Lorazepam is considered the safest sedative in patients with hepatic impairment because it undergoes conjugation via glucuronidation, an extrahepatic metabolic pathway largely independent of liver function. Unlike diazepam, midazolam, and chlordiazepoxide, which require oxidative metabolism by the liver’s cytochrome P450 system, lorazepam’s metabolism is less affected by hepatic dysfunction, resulting in more predictable pharmacokinetics and reduced risk of accumulation and toxicity. This makes lorazepam ideal for sedation in patients with compromised liver function.

Reference: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, Brunton et al., 13th Edition.