From the Department of Neurology and MR Institute, Leopold Franzens
University Innsbruck (F.T.A.); Department of Neurology, Karl Franzens
University, Graz (F.Z.); Neurological Clinic, Maria Gugging (M.B.); Institute
of System Sciences, Johannes Kepler University (W.P.), Linz; 2nd Neurological
Clinic, Rosenhügel (B.M.), Vienna; and Department of Neurology, Alma
Mater Rudolfina, Vienna (K.Z.), Austria.
Correspondence to Franz T. Aichner, MD, Department of Neurology and Magnetic Resonance, University Hospital, Anichstraße 35, 6020 Innsbruck, Austria. E-mail mri-institut{at}uibk.ac.at
Methods—MAHST is a randomized, double-blind, placebo-controlled
study of hypervolemic hemodilution (HHD) within 6 hours of a clinically
first ischemic stroke localized in the middle cerebral artery
territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5
(HES) and was tested against pure rehydration with Ringer's lactate
over a period of 5 days. Our primary outcome measure was clinical
improvement within 7 days as measured by the Graded Neurologic Scale
(GNS). We performed an adaptive interim analysis to reevaluate
the study goal after entering half of the projected number of
patients (n=200). At least 600 patients per group would have been
required for significant results, and therefore we decided to terminate
the trial.
Results—Ninety-eight patients received HHD and 102 patients
placebo. The baseline characteristics were comparable between both
groups. In the HHD group the absolute reduction of the hematocrit was
2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a
reduction in the placebo group of 1% and 1.9%, respectively.
Intention-to-treat analysis showed no significant difference of
the change of the GNS scores between HHD-treated (median, -8.5; 95%
confidence interval, -14.2 to -4.0) and placebo-treated patients
(median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and
GNS scores remained similar in both treatment groups throughout the
trial. At 3 months, slightly more HHD patients showed complete
independence on the Barthel Index (28 versus 24), and fewer HHD than
placebo patients had died (13 versus 17), but these differences were
not statistically significant. HHD treatment was not associated with
any specific adverse event.
Conclusions—Mild HHD is safe but failed to demonstrate a
significant beneficial effect over the pure rehydration regimen in
patients with acute ischemic stroke.
In part, negative and discordant clinical results may have resulted
from too long and variable intervals between ischemic
stroke and the onset of hemodilution therapy. The Scandinavian, North
American, and Italian hemodilution trials used entry times of 48, 24,
and 12 hours, respectively.11 13 14 The
proportion of patients in whom hemodilution was started within 6 hours
was only 6% in the Scandinavian trial and 55% in the Italian trial
and has not been indicated in the North American study.
Hypovolemia may have counteracted any beneficial rheological effect of
hemodilution even more seriously in some
trials.11 12 13 18 Intermittent reduction of the
circulatory volume is a consequence of phlebotomy before the adequate
substitution of fluids and may be even more dangerous in stroke victims
who are prone to dehydration. Data from the North American trial and
the experience of others strongly argue for an increase of cardiac
output in order to benefit from
hemodilution.14 17 19 However, vigorous fluid
therapy may have the drawback of invasive monitoring and could increase
the risk of cardiopulmonary complications.
Experience has also accumulated in regard to the choice of the
hemodiluting agent. Albumin and LMWD have been used in the
majority of previous trials.9 10 11 12 13 15 16 17 19 LMWD
is associated with an increase of viscosity when given for more than 3
days because of the accumulation of large dextran
molecules.22 23 24 Furthermore, LMWD may exacerbate
the formation of brain edema and conveys a potential risk of
anaphylactic side effects.22 Recently, the
complex polymer HES has been introduced, which seems to lack these
negative properties and also decreases thrombocyte and erythrocyte
aggregation.23 24
Based on these data, we designed a hemodilution trial that incorporated
the aspects of early treatment, ease of application, minimal risk for
the patient, and a well-defined patient population.
