From the Departments of Neurology and Neurosurgery (A.A.), University of
Heidelberg, Germany.
Correspondence to Dr Stefan Schwarz, Department of Neurology, University of Heidelberg, 400 Im Neuenheimer Feld, Heidelberg 69120, Germany. E-mail Stefan_Schwarz{at}ukl.uni-heidelberg.de
Methods—We studied 30 episodes of ICP crisis in 9 patients. ICP
crisis was defined as (1) a rise of ICP of more than 25 mm Hg
(n=22), or (2) pupillary abnormality (n=3), or (3) a combination of
both (n=5). Baseline treatment was performed according to a
standardized protocol. For initial treatment, the patients were
randomly assigned to either infusion of 100 mL HS-HES or 40 g
mannitol over 15 minutes. For repeated treatments the 2 substances were
alternated. ICP, blood pressure, and cerebral perfusion pressure (CPP)
were monitored over 4 hours. Blood gases, hematocrit, blood osmolarity,
and sodium were measured before and 15 and 60 minutes after the start
of infusion. Treatment was regarded as effective if ICP decreased
>10% below baseline value or if the pupillary reaction had
normalized.
Results—Treatment was effective in all 16 HS-HES–treated and in
10 of 14 mannitol-treated episodes. ICP decreased from baseline values
in both groups, P<0.01. The maximum ICP decrease was
11.4 mm Hg (after 25 minutes) in the HS-HES–treated group and
6.4 mm Hg (after 45 minutes) in the mannitol-treated group. There
was no constant effect on CPP in the HS-HES–treated group, whereas CPP
rose significantly in the mannitol-treated group. Blood osmolarity rose
by 6.2 mmol/L in the mannitol-treated group and by 10.5
mmol/L in the HS-HES–treated group; sodium fell by 3.2 mmol/L in
the mannitol and rose by 4.1 mmol/L in the HS-HES–treated
group.
Conclusions—Infusion of 40 g mannitol and 100 mL HS-HES
decreases increased ICP after stroke. The maximum effect occurs after
the end of infusion and is visible over 4 hours. HS-HES seems to lower
ICP more effectively but does not increase CPP as much as does
mannitol.
From that perspective, treatment with hypertonic fluids is still an
attractive means of decreasing the intracranial pressure without having
a negative effect on the CPP. Mannitol has been used extensively, and
various clinical and experimental studies have demonstrated that single
doses of mannitol—at least transiently—reduce increased
ICP.4 5 6 7 8 However, several factors limit the
indiscriminate use of mannitol in stroke patients. Almost all of
the larger clinical studies with mannitol have been performed in
patients with head injuries; comparable studies in stroke patients have
not been undertaken. The long-term beneficial effects of mannitol are
still controversial, and there is some evidence that repeated doses of
mannitol may even aggravate brain edema.9 10
Furthermore, mannitol is not effective in some patients. Therefore,
alternative therapies for increased ICP are warranted.
Hypertonic saline solutions have been primarily used for "small
volume resuscitation" (SVR) in patients with hemorrhagic shock.
Compared with standard shock therapy, SVR produces a more rapid volume
expansion; increases cardiac output, systemic blood pressure, and
microvascular perfusion; and may improve
survival.11 12 13 14 In particular, the subgroup of
patients with severe head injuries seems to have higher survival rates
after SVR.13 Various animal experiments of
hemorrhagic shock and head trauma have indicated that SVR lowers ICP
and improves CPP.15 16 17 18 19 20 21 Although SVR has been
used primarily in patients with hemorrhagic shock, hypertonic saline
with or without dextrans/HES has been successfully used in a few
anecdotal reports and in small clinical series of euvolemic head-trauma
patients even after the failure of conventional
therapy.22 23 24 25
Until now, HS-HES solutions have not been systematically used in stroke
patients. We prospectively evaluated a treatment protocol alternating
single-dose HS-HES and mannitol in stroke patients with elevated
ICP.
