The Journal of TRAUMA威 Injury, Infection, and Critical Care
Resuscitation With Normal Saline (NS) vs. Lactated
Ringers (LR) Modulates Hypercoagulability and Leads to
Increased Blood Loss in an Uncontrolled Hemorrhagic Shock
Swine Model
Laszlo N. Kiraly, MD, Jerome A. Differding, MS, T. Miko Enomoto, MD, Rebecca S. Sawai, MD,
Patrick J. Muller, MS, Brian Diggs, PhD, Brandon H. Tieu, MD, Michael S. Englehart, MD,
Samantha Underwood, MS, Tracy T. Wiesberg, MD, and Martin A. Schreiber, MD
Background: Lactated ringers (LR)
and normal saline (NS) are used interchangeably in many trauma centers. The
purpose of this study was to compare the
effects of LR and NS on coagulation in an
uncontrolled hemorrhagic swine model.
We hypothesized resuscitation with LR
would produce hypercoagulability.
Methods: There were 20 anesthetized
swine (35 ⴞ 3 kg) that underwent central venous and arterial catheterization, celiotomy,
and splenectomy. After splenectomy blinded
study fluid equal to 3 mL per gram of splenic
weight was administered. A grade V liver injury was made and animals bled without re-
suscitation for 30 minutes. Animals were resuscitated with the respective study fluid to,
and maintained, at the preinjury MAP until
study end. Prothrombin Time (PT), Partial
Thromboplastin Time (PTT), and fibrinogen
were collected at baseline (0ⴕ) and study end
(120ⴕ). Thrombelastography was performed
at 0ⴕand postinjury at 30ⴕ, 60ⴕ, 90ⴕ, and 120ⴕ.
Results: There were no significant baseline group differences in R value, PT, PTT,
and fibrinogen. There was no significant difference between baseline and 30 minutes R
value with NS (p ⴝ 0.17). There was a significant R value reduction from baseline to 30
minutes with LR (p ⴝ 0.02). At 60 minutes, R
value (p ⴝ 0.002) was shorter while alpha
angle, maximum amplitude, and clotting index were higher (p < 0.05) in the LR versus
the NS group. R value, PT, and PTT were
significantly decreased at study end in the LR
group compared with the NS group (p <
0.05). Overall blood loss was significantly
higher in the NS versus LR group (p ⴝ 0.009).
Conclusions: This data indicates that
resuscitation with LR leads to greater hypercoagulability and less blood loss than
resuscitation with NS in uncontrolled hemorrhagic shock.
Key Words: Coagulation, Trauma,
Thrombelastogram, Saline, Ringers.
J Trauma. 2006;61:57– 65.
T
he choice of intravenous fluid for the resuscitation of hemorrhagic shock has been a source of ongoing controversy
for over a century. Normal saline (NS) and lactated Ringers
(LR) are treated as equivalent resuscitation fluids in many
trauma systems. Numerous studies have examined differences in
outcomes and parameters in patients receiving a saline solution
versus a balanced salt solution. In vitro and in vivo experiments
suggest that crystalloid resuscitation may lead to a hypercoagulable state.1– 4 The majority of these trials have associated LR
with a hypercoagulable state. A recent trial compared Hetastarch
in a balanced salt solution, LR, and hetastarch in normal saline
in terms of coagulation during surgery.4 The normal saline based
hetastarch treated patients were hypocoagulable compared with
Submitted for publication December 20, 2005.
Accepted for publication March 14, 2006.
Copyright © 2006 by Lippincott Williams & Wilkins, Inc.
From the Oregon Health & Science University, Portland, Oregon.
This work was supported in its entirety by US Army Medical Research
Acquisition Activity Award# W81XWH-04-1-0104.
Presented at the 19th Annual Meeting of the Eastern Association for the
Surgery of Trauma, January 10 –14, 2006, Orlando, Florida.
Corresponding Author: Martin A. Schreiber, MD, FACS, Associate
Professor of Surgery, Director of Surgical Critical Care, Trauma/Critical
Care Section, Oregon Health & Science University, 3181 SW Sam Jackson
Road L223A, Portland, OR 97239; email: [email protected].
