ARDS
ARDS
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A specific Clinical Syndrome that
causes respiratory failure
Characterized by the acute onset of
diffuse bilateral pulmonary infiltrates
and severe hypoxemia without LV
failure as the cause
ARDS Definition
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Standardized definition developed in
1992 by the American-European
Consensus Conference (AECC).
Acute Bilateral Pulmonary Infiltrates
PaO2 to FiO2 Ratio of less than 200.
Pulmonary Artery Wedge Pressure
less than 18 mmHg
3. Bernard GR, Artigas A, Brigham, Carlet J; et al. The American-European Consensus Conference on ARDS.
Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:81824.
ARDS- Definition Modifiers
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Pulmonary artery wedge pressures-not routinely
done in all patients. Definition has been modified
to allow for any means of ruling out LV failure as
the cause
Acute Lung Injury (ALI) refers to the same
clinical syndrome but with PaO2/FiO2 ratio
between 201-300
Primarily a matter of semantics as the difference
in these gas exchange deficits does not reliably
predict the degree of underlying pathology. There
is also no difference in mortality between the two
groups
Bernard GR, Artigas A, Brigham, Carlet J; et al. The American-European Consensus Conference on ARDS.
Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med
1994;149:818-24
ARDS
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Affects about 200,000 people per year in
the United States alone
Hospital Mortality rate is 41%
Most patients tend to die from multi-organ
failure as opposed to the lung disease
itself.
Our understanding of this disease over the
last 40 years has increased dramatically
with mortality rates significantly reduced
from initial estimates of 70%.
5. Rubenfeld GD, Caldwell E, Peabody E, Weaver J. et al. Incidence and Outcomes of Acute Lung Injury. N Engl J Med
353:1685-93
6. Esteban, A, Anzueto, A, Frutos, F, et al. Characteristics and outcomes in adult patients receiving mechanical
ventilation: a 28-day international study. JAMA 2002; 287:345.
ARDS: A Clinical Syndrome
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Common endpoint of many different
processes
Sepsis is the most common cause
Can be seen with trauma, pancreatitis,
aspiration, certain medications, oxygen
toxicity and the effects mechanical
ventilation itself
Most commonly the inciting injury begins
in the lungs as with aspiration or PNA,
but may result from an inflammatory
reaction from any part of the body
ARDS Imaging
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Radiographic imaging is an integral
part of the diagnosis of ARDS
Classic CXR is one of bilateral
infiltrates, often with air
bronchograms
Main concern is to distinguish these
infiltrates from those of other causes
such as cardiogenic pulmonary
edema
ARDS Imaging- Typical CXR
ARDS Imaging
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CT scan imaging has been used to better
characterize the disease since the 1980s
The fact that it is a very non
homogeneous process became much more
obvious with this imaging
The dependent portions of the lung,
usually the lower and posterior areas are
generally more severely involved
This coincides with the areas of the lungs
that receive the greatest blood supply
7. Rommelsheim K, Lackner K, Westhofen P et al. [Respiratory distress syndrome of the adult in the computer
tomograph] Anasth Intensivther Notfallmed. 1983 Apr;18(2):59-64. German.
9. Maunder RJ, Shuman WP, McHugh JW et al. Preservation of normal lung regions in the adult respiratory distress
syndrome. Analysis by computed tomography. JAMA. 1986 May 9;255(18):2463-5.
ARDS- Typical CT
ARDS Pathophysiology
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ARDS results from an inflammatory
injury to the alveoli and vasculature
Lungs are particularly vulnerable as
they receive 100% of the cardiac
output, and thus filter any
inflammatory cytokines that are
released into the circulation
Prominent proiinflammatory
cytokines are: TNF-α, IL-6, and IL-8
14. Martin, TR. Lung cytokines and ARDS: Roger S. Mitchell Lecture. Chest 1999; 116:2S.
15. Colletti LM, Remick DG, Burtch GD, et al. Role of tumor necrosis factor-alpha in the pathophysiologic alterations
after hepatic ischemia/reperfusion injury in the rat. J Clin Invest 1990; 85:1936
ARDS Pathophysiology
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The presence of these cytokines (TNF-α,
IL-6, and IL-8) causes neutrophil
recruitment to the lung, where they are
then activated
These activated neutrophils produce more
inflammatory cytokines and proteases
which ultimately damage the endothelial
capillaries and alveoli
This produces significant edema and
further inflammation- creating a vicious
inflammatory cycle
16. Windsor, AC, Mullen, PG, Fowler, AA, et al. Role of the neutrophil in adult respiratory distress syndrome. Br J
Surg 1993; 80:10.
