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Donor Management Master Class

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Presentation on theme: "Donor Management Master Class"— Presentation transcript:

1 Donor Management Master Class
Dr Dermot McKeown Dr Paul McAndrew Andrew Broderick 15th June 2010 “Driving improved organ donation within your hospital”

2 UK Heartbeating Donors 2008-2009
Kidney Liver Pancreas Thoracic 612 584 (95%) 559 (91%) 308 (50%) 233 (38%) We have recent figures for numbers of UK Heartbeating donors. These are, of course, brainstem dead, and virtually all managed in ICU. (we will be discussing the interface with the Emergency Department later) I show those donation procedures at which various organs were retrieved. You will see that there is variation in organs retrieved from donors. 2 2

3 UK Heartbeating Donors 2008-2009
..and shown graphically you can see: 95% of donation procedures will result in kidney retrieval, 95% of those will result in 2 kidneys, and 94% of retrieved kidneys will be transplanted.- a remarkable record. 91% of donations will retrieve a liver, and 94% of those will be transplanted. Some, of course, are split-and may result in more transplants including facilitating transplants for children or small individuals. 20% of all deceased donor livers are reduced or split before transplantation We now see a considerable drop off. The selection criteria for pancreatic transplant are very tight, and were only increased to an upper age limit of 60 during this year. Of note, though, only 1 of 10 organs retrieved in the age group resulted in whole organ transplant-though islet cell transplant may be an option. And finally we come to the issue of thoracic transplant. Only 38% of heartbeating donors provide thoracic organs. Cardiothoracic transplantation is absolutely dependent on organs which will function well post implantation. There is increasing evidence that we can make more organs transplantable by active donor management. This is one of our main targets-and we believe that consistent, evidence-based donor management will assist us with this 3 3

4 But quite a few units with moderate numbers, and many with 0,1 or 2.
Unit Experience Not many units with high numbers, are there? These are clearly neurosurgical units, and SHOULD be good at donor management. But quite a few units with moderate numbers, and many with 0,1 or 2. 4 4

5 What Does This Mean? 65% of units have 2 or fewer donors per year
23% of donors are from ICU with 1-2 donors per year 4% of units have 10 or more donors per year, 28% of total donor population Need to increase thoracic donation So this gives us context for what we will do today. The vast majority of units have a handful of donors-yet they are responsible for a quarter of the donors. What I take from this is just think if they got one more donor each per year-that’s a real increase!! But also-how can you get good at managing donors on that sort of experience? OK, a lot is just good ICU care and we know that we can deliver that-but clearly support at the bedside is crucial to these units. We need to learn from the experience of those units who manage large numbers, and we look forward to your comments later in the day And we need to face the big issue of increasing opportunities for thoracic organ donation-and appreciating how that fits with other donation 5 5

6 Masterclass Objectives
To empower clinical leads to raise awareness of the importance of donor management in maximising the gift of donation and to put into place or facilitate effective measures that will increase the number and quality of organs retrieved from heartbeating brainstem dead donors To nurture a wider understanding of the principles of donor assessment To reduce the number of patients who are not tested for brainstem death on the grounds of cardio-respiratory instability 6 6

7 Agenda 1 Brainstem Death and Management of the Organ Donor
09.30 – 10.00 2 Cardiovascular Management and Cardiac Donation 10.00 – 10.25 3 Respiratory Management and Lung Donation 10.25 – 10.50 Break 10.50 – 11.05 4 Group Discussion 11.05 – 11.35 5 Donor Assessment and Process 11.35 – 12.00 6 Critical Care support to Donor Operation 12.00 – 12.20 7 Case Studies 12.20 – 12.50 8 Summary & Close 12.50 – 13.00

8 So this gives us context for what we will do today.
Plan for Session Review of physiology of typical donor Detailed review Cardiovascular management and cardiac donation Respiratory management, fluids and lung donation Practicalities of donor management Organisation and co-ordination Theatre management Case discussions So this gives us context for what we will do today. The vast majority of units have a handful of donors-yet they are responsible for a quarter of the donors. What I take from this is just think if they got one more donor each per year-that’s a real increase!! But also-how can you get good at managing donors on that sort of experience? OK, a lot is just good ICU care and we know that we can deliver that-but clearly support at the bedside is crucial to these units. We need to learn from the experience of those units who manage large numbers, and we look forward to your comments later in the day And we need to face the big issue of increasing opportunities for thoracic organ donation-and appreciating how that fits with other donation 8 8

9 Brainstem Death and management of the organ donor
Dermot McKeown

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13 Progression to Brainstem Death (BSD)
Increased ICP Bradycardia Hypertension “Sympathetic Storm” Irreversible loss of brainstem function can be induced by multiple pathologies: trauma, secondary swelling, hypoxic brain injury, intracranial haemorrhage. The physiological changes which occur can vary, particularly in duration, but careful review of observation charts can reveal the timing of final damage. 13 13

14 Level of Care Full ICU care facilitates appropriate BSD testing After BSD testing, continued care maintains potential for donation Discussion with relatives Donor Management Patients with severe neurological injury will be being treated intensively- can discuss ventilation, sedation, CVS and osmotic management. If BSD is suspected, and to be tested, full ICU care will be in progress and this will help fulfil the preconditions (mention perfusion, electrolytes, temperature) If 1st set tests shows patient is BSD, this must be communicated to relatives and discussion undertaken. ICU care should continue to allow for optimal opportunity to fulfil patient wishes (e.g. with donor card) Active Donor Management can commence if and when wish to donate confirmed. 14 14

