Comparison of HTK and UW in Abdominal Transplantation Dr. Richard S. Mangus, MD MS Indiana University, School of Medicine

Comparison of HTK and UW in Abdominal

Transplantation

Dr. Richard S. Mangus, MD MS

Indiana University, School of Medicine

OUTLINE

• Conversion from UW to HTK

Indiana Organ Procurement Organization

Indiana University

• Transplant outcomes: UW vs HTK

Kidney transplantation

Pancreas transplantation

Liver transplantation

Intestinal transplantation

• Future research

Indiana Organ Procurement Organization (IOPO)

Service area: Indiana

Population: 5.1 million

Hospitals: 130

Transplant centers: 7


Potential advantages to HTK:

Decreased cost

Decrease contamination risk

No mixing

No filter

Longer shelf life

Can store at cool room temperature

Faster preparation time for coordinator

- “hang it, spike it , infuse it”


Potential advantages to HTK:

Improved organ flushing

Lower viscosity

Faster organ cooling

No organ flushing before reperfusion

Lower K+ load decreases risks of hyperkalemia and bradycardia

Easier to work with on back bench

? Improved outcomes


Cost analysis: HTK vs UW

UW flush volume / donor: 3.5 litersUW cost / liter $306.00Total cost per donor $1071

HTK flush volume / donor 3.5 litersHTK cost / liter $150.00Total cost per donor $525

Cost savings per donor $546


Center cost savings

Cost savings / donor $546

Annual cost savings

for average OPO (200 donors) $109,200

Indiana University Medical Center

Abdominal Organ Transplants

Liver

Pancreas

Kidney

Islets

Small intestine / Multivisceral

Indiana University Medical Center

Abdominal Organ Transplants

2007 Rank *

Liver 155 Top 5

Pancreas 84 1st

Kidney 255 Top 10

Small intestine 22 Top 5OVERALL (+ thoracic) 562 Top 5

* www.unos.org, 2007 data report

http://www.unos.org/

Transplant Volume

Year Organs *

2001 259

2002 424

2003 506

2004 532

2005 604

2006 541

2007 562

Transplant Volume

Year Organs *

2001 259

2002 424

2003 506

2004 532

2005 604

2006 541

2007 562

Conversion to HTK

Natural Experiment

A naturally occurring instance which approaches or duplicates a scientific experiment. In contrast to laboratory experiments, these events aren't created by scientists, but yield scientific data. Natural experiments are a common research tool in fields where artificial experimentation is difficult, such as epidemiology.

Renal TransplantationRenal Transplantation

Transplants: 1990 to 1992

DGF: Need for dialysis 2 or more times during first 7-days post-transplant

Flush volume: HTK 5 – 6 LUW 1 – 2 LEC 4 L

Renal Transplantation


de Boer, et al, Transpl Proc, 1999; 31: 2065de Boer, et al, Transpl Proc, 1999; 31: 2065


de Boer, et al, Transpl Proc, 1999; 31: 2065de Boer, et al, Transpl Proc, 1999; 31: 2065

HTK vs UW: KIDNEY Transplantation

N=91 renal transplants HTK 50 UW 41

No differences in: Delayed graft function

Graft survival

Patient survival

Creatinine Clearance Post Transplantation

0

20

40

60

80

100

1 2 3 4 5 6 7 10 14 21 30

time (days)

ml/m

in UWHTK

Serum Creatinine Post Transplantation

0.0

2.0

4.0

6.0

8.0

10.0

12.0

0 3 6 9 12 15 18 21 24 27 30

time (days)

mg

/dL UW

HTK

HTK vs UW: Kidney Transplantation

N=149 renal transplants

> 16 hrs HTK 62, UW 87

No difference patient / graft survival

HTK lower DGF (24% vs 56%, p<0.01)

> 24 hrs HTK 31, UW 38

No difference in patient / graft survival

HTK lower DGF (16% vs 56%, p<0.05)

PANCREAS TRANSPLANTATION

Pancreas Transplantation

N= 20 pancreas transplants HTK 10 UW 10

No differences in: Graft survival

Patient survival

Serum fasting blood glucose

Peak serum amylase

Serial amylase levels



N= 87 pancreas transplants HTK 78 UW 9

No differences in: Graft survivalPatient survivalSerum fasting blood glucosePeak serum amylaseSerial amylase levels



Pancreas clinical allograft data for 246 consecutive adult pancreas transplants at Indiana University between 2003 and 2007.

Overall (%) SKP PAK PTA P-valueNumber 247 141 (57%) 62 (25%) 44 (18%)

Graft loss within 7 days 10 (4%) 7 (5%) 1 (2%) 2 (5%) 0.53

Graft loss within 90 days 6% 7% 5% 5% 0.82

1-year* Graft survival (n=193) 91% 90% 93% 90% 0.79 Patient survival (n=174) 95% 94% 97% 96% 0.75

*For patients with minimum of 1-year follow up time.

