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ARDS: An Evidence-based Update. By Mac Sweeney.
1. ARDS
An Evidence Based Update
Rob Mac Sweeney
SMACCgold 2014
rob@criticalcarereviews.com / @critcarereviews
2. Disclosure
• Research funding from Northern Ireland Health and Social Care
Research and Development Board
• Research into ARDS biomarkers
References
• http://www.criticalcarereviews.com/index.php/smacc-2014
3. ARDS
An Evidence Based Update
Rob Mac Sweeney
SMACCgold 2014
rob@criticalcarereviews.com / @critcarereviews
4. A Condition That….
1. can’t diagnose
2. of limited use
3. no specific treatment for
4. people don’t die from
……….. doesn’t actually exist
12. Original Description
• Syndrome of
• Severe Dyspnoea
• Tachypnoea
• Cyanosis refractory to oxygen therapy
• Loss of lung compliance
• Benefit with PEEP
• Possible benefit with steroids
• Diffuse alveolar infiltration
53. ARDS – A Condition That….
1. can’t diagnose (we can’t agree to diagnose)
2. of limited use (doesn’t change management)
3. no specific treatment for (getting to it)
4. people don’t die from (mostly)
5. doesn’t actually exist (half the time)
54. ARDS – A Condition That….
1. can’t diagnose (we can’t agree to diagnose)
2. of limited use (doesn’t change management)
3. no specific treatment for (getting to it)
4. people don’t die from (mostly)
5. doesn’t actually exist (half the time)
55. ARDS – A Condition That….
1. can’t diagnose (we can’t agree to diagnose)
2. of limited use (doesn’t change management)
3. no specific treatment for (getting to it)
4. people don’t die from (mostly)
5. doesn’t actually exist (half the time)
56. ARDS – A Condition That….
1. can’t diagnose (we can’t agree to diagnose)
2. of limited use (doesn’t change management)
3. no specific treatment for (getting to it)
4. people don’t die from (mostly)
5. doesn’t actually exist (half the time)
57. ARDS – A Condition That….
1. can’t diagnose (we can’t agree to diagnose)
2. of limited use (doesn’t change management)
3. no specific treatment for (getting to it)
4. people don’t die from (mostly)
5. doesn’t actually exist (half the time)
58. ARDS – A Condition That….
1. can’t diagnose (we can’t agree to diagnose)
2. of limited use (doesn’t change management)
3. no specific treatment for (getting to it)
4. people don’t die from (mostly)
…….doesn’t actually exist (half the time)
59.
60.
61. Therapeutic
Evidence-
Base
?
DAD
Severity Mortality
Temporary Function Clinical
Timing Oedema PaO2/FiO2 Infiltrates
63. Tidal Volume
• 861 ARDS patients (P/F < 300 cm H20)
• 6 ml/kg & Pplt ≤ 30 cm H20
versus
• 12 ml/kg & Pplt ≤ 50 cm H20
• 9% absolute risk reduction in 28 day
mortality
64. Tidal Volume
• 150 critically ill mechanically
ventilated patients
• 6 ml/kg vs 10 ml/kg
Development of ARDS
• 2.6% versus 13.5%; p = 0.01
65. Tidal Volume
• 400 patients undergoing major
abdominal surgery
• 10-12 ml/kg & ZEEP & no recruitment
versus
• 6-8 ml/kg & PEEP 6-8 cm H20 & RM
• Postoperative Respiratory Support
• 5% vs 17%
• RR 0.29 (95% CI 0.14 to 0.61)
66. Oscillate
• 548 ARDS patients
• PaO2/FiO2 < 200 cmH20
• Fi02 > 0.5
In-hospital mortality
• HFOV 47% vs Control 35%
(RR 1.33; 95% CI 1.09 to 1.64;
P = 0.005)
67. Oscar
• 548 ARDS patients
• PaO2/FiO2 < 200 cmH20
• PEEP > 5 cmH20
30 day mortality
• HFOV 41.7% vs Control 41.1%
• Difference 0.6%, 95% CI −6.1 to 7.5
70. ACURASYS Study
• 340 ARDS patients
• PaO2/FiO2 < 150 mmHg
Adjusted Mortality at Day 90
• NMB: 31.6% vs placebo: 40.7%
• HR 0.68 (95% CI 0.48 to 0.98; P = 0.04)
71. PROSEVA Study
• 466 ARDS patients
• PaO2/FiO2 < 150 cmH20
28 day mortality
• Prone: 16% vs Control 32.8%
Unadjusted 90-day mortality
• Prone: 23.6% vs supine 41.0%
72. Prone Ventilation
• 4 RCTS
• 1,573 patients
In the most hypoxaemic
• 486 patients
• PaO2/FiO2 < 100 mmHg
• absolute mortality reduction 10%
(6% to 21%)
