Barry Armstrong, trauma.org
7:10, October 2002
General Surgeon - Dryden, Ontario, Canada
Permissive hypotension is a hot
topic in trauma circles. In the late 20th century, the early care
for an injured person included “2 large-bore Intravenous lines,
running wide open”. The current trend, in ambulances and emergency
rooms, is to limit fluid resuscitation, at least until hemorrhage
is controlled -- by natural hemostasis, external pressure, angiography
or surgery. Metaphorically, the tide of fluid resuscitation is
ebbing; our bleeding patients are managed drier than previously.
- Permissive Hypotension
discussion of Permissive Hypotension in Trauma Resuscitation
To help you understand why the tide has turned, these references
include abstracts, plus access to some full text articles. Text
in blue gives a brief opinion
about the reference.
If you have additions, corrections or comments please email Barry
Armstrong or email@example.com.
resuscitation during active hemorrhage: Impact on in-hospital
Dutton RP, MacKenzie CF, Scalea
R Adams Cowley Shock Trauma Center, and the Departments
of Anesthesiology and Surgery,
University of Maryland School of Medicine, Baltimore,
Trauma 2002 June;52(6):1141-1146
fluid resuscitation strategy in the actively hemorrhaging
trauma patient emphasizes maintenance of a normal systolic
blood pressure (SBP). One human trial has demonstrated
improved survival when fluid resuscitation is restricted,
whereas numerous laboratory studies have reported improved
survival when resuscitation is directed to a lower than
normal pressure. We hypothesized that fluid resuscitation
titrated to a lower than normal SBP during the period
of active hemorrhage would improve survival in trauma
patients presenting to the hospital in hemorrhagic shock.
Methods: Patients presenting
in hemorrhagic shock were randomized to one of two fluid
resuscitation protocols: target SBP > 100 mm Hg (conventional)
or target SBP of 70 mm Hg (low). Fluid therapy was titrated
to this endpoint until definitive hemostasis was achieved.
In-hospital mortality, injury severity, and probability
of survival were determined for each patient.
Results: One hundred ten
patients were enrolled over 20 months, 55 in each group.
The study cohort had a mean age of 31 years, and consisted
of 79% male patients and 51% penetrating trauma victims.
There was a significant difference in SBP observed during
the study period (114 mm Hg vs. 100 mm Hg, p < 0.001).
Injury Severity Score (19.65 ± 11.8 vs. 23.64 ± 13.8,
p = 0.11) and the duration of active hemorrhage (2.97
± 1.75 hours vs. 2.57 ± 1.46 hours, p = 0.20) were not
different between groups. Overall survival was 92.7%,
with four deaths in each group.
Conclusion: Titration of
initial fluid therapy to a lower than normal SBP during
active hemorrhage did not affect mortality in this study.
Reasons for the decreased overall mortality and the lack
of differentiation between groups likely include improvements
in diagnostic and therapeutic technology, the heterogeneous
nature of human traumatic injuries, and the imprecision
of SBP as a marker for tissue oxygen delivery.
Effects of delaying fluid resuscitation
on an injury to the systemic arterial vasculature.
Sakles JC, Lewis G, Wisner DH.
Division of Emergency Medicine, University of California,
Davis, School of Medicine,
Sacramento, CA 95817-2282, USA.
Emergency Medicine 2002 Apr;9(4):267-74.
OBJECTIVES: To determine the effects of delaying
fluid on the rate of hemorrhage and hemodynamic parameters
in an injury involving the arterial system.
METHODS: Twenty-one adult, anesthetized, sheep
underwent left anterior thoracotomy and transection of
the left internal mammary artery. A chest tube was inserted
into the thoracic cavity to provide a continuous measurement
of blood loss. The animals were randomly assigned to one
of three resuscitation protocols: 1) no fluid resuscitation
(NR), 2) standard fluid resuscitation (SR) begun 15 minutes
after injury, or 3) delayed fluid resuscitation (DR) begun
30 minutes after injury. All of the animals in the two
resuscitation groups received 60 mL/kg of lactated Ringer's
solution over 30 minutes. Blood loss and hemodynamic parameters
were measured throughout the experiment.
RESULTS: Total hemorrhage volume (mean SD) at
the end of the experiment was significantly lower (p =
0.006) in the NR group (1,499 311 mL) than in the SR group
(3,435 721 mL) or the DR group (2,839 1549 mL). Rate of
hemorrhage followed changes in mean arterial pressure
in all groups. Hemorrhage spontaneously ceased significantly
sooner (p = 0.007) in the NR group (21 14 minutes) and
the DR group (20 15 minutes) than in the SR group (54
4 minutes). In the DR group, after initial cessation of
hemorrhage, hemorrhage recurred in five of six animals
(83%) with initiation of fluid resuscitation. Maximum
oxygen (O2) delivery in each group after injury was as
follows: 101 34 mL O2/kg/min at 45 minutes in the DR group,
51 20 mL O2/kg/min at 30 minutes in the SR group, and
35 8 mL O2/kg/min at 60 minutes in the NR group.
CONCLUSIONS: Rates of hemorrhage from an arterial
injury are related to changes in mean arterial pressure.
In this animal model, early aggressive fluid resuscitation
in penetrating thoracic trauma exacerbates total hemorrhage
volume. Despite resumption of hemorrhage from the site
of injury, delaying fluid resuscitation results in the
best hemodynamic parameters.
Fluid resuscitation of the patient
with major trauma
Fowler R, Pepe PE
University of Texas Southwestern Medical Center and
The Dallas Metropolitan Area Biotel (EMS) System,
Dallas, Texas, USA
Opinion in Anaesthesiology 2002 April;15:173-178
Current reviews and consensus
documents now recommend a more discriminating approach
to the traditional practices of delivering liberal infusions
of intravenous fluid to all major trauma patients with
suspected or known major hemorrhage. The evolving evidence
suggests that aggressive fluid resuscitation prior to
hemostasis leads to additional bleeding through hydraulic
acceleration of hemorrhage, soft clot dissolution, and
dilution of clotting factors.
Aggressive preoperative fluid
infusion is still considered appropriate for unconscious
patients without palpable blood pressure or for those
with controllable hemorrhage (e.g. isolated extremity
or head injury), However, the latest recommendations are
to limit or delay intravenous fluid resuscitation preoperatively
in those with uncontrollable hemorrhage (e.g. those with
penetrating torso injuries), even if they are hypoperfusing.
Although most clinicians still
generally support fluid resuscitation for multisystem
blunt trauma, particularly with head injury, the most
recent experimental data have begun to challenge this
traditional practice as well, suggesting a ‘slow infusion’
approach when there is risk for uncontrolled internal
bleeding. By providing oxygen delivery with slow, limited
infusion, new hemoglobin-based oxygen carriers might help
to resolve the current dilemma of having to limit preoperative
resuscitation when there is risk of uncontrolled hemorrhage.
Matter for debate--Fluid resuscitation
in pre-hospital trauma care: A consensus view
Greaves I, Porter
KM, Revell MP
Selly Oak Hospital,
Birmingham, B29 6JD, UK
2002 April;47:2, 451-457
Fluid administration for trauma
in the pre-hospital environment is a challenging and controversial
area. There is, as yet no equivocal answer or view, which
can be supported by clear, well-documented and reliable
evidence. Nevertheless, a careful evaluation of what evidence
is available does allow some provisional conclusions to
be drawn. We believe that the following represent the
best possible current expert consensus on pre-hospital
fluids in trauma. As future evidence brings clarity to
this area, these guidelines can be modified, and further
consensus statements will be issued taking into account
When treating trauma victims in
the pre-hospital setting:
- Cannulation should take place
en route, where possible
- Only two attempts at cannulation
should be made
- Transfer should not be delayed
by attempts to obtain intravenous access
- Entrapped patients require
cannulation at the scene
- Normal saline is recommended
as a suitable fluid for administration to trauma patients
- Boluses of 250 ml fluid may
be titrated against the presence or absence of a radial
pulse (caveats; penetrating torso injury, head injury,
Prehospital fluid resuscitation
of the patient with major trauma
PE, Mosesso Jr JV, Falk
University of Texas Southwestern Medical Center at Dallas,
Emergency Medicine, MC 8579, 5323 Harry Hines Boulevard,
Dallas, TX 75390-8579, USA.
Emergency Care 2002 Jan-Mar;6:81-91
The most appropriate prehospital
approach to resuscitative fluid interventions for trauma
patients involves: determining the mechanism of injury
(i.e., blunt versus penetrating versus thermal injury);
identifying anatomic involvement (i.e., truncal versus
isolated head injury versus isolated extremity injury);
and staging the condition (i.e., hemodynamic stability
versus instability versus moribund state). Based on available
data, the liberal use of fluid infusions for presumed
uncontrolled internal hemorrhage, such as that usually
occurring after penetrating abdominal and thoracic injuries,
is no longer advised. Although some infusion might be
appropriate in patients with extremely severe hemorrhage
(i.e., no palpable blood pressure, unconscious), the priority
in such patients is rapid evacuation to definitive surgical
intervention, with airway control and intravenous access
provided en route. The data are less clear for patients
with blunt injuries, particularly those with closed head
injury. Most researchers would still recommend that patients
with isolated extremity and head injuries, either blunt
or penetrating, are candidates for immediate support of
blood pressure through fluid infusions. However, the addition
of potential intra-abdominal, intrapelvic, or intrathoracic
injuries with uncontrolled hemorrhage confounds the decision-making
process. Although conventional wisdom has been to provide
aggressive blood pressure support under these circumstances
through judicious use of isotonic, or perhaps hypertonic,
fluid resuscitation, recent experimental data challenge
even this philosophy. Use of new blood substitutes might
help to resolve some of these issues by providing oxygen
delivery with limited volume in the face of uncontrolled
Continuous fluid resuscitation and
splenectomy for treatment of uncontrolled hemorrhagic
shock after massive splenic injury
Abu-Hatoum O, Bashenko Y, Hirsh
M, Krausz MM,
Department of General Surgery and the Laboratory for Shock
and Trauma Research,
Rambam Medical Center, and the Bruce Rappaport Faculty
Technion-Israel Institute of Technology, Haifa, Israel.
Trauma 2002 Feb;52:253-258
Background: Using a standardized
massive splenic injury (MSI) model of uncontrolled hemorrhagic
shock, we studied the effect of continuous fluid resuscitation
and splenectomy on the hemodynamic response and survival
Methods: The animals were
randomized into seven groups: group 1 (n = 8), sham-operated;
group 2 (n = 8), MSI untreated; group 3 (n = 8), MSI treated
with 7.5 mL/kg/h of 7.5% NaCl (hypertonic saline [HTS])
for 1 hour; group 4 (n = 8), MSI treated with 7.5 mL/kg/h
hydroxyethyl starch (HES-7.5) for 1 hour; group 5 (n =
8) MSI treated with 35 mL/kg/h Ringer’s lactate (RL) solution
(RL-35) for 1 hour; group 6 (n = 8) MSI treated with 70
mL/kg/h RL for 1 hour (RL-70); and group 7 (n = 8), MSI
treated with 105 mL/kg/h RL for 1 hour (RL-105). In all
MSI groups, splenectomy was performed 45 minutes after
Results: MSI in untreated
group 2 resulted in a fall of mean arterial pressure from
105.9 ± 10.7 mm Hg to 27.0 ± 6.7 mm Hg (p < 0.001) in
60 minutes. Mean survival time after splenectomy in this
group was 160.7 ± 29.7 minutes, and total blood loss was
34.8 ± 4.7% of blood volume. Continuous HTS infusion with
splenectomy in group 3 was followed by a total blood loss
of 38.7 ± 4.4% and mean survival time was 176.5 ± 23.2
minutes. HES-7.5 infusion and splenectomy was followed
by a total blood loss of 39.6 ± 2.5% and survival time
was 171.6 ± 19.5 minutes. Continuous infusion of increasing
volumes of RL in groups 5, 6, and 7 was followed by increase
in blood loss to 29.0 ± 4.1%, 50.2 ± 3.1% (p < 0.001),
and 62.7 ± 7.1% (p < 0.002) of total blood volume, respectively.
Mean survival time in groups 5, 6, and 7 was 233.5 ± 6.5
minutes (p < 0.04), 207.6 ± 17.0 minutes (p < 0.05), and
158 ± 26 minutes, respectively.
infusion of large-volume RL and splenectomy after massive
splenic injury resulted in a significant increase in intra-abdominal
bleeding and shortened survival time compared with small-volume
Low-volume fluid resuscitation
for presumed hemorrhagic shock: helpful or harmful?
Department of Emergency Medicine,
University of Michigan, Ann Arbor, Michigan
Opinion in Critical Care. 2001 Dec;7(6):422-30.
For the past 4 decades, the standard
approach to the trauma victim who is hypotensive from
presumed hemorrhage has been to infuse large volumes of
fluids as early and as rapidly as possible. The goals
of this treatment strategy are rapid restoration of intravascular
volume and vital signs towards normal, and maintenance
of vital organ perfusion. The most recent laboratory studies
and the only clinical trial evaluating the efficacy of
these guidelines however, suggest that in the setting
of uncontrolled hemorrhage, today's practice of aggressive
fluid resuscitation may be harmful, resulting in increased
hemorrhage volume and subsequently greater mortality.
This has been demonstrated in animal models representative
of penetrating trauma as well as those representative
of blunt trauma. The data strongly suggest that limited
or hypotensive resuscitation may be preferable for the
trauma victim with the potential for ongoing uncontrolled
hemorrhage. Limited resuscitation provides a mechanism
of avoiding the detrimental effects associated with early
aggressive resuscitation, while maintaining a level of
tissue perfusion that although decreased from the normal
physiologic range is adequate for short periods. Large
randomized clinical trials are necessary to confirm this
new laboratory data. Future research should focus on developing
resuscitation methods that may actually enhance tissue
perfusion during limited resuscitation and therefore offset
its potential detrimental effects.
Crystalloid and colloid resuscitation
of uncontrolled hemorrhagic shock following massive splenic
Krausz MM, Bashenko Y, Hirsh M.
Department of General Surgery,
Laboratory for Shock and Trauma Research,
Rambam Medical Center, Haifa, Israel.
Using a standardized massive splenic
injury (MSI) model of uncontrolled hemorrhagic shock we
studied the effect of vigorous crystalloid or colloid
fluid resuscitation on the hemodynamic response, and survival
in rats. The value of massive fluid infusion in uncontrolled
hemorrhagic shock following intra-abdominal solid organ
injury is still controversial. The effect of crystalloid
and colloid infusion was studied following massive splenic
The animals were randomized into
six groups: group 1 (n = 8) sham-operated, group 2 (n
= 12) MSI untreated, group 3 (n = 10) MSI treated with
41.5 mL/kg Ringer's lactate (large-volume Ringer's lactate,
LVRL), group 4 (n = 14) MSI treated with 5 mL/kg 7.5%
NaCl (hypertonic saline, HTS), group 5 (n = 10) MSI treated
with 7.5 mL/kg hydroxyethyl starch (HES-7.5), and group
6 (n = 11) MSI treated with 15 mL/kg hydroxyethyl starch
Following MSI mean arterial pressure
(MAP) in untreated group 2 decreased from 109.1+/-4.5
to 49.8+/-9.6 mmHg (P < 0.001) in 60 min. Mean survival
time was 132.1 18.7 min, and total blood loss was 30.2+/-4.1%
of blood volume. LVRL infusion resulted in an early rise
in MAP from 59.7+/-7.3 to 90.0+/-11.3 mmHg (P < 0.01),
which then rapidly dropped to 11.7+/-4.5 mmHg (P < 0.001)
after 60 min. The mean survival time was 82.5+/-18.2 min
(P < 0.01), and total blood loss was 53.7 2.9% (P < 0.01).
Total blood loss following HTS infusion was 32.2 4.0%
and survival time was 127.9+/-19.7 min. HES-7.5 infusion
only moderately increased bleeding to 44.2+/-3.9% (P <
0.05), but mortality remained unchanged. HES-15 infusion
resulted in an increase in blood loss to 47.8+/-7.1% (0.01),
survival time dropped to 100.7+/-12.3 min (P < 0.05).
Vigorous large volume infusion of Ringer's lactate or
HES following MSI resulted in a significant increase in
intra-abdominal bleeding and shortened survival time compared
to untreated, small volume HTS, or HES-7.5-treated animals.
The hemodynamic response to crystalloid
or colloid infusion in blunt abdominal trauma is primarily
dependent on the severity of injury and the rate of fluid
Longest survival was in the group with no fluids, shortest
survival with large volume infusion.
Permissive hypotension during primary
resuscitation from trauma and shock
Kreimeier U, Prückner S, Peter
in Yearbook of Intensive Care
and Emergency Medicine, 2001
Advances in fluid resuscitation of
Tremblay LN, Rizoli SB, Brenneman
Sunnybrook & Women's College Health Sciences Centre,
University of Toronto, Ont.
Journal of Surgery. 2001 Jun;44(3):172-9.
The optimal fluid for resuscitation
in hemorrhagic shock would combine the volume expansion
and oxygen-carrying capacity of blood without the need
for cross-matching or the risk of disease transmission.
Although the ideal fluid has yet to be discovered, current
options are discussed in this review, including crystalloids,
colloids, blood and blood substitutes. The future role
of blood substitutes is not yet defined, but the potential
advantages in trauma or elective surgery may prove to
Irreversible shock is not irreversible:
a new model of massive hemorrhage and resuscitation.
MA, Samphire J, Hoyt
DB, Liu F, Davis R, Loomis WH.
Department of Surgery, University of Saskatchewan,
Saskatoon, Saskatchewan, Canada.
Trauma. 2001 May;50(5):826-34.
BACKGROUND: Existing shock
models do not address the patient with massive hemorrhage
(> 1 blood volume). Such patients often die from irreversible
shock. This model simulates the clinical scenario of massive
hemorrhage and resuscitation (MHR) to determine if irreversible
shock can be reversed.
