1. AATS Guidelines: Bridge to Transplant and Extracorporeal Lung Support

2. J Thorac Dis. 2014 Aug; 6(8): 1070–1079.

3. Objectives Expert review committee to delineate recommendations for practice with use of ECLS as bridge to lung transplantation Recommendations based on available literature and expertise of members from committee

4. Members Marcelo Cypel (University of Toronto) Shaf Keshavjee (University of Toronto) Duane Davis (Duke University) Matthew Bacchetta (Columbia University) David Mason (Baylor University Medical Center, Dallas) William Lynch (University of Michigan) Martin Strueber (Spectrum Health) Walter Kepletko (University of Vienna)

5. Definitions ECLS: Extracorporeal Life Support ECMO: Extracorporeal Membrane Oxygenation ECCO2R: Extracorporeal CO2 removal iLA: Interventional lung assist

6. Search Strategy PubMED search Minimal 10 patients ECLS bridged to transplant (n=14 articles identified) 4 conference calls last 6 months amongst all members of the committee Final agreement was established for recommendations

7. Patient Selection End-stage lung disease Previously assessed by lung transplant team* Absence of multi-organ dysfunction ** Age less than 65 Absence of prolonged mechanical ventilation Absence of uncontrolled sepsis Absence of other significant comorbidities: high BMI (more 30), coronary artery disease, severe deconditioning * Some patients with acute deterioration can be considered for ECLS as bridge to decision if not previously assessed by the transplant team. Young age and general good health prior to deterioration are important concepts ** Patients with PAH can be considered for ECLS when presenting with acute kidney and liver dysfunction due to right heart failure

8. General Contra-Indications Relative: Age more than 65 BMI more than 30 or less 15 Sepsis Highly sensitized patient Other significant comorbidities Absolute: Severe Deconditioning Contra-indications for anticoagulation Multi-organ dysfunction

9. ECLS Bridge to Retransplant Outcomes are worse than ECLS bridge to primary transplant Conservative approach on patient selection All the relative contra-indications carry more weight on retransplant Patients with hypercapnic failure have better outcomes than patients with hypoxemia Bleeding in perioperative period is a major concern Transplant should be performed preferentially on ECMO with low anticoagulation targets

10. Timing for ECLS initiation Appropriate timing for ECLS is determined by patient condition and the circumstances surrounding the likelihood for donor organ acquisition. The decision typically considers utilizing short-term mechanical ventilation and conversion to ECLS within 24-48 hours or preemptive ECLS if short-term mechanical ventilation is likely to fail.

11. Patients are in general pre-selected transplant candidates who have had a preceding course of “progressive decline” despite escalating requirements of inspired oxygen content and non-invasive ventilation. Initiation should occur prior to any other end-organ dysfunction Limit protracted courses of mechanical ventilation before ECLS Timing for ECLS initiation

12. Disease specific indications Cystic Fibrosis: Usually fail due to hypercapnia. Consider ECLS when acidosis develops (pH less 7.2) or pre-emptive use of ECLS to enhance rehabilitation for patients that otherwise are not able to mobilize. Pulmonary Fibrosis: Usually develop hypoxemia. Consider ECLS when significant refractory hypoxemia develops (saturation less 90%) despite high flow oxygen. Pulmonary Hypertension: Usually develop hypoxemia associated with poor cardiac output. Consider ECLS when escalation of inotropes occur or any sign of second organ dysfunction.

13. Mode of ECLS Pure hypercapnia and respiratory acidosis -VV ECMO (single cannula preferred) -ECCO2R Hypoxemia due to parenchymal lung disease -VV ECMO (single cannula preferred) -VA ECMO if associated RV dysfunction/secondary pulmonary hypertension Right ventricular failure associated with PAH: -VA ECMO -PA-LA iLA -VV ECMO (if ASD present) – limited experience

14. ECLS Technology Membranes: PMP membranes – gold standard Cannulas: single insertion cannulas for VV ECMO or ECCO2R – recommended – facilitate mobilization Circuits: Heparin coated Pumps: New generation centrifugal pumps Integrated pump-oxygenator: facilitate mobilization

15. Cannulation Techniques Avalon for VV ECMO: Percutaneous insertion. Imaging mandatory -Fluoroscopy (imaging of choice) -TEE -TTE Dual Cannula VV ECMO: Percutaneous insertion. Imaging recommended (allows proper positioning) VA ECMO: Percutaneous or open insertion. Seldinger technique preferred. Distal perfusion cannula (minimum of 6fr) or side graft insertion are recommended to prevent ischemia. PA-LA iLA: Femoral VA ECMO initiation followed by sternotomy and cannulation of LA via right superior PV and PA. VA ECMO weaned at the end of PA-LA insertion or over next 48-72hs.

16. General Management

17. Anticoagulation with Heparin Protocols are center specific but most frequent protocols are: -Monitoring based on ACT. Usual targets:160-180 sec or 140-160 sec (if perioperative) -Monitoring based on aPTT. Usual targets 1.5-2 of normal levels -Monitoring based on anti-factor Xa. Usual targets 0.3 to 0.5 IU-ml. Heparin Administration: Bolus with 40 to 60 UI/Kg. (some centers use upper limit dose to 5000UI) Monitoring q. 6hours Once anticoagulation level is stable switch to q.12h

18. Anticoagulation - Perioperative Most centers would continue IV heparin based on low targets Stopping the heparin for 1-4 hours prior to surgical interventions in acceptable. Consider maintaining higher ECLS flows when heparin is on hold.

19. Transfusion Thresholds Hb 7.0 g/dl Platelets 50000/ul Fibrinogen 1.0 g/L INR > 1.8 Signs of spontaneous bleeding may prompt lower threshold for transfusion

20. Antibiotics Prophylactic antibiotics recommended: -Cefazolin 1 or 2g IV before insertion of cannulas. -Routine of antifungals not recommended. -Maintenance treatment based on cultures.

21. Tracheostomy and Mobilization Tracheostomy is recommended if patients cannot be extubated after few days of ECLS initiation. Generally heparin is held for 2 hours before and 2 hours after procedure. A committed ICU physiotherapy team with experience to mobilize patients on ECLS is critical. Full nutritional support should be continued orally or via enteral tube. Failing to meet this is a relative contra- indication for transplant. Failure or inadequacy of mobilization may suggest need for greater ECLS support.

22. Intra-operative management Continue VV support during surgery or switch to VA support depending on patient hemodynamics. (CPB generally not needed) Advantages of ECMO compared to CPB include: shorter circuit, no reservoir, lower anticoagulation targets. 3 recent comparative studies demonstrated advantages of ECMO over CPB in terms of blood utilization, primary graft dysfunction, hospital length of stay, and 1 year survival.

23. Weaning of ECLS Weaning from VV ECMO: Wean the sweep gas supplying the membrane. Sweep should be off for several hours before cannula removal. Weaning VA ECMO: ECMO flow is gradually weaned and patient hemodynamics and gas exchange are followed. TEE or TTE usually recommended prior to complete weaning. Pre-emptive use of ECLS in the post operative period has been proposed by some groups in the following situations: -As an extension of intraoperative support in PAH patients and slow weaning over few days in order to prevent PGD and cardiogenic shock. -In patients requiring high FiO2 and high pressure mechanical ventilation in order to protect the grafts

24. AATS Guidelines: Bridge to Transplant and Extracorporeal Lung Support