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Review
Clinical review: Hemorrhagic shock
Guillermo Gutierrez1, H David Reines 2 and Marian E Wulf-Gutierrez3
1Professor, Pulmonary and Critical Care Medicine Division, Department of Medicine, The George Washington University Medical Center,
Washington, District of Columbia, USA
2Professor, Virginia Commonwealth University and Vice-Chairman, Department of Surgery, Inova Fairfax Hospital, Falls Church, Virginia, USA
3Associate Professor, Department of Obstetrics and Gynecology, The George Washington University, Inova Fairfax Hospital, Falls Church, Virginia,
USA
Published online: 2 April 2004 Critical Care 2004, 8:373-381 (DOI 10.1186/cc2851)
This article is online at http://ccforum.com/content/8/5/373
© 2004 BioMed Central Ltd
Abstract
This review addresses the pathophysiology and treatment of hemorrhagic shock – a condition
produced by rapid and significant loss of intravascular volume, which may lead sequentially to
hemodynamic instability, decreases in oxygen delivery, decreased tissue perfusion, cellular hypoxia,
organ damage, and death. Hemorrhagic shock can be rapidly fatal. The primary goals are to stop the
bleeding and to restore circulating blood volume. Resuscitation may well depend on the estimated
severity of hemorrhage. It now appears that patients with moderate hypotension from bleeding may
benefit by delaying massive fluid resuscitation until they reach a definitive care facility. On the other
hand, the use of intravenous fluids, crystalloids or colloids, and blood products can be life saving in
those patients who are in severe hemorrhagic shock. The optimal method of resuscitation has not been
clearly established. A hemoglobin level of 7–8 g/dl appears to be an appropriate threshold for
transfusion in critically ill patients with no evidence of tissue hypoxia. However, maintaining a higher
hemoglobin level of 10 g/dl is a reasonable goal in actively bleeding patients, the elderly, or individuals
who are at risk for myocardial infarction. Moreover, hemoglobin concentration should not be the only
therapeutic guide in actively bleeding patients. Instead, therapy should be aimed at restoring
intravascular volume and adequate hemodynamic parameters.
Keywords blood loss, estimated blood volume, hemorrhage, oxygen consumption, oxygen delivery, shock, transfusion
Table 1
Classification of hemorrhage
Class
Parameter I II III IV
pulmonary artery pressures are needed to estimate the open capillaries increases in proportion to the degree of tissue
degree of fluid replacement that may be required. hypoxia [12]. Capillary recruitment shortens the
Figure 2 of ATP are not sufficient to maintain cellular function (Fig. 2).
Failure of membrane-associated ion transport pumps, in
Stages of Hemorrhage particular those associated with the regulation of calcium and
Stage IV
sodium, results in the loss of membrane integrity and in
Stage III Stage II Stage I
cellular swelling [27,28]. Among other mechanisms that lead
to irreversible cellular injury during hypoxia are depletion of
cellular energy, cellular acidosis, oxygen free
radical generation, and loss of adenine nucleotides from the
cell [29].
O2 Consumption
Clinical manifestations
Shock is a state of hypoperfusion associated with hemo-
dynamic abnormalities leading to the collapse of homeo-
stasis, or as poetically stated by John Collins Warren, a
‘momentary pause in the act of death’ [30]. The etiology of
shock in traumatized patients is likely to be massive blood
loss but other causes of shock must be considered. These
include blunt myocardial damage, spinal cord injury, tension
pneumothorax, or pericardial tamponade.
Gastrointestinal bleeding and trauma are the most common Obstetric/gynecologic Placenta previa
causes of hemorrhage. Other causes of hemorrhagic shock Abruptio placentae
include ruptured abdominal aortic aneurysms, spontaneous
Ruptured ectopic pregnancy
bleeding from anticoagulation, and postpartum bleeding
secondary to a placenta previa or placenta abruption Ruptured ovarian cyst
(Table 2). A ruptured ectopic pregnancy or a ruptured ovarian Pulmonary Pulmonary embolus
cyst also can cause hemorrhagic shock without an obvious
Lung cancer
source of blood loss [31]. The evaluation of shock in a
woman of childbearing age should include a pregnancy test Cavitary lung disease:
tuberculosis, aspergillosis
and possibly a culdocentesis. Stopping the bleeding, as well
as replacing the blood volume, is the treatment for shock Goodpasture’s syndrome
resulting from postpartum hemorrhage. Ruptured aneurysms
Retroperitoneal bleeding
Blood losses from external lacerations are difficult to Trauma Lacerations
estimate but usually respond to direct pressure and volume
Penetrating wounds to the
resuscitation. Intrathoracic injuries, especially to the lung,
abdomen and chest
heart, or the great vessels, can result in the loss of several
liters of blood into the thorax without external evidence of Ruptured major vessels
hemorrhage. Intra-abdominal injuries to solid organs (spleen
and liver) and great vessels (ruptured aneurysm, penetrating
injury to intra-abdominal vessels) can cause rapid loss of the Treatment of hemorrhagic shock
entire blood volume into the abdomen. Massive bleeding into
The main goals of resuscitation are to stop the source of
the gastrointestinal tract from ulcers or intestinal diverticuli
hemorrhage and to restore circulating blood volume. Actively
can likewise cause shock, but the patient usually manifests
bleeding patients should have their intravascular fluid
either hematochezia or hematemesis when blood loss is
replaced because tissue oxygenation will not be compro-
rapid and acute.