METHODS: Lewis rats were
bled at a rate of 1 estimated blood volume (EBV) per hour
for 2 hours with simultaneous infusion of resuscitation
mixture (RM) consisting of red blood cells and crystalloid.
Blood pressure was maintained at a mean arterial pressure
(MAP) of 50 mm Hg during the 2 hours of hemorrhage. Hemorrhage
was stopped and resuscitation continued for 1 hour until
6, 8, or 10 x EBV of RM was infused. Control animals were
subjected to a traditional fixed pressure hemorrhage to
MAP of 50 mm Hg for 2 hours followed by resuscitation
to MAP > 90 mm Hg for 1 hour with crystalloid alone. Two-week
survival was compared using a chi2 test.
RESULTS: Control animals
(n = 13) were hemorrhaged 48% 5% of EBV and had a mortality
rate of 23%. MHR animals had severity and duration of
hypotension identical to that of controls but were hemorrhaged
214% 8% of EBV. Despite receiving 390 mL/kg of RM and
a final hematocrit of 37%, 14 of 15 animals resuscitated
with 6 x EBV died from "irreversible" shock (mortality,
93%; p < 0.001 vs. controls). When very large volumes
of resuscitation were used, survival rates improved significantly.
The 10 x EBV group received 120% of lost red blood cells
and 530 mL/kg of crystalloid and had 64% survival at 2
weeks (p < 0.01 vs. 6 x EBV group).
CONCLUSION: This MHR model
is much more lethal than a traditional severe hemorrhage
model and reproduces the clinical picture of irreversible
shock. This irreversible shock can be reversed with very
large volumes of resuscitation.
The control group (rats) was bled down to a blood pressure
of 50 mm Hg and maintained there for 2 hours. The other
groups had continuing hemorrhage, while fluid infusion
was given. After 2 hours, hemorrhage was controlled. The
fluid resuscitation was given to the experimental animals,
during bleeding and after resuscitation.
until bleeding stopped : 23% 2-week mortality.
Giving fluids to 6 X EBV : 93% 2-week mortality.
Giving fluids to 10 X EBV : 36% 2-week mortality.
Improved survival with early fluid
resuscitation following hemorrhagic shock.
Santibanez-Gallerani AS, Barber
AE, Williams SJ, ZhaoB S Y, Shires GT
Department of Surgery, University of Nevada School of
Medicine, 2040 W. Charleston Boulevard, Suite 501,
Las Vegas, Nevada 89102, USA.
Journal of Surgery. 2001 May;25(5):592-7.
Recent studies have questioned the benefits
of early fluid resuscitation in hemorrhagic shock. The
purpose of the current study is to evaluate the effects
of early fluid resuscitation (HSE) (15 minutes), delayed
fluid resuscitation (HSD) (60 minutes), and no fluid resuscitation
(HSU) on cytokine levels, hepatic resting membrane potential
(Em), renal function, and mortality. Eighty male Sprague-Dawley
rats (350-450 g) were hemorrhaged 35% of their total blood
volume and then received 40, 80, or 100 ml of crystalloid
per kilogram as intravenous fluids (IVFs). The implementation
of HSE resulted in stabilization of the Em (-29 mV), which
was significantly different from that seen with HSD or
HSU (-24 and -29 mV, respectively). The timing of resuscitation
did not affect the elevation of tumor necrosis factor
(TNFalpha) levels. The interleukin-6 (IL-6) levels for
the HSE group were 81, 101, and 274 pg/ml for 40, 80,
and 100 ml/kg, respectively. In contrast, HSD group IL-6
levels were 440, 566, and 632 pg/ml for 40, 80, and 100
ml/kg (p < 0.0001). IL-6 levels for the HSU group was
427 pg/ml, which was significantly different from that
of the HSE group (p < 0.05). Urine output was present
in 58% of the HSE rats but only 24% in the HSD rats and
0% of the HSU rats. Mortality was 11% for HSE, 58% for
HSD, and 50% for HSU rats.
Despite the recent studies questioning
the benefits of early fluid resuscitation, these data
show marked improvement in hepatic stability, the presence
of urine output, decreased IL-6 levels, and significantly
lower mortality when IVFs were given early after hemorrhagic
shock. Furthermore, excessive fluid resuscitation (100
ml/kg) resulted in an increased inflammatory cytokine
level and mortality and may account for the controversy.
Fluid resuscitation for the trauma
Attempts at prehospital fluid
replacement should not delay the patient's transfer to
hospital. Before bleeding has been stopped, a strategy
of controlled fluid resuscitation should be adopted. Thus,
the risk of organ ischaemia is balanced against the possibility
of provoking more bleeding with fluids. Once haemorrhage
is controlled, normovolaemia should be restored and fluid
resuscitation targeted against conventional endpoints,
the base deficit, and plasma lactate. Initially, the precise
fluid used is probably not important, as long as an appropriate
volume is given; anaemia is much better tolerated than
hypovolaemia. Colloids vary substantially in their pharmacology
and pharmacokinetics and the experimental findings from
one cannot be extrapolated reliably to another. We still
lack reliable data to prove that any of the colloids reduce
mortality in trauma patients. In the presence of SIRS,
hydroxyethyl starch may reduce capillary leak. Hypertonic
saline solutions may have some benefit in patients with
head injuries although this has yet to be proven beyond
doubt. It is likely that one or more of the haemoglobin-based
oxygen carriers currently under development will prove
to be valuable in the treatment of the trauma patient.
in Recent Advances in Anaesthesia
and Analgesia 21.
ed. Adams AP & Cashman JN. Publ. Churchill Livingstone
A randomised controlled trial of prehospital
intravenous fluid replacement therapy in serious trauma.
Turner J, Nicholl J, Webber L,
Cox H, Dixon S, Yates D.
Technology Assessment 2000 Nov;4(31):1-57.
Summary points: The initiation
by paramedics of intravenous fluid replacement in injured
patients at the accident scene is becoming a routine procedure
although there is uncertainty surrounding this practice.
This pragmatic randomised study involving 1309 patients
compared the effects of two different fluid protocols:
A: intravenous fluids administered at the incident scene;
and B: fluids withheld until arrival at hospital. No significant
differences in outcome were found between the two protocol
groups; but protocol compliance was poor – 31% of group
A and 20% of group B received prehospital fluids. This
study does not support the idea that protocols recommending
fluid administration do harm. But it is possible that
either giving fluids early does no harm, or that the specific
protocols used make little difference. In the absence
of clear evidence, the authors suggest that Ambulance
services should concentrate on avoiding unnecessary delays
and speeding up transfer to definitive care in hospital
rather than concentrate on their fluids protocols.
U. Kreimeier, S. Prueckner, K.
Department of Anaesthesiology, Klinikum Grosshadern,
Ludwig-Maximilian University, Munich (D)
[Swiss Medical Weekly] 2000 Oct 21;130: 1516-24
In trauma patients restoration
of intravascular volume in an attempt to achieve normal
systemic pressure faces the risk of increasing blood loss
and thereby potentially affecting mortality. Due to the
lack of controlled clinical trials in this field, the
growing evidence that hypotensive resuscitation results
in improved long-term survival mainly stems from experimental
studies in animals. The main differences between concepts
for the reduction of blood loss in systemic hypotension
are between "deliberate hypotension" (synonym "controlled
hypotension", used intraoperatively), "delayed resuscitation"
(where the hypotensive period is intentionally prolonged
until operative intervention) and "permissive hypotension"
(where restrictive fluid therapy increases systemic pressure
without reaching normotension). In this review the concept
of "permissive hypotension" is delineated on the basis
of macro- and microcirculatory changes secondary to hypovolaemia
and low driving pressure, and the potential indications
and limitations are discussed.
Timing and volume of fluid administration
for patients with bleeding following trauma.
I, Bunn F, Roberts I,
WHO Pre-Hospital Trauma Care Steering Committee.
Department of Paediatric Epidemiology and Biostatistics,
Institute of Child Health, 30 Guilford Street, London,
UK, WC1N 1EH.
Database of Systematic Reviews. Last updated 2000
Repeated in the Cochrane
Library, Issue 3, 2002:
BACKGROUND: Treatment of
haemorrhagic shock involves maintaining blood pressure
and tissue perfusion until bleeding is controlled. Different
resuscitation strategies have been used to maintain the
blood pressure in trauma patients until bleeding is controlled.
However, while maintaining blood pressure may prevent
shock, it may worsen bleeding.
OBJECTIVES: To assess the
effects of early versus delayed, and larger versus smaller
volume of fluid administration in trauma patients with
SEARCH STRATEGY: We searched
the Cochrane Controlled Trials Register, the specialised
register of the Injuries Group, MEDLINE, EMBASE, the National
Research Register and the Science Citation Index. We checked
reference lists of identified articles and contacted authors
and experts in the field.
SELECTION CRITERIA: Randomised
trials of the timing and volume of intravenous fluid administration
in trauma patients with bleeding. Trials in which different
types of intravenous fluid were compared were excluded.
DATA COLLECTION AND ANALYSIS:
Two reviewers independently extracted data and assessed
MAIN RESULTS: We did not
combine the results quantitatively because the interventions
and patient populations were so diverse. Early versus
delayed fluid administration: Three trials reported mortality
and two coagulation data. In the first trial (n=598) relative
risk (RR) for death with early fluid administration was
1.26 (95% confidence interval of 1.00-1.58). The weighted
mean differences (WMD) for prothrombin time and partial
thromboplastin time were 2.7 (95% CI 0.9-4.5) and 4.3
(95% CI 1.74-6.9) seconds respectively. In the second
trial (n=50) RR for death with early blood transfusion
was 5.4 (95% CI 0.3-107.1). The WMD for partial thromboplastin
time was 7.0 (95% CI 6.0-8.0) seconds. In the third trial
(n=1309) RR for death with early fluid administration
was 1.06 (95% CI 0.77-1.47). Larger versus smaller volume
of fluid administration: Three trials reported mortality
and one coagulation data. In the first trial (n=36) RR
for death with a larger volume of fluid resuscitation
was 0.80 (95% CI 0.28-22.29). Prothrombin time and Partial
thromboplastin time were 14.8 and 47.3 seconds in those
who received a larger volume of fluid as compared to 13.9
and 35.1 seconds in the comparison group. In the second
trial (n=99) RR for death with a high (100 mm Hg) compared
to low (70 mm Hg) systolic blood pressure resuscitation
target was 1.02 (95% CI 0.27-3.85). In the third trial
(n=25) there were no deaths.
CONCLUSIONS: We found no
evidence from randomised controlled trials to support
early or larger volume of intravenous fluid administration
in uncontrolled haemorrhage. There is continuing uncertainty
about the best fluid administration strategy in bleeding
trauma patients. Further randomised controlled trials
are needed to establish the most effective fluid resuscitation
The role of intravenous therapy in
the pre-hospital trauma setting
Briefly covers types of shock. Dscusses recent trends
to restrict fluids until hemorrhage is controlled.
A good introduction to the science of fluid therapy for
Fluid resuscitation in the initial
management of post-traumatic shock: the concept of permissive
Intensive Care 2000 June;11(3):121-6.
Haemorrhage is one of the major
causes of death with the first hours after trauma. The
control of haemorrhage has been recognized as the single
most important intervention in the management of the bleeding
patient; a fact that was emphasized by WB Cannon in his
seminal description of the management of missile victims
on the Western Front. Cannon also identified the early
correction of hypothermia, careful transportation, opiate
analgesia, splintage, and appropriate dressings as measures,
which might influence the evolution of shock in the first
hours after wounding. Such measures remain essential features
of trauma resuscitation in the 21st century. Of critical
relevance to the subject of this review, Cannon warned
that the infusion of salt solutions to elevate the blood
pressure before a surgeon was in a position to control
bleeding might accelerate haemorrhage. The aim of this
narrative review is to present evidence from animal models
and clinical studies, so that clinicians and other healthcare
workers can make rational decisions regarding the goals
for fluid resuscitation in the initial phase of the resuscitation
of the bleeding trauma patient.
The effect of vigorous fluid resuscitation
in uncontrolled hemorrhagic shock after massive splenic
Solomonov E, Hirsh M, Yahiya
A, Krausz MM.
Department of Surgery A, Rambam Medical Center, Haifa,
Care Medicine. 2000 Mar;28(3):749-54.
Regardless of origin, uncontrolled hemorrhage is uncontrolled
Critical Care Medicine. 2000 Mar;28(3):892-4
OBJECTIVE: Using a standardized
massive splenic injury model of uncontrolled hemorrhagic
shock, we studied the effect of vigorous fluid resuscitation
on the hemodynamic response and survival time in rats.
DESIGN: Randomized, controlled study. Duration of follow-up
was 4 hrs.
SETTING: University research
SUBJECTS: Adult male Sprague-Dawley
rats, weighing 240-430 g.
massive splenic injury was induced by two transverse incisions
in the rat's spleen. The animals were randomized into
four groups: group 1 (n = 8) underwent sham operation;
in group 2 (n = 15), massive splenic injury was untreated;
in group 3 (n = 15), massive splenic injury was treated
with 41.5 mL/kg 0.9% sodium chloride (large-volume normal
saline); and in group 4 (n = 15), massive splenic injury
was treated with 5 mL/kg 7.5% sodium chloride (hypertonic
MEASUREMENTS AND MAIN RESULTS:
The hemodynamic and metabolic variables in the sham-operated
group 1 were stable throughout the experiment. Mean arterial
pressure in group 2 decreased from 86.5 +/- 4.0 to 50.3
+/- 6.3 mm Hg (p < .001) in the first 15 mins after massive
splenic injury. Mean survival time in group 2 was 127.5
+/- 17.0 mins; total blood loss was 33.8% +/-2.6% of blood
volume; and the mortality rate at 1 hr was 13.3%. Bolus
infusion of large-volume normal saline after 15 mins resulted
in an early increase in mean arterial pressure from 48.6
+/-7.4 to 83.3 +/- 7.2 mm Hg (p < .01); it then rapidly
decreased to 24.6 +/- 8.6 mm Hg (p < .001) after 60 mins.
The mean survival time (95.3 +/- 16.4 mins) was significantly
lower than in group 2 (p < .01); total blood loss (48.0%
+/- 4.3%) was significantly higher than in group 2 (p
< .01); and mortality rate in the first hour was 33.3%
(p < .05). Bolus infusion of hypertonic saline also decreased
survival time to 93.3 +/- 20.3 mins (p < .01), but total
blood loss was 35.2% +/- 3.0%, which was not significantly
different from the blood loss in group 2. The mortality
rate in the first hour (60.0%) was significantly higher
than in group 2 (p < .005).
CONCLUSIONS: Vigorous infusion
of normal saline after massive splenic injury resulted
in a significant increase in intra-abdominal bleeding
and decreased survival time. The hemodynamic response
to crystalloid infusion in blunt abdominal trauma is primarily
dependent on the severity of injury and the rate of blood
Crystalloid or colloid resuscitation
of uncontrolled hemorrhagic shock after moderate splenic
Krausz MM, Bashenko Y, Hirsh
Department of Surgery A, Rambam Medical Center, Haifa,
Using a standardized moderate
splenic injury (MSI) model of uncontrolled hemorrhagic
shock, we studied the effect of vigorous crystalloid or
colloid fluid resuscitation on the hemodynamic response
and survival time in rats. The animals were randomized
into 6 groups: group 1 (n = 8) sham-operated, group 2
(n = 10) MSI untreated, group 3 (n = 10) MSI treated with
41.5 mL/kg Ringer's lactate (large-volume Ringer's lactate
[LVRL]), group 4 (n = 10) MSI treated with 5 mL/kg 7.5%
NaCl (hypertonic saline [HTS]), group 5 (n = 10) MSI treated
with 7.5 mL/kg hydroxyethyl starch (HES-7.5), group 6
(n = 10) MSI treated with 15 mL/kg hydroxyethyl starch
(HES-15). After MSI, mean arterial pressure (MAP) in group
2 decreased from 105.0+/-5.6 to 64.0+/-12.7 mmHg (P <
0.001) after 60 min. Mean survival time was 157.4+/-28.9
min, and total blood loss was 24.0+/-5.4% of blood volume.
LVRL infusion resulted in an early rise in MAP from 75.2+/-8.7
to 96.7+/-9.0 mmHg (P < 0.01), which then rapidly dropped
to 43.0+/-9.7 mmHg (P < 0.001) after 60 min. The mean
survival time was 140.7+/-22.3 min, and total blood loss
was 41.4+/-4.8% (P < 0.05). Total blood loss following
HTS infusion was 24.7+/-3.7%, and mean survival time was
177.5+/-18.9 min. HES-7.5 infusion was followed by bleeding
of 25.6+/-5.1%, and mean survival time was 181+/-16.1.
HES-15 infusion resulted in an increase in blood loss
to 48.2+/-7.3% (P < 0.05), and mean survival time of 133.0+/-27.7
Large-volume Ringer's lactate
(LVRL) or hydroxyethyl starch (HES-15) infusion in uncontrolled
hemorrhagic shock after moderate splenic injury resulted
in a significant increase in intra-abdominal bleeding,
but survival time remained unchanged compared with untreated,
small-volume HTS-, or HES-7.5-treated animals. The hemodynamic
response to large-volume crystalloid or colloid infusion
was similar to moderate large-vessel injury.
Early changes in Oxygenation and Chest
Wall Compliance associated with Large Volume Shock Resuscitation
Marvin RG, McKinley BA, Cocanour
CS, Moore FA,
University of Texas-Houston Medical School, Houston, TX
Poster, AAST 2000
Conclusion: Patients who
sustain major trauma and are resuscitated with large volumes
of isotonic crystalloid solution have significant decreases
in oxygenation and pulmonary compliance. However, both
parameters start to improve within 48 hours. Sustained
respiratory failure due only to the volume of fluid administered
Effects of traditional versus delayed
resuscitation on serum lactate and base deficit.
