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Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: A randomized study*

Sen, Sambit MD, MRCP; Rose, Christopher PhD; Ytrebø, Lars M. MD, PhD; Davies, Nathan A. PhD; Nedredal, Geir I. MD; Drevland, Synnøve S. MD; Kjønnø, Marianne MD; Prinzen, Frits W. PhD; Hodges, Stephen J. PhD; Deutz, Nicolaas E. P. MD, PhD; Williams, Roger CBE, FRCP; Butterworth, Roger F. PhD; Revhaug, Arthur MD, PhD; Jalan, Rajiv MD, PhD, FRCP

doi: 10.1097/01.CCM.0000196203.39832.3C
Laboratory Investigations

Background: Increased intracranial pressure (ICP) worsens the outcome of acute liver failure (ALF). This study investigates the underlying pathophysiological mechanisms and evaluates the therapeutic effect of albumin dialysis in ALF with use of the Molecular Adsorbents Recirculating System without hemofiltration/dialysis (modified, M-MARS).

Methods: Pigs were randomized into three groups: sham, ALF, and ALF + M-MARS. ALF was induced by hepatic devascularization (time = 0). M-MARS began at time = 2 and ended with the experiment at time = 6. ICP, arterial ammonia, brain water, cerebral blood flow (CBF), and plasma inflammatory markers were measured.

Results: ICP and arterial ammonia increased significantly over 6 hrs in the ALF group, in comparison with the sham group. M-MARS attenuated (did not normalize) the increased ICP in the ALF group, whereas arterial ammonia was unaltered by M-MARS. Brain water in the frontal cortex (grey matter) and in the subcortical white matter at 6 hrs was significantly higher in the ALF group than in the sham group. M-MARS prevented a rise in water content, but only in white matter. CBF and inflammatory mediators remained unchanged in all groups.

Conclusion: The initial development of cerebral edema and increased ICP occurs independently of CBF changes in this noninflammatory model of ALF. Factor(s) other than or in addition to hyperammonemia are important, however, and may be more amenable to alteration by albumin dialysis.

From the Liver Failure Group, The UCL Institute of Hepatology, Division of Medicine, Royal Free and University College Medical School, London (SS, NAD, SJH, RW, RJ), London, UK; Department of Cellular Neuroscience, Max-Delbrück Center for Molecular Medicine (CR), Berlin, Germany; Department of Digestive Surgery, University Hospital Northern Norway (LMY, GIN, SSD, MK, AR), Tromsø, Norway; Department of Physiology, Cardiovascular Research Institute (FWP), and Department of Surgery (NEPD), Maastricht University, Maastricht, The Netherlands; and Neuroscience Research Unit, Hôpital Saint-Luc (RFB), Montreal, Quebec, Canada.

S. Sen and C. Rose contributed equally to this work and are joint first authors.

This work is part of an international multicenter collaboration studying various end-organ functions in acute liver failure. Different pathophysiological aspects will be dealt with in separate articles. This article does not contain data published or submitted elsewhere.

Supported by the Liver Research Foundation (London, UK), Norwegian Research Council (Oslo, Norway), and Sir Siegmund Warburg Voluntary Settlement (London, UK). Teraklin AG (Rostock, Germany) provided MARS kits. Dr. Rose was supported by a grant from the Alexander von Humboldt Foundation.

None of the authors have any financial interests to disclose.

© 2006 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins