Efficacy of hypertonic

7.5% saline and

6% dextran-70 in treating trauma: A
meta-analysis of controlled clinical
studies
Charles E. Wade, PhD, George C. Kramer, PbD, James J. Grady, Dr PH, Timothy
Riad N. Younes, MD, Davis, Cali$, Galveston,
Texas, Memphis,
Term., and 530 Pa&o,

C. Fabian, MD, and

Brazil

Background. Individual

trials of small-volume resuscitation of 7.5 % NaCl (HS) with and without

6 % de&ran 70 (HSD) for the treatment of trauma have failed to provide convincing evidence of ejjicacy. We performed a meta-analysisto evaluate the effects of HS and HSD on survival until discharge or
for 30 days. We identified eight double-blinded,
randomized controlled trials ofHSD and six trials of
HS. In all cases,administration
of 250 ml of HSD or HS was compared with a control group administration of 250 ml of isotonic crystalloid for the treatment of hypotension either in the field or at admission to the emergency department.
Methods. A fixed-effects meta-analysis
was performed with the Mantel-Haenszel
method of combining
results from multiple studies.
Results. Overall, HS was not effective in improving survival with a weighted mean difference in survival of the HS group versus the isotonic control group equal to 0.6%. The results with HSD were more
positive, with an increase in survival in seven of eight trials. The mean difference in survival rates
favoring HSD (n = 615) over controls (n = 618) was 3.5% (jr = 0.14, two-tailed; p = 0.07, one-tailed).
The odds ratio was estimated to be 1.20 in favor of HSD with a 95% confidence interval of 0.94 to
1.57.
Conclusions. The meta-analysis of the available data shows that HS is not diffaentfiom
the standard
of care and that HSD may be superior (Surgmy 1997;122:609-16.)
From the Department
of Neurobiology,
Physiology,
and Behavior;
University
of California,
Davis, Cal$,
the
Departments
of Anesthesiology
and of Preventive
Medicine
and Community
Health,
University
of Texas Medical
Branch,
Galveston,
Texas, the Department
of Surgery, University
of Tennessee, Memphis,
Tenn., and the
Department
of Surgery, University
of SGo Puulo, &io Pa&o, Brazil

TRAUMA IS THE LEADING

CAUSE of civilian death in
Americans younger than 45 years of age and is the
fourth-leading cause of death in the United States
for all ages.l The loss of life expectancy as a result
of trauma is greater than that caused by either
heart diseaseor cancer because trauma primarily
results in the deaths of children and young adults.
About 100,000 people lose their lives each year as
the result of trauma-related injuries.2 Many, if not
most, civilian trauma deaths are due to hemorrhagic shock. Hemorrhage was a leading cause of
battlefield mortality in Vietnam and was also the
Supported
Accepted

in part by Medisan
for publication

Reprint
requests:
George
Anesthesiology,
Clinical
77555-0749.
Copyright

March

+ 0

AB.

26, 1997.

C. Kramer,
PhD, UTMB,
Dept. of
Sciences
Bldg. 503, Galveston,
TX

0 1997 by Mosby-Year

0039-6060/97/$5.00

Pharmaceuticals

Book,

11/56/83282

Inc.

cause of death that was most likely treatable.3

Hemorrhagic hypovolemia and the resulting circulatory shock require prompt treatment. Unfortunately, this treatment is often too little and too
late to prevent death or severe morbidity, The economic and sociologic costs of civilian and military
trauma are immense and would be reduced if initial resuscitation efforts were more effective.
Extensive efforts have been directed to this end.4sj
The current regimen of prehospital fluid
administration consists of using isotonic solutions
such as lactated Ringers or normal saline. When
possible, fluids are aggressively administered in
large volumes as rapidly as possible because 2 to 4
liters of isotonic fluid are required to replace each
liter of blood lost. However, prehospital treatment
of hemorrhage with conventional isotonic fluids is
often inadequate because of the large volumes
required, the short transport times in which to
SURGERY

609

surgery

Wadeet al.

610

September 1997

Table I. Clinical experiences with HS and HSD for resuscitation of trauma

Patients per group
Study
Author

no.

1
2
3
4
5
6

Center

Holcroftzl*
Younesgs31
HolcroftPz*
Maningas32
Holcroft33*
Vassar23 (HS vs LR)
(HSD vs LR)
VassarrOt
Mattoxs

7
8
9
10
11

Younes14T
Vassar-r5
Fabianl

12
13

Vassarnil
Rocha e Silvar2

PH, Prehospital;
*Studies

air, helicopter;

tIncludes

29 patients

TData from

abstract,

&Jnpublished

abstract.

1112% dextmn

group

treated

Sacramento (PH, air)

Sao Paulo (ER)
Sacramento (PH) , ground
Houston (PH)
Sacramento (ER)
Sacramento (ER)
Sacramento (PH, air)
Houston, Denver,
Milwaukee (PH, ground)
Sao Paulo (ER)
Sacramento (PH, ground)
Memphis (PH, air)
Memphis (ER)
5 Centers (PH, air)
Multicenter,
Brazil (ER)

ground,

1, 3, and 5 not entered

into
with

subsequently

Included in
meta-analysis

Test
solutions
HSD
HS/HSD
HSD
HSD
HSD
HS
HSD
HSD
HSD

No
Yes
No
Yes
No
Yes
Yes
Yes
Yes

HSD
HS/HSD
HS
HS
HS/HSD
HSD

Yes
Yes
Yes
Yes
Yes
Ongoing

HSD

IS0

(10)

(10)

(2:;

(3;;

(1;

(1;
27
24
83
211

23
83
211

101
89

50

HS

111
84
75
113
45

35

32

85
67
71
50

ambulance.
meta-analysis

4.2%
published

dextran

because
instead

they contained

interim

data presented

in studies

6 and

7.

of 6% dextran.

as article.3*

not included.

administer the fluids, and the use of small-bore

peripheral venous cannulas.6 It has been argued
that the time needed for venous accesswill not be
recuperated in more rapid resuscitation because of
the limited amounts of fluid that can be infused. In
the military setting highly skilled combat medics
often provide prompt homeostasis and vascular
access, but timely fluid resuscitation is limited by
the size of the peripheral catheters and by how
much fluid can be carried into the field.
Trauma patients often arrive at the hospital
underresuscitated and in severe hypovolemic
shock. On the other hand, a recent study of penetrating trauma to the torso requiring operation
suggeststhat in an urban setting with well-trained
paramedics aggressive field resuscitation may be
deleterious. Higher survival rates were reported
for patients who were administered no fluid in
either the field or emergency room (ER) , but who
instead had resuscitation started in the operating
room. The hypothesized explanation for this
apparent paradox is that aggressive resuscitation
and rapid restoration of blood pressure can lead to
increased bleeding, which would increase the
severity of shock.
The development
of hyperosmotic
2400
mOsm/L saline formulations makes small-volume

resuscitation a possible answer to the logistic problems of field resuscitation by civilian paramedics
and military corpsmen. Most research has focused
on 7.5% NaCl combined with the colloid dextran
70 at a concentration of 6%, although there has
also been substantial work on hypertonic saline
alone. Animal studies show that such hypertonic
solutions can increase survival rates from severe
hemorrhagic shock and reduce. early volume
requirements to one tenth those of conventional
isotonic fluids for at least the first few hours of
treatment4 Several clinical trials suggest an overall
reduction in the mortality and rate of serious complications of civilian trauma.*-1 Data also suggest a
reduction in the need for blood, reducing hospital
costs and the risks of blood-borne diseases and
reactions.g Although promising, clinical trials have
not provided definitive data as to the efficacy of
hypertonic solutions. This has been in part due to
the limited numbers of patients enrolled into individual studies, the diversity of the cause and extent
of injury in patients with trauma, and underlying
factors, such asalcohol consumption and drug use,
complicating patient selection and treatment. In
the present study we performed a meta-analysis of
all known controlled randomized trials of hypertonic

