Ards Update Liverpool 2015
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1. ARDS is a condition that is difficult to diagnose consistently and has no specific treatments. 2. Half of patients who meet criteria for ARDS at autopsy do not actually have diffuse alveolar damage. 3. Low tidal volume ventilation has been shown to reduce mortality in ARDS, while therapies like HFOV and higher PEEP have not proven benefits.
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Ards Update Liverpool 2015
- 1. Rob Mac Sweeney Liverpool 2015 rob@criticalcarereviews.com / @critcarereviews ARDS An Evidence-Based Update
- 2. Disclosure • No conflicts of interest References • www.criticalcarereviews.com/index.php/meetings /2457-liverpool-2015
- 3. Rob Mac Sweeney Liverpool 2015 rob@criticalcarereviews.com / @critcarereviews ARDS An Evidence-Based Update
- 5. A Condition That…. 1. can’t diagnose
- 6. A Condition That…. 1. can’t diagnose 2. of limited use
- 7. A Condition That…. 1. can’t diagnose 2. of limited use 3. no specific treatment for
- 8. A Condition That…. 1. can’t diagnose 2. of limited use 3. no specific treatment for 4. people don’t die from
- 9. 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
- 15. Causes Pulmonary •Pneumonia •Pulmonary contusion •Inhalational injury •Aspiration •Fat embolism •Near Drowning Extra-Pulmonaryh •Extra-pulmonary sepsis •Trauma •Burns •Acute Pancreatitis •Massive Transfusion •Drug overdose
- 16. Acute Respiratory Distress Syndrome
- 17. Acute Respiratory Distress Syndrome
- 19. 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
- 22. Acute Lung Injury ALI ARDS 300 – 200 mmHg < 200 mmHg 40 – 26.6 kPa < 40 kPa
- 24. Acute Respiratory Distress Syndrome mild moderate severe < 300 mmHg < 200 mmHg < 40 kPa < kPa 26.6 < 100 mmHg < kPa 13.3
- 29. Definition Prediction Clinical Utility Autopsy Timing Oedema PaO2/FiO2 Radiograp h Infiltrates Oedema Origin
- 30. Definition Prediction Clinical Utility Autopsy Timing Oedema PaO2/FiO2 Oxygenatio n Oxygenation
- 31. Definition Prediction Clinical Utility Autopsy Timing Oedema PaO2/FiO2 Infiltrates Infiltrates Infiltrates
- 32. Definition Utility Clinical Utility Autopsy Timing Oedema PaO2/FiO2 Infiltrates Infiltrates
- 33. Definition Utility Clinical Utility Autopsy Timing Oedema PaO2/FiO2 Infiltrates Temporality Temporary Temporality
- 34. Definition Utility Clinical Utility Autopsy Timing Oedema PaO2/FiO2 Infiltrates Clinical Use Temporary Reality Clinical Reality
- 35. Definition Utility Clinical Utility Autopsy Timing Oedema PaO2/FiO2 Infiltrates Temporary Clinical Consequence Recognition Recognition Reality
- 36. Definition Utility Mortality Autopsy Timing Oedema PaO2/FiO2 Infiltrates Temporary RecognitionReality
- 37. Definition Utility Mortality Autopsy Timing Oedema PaO2/FiO2 Infiltrates Temporary Severity Cause Recognition Cause Reality
- 38. Definition Utility Mortality Autopsy Timing Oedema PaO2/FiO2 Infiltrates Temporary Severity Cause Prediction Recognition Prediction Reality
- 39. Definition Utility Mortality Autopsy Timing Oedema PaO2/FiO2 Infiltrates Temporary Severity Cause Prediction RecognitionReality
- 40. Definition Utility Mortality Autopsy Timing Oedema PaO2/FiO2 Infiltrates Temporary Diffuse Alveolar Damage Cause Prediction DAD RecognitionReality
- 42. 50%
- 44. One in Two
- 45. DAD ARDS
- 46. DAD ARDS
- 53. DAD ARDS
- 55. ARDS NON - ARDS
- 59. 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) 1.doesn’t actually exist (half the time)
- 60. 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) 1.doesn’t actually exist (half the time)
- 61. ARDS – A Condition That…. 1. can’t diagnose (we can’t agree to diagnose) 2. of limited use (doesn’t change management) 1.no specific treatment for (getting to it) 2.people don’t die from (mostly) 1.doesn’t actually exist (half the time)
- 62. 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)
- 63. 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)
- 64. 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)
- 67. Therapeutic Evidence- Base Timing InfiltratesOedema PaO2/FiO2 Temporary Function Clinical Severity Mortality DAD ?
- 69. 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
- 70. 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
- 71. 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)
- 72. 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
- 73. 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)
- 74. 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)
- 77. 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)
- 78. 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%
- 79. 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%)
- 82. 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 %
- 83. FACTT Study
- 84. FACTT Study
- 85. FACTT Study • 1000 patients with ALI • No difference • 60 day mortality (≈27%) • Ventilator-Free Days (≈13%) • Days not spent in ICU (≈12%)
- 88. Drugs
- 89. 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 12. Statins
- 90. 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 12. Statins Clinically Untested 1. Prostacyclin 2. Almitrine 3. Ibuprofen 4. N-Acetylcysteine 5. Mucolytics 6. Albumin
- 91. 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 12. Statins Clinically Untested 1. Prostacyclin 2. Almitrine 3. Ibuprofen 4. N-Acetylcysteine 5. Mucolytics 6. Albumin Next Wave 1. Aspirin 2. ACEI / ARB 3. Macrolides 4. Insulin 5. Vitamin D 6. Antibodies • Complement • Interleukins 7. Stem cells 8. Growth factors 9. Gene therapy
- 92. 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 12. Statins X Clinically Untested 1. Prostacyclin 2. Almitrine 3. Ibuprofen 4. N-Acetylcysteine 5. Mucolytics 6. Albumin Next Wave 1. Aspirin 2. ACEI / ARB 3. Macrolides 4. Insulin 5. Vitamin D 6. Antibodies • Complement • Interleukins 7. Stem cells 8. Growth factors 9. Gene therapy
- 93. 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
- 94. 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%,
- 95. 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
- 96. 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
- 97. 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
- 100. 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
- 101. ECMO ANZICS H1N1 ECMO Case Series • 2009 influenza A(H1N1) – ARDS • 68 patients • Median PaO2/FiO2 56 mmHg • 71% survival
- 108. To Summarise 1.The positive studies would likely be positive in any critical care condition 1.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)
- 109. 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)
- 110. 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)
- 111. 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)
- 112. 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)
- 113. 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
- 114. 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?