Moderate ICP elevation was tolerated until the ICP reached 25
mm Hg. Indications for intervention were (1) spontaneous ICP increase
of more than 25 mm Hg persisting for more than 5 minutes or (2) a
newly observed pupillary abnormality (unilateral or bilateral
enlargement). If 1 or both of these criteria for intervention were met,
the patient was randomly assigned to either HS-HES or mannitol
treatment.
The patients assigned to HS-HES therapy were treated with 100 mL of a
hypertonic saline solution prepared in low-molecular-weight HES,
containing 75 g/L NaCl and 60 g/L HES (average molecular weight 200,
degree of substitution 0.6 to 0.66, osmolarity 2570 mOsm/L).
The mannitol-treated patients were treated with 200 mL of a 20%
mannitol solution (osmolarity 1100 mOsm/L). With these doses,
the osmolar load of the two regimens was approximately identical.
Each drug was administered via a central venous catheter over a period
of 15 minutes. Efficacy of treatment was assessed 10 minutes after the
end of infusion (ie, 25 minutes after start). Therapy was classified as
successful if (1) the ICP fell >10% below the baseline value or
(2) pupillary reaction had normalized (in patients with a pupillary
abnormality). Patients in whom therapy was not successful were
immediately treated with the alternative drug in the same way as
described above. These secondary treatments were only analyzed
for effectiveness, and otherwise were not included in this study. If
this therapy failed anew after 25 minutes, THAM-buffer solution,
short-term hyperventilation, and barbiturates were used.
Osmotherapy was repeated in the same patient if the criteria for
intervention were met again. Only the initial treatment was randomized.
For treatment of repeated episodes of ICP in the same patient,
mannitol and HS-HES were alternated.
The following parameters were assessed at baseline and
after 5, 10, 15 (at end of infusion), 25, 35, 45, 60, 120, 180, and 240
minutes: ICP, MAP, CPP, and pupillary reaction. Pupillary reaction was
categorized as normal, unilaterally abnormal (enlarged or areactive),
or bilaterally abnormal. Hematocrit, sodium level,
PaO2, and
FIO2 were determined at baseline,
after 15 minutes (at end of infusion), and after 60 minutes.
PaCO2 was documented at baseline. In
addition, whole blood osmolarity was analyzed at baseline and
after 15 and 60 minutes.
During the first 60 minutes, manipulation of ventilation
parameters, variation of the concomitant medication (in
particular, rate of epinephrine infusion or additional volume
replacement), and nursing procedures such as turning or endotracheal
suction were kept to a minimum. Exclusion criteria for osmotherapy were
oliguric renal failure, pulmonary edema, and cardiac failure.
HS-HES was not used in patients with sodium levels >150 mmol/L.
Patient outcome was assessed 2 weeks after the insult with the
GOS.26 This study was conducted according to the
local ethics committee standards.
Statistical analysis was performed using the Wilcoxon
signed-rank test to compare differences between different time points
within 1 treatment group. Baseline characteristics between the 2
treatment groups were compared using the Mann-Whitney rank sum
test. Differences were considered significant at P<0.05.
Data are mean±SEM. Statistical analysis was performed for
parameters within the first 60 minutes only, because after
that time possible influencing factors such as nursing procedures,
ventilation parameters, or other medication could not be
maintained unchanged. Because of the sample size, a statistical
analysis of differences between mannitol-treated and
HS-HES–treated patients was not performed. For that purpose, a much
larger study with different doses would be necessary.
By the end of the study, 3 patients had died of uncontrollable
intracranial hypertension (GOS 5). The remaining 6 patients remained
severely disabled (GOS 3).
Effects of Mannitol
Mean baseline ICP in the mannitol group was 26.1±0.4 mm Hg.