7.5%

NaCl

solutions

to determine

whether

surgery
Volume 122, Number 3

Wade et al. 611

Table II. Study criteria and conclusions on effects of HS and HSD

Entry criteria

Exclusion criteria

Summary of results

Holcroft*l*

Trauma, SP
<70mmHg

<18 yr of age; >6 hr from

time of injury

BP better; SP increased;
heart rates increased
little change in GCS

Younes g,31

Hypovolemic
shock, SP
<SOmmHg

~18 yr of age; SP > 80 mm Hg; pregnancy; negative ECG; no palpable pulse;

history of cardiac or metabolic disease

BP better; less blood needed;

no significant difference in
survival ; less fluid needed

Holcroft***

Trauma, SP
< 100 mm Hg

~18 yr of age

Good CV response; overall

mortality trend better, signiticant only in patients with head
injuries

Maningas3*

Trauma, SP
<90mmHg

SP > 90 mm Hg; <18 yr of age; pregnancy; history of seizures,coagulopathy,

liver or renal disease;blunt trauma

Safe; higher BP; less 24hr

fluid apparent

Trauma, SP
<SOmmHg

SP > 90; <18 yr of age; pregnancy;

preexisting heart, liver, kidney disease

No adverse and no statistically

significant beneficial effects

Vassar23

Trauma, SP
< SO/90 mm Hg

SP > 80/90; ~18 yr of age;

pregnancy; preexisting heart,
liver, kidney disease

No adverse and no statistically

significant beneficial effects,
24hr fluid tended to be less

VassarlOt

Trauma, SP
< 100 mm Hg

SP > 100 mm Hg; no peripheral

pulse or ECG ; <18 yr of age;
pregnant; severe liver, kidney, heart, or
neurologic disease; peripheral
edema

BP better; improved survival

in patients with severe head
injuries; survival tended to
be improved

Mattox

Trauma, SP
<90mmHg

SP > 90 mm Hg; <16 yr of age;

pregnancy; history of seizures,
coagulopathy, liver or kidney
disease; antishock trousers applied

Better BP; trend overall better

survival; increased survival in
surgical patients; 24hr fluid
tended to be less

Younes14r

Hypovolemic
shock

~16 yr of age; pregnancy; history

of kidney or heart disease; arriving
in cardiac arrest

Improved 24hr and 30-day

survival, p < 0.05; less ER
volume therapy required

Vassarlj

Trauma, SP
<90mmHg

SP > 90 mm Hg; asystolic or

CPR in progress during transport;
~18 yr of age; >2 hr from injury;
pregnancy; burn; no IV access

7.5% NaCl improved survival

compared with predicted;
adding dextran did not offer
an apparent additional benefit

Fabianl

Trauma, SP
< 100 mm Hg

Not blinded,
other day

No beneficial
effect

Vassar11

Trauma, SP
<90mmHg

SP > 90 mm Hg; asystole or CPR;

~18 yr of age; >2 hr from time of injury;
pregnancy; history of seizures; burn
injury; liver, heart, or kidney disease;
no IV access

SP, Systolic

blood

pressure;

BP, blood

pressure;

CV, cardiovascular;

HS administered

CPR cardiopulmonary

*Studies
1, 3, 5 not entered
into meta-analysis
because they contained
tIncludes
29 patients
treated with 4.2% dextran
instead of 6% dextran.
IData from abstract, subsequently
published
as arti~le.~~
SUnpublished
II12% dextran

abstract.
group

not included.

every

interim

data presented

resuscitation;
in studies

or deleterious

HS and HSD were associated

with higher blood pressure;
greater survival compared with
predicted survival in all patients
and in several specific subgroup
GCS, Glascow
6 and 7.

coma score;

n: intravenous.

