Click below for each section:
Liver
Kidney
Pancreas
Heart
Other Organs
Biliary Complications
Non-Heart Beating Donor
Organ Preservation Solutions
Pump Perfusion
Thoracic Surgery
Hand Allograft Transplant
Comparison of Histidine-Tryptophan-Ketoglutarate (HTK) Solution versus University of Wisconsin (UW) Solution for Organ Preservation in Human Liver Transplantation J. Erhard, et al, Transp Int (1994) 7: 177-181
One of the original studies used in the approval of Custodiol in the United States for liver transplantation. This study is a prospective randomized study with 60 patients (30 in each group). Criteria studied were need for fresh-frozen plasma, length of ICU stay, SGOT, SGPT, GLDH, fibrinogen, TPZ, lactate, rejection episodes, complications (biliary) and survival time. The author found no significant differences in the two groups regarding the evaluation criteria, even when cold ischemia time exceeded 15 hours. A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group (as also reported by Pittsburgh in 2003).
Comparison of Histidine-Tryptophan-Ketoglutarate Solution (HTK) and University of Wisconsin Solution (UW) in Adult Liver Transplantation Richard S. Mangus et al, Liver Transplantation 12:226-230, 2006
This study compared the perioperative and first year outcomes of liver transplantation using UW or Custodiol. The study retrospectively matched UW patients to Custodiol HTK patients, with a total study population of 378 patients. Outcomes included 1-, 6-, and 12-month graft survival and patient survival and 1-, 7-, 14-, and 30-day liver function and serum creatinine. Custodiol group had higher day 1 median AST, ALT, and total bilirubin, but the two groups were similar thereafter. There were no differences in graft or patient survival. Cost savings with Custodiol were realized.
Preservation Solutions in Liver Transplantation: What are the Options? Bijan Eghtesad, Federico Aucejo, John J. Fung Liver Transplantation 12:196-198, 2006
This paper reviews historical outcomes with Custodiol, including the University of Pittsburgh’s groundbreaking work with Custodiol in the United States. Pittsburgh first reported results in 253 liver transplants comparing Custodiol to UW at the ATC meeting in 2003. Similar results were obtained between the two solutions in terms of primary nonfunction and graft function, and contrary to expectations there was no difference as ischemic times went beyond 14 hours. The paper notes reports or higher biliary complications with UW compared to HTK and why this may occur. Also reviewed is usage in DCD donors.
Experience with Histidine Tryptophan Ketoglutarate versus University of Wisconsin Preservation Solutions in Transplantation Ruben Canelo et al, Int. Surg 2003;88 145-151
This is a study comparing 63 liver transplants versus 71 UW transplants. The UW cohort is a retrospective analysis. This paper also provides a brief literature review of pancreas and kidney transplantation. Biochemical parameters, complications and survival were used to compare results. There were no differences in these findings, however, bilirubin was higher in the UW group. The rate of biliary complications was higher in the UW group. The author found that, with the exception of biliary complications, the two solutions are considered comparable. The same conclusions were made based on an analysis of the literature for kidneys and in smaller groups of pancreas transplants.
Safety and Efficacy of Living Donor Liver Preservation with HTK Solution B. Ringe et al, Transplantation Proceedings Vol. 37 No. 1 Jan/Feb 2005
This paper reviews 24 patients with living donor liver transplantation. There was no primary nonfunction and all partial livers showed good recovery. The results of this paper confirm that HTK solution is safe and effective when used in LDLTx. Potential advantages identified include low potassium concentration, low viscosity, no particles, no need to flush before reperfusion, improved biliary protection, better recovery of microcirculatory changes, ready to use, and lower costs.
Applicability of Histidine-Tryptophan-Ketoglutarate Solution in Right Lobe Adult-to Adult Liver Donor Liver Transplantation See Ching Chan et al, Liver Transplantation, Vol 10 No 11, 2004: pp1415-1421
Dr. Chan conducted a prospective study in a consecutive series of 60 right lobe adult-to-adult LDLTx comparing safety and efficacy of UW and HTK solutions. Main outcomes were post-transplant liver biochemistry, prothrombin time, recipient morbidity and graft and patient survival. There were no significant differences of the outcomes measures of the two groups. The low potassium content of the HTK offered logistical advantages.
New Preservation Solutions for use in Liver Transplantation David C. Mulligan et al Current Opinion in Organ Transplantation 2004, 9:159-162
This paper is a comprehensive review of several new preservation solutions, comparing them to each other and to UW solution. Dr. Mulligan reviews publications by Eghtesad et al, Canelo et al, Testa et al as well as the local results obtained at the Mayo Clinic in Scottsdale. Such studies showed at least comparability between Custodiol and UW, with several logistical and practical advantages being noted. The Mayo Clinic’s own results in living donor livers showed better 30 day graft survival with HTK
AMINALAI, A., et al, Morphological Investigation of the Porcine Liver Directly Following Preservation with EuroCollins, University of Wisconsin and Bretschneider’s HTK Solution, Langenbecks Arch. Chir. 376 (1992)
CANELO, R.. et al HTK vs. UW Preservation Solutions: Clinical Experience at a Single Center, Abstract
CHOK, K.S.H. et al, Bile Duct Anastomotic Stricture After Adult-to-Adult Right Lobe Living Donor Liver Transplantation, Liver Transplantation, 17:47-52, 2011
This study of prospectively collected data from 265 patients was collected between 1994 and 2008. The study aimed to establish the rates of biliary anastomotic stricture (BAS) and associated factors looking at adult-to-adult right lobe living donor liver transplantation (ARLDLT). BAS rates were 21.4% for recipients undergoing duct-to-duct anastomosis (DDA) during transplantation, 18.9% for recipients undergoing hepaticojejunostomy (HJ) and 18.2% for recipients who underwent both procedures. Prior to August 2002, UW solution was used but for the remainder of the study, HTK was instead used. The authors concluded that “BAS remains common after ARLDLT regardless of DDA or HJ. Operative findings found UW solution to be a risk factor for BAS, but this was not shown to be significant in the multi-variate analysis. The graft cold ischemia time and postoperative acute cellular rejection are significantly associated with postoperative BAS.”
