Mannitol Use in Acute Stroke

Case Fatality at 30 Days and 1 Year

Dniel Bereczki, MD, PhD, DHAS; Lszl Mihlka, MD, PhD; Szabolcs Szatmri, MD, DSci;
Klra Fekete, MD; David Di Cesar, MD; Bla Flesdi, MD, PhD;
Lszl Csiba, MD, PhD, DHAS; Istvn Fekete, MD, PhD

Background and PurposeMannitol is used worldwide to treat acute stroke, although its efficacy and safety have not been
proven by randomized trials.
MethodsIn a tricenter, prospective study, we analyzed the 30-day and 1-year case fatality with respect to mannitol
treatment status in 805 patients consecutively admitted within 72 hours of stroke onset. Confounding factors were
compared between treated and nontreated patients.
ResultsTwo thirds of the patients received intravenous mannitol as part of their routine treatment (mean dose, 4722
Downloaded from http://stroke.ahajournals.org/ by guest on October 23, 2016

g/d; mean duration, 63 days). The case fatality was 25% versus 16% (P0.006) at 30 days and 38% versus 25%
(P0.001) at 1 year in the-mannitol treated and nontreated groups, respectively. Mannitol treatment effect was adjusted
for age, stroke severity, fever in the first 3 days, and aspirin treatment (for ischemic strokes) in logistic regression
models. Depending on the factors entered into the model, either no effect or harm could be attributed to mannitol. When
the analysis was restricted to those admitted within 24 hours (n568), case fatality differed significantly only at 1 year
(35% in treated and 26% in nontreated patients, P0.044). Although the prognostic scores of the Scandinavian
Neurological Stroke Scale were similar in treated and nontreated patients, both in ischemic and hemorrhagic strokes, the
patient groups differed in several factors that might also have influenced survival.
ConclusionsBased on the results of this study, no recommendations can be made on the use of mannitol in acute stroke,
and properly randomized, controlled trials should be performed to come to a final conclusion. (Stroke. 2003;34:1730-
1735.)
Key Words: mannitol mortality stroke, acute stroke management

T he role of mannitol therapy in acute stroke is controver-

sial. Because of its osmotic effect, mannitol is assumed
to decrease cerebral edema. Mannitol might improve cerebral
perfusion by decreasing viscosity, and as a free-radical
scavenger, it might act as a neuroprotectant. Among the
possible adverse effects, fluid and electrolyte imbalances,
cardiopulmonary edema, and rebound cerebral edema have
been listed. Mannitol can activate the process of apoptotic
cell death and has the potential to activate the inflammatory
mediators that aggravate the neuronal injury due to ischemia.1
In acute stroke, mannitol preferentially shrinks the nonaf-
fected parts of the brain.2 In patients with cerebral edema
after large, hemispheric infarction, acute mannitol use did not
alter midline tissue shifts.3 Although mannitol decreases
elevated intracranial pressure after stroke4 and results in
increased cerebral perfusion pressure and brain oxygenation
in large, hemispheric strokes,5 its overall effect on stroke
outcome is unclear. Clinical observations could not prove the
beneficial effects of mannitol in ischemic or hemorrhagic
strokes in humans,6,7 and a systematic review of randomized
trials could not draw a conclusion on the effects of mannitol
in acute stroke.8 Despite the lack of evidence of an obvious
benefit, mannitol has been used to treat human stroke for 30
years, and both American and European guidelines9,10 men-
tion its use in certain clinical conditions of acute stroke. In an
initial analysis of almost 1000 consecutively admitted stroke
patients, we found that mannitol treatment was associated
with a higher hospital case fatality, regardless of the age of
the patient and the level of consciousness on admission.11 We
could not decide whether this higher case fatality was caused
by the effect of mannitol or by differences in prognostic
factors other than age and disturbance of consciousness
between the treated and nontreated patients. Therefore, in the
present article, by considering several additional prognostic
and confounding factors, we analyzed the case fatality at 30
days and 1 year after stroke in the same cohort in a

Received November 9, 2002; final revision received February 27, 2003; accepted March 7, 2003.
From the Department of Neurology (D.B., K.F., D.D.C., B.F., L.C., I.F.), University of Debrecen, Debrecen, Hungary; the Department of Neurology
(L.M.), University of Uzhgorod, Uzhgorod, Ukraine; and the Department of Neurology (S.S.), University of Targu Mures, Targu Mures, Romania.
Address correspondence to Dr Dniel Bereczki, Department of Neurology, Health Science and Medical Center, University of Debrecen, Debrecen,
Nagyerdei krt. 98, H-4012, Hungary. E-mail bereczki@jaguar.dote.hu
2003 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000078658.52316.E8

