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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the wide acceptance of liver transplantation as a therapeutic alternative in fulminant hepatic failure (FHF), the successful management of patients with this syndrome has acquired a new urgency. Topping the list of medical problems is the development of brain swelling. Two decades after the recognition of its importance, brain edema and intracranial hypertension still constitute a major cause of death in these patients. In a more recent classification of FHF, brain edema was especially prominent in those subjects with "hyperacute failure," in whom a period of 7 days or less elapsed between the development of jaundice and encephalopathy. The goal of this review is to discuss two aspects of this clinical problem. On one hand, elucidation of its pathogenesis should lead to a more rational therapeutic approach; such an information would also be valuable to understand the relationship between hepatic encephalopathy and brain edema, a source of controversy. Studies of pathogenic mechanisms are difficult to perform in humans and animal models of FHF have proven valuable, as brain swelling can be detected with some regularity. On the other hand, an increasing array of techniques is now available in the intensive care setting to monitor patients with FHF. Of these, intracranial pressure monitoring has received the most critical attention. However, concerns with the risks of craniotomy and the need to acquire more dynamic information has led several groups to explore non-invasive methods that evaluate the consequences of intracranial hypertension. Their role, though potentially exciting, is still uncertain.
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PMID:Cerebral edema and intracranial pressure monitoring. 934 64

Hyperventilation is frequently used to prevent or postpone the development of cerebral edema and intracranial hypertension in patients with fulminant hepatic failure (FHF). The influence of such therapy on regional cerebral blood flow (rCBF) remains, however, unknown. In this study the CBF-distribution pattern was determined within the first 12 hours after development of hepatic encephalopathy (HE) stage 4 before and during hyperventilation. Ten consecutive patients (median age 48 [range 33-57] years) with FHF and 9 healthy controls (median age 54 [24-58] years) had rCBF determined by single photon emission computed tomography (SPECT) using intravenous injection of 133Xenon. For determination of high resolution CBF pattern, the patients were also studied with 99mTc-hexa-methylpropyleneamine oxime (HMPAO) in the hyperventilation condition. There was no significant difference in the rCBF distribution pattern during normoventilation as compared with hyperventilation. The anterior to posterior (AP) ratio was significantly lower in patients as compared with healthy controls. After hepatic recovery and disappearance of HE, 3 patients had restored normal rCBF distribution pattern as compared with healthy controls. We conclude that in sedated patients with FHF, a relatively lower rCBF is found in the frontal regions and in the basal ganglia as compared with posterior regions. This rCBF-distribution pattern was not aggravated during hyperventilation. It is speculated that this change of rCBF in patients with FHF may render the frontal brain regions more susceptible to hypoxia. The relative frontal rCBF decrease was shown to be reversible with hepatic recovery and alleviation of HE.
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PMID:Regional cerebral blood flow during mechanical hyperventilation in patients with fulminant hepatic failure. 1057 13

Acute liver failure (ALF) is a devastating disease leading to multiorgan dysfunction. The most dramatic impact of ALF is on the brain, as hepatic encephalopathy and intracranial hypertension (IH) develop. IH is associated with systemic hemodynamic instability, alterations in the regulation of cerebral blood flow and the development of cerebral edema. This review focuses on the pathophysiology of IH with special emphasis on cerebral blood flow and the development of cerebral edema. Based on these considerations, both traditional and new treatments for the management of IH in the future are discussed.
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PMID:Intensive care management of patients with acute liver failure with emphasis on systemic hemodynamic instability and cerebral edema: a critical appraisal of pathophysiology. 1111 Jun 22