DOI: 10.1097/01.ta.0000220373.29743.69
Volume 61 • Number 1
baseline while the LR treated patients were hypercoagulable.
The in vivo experiments have mainly focused on elective surgery patients.1,3–5 In vitro studies usually use blood from healthy
volunteers diluted with a set amount of fluid. A study in an intact
large animal trauma model has not been previously performed.
Given the significant morbidity and mortality of both coagulopathic hemorrhage and thromboembolic disease in trauma patients, further investigation is warranted to assess the impact of
resuscitation fluids on the coagulation system.
Beyond the hypercoagulable state seen in the setting of
LR resuscitation, the use of NS has been associated with a
hyperchloremic acidosis that has the potential to affect coagulation. Waters et al. found that in patients undergoing abdominal aortic aneurysm repair, NS resuscitation resulted in
the use of significantly more blood products.5 This suggests
that NS may have a harmful effect on the coagulation system.
The purpose of this study was to compare coagulation
parameters after uncontrolled hemorrhage and resuscitation in
an animal model and to determine the etiology of the differences
seen between LR and NS. This model is intended to represent
the prehospital or battlefield scenario. In this setting, surgical
control has not been established and the treatment choices are
limited to fluid resuscitation. We hypothesized that, in a swine
grade V liver injury model, animals resuscitated with LR would
become hypercoagulable compared with animals resuscitated
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The Journal of TRAUMA威 Injury, Infection, and Critical Care
with NS. This model offers an excellent reproduction of the
massive resuscitation efforts commonly seen in the modern
trauma setting. Given the complex interplay of fluid shifts,
inflammatory mediators, and coagulation factors this model may
offer a more realistic scenario as compared with previous in vivo
and in vitro dilution studies.
MATERIALS AND METHODS
This was a randomized controlled trial using twenty
female Yorkshire crossbred pigs. The pigs underwent a 16hour preoperative fast except for water ad libitum and were
preanesthetized with an intramuscular injection of 8 mg/kg
Telazol (Fort Dodge Animal Health, Fort Dodge, Ind.). They
then underwent oro-tracheal intubation with a 7.0 mm or 7.5
mm endotracheal tube and were placed on mechanical ventilation. Respiratory rate was adjusted to keep pCO2 values
between 40 to 50 mm Hg. Anesthesia was maintained using
2% isoflurane in 100% oxygen. An esophageal thermometer
was inserted.
Animal temperature was controlled utilizing external
warming devices. Once the swine were anesthetized, left
cervical cut downs were performed and polyethylene catheters were inserted into the common carotid artery and external
jugular vein. The arterial catheter was used for continuous
blood pressure monitoring and blood sampling. Mean arterial
pressure (MAP) and heart rate (HR) were continuously recorded and averaged every 10 seconds using a digital data
collection system with a blood pressure analyzer (DigiMed,
Louisville, Ky.). The venous line was used for administration
of the resuscitation fluids.
The animals underwent a midline celiotomy, suprapubic
Foley catheter placement, and splenectomy. Splenectomies
are performed in swine hemorrhage models because of the
spleen’s distensibility and the resultant variation in amounts
of sequestered blood. The spleen was weighed and, based on
randomization, either LR or NS solution was infused to replace
three times the spleen weight. The abdomen was than closed
with towel clamps.
Following a 15-minute stabilization period, the abdomen
was opened and residual peritoneal fluid was removed. Preweighed laparotomy pads were placed in both paracolic gutters
and the pelvis to facilitate blood collection. A standardized
grade V liver injury (injury to a central hepatic vein) was
created with a specially designed clamp. The clamp was
positioned in the middle of the liver, placing the right hepatic
vein, the left hepatic vein, and the portal vein at risk for
injury. This protocol is based upon our experience in previous
studies of uncontrolled hemorrhagic shock using the grade V
liver injury model.6 The time of injury was considered the
start time of the two-hour study period. Following 30 minutes
of uncontrolled hemorrhage, the initial blood loss, measured
by wall suction and the preweighed laparotomy pads, was
determined. The abdomen was then closed.
We blindly randomized (using a random numbers table) the
swine to receive either NS or LR resuscitation at 165 mL/min.
58
This rate is approximately one half the rate delivered by the
Level I rapid infuser as the animals were approximately one half
the weight of an average human. Resuscitation fluid was administered to achieve and maintain the baseline MAP for 90 minutes
postinjury.
Upon completion of the 2-hour study period, the abdomen was reopened and the secondary blood loss was determined by adding the volume of intra-abdominal blood to the
weight of the intra-abdominal blood clots. After the completion of the study the animals were sacrificed by exsanguination. To ensure comparable injuries between the study groups,
we removed the liver and identified the number of hepatic
vessels injured.
Blood specimens were collected at baseline and every 30
minutes until completion of the 2-hour study. Blood assays
included lactate level, arterial blood gases, chemistry panel
and hematocrit. Coagulation studies included partial thromboplastin time (PTT), prothrombin time (PT), and fibrinogen.
A TEG analyzer (TEG) (Hemoscope Corporation, Niles,
Ill.) was used as a test for overall coagulation. This test was
performed immediately after blood was removed from the animal and kaolin activation was utilized. The TEG values were
measured every 30 minutes. Thrombelastography has been documented to be a more sensitive measure of coagulation disorders
as compared with standard coagulation measures.7 Previous studies have documented hypercoagulability in trauma
patients using thrombelastography.8,9 Individual parameters of the thrombelastograms (Fig. 1) can detail the cause of
coagulopathy. The R value or reaction time represents the
time to onset of clot formation. Elongation of the R value
signifies a deficiency in coagulation factors. The ␣ angle
represents the rapidity of fibrin buildup and cross-linking.
This value is affected by fibrinogen function and to a lesser
extent, platelets. The K time is a measure of the speed to
reach a certain level of clot strength. K is shortened by
increased fibrinogen function and, to a lesser extent, by platelet function, and is prolonged by anticoagulants that affect
both. The maximum amplitude (MA) measures the strength
of the clot and is affected primarily by platelets but also by
Fig. 1. Example of TEG tracing. R value or reaction time represents the time to onset of clot formation. The ␣ value represents the
rapidity of fibrin buildup and cross-linking. The K time is a measure
of the speed to reach a certain level of clot strength. The MA value
is maximum amplitude and measures the strength of the clot.
July 2006
Resuscitation With NS vs. LR
fibrinogen. The Clotting Index (CI) is a composite score of
coagulation taking into account all of the above values.
This protocol was approved by the Institutional Animal
Care and Use Committee at Oregon Health & Science University. This facility adheres to the National Institutes of
Health guidelines for the use of laboratory animals.
An independent samples t test was used to compare the
means of continuous variables between the two groups. Statistical significance was defined as a p value ⬍0.05. Values
within a group were compared using a post hoc analysis of
the variance (ANOVA). These values were calculated using
SPSS version 13.0 software (SPSS Inc., Chicago, Ill.) and
graphs were produced using Microsoft Excel 2003 (Microsoft
Inc., Redmond, Wash.).
RESULTS
Ten animals were randomized to each group. One animal
in the NS group died just before completion of the 2 hour
study period. All other animals survived. Table 1 shows the
mean initial weight, blood pressure, temperature, vessels injured, blood loss and fluid replacement compared between
groups. Despite the fact that the number of vessels injured
and initial blood loss were similar between groups, the NS
group had greater blood loss after resuscitation and required
more than twice the volume of resuscitation fluid to achieve
and maintain the baseline blood pressure during the 90
minute resuscitation study period.
The NS group was significantly more acidotic compared
with the LR pigs after resuscitation. Figures 2 through 4
detail the trend of laboratory parameters. pH was significantly lower in the NS group 30 minutes after injury until the
0.009*
end of study. Interestingly, at this point of the study, the only
difference in treatment between the two groups was the
equivalent volumes of splenic replacement fluids. The bicarbonate value and base excess were significantly lower 60
minutes after injury and beyond. The LR group did show an
elevation of lactate level compared with the NS group. The
elevation of lactate in the LR group was not accompanied by
acidosis and it probably reflects the load of Na lactate from
the rapid infusion.
Selected laboratory values are displayed in Table 2. The
two groups had equivalent hematocrit values at the start of the
study. By the end of the study, the NS group had a lower
hematocrit. The partial thromboplastin time (PTT) and prothrombin time (PT) were both significantly greater in the NS
group compared with the LR group. Fibrinogen was decreased in both groups compared with baseline.
Figures 5 through 8 show the R value, alpha angle, MA,
and CI of the two groups. All the parameters showed significant changes during the course of the study. At 60 minutes
after injury and beyond, the R value and the alpha angle were
significantly different in the LR group as compared with the
NS group. At 30 minutes after injury and beyond the MA and
CI were significantly higher in the LR group. By the end of
the study all of the values in the groups were significantly
different from baseline with the exception of the alpha angle
in the NS group. These results indicate relative hypercoagulability in both groups but significantly more so in the LR
group.
0.001*
DISCUSSION
Table 1 Baseline and Postinjury Values. Comparison
Between NS and LR Groups of Physiologic Parameters
Parameter
Survived
Weight (kg)
Starting Temp (C°)
Baseline MAP
Veins injured
Spleen replacement
fluid (cc)
EBL after injury per kg
EBL after resuscitation
per kg
Total EBL per kg
Fluids per kg
Study Fluid
Mean ⫾ SE
Statistical
Significance
NS
LR
NS
LR
NS
LR
NS
LR
NS
LR
NS
LR
NS
LR
NS
LR
NS
LR
NS
LR
9
10
33.6 ⫾ 1.0
35.6 ⫾ 0.9
37.3 ⫾ 0.6
37.9 ⫾ 0.2
70.4 ⫾ 2.7
68.6 ⫾ 3
1.8 ⫾ 0.25
1.5 ⫾ 0.22
627 ⫾ 52
612 ⫾ 33
23 ⫾ 2
19 ⫾ 2
12 ⫾ 2
5⫾1
34 ⫾ 3
24 ⫾ 2
331 ⫾ 38
148 ⫾ 20
0.343
* Signifies statistical significance with p ⬍ 0.05.
Volume 61 • Number 1
Fig. 2. pH values at discrete time intervals after injury in NS and
LR groups. *Indicates a significant difference (p ⬍ 0.05) between
groups at that time interval.
0.165
0.356
0.66
0.382
0.811
0.102
0.014*
This study evaluated multiple measures of coagulation in
a swine model of uncontrolled hemorrhage. There were sig59
The Journal of TRAUMA威 Injury, Infection, and Critical Care
Fig. 3. HCO3⫺ and Base Excess values at discrete time intervals after injury in NS and LR groups. *Indicates a significant difference (p ⬍
0.05) between groups at that time interval.
nificant differences between animals that received LR and NS
in nearly every marker of coagulation measured. It is important to note that the saline group did not develop a significant
hypocoagulable state in terms of the measured parameters.
The more significant changes reflected a hypercoagulable
state in the LR animals. There were multiple physiologic and
chemical differences between the two groups.
The NS group received a mean of 10.9 L of fluid compared with 5.2 L in the LR group. This indicates that the
saline group may have had a relative coagulation disorder secondary to a dilutional coagulopathy. Theoretically, this should
have the most notable effect on the R value as it involves
contact activation and fibrin formation. However, a previous
in vitro study measured the coagulation effects of LR and
hetastarch solutions by simple dilution. In vitro dilution of
blood with LR up to 75% resulted in no significant effect on
R time.10
There was a significant difference in several TEG parameters at the 30 minute interval. At this point in the study,
the only difference between the two groups was the type of
splenic replacement fluid. The actual volume of fluids was
equivalent. This suggests that the coagulation changes are at
Fig. 4. Lactate values at discrete time intervals after injury in NS and LR groups. *Indicates a significant difference (p ⬍ 0.05) between
groups at that time interval.
60
July 2006
Resuscitation With NS vs. LR
Table 2 Baseline and End Study Laboratories.
