Abstract
Managing trauma patients with hemorrhagic shock is complex and difficult. Despite our knowledge of the
pathophysiology of hemorrhagic shock in trauma patients that we have accumulated during recent decades, the
mortality rate of these patients remains high. In the acute phase of hemorrhage, the therapeutic priority is to stop
the bleeding as quickly as possible. As long as this bleeding is uncontrolled, the physician must maintain oxygen
delivery to limit tissue hypoxia, inflammation, and organ dysfunction. This process involves fluid resuscitation, the
use of vasopressors, and blood transfusion to prevent or correct acute coagulopathy of trauma. The optimal
resuscitative strategy is controversial. To move forward, we need to establish optimal therapeutic approaches with
clear objectives for fluid resuscitation, blood pressure, and hemoglobin levels to guide resuscitation and limit the
risk of fluid overload and transfusion.
Keywords: Trauma, Hemorrhagic shock, Fluid resuscitation, Vasopressors, Acute coagulopathy of trauma
Review
Introduction
Hemorrhage remains the major cause of preventable
death after trauma [ 1 ]. In the acute phase of hemorrhage,
the physician's therapeutic priority is to stop the bleeding
as quickly as possible. Hemorrhagic shock is a pathologic
state in which intravascular volume and oxygen delivery
are impaired. As long as this bleeding is not controlled,
the physician must maintain oxygen delivery to limit tis-
sue hypoxia, inflammation, and organ dysfunction. This
procedure involves fluid resuscitation, use of vasopressors,
and blood transfusion to prevent or correct traumatic coa-
gulopathy. However, the optimal resuscitative strategy is
controversial: choice of fluid for resuscitation, the target of
hemodynamic goals for hemorrhage control, and the opti-
mal prevention of traumatic coagulopathy are questions
that remain. This review focuses on new insights into re-
suscitative strategies in traumatic hemorrhagic shock.
Fluid resuscitation
Fluid resuscitation is the first therapeutic intervention in
traumatic hemorrhagic shock. We discuss the choice of
the type of fluid for resuscitation. There is no proof in
the literature that supports the superiority of one type of
fluid over another type of fluid in trauma patients. The
most important dual advantage that colloids have over
crystalloids is that colloids can induce a more rapid and
persistent plasma expansion because of a larger increase
in oncotic pressure, and they can quickly achieve circu-
latory goals. Although crystalloids are cheaper, research
findings have shown no survival benefit when colloids are
administered. However, resuscitation with large volumes
of crystalloids has been associated with tissue edema, an
increased incidence of abdominal compartment syndrome
[ 2 ], and hyperchloremic metabolic acidosis [3].
The SAFE study demonstrated that albumin adminis-
tration was safe for fluid resuscitation for intensive care
unit (ICU) patients and that there was no difference in
the mortality rate of patients who were treated with al-
bumin and saline [ 4] . In a subgroup of trauma patients,
the investigators observed a positive trend in benefit for
saline use over albumin use. This difference in the rela-
tive risk of death was due to the greater number of
patients, who had trauma and an associated brain injury
and who died after random assignment to the albumin-
treated group as opposed to the saline-treated group. No
mechanism was offered to account for this finding, but
the low hypo-osmolarity of albumin may increase the
* Correspondence: Jacques.Duranteau@bct.aphp.fr
1
Departement of Anesthesia and Intensive Care, Bicêtre Hospital, Hôpitaux
universitaires Paris-Sud, Université Paris-Sud, Assistance Publique-Hôpitaux de
Paris, 78, rue du Général Leclerc, 94275, Le Kremlin Bicêtre, France
Full list of author information is available at the end of the article
© 2013 Bouglé et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0) , which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work is properly cited.
Bouglé et al. Annals of Intensive Care 2013, 3 :1
http://www.annalsofintensivecare.com/content/3/1/1
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risk of brain edema. A recent Cochrane review [ 5 ] in
critically ill patients (patients with trauma, burns, or
after surgery) reported no evidence accumulated from
RCTs that resuscitation with colloids reduced the risk of
death compared with resuscitation with crystalloids. In a
review of clinical studies dating to 2002 with safety data
documented in ICU patients who received HES, gelatin,
dextran, or albumin, Groeneveld et al. [ 6] demonstrated
that impaired coagulation, clinical bleeding, and acute
kidney injury (AKI) were frequently reported after HES
infusion. Notably, this analysis was strongly influenced
by the VISEP study (Volume Substitution and Insulin
Therapy in Severe Sepsis study) [ 7 ], in which a former-
generation HES was used (200/0.5) with doses that
exceeded the recommended maximal doses. These meta-
analyses take into account heterogeneous populations of
patients with different therapeutic strategies. Recently,
Perner et al. [ 8] have shown an increased risk of death
(dead on day 90) in patients with severe sepsis who were
assigned to receive fluid resuscitation with HES 130/0.42
(6% HES 130/0.42 in Ringer's acetate, last generation of
HES) compared with those who received Ringer's acetate.
