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Uncommon reaction to a common prescription
Case Report
Uncommon reaction to a common prescription Kaveh Khodakaram, Neshro Barmano Lancet 2011; 378: 288 Department of Surgery (K Khodakaram MD); and Department of Internal Medicine, County Hospital Ryhov, Jönköping, Sweden (N Barmano MD) Correspondence to: Dr Kaveh Khodakaram, County Hospital Ryhov, 551 85 Jönköping, Sweden [email protected]
See Online for webappendix
A
In May, 2010, a 50 year-old man presented to us with a 10 day history of abdominal pain, fever, and shivering with elevated C reactive protein and leucocytes. He had a past history of congestive subvalvular aortic stenosis which had not required surgical treatment. He weighed 85 kg, had normal renal and hepatic function, and was not on any regular medication. CT of the abdomen suggested an abscess of the appendix. He was treated with intravenous cefotaxime 1 g three times a day and metronidazole 1 g daily for 2 days and discharged with oral metronidazole 400 mg three times a day and ciprofloxacin 500 mg twice a day. 5 days later, he returned with a complete loss of hearing, fatigue, dizziness, vomiting, impaired balance, ataxia and dysarthria. He was afebrile and CT of the brain was normal. We suspected an encephalopathy caused by an adverse effect of metronidazole and/or ciprofloxacin, and both drugs were discontinued. Within one hour after admission he became unconscious. He was transferred to the intensive care unit and was intubated. MRI of the brain showed bilateral and symmetric swellings of the cerebellar dentate nuclei, dorsal medulla, dorsal pons, midbrain, corpus callosum and increased signal intensity in the supratentorial periventricular white matter (figure A), which was in accordance with previously described cases of metronidazole induced encephalopathy.1 Meropenem, aciclovir and betamethasone were started to cover possible meningitis and encephalitis. The electroencephalogram, lumbar puncture, inflammatory markers, microbiological and viral testing, autoimmune markers, and thyroid function tests were all normal. Although the metronidazole concentration in plasma was not measured, an overdose was unlikely because our patient had only been prescribed one box B
Figure: MRI of brain in May, 2010 (A) compared to follow up in July, 2010 (B) Showing symmetric swelling and increased signal intensity of (A) the cerebellar dentate nuclei (arrow), and (B) complete resolution of signal changes in the dentate nuclei (arrow).
288
containing 30 pills of 400 mg, and had followed the prescription accordingly. His symptoms and MRI findings were not found to correlate with earlier described cases of ciprofloxacin-induced encephalopathy. Wernicke’s encephalopathy may produce similar clinical symptoms, however without MRI lesions of cerebellar dentate nuclei.2 Furthermore, thiamine was not administered to our patient. Viral encephalitis and bacterial meningitis were ruled out. According to the Naranjo probability scale3 our patient’s symptoms were classified as probably caused by metronidazole (Naranjo Score 5/13). The case was reported to and confirmed by the Swedish adverse effect register institute “SWEDIS” as a probable case of metronidazoleinduced encephalopathy. His symptoms gradually resolved and an MRI two months later, showed a clear resolution of the earlier described signal changes (figure B and webappendix). At final follow-up in September, 2010, he was well with only residual hearing impairment. Metronidazole has been used clinically for more than 30 years and is regarded as a safe antibiotic with few adverse reactions1,4 Encephalopathy is an extremely rare but serious, neurological side-effect.1,2 The pathophysiology of metronidazole encephalopathy is unknown, but an acute toxic insult producing axonal swelling may be responsible2 and the encephalopathy may be completely reversible. There are only twenty cases of metronidazole-induced encephalopathy currently reported in English medical literature.1 In these cases, neurological adverse effects of metronidazole occurred particularly with doses exceeding 2 g daily or when used for prolonged periods.2,5 Although MRI findings are typical for this condition, ignorance of metronidazole-induced encephalopathy may result in clinical misjudgment and delay of the diagnosis. Contributors KK and NB looked after the patient and wrote the report. Written consent to publish was obtained. References 1 Bottenberg MM, Hegge KA, Eastman DK, Kumar R. Metronidazole-induced encephalopathy: a case report and review of the literature. J Clin Pharmacol 2010; published online March 10. DOI:10.1177/0091270010362905. 2 Kim E, Na DG, Kim EY, Kim JH, Son KR, Chang KH. MR imaging of metronidazole-induced encephalopathy: lesion distribution and diffusion-weighted imaging findings. AJNR Am J Neuroradiol 2007; 28: 1652–58. 3 Naranjo CA, Busto U, Sellers EM et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239–45. 4 Lee SS, Cha SH, Lee SY, Song CJ. Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging. J Comput Assist Tomogr 2009; 33: 305–08. 5 Sharma P, Eesa M, Scott JN. Toxic and acquired metabolic encephalopathies: MRI appearance. AJR Am J Roentgenol 2009; 193: 879–86.
