Acute Respiratory Distress Syndrome Marty Black MD Concord Pulmonary Medicine 5/4/2018
Financial: none Disclosures
Objectives: Identify clinical features of ARDS Identify physiology and therapeutic benefit of lung-protective ventilation Identify evidence based rescue strategies for ARDS
Cases Pathophysiology Ventilator Basics Therapy Standard Rescue strategies Long-term Outcomes Quiz Outline:
Introductory Cases All of the following patients presented with acute respiratory distress symptoms, abnormal chest x-ray and severe hypoxemia.
67 yo M with HTN, AS with acute hypoxemia
56F with fever, dyspnea
72 yo M hemoptysis
ARDS Consensus Berlin definition: Acute onset (<1week) following compatible insult Bilateral parenchymal opacities Not explainable by cardiogenic edema Hypoxemia (PaO 2 /FiO 2 on PEEP 5 cmh 2 O) Mild: 200-300 Moderate: 100-200 Severe: <100 JAMA. 2012;307(23):2526-2533
Causes of ARDS Pulmonary Extrapulmonary Aspiration Toxic inhalation Pneumonia Near drowning PE - fat/air/amniotic fl. Lung contusion Sepsis Pancreatitis Multi-trauma Drug reaction/od Multiple transfusions Cardiac bypass
History WWI-Vietnam: shock lung ; traumatic wet lung ; Da Nang lung ; post-perfusion lung 1967: Ashbaugh, et. al: Acute respiratory distress in adults 1971: Ashbaugh and Petty: Adult respiratory distress syndrome 1980 s: Acute RDS vs. RDS (neonatal) 1990 s: Pulmonary vs. extrapulmonary ARDS Slide courtesy of Dr. Laura Rock
ARDS Mortality Mortality (%) 100 90 80 70 60 50 40 30 20 10 0 1975 1980 1985 1990 1995 2000 2005 Year Schuster Seattle Brow n U. Amato ARDS Net Liquivent Stew art Brochard Poly. Slide courtesy of Dr. Laura Rock Am J Respir Crit Care Med Vol 179. pp 220 227, 2009
ARDS Mortality Improving? AJRCCM 2008 meta-analysis Phua J, et al: Am J Respir Crit Care Med Vol 179. pp 220 227, 2009
Pathophysiology HETEROGENEOUS DISEASE-- Alveolar filling and consolidation occurs primarily in dependent lung zones NEJM 2000; 342:1334-49 Rad. Clin. North Amer. 1996;34:33-46
Stages of ARDS 1. Exudative phase 2. Proliferative phase 3. Fibrotic phase
NEJM 2000; 342:1334-49
NEJM 2000; 342:1334-49
Ventilator-Induced Lung Injury: Pathophysiology 1. Over-distension of patent lung units 2. Shear stresses due to repetitive opening and collapse of unstable lung units Volutrauma Barotrauma Atelectrauma Biotrauma Slide courtesy of Dr. Laura Rock Chest 1999; 116:9S-15S
Slutsky AS and Rainieri VM. N Engl J Med 2013;369:2126-36.
Slutsky AS and Rainieri VM. N Engl J Med 2013;369:2126-36.
Avoiding Ventilator-Induced Lung Injury There are two injury zones during mechanical ventilation Low Lung Volume Ventilation tears adhesive surfaces High Lung Volume Ventilation over-distends, resulting in Volutrauma The difficulty is finding the Sweet Spot Slide courtesy of Dr. Laura Rock Crit Care Med 1997; 25:906
Ventilator Terminology/Physics PIP Plat PIP = PEEPt + QR + Vt/C Plat = PEEPt + Vt/C Te Ti PEEPt Q = airflow R = resistance C = compliance Vt = tidal volume
How Bad are the Lungs? Murray Score = score for each variable divided by 4 Diaz JV et al: Crit Care Med 2010; 38(8):1-8
ARDS Therapies Strategy Low tidal volume (6cc/kg Vt) High PEEP Euvolemia Paralytics Prone positioning Steroids (within 7-14 days of ARDS) ECMO Outcome improved Survival advantage Small survival advantage in metaanalysis Shorter time on ventilator?survival advantage, shorter time on vent? Survival advantage in severe hypoxemia Shorter time on ventilator No prospective comparator trials
