ARDS AND ECLS JOSHUA HUELSTER, MD DEPARTMENT OF CRITICAL CARE ABBOTT NORTHWESTERN HOSPITAL
DISCLOSURES I have no financial disclosures I have no conflicts of interest I have my own biases (we all do)
OBJECTIVES Discuss the management of ARDS patients Discuss the rationale behind this care Briefly review veno-venous extra corporeal membrane oxygenation (VV ECMO)
WHAT I M LEAVING OUT Driving pressure: evidence suggests lower is better, but is this a target or a surrogate for severity? We don t know yet Esophageal balloons: surrogate measure of transpulmonary pressure. Promising early data, but waiting for more definitive evidence and not widely used, yet Recruitment maneuvers: no evidence of benefit and recent evidence of harm HFOV: stick a fork in it ECCO 2 R: Not approved in the US studies underway
CASE PRESENTATION 52-YEAR-OLD WOMAN CC: Cough and dyspnea PMHx: Dermatomyositis Obesity Anemia Migraines Family Hx: HTN Father Cancer - Mother Social Hx: Married; 4 children Never smoker, no alcohol Allergies: hydrocodone - acetaminophen Medications: Prednisone 40 mg daily Methotrexate 15 mg weekly Folic acid 1 mg daily Trazodone 100 mg qhs Omeprazole 40 mg daily Zolpidem 10 mg daily
ADMISSION HPI: Three day history of increasing and progressive dyspnea Non-productive cough and fever to 103F Recent diagnosis of dermatomyositis On prolonged prednisone taper current dose 50 mg daily No pneumocystis prophylaxis Started methotrexate 15 mg weekly Seen in Pulmonary clinic for cough no evidence for ILD Exam: T 103F BP 113/66 HR 110 SpO2 94% (4L NC) Gen: mild distress CV: tachycardic, regular Pulm: diffuse crackles Abd: obese, soft Skin: no rash Neuro: awake and alert
ADMISSION CXR Bilateral infiltrates Right greater than left Possible small effusion Infection vs pulmonary edema
ACUTE RESPIRATORY DISTRESS SYNDROME (A BRIEF HISTORY) First described by Ashbaugh and colleagues in 1967 (Lancet) 12 patients with tachypnea, refractory hypoxia and bilateral infiltrates after infection or trauma 7 died 6 of 7 had hyaline membranes lining alveoli at autopsy Up to then thought only to occur in neonates First named Adult Respiratory Distress Syndrome
AECC DEFINITION 1994 An acute condition with bilateral pulmonary infiltrates and severe hypoxemia: Acute Lung Injury : P/F* ratio less than 300 Acute Respiratory Distress Syndrome : P/F < 200 No evidence of cardiogenic pulmonary edema (PCWP < 18) *P/F: PaO2/FiO2 ratio
BERLIN DEFINITION 2012 Hypoxemic respiratory failure with bilateral opacities consistent with pulmonary edema on CXR or CT Onset within 7 days of known clinical insult or new or worsening respiratory symptoms Severity stratification (minimum PEEP or CPAP of 5 cm H2O): Mild: P/F 201 300 mm Hg Moderate: P/F 101 200 mm Hg Severe: P/F 100 mm Hg
Berlin Definition of the Acute Respiratory Distress Syndrome (ARDS). Thompson BT et al. N Engl J Med 2017;377:562-572.
THE CASE CONTINUED 52-YEAR-OLD WOMAN Likely community acquired pneumonia with sepsis Ceftriaxone and azithromycin plus sulfamethoxazole/trimethopr im due to steroid use and possible pneumocystis jiroveci pneumonia Continued steroids ABG 7.39/38/96/22.5 (10L O2 via oxymask)
DAY OF ADMISSION Seen by Pulmonary day of admission with plan for bronchoscopy Progressed to respiratory failure and intubated with transfer to ICU Vent: PRVC RR18 Vt 500 PEEP 5 FiO2 0.6 Her height = 64 inches PBW = 55 Kg Vt 6 ml/kg = 330 ml
ARDSNet NEJM 2000 Landmark trial Compared tidal volume 6 ml/kg PBW to 12 ml/kg PBW and Compared Pplateau 30 vs 50 cm H20 Stopped early due to significantly increased survival in low Vt group
Probability of Survival and of Being Discharged Home and Breathing without Assistance during the First 180 Days after Randomization in Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342:1301-1308.
