Article

Lescot T, Degos V, Zouaoui A, et al. Opposed effects of hypertonic saline on contusions and noncontused brain tissue in patients with severe traumatic brain injury

Université Pierre et Marie Curie-Paris 6, France.
Critical Care Medicine (Impact Factor: 6.31). 01/2007; 34(12):3029-33. DOI: 10.1097/01.CCM.0000243797.42346.64
Source: PubMed
ABSTRACT
The aim of this study was to quantify the effect of hypertonic saline solution on contused and noncontused brain tissue in patients with traumatic brain injury. We hypothesize that hypertonic saline would increase the volume of brain contusion while decreasing the volume of noncontused hemispheric areas.
Prospective observational study.
Neurosciences critical care unit of a university hospital.
Fourteen traumatic brain injury patients with increased intracranial pressure.
A computed tomography scan was performed before and after a 20-min infusion of 40 mL of 20% saline.
The volume, weight, and specific gravity of contused and noncontused hemispheric areas were assessed from computed tomography DICOM images by using a custom-designed software (BrainView). Physiologic variables and natremia were measured before and after infusion. Hypertonic saline significantly increased natremia from 143 +/- 5 to 146 +/- 5 mmol/L and decreased intracranial pressure from 23 +/- 3 to 17 +/- 5 mm Hg. The volume of the noncontused hemispheric areas decreased by 13 +/- 8 mL whereas the specific gravity increased by 0.029 +/- 0.027%. The volume of contused hemispheric tissue increased by 5 +/- 5 mL without any con-comitant change in density. There was a wide interindividual variability in the response of the noncontused hemispheric tissue with changes in specific gravity varying between -0.0124% and 0.0998%.
Three days after traumatic brain injury, the blood- brain barrier remains semipermeable in noncontused areas but not in contusions. Further studies are needed to tailor the use of hypertonic saline in patients with traumatic brain injury according to the volume of contusions assessed on computed tomography.

Full-text

Available from: Louis Puybasset, Mar 01, 2015
Neurologic Critical Care
Opposed effects of hypertonic saline on contusions and noncontused
brain tissue in patients with severe traumatic brain injury*
Thomas Lescot, MD; Vincent Degos, MD; Abderrezak Zouaoui, MD, PhD; Françoise Préteux, PhD;
Pierre Coriat, MD; Louis Puybasset, MD, PhD
H
ypertonic saline (HS) used
at various concentration (3–
23.4%) has been consis-
tently shown to decrease in-
tracranial pressure (ICP) and cerebral
water content in human traumatic brain
injury (TBI) (1, 2). The mean pressure
drop is usually 40% (3). HS is still used as
a second-line therapy in adults (4) and
children (5) with exhausted response to
mannitol and barbiturates. Experimen-
tally, HS is more efficient in reducing ICP
than equiosmolar doses of mannitol (6).
In addition, HS might also be beneficial
to the immune system by modulating cel-
lular immune function after trauma and
restoring the immune function of healthy
T cells (7–9).
However, the patient population that
is most likely to respond to HS needs to
be further defined. From a theoretical
point of view, it can be expected that HS
is effective only in the areas of the brain
where the blood-brain barrier (BBB) is
still functional after trauma. There are
numerous arguments in favor of a pro-
found alteration of the BBB in contusion
appearing areas on CT (10 –12) in part
secondary to regional ischemia (11, 13–
15). This study was thus designed to eval-
uate the regional effects of hypertonic
saline on contused and noncontused
brain tissue after TBI. Our hypothesis was
that HS would increase the volume of
brain contusion while decreasing the vol-
ume of the noncontused areas. This was
done by comparing global and regional
brain volume, weight, and specific grav-
ity, as assessed by a recently described
software (16) computing these variables
out of computed tomography (CT) im-
ages, before and after HS bolus adminis-
tration in a series of 14 patients with
severe head trauma.