ARDS Therapies Strategy HFOV LABA PA catheters Oxepa Outcome improved Worse survival No impact on outcomes No impact on outcomes Worse survival and # of days on ventilator
Low Tidal Volume Ventilation ARDS network Multi-center RCT 861 patients w/ ALI or ARDS randomized to Low Tidal Volume n = 432 6 ml/kg (IBW) Plateau pressure < 30 cm H 2 O Traditional Tidal Volume n = 429 12 ml/kg (IBW) Plateau pressure < 50 cm H 2 0 NEJM 2000;342:1301-08
Key Concept: Tidal Volumes are based on predicted body weight not actual Female ht 6cc/kg IBW 8cc/kg IBW 5 2 301 401 5 6 356 474 5 10 411 548 Male ht 6cc/kg IBW 8cc/kg IBW 5 4 355 474 5 8 410 547 6 466 621 http://www.ardsnet.org/pbwtables_2006_07_13.pdf
Mechanical Ventilation Protocol Summary http://www.ardsnet.org/lowvtrefcard.pdf
Modified Table 3. Respiratory values during first 7 days of treatment Day 1 Day 3 Day 7 Lower Higher Lower Higher Lower Higher Tidal volumes Plateau pressure 6.2 + 0.9 11.8 + 0.8 6.2 + 1.1 11.8 + 0.8 6.5 + 1.4 11.4 + 1.4 25 + 7 33 + 9 26 + 7 34 + 9 26 + 7 37 + 9 RR 29 + 7 16 + 6 30 + 7 17 + 7 30 + 7 20 + 7 FiO 2 0.56 +0.19 0.51 + 0.17 0.54 + 0.18 0.51 + 0.18 0.50 + 0.17 0.54 + 0.20 PaO2/ FiO2 158 + 73 176 + 76 160 + 68 177 + 81 165 + 71 164 + 88 PEEP 9.4 + 3.6 8.6 + 3.6 9.2 + 3.6 8.6 + 4.2 8.1 + 3.4 9.1 + 4.2 Take home: Subjects on low tidal volume have lower PaO 2 /FiO 2 ratios and lower plateau / peak pressures. P < 0.05
Mortality (%) 2.4% vascular mortality reduction for aspirin in ISIS-2 Lancet. 1988;2(8607):349 Significant decrease in mortality in subjects randomized to 6ml/kg tidal volumes 40 30 20 Absolute Mortality Reduction: 8.9% 10 p = 0.007 0 6 ml/kg 12 ml/kg
Outcomes
Adequate PEEP Benefit of PEEP is balance of lung-recruitment vs. raising intra-thoracic pressure (delay venous return and lowering cardiac output). However optimal PEEP trials have been disappointing for improving outcomes. Pelosi P, et al: AJRCCM 2001; 164: 122 130
Esophageal Pressure and Trans- Pulmonary Pressure Pressure transpulmonary = Pressure airway Pressure esophageal www.viasyshealthcare.com Respir Care 2005;50(1):68 75
Transpulmonary Pressure Plat = PEEPt + Vt(1/Ct) 1/Ct= 1/C cw + 1/C l Therefore measuring Plat does not directly measure lung compliance or pressure across lung units Levitzky MG: Pulmonary Physiology, 7 th edt.
How well does Pes correlate to Ppl in ARDS? Canine model of ARDS compared Pes with Ppl using wafer pressure probes inserted into pleural space. Non-Dependent Lung Middle Lung Am J Respir Crit Care Med Vol 164. pp 122 130, 2001
70pts with acute respiratory failure, observational trial Crit Care Med 2006 Vol. 34, No. 5
Lessons from High-PEEP Trial Conventional Set PEEP 13 +/-3 13 +/-5 Transpulmonary pressure (end-expiratory) -1.9 +/- 4.7-2.8 +/-5 Esophageal Balloon- Guided Briel M, et al: JAMA. 2010;303(9):865-873 Talmor D, et al: N Engl J Med 2008;359:2095-104
Dry Lungs are Happy Lungs RCT of 1001 patients to conservative fluid or liberal fluid strategy Essentially: If adequate perfusion (MAP and UOP), the groups were given diuretics if CVP > 4 (PCWP >8) or CVP > 10 (PCWP >14). Primary Outcome: death before discharge home during the first 60 Secondary Outcomes: vent-free days, days out of ICU, adverse events, etc. N Engl J Med 2006;354:2564-75
Results Cumulative I/O Balance (day 7) Conservative Liberal 136 +/- 491 cc 6992 +/- 502cc 60d-Mortality* 25.5% 28.5% VFD by 60 days 14.6 +/- 0.5 d 12.1 +/- 0.5 d Non-ICU days by 60 days 13.4+/- 0.4 d 11.2 +/- 0.4 d Dialysis by 60 days* 10% 14% * Not statistically significant difference. More metabolic alkalosis, hypokalemia, hypernatremia occurred in conservative group.