CLAIR CORPS, et al, The Influence of Preservation Solution on Ischemic Changes in the Liver 2006 July WTC Abstracts Abstract 2591
CYWINSKI, J. B. et al, Association Between Donor-Recipient Serum Sodium Differences and Orthotopic Liver Transplant Graft Function, Liver Transplantation 14:59-65, 2008
DALGIC, A. et al, Duct-to Duct Biliary Anastomosis with a "Corner-Saving-Suture" Technique in Living Related Liver Transplantation Transplantation Proceedings, 37, 3137-3140 2005
DE VERA, M.E. et al, Liver Transplantation Using Donation After Cardiac Death Donors: Long-Term Follow-Up from a Single Center, American Journal of Transplantation 2009, 9: 773-781
EHTESAD, B. et al, Technical Considerations in Liver Transplantation: What a Hepatologist Needs to Know (and Every Surgeon Should Practice) Liver Transplantation, Vol. 11 No. 8 August (2005) 261-271
EGHTESAD, B. et al, Comparison of HTK Solution vs. UW Solution for Organ Preservation in Liver Transplantation Abstract #1172
EGHTESAD, B. et al, Comparison of Histidine-Tryptophan-Ketoglutarate Solution vs. University of Wisconsin Solution For Organ Preservation in Liver Transplantation ATC 3-3-03 Abstract #1172
ERHARD, J. et al, Comparison of Histidine Tryptophan Ketoglutarate Solution vs. University of Wisconsin Solution for Organ Preservation in Human Liver Transplantation Abstract 198,
ERHARD, J., et al, Transplantation of the Liver after Preservation with the Cardioplegic Solution of Bretschneider, Lancet 2 (1990)
FENG, Li et al, Histidine Tryptophan Ketoglutarate Solution vs. University of Wisconsin Solution for Liver Transplantation: A Systematic Review Liver Transplantation 13:1125-1136, 2007
FENG, Li, et al Characteristics Associated with Liver Graft Failure: The Concept of a Donor Risk Index, American Journal of Transplantation 2006, 6: 783-789
FENG, X.-N. et al, Current status and perspective of liver preservation solutions, Hepatobility Pancreat Dis Int, Vol. 5, No. 4, November 15, 2006
FRIDELL, J. et al, A Comparison of Histidine Tryptophan Ketoglutarate and University of Wisconsin Solutions in Extended Criteria Liver Allografts 2006 WTC 7-06 Abstract #64
GOKHAN, M. et al, Comparison of Histidine Tryptophan Ketoglutarate and University of Wisconsin Solution in Living Donor Liver Transplantation 2006 WTC 7-06 Abstract #64
GONDALESI, G. et al, Biliary Complications in 96 Consecutive Right Lobe Living Donor Transplant Recipients Transplantation Vol. 77, 1842-1848 No. 12 June 2004
GUBERNATIS, G et al, Extended Cold Preservation Time (20 hours 20 minutes) of a Human Liver Graft by Using Cardioplegic HTK Solution Transplantation Proceedings Vol. 23 No.5(October), 1991 pp. 2408=409
GUBERNATIS, G., et al, Uniform Standardized Technique of Donor Liver Removal Irrespective of Arterial Anomalies, Transplantation Proceedings 25 (1993), 3160-3161
GUBERNATIS, G., et al, HTK-Solution (Bretschneider) for Human Liver Transplantation First Clinical Experiences, Langenbacks Arch. Chir. 375 (1990), 66-70
HATANO, E et al, Superiority of HTK Solution to UW Solution for Tissue Oxygenation in Living Related Liver Transplantation Transplantation Proceedings Vol 28, No 3 (June), 1996: pp. 1880-1881
HATANO, E et al, Hepatic Preservation with Histidine Tryptophan Ketoglutarate Solution in Living-Related and Cadaveric Liver Transplantation Clinical Science (1997) 93, 81-88
HELLINGER, A, et al, Preservation of Pig Liver Allografts after Warm Ischemia: normothermic perfusion vs. cold Storage Langenbacks Arch Chir (1997) 382: 175-184
HESSE, U.J., et al, Organ Preservation with HTK and UW Solution, Pabst Science Publishers, D-49525 Lengerich, 1999
JAIN, A. et al, Use of UW vs. HTK Perfusion and Preservation in Live Donor Liver Transplantation Abstract AT5SL , 2005 ATC
KEHRER, G., et al, Influence of Tissue Acidification and Halothane Anesthesia on Hepatic Electrical and Biochemical Properties during Ischemia, Z. Gastroenterol., 29 (1991), 22-30
LORF, T. et al, Is HTK Preservation Solution Suitable in Clinical Liver Transplantation? XVII World Congress of the Transplantation Society 1998 Book of Abstracts, Abstract 1604
MANGUS R. et al, Comparison of Histidine Tryptophan Ketoglutarate Solution and University of Wisconsin Solution in Adult Liver Transplantation Liver Transplantation 12:226-230, 2006
MANGUS, R. S. et al, Comparison of Histidine-Tryptophan-Ketoglutarate Solution and University of Wisconsin Solution in Extended Criteria Liver Donors, Liver Transplantation, 14: 365-373, 2008
MARTINEZ, J. et al, Histidine Tryptophan Ketoglutarate Solution is Clinically Equivalent but less Expensive than the University of Wisconsin Solution for Cadaveric Liver Transplantation. A Prospective Study 2006 WTC 7-06 Abstract #405
MARZI, I. et al, Microcirculatory Disturbances and Leukocyte Adherence in Transplant Livers after Cold Storage in Euro-Collins, UW and HTK Solutions Transplant Int. 1991 (4) 45-50
MEINE, M. et al, Graft Preservation with UW or HTK in Liver Transplantation Liver Transplant, Vol. 11 No.7 July 2005
MEINE, M. et al, Randomized Clinical Assay for Hepatic Grafts Preservation with UW or HTK Solutions in Orthotopic Liver Transplantation Abstract 104, WTC Congress 6-20-2007
MEYER-VENTER, R. et al, Is HTK Preservation Solution Suitable in Clinical Liver Transplantation, 8th Congress of the European Society for Organ Transplantation, 1997, Abstract 29
MOENCH, C. et al, Prevention of Ischemic Type Biliary Legions by Arterial Back Table Flush Pressure Perfusion, Liver Transplantation, Vol. 9 No. 3, March (2003) pp 285-289
MONBALIU, D. et al, Primary Graft Nonfunction and Kupffer Cell Activation After Liver Transplantation From Non-Heart-Beating Donors in Pigs Liver Transplantation 13:239-247, 2007
