDS Network Trial, 2000
Acute Respiratory Distress Syndrome

Management Issue #3: LOW TIDAL VOLUMES

 Mortality substantially reduced from 40% (traditional strategy) to 31% (lower lung volume strategy)  More
 Mortality substantially reduced from
40% (traditional strategy) to 31% (lower
lung volume strategy)
 More ventilator free days
 More organ failure free days
ARDS Network Trial, 2000
Acute Respiratory Distress Syndrome

Management Issue #3: LOW TIDAL VOLUMES

Most of the tidal volume in ALI/ARDS are directed to a relatively small amount of aerated
Most of the tidal volume in ALI/ARDS
are directed to a relatively small amount
of aerated lung
Traditional approaches to mechanical
ventilation exacerbate or perpetuate
lung injury by excessive stretch of
aerated regions during inspiration
Acute Respiratory Distress Syndrome

Management Issue #3: LOW TIDAL VOLUMES

 TV reduced further to 5-4 ml/k if necessary to maintain Pplat less than or equal
 TV reduced further to 5-4 ml/k if
necessary to maintain Pplat less than or
equal to 30
Acute Respiratory Distress Syndrome
NIH ARDS NETWORK LOWER TIDAL VOLUME VENTILATION PROTOCOL SUMMARY Variable Protocol Ventilator Mode TV Plateau Volume
NIH ARDS NETWORK LOWER TIDAL
VOLUME VENTILATION PROTOCOL
SUMMARY
Variable
Protocol
Ventilator Mode
TV
Plateau
Volume Assist Control
Less than or equal to 6 ml/k predicted BW
Less than equal to 30 cm H2O
Pressure
Rate
6-35/min adjusted to achieve arterial pH Above or
equal to 7.3
IE
1:1 to 1:3
Oxygenation
goal
PaO2 above or equal to 55 mm Hg or Sats between 88
to 95%
FiO2/ PEEP
combinations
0.3/5, 0.4/5, 0.4/8, 0.5/8, 0.5/10, 0.6/10, 0.7/10, 0.7/12,
0.7/14, 0.8/14, 0.9/14, 0.9/16, 0.9/18, 1.0/18, 1.0/22,
1.0/24
Acute Respiratory Distress Syndrome

Management Issue #3: LOW TIDAL VOLUMES

 Does the use of small tidal volume ventilation affect outcome in ALI/ARDS related to Sepsis?
 Does the use of small tidal volume
ventilation affect outcome in ALI/ARDS
related to Sepsis?
 Yes, Grade B
Acute Respiratory Distress Syndrome

Management Issue #4:

Applying Positive Airway Pressure

 Do manipulations of airway pressure improve oxygenation?  Does it improve outcome in patients with
 Do manipulations of airway pressure
improve oxygenation?
 Does it improve outcome in patients
with sepsis
 Should Positive End-Expiratory
Pressure (PEEP) be used to prevent
lung collapse at end expiration?
Acute Respiratory Distress Syndrome

Management Issue #4:

Applying Positive Airway Pressure

 No detectable oxygen toxicity occurred in normal subjects at FiO2 <50%  Impaired gas exchange
 No detectable oxygen toxicity occurred
in normal subjects at FiO2 <50%
 Impaired gas exchange at 100% O2 for
approximately 40 h
 PEEP minimizes potential for oxygen
induced lung injury from toxic levels of
inspired oxygen
– FiO2 <60 is considered safe
Acute Respiratory Distress Syndrome

Management Issue #4:

Applying Positive Airway Pressure

 PEEP reduces intrapulmonary shunt and improves arterial oxygenation  Adverse effects: increased pulmonary edema formation,
 PEEP reduces intrapulmonary shunt
and improves arterial oxygenation
 Adverse effects: increased pulmonary
edema formation, decreased cardiac
outputs, increased dead space,
increased resistance, increased lung
volumes and stretch during inspiration
which may cause further injury or
barotrauma
Acute Respiratory Distress Syndrome

Management Issue #4:

Applying Positive Airway Pressure

 Best strategy for using PEEP and FiO2 are not yet defined  Consensus among investigators
 Best strategy for using PEEP and FiO2
are not yet defined
 Consensus among investigators at the
NIH ARDS Network Centers since 1995
 Goal of therapy: maintain a PaO2 >58-
60 mmHg or an O2 Saturation of 90%
Acute Respiratory Distress Syndrome
NIH ARDS NETWORK LOWER TIDAL VOLUME VENTILATION PROTOCOL SUMMARY Variable Protocol Ventilator Mode TV Plateau Volume
NIH ARDS NETWORK LOWER TIDAL
VOLUME VENTILATION PROTOCOL
SUMMARY
Variable
Protocol
Ventilator Mode
TV
Plateau
Volume Assist Control
Less than or equal to 6 ml/k predicted BW
Less than equal to 30 cm H2O
Pressure
Rate
6-35/min adjusted to achieve arterial pH Above or
equal to 7.3
IE
1:1 to 1:3
Oxygenation
goal
PaO2 above or equal to 55 mm Hg or Sats between 88
to 95%
FiO2/ PEEP
combinations
0.3/5, 0.4/5, 0.4/8, 0.5/8, 0.5/10, 0.6/10, 0.7/10, 0.7/12,
0.7/14, 0.8/14, 0.9/14, 0.9/16, 0.9/18, 1.0/18, 1.0/22,
1.0/24
Acute Respiratory Distress Syndrome

