Download - Ards Update Liverpool 2015
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Disclosure
• No conflicts of interest
References• www.criticalcarereviews.com/index.php/
meetings/2457-liverpool-2015
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A Condition That….
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A Condition That….
1. can’t diagnose
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A Condition That….
1. can’t diagnose2. of limited use
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A Condition That….
1. can’t diagnose2. of limited use3. no specific treatment for
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A Condition That….
1. can’t diagnose2. of limited use3. no specific treatment for4. people don’t die from
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A Condition That….
1. can’t diagnose2. of limited use3. no specific treatment for4. people don’t die from
……….. doesn’t actually exist
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Wikimedia Commons
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Wikimedia Commons
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Source: Wikimedia Commons
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Causes
Pulmonary •Pneumonia•Pulmonary contusion•Inhalational injury•Aspiration•Fat embolism•Near Drowning
Extra-Pulmonary h
•Extra-pulmonary sepsis•Trauma•Burns•Acute Pancreatitis•Massive Transfusion•Drug overdose
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Acute Respiratory Distress Syndrome
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Acute Respiratory Distress Syndrome
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Original Description Case Series of 12
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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
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Acute Lung Injury
ALI ARDS
300 – 200 mmHg < 200 mmHg
40 – 26.6 kPa < 40 kPa
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Acute Respiratory Distress Syndrome
mild moderate severe
< 300 mmHg < 200 mmHg
< 40 kPa < kPa 26.6
< 100 mmHg
< kPa 13.3
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Wikimedia Commons
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Definition
Prediction
Clinical Utility
Autopsy Timing
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Definition
Prediction
Clinical Utility
Autopsy
Timing Oedema
Timing
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Definition
Prediction
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2
Radiograph Infiltrates
OedemaOrigin
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Definition
Prediction
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2
Oxygenation
Oxygenation
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Definition
Prediction
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2
Infiltrates
Infiltrates
Infiltrates
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Definition
Utility
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2
Infiltrates
Infiltrates
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Definition
Utility
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporality
Temporary
Temporality
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Definition
Utility
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Clinical Use
Temporary Reality
ClinicalReality
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Definition
Utility
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
ClinicalConsequence
Recognition
Recognition
Reality
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Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary Recognition Reality
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Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
Severity
Cause
Recognition
Cause
Reality
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Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
Severity
Cause Prediction
Recognition
Prediction
Reality
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Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
Severity
Cause Prediction
Recognition Reality
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Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
DiffuseAlveolarDamage
Cause Prediction
DAD
Recognition Reality
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Source: Wikimedia Commons
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50%
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50%
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One in Two
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DAD
ARDS
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DAD
ARDS
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Pneumonia No Lesion
Abscess
COPD
DAD
ARDS
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Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
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Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
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Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
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Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
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Pneumonia No Lesion
Abscess
COPD Cancer
DADPEBleedingFibrosisPOTB
ARDS
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DAD
ARDS
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DAD
NON - DAD
ARDS
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ARDS
NON - ARDS
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ARDS
NON - ARDS
Therapy
General
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ARDS
NON - ARDS
Therapy
DADSpecific
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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)
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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)
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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)
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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)
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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)
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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)
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?
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Therapeutic Evidence-Base
Timing InfiltratesOedema PaO2/FiO2
Temporary Function Clinical
Severity Mortality
DAD
?
