No abstract

Cerebral edema is a serious complication of the encephalopathy in fulminant hepatic failure. It is a major cause of death. The mechanisms responsible for its formation are unclear, and the aim of this study was to investigate the ultrastructural appearance of brain capillaries by scanning electron microscopy. Samples of cerebral cortex were obtained immediately after death from nine patients with fulminant hepatic failure (seven cases due to acetaminophen overdose, one caused by hepatitis B and one caused by non-A, non-B hepatitis) by needle biopsy at the site of insertion of an extradural pressure transducer to monitor intracranial pressure. The intercellular tight junctions between capillary endothelial cells were intact. The endothelial cells were swollen, with increased numbers of vesicles and vacuoles. The basement membranes were enlarged and vacuolized and the pericytes had increased numbers of vesicles and vacuoles, indicative of passage of fluid by this route. Marked intracellular swelling of the perivascular astroglial foot processes was present. Thus mainly cytotoxic mechanisms, with cellular swelling, and to a lesser extent vasogenic mechanisms, with altered blood-brain barrier permeability, appear to be involved in the cerebral edema of fulminant hepatic failure.

Fulminant liver failure is a syndrome that is frequently complicated by cerebral edema and increased intracranial pressure. Cerebral blood flow has been reported as high in some studies but low in others. This study undertook to measure cerebral blood flow and cerebral metabolic rate for oxygen in 30 patients with fulminant liver failure in grade 4 encephalopathy and to assess these parameters after intervention with hyperventilation and infusions of mannitol, epoprostenol and acetylcysteine. Cerebral blood flow varied widely, from 14 to 71 ml/100 gm/min (normal range, widely, from 14 to 71 ml/100 gm/min (normal range, 41 to 66), whereas the cerebral metabolic rate for oxygen was low in all patients, 0.16 to 2.03 ml/100 gm/min (normal range, 3.12 to 3.96). Twenty-one of the 30 patients had evidence of anaerobic metabolism with cerebral lactate production. Hyperventilation resulted in a significant decrease in both cerebral blood flow (median, 36 to 28 ml/100 gm/min) and cerebral metabolic rate for oxygen (median, 0.92 to 0.65 ml/100 gm/min); mannitol and acetylcysteine infusions resulted in significant increases in both of these parameters. Prostaglandin I2 infusion did not significantly after cerebral blood flow, but there was a significant increase in cerebral metabolic rate for oxygen. The depressed cerebral metabolic rate for oxygen in patients with fulminant liver failure is inappropriate to metabolic requirements, as demonstrated by both cerebral lactate production and the increase in cerebral oxygen consumption after improvement in cerebral blood flow. Mannitol infusion should remain the main treatment of the cerebral complications of fulminant liver failure.(ABSTRACT TRUNCATED AT 250 WORDS)

than others to choose oversubscribed specialties in which such difficulties would have been expected. It is unlikely that graduates from ethnic minorities were less well qualified than their native European counterparts as there is no evidence that medical school admission policies discriminate in favour of less able applicants from ethnic minorities, and there is considerable evidence that the opposite is the case. "' The strength and consistency of the associations found in this study leave little doubt that discrimination against British trained doctors of ethnic minority origin occurs in the competition for training posts.Most of this discrimination seems to have occurred in the process of shortlisting applicants for senior house Conclusions -These data indicate that a continued increase in prothrombin time on day 4 after overdose and a peak prothrombin time of ¢180 seconds identify at an early stage those patients with a less than 8% chance of survival. Liver transplantation should be considered in patients meeting either of these criteria.