Oxygenation Failure. Increase FiO2. Titrate end-expiratory pressure. Adjust duty cycle to increase MAP. Patient Positioning. Inhaled Vasodilators

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1 Oxygenation Failure Increase FiO2 Titrate end-expiratory pressure Adjust duty cycle to increase MAP Patient Positioning Inhaled Vasodilators Extracorporeal Circulation

2 ARDS Radiology

3 Increasing Intensity Rescue Strategies in ARDS Current State ECMO? HFOV Prone Inhaled Vasodilators NMB Low PEEP High PEEP NIV Low Tidal Volume Ventilation Mild Moderate Severe Increasing (P/F) Severity 3

4 Increased FiO2 Positive Airway Pressure

5 End Expiratory Pressure Term Inspiration Expiration Use PEEP Volume / Pressure Target PEEP CMV SIMV PC/VC CPAP CPAP CPAP Spont Vent Pressure Support EPAP IPAP EPAP BIPAP

6 P A C P A P A C P A P a C P a P a C P a C a C C a C a C C a

7 PEEP P A C P A P A C P A P a C P a P a C P a C a C C a BLOOD FLOW C a C C a

8 PEEP P A C P A P A C P A P a C P a Blood Flow C a C C a

9 Anatomical Recruitment Functional Recruitment

10 PEEP Adverse Effects Pulmonary Physiology Elevated airway pressures Decrease in PaO2 (increase in shunt fraction) Increase in PaCO2 (increase in deadspace)

11 PEEP Cardiovascular Physiology Reduced RV preload Increased RV afterload Reduced LV afterload

12 PEEP / FiO2 Settings Gas Exchange PEEP / FiO2 Tables Physiology Compliance, Best PEEP, Stress Index Visual CT Scan / Ultrasound

13 Low PEEP Fi PEEP High PEEP Fi PEEP F I and PEEP in ALI/ARDS Low PEEP High PEEP Brower et al. NEJM 2004;351:327-36

14 PEEP in ARDS Tidal Volume PEEP PaO2/FiO2 Plat Crs ALVEOLI LOVS EXPRESS High Low High Low High Low High Low High Low

15 ARDS Subphenotypes and PEEP Briel, M., et al. (2010). Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 303(9), ARDS No ARDS Hospital Mortality ICU Mortality Ventilator -free Use of Rescue Use of Vasopres High PEEP 324 (34.1) 288 (30.3) 12 (0-21) 130 (13.7) 627 (65.9) Low PEEP 368 (39.1) 344 (36.6) 7 (0-20) 200 (21.3) 647 (68.8) Adjusted RR 0.90 (0.81 to 1.00) 0.85 (0.76 to 0.95) 1.22 (0.39 to 2.05) 0.63 (0.53 to 0.75) (0.72 to 1.13) p valu High PEEP Low PEEP (27.2) 44 (19.4) (19.6) 37 (16.8) < (0-23) (51.6) 19 (5.5-24) 8 (4.4) 16 (7.3) 111 (50.5) Adjuste d RR 1.37 ( ) 1.07 (0.74 to 1.55) (-3.60 to 0.11) (0.25 to 1.43) (0.56 to 1.50) p valu

16 Volutrauma Normal Lung - Stretch Injury Atelectrauma Derecruitment -- Recruitment Injury Consolidated - ARDS Injury Biotrauma Stress Mediators

17 Oxygenation in ARDS Traditional Therapy Low tidal volume Supplemental inspired oxygen Positive end-expiratory pressure Salvage Therapy Paralysis Prone ventilation Alternative modes of ventilation Inhaled vasodilators Extracorporeal support

18 ARDS and Paralysis (ACURASYS) Papazian L et al. Neuromuscular blockers in early acute respiratory distress syndrome. NEJM. 2010;363(12): P/F < 150 with PEEP 5 48hrs of onset TV 6-8 ml/kg 90d mortality Paralytic Group (N=177) Control (N=162) Intervention Ramsey Score 6 15mg cisatracurium bolus 37.5mg /hr infusion x 24 hours no TOF Ramsey Score 6 15mg placebo bolus 37.5mg /hr placebo x 24 hours no TOF Therapeutic Targets PaO2 = mm Hg SaO2 = 88-95% ph Pplat < 32 cm H2O PaO2 = mm Hg SaO2 = 88-95% ph Pplat < 32 cm H2O Open Label Sedation, TV, PEEP adjustments 20mg cisatracurium bolus x 2 if Plat > 32 cm Sedation, TV, PEEP adjustments 20mg cisatracurium bolus x 2 if Plat > 32 cm 18

19 ARDS and Paralysis Papazian L et al. Neuromuscular blockers in early acute respiratory distress syndrome. NEJM. 2010;363(12): d Mortality (censored) AHR for P/F, Pplat, SAPS II 0.68, ( ) P=0.04) Crude 31.6% vs 40.7 % P=0.08 VFD AHR 1.41 ( ) P= 0.01 Pneumothorax 4.0 % vs 11.7 % (p = 0.01) 19

20 Crude 30.8 % vs 44.6% (P=0.04) ARDS and Paralysis Papazian L et al. Neuromuscular blockers in early acute respiratory distress syndrome. NEJM. 2010;363(