Moreover, more patients required renal-replacement ther-
apy in the HES 130/0.42 group (22%) than in the Ringer’s
acetate group (16%). In light of the shared pathophysio-
logical pathways with inflammation activation between
sepsis and trauma, the use of HES raises serious concerns
with respect to its safety in trauma patients [ 9] .
Thus, there is an imperative need to study trauma
patients who are in hemorrhagic shock. Recently, a
double-blind, randomized, controlled study that com-
pared 0.9% saline vs. hydroxyethyl starch (HES 130/0.4)
was conducted in penetrating blunt trauma patients
who required >3 liters of fluid resuscitation [ 10 ]. In
patients with penetrating trauma (n = 67), the use of
HES (130/0.4) was associated with a better lactate clear-
ance, thus suggesting early resuscitation. Furthermore,
lower maximum SOFA scores and an absence of acute
renal injury were observed in the HES group. However,
in patients with blunt trauma (n = 42), there was no dif-
ference in fluid requirements, lactate clearance, and
maximum SOFA scores between the two groups. In
addition, a greater requirement for blood and blood
products was reported in the HES group with a signifi-
cantly greater alteration in coagulation (thromboelasto-
graphy). It is difficult to draw conclusions, because
patients in the HES group were more severely injured
than patients in the saline group; we should apply cau-
tion when we interpret the results, because the study is
based on a small sample size.
The last European guidelines for the management of
bleeding after severe injury [ 11] recommended that crys-
talloids should be applied initially to treat the bleeding
trauma patients and that the addition of colloids should
be considered in hemodynamically unstable patients.
Among colloids, HES or gelatin solutions should be
used. The guidelines recommended using the new-
generation HES within the prescribed limits because of
the risks of AKI and alteration in coagulation.
Hypertonic saline (HTS) is an interesting tool in trau-
matic hemorrhagic shock. HTS has the major benefit of
rapidly expanding blood volume with the administration of
a small volume, especially if it is used with a colloid. Fur-
thermore, HTS can be used as a hyperosmolar agent in
patients with elevated intracranial pressure. However, HTS
failed to improve outcomes in recent RCTs [1 2, 13]. Bulger
et al. [1 2] reported that HTS + dextran out-of-hospital
resuscitation did not decrease survival without acute re-
spiratory distress syndrome at 28 days in a blunt trauma
population with a prehospital systolic blood pressure (SAP)
≤ 90 mmHg. However, benefit was observed in the sub-
group of patients who required 10 U or more of packed
red blood cells in the first 24 h. Recently, the same authors
were unable to demonstrate an improvement in survival as
a result of out-of-hospital administration of SSH + dextran
in patients in hemorrhagic shock (SAP ≤ 70 mmHg or
SAP 71–90 mmHg with heart rate ≥ 108 bpm) [ 13 ]. More-
over, a higher mortality rate was observed in patients
who received HTS in the subgroup of patients who did
not receive any blood transfusions in the first 24 hr. To
explain this effect, the authors hypothesized that the
out-of-hospital administration of SSH could mask the signs
of hypovolemia and delay the diagnosis of hemorrhagic
shock. Finally, the out-of-hospital administration of SSH to
patients with severe traumatic brain injury did not improve
their neurological function recovery.
Vasoactive agents
Fluid resuscitation is the first strategy to restore mean
arterial pressure in hemorrhagic shock. However, vaso-
pressor agents also may be transiently required to sus-
tain life and maintain tissue perfusion in the presence of
a persistent hypotension, even when fluid expansion is
in progress and hypovolemia has not yet been corrected.
This point is crucial, because tissue perfusion is directly
related to the driving pressure (the difference between
pressures at the sites of entry and exit of the capillary),
the radius of the vessel, and the density of capillaries;
additionally, tissue perfusion is inversely related to blood
viscosity. Thus, arterial pressure is a major determinant
of tissue perfusion.
Norepinephrine (NE), which often is used to restore
arterial pressure in septic and hemorrhagic shock, is
now the recommended agent of choice du