Acute Respiratory

Distress syndrome
Meron Yimen
PGY 3
 Historical Background

 Since WWI physicians have recognized a syndrome of

respiratory distress, diffuse lung infiltrates and
respiratory failure in pt with various medical conditions
including from battle trauma to severe sepsis,
pancreatitis, massive transfusions etc

 In 1967, Ashbaugh et al become the first to describe the

syndrome which they referred to as adult respiratory
distress syndrome in 12 such patients (1)
 Historical Background
 in 1971, Ashbaugh and Petty further defined the
syndrome in a form that summarized the clinical features
well (but lacked specific criteria to identify pts
systematically) (2)

        -  severe dyspnea

        -  cyanosis refractory to O2
        - decreased pulm compliance
        - diffuse alveolar infiltrates on CXR
        - atelectasis, vascular congestion, hemorrhage,
pulm edema and hyaline membranes at autopsy
 Historical Background
 in 1988, a more expanded definition was proposed that
quantified the physiologic respiratory impairment through
the use of 4-point lung injury scoring system (3)
        - level of PEEP
        - P/F RATIO    
        - static lung compliance
        - degree of infiltration on CXR
        - *also included nonpulm organ dysfunction
 This definition still had its shortcomings in that it specific
criteria to r/o cardiogenic pulm edema and is not
predictive of outcomes
 Historical Background
 1994 American - European Consensus Conference
Committee (AECC)  came up with definition that became
widely accepted

 also changed the name to acute respiratory distress

syndrome from adult respiratory distress

 defined it as a spectrum of ALI

        - Acute onset
        - bilateral infiltrates on CXR
        - PCWP =< 18 mmHg
        - P/F ratio =< 200
( ALI if P/F ratio =< 300 )
 Epidemiology
 the problem has always been how to identify the cases

 attempts at extrapolating incidences based on the various

definitions offered above have resulted in various numbers (1.5-8.3 -
75/100,000)

 the first study using the 1994 AECC definition was done in
Scandinavia (reported incidence of 17.6/100,000 for ALI and
13.5/100,000 for ARDS (4)

 More recently the ARDSNet study (done in King County,

Washington 4/1999-7/2000) reported much higher numbers for age-
adjusted incidence (5)
        -  ALI - 86.2/100,000 person-yrs (reaching 306 in ages 75-84)
        -  estimated annually cases base on these stats 190,600
        -  mortality 74, 500/yr
 Morbidity and Mortality
 prior to ARDSNet study - mortality rate for ARDS
has been estimated at 40-70%
 ARDSNet found a much lower overall mortality
rate 30-40% (6)
 notable that MR increases with age: 24 % ages
15-19 and 60 % in > 85 yrs
 2/2 co-morbid conditions
 Mortality is attributable to sepsis or multiorgan
dysfunction
 Morbidity and Mortality
 Morbidity

- prolonged hospital course- nosocomial

infections especially VAP
- wt loss
- muscle weakness
- functional impairment in months following
 Causes

DIRECT LUNG INJURY INDIRECT LUNG INJURY

COMMON COMMON
 PNA  Sepsis*
 Aspiration  Severe trauma with shock and
multiple transfusions
LESS COMMON
 Pulm contusion LESS COMMON
 Fat emboli  Cardiopulm bypass
 Near-drowning  Acute pancreatitis
 Inhalation injury  Transfusions
 Reperfusion injury (transplant  Drug overdose
etc)
 Pathophysiology

 Diffuse alveolar damage

 Lung capillary damage

 Inflammation/pulm edema*

 Resulting severe hypoxemia and

decreased lung compliance
 Pathophysiology

Occurs in stages
1. Exudative ( Acute Phase)
2. Proliferative
3. Fibrotic
4. Recovery
 Exudative phase (Acute Phase)
 Alveolar-capillary barrier is formed by
microvascular endothelium and alveolar
epithelium
 Under normal conditions epithelial barrier
is much less permeable than endothelium
 Epithelium is made up of type I and II cells
 Type I cells are injured easily and Type II
cells are more resistant
 Exudative Phase
 In ALI/ARDS – damage to either one occurs
resulting in increased permeability of the barrier
 influx of protein-rich edema fluid into the alveolar
space
 Injury of Type I cells results loss of epithelial
integrity and fluid extravasation (edema)
 Injury of Type II cells then impairs the removal of
the edema fluid
 Exudative Phase

 Dysfunction of Type II cells also leads to

reduced production and turnover of surfactant
which leads to alveolar collapse
 If severe injury to epithelium occurs –
disorganized/insufficient epithelial repair occurs
resulting in fibrosis
 In addition to inflammatory process, there is
evidence that the coagulation system is also
involved
Exudative Phase
 Fibrotic Phase
 After acute phase, some pt will have
uncomplicated course and rapid resolution

