Download Cardio-Thoracic Transplantation

UPDATE IN CARDIOTHORACIC
TRANSPLANTATION
Bartlomiej Zych, Diana Gracia-Saez, and Andre R Simon .
Department of Cardiothoracic Transplantation & Mechanical Circulatory Support,
Harefield Hospital, London, United Kingdom.
Royal Brompton & Harefield
NHS Foundation Trust
Heart transplant activity UK
•
Royal Brompton & Harefield
NHS Foundation Trust
Lung and heart/lung transplant activity UK
•
Royal Brompton & Harefield
NHS Foundation Trust
UK Donor Scout Pilot Project
 Early aggressive donor assessment and management
including:
 Invasive hemodynamic monitoring.
 TOE.
 Bronchoscopy.
 Performed by dedicated cardiothoracic transplant
teams.
Royal Brompton & Harefield
NHS Foundation Trust
Principle of donor management
“… in essence, donor management is a
continuation of previous critical care
management but with a shift in goals’’
McKeown DW. et al. BJA 2012
Royal Brompton & Harefield
NHS Foundation Trust
Impact of brain stem death on cardiovascular
system and lungs.
Royal Brompton & Harefield
NHS Foundation Trust
Impact of brain stem death on cardiovascular
system and lungs.
Arab D et al. Intensive Care Med 2003
Royal Brompton & Harefield
NHS Foundation Trust
Impact of brain stem death on carrdiovascular
system and lungs.
Phase I - Catecholamine Storm/hypertension:
 Increase in ICP , compensatory hypertension.
 Marked sympathetic stimulation, intense vasoconstriction,
raised SVR.
Consequences:
 Central redistribution of blood, increased afterload
decreased coronary flow, subendocardial ischemia.
 20 - 25% DBD donors with myocardial injury, approx. 40%
with echocardiographic proven myocardial dysfunction.
 Pulmonary oedema: raised hydrostatic pulmonary
pressure, endothelial damage – catecholamines.
Royal Brompton & Harefield
NHS Foundation Trust
Impact of brain stem death on cardiovascular
system and lungs.
Phase II: Hypotension and hemodynamic instability.
 Neurogenic component
 Result of defective vasomotor control and subsequent,
progressive loss of SVR.
 Hypovolaemic component
 Therapeutic dehydration for cerebral oedema.
 Haemorrhage.
 Diabetes insipidus with massive diuresis.
 Osmotic diuresis due to hyperglycaemia.
 Cardiogenic component
 Hypothermic depression of myocardial contractility.
 Left ventricular dysfunction (catecholamine storm).
Royal Brompton & Harefield
NHS Foundation Trust
Impact of brain stem death on cardiovascular
system and lungs.
Royal Brompton & Harefield
NHS Foundation Trust
Impact of brain stem death on cardiovascular
system and lungs.
 Incidence of pathophysiological changes following brain stem
death:
Physiologic changes During Brain Stem Death – Lessons for Management of the Organ
Donor. The Journal of Heart & Lung Transplantation Sept 2004 (suppl)
McKeown DW. et al. BJA 2012
Royal Brompton & Harefield
NHS Foundation Trust
Cardiovascular Management
McKeown DW. et al. BJA 2012
Royal Brompton & Harefield
NHS Foundation Trust
Changes in UK transplant activity 2013-2014
Royal Brompton & Harefield
NHS Foundation Trust
Changes in UK transplant activity 2013-2014
Royal Brompton & Harefield
NHS Foundation Trust
Transmedics – Organ Care System for heart
 Preservation-transport of a continuously perfused, beating heart at 34°C.
 Avoids the negative effect of prolongedcold ischemic storage.
 Additional assessment options.
Royal Brompton & Harefield
NHS Foundation Trust
Transmedics – Organ Care System for heart
Royal Brompton & Harefield
NHS Foundation Trust
1.
2.
At Donor site
A.
Donor management; Weaning inotropes, Hematocrit > 30%
B.
Donor blood collection (1500 ml) inmediately before aortic X Clamp
C.
Heart cannulation and instrumentation to OCS™
Heart management and assessment on OCS:
A.
Perfusion parameters (Aortic Pressure- AOP , Coronary flow-CF)
B.
