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Critical care considerations in the management of the trauma patient following
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2012,
Roger F Shere-Wolfe (email@example.com)
Samuel M. Galvagno Jr. (firstname.lastname@example.org)
Thomas E. Grissom (email@example.com)
27 February 2012
28 August 2012
18 September 2012
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Trauma, Resuscitation and
© 2012 Shere-Wolfe et al. ; licensee BioMed Central Ltd.
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Critical care considerations in the management of
the trauma patient following initial resuscitation
Roger F Shere-Wolfe1*
* Corresponding author
Samuel M Galvagno Jr1
Thomas E Grissom1
1 University of Maryland School of Medicine, R Adams Cowley Shock Trauma
Center, 22 S. Greene St, Ste. T1R77, Baltimore, MD 21201, USA
Care of the polytrauma patient does not end in the operating room or resuscitation bay. The
patient presenting to the intensive care unit following initial resuscitation and damage control
surgery may be far from stable with ongoing hemorrhage, resuscitation needs, and injuries
still requiring definitive repair. The intensive care physician must understand the respiratory,
cardiovascular, metabolic, and immunologic consequences of trauma resuscitation and
massive transfusion in order to evaluate and adjust the ongoing resuscitative needs of the
patient and address potential complications. In this review, we address ongoing resuscitation
in the intensive care unit along with potential complications in the trauma patient after initial
resuscitation. Complications such as abdominal compartment syndrome, transfusion related
patterns of acute lung injury and metabolic consequences subsequent to post-trauma
resuscitation are presented.
A non-systematic literature search was conducted using PubMed and the Cochrane Database
of Systematic Reviews up to May 2012.
Results and Conclusion
Polytrauma patients with severe shock from hemorrhage and massive tissue injury present
major challenges for management and resuscitation in the intensive care setting. Many of the
current recommendations for “damage control resuscitation” including the use of fixed ratios
in the treatment of trauma induced coagulopathy remain controversial. A lack of large,
randomized, controlled trials leaves most recommendations at the level of consensus, expert
opinion. Ongoing trials and improvements in monitoring and resuscitation technologies will
further influence how we manage these complex and challenging patients.
Coagulopathy, Trauma, Acute lung injury, Transfusion, Intensive care unit, Complications,
Resuscitation of the severely injured patient is a topic of ongoing evolution and controversy.
Since the early 1990’s, management of critically ill polytrauma patients has been governed by
the “damage control” paradigm first introduced in abdominal surgery  and subsequently
expanded to most areas of care, including orthopedic , vascular  and thoracic injuries.
 According to one definition, damage control surgery (DCS) is the “planned temporary
sacrifice of normal anatomy to preserve vital physiology”. Because severely injured
patients are too physiologically deranged to tolerate prolonged definitive repair, initial
surgical intervention is limited to minimally necessary stabilization and control of
hemorrhage. Thus, the patient presenting to the intensive care unit (ICU) following initial
resuscitation and DCS may be far from stable with ongoing hemorrhage, resuscitation needs,
and injuries still requiring definitive repair.
Table 1 Distinguishing TRALI from TACO and ARDS
Vital signs May be febrile; hypotension more common
Clinical examination Crackles
Crackles, S3, jugular venous
Decreased ejection fraction
ECHO findings Normal to slightly decreased ventricular
function; no evidence of left atrial
< 18 mmHg
Normal to slightly decreased ventricular
function; no evidence of left atrial
<18 mmHg Pulmonary artery
peptide (BNP) level
White blood cell
Leukocyte antibodies Donor leukocyte antibodies present;
crossmatch incompatibility between donor
Hyper-, hypo-, or normovolemic
< 200 pg/mL
Hyper-, hypo-, or normovolemic
< 200 pg/mL
> 1200 pg/mL
Typically decreased; may be transient Variable Usually unchanged from
Donor leukocyte antibodies
may or may not be present
Donor leukocyte antibodies may or may not
≤ 200 Variable
Care of the polytrauma patient does not end in the operating room or resuscitation bay. As
one authority has noted, “the best place for a sick person is in the ICU”. ICU physicians
must be prepared to receive patients at any point along the continuum of care, and must be
adept at assessing the patient’s physiologic status and addressing ongoing needs in a prompt
and expeditious fashion. As the patient stabilizes, the ICU physician must then begin to
transition the focus of care to longer term considerations such as potential for infectious and
thromboembolic complications, organ support, and the need for planned re-exploration and
staged definitive repair.
Although much focus has been placed on the initial management of the traumatized patient,
the transition between early resuscitation of the critically injured patient with hemorrhage
and/or polytrauma and the ICU has received less attention. These patients pose a number of
unique challenges for the ICU physician including the need for ongoing resuscitation,
determination of resuscitation endpoints, and management of early post-resuscitation
complications. How well these are addressed may have critical implications for long-term
outcome and survival. In this review, we will address early ICU considerations in the
polytrauma patient requiring aggressive early resuscitation. While no consensus definition for
“polytrauma” has been recognized, generally accepted definitions use an Injury Severity
Score (ISS) of greater than 15 to 17 or an Abbreviated Injury Scale (AIS) of greater than 2 in
at least two body regions .