Immediately after the start of mannitol infusion, the ICP decreased
significantly (P<0.01 for all time points). After 15
minutes, at the end of infusion, ICP had decreased by 17% to
21.5±1.2 mm Hg. The greatest decrease in the ICP from baseline
level occurred after 45 minutes, by 24% (to 19.7±1.1 mm Hg,
P<0.001) in the 10 events in which the observation period
was continued beyond 25 minutes (in the other 4 events, patients were
switched to HS-HES therapy) (Figure 1
CPP was significantly higher than at baseline after 15, 25, 35, and 60
minutes primarily as an effect of the changes in the ICP. The increase
in CPP was most marked after 35 minutes (mean increase, by 19.2%, to
84.9±3.9 mm Hg; P<0.01) (Figure 2
At the end of infusion, hematocrit had decreased from a baseline level
of 34.0%±1.7% to 32.0%±1.5% (P<0.01). After 15
minutes, the hematocrit rose again and did not differ from baseline
after 60 minutes. The serum sodium levels fell from 139.5±1.6 to
136.3±1.8 mOsm/L after 15 minutes (P<0.01), and were still
below baseline levels at 60 minutes (135.6±2.0 mOsm/L,
P<0.01) (Figure 3
Blood osmolarity was analyzed in 12 of 14 mannitol-treated
episodes. Osmolarity rose from a baseline level of 311.9±4.7 to
318.1±4.5 mOsm/L after 15 minutes (P<0.01). Thereafter,
osmolarity fell again. After 60 minutes, osmolarity was still higher
than at baseline (313.4±3.7 mOsm/L, P<0.01) (Figure 4
Inspiratory PaO2 (baseline
107.7±5.0 mm Hg), FIO2
(baseline 0.5±0.1 mm Hg), arterial oxygen saturation
(baseline 98.9%±0.3%), and heart rate (baseline 81.2±4.7 bpm)
remained unchanged during the observation period.
Effects of HS-HES Treatment
Initial MAP was 97.6±4.4 mm Hg and remained unchanged during the
observation period. CPP (baseline 69.0 mm Hg) was significantly
higher than at baseline after 25 and 35 minutes (P<0.05).
The increase of CPP was most marked after 35 minutes (mean increase, by
7.5%, to 78.2±5.3 mm Hg) (Figure 2
At the end of infusion, hematocrit levels had decreased from
baseline 35.5%±1.3% to 33.7%±1.3% (P<0.001). After 15
minutes, the hematocrit rose again, but was still below baseline after
60 minutes (34.4%±1.2%, P<0.01). Serum sodium levels
increased from 140.2±1.6 to 144.3±1.3 mOsm/L after 15 minutes
(P<0.001). Serum sodium decreased thereafter and did not
differ from baseline after 60 minutes (Figure 3
Blood osmolarity was analyzed in 11 of 16 HS-HES–treated
episodes. Osmolarity rose from a baseline level of 310.1±5.1 to
320.5±4.6 mOsm/L after 15 minutes (P<0.001). After 15
minutes, osmolarity fell again. After 60 minutes osmolarity was still
higher than at baseline (316.6±4.8 mOsm/L, P<0.001)
(Figure 4
Inspiratory PaO2 (baseline 102.3
mm Hg±3.2), FiO2 (baseline 0.5±0.01),
arterial oxygen saturation (baseline 98.8%±0.3), and
heart rate (baseline 78.9±3.8 bpm) remained unchanged during the
observation period.
Comparison Between the 2 Groups
Effects in Subsequent Events
For SVR of patients with hemorrhagic shock, a dose of 4 mL/kg 7.5%
saline with or without dextrans/HES has been
used.13 For treatment of refractory, highly
elevated intracranial hypertension without hemorrhagic shock,
Härtl et al22 administered HS-HES at a rate
of 20 mL/min until the ICP significantly decreased (average 171 mL). In
our patient group with an overall only moderately elevated ICP, only
100 mL HS-HES was effective in all events.