Lactate: Venous < Arterial << 5 mmol/L and Lactate decreasing over
time indicate good myocardial perfusion
Royal Brompton & Harefield
NHS Foundation Trust
ZONAL
Northwich
East Surrey
Southampton x2
Oxford x3
St George’s x2
Charing Cross
St Mary’s
NON ZONAL
Barnsley
Milton Keynes
Glasgow
Kings London
Bath
Newcastle x2
Dublin
North Wales
Exeter
Yeovil district
Edinburgh x3
Ashford x2
Belfast
Plymouth
Aberdeen
.
Extending Safe
Retrieval Range
Using OCS
.
. Edinburgh
Glasgow
. Newcastle
.
Belfast
Dublin
.
. Manchester
.
Nottingham
.
Oxford
. ..
Cardiff
Bristol
Bath
Royal Brompton & Harefield
NHS Foundation Trust
London
OCS Case Series
22February 2013 – 29 April 2014
Donor Hearts Assessed on OCS
36
Turned Down After OCS
Assessment = 6
Hearts Transplanted
30
Stable Perfusion &
Lactate Profile
Significant down-time
Rising Lactate
Unstable perfusion parameters
1 patient died after 44 days
(Death not related with heart function)
Royal Brompton & Harefield
NHS Foundation Trust
Donor-Recipient Profile
Tx Date
Donor
profile
Donor-Risk factors
Recipient
profile
Recipient Risk Factors
Feb 2013
44 ♂
Transport time165 min
39 ♂
High PVR (5.8  3.7)
Feb 2013
50 ♂
Cardiac arrest 40 min
Smoker, Diabetic
58 ♂
HVAD
5 previous sternotomies
Mar 2013
47 ♂
Transport time 180 min
NORAD 0.25; Vaso 6
29 ♂
-
Apr 2013
46 ♀
Smoker; Obese; Alcohol abuse
Palpable CAD; Cx
61 ♂
High PVR (2,7 2,5)
MVR: Previous sternotomy
Apr 2013
24 ♂
-
25 ♂
HVAD
Apr 2013
20 ♂
Cardiac arrest 20 min; Tn T 160;
Cocaine-Alcohol abuse, LVEF 50%
36 ♂
LVAD – Synergy
Jun 2013
54 ♂
Smoker, Obese
Coronary Disease Distal LAD
37 ♀
High PVR (2,8 1,8)
Royal Brompton & Harefield
NHS Foundation Trust
Donor-Recipient Profile
Tx Date
Donor
profile
Donor-Risk factors
Recipient
profile
Recipient Risk Factors
June 2013
23 ♂
Left ventricle hypertrophy
24 ♂
HVAD
June 2013
28 ♂
Transport time 270 min
44 ♀
High PVR (3.8 1.5)
June 2013
33 ♂
Transport time 205 min
56 ♂
HMII pump infection, Liver- Renal
failure, PVR (5.1 – 2.7)
June 2013
53 ♂
ECG changes lateral wall
61 ♂
HMII, Pump infection
July 2013
54 ♂
Transport time 210min
48 ♂
High PVR (5.2 1,7)
Sept 2013
44 ♂
Logistics
22 ♂
-
Sept 2013
49 ♂
Left ventricle hypertrophy. IVS 16 mm.