Rescue Strategies for Refractory Hypoxemia: Recruitment Maneuver My recruitment maneuver: CPAP 40cmH 2 0 x 40 secs. then return patient to controlled settings with PEEP increased. Risks: hypotension, arrhythmias, desaturation, or barotraumas Pelosi P, et al: AJRCCM 2001; 164: 122 130 Diaz JV, et al: Crit Care Med 2010; 39 (8)
Paralytics Rescue Paralysis vs Planned Paralysis - balance of improved gas exchange vs risk of prolonged neuromuscular weakness RCT of severe ARDS (P/F ~100, C ~30) 2 days of planned cis-atricurium vs. rescue paralysis was associated with increased survival at 90 days and no increase in prolonged ICU-acquired paresis Papazian L, et al: N Engl J Med 2010;363:1107-16.
Prone Positioning
Proning Physiology Change anterior chest wall compliance. Take heart off lung Match perfusion (gravity) to aerated lung Pulmonary toilet
Proning Trials Perhaps improved survival with more hypoxemic, early in course, with >20h/d prone Risks: device dislodgement, pressure ulcers Sud S, et al: Intensive Care Med (2010) 36:585 599
kci.com
PROSEVA Trial NEJM 2013 RCT of severe ARDS (P/F <150) after 12-24 hrs. to confirm ARDS criteria met Randomized to 16 hour prone vs supine Mortality by 28 days was primary outcome N = 474 patients Each center had been using prone positioning for 5 years Guerin C, et al: N Engl J Med 2013;368:2159-68
PROSEVA Trial NEJM 2013 28d Mortality: 16% vs 32.8% favoring prone group No increase in adverse care effects Guerin C, et al: N Engl J Med 2013;368:2159-68
ECMO extra-corporeal membrane oxygenation Veno-arterial Veno-venous
Davies A, et al: JAMA. 2009;302(17):1888-1895
Study Data Australia-New Zealand Experience: 2009 H1N1: 68 patients treated with ECMO. 71% survival to ICU discharge Median duration of ECMO support 10 days RCT data can only say that referral to ECMO center is better than conventional management at non-ecmo center. Davies A, et al: JAMA. 2009;302(17):1888-1895 Peek GJ, et al: Lancet 2009; 374: 1351 63
ELSO: Guidelines Contraindications: NO absolute contraindications to the consideration of ECMO Mechanical ventilation with high inflation pressures (Pplat > 30 cm H2O) or high oxygen concentrations (FiO2 > 0.9) for 7 days Contraindication to anticoagulation Irreversible brain injury CNS hemorrhage that is recent or expanding Active massive hemorrhage Severe immunosuppression or severely immunocompromised host Malignancy with limited life expectancy Severe co-morbidities Futile condition and/or pre-existing treatment limitations Severely limited vascular access Increasing age Morbid obesity or body habitus not conducive to cannulation History of heparin induced thrombocytopenia Unwilling to consent to blood products
Long term outcome - ARDS Cohort of 109 survivors of ARDS at 1 year Median age 45 RRT 12% Tracheostomy 51% LOS (hospital) 48 d (IQR 27 77) Herridge MS, et al: N Engl J Med 2003;348:683-93
Surviving ARDS is Just the Beginning PFTs nearly normal 49% are back to work 66% predicted distance on 6MWT Herridge MS, et al: N Engl J Med 2003;348:683-93
Neuro-Psychiatric Effects at 1 year 36% with moderate to severe PTSD 62% with moderate to severe anxiety Mikkelsen ME, et al: Am J Respir Crit Care Med 2012; 185(12), 1307 1315
Long-term Acute Care Outcomes Multicenter cohort of 1,419 patients at 23 LTAC to undergo ventilator weaning. Age - 71 (median) Median LOS prior to xfer - 27 d Median ventilator days - 25 d 5% on RRT Essentially all had trach/enteral feeding device Scheinhorn DJ, et al: Chest 2007; 131:85 93
LTAC outcomes Scheinhorn DJ, et al: Chest 2007; 131:85 93
Quiz 1.) Name the 4 types of trauma a ventilator can cause. Volutrauma Barotrauma Atelectrauma Biotrauma
Quiz 2.) Which of the following therapies is associated with a survival advantage for patients with ARDS? A. PA-catheter guided hemodynamic assessment B. Limiting Tidal Volumes to 6cc/kg IBW C. Treatment with ECMO D. Maintaining euvolemia over the first 7 days E. The superlative care provided by (insert your name here) B. Limiting Tidal Volumes to 6cc/kg IBW
Quiz 3.) Which of the following are long-term survivors of ARDS at risk to develop? A. Skeletal muscular weakness B. PTSD C. decreased in prior employment D. Residual pulmonary fibrosis E. All of the above E. All of the Above
Summary Despite critical care supports, ARDS is associated with high mortality. Few therapies are clearly associated with improved outcomes, and delivery of these is essential to provide high-quality care. Recovery for our patients does happen, but they have be prepared for a long road.