www.thelancet.com Vol 378 July 16, 2011
Uncommon reaction to a common prescription Kaveh Khodakaram, Neshro Barmano Lancet 2011; 378: 288 Department of Surgery (K Khodakaram MD); and Department of Internal Medicine, County Hospital Ryhov, Jönköping, Sweden (N Barmano MD) Correspondence to: Dr Kaveh Khodakaram, County Hospital Ryhov, 551 85 Jönköping, Sweden [email protected]
See Online for webappendix
A
In May, 2010, a 50 year-old man presented to us with a 10 day history of abdominal pain, fever, and shivering with elevated C reactive protein and leucocytes. He had a past history of congestive subvalvular aortic stenosis which had not required surgical treatment. He weighed 85 kg, had normal renal and hepatic function, and was not on any regular medication. CT of the abdomen suggested an abscess of the appendix. He was treated with intravenous cefotaxime 1 g three times a day and metronidazole 1 g daily for 2 days and discharged with oral metronidazole 400 mg three times a day and ciprofloxacin 500 mg twice a day. 5 days later, he returned with a complete loss of hearing, fatigue, dizziness, vomiting, impaired balance, ataxia and dysarthria. He was afebrile and CT of the brain was normal. We suspected an encephalopathy caused by an adverse effect of metronidazole and/or ciprofloxacin, and both drugs were discontinued. Within one hour after admission he became unconscious. He was transferred to the intensive care unit and was intubated. MRI of the brain showed bilateral and symmetric swellings of the cerebellar dentate nuclei, dorsal medulla, dorsal pons, midbrain, corpus callosum and increased signal intensity in the supratentorial periventricular white matter (figure A), which was in accordance with previously described cases of metronidazole induced encephalopathy.1 Meropenem, aciclovir and betamethasone were started to cover possible meningitis and encephalitis. The electroencephalogram, lumbar puncture, inflammatory markers, microbiological and viral testing, autoimmune markers, and thyroid function tests were all normal. Although the metronidazole concentration in plasma was not measured, an overdose was unlikely because our patient had only been prescribed one box B
Figure: MRI of brain in May, 2010 (A) compared to follow up in July, 2010 (B) Showing symmetric swelling and increased signal intensity of (A) the cerebellar dentate nuclei (arrow), and (B) complete resolution of signal changes in the dentate nuclei (arrow).
288
containing 30 pills of 400 mg, and had followed the prescription accordingly. His symptoms and MRI findings were not found to correlate with earlier described cases of ciprofloxacin-induced encephalopathy. Wernicke’s encephalopathy may produce similar clinical symptoms, however without MRI lesions of cerebellar dentate nuclei.2 Furthermore, thiamine was not administered to our patient. Viral encephalitis and bacterial meningitis were ruled out. According to the Naranjo probability scale3 our patient’s symptoms were classified as probably caused by metronidazole (Naranjo Score 5/13). The case was reported to and confirmed by the Swedish adverse effect register institute “SWEDIS” as a probable case of metronidazoleinduced encephalopathy. His symptoms gradually resolved and an MRI two months later, showed a clear resolution of the earlier described signal changes (figure B and webappendix). At final follow-up in September, 2010, he was well with only residual hearing impairment. Metronidazole has been used clinically for more than 30 years and is regarded as a safe antibiotic with few adverse reactions1,4 Encephalopathy is an extremely rare but serious, neurological side-effect.1,2 The pathophysiology of metronidazole encephalopathy is unknown, but an acute toxic insult producing axonal swelling may be responsible2 and the encephalopathy may be completely reversible. There are only twenty cases of metronidazole-induced encephalopathy currently reported in English medical literature.1 In these cases, neurological adverse effects of metronidazole occurred particularly with doses exceeding 2 g daily or when used for prolonged periods.2,5 Although MRI findings are typical for this condition, ignorance of metronidazole-induced encephalopathy may result in clinical misjudgment and delay of the diagnosis. Contributors KK and NB looked after the patient and wrote the report. Written consent to publish was obtained. References 1 Bottenberg MM, Hegge KA, Eastman DK, Kumar R. Metronidazole-induced encephalopathy: a case report and review of the literature. J Clin Pharmacol 2010; published online March 10. DOI:10.1177/0091270010362905. 2 Kim E, Na DG, Kim EY, Kim JH, Son KR, Chang KH. MR imaging of metronidazole-induced encephalopathy: lesion distribution and diffusion-weighted imaging findings. AJNR Am J Neuroradiol 2007; 28: 1652–58. 3 Naranjo CA, Busto U, Sellers EM et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239–45. 4 Lee SS, Cha SH, Lee SY, Song CJ. Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging. J Comput Assist Tomogr 2009; 33: 305–08. 5 Sharma P, Eesa M, Scott JN. Toxic and acquired metabolic encephalopathies: MRI appearance. AJR Am J Roentgenol 2009; 193: 879–86.
www.thelancet.com Vol 378 July 16, 2011