Resuscitation from haemorrhagic shock

remains one of the primary tasks of the

traumatologist, whether practising in the
emergency department (ED), the operating
theatre or the intensive care unit (ICU). Dia-
gnosis of haemorrhage, surgical strategy,
choice of fluids to administer, monitoring
and optimal endpoints for resuscitation are
all controversial, and recommendations in
each of these areas have evolved substantially
in the past decade. Actions taken in the first
minutes of care may profoundly affect the
patients subsequent clinical course, putting
a greater focus than ever on the dynamic pro-
cess of early resuscitation. This article will
review the pathophysiology of haemorrhagic
shock and will briefly address emerging and
controversial therapies.
Defining haemorrhagic shock
In simple terms, shock is failure of adequate
oxygen delivery to the tissues of the body.
Hypoperfusion leads to cellular ischaemia,
leading in turn to hibernation (the cell
reduces its level of metabolic activity), anaer-
obic metabolism (absent oxygen, the cell must
produce lactic acid as it generates energy),
apoptosis (the cell begins a programmed shut-
down process) and outright necrosis (cell
death). The ischaemic cell takes up interstitial
fluid (perhaps to dilute accumulating meta-
bolic poisons) and swells, reducing perfusion
to its neighbours. Lactate, and other toxic
metabolites, poison cells not affected by the
initial ischaemia, and mediators released in
response to metabolic stress trigger a response
from immune system cells. The net effect is a
biological cascade that, if unchecked, can be
fatal.
Uncontrolled haemorrhage leads to acutely
fatal shock, characterized by complete failure
of the cardiovascular system: loss of contract-
ile power in the heart and great vessels, inap-
propriate vasodilation, loss of response to
catecholamines and, eventually, brain death.
Even when haemorrhage is corrected and
the macrocirculation restored, shock can still
prove fatal through the pathophysiology of
organ system failure, beginning with the lungs
and progressing to the renal, gut, immune
and cardiovascular systems. Figure 1 is a
crude representation of the shock cascade,
demonstrating the amplification that begins
with a single ischaemic cell but can extend
to affect the entire body.
Clinically, shock is characterized by the
symptoms of the bodys response to hypo-
perfusion. Low blood pressure, tachycardia,
decreased urine output, pale skin and dia-
phoresis are all characteristic. However, it is
important to remember that hypotension
is not synonymous with shock. Low blood
pressure may occur in the absence of hypo-
perfusion, as in the vasodilated but euvolemic
patient undergoing general anaesthesia.
Normal blood pressure may also mask hypo-
perfusion, as in the intensely vasoconstricted
young patient with normal vital signs despite
loss of blood volume approaching 40%.
Diagnosis of shock thus depends on the
assimilation of a number of signs and sym-
ptoms: obvious bleeding or a suggestive
mechanism of injury, visible evidence of
vasoconstriction, diminished vital signs, loss
of pulse oximeter function and (most
importantly) confirmation of anaerobic
metabolism in the form of abnormal serum
lactate concentration or base deficit.
Anaesthetic and surgical
strategy
As with septic shock, the most important
component of resuscitation from haemor-
rhagic shock is source control. The Advanced
Trauma Life Support curriculum of the
American College of Surgeons emphasizes
the ABC of trauma care: Airway, Breathing,
and Circulation.
1
Control of the airway
facilitates patient management and ensures
adequate oxygen uptake by the blood
stream. Rapid assessment of the chest will
also identify tension pneumothorax or peri-
cardial tamponade as a mechanical source
of hypoperfusion.
Key points
Shock is defined by clinical
evidence of hypoperfusion
and a failure of adequate
oxygen delivery to some
tissues of the body.
The primary goal of
resuscitation from
haemorrhagic shock is to
identify the source of
haemorrhage and control it
as rapidly as possible.
Inappropriately vigorous fluid
resuscitation increases the
rate of uncontrolled
haemorrhage and may
worsen survival.
Early use of blood products is
appropriate in resuscitation
from haemorrhagic shock;
they maintainoxygen-carrying
capacity and coagulation
factor concentration.
Occult hypoperfusion may
occur even in the presence
of normal vital signs.
Resuscitation is not complete
until acidosis is resolved.
Richard P Dutton MD MBA
Division of Trauma Anaesthesiology
R Adams Cowley Shock Trauma Center
University of Maryland Medical System
22 South Greene Street
Baltimore
MD 21201
USA
Tel: 410 328 2628
Fax: 410 328 3138
E-mail: [email protected]
(for correspondence)
144
doi:10.1093/bjaceaccp/mkl025 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 4 2006
The Board of Management and Trustees of the British Journal of Anaesthesia [2006].
All rights reserved. For Permissions, please email: [email protected]
Fluid management for trauma;
where are we now?
Richard P Dutton MD MBA

