ECLS Bridge to Lung TransplantationOptimizing and Ambulating the Recipient

Shaf Keshavjee MD MSc FRCSC FACS

Surgeon-in-Chief, University Health NetworkJames Wallace McCutcheon Chair in SurgeryDirector, Toronto Lung Transplant ProgramProfessor, Division of Thoracic Surgery andInstitute of Biomaterials and Biomedical Engineering,Vice Chair, Innovation, Department of SurgeryUniversity of Toronto

Disclosure

• Founding Partner:• Perfusix Canada Inc. (CSO)

• Perfusix USA Inc. (Lung Bioengineering /UT)

• XOR Labs Toronto Inc. (CSO)

• XVIVO Perfusion – Research support and clinical trial• United Therapeutics – Research support and clinical trial• Xenios/Fresenius – Research support and investor in XOR

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UNOS database analysis

J Thorac Dis. 2014 Aug;6(8):1070-9.

ECLS Bridge to Lung Transplant

ECLS bridge to LTx is being increasingly applied

4

Selection of Large Published Series

Center year # of pts ECLS duration**

Successful bridge to LTx

1-year survival of transplanted pts

Hannover 2012 26 9d 62% 80%*

Lexington# 2013 31 14d NA 93%

Pittsburgh 2013 31 34d 78% 74%

Munich 2013 26 16d 50% 54%

Zurich 2015 26 21d 86% 68%

Columbia 2017 72 12d 56% 90%

Vienna 2017 124 5d 89% 67%

Toronto 2017 71 10d 89% 76%* 6-months survival# multicenter study** med vs. mean

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Toronto Experience

• To review our experience of ECLS in patients bridged to LTx –lessons learned

• To identify factors related to optimal bridging

J Thoracic Cardiovasc Surg 2017

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Indications for ECLS Bridging

• Indications: severe hypercapnic + hypoxemic failure or hemodynamic failure (PPH)

• Candidacy for ECLS bridging is discussed by a multidisciplinary team in advance at the time of listing

Exclusion (relative?) criteria:

• age > 65 years• severe deconditioning • BMI > 30• significant comorbidities (coronary artery disease, etc.)

• prolonged mechanical ventilation• uncontrolled sepsis and other multi-organ dysfunction (except isolated kidney

failure or liver dysfunction associated with PH)

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Bridging Strategy

Hypoxic failureHypercapnic failure

Novalung

Hemolung

Single-cannula VV ECMO

dual-cannula VV ECMO

VA ECMO

PA/LA Novalung

PH

RV failure

RV+LV failure

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Toronto Experience: Total Lung Transplants by Type(BLT, SLT, HLT)

1983 – 2017

0

20

40

60

80

100

120

140

160

180

COU

NT

(n)

YEARBLT SLT H/L

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ECLS activities by Indication/Year2000-06/2016 (YTD)*

0

10

20

30

40

50

60

70

80

90 Cardiac / OtherARDS (non-Tx)BTR (Post)BTT (pre)

Year

No. of ECLS/year

10

Percentage of Patients Bridged to LTx

Evolution in Practice

VV

VV

VA

VV

CF 23 yo femalepCO2 122 mmHgpH 7.18Continuous BIPAP

pCO2 68 mmHgpH 7.42

• 29 yo male • CLAD, Hypercapnia

91 days on VV ECMO prior to Re-LTx

• Discharge - going home and ambulatory!

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Ambulation37% were able to do physical therapy during bridging

full ambulatorystanding/steppingdanglebed exercisesimmobile

full ambulatorystanding/steppingdanglebed exercisesimmobile

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Bridging Devices and Success of Extubation:Is Tracheostomy Better Than Extubation?

