Day, R

Furukawa, H

Imventarza, O

Scotti, C

Starzl, TE

Todo, S

Wu, YM

English

PubMed

Name not available

Cold ischemia time vs outcome of human liver transplantation using UW solution

D-Scholarship@Pitt

Cold Ischemia Time vs Outcome of Human Liver Transplantation Using UW Solution H. Furukawa, S. Todo, O. Imventarza, Y.M. Wu, C. Scotti, R. Day, and T.E. Starzl L ABORATORY experiments· and clinical trials·') of University of Wisconsin (UW) solution have ShO\\.ll beyond a doubt the superior qualities of this preservation fluid. Successful liver replacement in dogs has been re-ported after as long as 2 days of refrigeration. 4 but in the canine model there is a slow deterioration of graft quality that is evident at the end of 24 hours.5 The extent of the penalty (if any) for increasingly long periods of preserva-tion of human livers is not known. The retrospective present study has examined this question. METHODS All cases of primary liver transplantation were examined from October 24. 1989 to May 19. 1990. Sufficient data were available for assessment in all but 31 cases. leaving 593 for analysis. There were 93 (15.7%) infants and children (S 18 years) and 500 EU4KP~F adults. In each case. the time was determined from devascular-ization in the donor to reperfusion in the recipient. This cold ischemia time (CIT) was used to stratify the recipients as follows: group I. <10 hours (n = 223): group 2.10 to 14 hours (n = 188): group 3. IS to 19 hours (n = lOll: group 4.20 to 24 hours (n = 52): and group S. >25 hours (n = 29). Between these groups there were no significant differences in recipient age. sex. mix of diagnoses. acceptance of positive cytotoxic crossmatches or ABO incompat· ibilities. or severity of illness as documented with the four·tier plus UN(),Stat delineation of urgency.b The donors for these grades of recipients were not different in respect to age. sex. li\Cr function. cardiopulmonary status. and time of hospitalization for the disease or conditions that brought them to donor status. During the first 5 months of the study. the UW solution .. as prepared from raw materials at the School of Pharmacy of the University of Pillsburgh. After this. it was pro\'ided by the Depanment of Medical Research of the Dupont Corporation (Waukegan. 1111. Throughout the study period. two factors dic-tated the conditions of UW solution use. First. the solution was a scarce resource that had to be used sparingly. usually with a limitation of no more than 2 L per donor. Second. host procure-mentteams that had no experience with and who had understand-able suspicion of a new technique usually insisted upon the use of conventional cold lactated Ringer's or Euro-Collins·like solutions for the in situ aonic perfusion. which is inherent in the multiorpn procurement methods that were used. 7•M Consequently. almost all of the livers were chilled first in situ by core cooling with either lactated Ringer's or Euro-Collins solutions. and reperfused .... ith the UW solution in what has been called the "mixed" technique. The preferred method of using UW solution for all phases of the procurement did not become feasible until the spring of 1989. All of the surviving recipients were followed until July J. 1990. The parameters used to assess the effect of CIT were patient and graft survival. and quality of graft function with panicular rder-ence to the first 2 postoperative weeks. When retransplantation became necessary. the reasons were classified as technical error. primary nonfunction. rejection. infection. or miscellaneous. Table 1. Highest Uver Enzymes ~ Prothrombin Time Within 7 Days After Liver Transplantation Group 1 Group 2 Group 3 Group 4 Group 5 CIT (h) <10 10.14.9 15-19.9 20-24.9 >25 n 223 188 101 52 29 SGOT (UtL) 1.169 1.333 1.410 1.099 1,403 SGPT (UIL) 824 930 931 800 939 PT (sec) 17.7 19.4 19.3 17.2 17.1 Abbreviations; SGOT, serum glutamate cxaloac:etic acid; SGPT. S8f\nI gluta· mate