mised, even at low hemoglobin concentrations, as long as
circulating volume is maintained. Hemoglobin concentration
Fractures of the pelvis can hide massive amounts of bleeding in an actively bleeding individual has dubious diagnostic value
with little external evidence [32]. An unstable pelvis on because it takes time for the various intravascular compart-
physical examination always raises the possibility ments to equilibrate. Rather, therapy should be guided by the
of significant blood loss. Spontaneous bleeding into rate of bleeding and changes in hemodynamic parameters,
the retroperitoneum can also cause shock without such as blood pressure, heart rate, cardiac output, central
significant physical findings. Fractures of the lower venous pressure, pulmonary artery wedge pressure, and
extremities, especially closed femur fractures, can easily hide mixed venous saturation.
2–3 units of blood, whereas open fractures can lacerate
major vessels and cause significant blood loss. Head injury is Restoration of the intravascular fluid volume
rarely a cause of hypotension and is never the cause of Since the time of World War II, the accepted therapeutic
massive blood loss, unless there is external bleeding. dogma has been to restore blood volume rapidly and achieve 377
Critical Care October 2004 Vol 8 No 5 Gutierrez et al.
Hypertonic saline
There is continuing interest in the role of hypertonic saline
during resuscitation from hypovolemic shock. There is some
evidence that the use of hypertonic saline in traumatized
patients with closed head injury may be efficacious [41], but
378 this is controversial and the U S Food and
Administration has not given approval for its use during the
resuscitation of patients. A prospective, randomized study
comparing hypertonic saline with dextran found no difference in
survival between the hypertonic saline group and the
dextran-treated group [42]. Small volume hypertonic saline
does hold some promise in cases of penetrating trauma [43].
Blood substitutes
Blood substitutes have been tried in many forms [44]. A
report by Gould and colleagues [45] on the effect of massive
doses of hemoglobin solutions in hemorrhagic trauma patients
demonstrated a possible benefit when compared with
infusion of crystalloids. In that study, 171 patients received
rapid infusion of 1–20 units of poly-HEME (Sigma, St. Louis,
MO, USA; human polymerized hemoglobin) in lieu of human
blood. Mortality was 25%, as compared with 64% for
historical matched control individuals. On the other hand, the
sobering results of a randomized, prospective, multicenter
study conducted by Sloan and coworkers [46], in which
traumatic hemorrhagic shock patients were treated with
diaspirin cross-linked hemoglobin, will remain an impediment to
further research in this area for many years to come. At 28
days, 24 (46%) of the 52 patients infused with diaspirin cross-
linked hemoglobin died compared with eight (17%) of the 46
patients infused with a saline solution (P = 0.003).
When to transfuse
The use of blood and blood products is necessary when the
estimated blood loss from hemorrhage exceeds 30% of the
blood volume (class III hemorrhage). Determining this point has
been extremely difficult during an acute hemorrhage because
of hemodilution produced by fluid resuscitation. As mentioned
previously, whereas formulas have been proposed to estimate
blood losses, the use of blood as a resuscitative fluid is
empirical [5,47].
patients without known risk factors. They also agree in their with acute myocardial infarction and a hematocrit of 24% or
disapproval of prophylactic blood transfusion, because patients lower may benefit from blood transfusion. In a retrospective
with hemoglobin levels greater than 10 g/dl are unlikely to analysis of data from 78,974 patients aged 65 years or older
benefit from blood transfusion. These guidelines have rapidly and who were hospitalized with acute myocardial infarction,
been incorporated into the everyday practice of medicine, those with lower hematocrit values (< 24%) on admission had
leading some to question whether blood transfusion is now higher 30-day mortality rates. Blood transfusion was asso-
under-used [55]. ciated with a reduction in 30-day mortality among patients
whose hematocrit on admission was in the 5–24% range.