Continued resuscitation in the ICU
Immediate assessment and basic physiologic support
Upon arrival to the ICU it is essential for the ICU physician to understand where the patient
is in the continuum of both surgical management and ongoing resuscitation (Figure 1), and to
assess overall stability and the extent of unresolved shock. Because shock is a cumulative
phenomenon in which the depth and duration determine the total “dose” in an integrative
fashion, the timeliness of resuscitation may have a significant impact on subsequent
morbidity and mortality (Figure 2). Virtually all critically injured patients require some
degree of immediate physiologic support on arrival to the ICU. This includes assurance of
adequate respiratory and ventilator support as well as aggressive intervention to minimize
secondary central nervous system (CNS) injury, resolve critical acid–base and electrolyte
disorders and restore normothermia.
Figure 1 A general approach to early versus late resuscitation
Figure 2 Prolonged tissue hypoperfusion creates a cumulative “oxygen debt” directly
related to the “dose” of shock, based on both the duration and depth of hypoperfusion.
Eventually this results in irreversible disruption of homeostasis such that patients will not
respond to resuscitative efforts even after the initial insults have been corrected [adopted
Volume loading remains the mainstay of circulatory support. Vasopressors seldom improve
microvascular perfusion and may mask underlying shock so their early role in the
resuscitation of the trauma should generally be cautioned.  Patients requiring
vasopressors are often either severely physiologically perturbed or under-resuscitated, and
their lack of response to fluid therapy may be suggestive of irreversible shock. There has
been some recent support for the use of low-dose vasopressin to treat underlying deficiency
and decrease overall fluid requirements [11-13] though this is not universally accepted, and
may impair the micro-circulation and produce splanchnic ischemia.  Patients with
concomitant CNS injuries may require vasopressor support to counteract spinal shock, or to
maintain cerebral perfusion in the setting of traumatic brain injury (TBI).
Respiratory support must continue to ensure adequate oxygenation and ventilation.
Inadequate oxygen delivery only worsens tissue hypoperfusion. This may be especially
deleterious in cases with concomitant CNS injury.  Respiratory acidosis superimposed on
metabolic acidosis may also be extremely detrimental. The use of positive end-expiratory
pressure and open lung ventilation techniques in the hypovolemic patient can increase
intrathoracic pressure and may critically impede venous return resulting in profound
hypotension. Physiologically deranged patients often present to the ICU with profound
metabolic acidosis and hypothermia. These impair both hemodynamic and hemostatic
function. Hypothermia should be corrected aggressively with full body passive or active re-
warming. Metabolic acidosis predicts both mortality and transfusion needs, [16,17] and is
generally best treated by restoration of tissue perfusion. Massive fluid shifts often produce
profound electrolyte disturbances, which should also be promptly corrected.
Polytrauma patients with concomitant CNS injuries pose an especially great challenge. Even
mild TBI can blossom into a life-threatening condition when compounded by hypoxia and
hypotension.  Prevention of secondary injury should be among the highest priories in any
patient with evidence or suspicion of CNS injury.  CNS assessment and/or monitoring
should be instituted at the earliest possible juncture.
Assessment of hemostasis and correction of coagulopathy
Cessation of bleeding, whether surgical or medical, is the sine qua non of resuscitation from
injury. There is little utility in targeting endpoints of resuscitation in the face of ongoing
hemorrhage. Life-threatening coagulopathy is one of the most serious complications of
patients in profound shock from massive hemorrhage, and is generally predictable at an early
stage.  Increased early transfusion requirements are also generally predictive of
subsequent organ dysfunction. [20-22] Studies have shown that ongoing coagulopathy on
admission to the ICU is independently associated with both an increase in morbidity and 30-
day mortality .
The majority of trauma patients initially present with normal or prothrombotic coagulation
profiles. However, those most seriously injured are likely to present with evidence of
hypocoagulability, accelerated fibrinolysis, or both. [24,25] Upon transfer to the ICU the
patient’s coagulation status may be in any of these states. It is essential therefore to promptly
re-assess the patient’s coagulation status in order to initiate appropriate therapy. “Standard”
laboratory tests such as prothrombin time (PT), partial thromboplastin time (PTT),
international normalized ratio (INR), fibrinogen level and platelet count are still the most
common coagulation assays in clinical use, despite considerable evidence that they provide
an extremely incomplete picture of in vivo hemostasis, [26,27] that they are poor predictors of
clinical bleeding,  and that they do not provide an adequate basis for rational targeted
hemostatic resuscitation. [29,30] Although significantly elevated admission PT and PTT
levels are predictive of increased mortality from injury,  there is little evidence that they
provide a realistic target for resuscitation. Moderately elevated values may have little clinical
significance, and correction to “normal” values may require large amounts of resuscitation
fluids, especially fresh frozen plasma (FFP). In the absence of active clinical bleeding,
attempts to normalize laboratory values have the potential to introduce transfusion- and
These deficiencies underscore the need for reliable point-of-care hemostatic monitoring with
clinical relevance in situations of generalized coagulopathy due to massive hemorrhage.
