Acute Respiratory Distress syndrome

1
Acute Respiratory Distress syndrome

• Meron Yimen
• PGY 3

2
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)

3
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

4
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

5
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 lt 18 mmHg        - P/F ratio
  lt 200( ALI if P/F ratio lt 300 )

6
Epidemiology

• the problem has always been how to identify the
  cases
• attempts at extrapolating incidences based on the
  variousdefinitions offered above have resulted
  in various numbers (1.5-8.3 - 75/100,000)
• the first study using the 1994 AECC definition
  was done inScandinavia (reported incidence of
  17.6/100,000 for ALI and13.5/100,000 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

7
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 gt 85 yrs
• 2/2 co-morbid conditions
• Mortality is attributable to sepsis or multiorgan
  dysfunction

8
Morbidity and Mortality

• Morbidity
• - prolonged hospital course- nosocomial
  infections especially VAP
• - wt loss
• - muscle weakness
• - functional impairment in months following

9
Causes

• DIRECT LUNG INJURY
• COMMON
• PNA
• Aspiration
• LESS COMMON
• Pulm contusion
• Fat emboli
• Near-drowning
• Inhalation injury
• Reperfusion injury (transplant etc)

• INDIRECT LUNG INJURY
• COMMON
• Sepsis
• Severe trauma with shock and multiple
  transfusions
• LESS COMMON
• Cardiopulm bypass
• Acute pancreatitis
• Transfusions
• Drug overdose

10
Pathophysiology

• Diffuse alveolar damage
• Lung capillary damage
• Inflammation/pulm edema
• Resulting severe hypoxemia and decreased lung
  compliance

11
Pathophysiology

• Occurs in stages
• Exudative ( Acute Phase)
• Proliferative
• Fibrotic
• Recovery

12
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

13
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

14
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

15
Exudative Phase
16
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

17
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

18
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

19
Proliferative Phase

• Type II cells begin to differentiate into Type I
  cells and reepithelialize denuded alveolar
  epithelium
• Further epithelialization leads to increased
  alveolar clearance

20
Proliferative Phase
21
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

22
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

23
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

24
Work UpUseful 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

25
CXR findingsdiffuse, fluffy alveolar infiltrates
with prominent air bronchograms
26
CT findings
27
Treatment

• No specific therapy for ARDS exists
• Mainstay of treatment is supportive care
• Treat underlying/inciting conditions

28
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

29
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

30
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

31
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

32
Treatment VentilationARDSNet ( 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

33
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

34
ARDSNet low vs traditional TVprotocol

• Calculated predicted body weight(pbw)
• male 502.3height(inches)-60
• female 45.52.3height(inches)-60
• Mode Volume assist-control
• Change rate to adjust minute ventilation
  (notgt35/min)
• PH goal 7.30-7.45
• Plateau presslt30cmh20
• PaO2 goal 55-80mmhg or SpO2 88-95
• FiO2/PEEP combination to achieve oxygenation
  goal.

35
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

36
Treatment - Ventilation What about PEEP?

• Another multicentered, randomized study involved
  549 pts
• Low Tidal volume strategy - calculated predicted
  body weight (pbw)
• male 502.3height(inches)-60
• female 45.52.3height(inches)-60
• Mode Volume assist-control
• Change rate to adjust minute ventilation(notgt35/mi
  n)
• PH goal 7.30-7.45
• Plateau presslt30cmh20
• PaO2 goal 55-80mmhg or SpO2 88-95
• FiO2/PEEP combination to achieve oxygenation goal

37
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!

38
How to select vent settings

• PEEP/FiO2 relationship to maintain adequate
  PaO2/SpO2
• PaO2 goal 55-80mmHg or SpO2 88-95 use FiO2/PEEP
  combination to achieve oxygenation goal

39
How to select vent settings
40
other ventilation strategies

• Recruitment maneuvers
• Prone
• Inhaled nitric oxide
• High frequency oscillation

41
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.

42
ARDSnet and Long-term outcome

• 120pts randomized to low Vt or high Vt
• a) 25mortality 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

43
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 60233-9
• 3. Murray JF, Matthay MA, Luce JM, Flick MR. An
  expanded definition of adult respiratory distress
  syndrome . Am Rev Respir Dis 1988 138720-3
• 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 1999159(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
  2005353(16)1685-93.
• 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 1999281(4)354-60
• Ware LB, Matthay MA. The acute respiratory
  distress syndrome. N Engl J Med. May
  4 2000342(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

44
References

• The NHLBI ARDS Clinical Trials Network. Comparison
  of two fluid-management strategies inacute lung
  injury. N Engl J Med. Jun 15 2006354(24)2564-75
• 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 2000342(18)1301-8
• 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 2004351(4)327-36
• 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 2000117(6)1690-6
• Griffiths MJ, Evans TW. Inhaled nitric oxide
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• Albert RK. The prone position in acute
  respiratory distress syndrome where we are, and
  where do we go from here. Crit Care
  Med. Sep 199725(9)1453-4
• Herridge MS, Cheung AM, Tansey CM. One-year
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  distress syndrome. N Engl J Med. Feb
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