Non-invasive detection of elevated ICP in acute liver failure  

Acute liver failure can be associated with marked cerebral edema and elevated intracranial pressure (ICP). Cerebral edema, and thereby elevated ICP, likely occurs as a result of increased concentration of ammonia in glial cells in the nervous system. Elevated ICP is a major cause of mortality and morbidity in patients with acute liver failure. ICP monitoring is important in acute liver failure, as it may permit intervention before devastating brain injury occurs. The gold standard for ICP monitoring is done via an invasive intracranial monitor; however, acute liver failure patients are coagulopathic and at risk of intracranial hemorrhage following monitor insertion.

Thus, non-invasive monitoring of ICP may prove particularly useful in patients with acute liver failure. Recently, optic nerve ultrasonography (ONU) and transcranial doppler (TCD) have been used to assess changes in intracranial pressure in a myriad of neurological diseases. Few studies have investigated the role of these non-invasive techniques in patients with acute liver failure.

The aim of this study is to compare the characteristics of ONU to the gold standard (an invasive ICP monitor) in patients with acute liver failure.

Study design
Prospective observational study

Study population
Study population: Cases will include all adult patients > 17 years with a diagnosis of acute liver failure (see below for definition) admitted at the ICU at the University of Alberta Hospital between April 1/2020 and April 1/2021.

​We estimate approximately 10-15 cases during the study period. Exclude those with pre-existing liver disease or conditions associated with optic nerve disease (i.e. optic neuritis) or sheath thickening (e.g.infiltrative granulatomaous disease, leukemic infiltrates)

Definitions of ALF
Acute liver failure: As per the American Association for the Study of Liver Diseases (AASLD), acute liver failure is defined as evidence of coagulation abnormality (INR 1.5) with any degree of encephalopathy and without pre-existing cirrhosis, in addition to an illness duration of less than 26 weeks duration.

Ultrasound protocol
On post-admission day 1, patients meeting the above criteria will have an invasive ICP monitor placed by neurosurgery. In addition, measurement of bilateral optic nerve sheath diameters, along with focused TCD will take place. Thereafter, measurement of bilateral optic nerve sheaths will take place daily, along with continuous ICP monitoring. Focused TCD will not continue past post-admission day 1.

Primary outcome: non-invasive versus ICP monitoring in patients with ALF.

Statistical analysis
Statistical analysis will be performed using the Statistical Package for Social Sciences version 23 (SPSS Inc., Chicago, Illinois).  Categorical variables will be expressed as a percentage and compared using the chi-square or Fisher exact test. Continuous variables will be expressed as means or medians, as appropriate, and compared using the t test or Mann-Whitney test.