There is increasing evidence that viscoelastic monitoring technologies such as TEG®
(Haemonetics Corp., Niles, IL, USA) and ROTEM® (Tem Innovations GmbH, Munich,
Germany) are superior for detecting clinically relevant hemostatic abnormalities in trauma
and surgical patients with massive bleeding and diffuse coagulopathy. [32,33] Viscoelastic
monitoring has been much more widely used in Europe than in the United States, for both
intra-operative and ICU management of bleeding surgical and trauma patients. Schöchl and
colleagues have recently published a detailed review on the use of viscoelastic monitoring
targeted resuscitations.  It should also be noted that both viscoelastic and standard
coagulation tests are generally performed after warming specimens to 37°C, and do not
reflect the potentially considerable effects of hypothermia on in vivo hemostasis .
Because of evidence that severely injured trauma patients are likely to develop an early and
aggressive endogenous coagulopathy separate from later loss and dilution of clotting factors
compounded from hypothermia and acidosis, [31,36-41] the practice of “hemostatic”
resuscitation has become commonplace in the most severely injured patients. This entails the
early and aggressive use of hemostatic products combined with red blood cells as the primary
resuscitation fluids in order to avoid rapid deterioration into the “bloody vicious cycle” and
the classic “lethal triad” of hypothermia, acidosis and coagulopathy.  Two very distinct
paradigms of hemostatic resuscitation have currently emerged: the damage control
resuscitation (DCR) model, which uses pre-emptive administration of empiric ratios of blood
and hemostatic products to approximate whole blood, often according to an established
institutional “massive transfusion protocol” [43-47]; and goal-directed hemostatic
resuscitation approaches (also often protocol-based), which generally use point-of-care
viscoelastic monitoring (Figure 3) combined with the prompt administration of hemostatic
concentrates. [24,26,27,34] Regardless, it is highly likely that the patient with massive
hemorrhage who arrives to the ICU under-resuscitated with a coagulopathy has been
managed according to some sort of hemostatic resuscitation approach which should be
continued in the ICU until it is clear that hemostasis has been achieved. It is beyond the scope
of this review to discuss the relative merits of these two approaches in detail, however, the
critical care provider should communicate with the trauma and operative team to see where
the patient is in terms of their hemostatic resuscitation.
Figure 3 One possible decision tree algorithm for the management of clinical bleeding
using ROTEM®-guided goal-directed resuscitation with targeted hemostatic factors
[adopted from ]
With DCR, large volumes of fresh frozen plasma are frequently administered as part of the
hemostatic resuscitation and this aggressive use of FFP may be continued into the ICU
setting. This aggressive use of FFP may substantially increase the risks of adverse
complications. One study attempting to correct the INR to 1.3 in the ICU documented a high
rate of severe ARDS. [48,49] Isolated PT/INR levels are poor predictors of clinical bleeding
in trauma patients, and thrombin generation is generally preserved or even increased after
significant blood loss because of dysregulation, with loss of clotting factors balanced by loss
of regulatory inhibitors.  If FFP is being used as the primary hemostatic resuscitation
fluid and viscoelastic monitoring is not available, the ICU physician should generally accept
an INR in the 1.5-1.7 range provided there is no evidence of active bleeding. This INR target
is based on studies demonstrating a limited ability of FFP transfusions to normalize
coagulation test results with an INR < 1.7 .
Recombinant activated factor VIIa (rFVIIa) has found considerable off-label use in the
management of refractory coagulopathy in hemorrhagic shock/trauma patients. Although
initially touted as a “total hemostatic agent”, it now seems clear that rFVIIa acts mainly as a
potent thrombin generator.  High dose rFVIIa (usually > = 80–90 μg/kg) works
predominantly by a direct effect on activated platelets rather than via its higher affinity
binding to tissue factor.  Because tissue factor is expressed by inflammatory cells, there is
significant potential for systemic micro-thrombi generation, and several studies have shown a
risk of thrombotic complications on the order of 5-7%.  Efficacy of rFVIIa is dependent
on the presence of adequate substrate for clot formation such as fibrinogen and platelets, and
may be significantly impaired under acidotic conditions.  Because of these
considerations, the use of high dose rFVIIa as rescue therapy in refractory hemorrhagic shock
is controversial, and should be undertaken with caution. The ICU physician should be aware
that patients who have received rFVIIa during their resuscitation may have a normal INR
upon arrival to the ICU, but this may only be a transient finding.
In addition to the coagulopathy associated with major trauma, fibrinolysis is especially
deleterious in severely injured trauma patients and carries an associated mortality well
upwards of 50%. [24,56,57] Many patients with primary fibrinolysis from severe
hemorrhagic shock may never survive to reach the ICU. The recently concluded CRASH-2
trial is the only class I evidence to date showing a 30 day survival benefit for a resuscitative
therapy.  Subgroup analysis showed that the benefit was greatest when therapy was
instituted within 1 hour of admission. However, subgroup analysis showed that mortality
actually increased when therapy was instituted after 3 hours, suggesting that the risks of
therapy outweighed the benefits in patients who survived beyond that timeframe.  It may
therefore be prudent to carefully consider whether to administer anti-fibrinolytic therapy in
the ICU, even if the patient has laboratory evidence of fibrinolysis.