17. Hogg, JC. Felix Fleischner Lecture. The traffic of polymorphonuclear leukocytes through pulmonary microvessels
in health and disease. AJR Am J Roentgenol 1994; 163:769.
Pathological Phases
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The three sequential phases of ARDS pathology
are: exudative, proliferative and then the fibrotic
phase
Exudative phase occurs over the first 2-7 days
Characterized by pulmonary edema, and the
formation of hyaline membrane (staining PASpositive).
Hyaline membranes are composed of fibrin and
cellular debris formed from the destruction of
Type 1 pneumocytes
Pathology described as DAD or diffuse alveolar
damage
19. Ware LB, Matthay MA The acute respiratory distress syndrome. N Engl J Med 2000;342:1334.
ARDS Pathological Phases
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Proliferative Phase usually seen during day 7 to
14
Driven by the ongoing inflammation as well as
the damaging effects of mechanical ventilation,
oxygen toxicity and physical barotrauma
Characterized by the repair and remodeling of the
injured lung cells with proliferation of Type II
alveolar cells
Fibroblasts also begin to proliferate
This lays the groundwork for the ensuing fibrotic
phase
20. Tomashefski JF Jr. Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med. 2000;21(3):435-66.
21. Meyrick B. Pathology of the adult respiratory distress syndrome. Crit Care Clin. 1986;2(3):405-28.
22. Ingbar DH. Mechanisms of repair and remodeling following acute lung injury.Clin Chest Med. 2000;21(3):589-616.
ARDS Pathological Phases
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Fibrotic phase generally develops around
day 14
Deposition of proteoglycans and collagen
can be seen
Fibroblasts now extensively proliferate and
incorporate the hyaline membranes
This leaves a fibrotic, acellular connective
tissue skeleton
Traction bronchiectasis may develop and
small cystic areas can often be seen
20. Tomashefski JF Jr. Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med. 2000;21(3):435-66.
21. Meyrick B. Pathology of the adult respiratory distress syndrome. Crit Care Clin. 1986;2(3):405-28.
22. Ingbar DH. Mechanisms of repair and remodeling following acute lung injury.Clin Chest Med. 2000;21(3):589-616.
ARDS Pathological Phases
Mechanical Ventilation
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Most patients with ARDS require
mechanical ventilation
Necessary for survival, but also
contributes to the lung disease itselfventilator induced lung injury (VILI)
VILI can be subclassified into two
broad categories- macrobarotrauma
and microbaroutrauma
VILI
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Macrobarotrauma refers to injuries such
as pneumothorax, pneumomediastinum or
any form of air leak
These types of injuries are relatively
uncommon with conventional ventilator
management
Microbarotrauma refers to injuries to the
smaller airways and alveoli themselves.
Microbarotrauma is felt to play a much
larger role in the pathogenesis of ARDS
29. Eisner MD, Thompson T, Hudson LD, et al. Efficacy of low tidal volume ventilation in patients with different clinical risk
factors for acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001;164(2):231-6
30. Brower RG, Lanken PN, MacIntyre N et al. Higher versus lower positive end-expiratory pressures in patients with the
acute respiratory distress syndrome.
N Engl J Med. 2004 Jul 22;351(4):327-36.
VILI- How the lungs are damaged
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VILI occurs in three basic ways:
Volutrauma, biotrauma and atelectrauma
Volutrauma refers to injury due to
insufflating large volumes of air during
PPV
This damages the alveoli walls by
increasing the amount of stretch and
tensile force on the alveoli
This causes direct damage to the alveoli
but also induces an inflammatory reaction
perpetuating the ongoing injury
Mechanical Ventilation in ARDS
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Low tidal volume strategy became the
standard of care after the ARDSNet
investigators completed a large
randomized control trial
Here they enrolled 861 patients with ARDS
and randomized them to either 12cc/kg
tidal volume vs 6cc/kg.
Trial was stopped early due to a significant
reduction in mortality from 40% to 31%
as well as a decrease in days on the
ventilator
44. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional
tidal volumes for acute lung injury and acute respiratory distress syndrome. N Engl J Med 2000;342:1301-8.
Mechanical Ventilation in ARDS
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The standard approach is now to start
with a TV of 6cc/kg, and to follow peak
and plateau pressures on the ventilator
Adjustments can then be made with
increases or decreases in the tidal volume
with a goal of keeping the plateau
pressures less than 30cm H2O
Permissive hypercapnea, (accepting a
respiratory acidosis) is frequently
required.
