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Outcomes and Complications of Intracranial Pressure Monitoring in Acute Liver Failure: A Retrospective Cohort Study*

Karvellas, Constantine J. MD, SM1; Fix, Oren K. MD2; Battenhouse, Holly MSc3; Durkalski, Valerie PhD3; Sanders, Corron PhD4; Lee, William M. MD4; for the U.S. Acute Liver Failure Study Group

doi: 10.1097/CCM.0000000000000144
Clinical Investigations

Objective: To determine if intracranial pressure monitor placement in patients with acute liver failure is associated with significant clinical outcomes.

Design: Retrospective multicenter cohort study.

Setting: Academic liver transplant centers comprising the U.S. Acute Liver Failure Study Group.

Patients: Adult critically ill patients with acute liver failure presenting with grade III/IV hepatic encephalopathy (n = 629) prospectively enrolled between March 2004 and August 2011.

Intervention: Intracranial pressure monitored (n = 140) versus nonmonitored controls (n = 489).

Measurements and Main Results: Intracranial pressure monitored patients were younger than controls (35 vs 43 yr, p < 0.001) and more likely to be on renal replacement therapy (52% vs 38%, p = 0.003). Of 87 intracranial pressure monitored patients with detailed information, 44 (51%) had evidence of intracranial hypertension (intracranial pressure > 25 mm Hg) and overall 21-day mortality was higher in patients with intracranial hypertension (43% vs 23%, p = 0.05). During the first 7 days, intracranial pressure monitored patients received more intracranial hypertension–directed therapies (mannitol, 56% vs 21%; hypertonic saline, 14% vs 7%; hypothermia, 24% vs 10%; p < 0.03 for each). Forty-one percent of intracranial pressure monitored patients received liver transplant (vs 18% controls; p < 0.001). Overall 21-day mortality was similar (intracranial pressure monitored 33% vs controls 38%, p = 0.24). Where data were available, hemorrhagic complications were rare in intracranial pressure monitored patients (4 of 56 [7%]; three died). When stratifying by acetaminophen status and adjusting for confounders, intracranial pressure monitor placement did not impact 21-day mortality in acetaminophen patients (p = 0.89). However, intracranial pressure monitor was associated with increased 21-day mortality in nonacetaminophen patients (odds ratio, ~ 3.04; p = 0.014).

Conclusions: In intracranial pressure monitored patients with acute liver failure, intracranial hypertension is commonly observed. The use of intracranial pressure monitor in acetaminophen acute liver failure did not confer a significant 21-day mortality benefit, whereas in nonacetaminophen acute liver failure, it may be associated with worse outcomes. Hemorrhagic complications from intracranial pressure monitor placement were uncommon and cannot account for mortality trends. Although our results cannot conclusively confirm or refute the utility of intracranial pressure monitoring in patients with acute liver failure, 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.

1Divisions of Hepatology and Critical Care Medicine, University of Alberta, Edmonton, AB, Canada.

2Division of Gastroenterology, University of California, San Francisco, CA.

3Faculty of Medicine, Medical University of South Carolina, Charleston, SC.

4Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX.

* See also p. 1304.

Dr. Karvellas designed the study, performed statistical analysis, drafted, and revised the final manuscript. Dr. Fix provided content expertise, provided advice on data collection and analysis, and made significant revisions to the final manuscript. Ms. Battenhouse prepared the database, performed significant statistical analysis, and made significant revisions to the final manuscript. Dr. Durkalski provided statistical expertise and significantly revised the final manuscript. Dr. Sanders assisted in preparation of the database, queried enrolling sites for missing data, and made significant revisions to the final manuscript. Dr. Lee (lead investigator, U.S. Acute Liver Failure Study Group) assisted in the design of the study, provided content expertise, and made significant revisions to the final manuscript. All authors have reviewed and approved the final manuscript.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Dr. Karvellas received support for article research from the National Institutes of Health (NIH) (United States Acute Liver Failure Study Group [U.S. ALFSG] is funded by an NIH grant [National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK, DK U-01 58369]). Dr. Fix is employed by University of California San Francisco and received support for article research from NIH. His institution received grant support from NIDDK/NIH. Ms. Battenhouse received support for article research from NIH. Her institution received grant support from NIH (U01-DK58369) and is employed by NIH. Dr. Durkalski is employed by Medical University of South Carolina and received support for article research from NIH. His institution received grant support from the Medical University of South Carolina (funding provided by ALFSG grant U01 DK0583691). Dr. Sanders received support for article research from NIH grant U-01 58369 (from NIDDK). Dr. Lee consulted for Lilly, Novartis, and Pfizer (drug safety review) and received support for article research from NIH. His institution received grant support from University of Texas Southwestern (UTSW) MCD (NIH grant U-01 58369 to UTSW) and UTSW Medical Center (Anadys, BMS, BI, Gilead, Merck, Siemens, Vertex).

For information regarding this article, E-mail: dean.karvellas@ualberta.ca

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins