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Chlordiazepoxide/phenobarbital Various toxicities: case report

A 54-year-old woman developed prolonged sedation, abnormal consciousness level, hepatic encephalopathy and aspiration pneumonia secondary to benzodiazepine overdose while receiving concomitant chlordiazepoxide and phenobarbital [routes not stated]. The woman, who had been diagnosed with anxiety, depression, hepatitis C, alcohol abuse, and liver cirrhosis was initially hospitalised for alcohol detoxification in 2019. She started receiving treatment with chlordiazepoxide 250mg and was discharged from hospital on the next day. After 1 week, she was again hospitalised for the treatment of depression and alcohol abuse. She was initiated on chlordiazepoxide due to abstinence symptoms. On day 4-7, a cumulative dose of 950mg chlordiazepoxide was administered and also phenobarbital was added to the therapy due to upper extremity tremor. On day 8, she was shifted to the department of neurological diseases because of deteriorating consciousness level. A cerebral magnetic resonance was suggestive of Wernickes encephalopathy, and serum ammonia level was 117 µmol/L. Furthermore, she was started on treatment with thiamine, and because of continued restlessness a total dose of 300mg chlordiazepoxide was given again on day 11-12 yielding a total dose of 1250mg administered over 8 days. Also, she was continued on phenobarbital until day 13 with a cumulated dose of 1600mg. On day 16, she was admitted to ICU due to reduced consciousness and tachypnoea. Glasgow coma score (GCS) was 3. She was intubated, and started on treatment for aspiration pneumonia and liver coma. At this time, serum phenobarbital level was 11.8 mg/ dl. Despite treatment with small doses of propofol and remifentanil, she was difficult to wake-up. On day 20, serum ammonia level reduced to 49 µmol/L. On day 22, she was suspected with benzodiazepine overdose for the cause of prolonged sedation, as urine drug screens had been tested positive for benzodiazepine on several occasions during hospitalisation. The woman was initiated on treatment with flumazenil; subsequently, her consciousness level improved. She was mechanically ventilated until day 34. Chlordiazepoxide was no longer present in her body on day 34. During the course, she experienced restlessness, mainly nocturnal, which was treated with quetiapine and propofol. The highest measured values of INR, ALAT and gamma-glutamyltransferase during the stay in the ICU were 1.4, 51 and 449 U/L, respectively. She was discharged from the ICU on day 42 in her usual condition. It was reported that, hepatic encephalopathy, aspiration pneumonia and concomitant treatment with phenobarbital may have contributed to her decreased consciousness level. Pedersen SA, et al. Active chlordiazepoxide metabolites in a patient needing life support after treatment of alcohol abstinence. Basic and Clinical Pharmacology and Toxicology 127: 438-441, No. 5, Nov 2020. Available from: URL: http://doi.org/10.1111/bcpt.13449

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