1730
 Bereczki et al
prospective, observational study to see whether mannitol
treatment results in obvious benefit or harm when adminis-
tered to patients admitted within 72 hours of stroke onset. We
further analyzed those admitted within 24 hours, and within
this group, we investigated those with ischemic and hemor-
rhagic strokes.
Methods
The database of the Mures-Uzhgorod-Debrecen study12 was ana-
lyzed. Data of all patients consecutively admitted with acute cere-
brovascular disease between October 1, 1999 and September 30,
2000 to the 3 centers were prospectively entered into a database. The
database includes information on risk factors; patient condition on
admission, including prognostic and long-term items of the Scandi-
navian Neurological Stroke Scale13 (SNSS); treatment on the ward;
and condition at discharge. For discharge condition, outcome accord-
ing to the International Stroke Trial14 was used, with a minor
addition. Follow-up was performed at 30 days and 1 year after stroke
by personal visits, postal questionnaires, or telephone calls to the
patients, their relatives, or their family practitioners. From the
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current analysis, we excluded those with transient ischemic attack,
cases of subarachnoid hemorrhage, and those who were admitted
after 72 hours of stroke onset. The study was approved by the ethics
committee of the University of Debrecen.
The database was originally designed for epidemiological and
audit purposes and not to test treatment effects in a controlled
fashion; therefore, some information important for the present
analysis had to be additionally obtained. Such information was
extracted from the patients documents retrospectively for this
analysis.
The following factors were considered in the analysis: age;
prestroke dependency; time to admission from stroke onset; diabetes;
previous stroke, malignancy, and peripheral arterial disease in the
history; smoking status; serum glucose level on admission; distur-
bance of the level of consciousness (LOC) on admission; the
prognostic and long-term scores according to the SNSS (smaller
SNSS scores indicate more severe strokes); white cell count in the
first 3 days after admission; fever in the first 3 days after admission,
defined as axillary temperature 37C; fever at any time during the
hospital stay; chronic obstructive pulmonary disease; atrial fibrilla-
tion during the hospital stay; antibiotic use, aspirin treatment, and
heparin treatment during hospitalization; respirator use other than
during attempts of resuscitation; and nasogastric tube feeding.
Continuous variables were compared by ANOVA. Stroke scale
scores were compared by the Mann-Whitney test. The Pearson 2 test
was used to compare frequencies. Logistic regression models were
used to evaluate whether 30-day and 1-year case fatalities depended
on mannitol treatment status. In the models, survival was the
dependent variable, and those factors that were found to be different
by univariate analyses between the treated and nontreated groups
were entered as continuous predictors or categorical factors. We used
Statistica for Windows, version 6.1 (StatSoft) and the Proc Logistic
procedure of SAS, version 8.02 (SAS Institute).
Results
Characteristics of Patients
Of the acute stroke patients registered in the database, 805
were admitted within 3 days of stroke onset. Of these
patients, 666 had ischemic stroke. The meanSD age was
6612.5 years; there were 471 men and 334 women. Time
from stroke to admission was 24 hours in 568 patients; of
these, 457 had ischemic and 111 had hemorrhagic strokes.
Thirty-day and 1-year survival data were available for 782 of
805 (97%) and for 768 of 805 (95.4%) patients, respectively.
The overall case fatality was 22.1% at 30 days and 33.6% at
1 year. Case fatality in the mannitol-treated subgroup was
Mannitol Use and Case Fatality 1731
significantly higher both at 30 days (25% versus 16%,
P0.006) and at 1 year (38% versus 25%, P0.001).
Characteristics of Mannitol Treatment
Based on local traditions, in 2 of the centers (Debrecen and
Targu Mures), mannitol was frequently administered,
whereas at the third center (Uzhgorod), mannitol was rarely
used. The rate of mannitol treatment significantly differed
among the 3 centers but did not differ between sexes.
Mannitol was given according to the discretion of the treating
physician, and when given, the mannitol solution was admin-
istered intravenously for 3 to 10 days. The mean dose of
mannitol was 4722 g/d, and the mean duration of mannitol
treatment was 63 days. Mannitol treatment was initiated on
the day of admission in 97%, and only 3% of the patients
received mannitol for worsening of their condition. Except
for mannitol, no other osmotically active medications (glyc-
erol, hypertonic saline, urea, etc) were used by the centers.
Comparison of Mannitol-Treated And
Nontreated Patients
All Patients
Characteristics of the mannitol-treated and nontreated groups
are given in Table 1. Mannitol-treated patients were older,
stayed longer in hospital, and had somewhat lower SNSS
prognostic and long-term scores than did those who were not
treated with mannitol. More of the mannitol-treated patients
were dependent before their current stroke. Artificial venti-
lation and nasogastric tube feeding were more frequent in
mannitol-treated patients. Of the 666 patients with ischemic
strokes, aspirin was given to 72% of the mannitol-treated and
to 50% of the nontreated patients (P0.001).
Patients Admitted <24 Hours After Stroke
Mannitol use was 70% in those admitted within 24 hours,
56% among those admitted between 24 and 48 hours, and
31% among those admitted between 48 and 72 hours; ie, with
a longer delay to admission, the application rate of mannitol
significantly decreased (P0.0001). Therefore, we per-
formed a separate analysis in the subgroup of those 568
patients who were admitted within the first 24 hours after
stroke onset, and within this group, 2 further analyses were
performed for those with ischemic and hemorrhagic strokes.
Characteristics of the patients admitted within 24 hours of
stroke onset are given in Table 2. Mannitol use was the same
in ischemic and hemorrhagic strokes. The proportion of
prestroke dependency was 3.6% in nontreated and 13.5% in
mannitol-treated patients (P0.001). Fewer patients in the
mannitol group were smokers. Disturbance of consciousness
on admission was more frequent in the nontreated group,
whereas fever within the first 72 hours, respirator use, and
nasogastric feeding was more common in the mannitol-
treated group. Although SNSS prognostic scores were simi-
lar, there was a tendency in the mannitol-treated group for a
higher 30-day case fatality (23% versus 17%, P0.13). The
marginally lower long-term SNSS score was associated with
higher 1-year case fatality in the mannitol group.
 1732 Stroke July 2003