 Some pts will progress to fibrotic lung

injury

 Such injury occurs histologically as early

as 5-7 days
 Fibrotic Phase
 Intense inflammation leads to obliteration of the
normal lung architecture
 Alveolar space is filled with mesenchymal cells
and their products
 Reepithelialization and new blood vessel
formation occurs in disorganized manner
 Fibroblasts also proliferate, collagen is
deposited resulting in thickening of interstitium
 Fibrosing alveolitis and cyst formation
 Proliferative Phase
 With intervention (mechanical ventilation)
there is clearance of alveolar fluid
 Soluble proteins are removed by diffusion
between alveolar epithelial cells
 Insoluble proteins are removed by
endocytosis and transcytosis through
epithelial cells and phagocytosis through
macrophages
 Proliferative Phase
 Type II cells begin to differentiate into
Type I cells and reepithelialize denuded
alveolar epithelium

 Further epithelialization leads to increased

alveolar clearance
Proliferative Phase
 Consequences
 Impaired gas exhange leading to severe
hypoxemia - 2/2 ventilation-perfusion mismatch,
increase in physiologic deadspace
 Decreased lung compliance – due to the
stiffness of poorly or nonaerated lung
 Pulm HTN – 25% of pts, due to hypoxic
vasoconstriction, Vascular compression by
positive airway compression, airway collapse
and lung parenchymal destruction
 Clinical Features
 Pts are critically ill
 develop rapidly worsening tachypnea, dyspnea,
hypoxia requiring high conc of O2
 Occurs within hours to days ( usually12-48
hours) of inciting event
 Early clinical features reflects precipitants of
ARDS
 Physical exam shows cyanosis, tachycardia,
tachypnea and diffuse rales and other signs of
inciting event
 Work Up
 ARDS is a clinical diagnosis
 No specific lab abnormality beyond
disturbance in gas exchange is evident
 Radiologic findings may be consistent but
not diagnostic
 w/u therefore is useful in identifying
inciting event or excluding other causes of
lung injury
 Work Up
Useful diagnostic workup may include

- CBC, Renal panel, Coags, LFTs, pancreatitic enzymes,

UA
- Blood cx, urine cx
- Tox screen
- BNP (low BNP may point to ARDS) (8)
- TTE
- CXR
- CT
- Bronchoscopy/BAL
- CVP, PCWP
 CXR findings
diffuse, fluffy alveolar infiltrates with prominent air
bronchograms
CT findings
 Treatment

 No specific therapy for ARDS exists

 Mainstay of treatment is supportive care

 Treat underlying/inciting conditions

 Treatment – Fluids
 ARDSNet study comparing a conservative and a
liberal fluid stategies (9)
 Rationale behind this study is decreasing pulm
edema by restricting fluids
 Randomized, using explicit protocols applied for
7 days in 1000 pts in ALI
 Randomization was into fluid liberal vs fluid
conservative
 Primary end point was death at 60 days
 Secondary end points included vent-free days,
organ failure free days
 Treatment – Fluids
 Study did not show any significant difference in 60 day
mortality
 However pts treated with fluid conservative strategy had
an improved oxygenation index and lung injury score
 In addition, there was an increased in vent-free days
without increase in nonpulm organ failures
 Also noted in this study is that in fluid conservative group
the fluid balance was more even than negative which
may indicate the observed benefit may be
underestimated
 Treatment - Ventilation
Goals of ventilation in ARDS are to:
 Maintain oxygenation by keeping O2 sats
at 85-90%
 Avoiding oxygen toxicity and
complication of mechanical ventilation –
decreasing FiO2 to less than 65% within
the 1st 24-48 hours
 Treatment - Ventilation
 Known – TV in normal persons at rest is 6-
7ml/kg
 But historically TV of 12-15ml/kg was
recommended in ALI/ARDS
 It was also recognized this strategy of high
TV causes Vent-associated lung injury as
early as 1970s
 Then came the land mark ARDSNet study
which compared traditional TV to lower TV
 Treatment – Ventilation
ARDSNet ( low vs traditional TV)
 861 pts with ALI/ARDS at 10 centers
 Patients randomized to tidal volumes of 12
mL /kg or 6 ml/kg (volume control, assist
control)
 In group receiving lower TV, plateau
pressure cannot exceed 30 cm H2O
 22% reduction in mortality in patients
receiving smaller tidal volume
 Number-needed to treat: 12 patients
 ARDSNet
6ml/kg 12m/kg
 PaCO2 43 ± 12 36 ±9
 Respiratory rate 30 ± 7 17 ± 7
 PaO2/F /FIO2 160 ± 68 177 ± 81
 Plateau pressure 26 ± 7 34 ± 9
 PEEP 9.2 ± 3.6 8.6 ± 4.2
 ARDSNet low vs traditional TV
protocol
 * Calculated predicted body weight(pbw)
male: 50+2.3[height(inches)-60]
female: 45.5+2.3[height(inches)-60]
Mode: Volume assist-control
Change rate to adjust minute ventilation (not>35/min)
PH goal 7.30-7.45
Plateau press<30cmh20
PaO2 goal: 55-80mmhg or SpO2 88-95%
FiO2/PEEP combination to achieve oxygenation goal.
 Treatment - Ventilation
What about PEEP?
 Another ARDS net study compared higher
vs lower PEEP in ARDS
 This study was conducted because of the
observation that low tidal volume pt
required high PEEP and this may have
contributed improved survival
 In the same token, there has always been
a concern that high levels of PEEP may
contribute to vent-associated lung injury
 Treatment - Ventilation
What about PEEP?
 Another multicentered, randomized study involved 549
pts
 Low Tidal volume strategy - calculated predicted body
weight (pbw)
male: 50+2.3[height(inches)-60]
female: 45.5+2.3[height(inches)-60]
Mode: Volume assist-control
Change rate to adjust minute ventilation(not>35/min)
PH goal 7.30-7.45
Plateau press<30cmh20
PaO2 goal: 55-80mmhg or SpO2 88-95%
FiO2/PEEP combination to achieve oxygenation goal
 Treatment - Ventilation
What about PEEP?
 Result of the study showed no benefit from
higher levels of PEEP in either mortality or
secondary outcomes ( vent- free days, icu-
free stays or organ failure)
 No significant increase in lung injury was
noted either
 So PEEP really does not matter!
 How to select vent settings
 PEEP/FiO relationship to maintain
2

