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Critical Care Combined Conference

Critical Care Combined Conference. R4 李建霖 / VS 吳允升 2013/08/29. Patient Profile. Age: 52 y/o Sex: female Marital status: married Occupation: housekeeper Smoking: nil Alcohol: nil. Family History. Brief History. Dyspnea  馬偕 UCG: pulmonary HTN Refer to Dr. 曾春典 ’s OPD

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Critical Care Combined Conference

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  1. Critical Care Combined Conference R4 李建霖 / VS 吳允升 2013/08/29

  2. Patient Profile • Age: 52 y/o • Sex: female • Marital status: married • Occupation: housekeeper • Smoking: nil • Alcohol: nil

  3. Family History

  4. Brief History • Dyspnea  馬偕 UCG: pulmonary HTN Refer to Dr. 曾春典’s OPD • Cardiac cath: MPA: 50mmHg, PAWP: 10mmHg • Chest CT: Compatible with primary pulmonary hypertension. No evidence of pulmonary embolism. • NO, high flow O2 & Viagra test: only partial response 2006/07 2006/08

  5. Brief History • CV OPD medication: • Viagra, Coumadin and Bosentan • UCG: ↑ pulmonary HTN • TRPG: 98.4mmHg • Cardiac cath: MPA: 57mmHg • Remodulin use 2006/08 2008/10 2012/10

  6. Present Illness • Progressive dyspnea • 為恭 hospital: • Desaturation + hypotension  intubation • VT  Cardioversion x 1  ED of NTUH • VT  Cardioversion x 2  CCU admission 2013/02/27 2013/02/28

  7. Treatment Course • Persistent hypoxia (SpO2~85%) under FiO2 1.0 • UCG: LVEF: 78.3%, TRPG: 70.6mmHg • Cashed epoprostenol + iNO • VA ECMO • Central VA ECMO 2013/02/28 2013/03/01 2013/03/04

  8. Central VA ECMO

  9. Treatment Course • Persistent hypoxia (SpO2~85%) under FiO2 1.0 • UCG: LVEF: 78.3%, TRPG: 70.6mmHg • Cashed epoprostenol + iNO • VA ECMO • Central VA ECMO • Improved daily activity under central VA ECMO (吃飯，看電視…)  Wait for lung transplantation 2013/02/28 2013/03/01 2013/03/04

  10. Treatment Course • Bleeding tendency under ECMO use • GI bleeding + wound bleeding  massive blood transfusion • First donor: cross match positive • Flow-PRA: • Class I: 100% • Class II: 99.78% 2013/02/28 2013/06/01

  11. Treatment Course • 2nd donor: still cross match positive • Consult Dr.蔡孟昆 for positive flow PRA • Desensitization protocol 2013/06/26

  12. Desensitization Protocol • Indication: 術前PRA > 74%, Virtual cross match (+) • OR: 術中3次的plasma exchange • 1) 5% albumin • BW x 80 x (1 – HCT%) ≈ total plasma volume (TPV) • Albumin volume = TPV x 0.05 • Albumin bottle = albumin volume / 10 • 2) 5% albumin • 3) FFP exchange

  13. Desensitization Protocol • ICU: • 當日: Simulect 20mg in N/S 50mL run 30 mins • POD1: FFP exchange • POD2: FFP exchange • POD3: 75% FFP + 25% albumin • POD4: Simulect 20mg in N/S 50mL run 30 mins • POD5: 50% FFP + 50% albumin • POD6: IVIG (2g/kg, Total volume / 2~3 days / 24 hours)

  14. Results of Cross Match

  15. Desensitization • 7/07 Plasma exchange x 3 during OP • 7/08 Plasma exchange + Simulect • 7/09 Plasma exchange • 7/10 Plasma exchange • 7/11 Simulect + IVIG (24-hour drip) • 7/13 DFPP (2A) • 7/14 IVIG • 7/15 Rituximab

  16. Panel Reactive Antibody

  17. Discussion Desensitization in Lung Transplantation

  18. Methods for Antibody Screening AMR, antibody-mediated rejection; CDC, complement-dependent lymphocytotoxicity; ELISA, enzyme-linked immunosorbent assay; FC, flow cytometry; HAR, hyperacute rejection; SAB, single-antigen beads; SPI, solid-phase immunoassays; vXM, virtual crossmatch; XM, crossmatch. • The comparative sensitivities are LUM > ELISA/FC > CDC Transplantation 2013;95: 19~47

  19. Kidney International(2011) 79, 583 – 586.

  20. Pretransplant Panel Reactive Antibodies in Lung Transplantation 1987~2005 USA 10236 lung transplant Ann Thorac Surg 2008; 85: 1919–24

  21. Pretransplant Panel Reactive Antibodies in Lung Transplantation Ann Thorac Surg 2008; 85: 1919–24

  22. Pretransplant Panel Reactive Antibodies in Lung Transplantation Ann Thorac Surg 2008; 85: 1919–24

  23. Pretransplant Panel Reactive Antibodies in Lung Transplantation Ann Thorac Surg 2008; 85: 1919–24

  24. Pretransplant Panel Reactive Antibodies in Lung Transplantation Ann Thorac Surg 2008; 85: 1919–24

  25. Preexisting HLA Antibodies in Lung Transplantation Transplantation 2013;95: 19~47

  26. Pretransplantation Donor-Specific Antibodies Transplantation 2013;95: 761~765

  27. Desensitization Therapies J Heart Lung Transplant 2010;29:914 –956

  28. Plasma Exchange in Desensitization • A single exchange of 1.0 PV removes ~63% of all solutes in the plasma • An exchange of 1.5 PV removes ~78% • In case of slowly forming antibodies, 5 separate treatments during a 7- to 10-day period will be required to remove 90% of the patients’ initial total-body burden Transfus Med Hemother 2012;39:234–240