15 Changes following Brainstem Death (BSD)
Cardiovascular Hypothermia Diabetes Insipidus Disseminated Intravascular Coagulation Pulmonary Inflammation As we have discussed, acute changes around the time of ‘coning’ are generally short-lived, although potentially acute and severe. The tendency therafter is towards a vasodilated state with low peripheral resistance. The magnitude of changes will be considerably affected by previous therapies. Heat loss will be increased by peripheral vasodilation and control lost because of hypothalamic damage. Heat production is also reduced and hypothermia can develop rapidly. This is not always appreciated as the patient appears well perfused and pink. Diabetes Insipidus is common. Posterior pituitary function is usually lost, and resulting polyuria (with associated hypovolaemia) and electrolyte disturbance augments the deleterious effects on CVS function (as does loss of vasopressin activity peripherally) DIC results from release of Tissue Thromboplastin from damaged neural tissue. Incidence varies but common in trauma Pulmonary changes during the sympathetic storm result from central hypervolaemia, raised atrial pressure and myocardial dysfunction. Pulmonary oedema is common, and the lungs are ‘activated’ and vulnerable to further damage. A generalised Inflammatory process is triggered by brain death, if not already present from critical illness. It remains the fact that similar organs from ‘good’ non-brain dead donors may function better than BSD organs. (Lungs, Kidneys) 15 15

16 Incidence of Changes Hypotension 81% Diabetes Insipidus 65% DIC 28%
Cardiac arrhythmias 25% Pulmonary oedema 18% Metabolic acidosis 11% Physiologic changes During Brain Stem Death – Lessons for Management of the Organ Donor. The Journal of Heart & Lung Transplantation Sept 2004 (suppl) J Heart Lung Transplantation 2004 (suppl) 16 16

17 Donor Management Shift of Goals, but still Intensive Care Increase numbers of donors Increase number of organs per donor Improve function of transplantable organs Donor management shifts emphasis, but is still very active critical care. May even be more active than previous treatment Aims are to ensure more donors proceed to donation operation by ensuring stability, increase the number of transplantable organs, and to try to ensure they function better after implantation. Particularly important with ‘marginal organs’ 17 17

18 Evidence for Donor Management
Totsuka Transplant Proc. 2000; 32; High sodium in liver donor doubles graft loss Rosendale Transplantation (4): Protocol increased organs per donor 3.1 to Increased probability of transplant. Snell J Heart Lung Transplant 2008;27:662-7 54% of Australian lung donations used for transplant vs. 13% in UK Active Donor Management is a developing area. It was always known that unstable donors and ‘crash’ retrieval of organs was associated with poor function. Totsuka in Pittsburgh showed that Sodium greater than 155 was associated with double graft loss over lower sodiums, including those who had previously high sodiums that were actively managed. Rosendale reported on the use of ‘Triple Hormone’ Therapy (in fact T4, Methylprednisolone and Insulin) and increased number and transplantability of organs, though it should be noted that the UNOS protocol for donor management was also being promoted, so this may represent a combined effect. The Australian use of a programme to actively manage potential lung donors resulted in large increases in the number of transplantable organs. Active Donor Management works. Investigation of the most effective component techniques is necessary, and is in progress, but use of a standard logical approach seems essential. There is little variation in 18 18

19 Donor Management All donors are potential multiorgan donors Aim to make all organs transplantable Maintain or improve function A proactive approach is encouraged. Even if the patient seems to have significant organ dysfunction, many patients on waiting lists may be desperate for any organ. Aiming to make all organs transplantable, and to maintain them that way is a good target 19 19

20 Mean Arterial Pressure
Goals General Stability Target Values Mean Arterial Pressure 60-80 mmHg CVP 4-10 mmHg Heart Rate 60-100 Rhythm sinus Unsurprisingly, a warm, well perfused donor on no vasopressor support with good blood results and no evidence of poor organ perfusion is likely to provide a full complement of well functioning organs. Converting unstable donors to this condition is the Challenge. Target values may well vary considerably from those aimed at during life, particularly if a high Cerebral Perfusion Pressure was being sought. It may well be possible to rapidly wean prior vasoactive infusions. There are some organ specific management techniques which we may consider. Thoracic organs are a particular issue, and early use of invasive monitoring, if not already in place, should be considered. Target Values Cardiac Index >2.1 l/min/m2 20 20

21 General Care Continue ICU care Temperature control Give methylprednisolone, review drugs Donor Management Guideline General ICU level staffing should be maintained, and in fact extra help may be required at bedside (equipment, monitoring, blood sampling) Temperature measurement, active warming (Bair Hugger, water blanket, HME) Methylprednisolone should be given. 15mg/Kg (1g for adult) to reduce inflammation. Also associated with reduced lung water in lung donors. Review drugs. Introduce insulin if not already in progress (ready to manage DI, inotropic) Stop non-essentials. Maintain indicated antibiotics. Start to wean vasopressors if possible. A guideline should be used. ICS, Canadian, various cardiac. Although confusing, ukbt are trying to clarify minor differences. Overall management principles are non-contentious More invasive monitoring may be required. This should have been discussed with relatives. Relatives may well be present at bedside and appropriate behaviours and conversations required to preserve dignity of donor, confidentiality of potential recipients, and support to grieving relatives. 21 21

22 Guidelines 22 22

23 Guidelines 23 23

24 24 24

25 General Care “Bundle” Continue ICU care Temperature control Give methylprednisolone, review drugs Donor Management Guideline Consider escalation of monitoring Relatives may be at bedside General ICU level staffing should be maintained, and in fact extra help may be required at bedside (equipment, monitoring, blood sampling) Temperature measurement, active warming (Bair Hugger, water blanket, HME) Methylprednisolone should be given. 15mg/Kg (1g for adult) to reduce inflammation. Also associated with reduced lung water in lung donors. Review drugs. Introduce insulin if not already in progress (ready to manage DI, inotropic) Stop non-essentials. Maintain indicated antibiotics. Start to wean vasopressors if possible. A guideline should be used. ICS, Canadian, various cardiac. Although confusing, ukbt are trying to clarify minor differences. Overall management principles are non-contentious More invasive monitoring may be required. This should have been discussed with relatives. Relatives may well be present at bedside and appropriate behaviours and conversations required to preserve dignity of donor, confidentiality of potential recipients, and support to grieving relatives. 25 25