BJ, Sinert RH, Sinha
AK, Buckley MC, Shaftan GW, Scalea TM.
Department of Emergency Medicine, SUNY Health Science
Center at Brooklyn,
New York, NY 11203, USA.
OBJECTIVE: To test the
hypothesis that delayed resuscitation of hemorrhagic shock
produces a less severe shock insult than traditional resuscitation,
characterized by repeated episodes of alternating hypotension
METHODS: Female pigs were
divided into three groups. Sham operated controls (C)
(n = 4), sustained hypotension (SS) (n = 6), and hypotension
with multiple cycles of shock and resuscitation (SR) (n
= 6). SS and SR animals were bled to a mean arterial pressure
(MAP) of 50 mmHg. SS animals were maintained at an MAP
of 50 mmHg for 65 min and then resuscitated to baseline
blood pressure with normal saline and shed blood. SR animals
were initially bled and maintained at an MAP of 50 mmHg
for 35 min, resuscitated to baseline BP, and subsequently
bled and resuscitated twice more. The total period of
shock was the same in both SS and SR.
RESULTS: Following hemorrhage,
there was a significant increase in lactate and base deficit
in SS as compared to C and SR.
CONCLUSION: Delayed resuscitation
produces a more profound shock insult than traditional
Medical Bulletin. 1999 Dec;55(4):821-43
Appropriate fluid replacement
is an essential component of trauma patient resuscitation.
Once haemorrhage is controlled, the restoration of normovolaemia
is a priority. In the presence of uncontrolled haemorrhage,
aggressive fluid resuscitation may be harmful. The crystalloid-colloid
debate continues, but existing clinical practice is more
likely to reflect local biases and dogma rather than evidence-based
medicine. Colloids vary substantially in their pharmacology
and pharmacokinetics and the experimental findings based
on one colloid cannot be extrapolated reliably to another.
In the initial stages of trauma patient resuscitation,
the precise fluid used is probably not important, as long
as an appropriate volume is given. Later, when the microcirculation
is relatively leaky, there may be some advantages to colloids
such as hydroxyethyl starch. Hypertonic saline solutions
may have some benefit in patients with head injuries.
A number of haemoglobin solutions are under development
but one of the most promising of these solutions will
eventually become routine therapy for trauma patient resuscitation.
In the mean time, contrary to traditional teaching, recent
data suggest that a restrictive strategy of red cell transfusion
may improve outcome in some critically ill patients.
Limited resuscitation with hypertonic
saline, hypertonic sodium acetate, and lactated Ringer's
solutions in a model of uncontrolled hemorrhage from a
Doucet JJ, Hall RI.
Department of Surgery, Dalhousie University, Queen Elizabeth
II Health Sciences Centre,
Halifax, Nova Scotia, Canada.
Trauma. 1999 Nov;47(5):956-63.
BACKGROUND: Hypertonic sodium
acetate-dextran solution (HAD) causes vasodilatation and
buffers metabolic acidosis. In controlled hemorrhage models,
HAD in small volumes increases cardiac output without
increasing blood pressure, thus creating a "high flow-low
pressure" state. The objective of this study was to determine
whether limited resuscitation of uncontrolled hemorrhage
with HAD solution improves gut perfusion as measured by
intestinal mucosal tonometry.
METHODS: Three groups of 10 swine
were bled 25 mL/kg by means of a femoral artery catheter
to produce a mean blood pressure of 30 mm Hg. A 4-mm abdominal
aortic laceration was then produced by pulling out a preimplanted
wire loop. Groups were then randomly assigned to be resuscitated
with either lactated Ringer's solution, a hypertonic saline-dextran
solution or HAD solution sufficient to maintain a mean
blood pressure of 45 mm Hg for 5 hours or until death.
Outcomes were measured by survival, intraperitoneal blood
loss, hemodynamic monitoring, and ileal mucosal tonometry.
RESULTS: HAD infusions caused
transient worsening of hypotension and were associated
with increased mortality (p = 0.038). Blood loss and volumes
required for resuscitation were significantly increased
in the lactated Ringer's solution group. HAD showed significant
buffering effect against metabolic acidosis in arterial
blood only, but intestinal ileal mucosal tonometry was
not different among the groups.
CONCLUSION: HAD did not improve
gut perfusion despite buffering the systemic acidosis
of shock and caused increased mortality. Limited resuscitation
with any of these solutions is associated with significant
Treatments to support blood pressure
increases bleeding and/or decreases survival in a rat
model of closed head trauma combined with uncontrolled
Talmor D, Merkind V, Artru AA,
Shapiro O, Geva D, Roytblat L, Shapira Y.
Division of Anesthesiology, Ben-Gurion University of the
Negev, Faculty of Health Sciences,
Soroka Medical Center, Beer Sheva, Israel.
Analg. 1999 Oct;89(4):950-6.
Hemorrhagic hypotension may aggravate
the detrimental effects of head trauma on neurologic outcome.
Our study examined whether using phenylephrine or large
volumes of saline IV to increase mean arterial blood pressure
(MAP) to 70, 80, or 90 mm Hg during the combination of
head trauma and uncontrolled hemorrhage would improve
neurologic outcome. Rats were assigned to one of 17 groups.
In Groups 1-5, the variables were head trauma (yes/no),
hemorrhage (yes/no), 0 or 3 mL saline per milliliter of
blood lost, and no target MAP. In Groups 6-11, hemorrhage
was or was not combined with head trauma, and large volumes
of saline were given IV to achieve target MAPs of 70,
80, or 90 mm Hg. Groups 12-17 were similar to Groups 6-11
except that phenylephrine was used rather than saline
to achieve target MAPs. Saline increased blood loss at
2 h to approximately 16 and 25 mL at a MAP of 80 and 90
mm Hg respectively, increased (worsened) the neurodeficit
score but not cerebral edema at 24 h, and decreased survival
rate at 2 and 24 h. Because phenylephrine was fatal for
62 of 63 rats, group mean values for blood loss, neurodeficit
score, and brain tissue specific gravity could not be
calculated. We conclude that supporting MAP with either
phenylephrine or large volumes of saline worsened the
neurodeficit score and/or survival and did not affect
cerebral edema formation in our rat model of head trauma
combined with hemorrhage.
IMPLICATIONS: The results
of this study indicate that maintaining mean arterial
blood pressure at 70, 80, or 90 mm Hg with either phenylephrine
or large volumes of saline worsened the neurodeficit score
and/or survival and did not affect cerebral edema formation
in our rat model of head trauma combined with hemorrhage.
Aggravated uncontrolled hemorrhage
induced by intravenous fluid administration
Article in Swedish
L, Hahn R.
Lakartidningen. 1999 Sep 15;96(37):3893-4.
A model of uncontrolled haemorrhage
where a 0.5 mm laceration is made in the porcine abdominal
aorta has shown outcome to be impaired by conventional
fluid therapy given to restore blood volume. Findings
in recent studies where the difference in blood flow rates,
proximal vs. distal to the site of vascular lesion, was
used as a measure of bleeding suggest the adverse effect
of fluid therapy to be strongly associated with re-bleeding
after primary haemostasis has occurred. Optimal survival
is dependent on a fluid infusion rate ensuring balance
between the risk of re-bleeding and the beneficial effects
of fluid therapy on oxygen consumption.
Logistics of parental fluids in battlefield
Peace FJ; Lyons WS.
Division of Surgery, Walter Reed Army Institute of Research,
Washington, DC 20307 USA
Military Medicine, 1999 Sept;
The paper discusses the substantial
reduction in weight and volume of the fluids of resuscitation
that is possible and desirable on the basis of sound physiology
and the vast experience of the U.S. Army in four major
wars in this century. We note the major shift in emphasis
from massive colloid and whole blood in World War II and
Korea to massive crystalloid and packed cells in Vietnam
and the serious complications with which this was associated.
These complications were edematous in nature and best
known as the Da Nang lung, or adult respiratory distress
syndrome, multiorgan dysfunction syndrome, and systemic
inflammatory response syndrome. The advantage of colloid
in reducing the weight and volume of resuscitation fluids
in forward areas by 60% to 90%, as well as in avoiding
the edematous complications of crystalloids, are emphasized.
Prehospital Fluid Administration for
Hyde AJ, Graham TR,
Immediate Care, 1999 June ;3:99-101
Fluid administration is an established
component of resuscitation in cases of trauma. Often this
occurs as part of a set protocol, and little thought is
given to the pathophysiology of the underlying injury.
This approach is often beneficial, particularly in hypovolaemic
patients, and in the majority of cases will be harmless.
Unfortunately, there are certain instances, particularly
with thoracic trauma, when such an indiscriminate policy
can be detrimental and even fatal. This has recently brought
into question the whole issue of fluid resuscitation,
and the concept of “hypotensive resuscitation has been
introduced. This relies on fluid resuscitation only to
the point of critical organ perfusion, and not beyond.
Unless specifically indicated, fluids may be withheld
until assessment in the emergency room. This policy not
only prevents the potential for disastrous consequences
of over transfusion, but reduces time spent at scene,
and therefore expedites transfer.
Mattox KL, Brundage SI, Hirshberg
New Horiz 1999 Spring;7(1): 4-9.
Initial resuscitation volume in uncontrolled
hemorrhage: effects on organ function.
Haizlip TM Jr, Poole GV, Falzon
Department of Surgery, University of Mississippi Medical
Jackson 39216, USA.
Surgeon 1999 Mar;65(3):215-7.
Conventional resuscitation of
hypovolemia due to hemorrhage has consisted of aggressive
fluid administration. Recent studies have suggested that
surgical control of bleeding before fluid resuscitation
might improve early survival. The effects of limited resuscitation
on organ function have not been assessed in these studies.
We developed a model of moderate intraperitoneal hemorrhage
designed to evaluate long-term end-organ function after
various resuscitation protocols. Male Sprague-Dawley rats
underwent ketamine anesthesia, followed by placement of
femoral artery and vein lines. Intraperitoneal hemorrhage
was induced by division of distal branches of the ileocolic
artery and vein. After 5 minutes of bleeding, the animals
were randomized to one of three resuscitation groups:
Group 1 received no fluid resuscitation before surgical
control of the hemorrhage; Group 2 received 0.5 mL of
lactated Ringer's solution (LR) every 5 minutes for a
mean arterial pressure (MAP) of less than 80 mm Hg; Group
3 received 2.0 mL of LR every 5 minutes for a MAP of less
than 80 mm Hg. In all three groups, after 20 minutes,
the bleeding was surgically controlled. All rats were
then resuscitated with LR to a MAP of 80 mm Hg. The intravascular
lines were removed, and the rats were allowed to recover
from anesthesia and were returned to animal holding. On
the 7th day, survivors were sacrificed, and their blood
was assayed for hematocrit and serum levels of bilirubin,
alanine aminotransferase, urea nitrogen, and creatinine.
Kidneys, lungs, and liver were harvested for microscopic
examination. Survival was lower in Group 2 than in the
other groups (90%, 60%, and 100%, respectively; P = 0.04),
but all deaths occurred within 3 hours of hemorrhage and
were due to either hypovolemia or anesthetic complications.
No histologic abnormalities were identified in the livers
of the animals that survived, but pulmonary atelectasis
and mild-to-moderate renal tubular necrosis were identified
uniformly. No histologic differences could be discerned
between the groups. Hematocrit and indices of liver and
renal function were similar in all groups, and no animal
developed organ dysfunction. In this model of moderate
uncontrolled intraperitoneal hemorrhage, the volume of
fluid resuscitation, or the absence of resuscitation,
had an inconsistent effect of 7-day survival and did not
influence function or histologic appearance of the liver,
lungs, or kidneys 7 days after hemorrhage.
Limited volume resuscitation in penetrating
de Guzman E. Shankar MN. Mattox
Trauma Services, Ben Taub General Hospital,
Houston, TX 77030, USA.
Clinical Issues. 1999 Feb;10(1):61-8,.
Trauma is the leading cause of
death in young adults. Development of trauma centers in
urban settings including emergency medical services has
contributed greatly to the improved quality of trauma
patient care. Based on animal experiments performed 3
decades ago, the traditional management of hypovolemic
hemorrhagic shock includes adequate circulatory volume
with aggressive initial infusion of crystalloid solution.
However, in several recent animal studies, investigators
have found that aggressive treatment with fluids before
control of bleeding results in a higher mortality rate,
especially if blood pressure is elevated. This notion
has been supported by findings in a recent prospective,
randomized study involving patients with penetrating injuries
to the torso. This article discusses briefly the pathophysiology
of shock and hemostasis and the current literature on
fluid resuscitation, with emphasis on limited volume resuscitation
in patients with penetrating thoracoabdominal injuries.
Controlled resuscitation for uncontrolled
D; Rhee P; Kaufmann
C; Pikoulis E; Austin B; Eror A; DeBraux S; Guzzi L; Leppaniemi
Department of Surgery, Uniformed Services University of
the Health Sciences,
Bethesda, Maryland 20814-4799 USA.
Trauma, 1999 Feb;46(2):216-23
OBJECTIVE: To test the hypothesis
that controlled resuscitation can lead to improved survival
in otherwise fatal uncontrolled hemorrhage.
METHODS: Uncontrolled hemorrhage
was induced in 86 rats with a 25-gauge needle puncture
to the infrarenal aorta. Resuscitation 5 minutes after
injury was continued for 2 hours with lactated Ringer's
solution (LR), 7.3% hypertonic saline in 6% hetastarch
(HH), or no fluid (NF). Fluids infused at 2 mL x kg(-1)
x min(-1) were turned on or off to maintain a mean arterial
pressure (MAP) of 40, 80, or 100 mm Hg in six groups:
NF, LR 40, LR 80, LR 100, HH 40, and HH 80. Blood loss
was measured before and after 1 hour of resuscitation.
RESULTS: Survival was improved
with fluids. Preresuscitation blood loss was similar in
all groups. NF rats did not survive 4 hours. After 72
hours, LR 80 rats (80%) and HH 40 rats (67%) showed improved
survival over NF rats (0%) (p < 0.05). Rebleeding increased
with MAP. Attempts to restore normal MAP (LR 100) led
to increased blood loss and mortality.
CONCLUSION: Controlled resuscitation
leads to increased survival compared with no fluids or
standard resuscitation. Fluid type affects results. Controlled
fluid use should be considered when surgical care is not
The effects of varying fluid
volume and rate of resuscitation during uncontrolled hemorrhage.
Soucy DM, Rudé M, Hsia WC, Hagedorn
FN, Illner H, Shires GT.
Department of Surgery, Texas Tech University Health Sciences
Lubbock 79430, USA
Trauma, 1999 Feb;46(2):209-15.
BACKGROUND: The role of rate and
volume of infusion in survival from experimental uncontrolled
hemorrhage was evaluated.
METHODS: Hemorrhage was initiated
using tail resection in 43 female rats assigned to the
following five groups: nonresuscitated; resuscitated with
moderate volume, slower rate; resuscitated with moderate
volume, faster rate; resuscitated with high volume, slower
rate; and resuscitated with high volume, faster rate.
RESULTS: A trend toward improved
survival was noted with faster rate of infusion (60 vs.
33.3% survival rate with moderate volume and 28.6 vs.
12.5% with high volume, compared with 16.7% in the nonresuscitated
CONCLUSION: Rapid infusion of
moderate volume of isotonic saline improved survival in
uncontrolled hemorrhage. Extreme volumes, infused rapidly,
also resulted in higher survival rates compared with those
observed in nonresuscitated rats
This is evidence against ‘permissive hypotension’ for
uncontrolled bleeding. This group published other studies
that similarly show decreased mortality with fluid infusion
(Surgery, 1998 and Annals of Surgery, 1995 – both in this
Early isotonic saline resuscitation
from uncontrolled hemorrhage in rats.
Greene SP, Soucy DM, Song WC,
Barber AE, Hagedorn FN, Illner HP, Shires GT.
Department of Emergency Medicine, Texas Tech University
Health Sciences Center,
El Paso, USA.
BACKGROUND: Attempts to
modify traditional fluid resuscitation have been based
on animal models that evaluate several variables including
anesthesia. This study presents the effects of early saline
resuscitation from severe uncontrolled hemorrhage unanesthetized
METHODS: Sixty-three female
Sprague-Dawley rats were equally divided into three groups:
group A, nonresuscitated; and groups B and C, resuscitated
with isotonic saline (40 and 80 mL/kg, respectively).
Hemodynamics, blood loss, survival time, and mortality
were recorded for 360 minutes after the hemorrhage, which
was initiated by 75% resection of the tail.
RESULTS: In group C, 80
mL/kg of saline significantly lowered mortality (24% vs
76% and 71% for groups A and B, respectively) with concomitant
increases in mean survival time (241 +/- 103 min vs 146
+/- 108 and 175 +/- 92 min for groups A and B, respectively).
There were no statistically significant differences in
blood loss, hematocrit, or hemodynamic parameters among
CONCLUSIONS: Early and
adequate isotonic saline resuscitation of unanesthetized
rats improved outcome despite continuing hemorrhage. The
significantly lower mortality rate and increased survival
time were not a result of transiently improved arterial
pressure and did not correlate with blood loss. No significant
bleeding increases were noted in the resuscitated groups.
Like other studies by this group, this demonstrates improve
survival with fluid infusion, in a rat experiment of uncontrolled
bleeding. Their findings are opposite to those found by
Delayed fluid resuscitation of
head injury and uncontrolled hemorrhagic shock.
Bourguignon PR, Shackford SR,
Shiffer C, Nichols P, Nees AV.
Department of Surgery, University of Vermont College of
Burlington 05401, USA.
of Surgery. 1998 Apr;133(4):390-8.
OBJECTIVE: To evaluate
the effects of delayed vs early fluid resuscitation on
cerebral hemodynamics after severe head injury and uncontrolled
DESIGN: Prospective, randomized,
controlled experimental trial.
