Management of ICU Psychosis in Patients with Chronic Liver Disease

Initial Assessment and Differential Diagnosis

Altered mental status in patients with chronic liver disease should not be automatically attributed to hepatic encephalopathy; it requires thorough investigation as HE is a diagnosis of exclusion 1
Common alternative causes include substance intoxication/withdrawal, drug-related issues, infections, electrolyte disorders, intracranial bleeding, seizures, and primary psychiatric disorders 1
Routine investigations should include metabolic laboratory assessment, drug and medication history and levels, and brain imaging in cases of first episode, seizures, focal neurological signs, or inadequate response to therapy 1

Transfer patients with altered mental status to a monitored setting to prevent aspiration and falls 2
Consider intubation for patients unable to maintain airway, with massive GI bleeding, or respiratory distress 2
Discuss goals of care before intubation when possible 2

Investigate for hepatic encephalopathy using West Haven criteria and Glasgow Coma Scale 1
Identify precipitating factors of HE, which include infections, GI bleeding, electrolyte disorders, acute kidney injury, alkalosis, dehydration, constipation, inappropriate lactulose use, and sedative medications 1

Start lactulose if HE is suspected (orally or via nasogastric tube) 1
For Grade 3-4 HE or ileus, consider lactulose enema (300 mL lactulose in 700 mL water) 1
Titrate to achieve 2-3 soft stools per day 3, 4
Consider polyethylene glycol if patients are at risk of ileus/abdominal distention 1
The role of rifaximin as add-on therapy remains under investigation but may be considered for recurrent episodes 1, 4

For sedation in intubated patients, use short-acting medications: propofol is preferred due to short half-life 2
Dexmedetomidine (alpha-2 adrenergic agonist) can reduce ventilation duration, preserve cognitive function, and reduce need for benzodiazepines in substance withdrawal 2
Avoid or minimize medications with sedative effects: benzodiazepines should be avoided due to synergistic impact 2
Minimize opioids but provide adequate pain control to prevent hyperalgesia 2

Routine ammonia level testing is not recommended for diagnosis of HE 1
A low ammonia level in patients with confusion should prompt investigation for other etiologies 1

Before discharge, confirm neurological status and educate caregivers that it may change as acute illness resolves 5
Plan outpatient consultations to adjust treatment and prevent recurrence of precipitating factors 5
Educate patients and relatives about medication effects, importance of adherence, early signs of recurring HE, and actions to take if recurrence happens 5
Consider liver transplantation evaluation for patients with recurrent intractable HE 6, 4

Benzodiazepines are contraindicated in patients with decompensated cirrhosis due to their ability to precipitate or worsen hepatic encephalopathy, according to the American Association for the Study of Liver Diseases 7, 8

It is essential to rule out hepatic encephalopathy before attributing altered mental status to primary delirium, and investigate precipitating factors such as infections, GI bleeding, electrolyte disorders, acute kidney injury, dehydration, constipation, and sedative medications, as recommended by the European Association for the Study of the Liver 7, 8
Hyponatremia is particularly important, and serum sodium levels should be maintained above 130 mmol/L to reduce the risk of hepatic encephalopathy, according to the American Association for the Study of Liver Diseases 7, 8

Systematically addressing precipitating factors, such as discontinuing proton pump inhibitors unless strictly necessary, monitoring and correcting electrolytes, and reviewing all medications for hepatotoxicity and CNS effects, can help reduce delirium risk in patients with decompensated cirrhosis, as recommended by the American College of Gastroenterology 7, 8

The American Association for the Study of Liver Diseases recommends using short-acting agents like zolpidem at reduced doses (5 mg) or dexmedetomidine for sedation and insomnia in decompensated cirrhosis, and avoiding benzodiazepines entirely as they precipitate hepatic encephalopathy 9
For pain management, the Clinical and Molecular Hepatology society suggests using acetaminophen at 2-3 g/day, tramadol at a maximum of 50 mg every 12 hours, and avoiding NSAIDs due to nephrotoxicity, gastric bleeding, and decompensation in cirrhosis 10

The Hepatology society recommends monitoring for excessive sedation, particularly in the first 48-72 hours of therapy, and checking electrolytes regularly to maintain sodium levels above 130 mmol/L to reduce the risk of hepatic encephalopathy 9
The Clinical and Molecular Hepatology society advises caution with tramadol interactions, avoiding SSRIs, SNRIs, and tricyclic antidepressants due to serotonin syndrome risk and lowered seizure threshold 10