Indomethacin in the Management of Elevated Intracranial Pressure: A Review

Harrigan, Mark R.; Tuteja, Sony; Neudeck, Brien L.

doi:10.1089/neu.1997.14.637

Cited by 43 publications

(24 citation statements)

References 86 publications

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“…17 The dose of indomethacin used in this study has been shown to affect CBF without concomitant changes in neuronal activity, as reflected by local cerebral glucose utilization. 21 However, the mechanisms responsible for indomethacin-mediated cerebral vasoconstriction are complex and include non-prostaglandin-related pathways.…”

Section: Discussionmentioning

confidence: 81%

“…17,24 However, we do not recommend the use of indomethacin to prevent the development of brain edema and cerebral hyperemia in human FHF. The administration of the drug at an early stage of the neurologic picture in FHF could result in renal vasoconstriction and pose risks of gastrointestinal hemorrhage.…”

Section: Discussionmentioning

confidence: 96%

“…14 It has also been proposed that glutamate-mediated activation of cyclooxygenase in astrocytes may result in the generation of vasodilatory prostaglandins such as PGE 1 and PGE 2 . 28 The poor penetration of indomethacin into brain tissue 17 makes the astrocyte a less-likely target for indomethacin's effect on CBF. We did observe, however, a reduction in the CSF levels of 6-keto PGF 1␣ with indomethacin, a sampling site that suggests nonvascular effects of the drug.…”

Section: Discussionmentioning

confidence: 99%

“…We designed an experiment in which indomethacin, a known cerebral vasoconstrictor, 17 was coadministered to PCA rats receiving an ammonia infusion. The drug is a nonselective inhibitor of endothelial cyclooxygenase and has minimal penetration into the brain.…”

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confidence: 99%

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Indomethacin prevents the development of experimental ammonia-induced brain edema in rats after portacaval anastomosis

Chung

2001

Hepatology

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Brain edema is a leading cause of death in fulminant hepatic failure (FHF). Patients with FHF who develop brain edema and intracranial hypertension exhibit an increase in cerebral blood flow (CBF). 1-3 Changes in cerebral perfusion have been documented with different techniques, are not related to alterations in systemic hemodynamics, 4 and contribute to intracranial hypertension by increasing cerebral blood volume. Although some subjects with FHF show a reduced CBF, 5,6 the majority of these patients do not exhibit brain edema. 1-2 An increase in cerebral perfusion has been described in experimental models of severe hyperammonemia. 7 Recent studies link elevated plasma ammonia levels to the development of cerebral herniation in FHF. 8,9 Insight into the importance of cerebral perfusion arises from work in an experimental model of brain edema, i.e., rats with portacaval anastomosis (PCA) infused with ammonium acetate. In this preparation, brain swelling and an increase in intracranial pressure (ICP) predictably develop after 3 hours of ammonia infusion in the absence of acute liver injury, allowing the performance of pathophysiologic studies in an otherwise stable model. 10 Using the radioactive microsphere technique, we have shown a selective increase in CBF at 3 hours of infusion, 11 without concomitant changes in systemic hemodynamics or flow to other regional beds. In this model, the increase in cerebral perfusion appears related to an intracerebral signal generated after the detoxification of ammonia to glutamine in astrocytes. Administration of methionine-sulfoximine, an irreversible inhibitor of glutamine synthetase, ameliorated the increase in CBF seen in this model. 12 The nature of the intracerebral signal has not been elucidated. Our initial postulate of increased nitric oxide synthesis in the brain 12,13 led to experiments using nonselective and selective inhibitors of nitric oxide synthase isoforms. Under these conditions, the rise in CBF was still present. 14 We proposed that the development of cerebral hyperemia is necessary for the appearance of cerebral swelling in this model. Mild hypothermia (33°C and 35°C) was shown to prevent the development of ammonia-induced brain edema 11 as well as forestall brain water accumulation in a model of FHF. 15 Clinical studies confirm the protective effect of hypothermia to 32°C in patients with FHF and severe intracranial hypertension. 3 The mechanisms by which hypothermia reduces ICP may be multiple, 16 but an effect on cerebral perfusion has been well documented in our experimental model 11 as well as in humans with FHF. 3 High values of CBF seen in both the experimental and human condition are normalized by hypothermia.We designed an experiment in which indomethacin, a known cerebral vasoconstrictor, 17 was coadministered to PCA rats receiving an ammonia infusion. The drug is a nonselective inhibitor of endothelial cyclooxygenase and has minimal penetration into the brain. 18 If a selective effect on cerebral blood flow influences the development of brain ...

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Indomethacin prevents the development of experimental ammonia-induced brain edema in rats after portacaval anastomosis

Chung

2001

Hepatology

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“…10 It was therefore suggested that alternative treatments should be developed for GC use in the management of patients with a solid tumor, to take care of inflammation and edema, nausea and emesis. 5,10 Several agents have been considered for the non-steroidal treatment of brain edema, including indomethacin, 5,11,12 which inhibits both COX-1 and COX-2, boswellic acid 13 and celecoxib. 14 Celecoxib is a selective non-steroidal anti inflammatory inhibitor of the COX-2 enzyme and inhibits edema development after experimental brain bleeding.…”

Section: Introductionmentioning

confidence: 99%

Avoiding glucocorticoid administration in a neurooncological case

Rutz

Höfer²,

Peghini³

et al. 2005

Cancer Biology & Therapy

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KEY WORDSglioblastoma, celecoxib, dexamethasone, cerebrospinal, blood brain barrier, temozolomide ABBREVIATIONS GC glucocorticoid GBM glioblastoma multiforme WHO Grade IV CSF cerebrospinal fluid ACKNOWLEDGEMENTSWe thank Ingrid Herr for valuable suggestions. Clinical Case ReportAvoiding Glucocorticoid Administration in a Neurooncological Case ABSTRACTRestricting glucocorticoid (GC) use in the treatment of patients with a solid tumor may help improving outcome. Here, we report administration of celecoxib rather than dexamethasone to prevent brain edema in a patient with a cerebellar glioblastoma multiforme WHO grade IV (GBM) upon the patient's request, as well as determining cerebrospinal fluid (CSF) and serum concentrations. CSF concentration (0.04 µM) was 54 times below serum concentration (2.18 µM), or 2500 times below levels inhibiting GBM cells in vitro (100 µM), revealing a blood CSF barrier for celecoxib. The patient did not require dexamethasone for the entire treatment. GC administration hence was avoided successfully in this case. The role of COX-2 inhibitors in treatment of GBM is detailed, leading to the conclusion of a pressing need for a clinical evaluation of non-steroidal COX-2 inhibitors with the ability to penetrate into brain tumors.

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