Patients with fulminant hepatic failure (FHF) frequently develop cerebral edema and intracranial hypertension. The aim of this study was to evaluate circulating S-100b and neuron-specific enolase (NSE) levels as markers of neurological outcome in patients with FHF. In a subgroup of patients, the cerebral flux of S-100b and NSE was measured. We included 35 patients with FHF, 6 patients with acute on chronic liver disease (AOCLD), 13 patients with cirrhosis of the liver without hepatic encephalopathy, and 8 healthy subjects. Blood samples were obtained from catheters placed in the radial artery and internal jugular bulb. The net cerebral flux of S-100b and NSE was measured, and the effect of short-term hyperventilation, as well as the effect of high-volume plasmapheresis, on circulating levels of these two biomarkers was determined. Blood levels of S-100b were greater in patients with FHF and AOCLD than patients with cirrhosis and healthy subjects (median, 0.39 microg/L; range, 0.02 to 10.31 microg/L; and 1.11 microg/L; range, 0.19 to 4.84 microg/L v 0.05 microg/L; range, 0.02 to 0.27 microg/L; and 0.09 microg/L; range, 0.02 to 0.15 microg/L, respectively; P <.05, ANOVA). Among patients with FHF, blood levels of NSE tended to be greater in patients who subsequently developed cerebral herniation than in survivors (median, 10.5 microg/L; range, 5.2 to 15.9 microg/L v 5.1 microg/L; range, 2.8 to 12 microg/L; P =.05). There was no net cerebral flux of S-100b or NSE. Short-term hyperventilation had no effect on any of these measures, whereas high-volume plasmapheresis reduced circulating S-100b levels from 0.45 microg/L (range, 0.19 to 10.31 microg/L) to 0.42 microg/L (range, 0.11 to 6.35 microg/L; P =.01). In conclusion, blood levels of S-100b were elevated in almost all patients with FHF and AOCLD, but were unrelated to survival. Conversely, NSE showed a clear tendency toward greater circulating levels in patients with FHF who subsequently developed cerebral herniation than in survivors. This finding encourages further evaluation of NSE as a marker of neurological outcome in FHF.
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PMID:S-100b and neuron-specific enolase in patients with fulminant hepatic failure. 1288 7

Hepatic encephalopathy (HE) in acute liver injury signifies a serious prognosis. Brain edema and intracranial hypertension are major causes of death in this syndrome. Comparison of HE in acute liver failure (ALF) with that of cirrhosis allows recognition of important differences and similarities. A key role for ammonia in the pathogenesis of both HE and brain edema is now firmly supported by clinical and experimental data. Additional factors, such as infection, products of the necrotic liver, and synergistic toxins, may contribute to an altered mental state. A low plasma osmolarity, high temperature, and both high and low arterial pressure may affect brain water content. A combined derangement of cellular osmolarity coupled with cerebral hyperemia can explain the development of brain edema in ALF. Increasingly, study of the mechanisms responsible for brain swelling provides critical information for understanding the pathogenesis of HE.
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PMID:Pathogenesis of hepatic encephalopathy in acute liver failure. 1452 79

There is increasing evidence that terlipressin is useful in patients with cirrhosis and hepatorenal syndrome, but there are no data of its use in patients with acute liver failure (ALF) in whom hepatorenal syndrome is common. Although terlipressin produces systemic vasoconstriction, it produces cerebral vasodilatation and may increase cerebral blood flow (CBF). Increased CBF contributes to intracranial hypertension in patients with ALF. The aim of this study was to evaluate the safety of terlipressin in patients with ALF with respect to cerebral hemodynamics. Six successive patients with ALF were ventilated electively for grade IV hepatic encephalopathy. Patients were monitored invasively and CBF was measured (Kety-Schmidt technique). Measurements were made before and at 1, 3, and 5 hours after intravenous (single bolus) administration of terlipressin (0.005 mg/kg), median, 0.25 mg (range, 0.2-0.3 mg). There was no significant change in heart rate, mean arterial pressure, or cardiac output. CBF and jugular venous oxygen saturation both increased significantly at 1 hour (P = 0.016). Intracranial pressure increased significantly at 1 hour (P = 0.031), returning back to baseline values at 2 hours. In conclusion, administration of terlipressin, at a dose that did not alter systemic hemodynamics, resulted in worsening of cerebral hyperemia and intracranial hypertension in patients with ALF and severe hepatic encephalopathy. These data suggest the need to exercise extreme caution in the use of terlipressin in these patients in view of its potentially deleterious consequences on cerebral hemodynamics.
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PMID:Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy. 1476 81