ARDS net TABLE
HYPOXEMIA IS BAD; IS HYPEROXIA? Retrospective study by Aggarwal et al in latest issue of CCM Dataset from 10 ARDSnet trials Patients with PaO2 > 80 and FiO2 > 0.5 above goal Association between higher above goal score and worse mortality Other studies support this idea, but none are definitive Conclusion (ie my bias): resist increasing FiO2 if PaO2 > 60 and SaO2 > 88%
ICU DAY 1 Continued worsening hypoxia ABG 7.32/46/67/23 Vent: PRVC* RR 22 Vt 300 PEEP 10 FiO2 1.00
Optimal PEEP level is not known, but there is an association to better outcomes if higher PEEP leads to lower tidal volume
LUNG SAFE TRIAL 2014 International, multicenter, prospective cohort study 10.4% (3022/29144) of ICU patients met criteria for ARDS Mild 30.0% Moderate 46.6% Severe 23.4% Recognition was only 51.3% for mild and 78.5% for severe Less than 2/3 received Vt 8 ml/kg; 82.6% had PEEP < 12 Only 16.3% of severe ARDS patients were proned Mortality Mild: 34.9% Moderate 40.3% Severe 46.1%
ICU DAY 1 Continued worsening hypoxia ABG 7.32/46/67/23 Vent: PRVC RR 22 Vt 300 PEEP 10 FiO2 1.00 Inhaled epoprostenol started without improvement in oxygenation
INHALED EPOPROSTENOL AND NITRIC OXIDE
HYPOXIC PULMONARY VASOCONSTRICTION Pulmonary arteries constrict in presence of moderate hypoxia Goal is to maintain ventilation-perfusion (V/Q) ratio during localized alveolar hypoxia Disease states, however, often lead to global hypoxia resulting in increased PVR and increased load on the right ventricle
RATIONALE FOR USE For use in Type I respiratory failure (Hypoxemic) Inhaled vasodilators selectively dilate ventilated areas of lung (because delivery via inhalation)
MECHANISM OF ACTION
MECHANISM OF ACTION
WHICH ONE TO USE? NEITHER has been shown to improve mortality BOTH improve oxygenation and pulmonary vascular resistance
ino IS 4.5-17X MORE $$$$
OTHER CONSIDERATIONS Inhaled nitric oxide (ino) may lead to methemoglobinemia ino is rapidly inactivated by oxyhemoglobin to form nitrosylmethemoglobin Occurs in pulmonary capillaries limiting systemic vasodilation Significant MetHgb formation should not occur below 40 ppm inhalation UK recommends testing within 6 hours of start and after every dose change There is an association between ino and acute kidney injury Both inhibit platelet aggregation variable clinical significance via inhaled route ino used in acute RHF and as vasodilator challenge in PAH (inhaled prostacyclin, as well) No clear evidence of additive effect by using both
MY BIAS ino only indicated if used as rescue therapy beyond all the other rescue therapies you can think of (meaning: I ve used it once in my albeit brief career for refractory hypoxemia)
ICU DAY 1 (IT GETS WORSE) Continued worsening hypoxia ABG 7.32/46/67/23 Vent: PRVC RR 22 Vt 300 PEEP 10 FiO2 1.00 Flolan started without improvement in oxygenation Proned
PRONE POSITIONING Has long been known to improve oxygenation PROSEVA trial showed a significant mortality benefit Now recommended by all societies involved in critical care for patients with severe ARDS
PROSEVA TRIAL NEJM 2013 Severe ARDS P/F < 150 FiO2 0.6, PEEP 5 Vt about 6 ml/kg IBW Less than 36 hours from onset Criteria confirmed after 12 24 hours of MV in ICU Patients proned at least 16 hours
PROSEVA TRIAL NO INCREASE IN COMPLICATIONS
PRONING Pictures courtesy of the interwebs
HOW IT WORKS SPONGE model of lung Proning changes pleural pressure of dorsal and ventral lung units Dorsal units open Ventral units may collapse Net effect is more ventilated units and better oxygenation
CONTRAINDICATIONS? High intracranial pressure (> 30 mm Hg) Massive hemoptysis Recent tracheal surgery or sternotomy Recent cardiac pacemaker placement Serious facial trauma Unstable spine, femur or pelvic fractures Others?