21 ARDS and Prone Position (ProSEVA) Guérin, C., et al. (2013). Prone Positioning in Severe Acute Respiratory Distress Syndrome. NEJM, 368(23), P/F < 150 with FiO2 > 0.60 and PEEP > 5 TV 6-8 ml/kg, 16 hours prone 28d mortality PaO2/FiO2 Supine Group (N=229) Prone Group (N=237) SAPS II TV (ml/kg PBW) PEEP Plateau pressure

22 ARDS and Prone Position (ProSEVA) Guérin, C., et al. (2013). Prone Positioning in Severe Acute Respiratory Distress Syndrome. NEJM, 368(23), d Mortality AHR for SOFA, NMB, vasopressors 0.42, ( ) P<0.001) 90d Mortality AHR for SOFA, NMB, vasopressors (0.48, ( ) P<0.001) Rescue Therapies S vs P ECM.6 vs 0.8% (P=0.14) ino 15.7 vs 9.7% (P=0.05) NMB 5.6d vs 5.7d (P=0.74) 22

23 Prone Position and Adverse Events Guérin, C., et al. (2013). Prone Positioning in Severe Acute Respiratory Distress Syndrome. NEJM, 368(23), Supine (n=229) Prone (n=237) Nonscheduled Extubation Mainstem Intubation 5 (2.2) 6 (2.5) 25 (10.9) 31 (13.3) ET Tube Obstruction 5 (2.2) 11 (4.9) Hemoptysis 12 (5.2) 6 (2.5) Cardiac Arrest 31 (13.5)* 16 (6.8) Desat SaO2<85 or PaO2<55 x 5 min Bradycardia HR < 30/min for > 1min Hypotension SBP < 60 mm Hg for > 5 min 164 (71.6) 155 (65.4) 27 (11.8) 26 (11.0) 48 (21.0) 35 (14.8) *p<

24 ARDS and Prone Position (ProSEVA) Guérin, C., et al. (2013). Prone Positioning in Severe Acute Respiratory Distress Syndrome. NEJM, 368(23), Termination Criteria oxygenation improvement defined as PaO2/FIO2 150 mmhg with PEEP 10 cm H2O and FIO2 0.6; in the prone group at least 4 hours after the end of the last prone session PaO2/FIO2 ratio deterioration by more than 20 % relative to supine before two consecutive prone sessions complications occurring during a prone session and leading to its immediate interruption, such as non-scheduled extubation, mainstem bronchus intubation, endotracheal tube obstruction, hemoptysis, SpO2<85% or PaO2<55mmHg for more than 5 minutes under FIO21, cardiac arrest, heart rate <30 beats/min for more than 1 minute, systolic blood pressure <60 mmhg for more than 5 minutes, or any other life-threatening reason for which the clinician decided to stop. After patients in the prone group were turned to supine, the prone session could be resumed at any time before the planned assessment at 4 hours in supine if the SpO2 and/or PaO2 criteria were fulfilled. at the clinician s discretion. Patients in supine were not allowed to cross over to prone except as a rescue therapy in case of life-threatening hypoxemia 24

25 Inhaled Prostacyclin (Flolan) UPMC Protocol Delivery via Mini Heart Low Flow Nebulizer ~ 2.25 L /min Flow = 8 mls/hour Nebulizer wet side humidifier / remove HME (radiology) Monitor expiratory port filter mechanics - change daily Discontinue nebulizer medications Location untested - Delivery untested Each patient provides a dose - response curve 25

26 ARDS and Inhaled Prostacyclin UPMC Protocol 26

27 ARDS and Prostacyclin UPMC Protocol Assume the nebulizer delivers a 8ml/hour The drug is ordered in dose ranges of 5-40 ng/kg/min. The dose is controlled by the syringe drug concentration 70kg (PBW) male at a dose of 40ng /kg / min deliver 168,000 ng per hour 168,000 ng / 1000 = 168 mcg x 6 hours = 1008 mcg per syringe epoprostenol 1.5mg (1,500,000 ng ) is added to the diluent (glycine) = 100 mcg/ml for 1008 mcg/6 hours combine 10.08ml of stock diluted to 48 ml 27

28 ARDS and ECMO (CESAR) Peek, G. J., et al. (2009). Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. The Lancet, 374(9698), Patient Population (n=180) Murray LIS > 3 or ph < 7.20 Reversibility Excluded > 7d or no heparin Treatment Protocol Best treatment at Center TV 4-8 ml/kg PBW, Pplat < 30 cm H20 No cross over ECMO Center PC Vent 30cm H20, SaO2 > 90, diuresis Prone ventilation, Hct 40% ECMO (75%) FiO2 > 0.90 for SaO2 > 90 Death or Severe Disability 6 mo RR 0.69 (95% CI ), p<

29 H1N1 and ECMO Pham 2013 France Noah 2011 UK Patroniti 2011 Italy Davies 2009 Australia Sample Size referred 69 treated Pre-ECMO P/F 63 (21) PEEP 13 (4) LIS 3.4 (0.6) P/F < 70 PEEP > 15 P/F 55 (48-65) PEEP 18 (15-20) LIS 3.8 ( ) Matched Propensity Score 1:1 no replacement 52 patients Propensity Score 75 patients No comparison No comparison Hospital Mortality 52 Matched (50%) NS 51 Unmatched (22%) ECM3.7% NonECMO 52.5% RR 0.45 ( ) p=. 006 ECM3% ECM1% Complications Bleeding (60%) ICH (4%) Bleeding (52%) Bleeding (27%) ICH (2%) Bleeding (54%) Infection (62%) ICH (9%) 29

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