MONBALIU, D. et al, Liver from Non-Heart-Beating Donors Tolerate Short Periods of Warm Ischemia Transplantation 2005;79:1-5
MORAY, G. et al, Comparison of Histidine Tryptophan Ketoglutarate and University of Wisconsin Solution in Living-Donor Liver Transplantation Transplantation Proceedings, 38, 3572-3575 (2006)
MULLIGAN, D., et al, New Preservation Solutions for Use in Liver Transplantation Current Opinion in Organ Transplantation 2004, 9:159-162
PICHLMAYR, R., et al, Technique and Preliminary Results of Extracorporeal Liver Surgery (Bench Procedure) and of Surgery on the In-Situ Perfused Liver, Br. J. Surg., 77 (1990), 21-26
POKORNY, H. et al, Liver Transplantation with HTK Infused Organs: A Multicenter Study XIX International Congress of The Transplantation Society, August 2002 Abstract 56
POKORNY, H., et al, Histidine Tryptophan Ketoglutarate Solution for Organ Preservation in Liver Transplantation – A Prospective Study Transpi mt, (2004), 256-260
POKORNY, H. et al Preservation of the Liver – Is it Possible to Extend the Time of Storage? Transplantation Proceedings, 31, 2074-2076 (1999)
RAMOS, R et al, Doppler Ultrasound Hepatic Arterial Resistive Indices are Similar after Histidine Tryptophan Ketoglutarate and University of Wisconsin Preservation in Liver Transplantation, Poster Session ATC Meeting, 5-7-07 Abstract #1285
RINGE, B. et al, Liver Preservation with HTK Solution in Live Donor Liver Presentation, Transplantation Volume 10 Number 6 – June 2004
SOTIL EVA URTASUN et al, Comparison of HTK to UW in Living Donor Liver Transplantation, Abstract 104, WTC Congress 6-20-2007
SPIEGEL, H.U., et al, Organ Preservation with EC, HTK and UW Solution in Orthotopic Rat Liver Transplantation Part II. A Morphological Study Journal of Investigative Surgery, 12:195-203, 1999
TELLIOGLU, G. et al, Histidine-Tryptophan-Ketoglutarate Solution VS University of Wisconsin Solution for Deceased Donor Liver Transplantation: Analysis of UNOS Database, P-281, ILTS Conference, New York, NY, (July 9, 2009)
This study evaluated the impact of organ preservation solutions (OPS) on outcomes in adult deceased donor liver transplant using a database analysis of the UNOS database which, reviews the cases of 20,908 patients who underwent transplants with organs preserved in an OPS, 17,559 (84%) of which used UW and 3349 (16%) used HTK. The data was further refined using the SRTR database to remove patients with missing data points. The study found that “HTK produces similar graft and patient survival outcomes compared to UW.”
TESTA, G. et al, Histidine Tryptophan Ketoglutarate vs. University of Wisconsin Solution in Living Related Liver Transplantation: Results of a Prospective Study Liver Transplantation, Vol. 9 No. 8, 2003 (August) pp. 822-826
TROISI, R. et al, HTK and UW Solutions for Flush and Preservation of Right Lobe Living Donor Grafts: Evaluation of Early Graft Function and Hemodynamics XIX Intl Congress of The Transplantation Society, Aug. 2002 Abstract 3217
WELLING, T. H. et al, Biliary Complications Following Liver Transplantation in the Model for End-Stage Liver Disease Era: Effect of Donor, Recipient, and Technical Factors, Liver Transplantation 14:73-80, 2008
This study conducted at the University of Michigan Medical Center, looked at 256 consecutive deceased donor liver transplants to evaluate variables associated with anastomotic biliary complications. Bile leak and stricture rates were analyzed. Over the course of the study, Welling et al came to observe that HTK had a protective effect. They ultimately concluded that “donor, recipient, and technical factors appear to differentially affect the incidence of anastomotic biliary complications, with warm ischemia, use of HTK, and use of a stent emerging as the most important variables.” Use of HTK was found to significantly reduce biliary complications in the multivariate analysis.
WELLING, T. et al Risk Factors for Biliary Strictures Following Liver Transplantation During the MELD Era: Effect of Donor, Recipient, and Preservation Principles, American Journal of Transplantation, 6: Supp 2, 726 Aug. 2006
Eurotransplant Randomized Multicenter Kidney Graft Preservation Study Comparing HTK and UW and Euro-Collins J. de Boer, et al Transl Int (1999) 12: 447-453
This paper provided the basis for approval of Custodiol in Kidney transplants in the United States. The study found Custodiol and UW equivalent in kidney transplant, and both superior to Euro-Collins. This is a large, randomized trial that involved a total of 659 donors and 1180 transplants. 1 and 3 year graft survival were numerically higher for Custodiol, though this was not statistically significant.
Comparison of Histidine-Tryptophan-Ketoglutarate Solution and University of Wisconsin Solution in Prolonged Cold Preservation in Kidney Allografts Avinash Agarwal, et al, Transplantation Volume 81, No. 3 February 15, 2006
This study compares UW to HTK for cold static storage of kidneys with cold ischemic times greater than 16 hours, and a subset analysis of CI over 24 hours. Graft and patient survival were similar in both groups, and the HTK cohort exhibited lower DGF. There was a trend towards improved survival in the HTK group with CI > 24 hours.
Comparison of Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solutions and Primary Preservation in Renal Allografts Undergoing Pulsatile Perfusion A, Agarwal, et al Transplantation Proceedings, 37, 2016-2019 (2005)
In this study from the Indiana University School of Medicine, UW and HTK were compared in cold preservation in kidneys that were subsequently put in pulsatile perfusion. 91 deceased renal and SKP transplants were performed. No significant differences were found in DGF, patient or graft survival. Volumes used were higher in the HTK group as anticipated.