pyruvic acid: PT. prolhrombtn time Statistical evaluation was by chi-square test. analysis of vari-ance. simple regression analysis. aoo logistic regression analysis. RESULTS Graft Function Liver function tests in the five groups of recipients were not significantly different at any time out to 1 year post-transplantation. The highest transaminases and prothrom-bin times in the first 7 days are ~hown in Table I. Because livers lost by death or retransp\;:.ntation no longer conuib-uted to the averages. these figu:-es represented a progres-sively culled group of satisfac""'rily performing organs. Patient and Graft Surv.val Overall patient survival at 3 m,-'nths and I year was 92% and 77.2C?c. respectivelr. There was no difference in the five groups. However. graft survival was t-etter in the patients with shorter preservation times in g!"0UpS I and 2 (Fig I). This meant that the equivalent patient survival in the different groups depended on a higher r.<lte of retransplantation in patients whose grafts were stored for longer times. Reasons for Retransplantahon Primary nonfunction was the le20ding indication for retrans-plantation (67.2C?c). followed t-~ technical or mechanical From the Department of Surgel"!. University Health Center of Pittsburgh, University of Pittsburgh. and the Veterans AdlTUnlstra-tion Medical Center. Pittsburgh, PA. Supported by research grants fro"Tl the Veterans Adminislration and project grant no. OK 29961 from the National InstiU8S of Heatth, Bethesda. MD. Address reprint requests to Thomas E. Starzl. MD. PhD. De-partment of Surgery. 3601 Fifth Ave. University of Pittsburgh, Pittsburgh, PA 15213. ~ 1991 by Appleton & Lange 0041-1345191J$3.001+0 1550 TransplantatiOn Proceedings, Vol 23, No 1 (February), 1991: pp 1550-1551 , .. ., .-" .; .. uw SOLUTION ON LIVER Tx 100 80 70 ..... Day 7,' ..... 14YII •• Day 14, lwa4 GROU'" -0- 1 -I - . - . - . ~+-----~--~r---~----~----D---~ o 10 120 II. 24. "OST OfOERATIYI DAYS UI FIg 1. Graft survival (actual) of dillerent CIT groups. n. imperfections (20.7%). and rejection (I0.3t;:f). Primary nonfunction was significantly more frequent in groups 4 and 5 than in groups I to 3 (P < .05). DISCUSSION AND CONCLUSIONS It is not profound to suggest that static preservation has finite limits. Livers were shown in these studies to have entered the danger zone once 20 hours had passed. The rate of primary nonfunction increased beyond this time. but patient survival was protected by aggressi~De retrans· 155,. plantation. What was equally evident was that the majority of livers were usable well beyond 20 hours. The liver with the longest CIT (>34 hours) functioned perfectly. There is no reliable way at present to test these organs on the back table for their safety and viability. The folly of complete indifference to CIT is evident from this study. The conditions of testing may not have aHowed the full value of UW to be seen since the potentially suboptimal policy was in effect at the time of preliminary flushing with electrolyte solutions. Since completion of this study. we have used the now freely available UW solution from the outset. However. the trend in the new cases is similar to that in the earlier experience. REFERENCES I. Jamieson NV. Sundberg R. Lindell S. ct al: Transplant Proc 2()(Suppl 1):945. 1988 2. Kalayoglu M. Sollinger NW. Stratta R. et al: Lancet 1:617. 1988 3. Todo S. Nery J. Yanaga K. et aI: JAMA 261:711. 1989 4. Jamieson N V. Sundberg R. Lindell S. et aI: Transplantation 46:517. 1988 5. Todo S. Podesta L. Ueda Y: Clin Transplant 3:253. 1989 6. Gordon R: Transplant Proc (in press) 7. Starzt TE. Hakala TR. Shaw BW. et al: Surg Gynecol Obstet 158:223. 1984 8. Starzt TE. Miller C. Broznick B. et aI: Surg Gynecot Obslel 165:343. 1987 I 

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Cold ischemia time vs outcome of human liver transplantation using UW solution

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