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R4 王建中 /VS 吳允升 Nov, 29 th , 2013

R4 王建中 /VS 吳允升 Nov, 29 th , 2013. Critical Combine Conference. A 65-year-old woman with progressive yellowish skin for 1 month. Patient Profile. Systemic disease: Denied Operation: Denied Allergy: NKA Personal history: Smoking & alcohol use: Nil Education: Elementary school

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R4 王建中 /VS 吳允升 Nov, 29 th , 2013

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  1. R4 王建中/VS 吳允升Nov, 29th, 2013 Critical Combine Conference

  2. A65-year-old woman with progressive yellowish skin for 1 month

  3. Patient Profile • Systemic disease: Denied • Operation: Denied • Allergy: NKA • Personal history: • Smoking & alcohol use: Nil • Education:Elementary school • Marital status: Married • Occupation: Housewife

  4. Patient Profile • Past Medical History: Atypical trigeminal neuralgia (Right CN V2) • Drug history: • Took Chinese herbs for right face pain for about 5 months; discontinued about 0.5 month ago • B.C. /cap 1# BID • Naposin 250 1# TID • Nacid 500 1# TID • Lyrica 75 1# BID

  5. Family History No HTN, CAD, Autoimmune Disease HX Laryngeal cancer Breast cancer 63 y/o 61 y/o 35 y/o 33 y/o

  6. Past History 2013 • Right facialpain: Atypical trigeminal neuralgia (Right CN V2) • Chinese herb used May • Progressive icteric skin • Decreased appetite • Weight loss about 10 Kg Sep • Yellow color and itchy skin and tea-color urine • NTUH GI OPD Oct,07

  7. Laboratory Data

  8. Laboratory Data

  9. Abdominal CT (2013.10.09) Suspected hilar cholangiocarcinoma, causing obstructive jaundice

  10. Physical Examination • BH: 160cm BW:67.2Kg BMI:26.25 • HEENT • Conjunctiva: not pale, Sclera: icteric (+) • Pupil: isocoric, 4mm/4mm, midposition Light reflex: R/L +/+, promptly • Oral thrush(-), oral ulcers(-) • Neck • Supple, tightness(-), JVE(-) , LAP(-), goiter(-) • Kernig’s sign (-), Brudzinski’s sign(-)

  11. Physical Examination • Chest • Symmetrically expanded, axillary LAP(-) • Breath sound: clear over bilateral lower lung fields • Heart • PMI displacement (-),RHB, thrill(-) • Murmur(-), distant heart sound (-) • Abdomen • Flat, normoactive bowel sound, tenderness(-) • Hepatosplenomegaly (-), • Extremity • Petechiae(-), purpura(-), cyanosis(-), cold (-) • Leg edema(-), clubbing finger(-) • Yellowish skin(+)

  12. CXR 201310/23

  13. ECG (2013.10.22)

  14. Past History 2013 • Left PTCD was performed • Improved hyperbillirubinemia • (T-bil:13.74->6.10) Oct, 09 • Liver biopsy: cholangiocarcinoma • Consult GS Oct, 16 • Exploratory laparotomy (2500mL of blood loss) • Intrahepatic tumor with hilar invasion • Portal vein injury, status post re-anastomosis • Suspect hepatic artery thrombosis Oct, 24

  15. Suspected ischemic injury of the liver

  16. UO: 15ml/day, initiate SLED on 10/27 10/31: Initiate CPFA (12:30-19:30)

  17. Coupled Plasma Filtration Adsorption

  18. Coupled Plasma Filtration Adsorption • Coupled Plasma Filtration Adsorption • An extracorporeal blood purification technic which includes 2 steps : • 1. A plasma adsorption loop • 2. A hemofiltration • This allows to remove small and medium molecules by hemofiltration while specific removal of larger ones such as inflammatory mediators of bilirubin are removed by adsorption

  19. Keep SLED(tachycardia) QD to QOD

  20. 11/09: Initiate plasma exchange !!

  21. Past History 2013 • Plasma exchange Nov, 09 • Plasma exchange • Sepsis(+) Nov, 11 • Plasma exchange • Consciousness became more drowsy • Palliative care, DNR(+) Nov, 16 • Passed away Nov, 21

  22. 11/09: Initiate plasma exchange 10/31: Initiate CPFA 10/16: Liver biopsy: cholangiocarcinoma 10/24: Exploratory laparotomy

  23. Final Diagnosis • Cholangiocarcinoma complicated with obstructive jaundice status post PTCD, status post exploratory laparotomy, complicated with hepatic failure, s/p CPFA, s/p plasma exchange • Acute kidney injury, RIFLE”F”, suspected hepatorenal syndrome related • Respiratory failure with ventilator support

  24. Discussion— • CPFA (Coupled Plasma Filtration Adsorption) • CPFA clinical use

  25. CPFA (Coupled Plasma Filtration Adsorption)

  26. 血液淨化 vs 器官替代 • Hemodialysis (HD) v.s 慢性腎衰 • CVVH/HDF v.s 急性腎衰 • PE/Albumin Dialysis/ Bilirubin adsorption MARS/ CPFA v.s 肝功能支持療法 • ECMO v.s 心/肺 • PE/CPFA v.s 敗血症/敗血症休克 • PE/DFPP v.s 神經、免疫

  27. 中分子，何時產生? • “Sepsis”時，會產生許多cytokine，如抗血小板活化因子 (PAF)、Interleukin-8、TNF-α。這些物質屬於「中、大」分子