Selection of Patients
Diagnostic Work-up
Outcome Measures
Treatment and Randomization
The randomization scheme was generated by permutation of random numbers
(Software Randomsys, University of Linz) in 150 blocks with a length of
four patients each by an external biometrics consultant. This
block formation should guarantee an even distribution between HES- and
placebo-treated patients within every center. In practice, Laevosan
Gesellschaft provided a numbered box containing active or placebo
treatment in identical bottles for every patient. These bottles were
stained transparently yellow to mask slight differences in color
between HES and Ringer's lactate. The difference between both
solutions was too discrete to become apparent in a regular infusion
set. Every medication box contained a sealed envelope with the
randomization code, which was allowed to be broken only in case of
emergency.
Sample Size and Interim Analysis
Statistical Analysis
The statistical tests performed on all baseline variables comprised
the Mann-Whitney U test for ordinal or interval
variables and Fisher's exact test or
For the neurological scores, the worst-case principle was used with
respect to missing subscores. In case of a missing score at a certain
time point, the respective score of the last visit was carried forward.
In cases of death, the worst possible scores were assigned.
After HHD there was an immediate drop of the hematocrit from 44.0% to
41.95% on day 2 (relative reduction, 4.7%). However, pure rehydration
was also associated with a reduction of hematocrit from 43.8% to
42.8% (relative reduction, 2.3%) on day 2. In the following days, the
hematocrit of HHD-treated patients continued to decline, with a maximum
relative reduction of 10% on day 5 (difference from hematocrit
reduction by rehydration, 7.6%), while the hematocrit of
placebo-treated patients remained rather stable. A significantly lower
hematocrit in HHD- than in placebo-treated patients was reached on day
4 of the trial, but the absolute differences remained small. Table 2
Neurological recovery as described by the GNS score was similar in both
HHD and placebo treated patients. The Figure
Four more patients of the HHD group gained full independence in
activities of daily living over the 3-month follow-up period compared
with placebo-treated patients. However, the median score of the Barthel
Index was not significantly different between the HHD group (median,
45; 95% CI, 25 to 65) and placebo-treated patients (50; 95% CI, 25.75
to 64.25) at the end of the study (P=.66). Thirteen patients
died in the HHD group and 17 patients in the placebo group. The causes
of death and the number of other serious adverse events observed in
both treatment groups are listed in Table 4
The time window beyond which the evolution of damage prohibits any
possible impact of hemodilution is not known. In previous trials,
patients were enrolled as long as 72 hours after stroke. The
Scandinavian Stroke Study investigated 363 patients with an inclusion
time of 48 hours. Treatment was started within less than 12 hours in
28% of patients, but this subgroup did not show a more favorable
effect of hemodilution than the remainder of the study
population.12 The American hemodilution trial
studied 88 patients within 24 hours and found a slight benefit for
those patients treated no later than 12 hours after
stroke.14 The Italian hemodilution trialists
included all their patients within 12 hours after onset of symptoms.
They found a treatment effect neither for the entire study population
in regard to case fatalities and disability at 6 months nor for the
55% of patients in whom treatment was started within 6
hours.13 MAHST is the first study that required
hemodilution to be initiated within 6 hours in all patients; however,
in the Italian study, 702 (55%) of the 1267 patients were already
randomized within 6 hours after their first symptoms. A maximal delay
of 6 hours has been considered a reasonable interval both on
pathophysiological and practical
grounds.31 However, this may still be too long
for hemodilution to become effective, especially when a mild
hemodilution regimen is used. Some support for this assumption has
recently come from a study by Yanaka et al.8
These investigators found that hemodilution in an animal model
significantly reduced the size of infarction and improved the
neurological outcome when initiated within 3 hours after onset of
ischemia. Hemodilution was ineffective when delayed for 6
hours.
Experimental studies suggest a hematocrit of 30% as the limit below
which oxygen delivery becomes compromised because increased
transportation from augmentation of cerebral blood flow no longer
compensates for the reduction of oxygen-carrying capacity. These
results cannot be directly transferred to stroke victims, who tend to
suffer from more widespread vascular disease and in whom compensatory
mechanisms may be already exhausted to some extent. It is therefore
assumed that the level of hematocrit at which oxygen delivery begins to
decline in ischemic brain tissue is much higher, but the exact
threshold is not yet known.18 Previous controlled
hemodilution trials targeted a hematocrit of 33% to 38% with an
absolute reduction by 4% to 7%. This was usually achieved by
phlebotomy and corresponded to a decrease of 9% to 16% in relative
terms.21 MAHST aimed at a more gradual reduction
of the hematocrit. We chose not to include venesection in our treatment
regimen because we wanted to avoid any possibility of hypovolemia and
because many patients dislike the procedure. We also decided not to
infuse larger amounts of fluid because we were concerned about the need
for more extensive monitoring and an increased risk of brain edema or
cardiac failure. Therefore, on day 2 the hematocrit of our HHD patients
had dropped by 2% (relative reduction, 4.7%), and maximal reduction
by 4% (relative reduction, 10%) was not obtained before day 5. This
mild hemodilution regimen might certainly be a further explanation for
the failure of MAHST. Otherwise, our treatment scheme was well
tolerated, and there has been no evidence of a better outcome of
patients with >15% relative reduction of hematocrit in the
Scandinavian and Italian trials.
In the HHD group there was a tendency toward a lower median
systolic blood pressure and a higher blood glucose level at
entry. Since these differences did not reach statistical significance,
their impact on the outcome of HHD treated patients cannot be
defined.
Differences between HHD- and placebo-treated patients in MAHST may have
been minimized by a positive treatment effect of rehydration therapy
alone. Changes in physical activity such as bed rest and placebo
treatment with crystalloids also exert some hemodiluting effect, as
noted previously and confirmed by MAHST. In the Amsterdam study,
Goslinga et al19 observed a significant
reduction in mortality and a higher rate of independence at home after
hemodilution of patients with a baseline hematocrit <45%. In patients
with a higher hematocrit, however, pure rehydration with crystalloids
was superior to hemodilution, and rehydrated patients with high
hematocrit (
Meta-analysis of previous trials has clearly shown that even
optimal hemodilution may not be expected to provide dramatic
benefits.21 Hemodilution could help to salvage
the ischemic penumbra but may not be able to reduce the core of
infarction. Recently, much more aggressive treatment strategies such as
intravenous thrombolysis resulted in only
modest treatment benefits at best.32 Although we
made every effort to reduce the heterogeneity of our
study population, the calculation of group sizes needed for obtaining
statistically significant results was still flawed by expectations that
were too high. This became evident from the interim analysis
that we performed after 200 patients were entered. In contrast to the
American Hemodilution in Stroke Study Group, MAHST showed only a 7%
difference regarding the primary end point, ie, the neurological
deficit before treatment versus day 7.14 Both a
conservative and a nonconservative calculation showed that a sample
size of 600 to 800 patients per group would be necessary for the
results to become statistically significant.
At present, no proven treatment strategies exist for acute
ischemic stroke except the intravenous application
of recombinant tissue plasminogen activator, as
suggested by the National Institute of Neurological Disorders and
Stroke trial.32 This medication is associated
with potentially serious complications and may be given only to a
well-defined patient population that seems to be relatively small. In
this context and in view of some previous hemodilution trials that were
terminated prematurely, the low rate of adverse events in MAHST is
noteworthy. Overall, the total number of deaths was smaller in HHD-
than in placebo-treated patients, and we observed no association of
treatment with any specific adverse event. Our mild HHD regimen and the
choice of the hemodiluting agent are likely to have been major
contributing factors.
HES is characterized by the average molecular weight (200 kD), the
degree of molar substitution (0.5=ratio of substituted/total of
anhydroglucose residues on the polymer chain), and the pattern of
substitution (ie, the ratio of substitution on residues
C2/C6).22 23 The latter two
parameters control the degradation of HES to smaller
molecules by serum amylase and its subsequent renal excretion. In
addition to being well tolerated, HES also decreases thrombocyte and
erythrocyte aggregation.23 Certain other trials
have used LMWD.11 13 17 This substance causes an
increase in viscosity when administered for more than 3 days because of
the accumulation of large dextran molecules. More importantly, LMWD may
exacerbate edema formation in cerebral ischemia and conveys a
potential risk of anaphylactic side effects; however, the
pharmacological evidence that HES may be superior to LMWD is not
substantiated by the findings of this clinical study.
In conclusion, mild HHD after the MAHST treatment protocol did not show
a statistically significant treatment effect. Consequently, there is
still no scientific support for the use of hemodilution in clinical
practice.
Sponsor
Contract Research Organization
Biometric Advisor
Control Committee
Scientific Committee
Received December 5, 1997;
revision received January 12, 1998;
accepted January 12, 1998.
© 1998 American Heart Association, Inc.
Original Contributions
Hypervolemic Hemodilution in Acute Ischemic Stroke
The Multicenter Austrian Hemodilution Stroke Trial (MAHST)
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
Background and Purpose—Experimental
studies suggest a beneficial effect of hemodilution on acute
ischemic stroke. This was not proven by previous multicenter
trials in the clinical setting. Various reasons have been suggested for
the failure of these studies, which we attempted to consider in the
Multicenter Austrian Hemodilution Stroke Trial (MAHST).
Key Words: clinical trials • hemodilution • hydroxyethyl starch • stroke, ischemic
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
Experimental
studies have shown hemodilution to increase cerebral blood flow in
areas of ischemic brain. This may translate into a reduction of
the size of infarction and improve neurological
outcome.1 2 3 4 5 6 7 8 These beneficial results were
accomplished by a maximum interval between ischemia and
hemodilution of less than 3 hours, a low target hematocrit of 32%, and
the use of low-molecular-weight HES. However, a number of controlled
clinical trials and a subsequent meta-analysis failed to
confirm the clinical benefit of hemodilution
therapy.9 10 11 12 13 14 15 16 17 18 19 20 21 This discrepancy may be explained
by various differences between experimental and clinical
conditions.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
This double-blind study was performed at 15 hospitals in Austria
between October 1992 and December 1996. It tested whether mild HHD with
low substituted HES is safe and conveys any benefit over pure
rehydration with crystalloid fluid regarding neurological recovery from
acute ischemic stroke.
Consecutive stroke patients were considered for inclusion if
they had sudden onset of focal neurological symptoms and signs
characteristic of middle cerebral artery infarction such as
hemiparesis, sensory impairment, and aphasia25 ;
if they scored <70 points on the Mathew Scale; and if therapy could be
initiated within 6 hours after the onset of
stroke.26 Patients were required to give informed
consent and to be available for a follow-up period of 3 months. The
study design was approved by the local ethical committees. For
pathophysiological reasons we did not consider
patients with an initial hematocrit <42% or >50% in women and
<42% or >52% in men and excluded patients with a body weight <40
kg or >110 kg. Further reasons for exclusion were the need for
thrombolytic therapy or full heparinization according
to the treating physician's opinion, a systolic blood pressure
>200 mm Hg or a diastolic blood pressure
>110 mm Hg at the start of infusion, impaired consciousness
with a score of <11 points on the Glasgow Coma Scale, any previous
cerebrovascular event lasting more than24 hours, vascular surgery
within the preceding 4 weeks, and evidence of any other neurological
disease or of another preexisting condition possibly affecting the
course of stroke or obscuring the evaluation of stroke severity.
Patients were excluded for considerations of general and systemic
safety if they were <40 years of age; pregnant or lactating; had any
serious systemic infection or other acute life-threatening diseases,
obstructive lung disease, hemorrhagic diathesis, significant renal
insufficiency as indicated by serum creatinine >2 mg/dL,
or had suffered from myocardial infarction within the past 4 weeks; or
if they met any other conditions contraindicated for the drugs to be
used. Patients were not allowed to have had any colloidal volume
substitution within the week before study entry, nor were they allowed
to participate or be considered for participation in another study over
the entire treatment and follow-up period.
All patients underwent ECG and sonographic examination of the
carotid arteries within 3 days of stroke onset.
Hemodynamically significant carotid artery obstruction
was defined as a stenosis >80% or occlusion. CT was not
available within 6 hours after the onset of stroke in some of the
participating centers, and therefore we allowed CT or MRI of the brain
to be performed within the first week. Infarcts were classified as
lacunar or nonlacunar. Each scan was reviewed centrally by a
neuroradiologist blinded to all clinical information, including
treatment group.
Stroke severity was determined according to the GNS (inverted
Glasgow Coma Scale, language and other cortical functions, cranial
nerves, motor function, sensory function), which ranged from 0 to 100
points, immediately at the start of therapy.27
The GNS was repeatedly performed after 24 ±4 hours, on day 7, 3 weeks
±2 days, and 3 months ±5 days after the acute event. Improvement in
the GNS scores over the treatment period, ie, between the start of HHD
and day 7, was the primary outcome variable. Domains that could not
be properly assessed by the GNS were given the worst rating, ie, death
was 100 points on the GNS. Stroke severity was additionally rated
according to the Mathew Scale on day 7 and during the follow-up visits.
The patients' ability to perform activities of daily living was
measured by means of the Barthel Index.28 Care
was taken to have these evaluations consistently performed by
the same investigator. To homogenize the interpretation of
stroke severity between centers, a training video was rated by every
participating physician before the start of the trial. Recurrent stroke
and death of any cause were pretermination study end points. Adverse
events were monitored by a Safety Committee.
A loading dose of 250 mL 10% HES in
physiological saline (Expahes 10%, Laevosan
Gesellschaft) was given within 1 hour. This infusion was followed by
another 250 mL of HES and 250 mL of Ringer's lactate administered over
a period of 4 hours. After an interval of at least 3 hours, patients
received 250 mL HES parallel with or prior to 250 mL Ringer's lactate
(over 3 to 4 hours) twice daily for a total of 10 doses. Placebo
treatment consisted of equivalent volumes of Ringer's lactate. During
the treatment phase patients were allowed to receive a maximum daily
dose of 5000 IU of low-molecular-weight heparin or of 15 000 IU of
unfractionated heparin for the prevention of deep venous thrombosis.
Acetylsalicylic acid (in an initial dose of 250 to
300 mg and subsequent daily doses of 100 mg) was recommended for
secondary stroke prevention. This comedication was at the discretion of
the treating physician. Any further concomitant use of drugs with a
potential effect on cerebrovascular ischemic diseases was
prohibited.
The North American Hemodilution in Stroke Study Group reported a
difference of 40% on the GNS over 3 days of treatment in favor of the
hemodiluted group.14 In view of the possible
therapeutic efficacy of the rehydration therapy of controls and our
moderate hemodilution regimen, we estimated a smaller difference of
15% to 20% in the change of the GNS during an interval of 7 days.
This was also in agreement with other clinical
data.10 15 With 
=5% (two-tailed), ß=10%,
the required sample size was 200 patients per group
(intention-to-treat). The determination of the sample size was made
with the software N (IDV-Gauting). After 200 inclusions, an adaptive
interim analysis was performed because of slow recruitment and
limited financial resources.29 An of 24% and
the observed difference in the improvement of the GNS scores between
the HHD group and the placebo group of only 7% resulted in an adjusted
of 3.6% for continuing the study. From both a conservative and a
nonconservative view (per protocol, intention-to-treat, with and
without death), this would have implied a sample size of 600 to 800
patients per group. Because this figure clearly exceeded the initially
planned sample size, the trial was stopped.
After termination of the trial, all 200 patients were included
in the intention-to-treat analysis. The per-protocol
analysis comprised 158 patients. In addition to a descriptive
analysis, a confirmatory analysis was performed on both
the basis of the intention-to-treat and per-protocol principles.
Decisions concerning valid cases or dropouts were made by the blinded
control committee in accordance with the study protocol before the
codes were broken. 
2
test for nominal variables in the form of frequency tables. The
Mann-Whitney U test was used to test the group differences
of the GNS scores between onset of therapy and day 7 (primary outcome
variable). The Mann-Whitney U test and Fisher's exact
test were also used for testing secondary outcome variables, as
appropriate.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
At the termination of the study 98 patients had been randomized to
HHD and 102 patients to placebo treatment. Both groups were comparable
in regard to age, sex, hematocrit, type of stroke and pathogenetic
factors, interval to treatment, and severity of stroke symptoms as
measured by the GNS and the Mathew Scale (Table 1
). There was a tendency toward a lower
median systolic blood pressure and a higher blood glucose level
in the HHD group, but these differences did not reach statistical
significance (Table 1). Acetylsalicylic acid and
subcutaneous heparin were given to almost all patients, except for one
patient in the HHD group and one in the placebo group. Seventy-seven
patients in the HHD group and 81 patients in the placebo group
completed the study per protocol. The baseline characteristics of these
subsets were distributed to the intention-to-treat population in a
similar manner, and there were no significant differences between the
HHD and the placebo groups except for a lower median systolic
blood pressure in HHD-treated individuals (150 versus 160 mm
Hg; P=.04). Forty-two patients were not considered for the
per-protocol analysis for the following reasons: cerebral
hematomas (n=11), brain stem and cerebellar infarcts (n=3), protocol
violations such as Mathew score >70, low hematocrit, elevated
creatine, cardiac complications, and others.
View this table:
[in a new window]
Table 1. Group Characteristics at Randomization into
MAHST (Intention-to-Treat) illustrates the time course of the
hematocrit in both treatment groups according to intention-to-treat
analysis.
View this table:
[in a new window]
Table 2. Time Course of Hematocrit in MAHST
(Intention-to-Treat)
shows clinical improvement to have been
greatest within the first 7 days of the trial, with a parallel course
of the median of the GNS scores of both treatment groups throughout the
trial. Accordingly, there was no significant difference in the absolute
increase in the GNS scores over time between HHD- and placebo-treated
patients. This was true for intention-to-treat as well as for
per-protocol analysis (Table 3).
Similar results were obtained when we analyzed patients'
improvement by means of the Mathew Scale. In the HHD group, the median
of the Mathew score (intention-to-treat) improved from 57 (95% CI, 55
to 60.2) before treatment to 65 (57 to 68.2) on day 7 and 66.5 (62.0 to
75.4) after 3 months. This compares with 56 (54 to 58) before treatment
(P=.5), 60.5 (56.6 to 65) on day 7 (P=.31), and
65 (61.6 to 69) after 3 months (P=.32) in the placebo
group.
View larger version (38K):
[in a new window]
Figure 1. Barthel Index at 3 months according to intention-to-treat and
per-protocol analysis. Number of patients is indicated for
different ranges according to the National Institute of Neurological
Disorders and Stroke trial.
View this table:
[in a new window]
Table 3. Improvement of the GNS in MAHST . HHD treatment was not associated with
any specific type of serious adverse event, and we observed no
anaphylactic reactions.
View this table:
[in a new window]
Table 4. Serious Adverse Events and Deaths
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
The beneficial effect of hemodilution in experimental settings has
been attributed to the augmentation of cerebral blood flow that follows
the decrease of blood viscosity and is expected to surpass a lowering
of the oxygen capacity of the blood.30
Simultaneously increasing cardiac output is believed to
enhance this effect.14 In view of these
considerations, we decided to use an HHD regimen. We attempted to
choose a reasonable time window for the start of therapy and to select
patients in whom treatment response would not be obscured by poorly
defined neurological deficits or preceding cerebrovascular damage.
Despite these efforts, MAHST failed to demonstrate a significant
clinical benefit. Various aspects deserve discussion. 
