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ARDS - Tidal Volume Has Decreased...
But Has Mortality?
Niall D. Ferguson, MD, FRCPC, MSc
Assistant Professor
Interdepartm...
ARDS - Tidal Volume Has Decreased...
But Has Mortality?
ARDS - Tidal Volume Has Decreased...
But Has Mortality?

Niall D. Ferguson, MD, FRCPC, MSc
Assistant Professor
Interdepart...
Acute Respiratory Distress in Adults
Ashbaugh et al. Lancet 1967 2:319-323
Who Cares About ARDS?
• Incidence:
 estimates range from 1.5 - 72 cases/100 000
Who Cares About ARDS?
• Incidence:
 estimates range from 1.5 - 72 cases/100 000

• Prognosis:
 mortality rate 30 - 70%
...
MS Herridge, AM Cheung, et al.
New Engl J Med 2003;348:683-93
361 ICUs

March 1998
5183 Pts
Ventilated >12 hrs
Followed for 28 days
England
France
Greece
Ireland
Italy
Portugal
Spain
Tunizia

Canada
U.S.A.

Argentina
Bolivia
Brazil
Chile
Colombia
Ecuador...
1998
Prospective Observational Study
361 ICUs - 20 Countries
Esteban et al. JAMA 2002

2004
Prospective Observational Stud...
International Study of Mechanical
Ventilation – 2004 - Coinvestigators
•
•
•
•
•
•
•
•
•
•
•
•
•
•

A Esteban
F Frutos- Vi...
1998

N = 5183
Age
Mean (SD)

Female, %

SAPS II
Mean (SD)

2004

N = 4968

59 (17)

59 (17)

37%

40%

44 (17)

43 (17)
Reason for Initiation of
Mechanical Ventilation
69
72

ARF

17
21

Coma

10
COPD
Neuromuscular
disease

6
2
1

1998
2004
21

Postoperative

16
14

Pneumonia

11
9

Sepsis

10

Trauma

5

10

CHF

7
4.5
4

ARDS
Aspiration

8

2.5
3

1998
2004
How has practice changed?
Has the ‘evidence’
been a factor?
1998
1383 Patients in
103 Repeat
ICUs

∆

2004
1675 patients
in 103 Repeat
ICUs

Literature Review
Practice-change
Hypothe...
Systematic Analysis of Trials
1992-1997 and 1998-2003
• Searched for mechanical ventilation RCTs and
systematic reviews in...
Hypotheses
NOT
Recommedations
Endorsements
Guidelines
Necessarily what we would do

Simply predictions...
Practice Change Groups
• Non-invasive Ventilation

• Weaning
• ARDS/ALI Lung-Protection
Summaries: ARDS Lung Protection
• 11 RCTs
Hypotheses: ARDS
• Decreased tidal volumes in ALI/ARDS
• A minimal increase in PEEP

• No significant increase in PC mode ...
Tidal volume (mL/kg ABW)
20

P < 0.001
15

9.1 ± 1.9

7.4 ± 1.8 (8.8 ml/kg PBW)

10

5
1998

2004

0

ARDS
PEEP (cm of water)
20

7.7 ± 3.4 8.7 ± 4.4

15

10

5

p=0.02

ARDS
ARDS Ventilator Management
1998
(n=135)

2004
(n=198)

p-value

VT > 10
ml/kg ABW

27%

8%

<0.001

VT < 6
ml/kg ABW

4%

...
Ventilator Mode
60
0
50
0

Daysper1000ARDSDays

40
0
30
0
20
0
10
0
0
V
C

P
C

P
S

S V
I
M

20 19
04 98

N
I
V

Oe
t r
h
Prone Ventilation
8

7.1
1998

7
6

p=0.03

5
4

3.4

3
2
1
0

Prone

2004
Hypotheses: ARDS
• Decreased tidal volumes in ALI/ARDS
• A minimal increase in PEEP





• No significant increase in PC...
Conclusions
• Mechanical ventilation practice has
changed significantly from 1998 to 2004