SETTING: Surgical research
swine (N=16) weighing 40 to 50 kg.
swine were subjected to cryogenic brain lesion and hemorrhage
to maintain a mean arterial pressure (MAP) of 50 mm Hg.
Animals were randomized to receive 1 L of Ringer lactate
solution in 20 minutes, starting 20 minutes after injury
and hemorrhage, followed by 1 L of Ringer lactate solution
in 30 minutes (ER group) (n=6), or no fluid resuscitation
(DR group) (n=6). The 4 control animals underwent instrumentation
only. The study ended 70 minutes after head injury and
MAIN OUTCOME MEASUREMENTS:
Measurements of MAP, bilateral regional cerebral blood
flow, serum hemoglobin level, systemic and regional cerebral
oxygen delivery, and intracranial pressure performed at
baseline and 20 (phase 1), 50 (phase 2), and 70 minutes
(phase 3) after head injury and hemorrhage. Lesion size
(percentage of ipsilateral cortex) was measured post mortem.
RESULTS: All animals survived
the experimental period. Systemic cerebral oxygen delivery
in the DR group was significantly lower at phase 3 compared
with that of the ER group (31.5% vs 53.1% at baseline)
(P=.03). However, bilateral regional cerebral oxygen delivery
was significantly greater in the DR group at phase 3 compared
with that of the ER group (71.5% vs 47.0% at baseline
in the injured side; 72.9% vs 48.4% at baseline in the
noninjured side) (P=.02). Bilateral cerebral blood flow
was similar in all groups at all times. The ER group showed
a trend toward a greater intracranial pressure elevation
(6.8 vs -0.25) (P=.07) and lesion size (37.0% vs 28.6%)
(P=.07). Hemoglobin level became significantly lower in
the ER group at phase 2 (7.0 vs 10.7) (P=.03) and remained
lower at phase 3 (6.9 vs 11.7) (P=.01).
CONCLUSIONS: Early fluid
resuscitation with Ringer lactate solution following head
injury and uncontrolled hemorrhagic shock worsens cerebral
hemodynamics. Cerebral pressure autoregulation is sufficiently
intact following head injury to maintain regional cerebral
oxygen delivery without asanguineous fluid resuscitation.
They found that routine aggressive resuscitation (with
Ringer's Lactate) in uncontrolled hemorrhage with severe
head injury worsens cerebral hemodynamic parameter. Such
fluid administration and could possibly contribute to
secondary brain injury.
Resuscitation after uncontrolled
venous hemorrhage: Does increased resuscitation volume
improve regional perfusion?
Smail N, Wang P, Cioffi WG, Bland
KI, Chaudry IH.
Center for Surgical Research and Department of Surgery,
Brown University School of Medicine and Rhode Island Hospital,
Providence 02903, USA.
Trauma. 1998 Apr;44(4):701-8.
BACKGROUND: Recent studies
have questioned the use of aggressive fluid resuscitation
after uncontrolled arterial hemorrhage until the bleeding
is controlled. However, it remains unknown whether resuscitation
after hemorrhage from a venous origin (usually nonaccessible
to surgical intervention) has any beneficial or deleterious
effects on regional perfusion. The aim of this study,
therefore, was to determine whether increased volume of
fluid resuscitation after uncontrolled venous hemorrhage
improves hemodynamic profile and regional perfusion in
MATERIALS AND METHODS:
After methoxyflurane anesthesia and midline laparotomy,
both lumbar veins in the rat were severed, which resulted
in lowering the mean arterial blood pressure to approximately
40 mm Hg. This pressure was maintained for 45 minutes
by allowing further bleeding from the lumbar veins. The
abdominal incision was then closed in layers and the animals
received either 0, 10, or 30 mL of lactated Ringer's solution
intravenously over a period of 60 minutes. Cardiac output
and regional blood flow were determined by radioactive
microspheres immediately or at 1.5 hours after the completion
RESULTS: Fluid resuscitation
with 10 or 30 mL lactated Ringer's solution increased
mean arterial blood pressure and cardiac output immediately
after resuscitation compared with the nonresuscitated
animals. At both time points, regional perfusion in the
heart, kidney and intestines remained significantly decreased
compared with the sham values, irrespective of the volume
of fluid resuscitation. Moreover, no further improvements
in hemodynamics or regional perfusion occurred when volume
resuscitation was increased from 10 mL to 30 mL. Total
hepatic blood flow, however, increased with 10 mL lactated
Ringer's solution compared with the other hemorrhage groups
and the increase was evident even at 1.5 hours after resuscitation.
CONCLUSIONS: Fluid resuscitation
after uncontrolled venous bleeding transiently increased
cardiac output and mean arterial blood pressure compared
with nonresuscitated animals. Moderate fluid administration,
i.e., 10 mL, however, did increase total hepatic blood
flow. In contrast, increasing the resuscitation volume
to 30 mL did not improve hemodynamic parameters or regional
perfusion. Thus moderate instead of no resuscitation or
larger volume of resuscitation is recommended in an uncontrolled
model of venous hemorrhage.
Central and regional hemodynamics
during crystalloid fluid therapy after uncontrolled intra-abdominal
Riddez L, Johnson L, Hahn RG.
Trauma 1998 Mar;44:433-439
OBJECTIVE: To study the
effect of graded crystalloid fluid resuscitation on central
hemodynamics and outcome after intra-abdominal hemorrhage.
METHODS: Ten minutes after
a 5-mm long laceration was produced in the infrarenal
aorta, 32 pigs were randomized to receive either no fluid
or Ringer's solution in the proportion 1:1, 2:1, or 3:1
to the expected amount of blood lost per hour (26 mL kg[-1])
over 2 hours. The hemodynamics were studied using arterial
and pulmonary artery catheters and four blood flow probes
placed over major blood vessels.
RESULTS: During the first
40 minutes after the injury, the respective blood flow
rates in the distal aorta were 39% (no fluid), 41% (1:1),
56% (2:1), and 56% (3:1) of the baseline flow. Fluid resuscitation
increased cardiac output but had no effect on arterial
pressure, oxygen consumption, pH, or base excess. Rebleeding
occurred only with the 2:1 and 3:1 fluid programs. Survival
was highest with the 1:1 and 2:1 programs.
fluid therapy improved the hemodynamic status but increased
the risk of rebleeding. Therefore, a moderate fluid program
offered the best chance of survival Reviewer’s note: The
authors wanted to test the "low fluid hypothesis" of transport.
Limited volume resuscitation was more likely to result
in survival than fluid therapy at the standard 3 litres
given:1litre of lost blood ratio. (Then) standard resuscitation
caused a higher bleeding rate.
Hypothermia from realistic fluid
resuscitation in a model of hemorrhagic shock.
Silbergleit R, Satz W, Lee DC,
Department of Emergency Medicine, George Washington University,
Washington, DC, USA.
Annals of Emergency Medicine 1998
STUDY OBJECTIVE: To correlate
changes in core body temperature with changes in mean
arterial pressure (MAP) and cardiac output (CO) and with
the administration of room-temperature intravenous fluids
in a clinically relevant large-animal model of uncontrolled
METHODS: Ten swine were
subjected to uncontrolled hemorrhage through a flow-monitored
shunt placed between the femoral artery and the peritoneal
cavity. Animals were randomly assigned to a treatment
or a control group. The control group (n=5) received no
intravenous fluids. The treatment group (n=5) received
80 mL/kg (3:1 crystalloid/blood loss) ambient-temperature
lactated Ringer's solution over a 10-minute resuscitation
phase initiated 10 minutes after injury. CO and core body
temperature, measured with the use of a pulmonary artery
catheter, and MAP were the primary outcomes. We analyzed
differences between groups with the use of repeated-measures
ANOVA. Change of temperature was analyzed against the
change in CO, and against fluid infusion for each interval,
by means of regression analysis.
RESULTS: The unresuscitated
control animals had no change in core temperature despite
profound hemorrhagic shock and hypotension. The animals
treated with fluids had a mean 2.6 degrees C decrease
in core temperature during fluid resuscitation (95% confidence
interval [CI], 1.8 to 3.5). A 1.5 degrees C decrease in
core temperature (95% CI, .1 to 2.0) persisted at the
end of 60 minutes (40 minutes after fluid resuscitation
was discontinued). Core temperatures in control animals
were 2.8 degrees C lower than those in treated animals
after fluid resuscitation (95% CI, .8 to 4.8). Decreases
in core temperature correlated with fluid infusion (beta=-35.2
mL/kg x degrees C, R2=.75) and increases in CO (beta=-1.46
L/min x degrees C, R2=.69).
crystalloid resuscitation in a clinically relevant large-animal
model of hemorrhagic shock causes small decreases in core
body temperature. Resuscitation rather than shock is the
main cause of decreased body temperature in this model.
Reappraising the prehospital care of
the patient with major trauma.
Pepe PE, Eckstein M.
Department of Emergency Medicine, Allegheny University
of the Health Sciences,
Pittsburgh, Pennsylvania, USA.
Emerg Med Clin North Am. 1998
Recent research efforts have demonstrated
that many long-standing practices for the prehospital
resuscitation of trauma patients may be inappropriate,
particularly in certain circumstances. Traditional practices,
such as application of antishock garments and IV fluid
administration, may even be detrimental in certain patients
with uncontrolled bleeding. Endotracheal intubation, although
potentially capable of prolonging a patient's ability
to tolerate circulatory arrest, may be harmful if overzealous
ventilation further compromises cardiac output in such
severe hemodynamic instability. If these procedures delay
patient transport, any benefit they may offer could be
outweighed by delaying definitive care. To improve current
systems of trauma care, future trauma research must address
the different mechanisms of injury, the anatomic areas
involved, and the physiologic staging in a given patient.
Department of Emergency Medicine, Royal Brisbane Hospital,
Eur J Emerg Med. 1997 Dec;4(4):224-32.
Contention over fluid resuscitation
is not new. The issues however have changed considerably.
The crystalloid/colloid debate has largely reached a stalemate
with little to define clear differences between the two
especially early in traumatic shock when increased capillary
permeability is a minor issue. Blood, despite its difficulties
and its cost is now safer than ever before and we will
have to wait a number of years before routine use of blood
substitutes becomes possible. Hypertonic saline and hypertonic
saline dextran solutions used as an early bolus of 4-6
ml/kg and in conjunction with isotonic crystalloids and
blood appear to be the new resuscitation fluids of first
choice for haemorrhagic shock and there will be a progressive
swing towards these fluids over the next 5 years. Application
of the principles of minimal volume or delayed resuscitation
requires the reconsideration of many entrenched attitudes
and expectations present in the traditional management
of haemorrhagic shock. Currently there is hard evidence
to support its use only in ruptured AAA and penetrating
truncal trauma but the application of the principles should
be much more widespread. Minimal volume resuscitation
emphasizes the need for urgent investigation and definitive
management of uncontrollable haemorrhage reserving the
early use of fluid resuscitation to maintain life only,
until the integrity of the vascular circuit has been verified
or restored. Thus it is the timing rather than the quantity
of fluid which is the underlying issue. The questions
which these new models of haemorrhage raise and the reconsideration
of the physiology of haemorrhagic shock must be our focus.
It would be foolish to replace the long-held dogma of
aggressive fluid resuscitation in all situations with
the new dogma of minimal volume resuscitation in all situations.
Instead we must walk the tightrope attempting to understand
the likely physiological mechanisms of our patients at
an individual level. Fluid resuscitation has necessarily
become more complex as the potential to do harm has been
more clearly demonstrated. The use of resuscitation fluids
must now receive as much care and consideration as is
currently given to the prescription of potent drugs, weighing
the potential benefits of a course of action against its
possible side effects. Much research is required to clarify
and refine the data on fluid resuscitation but there is
little doubt that the conceptual changes which underlie
this work on haemorrhagic shock offer the most exciting
advances in fluid resuscitation seen in the past 30 years.
Restriction of fluid resuscitation
in posttraumatic hypotension.
Tisherman SA, Peitzman AB.
Opin Critical Care 1997;3(6):448-454.
Neurologic outcome with hemorrhagic
hypotension after closed head trauma in rats: effect of
early versus delayed conservative fluid therapy.
Feldman Z, Gurevitch B, Artru
AA, Shapira Y, Reichenthal E.
Department of Neurosurgery, Soroka Medical Center, Faculty
of Health Science, Ben-Gurion University,
Trauma. 1997 Oct;43(4):667-72.
OBJECTIVE: This study examined
(1) whether two previously reported, well-established
models in rats, one a model of hemorrhagic hypotension
and the other a model of closed head trauma, could be
combined to evaluate neurologic outcome when hemorrhage
occurs subsequent to head injury, and (2) the ability
of the traditional, conservative approach to fluid therapy
(3 mL of intravenous fluid for 1 mL of blood loss) to
reverse the detrimental effects of hemorrhagic hypotension
after closed head trauma. In addition, two strategies
of fluid therapy (early and delayed) were examined.
METHODS: Fifty-six Sprague-Dawley
male rats were divided into five groups with head injury
at time 0 in groups 3 to 5, hemorrhage at 1 hour in groups
1, 2, 4, and 5, and intravenous fluid at 15 minutes (groups
2 and 5) or 60 minutes (groups 1 and 4) after hemorrhage.
Head injury was delivered using a weight-drop impact of
0.5 J onto the closed cranium. Neurologic Severity Score
(NSS) was determined at 1 hour (just before hemorrhage)
and at 4 hours.
RESULTS: NSS at 1 hour did not
differ between groups 3 to 5 (15.5 (9-24) to 16 (2-21),
median (range)). The amount of bleeding did not differ
between groups during the first 15 minutes of hemorrhage
(2.8 0.8 to 3.7 2.0 mL, mean SD). After 60 minutes, cumulative
blood loss in the delayed fluid therapy groups was less
(3.1 1.13 mL in group 1 and 4.25 2.39 mL in group 4) than
in the early fluid therapy groups (7.73 4.41 mL in group
2 and 6.85 2.36 mL in group 5) (analysis of variance,
p < 0.01). The NSS of group 3 (head injury only) improved
at 4 hours after injury (12 (5-20)), whereas the NSS of
groups 4 and 5 (head injury followed by hemorrhage) deteriorated
(24 (17-25) and 19.5 (9-25), respectively) (Kruskal-Wallis
test,p < 0.05). In all the hemorrhage groups, fluid therapy
failed to restore blood pressure to prehemorrhage levels.
CONCLUSION: It is concluded that
the two individual models of hemorrhagic hypotension and
closed head trauma in rats can be combined to evaluate
outcome when hemorrhage occurs subsequent to head injury.
Furthermore, traditional, conservative fluid therapy,
whether early or delayed, failed to restore blood pressure
or to improve NSS when hemorrhage occurred after head
injury. Blood loss was greater with early fluid therapy
whether or not head injury was present.
Ineffectiveness of On-Site Intravenous
Lines: Is Prehospital Time the Culprit?
Sampalis JS. Tamim H. Denis R.
Boukas S. Ruest SA. Nikolis A. Lavoie A. Fleiszer D. Brown
R. Mulder D. Williams JI.
Department of Surgery, Trauma Programme, Montreal General
Hospital, McGill University,
Trauma 1997 Oct;43(4):608-617 (including discussion).
The purpose of the present study
was to test the association between on-site intravenous
fluid replacement and mortality in patients with severe
trauma. The effect of prehospital time on this association
was also evaluated. The design was that of an observational
quasi-experimental study comparing 217 patients who had
on-site intravenous fluid replacement (IV group) with
an equal number of matched patients for whom this intervention
was not performed (no-IV group). The patients were individually
matched on their Prehospital Index obtained at the scene
and were included in the study if they had an on-site
Prehospital Index score > 3 and were transported alive
to the hospital. The outcome measure of interest was mortality
because of injury. The patients in the IV group had a
significantly lower mean age (37 vs. 45 years; p < 0.001)
and higher incidence of injuries to the head or neck (46
vs. 32%; p = 0.004), chest (34 vs. 17%; p < 0.001), and
abdomen (28 vs. 12%; p < 0.001). The IV group also had
a higher proportion of patients injured by motor vehicle
crashes (41 vs. 27%; p = 0.003), firearms (9 vs. 2%; p
= 0.001), and stabbing (20 vs. 9%; p = 0.001). The rate
of extremity injuries (38 vs. 59%; p < 0.001) and falls
(12 vs. 40%; p < 0.001) was lower for the IV group. In
addition, the mean Injury Severity Score was significantly
higher for the IV group (15 vs. 9; p < 0.001). The mortality
rates for the IV and no-IV groups were 23 and 6% (p <
0.001). Logistic regression analysis showed that after
adjusting for patient age, gender, Injury Severity Score,
mechanism of injury, and prehospital time, the use of
on-site intravenous fluid replacement was associated with
a significant increase in the risk of mortality (adjusted
odds ratio = 2.3; 95% confidence interval = 1.02-5.28;
p = 0.04). To further evaluate the effect of prehospital
time on the association between on-site IV use and mortality,
the analysis was repeated separately for the following
time strata: 0 to 30 minutes, 31 to 60 minutes, and >60
minutes. The adjusted odds ratios (95% confidence interval)
for these strata were 1.05 (0.08-14.53; p = 0.97), 3.38
(0.84-13.62; p = 0.08), and 8.40 (1.27-54.69; p = 0.03).
These results show that for prehospital times of less
than 30 minutes, the use of on-site intravenous fluid
replacement provides no benefit, and that for longer times,
this intervention is associated with significant increases
in the risk of mortality.
The results of this observational
study have shown that the use of on-site intravenous fluid
replacement is associated with an increase in mortality
risk and that this association is exacerbated by, but
is not solely the result of, increased prehospital times.
Our findings are consistent with the hypothesis that early
intravenous fluid replacement is harmful because it disrupts
the normal physiologic response to severe bleeding. Although
this evidence is against the implementation of on-site
intravenous fluid replacement for severely injured patients,
further studies including randomized controlled trials
are required to provide a definitive answer to this question.
Timing of Trauma Resuscitation – Where
on the spectrum should it occur?
Commentary – timing of trauma
Advances in Fluid Resuscitation
The Canberra Hospital. Department of Emergency Medicine
notes on Emergency Medicine, August 31 1997
Central and regional hemodynamics
during acute hypovolemia and volume substitution in volunteers.
Riddez L, Hahn R G, Brismar B,
Strandberg Å, Svens‚n C, Hedenstierna G.
Care Medicine 1997 April;25:635-640.
Objectives: To study the
central and regional hemodynamics and oxygen consumption
during acute hypovolemia and volume replacement with crystalloid
and colloid solutions. Design: Prospective, randomized,
Setting: Clinical physiology
department at a university hospital. Subjects: Eighteen
healthy male volunteers, between 21 and 35 yrs of age
were inserted in the cubital vein, brachial artery, pulmonary
artery, thoracic aorta, right hepatic vein, and left renal
vein for measurements of systemic arterial and pulmonary
arterial pressures, total and central blood volumes, extravascular
lung water, and the splanchnic (liver) and renal blood
flow rates. The exchange of respiratory gases was measured,
using the Douglas bag technique. Measurements were made
before and after a venesection of 900 mL and again after
the subjects had been randomized and received volume replacement
with either 900 mL of Ringer's acetate solution 900 mL
of albumin 5%, or 900 plus 900 mL of Ringer's solution.
Measurements and Main Results:
Withdrawal of 900 mL of blood decreased cardiac output
and the splanchnic and renal blood flow rates by between
-16% and -20%. The oxygen uptake decreased by 13% in the
whole body, while it remained unchanged in the liver and
kidney. The systemic and pulmonary vascular resistances
increased, while the extravascular lung water decreased.
Autotransfusion of fluid from tissue to blood was indicated
by hemodilution, which was most apparent in subjects showing
only a minor change in peripheral resistance. Cardiac
output, blood volume, and systemic vascular resistance
were significantly more increased by infusion of 900 mL
of albumin 5% than by 900 mL of Ringer's solution. However,
infusion of 1800 mL of Ringer's solution increased the
extravascular lung water and the pulmonary arterial pressures
to significantly above baseline, while no significant
difference from baseline was found after 900 mL of Ringer's
of 900 mL of blood induces similar reductions in cardiac
output as in the splanchnic and renal blood flow rates.
A fluid shift from the extravascular to the intravascular
fluid compartment might restore up to 50% of the blood
loss. Optimal volume substitution with Ringer's solution
can be effectuated by infusing between 100% and 200% of
the amount of blood lost.
Hypothermia and minimal fluid resuscitation
increase survival after uncontrolled hemorrhagic shock
Kim SH, Stezoski SW, Safar P,
Capone A, Tisherman S.
Department of Anesthesiology/Critical Care Medicine, University
of Pittsburgh Medical Center,
Pennsylvania 15260, USA
Trauma. 1997 Feb; 42: 213-22.
OBJECTIVE: To test the
hypothesis that protective-preservative moderate hypothermia
during uncontrolled hemorrhagic shock (UHS) in rats increases
DESIGN: Randomized outcome
study in rats.
MATERIALS AND METHODS:
UHS phase I of 90 minutes, with initial withdrawal of
3 mL/100 g of blood plus tail amputation, was followed
by hemostasis and all-out resuscitation phase II from
90 to 150 minutes, and observation phase III to 72 hours.
Forty male rats under light anesthesia and spontaneous
breathing were randomized into four groups: Group 1 received
no fluid resuscitation during UHS and normothermia (37.5
degrees C) throughout. Group 2 received no fluid resuscitation
and hypothermia (30 degrees C) from 15 to 120 minutes.
Group 3 received lactated Ringer's solution to maintain
mean arterial pressure at 40 mm Hg during UHS and normothermia.
Group 4 received lactated Ringer's solution to a mean
arterial pressure of 40 mm Hg during UHS and hypothermia
from 15 to 120 minutes.
RESULTS: UHS phase I was
survived by 0 of 10 rats in group 1, 7 of 10 in group
2, 5 of 10 in group 3, and 10 of 10 in group 4 (p < 0.01
for group 1 vs. 2, 3, or 4; p <0.05 for group 4 vs. 3).
Survival to 72 hours was achieved by 0 of 10 rats in group
1, 3 of 10 in group 2 (p < 0.001 vs. group 1), 1 of 10
in group 3, and 7 of 10 in group 4 (p < 0.001 vs. group
1, and p < 0.01 vs. group 3). All 72-hour survivors were
neurologically normal. Necropsies in rats that died early
during phase III showed edema and gastrointestinal hemorrhages.
CONCLUSIONS: Moderate hypothermia
or limited (hypotensive) fluid resuscitation --best both
combined—increases survival during and after UHS in rats.
Shock 1996 Nov; 6:311-316
While the mechanism remains unclear,
a growing body of experimental and clinical evidence suggests
that aggressive crystalloid resuscitation in near fatal
uncontrolled hemorrhage is associated with poor outcome.
Limited attempts to restore blood pressure improve cardiac
output, tissue perfusion, and survival while attempts
to restore normal tension with crystalloid result in increased
hemorrhage volume and higher mortality. The current standard
of therapy for treatment of hemorrhagic shock includes
initial aggressive crystalloid resuscitation. This mini-review
summarizes some of the experimental and clinical data
suggesting that this approach may not be desirable in
the presence of uncontrolled hemorrhage following injury.
Effect of permissive hypotension
in continuous uncontrolled intra-abdominal hemorrhage.
Silbergleit R, Satz W, McNamara
RM, Lee DC, Schoffstall JM.
Medical College of Pennsylvania, Department of Emergency
Philadelphia 19129, USA.
Emergency Medicine 1996 Oct;3(10):922-6.
OBJECTIVE: To determine
the effects of aggressive fluid administration vs permissive
hypotension on survival, blood loss, and hemodynamics
in a model of uncontrolled hemorrhage in which bleeding
has been shown to be continuous.
METHODS: In this porcine
model, 10 animals were bled through a flow-monitored shunt
placed between the femoral artery and the peritoneal cavity.
The animals received either no fluid (n = 5) or 80 mL/kg
lactated Ringer's solution (n = 5) during a resuscitation
phase between 10 and 20 minutes postinjury, followed by
a 40-minute evaluation phase. Arterial pressures, cardiac
output (CO), and hemorrhage rate were measured. Survival
and blood loss were calculated outcome measures.
RESULTS: The difference
in survival between the animals left hypotensive (40%)
and those receiving normotensive resuscitation (20%) was
not significant (p = 0.49). In the animals receiving fluid
resuscitation, mean arterial pressure (MAP) and CO increased
during the resuscitative phase, but all the animals suffered
the same pattern of hemodynamic deterioration in the evaluation
phase. Rate of hemorrhage during the resuscitative phase
was 20 +/- 5 mL/min in the animals not receiving fluid
and 56 +/- 9 mL/min in the animals receiving fluids. Total
blood loss was subsequently 20 mL/kg greater in the animals
receiving fluids than in the animals without fluid resuscitation.
CONCLUSIONS: In this model
of continuous uncontrolled hemorrhage, the difference
in survival between the animals left hypotensive and the
animals receiving fluid resuscitation was not statistically
significant. Increases in MAP and CO with fluid resuscitation
were transient and were offset by larger volumes of blood
loss. In contrast to the aortotomy model (where thrombosis
is likely and hypotensive resuscitation has proven beneficial),
this model suggests that in continuous bleeding avoiding
fluid resuscitation has a much smaller effect on outcome.
Much of the benefit from hypotensive resuscitation may
depend on having an injury that can stop bleeding.
Resuscitation of uncontrolled
liver hemorrhage: effects on bleeding, oxygen delivery,
and oxygen consumption.
Matsuoka T, Wisner DH.
Department of Surgery, University of California, Davis
Trauma. 1996 Sep;41(3):439-45.
Using a standardized liver injury
model of uncontrolled hemorrhage, we tested the effect
of different fluid resuscitation regimens on hemodynamics,
oxygen delivery, oxygen consumption, bleeding volume,
and fluid resuscitation requirements. Rats were randomized
into three bolus resuscitation groups 15 minutes after
liver injury: lactated Ringer's solution (LR, n = 10),
hypertonic saline (HS, n = 10), and hypertonic sodium
acetate (HA, n = 10). In all resuscitation groups, a 4
mL/kg bolus was first infused at a rate of 0.4 mL/min.
Continuous supplemental LR infusion was then given for
90 minutes to maintain a mean arterial pressure of 80
mm Hg. An initial bolus of LR led to minimal changes in
hemodynamics. Initial resuscitation with HS markedly increased
blood pressure and cardiac index. The bolus of HA increased
cardiac index but did not increase blood pressure; systemic
vascular resistance was significantly decreased and bleeding
significantly increased. Resuscitation with HS did not
increase bleeding compared with LR and resulted in the
smallest total resuscitation volume requirement. Resuscitation
with HS and HA both resulted in a rapid increase in oxygen
consumption; LR did not increase oxygen consumption. Animals
in the HS group had significantly higher oxygen extraction
ratios at the conclusion of the experiment. The use of
different bolus fluids for the resuscitation of uncontrolled
hemorrhage resulted in significant differences in hemodynamics,
oxygen metabolism, and blood loss even when subsequent
resuscitation was the same in all groups. Results from
large vessel injury animal models and clinical studies
of patients with penetrating trauma may not apply to solid
Fluid Resuscitation in a Model
of Uncontrolled Hemorrhage: Too Much Too Early, or Too
Little Too Late?
Leppaniemi A. Soltero R. Burris
D. Pikoulis E. Waasdorp C. Ratigan J. Hufnagel H. Malcolm
Department of Surgery, Uniformed Services University of
Bethesda, MD 20814-4799, USA.
of Surgical Research 1996 July; 63: 413-418.
Early fluid resuscitation in hypotensive
trauma patients is controversial due to the risk of increasing
blood loss and mortality. We determined the effects of
infusion rate and time of resuscitation on blood loss
and mortality and compared the outcome to nonresuscitated
animals in severe, uncontrolled hemorrhagic shock in a
rat model. In anesthetized rats, piercing of the infrarenal
aorta with a 25-G needle caused a fall of mean arterial
pressure to <20 mm Hg and blood loss of about 20 ml/kg
in 90% of the animals. Animals were assigned to the following
treatment groups (n = 6): 60 ml/kg of lactated Ringer's
solution (LR) infused at a rate of 1.5 ml/min and given
at 2.5 min (Group I), 5 min (Group II), or 10 min (Group
III) postinjury, or LR infused at a rate of 3.0 ml/min
and given at 5 min (Group IV) or 10 min (Group V) postinjury.
Another group (n = 9) was not resuscitated. The animals
were followed for 3 hr. Total blood loss in Group I (30.5
+/- 2.6 ml/kg) was significantly (P < 0.05) higher when
compared to nonresuscitated animals (22.1 +/- 0.8 ml/
kg) or Group III (22.7 +/- 1.0 ml/kg), and also significantly
higher in Group IV (35.8 +/- 4.1 ml/kg) when compared
to nonresuscitated animals or Group V (23.0 +/- 1.2 ml/kg).
The mortality rate was 7/9 in nonresuscitated animals
and 5/6 in Group IV, both were significantly higher than
in Groups II, III, and V (0 or 1/6) and markedly higher
than in Group I (2/6).
Conclusions: In this model of
uncontrolled hemorrhage, initially uncorrected severe
shock resulted in a high mortality rate. The risk of increased
blood loss and mortality associated with early fluid resuscitation
could be diminished by avoiding too fast of infusion rates
early after the injury.
Uncontrolled Hemorrhage from
Parenchymal Injury: Is Resuscitation Helpful?
Matsuoka T, Hildreth J, and Wisner
Department of Surgery, University of California, Davis
Trauma 1996 June; 40 (6): 915-922.
Fluid resuscitation increases
blood pressure and may increase hemorrhage. We tested
this hypothesis in a model of liver injury. After standardized
injury, rats were randomized into four groups: no resuscitation
(NR, n = 30), small volume lactated Ringer's solution
(SVLR, 4 mL/kg, n = 30), large volume lactated Ringer's
solution (LVLR, 24 mL/kg, n = 30), and hypertonic saline
(HS, 4 mL/kg, n = 30). Terminal circulating volume was
estimated using controlled hemorrhage experiments. Survival
times and mortality rates were significantly lower in
HS animals (10%) than in NR (50%) or SVLR (47%) animals.
Blood pressure was significantly higher after HS, and
this difference was sustained. Intraperitoneal blood volume
was significantly higher with HS (26.0 +/- 0.7 mL/kg)
and LVLR (26.9 +/- 0.6 mL/kg) compared with NR (21.5 +/-
0.7 mL/kg) and SVLR (22.5 mL/kg). Estimated terminal blood
volume was significantly decreased in LVLR (29.3 +/- 0.6
mL/kg) compared with NR (33.3 +/- 0.7 mL/kg), SVLR (33.7
+/- 0.8 mL/kg), and HS (31.7 +/- 0.7 mL/kg).
CONCLUSION: Vigorous resuscitation
increased bleeding from solid viscus injury. Small volume
HS improves blood pressure and survival compared with
no resuscitation. Results of large vessel hemorrhage models
may not apply to parenchymal viscus injury.
Effects of isotonic saline solution
resuscitation on blood coagulation in uncontrolled hemorrhage.
Selby JB, Mathis JE, Berry CF,
Hagedorn FN, Illner HP, Shires GT.
Department of Surgery, Texas Tech University Health Sciences
Lubbock 79430, USA.
Surgery. 1996 May;119(5):528-33.
BACKGROUND: It has been
suggested that fluid resuscitation before surgical control
of hemorrhage may lead to increased bleeding because of
the elevated blood pressures and clotting factor dilution.
This study was designed to assess the effects of isotonic
saline solution resuscitation on blood coagulation during
METHODS: Twenty-four female
Sprague-Dawley rats were randomized into four groups with
different resuscitation regimens: group A, no resuscitation;
group B, 40 ml/kg in 4 minutes; group C, 80 ml/kg in 4
minutes; and group D, 80 ml/kg in 1 minute. Baseline blood
samples were collected just before a sharp resection of
75% of the tail to initiate the hemorrhage; 15 minutes
later the resuscitation began. Additional blood samples
were obtained at 60 minutes after resection. The blood
was analyzed for platelets, fibrinogen, prothrombin time,
and activated partial thromboplastin time.
RESULTS: The largest differences
between time 0 and 60 minutes were observed in group D
with platelets decreasing 43.36% 7.86%, fibrinogen decreasing
57.10% 16.88%, and prothrombin time increasing from an
average 16.5 to 19.2 seconds. These differences were statistically
significant (p <0.05) with the Student's test.
CONCLUSIONS: The results
suggested that even though the volume of resuscitation
fluid did not appear to affect clotting time when compared
with that of nonresuscitated animals, the rate of extremely
large volume infusions may play an important role in the
cessation of bleeding and consequently in the management
of uncontrolled hemorrhagic shock.
Small-volume resuscitation restores
hemorrhage-induced microcirculatory disorders in rat pancreas.
Vollmar MD, Preissler G, Menger
Institute for Clinical and Experimental Surgery, University
of Saarland, Germany.
Care Medicine 1996 Mar;24(3):445-50.
hypoxia/ischemia, as a consequence of shock-induced microcirculatory
failure, is considered a causative factor in the initiation
and/or progression of pancreatic tissue injury. The aim
of this study was to compare the effects of "small volume
resuscitation" with conventional isovolemic colloid and
hypervolemic crystalloid resuscitation on pancreatic microcirculation
after hemorrhagic shock. DESIGN: Randomized, controlled
SETTING: University laboratory.
male Sprague-Dawley rats anesthetized with Ã¡-chloralose
mechanically and ventilated. Interventions: Rats subjected
to 1 hr of hemorrhagic shock (mean arterial pressure of
40 mm Hg) were resuscitated with lactated Ringer's solution
(four-fold shed volume/20 mins), 10% hydroxyethyl starch
(shed volume/5 mins), or 7.2% sodium chloride-10% hydroxyethyl
starch (10% shed volume/2 mins).
MEASUREMENTS AND MAIN RESULTS:
The microcirculation of pancreatic acinar tissue was
studied by means of intravital fluorescence microscopy
and laser Doppler flowmetry. At 1 hr after resuscitation,
mean arterial pressure, pancreatic capillary erythrocyte
velocity, and erythrocyte flux were found to be significantly
increased when compared with those values in the shock
state. However, mean arterial pressure, pancreatic capillary
erythrocyte velocity, and erythrocyte flux did not completely
return to preshock values, regardless of the type of fluid
used for resuscitation. At 15 mins and 1 hr after resuscitation,
shock-induced capillary perfusion failure (reduction of
functional capillary density) was restored to 91% to 94%
of baseline values in all groups. Pancreatic capillary
narrowing, indicating microvascular endothelial cell swelling,
was abolished by resuscitation with both isotonic hydroxyethyl
starch and hypertonic hydroxyethyl starch (p<.05 vs. lactated
CONCLUSIONS: Despite replacement
of only 10% of actual blood loss, small-volume resuscitation
with hypertonic hydroxyethyl starch is as effective as
the ten-fold volume of isotonic hydroxyethyl starch and,
due to prevention of microvascular endothelial cell swelling,
superior to the 40-fold volume of isotonic lactated Ringer's
solution in regard to restoration of the shock-induced
microcirculatory disturbances of rat pancreatic acinar
Resuscitation from severe hemorrhage.
Shoemaker WC, Peitzman AB, Bellamy
R, Bellomo R, Bruttig SP, Capone A, Dubick M, Kramer GC,
McKenzie JE, Pepe PE, Safar P, Schlichtig R, Severinghaus
JW, Tisherman SA, Wiklund L.