Mean time of ECLS bridging: 14 days (range 0-95)

HemolungNovalungSingle cannula VV ECMOTwo cannula VV ECMOVA ECMOPA/LA NovalungMultiple devices

extubatedtracheostomizedintubated

32 yo female with Cystic Fibrosis

• 32yo female• Cystic Fibrosis

Chronically infected with PseudomonasProgressive drop in lung function over last year

(FEV1 1.4L)Frequent exacerbations IV antibiotics and steroid

• Considering lung transplant assessment but doing relatively well

• Exocrine pancreatic insufficient, CF related diabetes, DIOS

• Married, 3 yo daughter

Past Medical History

Mar 2, 2016: Acute worsening of SOB, hypoxemia; FEV1 dropped to 0.79L (23% Pred)

Mar 9, 2016 Developed H1N1 pneumonia treated with Tamiflu

Respiratory failure on BIPAP at outside hospital - developed worsening hypercapnia

Apr 7, 2016 Intubated and transferred to TGH for urgent lung transplant assessment /bridge to LTx

Current Medical History

Apr 7, 2016 on admission

Assessment Summary

Listed on Apr 8, 2016 Status 2, Bilateral only

Cardiac Echo: • Normal sized LV with moderate LV dysfunction• LVEF estimated at 30-40%• Normal sized RV with mildly reduced function• Enable to estimate RVSP

ABG: pH 7.30, pCO2 121, pO2 216 (Apr 7 on ICU arrival)

• TLC (P): 5.5 (L)

LAB DATA:• Cr: 57 AST: 15 ALT: 18 ALP: 144 BILT: 3• INR: 1.05 ALB: 24 HbA1C: 0.091• Hb: 93 WBC: 24.0 Plt: 272

VV-ECMO was placedvia 22 Fr RIJ and 25 Fr RF

VV-ECMO for bridge to recovery/ bridge to lung transplant

Resp. condition deteriorated acutely pH 7.16, pCO2 >140, pO2 87

Apr 7

Gradually Deteriorated, Needed increased ECLS Flow

Apr 8 Apr 15

After admission to ICU

Tracheostomy

ABG: pH 7.27 pCO2 61 pO2 67

After ECMO insertion

• Developed septic shock• Bacteremia with gram-negative Pseudomonas

• 3 vasopressors at maximum dose VASOPRESSIN, LEVOPHED, and ADRENALIN

• Despite VV ECMO (flow of 7 L/min), Significant hypoxemia (without pump recirculation)

• ABG: pH 7.14 pCO2 52, pO2 60

• Refractory vasodilation - sepsis

Septic Shock and Persistent Bacteremia

April 17, 2016

Remove the Septic Source: Bilateral Pneumonectomy

Switch to Central VA-ECMO (22Fr aortic cannula, 34/46 two-stage IVC venous cannula

Right-sided pneumonectomy first, then left pneumonectomy

Insertion of Right lung PA-LA Novalung

Outflow: Pulmonary arterial (34 Fr single-stage venous cannula)Inflow: right superior pulmonary vein (28 Fr Pacifico)

April 17, 2016

Remove Septic Source: Bilateral Pneumonectomies

Immediate Postop BLT

Bilateral Lung Transplant

• On central VA-ECMO

• Left side implantation first ( CIT: 3h 15 min, WIT: 49 min)

• Removed the PA cannula from right PA (for the PA-LA Novalung)

• Removed the LA cannula from right superior pulmonary vein

• Right lung implantation ( CIT: 4h 45 min, WIT: 50 min)

• 6 U pRBC and 2 U platelets

April 22, 2016 (5 days after pneumonectomy)

October 2016

Oct 19, 2016

J Thor Cardiovasc Surg 2016

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Toronto Experience

Retrospective analysis of our institutional ECLS bridging practice over the last 10 years

January 2006 - September 2016Total 1111 LTx

71 patients bridged to LTx

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Outcomes

Time to extubation (median, IQR) 18 (4;33)Total hospital days (median, IQR) 72 (50;122)

Survived until LTx- yes 63 (89%)- no 8 (11%)

PGD at 72hrs- PGD 0/1 9%- PGD 2 33%- PGD 3 57%

Postoperative ECMO- no 36 (59%)- VV ECMO 16 (26%)- VA ECMO 9 (15%)

Bridged patients Total n=71

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Outcomes

Time to extubation (median, IQR) 18 (4;33)Total hospital days (median, IQR) 72 (50;122)