TABLE 1. Characteristics of All Patients Admitted Within 72 Hours

Mannitol-Treated Untreated

MeanSD MeanSD
or n % or n % P
No. of patients 546 67.8 259 32.2
Age, y 67.812.2 62.412.5 0.001
SNSS prognostic score 15.36.3 16.55.9 0.001
SNSS long-term score 25.015.4 29.515.8 0.001
Admission glucose, mmol/L 7.32.8 7.93.8 0.088
M:F 315:231 156:103 0.49
Debrecen 341 83 68 17
Targu Mures 192 85 35 15
Uzhgorod 13 8 156 92
Prestroke dependent 68/518 13 9/249 4 0.001
Diabetes 84/535 16 47/255 18 0.33
COPD 76/506 15 11/119 9 0.1
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PAD 50/534 9 26/256 10 0.72

Malignancy 26/507 5 5/120 4 0.66
Stroke in history 120/545 22 45/258 17 0.13
Smoker 119/462 26 66/228 29 0.37
Disturbed LOC on admission 115/545 21 63/259 24 0.3
Fever in first 72 h 147/499 29 20/115 17 0.009
Fever at any time 227/499 45 29/115 25 0.001
Atrial fibrillation 46/504 9 10/117 9 0.84
ASA given for ischemic 315/440 72 112/226 50 0.001
Heparin given for ischemic 65/440 15 43/226 19 0.16
Antibiotic given anytime 183/500 37 33/117 28 0.09
Respirator use 30/516 6 6/248 2 0.03
Tube feeding 69/516 13 10/248 4 0.001
Dead or dependent at discharge 292/517 56 112/142 44 0.0012
Case fatality at 30 d 131/524 25 42/258 16 0.006
Case fatality at 1 y 195/512 38 63/256 25 0.001
COPD indicates chronic obstructive pulmonary disease; PAD, peripheral artery disease; ASA,
acetylsalicylic acid (aspirin).