Hepatic encephalopathy and brain edema are important complications in the course of a patient with acute liver failure. Presumed unrelated for many years, increasing evidence suggests that an increase in brain water is seen in all forms of hepatic encephalopathy. Ammonia, traditionally linked to the pathogenesis of hepatic encephalopathy, plays an important role in the increase in brain water. In acute liver failure, an osmotic disturbance in the astrocyte, in combination with an alteration of cerebral blood flow results in overt brain edema and intracranial hypertension. In cirrhosis, magnetic resonance techniques indicate the presence of a brain osmotic disturbance. Several clinical factors modulate the development of brain swelling.
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PMID:Brain edema in acute liver failure. A window to the pathogenesis of hepatic encephalopathy. 1509 1

Portal hypertension, the main complication of cirrhosis, is responsible for its most common complications: variceal hemorrhage, ascites, and portosystemic encephalopathy. Portal hypertension is the result of increased intrahepatic resistance and increased portal venous inflow. Vasodilatation (splanchnic and systemic) and the hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and portal hypertension. Gastroesophageal varices result almost solely from portal hypertension, although the hyperdynamic circulation contributes to variceal growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium retention, which, in turn, is secondary to vasodilatation and activation of neurohumoral systems. The hepatorenal syndrome represents the result of extreme vasodilatation, with an extreme decrease in effective blood volume that leads to maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous bacterial peritonitis is a potentially lethal infection of ascites that occurs in the absence of a local source of infection. Portosystemic encephalopathy is a consequence of both portal hypertension (shunting of blood through portosystemic collaterals) and hepatic insufficiency that result in the accumulation of neurotoxins in the brain. This review covers the recent advances in the pathophysiology and management of the complications of portal hypertension.
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PMID:Portal hypertension. 1570 65

In patients with recent onset renal insufficiency, the decision to perform combined kidney/liver transplantation (CKLT) vs. orthotopic liver transplantation alone (OLTa) can be difficult. We hypothesized that duration of renal dysfunction may correlate with creatinine elevation after liver transplantation. We retrospectively identified 69 liver transplantation patients with pretransplantation creatinine > or =1.5 mg/dL (53 OLTa, 13 CKLT). Variables analyzed were presence of hepatorenal syndrome, creatinine, Model for End-Stage Liver Disease score, albumin, age, race, gender, cause of liver disease, diabetes mellitus, hypertension, and history of ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, renal replacement therapy (RRT), and transjugular intrahepatic portosystemic shunting. Duration of pretransplantation renal dysfunction was predictive of 6- and 12-month creatinine post-OLTa. Area under the receiver operating characteristic (ROC) curve for prediction of 12-month renal insufficiency by renal dysfunction duration was 0.71; optimal duration cutoff was 3.6 weeks. We applied a multivariable model, derived from OLTa patients, to CKLT subjects with definite or possible hepatorenal syndrome. Predicted 12-month creatinine without renal transplantation was >2.0 mg/dL for each patient. CKLT patients as opposed to OLTa patients had longer duration of renal dysfunction (median, 18.1 vs. 2.7 weeks, P < 0.001), higher creatinine (median 4.0 versus 1.7 mg/dL, P < 0.001), and higher rate of pretransplantation RRT (62% vs. 7%, P < 0.001). Adjusting for baseline characteristics, CKLT patients had lower creatinine than OLTa patients at 6 months (P =0.15) and 12 months (P =0.01) after transplantation. In conclusion, duration, but not cause, of renal dysfunction predicts renal outcome in OLTa recipients. Prospective studies may use duration of renal dysfunction to help identify CKLT candidates.
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PMID:Renal function after orthotopic liver transplantation is predicted by duration of pretransplantation creatinine elevation. 1612 56

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with both acute and chronic liver dysfunction. It defines prognosis in acute liver injury in which patients can succumb with brain oedema and intracranial hypertension. In cirrhosis, it occurs insidiously, causing a range of neuropsychiatric disturbances. For over a century, we have known that ammonia is important in its pathogenesis and astrocytes are the cells that have been most commonly found to be affected neuropathologically. In this review we centre on the story of the 'sick astrocyte', focusing on the molecular pathogenesis of HE and the important role that inflammation has on its modulation. We describe new developments in this area with respect to potential targets for future therapies.
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PMID:The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. 1615 92


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