b
y

g
u
e
s
t

o
n

M
a
r
c
h

2
7
,

2
0
1
4
h
t
t
p
:
/
/
c
e
a
c
c
p
.
o
x
f
o
r
d
j
o
u
r
n
a
l
s
.
o
r
g
/
D
o
w
n
l
o
a
d
e
d

f
r
o
m

Once these preliminary steps are taken, the focus of care
shifts to a search for haemorrhage as the cause of circulatory
shock. Bleeding must be diagnosed and treated as swiftly as pos-
sible, and this priority should inform all subsequent decision-
making. Clinically significant haemorrhage occurs into one of
only five compartments: the thoracic cavity, the peritoneum,
the retroperitoneal space, the tissue compartments of the thigh
and outside the body. These are investigated by direct inspection
of the patient, chest X-ray, abdominal sonography, pelvic
X-ray and computer tomography. External bleeding is managed
by direct pressure and ligation of exposed cutaneous vessels.
Haemorrhage in the chest is managed initially by tube thora-
costomy, as bleeding from the low-pressure pulmonary circuit
will usually resolve spontaneously unless a major vessel has
been injured. Bleeding in the abdomen or persistent bleeding
in the chest is addressed by surgical exploration. Pelvic or ret-
roperitoneal haemorrhage is difficult to access surgically; where
logistically possible, angiographic embolization is the preferred
approach. Bleeding into the thigh may be substantial at the time
of injury (up to 1500 ml) but will almost always resolve spontan-
eously through tamponade in the muscle compartment and vaso-
constriction of the feeding vessels. Traction, splinting or external
fixation of fractures will facilitate spontaneous haemostasis in the
associated soft tissue beds.
For the patient who requires exploratory surgery, the
emphasis is on damage control. While the patient is hypo-
perfused and resuscitation is under way, the goal is to perform
the fastest surgery possible to achieve control of haemorrhage.
Large vessels are ligated or shunted whenever possible, and not
reconstructed or bypassed. Bleeding from the spleen, kidney,
lung-lobe or bowel segments is managed by excision, without
anatomical reconstruction. Hepatic or retroperitoneal haemor-
rhage is controlled with cautery, topical haemostatic agents
and packing. When haemostasis is achieved, the chest or
abdomen is drained, packed open and covered with a temporary
sterile dressing. This allows monitoring of recurrent or ongoing
haemorrhage, permits tissue oedema without fear of com-
partment syndrome and offers easy access for subsequent thera-
peutic or reconstructive surgery. The patient is moved through
theatre and angiography suite or both as swiftly as possible,
subsequently returning to the trauma bay or ICU for completion
of resuscitation.
Surgical strategy for managing haemorrhagic shock must be
focused on control of haemorrhage. The same is also true of the
DECREASED OXYGEN DELIVERY
NO REFLOW
CELLULAR
OEDEMA
DECREASED FLUID
VOLUME
TRIGGER CELL
ISCHAEMIA
REACTIVE CELL
(IMMUNE SYSTEM, LIVER, LUNG)
MEDIATORS
OTHER REACTIVE CELLS
(AMPLIFIED RESPONSE)
INJURY TO NON-ISCHAEMIC ORGANS
LUNG
LIVER BRAIN HEART
KIDNEY
ENDOCRINE
ORGANS
BONE
MARROW
METABOLIC BYPRODUCTS
LACTIC ACID
FREE RADICALS
CELL
DAMAGE
CYTOTOXINS
ACTIVATED
NEUTROPHILS
AND
MICROPHAGES
MEDIATORS
Fig. 1 The shock cascade. Ischaemia in one organ system triggers a systemic response that persists even after adequate resuscitation. This is the
pathophysiology of the multiple organ system failure that commonly follows severe haemorrhagic shock.
Fluid management for trauma
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 4 2006
145