When it comes to high risk or critically ill patients, clinical Blood transfusion did not improve survival among those
evidence in support of transfusion guidelines is more difficult to whose hematocrit values fell in the higher ranges.
obtain and therapy has often been guided by clinical judgment.
A study of transfusion practices in Canada noted that 28% of Delayed versus immediate resuscitation
patients admitted to tertiary level intensive care units received Recent data question the practice of initial aggressive
red cell transfusions [56]. The most frequent reason for resuscitation of hemorrhagic shock. Cannon and coworkers
administering red cells was not the patient’s hemoglobin [33] raised the concern that raising blood pressure in a
concentration. Instead, blood transfusions were ordered if bleeding patient would eliminate the clot and increase
patients were acutely bleeding (35% of patients transfused) or bleeding. This theory was replaced in World War II and in
in order to increase D O2 (25% of patients transfused). Vietnam by the concept that restoration of blood volume as
soon as possible was the key to survival. The concept of the
A multi-institutional, prospective, randomized study was ‘golden hour’ as the time period allowed for medical personnel
conducted to determine whether a restrictive strategy of red to reverse shock and prevent organ system damage has
cell transfusion and a liberal strategy produced equivalent dominated the thinking of trauma surgeons for a generation.
results in critically ill patients [57]. Patients were enrolled in
the study within 72 hours of admission to the intensive care Bickell and coworkers [60] challenged this approach when
unit if their hemoglobin concentrations was below 9 g/dl. they performed a randomized prospective study of patients
Patients were randomly assigned either to a liberal strategy of with penetrating truncal injuries who were hypotensive in the
transfusion (n = 420), in which hemoglobin values were main- field (systolic blood pressure < 90 mmHg). Patients were
tained at a level between 10 and 12 g/dl, or to a restrictive randomized according to the day of the month to receive
strategy of transfusion, in which hemoglobin values were either standard resuscitation with Ringers lactate or place-
maintained between 7 and 9 g/dl (n = 418). Mortality at ment of intravenous catheters without intravenous fluid admini-
30 days was similar for the two groups (19% versus 23%). stration. Patients were excluded if they had cardiopulmonary
Subgroup analysis showed that mortality rates were lower collapse in the field, severe head injury, or did not need
with the restrictive transfusion strategy among less acutely ill surgical intervention. A total of 598 matched control patients
patients and among those under 55 years old. Furthermore, were included in the study group. The immediate resusci-
the mortality rate during hospitalization was significantly lower tation group received an average of 900 ml fluid before
in the restrictive strategy group (22% versus 28%). These hospitalization compared with 100 ml fluid in the delayed
data suggest that a restrictive strategy of red cell transfusion resuscitation group. Of the delayed resuscitation group 70%
in critically ill patients is at least as effective as a liberal were discharged, as compared with 62% of the immediate
transfusion strategy. Moreover, a prospective observational fluid group (P = 0.04), and the delayed group trended to have
study of 1136 patients conducted in Europe showed an fewer complications.
association between transfusions and decreased organ
function and increased mortality [58]. Animal data demonstrate a reduced risk for death with
fluid resuscitation in severe hemorrhage. On the other
Transfusion in elderly patients hand, a systematic review of the animal studies also
Tolerance of anemia is dependent on the recruitment of showed an increased risk for death from aggressive
physiologic reserve, mainly by increasing cardiac output. Low resuscitation in animals with less severe hemorrhage [61].
levels of hemoglobin that are tolerated by younger patients This finding suggests that excessive fluid resuscitation can
may be deleterious in the elderly. Reserve mechanisms in the be lethal when severe hemorrhage is not present.
elderly may be blunted with advanced age and the presence Another study [62] found no differences in survival in
of coronary artery stenosis. This also may explain why elderly patients presenting in hemorrhagic shock treated with two
patients with acute myocardial infarction are at extremely high fluid replacement protocols, one that required fluid
risk for death despite having infarct sizes similar to those in replacement to a systolic blood pressure in excess of
younger patients. 100 mmHg (conventional) and another that required fluid
replacement to a systolic blood pressure in excess of 70 mmHg.
A study conducted by Wu and coworkers [59] indicated that
a substantial number of people who present to the hospital Whether or not one fully resuscitates a bleeding patient
depends on the rate of bleeding, the ability to control the
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