In a sheep model, an identical volume of either 20% mannitol or
7.5% saline yielded similar responses.30 We
chose the dose of 100 mL HS-HES (257 mOsm) to achieve a osmolar
load similar to the standard dose of 200 mL 20% mannitol (220 mOsm).
Although osmolarity was similar, blood osmolarity rose faster and
remained elevated for a longer time after HS-HES, indicating that the
osmolar load is not the only relevant parameter of
hypertonic solutions (Figure 4
The mechanisms by which hypertonic fluids act are still a matter of
controversy. The traditional and still most widely accepted theory,
advocated since 1919, postulates that hypertonic fluids create an
osmotic gradient between the intracerebral
intravascular compartment and the cerebral parenchyma, resulting in
dehydration and shrinkage of endothelial cells and
brain tissue. For mannitol, this effect has been repeatedly
demonstrated in radiological studies in humans and in animal
experiments.7 28 31 32 33 34 35 A reduced brain water
content has been also demonstrated after the infusion of hypertonic
saline.16 17 18 19 36 37 An intact blood-brain barrier
is the prerequisite for establishing an osmotic gradient. It has been
assumed that dehydration of brain tissue is more pronounced on the side
contralateral to the lesion where the brain tissue is preserved.
Studies with hypertonic saline and most studies with mannitol support
this hypothesis.16 17 19 28 31 33 37
It has been proposed that the almost immediate decrease in ICP
after mannitol infusion cannot be explained solely by dehydration of
brain tissue.31 A variety of alternate mechanisms
of mannitol effects have been subjected to extensive experimental
studies. These postulated effects include improvement of cerebral blood
flow and CPP via reactive cerebral vasoconstriction, a decrease in
cerebral spinal fluid formation and resorption, increased cardiac
output and blood pressure, effects on blood viscosity, brain
oxygenation and microcirculation, and neuroprotective
properties.5 6 7 16 27 29 31 32 38 39 40 Several
authors have assumed that the effects of mannitol on the cerebral
hemodynamics depend on the autoregulative
capacities. If the vascular autoregulation is intact, mannitol
may lead to a reactive vasoconstriction either through increased
systemic blood pressure or hemodilution with improved red cell
deformability and decreased blood
viscosity.5 7 39 40 Rosner and
Coley40 concluded that the effect of mannitol
would be small if the CPP >70 mm Hg because in this situation
vasoconstriction is already maximal.
In our euvolemic patients, SABP did not consistently
change after the infusion of HS-HES or mannitol. This finding is in
agreement with the results of several clinical and animal studies in
which the SABP remained unaffected or even decreased after mannitol,
probably due to a reactive decrease in the peripheral
resistance.6 7 27 31 41 Similarly, in contrast to
patients with hemorrhagic shock, HS-HES does not increase SABP in
euvolemic patients.22 42 43
Mechanisms of HS-HES are complex, because HS-HES consists of 2
components: sodium chloride, which is mainly responsible for the
osmotic gradient, and HES, which is added to maintain the short-lived
volume effect of hypertonic saline. Similar to mannitol, the postulated
mechanisms of HS-HES, aside from osmotic dehydration of brain tissue,
include improved cerebral blood flow, increased oxygen delivery and
rheology, and clearance of toxic metabolites from the
brain.14 16 21 36 42 44 45 To improve cerebral
microcirculation, HES or dextrans have been used for many years in
stroke, but have failed to improve patient
outcome.46 47 A major effect on brain edema and
ICP cannot be expected from colloid solutions, since the main
determinant of water exchange in the brain is mediated by the osmotic
pressure, whereas the oncotic pressure has no or only limited
effect.48 HS without dextrans or HES has been
