Elsevier

Clinical Therapeutics

Volume 32, Issue 1, January 2010, Pages 60-64
Clinical Therapeutics

Irreversible encephalopathy after treatment with high-dose intravenous metronidazole

https://doi.org/10.1016/j.clinthera.2010.01.018Get rights and content

Abstract

Background: Encephalopathy associated with metronidazole is rare and, in most cases, reversible following discontinuation.

Objective: We describe a case of fatal encephalopathy after treatment with high-dose intravenous metronidazole and the potential causes of the irreversibility.

Case summary: A 38-year-old white woman (weight, 45 kg) received metronidazole among other medications to treat osteomyelitis for 74 days after surgery to correct a spinal neuroarthropathy. An initial dose of 500 mg IV QID was administered. After 6 weeks, the patient was discharged and the dose was changed to 1500 mg IV administered once daily (over 90 minutes) by a visiting nurse. Other treatments included teicoplanin 400 mg once daily and trimethoprimsulfamethoxazole 480 mg BID for the infection, baclofen 25 mg TID for pain associated with a congenital spinal cord lesion with paraplegia, and omeprazole 20 mg once daily for pyrosis. Ten weeks after the start of metronidazole, the patient developed somnolence and dysarthria, changing to encephalopathy with coma on admission 2 weeks later. Despite discontinuation of all medication, including metronidazole, 2 days after admission, the patient's condition appeared to be irreversible. After 8 weeks, her coma was considered permanent, mechanical ventilation was discontinued, and she died. Evaluating all medicines administered, metronidazole, with a Naranjo adverse drug reaction score of 5 (probable), was the most plausible cause of the encephalopathy. The other medicines, including baclofen, had a negative score of −3 to −2 (doubtful). All tests on infections, metabolic disorders, or interactions between medications were negative.

Conclusion: This patient had a fatal encephalopathy, probably associated with long-standing exposure to high plasma concentration peaks of metronidazole, due to a once-daily dose of 1500 mg IV over several weeks.

References (16)

There are more references available in the full text version of this article.

Cited by (38)

  • A potential new role for ASL perfusion imaging: Diagnosis of metronidazole induced encephalopathy – Two companion cases

    2020, Radiology Case Reports
    Citation Excerpt :

    When administered in high dosages, generally 1.5 g/day or higher or for long periods, this medication can rarely induce an encephalopathy (MIE) characterized by altered mental status, gait abnormalities, dysarthria, extremity weakness in addition to other findings. Although most often reversible after medication cessation, there have been reports of irreversible encephalopathy as well. [17],[5],[18] The incidence of MIE is still unknown but generally considered rare. [2]

  • Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge

    2016, Journal of Emergency Medicine
    Citation Excerpt :

    Therefore, it is preferable to keep the cumulative dose of metronidazole to < 20 g, especially in cirrhotic and real dysfunction patients. If not recognized early, MIE can be lethal due to progressive toxic encephalopathy (13). Brain imaging (MRI) typically shows characteristic symmetrical lesions in the cerebellar region near the dentate nuclei, as seen in this case.

  • An 82-year-old man with ataxia and dysarthria

    2016, CMAJ
    Citation Excerpt :

    Most reported cases of metronidazole-induced encephalopathy have had good outcomes with resolution of signs, symptoms and MRI findings after drug cessation. Although the prognosis appears to be favourable overall, there are two case reports in which metronidazole-induced encephalopathy contributed to death,10,11 emphasizing the importance of timely recognition of a condition that is largely reversible. This case highlights a rare adverse effect of a commonly prescribed medication.

View all citing articles on Scopus
View full text