METHODS
Patients. We prospectively included 14 pa-
tients who were admitted to our neurosurgical
intensive care unit with severe traumatic
brain injury or nonsevere traumatic brain in-
jury with secondary neurologic deterioration
requiring intubation, mechanical ventilation,
and ICP monitoring as part as their manage-
ment. Inclusion criteria were the combination
of an ICP 20 mm Hg for 15 mins, a natre-
mia 155 mmol·L
1
, and a delay since the
onset of head trauma of 1–5 days. Patients
were not included if transportation to the CT
suite was considered too dangerous by the
clinician in charge of the patient because of a
permanently increased ICP or because of he-
modynamic instability. This study received
ethical approval by our local institutional re-
view board (CCPPRB Pitié-Salpêtrière’s Hospi-
tal), and written informed consent was ob-
tained from the patient’s next of kin.
*See also p. 3057.
From the Department of Anesthesiology and Critical
Care (TL, VD, PC, LP) and Department of Neuroradiology
(AZ), Hôpital Pitié-Salpêtrière, Assistance Publique-
Hôpitaux de Paris; Université Pierre et Marie Curie-Paris 6,
France; and the Artemis Project Unit, Institut National
des Télécommunications, Evry, France (FP).
Supported, in part, by grant CRC 0325 from the
Assistance Publique-Hôpitaux de Paris and by grant
from the Fondation des Gueules Cassées.
The authors have not disclosed any potential con-
flicts of interest.
Copyright © 2006 by the Society of Critical Care
Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/01.CCM.0000243797.42346.64
Objective: The aim of this study was to quantify the effect of
hypertonic saline solution on contused and noncontused brain
tissue in patients with traumatic brain injury. We hypothesize that
hypertonic saline would increase the volume of brain contusion
while decreasing the volume of noncontused hemispheric areas.
Design: Prospective observational study.
Setting: Neurosciences critical care unit of a university hospital.
Patients: Fourteen traumatic brain injury patients with in-
creased intracranial pressure.
Interventions: A computed tomography scan was performed
before and after a 20-min infusion of 40 mL of 20% saline.
Measurements and Main Results: The volume, weight, and
specific gravity of contused and noncontused hemispheric areas
were assessed from computed tomography DICOM images by
using a custom-designed software (BrainView). Physiologic vari-
ables and natremia were measured before and after infusion.
Hypertonic saline significantly increased natremia from 143 5
to 146 5 mmol/L and decreased intracranial pressure from
23 3to17 5 mm Hg. The volume of the noncontused
hemispheric areas decreased by 13 8 mL whereas the specific
gravity increased by 0.029 0.027%. The volume of contused
hemispheric tissue increased by 5 5 mL without any con-
comitant change in density. There was a wide interindividual
variability in the response of the noncontused hemispheric tissue
with changes in specific gravity varying between 0.0124% and
0.0998%.
Conclusions: Three days after traumatic brain injury, the blood-
brain barrier remains semipermeable in noncontused areas but
not in contusions. Further studies are needed to tailor the use of
hypertonic saline in patients with traumatic brain injury according
to the volume of contusions assessed on computed tomography.
(Crit Care Med 2006; 34:3029–3033)
K
EY WORDS: head trauma; specific gravity; computed tomogra-
phy; contusion; blood-brain barrier
3029Crit Care Med 2006 Vol. 34, No. 12
Page 1
All patients were orotracheally intubated
and mechanically ventilated and had an inter-
nal ventricular drain inserted after they met
international criteria for ICP monitoring. ICP
was monitored through the external ventric-
ular derivation catheter (Sophysa, Orsay,
France), connected to a calibrated pressure
transducer (Transpac, Abbott, Sligo, Republic
of Ireland), zeroed at the external eye angle,
and inserted during the first 24 hrs after
trauma. Doppler of the mean cerebral arteries
were performed at least once a day. Patients
were treated according to our intensive care
guidelines including 30° head up positioning,
cerebrospinal fluid drainage if ICP increased
above 20 mm Hg, cerebral perfusion pressure
maintained between 70 and 80 mm Hg, pul-
satility index maintained 1.2 through the
use of fluid loading and continuous infusion of
norepinephrine, sedation with a continuous
intravenous infusion of sufentanil and mida-
zolam and propofol as required for ICP con-
trol, and maintenance of normocapnia, nor-
moxia, and normoglycemia.