45%) fared significantly better than their counterparts
in the normal to low hematocrit range. In this context it seems
important to note that MAHST was the first study to test hemodilution
against a predetermined treatment regimen of the placebo group.
Moreover, because we avoided phlebotomy, MAHST could be performed in a
truly blinded fashion.
Selected Abbreviations and Acronyms
CI
=
confidence interval
GNS
=
Graded Neurologic Scale
HES
=
hydroxyethyl starch 200/0.5
HHD
=
hypervolemic hemodilution
LMWD
=
low-molecular-weight dextran
MAHST
=
Multicenter Austrian Hemodilution Stroke Trial
Appendix 1
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
Centers
Universitat-Klinik für Neurologie Innsbruck:
Franz Aichner, Christoph Schmidauer, Hans-Peter Haring, Gregor Rungger.
Landesnervenkrankenhaus Graz, Neurologische Abteilung: Hans
Werner Wege, Karin Lambauer, Wolfgang Doppler, Walter Kreuzig.
A.ö. KH der Barmherzigen Schwestern Wels, Neurologische
Abteilung: Felix Holzner, Peter Wolf. A.ö. KH St.
Pölten, Abteilung für Neurologie und Psychiatrie: Ulf
Baumhackl, Andreas Gatterer, Andrea Taut. Neurologische
Universitätsklinik Graz: Franz Fazekas, Kurt Niederkorn,
Susanne Horner, Peter Kapeller, Reinhold Schmidt. N.ö.
Landesnervenklinik Gugging, Neurologische Abteilung: Michael
Brainin, Peter Bosak, Ulrike Brix, Georg Funk, Andreas Seiser, Michaela
Maria Steiner, Sigrid Schwarz. Kaiser-Franz-Josef-Spital der
Stadt Wien, Neurologische Abteilung: Wolfgang Grisold,
Peter Hitzenberger, Klaus Lindner, Udo Zifko.
Wagner-Jauregg-Krankenhaus Linz, Neurologische Abteilung:
Eberhard Deisenhammer, Arthur Bernhard Brucker. Krankenhaus der
Stadt Wien Lainz, Neurologische Abteilung: Kurt Jellinger, Rembert
Vollmer, Barbara Zeman. A.ö. Krankenhaus der Stadt Linz,
Neurologische Abteilung: Dieter Klingler, Eduard Diabl.
Landesnervenklinik-Salzburg, Neurologische Abteilung:
Gunther Ladurner, Oliver Lesicky. Neurologisches Krankenhaus der
Stadt Wien Rosenhügel, II. Neurologische Abteilung: Bruno
Mamoli, Wolfgang Pankl. A.ö. Landeskrankenhaus Klagenfurt,
Neurologische Abteilung: Erik Rumpl, Dieter Christofl, Hannelore
Fischer, Gerhard Noisternig, Christian Stadler. A.ö.
Landeskrankenhaus Villach, Neurologische und Psychosomatische
Abteilung: Herwig Scholz, Gustav Raimann, Alexander Kronfuss.
Wilhelminenspital der Stadt Wien, Neurologische Abteilung:
Elfriede Sluga, Johann Donis, Johannes Mikocki.
Laevosan Gesellschaft mbH, Estermannstraße 17, Linz, Austria.
Project manager, Wolfgang Schimetta.
KFM-Klinische Forschung GmbH, München Mercedes Apecechea,
Siegfried Freytag, Ira Kurz, Wolfgang Kleiber, and Günther
Kleiber.
Werner Pölz, Institut für Systemwissenschaften,
Universität Linz.
Michael Hennerici, Universität Mannheim; Dieter Volc,
Prosenex-Ambulatorium Schottenfeld, Wien; and Hermann Zeumer,
Universität Hamburg.
