Bartlomiej Zych, Diana Gracia-Saez, and Andre R Simon. Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Harefield Hospital,

Royal Brompton & HarefieldNHS Foundation Trust

Bartlomiej Zych, Diana Gracia-Saez, and Andre R Simon .

Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Harefield Hospital, London, United Kingdom.

UPDATE IN CARDIOTHORACIC TRANSPLANTATION


•

Heart transplant activity UK


•

Lung and heart/lung transplant activity UK


Early aggressive donor assessment and management including:

Invasive hemodynamic monitoring. TOE. Bronchoscopy.

Performed by dedicated cardiothoracic transplant teams.

UK Donor Scout Pilot Project


“… in essence, donor management is a continuation of previous critical care management but with a shift in goals’’

Principle of donor management

McKeown DW. et al. BJA 2012


Impact of brain stem death on cardiovascular system and lungs.



Arab D et al. Intensive Care Med 2003


Phase I - Catecholamine Storm/hypertension:

Increase in ICP , compensatory hypertension. Marked sympathetic stimulation, intense vasoconstriction,

raised SVR.

Consequences:

Central redistribution of blood, increased afterloaddecreased 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.

Impact of brain stem death on carrdiovascular 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).





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)




Cardiovascular Management



Changes in UK transplant activity 2013-2014


Changes in UK transplant activity 2013-2014


Preservation-transport of a continuously perfused, beating heart at 34°C.

Avoids the negative effect of prolongedcold ischemic storage.

Additional assessment options.

Transmedics – Organ Care System for heart


Transmedics – Organ Care System for heart


1. 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™

2. 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


..Belfast

.... Edinburgh

Glasgow

..Aberdeen

.Dublin

. .

..

Bristol

Bath

Oxford.

Nottingham

Manchester

London.Cardiff

.Newcastle

ZONALNorthwichEast SurreySouthampton x2Oxford x3St George’s x2Charing CrossSt Mary’s

Extending Safe Retrieval Range Using OCS

NON ZONALBarnsleyMilton KeynesGlasgow Kings LondonBathNewcastle x2 DublinNorth WalesExeter Yeovil districtEdinburgh x3Ashford x2BelfastPlymouth


OCS Case Series 22February 2013 – 29 April 2014

Donor Hearts Assessed on OCS36

Hearts Transplanted 30

Turned Down After OCS Assessment = 6

Significant down-timeRising Lactate

Unstable perfusion parameters

Stable Perfusion & Lactate Profile

1 patient died after 44 days(Death not related with heart function)


Donor-Recipient Profile










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) 27 ( 90%)

RV Function TAPSE 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


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


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


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)


• 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)

Process of Withdrawal of Life Sustaining Treatment


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!


• Patient transferred to theatre ( 5 min after cardiac arrest)

• Reintubation –anaesthetist ( 10 min after cardiac arrest)

• Bronchoscopy ( rule out aspiration, secretion) by one SurgeonSimultaneously 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

Process of organ retrieval


Lungs from donation after circulatory death donors: an alternativesource 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


Results

Donor characteristics

ICH – intracranial hemorrhage HBI – hypoxic brain injury TBI - traumatic brain injury CVA – cerebrovascular accident

DCD N - 26 DBD N - 130 p AGE 45 (38.75;52) 45 (34.5;53.5) NS

GENDER: FEMALE MALE

17 (65%) 9 (35%)

82 (63%) 48 (37%)

NS NS

CAUSE OF DEATH: ICH HBI TBI CVA Meningitis other

16 (61.5%) 5 (19%) 2 (8%) 3 (11.5%) 0 0

89 (68.6) 13 (10%) 14 (11%) 6 (4.5%) 6 (4.5%) 2 (1.5%)

NS NS NS NS NS NS

SMOKING HISTORY 15 (58%) 67 (52%) NS MECHANICAL VENTILATION (days) 1 (1;3) 1 (1;3) NS PaO2 (mmHg) 498.375 (451.5;525) 442.5 (371.25;502) 0.009 TOTAL ISCHEMIC TIME (min.) 320 (298.75;393.25) 285.5 (240;373) 0.025 AGONAL TIME (min.) 15 (12;24) NA WARM ISCHEMIC TIME 15 (12;19.25) NA


Results

DCD N - 26 DBD N - 129 p AGE 47 (30;53.7) 47 (33;55) NS GENDER MALE: FEMALE:

13 (50%) 13 (50%)

64 (49.6%) 65 (50.4%)

NS NS

DIAGNOSIS CF: EMPHYSEMA: α1-ANTITRYPSIN DEFICIENCY: PF LAM SARCOIDOSIS PH OB

11 (42%) 10 (38%) 2 (8%) 1 (4%) 1 (4%) 1 (4%) 0 0

43 (33.5%) 38 (29.5%) 21 (16%) 9 (7%) 5 (4%) 2 (1.5%) 7 (5.5%) 4 (3%)

NS NS NS NS NS NS NS NS

ON-PUMP: OFF-PUMP

21 (80%) 5 (20%)

97 (75%) 32 (25%)

NS NS

DLTx: SLTx:

25 (96%) 1 (4%)

109 (85%) 20 (15%)

NS NS

POSTOPERATIVE ECMO: 4 (16%) 6 (5%) 0.066 MECHANICAL VENTILATION (h) 47 (24;144) 27 (12;204) NS ICU LOS (d) 5 (3;33) 5 (3;21.5) NS HOSPITAL LOS (d) 35.5 (20.5;79.25) 35 (25;54) NS

Recipient’s characteristics and postoperative outcome


ResultsSurvival

p=ns

Time after transplant (days)

Patient at risk 1 year 2 years 3 years 4 yearsDCD 18(88.5%) 10(81.7%) 4(81.7%) 1(81.7%)DBD 93(86.5%) 61(76.6%) 32(74.8%) 5(70.9%)

2000.001500.001000.00500.000.00

100%

80%

60%

40%

20%

0%

DBD DCD


Results

DCD DBD P

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) NS

N 21 110

FEV1 – 6 months (% predicted) 80 (52;88) 75 (56;90.35) NS

N 14 80

FEV1 – 1 year (% predicted) 77.5 (66.25;96.25) 78 (56;94) NS

N 8 45

FEV1 – 2 years (% predicted) 79 (66.5;96.25) 81 (48;95.75) NS

N 4 26

FEV1 – 3 years (% predicted) 77.5 (63.5;91) 78 (52.5;92.5) NS

p=ns

Time after transplantation (days)

Patient at risk 1 year 2 years 3 years 4 years DCD 15(94.7%) 9(82.9%) 4(82.9%) 1(82.9%) DBD 85(90.6%) 54(82.8%) 29(80.8%) 3(80.8%)

2000.00

1500.00

1000.00500.000.00

100 %

80 %

60 %

40 %

20 %

0 %

DBDDCD

Freedom from BOS

Lung function tests and freedom from BOS

p=ns


Results

p=ns

Primary Graft Dysfunction


ResultsRejection

p=ns


Conclusions

• DCD lungs are a valuable source of good quality organs for transplantation providing a similar results compare to standard DBD lung transplantations.




Thank you very much for your kind attention

Documents

Bartlomiej Zych, Diana Gracia-Saez, and Andre R Simon. Department of Cardiothoracic Transplantation & Mechanical Circulatory Support, Harefield Hospital,