• Many factors may have contrib...
• Reasons for lack of mortality change
 Changes in admission patterns over time
 Insufficient magnitude of change
 Unde...
HAS MORTALITY FROM ARDS
TRULY DECREASED OVER TIME ?
A SYSTEMATIC REVIEW

J Phua, JR Badia, NKJ Adhikari, JO Friedrich,
RA ...
Am J Resp Crit Care Med 2009 IN PRESS
Observational

RCTs
Am J Resp Crit Care Med 2009 IN PRESS
Pooled Weighted Mortality by Year

Am J Resp Crit Care Med 2009 IN PRESS
Meta-regression

Am J Resp Crit Care Med 2009 IN PRESS
Conclusions
• Mortality from ARDS has remained
relatively stable since 1994
• Higher mortality was associated with
observa...
Importance of recognising ARDS
From Ware & Matthay NEJM 2000
Definition Testing: Autopsy
Correlations
Results
• 145 autopsies fulfilling the selection
criteria were idenditified
 3 cases missing clinical history; 3 cases
mi...
The American-European
Consensus Conference on ARDS
Bernard et al. AJRCCM 1994; 149:818-24

• American-European Consensus (...
An Expanded Definition of the Adult
Respiratory Distress Syndrome
Murray et al. ARRD 1987 317:1565-70

Lung Injury Score (...
Clinical Diagnoses of ARDS
• Diagnosis of ARDS on the chart in
20/42 DAD (sensitivity = 48%)
• Among 96 cases without DAD ...
AECC ROC Curves
AECC ROC Curves
1

≥ 2 Quads

0.9
0.8

Bilateral
Infiltrates

Bilateral Alveolar
Infiltrates

P/F 350

≥ 3...
Conclusions
• ARDS appears under-recognised in clinical
practice
 This may have important implications on the
translation...
Conclusions
• ARDS practice is changing and is influenced
by the literature
• Mortality in ARDS has not been declining as
...
n.ferguson@utoronto.ca

October 25-28, 2009
Metro Toronto Convention Centre
n.ferguson@utoronto.ca
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Presented by D.Niall Ferguson at 9th Pulmonary Medicine Update Course held at Cairo, Egypt.
This course is the leading Pulmonary Critical Care event in Egypt. The course is organized by Scribe (www.scribeofegypt.com)