Comparison Between NS and LR Groups of
Hematologic Laboratory Parameters Drawn at Discrete
Time Points
Parameter
Baseline Hct
HCT 120 min
post injury
Baseline PTT
PTT 120 min
post injury
Baseline PT
PT 120 min
post injury
Baseline
Fibrinogen
Fibrinogen 120 min
post injury
Study Fluid
Mean ⫾ SE
Statistical
Significance
NS
LR
NS
26.0 ⫾ 0.8
26.2 ⫾ 0.9
12.7 ⫾ 1.1
0.870
LR
NS
LR
NS
16.6 ⫾ 1.2
24.2 ⫾ 1.0
22.9 ⫾ 0.7
25.2 ⫾ 1.1
LR
NS
LR
NS
21.4 ⫾ 0.5
13.3 ⫾ 0.2
13.2 ⫾ 0.1
19.0 ⫾ 1.5
LR
NS
LR
NS
LR
15.5 ⫾ 0.6
149.8 ⫾ 12.2
146.1 ⫾ 12.8
68.2 ⫾ 8.2
80.5 ⫾ 5.5
0.028*
0.314
0.004*
0.893
0.037*
0.838
0.219
Signifies statistical significance with p ⬍ 0.05.
least partially explained by the chemical composition of LR
versus NS.
The acid base status of the groups was another area of
significant difference. At 30 minutes, the mean pH of the NS
group was significantly lower than the LR group. This difference progressively increased throughout the course of the
study. Our laboratory has previously shown that, in this
model, resuscitation with NS results in a profound hyperchloremic acidosis.11 Chloride levels were not measured in this
experiment. However, as described in Figure 4, lactate levels
were not elevated in the NS group. The resultant acidosis
likely accounts for the physiologic differences between
groups. Acidosis decreases cardiac contractility, and decreases the effectiveness of circulating catecholamines. Subsequent trials in our laboratory that are not yet published have
documented a profound vasodilation in NS resuscitated
swine. It is likely that increased blood loss during resuscitation combined with systemic vasodilatation resulted in the
high fluid requirements seen with the NS animals.
Acidosis has been implicated as a contributor to ongoing
bleeding in trauma patients.12 The overall mechanism has not
been completely elucidated. An in vitro study documented a
decrease in FVIIa and FVIIa tissue factor complex.13 Acidosis has been associated with coagulation changes in vivo as
well.14 A recent in vivo model examined the independent
contribution of acidosis to coagulopathy. The findings suggested that the acidosis caused a decrease in thrombin generation rates reflected as a decrease in the alpha angle of the
TEG. The LR group did have a significantly higher alpha
value compared with the NS group at 60 minutes. However,
at this time point, the NS value was not significantly different
from its baseline value.
Given the large blood loss in both groups and the significantly higher volume of fluid given to the NS group, the
more pronounced hypercoagulable state in the LR group may
be affected by relative hemoconcentration. The difference in
hematocrit between the LR and NS groups at 120 minutes
was significant ( p ⫽ 0.028). The difference in actual red
Fig. 5. TEG R values at discrete time intervals after injury in NS and LR groups. *Indicates a significant difference (p ⬍ 0.05) between
groups at that time interval. #Indicates a significant difference from the baseline value (p ⬍ 0.05). The shaded area indicates normal ranges.
Volume 61 • Number 1
61
The Journal of TRAUMA威 Injury, Infection, and Critical Care
Fig. 6. TEG Alpha Angle values at discrete time intervals after injury in NS and LR groups. *Indicates a significant difference (p ⬍ 0.05)
between groups at that time interval. #Indicates a significant difference from the baseline value. (p ⬍ 0.05) The shaded area indicates normal
ranges.
blood cell concentration contributes to coagulation. Several
studies have detailed red blood cell membrane effects on the
coagulation cascade. Activation of factor IX by erythrocyte
membranes may cause intrinsic coagulation.15
A third notable difference between the groups was the
calcium level. Along with volume dilution, the nontrivial
amount of calcium in LR most likely explains this difference.
At study end, the LR group had a concentration of 1.34 versus
1.22 for the NS group. Calcium is an important cofactor in the
coagulation cascade. Though this difference reached statistical significance, the actual clinical relevance of this decrease
is unclear. A recent study investigated coagulopathy and
hypocalcemia in humans.16 Using citrated blood from healthy
volunteers, various concentrations of calcium were added and
TEGs were performed. Coagulopathy was only notable at
concentrations less than 0.56 mmol/L. Given the small absolute difference, calcium likely does not account for the coagulation changes seen.