Study Design. After a period of stabiliza-
tion in the CT suite, a first cerebral CT scan
(CT 1) was performed on a high-speed advan-
tage CT scan (GE Medical Systems). On com-
pletion of imaging, an intravenous infusion of
40 mL of 20% HS was injected over 20 mins
through a central venous catheter while the
patient was maintained sedated and ventilated
on the CT stretcher. Great care was taken to
maintain the patient perfectly still during the
infusion period. A second CT (CT 2) was per-
formed 2 mins after HS infusion ended. The
intraventricular drainage was clamped and the
infusion rates of norepinephrine and sedation
were maintained unchanged during the study
period. Heart rate, mean arterial blood pres-
sure, intracranial pressure ICP, and end-tidal
CO
2
were measured before each CT and just
before and right after HS infusion. Natremia
was measured in the intensive care unit before
and after transportation to the CT.
Images Analysis. CT images were acquired
as 5-mm-thick contiguous slices and analyzed
using a custom-designed software package
(BrainView 1.8) recently described by our
group (16). BrainView provides semiautomatic
tools for brain analysis and quantification
from images obtained from cerebral CT scan.
For each CT image, BrainView input a series of
continuous axial scans of the brain. It then
automatically excluded extracranial compart-
ments on each CT section by means of a math-
ematical morphology-based algorithm. Inter-
active slice-by-slice segmentation allowed
selection of different anatomical territories in-
dexed throughout the whole sequence.
As a first step, the overall intracranial con-
tent was delineated. Two subsets of analysis
were then performed: The first one was on
different anatomical segments: left and right
hemispheres together called “hemispheres,”
brainstem, cerebellum, and intraventricular
and cisternal cerebrospinal fluid. The second
analysis focused on contused and noncontused
hemispheric tissue. The hemispheric contused
tissue was identified and delineated on each
slice using the thresholding function of the
image analysis software. The contusion was
definite as abnormal hemispheric tissue in-
cluding the hyperdense core (radiologic atten-
uation 40 HU) and the hypodense pericon-
tusional tissue (radiologic attenuation 20
HU) together (Fig. 1). In case of plurifocal
contusions, all of them were delineated on
each slice. Noncontused hemispheric tissue
was identified as normal appearing tissue on
each slice.
For each compartment of a known number
of voxels, the volume, weight, and specific
gravity were computed using the following
equations:
1. Volume of the voxel (size of the
pixel)
2
section thickness.
2. Weight of the voxel (1 CT/1000)
volume of the voxel, where CT is the CT
number of the voxel.
3. Volume of the compartment number
of voxels volume of the voxel.
4. Weight of the compartment summa-
tion of the weight of each individual
voxel included in the compartment.
5. Specific gravity of the compartment
weight of the compartment/volume of
the compartment. The specific gravity is
expressed as a physical density in g/mL.
Patients were classified according to the
response of their noncontused areas to HS.
Responders were defined a priori as patients
having a change of the specific gravity (SG)
0.03%. This threshold was chosen as the one
that discriminates half of the patients included.
Statistical Analysis. The data are expressed
as mean
SD for Gaussian and non-Gaussian
variables. The effects of HS on the physiologic
variables measured and on the different ana-
tomical compartments (hemispheres, brain-
stem, cerebellum, cerebrospinal fluid) were
analyzed by paired Student’s t-test. The effects
of HS on contused and noncontused areas
were compared by a two-way analysis of vari-
ance for two within factors: factor “HS” (be-
fore, after) and factor “Contusion” (contused
areas vs. noncontused areas). A significant in-
teraction between these two factors indicates
that HS has a different effect in contused areas
and noncontused areas. The change in the
weight of contusion according to its initial
volume assessed in percentage of the hemi-
spheres was analyzed by linear regression
analysis. Statistical analyses were performed
using JMP IN 5.1 statistical software (SAS In-
stitute, Cary, NC). Considering the fact that
weight was derived from the computation of
volume and SG, the significance level was
fixed at 2.5% to accommodate two indepen-
dent tests.
