ECMO: a breakthrough in care for respiratory failure. PD Dr. Thomas Müller Regensburg no conflict of interest

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ECMO: a breakthrough in care for respiratory failure? PD Dr. Thomas Müller Regensburg no conflict of interest 1

Overview Mortality of severe ARDS Indication for ECMO PaO 2 /FiO 2 Efficiency of ECMO: gas transfer, ventilation, outcome Problems of ECMO Conclusion 2

ARDS - Mortality Legionellosis Phua et al, Am J RespirCrit Care Med 2009;179:220-27 3

ARDS - Mortality These results highlight the need for future effective therapeutic interventions in this highly lethal syndrome Phua et al, Am J RespirCrit Care Med 2009;179:220-27 4

459 ICUs from 50 countries 3022 patients (10.4 %) with ARDS hospital mortality 40 %: 34.9 % - 40.3 % - 46.1 % mild moderate - severe JAMA 2016;315:788-800 5

LUNG SAFE: Mortality and Driving/Plateau Pressure Driving Pressure Plateau Pressure JAMA 2016;315:788-800 6

Case Presentation 49 yr, female, past history empty 30.01: dry cough, fatigue, flu-like symptoms, diarrhoea, temp 38.5 C 01.02.: admission to external hospital, progressive dyspnoe PCT 20 µg/l, CRP 177 mg/l, lactate 113 mg/l, WBC 2.2/µl, Platelets 78/nl, INR 1.63, aptt 54 sec Ampicillin, Sulbactam, Clarithromycin CT-Scan: intubation referral broad spectrum antibiotic coverage expected mortality? 7

02.02: septic shock and MOF: + 11 liters volume PCT 177 ng/ml, CK 3475 U/l, troponin I 22.6 ng/ml, platelets 77/nl, INR 1.84, aptt 87 sec, AT-III 19 %, D-Dimers > 35 mg/l PaO 2 /FiO 2 98 mmhg, PaCO 2 40 mmhg PEEP/PIP 14/27 17/31 cm H 2 O noradrenaline 6 mg/h, epinephrine 0.5 mg/h lactate 90 mg/dl Case Presentation ECHO: septic cardiomyopathy 12:00 o clock decision for ECMO: veno-arterial cannulation, blood flow 3.8 l/min plasma exchange expected mortality? 8

18:00 o clock: Case Presentation noradrenaline 1.8 mg/h, epinephrine 0.3 mg/h lactate 110 mg/dl PaO 2 /FiO 2 50 mmhg, PaCO 2 45 mmhg PEEP/PIP 17/31 24/38 cm H 2 O decision for additional venous cannula: VAV ECMO: blood flow 2.8 + 2.2 l/min chest X-ray: expected mortality? 9

Extracorporeal Gas Transfer 1. O 2 Transfer efficiency depends on blood flow and blood sat effects: avoid hxpoxemia protective ventilation: VILI, right heart strain gain of time po 2 Gas 760 mmhg p0 2 Blood ~ 500 mmhg p0 2 Blood ~ 35 mmhg 2. CO 2 Elimination efficiency depends on blood flow, gas flow and PvCO 2 (recirculation!) effects: protective ventilation over-inflation work of breathing facilitation of extubation? avoidance of intubation? pco 2 Gas 0 mmhg pc0 2 Blood ~ 25 mmhg pc0 2 Blood ~ 50 mmhg 10

Gas-transfer Capacity of MOs Lehle K et al, ICM 2014;40:1870-77

Indication: ELSO 1. In hypoxic respiratory failure due to any cause (primary or secondary) ECLS should be considered when the risk of mortality is 50% or greater, and is indicated when the risk of mortality is 80% or greater. a. 50% mortality risk is associated with a PaO 2 /FiO 2 < 150 on FiO 2 > 90% and/or Murray score 2-3. b. 80% mortality risk is associated with a PaO 2 /FiO 2 < 100 on FiO 2 > 90% and/or Murray score 3-4 despite optimal care for 6 hours or more. 2. CO 2 retention on mechanical ventilation despite high Pplat (>30 cm H 2 O) 3. Severe air leak syndromes 4. Need for intubation in a patient on lung transplant list 5. Immediate cardiac or respiratory collapse (PE, blocked airway, unresponsive to optimal care) www.elso.org/resources/guidelines 12

