Background &Aims: About 20% of patients with acute liver failure (ALF) die from increased intracranial pressure (ICP)while awaiting transplantation. This study evaluates the clinical effects and pathophysiologic b...Background &Aims: About 20% of patients with acute liver failure (ALF) die from increased intracranial pressure (ICP)while awaiting transplantation. This study evaluates the clinical effects and pathophysiologic basis of hypothermia in patients with ALF and intracranial hypertension that is unresponsive to standard medical therapy. Methods: Fourteen patients with ALF who were awaiting orthotopic liver transplantation (OLT) and had increased ICP that was unresponsive to sta ndard medical therapy were studied. Core temperature was reduced to 32°C-33°C using cooling blankets. Results: Thirteen patients were successfully bridged to OLT with a median of 32 hours (range, 10-118 hours) of cooling. They underwent OLT with no significant complications related to cooling either before or after OLT and had complete neurologic recovery. ICP before cooling was 36.5 ±2.7 mm Hgand was reduced to 16.3 ±.7 mm Hg at 4 hours, which was sustained at 24 hours (16.8 ±1.5 mm Hg) (P < .0001). Mean arterial pressure and cerebral perfusion pressure increased significantly, and the requirement for inotropes was reduced significantly. Hypothermia produced sustained and significant reduction in arterial ammonia concentration and its brain metabolism, cerebral blood flow, brain cytokine production, and markers of oxidative stress. Conclusions: Moderate hypot hermia is an effective and safe bridge to OLT in patients with ALF who have incr eased ICP that is resistant to standard medical therapy. Hypothermia reduces ICP by impacting on multiple pathophysiologic mechanisms that are believed to be important in its pathogenesis. A large multicenter trial of hypothermia in ALF is justified.展开更多
Background/Aims The study aims were to determine the role of inflammation in the pathogenesis of increased intracranial pressure (ICP) in patients with acute liver failure (ALF) and its interplay with cerebral blood f...Background/Aims The study aims were to determine the role of inflammation in the pathogenesis of increased intracranial pressure (ICP) in patients with acute liver failure (ALF) and its interplay with cerebral blood flow (CBF) and ammonia. Methods Twenty one patients with ALF were studied from the time they were ventilated for grade 4 encephalopathy until receiving specific treatment for increased ICP. Depending upon the ICP, the patients were divided into two groups; those that required specific treatment (ICP>20 mmHg, group 1: n=8, ICP: 32 (28-54) mmHg); and those that did not (ICP≤20 mmHg, group 2: n=13, ICP: 15 (10-20) mmHg). Results Inflammatory markers, arterial ammonia and CBF were significantly higher in the group 1 patients. TNF αlevels correlated with CBF (r=0.80). Four patients from group 2 developed surges of increased ICP (32 (15-112) hours from enrolment). These were associated increases in markers of inflammation and TNF α, and an increase in CBF. There was no change in these inflammatory markers, CBF or ICP in the other 9 group 2 patients. Conclusions The results of this study suggest that inflammation plays an important synergistic role in the pathogenesis of increased ICP possibly through its effects on CBF.展开更多
文摘Background &Aims: About 20% of patients with acute liver failure (ALF) die from increased intracranial pressure (ICP)while awaiting transplantation. This study evaluates the clinical effects and pathophysiologic basis of hypothermia in patients with ALF and intracranial hypertension that is unresponsive to standard medical therapy. Methods: Fourteen patients with ALF who were awaiting orthotopic liver transplantation (OLT) and had increased ICP that was unresponsive to sta ndard medical therapy were studied. Core temperature was reduced to 32°C-33°C using cooling blankets. Results: Thirteen patients were successfully bridged to OLT with a median of 32 hours (range, 10-118 hours) of cooling. They underwent OLT with no significant complications related to cooling either before or after OLT and had complete neurologic recovery. ICP before cooling was 36.5 ±2.7 mm Hgand was reduced to 16.3 ±.7 mm Hg at 4 hours, which was sustained at 24 hours (16.8 ±1.5 mm Hg) (P < .0001). Mean arterial pressure and cerebral perfusion pressure increased significantly, and the requirement for inotropes was reduced significantly. Hypothermia produced sustained and significant reduction in arterial ammonia concentration and its brain metabolism, cerebral blood flow, brain cytokine production, and markers of oxidative stress. Conclusions: Moderate hypot hermia is an effective and safe bridge to OLT in patients with ALF who have incr eased ICP that is resistant to standard medical therapy. Hypothermia reduces ICP by impacting on multiple pathophysiologic mechanisms that are believed to be important in its pathogenesis. A large multicenter trial of hypothermia in ALF is justified.
文摘Background/Aims The study aims were to determine the role of inflammation in the pathogenesis of increased intracranial pressure (ICP) in patients with acute liver failure (ALF) and its interplay with cerebral blood flow (CBF) and ammonia. Methods Twenty one patients with ALF were studied from the time they were ventilated for grade 4 encephalopathy until receiving specific treatment for increased ICP. Depending upon the ICP, the patients were divided into two groups; those that required specific treatment (ICP>20 mmHg, group 1: n=8, ICP: 32 (28-54) mmHg); and those that did not (ICP≤20 mmHg, group 2: n=13, ICP: 15 (10-20) mmHg). Results Inflammatory markers, arterial ammonia and CBF were significantly higher in the group 1 patients. TNF αlevels correlated with CBF (r=0.80). Four patients from group 2 developed surges of increased ICP (32 (15-112) hours from enrolment). These were associated increases in markers of inflammation and TNF α, and an increase in CBF. There was no change in these inflammatory markers, CBF or ICP in the other 9 group 2 patients. Conclusions The results of this study suggest that inflammation plays an important synergistic role in the pathogenesis of increased ICP possibly through its effects on CBF.