RESULTS
Physiologic Variables. Fourteen pa-
tients (12 male, two female) were prospec-
tively studied 3 2 days after injury (1–5
days). Ages ranged from 18 to 69 (36 15)
years. The Glasgow Coma Scale score at the
scene of accident ranged from 4 to 14 with
a median score of 7 (Table 1).
At baseline, heart rate was 68 12 per
min, mean arterial blood pressure was
103 9 mm Hg, and ICP was 23 3mm
Hg. HS significantly decreased ICP by 6
3mmHg(p 001) with no concomitant
effect on heart rate, mean arterial blood
pressure, cerebral perfusion pressure, or
end-tidal CO
2
(data not shown). HS signif-
icantly increased natremia by 3 1 from
143 5 mmol/L (p .01).
Effects of HS on Anatomical Struc-
tures. The effects of HS differed between
the various anatomical regions of the
brain. HS decreased the volume of the
hemispheres while increasing their spe-
cific gravity (Table 2). No significant
changes in the weight, volume, and SG of
the cerebellum, brainstem, and cerebro-
spinal fluid were noted.
Effects of HS on Contused and Non-
contused Tissue. HS had opposite effects
on noncontused and contused hemi-
spheric areas (Table 3, Fig. 2, significant
interaction, p .0001). HS decreased the
Figure 1. Original computed tomography scan image (left panel). Automatic isolation of the intra-
cranial compartment by the software (middle panel). Isolation of the contused and noncontused tissue
(right panel). Note that the intraventricular derivation catheter is excluded from intracranial com-
partment.
3030 Crit Care Med 2006 Vol. 34, No. 12
Page 2
volume of the noncontused hemispheric
tissue by 13 8 mL while increasing the
SG by 0.029 0.027%. There was a wide
variability in the response of noncon-
tused hemispheric tissue to HS, with
changes in SG varying between 0.0124%
and 0.0998% (Fig. 3). Age, initial Glasgow
Coma Scale Score, initial Simplified
Acute Physiology Score II, mechanism of
accident, delay between trauma and CT,
initial SG, and ICP decrease were similar
between responders and nonresponders
to HS.
The volume of the contused tissue
ranged from 3 to 157 mL (62 55 mL).
HS increased the volume of contused
hemispheric tissue by 5 5 mL without
any concomitant change in density. The
increase of the contusion’s weight with
HS injection was significantly related to
baseline contusion volume expressed as a
percentage (r
2
.62, p .01) (Fig. 4).
DISCUSSION
The main result of the study is the
observation of a differential effect of HS
on noncontused and contused hemi-
spheric areas. HS consistently decreased
the weight of the noncontused areas
while increasing the SG, indicating a net
decrease in water content and conse-
quently a functional BBB. At the oppo-
site, HS always increased the weight of
contusion. Interestingly, the response to
HS, quantified as the change in SG in
normally appearing areas on CT, varied to
a great extent among TBI patients.
Different types of edema coexist in TBI
patients: vasogenic edema due to BBB
breakdown, cytotoxic edema secondary to
ischemic insult, or cellular edema result-
ing from neurotoxic insult. Clearly, there
is a time and regional dependency in the
occurrence of these different edema sub-
types. There are many experimental ar-
guments showing that the BBB is tempo-
rarily damaged by trauma. Time window
studies indicate that the barrier seals
within a few hours following severe head
injury (17). In the experimental model of
Barzo et al. (18), permeability of the BBB
returned to control values as soon as 30
mins after the head trauma. Tanno et al.
