ards: an evidence-based update. by mac sweeney
DESCRIPTION
Rob mac Sweeney dissects the current evidence base that governs our diagnosis and management of ARDS. Distressing results.TRANSCRIPT
Disclosure• Research funding from Northern Ireland Health and Social Care
Research and Development Board• Research into ARDS biomarkers
• http://www.criticalcarereviews.com/index.php/smacc-2014
References
A Condition That….
1. can’t diagnose2. of limited use3. no specific treatment for4. people don’t die from
……….. doesn’t actually exist
Wikimedia Commons
Wikimedia Commons
Wikimedia Commons
Causes
Pulmonary • Pneumonia• Pulmonary contusion• Inhalational injury• Aspiration• Fat embolism• Near Drowning
Extra-Pulmonary • Extra-pulmonary sepsis• Trauma• Burns• Acute Pancreatitis• Massive Transfusion• Drug overdose
Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome
Original Description • Case Series of 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
Acute Lung Injury
ALI ARDS
300 – 200 mmHg < 200 mmHg
40 – 26.6 kPa < 40 kPa
Acute Respiratory Distress Syndrome
mild moderate severe
< 300 mmHg < 200 mmHg
< 40 kPa < kPa 26.6
< 100 mmHg
< kPa 13.3
Wikimedia Commons
Definition
Prediction
Clinical Utility
Autopsy Timing
Definition
Prediction
Clinical Utility
Autopsy
Timing Oedema
Timing
Definition
Prediction
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2
Radiograph InfiltratesOedemaOrigin
Definition
Prediction
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2
OxygenationOxygenation
Definition
Prediction
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2
Infiltrates
Infiltrates
Infiltrates
Definition
Utility
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2
Infiltrates
Infiltrates
Definition
Utility
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporality
Temporary
Temporality
Definition
Utility
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Clinical Use
Temporary Reality
ClinicalReality
Definition
Utility
Clinical Utility
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
ClinicalConsequence
Recognition
Recognition
Reality
Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary Recognition Reality
Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
Severity
Cause
Recognition
Cause
Reality
Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
Severity
Cause Prediction
Recognition
Prediction
Reality
Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
Severity
Cause Prediction
Recognition Reality
Definition
Utility
Mortality
Autopsy
Timing Oedema PaO2/FiO2 Infiltrates
Temporary
DiffuseAlveolarDamage
Cause Prediction
DAD
Recognition Reality
Source: Wikimedia Commons
50%
50%
One in Two
DAD
ARDS
DAD
ARDS
Pneumonia No Lesion
Abscess
COPD
DAD
ARDS
Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
Pneumonia No Lesion
Abscess
COPD Cancer
DAD
ARDS
Pneumonia No Lesion
Abscess
COPD Cancer
DADPEBleedingFibrosisPOTB
ARDS
DAD
ARDS
DAD
NON - DAD
ARDS
ARDS
NON - ARDS
ARDS
NON - ARDS
Therapy
General
ARDS
NON - ARDS
Therapy
DADSpecific
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)
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)
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)
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)
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)
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)
?
Therapeutic Evidence-Base
Timing InfiltratesOedema PaO2/FiO2
Temporary Function Clinical
Severity Mortality
DAD
?
Ventilatory Adjuncts
Haemodynamics
Drugs
ECMO
Ventilation
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
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
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)
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)
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
Haemodynamics
Drugs
ECMO
Ventilation
Ventilatory Adjuncts
Haemodynamics
Drugs
ECMO
Ventilation
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)
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%
Prone Ventilation
• 4 RCTS• 1,573 patients
In the most hypoxaemic• 486 patients• PaO2/FiO2 < 100 mmHg• absolute mortality reduction 10%
(6% to 21%)
Ventilatory Adjuncts
NMBs
Drugs
ECMO
Ventilation
Prone
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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
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
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
Ventilatory Adjuncts
Fluids
Fluids CVC
ECMO
Ventilation
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
Drugs
Drugs
Clinically 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 X
Drugs
Clinically 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 X
Clinically Untested1. Prostacyclin2. Almitrine3. Ibuprofen4. N-Acetylcysteine5. Mucolytics6. Albumin
Drugs
Clinically 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 X
Clinically Untested1. Prostacyclin2. Almitrine3. Ibuprofen4. N-Acetylcysteine5. Mucolytics6. Albumin
Next Wave1. Statins2. Aspirin3. ACEI / ARB4. Macrolides5. Insulin6. Vitamin D7. Antibodies• Complement• Interleukins
8. Stem cells9. Growth factors10. Gene therapy
Drugs
Clinically 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 X
Clinically Untested1. Prostacyclin2. Almitrine3. Ibuprofen4. N-Acetylcysteine5. Mucolytics6. Albumin
Next Wave1. Statins2. Aspirin3. ACEI / ARB4. Macrolides5. Insulin6. Vitamin D7. Antibodies• Complement• Interleukins
8. Stem cells9. Growth factors10. Gene therapy
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 =
0.087Hospital death • albuterol 23.0% vs control 17.7%• 95% CI difference –4.0 to 14.7%, P=0.30
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∙ ∙ ∙
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
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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
ECMO
ANZICS H1N1 ECMO Case Series• 2009 influenza A(H1N1) - associated
ARDS• 68 patients
• Median PaO2/FiO2 56 (48-63) mmHg• 71% survival
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
Ventilatory Adjuncts
Fluids
Drugs
ECMO
Ventilation
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)
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)
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)
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)
ARDS – A Condition That….
1. can’t diagnose2. of limited use3. no specific treatment for4. people don’t die from
…….doesn’t actually exist
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?
http://www.flickr.com/photos/furlined/6744550629
References at: www.criticalcarereviews.com/SMACC
Autopsy Case Series
• 712 Autopsies
• 356 ARDS patients
• 159 had DAD (45%)
• 75% of severe ARDS had DAD