Department of Emergency Medicine, King/Drew Medical Center,
Los Angeles, CA 90059, USA.
Care Medicine 1996 Feb;24(2 Suppl):S12-23
The potential to be successfully
resuscitated from severe traumatic hemorrhagic shock is
not only limited by the "golden 1 hr", but also by the
"brass (or platinum) 10 mins" for combat casualties and
civilian trauma victims with traumatic exsanguination.
One research challenge is to determine how best to prevent
cardiac arrest during severe hemorrhage, before control
of bleeding is possible. Another research challenge is
to determine the critical limits of, and optimal treatments
for, protracted hemorrhagic hypotension, in order to prevent
"delayed" multiple organ failure after hemostasis and
all-out resuscitation. Animal research is shifting from
the use of unrealistic, pressure-controlled, hemorrhagic
shock models and partially realistic, volume-controlled
hemorrhagic shock models to more realistic, uncontrolled
hemorrhagic shock outcome models. Animal outcome models
of combined trauma and shock are needed; a challenge is
to find a humane and clinically realistic long-term method
for analgesia that does not interfere with cardiovascular
responses. Clinical potentials in need of research are
shifting from normotensive to hypotensive (limited) fluid
resuscitation with plasma substitutes. Topics include
optimal temperature, fluid composition, analgesia, and
pharmacotherapy. Hypotensive fluid resuscitation in uncontrolled
hemorrhagic shock with the addition of moderate resuscitative
(28 degrees to 32 degrees C) hypothermia looks promising
in the laboratory. Regarding the composition of the resuscitation
fluid, despite encouraging results with new preparations
of stroma-free hemoglobin and hypertonic salt solutions
with colloid, searches for the optimal combination of
oxygen-carrying blood substitute, colloid, and electrolyte
solution for limited fluid resuscitation with the smallest
volume should continue. For titrating treatment of shock,
blood lactate concentrations are of questionable value
although metabolic acidemia seems helpful for prognostication.
Development of devices for early noninvasive monitoring
of multiple parameters in the field is indicated. Molecular
research applies more to protracted hypovolemic shock
followed by the systemic inflammatory response syndrome
or septic shock, which were not the major topics of this
Fluid resuscitation of the trauma
patient: how much is enough?
Hamilton SM; Breakey P. From the
Department of Surgery, University of Alberta Hospitals,
University of Alberta,
Canadian Journal of Surgery,
1996 Feb; 39(1): 11-16
Patient management in the prehospital
resuscitative phase after trauma is vitally important
to the outcome. Early definitive care remains the essential
element in improving morbidity and mortality. In Canada,
where a large proportion of trauma occurs at sites distant
from a trauma centre, the prehospital resuscitative phase
is long and has even greater potential to affect outcome.
Conventional teaching about the end points of resuscitation
has promoted the concept of normalization of hemodynamic
parameters with maintenance of end-organ perfusion, as
measured by the hourly urine output. Recent work in patients
with a closed head injury and in patients with penetrating
torso trauma challenge the notion that trauma patients
are homogeneous with respect to these end points. In the
Canadian setting of blunt injury, where a closed head
injury is usually suspected and often present, the evidence
from clinical studies suggests that an aggressive approach
to maintaining blood pressure is warranted. In penetrating
torso injury in an urban setting, there is evidence to
suggest that delaying resuscitation until hemorrhage is
controlled is beneficial. More Canadian clinical trials
are required in this area. In the meantime, the priorities
of resuscitation must be carefully assessed for each patient
and pattern of injury.
Limiting Initial Resuscitation
of Uncontrolled Hemorrhage Reduces Internal Bleeding and
Subsequent Volume Requirements
Owens TH, Watson WC, Prough DS,
Uchida T, Kramer GC
Department of Anesthesiology, University of Texas Medical
Galveston 77555-0591, USA.
Trauma August 1995, 39(2):200-209 (including discussion)
We tested the hypothesis that
full or "standard resuscitation" (SR) with Lactated Ringer's
solution (LRS) results in increased bleeding in uncontrolled
hemorrhagic shock, compared with a "limited prehospital
resuscitation" (LPR) regimen and a control group of "no
resuscitation" (NR). Cardiac output was used as physiological
endpoint for resuscitation. Twenty swine had 25 mL/kg
of blood withdrawn during a 30-minute controlled hemorrhage,
followed by a 20-minute "prehospital" resuscitation regimen
was conducted in three groups: the SR group (n = 6), LRS
infused as needed to restore cardiac index (CI) to 100%
baseline; the LPR group (n = 8), with resuscitation using
LRS to 60% of baseline CI, with volume limited to 10 mL/kg;
and the NR group (n = 6). After aortotomy repair, intraoperative
resuscitation was continued for 120 minutes using LRS
to achieve and maintain 80% of baseline mean arterial
pressure. Blood pressure and cardiac index were greatly
reduced, to 34% and 39% of baseline, respectively, by
hemorrhage. During prehospital resuscitation, the SR group
required 48.8 +/- 6.5 mL/kg of LRS, whereas the LPR group
received 9.4 +/- 0.6 mL/kg (p < 0.05). Mean arterial pressure
increased in all three groups during prehospital resuscitation
(p < 0.05). Pulse pressures increased in the SR and LPR
groups only (p < 0.05). The increment in oxygen delivery
was significantly greater in the SR group, compared with
the LPR group (p < 0.05), which in turn was significantly
greater than the NR group (p < 0.05). Peritoneal blood
volume was significantly higher in the SR group (20.6
+/- 5.6 mL/kg), versus the LPR (7.3 +/- 1.3 mL/kg; p <
0.05) and NR groups (3.0 +/- 0.9 mL/kg; p < 0.05). Crystalloid
and whole blood requirements during the intraoperative
resuscitation phase were significantly higher in the SR
group (193 +/- 16.0 and 9.0 +/- 2.5 mL/kg), than in LPR
(111.8 +/- 15.6 and 4.5 +/- 1.8 mL/kg; p < 0.05) and NR
groups (128.5 +/- 32.3 and 3.9 +/- 2.3 mL/kg; p < 0.05).
In the presence of uncontrolled hemorrhagic shock, LPR
and NR can significantly reduce internal hemorrhage and
subsequent intraoperative crystalloid and blood requirements.
20 pigs, with aortotomy- induced uncontrolled haemorrhage.
They compared pre-operative fluid trategies of ‘standard’
vs. ‘limited’ fluids vs. ‘no resuscitation’. Total blood
lost was highest with standard fluid resuscitation, and
least with no pre-operative fluid resuscitation.
Isotonic saline resuscitation
in uncontrolled hemorrhage under various anesthetic conditions
Soucy DM, Sindlinger JF, Greene
SP, Barber AE, Illner HP, Shires GT.
Department of Surgery, Texas Tech University Health Sciences
Center, Lubbock. USA
Annals of Surgery, 1995 July;
OBJECTIVE: The authors
evaluated the effect of early fluid resuscitation with
isotonic saline (NaCl, 0.9%) on uncontrolled hemorrhage
in rats under different anesthetic conditions.
SUMMARY/BACKGROUND DATA: Recently,
it has been suggested that administration of fluids to
patients during uncontrolled hemorrhage may produce adverse
effects, and a postponement of resuscitation until surgical
control of bleeding was recommended. Past clinical trials
were inconclusive, and the results of recent experimental
studies were affected by use of vasoactive anesthetics.
METHODS: One hundred thirty-five
female Sprague-Dawley rats were randomly divided into
three groups: group 1--unanesthetized; group 2—anesthetized
with sodium pentobarbital; and group 3--anesthetized with
a mixture of droperidol and ketamine. Uncontrolled hemorrhage
was initiated with a 75% tail resection, and each group
was further subdivided into three subgroups for the following
treatment: (A) no resuscitation; (B) 40 mL/kg of isotonic
saline; or (C) 80 mL/kg of isotonic saline, administered
15 minutes after the initiation of hemorrhage. Blood loss
volume and survival time were recorded, and animals were
observed up to 360 minutes.
RESULTS: At 6 hours, nonresuscitated
animals of all groups exhibited the highest mortality
rates (93%, 73%, 100% in groups 1, 2, and 3, respectively).
Resuscitation significantly improved the survival; lowest
mortality rates were observed after resuscitation with
80 mL/kg in groups 1 and 3 (33%) and 40 mL/kg in group
2 (40%). Fluid infusion increased hemorrhage rates in
all anesthetized rats. No such increases in bleeding were
observed in group 1.
with isotonic saline improved mortality in uncontrolled
hemorrhage, even with concomitant increases in hemorrhage
rates, under all three anesthetic conditions tested. Unanesthetized
rats bled less than the animals under anesthesia and did
not exhibit an increased blood loss in response to fluid
infusion. Reviewer’s Note: This is evidence against ‘permissive
hypotension’ in uncontrolled hemorrage. Fluid infusion
improved mortality in bleeding animals, unlike most studies.
The experimental animals were observed only 6 hours, or
Uncontrolled hemorrhagic shock
outcome model in rats.
Capone A, Safar P, Stezoski SW,
Peitzman A, Tisherman S.
Department of Surgery, Safar Center for Resuscitation
University of Pittsburgh Medical Center, PA 15260, USA.
Resuscitation. 1995 Apr;29(2):143-52.
During uncontrolled hemorrhagic
shock (UHS) in acute animals models, attempts to achieve
normotension with i.v. fluid resuscitation (FR) caused
further bleeding and higher acute mortality. In the absence
of a published clinically realistic long-term animal outcome
study of UHS, we developed such a model in rats. In the
preliminary study, phase I of the model involved 60 min
of simulated 'pre-hospital' UHS by tail amputation and
different FR regimens. Phase II involved 120 min of simulated
'hospital' treatment with hemostasis and all-out FR, including
blood infusion. Phase III involved observing recovery
and survival to 72 h (3 days). Rats were maintained under
very light N2O-O2-halothane anesthesia and spontaneous
breathing via mask during phases I and II and were awake
during phase III. Tail amputation-induced UHS alone, studied
in 4 groups of 10 rats each, resulted in unpredictable
spontaneous hemostasis and great variability in shed blood
volume, severity of shock, and mortality. The final model,
which achieved consistent blood loss and outcome, included
an initial volume-controlled hemorrhage of 3 ml/100 g
over 15 min and untreated HS for another 15 min, followed
by tail amputation for UHS over another 60 min. This phase
I of 90 min was followed by phase II of 60 min. In group
1, without FR in phases I and II, all 10 rats died by
12 h. In group 2, without FR in phase I and hemostasis
plus all-out FR with lactated Ringer's solution and blood
to hematocrit (Hct) 30% in phase II, 5 of 10 rats died
at the end of phase I and 9 of 10 died at the end of phase
III. This final volume-initiated UHS model may be suitable
for comparing different pre-hospital treatment modalities
in terms of outcome.
Multiple Resuscitation Regimens
in a Near-Fatal Porcine Aortic Injury Hemorrhage Model
Stern SA. Dronen SC. Wang X.
Department of Surgery, University of Michigan, Ann Arbor,
Emergency Medicine 1995 Feb;2(2):89
Comment in: Acad Emerg Med. 1995 Feb;2(2):81-2
OBJECTIVE: To compare early and
delayed blood administrations in animals subjected to
near-fatal hemorrhage in the presence of a vascular injury
and resuscitated to different mean arterial pressures
METHODS: Fifty-four immature
swine with 4-mm infrarenal aortic tears were bled to a
pulse pressure of 5 torr and then resuscitated (estimated
blood loss 40 to 45 mL/kg). Groups I, II, and III were
resuscitated with shed blood at a rate of 2 mL/kg/min,
followed by normal saline at a rate of 6 mL/kg/min. Groups
IV, V, and VI received the same fluids in reverse order.
The fluids were infused intermittently to maintain MAPs
of 40, 60, and 80 torr. The animals were observed for
60 minutes or until death.
RESULTS: The animals resuscitated
to a MAP of 80 torr experienced significantly higher intraperitoneal
hemorrhage volumes and mortality than did the animals
intentionally maintained hypotensive, regardless of whether
blood or normal saline was administered first. There was
no significant difference in mortality or hemorrhage volumes
between any of the groups intentionally maintained hypotensive.
The animals maintained at a MAP of 60 torr were significantly
less acidotic than were the animals resuscitated with
the same fluid regimen but to a MAP of 40 torr. Early
blood administration also minimized the acidosis associated
with hypotensive resuscitation.
CONCLUSION: In this model of near-fatal
hemorrhage with a vascular injury, maintenance of the
hypotensive state produced comparable improvements in
one-hour survival and reductions in hemorrhage volume
regardless of whether blood or saline was administered
first. Although hypotensive resuscitation resulted in
improved outcome, it was associated with significant acidosis.
This effect was minimized with moderate rather than severe
underresuscitation and early blood administration.
54 swine bled to MAP 30 mmHg then Aortotomy performed
Resuscitated with shed blood plus Normal Saline to either
MAP 40, 60 or 80mmHg.
78% if target was MAP 80mmHg
if target was MAP 60mmHg
if target was MAP 40mmHg (Lowest mortality with hypotensive
Improved outcome with fluid restriction
in treatment of uncontrolled hemorrhagic shock.
Capone AC, Safar P, Stezoski W,
Tisherman S, Peitzman AB.
Department of Surgery, University of Pittsburgh Medical
Journal of the American College
of Surgeons. 1995 Jan;180(1):49-56
BACKGROUND: Recent studies have
challenged current guidelines for prehospital fluid resuscitation.
However, long-term studies evaluating the consequences
of fluid restriction in uncontrolled hemorrhagic shock
are lacking. This study was done to examine the long-term
effects of deliberate hypotension in the treatment of
STUDY DESIGN: Uncontrolled hemorrhagic
shock was produced in 40 rats by a preliminary bleed (3
mL per 100 g) followed by 75 percent tail amputation.
Experimental design consisted of three phases: a "prehospital
phase" (90 minutes of uncontrolled bleeding with or without
treatment with lactated Ringer's [LR] solution), followed
by a "hospital phase" (60 minutes, including control of
hemorrhage and fluid resuscitation including blood), and
a three-day observation phase. Forty rats were studied
in four treatment groups (ten rats per group). Group 1
consisted of untreated controls (no resuscitation). Group
2 had no fluid during the prehospital phase. Group 3 had
prehospital resuscitation to a mean arterial pressure
(MAP) of 40 mm Hg with LR, and group 4 had prehospital
resuscitation to MAP of 80 mm Hg with LR. Groups 2, 3,
and 4 received fluid and blood to MAP of 80 mm Hg and
hematocrit of 30 percent in the hospital phase.
RESULTS: All rats in group 1 (untreated)
died within 2.5 hours. Five rats in group 2 (no prehospital
FR) survived 90 minutes; however, only one survived three
days. In group 3, all ten rats survived 2.5 hours and
six survived three days. In group 4, eight rats died within
90 minutes, but none survived long-term. Blood loss (mL
per 100 g) for each group was 3.75 0.6 for group 1, 3.35
0.1 for group 2, 4.15 0.8 for group 3, and 8.45 0.6 for
group 4, (p < 0.05, group 4 compared with groups 1, 2,
CONCLUSIONS: Attempts to achieve
normal MAP during uncontrolled bleeding increased blood
loss, hemodilution and mortality. Hypotensive resuscitation
resulted in less acidemia and improved long-term survival.
Reviewer’s Note: Improved outcome with fluid restriction
in treatment of uncontrolled hemorrhagic shock - mortality
at 90 min was least in the hypotensive resuscitation group.
Immediate versus delayed fluid
resuscitation for Hypotensive patients with penetrating
Bickell WH, Wall MH, Pepe PE,
Martin RR, Ginger VF, Allen MK, Mattox KL,
Department of Emergency Services, Saint Francis Hospital,
Tulsa, Oklahoma, USA
Engl J Med 1994 Oct 27; 331:1105-9
N Engl J Med 1994 Oct 27;331(17):1153-4
N Engl J Med 1995 Mar 9;332(10):681-3
BACKGROUND. Fluid resuscitation
may be detrimental when given before bleeding is controlled
in patients with trauma. The purpose of this study was
to determine the effects of delaying fluid resuscitation
until the time of operative intervention in hypotensive
patients with penetrating injuries to the torso.
METHODS. We conducted a prospective
trial comparing immediate and delayed fluid resuscitation
in 598 adults with penetrating torso injuries who presented
with a pre-hospital systolic blood pressure of < or =
90 mm Hg. The study setting was a city with a single centralized
system of pre-hospital emergency care and a single receiving
facility for patients with major trauma. Patients assigned
to the immediate-resuscitation group received standard
fluid resuscitation before they reached the hospital and
in the trauma center, and those assigned to the delayed-resuscitation
group received intravenous cannulation but no fluid resuscitation
until they reached the operating room.
RESULTS. Among the 289 patients
who received delayed fluid resuscitation, 203 (70 percent)
survived and were discharged from the hospital, as compared
with 193 of the 309 patients (62 percent) who received
immediate fluid resuscitation (P = 0.04). The mean estimated
intraoperative blood loss was similar in the two groups.
Among the 238 patients in the delayed-resuscitation group
who survived to the postoperative period, 55 (23 percent)
had one or more complications (adult respiratory distress
syndrome, sepsis syndrome, acute renal failure, coagulopathy,
wound infection, and pneumonia), as compared with 69 of
the 227 patients (30 percent) in the immediate-resuscitation
group (P = 0.08). The duration of hospitalization was
shorter in the delayed-resuscitation group.
CONCLUSIONS: For hypotensive patients
with penetrating torso injuries, delay of aggressive fluid
resuscitation until operative intervention improves the
Prospective, randomized pre-hospital trial had 598 patients
with penetrating torso trauma and systolic BP < 90
Initial BP averaged 72 mmHg in ‘limited’ resusc, 78mm
Study comparing Standard resuscitation vs Limited resuscitation
(until surgical intervention)
Limited resuscitation gave ~ 375 ml IV fluids - 30% mortality
and 23% complication rate
Standard Resuscitation averaged 2,480 mls IV fluid - 38%
mortality (p=0.04) and 30% complication rate
Higher than ‘limited fluid’ group.
