Critical Combine Conference

R4 王建中 /VS 吳允升Nov, 29th, 2013

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

Marital status: Married

Occupation: Housewife

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# BIDNaposin 250 1# TIDNacid 500 1# TIDLyrica 75 1# BID

Family History

61 y/o

No HTN, CAD, Autoimmune Disease HX

63 y/o

35 y/o 33 y/o

Laryngeal cancer Breast cancer

Past History2013

Oct,07

Sep Progressive icteric skin Decreased appetite Weight loss about 10 Kg

Yellow color and itchy skin and tea-color urine NTUH GI OPD

May Right facial pain: Atypical trigeminal neuralgia (Right CN V2)Chinese herb used

Laboratory Data

Laboratory Data

Abdominal CT (2013.10.09)

Suspected hilar cholangiocarcinoma, causing obstructive jaundice

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(-)

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(+)

Physical Examination

CXR 201310/23

ECG (2013.10.22)

Past History2013

Oct, 09 Left PTCD was performed Improved hyperbillirubinemia (T-bil:13.74->6.10)

Oct, 16 Liver biopsy: cholangiocarcinoma Consult GS

Oct, 24 Exploratory laparotomy (2500mL of blood loss)

Intrahepatic tumor with hilar invasion Portal vein injury, status post re-anastomosis Suspect hepatic artery thrombosis

Suspected ischemic injury of the liver

UO: 15ml/day, initiate SLED on 10/27

10/31: Initiate CPFA (12:30-19:30)

Coupled Plasma Filtration Adsorption

Coupled Plasma Filtration Adsorption An extracorporeal blood purification technic which includes 2 steps :1. A plasma adsorption loop2. 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

Coupled Plasma Filtration Adsorption

Keep SLED(tachycardia) QD to QOD

11/09: Initiate plasma exchange !!

Past History2013

Nov, 09 Plasma exchange

Nov, 11

Nov, 16

Plasma exchange Sepsis(+)

Plasma exchange Consciousness became more drowsy Palliative care, DNR(+)

Nov, 21 Passed away

10/16: Liver

biopsy: cholangiocarcino

ma

10/24: Explorat

ory laparoto

my

10/31:

Initiate

CPFA

11/09: Initiate plasma exchan

ge

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

Discussion— CPFA (Coupled Plasma Filtration

Adsorption)

CPFA clinical use

CPFA (Coupled Plasma Filtration

Adsorption)

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

血液淨化 vs 器官替代

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

有效清除中大分子

IL-6 19 - 28KDIL-8 8KDIL-10 35 - 40KDTNFα 52.5KD

人工肝支持系統 Artificial liver support system (ALSS)

合成

代謝運輸調節

人工肝支持療法

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

肝衰竭的主要毒素

Therapeutic Apheresis 1998 May 2(2): 129–133

• 1998 年 , 日本學者提出1. 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2. 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3. 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

Bilirubin Adsorbent Column for Plasma Perfusion

血漿吸附 - Plasma Perfusion(PP)

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

PS

PP

CPFA: Coupled Plasma Filtration Adsorption

Coupled Plasma Filtration Adsorption An extracorporeal blood purification technic which includes 2 steps :1. A plasma adsorption loop2. 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

Coupled Plasma Filtration Adsorption

Invention of CPFA by Ciro Tetta (Bellco)

CPFA is integrated on the HF440 and

becomes as easy to

operate as CRRT

Researches on CPFA’s

clinical interest.

Democratization of the CPFA

use: 2000

treatments done

Results of the COMPACT study on 330 patient’s

CPFA : A recent story

2011

1998

2005

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

肝臟支持療法 - PP + CVVH

毒物清除方式

Ther apher Dial, Vol. 8, NO. 3, 2004, p217-222Therapeutic 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

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

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

Coupled Plasma Filtration Adsorption

CPFA 的靈魂人物 - 吸附器

Adsorbent Cartridge, AC-2

用途對血漿中的致病因數進行吸附( 膽紅素、白蛋白結合之毒素與其它發炎介質等等 )

適應症 急性肝衰、肝昏迷、高膽紅素血症

適用療程 血漿灌流 (PP) 、血漿過濾吸附 (CPFA)