Effects of Preservation Conditions and Temperature on Tissue Acidification in Canine Kidneys M. Kallerhoff et al, Transplantation, Vol. 39, No. 5 pp:485-489 (1985)
This older animal model paper is of interest as it investigates the influence of temperature on the degree of tissue acidification in the kidneys. Over the time of a transplant, temperature can vary significantly. Temperatures studies were 5, 15, 25, and 35ºC. The author found that HTK Solution guarantees satisfactory protection against damaging acidosis over the whole temperature range.
ALBRECHT, K. et al Impact of Preservation Solution on Early Function and Graft Survival in Cadaveric Renal Transplantation, Transplantation Proceedings, Vol. 25 No. 4 (August) 1993: pp 2561-2562
AMORTEGUI, J.D. et al, Comparison of University of Wisconsin (UW) and Histidine-Tryptophan-Ketoglutarate (HTK) Preservation Solutions in Renal Transplantation with Prolonged Cold Ischemia Time, Abstract # 1406, June 1, 2009
This abstract is a retrospective review of 200 kidney grafts that were cold preserved with HTK or UW solution (100 each) by a single OPO and transplanted as kidney-only organs in different Tx centers. Donor and recipient demographics, patient and graft survival at 1 year, incidence of acute rejection, DGF, and PNF were all considered and compared. The authors concluded that HTK and UW provide similar outcomes even in prolonged cold storage times.
DAEMEN, J.H.C. et al, Non-Heart-Beating Donor Program Contributes 40% of Kidneys for Transplantation, Transplantation Proceedings Vol. 28 No. 1 (February) 1996; pp 105-106
DAVIDSON, I.J., Renal Impact of Fluid Management with Colloids: A Comparative Review, European Journal of Anesthesiology, 2006 p. 1-18
DEBROY M. et al, Cost Effectiveness of the Use of HTK as an Alternative Preservation Solution in Live Donor Renal Transplantation, American Journal of Transplantation Supp 8 Vol. 4 2004 p. 242
ENGLESBE, M. et al, Does Using HTK Solution for Cold Preservation of Cadaveric Kidneys Save Money? Transplantation, Vol. 81 No. 12, June 27, 2006
GANDOLFO M. T. , et al, Impact of Ischemia Times on Kidney Transplant Outcomes, Transplantation, Vol. 83 No. 3, Feb 2007 p. 254
GROENEWOUD, A.F., et al, A Final Report of the Eurotransplant Randomised Multicenter Study Comparing Kidney Graft Preservation with HTK, UW, and EC Solution, 7th Congress of Europ. Soc. For Organ Transplantation, ESOT ’95, Vienna
GROENEWOUD, A.F., et al, A Preliminary Report of the HTK Randomized Multicenter Study Comparing Kidney Graft Preservation with HTK and EuroCollins Solutions, Transplant mt. 5 (Suppl. 1), (1992), 429-432
GSCHWEND, J.E., et al, Continuous in-Situ Cold Preservation with Histidine Tryptophan Ketoglutarate Solution in Nephron Sparing Surgery in Renal Tumors, J. of Urology, 154 (1995), 1307-1311
ISEMER, F.E., et al, Kidney Procurement with the HTK Solution of Bretschneider, Transplantation Proceedings, Vol. XX, No. 5, (Oct) 1988, 855-866
KALLERHOFF, M. et al Metabolic, Energetic and Structural Changes in Protected and Unprotected Kidneys at 1º C and 25 º C, Urological Research, 1988 16:57-62
KALLERHOFF, M., et al, Kidney Preservation in Situ and Conservative Treatment of Renal Cell Carcinoma: Application of HTK Solution (Custodiol® ), Investigative Urology V, Chapman + Hall, (1994)
KALLERHOFF, M., et al, Post-Ischemic Renal Function After Kidney Protection with HTK Solution of Bretschneider, Urol. Res. 14 (1986), 271-277
KALLERHOFF, M., et al, Short-Term Perfusion and "Equilibration" of Canine Kidneys with Protective Solutions, Urol. Res. 15 (1987), 5-12
KALLERHOFF, M., et al, A New Method for Conservative Renal Surgery – Experimental and Clinical First Results, Langenbecks Arch. Chir., 375 (1990), 340-346
KEHRER, G., et al, Postischemic Interrelations Between Energy Metabolism and Functional Recovery of Protected Canine Kidneys, Europ. J. Clin. Invest 19 (1989) 328-336
KLAUS, F. et al Kidney Transplantation with Belzer or Custodiol Solution: A Randomized, Prospective Study, Transplantation Proceedings, 39, 353-354 2007
LYNCH, R.J. et al, Comparison of Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Preservation in Renal Transplantation, American Journal of Transplantation, 2008, 8: 567-573
This large study is a retrospective analysis comparing patient and graft outcomes of 475 living donor and 317 deceased donor transplants, half of which were preserved with HTK, with the same number of grafts preserved using UW solution. Multi-variate analysis revealed “HTK was associated with a significant risk reduction on the incidence of DGF.” Prolonged preservation time with HTK compared to UW was not associated with excess risk to the graft or patient. HTK demonstrated “efficacy similar to UW in terms of patient and graft survival.”
LYNCH, R. J. et al, Comparison of Outcomes with HTK and UW Solutions in Renal Transplantation, American Journal of Transplantation, 2008, 8: 1958
MANEKELLER, S. et al, Conditioning Predamaged Grafts after Cold Storage: Influence of Oxygen and Nutritive Stimulation, Transplantation International 19 (2006) p. 667-674
MOISIUK, Y. et al, Histidine-Tryptophan-Ketoglutarate versus Euro-Collins for Preservation of Kidneys from Non-Heart-Beating Donors, Transplantation Proceedings Vol. 28 No. 1 (February) 1996 p. 202
O'CALLAGHAN, J.M. et al, Preservation Solutions for Static Cold Storage of Kidney Allografts: A Systematic Review and Meta-Analysis, American Journal of Transplantation, October 2011.
