Reactions 869 - 15 Sep 2001

Bupivacaine

Liver disorders following epidural administration inelderly patients: 4 case reports

Four patients developed liver disorders while receivingepidural bupivacaine for pain management.

The first patient, a 62-year-old man with a 4-month historyof T4–5 postherpetic neuralgia, had started treatment with 4daily epidural injections of bupivacaine 0.25% 4ml and a12-day continuous epidural infusion of bupivacaine 0.25% 2ml/h; he was also receiving amitriptyline and amlodipine. Thefrequency of the bolus injections was gradually decreased.After 18 days’ treatment, he developed erythema involving histrunk, general malaise and a fever of 38–39°C. At that time, atotal of 1980mg of bupivacaine had been administered. Hisliver enzyme and C-reactive protein levels were elevated.During the following week, these levels increased further, andhis bilirubin level and eosinophil differential also becameelevated. All his medications, including bupivacaine, werediscontinued, and laser therapy was started for his pain. Oneweek after his medications were stopped, his fever and skineruptions had resolved. During the following 2 weeks, his liverenzyme levels normalised. Two months later, he receivedlidocaine without incident for severe pain.

The second patient, a 72-year-old woman with anintervertebral disc displacement at L4–5, began receiving 4daily epidural injections of bupivacaine 0.125% 6ml for 2weeks, after which the frequency was reduced to twice daily.On treatment day 20, she developed a headache, nausea anderythema involving her trunk; at that time, she had received atotal bupivacaine dose of 495mg. Her liver enzyme levels hadbecome elevated and, 1 week later, they peaked and her C-reactive protein and eosinophil differential became elevated.Treatment with bupivacaine was stopped and her skineruption and fever resolved within 1 week. Her pain wassubsequently managed with lidocaine and corticosteroids. 32days later, her liver enzyme levels had normalised.

The third patient, a 67-year-old woman with T5–6postherpetic and trigeminal neuralgias, started treatment withbupivacaine 0.25% as 4 daily injections of 5ml and acontinuous infusion at 2 ml/h; she was also receivingamitriptyline, diclofenac and carbamazepine. On treatmentday 14, when she had received a total bupivacaine dose of2210mg, her liver enzyme levels were found to be elevated.Her liver function deteriorated during the next 20 days and hereosinophil differential became elevated. Bupivacaine therapywas withdrawn and laser therapy was started. Her liverenzyme levels had normalised 48 days later. She subsequentlyreceived treatment with amitriptyline and lidocaine withoutincident.

The fourth patient, an 84-year-old woman with a 3-monthhistory of T2–3 postherpetic neuralgia, started treatment with4 daily epidural injections of bupivacaine 0.25% 4ml and acontinuous epidural infusion of bupivacaine 0.125% at 2 ml/h.On treatment day 13, she reported a loss of appetite andgeneral malaise, and she had a fever of 38–39°C. At that time,she had received a total bupivacaine dose of 1200mg. Her liverenzyme and C-reactive protein levels, and eosinophildifferential, were elevated. Her fever resolved within 5 days.Bupivacaine was replaced with lidocaine, and her elevatedliver enzyme levels normalised over the next 25 days.

Author comment: ‘We consider bupivacaine to be the mostpossible cause of liver injury in these patients.’Yokoyama M, et al. Drug-induced liver disease during continuous epidural blockwith bupivacaine. Anesthesiology 95: 259-261, Jul 2001 - Japan 800871760

» Editorial comment: A search of AdisBase and Medlinerevealed only 1 previous case report of liver disordersassociated with bupivacaine, which involved the development ofcholestasis following interpleural administration [see Reactions455: 6, 12 Jun 1993; 800200163].

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Reactions 15 Sep 2001 No. 8690114-9954/10/0869-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved