Reye's syndrome: assessment of intracranial monitoring.

Jenkins, J. G.; Glasgow, J. F. T.; Black, G. W.; Fannin, T. F.; Hicks, Elaine; Keilty, S. R.; Crean, Peter

doi:10.1136/bmj.294.6568.337

Cited by 41 publications

(9 citation statements)

References 8 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[19][20][21] Swelling of cerebral cortical astrocytes, the characteristic feature of experimental ALF, 5 is observed following ammonia infusions to young primates, 22 and exposure of rat cortical astrocytes in culture to ammonia results in significant cell swelling. 6 precipitous increases in blood ammonia, similar to those reported in ALF, are associated with brain edema in other conditions such as Reye' s syndrome 7 and urea cycle enzymopathies. 8 The hepatic devascularized rat has been widely used for the study of pathophysiological mechanisms implicated in the phenomenon of brain edema in ALF.…”

Section: Discussionsupporting

confidence: 52%

“…Exposure of various brain preparations to millimolar concentrations of ammonia in vitro results in significant cell swelling. 5,6 Furthermore, precipitous increases in blood ammonia concentrations are associated with brain edema in conditions such as Reye' s syndrome 7 and urea cycle enzymopathies. 8 L-Ornithine-L-aspartate (OA) has been proven to be effective in lowering blood ammonia concentrations in both experimental and human chronic liver failure.…”

mentioning

confidence: 99%

See 1 more Smart Citation

L-Ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure

et al. 1999

View full text Add to dashboard Cite

Brain edema sufficient to cause intracranial hypertension and brain herniation remains a major cause of mortality in acute liver failure (ALF). Studies in experimental animal models of ALF suggest a role for ammonia in the pathogenesis of both encephalopathy and brain edema in this condition. As part of a series of studies to evaluate the therapeutic efficacy of ammonia-lowering agents, groups of rats with ALF caused by hepatic devascularization were treated with L-ornithine-L-aspartate (OA), an agent shown previously to be effective in reducing blood ammonia concentrations in both experimental and human chronic liver failure. Treatment of rats in ALF with infusions of OA (0.33 g/kg/h, intravenously) resulted in normalization of plasma ammonia concentrations and in a significant delay in onset of severe encephalopathy. More importantly, brain water content was significantly reduced in OA-treated rats with ALF. These protective effects of OA were accompanied by increased plasma concentrations of several amino acids including glutamate, ␥-aminobutyric acid (GABA), taurine, and alanine, as well as the branched-chain amino acids, leucine, isoleucine, and valine. Increased availability of glutamate following OA treatment provides the substrate for the major ammonia-removal mechanism (glutamine synthetase). Plasma (but not cerebrospinal fluid) glutamine concentrations were increased 2-fold (P F .02) in OAtreated rats, consistent with increased muscle glutamine synthesis. Direct measurement of glutamine synthetase activities revealed a 2-fold increase following OA treatment. These findings demonstrate a significant ammonia-lowering effect of OA together with a protective effect on the development of encephalopathy and brain edema in this model of ALF. (HEPATOLOGY 1999;30:636-640.)Brain swelling culminating in increased intracranial pressure and subsequent brain herniation remains the major cause of death in acute liver failure (ALF). Although the pathogenesis of brain edema in ALF has not been fully elucidated, there is a growing body of evidence to suggest that ammonia (either directly or indirectly) plays a predominant role. In experimental animal models of ALF resulting from hepatectomy, 1 hepatic devascularization, 2,3 or toxic liver injury, 4 brain edema is a consistent finding, and brain ammonia frequently reaches millimolar concentrations. Exposure of various brain preparations to millimolar concentrations of ammonia in vitro results in significant cell swelling. 5,6 Furthermore, precipitous increases in blood ammonia concentrations are associated with brain edema in conditions such as Reye' s syndrome 7 and urea cycle enzymopathies. 8 L-Ornithine-L-aspartate (OA) has been proven to be effective in lowering blood ammonia concentrations in both experimental and human chronic liver failure. 9-11 A recent randomized, clinical trial of OA treatment revealed significant reductions in blood ammonia in cirrhotic patients concomitant with a significant improvement of neuropsychiatric symptoms. 10 In view of these findin...

show abstract

Section: Discussionsupporting

confidence: 52%

mentioning

confidence: 99%

L-Ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Brain am-monia concentrations at coma/edema stages of encephalopathy in experimental ALF may reach concentrations as high as 5 mM (Swain et al, 1992a,b). Hyperammonemia of a similar magnitude to that seen in ALF is observed in patients with Reye's syndrome or urea cycle enzymopathies (Brusilow, 1985;Jenkins et al, 1987) and, in both cases, brain edema is a significant feature. Furthermore, exposure of brain cells to millimolar concentrations of ammonia in vitro leads to significant cell swelling (Norenberg et al, 1991).…”

Section: Introductionmentioning

confidence: 60%

Untitled

Chatauret¹,

Rose²,

Butterworth³

2002

Metabolic Brain Disease

View full text Add to dashboard Cite

Mild hypothermia (32 C-35°C) reduces intracranial pressure in patients with acute liver failure and may offer an effective adjunct therapy in the management of these patients. Studies in experimental animals suggest that this beneficial effect of hypothermia is the result of a decrease in blood-brain ammonia transfer resulting in improvement in brain energy metabolism and normalization of glutamatergic synaptic regulation. Improvement in brain energy metabolism by hypothermia may result from a reduction in ammonia-induced decrease of brain glucose (pyruvate) oxidation. Restoration of normal glutamatergic synaptic regulation by hypothermia may be the consequence of the removal of ammonia-induced decreases in expression of astrocytic glutamate transporters resulting in normal glutamate neurotransmitter inactivation in brain. Randomized controlled clinical trials of hypothermia are required to further evaluate its clinical impact.

show abstract

“…This hypothesis derived from the accepted beneficial effects of ICP monitoring (and closely linked treatment of ICH) on survival both in comatose patients with traumatic brain injury 2,3 and, less convincingly, in patients with the most severe forms of Reye's syndrome. 4 Up to now, no randomized controlled trial (RCT) supports this hypothesis and this lack of evidencebased practice makes the prospective, albeit uncontrolled, study by Vaquero et al, 5 an important piece of work regarding the still controversial issue: is it useful to monitor ICP in patients with grade III-IV encephalopathy secondary to ALF?…”

Section: Commentsmentioning

confidence: 96%

Intracranial pressure monitoring in patients with acute liver failure: A questionable invasive surveillance

Bernuau

Durand

2006

Hepatology

View full text Add to dashboard Cite

Monitoring of intracranial pressure (ICP) in acute liver failure (ALF) is controversial as a result of the reported complication risk (approximately 20%) and limited therapeutic options for intracranial hypertension. Using prospectively collected information from 332 patients with ALF and severe encephalopathy, we evaluated a recent experience with ICP monitoring in the 24 centers constituting the U.S. ALF Study Group. Special attention was given to the rate of complications, changes in management, and outcome after liver transplantation (LT). ICP monitoring was used in 92 patients (28% of the cohort), but the frequency of monitoring differed between centers (P < .001). ICP monitoring was strongly associated with the indication of LT (P < .001). A survey performed in a subset of 58 patients with ICP monitoring revealed intracranial hemorrhage in 10.3% of the cohort, half of the complications being incidental radiological findings. However, intracranial bleeding could have contributed to the demise of 2 patients. In subjects listed for LT, ICP monitoring was associated with a higher proportion of subjects receiving vasopressors and ICP-related medications. The 30-day survival post-LT was similar in both monitored and nonmonitored groups (85% vs. 85%). In conclusion, the risk of intracranial hemorrhage following ICP monitoring may have decreased in the last decade, but major complications are still present. In the absence of ICP monitoring, however, patients listed for LT appear to be treated less aggressively for intracranial hypertension. In view of the high 30-day survival rate after LT, future studies of the impact of intracranial hypertension should also focus on long-term neurological recovery from ALF.

show abstract

Reye's syndrome: assessment of intracranial monitoring.

Abstract: Direct measurements of arterial blood pressure and intracranial pressure were recorded in 39 patients aged 3-6 months to 5 years 11 months with Reye's syndrome judged to be stage 2 or beyond. Of 33 patients who survived, 27 made a full recovery and six were

Cited by 41 publications

References 8 publications

L-Ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure

L-Ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure

Untitled

Intracranial pressure monitoring in patients with acute liver failure: A questionable invasive surveillance

Contact Info

Product

Resources

About