Mild-mod MR
57 ♂
High PVR (5.3 1.95)
Royal Brompton & Harefield
NHS Foundation Trust
Donor-Recipient Profile
Tx Date
Donor
profile
Donor-Risk factors
Recipient
profile
Recipient Risk Factors
Sept 2013
17 ♀
LVEF 40-44%. Transport time 240 min
26 ♀
High PVR (4.591.5)
Sept 2013
34 ♂
Left ventricle hypertrophy
IVS 14, PWD 15 - PWS18
33 ♂
HVAD
Sept 2013
26 ♀
Transport time 210 min
48 ♂
High PVR (3.16 1.68)
Sept 2013
52 ♂
Transport time 210 min
33 ♂
HMII Pump infection
Nov 2013
40 ♂
Palpable CAD; LAD, RCA
48 ♂
HMII Pump infection
Dec 2013
24 ♂
COD Trauma, ECG ischemia. Tn 2 (<0.05)
56 ♂
-
Dec 2013
35 ♂
Transport time 180 min
Cardiac arrest (30 min) Inferolat ischemia
58 ♂
HVAD, RVAD
Royal Brompton & Harefield
NHS Foundation Trust
Donor-Recipient Profile
Donor
profile
Donor-Risk factors
Recipient
profile
Recipient Risk Factors
Dec 2013
51 ♂
LVEF 45%. Palpable CAD; LMCA
34 ♂
-
Jan 2014
48 ♀
Transport time 210 min
Palpable CAD; LAD-diagonal
59 ♀
HVAD, 3 sternotomies, PVR 4.9
30 ♂
IABP
Tx Date
Transport time 210 min
Mild RV dysfunction. Cocaine abuse
Jan 2014
38 ♂
Jan 2014
42 ♂
Cardiac arrest 30 min, TnT, ECG, LVEF 48%,
Moderate LVH (IVS 15, PWd 15)
57 ♂
High PVR 4
Jan 2014
21 ♀
Cardiac arrest 40 min
56 ♀
-
Jan 2014
50 ♂
-
25 ♂
HVAD Pump infection
Mar 2014
35 ♂
Cardiac arrest 40 min, Moderate LVH (IVS 16)
52 ♂
HVAD
Royal Brompton & Harefield
NHS Foundation Trust
Donor-Recipient Profile
Tx Date
Donor
profile
Donor-Risk factors
April 2014
April 2014
32 ♀
LVEF 50% Mild – Moderate MR. Sepsis
Royal Brompton & Harefield
NHS Foundation Trust
Recipient
profile
Recipient Risk Factors
45 ♂
LVAD Levitronix
42 ♀
HVAD
POSTOPERATIVE OUTCOME
Mechanical circulatory support
4 (13%)
RV Failure ( NO/Inotr > 1 week)
7 (23%)
Duration Inotropic support (h)
116±90
Duration Nitric Oxide (h)
23 (16 ; 40)
Blood loss in 24h
885 ± 556
Renal failure (CVVHDF)
14 (46%)
ITU stay (days)
9.3 ± 10.4 days (2 – 44)
Hospital stay (days)
33 ± 22
Survival 30 days
100%
FOLLOW UP
255 ± 96 (142-395)
Current Survival
95%
LVEF
66 ± 5% (51 – 73%)
Graft function preserved (LVEF>60)
RV Function TAPSE
Royal Brompton & Harefield
NHS Foundation Trust
27 ( 90%)
13.5 mm (12 ;16)
Donation after circulatory death - DCD
•
•
•
Brain dead donors (DBD) are the main source of the organs
for transplantation.
Donation after circulatory dead (DCD) donors were introduced
to lung transplantation by Love in 1995.
Maastricht classification was introduced in 1995 and amended
in 2000.
•
•
•
•
•
Category I – dead on arrival to hosital
Category II – unsucceful resuscitation
Category III – awaiting cardiac arrest
Category IV – cardiac arrest after brain death diagnosis
Category V – in-hospital cardiac arrest
Royal Brompton & Harefield
NHS Foundation Trust
Background
• Organ donor shortage is a main limitation of transplantation. Only
20 % of actual donors are donating lungs.
2009 OPTN/SRTR Annual Report.
Transplant Activity in the UK.. Activity Report 2009/2010.
• Lungs tolerate well warm ischemia up to 60-90 minutes in
research settings.
Egan TM et al. Ann Thorac Surg 1991;52:1113-1120
Van Redmonck DE et al. Ann Surg 1998;228:788-796
Loehe F et al. Ann Thorac Surg 2000;69:1556-1562
• Preliminary studies evaluating results of controlled DCD lung
transplantation showed promising results comparable to standard
procedures utilizing the organs from brain-dead donors.