26 Review Notes Intravascular volume Review treatment goals Osmotic therapy and urine output Co-ordinator will review in detail Review of previous management is essential at an early stage. Many patients will be relatively hypovolaemic from injury, therapy, or DI. Review at this stage will inform clinical findings. The co-ordinator will review the notes in greta detail, and often pick up issues you will be unaware of! 26 26

27 27 27

28 Cardiovascular Increased Activity: Assess clinically Invasive monitoring Intravenous fluid Vasoactive drugs: vasopressor/inotrope ECHO Flow Monitoring Clinical examination-usually vasodilated, warm. Assess pulse volume and JVP. Review bp chart for trends Assess invasive monitoring. Arterial and CVP monitoring are essential except in exceptional circumstances. Rt IJ for central line. Upper limb for arterial line (lower aorta tied off during donation operation) Pulse Pressure Variation may suggest need for iv fluids. Volume expansion as dictated by clinical examination and notes review. Cardiac units prefer colloid loading, but balance salt crystalloid widely used. Small boluses and review. Very positive fluid balances definitely associated with less likely lung donation. It may be possible to reduce prior vasoactive infusions with lower goals and some volume expansion. If a new vasopressor seems required, consider flow monitoring strongly, and the use of vasopressin as first line agent. It is, as with general ICU care, important to ensure adequate volume loading before pressor use. Echocardiography may provide useful information on LVH and overall function, but can rarely be repeated frequently. 50% of hearts with subnormal function on first assessment can reach transplant criteria with active management (Venkateswaran et al, Bonser’s group, Transplantation 2000) UK guidelines have suggested use of T3, particularly in patients with documented poor function on the basis that it is unlikely to do harm, and might benefit a group of patients. We will discuss that in detail later. Hormonal Package 28 28

29 xxx 29 29

30 Figure 1: Odds of an organ being recovered and transplanted: Hormonal Resuscitation (HR) verses Non-Hormonal Resuscitation (NHR) 30 30

31 Respiratory Head up positioning Lung protective ventilation PEEP and lowest possible FiO2 Recruitment Avoid overhydration We will speak in more detail about lungs later. General modern ICU care is the baseline. Head-up positioning, avoiding aspiration (the cuff can be blown up ‘tight’ if desired) and regular gentle suction 2 hourly or as indicated. Without any randomised trial, most ICUs have used lower tidal volumes (6-8 ml/Kg) than previously suggested (12ml/Kg) and these seem associated with higher rates of usable lungs. Modest levels of PEEP and gentle recruitment techniques. 31 31

32 Difficult often to work out complex relationship between:
Diabetes Insipidus Common in BSD Posterior pituitary Polyuria, electrolyte disturbance Hypovolaemia Fluids Vasopressin/DDAVP DI is common. Difficult often to work out complex relationship between: Previous osmotic therapy Volume status BP and vasopressor effects Fluid management will require replenishment of previous losses, often with essentially free water (don’t forget enteral route) and don’t forget insulin running may help avoid problems with dextrose administration with high dose steroids. And administration of vasopressin or DDAVP. Although vasopressin has less 32 32

33 Other Issues Electrolyte disturbances Blood and Coagulopathy Spinal reflexes Electrolytes-particularly if polyuric. Potassium, Magnesium, Calcium, Phosphate. Actively treat Potassium and Magnesium (arrythmias) Coagulopathy is common. Blood loss may occur from injuries or after operations or prolonged ICU stay. Local policy will govern transfusion threshold, but preoperatively should be prepared for a major procedure with potential blood loss. Treatment with blood products is indicated for active bleeding or worsening coagulopathy. Spinal reflexes can on occasion be very disturbing to patient relatives, and they should be warned about these. (if pronounced, consider muscle relaxant) 33 33

34 Other Issues 34 34

35 Lost donors (CVS) 39 to 5 (-87%) Organs per donor 3.8-3.6 (-6.5%)
Donor Referrals + 57% Potential Donors + 19% Actual donors % Lost donors (CVS) 39 to 5 (-87%) Organs per donor (-6.5%) Organs recovered % 35 35

36 In the midst of all this, they will be involved in offering organs
Donor Co-ordination Donor assessment Donor management Offering organs Thoracic units Retrieval team Theatre time Transport We will hear later the details of co-ordinator duties, suffice to say that if mobile phones cause problems, we have a large class action waiting! Assessment is an intensive process, and many SNOD / SODs also provide significant input to clinical management, particularly in units which rarely refer donors. In the midst of all this, they will be involved in offering organs 36 36

37 Summarise BSD physiology
Questions? Summarise BSD physiology Active Donor Management including continued (and/or escalated) ICU care with defined goals will: Bring more donors to theatre Allow retrieval of more organs per donor Ensure best function of those organs in recipients Remind that guidelines are available. Core principles common. Ongoing research on some aspects of thoracic organ retrieval. 37 37

38 Summarise BSD physiology
Summary Brainstem death triggers complex pathophysiology Active Donor Management can treat this, and maximise donation Guidelines assist standard management Future developments Summarise BSD physiology Active Donor Management including continued (and/or escalated) ICU care with defined goals will: Bring more donors to theatre Allow retrieval of more organs per donor Ensure best function of those organs in recipients Remind that guidelines are available. Core principles common. Ongoing research on some aspects of thoracic organ retrieval. 38 38

39 Cardiovascular Management and Cardiac Donation
Increasing Cardiac Donation

40 UK Heartbeating Donors 2008-2009
..and shown graphically you can see: 95% of donation procedures will result in kidney retrieval, 95% of those will result in 2 kidneys, and 94% of retrieved kidneys will be transplanted.- a remarkable record. 91% of donations will retrieve a liver, and 94% of those will be transplanted. Some, of course, are split-and may result in more transplants including facilitating transplants for children or small individuals. 20% of all deceased donor livers are reduced or split before transplantation We now see a considerable drop off. The selection criteria for pancreatic transplant are very tight, and were only increased to an upper age limit of 60 during this year. Of note, though, only 1 of 10 organs retrieved in the age group resulted in whole organ transplant-though islet cell transplant may be an option. And finally we come to the issue of thoracic transplant. Only 38% of heartbeating donors provide thoracic organs. Cardiothoracic transplantation is absolutely dependent on organs which will function well post implantation. There is increasing evidence that we can make more organs transplantable by active donor management. 40 40