WHAT S MISSING? PARALYSIS!
ACURASYS TRIAL - NEJM 2010 Double blinded randomized control trial Cisatracurium vs placebo in severe ARDS (P/F < 150 with PEEP 5 and Vt 6-8 ml/kg) Given for 48 hours after diagnosis Primary outcome was mortality at 90 days Mortality: 31.6% study group vs 40.7% in placebo group No difference in ICU weakness
ICU DAY 1 (RAPID DECLINE) Continued worsening hypoxia ABG 7.32/46/67/23 Vent: PRVC RR 22 Vt 300 PEEP 10 FiO2 1.00 Flolan started without improvement in oxygenation Proned No improvement with increased PEEP and continued proning VV ECMO initiated and patient transferred to ECMO center
VV ECMO Veno-venous Extracorporeal Membrane Oxygenation Essentially this is bypass for lung support Blood is removed from the body via a large bore venous cannula Blood pumped through an oxygenator (gas exchange) Oxygenated/decarboxylated blood is returned to the vena cava/right ventricle Allows for lung rest : very low tidal volumes at low pressure
THE CIRCUIT NORTH/SOUTH CANNULATION: Drainage via femoral vein Return in SVC Some centers use opposite setup Can do bifemoral, but more problems BICAVAL CANNULATION: Single dual lumen catheter Drainage and return Drainage from SVC and IVC Return aimed at tricuspid valve
THE CIRCUIT FLOW SWEEP FIO2
THE OXYGENATOR
QUICK CO2 PHYSIOLOGY CO2 removal much more efficient than oxygenation CO2 clearance is almost exclusively dependent on sweep gas flow To improve ventilation increase sweep Rarely need the vent to clear CO2
QUICK O2 PHYSIOLOGY VV ECMO oxygenation depends on: Amount of flow through the circuit Achieving at least 60% of patient cardiac output Limiting recirculation To raise PaO2 Increase circuit flow Increase circuit FiO2 Decrease recirculation Decrease patient cardiac output and/or oxygen consumption (treat fever, sedation/paralysis, decrease inotropes)
QUICK O2 PHYSIOLOGY
WHY NOT VENO ARTERIAL ECMO? Differential hypoxia! AKA Harlequin Syndrome Native cardiac output pushes mixing cloud down Poorly oxygenated blood from lungs supplied to: Head Neck Right arm before left Right radial blood gas! learnecmo.com
ECMO DAY 1 XRAY THESE LUNGS NEED REST! (THOUGH I CAN T REALLY PROVE IT )
CESAR TRIAL LANCET 2009 UK-based multicenter trial Severe ARDS for less than 7 days Randomized to transfer to ECMO center or continued usual care Primary outcome was death or severe disability at 6 months Referral patients did better 63% vs 47%, BUT ONLY 75% of referred patients actually received ECMO Conslusion: referral to an ECMO center is better (but didn t prove ECMO was better )
RESOURCE ALLOCATION? HCMC UM ABBOTT UK Population: 66 million. MN pop: 5.57 million MAYO
MECHANICAL VENTILATION WHILE ON VV ECMO No data to support any particular mode of ventilation Expert consensus supports: Low driving pressure Low respiratory rate Low FiO2 Example: Ppl < 20-25, PEEP 10-15, RR 10, FiO2 0.3 (CESAR trial) Some patients will have such low Vt the ventilator must be set to Pediatric mode (if able)
WEANING FROM VV ECMO WHEN? As with ventilator settings there is no established ideal Generally when you feel patient s lungs have recovered and think you can support patient with low Ppl Vt 6 ml/kg? Ppl < 25? RR < 25 to maintain ventilation? Depends on the underlying condition Really just a gut feeling which is the worst level of evidence