PLAS, E., et al, Experience in Renal Autotransplantation: Analysis of a Clinical Series, British Journal of Urology(1996) 77: p 518-523
RAYHILL, S. et al Renal Transplantation: Surgical Procedure and Complications Urology Vol. 12 Part 1, (February) 2004 pp. 2-8
ROZIER, E. et al, Effects of Preservation Solution on Early Kidney Graft Function: Comparison of University of Wisconsin Solution vs. Histidine Tryptophan Ketoglutarate Solution, American Journal of Transplantation, Supp. 11 Vol. 5, 2005 #767
TRUSHKOV S. et al, Use of HTK Solution in Kidney Preservation Transplantation Proceedings, 35, 766 (2003)
WILSON, C.H. et al Comparison of HTK and Hypertonic Citrate to Intrarterial Cooling in Human Non-Heart-Beating Donors, Transplantation Proceedings, 39, 351-352 (2007)
Follow Up Experience Using Histidine-Tryptophan-Ketoglutarate Solution in Clinical Pancreas Transplantation
1. Agarwal, et al, Transplantation Proceedings, 37, 3523-3526 (2005)
This study expands and updates on an earlier study done by the Indiana group in pancreas transplantation. 87 pancreas transplants were performed (78 utilizing HTK). Surgical procedures performed included SKP, PAK and solitary pancreas transplantation. Primary outcomes were primary nonfunction and 30-day graft and patient survival. There were no cases of primary nonfunction, and 30-day and 1-year patient survival was 99% and 93%, with graft survivals being 96% and 93%. This is compared to the UW cohort from the original report. The author concludes that HTK appears to provide effective pancreas preservation.
Initial Experience Using Histidine-Tryptophan-Ketoglutarate Solution in Clinical Pancreas Transplantation Potdar S. Malek et al, Clin Transplant 2004: 18: 661-665
This retrospective study reports results of Custodiol HTK in clinical pancreas transplantation and compares this to a contemporary experience with UW solution in conventional multiorgan deceased donors. SPK, PAK, and PTA transplants are included. Patient and graft survival, amylase, lipase, glucose and creatinine levels were investigated. The author concludes that early graft function and complications are comparable with HTK and UW solutions for pancreas allograft preservation.
Pancreas Transplantation with Histidine-Tryptophan-Ketoglutarate (HTK) Solution and University of Wisconsin (UW) Solution: Is there a Difference? Thomas Becker et al, Journal of the Pancreas 2007; 8(3): 304-311
The author proposes that the choice of preservation solution can impact graft pancreatitis, and experience with HTK is limited while UW is currently the preferred perfusate in pancreas transplantation. The study reports on actual results in a retrospective analysis of 95 SPK transplants. Patient and graft survival and early graft function are compared. No significant differences in patient and graft survival were found. Peak lipase was higher in the HTK group on day 1 (not significant). No differences were noted for amylase and C-reactive protein. The author notes the ongoing debate in pancreas transplant, but with experience in abdominal transplants with HTK going back to 1992, he finds that while preservation solution can be a factor, skilled organ procurement technique and transplant experience is mandatory in this field. Therefore, retrieval should be by an experienced transplant surgeon. It is noted that as a low volume organ, the pancreas is susceptible to edema. Only 5-7 L of Custodiol need be used in pancreas recoveries.
AGARWAL, A. et al, Comparison of Histidine Tryptophan Ketoglutarate Solution and University of Wisconsin Solution for Organ Preservation in Clinical Pancreas Transplantation, Canadian Society of Transplantation Abstracts, p25. 11-04
AGARWAL, A. et al, Organ Preservation With Histidine-Tryptophan Ketoglutarate Solution in Clinical Pancreas Transplantation: An Update of the Indiana University Experience, Transplantation Proceedings, 40, 498-501 (2008)
This paper published in 2008 updates on the clinical experience of the University of Indiana in pancreas transplant with Custodiol® HTK. The authors found 1 and 3 year patient survival s are 95% and 92% respectively. 1 and 3 year graft survival rates were 90% and 86% respectively. They determined that HTK had comparable outcomes to UW, and noted that HTK offered advantages such as lower viscosity, less potassium and reduced cost. It concludes that “HTK appears to provide effective pancreas preservation.”
Pancreas continued
BECKER, T., et al, Use of HTK Solution in Pancreas-Kidney Transplantation, Abstract O1-02, 2001 IPITA, Nov. 2003, p. 2
BECKER, T. et al, Pancreas Transplantation with Histidine-Tryptophan-Ketoglutarate (HTK) Solution and University of Wisconsin (UW) Solution: Is There A Difference?, Journal of the Pancreas, Vol. 8, No. 3, May 2007
This retrospective study, analyzes what impact the preservation solution has in clinical pancreas transplantation. 95 simultaneous kidney-pancreas transplants were reviewed with 48 using HTK, and 47 using UW. The findings revealed no significant differences in 1, 3, or 12 month patient and graft survival, even in prolonged ischemic times.
BRANDHORST, H. et al, Comparison of Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solution for Pancreas Perfusion Prior to Islet Isolation, Culture and Transplantation, Transplantation Proceedings, Vol. 27 No. 6, December (1995), 3175-3176
BRENDEL, MD et al, HTK Storage for Human Pancreatic Grafts Prior to Islet Isolation and Transplantation, Transplants 98 Book of Abstracts, XVII World Congress of Transplantation, 1998
ENGLESBE, M. et al, Early Pancreas Transplant Outcomes with Histidine-Tryptophan-Ketoglutarate Preservation: A Multicenter Study, Transplantation 2006; 82: 136-139
ENGLESBE, M. et al, Single Center Comparison of HTK Solution vs. UW Solution in Clinical Pancreas Transplantation, Transplantation Supplement, OP-009
FRIDELL, J. et al, Comparison of Histidine-Tryptophan Ketoglutarate Solution and University of Wisconsin Solution for Organ Preservation in Clinical Pancreas Transplantation, Transplantation, 2004 April 27; 77(8) 1304-1306
FRIDELL, J. et al, Histidine-Tryptophan-Ketoglutarate for Pancreas Allograft Preservation: The Indiana University Experience, American Journal of Transplantation, 2010, 10:1-6
This paper is a retrospective review which looks at the use of Custodiol® HTK and UW solutions in the 308 pancreas transplants that were performed at the Indiana University Medical Center between 2003 and 2009. The study evaluates whether 7-day, 9- day, or 1-year graft survival, peak 30 day serum amylase and lipase, HbA1c, or C-peptide level led to an increased risk of allograft pancreatitis or graft loss with either solution. The authors conclude that there is “no significant difference in 7-day, 90-day or 1-year graft survival” as well as “no clinically significant difference between HTK and UW for pancreas allograft preservation.”