b
y

g
u
e
s
t

o
n

M
a
r
c
h

2
7
,

2
0
1
4
h
t
t
p
:
/
/
c
e
a
c
c
p
.
o
x
f
o
r
d
j
o
u
r
n
a
l
s
.
o
r
g
/
D
o
w
n
l
o
a
d
e
d

f
r
o
m

anaesthesia plan. While not as obvious as the ligation of a
bleeding vessel, the actions of the anaesthetist may play just as
great a role in the patients survival. Fluid administration is
one aspect of this, titrated to maintain or improve perfusion
while at the same time encouraging native haemostasis. Main-
tenance of body temperature, blood composition, electrolyte
balance, respiratory function and depth of muscle relaxation
and anaesthesia are also critical tasks. Finally, the appearance
in clinical practice of systemic haemostatic agents (i.e. recombin-
ant human coagulation factor VIIa) offers a new option. Most
important of all, perhaps, is the anaesthetists ability to facilitate
the patients movement between the ED, operating theatre,
angiography and ICU such that no moments are wasted in the
organized care of the actively haemorrhaging patient.
Fluids in resuscitation
Quantity of fluid
One of the most remarkable changes in resuscitation practice
has been the growing realization in the past decade that too
much of a good thing can itself become a bad thing. Although
isotonic fluid administration is clearly necessary for a complete
recovery from shock, due both to haemorrhagic losses from
the circulation and the tendency of ischaemic cells to take up
interstitial fluid, it is clear that the indiscriminate administra-
tion of crystalloid fluid has the potential to make the patients
condition worse, especially early in resuscitation. I.V. fluid
administration increases ventricular preload, resulting in an
immediate increase in blood pressure. This may reverse vaso-
constriction that was contributing to haemostasis and may
directly displace early fibrin clots. Furthermore, isotonic crys-
talloid solutions dilute the oxygen-carrying capacity of the
blood and the concentration of clotting factors and platelets.
Unless rigorous attention is paid to warming infused fluids
(unlikely in early resuscitation), significant hypothermia may
also develop, contributing to both metabolic acidosis and
coagulopathy. The clinical result is a downward spiral of hypo-
tension, fluid bolus, re-bleeding and recurrent hypotension.
Bench research in the 1980s and 1990s demonstrated
decreased survival with aggressive fluid administration in a
variety of uncontrolled haemorrhage models in swine, rats,
sheep and dogs.
2,3
Optimal survival was attained with fluid
therapy titrated to lower than normal blood pressure and
cardiac output, for the duration of active haemorrhage. This
concept of deliberate hypotensive resuscitation has been tested
in two noteworthy clinical trials (Table 1). Bickell and col-
leagues
4
randomized victims of penetrating trauma to fluid
or no fluid in the pre-hospital and ED phases of care, even-
tually documenting a significant improvement in outcome with
the experimental therapy. Dutton and colleagues
5
studied both
blunt- and penetrating-injured patients in haemorrhagic shock
using a fluid resuscitation protocol titrated to maintain a sys-
tolic blood pressure of 7080 mm Hg until definitive control
of bleeding. This smaller study showed no difference in
mortality, despite a higher average injury severity in the low
pressure group, suggesting that this approach was at least
worthy of consideration. While neither study was scientifically
definitive, largely owing to the tremendous logistical difficulty
in studying an intrinsically heterogeneous problem, clinical
practice has now evolved to a much more careful administra-
tion of fluids in early resuscitation (especially isotonic crystal-
loid solutions). Fluids are now administered in prescribed small
boluses and titrated to a specific physiological endpoint such
as blood pressure or, even better, base deficit and lactate.
Type of fluid
The composition of fluid administered to the actively haemor-
rhaging patient is as important as the rate and quantity. While
isotonic crystalloid solutions are important for making up
third space losses, and are inexpensive and readily available,
they do not adequately replace the whole blood that the patient
is losing. One concern is that the intravascular persistence of
these solutions is low, with estimates of as little as 12% of an
administered bolus of 0.9% saline remaining in the circulation
30 min later. Colloidal solutions, such as hypertonic saline-
dextran, have been recommended for early resuscitation; how-
ever, so far, there has been no definitive evidence of benefit.
The recently completed safe vs albumin fluid evaluation
(SAFE) trial in Australia showed no difference in outcomes
among ICU patients receiving crystalloid vs colloid (albumin)
as their primary resuscitative fluid.
6
Early transfusion therapy with red cells, plasma and plate-
lets is thus essential to successful resuscitation. While in the
long term blood transfusion has been associated with an
increased incidence of organ system failure and death in closely
matched groups of patients, as well as profound immune sup-
pression, in the short term there is no available substitute.
Early replacement of oxygen-carrying capacity, in the form
of red blood cells, may be life-saving. Many trauma centres
maintain a supply of un-cross-matched, type-O red blood cells
available in the ED for immediate use in patients presenting
with severe haemorrhagic shock. The safety of this therapy has
been well established, and the advantage of immediate trans-
fusion vs waiting 30 min for group-specific or 60 min for cross-
matched blood may be substantial.
Table 1 Clinical trials of deliberate hypotensive resuscitation
Trial Bickell et al.
4
Dutton et al.
5
Mechanism of injury Penetrating Blunt and penetrating
Site of resuscitation Pre-hospital,
emergency
department
Trauma resuscitation
unit, operating room
Study mechanism No fluid given Blood pressure titration
N 598 110
Study Group Mortality 30% 7%
Control Group Mortality 38% 7%
P-value 0.04 Not significant
146
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 4 2006
Fluid management for trauma