612

Wade et al.

Table

surgery
September 1997

III. Discharge or 30-day survival in HS versus isotonic controls for initial treatment of trauma
HS

Reference

Younesgs31
Vassarz3(HS vs LR)
VassarI

28/35
15,32
73/85
43/67
46/71
30/50

Fabian* (Prehospital)
Fabian* (Hospital)
Vassar16t
Weighted mean difference
Data shown

are number

*Data

from unpublished

tl2%

dextran

group

of surviving

divided

VassarlO*

VassarI
Vassar@
Weighted

from

published
group

+2.9%
-16.1%
+2.6%
t1.5%
-6.9%
+11.1%
-0.6%

survival.

controls

(ISO) for initial

IS0
27/35
20/25
11/24
49/83
169/211
71/111
70/84
22/45

mean difference

are number
29 patients

dextran

percent

28/35 (80.0%)
20/23 (87.0%)
11/23 (47.8%)
53/83 (63.9%)
176/211 (83.4%)
74/101 (73.3%)
69/89 (77.5%)
28/50 (56.0%)

Mattox*
Younes14t

iData

and

(77.1%)
(63.0%)
(83.3%)
(62.7%)
(71.7%)
(48.9%)

HSD

Maningas3
Vassar23

112%

patients

or 30-day survival of HSD versus isotonic

Younesg,31

*Includes

by total

27/35
17,27
70/84
47/75
81/113
22/45

not included.

Reference

Data shown

(80.0%)
(46.9%)
(85.9%)
(64.2%)
(64.8%)
(60.0%)

abstract.

IV. Discharge

Table

patients

HS-Iso A %

IS0

of surviving
treated

patients

with 4.2%

dextran

divided
instead

by total

patients

and percent

(77.1%)
(80.0%)
(45.8%)
(59.0%)
(80.1%)
(64.0%)
(83.3%)
(48.9%)

treatment

of trauma
HSD-Iso A %
t2.9
+7.0
t2.0
+4.9
t3.3
t9.3
-5.8
t7.1
t3.6

survival.

of 6% dextran.

abstract.
not included.

hypertonic saline improves survival in patients with

hypotension associated with traumatic injury.
We separated our analysis into the effects of an
initial 250 ml bolus of hypertonic saline (HS) alone
and hypertonic saline dextran (HSD). The two
hypertonic groups were compared with matched
groups given an initial 250 ml bolus of isotonic
saline. In all cases,additional isotonic therapy was
administered after the administration of a test solution, as per center policy and per the American
College of Surgeons Guidelines for Advanced
Trauma Life Support.
METHODS
Av+lable
studies. We conducted a variety of literature searches to identify studies to be used in
the meta-analysis. This included a review of recent
meeting abstracts and proceedings. In addition, an
attempt was made to identify all unpublished studies. Letters requesting information as to knowledge of unpublished controlled randomized studies were sent to international researchers and
clinicians active in the area of trauma research.

We are aware of 10 published studies, 1 study in

press, and 1 unpublished study, for a total of 12
studies, on the use of 7.5% NaCl (HS) alone or in
combination with dextran 70 (HSD, usually at a
concentration of 6%) for the initial treatment of
trauma (Table I). We are also aware of one ongoing
study of HSD. I2 Studies 1, 3, and 5 in Table I report
on interim data also reported in studies 6 and 7. In
completed studies, 615 patients were treated with
HSD and 340 were treated with HS. In all cases,
comparisons against a similar number of isotonic
controls were made. Several publications reported
on more than one trial or on more than one hypertonic solution. Both HS and HSD were studied
together or asseparate trials in studies 2, 6, 10, and
12. In study 12 in Table I a 7.5% NaCl-12% dextran
70 solution was evaluated. One study, number 11 in
Table I, consisted of separate studies conducted in
the ER and in the field or prehospital. HSD was
evaluated in five prehospital trials and three ER
studies, and HS was evaluated in three prehospital
and four ER trials.
Studies had to meet the following criteria to be

surgery

Wadeet al.