HANSEN, M., et al, Human Islet Isolation of Pancreata Preserved with HTK vs. UW Solution, Abstract #613, American Transplant Congress, May 23, 2005,
HESSE, U.J, et al, Cold Preservation of the Porcine Pancreas with Histidine Tryptophan Ketoglutarate Solution, Transplantation, Vol. 66 No. 9; 1137-1141 Nov. 15, 1993
HESSE, U.J., et al, Pancreas Preservation with HTK in the Pig, Transplantation Proceedings, 29, 3522-3523, 1997
HESSE, U.J., et al, The Use of HTK and UW Solution for 24-hour Cold Storage in Porcine Pancreatic Autotransplantation, XXXII Congress of the European Society for Surgical Research, Abstracts, pg. 102 No. 172
KIN, T., et al, Comparison of HTK Solution vs. UW Solution for Pancreas Preservation Prior to Islet Isolation, Transplantation 83(1); January 2007
LEONHARDT, U., et al, The Effect of Different Solutions for Organ Preservation on Immediate Post-ischemic Pancreatic Function In-vitro, Transplantation Vol. 55; 11-14, January 1993
RIEGE, R., et al, Preservation of the Pancreas for Transplantation, Transplantation Proceedings, 31, 2095-2096, 1999
SALEHI, P., et al, Human Islet Isolations for Pancreata Preserved with Histidine Tryptophan Ketoglutarate vs. University of Wisconsin Solution, Transplantation, 2006; 82: 983-985
SCHNEEBERGER, S. et al, A prospective randomized multicenter trial comparing histidine-tryptophane-ketoglutarate versus University of Wisconsin perfusion solution in clinical pancreas transplantation, Transplant International, 2008, 9:1-8
This randomized study evaluates early pancreas transplant graft function comparing HTK to UW at multiple centers. Primary endpoint was pancreas graft survival at 6months. Serum amylase, lipase c-peptide, HbAk and exogenous insulin were also compared. 6 month patient survival rates were comparable amongst both the HTK and UW groups and the authors of the study concluded that both “solutions appear to be equally suitable for perfusion and organ preservation in clinical pancreas transplantation.”
TROISI, R., et al, Structural and Functional Integrity of Porcine Pancreatic Grafts Subjected to a Period of Warm Ischemia and Cold Preservation with Histidine Tryptophan Ketoglutarate or University of Wisconsin Solution, Transplantation, Vol. 75, No. 11, June 2003, 1793-1799
TROISI, R., et al, Suitability of Histidine Tryptophan Ketoglutarate Solution for Pancreas Preservation and Transplantation from Non-Heart Beating Donors, Eur Surg Res;2002; Supp. 1: No. 53
TROISI, R., et al, Physiologic and Metabolic Results of Pancreatic Cold Storage with Histidine Tryptophan Ketoglutarate Solution in the Porcine Autotransplantation Model, Transplant International (2000), 13;98-105
TROISI, R. et al, Segmental Porcine Pancreatic Autotransplantion as Model for Pancreas Autotransplantation Studies Using Two Different Techniques for Vascular Reconstruction, Journal of Investigative Surgery, 13;203-211, 2000
ARSLAN, A., et al, Low-Dose Histidine-Tryptophan-Ketoglutarate for Myocardial Protection, Transplantation Proceedings, 37, 3219-3222 (2005)
Comparison of UW vs. HTK Solution for Myocardial Protection in Heart Transplantation H. Reichenspurner et al, Transp Int (1994) 7 (Supp 1) S481–S484
This studies aim was to investigate the protective effect of UW in heart transplant. A retrospective comparative study with Custodiol HTK was done with 160 patients with HTK protection and 50 patients with a transplanted heart protected with UW.
A Comparison of Intracellular Solutions for Donor Heart Preservation Paul J. Hendry et al, J Thoracic Cardiovascular Surgery, 1993;105:667-73
This study compared the effects of Euro-Collins, University of Wisconsin and Bretschneider’s (Custodiol HTK) solutions with the use of an in vitro human right atrial muscle preparation to assess recovery of function after a 24-hour period of simulated cardiac arrest. Bretschneider’s solution resulted in greatly improved recovery compared to E-C and UW solutions. UW was also found to be better than E-C. Recovery of developed force was affected by temperature for EC and UW, but not for Bretschneider’s. The author noted this is of importance because uniform temperatures are seldom maintained during heart transplantation. Bretschneider’s has a very high buffering capacity, which the author speculates may be beneficial for long-term preservation.
BOTTA, L., et al, Cardiac transplantation with a donor hear rescued from deep hypothermia, The Journal of Heart and Lung Transplantation, Vol. 30, No. 10, October 2011, 1203-1204
COURAD, L., et al, Lung and Heart-Lung Transplantation for End Stage Lung Disease, Cardiothoracic Surgery, Vol.4 (1990)
GKOUZIOUTA, A. et al, Heart Transplantation in a Low-Organ-Donation Environment: A Single Center Experience, Transplantation Proceedings, 41, 4289-4293 (2009)
GU, K., et al, HTK Solution More Effective than UW Solution for Cardiac Preservation, Transplantation Proceedings, Vol.28, No. 3 (June) 1996; 1906-1907
KOBER, I.M., et al, HTK vs. UW Solution for Myocardial Protection during Moderate Hypothermia, Eur. Surg. Res., 29 (1997), 264-272
KOERNER, M.M., et al, Cardiac Transplant Survival in Relation to Preservation, Procurement, Preservation, and Allocation of Vascularized Organs, pp. 285-289, 1997, Kluwer Academic Publishers
KU, K., et al, Prolonged Hypothermic Cardiac Storage with Histidine Tryptophan Ketoglutarate Solution, Transplantation, Vol. 64; 971-975, No. 7, Oct. 15 1997
LEE, S. et al, Superior myocardial preservation with HTK solution over Celsior in rat hearts with prolonged cold ischemia, Surgery (2010), 148:463-73
This study evaluates the myocardial protection of Custodiol® HTK to Celsior in cases with extended cold storage in a rat model. The markers measured to analyze graft injury were tissue adenosine triphosphate (ATP) levels, as well as serum creatine phosphokinase (CPK), serum troponin I, graft-infiltrating cells, graft mRNA levels for inflammatory mediators. Results indicated that HTK was found to provide "superior protective effects against prolonged cold ischemia" in heart transplant.