PEEP
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Several studies have shown that
using higher levels of PEEP improve
oxygenation
Varying levels of PEEP however have
not been shown to impact on survival
The ARDSNet investigators
addressed this in a study called
ALVEOLI
ALVEOLI Study
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A follow up study to compare high
PEEP vs. low PEEP
Used low TV strategy in all patients
Higher PEEP group had better
oxygenation, increased PaO2/FiO2
ratios, and improved lung compliance
Clinical outcomes of the two groups
were same and mortality was not
affected
45. Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive end-expiratory pressures in patients with the
acute respiratory distress syndrome. N Engl J Med. 2004;351(4):327-36.
ARDSNet standard PEEP guide
Practical PEEP
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Balance between PEEP’s beneficial effects and
deleterious side effects
Barotrauma
Increased complication risk with procedures ie.
central lines
Increased intrathoracic pressure- causes
decrease preload and decreased cardiac output
Ultimately decreased renal blood flow,
stimulating RAS adding to more fluid retention
and edema
Increased intracranial pressures
Recruitment Maneuvers
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Usually entails giving a ventilated patient a
sustained level of high PEEP 30-40 cm H2O for 30
to 40 seconds
Some evidence of sustained improved
oxygenation in animal models
Response in humans is unreliable
ARDSNet addressed this on the first 80 enrolled
patients in the ALVEOLI study, as well as in a
separate clinical trial
Both studies found only transient rises in
oxygenation which quickly return to baseline
46. Rimensberger PC, Cox PN, Frndova H, et al. The open lung during small tidal volume ventilation: Concepts of
recruitment and “optimal” positive end-expiratory pressure. Crit Care Med 1999; 27: 1946–1952
47. Verbrugge S, Lachman B. Mechanisms of ventilation-induced lung injury and its prevention: Role of surfactant. Appl
Cardiopulm Pathophysiol 1998; 7: 173–198
48. Brower RG, Morris A, MacIntyre N, et al. Effects of recruitment maneuvers in patients with acute lung injury and acute
respiratory distress syndrome ventilated with high positive end-expiratory pressure. Crit Care Med. 2003;31(11):2592-7.
Prone Position
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First used in the 1970s with two case
series published
Demonstrated improved oxygenation in
most, but not all patients
Takes advantage of the heterogeneity of
ARDS, and that the oxygen deficit is
secondary to the amount of consolidated
and collapsed lung not being inflated
Majority of non-inflated lung is at the
dependent areas- typically posterior lung
bases
50. Douglas WW, Rehder K, Beynen FM, et al. Improved oxygenation in patients with acute respiratory failure: The
prone position. Am Rev Respir Dis 1977; 115:559.
51. Piehl MA, Brown RS. Use of extreme position changes in acute respiratory failure. Crit Care Med 1976; 4:13.
Prone Position
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By placing a patient in the prone position
perfusion is increased to the dorsal areas
of the lung which are generally less
affected.
Improves ventilation/perfusion ratio
Reduces shunt fraction
Improves oxygenation
Oxygen improvement may also be
secondary to decreasing pleural pressures
in the dependent portions of the lung and
decreasing the amount of lung
compressed by the weight of the heart
52. Albert RK, Hubmayr RD. The prone position eliminates compression of the lungs by the heart. Am J Respir Crit
Care Med 2000;161:1660-5
Prone Position
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Some studies demonstrate sustained
improvement in the oxygenation with
using the prone position
No documented mortality benefit
Associated morbidity with complications of
repositioning
Pressure sores, selective intubation, ETT
obstruction, catheter removals, facial
edema
Labor intensive
CPR problematic
53. Vollman KM, Bander JJ. Improved oxygenation utilizing a prone positioner in patients with acute respiratory distress
syndrome. Intensive Care Med 1996; 22:1105.
54. Curley MA. Prone positioning of patients with acute respiratory distress syndrome: a systematic review. Am J Crit Care
1999; 8:397.
55. Fridrich P, Krafft P, Hochleuthner H, Mauritz W. The effects of long-term prone positioning in patients with trauma-induced
Prone Position General Suggestions
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Select patients properly
Newer commercial beds make this
somewhat easier
Recent abdominal/thoracic surgery
considerations- towel rolls, inner
tubes, abdominal binders
Spinal instability- contraindication
Volume Status
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Increasing data also now favors a
conservative fluid management strategy
Simmons- retrospective 113 pts.