De Oliveira NC et al. J Thora Cardiovasc Surg 2010;139:1306-1315
De Vleeshauwer SI et al. J Heart Lung Transplant 2011;30:975-981
Van De Wauwer C et al. Eur J Cardiothoracic Surg 2011; 39:e175-180
Royal Brompton & Harefield
NHS Foundation Trust
Background
• AGONAL TIME
• WOT – CARDIAC ARREST
• WARM ISCHEMIC TIME BEGINNING:
• Sat O2<70%
• SBP<50 mmHg
• WARM ISCHEMIC TIME END
• PA flush
• Acceptable warm ischemic time up to 1 hour
Royal Brompton & Harefield
NHS Foundation Trust
Management before Withdrawal of Life sustaining Treatment:
•
“Maintenance of life-sustaining treatment may be considered
to be in the best interests of someone who wanted to be a
donor if it facilitates donation and does not cause them harm
or distress, or place them at significant risk of experiencing
harm or distress.”
•
No treatment specifically aimed at organ donation should be
instituted before the decision to withdraw treatment has been
made.
•
Potential DCD donors should be cared for by staff with the
appropriate competencies, particularly in end of life care. This may
involve moving a patient from the ED to an ICU if possible,
according to local policy.
DCD CONSENSUS MEETING REPORT (June 2010)
Royal Brompton & Harefield
NHS Foundation Trust
Process of Withdrawal of Life Sustaining Treatment
• Withdrawal of cardio-respiratory support should always be
conducted under the close supervision of senior medical staff
(ITU)
• Airway management (differs across UK)
Actions after the withdrawal of Life Sustaining Treatment
• Theatre teams are ready
• Every 5 minutes coordinator to communicate vital signs
• Abandon retrieval if patient remains stable for 120 min or
functional warm ischemia ( RR below 50 mmHg, O2Sat below
70%) exceeds 60 min for lungs (different for each organ)
Royal Brompton & Harefield
NHS Foundation Trust
Diagnosis of death:
•“the individual should be observed by the person
responsible for confirming death for a minimum of five
minutes to establish that irreversible cardio respiratory
arrest has occurred” (Academy of Medical Royal
Colleges Code of Practice)
•Confirm absence of circulation: arterial line/
echocardiography/ asystole on ECG
•No intervention that can potentially restore cerebral
circulation and function is allowed under any
circumstances!
Royal Brompton & Harefield
NHS Foundation Trust
Process of organ retrieval
•
Patient transferred to theatre ( 5 min after cardiac arrest)
•
Reintubation –anaesthetist ( 10 min after cardiac arrest)
•
Bronchoscopy ( rule out aspiration, secretion) by one Surgeon
Simultaneously by 2 Surgeon:
- opening of chest
- cross clamp on aorta ( isolate cerebral circulation)
- insertion of cannula into pulmonary artery
- ventilate lungs – recruit atelectatic lung areas
- start pulmoplegia
- apply topical cooling with crushed ice
•
Organ harvest
Royal Brompton & Harefield
NHS Foundation Trust
Lungs from donation after circulatory death donors: an alternative
source to brain-dead donors? Midterm results at a single
institution
Bartlomiej Zych,*, Aron-Frederik Popov, Mohamed Amrani, Toufan Bahrami, Karen
Christina Redmond, Heike Krueger, Martin Carby and André Ruediger Simon
European Journal of Cardio-Thoracic Surgery 2012 Sep;42(3):542-9
Royal Brompton & Harefield
NHS Foundation Trust
Results
Donor characteristics
AGE
GENDER:
FEMALE
MALE
CAUSE OF DEATH:
ICH
HBI
TBI
CVA
Meningitis
other
SMOKING HISTORY
MECHANICAL VENTILATION (days)
PaO2 (mmHg)
TOTAL ISCHEMIC TIME (min.)
AGONAL TIME (min.)