Management Issue #4:

Applying Positive Airway Pressure

 Do manipulations of airway pressure improve oxygenation? Yes, Grade C  Does it improve outcome
 Do manipulations of airway pressure
improve oxygenation? Yes, Grade C
 Does it improve outcome in patients
with sepsis? Uncertain, Grade B
 Should Positive End-Expiratory
Pressure (PEEP) be used to prevent
lung collapse at end expiration? Yes,
Grade E
Acute Respiratory Distress Syndrome

Management Issue #5: Permissive Hypercapnea

 Is normalization of the pH or PCO2 necessary in ALI/ ARDS?  Should permissive hypercapnea
 Is normalization of the pH or PCO2
necessary in ALI/ ARDS?
 Should permissive hypercapnea be
used in patients with ALI/ARDS?
Acute Respiratory Distress Syndrome

Management Issue #5: Permissive Hypercapnea

 Acute rises in PCO2 can cause vasodilation, increased heart rate, BP and cardiac output 
 Acute rises in PCO2 can cause vasodilation,
increased heart rate, BP and cardiac output
 Allowing modest hypercapnea in conjunction
with limiting tidal volume and minute
ventilation has been demonstrated to be safe
Hickilng et. al., N Engl J Med 2000
Tasker, Intensive Care Medicine 1998
Acute Respiratory Distress Syndrome

Management Issue #5: Permissive Hypercapnea

 Permissive hypercapnea not a primary treatment goal in ARDS Network Trial  No upper limit
 Permissive hypercapnea not a primary
treatment goal in ARDS Network Trial
 No upper limit for PCO2 has been
established
– Maintain pH >7.2-7.25
Acute Respiratory Distress Syndrome

Management Issue #5: Permissive Hypercapnea

 Limited use in patients with pre-existing metabolic acidosis and is contraindicated in those with increased
 Limited use in patients with pre-existing
metabolic acidosis and is
contraindicated in those with increased
ICP
Acute Respiratory Distress Syndrome

Management Issue #5: Permissive Hypercapnea

 Is normalization of the pH or PCO2 necessary in ALI/ ARDS? No, Grade D 
 Is normalization of the pH or PCO2
necessary in ALI/ ARDS? No, Grade D
 Should permissive hypercapnea be
used in patients with ALI/ARDS? Yes,
Grade E
Acute Respiratory Distress Syndrome

Management Issue #6: Prone Positioning

 Does prone positioning affect gas exchange or outcome in sepsis related ALI?  Should prone
 Does prone positioning affect gas
exchange or outcome in sepsis related
ALI?
 Should prone position be used in
patients with ARDS requiring potentially
injurious levels of FiO2 or plateau
pressure?
Acute Respiratory Distress Syndrome

Management Issue #6: Prone Positioning

Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome

Management Issue #6: Prone Positioning

 In facilities with adequate experience, prone positioning should be considered Crit Care Med, 2004 Acute
 In facilities with adequate experience,
prone positioning should be considered
Crit Care Med, 2004
Acute Respiratory Distress Syndrome

Management Issue #6: Prone Positioning

 Investigations inexperimental pig models – Supine: pleural pressure were highest in the dorsal regions due
 Investigations inexperimental pig models
– Supine: pleural pressure were highest in the dorsal regions
due to hydrostatic gradients
• Translated to atelectasis
– Prone positioning
• Uniform pleural pressures
• Allowed dorsal regions to “open up” and participate in gas
exchange
 Suggests probable protection from ventilator
associated lung injury
– Equal distirbution of TV
– Prevented repeated opening and collapse of small airways
Lamm, et. al. Am J Resp Crit Care Med, 1994
Acute Respiratory Distress Syndrome

Management Issue #6: Prone Positioning

 Lung mechanics and analyzed CT images of ARDS – Decrease in chest wall compliance –
 Lung mechanics and analyzed CT images of
ARDS
– Decrease in chest wall compliance
– TV tended to redistribute
– Recruitment of dorsal lung regions
– Improved arterial oxygenation
– Potential lung protecting effect from overall
decrease in atelectasis at end expiration
Pelosi, AM J Resp Crit Care Med 1998
Acute Respiratory Distress Syndrome

Management Issue #6: Prone Positioning

 Requires more personnel to safely implement  Duration of prone positioning not established – 6
 Requires more personnel to safely
implement
 Duration of prone positioning not
established
– 6 h no difference with supine position
ventilation (Gattinoni et. al., Lancet 1997)
 No clear guidelines on when it should
be initiated or discontinued
Acute Respiratory Distress Syndrome

Management Issue #6: Prone Positioning

 Expert opinion: aggressive approach of >20 h/d with relatively brief periods of supine positioning for
 Expert opinion: aggressive approach of
>20 h/d with relatively brief periods of
supine positioning for bathing servicing
vascular catheters started early in the
course and continued until weaning is
feasible
Albert, RK, Clinical Chest Med 2000
Acute Respiratory Distress Syndrome

Management Issue #6: Prone Positioning

 Does prone positioning affect gas exchange or outcome in sepsis related ALI? – Gas Exchange,
 Does prone positioning affect gas exchange
or outcome in sepsis related ALI?
– Gas Exchange, Yes Grade B
– Sepsis Outcome, Uncertain, Grade B
 Should prone position be used in patients
with ARDS requiring potentially injurious
levels of FiO2 or plateau pressure? Yes,
Grade E
Acute Respiratory Distress Syndrome