Outcomes and Complications of Intracranial Pressure Monitoring in Acute Liver Failure

Abstract

Objective To determine if intracranial pressure (ICP) monitor placement in acute liver failure (ALF) patients is associated with significant clinical outcomes. Design Retrospective multicenter cohort study. Setting Academic liver transplant centers comprising the US ALF Study Group. Patients and participants Adult critically ill ALF patients presenting with Grade III/IV hepatic encephalopathy (n=629) prospectively enrolled between 3/2004 to 8/2011. Intervention ICP monitored (ICPM; n=140) vs. non-monitored controls (n=489). Measurements and Results ICPM patients were younger than controls (35 vs. 43 years, p<0.001) and more likely to be on renal replacement therapy (52% vs. 38%, p=0.003). Of 87 ICPM patients with detailed information, 44 (51%) had evidence of intracranial hypertension (ICH ~ ICP >25 mmHg) and overall 21-day mortality was higher in patients with ICH (43% vs. 23%, p=0.05). During the first 7 days, ICPM patients received more ICH-directed therapies (mannitol: 56% vs. 21%; hypertonic saline: 14% VS. 7%; hypothermia: 24% vs. 10%; p< 0.03 for each). 41% of ICPM patients received LT (vs. 18% controls; p<0.001). Overall 21-day mortality was similar (ICPM 33% vs. controls 38%, p=0.24). Where data were available, hemorrhagic complications in ICPM patients were rare (4/56 (7%); 3 died). When stratifying by acetaminophen (APAP) status and adjusting for confounders, ICPM placement did not impact 21-day mortality in APAP patients (p=0.89). However, ICPM was associated with increased 21-day mortality in non-APAP patients (OR ~ 3.04, p=0.014). Conclusions In ICP monitored ALF patients, ICH is commonly observed. The use of ICPM in APAP ALF did not confer a significant 21-day mortality benefit while in non-APAP ALF it may be associated with worse outcomes. Hemorrhagic complications from ICPM placement were uncommon and cannot account for mortality trends. While our results cannot conclusively confirm or refute the utility of ICP monitoring in ALF patients, patient selection and ancillary assessments of cerebral blood flow likely have a significant role. Prospective studies would be required to conclusively account for confounding by illness severity and transplant.

Intracranial Pressure in Acute Liver Failure

“…Among the patients listed for LT in the study by Karvellas et al (6) (Supplemental Table 1), which represents a more homogeneous group than the overall cohort, those undergoing ICP monitoring did not show an increased mortality despite a lower rate of LT, suggesting a potential benefit of the measure. Consistent with prior studies, Karvellas et al (6,12) also found that patients with ICP monitoring received more ICP-directed therapies than those without. Knowing ICP values, therefore, provides valuable information for performing informed prognostic and therapeutic decisions in patients with ALF.…”

“…Among 56 patients in the study by Karvellas et al (6) who had ICP monitoring and complete complication data, four (7%) of them presented hemorrhagic complications (three intracranial, one spinal), three of which were fatal. ICP monitoring unnecessarily exposes patients who would never show increased ICP (-49% in the study by Karvellas et al 6]) to hemorrhagic complications; the "primum non nocere" principle, however, can also be applied for the misdiagnosis and mistreatment of intracranial hypertension that is assumed without ICP monitoring.…”

Outcomes in Adults With Acute Liver Failure Between 1998 and 2013

“…Blood products were given less frequently over time, possibly as the deleterious effects of unnecessary blood transfusion in intensive care (15) and the futility of routine use and overuse of plasma administration in ALF (16) became better appreciated. Although the prevalence of patients with advanced encephalopathy remained unchanged, we observed less reliance on intracranial pressure monitoring during the later period, which may reflect concern over its limited clinical utility and associated risks (17, 18). The increased prophylactic use of antibiotics seen in the later period preceded the recognition (19) that this therapy does not seem to reduce bloodstream infections in ALF.…”

23.4% Saline Decreases Brain Tissue Volume in Severe Hepatic Encephalopathy as Assessed by a Quantitative CT Marker

“…This quantitative imaging data combined with knowledge of corresponding neurologic function and response to therapy at prior time points may help the physician identify instances of neurologic deterioration with potential to benefit from cerebral edema directed therapies. The contentious role of ICP monitoring in hepatic encephalopathy management (3, 10, 16), failure of studies to show a benefit of invasive ICP monitoring and an association with worse outcome in some patients with liver failure (3, 10), and a large clinical trial that showed equivalence of invasive monitor-guided therapy to therapy guided by surveillance neurologic exams and neuroimaging in traumatic brain injury (29) suggest that there may be a growing role for non-invasive approaches to evaluating disease evolution in select patients.…”

“…However, ICP change is an indirect measure of volume change and because CSF displacement to the spinal subarachnoid space has a buffering effect it is possible for cerebral edema to progress without clearly pathologic ICP elevation (4). Furthermore, invasive ICP monitoring is controversial in hepatic encephalopathy management because of the potential hemorrhagic complications of monitor placement, failure of several studies to identify a survival benefit, and recent evidence that invasive monitoring may be associated with worse outcome for some patients (3, 10). Additionally, the subdural and intraparenchymal ICP monitors most commonly used in liver failure may not accurately reflect compression of brain structures, such as the thalami and brainstem, distant from the device’s pressure transducer (11).…”