Hemorrhagic Shock in the Pediatric Patient: New Therapies and Practices

Richard P. Dutton, M.D., M.B.A.

In trauma, as in other subspecialties, randomized controlled trials focused on pediatric patients

are few and far between. This is especially so in emergency research, where issues of consent
make a difficult challenge even harder. Nonetheless, resuscitation from hemorrhagic shock in
adult trauma patients has seen a remarkable evolution in care over the past decade, and many of
the lessons learned will be equally applicable or more so in children.

Introduction: Why we like fluids.

The concept of giving fluids as a treatment for hemorrhage is obvious, especially when blood
loss is readily visible. If the body loses fluid it makes sense to replace it. Classic war movies
portray the wounded soldier as thirsty, with the compassionate medic giving water to ease the
distress. Modern TV shows emphasize 1 liter of normal saline, STAT. And indeed, few
therapies are so immediately gratifying. In a fluid depleted, vasoconstricted patient,
administration of an intravenous fluid bolus predictably increases myocardial wall tension,
resulting (through Starlings law) in increased contractility and thus increased blood pressure.
The thing we measure (blood pressure) responds immediately to the thing we do (give fluids).
This makes us feel better, and in control. This physiology is even more compelling in children,
with fewer chronic diseases to obscure the normal relationship of fluid to volume to pressure.

Further, there is a wealth of research demonstrating the value of fluid therapy when the body is
hypovolemic. The modern era of resuscitation science began with development of the Wiggers
model of controlled hypotension in the 1950s,1 followed by the work of Shires a decade later.2
Bleeding was found to produce consistent organ system hypoperfusion, which led to a variety of
bad outcomes, including mortality. Ischemic animals benefitted from fluid therapy: tissue
perfusion improved, and morbidity and mortality were reduced. Even within the past few years,
this concept has been further hammered home. Blow et al demonstrated worse outcomes in the
ICU if occult hypoperfusion in trauma patients was not recognized and addressed,3 while
Rivers and colleagues showed the benefit of Early Goal Directed Therapy a thinly veiled
excuse for greater fluid administrationin patients presenting to the Emergency Department in
septic shock.4

Within anesthesia the concept of treating hypoperfusion with fluids is a cornerstone of residency
training. We know how much anesthesia the patient needs1 MAC, right?so if theyre
hypotensive it must be because theyre hypovolemic. Failure to give fluids will lead to
postoperative visual loss (maybe), acute renal failure (maybe) and the twin boogeymen called
stroke and MI. Yet the data does not support these fears. Deliberate hypotension during
anesthesia has been studied many, many times and generally found to be safe.5 And all of us
have seen adult patients with mean arterial pressure as low as 40 mmHg who woke up just fine.
In fact, absent patients who need CPR, ischemic injury caused by hypotension is vanishingly
rare. In children, these boundaries can likely be pushed even further.
Risks of Fluid Administration

But why not give the fluid? Wheres the harm in it? Not surprisingly, there are risks as well as
benefits to fluid administration. The first is increased bleeding. Any elevation of blood pressure
will increase bleeding from open vessels and will tend to wash away clots that have already
formed. In the vasoconstricted shock patient even small boluses of fluid can produce sharp
increases in pressure and subsequent rebleeding. And in the case of new tissue injury (i.e.
surgery), the higher the blood pressure, the more blood will be lost and the harder the bleeding
will be to control.6

Further is the issue of blood dilution. Crystalloid or colloid fluids will dilute native clotting
factors and red cell mass. While red cell dilution will not decrease oxygen delivery, it will
increase the rate of tissue bleeding through a decrease in viscosity and a loss of red cell
facilitation of clotting. It is well established (although little known) that clotting occurs more
rapidly at a higher hematocrit.7 Plasma dilution also lowers the concentration of soluble clotting
factors and platelets at the site of bleeding, leading to slower and less solid clot formation. While
the body has some capacity to respond by releasing stored factors, this capacity is limited and
rapidly overwhelmed by trauma or major surgery.

Then there is the potential for volume overload. Previously healthy adults can generally
compensate for excessive fluid administration by rapid renal excretion, but in children, especially
infants, this is not always true. Excessive administration of fluid can result in myocardial
distention and dysfunction, with resultant pulmonary edema. Depending on the fluid
administered, there is also a risk of electrolyte abnormalities and hypo- or hyper-glycemia.

Finally, it is clear that the fluids themselves are not as benign as we would like. Both crystalloid
and colloid fluids have immune-mediating effects, usually suppressive.8 Fluid therapy by itself
can damage vascular endothelium and lead to increased permeability.9 Unless carefully
managed, fluid administration will also make the patient colder, further contributing to both
coagulopathy and immune suppression, and this is even more true in the pediatric population.

Animal Studies of Fluid Restriction

Although identified repeatedly during wartime surgery (all the way back to World War I), the
concept of deliberate hypotension during active bleeding has been slow to sink in. In 1964
Shaftan published a study of coagulation in dogs, demonstrating that it is formation of a soft
extraluminal clot that limits bleeding following arterial trauma.10 This study compared blood
loss from a standard arterial injury under various conditions. The least blood loss occurred in
hypotensive animals (whether hypotensive from hemorrhage or from vasodilator administration),
followed by controls, followed by vasoconstricted animals. Greatest blood loss occurred in
animals that received vigorous fluid reinfusion during hemorrhage.
A series of reports in swine, rats, sheep and dogs established that, while some resuscitation was
needed to prevent early death from exsanguination, the optimal target systolic pressure for best
survival was in the range of 70-80 mmHg.11-15 Attempts to normalize systolic pressure prior to
anatomic control of hemorrhage lead to rebleeding, increased requirement for resuscitation,
increased blood loss, and increased mortality.