Pulmonary edema and rapid transfusion:
the comparison between rapid intravenous and intraarterial
infusion in the severely hemorrhagic anesthesized pigs.
P'eng FK, Ho WM, Chan LP, Lin
NN, Chen WY, Cheng FC, Kuo JS.
Veterans General Hospital-Taipei, Taiwan, R.O.C.
Zhonghua Yi Xue Za Zhi [a.k.a.
Chung Hua i Hsueh Tsa Chih] (Taipei) 1994 Aug;54(2):73-81.
BACKGROUND. Patients with shock
often develop pulmonary edema (PE) after rapid and massive
fluid supplement and intravenous infusion. Rapid intraarterial
infusion (RIA) is often used for fluid supplement in cardiac
surgery, but has not yet been applied to treatment of
hemorrhagic shock. However, by perfusing the ischemic
peripheral organs through RIA, the fluid should flow first
through the venous system to the heart and lung in less
volume at lower speed. Therefore, the probability of developing
PE should be less than that in rapid intravenous infusion
(RIV) to the heart and lung in the same condition regarding
volume and speed. Accordingly, we compared RIV and RIA
in the treatment of hemorrhagic shock (HS) to determine
if RIA provides any beneficial effect in reducing the
development of PE.
METHODS. Eleven male mini-pigs
weighing 17.5-32 kg were randomly divided into two groups
to have RIV and RIA. Under general anesthesia, HS was
induced by shedding blood (about 35 ml/kg) through the
femoral artery until the mean arterial blood pressure
(MAP) fell to 50 mm Hg. This condition was maintained
for three hours. Then, lactated Ringer's solution (LRS)
was infused thrice by force through a femoral artery (RIA)
or an external jugular vein (RIV) at a speed of 25 ml/kg/min
for 3 min. Data include hemodynamics, arterial blood gases,
urine output, total extravascular lung water index (ETVI),
and total amount of infused LRS used to induce gross PE
(endotracheal release of pinkish foamy sputum). Serum
concentrations of catecholamines, platelet activating
factor (PAF) and thromboxane B2 (TxB2) were measured.
RESULTS. The total amount of LRS
needed to induce gross PE was significantly greater in
RIA than in RIV group. ETVI after rapid transfusion with
a total of 225 ml/kg LRS was significantly less in RIA
than in RIV group. Also, TxB2 concentrations in serum
were less in RIA group. However, there was no difference
in changes of hemodynamics, blood gases, acid-base, pulmonary
shunting, urine output, serum concentrations of PAF or
catecholamines between these two groups.
CONCLUSIONS. RIA may be a better
choice for fluid replacement in HS in terms of decreasing
the development of PE and lessening the release of ETVI
and TxB2 in severely hemorrhagic anesthetized pigs. Further
human investigation is warranted.
Arterial infusion of resuscitation fluids is perhaps a
better choice than IV for rapid infusion of fluids. Arterial
infusion causes significantly less pulmonary edema. There
is also extensive literature from Russia/Eastern Europe
supporting the intra-arterial route for resuscitation.
Resuscitation in uncontrolled
Craig RL, Poole GV.
Dept. of Surgery, University of Mississippi Medical Center,
American Surgeon. 1994 Jan;60(1):59-62.
Fluid resuscitation is considered
to be an integral component of the management of hemorrhagic
shock. Numerous experimental studies of hypovolemic shock
have confirmed the value of volume infusions, but in these
models the rate, volume, and duration of bleeding are
carefully controlled. The results of such studies may
not be applicable to clinical hemorrhage, in which bleeding
continues unabated. Male Sprague-Dawley rats weighing
250 to 390 g were anesthetized, and a femoral artery and
vein were cannulated for constant blood pressure monitoring
and fluid infusion. Through a midline abdominal incision,
the distal ileocolic artery and vein were transected and
allowed to bleed freely into the peritoneal cavity. The
abdomen was closed and the animals were randomized to
one of five groups: no resuscitation; small volume lactated
Ringer's solution; large volume lactated Ringer's; small
volume hetastarch; or large volume hetastarch. After 3
hours or at spontaneous death, blood was withdrawn to
measure hematocrit, platelet count, and fibrinogen. Blood
in the peritoneal cavity was collected and measured. Animals
that received either lactated Ringer's or hetastarch had
more bleeding into the peritoneal cavity and a greater
dilution of clotting factors than animals that received
no resuscitation fluids (P < 0.05). In addition, survival
was highest in unresuscitated animals, although only the
small volume hetastarch group had a significantly lower
survival when independently compared with no resuscitation
(P < 0.05). These results suggest that in traumatic shock,
fluid resuscitation should be minimized until mechanical
control of bleeding can be achieved.
The effects of isotonic saline
volume resuscitation in uncontrolled hemorrhage.
Sindlinger JF, Soucy DM, Greene
SP, Barber AE, Illner H, Shires GT.
Department of Surgery, Texas Tech University Health Sciences
Surg Gynecol Obstet. 1993 Dec;177(6):545-50.
In the present study, the effects
of early isotonic fluid resuscitation on uncontrolled
hemorrhage in rats under pentobarbital anesthesia were
assessed. Forty-five female Sprague-Dawley rats, weighing
between 230 and 295 grams, were anesthetized and cannulated.
Uncontrolled hemorrhage was initiated by a 75 percent
tail resection, and the rats were randomly divided into
three groups: group 1, no resuscitation; groups 2 and
3, saline solution administration over a four minute interval
(40 and 80 milliliters per kilogram, respectively), 15
minutes after the initial hemorrhage. Changes in blood
pressure, blood loss and mortality rates were recorded
and the rats were observed for up to 360 minutes. The
mortality rates were 73, 40 and 53 percent for groups
1, 2 and 3, respectively. The corresponding average survival
times for these groups were 135, 195 and 178 minutes.
The difference between groups 1 and 2 were above the 95
percent confidence level using the chi-square test (mortality)
and the Student's t test. The average total blood loss
in groups 2 and 3 was 31.7 and 41.4 milliliters per kilogram
of body weight; when compared with group 1 (24.6 milliliters
per kilogram), the difference between the two latter groups
(1 and 3) was statistically significant with a p < 0.001.
These results suggest that early infusion of isotonic
fluid improves survival time and reduces short term mortality
in uncontrolled hemorrhage regardless of the associated
increases in blood loss.
This is evidence that permissive hypotension may have
limits/restrictions. In this experiment, fluid resuscitation
increased survival time (but not overall mortality). Fluid
resuscitation increased blood loss.
A computer model for analysis
of fluid resuscitation.
Barnea O, Sheffer N.
Biomedical Engineering Program, Fleishmann Faculty of
Tel Aviv University, Israel.
Comput Biol Med. 1993 Nov;23(6):443-54.
Injuries involving massive blood
loss, such as burns, combat wounds, and injuries resulting
from car accidents, require fluid resuscitation. The risk
involved in fluid therapy is overloading of the circulation,
resulting in pulmonary edema, which can lead to death.
The risk of pulmonary edema may be eliminated by proper
determination of maximal infusion volume and rate. Reabsorption
of fluid from the extravascular compartment and infusion
of fluid following blood loss results in reduction of
the hematocrit. This is accompanied by an increase in
the heart's preload and afterload. Coronary driving pressure
and flow increase due to increased volume. However, because
of the reduced hematocrit this increase in coronary flow
may not be sufficient to compensate the myocardium, in
terms of oxygen supply, for the increase in oxygen consumption.
A model of the cardiovascular system, including an extravascular
compartment, was designed to analyze the effects of fluid
infusion on hemodynamic variables, cardiac oxygen balance,
and the redistribution of fluid between intravascular
and extravascular compartments. The results indicate that
edema is not the only possible adverse effect of overloading
the cardiovascular system with fluid. The simulation demonstrated
that in certain cases the heart's oxygen balance can become
negative. Limiting the rate of infusion can reduce this
A comparison of the response
of near-fatal acute hemorrhage models with and without
a vascular injury to rapid volume expansion
Dronen SC, Stern SA, Wang X, Stanley
Department of Emergency Medicine, University of Cincinnati,
Am J Emerg Med, 1993 July;11(4):331-5
Recent studies in which animals
were bled from a vascular injury rather than an intravascular
catheter demonstrate increased blood loss and mortality
with rapid volume expansion. The purpose of this study
was to better define the importance of incorporating a
vascular injury in animal models of acute hemorrhage.
We directly compared the response to resuscitation from
hemorrhage of comparable severity in animals with and
without a vascular injury. Thirty-four immature swine
(14.6 to 23.2 kg) were instrumented and subjected to severe
blood loss (40 to 46 mL/kg). Groups I and II were hemorrhaged
from a femoral artery catheter only. Groups III and IV
were initially bled in the same manner; however, when
the mean arterial pressure (MAP) decreased to 30 mm Hg,
a 4-mm tear was created in the infrarenal aorta, allowing
free intraperitoneal hemorrhage. In all groups, the catheter
hemorrhage was discontinued once the pulse pressure reached
5 mm Hg. Groups II and IV were resuscitated with normal
saline (NS) infused at a rate of 6 mL/kg/min followed
by shed blood at a rate of 2 mL/kg/min. The resuscitation
fluids were infused as needed to maintain a MAP of 80
mm Hg. Groups I and III served as controls and were not
resuscitated. All animals were observed for 60 minutes
or until death. The data were compared using repeated
measures analysis of variance with a post hoc Tukey Kramer
and the Fisher's exact test. Mortality was 100%, 0%, 88%,
and 78% for groups I, II, III, and IV, respectively (P
< .05 for group II vs groups I, III, and IV).
The groups without fluid infusion had higher mortality
in the first hour. The findings likely do not have clinical
importance, since the experimenters did not follow the
pigs beyond one hour – mortality may have been 100% in
all groups if the experiment had been continued.
of blood pressure on hemorrhage volume and survival in
a near-fatal hemorrhage model incorporating a vascular
Stern, SA Dronen SL, Birrer P.
Department of Emergency Medicine, University of Cincinnati
College of Medicine, Ohio.
Ann Emerg Med 1993 Feb;22 :155.
Comment in: Ann Emerg Med. 1993 Feb;22(2):225-6
STUDY HYPOTHESIS: In a
model of near-fatal hemorrhage that incorporates a vascular
injury, stepwise increases in blood pressure associated
with aggressive crystalloid resuscitation will result
in increased hemorrhage volume and mortality.
DESIGN: This study used
a swine model of potentially lethal hemorrhage in the
presence of a vascular lesion to compare the effects of
resuscitation with mean arterial pressures of 40, 60,
and 80 mm Hg. Twenty-seven fully instrumented immature
swine (14.8 to 20 kg), each with a surgical-steel aortotomy
wire in place, were bled continuously from a femoral artery
catheter to a mean arterial pressure of 30 mm Hg. At that
point the aortotomy wire was pulled, producing a 4-mm
aortic tear and uncontrolled intraperitoneal hemorrhage.
When the animal's pulse pressure reached 5 mm Hg, the
femoral artery hemorrhage was discontinued and resuscitation
INTERVENTIONS: Saline infusion
was begun at 6 mL/kg/min and continued as needed to maintain
the following desired endpoints: group 1 (nine) to a mean
arterial pressure of 40 mm Hg, group 2 (nine) to a mean
arterial pressure of 60 mm Hg, and group 3 (nine) to a
mean arterial pressure of 80 mm Hg. After 30 minutes or
a total saline infusion of 90 mL/kg, the resuscitation
fluid was changed to shed blood infused at 2 mL/kg/min
as needed to maintain the desired mean arterial pressure
or to a maximum volume of 24 mL/kg. Animals were observed
for 60 minutes or until death.
MEASUREMENTS AND MAIN RESULTS:
Data were compared using repeated-measures analysis
of variance with a post hoc Tukey-Kramer, Fisher's exact
test, and Kruskal-Wallis. Mortality was significantly
greater in group 3 (78%) compared with either group 1
(11%; P = .008) or group 2 (22%; P = .028). Mean survival
times were significantly shorter in group 3 (44 +/- 12
minutes) compared with either group 1 (58 +/- 6 minutes;
P = .007) or group 2 (59 +/- 3 minutes; P = .006). The
average intraperitoneal hemorrhage volumes were 13 +/-
14 mL/kg, 20 +/- 25 mL/kg, and 46 +/- 11 mL/kg for groups
1, 2, and 3, respectively (group 1 versus 2, P = .425;
group 1 versus 3, P < .001; group 2 versus 3, P = .014).
Group 2 animals demonstrated significantly greater oxygen
deliveries compared with groups 1 and 3.
CONCLUSION: In a model
of near-fatal hemorrhage with a vascular injury, attempts
to restore blood pressure with crystalloid result in increased
hemorrhage volume and markedly higher mortality.
Prospective evaluation of preoperative
fluid resuscitation in hypotensive patients with penetrating
truncal injury: a preliminary report.
Martin RR. Bickell WH. Pepe PE.
Burch JM. Mattox KL.
Cora & Webb Mading Department of Surgery, Baylor College
Houston, Texas 77030.
Journal of Trauma. 1992 Sep;33(3):354-61;
Although intravenous (IV) fluid
therapy is routinely prescribed for hypotensive injury
victims, there are concerns that elevating the blood pressure
before hemorrhage is controlled may be detrimental. This
is a preliminary report of an ongoing randomized study
designed to evaluate the effect fluid resuscitation, delayed
until surgical intervention, has on the outcome for hypotensive
victims of penetrating truncal injury. In the first year,
300 consecutive patients with gunshot or stab wounds to
the trunk who had a systolic blood pressure of 90 mm Hg
or less were entered into the study. Patients were excluded
from the outcome analysis because of death at the scene
or minor injury not requiring surgical intervention. The
remaining study patients were randomized into (1) an immediate
resuscitation group (n = 96) for whom IV fluid resuscitation
was initiated in the ambulance and in the emergency center
before surgical intervention, or (2) a delayed resuscitation
group (n = 81) for whom IV fluid resuscitation was delayed
until the time of surgical intervention. The two study
groups were found to be well balanced with respect to
anatomic injury severity, pretreatment vital signs, survival
probability, and preoperative treatment times. There were
no significant differences in the rate of survival to
hospital discharge (immediate resuscitation group, 56%;
delayed resuscitation group, 69%). There were no significant
differences in the rate of postoperative complications.
Further study is necessary to determine if it is advantageous
to delay fluid resuscitation until surgical intervention.
Improved Outcome With Hypotensive Resuscitation
of Uncontrolled Hemorrhagic Shock in a Swine Model
Kowalenko T, Stern S, Dronen S,
Department of Emergency Medicine, University of Cincinnati
College of Medicine, Ohio.
Journal of Trauma 1992 Sep;33(3):349,1992:349-53;
Recent animal studies have shown
that aggressive saline infusion may produce significant
mortality in models of moderately severe (20-30 mL/kg)
uncontrolled hemorrhage. The postulated mechanism is an
increase in hemorrhage that accompanies restoration of
normal blood pressure. Although aggressive saline infusion
and restoration of blood pressure appear indicated when
hemorrhage is potentially lethal (40-45 mL/kg), we hypothesized
that the attempt to restore blood pressure with aggressive
saline infusion would not improve survival. This study
used a swine model of severe uncontrolled hemorrhagic
shock to compare the effects of resuscitation to mean
pressures of 40 and 80 mm Hg. Twenty-four immature swine,
each with a surgical steel aortotomy wire in place, were
bled rapidly from a femoral artery catheter to a mean
arterial pressure (MAP) of 30 mm Hg. The aortotomy wire
was then pulled, producing a 4-mm aortic tear and free
intraperitoneal hemorrhage. When the pulse pressure decreased
to 5 mm Hg, saline infusion was begun at 6 mL/kg/minute
and continued as needed to maintain the following endpoints:
group I (MAP = 40 mm Hg), group II (MAP = 80 mm Hg), and
group III (no resuscitation). After a maximum saline infusion
of 90 mL/kg, the infusate was changed to shed blood at
2 mL/kg/minute. Data were compared using analysis of variance
and Fisher's exact test. One-hour survival was 87.5%,
37.5%, and 12.5% for groups I, II, and III, respectively.
Intraperitoneal hemorrhage for the three groups was 8.2
mL/kg, 39.9 mL/kg, and 6.7 mL/kg. The amount of saline
infused was 55.8 mL/kg in group I and 90 mL/kg in group
60 minute survival rate was higher in the hypotensive
resuscitation group (target BP = 40 mm Hg) than in the
standard resuscitation group(target BP = 80mm Hg). Since
the experiment ended after just 60 minutes, the clinical
relevance is uncertain.
Use of Hypertonic Saline/Dextran Versus
Lactated Ringer's Solution As a Resuscitation Fluid After
Uncontrolled Aortic Hemorrhage in Anaesthetised Swine
Bickell WH, Bruttig SP, Millnamow
GA, O’Benar J, Wade CE
Division of Military Trauma
Research, Letterman Army Institute of Research,
Presidio of San Francisco, California.
Ann Emerg Med 1992 Sep;21(9):1077-1085
STUDY OBJECTIVE: We tested
the hypothesis that following aortotomy, administration
of hypertonic saline/dextran increases hemorrhage and
mortality. We also compared hypertonic saline/dextran
with the standard therapy of attempting to replace three
times the amount of lost blood with lactated Ringer's
DESIGN: In this model of
uncontrolled arterial hemorrhage resulting from aortotomy,
24 anesthetized Yorkshire swine underwent splenectomy,
stainless steel wire placement in the infrarenal aorta,
and instrumentation with Swan-Ganz and carotid artery
catheters. The wire was pulled, producing a 5-mm aortotomy
and spontaneous intraperitoneal hemorrhage.