reported anecdotally to be successful in patients with intracranial
hypertension23 and is effective in
animals.15 17 18 19 21 30 49 HS may possibly be as
effective as HS-HES in reducing elevated ICP, in particular because
HS-HES does not increase the SABP in euvolemic patients. However, with
HS, more sodium chloride may be necessary to achieve the same effects
as HS-HES, which could limit repeated use of
HS-HES.18
In this study, we assessed the early effects of mannitol and HS-HES. It
appears to be indisputable that hypertonic solutions can at least
transiently decrease an elevated ICP and, therefore, that they may be
beneficial in emergency situations in an acutely deteriorating patient
before therapies such as hematoma evacuation or decompressive surgery
can be initiated. For that indication, HS-HES apparently acts more
rapidly and effectively. The long-term effects of repeated treatments
with hypertonic solutions remain unclear. Repeated infusions of
mannitol could aggravate cerebral edema if the osmotic substances
migrate through a damaged blood-brain barrier into the brain tissue,
reversing the osmotic gradient.9 It seems
unlikely that a damaged blood-brain barrier would maintain its
selective permeability, and, therefore, this presumed negative effect
would probably occur with HS-HES as well. In contrast to most other
body tissues, sodium ions cannot cross an intact blood-brain barrier,
because the intercellular junctions between the cerebral capillary
endothelial cells are extremely
tight.48 Furthermore, osmotic agents lead
predominantly to dehydration and shrinkage of normal brain tissue and
may facilitate displacement of brain tissue and even increase the risk
of herniation.50 However, these largely
theoretical considerations have not been substantiated in clinical
studies to date. In 3 of 4 episodes in which mannitol had failed to
reduce ICP, infusion of HS-HES was still effective. Of course, the
repeated administration of mannitol could have evoked the same effect,
but in this emergency situation with acutely elevated ICP, we believed
it was not reasonable to repeat a treatment that was initially
unsuccessful.
In our series, we did not observe any negative systemic effects after
treatment with either drug. In 1 patient, we discontinued osmotherapy
after blood osmolarity reached 350 mOsm/L. To date, relevant systemic
side effects have not been reported after a single dose of
HS-HES.13 51 52 However, the effects of repeated
infusion of HS-HES are still to be evaluated. Its repeated use may lead
to an excessive increase in sodium levels and osmolarity, resulting in
volume overload with heart failure and lung edema, or may induce
hyperchloremic metabolic acidosis and coagulation
disorders.53 54 Similar side effects have
been attributed to mannitol, except for sodium levels that decrease
after mannitol. Therefore, the use of hypertonic solutions in patients
with a compromised cardiac function should be restricted to a minimum
under close cardiac monitoring. The use of hypertonic solutions may be
hazardous, particularly for elderly stroke patients who already receive
volume load or vasopressor drugs. Because of its complementary effects
on sodium levels that may limit the repeated use of either drug, we
suggest that the 2 drugs be alternated if repeated treatments are
needed.
Conclusions
Received February 13, 1998;
revision received April 27, 1998;
accepted May 12, 1998.
© 1998 American Heart Association, Inc.
Original Contributions
Effects of Hypertonic Saline Hydroxyethyl Starch Solution and Mannitol in Patients With Increased Intracranial Pressure After Stroke
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—The purpose
of this study was to prospectively evaluate a protocol with hypertonic
saline hydroxyethyl starch (HS-HES) and mannitol in stroke patients
with increased intracranial pressure (ICP).
