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Changing strategies in the treatment of aneurysmal subarachnoid haemorrhage: challenging the second bleed
Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
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: urn:nbn:se:liu:diva-23794Local ID: 3312ISBN: 91-7373-849-2 (print)OAI: oai:DiVA.org:liu-23794DiVA: diva2:244109
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
List of papers
1. Sudden onset headache: a prospective study of features, incidence and causes
Open this publication in new window or tab >>Sudden onset headache: a prospective study of features, incidence and causes
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2002 (English)In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 22, no 5, 354-360 p.Article in journal (Refereed) Published
Abstract [en]

Sudden onset headache is a common condition that sometimes indicates a life- threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache = TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants > 18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26956 (URN)10.1046/j.1468-2982.2002.00368.x (DOI)11589 (Local ID)11589 (Archive number)11589 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
2. Education of referring doctors about sudden onset headache in subarachnoid hemorrhage
Open this publication in new window or tab >>Education of referring doctors about sudden onset headache in subarachnoid hemorrhage
2001 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 103, no 4, 238-242 p.Article in journal (Refereed) Published
Abstract [en]

Objectives – Forty percent of patients with aneurysmal subarachnoid hemorrhage have prodromal warning episodes and difficulties in identifying these events are repeatedly documented. Modifications of diagnostic and referral patterns through educational programs of local doctors may help to identify such patients before a major devastating rupture occurs.

Materials and methods– A teaching program about sudden onset headache, targeting referring doctors, was systematically applied and its impact on early misdiagnosis of ruptured aneurysms was prospectively studied.

Results– Forty percent of all studied patients experienced a warning episode, manifested as apoplectic headache, prior to hospitalization. An initial diagnostic error was evident in 12% of the patients. Diagnostic errors were reduced by 77% as a result of continuous interaction between neurosurgeons and local physicians.

Conclusion– Misdiagnosed warning episodes cause greater loss of lives and higher morbidity on a population basis than does delayed ischemic complications from vasospasm in aneurysmal SAH. Teaching programs focused on local physicians have a profound impact on outcome at low cost.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27678 (URN)10.1034/j.1600-0404.2001.d01-27.x (DOI)12416 (Local ID)12416 (Archive number)12416 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
3. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study
Open this publication in new window or tab >>Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study
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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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27755 (URN)10.3171/jns.2002.97.4.0771 (DOI)12500 (Local ID)12500 (Archive number)12500 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
4. Intraoperative complications in aneurysm surgery: a prospective national study
Open this publication in new window or tab >>Intraoperative complications in aneurysm surgery: a prospective national study
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2002 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 96, no 3, 515-522 p.Article in journal (Refereed) Published
Abstract [en]

Object. With increasing use of endovascular procedures, the number of aneurysms treated surgically will decline. In this study the authors review complications related to the surgical treatment of aneurysms and address the issue of maintaining quality standards on a national level.

Methods. A prospective, nonselected amalgamation of every aneurysm case treated in five of six neurosurgical centers in Sweden during 1 calendar year was undertaken (422 patients; 7.4 persons/100,000 population/year). The treatment protocols at these institutions were very similar. Outcome was assessed using clinical end points. In this series, 84.1% of the patients underwent surgery, and intraoperative complications occurred in 30% of these procedures. Poor outcome from technical complications was seen in 7.9% of the surgically treated patients. Intraoperative aneurysm rupture accounted for 60% and branch sacrifice for 12% of all technical difficulties. Although these complications were significantly related to aneurysm base geometry and the competence of the surgeon, problems still occurred apparently at random and also in the best of hands (17%). The temporary mean occlusion time in the patients who suffered intraoperative aneurysm rupture was twice as long as the temporary arrest of blood flow performed to aid dissection.

Conclusions. The results obtained in this series closely reflect the overall management results of this disease and support the conclusion that surgical complications causing a poor outcome can be estimated on a large population-based scale. Intraoperative aneurysm rupture was the most common and most devastating technical complication that occurred. Support was found for a more liberal use of temporary clips early during dissection, regardless of the experience of the surgeon. Temporary regional interruption of arterial blood flow should be a routine method for aneurysm surgery on an everyday basis. A random occurrence of difficult intraoperative problems was clearly shown, and this factor of unpredictability, which is present in any preoperative assessment of risk, strengthens the case for recommending neuroprotection as a routine adjunct to virtually every aneurysm operation, regardless of the surgeon's experience.

Keyword
intracranial aneurysm, intraoperative aneurysm rupture, complication, hypothermia, neuroprotection
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27754 (URN)10.3171/jns.2002.96.3.0515 (DOI)12499 (Local ID)12499 (Archive number)12499 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
5. Routine application of neuroprotection in surgery of intracranial aneurysms
Open this publication in new window or tab >>Routine application of neuroprotection in surgery of intracranial aneurysms
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

To evaluate the value of routine application ofneuroprotection and the use of temporary clips (TCL) in every day aneurysm surgery 203 patients with a total of 236 aneurysms were included in the a perioperative moderate hypothermia (MHT, <34° C) protocol. Poor grade patients (Hunt & Hess IV-V) were excluded fi·om the study. Induction of MHT averaged 0.98+/-0.37 hours and was based on a protocol for administration of cold, intravenous crystalloid fluid and barbiturates. Blood pressure was stable throughout MHT. 40% of the patients needed inotropic support during the first 12 postoperative hours. Cardiac arrhythmia was infrequent and when occurring always of benign character. In 8%, pulmonary problems with central venous congestion and/or poor systemic oxygenation occurred.

In total, temporary clipping was used in 66 cases (mean occlusion time being 10.5 ±7.3 min), 50% of which had not been expected pre-operatively. Overall, 40 aneurysms (75% 1-12 mm in size) ruptured during dissection - corresponding to 20% of the cases without preplanned use of TCL.

Excluding biasing confounding factors, TCL did not affect the outcome following aneurismal surgery. The study lends support to the idea that TCL should be considered a routine method for all aneurysm surgery.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84851 (URN)
Available from: 2012-10-24 Created: 2012-10-24 Last updated: 2012-10-24Bibliographically approved

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Fridriksson, Steen M.

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