b
y

g
u
e
s
t

o
n

M
a
r
c
h

2
7
,

2
0
1
4
h
t
t
p
:
/
/
c
e
a
c
c
p
.
o
x
f
o
r
d
j
o
u
r
n
a
l
s
.
o
r
g
/
D
o
w
n
l
o
a
d
e
d

f
r
o
m

Early transfusion of plasma and platelets is similarly advant-
ageous, as coagulopathy complicating haemorrhagic shock is
easier to prevent than to reverse. For the patient who requires a
transfusion of >1 blood volume (approximately 10 units of red
blood cells) in a short period, dilutional coagulopathy is almost
certain. Our own preference is to begin therapy with plasma
and platelet concentrates as soon as this need is recognized,
with maintenance over the course of early resuscitation of an
approximately 1 : 1 : 1 ratio of blood components. Once haem-
orrhage has been anatomically controlled, further transfusion
therapy can be managed in a much more conservative fashion
and titrated to specific levels of haemoglobin, prothrombin
time and platelet concentration. Haemoglobin as low as
60 g litre
1
is now routinely tolerated in an asymptomatic
patient, while plasma and platelets are rarely given to the stable
patient without evidence of haemorrhage.
Finally, the anaesthetist must monitor the other components
of blood. Electrolyte concentration should be followed closely
during early resuscitation, with particular attention to the
blood calcium concentration. Rapid transfusion can lead to
intravascular chelation of free calcium (with a negative effect
on myocardial performance) because banked blood components
are packaged with citrate to prevent clotting. The anaesthetist
must monitor ionized calcium closely and replace it as needed
during rapid transfusion. Respiratory acidosis should be man-
aged by adjustment of mechanical ventilation, while metabolic
acidosis can only really be treated by control of haemorrhage and
restoration of adequate intravascular volume. The use of bicar-
bonate to elevate serum pH has been advocated in the past, but
has not been found beneficial in the treatment of haemorrhagic
shock. On the other hand, there is mounting evidence that close
management of serum glucose concentrations with i.v. insulin
improves patient outcomes. Although a definitive study
in early resuscitation has not yet been completed, tight glucose
control is an emerging standard of care in most centres.
Completion of resuscitation
After definitive control of haemorrhage, the emphasis of resus-
citation shifts to the restoration of normal tissue perfusion. The
phenomenon of occult hypoperfusion has been used to describe
patients (specially young patients) who reach the ICU with nor-
mal vital signs, but persistently elevated serum lactate.
7
These
patients are hypovolaemic owing to under-resuscitation, but
supporting their blood pressure on the basis of profound vaso-
constriction. If not promptly recognized, this situation creates
the potential for sustained shock, organ system failure and
death. When receiving such a patient, it is imperative that the
ICU practitioner examines the patients arterial blood gas and
serum lactate concentration for any evidence of persisting anaer-
obic metabolism. If present, the patient should be aggressively
fluid resuscitated until the lactate concentration has cleared to
normal.
8
Warming to normal body temperature and adequate