Outcome in All Patients disturbance of consciousness on admission, and mannitol

Odds ratios and their 95% confidence intervals for survival
regarding mannitol treatment status, after adjustment for
other variables, are given in Table 3. Without considering
other factors, mannitol treatment was associated with signif-
icantly decreased odds of 30-day and 1-year survival
(P0.005 and P0.0002, respectively). When mannitol
treatment status was adjusted for age and the presence of
disturbance of consciousness on admission, mannitol still
seemed to have an adverse effect (P0.0028 for 30-day and
P0.0017 for 1-year survival). When the prognostic score of
the SNSS (ie, the sum score of the LOC, eye movements, and
arm and leg strength items; score range, 0 to 22) was used in
the model instead of the presence or absence of disturbance of
consciousness, mannitol treatment did not have a significant
effect on survival (P0.1931 and P0.1241 for 30-day and
1-year survival, respectively).
Case fatality at 1 year was 38% in the mannitol group and
25% in the nontreated group (P0.0002). Age, presence of a
treatment were significantly associated with 1-year case
fatality (P0.002 for all). In an extended model, age
(P0.001), SNSS long-term score (P0.001), and fever in
the first 72 hours (P0.011) were significantly associated
with case fatality, whereas mannitol treatment had no effect
(P0.8).
Outcome in Patients Admitted Within 24 Hours of
Stroke Onset
In those admitted in the first 24 hours of stroke, case fatality
was significantly associated with mannitol treatment at 1 year
but not at 30 days (P0.0388 and P0.12, respectively;
Table 3). When the effect of mannitol was adjusted for age
and the presence of disturbed LOC on admission, mannitol
had a significant adverse effect on both 30-day and 1-year
survival (P0.024 and P0.0277, respectively). When the
SNSS prognostic score was used instead of the LOC, the
effect of mannitol became nonsignificant.
 Bereczki et al Mannitol Use and Case Fatality 1733

TABLE 2. Characteristics of Patients Admitted Within 24 Hours

Mannitol-Treated Untreated

MeanSD MeanSD
or n % or n % P
No. of patients 399 70 169 30
Age, y 68.012.1 63.212.6 0.001
SNSS prognostic score 15.16.2 15.86.1 0.15
SNSS long-term score 24.415.3 27.316.1 0.02
Admission glucose, mmol/L 7.32.7 7.83.3 0.2
M:F 227:172 106:63 0.2
Debrecen 256 86 42 14
Targu Mures 134 86 21 14
Uzhgorod 9 8 106 92
Hemorrhagic stroke 84/399 21 27/169 16 0.16
Prestroke dependent 54/398 14 6/168 4 0.001
Diabetes 59/395 15 30/168 18 0.38
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COPD 62/389 16 7 /81 9 0.09

PAD 38/394 10 19/169 11 0.56
Malignancy 19/389 5 3 /81 4 0.65
Stroke in history 91/398 23 29/169 17 0.13
Smoker 79/347 23 47/146 32 0.028
Disturbed LOC on admission 88/398 22 51/169 30 0.041
Fever in first 72 h 120/383 31 15 /78 19 0.032
Fever at any time 187/383 49 23 /78 29 0.002
Atrial fibrillation 36/387 9 5 /79 6 0.4
ASA given for ischemic 225/314 72 74/142 52 0.001
Heparin given for ischemic 43/314 14 33/142 23 0.011
Antibiotic given anytime 150/384 39 26 /80 33 0.27
Respirator use 25/396 6 4/167 2 0.055
Tube feeding 58/396 15 8/167 5 0.001
Dead or dependent at discharge 217/379 57 81/166 47 0.068
Case fatality at 30 d 87/381 23 29/169 17 0.13
Case fatality at 1 y 131/373 35 44/167 26 0.044
Abbreviations as in Table 1.

Ischemic Stroke Patients Admitted Within
24 Hours
When the analysis was further restricted to those 457 patients
who had ischemic stroke and were admitted within 24 hours,
mannitol treatment status was not associated with 30-day case
fatality (15% in treated and 12.7% in nontreated groups,
P0.51). SNSS prognostic score and case fatality at 30 days
and 1 year are shown in Figure 1. The SNSS prognostic score
was 16.35.6 and 16.85.4 in the treated (n315) and
nontreated (n142) patients, respectively (P0.21). There
was no difference in the frequency of patients with disturbed
LOC on admission (P0.08). Respirator use was similar,
whereas nasogastric tube feeding was more frequent in the
mannitol group. SNSS long-term score was 26.814.7 and
29.915.3 in the treated and nontreated groups, respectively
(P0.01). Case fatality at 1 year was 27.7% in treated and
22.9% in nontreated patients (P0.28). Although mannitol
treatment had the tendency to increase the chances for
survival, when treatment effect was adjusted for age, SNSS
long-term score, fever in the first 3 days, and aspirin
treatment in the acute phase (odds ratio, 1.869; Table 3), the
confidence intervals were wide and included the possibility of
harm.
Cerebral Hemorrhage Patients Admitted Within
24 Hours
Of the 111 patients with cerebral hemorrhages, 84 were
treated and 27 were not treated with mannitol. Although
treated patients were older than nontreated patients (65.012
and 56.312.3 years, respectively; P0.002), they had
similar scores on both the prognostic and long-term items of
the SNSS (10.56.5 versus 10.16.4, P0.82, and
15.014.1 versus 13.613.4, P0.74, in treated and non-
treated patients, respectively) and had similar white cell
counts and glucose levels on admission than nontreated
patients. Disturbance of the LOC on admission was more
frequent in the nontreated group (P0.02). Treated and
nontreated patients did not differ significantly regarding the
 1734 Stroke July 2003