  29. Plasma Exchange in Desensitization • TPE should be repeated daily for a minimum of 3 days • 5–7 days • Until the circulating antibodies are reduced to very low titer • The effect appears to be long lasting • No return of DSA observed in patients followed for an average of 13 months Transfus Med Hemother 2012;39:234–240

  30. Plasmapheresis + IVIG Therapeutic Apheresis (1997) 1(2):147-151

  31. Plasmapheresis + IVIG • Plasmapheresis was begun as soon as possible after notification that a suitable organ was available and accepted • 1 session, 1.5 plasma volume • 5% albumin + 4U FFP • Immediately after plasmapheresis  20 g of 5% IVIG Therapeutic Apheresis (1997) 1(2):147-151

  32. Peritransplant IVIG &Extracorporeal Immunoadsorption • January 1992 ~ July 2003 • Duke University Medical Center, Durham, NC, USA Human Immunology 66, 378 –386 (2005)

  33. Peritransplant IVIG &Extracorporeal Immunoadsorption • An averaged median of 83.5 days (3rd-party) Human Immunology 66, 378 –386 (2005)

  34. Peritransplant IVIG &Extracorporeal Immunoadsorption P = 0.32 (23) (12) (345) Human Immunology 66, 378 –386 (2005)

  35. P = 0.05 P = 0.03 Human Immunology 66, 378 –386 (2005)

  36. Therapeutic apheresis in lung transplantation in Jena 2008 ~ 2012 Atherosclerosis Supplements 14 (2013) 33-38

  37. Therapeutic apheresis in lung transplantation in Jena • 3 consecutive days • When necessary, every second or third day after that until graft functionality was established or the graft was lost • Average 1.3 times the plasma volume • Replacement fluid: • Early postoperative phase: therapeutic plasma • Later: 1:1 mix of Octaplas LG and 5% human albumin Atherosclerosis Supplements 14 (2013) 33-38

  38. Donor-specific HLA AntibodiesFollowing Plasma Exchange Therapy St. Louis Children’s Hospital from 2007 to 2010 • A cycle of TPE: daily for 5 days using 1.5-volume exchanges • Replacement fluid: 5% albumin • Risk of bleeding: FFP J. Clin. Apheresis 28:301–308, 2013

  39. Donor-specific HLA AntibodiesFollowing Plasma Exchange Therapy J. Clin. Apheresis 28:301–308, 2013

  40. Donor-specific HLA AntibodiesFollowing Plasma Exchange Therapy P = 0.02 P = 0.58 J. Clin. Apheresis 28:301–308, 2013

  41. Therapeutic strategies antibody-mediatedrejection

  42. Guidelines for Heart Transplant • A PRA10% indicates significant allosensitization • Desensitization therapy should be considered when the calculated PRA is considered by the individual transplant center to be high enough to significantly decrease the likelihood for a compatible donor match or to decrease the likelihood of donor heart rejection where unavoidable mismatches occur • Average threshold PRA level for initiation of treatment: 35% (range 10 –100%) • Choices to consider as desensitization therapies include IV immunoglobulin (Ig) infusion, plasmapheresis, either alone or combined, rituximab, and in very selected cases, splenectomy J Heart Lung Transplant 2009;28:213–25 J Heart Lung Transplant 2010;29:914 –956

  43. Desensitization Protocol in NTUH • Indication: 術前PRA > 74%, Virtual cross match (+) • OR: 術中3次的plasma exchange • 1) 5% albumin • BW x 80 x (1 – HCT%) ≈ total plasma volume (TPV) • Albumin volume = TPV x 0.05 • Albumin bottle = albumin volume / 10 • 2) 5% albumin • 3) FFP exchange

  44. Desensitization Protocol in NTUH • ICU: • 當日: Simulect 20mg in N/S 50mL run 30 mins • POD1: FFP exchange • POD2: FFP exchange • POD3: 75% FFP + 25% albumin • POD4: Simulect 20mg in N/S 50mL run 30 mins • POD5: 50% FFP + 50% albumin • POD6: IVIG (2g/kg, Total volume / 2~3 days / 24 hours)

  45. 58008C血漿置換術（支付點數2475點） Plasma exchange：限下列病患實施 SLE，CNS involvement Myasthenia gravis crisis Macroglobulinaemia RPGN Goodpasture's disease Multiple myeloma Guillain-Barre syndrome Thrombocytopenic purpura Multiple sclerosis and neuromyelitis optica 其他經專案向保險人申請同意實施者 58016C二重過濾血漿置換療法（支付點數2475點） Double filtration plasmapheresis：施行本項之適應症請依支付標準58008C「血漿置換術」之規定辦理。 健保給付之適應症 全民健保醫療費用支付查詢網站:http://www.nhi.gov.tw/query/query2_list.aspx

  46. Devices for plasma exchnage in NTUH Centrifugal Device Membrane apheresis KM8800 (MCS+) KPS8800 HF400

  47. Centrifugal seperation of plasma Transfus Apher Sci. 2005 Apr;32(2):209-20 J Clin Apher. 2010;25(5):240-9

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