Survived until LTx- yes 63 (89%)- no 8 (11%)

PGD at 72hrs- PGD 0/1 9%- PGD 2 33%- PGD 3 57%

Postoperative ECMO- no 36 (59%)- VV ECMO 16 (26%)- VA ECMO 9 (15%)

Bridged patients Total n=71

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Outcomes

Time to extubation (median, IQR) 18 (4;33)Total hospital days (median, IQR) 72 (50;122)

Survived until LTx- yes 63 (89%)- no 8 (11%)

PGD at 72hrs- PGD 0/1 9%- PGD 2 33%- PGD 3 57%

Postoperative ECMO- no 36 (59%)- VV ECMO 16 (26%)- VA ECMO 9 (15%)

bridged to LTxbridged to Re-LTx

70%

63%

51%53%

32% 32%

Bridged patients Total n=71

p=0.045

Survival per intention-to-treat

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Successful vs. Unsuccessful bridging

Ventilation during bridging- no invasive MV 31 (49%) 1 (13%) 0.049

No differences in: age, diagnosis, first/re-transplant, type of device, time on ECLS

successful bridging unsuccessful bridging p-valuen=63 n=8

BUT !!!

Ambulatory status- mobile/awake 25 (40%) 1 (13%) 0.133

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Age (mean; range) 38 (18-62) 53 (18-77) < 0.001Gender (m/f) 48%/52% 58%/42% 0.101Height (mean±SD; cm) 165.3±10.3 168.2±9.8 0.021Weight (mean±SD; kg) 62.3±15.5 67.5±15.4 0.006BMI (mean±SD; kg/m2) 22.4±5.2 23.8±4.6 0.014Diagnosis (n; %)

- COPD 3% 22%

< 0.001

- Interstitial lung disease 37% 38%- Cystic Fibrosis 23% 16%- Pulmonary hypertension 18% 3%- CLAD 16% 2%- others 4% 19%

Type of LTx- Double-LTx 92% 81%

< 0.001- Single-LTx 5% 18%- Heart-Lung Tx 3% 1%

Bridge to LTx LTx without Bridgingn=71 n=1040 p-value

Comparison of Bridged pts to LTx w/o Bridging

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Age (mean; range) 38 (18-62) 53 (18-77) < 0.001Gender (m/f) 48%/52% 58%/42% 0.101Height (mean±SD; cm) 165.3±10.3 168.2±9.8 0.021Weight (mean±SD; kg) 62.3±15.5 67.5±15.4 0.006BMI (mean±SD; kg/m2) 22.4±5.2 23.8±4.6 0.014Diagnosis (n; %)

- COPD 3% 22%

< 0.001

- Interstitial lung disease 37% 38%- Cystic Fibrosis 23% 16%- Pulmonary hypertension 18% 3%- CLAD 16% 2%- others 4% 19%

Type of LTx- Double-LTx 92% 81%

< 0.001- Single-LTx 5% 18%- Heart-Lung Tx 3% 1%

Bridge to LTx LTx without Bridgingn=71 n=1040 p-value

Comparison of Bridged pts to LTx w/o Bridging

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Bridge to Lung Transplant Survival

IPF CF PPH CLAD

surv

ival

38

LTx without bridging

bridged to LTx

Comparison of Bridged Pts to LTx w/o Bridging

Re-LTx without bridging

bridged to Re-LTx

Survival after LTx Survival after Re-LTx

Successful ECLS Bridge to LTx

1. Patient Selection

2. Avoid prolonged mechanical ventilation pre- ECLS

3. Provide appropriate pump support

4. Avoid groin cannulation if possible

5. Ambulatory and non intubated preferred (but avoid lung de-recruitment)

6. Nutritional support, consider early tracheostomy

7. Need an engaged AND persistent multidisciplinary team

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Take Home Messages…

• ECLS bridge to first lung transplant leads to very good short and long-term outcomes

• Bridge to re-transplantation requires strict patient selection – RAS appears to be a higher risk group

• Successful bridging is associated with ambulation and weaning from mechanical ventilation