As the number of patients waiting to receive transplants increases, there is a need to explore all possible donation opportunities. In this case report, we describe the transplantation of a liver from a donor who died following ethylene glycol poisoning into a female with alcoholic liver disease with cirrhosis and associated ascites. Prior donor management, including ethanol, fomepizol and haemodialysis, hastened clearance of ethylene glycol from the circulation, and following liver transplantation the recipient exhibited no adverse effects suggestive of ethylene glycol toxicity, although recipient hepatic artery dissection and thrombosis necessitated re-transplantation. Our experience suggests that donor death due to ethylene glycol intoxication should not contraindicate liver transplantation, particularly after appropriate donor management

Burman, A

Kosmoliaptsis, V

Watson, CJE

Alisha Burman

Christopher J. E. Watson

Vasilis Kosmoliaptsis

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Transplantation Direct

Ethylene Glycol Poisoning Should Not Contraindicate Liver Donation

Apollo (Cambridge)

Liver TransplantationEthylene Glycol Poisoning Should NotContraindicate Liver DonationAlisha Burman,1 Christopher J. E. Watson, MD, FRCS,2,3 and Vasilis Kosmoliaptsis, PhD, FRCS2,3Abstract:As the number of patients waiting to receive transplants increases, there is a need to explore all possible donationopportunities. In this case report, we describe the transplantation of a liver from a donor who died after ethylene glycol poisoninginto a woman with alcoholic liver disease with cirrhosis and associated ascites. Donor management, including ethanol, fomepizoland haemodialysis, hastened clearance of ethylene glycol from the circulation, and after liver transplantation, the recipient exhibited noadverse effects suggestive of ethylene glycol toxicity, although recipient hepatic artery dissection and thrombosis necessitatedretransplantation. Our experience suggests that donor death due to ethylene glycol intoxication should not contraindicate liver trans-plantation, particularly after appropriate donor management.(Transplantation Direct 2017;3:e212; doi: 10.1097/TXD.0000000000000729. Published online 8 September, 2017.)E thylene glycol (EG) is an odorless, sweet-tasting liquidfound in industrial solutions such as antifreeze and wind-shieldwiper fluid.Due to its sweet taste, it is sometimes consumedaccidentally by children. Adults tend to ingest it intentionally as asubstitute for alcohol or in an attempt at committing suicide. Thelethal dose of EG is thought to be 1.4 to 1.6 mL/kg1; it exertsmost of its toxicity via its metabolites glycolate and oxalate.The liver metabolizes approximately 80% of EG (Figure 1),Received 19 May 2017. Revision requested 24 July 2017.Accepted 26 July 2017.1 School of ClinicalMedicine, University of Cambridge, Cambridge, UnitedKingdom.2 Department of Surgery, Addenbrooke's Hospital, University of Cambridge,Cambridge, United Kingdom.3 The NIHR Cambridge Biomedical Research Centre and the NIHR Blood andTransplant Research Unit in Organ Donation and Transplantation, University ofCambridge, Cambridge, United Kingdom.C.J.E.W. and V.K. are funded by the National Institute for Health ResearchBlood and Transplant Research Unit (NIHR BTRU) in Organ Donation andTransplantation at the University of Cambridge in collaboration with NewcastleUniversity and in partnership with NHS Blood and Transplant (NHSBT). The viewsexpressed are those of the authors and not necessarily those of the NHS, theNIHR, the Department of Health or NHSBT.The authors declare no conflicts of interest.A.B., C.J.E.W., and V.K. participated in the writing of the article and approved thefinal article.Correspondence: Christopher J.E. Watson, MD, FRCS, Department of Surgery,University of Cambridge, Box 202, Addenbrooke’s Hospital, Cambridge CB22QQ, United Kingdom. (cjew2@cam.ac.uk).Copyright © 2017 The Author(s). Transplantation Direct. Published by WoltersKluwer Health, Inc.This is an open-access article distributed under the terms of theCreative Commons Attribution-Non Commercial-No Derivatives License 4.0(CCBY-NC-ND), where it is permissible to download and share the work providedit is properly cited. The work cannot be changed in any way or used commerciallywithout permission from the journal.ISSN: 2373-8731DOI: 10.1097/TXD.0000000000000729Transplantation DIRECT ■ 2017and the remaining 20% is excreted unchanged by the kidneys.2Ethylene glycol exerts its toxicity in 3 stages. In the first12 hours, its effects are primarily neurological with centralnervous system depression. This is followed by a metabolicacidosis, with associated cardiopulmonary effects, such aspulmonary edema and acute congestive cardiac failure. Finally,after 24 hours, acute renal failure