41 UK Heartbeating Donors 2008-2009
..and shown graphically you can see: 95% of donation procedures will result in kidney retrieval, 95% of those will result in 2 kidneys, and 94% of retrieved kidneys will be transplanted.- a remarkable record. 91% of donations will retrieve a liver, and 94% of those will be transplanted. Some, of course, are split-and may result in more transplants including facilitating transplants for children or small individuals. 20% of all deceased donor livers are reduced or split before transplantation We now see a considerable drop off. The selection criteria for pancreatic transplant are very tight, and were only increased to an upper age limit of 60 during this year. Of note, though, only 1 of 10 organs retrieved in the age group resulted in whole organ transplant-though islet cell transplant may be an option. And finally we come to the issue of thoracic transplant. Only 38% of heartbeating donors provide thoracic organs. Cardiothoracic transplantation is absolutely dependent on organs which will function well post implantation. There is increasing evidence that we can make more organs transplantable by active donor management. 41 41

42 UK Cardiothoracic Donors 2008-9
Age 0-17 18-34 35-49 50-59 60+ Donors 23 74 87 51 15 Now if we look at cardiothoracic donors in general (*and this incudes lung donors) we see that the 18 year old motorcyclist isn’t highly represented. 42 42

43 (Talk to components of ideal donor)
Ideal Heart Donor < 55 Female, < 50 Male, Good PMH No diabetes Non-smoking No drugs CVS stable Rhythm, normal ECG, no or minimal support Good function on ECHO, no LVH (Talk to components of ideal donor) 43 43

44 Expanded Criteria Age < 65
No cardiac PMH that precludes transplantation ECG without definitive pathology Consider smokers, hypertension, arrest or arrythmia, drug abuse, vasopressor use Driven by recipient characteristics Introduce need for expanded criteria donors. Cardiac PMH can be very broad-in other countries hearts with grafts used. 44 44

45 Assume all donors can be cardiac donors
Introduce need for expanded criteria donors. Cardiac PMH can be very broad-in other countries hearts with grafts used. 45 45

46 Click for animation. Speaker notes after click:
Targets Rate , sinus MAP mmHg CVP ~ 4-10 mmHg CI > 2.1 l.min-1.m-2 The suggested targets for cardiac donation aren’t particularly challenging. Emphasise that REDUCING current levels of current support may be the appropriate therapy-may have been driving perfusion pressure to deliver a cerebral perfusion pressure. Click for animation. Speaker notes after click: BUT emphasise that knowledge of flow characteristics gives more valuable information. Post implantation function correlates well with donor function. Clearly mandates some form of monitoring of CO. 46 46

47 Clinical and Translational Research
47 47

48 48 48

49 But let’s think about what the cardiovascular problems are.
This individual giving the early ‘High Five’ is a medical student at Johns Hopkins. Looks pretty much like any student 49 49

50 Though (middle) went on to be chief surgical resident.
Developed (with a student friend) the ‘ether chart’ to monitor and document physiology during anaesthesia. Prompted by the fact that his first patient anaesthetised as a student died! Also introduced bp monitoring to surgical practice. 50 50

51 Harvey Cushing 51 51

52 Famous for many things, but response of body to raised intracranial pressure certainly very famous, and relevant to us. 52 52

53 53 53

54 Adverse Factors Effects of ‘Sympathetic Storm’
Potentially huge rise in catecholamines Worse with rapid ICP rise Effects of vasodilation Relative hypovolaemia Afterload reduction Volume status 54 54

55 Assessing Volume Status
Review charts, examine patient Vital signs and postural effects ‘Numbers’ 55 55

56 Make sure they aren’t hypovolaemic, please Decent perfusion, good gases and bp, it can only get worse Give me a CVP of 6-10 Just get on with it!! Lots of fluid please -better function earlier Fluid overload is a problem for us-if we get goals with less that’s good I’d like 10-12 Too much-less than 6

57 Effective Circulating Volume:
Priorities Effective Circulating Volume: Myocardial perfusion Cardiac function Organ perfusion Avoid Overload Volume Restore Tone Optimise cardiac output Inotropes? 57 57

58 Assessing Volume Status
Review charts, examine patient Vital signs and postural effects ‘Numbers’ Systolic pressure variation Response to therapy 58 58

59 Flow Measurement Clinical Waveforms LiDCO PiCCO Doppler Serial ECHO
PAWPC 59 59

60 Volume Therapy Consider vascular tone Restore tone: Vasopressin
Balanced Colloid or Crystalloid Look for significant response Flow monitoring 60 60

61 Vasopressin Vasoconstriction: V1 receptor
Water reabsorption: V2 receptor Increased ACTH secretion: V3 receptor (Vasodilation at low concentration - Oxytocin receptors) 61 61

62 Priorities (cont’d) Intravascular Volume Vascular tone / Vasopressin
Flow parameters Direct Cardiac Index Adequacy of resuscitation Appropriate catecholamines (T3 , Hydrocortisone, GTN) 62 62

63 Cardiac index (mean ± 95% confidence interval) between initial (I) assessment and end-assessment (E) in the four treatment groups. Cardiac index improved significantly in the entire cohort (P < 0.001), but there was no difference between groups (T3, P = 0.22; MP, P = 0.14; MP + T3, P = 0.15). Published on behalf of the European Society of Cardiology. All rights reserved. © The Author For permissions please Venkateswaran R V et al. Eur Heart J 2009;30: 63 63

64 Organization chart of donor heart outcomes within the study.
Venkateswaran R V et al. Eur Heart J 2009;30: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author For permissions please 64 64

65 Intensive management benefits all organs
65 65

66 Continued Review CVS and adequacy of resuscitation
Fluid and Electrolytes Offering system and liasion with accepting units Specialist treatments or investigations Continued ICU and theatre management 66 66