Finally, trauma patients frequently convert from a hypocoagulable to a hypercoagulable
profile once they survive the initial insult and hemorrhage.  This is important to monitor
in the ICU, as long term morbidity and mortality from thromboembolic events has a
significant impact; and it is important to discontinue hemostatic support once the patient is no
Fluid support in the ICU
Until definitive hemostasis has been achieved in the ICU, use of non-hemostatic/non-
oxygenating fluids should generally be minimized, unless concentrates are used.
Resuscitation fluids should consist mainly of blood products and hemostatic agents. Over-
aggressive fluid administration in the bleeding patient can lead to clot disruption and
exacerbate hemorrhage, resulting in the vicious cycle of increased blood loss and fluid
administration known as “fluid creep” (Figure 4). Moderate hypotension during the period of
“early resuscitation” is generally acceptable in our experience, with possible adjustment for
patients with pre-existing cardiac dysfunction or co-existing CNS injury. [8,29] Transfusion
should aim for a hemoglobin between 8 and 10 g/dL while the patient is actively bleeding, to
provide a margin for error and also to support hemostasis .
Figure 4 Potential impact of overaggressive fluid administration
Once definitive hemostasis has been achieved, the patient may still be significantly hypo-
perfused. Prolonged activation of the noradrenergic axis results in profound vasoconstriction,
which may be aggravated by hypothermia. Hypoperfusion impairs cellular energetics and
results in loss of endothelial integrity. Inflammatory cytokines and ischemia-reperfusion
injury may result in cellular edema reducing the lumen of capillaries and producing the “no-
reflow” phenomenon.  Full resuscitation of the severely injured patient requires not only
arrest of bleeding and restoring hemodynamic stability but also re-establishing micro-
circulatory flow, restoring end-organ homeostasis, and repaying the “oxygen debt”. Failure to
do this may result in the development of subsequent organ dysfunction in the
hemodynamically stable but still under-resuscitated patient.  Therefore, assuring adequate
completeness of resuscitation is the next critical challenge for the ICU physician after
establishing hemostasis. Unfortunately, over-resuscitation as well as under-resuscitation may
have adverse consequences, and the “optimal” endpoint of resuscitation may not be at all
Fluid selection may have implications for micro-circulatory perfusion, which should be the
primary goal of resuscitation once hemostasis has been attained. Some data suggest that
fluids exert micro-circulatory effects independent of volume expansion or oxygen-carrying
capacity. [63-65] There is some evidence that hyperviscous solutions such as hydroxyethyl
starch 130/0.4 or hypertonic solutions such as 7% saline with dextran may have a greater
benefit in re-establishing microvascular perfusion than standard crystalloids, [65-68] and that
the micro-circulatory benefit may be limited to a relatively small initial bolus.  “Small
volume resuscitation” has been studied more in the pre-hospital and early stages of
resuscitation as an adjunct to hypotensive resuscitation, [8,14,29,69] further study is required
to understand the effects of different resuscitation fluids on microvascular perfusion separate
from their effects as volume expanders and their potential role in the ICU resuscitation phase.
A detailed review of fluid selection for the post-resuscitation trauma patient is beyond the
scope of this review and available elsewhere .
Need for further interventions
In some cases it may be extremely difficult to differentiate surgical from coagulopathy-
associated bleeding. Continuing transfusion requirement and evidence of ongoing blood loss
in the setting of aggressive corrective efforts usually imply ongoing surgical bleeding,
irreversible shock, or profound hepatic dysfunction. Because blood products generally
increase the risk of infection, organ failure, and mortality, and because of the cumulative
effect of ongoing shock, it may be prudent to set a limit on ongoing transfusion requirements
before mandating surgical or angiographic re-evaluation of the patient to rule out occult
injury. The ICU physician should discuss this issue at an early juncture with the surgical
team. Wounds with particularly difficult anatomy and a propensity for missed injuries should
prompt even greater vigilance.
Monitoring, assessment, and endpoints of resuscitation in the ICU
Endpoints of resuscitation
While the patient is actively bleeding – whether from surgical or medical causes –
resuscitation is aimed at minimally acceptable levels of organ perfusion and homeostasis,
with the goal of avoiding irreversible shock while not exacerbating hemorrhage. It is not
possible to focus on definitive “endpoints” when the target is still moving. Physiologic
assessment and resuscitative efforts are focused during this stage on hemostasis and on
attaining basic goals with respect to temperature, acidosis, urine output and hemodynamics
Once hemostasis has been attained, resuscitation should aim at the complete restoration of
macro- and micro-circulatory stability and of end-organ homeostasis in the ICU. Although
not directly supported by randomized trials, this may be achieved with additional fluid
administration to restore circulating blood volume, in combination with analgesic and
sedative agents to dilate constricted blood vessels and improve microvascular perfusion.
Basic hemodynamic goals include a stable systolic pressure > 100 mm Hg and a heart rate
less than 100 bpm. Urine output should be normal. Normalization of pH, lactate and base
deficit are all suggestive of restored micro-circulatory perfusion. [8,29] Aggressive correction
of any residual hypothermia and coagulopathy should also be priorities during this phase.
These goals may need to be modified based on patient co-morbidities and/or the presence of
concomitant CNS injury.
