1. Ante mortem interventions in DCD Dr Malcolm Watters Regional Clinical Lead for Organ Donation 1

2. Donation and transplantation rates of organs from DBD organ donors in the UK, 1 April 2014– 31 March 2015 % of all organs 85% 82% 23% 22% 17% 1 3%

3. Donation and transplantation rates of organs from DCD organ donors in the UK, 1 April 2014–31 March 2015 % of all organs 80% 35% 12% 7%

4. Background Legal guidance issued in 2009 - 11 –Conservative –Effective prohibition on ante-mortem heparin Call for revision in 2012 / 2013 by UK DEC –Generic overarching guidance –Separate documents covering specific interventions (e.g. heparin, extubation) –Specific recommendations regarding heparin Further evidence required by Department of Health –Risks and benefits –Clinical and public acceptability –NHSBT asked to conduct this review

5. Review deliverables Literature review of risks and benefits of ante-mortem interventions Description of international practices Better understanding of physiological changes following treatment withdrawal Public and professional survey of acceptability of ante- mortem interventions –Expert workshop –Focus groups –On-line survey Recommendations to the Department of Health

6. Potential ante-mortem interventions Interventions to assess organs –Trans thoracic echocardiography –Trans-oesophageal echocardiography –Bronchoscopy Interventions to preserve organs –Heparin, steroid, phentolamine –Femoral cannulation –Elective intubation and ventilation –Emergency resuscitation –Terminal extubation

7. International practice USACanadaAustraliaFranceBelgiumUK Heparin ++±++- Phentolamine ±+-- Femoral cannulation ±-+- Withdrawal in operating theatre +++++± bronchoscopy ±±

8. Evidence Heparin Established in DBD. Strong clinical conviction of benefit (liver, lung, paediatric heart). Reduced thrombus formation in experimental lung models PhentolamineNo evidence Femoral cannulation Evidence for lack of benefit in rapid cold preservation. May be of benefit for rapid normothermic regional perfusion Withdrawal in operating theatre Strong clinical conviction of benefit (ischaemic cholangiopathy) BronchoscopyEstablished practice in DBD.

9. Avoiding harm? Can heparin be given after treatment withdrawal? –Does the patient always die if BP goes below a certain level? –Does donation always happen if BP goes below a certain level? –Is there time to give heparin once point of no return is identified for it to have a systemic effect? Do all potential DCD donors die following treatment withdrawal? –Lessens the risk of ante mortem interventions carried out before treatment withdrawal

10. Physiological changes following treatment withdrawal Can a point of ‘no-return’ be identified following treatment withdrawal? –Does the patient always die if BP goes below a certain level? –Does donation always happen if BP goes below a certain level? Is there time to give heparin once point of no return is identified for it to have a systemic effect? What happens to non-proceeding DCD donors? –Do all potential DCD donors die following treatment withdrawal?

11. Methodology Review of SN-OD records of proceeding and non- proceeding DCD donors –April – Dec 2013 –Yorkshire, South Central, South West, Northern, Midlands, Scotland, Northern Ireland, South Wales –255 proceeding donors, 153 non-proceeding donors Measures –Outcome –Time to asystole –Physiological changes following treatment withdrawal Systemic arterial BP (systolic, mean, diastolic) S a O 2 Heart rate Respiratory rate

12. Time to asystole in proceeding DCD donors Time% asystole 10 min18.8 20 min61.5 30 min74.8

13. Time to death in non-proceeding DCD donors (n=153, data on three patients missing)

14. Systolic BP in proceeding DCD donors, South West

15. Timings in proceeding DCD donors Systolic BP of 50 mmHg to asystole (minutes) MinimumMaximum Mean5.98.1 Median56 Range1 – 56 Systolic BP of 90 mmHg to asystole (minutes) MinimumMaximum Mean12.816.2 Median812 Range1-86 Minimum: time from first recording below selected BP to asystole Maximum: time from last recording over selected BP to asystole