(19) also observed a pronounced abnor-
mal permeability to immunoglobulin G
and horseradish peroxidase occurring
within the first hour after injury that was
widespread throughout both hemi-
spheres after a lateral, fluid percussive
brain injury in the rat. Maximal perme-
ability occurred at 1 hr after injury. This
was confirmed by Baldwin et al. (10). In
humans, this early, transient, and diffuse
opening of the BBB might increase the
brain SG since the edematous fluid could
have a specific gravity higher than the
brain parenchyma. This might account
for the increased SG observed in human
TBI (16). The state of the BBB after this
Table 1. Patient details
Age,
Yrs Gender
Injury
Mechanism GCS Marshall Surgery SAPS II LOS GOS
69 M Traffic injury 7 NEML 69 44 2
36 M Traffic injury 7 EML LSDH 38 9 1
37 M Assault 7 3 41 28 5
18 M Traffic injury 7 EML RSDH, LEDH 39 28 3
40 M Fall 6 NEML 41 20 5
20 F Traffic injury 11 2 40 9 4
21 M Traffic injury 8 3 47 28 3
22 F Traffic injury 8 2 42 39 4
45 M Fall 7 EML REDH 48 27 3
57 M Traffic injury 7 2 48 75 1
31 M Assault 7 2 41 7 1
33 M Fall 10 EML LSDH 43 27 3
26 M Traffic injury 14 NEML 28 11 1
44 M Fall 4 EML LSDH 67 10 1
GCS, Glasgow Coma Scale score; SAP, Simplified Acute Physiology Score; LOS, length of stay in
the intensive care unit; GOS, Glasgow Outcome Score at ICU discharge (5 good recovery; 1
death), NEML, nonevacuated mass lesion; EML, evacuated mass lesion; LSDH, left subdural hema-
toma; RSDH, right subdural hematoma; LEDH, left extradural hematoma; REDH, right extradural
hematoma.
Table 2. Effects of hypertonic saline on weight, volume, and specific gravity (SG) of the different
anatomical structures
Before HS Infusion After HS Infusion p
Hemispheres
Weight, g 1161 76 1153 75 .01
Volume, mL 1123 76 1115 75 .01
SG, g/mL 1.0338 0.0032 1.0341 0.0031 .01
Brainstem
Weight, g 27 626 6NS
Volume, mL 26 625 6NS
SG, g/mL 1.0289 0.0019 1.0294 0.0021 NS
Cerebellum
Weight, g 131 14 133 14 NS
Volume, mL 126 14 128 13 NS
SG, g/mL 1.0359 0.0037 1.0363 0.0035 NS
Cerebrospinal fluid
Weight, g 43 31 43 31 NS
Volume, mL 44 32 43 31 NS
SG, g/mL 1.0164 0.0057 1.0168 0.0051 NS
HS, hypertonic saline; NS, not significant.
Table 3. Effects of hypertonic saline on weight, volume, and specific gravity (SG) of the contused and
noncontused hemispheric areas
Before HS Infusion After HS Infusion p
Normal appearing hemispheres
Weight, g 1096 91 1082 93 .0001
Volume, mL 1060 90 1047 92 .0001
SG, g/mL 1.0336 0.0029 1.0339 0.0029 .005
Contusion appearing hemispheres
Weight, g 65 58 70 61 .001
Volume, mL 62 55 68 59 .001
SG, g/mL 1.0364 0.0069 1.0365 0.0070 NS
HS, hypertonic saline; NS, not significant.
3031Crit Care Med 2006 Vol. 34, No. 12
Page 3
initial opening is still partly unknown.
Clearly, one has to consider the noncon-
tused and the contused areas differently
in this respect.