TABLE 3. Effect of Mannitol: Odds Ratios and Their 95% CIs for 30-Day and 1-Year Survival
All All Admitted Ischemic Hemorrhagic
Model Patients 24 h 24 h 24 h
30-day survival
Mannitol 0.577 (0.392, 0.847) 0.693 (0.435, 1.104) 0.823 (0.457, 1.480) 0.585 (0.244, 1.406)
P0.0050 P0.1224 P0.5145 P0.2311
Mannitol, age, disturbance of LOC 0.503 (0.321, 0.789) 0.537 (0.313, 0.921) 0.708 (0.368, 1.360) 0.435 (0.151, 1.254)
P0.0028 P0.0240 P0.2998 P0.1235
Mannitol, age, SNSS prognostic score 0.735 (0.462, 1.169) 0.776 (0.443, 1.359) 0.986 (0.501, 1.941) 0.574 (0.200, 1.651)
P0.1931 P0.3745 P0.9674 P0.3033
Mannitol, age, SNSS prognostic score, 0.963 (0.477, 1.944) 0.926 (0.413, 2.077) 1.289 (0.439, 3.786) 0.445 (0.113, 1.757)
fever in first 3 d P0.9164 P0.8523 P0.6443 P0.2475
Mannitol, age, SNSS prognostic score, 1.296 (0.437, 3.840)
fever in first 3 d, ASA for ischemic stroke P0.6399
1-year survival
Mannitol 0.526 (0.376, 0.736) 0.653 (0.436, 0.978) 0.772 (0.482, 1.235) 0.450 (0.188, 1.079)
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P0.0002 P0.0388 P0.2805 P0.0736

Mannitol, age, disturbance of LOC 0.529 (0.356, 0.787) 0.584 (0.362, 0.943) 0.740 (0.428, 1.279) 0.440 (0.152, 1.275)
P0.0017 P0.0277 P0.2808 P0.1305
Mannitol, age, SNSS prognostic score 0.720 (0.473, 1.095) 0.777 (0.465, 1.299) 0.983 (0.541, 1.786) 0.523 (0.181, 1.511)
P0.1241 P0.3364 P0.9542 P0.2313
Mannitol, age, SNSS prognostic score, 1.006 (0.555, 1.822) 0.953 (0.468, 1.939) 1.499 (0.626, 3.590) 0.448 (0.116, 1.728)
fever in first 3 d P0.9844 P0.8947 P0.3640 P0.2435
Mannitol, age, SNSS prognostic score, 1.513 (0.633, 3.617)
fever in first 3 d, ASA for ischemic stroke P0.3515
Mannitol, age, SNSS long-term score 0.760 (0.499, 1.159) 0.839 (0.503, 1.400) 1.123 (0.616, 2.048) 0.498 (0.175, 1.415)
P0.2022 P0.5014 P0.7053 P0.1907
Mannitol, age, SNSS long-term score, 1.081 (0.588, 1.988) 1.025 (0.499, 2.107) 1.845 (0.734, 4.635) 0.396 (0.103, 1.528)
fever in first 3 d P0.8016 P0.9469 P0.1927 P0.1790
Mannitol, age, SNSS long-term score, 1.869 (0.745, 4.690)
fever in first 3 d, ASA for ischemic stroke P0.1830
Bolded values indicate statistically significant differences.