How much fluid loading is beneficial is a matter of debate. Numerous studies have shown
that under-resuscitation results in “occult” or “cryptic” shock, a state of compensated shock,
which predisposes to organ dysfunction in the ICU. [62,71] Some series have found that 85%
of severely injured patients with normal hemodynamics may be hypoperfused. [72,73]
Studies have consistently indicated that persistent elevations of serum base deficit or lactate
levels are suggestive of occult hypoperfusion and are predictive or poor outcome in critically
ill patients. [16,62,74-76]. Some authors have proposed that lactate is a better marker of
occult hypoperfusion than base deficit in this population.  A recent study found that using
serial serum lactate levels to guide treatment of critically ill patients reduced overall in-
hospital mortality .
The above data, combined with observations that survivors of critical injury tended to exhibit
hyperdynamic (or “supranormal”) cardiac output  and that young severely injured trauma
patients frequently manifested significant occult myocardial dysfunction,  led to the
practice of aggressive volume loading augmented by the use of inotropes to achieve pre-
specified goals for oxygen delivery and cardiac function in the ICU. [80-86] These goals
were often difficult to achieve, required substantial volume loading and pharmacologic
support, and had mixed results [86-90] with a high rate of intra-abdominal hypertension,
pulmonary dysfunction, and other complications. [69,91] Although there seems to be some
evidence that patients who are able to mount a hyperdynamic response to injury may have
better outcomes,  current evidence suggests that supportive care with fluids to “normal”
resuscitation endpoints produces equivalent results to goal-directed resuscitation to preset
“supranormal” DO2 values, and avoids the adverse consequences of over-resuscitation. 
Taken together, it appears that the physiologic cost of supranormal resuscitation is high, and
the results at the micro-circulatory level are too questionable to support routine use of this
The particular endpoint chosen may also play a role. [92-95] Mixed venous oxygen
saturation,  central venous oxygen saturation  and left ventricular function [97-99]
have all been studied as possible endpoints, as have indicators of regional perfusion. In all
likelihood, the majority of the time these are functionally equivalent: responders tend to do
well by all endpoints, and non-responders tend to do poorly.  It is unclear how useful
these are as specific targets for resuscitation, as opposed to simply being markers of
Supranormal and goal-directed approaches to resuscitation presume that attaining macro-
circulatory targets such as cardiac output and oxygen delivery will directly lead to perfusion
at the level of the micro-circulation (Figure 5).  It is far from clear that this is actually
the case. Evolving evidence suggests that beyond a minimal level of cardiac output and
arterial pressure, there may be considerable disassociation between the micro- and macro-
circulation. [101,102] Several studies have shown not only a lack of coupling between
hemodynamics and the microcirculation, but also considerable individual variation in the
microvascular response to interventions targeting upstream endpoints. [103-105]
Figure 5 Macro- and micro-circulatory endpoints for resuscitation [adopted from
In summary, the patient in whom hemostasis is achieved early, limiting the dose of shock and
the extent of underlying organ dysfunction, may respond well to aggressive fluid loading to
restore tissue perfusion; whereas the patient with prolonged hemorrhage and shock resulting
in significant organ dysfunction may not. While a specific, targeted endpoint for resuscitation
is important for guiding subsequent therapy, the actual endpoint selected may not be
important as the use of goal-directed approach. Other considerations may influence the ICU
physician’s approach in specific cases. Regardless, it is evident that there is considerable
inter- and intra-patient variation in the Frank-Starling curves of fluid responsiveness,  and
therapy must be carefully tailored to individual needs and responses.
Missed injuries and determinants of futility
Not all patients respond to aggressive resuscitative measures. This can be due to occult injury
or poor physiologic response. A recent review of undiagnosed injuries and outcomes,
suggested up to 6.5% of all trauma-related deaths were attributable to clinically undiagnosed
injury.  Inability to explain the patient’s declining physiologic status should generally
prompt an aggressive search for missed injuries, which may entail radiographic, angiographic
and sonographic evaluation, and in some cases operative re-exploration.
After having ruled out occult injury and possible sources of ongoing hemorrhage, further lack
of response to continued resuscitation may suggest exhaustion of physiologic reserves
consistent with irreversible shock. Acidosis and hypothermia refractory to aggressive
supportive measures, decreasing responsiveness to fluids or to vasopressors (“vasoplegia”),
evidence of persistent hyperfibrinolysis on viscoelastic monitoring and diminished tissue
oxygen saturation levels have all been suggested to correlate with likelihood of irreversible
shock and non-survivable injury. While early prediction of mortality and organ dysfunction is
possible, irreversible shock can generally only be identified after repeated and persistent
efforts to resuscitate have proven unsuccessful. Futility may become an issue for these
patients. The nature and severity of the injuries and the amount of resources already
expended should certainly factor into the equation of when to discontinue further
Post-resuscitation complications in the trauma patient
As previously discussed, aggressive resuscitation of the polytrauma patient is not without the
potential for significant complications. This section will focus systematically on commonly
encountered clinical problems in the ICU that arise as a consequence of severe hemorrhagic
shock and resuscitation, including complications of transfusion and fluid therapy.