613

Volume 122, Number 3

included in the meta-analysis: they had to (1) use

250 ml of a saline solution of 7.5%; (2) have an
enrollment criterion of a systolic blood pressure of
less than 100 mm Hg associated with traumatic
injury; (3) be conducted in a randomized manner;
(4) include a control group in which patients
received the isotonic standard of care; and (5) have
as the end point discharge or 30-day survival. A
summary of the results of the various studies are
shown in Table II. In Tables III and IV the survival
statis
4 KS of these studies are listed separately for
comparison of survival with HS (Table III) or HSD
(Table IV) versus standard of care; the patient
numbers in each group are presented. All studies
were double-blinded except 11, which had HS or
standard of care administered on alternate days. In
all casesno therapy waswithheld, that is, additional crystalloid fluid (lactated Ringers, plasmalyte, or
normal saline) was infused as deemed necessary
per Advanced Trauma Life Support guidelines and
each centers policy.
End point. We defined our end point as survival
of the patient 30 days after injury or until discharge. Table I lists the studies. Studies 1, 3, and 5
on Table I were omitted from the meta-analysis
because they report on interim data included in
studies 6 and 7. Meta-analysis of survival was performed by combining results from the studies
meeting the entry criteria. The differences in survival rates between the experimental solution
(HSD or HS) and the isotonic standard of care
(ISO) were estimated. We used the MantelHaenszel method of combining data across studies.l3 A summary estimated odds ratio was used to
indicate the strength of the relationship of treatment with discharge survival. We used the
Cochran-Mantel-Haenszel test to assessthe statistical significance of the association of treatment with
discharge survival. Mean differences were weighted
by the inverse of the variance.
RESULTS
The overall qualitative results of each study are
listed in Table II for the HS and HSD comparisons.
The infusion of 250 ml of hypertonic saline solution (2400 mOsm/L) appears to be remarkably
safe because not one complication was attributed
to the use of HSD or HS. Groups treated with HS
generally exhibited larger blood pressure increases
than were observed in groups treated with isotonic
solutions (studies 1, 2, 6, 8, and 12). Also, hypertonic resuscitation usually reduced early and 24hour total fluid and blood requirements (studies 2,
6, 8, and 9).
Table III shows the six studies in which HS was

compared with isotonic resuscitation; survival rates

did not differ. The weighted mean difference in
survival was small, -0.6%; HS survival minus isotonic control survival. Our hypothesis was that the use
of HS would increase survival rates compared with
isotonic resuscitation. For the meta-analysis we
used a 95% confidence interval (CI) for elimination of Type 1 error and an 80% CI for elimination
of Type 2 error, Meta-analysis showed that the twotailed p value was 0.919 and the one-tailed p value
was 0.460. The odds ratio estimate was equal to
0.98, with a 95% CI of 0.71 to 1.36.
Overall survival rates in individual hypertonic
saline dextran groups and their paired isotonic
control groups are shown in Table IV. Survival was
greater in seven of eight studies with HSD; however, these differences reached statistical significance
in only one of the individual studiesI and in specific subpopulations, patients with head injuries,O
or trauma patients requiring operation.* Together
the eight studies in which HSD was compared with
IS0 had a weighted mean survival that was 3.6%
higher with HSD. Meta-analysis showed that we
could not reject the null hypothesis (p = 0.142, twotailed; p = 0.071, one-tailed). The odds ratio was
estimated to be 1.20 in favor of HSD with a 95%
confidence interval of 0.94 to 1.57.
A sensitivity analysis was performed to identify
studies that were influential in the overall results of
each meta-analysis.For the HS analysis, deletion of
the studies with the largest positive changes, largest
negative changes, or the largest number of patients
gave odds ratios (95% CI) of 0.90 (0.63, 1.28), 1.06
(0.75, 1.49), and 1.10 (0.75, 1.61), respectively. The
sensitivity analysisshowed that removal of potentially influential studies had little effect on the HS metaanalysis because the 95% CIs remained similar to
those of the overall results. For the HSD analysis
omission of the studies with the largest increase gave
an odds ratio of 1.15 (0.86, 1.53), the largest negative change, 1.31 (0.99, 1.73), or the largest number
of patients, 1.20 (0.89, 1.63). In the sensitivity analysisof the HSD meta-analysisthe lower bounds of the
95% CI approached 1.0 when the study with the
largest negative result wasdeleted; however, the confidence intervals for the other two conditions were
similar to the overall results. The sensitivity analysis
suggests no single study significantly affected the
results of the overall meta-analysis.
DISCUSSION
Of the eight studies comparing HSD with the
standard of care, seven had positive results. In the
one negative study15 in which the survival rate with
IS0 (normal saline, 83.3%) was greater than with