  28. 有效清除中大分子 • IL-6 19 - 28KD • IL-8 8KD • IL-10 35 - 40KD • TNFα 52.5KD

  29. 人工肝支持系統Artificial liver support system (ALSS) 調節 合成 運輸 代謝

  30. 爭取時間：使可逆性肝損傷患者肝功能得到 恢復，避免肝臟移植 創造條件：避免毒素累積造成多器官衰竭而 無法進行肝臟移植 橋樑：在手術期間or手術後替代暫時無法運 作的肝臟功能 人工肝支持療法

  31. 肝衰竭的主要毒素

  32. Bilirubin Adsorbent Column for Plasma Perfusion • 1998年, 日本學者提出 • Hemodialysis, HD: 只能清除小分子水溶性毒素，無法有效移除膽紅素以改善肝衰竭病徵 • Hemofiltration, HF: 無法有效清除與白蛋白結合之膽紅素，因此也不建議使用 • Plasma Exchange, PE: 大量輸注血漿，需考量有感染血液傳播性疾病以及過敏反應等之風險 Therapeutic Apheresis 1998 May 2(2): 129–133

  33. 血漿吸附- Plasma Perfusion(PP) PP PS 血液分離器：分離血漿 吸附器：對血漿進行直接性吸附 處理白蛋白結合的毒物

  34. CPFA: Coupled Plasma Filtration Adsorption

  35. Coupled Plasma Filtration Adsorption • Coupled Plasma Filtration Adsorption • An extracorporeal blood purification technic which includes 2 steps : • 1. A plasma adsorption loop • 2. A hemofiltration • This allows to remove small and medium molecules by hemofiltration while specific removal of larger ones such as inflammatory mediators of bilirubin are removed by adsorption

  36. CPFA : A recent story Results of the COMPACT study on 330 patient’s CPFA is integrated on the HF440 and becomes as easy to operate as CRRT Invention of CPFA by Ciro Tetta (Bellco) Democratization of the CPFA use: 2000 treatments done Researches on CPFA’s clinical interest. 1998 2005 2011

  37. 肝臟支持療法 - PP + CVVH PP ：處理白蛋白結合性毒物 CVVH：處理中小溶性毒物 優點 ：無輸他人血液(or其衍生物)降低交叉感染的風險

  38. 毒物清除方式 • 1. HD, HDF無法有效移除白蛋白結合毒素 • 2. PE 有輸血感染或過敏的風險且血漿取得不易  PP + CVVH 或 CPFA 結合所有優點，有利於毒物的去除 Ther apher Dial, Vol. 8, NO. 3, 2004, p217-222 Therapeutic Apheresis 1998 May 2(2): 129–133 CN 101559245A 用陰離子交換樹脂吸附細胞因子在血液/漿灌流中的應用

  39. Coupled Plasma Filtration Adsorption • 血液分離器：分離血漿 • 吸附器 ：對血漿進行直接性吸附處理白蛋白結合物質 • 血液過濾器：濾除中、小分子

  40. CPFA的靈魂人物-吸附器

  41. Adsorbent Cartridge, AC-2

  42. 吸附原理--擴散理論/離子鍵

  43. CPFA in ICU • For Liver Failure • The sorbent removes bilirubin, pro and anti-inflammatory mediators • Blood flow : 180-200 ml/min • Hemofiltration flow : 35ml/kg/hr • Plasma flow : 20% x blood flow • Duration : 4-8 hours • Sessions :Based on the clinical condition, 1-4 per patient Note : the same circuit with different sorbents can be used for severe sepsis or septic shock, or renal ABO incompatibility

  44. HF 440 全機種 連續性和閒歇性 CPFA

  45. CPFA clinical use

  46. Case Report 1 • 27-year-old man with Weil’s syndrome who was admitted to ICU with septic shock and anuria refractory to fluid therapy, ARDS, and hepatic involvement (intubation, MV support and vasopressor infusion) • Weil’s syndrome: leptospirosis characterized by jaundice, renal failure and hemorrhagic diathesis. • Pathogenesis: leptospires and with the subsequent systemic inflammatory response Coupled plasma filtration-adsorption in Weil’s syndrome: case report, R. MORETTI,MINERVA ANESTESIOLOGICA, 2011/08

  47. Case Report 1 • CPFA was started early after the onset of septic shock • Five courses of CPFA were performed. • Each course lasted for 10 h with 14 h interval • Day 2: Weaning from vasopressors • Day 6: Weaning from ventilation • Day 8: Creatinine clearance: 63 ml/min • Day 11: Discharged Coupled plasma filtration-adsorption in Weil’s syndrome: case report, R. MORETTI (Italy),MINERVA ANESTESIOLOGICA, 2011/08

  48. Case Report 2 • 2 patients: • After liver transplantation • 1#: Aarly allograft dysfunction (Bil: 25.5) • 2#: Hyperbilirubinemia linked to chronic rejection (Bil:22) • Accept 3 cycles (6 hours) of CPFA • Bilirubin promptly decreased in both cases (Bil: 4; 2) • Each cycle of treatment lowered the bilirubin by ~40% • CPFA: a potential inexpensive short-lasting device to treat hyperbilirubinemia after liver surgery or transplantation. U. Maggi (Italy),Transplantation Proceedings, 45, 2715e2717 (2013)

  49. A pilot study • Subjects: Ten patients with hyperdynamic septic shock • Interventions: Patients were randomly allocated to 10 hrs of either • CPFA (treatment A) or • CVVHDF (Continuous venovenous hemodiafiltration (treatment B) Claudio Ronco (Italy), MD,Crit Care Med 2002 Vol. 30, No. 6

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