IL TRAPIANTO DA CUORE NON BATTENTE

Transcription

1 IL TRAPIANTO DA CUORE NON BATTENTE Teresa Rampino

2 I TRAPIANTO NHBD 11 Settembre

3 TRAPIANTI DA DONATORE A CUORE NON BATTENTE O DOPO MORTE CIRCOLATORIA ( DCD) in Italia 107 TX RENE Dati CNT 2018 parziale

4 Milano Pavia Firenze Siena Padova Verona Bologna Palermo

5 Un rene di serie B? DCD DBD

6 Criteria for determination of death Donor after Circulatory Death Permanent absence of circulation and respiration

7 Irreversible Injury DONOR IN ASYSTOLE Cardiac Arrest Loss of perfusion 24 h tissues ISCHEMIA ANOXIA >5 Patient death Anoxic Injury

8 Maximum tolerable warm ischaemia time in transplantation from non-heart-beating-donors Trends in Anaesthesia and Critical Care (2013); 72-76

9 PERIODO NO TOUCH IL PERIODO IMPOSTO DALLA LEGGE PER LA DICHIARAZIONE DELLA MORTE CARDIACA 20 min

10 Variability of DCD protocols in Europe COUNTRY NO-TOUCH TIME (MINUTES) AUSTRIA 10 BELGIUM 5 CZECH REPUBLIC 10 FRANCE 5 ITALY 20 LATVIA 15 THE NETHERLANDS 5 UNITED KINGDOM 5 SPAIN 5 SWITZERLAND 10 Wind et al. Crical Care 2013, 17:R217

11 AUTORESUSCITATIONE «Lazarus phenomenon» Ritorno spontaneo alla circolazione non assistita dopo l arresto cardiaco

12 Homby K, Homby L, Shemie SD Crit Care Med 2010 (38), 5

13 Nel contesto italiano Dopo un perioido no-touch di 20 minuti non esiste la possibilità di autoresuscitazione

14 Coordinamento Protocollo ben definito Esperienza Risorse tecniche adeguate

15 (1995) The Maastricht categories of NHBD Uncontrolled Controlled Partially controlled Modified Thuong M et al, Transplant International 2016; 29:

16 ECMO prior to death (EPD) ACC Cardiac criteria ADVANCED RESUSCITATION PROGRAM ECMO Neurological criteria DCD Donor DEATH Heart activity

17 Class I II UNCONTROLLED Dead on arrival Unsuccessful resuscitation

18 ECG DCD - UNCONTROLLED Cardiac Arrest DECLARATION OF DEATH Harvesting ACLS CPR Organ Preservation in situ Cold Storage / Machine Perfusion Transplant 15-20m 20 min 1 4 hs (max 6) 150 min TOTAL WARM ISCHEMIA TIME Low flow No flow ACLS Advanced Cardiovascular Life Support CPR Cardiopulmonary Resuscitation

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20 Class III IV CONTROLLED Awaiting cardiac death Cardiac death in a brain-dead donor

21 ECG DCD - CONTROLLED withdrawal life sustaining treatment DECLARATION OF DEATH 20 min Harvesting Agonal phase Blood Pressure Asystole Organ Preservation 1 4 hs (max 6) Cold Storage/ Machine Perfusion Transplant Functional WIT TOTAL WARM ISCHEMIA TIME Low flow No flow

22 DIFFERENCES IN ORGAN PERFUSION VS Category III CONTROLLED Category II UNCONTROLLED

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24 filmato

25 NORMOTERMIC REGIONAL PERFUSION

26 KIDNEY EVALUATION CRITERIA MACROSCOPIC HISTOLOGIC PERFUSION MACHINE

27 PRE -TRANSPLANT KIDNEY BIOPSY ACUTE DAMAGE CHRONIC DAMAGE REMUZZI HISTOPATHOLOGICAL SCORE

28 ACUTE DAMAGE TX TUBULAR NECROSIS YES CAPILLARY AND ARTERIOLAR TROMBOSIS NO

29 DCD KIDNEY BIOPSY AT RETRIEVAL

30 DCD KIDNEY BIOPSY AFTER PULSATILE PERFUSION RR 0,33 F 0,68 ml/min

31 Perfusional Criteria Renal Resistance (RR): RR < 0,40 Perfusion Flow: > 60 ml/min

32 RENAL RESISTENCE TREND DURING HYPOTHERMIC MACHINE PERFUSION IS PREDICTIVE OF GRAFT OUTCOME

33 RISORSE TECNOLOGICHE

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35 VS PRESERVATION EX SITU

36 MACHINE PERFUSION HYPOTHERMIC SUBNORMOTHERMIC NORMOTHERMIC 4 C C C + O2 + O2

37 EX-VIVO MACHINE PERFUSION FOR KIDNEY PRESERVATION Curr Opin Organ Transplant 2018, 23:

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40 Trapianto DCD: ne vale la pena?

