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Chief Poison Specialist Illinois Poison Center Chicago, Illinois
Certified Specialist, Poison Information Illinois Poison Center
Nursing Supervisor Herrin Clinic Herrin, Illinois
Certified Specialist, Poison Information Illinois Poison Center 222 South Riverside Plaza, Suite 1900 Chicago, Illinois 60606-6010 fax 312/627-8006 tsigg{at}ilpoison.org
Managing Director/Medical Director Illinois Poison Center/Toxikon Consortium Chicago
Published Online, June 14, 2005. www.theannals.com, DOI 10.1345/aph.1G052
A MEDLINE search from 1966 to May 2005 using the terms metronidazole, kinetics, dialysis, and related search terms was performed, and no studies or case reports of metronidazole clearance by hemodialysis following acute or acute-on-chronic overdose were found. To our knowledge, as of May 2005, this is the first reported case showing the hemodialysis clearance of metronidazole after acute-on-chronic overdose.
Case Report. A 62-year-old, 76-kg man ingested 17 tablets of metronidazole 500 mg (8.5 g) in a therapeutic error. The patient had an extensive past medical history, including end-stage renal disease requiring multiple daily medications and dialysis 3 times per week. The overdose occurred on the morning of his scheduled dialysis. The patient had taken 4 doses of metronidazole over the previous 2 days (one tablet twice a day).
The poison center was contacted 5 hours after ingestion. No gastrointestinal decontamination was recommended or performed. The recommendation was to continue with routine scheduled hemodialysis. Pre-dialysis blood urea nitrogen was 80 mg/dL, serum creatinine 9.2 mg/dL, and aspartate aminotransferase 21 U/L. It was requested that pre- and post-dialysis serum metronidazole concentrations be obtained to determine the clearance of metronidazole by hemodialysis in the overdose setting.
The pre-dialysis venous metronidazole concentration was 120 µg/mL (9.5 h after ingestion). The patient underwent 4 hours of dialysis with a Fresenius 2008H machine at a blood flow rate of 450 mL/min using an Optiflux 200NR dialyzer at a dialysate flow rate of 800 mL/min. The post-dialysis venous metronidazole concentration was 32 µg/mL one hour after dialysis. All drug assays were performed by HPLC. The expected peak concentration following a single 250-mg dose is 5.1 ± 1.7 µg/mL, and the expected concentration following a 2-g dose is 40.6 ± 9.3 µg/mL.5 The assays of hydroxy and acetic acid metabolites were not determined.
The patient was stable the entire time and did not demonstrate any evidence of metronidazole toxicity such as nausea, vomiting, diarrhea, impairment of the central nervous system or peripheral nervous system, or hepatotoxicity.
Discussion. Previous studies have documented hemodialysis clearance rates of 24–45% of therapeutic doses of metronidazole administered orally or intravenously.2,3 Following an 8.5-g acute-on-chronic ingestion of metronidazole, a standard 4-hour dialysis procedure (along with endogenous hepatic metabolism) demonstrated a significant reduction in blood concentrations of 73.3% with an approximate half-life of 2.5 hours. Assuming complete oral absorption, nearly one half-life elapsed prior to dialysis. The patient had a volume of distribution of 0.6 L/kg and steady-state drug concentrations before and after dialysis. The total body metronidazole concentration fell from 5.5 to 1.5 g (4 g) or 47% of the ingested 8.5-g dose. This is within range of therapeutic hemodialysis clearance of metronidazole.3
Hemodialysis is not routinely recommended following metronidazole overdose. We speculate, however, that early hemodialysis in this patient with end-stage renal disease may have prevented neurologic toxicity by avoiding prolonged high concentrations of the potentially neurotoxic hydroxyl metabolite.
References
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