The development of hypothermia in trauma patients is complex and related to multiple
factors including presence of shock, vasodilation from anesthetic agents, environmental
exposure, infusion of large volumes of fluids, and surgical exposure. [107,108] Polytrauma
patients presenting with uncontrolled, nontherapeutic hypothermia (<35°C) appear to have an
associated increase in mortality [107,109-112] although this is an inconsistent finding in
published studies.  Whether applied therapeutically or associated with severely injured
trauma patients, hypothermia has multifactorial effects on the coagulation system with
moderate hypothermia (32°C-34°C) reducing coagulation activity by 10% for every decrease
in temperature by one degree Celsius as well as reducing the number and function of
platelets. [35,44,114] In the setting of mild to moderate, controlled hypothermia (> 33°C),
this degree of coagulopathy does not independently contribute to clinically significant
bleeding.  During active hemorrhage and resuscitation, however, avoidance of severe
hypothermia through active warming measures can be recommended based on the association
of hypothermia with increased mortality as stated above.
In addition to alterations in coagulation, hypothermia has been associated with dysrhythmias
and infections. Dysrhythmias may occur with moderate to severe hypothermia including
bradycardia, first degree heart block and QT prolongation.  Although there are no
consistent findings reported in the hypothermic trauma patient, continuous cardiac
monitoring and evaluation of metabolic parameters is warranted. Infection risk for surgical
site infections and pneumonia has been shown to be associated with hypothermia. [117-119]
Although data to support a strong cause and effect relationship for hypothermia and increased
morbidity and mortality, does not exist, our institution targets normothermia throughout the
resuscitation and early ICU phase of care. Thus, active rewarming efforts initiated in the
resuscitation bay or operating room are aggressively continued in the ICU. Targeted
temperature management systems, preferably as part of an institutional protocol, can be used
to achieve normothermia. Combination of different techniques including surface,
intravascular, fluid, and forced-air warming systems provide a multi-modal approach to
achieving and maintaining normothermia. A recent review of the relationship of hypothermia
with acidosis and coagulopathy can be accessed for more details .
Transfusion-related acute lung injury (TRALI) is underreported and under-recognized, yet
remains the leading cause of transfusion-related mortality. [121,122] TRALI is defined as an
acute lung injury (ALI) that occurs during or within 6 hours of a transfusion, with no
temporal relationship to alternative risk factors, and no evidence of circulatory overload.
[122-125] As an ALI by definition, TRALI is associated with acute onset hypoxemia
(PaO2/FiO2 gradient ≤ 300) and bilateral infiltrates on the chest radiograph. [122,124]
“Possible TRALI” is the diagnostic nomenclature used when alternative explanations for ALI
exist, such as aspiration pneumonitis, near drowning, lung contusion, or other trauma-related
etiologies. TRALI is thought to be the result of two critical events: activation of the
pulmonary vascular endothelium with priming of neutrophils, followed by transfusion of
antibodies to leukocyte antigens with resultant activation and neutrophil-mediated
cytotoxicity.  TRALI may occur as often as once for every 1271 units transfused 
with an incidence up to 8% in ICU patients.  Watson and colleagues estimated a
cumulative increase in the risk of ALI from each unit of FFP at 2.5%, and of multiple organ
failure from each unit at 2.1% .
Treatment for TRALI is supportive, and a lung-protective, low tidal volume strategy is
recommended to prevent additional lung injury.  Subsequent transfusions should be
limited when possible since repeated transfusions worsen outcomes in existing ALI.
[130,131] If a restrictive transfusion strategy is not practicable, then avoidance of plasma
from donors with pathogenic antibodies, administration of washed blood components, and
use of products with the shortest length of storage possible are recommended.  In one
study of 284 trauma patients, patients transfused with ABO-compatible plasma had over a
10% higher rate of acute respiratory distress syndrome.  Hence ABO identical blood
products, as opposed to ABO-compatible products, should be used whenever possible.
Although the reported incidence varies widely, transfusion-associated circulatory overload
(TACO) is currently the second most common cause of transfusion-related mortality.
[133,134] TACO may be confused with TRALI since both conditions present with similar
clinical and radiological findings. Large volume transfusions are not required for the
development of TACO, which may particularly affect infants and the elderly. The key
pathophysiologic difference between the two syndromes is lack of an antibody-mediated
phenomenon with TACO.  Brain natriuretic peptide may be a helpful laboratory test for
differentiating TACO from TRALI; levels are typically increased more than fourfold in the
former.  Treatment consists of supportive care, diuretic therapy, and administration of
any future transfusions at a reduced infusion rate.
Distinguishing TACO and TRALI from acute respiratory distress syndrome can be
challenging since these disorders share several clinical characteristics, including the presence
of bilateral, diffuse, infiltrates on the chest radiograph, and acute onset of respiratory distress
and hypoxemia. Table summarizes key criteria that may be used to differentiate these
Renal and electrolyte complications
Rhabdomyolysis is defined by the serum elevation of creatinine kinase (CK) as the result of
destruction or disintegration of striated muscle.  Muscular trauma is the most common
etiology, but the in some cases the cause can remain elusive. Heat stroke, inherited disorders
of carbohydrate metabolism, electrical injuries, neuroleptic malignant syndrome, and
medications can also cause rhabdomyolysis. Approximately 10-50% of patients with
rhabdomyolysis develop acute renal failure. [137,138] CK and myoglobin levels are the most
commonly used laboratory tests used to diagnose and monitor rhabdomyolysis. Normal CK
levels are less than 260 U/L, and levels greater than 5000 U/L are associated with renal
failure. With appropriate treatment, CK levels rise within 12 hours of injury, peak by 3 days,
and fall 3–5 days afterwards.  Myoglobin has a half-life of less than 3 hours and may be
a more sensitive laboratory indicator. Normal myoglobin levels are less than 1.5 mg/dL.