Regarding the noncontused areas, our
data suggest that BBB permeability is un-
equally affected among patients since we
observed a wide variability in response to
hypertonic saline infusion in terms of SG
change in these areas. As a mean, patients
with TBI increased their SG in these ar-
eas after HS administration indicating an
efficient BBB. We were not able to show
differences in terms of age, initial Glas-
gow Coma Scale score, initial Simplified
Acute Physiology Score II, mechanism of
accident, delay between trauma and CT,
mechanism of TBI, initial SG, and ICP
between responders and nonresponders
to HS. These results are coherent with
most of the magnetic resonance imaging
data available in experimental and human
TBI showing that BBB is functional in the
noncontused areas (18, 20, 21). However,
one should acknowledge that the mole-
cule used to test the BBB permeability
might, by itself, affect the results. A pas-
sage through the BBB of large molecules
such as gadolinium, gadolinium-DTPA
(Gd-DTPA), or iodine might occur only in
case of extensive damage. On the other
hand, a slight change in BBB permeabil-
ity could be evidenced only through the
use of a small molecule such as salt. In
this respect, we think that our study de-
sign gave us a unique opportunity to test
the BBB permeability in human. In this
context, the increase in SG that we ob-
served after salt administration indicates
that BBB is acting as a semipermeable
membrane. Such a result was also ob-
served by Saltarini et al. (22) in a patient
with refractory intracranial hypertension
using magnetic resonance imaging to as-
sess cerebral water content. It is notewor-
thy that our measurements could be
slightly biased by the fact that HS in-
creases cerebral blood flow through a re-
duction in blood viscosity (23). When au-
toregulation is preserved, this increase in
cerebral blood flow is combined with a
decrease in cerebral blood volume that
could slightly underestimate the effect of
HS on SG since blood has a higher SG
than brain tissue.
Regarding the contused areas, experi-
mental data suggest that BBB remains
open for a prolonged period of time after
trauma. Our data suggest that this is true
in human TBI, since HS consistently in-
creased the weight and volume of con-
tused areas. In the experiment by Tanno
et al. (19), at 24 hrs after injury, abnor-
mal permeability was restricted to the
impact site and this area remained per-
meable up to 72 hrs after trauma. In ten
patients with cerebral contusions 1–2
days after trauma, Kushi et al. (24) ob-
served that contusion edema areas were
frequently enhanced by Gd-DTPA indicat-
ing that an increased cerebrovascular
permeability occurs early after trauma
and suggesting that contusion edema
may be at least partially vasogenic in na-
ture. There are numerous arguments
showing that the state of the BBB in the
Figure 2. Mean effect of hypertonic saline on the weight and volume of contused and noncontused areas. The box plots summarize the distribution of points
at each factor level. The ends of the box are the 25th and 75th quartiles. The line across the middle of the box identifies the median sample value. The
whiskers extend from the ends of the box to the outermost data point that falls within the distances computed.
Figure 3. Change in specific gravity (SG) of the noncontused hemispheric areas induced by hypertonic
saline (HS) according to baseline specific gravity.
Figure 4. Change in the weight of contusion
according to their initial volume assessed in per-
centage of the hemispheres.
3032 Crit Care Med 2006 Vol. 34, No. 12
Page 4
contusion area might be very different in
its time course than in noncontused ar-
eas. Experimentally, Beaumont et al. (25)
demonstrated using an intravenous bolus
of 0.2 mmol/kg Gd-DTPA with serial T1
MR images that BBB permeability was
greatest in the site of contusion. Gd-
DTPA accumulation was greatly en-
hanced by secondary insult such as hyp-
oxia and hypotension. Bradykinin and
arachidonic acid have been suspected as
mediators of this secondary opening (26).
The maximum effect of HS has been
consistently observed 20–25 mins follow-
ing the end of bolus infusion. The mean
duration of action has been reported at 93
mins (3). In the present study, we chose
to perform the second CT right after the
end of the bolus injection. This timing
was chosen to reduce a potential time
confounding effect and to avoid the dis-
placement of the patient from the CT
table, allowing us to maintain the head in
the exact same position between the two
CTs. Because of this timing, it is possible
that we did not evaluate the effect of HS
at its peak but slightly before. Neverthe-
less, this could change the absolute val-
ues that we measured but not the trends
that we observed. Regarding natremia
change, our measures were very closed to
the one observed by Horn et al. (4). In
their study, plasma Na
concentration
increased from 141 6 mmol/L to 143
5 mmol/L 1 hr after 2 mL/kg of body
weight 7.5% HS.
CONCLUSION
HS consistently increased the vol-
ume of contusion, whereas its effect on
noncontused areas, although signifi-
cant when taking all the patients to-
gether, showed marked interindividual
variations.