41 Kidneys from DCD provide survival benefit Snoejis MG et al. JASN 2010

42 Kidney donation after circulatory death (DCD) versus donation after brain death ( DBD) Kidney International (2015)

43 Kidneys transplantation from DCD Snoeijs MGJ et al. Transplantation 2010

44 DONOR IN ASYSTOLE

45 PRIMARY NON FUNCTION (PNF) perdita permanente della funzione del rene subito dopo il Tx

46 PRIMARY NON FUNCTION (PNF)FREQUENCY ACCORDING TO TYPE OF DONATION

47 CAUSE PNF Rigetto iperacuto CID Sindrome Emolitica Uremica Recidiva immediata di malattia di base Ossaluria primaria Trombosi Emodinamica intraoperatoria

48 Risk factors for primary non-function in DCD Central venous BP <4cmH2O Intra op sys BP<110mmHg Pre op sys BP<130 mmhg Cause of death (CV) Donor age>40y Donor category Warm ischemia time>30 min Resistive index > 0,4 HLA mismatch Flow rate > 70 Recipient age Terminal creat. BMI > 25 kg/mq

49 Post-operative graft function According to average intra operative Central Venous Pressure

50 RENAL CORTICAL NECROSIS TAC ISTOLOGIA ECOGRAFIA CON MDC

51 DELAYED GRAFT FUNCTION (DGF) Necessità di dialisi entro la prima settimana dopo trapianto renale

52 DGF DELAYED GRAFT FUNCTION in Kidney Transplantation From Donors After Cardiac Death DCD DBD ODDS p VALUE DGF 72% 18% 10,3 < 0, % 80% 60% 40% 20% 0% DBD DCD Transplantation, Volume 90, Number 10, November 27, 2010

53 DGF in Kidney Transplantation from controlled versus uncontrolled donation after circulatory death Controlled DCD Uncontrolled DCD Transplant International (2011)

54 DAMPs Interleukines ROS Cellule dendritiche Attivazione linfociti T

55 DGF influenza la sopravvivenza di un trapianto da donatore a cuore non battente

56 Graft survival DCD GRAFT SURVIVAL Delayed Graft Function Immediate Graft Function Time after transplantation (Yr) Snoeijs et al..transplantation 90, 10-27, 2010

57 Graft survival of DCD and DBD kidney with DGF DCD with DGF DBD with DGF

58 DONATION AFTER BRAIN DEATH DONATION AFTER CIRCULATORY DEATH Catecholamine storm Vasoconstriction Peripheral ischemia ischemia Organ inflammation Cytokines Activation of endothelium Immune response Necrosi tubulare acuta MHC IL 1 IL 6 TNF IL 6 TNF IL 1

59 COMPLICATIONS AFTER DCD KIDNEY TRANSPLANTATION

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61 * PAVIA DCD-EPD KIDNEY TRANSPLANTS Modified Maastricht classification DCD Number of transplanted patients Sex of recipients II M 6F III 6 4M 2F IV 1 1M ECMO prior to Death (EPD) 13 8M 5F 24 DCD 13 ecmo ECLS

62 DEMOGRAPHIC CHARACTERISTICS Donor Age (years) ( mean and sd) DCD group 51± 8.3 Recipient Age (years) ( mean and sd) DCD group 53.8±11.2 Sex of donor M/F DCD group 20/3 Sex of recipient M/F DCD group 16/7

63 Delayed Graft Function EPD Group VARIABLE MEDIAN IQR DCD Group VARIABLE MEDIAN IQR DAYS OF DGF DAYS OF DGF NUMBER OF DIALYSIS NUMBER OF DIALYSIS DGF 53% DGF 90%

64 GRAFT SURVIVAL DCD Trombosi vena renale 13% PNF Sepsi severa EPD 8% PNF 92% 87% graft survival graft loss graft survival graft loss

65 PATIENT SURVIVAL 13% DCD EPD 31% 87% 69% surviving patients dead patients Cancro Complicanze cerebrovascolari surviving patients dead patients Cancro Complicanze cardiovascolari

66 RENAL FUNCTION in DCD, EPD and DBD serum creatinine mg% *p<0.001 vs DBD and EPD week 1 * p<0.001 vs DBD, DCD, EPD year 1,3 0 DBD week 1 DCD week 1 EPD week 1 DBDyear 1 DCD year 1 EPD year 1 DBD year 3 DCD year 3 EPD year 3

67 Induction Immunosuppressive therapy PAVIA Thymoglobuline Basiliximab Thymoglobuline [iperimmune/diabetic patients] + steroid, CNI inhibitors and MMF

68 DGF and PNF THYMOGLOBULINE BASILIXIMAB IR 15% IR 15% PNF; 9% DGF; 85% 9 days (Median) DGF 76% 11 days (Median)

69 DBD DCD STESSO PROGRAMMA VISITE FOLLOW UP STESSE TERAPIA IMMUNOSOPPRESSIVA STESSO PROGRAMMA BIOPSIE PROTOCOLLARI

70 THE FUTURE

71 Kidney conditioning with Stem cells Pharmaco therapy Anti inflammatory reagents Gene transfer Oxygenation

72 Rene umano Rampino T et al.

73 Un rene di serie B? DCD DBD

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