The total measured blood loss was significantly higher in
the NS group suggesting that the differences in coagulation
seen were clinically relevant. There is limitation in this measurement as the total intra-abdominal fluid represents both
Fig. 7. TEG MA values at discrete time intervals after injury in NS and LR groups. *Indicates a significant difference (p ⬍ 0.05) between
groups at that time interval. #Indicates a significant difference from the baseline value. (p ⬍ 0.05) The shaded area indicates normal ranges.
62
July 2006
Resuscitation With NS vs. LR
Fig. 8. TEG CI values at discrete time intervals after injury in NS and LR groups. *Indicates a significant difference (p ⬍ 0.05) between
groups at that time interval. #Indicates a significant difference from the baseline value. (p ⬍ 0.05) The shaded area indicates normal ranges.
blood and ascites. The NS group presumably had more ascites
secondary to higher volumes of crystalloid administered.
The relative hypercoagulability seen in both animal
groups is likely the result of significant tissue trauma. Following injury tissue factor is exposed, de-encrypted and released into the bloodstream. It then complexes with activated
factor VII resulting in activation of factors IX and X.17
Additional mechanisms relate to an imbalance of procoagulant and anticoagulant factors. A study measuring extensive
coagulation profiles in critically injured patients found a negative correlation of functional protein C with severity of injury.18
Further studies show a decrease in plasma antithrombin III in
the setting of trauma.18,19 These mechanisms combined with
post-traumatic inflammation lead to a hypercoagulable state
that has been documented in trauma patients early after
admission.8,9
We have previously shown, using TEG, that Grade V
liver injury without resuscitation results in a hypercoagulable
state that is not affected by resuscitation with LR.20 This
suggests that the use of LR for resuscitation has minimal
effects on the coagulation changes after trauma. Alternatively,
NS appears to modulate the post-trauma hypercoagulability by a
series of physiologic derangements including acidosis and increased volume requirements.
Our study did have limitations in that the volume of fluid
given was variable. However, the fluid was given with set
resuscitation endpoints. In this way the physiology guided the
resuscitation. This algorithm helped recreate the setting of a
clinical trauma resuscitation. Therefore, the difference in volume reflects a more realistic scenario.
CONCLUSION
In a swine model of uncontrolled hemorrhage, resuscitation with NS resulted in modulation of the hypercoagulable
Volume 61 • Number 1
state seen after injury and LR resuscitation. This effect most
likely relates to acidosis and may be contributed to by the
increased volume of fluid given to NS animals. This study
suggests that the choice of crystalloid resuscitation has significant effects on coagulation. Administration of LR during
resuscitation appears to have no effect on the hypercoagulable state induced by trauma. This hypercoagulable state may
reduce bleeding and be protective initially, but may lead to
thromboembolic complications later in the course of trauma
admission. Resuscitation with NS modulates hypercoagulability after trauma and results in increased fluid requirements.
These changes are associated with increased blood loss after
injury and uncontrolled hemorrhage.
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DISCUSSION
Dr. Stephen M. Cohn (San Antonio, Texas): In this
investigation, the authors have expanded their work focusing
on the effects of various resuscitation fluids upon changes in
coagulation following trauma.
In this experiment, pigs were resuscitated to baseline
blood pressure with either lactated ringer’s or normal saline
following 30 minutes of uncontrolled hemorrhage from a
severe liver injury.
The animals receiving lactated ringer’s developed a hypercoagulable state, noted by a reduction in PT, PTT, and
TEG values. Swine infused with normal saline required much
greater fluid volumes to achieve baseline vital signs and did
not become hypercoagulable.
I have a few questions for the authors. Why did the
authors choose to resuscitate animals to baseline parameters,
rather than, say, a mean pressure of 60? Resuscitation to
lower target blood pressure would more closely replicate the
64
typical clinical scenario and might have impacted on outcome
measures, such as the volume of fluid required, the degree of
blood loss and the subsequent coagulopathy noted.
What is the impact of the type of anesthesia administered
on this animal hemorrhage model? Have the authors tried
other methods of anesthesia with similar results?
