Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient

Abstract

Acute overdose of tacrolimus appears to cause no or minimal adverse clinical consequences. We encountered a pediatric case who underwent liver transplantation associated with hepatic artery thrombosis (HAT), which recurred following acute tacrolimus overdose. A 10-month-old girl underwent living-related liver transplantation because of biliary atresia. To reconstruct the hepatic artery, the right gastroepiploic artery of the donor was interposed between the right hepatic artery of the recipient (2.5 mm in diameter) and the left hepatic graft artery (1 mm in diameter) under microscopy. On postoperative day 4, Doppler ultrasonography showed a remarkable reduction in hepatic arterial flow, which was consistent with HAT. The patient underwent immediate hepatic arteriography and balloon angioplasty. The stenotic sites were dilated by the procedure. Tacrolimus was infused intravenously after transplantation and the infusion rate was adjusted to achieve a target concentration of 18-22 ng/mL, which remained stable until the morning of day 6. An unexpectedly high blood concentration of tacrolimus (57.4 ng/mL) was detected at 6:00 PM on day 6, and tacrolimus was discontinued at 9:00 PM; however, the tacrolimus level reached 119.5 ng/mL at 0:00 h on day 7. While the concentration decreased to 55.2 ng/mL on the morning of day 7, the hepatic arterial flow could not be observed by Doppler ultrasonography. Emergent hepatic arteriography showed stenosis of the artery at the proximal site of the anastomosis. Balloon angioplasty was again performed and the stenotic site was successfully dilated. High level of tacrolimus exposure to the hepatic artery with injured endothelium by preceding angioplasty may have been related to the recurrence of HAT in the present case.

Acute Calcineurin Inhibitor Overdose: Analysis of Cases Reported to a National Poison Center Between 1995 and 2011

“…Our data did not include similar cases, but did include a case of fatal intravenous overdose in an adult. Overdose of intravenous TAC have previously also been reported to be more toxic than enteral overdose . Taken together with our findings, these observations suggest that excessively high blood concentrations over several hours are more likely to cause significant toxicity than a short‐lived high peak concentration following a single oral ingestion.…”

Acute tacrolimus toxicity in a non-transplant patient

“…Tacrolimus toxicity is primarily derived from adverse effects at therapeutic doses in patients with organ transplants and includes nephrotoxicity, hypertension, nausea, vomiting, diarrhea, altered glucose metabolism, and increased risk of infection and malignancies [1][2][3][7][8][9][10][11][12]. Anaphylaxis has been reported with IV administration, although it is thought to be due to the castor oil derivative in the injectable formulation [13].…”

Hepatic artery reconstruction with interposition of donor’s right gastroepiploic artery graft in pediatric living donor liver transplantation for metabolic disease

“…13 The RGEA was first described as an interposition artery in 1987 for coronary artery bypass graft 14 and in 2005 for artery reconstruction of liver transplantation. 15 However, in that case, arterial thrombosis occurred 4 days after operation. After balloon dilation, arterial stenosis occurred on the 7th day after operation ascribe to tacrolimus overdose.…”

“…Although the use of splenic artery, left gastric artery, RGA, cystic artery, GDA, and even middle colon artery has been reported successively, RGEA has always been the first choice for arterial reconstruction . The RGEA was first described as an interposition artery in 1987 for coronary artery bypass graft and in 2005 for artery reconstruction of liver transplantation . However, in that case, arterial thrombosis occurred 4 days after operation.…”