Primary preservation solution: HTK, 2003 to 2007:

Pancreas Islet Transplantation

Pancreas Islet Transplantation

LIVER TRANSPLANTATION

Liver Transplantation

N=378 liver transplants HTK 174UW 204

Graft survival 1-month 6-month 12-month UW 91.7% 86.2% 81.7% HTK 92.0% 85.5% 80.8%

Patient survival UW 93.1% 87.7% 84.6% HTK 93.1% 86.2% 82.1%

Liver Transplantation: ECD

N=698 liver transplants HTK 371UW 327

Groups: Standard 209 (30%)

ECD (old age) 70 (10%)

ECD (physiologic stress) 435 (62%)



N=698 HTK 371 UW 327


Standard donors, n=209 Extended criteria donors, n=489


Donor < 60 years, n=628 Donor ≥ 60 years, n=70


No physiologic stress, n=263 Physiologic ECD, n=435


Figure. Liver enzymes in the first 30-days post-transplant for the STANDARD criteria donors comparing HTK (n=111) and UW (n=98)

preservation solutions.

0

100

200

300

400

500

600

700

800

0 5 10 15 20 25 30

Days post-transplant

AS

T/A

LT

in u

/L

AST - HTK

AST - UW

ALT - HTK

ALT - UW


Biliary complications

Elevated liver enzymes post-transplant

Liver U/S with doppler

Biliary imaging

Liver biopsy


Biliary complications

Overall HTK UW p-valueOverall 698* 371* 327*

Need for biliary imaging 384/693 (55.4%) 188/367 (51.2%) 196/326 (60.1%) 0.01 Choledochocholedochostomy (n=593) 333/593 (56.2%) 163/316 (51.6%) 170/277 (61.4%) 0.02 Roux-y hepaticojejunostomy (n=100) 51/100 (51.0%) 25/51 (49.0%) 26/49 (53.1%) NS

Biliiary Leak 22/693 (3.2%) 9/367 (2.5%) 13/326 (4.0%) NS

Diffuse intrahepatic stricturing 26/693 (3.8%) 9/367 (2.5%) 17/326 (5.2%) NS

Presence of choledocholithiasis 115/693 (16.6%) 48/367 (13.1%) 67/326 (20.6%) 0.06

Presence of bile duct gravel (sludge) 51/693 (7.4%) 14/367 (3.8%) 37/326 (11.3%) 0.001* 5 patients died intraoperatively and had no biliary reconstruction, 4 HTK and 1 UW


Donation after cardiac death, n=43HTK 35 UW 7

Liver Transplantation: Recent

Variables in the Equation

.263 .146 3.271 1 .071 1.301

.001 .008 .035 1 .851 1.001

.028 .009 8.930 1 .003 1.028

.014 .005 8.682 1 .003 1.014

PreservationSolution

Ageattxp

MELDTXP

DonorAge

B SE Wald df Sig. Exp(B)

Intestinal / Multivisceral Transplantation

“Comparison of HTK and UW in Intestinal and Multivisceral Transplantation”

- Mangus, et al. Transplantation, 2008; In Press

Intestinal Transplantation

N=57 intestinal transplants HTK 35 UW 22

Intestinal TransplantationHTK UW

TOTAL n=35 (61%) n=22 (39%)Allograft transplanted Isolated small intestine (intestine alone) 5/35 (14%) 8/22 (36%) Modified multivisceral 3/35 (9%) 2/22 (9%) (stomach, duodenum, intestine, pancreas) Multivisceral 27/35 (77%) 12/22 (55%) (stomach, duodenum, intestine, pancreas, liver)Indication Pediatric (n=15) n = 6 n = 9 Necrotizing enterocolitis 4/6 3/9 Gastroschisis / Atresia 1/6 1/9 Volvulus 1/6 2/9 Microvillus inclusion 1/9 Pseudoobstruction 1/9 Retransplantation 1/9 Adult (n=42) n = 29 n = 13 Portomesenteric thrombosis 9/29 6/13 Short gut syndrome 6/29 3/13 Pseudoobstruction 1/29 3/13 Chron's disease 5/29 1/13 Non-resectable tumor 3/29 Retransplantation 2/29 1/13 Abdominal catastrophe 3/29 1/13


N=57 intestinal transplants HTK 35 UW 22


• No difference between HTK and UW in graft and patient survival at 30- and 90-days, and 1-year post-transplant

• No differences noted in:

* Initial function

* Appearance on early magnification endoscopy

* Rejection episodes

* Transplant pancreatitis

CONCLUSIONS

• Cost savings associated with HTK use

• No demonstrated difference in outcomes for: kidney

pancreas

pancreatic islets

liver

intestine

• Possible decrease in biliary complications for HTK in liver transplantation

• Possible long-term improvement in survival with HTK in liver transplantation

HTK vs UW: FUTURE RESEARCH

HTK vs UW

• Prolonged cold ischemia time

• Transplant pancreatitis

• DCD allografts

• Biliary complications / Flush of microcirculation

• Multicenter data – large volume data analysis

Documents

Comparison of HTK and UW in Abdominal Transplantation Dr. Richard S. Mangus, MD MS Indiana University, School of Medicine