614 Wade et al.

HSD (77.5%), the results may reflect groups

unevenly matched as to the extent of injury. The
injury severity score in the control group of this
study was 17 + 13 versus 21 f 17 in the HSD group.
The higher the injury severity score was, the
greater was the degree of injury. The total number
of patients with anatomic injury scores equal to or
greater than 4 for one or more body regions was31
(37%) in the isotonic control group and 46 (52%)
in the HSD group. The number of patients with a
Glasgow Coma Scale score of 8 or lesswas 14 (17%)
in the IS0 group and 27 (30%) in the HSD group.
Clearly the two groups were not well matched as to
extent of injuries. These data suggest that using an
injury score as a covariant may provide better resolution of the true effectiveness of HSD compared
with the standard of care.
There are a number of other issues that confound the interpretation of data as to the efficacy
of HSD. As noted above, in a randomized trial of
patients with traumatic injuries, both the mode and
the extent of the injuries are diverse. There is evidence that HSD is more effective in patients who
are severely injured. Although HSD administration
did not significantly improve survival overall in the
multicenter study of Mattox et al.,s those patients
requiring operation showed a significant benefit.
Vassaret al? compared observed survival with predicted survival and noted improvements in those
patients with severe injuries (lessthan 25% chance
of surviving) requiring operation or with nontamponaded injuries. It has been suggested that
patients with head trauma benefit greatly from
treatment with HS and HSD.1,16
Despite the generally effective use of 7.5% NaCl,
usually infused with 6% dextran (HSD) or hetastarch (HSS) , in more than 1400 patients from 35
trialsl concerns remained about the safety of
small-volume hypertonic resuscitation.lsJ1g The
greatest concern has been derived from the
hypothesis that fluid resuscitation of prehospital
trauma can exacerbate uncontrolled internal hemorrhage and increase mortality. Animal studies
have shown that aggressive resuscitation after large
internal vesselsare cut can lead to increased bleeding and increased mortality with either lactated
Ringers or HSD. l*-*O This has suggested to some
surgeons and trauma experts that all fluid resuscitation of prehospital trauma is counterproductive.
This might be particularly true in regard to HSD,
which has been shown to increase blood pressure
more than isotonic solutions and has led to
increased bleeding and a higher mortality in animal models of uncontrolled hemorrhage.20 In a
recent study of patients with major truncal pene-

