LETTER TO THE EDITORS
Liver donation after ethylene glycol overdose: when is it safe?
Article first published online: 16 FEB 2012
© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation
Volume 25, Issue 4, pages e55–e57, April 2012
How to Cite
McClain, J., Uemura, T., Sathishkumar, S. and Kadry, Z. (2012), Liver donation after ethylene glycol overdose: when is it safe?. Transplant International, 25: e55–e57. doi: 10.1111/j.1432-2277.2012.01436.x
- Issue published online: 14 MAR 2012
- Article first published online: 16 FEB 2012
Ethylene glycol is a sweet tasting compound found in high concentrations in substances like automotive antifreeze, brake fluids, and industrial solvents  and is often used as an alcohol substitute by alcoholics, or as a means of suicide. Ethylene glycol gets metabolized by alcohol dehydrogenase into glycoaldehyde which is then converted into glycolic acid, the main cause of the metabolic acidosis which characteristically develops. Glycolic acid gets converted through glyoxylic acid into oxalic acid, which precipitates with calcium into calcium oxalate crystals. These crystals are primarily responsible for the cerebral edema and renal failure which are characteristic late sequelae of ethylene glycol overdose . We recently made a decision to utilize a liver from a donor who overdosed on ethylene glycol.
The donor was a 26-year-old B-positive male with schizophrenia, who was otherwise healthy. He was found unresponsive and taken to the emergency department, where his anion gap was 26 with a bicarbonate of 12 mmHg, sodium of 142 mEq/l, potassium of 5.2 mEq/l, glucose of 84 mEq/l, and creatinine of 2.7 mg/dl. His toxicology work-up came back positive for ethylene glycol and he was then dialyzed until the toxicology screens came back negative. Despite aggressive attempts at saving his life, the donor succumbed to the damage from his overdose 4 days later.
Prior to procurement, the donor’s labs revealed a total bilirubin of 0.5 mg/dl, direct bilirubin of 0.1 mg/dl, aspartate transaminase (AST) of 28 IU/l, alanine transaminases (ALT) of 7 IU/l, and gamma-glutamyl transpeptidase of 23 IU/l. He was, however, in renal failure with a creatinine ranging from 4.5 to 5 mg/dl. Both kidneys were biopsied and discarded at procurement because of bilateral crystallization. The liver was biopsied twice at procurement and both specimens showed no evidence of crystallization, hepatitis, centrilobular necrosis, carcinomas, granulomas, or alcohol-induced injury. It was orthotopically transplanted using standard technique  without bypass into a 51-year-old male patient with end-stage liver disease secondary to hepatitis C, complicated by hepatocellular carcinoma. His Model for End-Stage Liver Disease score was 25 prior to the transplantation and during the case he was hemodynamically stable.
To the best of our knowledge, this is the third case of orthotopic liver transplantation from an ethylene glycol overdosed donor (Table 1) [4,5]. In the prior examples, the recipients recovered without any published renal injury. Our patient developed acute renal failure post-transplantation that has progressed to chronic kidney disease (defined as a GFR of less than 60 ml/min/1.73m2 for ≥3 months). During and after liver transplantation, the patient was hemodynamically stable. His pre-operative creatinine of 0.97 mg/dl rose to 3.95 mg/dl by postoperative day 4, at which point it began to slowly recede. At 6 months postop, the patient’s creatinine stabilized at approximately 2 mg/dl, with an estimated glomerular filtration rate (GFR) consistently falling between 40 and 50 ml/min/1.73 m2.
|Characteristics||Dy-Liacco et al.||Wolff et al.||McClain et al.|
|Age/gender of donor||Male – age 41||Female – age 44||Male – age 26|
|Time from overdose to brain death||48 h||8 days||4 days|
|Liver function tests at procurement:|
|Aspartate aminotransferase (AST), U/l||36||59||28|
|Alanine aminotransferase (ALT), U/l||27||35||7|
|Alkaline phosphatase, U/l||48||–||52|
|Total bilirubin mg/dl||1||0.9||0.5|
|Prothrombin time (PT), s||12.3||–||12.1|
|Liver biopsy findings||Normal hepatocytes with no evidence of inflammation or crystal deposition||Mild perivenous microvesicular steatosis, scarce periportal round cell infiltration. No crystals||No evidence of hepatitis, centrilobular necrosis, carcinomas, granulomas, or alcohol induced injury|
|Age/gender of recipient||Male – age 54||Unknown – age 32||Male – age 51|
|Recipient liver injury and complications||Alcoholic cirrhosis, ascites & encephalopathy||Hemophilia A, hepatitis C, HIV||Hepatitis C, hepatocelluar carcinoma|
|Model for end-stage liver disease (MELD) score at transplant||28||18||22|
|Peak postop liver function tests:|
|Aspartate aminotransferase (AST)||345||–||1798|
|Alanine aminotransferase (ALT)||197||375||430|
|Prothrombin time (PT)||23.2||–||–|
|Days until normal liver function tests:||2||8||9|
|Days until discharge||7||15||10|
This led us to ask when it should be considered safe to transplant a liver from an ethylene glycol overdosed donor. The half-life of ethylene glycol in humans has been estimated at 3–8.4 h in untreated adults , and renal failure has been demonstrated to occur up to 72 h after ethylene glycol ingestion ; however, considering the estimated half-life of oxalic acid of 92 ± 8 min , this damage most likely depends on the continued presence of oxalic acid precursors in the blood stream multiple days after the patient’s initial presentation. With dialysis, ethylene glycol and glycolic acid levels are typically reduced to concentrations less than 5 mmol/l within the first 10 h . As glycolic acid causes metabolic acidosis in these patients, this may be a useful surrogate marker for the levels of residual toxic chemicals in the patient’s system. Waiting for at least 12 h after a negative ethylene glycol and glycolic acid toxicology screen or for 12 h after the metabolic acidosis has been corrected should allow ample time for the body to rid itself of excess oxalic acid.
Fomepizole therapy without dialysis increases the ethylene glycol half-life in the body from 3 to 8 h up to 19.7 ± 1.3 h . As conversion to GA will occur at a slower rate, but for a longer period of time, both GA and OA may be present at potentially damaging levels for longer than the 72 h seen without intervention. In view of this, more time should be allowed before organ donation is attempted from a patient treated with fomepizole. The exact time would depend on the potential donor’s clinical picture, but like a dialyzed patient, the donor should be free from metabolic acidosis or exhibit a negative toxicology screen for at least 12 h prior to transplant allowing time for oxalic acid clearance from the system.
In either case, the proposed recipient should be informed about the nature of the liver they are about to receive. It would be appropriate to tell them that the liver is coming from an individual who overdosed on a toxic substance, and that this might pose some degree of increased risk to them. However, they should also be told that every published case of such a procedure has been successful. They should be aware of the time that has passed since the overdose, and be informed whether or not this is sufficient for clearance of the toxic substances. It should be emphasized that the overdose does not change the nature of the procedure that will be performed.
- 1Oxalate-crystals in different tissues following intoxication with ethylene glycol: three case reports. Legal Med (Tokyo) 2009; 11: 488., , , .
- 2US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry. Toxicological profile for ethylene glycol. November 2010. http://www.atsdr.cdc.gov/toxprofiles/tp96.pdf, last accessed on February 3, 2012.
- 3Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice. Philadelphia, PA: Saunders/Elsevier, 2008: pp. 710–712. http://www.mdconsult.com. Elsevier Inc. Web. 25 Sept. 2011., .