occurs due to calcium oxalatedeposition and metabolic acidosis.3 Oxalate, a metabolite ofEG, binds circulating calcium-forming crystals that deposit inthe renal cortex, causing reduced glomerular filtration. Deathusually occurs during the metabolic acidosis phase, which isassociated with multiorgan failure and cerebral edema, thelatter resulting in brain stem herniation and death.4In this article, we present a case of transplantation of aliver from a donor with EG poisoning, and review the rele-vant literature.CASE DESCRIPTIONThe donor liver was recovered from a 26-year-old womanfound collapsed at home after ingesting a bottle of windshieldwiper fluid. She had a history of self-harm and previous EGoverdose attempts. She was intubated upon arrival to thehospital and given ethanol. Her blood results on admissionincluded a sodium of 148 mmol/L, potassium of 6 mmol/L,creatinine of 195 μmol/L (2.2 mg/dL), glucose of 14.9 mmol/L,aspartate aminotransferase (AST) of 58 iU/L, alanine amino-transferase (ALT) of 30 iU/L, alkaline phosphatase (ALP) of209 iU/L, and a total bilirubin of 3 μmol/L (0.18 mg/dL).On day 2, fomepizole was given instead of ethanol, and shewas started on intermittent hemodialysis. This was stoppedon day 3, because there was no trace of EG or its metabolitesin the blood sample. She was then transferred to intensivecare, where she coned the same day, and brain stem deathwas confirmed. The liver was recovered for transplantation5 days after ingestion of EG.www.transplantationdirect.com 1FIGURE 1. Metabolismof EGand the possible effect of itsmetabolites.TABLE 1.Comparison of reported cases of liver transplantation from donors wDy-Liacco WollfDonor Age, y 41 4Sex Male FeBlood groupTime from overdoseto brain death48 h 8AST, U/I 36 5ALT, U/I 27 3GGT, U/I 4ALP, U/I 48Total bilirubin, mg/dL 1 0PT, sec 12.3Treatment for ingestionCreatinine, mg/dLeGFR, mL/min per 1.73 m2Liver biopsy findings Normal hepatocytes;no evidence ofinflammation orcrystal depositsMild perivenmicrovessteatosisperiportainfiltratioRecipient Age 54 3Sex MaleLiver injury Alcoholic cirrhosis,ascites,encephalopathyHaemophiliahepatitisMELD score at transplant 28 1Peak postoperative LFTs AST 345ALT 197 3ALP 35Total bilirubin 3.3PT 23.2Days until normal LFTs 2Days until discharge 7 1Kidney functionpostoperativeSerum creatinine, mg/dLCreatinine (mg/dL) at 6 moeGFR at 6 moComplicationseGFR, estimated glomerular filtration rate; MELD, Model of End-Stage Liver Disease; LFTs, liver function t2 Transplantation DIRECT ■ 2017 www.transplantationdirect.comAt the time of organ recovery, the serum ASTwas 26 iU/L,ALT was 26 iU/L, ALP was 109 iU/L, total bilirubin was64 μmol/L (3.7 mg/dL), and prothrombin time (PT) at 13 sec-onds. A liver biopsy before transplantation showed no evidenceof oxalate crystal deposition. The liver was orthotopicallytransplanted into a 62-year-old womanwith alcoholic liver cir-rhosis and ascites. Her Model of End-stage Liver Disease scorewas 26 before the transplantation, and her renal function wasnormal (creatinine, 42 μmol/L or 0.48 mg/dL). The operationwas complicated by massive hemorrhage, estimated blood lossof 23 L, and she developed acute kidney injury perioperatively(peak creatinine, 127 μmol/L or 1.44mg/dL on day 2). Her post-operative liver function tests on day 7 were ALT of 102 U/L,ALP of 74 U/L, total bilirubin of 37 μmol/L (2.2 mg/dL),and PTon day 8 was 12.1 seconds. A computed tomographyscan on day 10 posttransplantation revealed she had an ex-tensive dissection of the native hepatic artery proximal tothe anastomosis to the donor for which she underwent re-transplantation on day 22 posttransplant. At that time, shehad recovered normal renal function.ith EG poisoningMcClain Fujji Current case4 26 31 26male Male Male FemaleB+ O+d 4 d 5 d 3 d9 28 32 265 7 17 269 23 4852 109.9 0.5 0.6 3.712.1 13Dialysis until toxicologyis negativeEthanol, fomepizole,dialysis untilnegative toxicology5 6.438ousicularscarcel round celln; no crystalsNo evidence of hepatitis,centrilobular necrosis,carcinomas, granulomasor alcohol inducedinjury, no crystalsNo evidenceof crystals2 51 61 62Male Male FemaleA,C, HIVHep C, hepatocellularcarcinomaESLD secondaryto nonalcoholicsteatohepatitisAlcoholic cirrhosis,ascites8 22 35 26179875 430 88239 476.7 7.125.68 95 103.95 1.44250AKI that progressedto chronic kidneydiseaseAcute kidney injury;native hepaticartery dissectionest; HIV, human immunodeficiency virus AKI; acute kidney injury; ESLD, end stage liver disease.