adequate PaO2/SpO2
 PaO2 goal: 55-80mmHg or SpO2 88-95%
use FiO2/PEEP combination to achieve
oxygenation goal
How to select vent settings
 other ventilation strategies
 Recruitment maneuvers

 Prone

 Inhaled nitric oxide

 High frequency oscillation

 Treatment

 Treatment strategy is one of low volume and high frequency

ventilation (ARDSNet protocol)
- Low Vt (6ml/kg) to prevent over-distention
- increase respiratory rate to avoid very high level of hypercapnia
- PaCO2 allowed to rise, usually well tolerated
- May be beneficial
- low CVPs

 Search for and treat the underlying cause; surgery if needed

 Ensure adequate nutrition and place on GI/DVT prophylaxis
 Prevent and treat nosocomial infx
 Consider short course of high dose steroids in pts w/ severe dz that
is not resolving.
 ARDSnet and Long-term outcome
120pts randomized to low Vt or high Vt
a) 25%mortality w/ low tidal volume
b) 45% mortality w/ high tidal volume
20% had restricitve defect and 20% had obstructive defect 1 yr after
recovery
About 80% had DLCO reduction 1 yr after recovery
Standardized tested showed health-related quality of life lower than
normal
No difference in long-term outcomes between tidal volume group
 References
1. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute Respiratory distress in Adults.
Lancet 1967; 2: 319-23
2. Petty TL, Ashbaugh DG. The adult respiratory distress syndrome: clinical features, factors
influencing prognosis and principles of management. Chest 1971; 60:233-9
3. Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of adult respiratory
distress syndrome . Am Rev Respir Dis 1988; 138:720-3
4. Luhr OR, Antonsen K, Karlsson M. Incidence and mortality after acute respiratory failure
and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study
Group. Am J Respir Crit Care Med. Jun 1999;159(6):1849-61.
5. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M.Incidence and outcomes
of acute lung injury. N Engl J Med. Oct 20 2005;353(16):1685-93.
6. Davidson TA, Caldwell ES, Curtis JR. Reduced quality of life in survivors of acute
respiratory distress syndrome compared withcritically ill control patients. JAMA. Jan 27
1999;281(4):354-60
7. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. May
4 2000;342(18):1334-49.
8. Levitt JE, Vinayak AG, Gehlbach BK, et al. Diagnostic utility of BNP in critically ill patients
with pulmonary edema: a prospective cohort study. Crit Care 2008; 12: R3
 References
9. The NHLBI ARDS Clinical Trials Network. Comparison of two fluid-management
strategies inacute lung injury. N Engl J Med. Jun 15 2006;354(24):2564-75
10. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal
volumes as compared with traditional tidal volumes for acute lung injury and the acute
respiratory distres syndrome. N Engl J Med. May 4 2000;342(18):1301-8
11. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M. Higher
versus lower positive end-expiratory pressures in patients with the acute respiratory
distress syndrome. N Engl J Med. Jul 22 2004;351(4):327-36
12. Esteban A, Alia I, Gordo F. Prospective randomized trial comparing pressure-controlled
ventilation and volume-controlled ventilation in ARDS. For the Spanish Lung Failure
Collaborative Group. Chest. Jun 2000;117(6):1690-6
13. Griffiths MJ, Evans TW. Inhaled nitric oxide therapy in adults. N Engl J Med. Dec
22 2005;353(25):2683-95.
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we are, and where do we go from here. Crit Care Med. Sep 1997;25(9):1453-4
15. Herridge MS, Cheung AM, Tansey CM. One-year outcomes in survivors of the acute
respiratory distress syndrome. N Engl J Med. Feb 20 2003;348(8):683-93