surgery
September 1997

trating injury requiring operation the withholding

of fluid until surgical control of the bleeding was
attained increased survival. It was suggested that
the difference in outcome was due to the administration of fluids increasing blood pressure and subsequent bleeding. However, the clinical data on
HSD strongly dispute the concept that increased
bleeding has a dominant effect in human trauma
as a whole because overall mean survival is generally improved by HSD despite an increase in blood
pressure.8,21Furthermore, internal blood lossmeasured during operations has not been greater in
patient groups treated with hypertonic saline solutions.r6 In fact, blood requirements have generally
tended to be lower after HSD treatment9 It
appears that internal bleeding in patients with traumatic injuries is different than in the presented animal models and does not seem to be adversely
affected by the administration of HS or HSD.
Additional concerns about HSD (central neurologic dysfunction, coagulopathies, interference
with blood matching, electrolyte abnormalities)
have been well addressed and convincingly dismissed by completed clinical studies.8,22>23
No neurologic dysfunction or central pontine myelinolysis
has been reported in any patient to date.23 There
have also been no neurologic or other histopathologic findings in extensive toxicologic studies, in
which doses of up to four times the recommended
clinical dose were evaluated in a number of
species.24-26Coagulation and blood matching are
not affected by the clinical dose of 250 ml of
HSD.8~23Hypernat r emia is milder than expected
and is quite transient. Hypokalemia has not been
found in human beings.8,23 A significant hyperchloremic acidosis was present in 8 of the 58
patients given HSD. 23 However, the acidemia in
that study was attributed to the patients preexisting morbidity and was not sustained or deemed
clinically significant.
Previous reviews4,5,27of the effect of hypertonic
solutions on survival outcome in patients with traumatic hypotension have been inconclusive. We conclude from the meta-analysis of studies of HS and
HSD for the treatment of traumatic hypotension
that small-volume resuscitation with HSD is likely
to be more effective than standard of care isotonic
solutions. Further, HS alone is not more effective
than standard isotonic solutions However, simple
meta-analysis does not make use of primary data
and does not entail any covariant analysis. Greater
statistic discriminatory power or a larger patient
population is required to confirm these conclusions. It has been suggested that a meta-analysis
should be an ongoing process and that as new tri-

surgery
Volume 122, Number 3

als are completed, their results should be incorporated into the analysis.28 There is presently one
ongoing study looking at the efficacy of HSD.12
This would result in an increase in the size of the
HSD and IS0 patient populations being studied.
Further, meta-analysis with individual patient data
can increase discriminatory power and allow the
use of covariant analysis to adjust for factors such as
the difference in the degree of injury.2g>30These
approaches should be considered in evaluating the
efficacy of interventions for the treatment of traumatic injuries.
The data used in the present analysis were
obtained from published reports or from the
authors, The data were provided in one of two
forms, as intent-to-treat and per protocol (elimination of patients who violated protocol inclusion
or exclusion criteria). The inclusion of patients
who violated the protocol could complicate the
ability to discern differences between treatments,
depending on which group they were enrolled in.
In contrast, elimination of too many patients by
exclusion and inclusion criteria could be an unrealistic assessmentof the efficacy of an intervention.
For example, HSD intent-to-treat data were published in one study and used in the present metaanalysis.8 However, when the per-protocol data
were
analyzed
(obtained
from
Medisan
Pharmaceuticals; HSD = 85.9% [158/184] compared with IS0 = 78.3% [137/175]), there was a
difference in the strength of the interpretation of
the meta-analysis ($ = 0.05 versus p = 0.14; odds
ratio of 1.30 compared with 1.20). Thus differences
in the type of data populations available in published studies could lead to confounding of a classic meta-analysis. Meta-analysis with individual
patients would allow the construct of uniform criteria to address the group of patients for which an
intervention is intended.
In summary, patients with injuries as a result of
trauma that were treated with HSD showed no
adverse effects of the solution, and in seven of eight
trials patients had higher mean survival rates than
matched isotonic groups. This meta-analysis suggestsa favorable survival benefit for HSD treatment
of traumatic hypotension.
REFERENCES
1. MacKenzie
EJ, MorrisJA,
Smith GS, Fahey M. Acute hospital costs of trauma in the United States: implications
for
regionalized
systems of care. J Trauma 1990;30:1096-103.
2. National
Institute
of Neurological
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