Treatment of rhabdomyolysis consists of early and aggressive fluid therapy, with a target of
100 to 200 mL of urine per hour. Mannitol, bicarbonate, and various antioxidants are often
used, but there are limited data to support the efficacy of these agents, and in these agents are
generally avoided in the authors’ institution.  At least one study showed a benefit of
forced diuresis with furosemide in casualties suffering from crush injuries.  Renal
replacement therapy may be required, especially for patients with severe acidosis and
hyperkalemia. It should be noted that during the renal recovery phase in rhabdomyolysis,
hypercalcemia is a common electrolyte derangement; supplemental calcium should be
avoided during this period unless hypocalcemia is symptomatic.
Hyperkalemia and hypocalcemia
While a comprehensive review of fluid and electrolyte management in the ICU is beyond the
scope of this paper, a few electrolyte derangements unique to resuscitation from hemorrhage
and severe shock are worth noting. Hyperkalemia can occur as the result of stored red blood
cell membrane degradation, loss of cellular potassium pumps, and decreased adenosine
triphosphate synthesis.  In one reported series, 16 patients who received red blood cell
transfusions developed serum potassium levels between 5.9-9.2 mEq/L and sustained cardiac
arrest.  Hyperkalemia should be treated promptly with insulin, glucose and calcium to
protect the myocardium and increase intracellular potassium shifts. Emergent renal
replacement therapy is indicated for life-threatening hyperkalemia, with or without
concomitant renal failure. Hypocalcemia, owing to the binding of calcium to citrate
preservatives in blood products, is another commonly encountered electrolyte derangement
that may persist after admission to the ICU following damage control resuscitation.
Hypocalcemia may impair hemostasis and contribute to hypotension, and should be promptly
corrected if symptomatic.
Intra-abdominal hypertension and abdominal compartment syndrome
With the advances in DCS and DCR, an improved understanding of intra-abdominal
hypertension (IAH) and abdominal compartment syndrome (ACS) has evolved.  IAH is
defined as sustained or repeated pathologic elevation of intra-abdominal pressure ≥ 12 mmHg
and ACS is defined as the sustained elevation of intra-abdominal pressures ≥ 20 mmHg that
are associated with new organ dysfunction. [142,143] Risk factors for ACS include more than
3 L of crystalloid infusion or more than 3 units of PRBCs in the emergency department,
hypothermia below 34°C, acidosis (base deficit < −14 mmol/L), and anemia (hemoglobin < 8
g/dL.  Additional factors include circulatory shock conditions and the amount of
crystalloid fluids administered. Aggressive fluid resuscitation to targeted “supranormal”
endpoints has been shown to result in an increased incidence of ACS .
IAH and ACS have profound effects on multiple organ systems. Elevation of the intra-
abdominal pressure to levels of 10 to 15 mmHg can cause cardiac failure as the result of
inferior vena cava compression and compromised venous return.  Direct compression of
the heart and pulmonary vessels results in elevated intra-thoracic pressures and a rightward
shift and flattening of the Starling curve.  At intra-abdominal pressures as low as 10 mm
Hg, oliguria may manifest as the result of compression of intrarenal blood vessels.  The
low-pressure postglomerular intrarenal vascular network is highly sensitive to compressive
forces; and renal artery blood flow has been shown in animal models to decrease in a linear
fashion with increases in intra-abdominal pressure.  IAH and ACS can cause an
imbalance between vasodilatory and vasoconstrictive mediators, mimicking the
pathophysiology of hepatorenal syndrome, and causing hepatic insufficiency. Transmission
of abdominal pressure to other compartments may result in the “multiple compartment
Successful management of IAH and ACS begins with prompt diagnosis. Physical
examination has proven unreliable with a sensitivity of less than 60%, and the current
standard of care is to measure intra-abdominal pressure by transducing urinary bladder
pressure via an indwelling catheter. [143,148] Bladder pressures should be measured in the
supine position at end-expiration, with the transducer zeroed at the iliac crest in the mid-
axillary line. [142,143] Once diagnosed, there are few nonsurgical management options.
Sedation, analgesia, and neuromuscular blockade, when combined with diuresis, fluid
restriction, dialysis, or other interventions to attenuate hypervolemia, may avert the need to
proceed to laparostomy. In many cases, prompt opening of the abdomen is the only effective
intervention for restoring end-organ function. [145,149] Laparostomy practices have become
more prevalent with the practice of DCS, with reported mortality improvements for severe
abdominal trauma approaching 50%.
