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


CONCLUSIONS
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.
Sen
Sambit
S
Liver Failure Group, The UCL Institute of Hepatology, Division of Medicine, Royal Free and University College Medical School, London.
Rose
Christopher
C
Ytrebø
Lars M
LM
Davies
Nathan A
NA
Nedredal
Geir I
GI
Drevland
Synnøve S
SS
Kjønnø
Marianne
M
Prinzen
Frits W
FW
Hodges
Stephen J
SJ
Deutz
Nicolaas E P
NE
Williams
Roger
R
Butterworth
Roger F
RF
Revhaug
Arthur
A
Jalan
Rajiv
R
D000418:Albumins / Q000494:pharmacology*; D000641:Ammonia / Q000032:analysis; D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D018836:Inflammation Mediators; D019586:Intracranial Hypertension / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D007427:Intracranial Pressure; D017114:Liver Failure, Acute / Q000150:complications* / Q000401:mortality; D011897:Random Allocation; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D034421:Sus scrofa
D000418:Albumins; D018836:Inflammation Mediators; D000641:Ammonia