Key Words: brain edema • hypertonic hydroxyethyl starch • mannitol • intracranial pressure • stroke
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Brain edema is the
major cause of increased ICP, secondary deterioration, and death
in patients after stroke.1 Over the past few
years, the use of previously recommended therapies such as barbiturates
or hyperventilation has been increasingly questioned since it was
recognized that they may critically reduce the CPP through negative
effects on the systemic blood pressure or excessive cerebral
vasoconstriction with secondary ischemic
damage.2 3
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
From March through August 1997, 9 consecutive patients
with elevated ICP after acute space-occupying hemispheric stroke (n=8)
or hypertensive putaminal hemorrhage with massive perifocal
edema (n=1) were included in this study. All patients were treated in
the neurointensive care unit at the Department of Neurology of the
University of Heidelberg. The patients were treated according to an
institutional protocol for stroke patients with elevated ICP. All
patients were intubated, artificially ventilated, and
anesthetized with analgesics and sedatives. The patients were
maintained in a 30° upright position. Ventilation
parameters were adjusted to achieve normocapnia and a
PaO2 >90 mm Hg. Serum
electrolytes and glucose were kept within normal limits, and
hyperthermia was avoided. The ICP was continuously monitored with an
epidural (n=2) or intraparenchymatous (n=5) ICP device
(Spiegelberg, Hamburg, Germany) ipsilateral to the lesion or via a
ventricular catheter (n=2). ICP, oxygen saturation, heart
rate, and MAP were monitored continuously. Gelatinous solutions and
crystalline fluids were administered to achieve euvolemia (a central
venous pressure between 12 and 16 cm H2O). If
volume substitution was not sufficient to reach a CPP of at least
70 mm Hg, the MAP was increased with a continuous infusion of
epinephrine and/or dobutamine.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
In all, 30 ICP episodes were treated in 9 patients (6 men, 3
women; mean age, 56.6 years [range, 43 to 75 years]). The
Table
shows baseline characteristics. HS-HES was used in
16 episodes and mannitol in 14 episodes. Indications for intervention
were (1) a rise in ICP >25 mm Hg in 22 episodes, (2) a newly
observed pupillary abnormality in 3 episodes, and (3) both, ICP crisis
in combination with pupillary abnormality, in the remaining 5 events.
The mean interval between stroke onset and initial osmotherapy was 57
hours (range, 33 to 85 hours). Concomitant therapy included continuous
infusion of vasopressors (most frequently norepinephrine)
during the observation period in 18 episodes.
View this table:
[in a new window]
Table 1. Baseline Characteristics of Patients
Therapy was classified as successful 10 minutes after the end of
infusion in 10 of 14 mannitol-treated episodes. In 3 of 4 episodes in
which mannitol failed, a subsequent infusion of HS-HES was effective.
In 1 patient, osmotherapy was not continued because blood osmolarity
had already reached 350 mOsm/L. ).
The initial MAP was 98.5±3.2 mm Hg and remained unchanged except
for the time after 25 minutes (mean increase, by 6.5%, to
104.9±2.2 mm Hg, P<0.05).
View larger version (15K):
[in a new window]
Figure 1. ICP in 16 HS-HES–treated and 14 mannitol-treated
events. In both groups, ICP has already fallen during the infusion
period and reached its lowest level at 25 and 45 minutes, respectively.
The difference compared with baseline values was significant for all
time points in both groups (P<0.01 for all points). In
the initial phase, HS-HES seems to lower the ICP more effectively and
faster compared with mannitol. (After 25 minutes, mannitol treatment of
4 ICP episodes was terminated because of ineffectiveness.) ).
View larger version (15K):
[in a new window]
Figure 2. CPP in 16 HS-HES–treated and 14 mannitol-treated
events. The rise in CPP reached statistical significance at 15, 25, 35,
and 60 minutes in the mannitol-treated group (*) and at 25 and 35
minutes in the HS-HES–treated group ( 
). (After 25 minutes, mannitol
treatment of 4 ICP episodes was terminated because of
ineffectiveness.)).
View larger version (15K):
[in a new window]
Figure 3. Serum sodium levels in 16 HS-HES–treated and 14
mannitol-treated events. Sodium level rose in the HS-HES–treated group
and fell in the mannitol-treated group (P<0.01). (After
25 minutes, mannitol treatment of 4 ICP episodes was terminated because
of ineffectiveness.) ).
View larger version (14K):
[in a new window]
Figure 4. Whole blood osmolarity in 11 HS-HES–treated and
12 mannitol-treated events. Osmolarity had increased at the end of
infusion (P<0.001) in both groups. After 60 minutes,
osmolarity was still elevated in both groups, compared with initial
values (P<0.05). (After 25 minutes, mannitol treatment
of 3 ICP episodes was terminated because of ineffectiveness.)