INTERVENTIONS: The animals
were randomly assigned to one of three study groups: control;
hypertonic saline/dextran group in which six minutes after
aortotomy a 4-mL/kg mixture of IV 7.5% NaCl and 6% Dextran-70
was given over one minute; or lactated Ringer's group
in which six minutes after aortotomy 80 mL/kg IV lactated
Ringer's was given over nine minutes.
MEASUREMENTS AND MAIN RESULTS:
The volume of hemorrhage and the mortality rate in
hypertonic saline/dextran-treated animals were significantly
greater than in the nonresuscitated controls (1,340 +/-
230 mL versus 783 +/- 85 mL and five of eight versus zero
of eight, respectively; P less than .05). Although the
mortality rate in the lactated Ringer's group was not
significantly different from the hypertonic saline/dextran
group, survival time was significantly shorter than in
the hypertonic saline/dextran group.
CONCLUSION: In this model
of uncontrolled hemorrhage, immediate IV administration
of hypertonic saline/dextran significantly increased hemorrhage
volume and mortality. However, the accentuation of hemorrhage
and reduction in survival were not as great as that produced
by the standard practice of attempting to replace the
lost blood with three times that volume of lactated Ringer's.
They sought to compare hypertonic saline/dextran with
lactated Ringer’s. The experiment uncovered the serendipitous
result that 120 min survival was highest in control group
(no fluid resuscitation) !
Saline resuscitation after fixed-volume
hemorrhage. Role of resuscitation volume and rate of infusion.
Lilly MP, Gala GJ, Carlson DE,
Sutherland BE, Gann DS.
Department of Surgery, University
of Maryland, School of Medicine, Baltimore.
Annals of Surgery. 1992 Aug;216(2):161-71.
The authors have reported previously
that small-volume resuscitation (1.8 x bled volume) with
0.9% NaCl restores blood volume and attenuates hormonal
responses after large hemorrhage without correction of
arterial hypotension. The authors studied the role of
rate of infusion in this observation in chronically prepared
dogs (aortic flow probe, right atrial pressure and volume,
and arterial catheters) after 30% hemorrhage (24.1 0.4
mL/kg). After 30 minutes, subjects were observed either
without treatment (no resuscitation) or with infusion
of 43 mL/kg 0.9% NaCl over 3 hours by one of three protocols:
(1) impulse infusion over 10 minutes, (2) variable rate
infusion, bolus with tapering infusion, or (3) constant
rate infusion. Significant improvement in cardiac output
and in blood volume and significant decreases of vasopressin
and arterial catecholamines were observed in all fluid-treated
groups. This benefit was relatively independent of rate
of infusion, although impulse infusion produced greater
early improvement, which dissipated with time, and constant
rate infusion produced better late results. In none of
the fluid-treated groups were these improvements reflected
in improved mean arterial pressure compared with the no
The authors conclude that small-volume,
slow-rate saline infusion produces physiologic benefits
that cannot be assessed by easily measured clinical parameters.
Thus, early resuscitation after trauma could aid patients
even if arterial pressure is unchanged. This benefit might
be even greater in patients with uncontrolled bleeding
because arterial pressure, and hence bleeding, may not
be increased by resuscitation of this type. A reassessment
of the value of prehospital fluid resuscitation in the
injured patient is warranted.
"Scoop and run" or stabilize
hemorrhagic shock with normal saline or small-volume hypertonic
Krausz MM, Bar-Ziv M, Rabinovici
R, Gross D.
Department of Surgery, Hadassah University Hospital, Jerusalem,
J Trauma. 1992 Jul;33(1):6-10.
The controversy over a policy
of "scoop and run" or stabilizing hemorrhagic shock when
evacuation time is short has not yet been settled. Small
volumes of hypertonic saline have been suggested as effective
therapy when the scoop-and-run policy is adopted. In the
present study small-volume hypertonic saline treatment
and normal saline treatment of "uncontrolled" hemorrhagic
shock (UCHS) in rats were compared with no treatment,
which best simulates the scoop-and-run policy. The rats
were randomly assigned to three groups. Uncontrolled hemorrhagic
shock was induced by 12% resection of the terminal portion
of the rats' tails. In group I (n = 13) the animals were
untreated. In group II (n = 6) UCHS was treated by administering
41.5 mL/kg 0.9% NaCl (NS). In group III (n = 6) UCHS was
treated by administering 5 mL/kg 7.5% NaCl (HTS). Resection
of the rats' tails in group I was followed by bleeding
of 3.3+/- 0.3 mL in 15 minutes with a fall in mean arterial
pressure (MAP) from 100.9 7 to 63.5 5 mm Hg (p less than
0.001). The early bleeding and hemodynamic responses were
similar in all three groups. Further blood loss in the
first hour in group I was 0.5+/- 0.2 mL, and MAP rose
spontaneously to 73.2+/- 6 mm Hg (p less than 0.05). The
NS infusion in group II was followed by further bleeding
of 4.1+/- 0.9 mL (p less than 0.01) and a further fall
in MAP to 53.8+/- 7 mm Hg (p less than 0.01) after 60
The rats whose bleeding was untreated had spontaneous
improvement in blood pressure, and lower blood loss.
Fluid infusion led to greater bleeding.
See related work by the same research group, published
in SGO, May 1992 and Archives of Surgery, January 1992
The combined effect of small
volume hypertonic saline and normal saline solutions in
uncontrolled hemorrhagic shock.
Krausz MM, Horn Y, Gross D.
Department of Surgery B, Hadassah University Hospital,
Surg Gynecol Obstet. 1992 May;174(5):363-8.
Recently, small volume hypertonic
saline solution (HTS) has been suggested for treatment
of trauma casualties. Previously, we reported that small
volume HTS treatment of uncontrolled hemorrhagic shock
(UCHS) leads to increased bleeding, hemodynamic deterioration
and early mortality. In the present study, large volume
normal saline solution (NS) combined with small volume
HTS was used to treat UCHS in rats. The rats were randomly
assorted into four groups. Group 1 (n = 9) included rats
in which UCHS induced by 12 per cent resection of the
tail was untreated; group 2 (n = 8) consisted of those
in which UCHS was treated after 15 minutes with 41.5 milliliters
per kilogram of sodium chloride, 0.9 per cent (NS); group
3 (n = 7) included rats in which UCHS was treated with
5 milliliters per kilogram sodium chloride, 7.5 per cent
(HTS); and group 4 (n = 9) included rats in which UCHS
was treated by a combination of HTS and NS. In group 1,
resection of the tail was followed by bleeding of 4.9
+/- 0.3 milliliters in 15 minutes, a decrease in mean
arterial pressure (MAP) from 105 +/- 5 to 51 +/-3 torr
(p less than 0.001) and pulse rate from 377 +/- 9 to 305
+/- 22 beats per minute (p less than 0.05). Further loss
of blood after 30 minutes was 0.5 +/- 0.2 milliliters,
MAP rose to 58 +/- 6 torr (p less than 0.05) with the
death of two rats. Infusion of NS in group 2 was followed
by further bleeding of 3.3 +/- 1.0 milliliters (p less
than 0.01) and rise in MAP to 76+/- 9 after 30 minutes.
Infusion of HTS in group 3 was followed by bleeding of
1.9+/- 0.3 milliliters (p less than 0.05) and fall in
MAP to 57 +/- 14 torr (p less than 0.05). Continued loss
of blood in this group resulted in further fall in MAP
to 36 +/-11 torr (p less than 0.01) with death of 71 per
cent (p less than 0.01) of the rats in four hours. Combined
HTS and NS infusion in group 4 was followed by bleeding
of 2.0 +/- 0.4 milliliters (p less than 0.05) and an increase
in MAP to 93.0 +/- 3.0 torr (p less than 0.005) after
30 minutes with the death of only one animal in four hours.
Total loss of blood in the three treated groups was similar
and significantly higher than in the untreated group.
Hypertonic saline treatment of
uncontrolled hemorrhagic shock at different periods from
Krausz MM, Landau EH, Klin B,
Department of Surgery B, Hadassah University Hospital,
Archives of Surgery. 1992 Jan;127(1):93-6.
Hypertonic saline has been recently
recommended for treatment of patients in hemorrhagic shock.
Infusion of hypertonic saline at different periods in
cases of uncontrolled hemorrhagic shock was studied in
rats. The animals were divided into six groups: in group
1 uncontrolled hemorrhagic shock was induced by tail resection
and no hypertonic saline was administered; in group 2
hypertonic saline was administered 5 minutes after shock
was induced; in group 3 hypertonic saline was administered
15 minutes after shock was induced; in group 4 hypertonic
saline was administered 30 minutes after shock was induced;
in group 5 hypertonic saline was administered 60 minutes
after shock was induced; and in group 6 hypertonic saline
was administered 120 minutes after shock was induced.
Tail resection in rats in group 1 was followed by a mean
SEM bleeding of 2.7+/-.03 mL in 5 minutes. Infusion of
hypertonic saline after 5 and 15 minutes resulted in additional
bleeding of 6.3+/-1.0 mL and 3.8+/-0.5 mL, respectively,
and a drop in mean arterial pressure to 36+/-8 mm Hg and
56+/-9 mm Hg, respectively. Mortality was 80% in group
2 and 53% in group 3. Infusion of hypertonic saline 30
and 60 minutes after shock was induced did not alter bleeding,
mean arterial pressure, or survival. Infusion of hypertonic
saline within 15 minutes of hemorrhagic shock resulted
in increased bleeding, hypotension, and early death. Infusion
30 minutes or later did not alter these variables. This
potential danger of early hypertonic saline therapy should
be considered in the treatment of patients in trauma.
Future trends in emergency fluid
resuscitation: Small-volume resuscitation by means of
hypertonic saline Dextran
Kreimeier U, Messmer K.
Intensive Care World 1992; 9 (1):
The detrimental effects of intravenous
crystalloid after aortotomy in swine.
Bickell, WH, Brutting SP, Millnamow
GA, O’Benar J, Wade CE
Division of Military Trauma Research, Letterman Army Institute
Presidio of San Francisco, CA 94129-6800
Surgery 1991 Sep;110:529-536 Comment
in: Surgery. 1991 Sep;110(3):573-4
We tested the hypothesis that,
after aortotomy, rapidly replacing three times the blood
volume deficit with intravenous crystalloid will increase
hemorrhage and decrease survival. Sixteen anesthetized
Yorkshire swine underwent splenectomy and stainless steel
wire placement in the infrarenal aorta and were instrumented
with pulmonary artery and carotid artery catheters. The
wire was pulled, producing a 5 mm aortotomy and spontaneous
intraperitoneal hemorrhage. The animals had been alternately
assigned to either an untreated control group (n = 8)
or a treatment group (n = 8), which received 80 ml/kg
lactated Ringer's solution intravenously. The volume of
hemorrhage and the mortality rate were significantly increased
(p less than 0.05) in the treatment group receiving lactated
Ringer's solution relative to the control animals (2142
178 ml versus 783 85 ml, and eight of eight animals versus
zero of eight animals, respectively). From these data
we conclude that, in this model of uncontrolled arterial
hemorrhage resulting from abdominal aortotomy, rapidly
administering lactated Ringer's solution intravenously
significantly increases hemorrhage and death.
Control of bleeding is essential
for a successful treatment of hemorrhagic shock with 7.5
per cent sodium chloride solution.
Rabinovici R, Krausz MM, Feuerstein
Department of Surgery, Jefferson Medical College, Philadelphia,
Surg Gynecol Obstet. 1991 Aug;173(2):98-106.
Small volume hypertonic saline
(HTS) solution resuscitation has been shown to restore
hemodynamic derangements and to protect against mortality
in "controlled" hemorrhagic shock (CHS), but it exacerbates
the shock state in "uncontrolled" hemorrhagic shock (UCHS).
To study the mechanisms associated with the divergent
outcome of HTS treatment in CHS versus UCHS, HTS was administered
to anesthetized rats (n = 7) subjected to 15 per cent
resection of the tail followed by controlled or uncontrolled
bleeding. HTS treatment of UCHS increased bleeding (13.3
+/- 1.6 milliliters, p less than 0.05), dropped mean arterial
pressure (MAP) (-84.5 +/- 8.9 millimeters of mercury,
p less than 0.001), central venous pressure (zero millimeters
of mercury, p less than 0.001) and cardiac index (CI)
(41 per cent of basal value, p less than 0.001) and increased
acidosis (pH 7.23 +/- 0.12, p less than 0.05) and mortality
(mean survival time 75 +/- 15 minutes versus 122 +/- 23
minutes of untreated rats, p less than 0.05). In contrast,
when administered after application of a ligature proximal
to the resection site (at 15 minutes), HTS completely
reversed the changes in MAP, CI and total peripheral resistance
index (TPRI), and improved mean survival time (172 +/-
7 minutes, p less than 0.05). These data support the assumption
that HTS should be used in the treatment of hemorrhagic
shock only after bleeding was controlled.
The effects of prehospital fluids
on survival in trauma patients.
Kaweski SM, Sise MJ, Virgilio
Trauma Research and Education Foundation, San Diego, California
J Trauma 1990;30(10):1215-1218
Comment in: J Trauma 1991 Sep;31(9):1325
The effect of prehospital intravenous
fluids upon survival was studied in 6,855 trauma patients.
Mean prehospital time was 36 minutes in both the group
of patients who received fluids and the group that did
not. The volume of fluid administered was not significantly
different in the group who survived compared to those
who died. Eighty-five per cent of the patients had an
Injury Severity Score (ISS) less than 25 and the mortality
rate in the 56% of patients in this group who received
fluids was similar to that of the patients who did not
receive fluids (0.7% vs. 0.5%). Twelve per cent of the
patients had n ISS between 25 and 50. Sixty per cent of
these patients received fluids and the mortality rates
were similar to the patients who received fluids compared
to those who did not (23% vs. 22%). Three per cent of
patients had an ISS of greater than 50 and the mortality
rate was highest in this group but was not influenced
by the administration of fluids (90% vs. 86%). Comparison
of groups with similar probability of survival according
to the TRISS methodology also failed to show an influence
of fluid administration on survival. The mortality rate
in patients with an initial systolic blood pressure (BP)
of 90 torr or greater was compared to the rate in patients
with an admission BP less than 90 torr. Although hypotension
was associated with a significantly higher mortality rate,
the administration of fluids had no influence on this
Early versus late fluid resuscitation:
lack of effect in porcine hemorrhagic shock.
Chudnofsky CR, Dronen SC, Syverud
SA, Hedges JR, Zink BJ.
Department of Emergency Medicine, University of Cincinnati,
Ann Emerg Med. 1989 Feb;18(2):122-6.
The benefit of IV fluid therapy
in the prehospital management of hemorrhagic shock is
unproven. We used a reproducible, lightly anesthetized
model of porcine continuous hemorrhage to evaluate the
usefulness of pre-hospital IV fluid therapy. Incorporated
into the model were time delays associated with ambulance
request and dispatch, patient evaluation and treatment,
and transport to the hospital in the average urban prehospital
care system. Treatment occurred concurrently with hemorrhage.
Twenty-eight immature swine (15 to 20 kg) were bled at
a rate of 1.25 mL/kg/min. Animals in the prehospital IV
group (n = 14) received fluid resuscitation at 1 mL/kg/min
beginning 20 minutes after initiation of hemorrhage; those
in the in-hospital IV group (n = 14) received fluid at
a rate of 3 mL/kg/min beginning 35 minutes after hemorrhage.
Both groups received blood and saline at 3 mL/kg/min 45
minutes after hemorrhage began, and both groups had hemorrhage
controlled 25 minutes after simulated hospital arrival.
Survival was 57% in both groups, and there were no statistically
significant differences seen in measured hemodynamic or
biochemical parameters. We conclude that early administration
of IV normal saline has no effect on hemodynamics or survival
in this porcine hemorrhagic shock model simulating an
urban prehospital care system.
Fluid resuscitation after an otherwise
Traverso LW, Lee WP, Langford
I. Crystalloid solutions. Journal
of Trauma 1986;26(2):168-75
Fluid resuscitation after an
otherwise fatal haemorrhage: II. Colloid solutions.
Traverso LW, Hollenbach SJ, Bolin
RB, Langford MJ, DeGuzman LR.
Journal of Trauma 1986;26(2):176-82
Although favouring aggressive fluid resuscitation, haemorrhage
is controlled in these two studies prior to fluid administration
and they are hence not applicable to the bleeding trauma
A Review of Postmortem Examinations
in Combat Casualties
Strawitz JG , Scully R.E., Vickery
A., Howard JM MC, USAR
of Surgery 1955; 70: 260
Because of the clinical responsibilities
of medical officers in a combat theater, complete postmortem
examinations have seldom been routine. Pathologists are
rarely available at a surgical hospital and frequently
facilities for postmortem study are not available. Although
it is obvious that combat casualties die from wounds received
in action, the mechanisms of death are not clear. During
a 10-month period in 1952 and 1953, autopsies were performed
routinely by the Surgical Research Team in Korea at the
46th Surgical Hospital on the eastern front. Deaths were
investigated which resulted from wounds received in combat,
vehicular accidents, burns, medical illnesses, and self-inflicted
injuries. This report deals only with 35 patients who
died in the hospital after being wounded in combat. Analyses
of the other traumatic deaths have been deleted in an
effort to emphasize the problems encountered in treating
the combat casualty…(See HTML
link, above, for full text)
Surgery in World War II, General
Office of the Surgeon General.
US Government Printing Office;
Experimental Haemorrhage Shock.
In: Physiology of Shock: The Commonwealth
Fund, New York;1950. p. 121-143
Although favouring aggressive fluid resuscitation, haemorrhage
is controlled in this model prior to fluid administration
and hence not aplicable to the bleeding trauma patient
The Preventative Treatment of Wound
Cannon W, Fraser J, Cowell E.
trauma.org 7:10, October 2002