16. Systolic BP, non-proceeding donors, n=153

17. Non-proceeding DCD donors with one or more SBP < 90 mmHg (n=13)

18. Non-proceeding DCD donors with one or more SBP < 50 mmHg (n=4)

19. Conclusions Most but not all potential DCD donors die following treatment withdrawal –3 / 408 patients discharged from hospital All patients die if BP falls below 90 mmHg –Donation does not always happen Limited time to give heparin –Systolic BP 50 mmHg: 5-6 minutes –Systolic BP 90 mmHg: 8–12 minutes

20. Heparin In which circumstance would you consider it acceptable for a single dose of heparin to be given to a potential DCD donor, where family consent for organ donation has been given? All potential DCD donors at the time of treatment withdrawal All potential DCD donors who are not at particular risk of bleeding at the time of treatment withdrawal All potential DCD donors at the point where death is inevitable and imminent All potential DCD donors who are not at particular risk of bleeding at the point where death is inevitable and imminent Never Don't know

21. Heparin Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same All potential DCD donors at the time of treatment withdrawal All potential DCD donors who are not at particular risk of bleeding at the time of treatment withdrawal All potential DCD donors at the point where death is inevitable and imminent All potential DCD donors who are not at particular risk of bleeding at the point where death is inevitable and imminent Never Don't know

22. Steroids In which circumstance would you consider it acceptable for a single dose of steroid to be given to a potential DCD donor, where family consent for organ donation has been given? I do not think that steroids should ever be given. I think that steroids should be given if the family agree. I think that steroids should be given whenever they might improve transplantation. I don’t know None of the above. I think that:

23. Steroids Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same I do not think that steroids should ever be given. I think that steroids should be given if the family agree. I think that steroids should be given whenever they might improve transplantation. I don’t know None of the above. I think that:

24. Phentolamine In which circumstance would you consider it acceptable for a single dose of phentolamine to be given to a potential DCD donor, where family consent for organ donation has been given? I do not think that phentolamine should ever be given. I think that phentolamine should be given if the family agree. I think that phentolamine should be given whenever it might improve transplantation. I don’t know None of the above. I think that:

25. Phentolamine Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same. I do not think that phentolamine should ever be given. I think that phentolamine should be given if the family agree. I think that phentolamine should be given whenever it might improve transplantation. I don’t know None of the above. I think that:

26. Additional non-invasive tests Trans-thoracic echocardiography Trans-thoracic echocardiography may become part of the ante-mortem assessment of potential DCD heart donors. How do you feel about this? I think that the scan should be carried out whenever it is needed to assess whether a person can donate their heart for transplant. I think that doctors can do the scan as long as the family agree to it. I don’t think that the scan should ever be done, even if this means that heart transplantation cannot happen. I don't know. None of these. I think ……….

27. Additional non-invasive tests Trans-thoracic echocardiography Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same. I think that the scan should be carried out whenever it is needed to assess whether a person can donate their heart for transplant. I think that doctors can do the scan as long as his family agree to it. I don’t think that the scan should ever be done, even if this means that a heart transplant cannot happen. I don't know. None of these. I think ……….

28. Additional invasive tests Trans-oesophageal echocardiography Trans-oesophageal echocardiography may become part of the ante- mortem assessment of potential DCD heart donors. How do you feel about this? I think that the scan should be carried out whenever it is needed to assess whether a person can donate their heart for transplant. I think that doctors can do the scan as long as the family agree to it. I don’t think that the scan should ever be done, even if this means that heart transplantation cannot happen. I don't know. None of these. I think ……….

29. Additional invasive tests Trans-oesophageal echocardiography Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same I think that the scan should be carried out whenever it is needed to assess whether a person can donate their heart for transplant. I think that doctors can do the scan as long as his family agree to it. I don’t think that the scan should ever be done, even if this means that a heart transplant cannot happen. I don't know. None of these. I think ……….