Therapy was successful in all 16 HS-HES–treated episodes.
Baseline ICP in the HS-HES group was 28.6±1.2 mm Hg. Immediately
after the start of mannitol infusion, the ICP fell significantly
(P<0.001 for all time points). After 15 minutes, at the end
of infusion, ICP had decreased by 34% to 18.9±1.3 mm Hg. The
greatest decrease in the ICP from baseline level occurred after 25
minutes, by 38% to 17.6±1.3 mm Hg (P<0.001) (Figure 1
). ). ). ).
Baseline values were not different between the 2 groups (Table).
As mentioned above, a statistical comparison was not possible. However,
after HS-HES treatment, the drop in the ICP seemed to be greater and
faster (Figure 1). After 25 minutes, the mean decrease of the ICP from
baseline was 11.0 mm Hg in the HS-HES–treated ICP episodes, but
only 5.3 mm Hg in the mannitol-treated events. After 25 minutes
the difference became smaller probably because after 25 minutes, 4
mannitol-treated patients were switched to HS-HES treatment.
HS-HES–treated patients had higher serum sodium levels after 15 and 60
minutes (Figure 3). The mean increase of osmolarity after 15 minutes
was greater for HS-HES–treated events (10.5 versus 6.2 mOsm/L) (Figure 4).
Repeated interventions became necessary in all but 1 patient
(mean, 3.3 events per patient; range, 1 to 7 events). Because of the
small number of repeated events, further analysis was not
performed.
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
In this study, HS-HES and mannitol were both effective in
reducing elevated ICP. HS-HES seemed to lower the ICP more effectively,
but comparison between the 2 treatments has its limitations, since the
optimum dose and infusion rate are largely unknown for both substances.
Because of the lack of exact experimental or clinical data, dose, and
mode of application, the end point of 10 minutes after the end of
infusion for determining efficacy and the definition of treatment
"success" in our clinical study are based primarily on personal
experiences and general recommendations. Although mannitol is used in
many patients with intracranial hypertension, larger dose-finding
studies in humans have not been performed. Single doses of mannitol
from 0.25 up to 2.27 g/kg body wt have been
used.5 27 28 29 Marshall et
al4 studied the effect of different mannitol
doses in 8 patients and concluded that small doses (0.25 g/kg) were as
effective as larger doses. Our dose of 40 g mannitol equals
approximately 0.4 to 0.6 g/kg. ).
Single doses of 100 mL HS-HES and 40 g mannitol are effective
in reducing elevated ICP in patients with brain edema after stroke
without a negative effect on MAP or CPP. HS-HES seems to lower elevated
ICP more rapidly and effectively. HS-HES can still be successfully used
after mannitol has failed. HS-HES has no major effect on the CPP,
whereas mannitol increases CPP.
Selected Abbreviations and Acronyms
CPP
=
cerebral perfusion pressure
GOS
=
Glasgow outcome scale
HES
=
hydroxyethyl starch
HS
=
hypertonic saline
HS-HES
=
hypertonic saline hydroxyethyl starch
ICP
=
intracranial pressure
MAP
=
mean arterial blood pressure
SABP
=
systemic arterial blood pressure
SVR
=
small volume resuscitation
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
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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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R. P. Paczynski, R. Venkatesan, M. N. Diringer, Y. Y. He, C. Y. Hsu, W. Lin, and P. H. Chan Effects of Fluid Management on Edema Volume and Midline Shift in a Rat Model of Ischemic Stroke Editorial Comment Stroke, July 1, 2000; 31(7): 1702 - 1708. [Abstract] [Full Text] [PDF]
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E. M. Manno, R. E. Adams, C. P. Derdeyn, W. J. Powers, and M. N. Diringer The effects of mannitol on cerebral edema after large hemispheric cerebral infarct Neurology, February 1, 1999; 52(3): 583 - 583. [Abstract] [Full Text]
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