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  1. 1. ARDS - Tidal Volume Has Decreased... But Has Mortality? Niall D. Ferguson, MD, FRCPC, MSc Assistant Professor Interdepartmental Division of Critical Care Medicine University of Toronto
  2. 2. ARDS - Tidal Volume Has Decreased... But Has Mortality?
  3. 3. ARDS - Tidal Volume Has Decreased... But Has Mortality? Niall D. Ferguson, MD, FRCPC, MSc Assistant Professor Interdepartmental Division of Critical Care Medicine University of Toronto
  4. 4. Acute Respiratory Distress in Adults Ashbaugh et al. Lancet 1967 2:319-323
  5. 5. Who Cares About ARDS? • Incidence:  estimates range from 1.5 - 72 cases/100 000
  6. 6. Who Cares About ARDS? • Incidence:  estimates range from 1.5 - 72 cases/100 000 • Prognosis:  mortality rate 30 - 70%  majority of deaths from MODS  median LOS in survivors is 5 weeks  reduced HRQL in survivors
  7. 7. MS Herridge, AM Cheung, et al. New Engl J Med 2003;348:683-93
  8. 8. 361 ICUs March 1998 5183 Pts Ventilated >12 hrs Followed for 28 days
  9. 9. England France Greece Ireland Italy Portugal Spain Tunizia Canada U.S.A. Argentina Bolivia Brazil Chile Colombia Ecuador México Perú Uruguay Venezuela
  10. 10. 1998 Prospective Observational Study 361 ICUs - 20 Countries Esteban et al. JAMA 2002 2004 Prospective Observational Study 424 ICUs - 26 Countries
  11. 11. International Study of Mechanical Ventilation – 2004 - Coinvestigators • • • • • • • • • • • • • • A Esteban F Frutos- Vivar ND Ferguson MO Meade A Anzueto K Raymondos C Apezteguia J Hurtado M Gonzalez V Tomicic F Abroug N Nin M Kuiper A Rezende • • • • • • • • • • • • • L Brochard J Elizalde Y Arabi P Pelosi P Nightingale D Matamis M Jibaja G D’Empaire AM Montanez F Sandi E Tejerina G Turan CM David
  12. 12. 1998 N = 5183 Age Mean (SD) Female, % SAPS II Mean (SD) 2004 N = 4968 59 (17) 59 (17) 37% 40% 44 (17) 43 (17)
  13. 13. Reason for Initiation of Mechanical Ventilation 69 72 ARF 17 21 Coma 10 COPD Neuromuscular disease 6 2 1 1998 2004
  14. 14. 21 Postoperative 16 14 Pneumonia 11 9 Sepsis 10 Trauma 5 10 CHF 7 4.5 4 ARDS Aspiration 8 2.5 3 1998 2004
  15. 15. How has practice changed? Has the ‘evidence’ been a factor?
  16. 16. 1998 1383 Patients in 103 Repeat ICUs ∆ 2004 1675 patients in 103 Repeat ICUs Literature Review Practice-change Hypotheses
  17. 17. Systematic Analysis of Trials 1992-1997 and 1998-2003 • Searched for mechanical ventilation RCTs and systematic reviews in 10 key journals  NEJM, Lancet, JAMA, Annals, BMJ  AJRCCM, CCM, ICM, Chest, Crit Care • 2 Investigators (NF, MM) blinded to 2004 results independently:     Selected papers for inclusion Abstracted study data (incl. quality indicators) Generated summary statements Generated a priori practice change hypotheses
  18. 18. Hypotheses NOT Recommedations Endorsements Guidelines Necessarily what we would do Simply predictions...
  19. 19. Practice Change Groups • Non-invasive Ventilation • Weaning • ARDS/ALI Lung-Protection
  20. 20. Summaries: ARDS Lung Protection • 11 RCTs
  21. 21. Hypotheses: ARDS • Decreased tidal volumes in ALI/ARDS • A minimal increase in PEEP • No significant increase in PC mode use • No significant increase in prone ventilation
  22. 22. Tidal volume (mL/kg ABW) 20 P < 0.001 15 9.1 ± 1.9 7.4 ± 1.8 (8.8 ml/kg PBW) 10 5 1998 2004 0 ARDS
  23. 23. PEEP (cm of water) 20 7.7 ± 3.4 8.7 ± 4.4 15 10 5 p=0.02 ARDS
  24. 24. ARDS Ventilator Management 1998 (n=135) 2004 (n=198) p-value VT > 10 ml/kg ABW 27% 8% <0.001 VT < 6 ml/kg ABW 4% 20% <0.001 PEEP > 10 28% 40% <0.001 PEEP < 5 26% 22% 0.42
  25. 25. Ventilator Mode 60 0 50 0 Daysper1000ARDSDays 40 0 30 0 20 0 10 0 0 V C P C P S S V I M 20 19 04 98 N I V Oe t r h
  26. 26. Prone Ventilation 8 7.1 1998 7 6 p=0.03 5 4 3.4 3 2 1 0 Prone 2004
