Multicentre Trial of Ethamsylate for Prevention of Periventricular Haemorrhage in Very Low Birthweight Infants

Benson, JohnW.T; Hayward, Christine; Osborne, J P; Schulte, JaneF; Drayton, M.R.; Murphy, J. D.; Rennie, J; Speidel, B D; Cooke, R W

doi:10.1016/s0140-6736(86)91432-7

Cited by 62 publications

(25 citation statements)

References 28 publications

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“…22 -25 Although intraventricular hemorrhage has been attributed to changes in cerebral blood flow to damaged germinal matrix microvessels, the pathophysiology of prevention of hemorrhage remains unclear. 22 Multiple pharmacological agents including phenobarbital, 26 -27 ethamsylate, 28 vitamin E, 29 ' 30 pancuronium, 31 vitamin K, 32 and indomethacin 1 -4 ' 9 have been investigated with varying results in both animal and clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.

Ment

Stewart

Ardito

et al. 1992

Stroke

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Background and Purpose:Although indomethacin has been demonstrated to prevent germinal matrix and intraventricular hemorrhage in clinical and animal studies, the mechanism of action of this agent to prevent hemorrhage remains unclear. Previous studies have demonstrated both that the microvessels in the germinal matrix of newborn beagle pups undergo basement membrane maturation during the first 4 postnatal days and that indomethacin may promote laminin deposition in tumor cell culture systems.Methods: We employed the newborn beagle pup model to test the hypothesis that indomethacin may stimulate laminin deposition in germinal matrix microvessels. Newborn pups were randomized to receive either 0.1 nig/ kg/dose i.p. indomethacin or an equal volume of saline diluent. Pups received doses of study medication once a day for 1, 2, or 3 days and were studied on postnatal days 1, 2, 3, or 4. Pups were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study.Results: Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density among the postnatal ages studied; similarly, there were no differences in vessel density between saline-and indomethacin-treated animals at any postnatal age. Quantification of germinal matrix stained intensity by confocal microscopy demonstrated significant increases in indomethacin-treated pups for both laminin staining at postnatal days 2 (p=0.05) and 3 (/?=0.0009) and type V collagen staining at postnatal day 2 (p=0.011). Although staining for /3 t integrins increased across postnatal ages, there were no differences between saline-and indomethacin-treated animals.Conclusions: These data suggest that indomethacin may stimulate basement membrane deposition in the germinal matrix microvessels of newborn beagle pups to prevent germinal matrix and/or intraventricular hemorrhage. (Stroke 1992;23:1132-1137

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Section: Discussionmentioning

confidence: 99%

Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.

Ment

Stewart

Ardito

et al. 1992

Stroke

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“…However, a meta-analysis found no effect of indomethacin on mortality or long-term neurodevelopmental outcomes on follow-up at 18 to 36 months of age (Fowlie et al, 2010). Two major clinical trials studied the use of ethamsylate for prophylaxis against IVH (Benson et al, 1986;EC Ethamsylate Trial Group, 1994). The first trial in 360 preterm newborns showed a reduction in incidence of IVH, especially the severe form.…”

Section: Prostacyclin Metabolism and Cerebral Intraventricular Hemmentioning

confidence: 99%

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

2012

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“…Ethamsylate has been shown to significantly reduce menorrhagia (Jaffe & Wickham, 1973). Perhaps the most striking result has been a reduction from 30% to 10% in the incidence of intraventricular or parenchymal haemorrhage in very low birth weight infants (Benson et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…It reduces blood loss in menorrhagia (Jaffe & Wickham, 1973) and after surgery (Arnot et al, 1975;Arora & Manford, 1979;Papathodossiou, 1973;Symes et al, 1975). It also reduces neonatal intraventricular haemorrhage (Benson et al, 1986 have previously been shown to be effective (Hawkey et al, 1986;Kitchingman et al, 1988 aspirated and the stomach rinsed of accumulated blood and debris three times with distilled water. The first of three 10 min study periods then commenced.…”

Section: Introductionmentioning

confidence: 99%

Failure of ethamsylate to reduce aspirin‐induced gastric mucosal bleeding in humans.

Daneshmend¹,

Stein²,

Bhaskar³

et al. 1989

Brit J Clinical Pharma

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1 We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding.2 Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3 At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction.4 Aspirin increased bleeding from a rate on placebo of 1.2 ,ul 10 min-' geometric mean (95% confidence limits) (0.7-1.8) p1 10 min-' to 20.0 (11.6-34.2) plI 10 min-', (P < 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) ,ul 10 min-'] was not significantly different from that after aspirin alone. 5 We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

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Multicentre Trial of Ethamsylate for Prevention of Periventricular Haemorrhage in Very Low Birthweight Infants

Cited by 62 publications

References 28 publications

Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.

Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

Failure of ethamsylate to reduce aspirin‐induced gastric mucosal bleeding in humans.

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