67 Questions? Summarise BSD physiology
Active Donor Management including continued (and/or escalated) ICU care with defined goals will: Bring more donors to theatre Allow retrieval of more organs per donor Ensure best function of those organs in recipients Remind that guidelines are available. Core principles common. Ongoing research on some aspects of thoracic organ retrieval. 67 67

68 Summary Heart donors are precious
Treat all donors as potential heart donors Donor management crucial Volume status, Vascular tone (Vasopressin) Role of Flow monitoring Summarise BSD physiology Active Donor Management including continued (and/or escalated) ICU care with defined goals will: Bring more donors to theatre Allow retrieval of more organs per donor Ensure best function of those organs in recipients Remind that guidelines are available. Core principles common. Ongoing research on some aspects of thoracic organ retrieval. 68 68

69 Respiratory Management and Lung Donation
Increasing Lung Donation

70 Objectives Understand the effects of the pathophysiology of brainstem death on lung function Understand the consequences of the necessary ventilatory support for lung function Understand how active donor management can improve the number of lungs offered Understand how lung management conflicts with management of other systems The objectives are as shown here [GO OVER EACH OBJECTIVE IN TURN], [THEN] [NEXT SLIDE] 70 70

71 UK Heartbeating Donors 2008-2009
..and shown graphically you can see: 95% of donation procedures will result in kidney retrieval, 95% of those will result in 2 kidneys, and 94% of retrieved kidneys will be transplanted.- a remarkable record. 91% of donations will retrieve a liver, and 94% of those will be transplanted. Some, of course, are split-and may result in more transplants including facilitating transplants for children or small individuals. 20% of all deceased donor livers are reduced or split before transplantation We now see a considerable drop off. The selection criteria for pancreatic transplant are very tight, and were only increased to an upper age limit of 60 during this year. Of note, though, only 1 of 10 organs retrieved in the age group resulted in whole organ transplant-though islet cell transplant may be an option. And finally we come to the issue of thoracic transplant. Only 38% of heartbeating donors provide thoracic organs. Cardiothoracic transplantation is absolutely dependent on organs which will function well post implantation. There is increasing evidence that we can make more organs transplantable by active donor management. 71 71

72 UK Heartbeating Donors 2008-2009
..and shown graphically you can see: 95% of donation procedures will result in kidney retrieval, 95% of those will result in 2 kidneys, and 94% of retrieved kidneys will be transplanted.- a remarkable record. 91% of donations will retrieve a liver, and 94% of those will be transplanted. Some, of course, are split-and may result in more transplants including facilitating transplants for children or small individuals. 20% of all deceased donor livers are reduced or split before transplantation We now see a considerable drop off. The selection criteria for pancreatic transplant are very tight, and were only increased to an upper age limit of 60 during this year. Of note, though, only 1 of 10 organs retrieved in the age group resulted in whole organ transplant-though islet cell transplant may be an option. And finally we come to the issue of thoracic transplant. Only 38% of heartbeating donors provide thoracic organs. Cardiothoracic transplantation is absolutely dependent on organs which will function well post implantation. There is increasing evidence that we can make more organs transplantable by active donor management. 72 72

73 UK Cardiothoracic Donors 2008-9
Age groups 0-17 18-34 35-49 50-59 60+ Number of donors 23 74 87 51 15 Now if we look at cardiothoracic donors in general (*and this includes lung donors) we see that the 18 year old motorcyclist isn’t highly represented. In other words, the majority of organs come from the older donors. [NEXT SLIDE] 73 73

74 The Lung Donor Lung donors, in common with other organ donors are often classified into : Ideal Extended criteria It has become clear that both donor pools are important and can meet with clinically successful outcomes Before we proceed, it is useful at this point to consider two concepts, those of the “ideal” and “extended criteria” lung donor. Lung donors, in common with other organ donors are often classified into “ideal” and “extended criteria” donors. With advances in research, management and clinical experience, it has become clear that both donor pools are important and can meet with clinically successful outcomes. 74 74

75 The Ideal Lung Donor (1/2)
Age <55 years Chest X ray clear PaO2 > 39.4 kPa (300mmHg) when FiO2 = 1.0 & PEEP = 5cmH2O? Absence of chest trauma No evidence of aspiration or sepsis Absence of purulent secretions at bronchoscopy These are considered to be the criteria applicable to the “ideal” lung donor. They are not level 1 evidence based. They are derived from years of clinical experience, together with data analysis of transplant survival. They aim to minimise the failure of transplanted organs. It is worth noting that lungs are more complicated when it comes to transplantation, and the criteria are necessarily more restrictive. [TALK THROUGH EACH CRITERION] [MAKE THE POINT THAT THEY SHOULD NOT BE VIEWED IN ISOLATION, BUT AS PART THE WHOLE] As time has passed and experience has increased, there has been a realisation that these criteria are extendable. This raises the (appropriate) question: “Is their any such thing as ideal or extended?”. The answer is probably “No”! Additionally, those individuals that do not come into the “ideal” category can (in some cases) be converted to “ideal” by active AND appropriate donor management. [NEXT SLIDE] 75 75

76 The Ideal Lung Donor (2/2)
Absence of organisms on sputum gram stain No history of primary pulmonary disease Tobacco history <20 pack-years ABO compatibility No prior cardiopulmonary surgery Size match These are considered to be the criteria applicable to the “ideal” lung donor. They are not level 1 evidence based. They are derived from years of clinical experience, together with data analysis of transplant survival. They aim to minimise the failure of transplanted organs. It is worth noting that lungs are more complicated when it comes to transplantation, and the criteria are necessarily more restrictive. [TALK THROUGH EACH CRITERION] [MAKE THE POINT THAT THEY SHOULD NOT BE VIEWED IN ISOLATION, BUT AS PART THE WHOLE] As time has passed and experience has increased, there has been a realisation that these criteria are extendable. This raises the (appropriate) question: “Is their any such thing as ideal or extended?”. The answer is probably “No”! Additionally, those individuals that do not come into the “ideal” category can (in some cases) be converted to “ideal” by active AND appropriate donor management. [NEXT SLIDE] 76 76