In the most sophisticated models, direct assessment of cardiac output and regional perfusion
show no difference between moderate or large volume resuscitation in cardiac output, blood
pressure, or regional perfusion of the heart, kidneys, and intestines. Burris studied both
conventional resuscitation fluids and various combinations of hypertonic saline and dextran,
finding that rebleeding was correlated with higher mean arterial pressure (MAP), and survival
was best in groups resuscitated to lower than normal MAP.16 A 1994 consensus panel on
resuscitation from hemorrhagic shock noted that mammalian species are capable of sustaining
MAP as low as 40 mmHg for periods as long as 2 hours without deleterious effects.17 The panel
concluded that spontaneous hemostasis and long-term survival were maximized by reduced
administration of resuscitation fluids during the period of active bleeding, seeking to keep
perfusion only just above the threshold for ischemia. This same principle is likely true in
children (although poorly studied), when adjusting for the age-normal blood pressure.

Human Trials of Deliberate Hypotensive Resuscitation

Two large trials of deliberate hypotensive resuscitation have been conducted in adult trauma
patients. The first, in Houston in the early 1990s, randomized hypotensive victims of penetrating
torso trauma to conventional management or to no intravenous fluid during prehospital and ED
care.18 This trial demonstrated a significant improvement in outcome (62% vs. 70% survival)
with fluid restriction, but was controversial because of its focus on penetrating trauma only, its
failure to continue fluid restriction into the early operative period, and its all or none
methodology. Following this, a retrospective review of resuscitation strategy in a large
population of hemorrhagic shock patients demonstrated increased mortality when a rapid
infusion system was used.19 A second prospective trial enrolled both blunt and penetrating
trauma patients at the time of hospital arrival, and randomized fluid therapy to target a systolic
pressure of either 80 mmHg or 100+ mmHg.20 There was no difference in mortality between
groups, although the overall mortality (8%) was much lower than in the earlier trial due to the
exclusion of moribund patients.

Although not of themselves perfect evidence, these trials were convincing enough regarding the
safety and potential benefit of deliberate hypotension that this approach has become the
recommended policy in most major trauma centers.21 Even so, fluid restriction requires very
close attention to detail in the ED and OR, and a willingness to tolerate systolic blood pressures
that would demand action in most other settings. This kind of discipline is rare, and it is likely
that most bleeding patients, in most settings, still receive too much crystalloid fluid.
New Thinking about Fluid Resuscitation

In the new millennium thinking about resuscitation has evolved even further, in an effort to
reduce the long-term harms from hypoperfusion while maintaining the hemostatic benefits of
keeping the blood pressure low. With the recognition that the coagulopathy of trauma is caused
not just by dilution, hypothermia and acidosis (the so-called lethal triad) but also by an acute
inflammatory response to tissue injury,22 there has been increasing focus on early support of the
coagulation system. Several large retrospective series in both military and civilian trauma have
demonstrated improved outcomes when plasma and platelets are given earlier, and in greater
quantities.23-27 Although not yet demonstrated in a prospective trial, these observations have led
to the recommendation of empiric 1:1:1 RBC:plasma:platelet administration (instead of
crystalloids or colloids) as the indicated fluid therapy for hemodynamically unstable patients
with ongoing bleeding. Uncrossmatched type-O RBC have been used by major trauma centers
for many years, and have a superior safety record.28,29 In the past few years large centers have
also begun using prethawed or liquid universal donor (type AB) plasma early in resuscitation.

Using a whole blood mix as the resuscitation fluid for hemorrhaging patients largely avoids the
issue of dilution, but what about concern for hypoperfusion? Postulated as beneficial, but not yet
studied even retrospectively, is the aggressive use of anesthetic agents early in resuscitation. In
theory, this approach would reverse vasoconstriction and improve perfusion while maintaining
low blood pressure during the period of active hemorrhage. Rather than maintaining
hypotension by fluid restriction, this approach accomplishes it by vasodilatation. The downside
to this approachthe risk of complete circulatory failure caused by administering anesthetics to
a patient in shockrequires careful management. In the early going, titration of small doses of
anesthesia (usually fentanyl) are balanced by small boluses of fluid (1:1:1 blood products) until
an adequate anesthetic state is achieved. In the face of the dynamic changes produced by injury
and surgery, this requires excellent intravenous access, an efficient rapid infusion system, close
monitoring of blood pressure, and an experienced provider. When successful, the result is a
stable, vasodilated physiology that keeps blood pressure low, blood composition close to normal,
and the circulation largely intact.

Validation of these theories is lacking, even in adults, but will hopefully be accomplished by the
next generation of resuscitation researchers.

Summary and Recommendations

Based on the evidence presented, the following is this authors recommended approach to early
resuscitationwhile the patient is still actively bleedingfollowing traumatic injury or major
surgical misadventure:

Maintain systolic blood pressure 80 100 mmHg

Maintain functional blood composition, using empriric 1:1:1 transfusion therapy
Maintain normal serum ionized calcium
Maintain core temperature > 35 degrees C
Follow base deficit and serum lactate as markers for hypoperfusion
 Transition the patient to deep anesthesia

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