1. E XTRACORPOREAL M EMBRANE O XYGENATION IN A WAKE P ATIENTS AS B RIDGE TO L UNG T RANSPLANTATION Am J Respir Crit Care Med 2012;185(7):763–8. R3 이민혜 Thomas Fuehner, Christian Kuehn, Johannes Hadem, Olaf Wiesner, Jens Gottlieb, Igor Tudorache, Karen M. Olsson, Mark Greer, Wiebke Sommer, Tobias Welte, Axel Haverich, Marius M. Hoeper, and Gregor Warnecke

2. I NTRODUCTION Lung transplantation (LuTx) : performed in patients with progressive lung diseases  Chronic obstructive pulmonary disease  Idiopathic pulmonary fibrosis (IPF)  Cystic fibrosis (CF)  Pulmonary arterial hypertension (PAH) Bridging strategies for patients with end-stage lung disease  Endotracheal intubation and mechanical ventilation (MV)  most patients fail to reach transplantation, poor postoperative outcome  Extracorporeal life support (ECLS) in patients who are intubated in whom gas exchanged  insufficient despite optimized ventilator settings  overall results have been disappointing 2

3. I NTRODUCTION Technical improvements in ECLS  (1) Pumpless arteriovenous extracorporeal lung assist (ECLA) for carbon dioxide removal  (2) Venovenous extracorporeal membrane oxygenation (ECMO) for hypercapnia or hypoxemia  (3) Venoarterial ECMO for hypoxemia or hemodynamic failure Using ECMO in patients who are nonintubated (“awake ECMO”) as the preferred bridging strategy in patients with end-stage respiratory failure 3

4. M ETHODS Retrospective, single-center, intention-to treat analysis Specific indications for awake ECMO  (1) Right ventricular failure refractory to intravenous prostacyclin treatment and catecholamines with systemic hypotension and secondary organ dysfunction  (2) Profound hypoxemia with prolonged or continuous arterial oxygen saturations less than 80% despite maximum noninvasive support  (3) Refractory hypercapnia with respiratory acidosis and altered mental state despite optimized medical therapy and noninvasive ventilation. Choice of ECMO Procedure  Venoarterial ECMO : right ventricular failure or profound hypoxemia  Venovenous ECMO : hypoxemic or hypercapnic respiratory failure but stable hemodynamics  Single-site approach : hypercapnia but preserved oxygenation  Two-site approach : severe hypoxemia 4 August 2008 ~ March 2011 (32mo) Awake ECMO Group Previous 32 months (January 2006 ~ August 2008) MV Group

5. 5 R ESULTS

6. 6 Bleeding complications (puncture sites, n = 6; epistaxis, n = 1; hemoptysis, n = 1) 3 of 4 patients with hemoptysis or epistaxis required intubation Blood cultures remained negative in all cases All of these patients received empirical broad-spectrum antibiotics but only one recovered Died before transplantation

7. 7

8. 8 Cardiac arrest during cannulation, n = 1 Septic multiorgan failure, n = 2 Died 2 months after trancsplantation from multiorgan failure Discharged from the hospital 70, 82, and 87 days after transplantation

9. 9 Septic multiorgan failure, n = 2 Cardiac arrest during oxygenator membrane exchange, n = 1 Two of these patients died from septic multiorgan failure 15 and 49 days, respectively, after transplantation Another patient died 60 days after transplantation from lung cancer Discharged from the hospital 20–87 days after transplantation All of these patients remained alive during the follow-up period (7–39 mo)

10. 10 10 (29%) of 34 patients died before transplantation, all of them from septic multiorgan failure The major cause of death after transplantation was septic multiorgan failure

11. 11 R ESULTS

12. 12 Figure 2. (A) Kaplan-Meier survival estimates of lung transplant candidates undergoing awake ECMO (from the time of ECMO insertion) or mechanical ventilation (from the time of intubation). (B) Kaplan-Meier survival estimates of lung transplant candidates undergoing awake ECMO or mechanical ventilation from the time of transplantation. ECMO = extracorporeal membrane oxygenation; ITN = endotracheal intubation. 62% in the awake ECMO group and 35% in the MV group (P = 0.05) 80% in the awake ECMO group and 50% in the MV group (P = 0.02) A B

13. D ISCUSSION First sizable series of patients undergoing awake ECMO as bridge to LuTx Venoarterial ECMO is a highly effective bridging strategy for patients with pulmonary hypertension and right heart failure  Low cardiac output and pulmonary blood flow is further reduced after ECMO insertion  Takes over most of the systemic blood flow and satisfactory whole-body oxygenation Single-site venovenous approach  Hypercapnic respiratory failure capable of maintaining sufficient oxygenation  Pumpless arteriovenous ECLA represents another option for these patients  Favor the single-site venovenous approach for these patients, because it is less invasive and allow additional oxygenation No approach was fully satisfactory  Still experiencing episodes of insufficient oxygenation  Presumably as a result of the ongoing admixture of poorly oxygenated blood caused by persistent high pulmonary blood flow 13

14. D ISCUSSION Benefit of the awake ECMO  Avoidance of the complications and drawbacks associated with general anesthesia, intubation, and long-term ventilation  Breathe spontaneously and can eat and drink  Active physiotherapy is feasible  Much better conditioned for transplantation than those on the ventilator Prolonged MV  General muscular atrophy  Leading to difficult and prolonged weaning after transplantation  More respirator days longer ICU stays after transplantation  Pulmonary and systemic inflammation  Prone to infections  Septic multiorgan failure was the leading cause of death 14

15. D ISCUSSION Recent success of ECMO therapy  Low resistance gas exchange membranes  High-durability centrifugal blood pumps  Heparin-coated tubing  Improved cannulae  Culminating in a much safer medical device ECMO cannot solve all of the problems presented by patients with end- stage cardiopulmonary disease ECMO : severe, sometimes fatal complications  Serious bleeding  Life threatening infections  Should be used only in experienced centers and only in patients in whom noninvasive treatment options have been exhausted Limitations  The number of patients was small  Data originating from a single center  Analyses were performed retrospectively with a historical control group rather than a parallel group 15

16. C ONCLUSION Bridging strategy for patients with end-stage lung disease to transplantation ECMO : support in patients who are awake and nonintubated 16