Franz T. Aichner (Innsbruck), Ulf Baumhackl (St Pölten),
Michael Brainin (Gugging), Arthur Bernhard Brucker (Linz), Eberhard
Deisenhammer (Linz), Eduard Diabl (Linz), Franz Fazekas
(Graz), Franz Gerstenbrand (Innsbruck), Wolfgang Grisold (Wien),
Hans-Peter Haring (Innsbruck), Peter Hitzenberger (Wien), Felix Holzner
(Wels), Kurt Jellinger (Wien), Dieter Klingler (Linz), Walter Kreuzig
(Graz), Gunther Ladurner (Salzburg), Helmut Lechner (Graz), Bruno
Mamoli (Wien), Kurt Niederkorn (Graz), Wolfgang Pankl (Wien), Paul
Pürgyi (Linz), Erik Rumpl (Klagenfurt), Christoph
Schmidauer (Innsbruck), Reinhold Schmidt (Graz), Herwig Scholz
(Villach), Andreas Seiser (Gugging), Elfriede Sluga (Wien), Hans Werner
Wege (Graz), and Karl Zeiler (Wien).
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
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  H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, May 22, 2007; 115(20): e478 - e534. [Abstract] [Full Text] [PDF]
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 H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Stroke, May 1, 2007; 38(5): 1655 - 1711. [Abstract] [Full Text] [PDF]
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E. Ruttmann, J. Willeit, H. Ulmer, O. Chevtchik, D. Hofer, W. Poewe, G. Laufer, and L. C. Muller Neurological Outcome of Septic Cardioembolic Stroke After Infective Endocarditis Stroke, August 1, 2006; 37(8): 2094 - 2099. [Abstract] [Full Text] [PDF]
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 Evidence-based Colloid Use in the Critically Ill: American Thoracic Society Consensus Statement Am. J. Respir. Crit. Care Med., December 1, 2004; 170(11): 1247 - 1259. [Full Text] [PDF]
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C. S. Weaver, J. Leonardi-Bee, F. J. Bath-Hextall, and P. M.W. Bath Sample Size Calculations in Acute Stroke Trials: A Systematic Review of Their Reporting, Characteristics, and Relationship With Outcome Stroke, May 1, 2004; 35(5): 1216 - 1224. [Abstract] [Full Text] [PDF]
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K. Uchino, D. Billheimer, and S. C. Cramer Entry Criteria and Baseline Characteristics Predict Outcome in Acute Stroke Trials Stroke, April 1, 2001; 32(4): 909 - 916. [Abstract] [Full Text] [PDF]
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L. Belayev, Y. Liu, W. Zhao, R. Busto, and M. D. Ginsberg Human Albumin Therapy of Acute Ischemic Stroke : Marked Neuroprotective Efficacy at Moderate Doses and With a Broad Therapeutic Window Stroke, February 1, 2001; 32(2): 553 - 560. [Abstract] [Full Text] [PDF]
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H. C. Diener, M. Cortens, G. Ford, J. Grotta, W. Hacke, M. Kaste, P. J. Koudstaal, and T. Wessel Lubeluzole in Acute Ischemic Stroke Treatment : A Double-Blind Study With an 8-Hour Inclusion Window Comparing a 10-mg Daily Dose of Lubeluzole With Placebo Stroke, November 1, 2000; 31(11): 2543 - 2551. [Abstract] [Full Text] [PDF]
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S. S. Kaplan, T. S. Park, E. R. Gonzales, J. M. Gidday, and J. A. Zivin Hydroxyethyl Starch Reduces Leukocyte Adherence and Vascular Injury in the Newborn Pig Cerebral Circulation After Asphyxia Editorial Comment Stroke, September 1, 2000; 31(9): 2218 - 2223. [Abstract] [Full Text] [PDF]
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J. Berrouschot, H. Barthel, J. Koster, S. Hesse, A. Rossler, W. H. Knapp, and D. Schneider Extracorporeal Rheopheresis in the Treatment of Acute Ischemic Stroke : A Randomized Pilot Study Stroke, April 1, 1999; 30(4): 787 - 792. [Abstract] [Full Text] [PDF]
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