From the Guidelines
Lorazepam should be used with caution in patients with acute hepatitis, as it may be preferred over other benzodiazepines when sedation or anxiety management is needed, due to its pharmacokinetic profile which is less dependent on hepatic cytochrome P450 metabolism 1. The typical dose ranges from 0.5-2 mg orally every 4-6 hours as needed, with lower initial doses (0.5-1 mg) recommended in hepatic impairment. Lorazepam is advantageous in liver disease because it undergoes direct glucuronidation without forming active metabolites, making it less dependent on hepatic cytochrome P450 metabolism. This results in more predictable clearance even when liver function is compromised. However, dose reduction is still necessary as elimination may be prolonged. Some key points to consider when using lorazepam in patients with acute hepatitis include:
- Monitor patients closely for excessive sedation, respiratory depression, and worsening encephalopathy.
- Avoid prolonged use due to risk of dependence, and consider alternatives like oxazepam when appropriate.
- Remember that any benzodiazepine can precipitate or worsen hepatic encephalopathy, so use only when benefits clearly outweigh risks and discontinue if mental status deteriorates. It is also important to note that the presence of a decompensated liver disease must encourage prioritisation of a personalised prescription that is symptom adapted and favours short-acting drugs 1. Additionally, thiamine should be prescribed as part of the withdrawal process in order to prevent the onset of Wernicke's encephalopathy, as thiamine deficiency is common in alcohol-dependent people 1. In terms of sedation practices in patients with acute liver failure, protocol-based sedation (to minimise its depth and duration) seems to reduce overall morbidity and mortality, and the use of benzodiazepines should be avoided if possible 1. However, if benzodiazepines are necessary, lorazepam may be a preferred option due to its pharmacokinetic profile. Ultimately, the decision to use lorazepam in patients with acute hepatitis should be made on a case-by-case basis, taking into account the individual patient's needs and medical history.
From the FDA Drug Label
As with all benzodiazepines, the use of lorazepam may worsen hepatic encephalopathy; therefore, lorazepam should be used with caution in patients with severe hepatic insufficiency and/or encephalopathy. Dosage for patients with severe hepatic insufficiency should be adjusted carefully according to patient response; lower doses may be sufficient in such patients
The role of lorazepam in acute hepatitis patients is to be used with caution due to the potential to worsen hepatic encephalopathy.
- Key considerations:
- Use with caution in patients with severe hepatic insufficiency and/or encephalopathy.
- Dosage adjustment may be necessary, with lower doses potentially being sufficient.
- Monitor patients closely for signs of hepatic encephalopathy. 2
From the Research
Role of Lorazepam in Acute Hepatitis Patient
- Lorazepam is a benzodiazepine, and its use in patients with liver disease is a concern due to the potential risk of precipitating coma 3.
- Benzodiazepines, including lorazepam, are best avoided in patients with hepatic encephalopathy, as they can exacerbate the condition 3.
- The use of benzodiazepines in patients with cirrhosis and ascites may increase the risk of developing hepatic encephalopathy, particularly during the first 10 days of use 4.
- However, there is limited evidence to support the belief that benzodiazepines increase the risk of hepatic encephalopathy in patients with cirrhosis and ascites 4.
Alternative Treatments
- Haloperidol is considered a safer choice for managing agitation in patients with liver disease 3.
- Phenytoin and gabapentin are relatively preferred drugs for managing seizures in patients with hepatic encephalopathy, but monitoring of drug levels is desirable 3.
- Flumazenil, a benzodiazepine receptor antagonist, has been shown to have a beneficial effect on patients with hepatic encephalopathy, particularly in improving short-term outcomes 5, 6.
Considerations
- The management of neuropsychiatric symptoms in patients with liver disease aims at managing the underlying pathology, and the resolution of which leads to improvement in clinical symptomatology 3.
- The pathophysiological basis of hepatic encephalopathy is complex, and the lack of direct correlation between pathogenic factors and the severity of the disease makes it difficult to select appropriate therapy 7.