77 Assume all donors can be lung donors
In other words [READ OUT THE SLIDE] [EMPHASISE]. If you don’t try you’ll never know. 77 77

78 Pathophysiology Pre-brainstem death Brainstem death
Post brainstem death Moving beyond the “ideal” lung donor, to understand the “extension” we must first review the pathophysiology, specifically as it relates to the lungs. We can divide this in to three stages – pre-BSD, BSD and post-BSD. Some of this was touched on in the introduction, but deserves review here. It cannot be overemphasised that general best practice measures are appropriate throughout the care of our patient; these apply equally before and after death. These include maintenance of normothermia, good fluid/electrolyte balance and haemodynamic management to ensure adequate flow (EMPHASISE FLOW) and perfusion. We can now deal with each of these in turn. There are common themes. [NEXT SLIDE] Brainstem death has many precipitants, and often is not immediately related to the time of injury. In consequence the lungs may already be less than pristine. As you can see here, trauma may have been involved, leading to direct (contusion, haemorrhage, etc) or indirect (fat embolism) damage. Aspiration at the time of onset may have occurred; it can also happen whilst ventilated, leading to infection. Infection is obviously a significant risk if ventilated, particularly for a prolonged period. [NEXT SLIDE] 78 78

79 Pathophysiology Trauma Aspiration Infection Catecholamine surge
Pre-Brainstem Death 1 Catecholamine surge Systemic inflammatory response Brainstem Death 2 Conflict Lungs v The Rest Post Brainstem Death 3 Pre-Brainstem Death (Click 1) Brainstem death has many precipitants, and often is not immediately related to the time of injury. In consequence the lungs may already be less than pristine. As you can see here, trauma may have been involved, leading to direct (contusion, haemorrhage, etc) or indirect (fat embolism) damage. Aspiration at the time of onset may have occurred; it can also happen whilst ventilated, leading to infection. Infection is obviously a significant risk if ventilated, particularly for a prolonged period. [NEXT SLIDE] Brainstem Death (Click 2) Brainstem death is associated with two significant events that directly impact upon the lungs. The catecholamine surge Pulmonary oedema is a frequent consequence of this, more commonly in the younger patient. This has a detrimental effect on lung function, in addition to creating a difficult balancing act with haemodynamic and fluid balance. Systemic inflammatory response syndrome (SIRS) SIRS produces a surge of cytokines, attracting neutrophils and other cells to the lungs, creating a destructive inflammatory milieu. In common with the pre-BSD phase, either of these processes can develop into acute lung injury (ALI) or progress to acute respiratory distress syndrome (ARDS) [NEXT SLIDE] [QUESTION: DO WE DEFINE ALI & ARDS?] Post Brainstem Death (Click 3) Post-BSD we meet with the conflict of “what is best for one organ is not necessarily best for another organ”. However, the lung has its targets [NEXT SLIDE] 79 79

80 Targets Protective lung ventilation Lowest FiO2 possible
Lung recruitment Early steroids Minimise lung water These are detailed here. These are general targets, which will be explored in more detail. [TALK ABOUT TARGETS. IN PARTICULAR WE NEED TO TALK ABOUT “CONFLICTS”. THAT IS WHY “Minimise lung water” IS LAST, AS IT MOVES US TO THE NEXT SLIDE…] [NEXT SLIDE] 80 80

81 The Conflicts Fluid management and lung water
The lungs versus the circulation Flow Lung damage Acute Lung Injury (ALI) Acute Respiratory Distress Syndrome (ARDS) Ventilatory strategies We have examined the pathophysiology of brainstem death previously. The lungs can be damaged as a result of the sympathetic storm, where pulmonary oedema can occur (secondary to the surges in catecholamines). In addition, large volumes of crystalloids are often employed in resuscitation, before, during or after BSD. This can result in the lungs becoming “wet”, with subsequent reduction in function. Colloid may provide an answer, with greater likelihood of remaining in the circulation. However, this is by no means certain, with some evidence to suggest that the fluid is not as important as the volume administered and the CVP/PAOP obtained. In addition, there has been controversy surrounding the older starches and retention in the circulation, compared to modern lower molecular weight/lesser substituted solutions. Flow is of key importance. Pulmonary artery catheters were once mandatory as the means for assessing cardiac output. However, they have fallen out of favour in the intensive care community, to such a degree that current trainees have little experience with them. They have been superseded by LiDCOs, PICCOs, oesophageal dopplers and so on. The importance is to know how to use the equipment, so that flow guided therapy is utilised. In addition there is anecdotal evidence to suggest that up to 15% of donors present with ALI/ARDS. This IS beyond our control. However, in managing ALI/ARDS, we can help minimise lung water and the damage that can develop as a result of ventilation. The tr[NEXT SLIDE] (Crit Care Med Feb;34(2):321-7; quiz 328. Ventilatory and hemodynamic management of potential organ donors: an observational survey. Mascia L, Bosma K, Pasero D, Galli T, Cortese G, Donadio P, Bosco R. Department of Anesthesia and Intensive Care Medicine, University of Turin, Turin, Italy. ) McIlroy DR, Pilcher DV, Snell GI. Does anaesthetic management affect early outcomes after lung transplant? An exploratory analysis. Br J Anaesth Apr;102(4): Epub 2009 Feb 17. PubMed PMID: Pennefather SH, Bullock RE, Dark JH. The effect of fluid therapy on alveolar arterial oxygen gradient in brain-dead organ donors. Transplantation Dec;56(6): PubMed PMID: 81 81

