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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
3
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
5
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
6
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)
7
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
8
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
9
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!
17
Ambulation37% were able to do physical therapy during bridging
full ambulatorystanding/steppingdanglebed exercisesimmobile
full ambulatorystanding/steppingdanglebed exercisesimmobile
18
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
30
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
31
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
32
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
33
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
34
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
35
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
36
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
37
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
40
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
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