LIAO, K., et al, Operative Technique in Orthotopic Heart Transplantation, Thoracic and Cardiovascular Surgery, Elsevier Inc. 2004, 370-377
MINTEN, J., et al, Optimal Storage Temperature and Benefit of Hypothermic Cardioplegic Arrest for Long-Term Preservation of Donor Hearts: A Study in the Dog, Transplant International (1988) 1: 19-25
MUSCI, M., et al, Comparison of Bretschneider Solution (HTKS) and University of Wisconsin Solution (UWS) for Myocardial Preservation in Heart Transplantation: A Clinical Follow-up, Cardiovascular Surgery, 1997, presented at 23rd World Congress of ISCVS, #14.10
REICHART, B., et al, Heart and Heart-Lung Transplantation: - Organ Preservation, R.S. Schulz-Verlag 1990
RENNER, A., et al, Heterotypic Rat Heart Transplantation: Severe Loss of Glutathione in 8-Hour Ischemic Hearts, Journal of Heart and Lung Transplantation, Vol. 23, No. 9; (Sept) 2004: pp. 1093-1102
SAITOH, Y. et al, Heart Preservation in HTK Solution: Role of Coronary Vasculature in Recovery of Cardiac Function, Annals of Thoracic Surgery 2000, 69:107-112
This study investigates Custodiol® HTK versus UW in terms of protecting the coronary vasculature. Rat hearts were arrested, stored in one of the two preservation solutions at 4 degrees Celsius for 8 hours and then reperfused. Coronary vascular responsiveness was examined before flushing, before storage, after storage and after reperfusion. The authors found that "HTK is superior to UW solution for cardiac preservation" by measuring pre- and post- storage ATP and ADP levels. Additionally, recovery of AF, CF, CO, RPP and LV dp/dt were found to be significantly better in the HTK group.
SCHELD, H.H., et al, Resection of a Heart Tumor using Autotransplantation, Thorac. Cardiovasc. Surg 36 (1988), 40-43
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WEI, J., et al, Successful Heart Transplantation after 13 Hours of Donor Heart Ischemia with the Use of HTK Solution: A Case Report, Transplantation Proceedings, 37, 2253-2254 (2005)
YANG, Q., et al, HTK Solution Maximally Preserves Endothelial Derived Hyperpolarizing Factor-Mediated Function During Heart Preservation: Comparison with University of Wisconsin Solution, The Journal of Heart and Lung Transplantation, Vol. 23., No. 3, (March) 2004, 352-359
BOND, G., et al, Is Histidine Tryptophan Ketoglutarate (HTK) Better Than University of Wisconsin (UW) Solution for the Cold Preservation of Intestinal and Multivisceral Allografts, Transplantation, July 27, 2004, Vol. 78, No. 2: 209
BOND, G. et al, Histidine Tryptophan Ketoglutarate (HTK): An Alternative Cold Perfusion and Preservation Solution for Intestinal and Multivisceral Grafts, American Journal of Transplantation, Supp. 11, Vol. 5, 2005: 219
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MANGUS, R., et al, A Comparison of Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solutions in Bowel Transplantation, Abstract, Transplant International, Vol. 20, Supplement 2, September 2007
MANGUS, R., et al, Comparison of Histidine-Tryptophan-Ketoglutarate Solution and University of Wisconsin Solution in Intestinal and Multivisceral Transplantation, Transplantation, Vol. 86, Number 2, July 27, 2008
OPELL, U. von., et al, Endothelial Cell Toxicity of Solid-Organ Preservation Solutions, Ann. Thorac. Surg., 50 (1990), 902-910
SIMOES, E.A., et al, Comparing the Performance of Rat Lungs Preserved for 6 or 12 Hours After Perfusion With Low Potassium Dextran or Histidine-Tryptophan-Ketoglutarate, Transplantation Proceedings, 43, 1520-1524 (2011)
ULRICH, O., et al, Endothelial Cell Toxicity of Solid-Organ Preservation Solutions, Annals of Thoracic Surgery, 1990;902-910
WILSON, C., et al, Evaluation of 8 Preservation Solutions for Endothelial in Situ Preservation, Transplantation, Vol. 78, No. 7, Oct. 2004: 1008-1013
ABOU ABBASS, A. et al, Biliary Complications After Orthotopic Liver Transplantation From Donors After Cardiac Death: Broad Spectrum of Disease, Transplantation Proceedings, Vol. 42, 3392-3398, Dec. 2010
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CUI, D.X. et al, Effect of Different Bile Duct Flush Solutions on Biliary Tract Preservation Injury of Donated Livers for Transplantation, Transplantation Proceedings , Vol 42. 1576-1581, June 2010
ENGLESBE, M. J., et al, Who Pays for Biliary Complications Following Liver Transplant? A Business Case for Quality Improvement, American Journal of Transplantation, 2006, 6:2978-2992
FURUKAWA, H., et al, Disturbance of Microcirculation Associated with Prolonged Preservation of Dog Livers Under University of Wisconsin Solution, Transplantation Proceedings, Vol 25, No 1 (Feb), 1993: 1591-1592
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MANGUS R.S., et al, Biliary Complications in Whole Organ, Cadaveric Liver Transplantation Using Histidine Tryptophan Ketoglutarate and University of Wisconsin Solutions, Liver Transplantation Vol. 11, Issue 7, p. 154
MARZI, I., et al, Microcirculatory Disturbances and Leukocyte Adherence in Transplanted Livers after Cold Storage in Euro-Collins, UW, and HTK Solution, Transplant International (1991) 4:45-50
MOR, E., et al, Prolonged Preservation in UW Solution Associated with Hepatic Artery Thrombosis after Orthotopic Liver Transplantation, Transplantation, 1993;Dec;56(6): 1399-1402