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3033Crit Care Med 2006 Vol. 34, No. 12
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    • "The principles of identifying areas of BBB compromise and edema can be translated into clinical practice . In 2006, Lescot et al. [19] used computed tomography to measure volume, weight, and specific gravity of contused and noncontused areas in patients with severe TBI. Recently, preclinical investigators using MRI with diffusion weighted imaging technology have been able to identify temporal and regional differences in edema after TBI in rabbits. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Blood brain barrier (BBB) compromise is a key pathophysiological component of secondary traumatic brain injury characterized by edema and neuroinflammation in a previously immune-privileged environment. Current assays for BBB permeability are limited by working size, harsh extraction processes, suboptimal detection via absorbance, and wide excitation fluorescence spectra. In this study, we evaluate the feasibility of Alexa Fluor 680, a far-red dye bioconjugated to dextran, as an alternative assay to improve resolution and sensitivity. Methods: Alexa Fluor was introduced intravenously on the day of sacrifice to three groups: sham, controlled cortical impact (CCI), and CCI treated with a cell based therapy known to reduce BBB permeability. The brains were sectioned coronally and imaged using an infrared laser scanner to generate intensity plot profiles as well as signal threshold images to distinguish regions with varying degrees of permeability. Results: Linear plot profile analysis demonstrated greater signal intensity from CCI than treated rats at corresponding injury depths. Threshold analysis identified rims of signal at low + narrow threshold ranges. The integrated signals from a treatment group known to preserve the BBB were significantly less than the groups with CCI injury alone. There was no significant difference at high + wide signal intensity threshold ranges. Conclusions: Alexa Fluor 680 infrared photodetection and image analysis can aid in detecting differential degrees of BBB permeability after traumatic brain injury and maybe particularly useful in demonstrating BBB preservation of at-risk regions in response to therapeutic agents.
    Full-text · Article · May 2014 · Journal of Surgical Research
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    • "First, there is no established dose of HTS or target serum sodium when instituting therapy. Hyperosmolarity from hypernatremia works in areas of " normal brain " where the blood–brain barrier remains intact and can result in increased brain volume in contusional areas [19] . Furthermore , the brain accommodates to HTS-induced sustained hypernatremia by intracellular idiogenic osmoles accumulation, which raises brain water content, restores brain volume, and leads to rebound increased ICP [12,20]. "
    [Show abstract] [Hide abstract] ABSTRACT: Hypernatremia is common following traumatic brain injury (TBI) and occurs from a variety of mechanisms, including hyperosmotic fluids, limitation of free water, or diabetes insipidus. The purpose of this systematic review was to assess the relationship between hypernatremia and mortality in patients with TBI. We searched the following databases up to November 2012: MEDLINE, EMBASE, and CENTRAL. Using a combination of MeSH and text terms, we developed search filters for the concepts of hypernatremia and TBI and included studies that met the following criteria: (1) compared hypernatremia to normonatremia, (2) adult patients with TBI, (3) presented adjusted outcomes for mortality or complications. Bibliographic and conference search yielded 1,152 citations and 11 abstracts, respectively. Sixty-five articles were selected for full-text review with 5 being included in our study. All were retrospective cohort studies totaling 5,594 (range 100--4,296) patients. There was marked between-study heterogeneity. The incidence of hypernatremia ranged between 16% and 40%. Use of hyperosmolar therapy was presented in three studies (range 14-85% of patients). Hypernatremia was associated with increased mortality across all four studies that presented this outcome. Only one study considered diabetes insipidus (DI) in their analysis where hypernatremia was associated with increased mortality in patients who did not receive DDAVP. Although hypernatremia was associated with increased mortality in the included studies, there was marked between-study heterogeneity. DI was a potential confounder in several studies. Considering these limitations, the clinical significance of hypernatremia in TBI is difficult to establish at this stage.
    Full-text · Article · Nov 2013 · Annals of Intensive Care
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    • "Studies performed in murine models of head trauma report a decrease in eSG with a rise in the cerebral water content [17, 18]. However, and as in our three different studies141516, Bullock at al. observed an increased SG with severe TBI in the same proportion [19]. In another human TBI study, specific gravity determined on small pieces of subcortical tissue using a graduated specific-gravity column was also increased [20]. "
    Full-text · Chapter · Nov 2011
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