© 2017 Wolters Kluwer Burman et al 3DISCUSSIONThere have been 4 previous reports of liver transplantationfrom a donor who has died after ingestion of EG. Acute kid-ney injury is described in just one of the cases.5 Renal failurein donors is due to metabolic acidosis secondary to glycolateand calcium oxalate deposition and can occur 24 to 72 hoursafter consumption.6One concernwhen accepting the liver fromsuch a donor is the possibility of EG still being present whichcould result in renal failure in the recipient. This seems unlikelyin our case, because after treatment at the donor hospital, therewas no trace of EG in the donor at the time of donation.After being rapidly absorbed by the gastrointestinal tract,serum level of EG peaks between 1 and 4 hours postingestion,and the elimination half-life with preserved renal function is 3to 8 hours.6 However, ethanol and fomepizole are often givento prevent the metabolism of EG into its toxic metabolites.Ethanol is the preferred substrate of alcohol dehydrogenaseand is thus, metabolized in preference to EG, whereasfomepizole inhibits alcohol dehydrogenase activity, which isthe rate-limiting step in EG metabolism. Because this slowsdown the conversion of EG into its metabolites, it changesthe half-life of EG to 19.7 hours.5 This is important to takeinto account when working out when EG is fully clearedand whether the organ is safe to transplant. Hemodialysis ofthe donor also reduces the levels of EG and its metabolites. Itshould be continued until the blood shows no traces of EGand its metabolites to prevent acute kidney injury and otherpathologies attributed to EG metabolites in the recipient.As the number of patients waiting to receive transplants in-creases, there is a need to explore all possible donation oppor-tunities. Transplanting the liver from donors who died due toan EG overdose would appear to be safe, subject to appropri-ate donormanagement to eliminate EG and its metabolites be-fore donation. The liver appears to be less susceptible tooxalate deposits.2 Table 1 updates the table in a previous pub-lication5 and summarizes all the reported cases to date. In allcases, liver enzymes were normal before removal of the liverand the liver biopsies showed no evidence of oxalate crystaldeposits. In addition, Fujii et al2 showed that the allograftwas still functioning 5 years after transplantation. As a result,so long as the donor is hemodynamically stable, and there areno contraindications to transplanting the liver, it is acceptableto use livers from donors who died from EG overdose. How-ever, the recipient should be informed about the liver comingfrom an individual who had overdosed and the increased risksthis may pose on them. The adverse result in our case was dueto a dissection of the native hepatic artery extending back intothe celiac trunk and compromising arterial flow into the graft.It was not related to the cause of donor death.Although it seems safe to transplant livers, the safety oftransplanting other organs from donors with EG poisoningis yet to be established. Because the third stage of EG toxicityinvolves calcium oxalate crystal deposition often in the renalcortex, causing acute kidney injury, one must be weary be-fore using kidneys as allografts.7 However, there have beenreports of successful transplantation of a kidney8 and of akidney and pancreas7 in this setting. Because there is a needfor all viable allografts to be used, organs from EGoverdoseddonors should not be dismissed. Rather careful evaluation oftheir organs is needed on an individual basis to assess theirsuitability, because it is indeed possible to gain successful al-lograft function.REFERENCES1. Walder AD, Tyler CK. Ethylene glycol antifreeze poisoning. Three case re-ports and a review of treatment. Anaesthesia. 1994;49:964–967.2. Fujji M, Goerlach J, Alami S, et al. Case report demonstrating the safe andeffective means of expanding the donor pool with livers recovered frombrain-dead donors after ethylene glycol toxicity. Transplant Proc. 2016;48:3064–3066.3. Wolff M, Schaefer N, Rabe C, et al. Successful transplantation of a liver froma donor with fatal ethylene glycol poisoning. Liver Transpl. 2005;11:990–992.4. Dy-Liacco M, Tuttle-Newhall E, Collins B, et al. Liver transplantation from acadaver donor with ethylene-glycol-induced brain death. Transplantation.2003;75:1056.5. McClain J, Uemura T, Sathishkumar S, et al. Liver donation after ethyleneglycol overdose: when is it safe?. Transpl Int. 2012;25:e55–e57.6. Leth P, GregersenM. Ethylene glycol poisoning. Forensic Sci Int. 2005;155:179–184.7. Barbas AS, Sweeney TE, Collins BH, et al. Kidney-pancreas transplantationin the setting of donor ethylene glycol poisoning. Dial Transplant. 2010;39:216–217.8. Sifontis N, Kim R, Birkenbach M, et al. Deceased-donor kidney transplantfollowing ethylene glycol-induced brain death. Dial Transplant. 2011;40:126–128.

Ethylene glycol poisoning should not contraindicate liver donation

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Ethylene glycol poisoning should not contraindicate liver donation

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