Indication for VV ECMO 1. rescue vital gas exchange can not be secured by conventional means, and rapidly progressive hemodynamic instability (P/F < 60 mm Hg, and ph < 7.2, and PIP > 35 cm H 2 O, and Nor > 1.5 mg/h) 2. semielektive lung protective ventilation not possible to secure vital gas exchange; no improvement after 12 24 hours 3. given that: treatable cause all conventional therapeutic methods optimized no contraindication PaO 2 /FiO 2 < 80 mm Hg with PEEP > 15 cm H 2 O uncompensated respiratory acidosis: ph < 7,15 Brodie D, Bacchetta M, New Engl J Med 2011; 365:1905-14 13

Vv-ECMO: PaO 2 /FiO 2,PaCO 2 and TV NOR Müller et al, Dtsch Arztebl Int 2013;110:159-66 14

Ventilation on ECMO TV FiO 2 MV PEEP n = 375 PIP

Survival with modern ECMO Study Literature Number Age Survival ANZ ECMO Italian ECMOnet ELSO H1N1 registry (adults > 20 yrs) CESAR UK ECMO for H1N1 REVA Research Network JAMA 2009;302:online Oct 12 Intensive Care Med 2011;37:1447 www.elso.med. umich.edu/ April 13, 2011 Lancet 2009;374:1351-63 JAMA 2011;306:online Oct 5 Am J Respir Crit Care Med 2013;187:276-85 68 34.4 75 % 60 40 68 % 218? 70 % 68 39.9 63 % 69 36.5 71 % 123 42 64 % 16

incidence VV-ECMO 2014: 2.4/100 000 (n = 1944) in-hospital mortality 2014: 58 % case numbers mortality Intensive Care Med 2016, March 4 epub ahead of print 17

Survival RESP-Score Population N = 2355 Age (years) 41 (28-54) Schmidt M et al, AJRCCM in press 02.April 2014 18

Model 2 (day 1): age day 1 FiO 2 immunocompromised state day 1 fibrinogen minute ventilation day 1 norepi. pre ECMO Hb day 1 CRP TB Enger...T Müller, Crit Care 2014;18:R67

Outcome according to age (n = 551) 100% 80% 60% 14 40 56 59 80 50 34 40% 20% 0% 20 12 2 9 21 4 5 6 29 10 14 33 33 20 < 20 20-29 30-39 40-49 50-59 60-69 > 69 Tod an ECMO Tod nach ECMO Überleben 20

Crit Care Med. 2017 Feb;45(2):164-170 21

Crit Care Med. 2017 Feb;45(2):164-170 22

Risks of ECMO Ruptur of femoral vein tamponade broken cannula

Risk of Technical Failure 3500 3000 LDH [U/l} free hemoglobin [mg/dl] 2500 2000 1500 1000 500 0 pre 24hrs exchange +12 hrs +24 hrs + 36 hrs +48 hrs

Avoid unnecessary interventions risk of bleeding: platelets 173 000 105 000 day 4 (61%) (n = 440) no unnecessary blood transfusions Hb transfusion threshold 8.0 g/dl RBCs/day on ECMO: 0.31 (0.00;0.78)

VV-ECMO and Cerebral Complications: 04/2006 10/2015 preliminary results 495 vv ECMO runs CCT n=290 no pathology n = 226 (78 %) survival n = 142 (63%) ICB n = 53 (18 %) survival n = 27 (51%) ischemia n = 11 (4 %) survival n = 8 (73%) 26

Requirements for an ECMO Center 1. experience in the treatment of severe ARDS: tertiary care ICU 2. transport possible with ECMO: mobile team 3. experience with ECMO: > 10 (20) cases per year 24/7 trained personel: intensivists, nurses, (perfusionists) 4. management of complications: blood bank, lab, CT 24/7 ECMO replacement equipment vascular surgery, (abdominal-, thoracic surgery) 5. quality managment: regular training data base M + M conference participation in national or international registry Am J Respir Crit Care Med. 2014 Sep 1;190(5):488-96.

Conclusion: ECMO: a breakthrough in care for respiratory failure? 1. ECMO safes lifes. 2. indications: relatively sure: severe refractory ARDS uncertain: CO 2 elimination (avoidance of intubation? facilitated weaning?) 3. balance benefits versus risks 4. costs! 5. experience necessary: ECMO Center 28

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