systemic analgesia will also help reverse vasoconstriction.
It is not unusual to see overshoot in the vital signs
after resuscitation from severe haemorrhage, characterized by
hypertension, tachycardia, fever and other signs of a hyperdy-
namic circulation. While this phenomenon has been associated
with improved survival from shock, attempts to artificially create
it (through the use of inotropic agents) have not generally been
successful. Optimal results depend on adequate fluid loading,
with inotropes reserved for those patients who do not resuscitate
(clear their lactate) despite adequate intravascular volume as
measured by pulmonary artery catheter or trans-oesophageal
echocardiography.
The future of resuscitation
Future efforts to improve outcomes fromhaemorrhagic shock will
focus on more rapid diagnosis and control of bleeding (as with
recombinant Factor VIIa or various topical haemostatic agents),
better monitoring of the shock state allowing more precise limita-
tion of fluid administration during active haemorrhage and active
manipulation of the inflammatory cascade illustrated in Fig. 1.
The success of activatedprotein-Cinfusion in mitigating the sever-
ity of the sepsis syndrome
9
is the tip of an iceberg of practice that
will one day include assessment of the patients genomic and pro-
teonomic inflammatory predilections, direct assay of serum medi-
ators and manipulation of the level of inflammatory response
during each hour and day after the initial shock insult. In the
meanwhile, informed resuscitation from shock in both the early
and late phases will help improve outcomes and save lives.
References
1. Committee on Trauma, American College of Surgeons: Advanced Trauma
Life Support Program for Doctors. Chicago: American College of
Surgeons, 1997
2. Stern A, Dronen SC, Birrer P, Wang X. Effect of blood pressure on
haemorrhagic volume in a near-fatal haemorrhage model incorporating
a vascular injury. Ann Emerg Med 1993; 22: 15563
3. Capone A, Safar P, Stezoski SW, Peitzman A, Tisherman S. Uncontrolled
hemorrhagic shock outcome model in rats. Resuscitation 1995; 29: 14352
4. Bickell WH, Wall MJ, Pepe PE, et al. Immediate versus delayed resuscitation
for hypotensive patients with penetrating torso injuries. N Engl J Med
1994; 331: 11059
5. Dutton RP, Mackenzie CF, Scalea TM. Hypotensive resuscitation during
active hemorrhage: impact on in-hospital mortality. J Trauma 2002; 52:
11416
6. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline
for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350:
224756
7. Blow O, Magliore L, Claridge JA, et al. The golden hour and the silver day:
detection and correction of occult hypoperfusion within 24 hours
improves outcome from major trauma. J Trauma 1999; 47: 9649
8. Abramson D, Scalea TM, Hitchcock, et al. Lactate clearance and survival
following injury. J Trauma 1993; 35: 5848
9. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant
human activated protein C for severe sepsis. N Engl J Med 2001; 344:
699709
Please see multiple choice questions 48.
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 4 2006
147
Fluid management for trauma

b
y

g
u
e
s
t

o
n

M
a
r
c
h

2
7
,

2
0
1
4
h
t
t
p
:
/
/
c
e
a
c
c
p
.
o
x
f
o
r
d
j
o
u
r
n
a
l
s
.
o
r
g
/
D
o
w
n
l
o
a
d
e
d

f
r
o
m