82 Ventilation Ventilation is associated with characteristic types of damage: Barotrauma Volutrauma Infection Aspiration Ventilation is associated with characteristic types of damage: Barotrauma typically creates sheer stresses, resulting in damage to type 2 alveolar cells, loss of surfactant and decreased compliance Volutrauma typically results in pneumothoraces, or pneumomediastinum [INFECTION AND ASPIRATION ARE SELF EVIDENT, JUST A QUICK MENTION THAT THEY OBVIOUSLY LEAD TO DAMAGE; INFECTION CLEARLY NOT GOOD FOR AN IMMUNOCOMPROMISED INDIVIDUAL] Evidence continues to emerge that active and appropriate management can mitigate against such adverse effects and convert the non-ideal donor to the ideal donor. [NEXT SLIDE] 82 82

83 Management Lung protocols:
San Antonio Lung Transplant donor management protocol (SALT) Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes Am J Respir Crit Care Med Sep 15;174(6):710-6 Ventilator care bundles: Head of the bed elevated to 30 degrees Ulcer prophylaxis DVT prophylaxis (Daily sedation hold) Pmax < 30cmH2O, Pplat < 25cmH2O Lowest FiO2 to maintain SpO2 > 95% There are general and specific management principles that can be adopted. Some of these are familiar to those who already work in intensive care – the so-called “ventilator care bundle”. Clearly the daily sedation hold does not apply, but the other standards of care are appropriate. In particular, the strategies of the bundle are aimed at minimising aspiration risk. Protective ventilation strategies are important, concentrating on low tidal volume/pressure strategies. This is based on work from several studies, including the ARDSNet study of Amato et al. in 1998. The San Antonio Lung Protocol demonstrated the success that can be achieved with coordinated active donor management. In particular, they not only increased the number of donors (mean lung procurement rate 11.5% to 25.5%), but more than doubled the number of transplants (53 to 121). This success has been repeated by others and such protocolised management is now commonplace, although the exact make up of the protocols varies between institutions. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi- Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347–54 Semin Thorac Cardiovasc Surg Summer;20(2): Current strategies in donor selection and management. Botha P, Rostron AJ, Fisher AJ, Dark JH. Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom. Angel LF, Levine DJ, Restrepo MI, Johnson S, Sako E, Carpenter A, Calhoon J, Cornell JE, Adams SG, Chisholm GB, Nespral J, Roberson A, Levine SM. Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes. Am J Respir Crit Care Med Sep 15;174(6): Epub 2006 Jun 23. PubMed PMID: Noiseux N, Nguyen BK, Marsolais P, Dupont J, Simard L, Houde I, Lallier M, Langevin S, Cantin B, Ferraro P. Pulmonary recruitment protocol for organ donors: a new strategy to improve the rate of lung utilization. Transplant Proc Oct;41(8): PubMed PMID: 83 83

84 SALT The SALT protocol adopted a number of strategies: Education
Active donor management Prevent aspiration Recruitment Restricting fluid administration Diuretics Flow directed therapy The SALT protocol adopted a number of strategies: Education Every donor a potential lung donor Active donor management Active management Prevent aspiration, ALREADY DISCUSSED Recruitment This is a key point. In the SALT protocol, they ventilated the lungs at 25cmH2O/15cmH2O for 2 hours, before returning to (what some would consider a high) tidal volume of 10ml/kg Restricting fluid administration Diuretics Do not forget, as we have referred to earlier, flow directed treatment is critical. Again this returns us to the issue of conflicts; “drying someone out” may not be in the best interests of the kidneys, for example. [NEXT SLIDE] Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi- Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347–54 Determann RM, Royakkers A, Wolthuis EK, Vlaar AP, Choi G, Paulus F, Hofstra JJ, de Graaff MJ, Korevaar JC, Schultz MJ. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care Jan 7;14(1):R1. [Epub ahead of print] PubMed PMID: ============================================================================== Recruitment, USS paper assessment ESICM 84 84

85 85 85

86 Lung Computed Tomography during a Lung Recruitment Manoeuvre in Patients with Acute Lung Injury
Here we see recruitment in a number of lungs: Can have a dramatic effect on PaO2 values and PaO2/FiO2 ratios, creating the ideal donor Can also reduce lung water After procedures Lung computed tomography during a lung recruitment maneuver in patients with acute lung injury Guillermo Bugedo, Alejandro Bruhn, Glenn Hernández, Gonzalo Rojas, Cristián Varela, Juan Carlos Tapia, Luis Castillo Volume 29, Number 2 / February, 2003 Here we see recruitment in a number of lungs. It can vary in its success, and there can be issues with both cardiovascular instability and volutrauma. However, such recruitment manoeuvres can have a dramatic effect on PaO2 values and PaO2/FiO2 ratios, creating ideal donor. Such manoeuvring can also reduce lung water. [NEXT SLIDE] 86 86