  27. 27. Hypotheses: ARDS • Decreased tidal volumes in ALI/ARDS • A minimal increase in PEEP   • No significant increase in PC mode use • No significant increase in prone ventilation X 
  28. 28. Conclusions • Mechanical ventilation practice has changed significantly from 1998 to 2004 • Many factors may have contributed to these changes  The concordance of these changes with our a priori predictions suggests that the literature does influence practice
  29. 29. • Reasons for lack of mortality change  Changes in admission patterns over time  Insufficient magnitude of change  Underpowered to detect differences  Unselected population vs. RCTs
  30. 30. HAS MORTALITY FROM ARDS TRULY DECREASED OVER TIME ? A SYSTEMATIC REVIEW J Phua, JR Badia, NKJ Adhikari, JO Friedrich, RA Fowler, JM Singh, DC Scales, DR Stather, A Li, A Jones, DJ Gattas, D Hallett, G Tomlinson, TE Stewart, and ND Ferguson Am J Resp Crit Care Med 2009 IN PRESS
  31. 31. Am J Resp Crit Care Med 2009 IN PRESS
  32. 32. Observational RCTs Am J Resp Crit Care Med 2009 IN PRESS
  33. 33. Pooled Weighted Mortality by Year Am J Resp Crit Care Med 2009 IN PRESS
  34. 34. Meta-regression Am J Resp Crit Care Med 2009 IN PRESS
  35. 35. Conclusions • Mortality from ARDS has remained relatively stable since 1994 • Higher mortality was associated with observational study design & patient age • Benchmark mortality  Observational – 40-45%  RCT – 35-40% Am J Resp Crit Care Med 2009 IN PRESS
  36. 36. Importance of recognising ARDS
  37. 37. From Ware & Matthay NEJM 2000
  38. 38. Definition Testing: Autopsy Correlations
  39. 39. Results • 145 autopsies fulfilling the selection criteria were idenditified  3 cases missing clinical history; 3 cases missing CXR; 1 case palliative without tests • 138 cases included in this study • Prevalence of ARDS: 42 / 138 (30.4%)
  40. 40. The American-European Consensus Conference on ARDS Bernard et al. AJRCCM 1994; 149:818-24 • American-European Consensus (AECC)  PaO2/FIO2 ≤ 200 * &  Acute onset &  CXR with bilateral infiltrates &  PAWP ≤ 18 † *Regardless of PEEP level †or no clinical evidence of left atrial hypertension
  41. 41. An Expanded Definition of the Adult Respiratory Distress Syndrome Murray et al. ARRD 1987 317:1565-70 Lung Injury Score (LIS) • • • • PaO2/FIO2 PEEP Nº CXR quadrants alveolar filling Respiratory system compliance 0-4 points for each component - then divide by number components used Diagnose ARDS if LIS > 2.5
  42. 42. Clinical Diagnoses of ARDS • Diagnosis of ARDS on the chart in 20/42 DAD (sensitivity = 48%) • Among 96 cases without DAD only 9 had a mention of ARDS (specificity = 91%) • Using AECC definition as the reference standard  Sensitivity of only 32% for chart diagnosis
  43. 43. AECC ROC Curves AECC ROC Curves 1 ≥ 2 Quads 0.9 0.8 Bilateral Infiltrates Bilateral Alveolar Infiltrates P/F 350 ≥ 3 Quads P/F 300 P/F 200 sensitivity 0.7 ≥ 3.5 Quads 0.6 P/F 150 P/F 100 0.5 0.4 P/F 75 P/F 75 0.3 0.2 0.1 0 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 1-specificity Oxigenación Radiográfia de Tórax 0.8 0.9 1
  44. 44. Conclusions • ARDS appears under-recognised in clinical practice  This may have important implications on the translation of positive research findings • AECC definition specificity is low when strictly applied  May contribute to false negative results • Strategies do exist to improve accuracy of ARDS definitions
  45. 45. Conclusions • ARDS practice is changing and is influenced by the literature • Mortality in ARDS has not been declining as much as people think  Exercise caution when using RCTs to make epidemiological inferences • The way in which we define ARDS and how we use this definition impacts our understanding of the disease
  46. 46. n.ferguson@utoronto.ca October 25-28, 2009 Metro Toronto Convention Centre
  47. 47. n.ferguson@utoronto.ca

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