材質 苯乙烯 - 二乙烯苯共聚物

外殼材質 Polycarbonate

滅菌方式 Gamma 滅菌

預沖洗液 注射用生理食鹽水

保存方式 室溫，避免潮濕、日曬

吸附原理 --擴散理論 / 離子鍵

• 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 patientNote : the same circuit with different sorbents can be used

for severe sepsis or septic shock, or renal ABO incompatibility

CPFA in ICU

HF 440 全機種 連續性和閒歇性

連續腎臟替代療法 (CRRT)連續性靜靜脈血液濾過 (CVVH)高置換量血液濾過 (HVHF)超濾 (UF)血液濾過透析 (CVVHDF)血液透析 (CVVHD)血液灌流 (HP)小兒連續性靜靜脈血液濾過 (p-CVVH)

血漿療法 (Plasma therapy )血漿置換 (PE/PEX)小兒 血漿置換 (pedPE)

雙重濾過 (DFPP)血漿吸附 (PP)

CPFA clinical use

Coupled plasma filtration-adsorption in Weil’s syndrome: case report, R. MORETTI,MINERVA ANESTESIOLOGICA, 2011/08

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

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

U. Maggi (Italy),Transplantation Proceedings, 45, 2715e2717 (2013)

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.

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

Claudio Ronco (Italy), MD,Crit Care Med 2002 Vol. 30, No. 6

CPFA: A Single Center Experience(Universiti Kebangsaan Malaysia Medical Centre) Patients and Methods:

A retrospective review: septic patients who received CPFA

All patients were initially treated according to the ‘surviving sepsis care bundle’ with fluid resuscitation, antibiotics, and inotropes

CPFA was started after a nephrologists’ assessment (already had AKI and metabolic acidosis)

Rizna Abdul Cader ,Nephro-Urology Monthly. 2013 September; 5(4):891-6

25 patients with sepsis received CPFA 15 M, 10 F, mean age 49.60 ± 18.97

years All patients received one cycle of CPFA

with median duration of 5 (1-10) hours Technical problems: filter clotting as CPFA

was performed heparin free (citrate) 14 (56%) patients died within 28 days of

treatment.

CPFA: A Single Center Experience(Universiti Kebangsaan Malaysia Medical Centre)

Rizna Abdul Cader ,Nephro-Urology Monthly. 2013 September; 5(4):891-6

CPFA in Patients With Severe Acute Pancreatitis Observational cohort study, 25 patients with SAP

12 received CPFA plus CVVH treatment(group 1) 13 received CVVH therapy (group 2) All the patients underwent 10-day intervention.

Compared with 2 group Better in grope 1 (P<0.01): PaO2/FiO2, mean arterial

pressure, serum amylase, and blood urine nitrogen Reduced in group 1 (all P<0.01): Serum TNF-a, IL-1b,

IL-6 28-day survival rate of group 1 was higher than that

in group 2

Chaosheng He (China), MD ,Clin Gastroenterol Volume 47, Number 1, January 2013

CPFA combined with CVVH was an effective and safe method for treatment of SAP patients

Mechanism: effect on regulating the level of cytokines and serum amylase

CPFA in Patients With Severe Acute Pancreatitis

Chaosheng He (China), MD ,Clin Gastroenterol Volume 47, Number 1, January 2013

COMPACT - COMbining Plasma-filtration and Adsorption Clinical Trial (2006/05-2012/07) Clarify whether the application of CPFA is

able to reduce mortality and prevent organ failures in septic shock patients in intensive care unit (ICU) Study Type: Interventional Study Design:

Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Primary Outcome Measures : Hospital mortality

Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva

http://clinicaltrials.gov/ct2/show/study/NCT00332371

COMPACT 2 – COMbining Plasma-filtration and Adsorption Clinical Trial 2

http://clinicaltrials.gov/ct2/show/record/NCT01639664

The result was pending ......

Take Home Message

CPFA , as an artificial liver support system, can be also used for treatment of sepsis, septic shock and severe acute pancreatitis

Circuit and seeting:

Large RCT for the relationship of CPFA used and mortality was still proceeding

高貴血液淨化

Plasma exchange: 10000 元 / 次 (5 次 : 約 50000 元 )

DFPP: 15000 元 / 次 ECMO: 100000 元 /1 套 Polymycin B: 150000 元 *2 = 300000元

CPFA: 90000 元 / 次 MARS: 150000~200000 元 / 次

Thank you for your attention!