Advances in Anesthesia 36 (2018) 1–22

ADVANCES IN ANESTHESIA

Care of the Severely Injured

Orthopedic Trauma Patient
Considerations for Initial Management, Operative
Timing, and Ongoing Resuscitation

Justin E. Richards, MD, Bianca M. Conti, MD,

Thomas E. Grissom, MD, MSIS, FCCM*
Department of Anesthesiology, University of Maryland School of Medicine, R Adams Cowley
Shock Trauma Center, 22 South Greene Street, Suite T1R77, Baltimore, MD 21201, USA

Keywords

Orthopedic surgery
Trauma
Tranexamic acid
Hemorrhagic shock

Tourniquet
Resuscitation
Polytrauma
Key points

Perioperative management of the orthopedic polytrauma patient requiring
operative intervention can be extremely challenging.

An understanding of prehospital and initial management of hemorrhage control,
including the increasing use of tourniquets and REBOA, will affect operative planning.

Decisions regarding operative timing for non–life-saving orthopedic surgical
intervention requires consultation among anesthesiologists, surgeons, and other
specialists to determine whether a definitive repair is appropriate given the
overall patient condition. Most patients, however, will be appropriate for early
definitive care and likely to benefit from this approach.

Intraoperative resuscitation of these patients starts at the point of initial contact
and will frequently continue into the operative setting. Use of antifibrinolytic
therapy has a role in the management of orthopedic trauma, although additional
study is required to assess the impact on the subpopulation with fibrinolytic
shutdown on arrival to the hospital.

Note: All authors played a role in the preparation of the article, figures, and tables. All authors attest to hav-
ing approved the final article.
Funding Source: None.
Conflicts of Interest: The authors have identified no conflicts of interest.

*Corresponding author. E-mail address: tgrissom@som.umaryland.edu

https://doi.org/10.1016/j.aan.2018.07.001
0737-6146/18/ª 2018 Elsevier Inc. All rights reserved.
2 RICHARDS, CONTI, & GRISSOM

INTRODUCTION
In the setting of major trauma, musculoskeletal injuries are the most common
indication for surgery in the severely injured polytrauma patient [1–3]. The
current consensus statement for polytrauma defines it as an abbreviated injury
score (AIS) 3 points in at least 2 body regions with a least 1 pathologic value
(systolic blood pressure 90 mm Hg, Glasgow Coma scale 8, base deficit 6,
partial thromboplastin time 40 s, or age 70) with the presence of concom-
itant limb and pelvic fractures counting as a single body region [4]. In a recent
analysis of the UK Trauma Audit and Research Network (TARN) database,
there was a 50% incidence of at least 1 limb or pelvic fracture in polytrauma
cases with an overall incidence of 81% when including isolated extremity in-
juries [5]. More than 95% of polytrauma cases occur due to blunt trauma,
with thoracic and traumatic brain injuries being the most commonly associated
injuries. Although traumatic brain injury (TBI) and exsanguination due to
hemorrhage continue to be the leading causes of death in the polytrauma pa-
tient [6,7], the presence of significant extremity injury is associated with worse
outcomes, including an increased hospital length of stay, transfusions, and
operative procedures [1]. Recent advances in management of the severely
injured orthopedic trauma patient can affect perioperative management. In
this review, we focus on some key considerations for prehospital and initial
management, operative timing, and ongoing resuscitation strategies that have
the potential to affect operative planning as well as improving outcomes.

PREHOSPITAL AND INITIAL MANAGEMENT

Prehospital management of the polytrauma patient with orthopedic injuries will
focus on the early and aggressive management of any immediate, life-
threatening injuries, including airway management and hemorrhage control, fol-
lowed by triage and transport to an appropriate treatment facility. Specific to the
management of orthopedic injuries, prehospital care focuses on reduction and
splinting of extremity fractures and control of hemorrhage using direct pressure,
topical agents, and tourniquet application. In the setting of obvious or likely un-
stable pelvic injury based on examination and/or mechanism, placement of a
pelvic binder, either commercial or improvised, also can be considered.
On arrival to the hospital, ongoing resuscitation, evaluation, and treatment
will continue to focus on the likely sources of life-threatening conditions,
including active hemorrhage. Aspects of the prehospital and initial emergency
department (ED) management may have an impact on operative planning and
can affect the anesthetic management of those patients presenting to the oper-
ating room (OR) for orthopedic procedures. This includes the use of tourni-
quets and other methods for controlling orthopedic trauma–related
hemorrhage in the setting of polytrauma.

Use of tourniquets in extremity trauma

Tourniquets, limb constrictive devices either commercially manufactured or
improvised, have been used to stop extremity hemorrhage since at least the
SEVERELY INJURED ORTHOPEDIC TRAUMA PATIENT 3