PIRENNE, J., et al, Type of Donor Aortic Preservation Solution and not Cold Ishemia Time is a Major Determinant of Biliary Strictures after Liver Transplantation, Liver Transplantation, Vol 7, No 6 (June) 2001; 540-545
WALCHER, F. et al, The impact of liver preservation in HTK and UW solution on microcirculation after liver transplantation, Transplant International, (1992) 5 [Suppl 1]: S 340-S 342
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CAUMARTIN, Y., et al, Initial Experience with Kidney Transplantation from Donors after Cardiocirculatory Death, from The Canadian Council for Donation and Transplantation, Report and Recommendations, Feb.17-20, 2005
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WIJNEN, R.M.H., et al, Outcome of Transplantation on Non-Heart-Beating Donor Kidneys, The Lancet, Vol. 345, April 29, 1995: 1067-1070
TROISI, R., et al, Preservation of the Pancreas with HTK Solution (Custodiol): Tolerance to Warm and Cold Ischemia Using a Non-Heart Beating Donor Model, Eur. Surg. Res., 2003;35
WILSON, C.H., et al, Comparison of HTK and Hypertonic Citrate to Intraarterial Cooling in Human Non-Heart-Beating-Donor Kidneys, Transplantation Proceedings, 39; 351-352: 2007
ALBRECTH, K., et al, Impact of Organ Preservation Solution on Early Function and Graft Survival in Cadaveric Renal Transplantation, Transplantation Proceedings, Vol 25, No 4, (August) 1993: 2561-2562
ANAYA-PRADO, R. et al, Scientific basis of organ preservation, Current Opinion in Organ Transplantation, 2008 13:129-134
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GEBHARD, M.M., The Importance of α-Ketoglutarate in Bretschneider’s Organoprotective HTK Solution (Custodiol® ) and the Importance of Tryptophan in Custodiol® , European Surgical Research Clinical and Experimental Surgery, Vol. 33, No. 2 Abstracts, 2001 pp. 1-4
HOLSCHER, M., et al, Current Status of HTK Solution of Bretschneider in Organ Preservation, Transplantation Proceedings, Vol 23 No 5 (October), 1991: 2334-2337
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AGARWAL, A., et al, Comparison on Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solutions as Primary Preservation in Renal Allografts Undergoing Pulsatile Perfusion, Transplantation Proceedings, 37, 2016-2019, 1995
AGARWAL, A. et al, Comparison of Histidine-Tryptophan Ketoglutarate and University of Wisconsin Solutions as Primary Preservation in Renal Allografts Undergoing Pulsatile Perfusion, Transplantation Proceedings, 37, 2016-2019 (2005)
MANEKELLER, S., et al, Oxygenated Machine Perfusion Preservation of Pre-damaged Kidneys with HTK and Belzer Machine Perfusion Solution: An Experimental Study in Pigs, Transplantation Proceedings, 37, 3274-3275 (2005)\
MINOR, T., et al, Endoplasmic and Vascular Surface Activation During Organ Preservation: Refining Upon the Benefits of Machine Perfusion, American Journal of Transplantation, 2006;6: 1355-1366:
MINOR, T., et al, Liver Transplantation with HTK: Salutary Effect of Hypothermic Aerobiosis by Either Gaseous Oxygenation or Machine Perfusion, Clinical Transplantation, 2002, 16(3);206-211
MINOR, T., et al, Kidney Transplantation from Non-Heart-Beating Donors after Oxygenated Low-flow Machine Perfusion Preservation with Histidine Tryptophan Ketoglutarate, Transplant International, 2005; 17-11(707-712)
OLSCHEWSKI, P., et al, Use of HTK Solution for Hypothermic Machine Perfusion: An Alternative for the Preservation of Less than Optimal Donor Livers – An Experimental Study in Rats, Transplantation Proceedings, 35, 767 9(2003)
OLSCHEWSKI, P., et al, Improved Preservation of Marginal Donor Livers and Reduced Expression of ICAM-1 and MHC Class II Antigen Expression by Oxygented Machine Perfusion, 8th Congress of the Asian Society of Transplantation, Book of Abstracts, Abstract FP4-4, 2003
ACKEMANN, J., et al, Celsior Vs. Custodiol – Early Postischemic Recovery after Cardioplegia at 5ºC., Annals of Thoracic Surgery, 2002;74:522-529
ARSLAN, A., et al, Low-Dose Histidine-Tryptophan-Ketoglutarate for Myocardial Protection, Transplantation Proceedings, 37, 3219-3222 (2005)
BRETSCHNEIDER, H.J., et al, Cardioplegia – Principles and Problems. Physiol. And Pathophysiololgy of the Human Heart., M. Nijhoff Public. Boston, 1984, p. 605-616
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GALLANDAT, R.C.G., et al, Clinical Effect of Bretschneider HTK and St. Thomas Cardioplegia on Hemodynamic Performance after Bypass Measured, Thorac. Cardiovasc. Surg. 36 (1988), 151-156
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GEBHARD, M., et al, Different Effects of Cardioplegic Solution HTK During Single or Intermittent Administration, Thorac. Cardiovasc. Surg., 32 (1984), 271-276
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HEINEMEYER, D., et al, Intracellular pH Measurement During Cardiac Arrest in Ventricular Myocardium by Bretschneider’s Cardioplegic Solution HTK and St. Thomas-Hospital Solution With and Without Procaine, Thorac. Cardiovasc. Surg. 35 (1987), 48-52
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SUCHER, R. et al, Investigation of the Role of Ischemia and Reperfusion in Limb Transplantation, American Transplant Congress 09, Boston, MA, Abstract 1062, (May 31, 2009)