87 Other Options Hormone therapy Vasopressin & the dual role Antidiuresis
Vasoconstriction T3 Cardiovascularly unstable Steroids Methylprednisolone 15mg/kg As soon as brain death confirmed Other options refers to such strategies as hormonal manipulation and steroids. The consensus in the transplant community is that T3 therapy is now reserved for the cardiovascularly unstable patient, and as such, the benefits to the lungs are derived from a reduction in inotrope requirements and an improvement in flow. Bonser (Birmingham, UK) has carried out a lot of research in this area. His research, and that of others, points to T3 having no benefit, although methylprednisolone appears to reduce the degree of EVLW. In addition, by counteracting any diuresis, vasopressin reduces the amount of additional “water” that the lungs may be exposed to. Methylprednisolone should be given as early as possible, with a strong argument being advanced for its administration as soon as brainstem death is suspected. Dark JH. More and better donors for cardiac transplantation. Eur Heart J Jul;30(14): Epub 2009 May 27. PubMed PMID: Venkateswaran RV, Patchell VB, Wilson IC, Mascaro JG, Thompson RD, Quinn DW, Stockley RA, Coote JH, Bonser RS. Early donor management increases the retrieval rate of lungs for transplantation. Ann Thorac Surg Jan;85(1):278-86; discussion 286. PubMed PMID: The haemodynamic effects of adjunctive hormone therapy in potential heart donors: a prospective randomized double-blind factorially designed controlled trial Rajamiyer V. Venkateswaran1, Richard P. Steeds2, David W. Quinn1, Peter Nightingale1, Ian C. Wilson1, Jorge G. Mascaro1, Richard D. Thompson3, Jonathan N. Townend2 and Robert S. Bonser1,* + Author Affiliations 1Department of Cardiothoracic Surgery, University Hospital Birmingham NHS foundation Trust, Birmingham and University of Birmingham, Edgbaston, Birmingham B15 2TH, UK 2Department of Cardiology, University Hospital Birmingham NHS foundation Trust, Birmingham and University of Birmingham, Birmingham, UK 3Department of Medicine, University Hospital Birmingham NHS foundation Trust, Birmingham and University of Birmingham, Birmingham, UK *Corresponding author. Tel:               +44 121 627 2543         +44 121 627 2543, Fax: , Received June 27, 2008. Revision received January 28, 2009. Accepted February 18, 2009. Abstract Aims The aim of this study was to assess the haemodynamic effects of tri-iodothyronine (T3) and methylprednisolone in potential heart donors. Methods and results In a prospective randomized double-blind trial, 80 potential cardiac donors were allocated to receive T3 (0.8 µg kg−1 bolus; µg kg−1 h−1 infusion) (n = 20), methylprednisolone (1000 mg bolus) (n = 19), both drugs (n = 20), or placebo (n = 21) following initial haemodynamic assessment. After hormone or placebo administration, cardiac output-guided optimization was initiated, using vasopressin as a pressor and weaning norepinephrine and inotropes. Treatment was administered for 5.9 ± 1.3 h until retrieval or end-assessment. Cardiac index increased significantly (P < 0.001) but administration of T3 and methylprednisolone alone or in combination did not affect this change or the heart retrieval rate. Thirty-five per cent (14/40) of initially marginal or dysfunctional hearts were suitable for transplant at end-assessment. At end-assessment, 50% of donor hearts fulfilled criteria for transplant suitability. Conclusion Cardiac output-directed donor optimization improves donor circulatory status and has potential to increase the retrieval rate of donor hearts. Tri-iodothyronine and methylprednisolone therapy do not appear to acutely affect cardiovascular function or yield. 87 87

88 Assessment Ventilation parameters History CXR Gas exchange
Bronchoscopy Donor assessment forms a key component of the procurement of lungs. Here we see some of the issues that will be considered. As we will see in the next slide (that deals with the extended criteria donor) this part of the process offers real hope for an increase in the numbers of donor lungs. The slide illustrates some of the key factors that will be considered. We have seen previously that they are important in the “ideal” lung donor, but consider now the case for the extended criteria donor, and how these factors fit in… [NEXT SLIDE] 88 88

89 The Expanded Criteria Lung Donor
Age >55 years, up to 70 years CXR infiltrates are not important Purulent secretions Organisms Pack-years > 20 Unilateral lung damage PaO2 > 30kPa (FiO2 1.0, PEEP 5cmH2O) Pulmonary Venous PvO2 >40kPa Having pursued our active management, it is now time to re-examine the extended criteria donors. Age Donors will be considered up to the age of 70, although in reality it is rare for donors to be accepted over 65. CXR infiltrates [STRESS INACCURACY] These are unreliable, often disappearing during recruitment manoeuvres. In addition, unilateral infiltrates are common. Pack years have an impact on early outcomes, but are of no significance on late outcomes Purulent secretions are not a contraindication – consider the number of “normal” patients at extubation that have “purulent” secretions within their endotracheal tubes. Likewise, the only strong evidence for positive organisms having a negative effect on recipient outcome is when there are positive Gram negative cultures. PaO2 [STRESS RECRUITMENT] Recruitment manoeuvres can significantly improve PaO2 values. A “global” PaO2 of >30kPa (FiO2 1.0, PEEP 5cmH2O) makes lungs worthy of consideration. The critical component is then the partial pressure of oxygen in each of the 4 pulmonary veins (PvO2). It should be >40kPa. This clearly requires direct inspection, something that is increasingly recognised as important and necessary. Unilateral lung damage is one such area where this is important… [NEXT SLIDE] Oto T, Griffiths AP, Levvey B, Pilcher DV, Whitford H, Kotsimbos TC, Rabinov M, Esmore DS, Williams TJ, Snell GI. A donor history of smoking affects early but not late outcome in lung transplantation. Transplantation Aug 27;78(4): PubMed PMID: 89 89

90 Maximizing the number of Lungs for LTx
Nasty scan. Make it real one with ultimate good outcome ==================================== PAUL: I only have nasty scans with bad outcomes! 90 90

91 Maximizing the number of Lungs for LTx
PaO2 231mmHg (30.8 kPa) Nasty scan. Make it real one with ultimate good outcome ==================================== PAUL: I only have nasty scans with bad outcomes! 91 91

92 Maximizing the number of Lungs for LTx
PaO2 231mmHg (30.8 kPa) PV PaO2 94 mmHg (12.4kPa) Nasty scan. Make it real one with ultimate good outcome ==================================== PAUL: I only have nasty scans with bad outcomes! 92 92

93 Maximizing the number of Lungs for LTx
PaO2 231mmHg (30.8 kPa) PV PaO2 94 mmHg (12.4kPa) PV PaO2 353 mmHg (47 kPa) Nasty scan. Make it real one with ultimate good outcome ==================================== PAUL: I only have nasty scans with bad outcomes! 93 93

94 Assessment Strategies
Bronchoscopy Direct inspection Extra-corporeal perfusion Of course bronchoscopy is “direct inspection”, and this is useful for assessment of the airways. There is evidence that the association of erythema of the airways and purulent secretions is a contraindication to procurement. Direct inspection can also occur at sternotomy, and this allows for selective venous gas sampling, as we have mentioned in the previous slide. Finally, we come to the cutting edge of assessment – extracorporeal assessment by hyperosmolar perfusion. [NEXT SLIDE] 94 94

95 Extracorporeal Perfusion
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96 Questions? 96 96


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