Whereas hyperglycemia in ICU patients has remained a topic of debate over the past two
decades, glucose elevations are very common in critically injured trauma patients, and tight
glucose control has been associated with improved outcomes in this population. In a
retrospective cohort of 2,028 adult trauma patients, maintenance of blood glucose between
80–110 mg/Dl (4.4-5.6 mmol/L) utilizing an intensive insulin infusion protocol was
associated with a decrease in hospital length of stay and mortality. In another case
control study, improved mortality was demonstrated in a trauma population when the blood
glucose was maintained less than 150 mg/dL.
Adrenal insufficiency has a high incidence amongst critically injured patients.  In one
prospective observational study, up to 12% of all patients in shock had simultaneous
hypothyroidism and adrenal insufficiency.  Trauma-related adrenal insufficiency has
been correlated with systemic inflammatory response syndrome, and the multicenter
HYPOLYTE study found that a continuous infusion of hydrocortisone (200 mg/d for 5 days,
followed by a taper) resulted in a statistically significantly lower rate of hospital-acquired
pneumonia (hazard ratio 0.51; 95% CI 0.30-0.83; p = 0.007) and hyponatremia.  The
hydrocortisone group had more days of mechanical ventilation, but no differences regarding
other infections, organ failure, or mortality were observed. The results of this study contrast
with the CRASH study, which showed an increased risk of death in TBI patients treated with
high-dose methylprednisolone.  Before the use of steroids can be widely recommended,
the findings from HYPOLYTE should be confirmed with additional studies involving
traumatically injured ICU patients, including TBI patients.
Allogeneic blood transfusions introduce foreign antigens into the recipient, and can cause a
constellation of beneficial or deleterious clinical effects that are collectively known as
transfusion-related immunomodulation (TRIM).  Though TRIM has been thought to
have beneficial effects for renal allograft patients as evidenced by improved graft survival,
deleterious effects in the trauma population include increased risk of infections and
potentially higher mortality. The deleterious effects of TRIM on trauma patients are
purportedly caused by soluble, white blood cell derived mediators accumulating in the
supernatant fluid of stored red blood cells and soluble HLA peptides circulating in allogeneic
plasma.  A host of pro-inflammatory effects are postulated in TRIM, leading to an
increased incidence of postoperative bacterial infections, activation of endogenous
cytomegalovirus or human immunodeficiency infection, and increased short-term mortality.
TRIM appears to be a biological phenomenon that may be attenuated by the use of white
blood cell (WBC) reduced blood products, although based on limited data from randomized
controlled trials, universal WBC reduction is still not widely practiced.
Although CPDA red cell preservation techniques allow storage for up to 42 days, there is
evidence that storage beyond 14 days significantly increases inflammatory mediators and by-
products which may contribute to immune dysfunction. [157,158] Long-term storage also
leads to red cell deformity which can cause trapping in the microcirculation and ischemia.
Red cell hemolysis may lead to the accumulation of free radicals and to regional and systemic
vasoconstriction, as well as oxidative injury.  These effects could potentially be
synergistic with red blood cell damage and decreased micro-circulatory flow directly
produced by hemorrhagic shock.  Duration of transfused red cell storage has been
independently associated with an increased mortality and risk of multiple organ failure in
trauma patients even with leukoreduction. [159-163] Although the data are mostly based on
observational studies,  trauma patients are the largest surgical consumers of blood
products, and often receive the oldest blood. During acute resuscitation of massive
hemorrhage it may not be feasible to choose only more recently stored units, but as
transfusion requirements decrease the ICU physician may wish to be more selective.
Polytrauma patients with severe shock from hemorrhage and massive tissue injury present
major challenges for management and resuscitation in the intensive care setting. ICU
physicians must be prepared to receive patients in varying degrees of stability and be ready to
take over and complete the resuscitative process. In some cases “fine tuning” may be all that
is required before addressing long-term critical care needs; in others, the intensivist must be
prepared to undertake immediate massive resuscitation and correction of severe physiologic
derangements if the patient is to survive the first 24 hours of admission. How well the ICU
physician is prepared to meet these challenges may critically affect 24 hour survival after
severe injury, and also the development of potentially life-threatening complications. As the
patient becomes more fully stable, the ICU physician can then transition priorities towards
longer-range management issues.
The past decade has seen radical changes in our approaches to resuscitation from hemorrhage
and polytrauma. These changes have drastically influenced how resuscitation is carried out
both in the resuscitation bay and operating room with carryover to the ICU. Future
developments will improve our understanding of the micro-circulation and the interaction
between hemostasis, inflammation and the endothelium and will influence how we manage
these complex and challenging patients.
ACS, Abdominal compartment syndrome; ALI, Acute lung injury; CK, Creatinine kinase;
CNS, Central nervous system; DCR, Damage control resuscitation; DCS, Damage control
surgery; FFP, Fresh frozen plasma; IAH, Intra-abdominal hypertension; ICU, Intensive care
unit; INR, International normalized ratio; PT, prothrombin time; PTT, Partial thromboplastin
time; rFVIIa, Activated factor VIIa; TACO, Transfusion-associated circulatory overload;
TBI, Traumatic brain injury; TRALI, Transfusion-related acute lung injury; TRIM,
The authors declare that they have no competing interests.
All authors contributed to review concept, design and acquisition, analysis and interpretation
of the literature. Finally all authors read and approved the submitted manuscript.
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