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)

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. ARDS - Tidal Volume Has Decreased...
But Has Mortality?

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. Acute Respiratory Distress in Adults
Ashbaugh et al. Lancet 1967 2:319-323

5. Who Cares About ARDS?
• Incidence:
 estimates range from 1.5 - 72 cases/100 000

7. 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

9. MS Herridge, AM Cheung, et al.
New Engl J Med 2003;348:683-93

15. 361 ICUs
March 1998
5183 Pts
Ventilated >12 hrs
Followed for 28 days

16. England
France
Greece
Ireland
Italy
Portugal
Spain
Tunizia
Canada
U.S.A.
Argentina
Bolivia
Brazil
Chile
Colombia
Ecuador
México
Perú
Uruguay
Venezuela

21. 1998
Prospective Observational Study
361 ICUs - 20 Countries
Esteban et al. JAMA 2002
2004
Prospective Observational Study
424 ICUs - 26 Countries

22. 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

23. 1998
N = 5183
Age
Mean (SD)
Female, %
SAPS II
Mean (SD)
2004
N = 4968
59 (17)
59 (17)
37%
40%
44 (17)
43 (17)

24. Reason for Initiation of
Mechanical Ventilation
69
72
ARF
17
21
Coma
10
COPD
Neuromuscular
disease
6
2
1
1998
2004

25. 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

26. How has practice changed?
Has the ‘evidence’
been a factor?

27. 1998
1383 Patients in
103 Repeat
ICUs
∆
2004
1675 patients
in 103 Repeat
ICUs
Literature Review
Practice-change
Hypotheses

28. 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

29. Hypotheses
NOT
Recommedations
Endorsements
Guidelines
Necessarily what we would do
Simply predictions...

30. Practice Change Groups
• Non-invasive Ventilation
• Weaning
• ARDS/ALI Lung-Protection

31. Summaries: ARDS Lung Protection
• 11 RCTs

32. 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

33. 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

34. PEEP (cm of water)
20
7.7 ± 3.4 8.7 ± 4.4
15
10
5
p=0.02
ARDS

35. 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

36. 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

37. Prone Ventilation
8
7.1
1998
7
6
p=0.03
5
4
3.4
3
2
1
0
Prone
2004

38. 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


39. 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

41. • Reasons for lack of mortality change
 Changes in admission patterns over time
 Insufficient magnitude of change
 Underpowered to detect differences
 Unselected population vs. RCTs

42. 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

46. Am J Resp Crit Care Med 2009 IN PRESS

48. Observational
RCTs
Am J Resp Crit Care Med 2009 IN PRESS

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

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

51. 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

52. Importance of recognising ARDS

53. From Ware & Matthay NEJM 2000

55. Definition Testing: Autopsy
Correlations

56. 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%)

57. 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

58. 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

59. 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

60. 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

61. 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

62. 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

63. n.ferguson@utoronto.ca
October 25-28, 2009
Metro Toronto Convention Centre

64. n.ferguson@utoronto.ca