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Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study
Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
Neurosurgical Department, Sahlgrenska University Hospital, Gothenburg, Sweden.
Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
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2002 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 97, no 4, 771-778 p.Article in journal (Refereed) Published
Abstract [en]

Object. By pursuing a policy of very early aneurysm treatment in neurosurgical centers, in-hospital rebleeds can be virtually eliminated. Nonetheless, as many as 15% of patients with aneurysm rupture suffer ultraearly rebleeding with high mortality rates, and these individuals are beyond the reach of even the most ambitious protocol for diagnosis and referral. Only drugs given immediately after the diagnosis of subarachnoid hemorrhage (SAH) has been established at the local hospital level can, in theory, contribute to the minimization of such ultraearly rebleeding. The object of this randomized, prospective, multicenter study was to assess the efficacy of short-term antifibrinolytic treatment with tranexamic acid in preventing rebleeding.

Methods. Only patients suffering SAH verified on computerized tomography (CT) scans within 48 hours prior to the first hospital admission were included. A 1-g dose of tranexamic acid was given intravenously as soon as diagnosis of SAH had been verified in the local hospitals (before the patients were transported), followed by doses of 1 g every 6 hours until the aneurysm was occluded; this treatment did not exceed 72 hours. In this study, 254 patients received tranexamic acid and 251 patients were randomized as controls. Age, sex, Hunt and Hess and Fisher grade distributions, as well as aneurysm locations, were congruent between the groups. Outcome was assessed at 6 months post-SAH by using the Glasgow Outcome Scale (GOS). Vasospasm and delayed ischemic neurological deficits were classified according to clinical findings as well as by transcranial Doppler (TCD) studies. All events classified as rebleeding were verified on CT scans or during surgery.

Conclusions. More than 90% of patients reached the neurosurgical center within 12 hours of their first hospital admission after SAH; 70% of all aneurysms were clipped or coils were inserted within 24 hours of the first hospital admission. Given the protocol, only one rebleed occurred later than 24 hours after the first hospital admission. Despite this strong emphasis on early intervention, however, a cluster of 27 very early rebleeds still occurred in the control group within hours of randomization into the study, and 13 of these patients died. In the tranexamic acid group, six patients rebled and two died. A reduction in the rebleeding rate from 10.8 to 2.4% and an 80% reduction in the mortality rate from early rebleeding with tranexamic acid treatment can therefore be inferred. Favorable outcome according to the GOS increased from 70.5 to 74.8%. According to TCD measurements and clinical findings, there were no indications of increased risk of either ischemic clinical manifestations or vasospasm that could be linked to tranexamic acid treatment. Neurosurgical guidelines for aneurysm rupture should extend also into the preneurosurgical phase to guarantee protection from ultraearly rebleeds. Currently available antifibrinolytic drugs can provide such protection, and at low cost. The number of potentially saved lives exceeds those lost to vasospasm.

Place, publisher, year, edition, pages
2002. Vol. 97, no 4, 771-778 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-27755DOI: 10.3171/jns.2002.97.4.0771Local ID: 12500OAI: oai:DiVA.org:liu-27755DiVA: diva2:248307
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Changing strategies in the treatment of aneurysmal subarachnoid haemorrhage: challenging the second bleed
Open this publication in new window or tab >>Changing strategies in the treatment of aneurysmal subarachnoid haemorrhage: challenging the second bleed
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Despite considerable advances in the management of aneurysmal subarachnoid haemorrhage (SAH) over the past decades, the overall outcome is still disappointing. Currently, not more than six patients out of every ten with a ruptured aneurysm, reaching hospital alive, will recover to a normal life. Apart from the direct effects of the initial haemorrhage, vasospasm and rebleeding clearly stand out as the leading causes of unfavourable results in this capricious disease, and both of these factors seem potentially amenable to further improvement in therapeutic intervention.

Ever since the concept of early aneurysm surgery gained wider acceptance, the focus of the neurosurgical community has shifted from re bleeding towards the problem of vasospasm and delayed ischaemic neurological deficits (DIND). During recent years, vasospasm has attracted at least five times more attention than rebleeding in terms of published articles, and huge research efforts have been offered in the pursuit of a medical solution to this problem. Although progress has been made in the treatment of vasospasm during the last decades, DIND continues to contribute significantly to unfavourable outcome in the management of aneurysmal SAH victims. Recent series report an average of 13.5% of patients suffering DIND, leading to unfavourable outcome in 7% of all cases reaching hospital for treatment. Contrary to rebleeding, there is a dominance of morbidity (4.5%) over mortality (2.5%).

Historically, the efforts aimed at reducing the risk of rebleeding have mostly been related to the controversial question of the timing of surgery. The current performance in many centers, with over 90% of all ruptured aneurysms seen being occluded within 24 hours from the haemorrhage, gives the impression that we have reached the ultimate protection against rebleeding, with little left to improve in that field. However, the term rebleeding, as we are used to defming it, apparently only represents a part of a wider spectrum of recurrent aneurysm ruptures. Index haemorrhages preceeded by warning leaks and intraoperative ruptures occurring after index haemonhages also share the features of devastating impact on clinical condition and on outcome, and from a practical point of view it may be meaningful to consider all these recurrent ruptures as a common entity - the second bleed.

In the studies presented in this thesis, the second bleed has shown to have a profound impact on management outcome in aneurysmal SAH. It accounts for morbidity and mortality in at least 12% of all patients receiving treatment, which is roughly one-third of all patients with poor management outcome. Evidently, prevention of most recurrent bleeds are within the reach of current management protocols. Modifications of strategies in use are presented, that include new guidelines for the pre-neurosurgical care to ensure detection of warning leaks and to provide protection against ultra-early rebleeds, that cannot be reached by early aneurysm occlusion. In the neurosurgical phase, modifications of the surgical protocol allowing for a routine application of intraoperative neuroprotection and liberal use of temporary clipping are advocated.

By refocusing the second bleed, identification of it's various forms and modification of treatment protocols for ruptured aneurysms aimed at reducing these recurrent bleeds, many losses can be turned into good outcome, at a cost that is much lower than the cost of pursuing the final solution of vasospasm.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2004. 69 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 870
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-23794 (URN)3312 (Local ID)91-7373-849-2 (ISBN)3312 (Archive number)3312 (OAI)
Public defence
2004-11-26, Föreläsningssal Eken, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-24Bibliographically approved

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Hillman, JanFridriksson, SteenYu, Zhengquan

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