WEANING FROM VV ECMO HOW? DO NOT reduce flow of the circuit Increase vent support while decreasing sweep gas Clamp sweep gas When sweep gas is off, patient is off ECMO If tolerates 4-24 hours, then decannulate Timing is another judgment call
ECMO DAY 38 Decannulated Day 43 LTACH for 2.5 months Walked back into the ICU to visit several months later
CXR 3 MONTHS POST ECMO
CONCLUSION: ARDS Still has high mortality/morbidity Remains underdiagnosed and undertreated Use enough PEEP (but not too much) Use enough oxygen (but not too much) Paralyze patients with P/F 150 Prone patients with moderate to severe ARDS Avoid ino, but maybe try epoprostenol Strongly consider transferring severe ARDS patients to an ECMO center
CONCLUSION: VV ECMO Facilitates lung rest (ultra-low tidal volumes) Though increasingly popular there is a lack of RCT s to support widespread use (bias warning: I m a believer) Best evidence in severe patients (P/F < 100) EOLIA trial is in the pipeline will this give the answer?
EMAIL: Joshua.Huelster@allina.com QUESTIONS?
REFERENCES 1. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 1967;2:319-323 2. Thompson BT, Chambers RC and Liu KD. Acute Respiratory Distress Syndrome. NEJM 2017;377:562-572 3. Ferguson ND, Fan E, Camporota L, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 2012;38:1573-1582 4. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. NEJM 2000; 342:1301-8 5. ARDSnet.org accessed 3/31. 6. Aggarwal NR, Brower RG, Hager DN, et al; for the National Institutes of Health Acute Respiratory Distress Syndrome Network Investigators: Oxygen Exposure Resulting in Arterial Oxygen Tensions Above the Protocol Goal Was Associated With Worse Clinical Outcomes in Acute Respiratory Distress Syndrome. Crit Care Med 2018; 46:517 524 7. Bellani G, Laffey J, Pham T; et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 2016;315(8): 788-800 8. Briel M et al Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA2010 303(9):865 873 9. Aaronson P., Robertson TP, Knock GA, Becker S, Lewis TH, Snetkov V, Ward J. Hypoxic pulmonary vasoconstriction: mechanisms and controversies. J Physiol. 2006 Jan1; 570(Pt 1): 53-58 10. Griffiths M, Evans TW. Inhaled Nitric Oxide Therapy in Adults. NEJM 2005 353:2683-2695 11. Torbic H, Szumita PM, Anger KE, Nuccio P, LaGambina S, Weinhouse G. Inhaled epoprostenol vs inhaled nitric oxide for refractory hypoxemia in critically ill patients. J Crit Care 2013;28(5):844-848. 12. Yen-Chun Lai et al. Classic vasodilator and vasoconstrictor systems and their translational therapies for pulmonary arterial hypertension (PAH). Circ Res. 2014;115:115-130 13. Papazian L et al. Neuromuscular blockers in early acute respiratory distress syndrome. NEJM 2010; 363: 1106-1117. 14. Maquet AG. Maquet.com accessed 3/30/2017 15. Schmidt M et al. Blood oxygenation and decarboxylation determinants during venovenous ECMO for respiratory failure in adults. Intensive Care Med. 2013;39(5):836-46. 16. Peek G, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009;374:1351-1363