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# BID
 Naposin 250 1# TID
 Nacid 500 1# TID
 Lyrica 75 1# BID
Family History
No HTN, CAD, Autoimmune
Disease HX
Laryngeal cancer
63 y/o
35 y/o
Breast cancer
61 y/o
33 y/o
Past History
2013
May
 Right facial pain: Atypical trigeminal
neuralgia (Right CN V2)
Chinese herb used
Sep
 Progressive icteric skin
 Decreased appetite
 Weight loss about 10 Kg
Oct,07
 Yellow color and itchy skin and tea-color
urine
 NTUH GI OPD
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(-)
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(+)
CXR
2013
10/23
ECG (2013.10.22)
Past History
2013
Oct, 09
Oct, 16
Oct, 24
 Left PTCD was performed
 Improved hyperbillirubinemia
(T-bil:13.74->6.10)
 Liver biopsy: cholangiocarcinoma
 Consult GS
 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
 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
Keep SLED(tachycardia) QD to QOD
11/09: Initiate plasma exchange !!
Past History
2013
Nov, 09
 Plasma exchange
Nov, 11
 Plasma exchange
 Sepsis(+)
Nov, 16
Nov, 21
 Plasma exchange
 Consciousness became more drowsy
 Palliative care, DNR(+)
 Passed away
10/31:
Initiate
CPFA
10/16: Liver
biopsy:
cholangioc
arcinoma
10/24:
Exploratory
laparotomy
11/09:
Initiate
plasma
exchange
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)
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
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 - 28KD
 IL-8
8KD
 IL-10 35 - 40KD
 TNFα 52.5KD
人工肝支持系統
Artificial liver support system
(ALSS)
調節
合成
運輸
代謝
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
小分子
中分子
白蛋白結合物質
Ammonia
IL-1
Bilirubin
Urea
IL-6
Cholic acid
Phenols
IL-8
Lactic acid
GABA
TNF-α
Others
Bilirubin Adsorbent Column for Plasma
Perfusion
• 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
Therapeutic Apheresis 1998 May 2(2): 129–133
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
CPFA: Coupled Plasma Filtration
Adsorption
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
CPFA : A recent story
CPFA is integrated
on the HF440 and
becomes as easy to
operate as CRRT
Results of the
COMPACT study on 330
patient’s
Invention of CPFA
by Ciro Tetta
(Bellco)
2005
1998
Researches on
CPFA’s clinical
interest.
2011
Democratization of
the CPFA use:
2000 treatments
done
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
毒物清除方式
小分子
以Hemofilter 清除
• 血氨、尿素、肌酐酸
• 水、乳酸
中分子
以Hemofilter & Adsorbent清除
• IL-1、IL-6、IL-8
• TNF-α
白蛋白結合物質
• 膽紅素
• 膽酸
 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
以Adsorbent 清除
 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
Coupled Plasma Filtration Adsorption

血液分離器：分離血漿

吸附器

血液過濾器：濾除中、小分子
：對血漿進行直接性吸附處理白蛋白結合物質
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
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
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
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
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
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)
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
CPFA: A Single Center Experience
(Universiti Kebangsaan Malaysia Medical Centre)
 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.
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 in Patients With Severe Acute Pancreatitis
 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
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
The result was pending ......
http://clinicaltrials.gov/ct2/show/record/NCT01639664
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!