Who ran the TEG analysis? And how did hypothermia
impact on the results? This is a very user-dependent test. In
fact, that’s, I think, one of the major reasons why we have not
applied it clinically in the trauma scenario.
Why did the normal saline group receive twice the volume of resuscitative fluid? Were these animals actually more
severely injured or more ill at baseline?
The volume of resuscitative fluid may have diluted out
the effects of various coagulation factors as well as impacted
on platelet aggregation.
How can we be assured that the impact of fluid volume
was not the primary factor causing differences in coagulation
between lactated ringer’s and normal saline rather than the
type of fluid itself?
Another interesting question for the authors is what
changes in coagulation would you expect to see over time in
a hemorrhage model like this one? It would appear that
becoming hypercoagulable after injury would lead to a survival advantage. Do you have survival data?
We currently routinely use normal saline for the resuscitation of trauma patients in the setting of head injury. Do
the authors think that normal saline is dangerous? Should we
avoid this in clinical care?
Dr. L. N. Kiraly (Portland, Oregon): In response to your
first question, why we resuscitated to a MAP of 60, our
previous models have resuscitated to a baseline blood pressure. We were varying one element of this model.
However, the mean pressures of these animals were a
MAP of 70, so we were not going to the point of extreme
resuscitation. The pigs do have a variable baseline blood
pressure. And we were trying to keep things consistent from
that point.
Next, in terms of anesthesia, we actually have developed
a model, which was completed this summer, of a total IV
anesthesia regimen and compared it to the isoflurane regimen. Preliminary results indicate that the isoflurane Does
have a vaso dilatory response and results in a lower blood
pressure.
Next, who ran the TEGs? We had an overwhelming
majority of the TEGs run by a skilled technician that has done
hundreds of these TEGs.
In terms of hypothermia, these animals were actively
externally re-warmed to keep their temperature within a range
of 36 to 38 degrees, so hypothermia was not an issue in these
patients. The TEG machine can account for that by setting a
different temperature if so desired.
Next, why they required different volumes of fluid? We
have done some subsequent analysis and found that the normal saline group does have a profound vasodilatory response,
July 2006
Resuscitation With NS vs. LR
making it more difficult for them to be resuscitated to their
baseline MAPs.
In terms of the question of why is this alone responsible
for the coagulation differences, as I mentioned, previous in
vitro studies haven’t shown this from just a simple dilution of
blood products with crystalloid fluid in terms of the TEG
values that we found.
Furthermore, another point is just with acidosis alone, a
previous swine model by another group showed TEG changes
similar to ours. That leads me to believe that acidosis is more
responsible rather than just simple volume.
The next question is, is this clinically relevant? Do we
have survival data? We plan to expand our animal model to
a survival model to really investigate how these animals will
do in the days following a trauma like this. But the clinically
relevant point to take from this study is the blood loss, which
does seem to be increased in the normal saline group.
Finally, in terms of head injury, based on this study, we
see the normal saline animals required much more resuscitation fluid. They had increased bleeding and were more acidotic and made it difficult to maintain blood pressure.
I think all these argue against using normal saline in the
setting of head injuries based on this study.
Volume 61 • Number 1
We have alternatives such as the judicious use of
hypertonic saline or diuretics. But I have not seen evidence
saying that the LR would be harmful in the setting of a
head trauma.
Dr. Michael F. Rotondo (Greenville, North Carolina): I
have one question from the podium. Your acid base status,
you sort of suggested that animals develop an acidosis, yet
they were getting a lot of normal saline.
Is this a hyperchloremic acidosis, or do you have any
lactate levels to suggest what ideology this acidosis is?
Dr. L. N. Kiraly: From this study, we didn’t gather the
chloride levels. We had a previous model that used normal
saline and showed a similar acidosis, and it was clearly a
hyperchloremic acidosis.
Dr. Ken Proctor (Miami, Florida): Did you control
PCO2?
Dr. L. N. Kiraly: PCO2 was controlled within a range of
40 to 50, and we did that based on the ABGs we did every
half hour.
Dr. Ken Proctor: So why, then, as the Ph was falling in
the normal saline group, didn’t you hyperventilate?
Dr. L. N. Kiraly: The method we used, we based our
ventilatory maneuvers based on the PCO2, not the pH.
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