75. FACTT Study
• 1000 patients with ALI
• 0 ml vs 7000 ml fluid balance at day 7
60 Day Mortality
• Conservative: 25.5% vs liberal 28.4%
95% CI difference −2.6 to 8.4 %, P=0.3
76. FACTT Study
• 1000 patients with ALI
• 0 ml vs 7000 ml fluid balance at day 7
60 Day Mortality
• Conservative: 25.5% vs liberal 28.4%
95% CI difference −2.6 to 8.4 %, P=0.3
77. FACTT Study
• 1000 patients with ALI
• 0 ml vs 7000 ml fluid balance at day 7
60 Day Mortality
• Conservative: 25.5% vs liberal 28.4%
95% CI difference −2.6 to 8.4 %, P=0.3
81. Drugs
Clinically Tested
1. NMBs √
2. Steroids ?
3. Surfactant X
4. β2 agonists X
5. Diuretics ?
6. Ketoconazole X
7. Activated Protein C X
8. Nitric Oxide X
9. Silvelestat X
10. Lisofylline X
11. Pharmaconutrients X
82. Drugs
Clinically Tested
1. NMBs √
2. Steroids ?
3. Surfactant X
4. β2 agonists X
5. Diuretics ?
6. Ketoconazole X
7. Activated Protein C X
8. Nitric Oxide X
9. Silvelestat X
10. Lisofylline X
11. Pharmaconutrients X
Clinically Untested
1. Prostacyclin
2. Almitrine
3. Ibuprofen
4. N-Acetylcysteine
5. Mucolytics
6. Albumin
83. Drugs
Clinically Tested
1. NMBs √
2. Steroids ?
3. Surfactant X
4. β2 agonists X
5. Diuretics ?
6. Ketoconazole X
7. Activated Protein C X
8. Nitric Oxide X
9. Silvelestat X
10. Lisofylline X
11. Pharmaconutrients X
Clinically Untested
1. Prostacyclin
2. Almitrine
3. Ibuprofen
4. N-Acetylcysteine
5. Mucolytics
6. Albumin
Next Wave
1. Statins
2. Aspirin
3. ACEI / ARB
4. Macrolides
5. Insulin
6. Vitamin D
7. Antibodies
• Complement
• Interleukins
8. Stem cells
9. Growth factors
10. Gene therapy
84. Drugs
Clinically Tested
1. NMBs √
2. Steroids ?
3. Surfactant X
4. β2 agonists X
5. Diuretics ?
6. Ketoconazole X
7. Activated Protein C X
8. Nitric Oxide X
9. Silvelestat X
10. Lisofylline X
11. Pharmaconutrients X
Clinically Untested
1. Prostacyclin
2. Almitrine
3. Ibuprofen
4. N-Acetylcysteine
5. Mucolytics
6. Albumin
Next Wave
1. Statins
2. Aspirin
3. ACEI / ARB
4. Macrolides
5. Insulin
6. Vitamin D
7. Antibodies
• Complement
• Interleukins
8. Stem cells
9. Growth factors
10. Gene therapy
85. ALTA Study
• 282 patients with ALI
• Aerosolized albuterol vs saline
Ventilator-free days
• albuterol 14.4 vs control 16.6 d
• 95% CI difference –4.7 to 0.3 d; P =
0.087
Hospital death
• albuterol 23.0% vs control 17.7%
• 95% CI difference –4.0 to 14.7%, P=0.30
86. BALTI 2 Study
• 326 ARDS patients
• PaO2/FiO2 < 200 mmHg
• IV salbutamol vs placebo
28 day mortality
• salbutamol: 34% vs Control 23%
• RR 1∙47, 95% CI 1∙03 to 2∙08
87. Nitric Oxide
Severe ARDS
• n = 329, six trials
• RR 1.01; 95% CI 0.78 to 1.32; p = 0.93
Mild to Moderate ARDS
• n = 740, seven trials
• RR1.12, 95% CI 0.89 to 1.42; p = 0.33
90. ECMO
CESAR STUDY
• 170 patients with severe respiratory
failure
6 month mortality outcome
• ECMO centre 63% vs referral 47%
• RR 0·69; 95% CI 0·05 to 0·97, p=0·03
91. ECMO
ANZICS H1N1 ECMO Case Series
• 2009 influenza A(H1N1) - associated
ARDS
• 68 patients
• Median PaO2/FiO2 56 (48-63) mmHg
• 71% survival
98. To Summarise
1. The positive studies would likely be positive in
any critical care condition
2. The negative studies are probably negative
because they have been studied in any critical
care condition (i.e. ARDS) rather than the
specific condition that they are intended for
(i.e. DAD)
99. To Summarise
1. The positive studies would likely be positive in
any critical care condition
2. The negative studies may be negative because
they have been studied in any critical care
condition (i.e. ARDS) rather than the specific
condition that they are intended for (i.e. DAD)
100. To Summarise
1. The positive studies would likely be positive in
any critical care condition
2. The negative studies may be negative because
they have been studied in any critical care
condition (i.e. ARDS) rather than the specific
condition that they are intended for (i.e. DAD)
101. To Summarise
1. The positive studies would likely be positive in
any critical care condition
2. The negative studies may be negative because
they have been studied in any critical care
condition (i.e. ARDS) rather than the specific
condition that they are intended for (i.e. DAD)
102. ARDS – A Condition That….
1. can’t diagnose
2. of limited use
3. no specific treatment for
4. people don’t die from
…….doesn’t actually exist
103. Final Thoughts
1. ARDS studies need to be able to identify
alveolar injury
2. Did the AECCC prevent us from adequately
investigating some therapies?
3. Are critical care syndromes really of any use?