WARM ISCHEMIC TIME
ICH – intracranial hemorrhage
DCD N - 26
45 (38.75;52)
DBD N - 130
45 (34.5;53.5)
p
NS
17 (65%)
9 (35%)
82 (63%)
48 (37%)
NS
NS
16 (61.5%)
5 (19%)
2 (8%)
3 (11.5%)
0
0
15 (58%)
1 (1;3)
498.375 (451.5;525)
320 (298.75;393.25)
15 (12;24)
15 (12;19.25)
89 (68.6)
13 (10%)
14 (11%)
6 (4.5%)
6 (4.5%)
2 (1.5%)
67 (52%)
1 (1;3)
442.5 (371.25;502)
285.5 (240;373)
NA
NA
NS
NS
NS
NS
NS
NS
NS
NS
0.009
0.025
HBI – hypoxic brain injury TBI - traumatic brain injury CVA – cerebrovascular accident
Royal Brompton & Harefield
NHS Foundation Trust
Results
Recipient’s characteristics and postoperative outcome
AGE
GENDER
MALE:
FEMALE:
DIAGNOSIS
CF:
EMPHYSEMA:
α1-ANTITRYPSIN DEFICIENCY:
PF
LAM
SARCOIDOSIS
PH
OB
ON-PUMP:
OFF-PUMP
DLTx:
SLTx:
POSTOPERATIVE ECMO:
MECHANICAL VENTILATION (h)
ICU LOS (d)
HOSPITAL LOS (d)
DCD N - 26
47 (30;53.7)
DBD N - 129
47 (33;55)
p
NS
13 (50%)
13 (50%)
64 (49.6%)
65 (50.4%)
NS
NS
11 (42%)
10 (38%)
2 (8%)
1 (4%)
1 (4%)
1 (4%)
0
0
21 (80%)
5 (20%)
25 (96%)
1 (4%)
4 (16%)
47 (24;144)
5 (3;33)
35.5 (20.5;79.25)
43 (33.5%)
38 (29.5%)
21 (16%)
9 (7%)
5 (4%)
2 (1.5%)
7 (5.5%)
4 (3%)
97 (75%)
32 (25%)
109 (85%)
20 (15%)
6 (5%)
27 (12;204)
5 (3;21.5)
35 (25;54)
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
0.066
NS
NS
NS
Royal Brompton & Harefield
NHS Foundation Trust
Results
Survival
100%
DCD
DBD
80%
60%
40%
20%
p=ns
0%
0.00
500.00
1000.00
1500.00
2000.00
Time after transplant (days)
Patient at risk
DCD
DBD
1 year
18(88.5%)
93(86.5%)
2 years
10(81.7%)
61(76.6%)
Royal Brompton & Harefield
NHS Foundation Trust
3 years
4(81.7%)
32(74.8%)
4 years
1(81.7%)
5(70.9%)
Results
Lung function tests and freedom from BOS
Freedom from BOS
100 %
DCD
DBD
80
%
p=n
s
60 %
40 %
20 %
p=ns
0%
0.00
500.00
1000.00
1500.0
0
2000.0
0
Time after transplantation (days)
Patient at risk
DCD
DBD
1 year
15(94.7%)
85(90.6%)
2 years
9(82.9%)
54(82.8%)
3 years
4(82.9%)
29(80.8%)
P
DCD
DBD
N
22
114
FEV1 – best (% predicted)
84 (72.5;95)
83 (63.65;98)
NS
Number of days achieved (d)
184.5 (130;298.75)
185 (107.5;298)
NS
N
21
114
FEV1 – 3 months (% predicted)
63 (60;75)
69 (52.3;86)
N
21
110
FEV1 – 6 months (% predicted)
80 (52;88)
75 (56;90.35)
N
14
80
FEV1 – 1 year (% predicted)
77.5 (66.25;96.25)
78 (56;94)
N
8
45
FEV1 – 2 years (% predicted)
79 (66.5;96.25)
81 (48;95.75)
N
4
26
FEV1 – 3 years (% predicted)
77.5 (63.5;91)
78 (52.5;92.5)
4 years
1(82.9%)
3(80.8%)
Royal Brompton & Harefield
NHS Foundation Trust
NS
NS
NS
NS
NS
Results
Primary Graft Dysfunction
p=ns
Royal Brompton & Harefield
NHS Foundation Trust
Results
Rejection
p=ns
Royal Brompton & Harefield
NHS Foundation Trust
Conclusions
• DCD lungs are a valuable source of good
quality organs for transplantation
providing a similar results compare to
standard DBD lung transplantations.
Royal Brompton & Harefield
NHS Foundation Trust
Royal Brompton & Harefield
NHS Foundation Trust
Royal Brompton & Harefield
NHS Foundation Trust
Thank you very much for your
kind attention
Royal Brompton & Harefield
NHS Foundation Trust