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Ventilatory Adjuncts
Haemodynamics
Drugs
ECMO
Ventilation
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Tidal Volume • 861 ARDS patients (P/F < 300)
• 6 ml/kg & Pplt ≤ 30 cm H20 versus• 12 ml/kg & Pplt ≤ 50 cm H20 • 9% absolute risk reduction in 28 day mortality
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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
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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)
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Driving Pressure
• 3,562 ARDS patients • 9 previous RCTs• ΔP = VT / CRS
• ↑ Mortality with 1 SD (7 cm H20) • RR 1.41; 95% CI 1.31 – 1.51; P < 0.001
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Oscillate
• 548 ARDS patients • P/F < 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)
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Oscar
• 795 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)
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Haemodynamics
Drugs
ECMO
Ventilation
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Ventilatory Adjuncts
Haemodynamics
Drugs
ECMO
Ventilation
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ACURASYS Study
• 340 ARDS patients• PaO2/FiO2 < 150 mmHg
Adjusted Mortality Day 90 • NMB: 31.6% vs placebo: 40.7%• HR 0.68 (95% CI 0.48 to 0.98; P = 0.04)
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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%
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Prone Ventilation
• 4 RCTS• 1,573 patients
In the most hypoxaemic• 486 patients• PaO2/FiO2 < 100 mmHg• absolute mortality reduction 10% (95% CI 6% to 21%)
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Ventilatory Adjuncts
NMBs
Drugs
ECMO
Ventilation
Prone
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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FACTT Study
• 1000 patients with ALI• 0 ml vs 7000 ml fluid balance at day 7
60 Day Mortality• Conservative: 25.5% • Liberal 28.4% • 95% CI difference −2.6 to 8.4 %
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FACTT Study
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FACTT Study
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FACTT Study
• 1000 patients with ALI• No difference • 60 day mortality (≈27%)• Ventilator-Free Days (≈13%)• Days not spent in ICU (≈12%)
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Ventilatory Adjuncts
Fluids
Fluids CVC
ECMO
Ventilation
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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Drugs
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DrugsClinically Tested1. NMBs √2. Steroids ?3. Surfactant X4. β2 agonists X5. Diuretics6. Ketoconazole X7. Activated Protein C X8. Nitric Oxide X9. Silvelestat X10. Lisofylline X11. Pharmaconutrients12. Statins
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DrugsClinically Tested1. NMBs √2. Steroids ?3. Surfactant X4. β2 agonists X5. Diuretics6. Ketoconazole X7. Activated Protein C X8. Nitric Oxide X9. Silvelestat X10. Lisofylline X11. Pharmaconutrients12. Statins
Clinically Untested1. Prostacyclin2. Almitrine3. Ibuprofen4. N-Acetylcysteine5. Mucolytics6. Albumin
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DrugsClinically Tested1. NMBs √2. Steroids ?3. Surfactant X4. β2 agonists X5. Diuretics6. Ketoconazole X7. Activated Protein C X8. Nitric Oxide X9. Silvelestat X10. Lisofylline X11. Pharmaconutrients12. Statins
Clinically Untested1. Prostacyclin2. Almitrine3. Ibuprofen4. N-Acetylcysteine5. Mucolytics6. Albumin
Next Wave1. Aspirin2. ACEI / ARB3. Macrolides4. Insulin5. Vitamin D6. Antibodies• Complement• Interleukins
7. Stem cells8. Growth factors9. Gene therapy
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DrugsClinically Tested1. NMBs √2. Steroids ?3. Surfactant X4. β2 agonists X5. Diuretics ?6. Ketoconazole X7. Activated Protein C X8. Nitric Oxide X9. Silvelestat X10. Lisofylline X11. Pharmaconutrients X12. Statins X
Clinically Untested1. Prostacyclin2. Almitrine3. Ibuprofen4. N-Acetylcysteine5. Mucolytics6. Albumin
Next Wave1. Aspirin2. ACEI / ARB3. Macrolides4. Insulin5. Vitamin D6. Antibodies• Complement• Interleukins
7. Stem cells8. Growth factors9. Gene therapy
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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
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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
Hospital death • albuterol 23.0% vs control 17.7%• 95% CI difference – 4.0 to 14.7%,
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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∙ ∙ ∙
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HARP-2
• Simvastatin 80 mg vs placebo• 540 ARDS patients
• Ventilator-free days• 12.6 vs 11.5; P=0.21
• Nonpulmonary organ failure• 19.4 vs 17.8; P=0.11
• Mortality at day 28• 22.0 vs 26.8%; P=0.23
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SAILS
• Rosuvastatin vs placebo• 745 ARDS patients
• Mortality at day 60• 28.5 vs 24.9%; P=0.23
• Ventilator-free days• 15.1 vs 15.1; P=0.96
• ↑ Nonpulmonary organ failure
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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ECMO
CESAR STUDY• 170 patients with severe respiratory failure
6 month mortality / disability• ECMO centre 63% • Referral 47%• RR 0·69; 95% CI 0·05 to 0·97, p=0·03
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ECMO
ANZICS H1N1 ECMO Case Series• 2009 influenza A(H1N1) – ARDS • 68 patients
• Median PaO2/FiO2 56 mmHg• 71% survival
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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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)
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To Summarise
The positive studies would likely be positive in any critical care condition
1.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)
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To Summarise
The negative studies may be negative because they have been studied in any critical care condition than the specific condition that they are intended for (i.e. DAD)
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To Summarise
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)
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To Summarise
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)
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ARDS – A Condition That….
1. can’t diagnose2. of limited use3. no specific treatment for4. people don’t die from
…….doesn’t actually exist
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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?
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http://www.flickr.com/photos/furlined/6744550629
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