Survivors have lower fluid balance
Humphrey- Improved survival seen in
patients with decreased wedge pressures
Ferguson- Persistently elevated PAOP was
predictor of mortality
65. Simmons RS, Berdine GG, Seidenfeld JJ, et al. Fluid balance and the adult respiratory distress syndrome. Am Rev Respir
Dis 1987;135:924-929.
66. Humphrey H, Hall J, Sznajder I, et al. Improved survival in ARDS patients associated with a reduction in pulmonary capillary
wedge pressure. Chest 1990;97:1176-1180.
68. Ferguson ND, Meade MO, Hallett DC, et al. High values of the pulmonary artery wedge pressure in patients with acute lung
injury and acute respiratory distress syndrome. Intensive Care Med 2002;28:1073-1077.
Volume Status/ PA catheters
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PA Catheters less frequently used, and not
necessary in most patients
Early studies demonstrated conflicting evidence
regarding benefit
FACTT trial performed by ARDSNet investigators 1001 patients randomized to a fluid management
strategy using PAC vs CVC.
FACTT trial demonstrated no difference in
primary outcomes of mortality or organ function
between the two groups- but PAC group had a
higher complication rate
66. Humphrey H, Hall J, Sznajder I, et al. Improved survival in ARDS patients associated with a reduction in pulmonary
capillary wedge pressure. Chest 1990;97:1176-1180.
67. Marinelli WA, Weinert CR, Gross CR, et al. Right heart catheterization in acute lung injury: an observational study. Am
J Respir Crit Care Med 1999;160:69-76.74. The Acute Respiratory Distress Syndrome Network.
74. Pulmonary artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006;354;22132224.
Volume Status
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ARDSNet investigators using same patient data
as FACTT trial performed a large randomized
control trial comparing a conservative vs. a
liberal fluid management strategy. 1001 patients
enrolled
Primary endpoint: Mortality. Secondary
Endpoints: ventilator free days, organ
dysfunction, lung function
No difference in 60 day mortality
Conservative management group had
significantly less ventilator days, and improved
pulmonary function, without affecting organ
dysfunction
75. The Acute Respiratory Distress Syndrome Network. Comparison of two fluid-management strategies in acute
lung injury. N Engl J Med 2006;354:2564-75.
Pharmacologic Treatments:
Steroids
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The use of steroids in ARDS has been
controversial and dates back to the
1970s and early eighties when their
use was fairly routine
In the mid eighties data began to
emerge regarding increased infection
rates associated with their use
There has been significant conflicting
data since then
Steroids
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Meduri et al (1991) used steroids in
a small series of patients to treat
pulmonary fibrosis secondary to
ARDS in the late, fibrotic phase
They demonstrated improved gas
exchange and lower mortality rates
in this population
These results were unable to be
repeated
79. Meduri GU, Belenchia JM, Estes RJ, et al. Fibroproliferative phase of ARDS. Clinical findings and effects of
corticosteroids. Chest 1991;100:943-52.
Steroids
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Meduri et al then studied a prolonged
course of steroids (32 days) in ARDS using
a RCT. They gave methylprednisolone
2mg/kg per day, and performed extensive
infection surveys
They were able to demonstrate a decrease
in mortality as well as improvement in
lung injury and MODS scores.
Small study with 24 patients
Meduri GU, Headley AS, Golden E, et al. Effect of prolonged methylprednisolone therapy in unresolving acute
respiratory distress syndrome: a randomized controlled trial. JAMA 1998;280:159-165
Steroids
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ARDSNet investigators studied 180
patients with ARDS of at least seven days
duration termed “persistent ARDS”
Steroids were administered in a similar
manner to Meduri et al but with a more
rapid taper
Primary outcome was 60 day mortality
No mortality benefit was shown
80. Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory
distress syndrome. N Engl J Med 2006;354:1671-84.
Steroids: Clinical Guidelines
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May be useful in select cases
If use, consider infectious risks
Intensive infection surveillance may
be necessary as was done in the
Meduri trial.
This may include bronchoscopy with
BAL to watch closely for development
of pneumonia in these susceptible
patients
Other Pharmacologic Treatments
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Antioxidants
Surfactant
No clear benefits shown
Alternate Ventilator Strategies
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HFOV- High frequency Oscillatory
ventilation
IRV- Inverse ratio ventilation
APRV-Airway pressure release
ventilation
Overall few clinical trials and no
mortality benefits have been shown
Further studies ongoing