Sen Sambit, Rose Christopher, Ytrebø Lars M, Davies Nathan A, Nedredal Geir I, Drevland Synnøve S, Kjønnø Marianne, Prinzen Frits W, Hodges Stephen J, Deutz Nicolaas E P, Williams Roger, Butterworth Roger F, Revhaug Arthur, Jalan Rajiv
Liver Failure Group, The UCL Institute of Hepatology, Division of Medicine, Royal Free and University College Medical School, London.
Crit Care Med. 2006 Jan;34(1):158-64. doi: 10.1097/01.ccm.0000196203.39832.3c.
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).
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.
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.
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.
颅内压（ICP）升高会使急性肝衰竭（ALF）的预后恶化。本研究调查其潜在的病理生理机制，并使用无血液滤过/透析的分子吸附循环系统（改良型，M-MARS）评估白蛋白透析对ALF的治疗效果。
将猪随机分为三组：假手术组、ALF组和ALF + M-MARS组。通过肝脏去血管化诱导ALF（时间 = 0）。M-MARS在时间 = 2时开始，在时间 = 6时结束实验。测量ICP、动脉血氨、脑含水量、脑血流量（CBF）和血浆炎症标志物。
与假手术组相比，ALF组的ICP和动脉血氨在6小时内显著升高。M-MARS减轻了（未使其恢复正常）ALF组中升高的ICP，而M-MARS对动脉血氨没有影响。ALF组6小时时额叶皮质（灰质）和皮质下白质的脑含水量显著高于假手术组。M-MARS阻止了含水量的升高，但仅在白质中。所有组的CBF和炎症介质均保持不变。
在这种非炎症性ALF模型中，脑水肿和ICP升高的初始发展独立于CBF变化。然而，除高氨血症之外或与之并存的其他因素很重要，并且可能更易于通过白蛋白透析改变。