frequency of prestroke dependency, chronic obstructive pulmo-
nary disease, malignancy, fever in first 72 hours, atrial fibrilla-
tion, antibiotic use, respirator use, and nasogastric tube feeding.
Case fatality was not significantly higher in the treated group at
30 days and 1 year (52% versus 41%, P0.31, and 62% versus
44%, P0.12; Figure 2). Although the odds ratios for survival
were 0.6 in all models (Table 3), suggesting an adverse effect
of mannitol treatment, the 95% confidence intervals were wide
and included the possibility of a beneficial effect.
Discussion
Although the results of observational studies on treatment effects
and on case fatality should be very cautiously interpreted
because of the potential of large biases,15 the results were
surprising to us. In contrast to the expected favorable effect of
mannitol, we could not find any association between mannitol
use and better prognosis at 30 days and 1 year after stroke.
Depending on the factors included in the logistic regression
models, mannitol either did not have a significant effect on case
fatality or was associated with an adverse outcome. Of the
neurologic signs on admission, in the analysis we first used only
the LOC, because among the clinical signs, this was found to be
the most significant prognostic factor in ischemic and hemor-
rhagic strokes.16,17 When disturbed LOC and age were used as
confounding factors in the model, mannitol had a significant
negative effect. However, when LOC was changed to a more
complex, quasi-continuous index of neurologic damage, ie, the
prognostic score of the SNSS including LOC, eye movements,
and severity of paresis of the affected upper and lower extrem-
ities, the effect of mannitol became nonsignificant. When the
analysis was restricted to those who were admitted within 24
hours, the findings were similar.
The fact that mannitol use was associated with higher short-
term and long-term case fatality in the total group might be
partly or totally explained by the differences between treated and
nontreated patients in prognostic factors. The absolute difference
in SNSS prognostic scores between treated and nontreated
patients was small, though statistically significant, in the total
group, but was not significant in the subgroup comparisons.
Most prognostic and confounding factors did not differ signifi-
cantly between treated and nontreated patients admitted within
24 hours with ischemic stroke, and several factors were even
more favorable for treated patients in the hemorrhagic subgroup.
This analysis has several limitations. First, this is a pro-
spective, observational study and not a randomized, con-
trolled trial; therefore, selection bias could have affected the
 Bereczki et al
Figure 1. SNSS prognostic score and 30-day and 1-year case
fatality in mannitol-treated versus nontreated patients admitted
Downloaded from http://stroke.ahajournals.org/ by guest on October 23, 2016
with ischemic stroke within 24 hours of stroke onset.
results. Second, computed tomography (CT) was performed
in only 73% of the patients, and in 10% of the patients, no
lesion was detected. In these patients, no repeated scans were
performed. Therefore, it was not possible to perform an
analysis by the volume of the lesions. It has been reported that
although a visible infarct on the CT scan is associated with
adverse prognosis, at least 30% of patients with ischemic
strokes have normal CT scans.18 Third, there were missing
data for some of the patients for several parameters; eg, white
cell count was present for 95% of patients, but data for
glucose level on admission were missing in close to 20% of
patients. Fourth, mannitol was administered according to the
discretion of the treating neurologist, and the dose of manni-
tol used and the duration of treatment varied.
We attempted to analyze the effect of mannitol on case
fatality by considering as many confounding factors as possible.
It was not possible to enter into the model all factors that
possibly influence short- and long-term survival. Depending on
the number and type of prognostic factors used in the multivar-
Figure 2. SNSS prognostic score and 30-day and 1-year case
fatality in mannitol-treated versus nontreated patients admitted
with hemorrhagic stroke within 24 hours of stroke onset.
Mannitol Use and Case Fatality 1735
iate analysis, mannitol had either a nonsignificant or an adverse
effect. This observational study does not prove that mannitol is
harmful if given for acute stroke, but it raises concerns and
emphasizes the need for properly designed, randomized, clinical
trials to decide whether the practice of routine mannitol use in
patients with acute stroke is justified, should be restricted to
subgroups, or should be stopped altogether.
Acknowledgments
The work was supported by grants No. ETT 490/2000, ETT
578/2000, and RO-8/2000. The authors thank Jnos Steiber (Biosta-
tistical Group, Gedeon Richter Ltd, Hungary) for calculating the
odds ratios and their confidence intervals for Table 3.
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 Mannitol Use in Acute Stroke: Case Fatality at 30 Days and 1 Year
Dniel Bereczki, Lszl Mihlka, Szabolcs Szatmri, Klra Fekete, David Di Cesar, Bla
Flesdi, Lszl Csiba and Istvn Fekete
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Stroke. 2003;34:1730-1735; originally published online June 19, 2003;

doi: 10.1161/01.STR.0000078658.52316.E8
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