30. Additional invasive tests Bronchoscopy Bronchoscopy may assist in the assessment of potential DCD lung donors. The patient would receive appropriate sedation for the procedure. How do you feel about a bronchoscopy being carried out? I think that a bronchoscopy should be carried out whenever it is needed to assess whether a person can donate their lungs for transplant. I think that the bronchoscopy can be performed as long as the family agrees. I don’t think that a bronchoscopy should ever be done, even if this means that a lung transplant cannot happen. I don't know. None of these. I think ……….

31. Additional invasive tests Bronchoscopy Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same. I think that a bronchoscopy should be carried out whenever it is needed to assess whether a person can donate their lungs for transplant. I think that the bronchoscopy can be performed as long as the family agrees. I don’t think that a bronchoscopy should ever be done, even if this means that a lung transplant cannot happen. I don't know. None of these. I think ……….

32. Intubation and ventilation What do you think about a dying patient, in whom donation would be possible, being intubated and ventilated in order to facilitate organ donation. I think that a dying patient should be intubated and ventilated whenever organ donation is a possibility. I think that a dying patient should be intubated and ventilated whenever organ donation is a possibility, but only if the next of kin agree to it. I don’t think that a dying patient should ever be intubated and ventilated just for the purposes of organ donation. I don’t know. None of these. I think …………..

33. Intubation and ventilation Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same. I think that a dying patient should be intubated and ventilated whenever organ donation is a possibility. I think that a dying patient should be intubated and ventilated whenever organ donation is a possibility, but only if the next of kin agree to it. I don’t think that a dying patient should ever be intubated and ventilated just for the purposes of organ donation. I don’t know. None of these. I think …………..

34. Emergency resuscitation A potential DCD donor suffers a cardiac arrest before the retrieval team are ready for treatment withdrawal. What do you think about cardiac resuscitation in such circumstances? I think that resuscitation should begin immediately. I think that resuscitation should begin as soon as the family have given permission for it. I don’t think that resuscitation should be instituted in any circumstances. The patient should be allowed to die. I don’t know. None of these. I think …………..

35. Emergency resuscitation Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same. I think that resuscitation should begin immediately. I think that resuscitation should begin as soon as the family have given permission for it. I don’t think that resuscitation should be instituted in any circumstances. The patient should be allowed to die. I don’t know. None of these. I think …………..

36. Changing how treatments are withdrawn Donation may be more likely if treatment withdrawal includes terminal extubation. How would you feel about a potential DCD donor being extubated if this is not something normally done when withdrawing treatments? I think that if it has been decided that donation should go ahead, treatments should be withdrawn in a way that makes this most likely to happen. I think that if it has been decided that donation should go ahead, medical staff should discuss with the family about how best to withdraw treatments. I do not think that there should ever be any change to how treatments are withdrawn to make donation more likely to happen. I don’t know. None of these. I think that……

37. Changing how treatments are withdrawn Would your answer be different if the patient had registered a wish to donate on the NHS Organ Donor Register? If so, what would it now be? My answer would be the same. I think that if it has been decided that donation should go ahead, treatments should be withdrawn in a way that makes this most likely to happen. I think that if it has been decided that donation should go ahead, medical staff should discuss with the family about how best to withdraw treatments. I do not think that there should ever be any change to how treatments are withdrawn to make donation more likely to happen, even if the person wanted to be a donor. I don’t know. None of these. I think that……

38. Overview Which interventions would you be willing to undertake or allow when caring for a potential DCD donor within the current professional, ethical and legal framework of practice for DCD in the UK? Drug therapy - heparin Drug therap - steroids Drug therapy - phentolamine Trans-thoracic echocardiogram Trans-oesophageal echocardiogram Bronchoscopy Elective intubation and ventilation Emergency resuscitation Changing how treatments are withdrawn (extubation of the airway)