Middle Ages [8]. They are applied proximal to the injury, never over a joint,
and are effective when they eliminate distal arterial flow to the injured extrem-
ity. Although application time can be prolonged due to extended transport
times, it should be minimized where possible to limit tourniquet-related compli-
cations. Although no human trials have been conducted to determine the
maximum safe duration, most recommendations advise 2 hours as the
maximum tourniquet time, with deflation intervals if required beyond that
limit [9].
Bleeding from extremity wounds, with and without concomitant bony injury,
is a major cause of potentially preventable death in the military and civilian set-
tings [7]. Cumulative experience from recent military conflicts has shown tour-
niquets to be effective in achieving temporary hemostasis and reducing
mortality from extremity hemorrhage [10–16]. This is now translating to a
change in civilian practice, emphasizing earlier application (at the point of
injury) for blunt and penetrating trauma. The American College of Surgeons
Committee on Trauma has published evidence-based guidelines including a
recommendation for the civilian use of tourniquets when direct pressure is inad-
equate to control hemorrhage [17]. Since those recommendations, several
studies have offered additional support for tourniquet use. The first reports in
2015 focused on safety and efficacy in achieving hemostasis. Inaba and col-
leagues [18] reported their single-center experience with 87 adult patients
arriving with extremity injuries and a tourniquet applied in the ED, OR, or pre-
hospital setting. They found blunt trauma with a high Injury Severity Score
(ISS) to account for 33% of this patient group. They noted that tourniquet
use was associated with a low rate of complications with a high potential for
benefit. Similarly, Schroll and colleagues [19] reported on 197 patients admitted
to 9 Level 1 trauma centers with prehospital tourniquet application. Blunt
trauma accounted for 36% of the patients with 89% of patients having effective
hemorrhage control with tourniquet application. Compared with a military
combat casualty population, mortality and limb amputation rates were lower
in the civilian group. The investigators concluded that this large sample popu-
lation demonstrated prehospital tourniquet application was safe and effective in
a civilian population. More recently, a multicenter retrospective study by Teix-
eira and colleagues [20] compared mortality and other outcomes in 1026 pa-
tients with peripheral vascular injuries with and without prehospital
tourniquet application. The overall tourniquet use was 17%, ranging from
1.4% to 61.9% between sites. Blunt injury accounted for 45% in the tourniquet
group with the remainder from penetrating trauma. They also noted that tour-
niquet use was independently associated with a significant survival benefit
without increasing the risk of delayed amputation, although the application
rate remains low even when potentially beneficial. In general, it is anticipated
that prehospital tourniquet usage is likely to increase over the next several years.
In the perioperative setting, tourniquet application in the prehospital or ED
setting may necessitate more urgent access to the OR due to concern for limb
ischemia or damage with prolonged inflation time. Typically, however, many
4 RICHARDS, CONTI, & GRISSOM

field-applied tourniquets can be removed in the ED. In our institution, patients

with a field-applied tourniquet are evaluated for tourniquet removal after their
primary assessment. A pneumatic tourniquet is applied proximal to the existing
tourniquet that is then removed (Fig. 1). If active hemorrhage is noted, the
pneumatic tourniquet is inflated with a plan for immediate operative interven-
tion. If no active hemorrhage is noted, the pneumatic tourniquet is left unin-
flated and in place while further workup is completed before any required
operative intervention.

Initial management of severe pelvic trauma

High-energy injuries, such as those from a motor vehicle crash, can produce
significant pelvic injury and associated hemorrhage leading to hemodynamic
instability. These patients are at increased risk of morbidity and death [21].
Torso and pelvic fractures are not as amenable to tourniquet use or direct pres-
sure requiring other measures to control active hemorrhage. A recent review of
treatment options for life-threatening truncal and junctional hemorrhage pro-
vides an overview of devices available for controlling or limiting ongoing
bleeding in the prehospital or ED setting [22]. This review included a discus-
sion of junctional tourniquet systems; however, they found no documented
clinical use of these devices in the setting of hemorrhage due to pelvic fracture.
The most common initial management of severe pelvic trauma includes pelvic
stabilization with a pelvic binder (prehospital, ED, or OR) [23] or anterior
external fixation (ED or OR) [24]. Pelvic stabilization serves multiple purposes,
including the following:

Prevention of additional injury from pathologic pelvic motion

Reduction in pelvic volume limiting further blood loss

Tamponade and limitation of pelvic hemorrhage

Management of pain

Fig. 1. Bilateral lower extremity traumatic amputations with field-placed tourniquets. Note
proximal placement of pneumatic tourniquets before removal of field tourniquets and time
annotation on thigh indicating time of initial tourniquet placement.
SEVERELY INJURED ORTHOPEDIC TRAUMA PATIENT 5

With significant hemodynamic instability and rapid, ongoing exsanguination

due to arterial injury below the diaphragm, arterial inflow arrest with open
cross clamping or via percutaneous or open balloon occlusion techniques is
another option for controlling or limiting bleeding. In some patients, this
may serve as a temporary measure to allow for surgical or angioembolization
attempts at control of ongoing hemorrhage. This includes a recent surge of in-
terest in the use of resuscitative endovascular balloon occlusion of the aorta
(REBOA), which is described in more detail later in this article.
Patients with pelvic fractures can initially be divided into 2 groups: (1) stable
pelvic fracture, or (2) displaced pelvic ring fractures with hemodynamic insta-
bility or high risk for deterioration. This second group has the highest risk for
complications and mortality related to their injuries. The presence of associated
injuries to the head, chest, and abdomen can lead to conflicting priorities in
management of these patients. For example, a computed tomography (CT)
finding of a high-grade splenic injury in the setting of a severe pelvic injury
and hemodynamic instability may require an exploratory laparotomy before
addressing the pelvic injury. These patients may present for operative proced-
ures with or without early interventions, such as placement of a pelvic binder
or REBOA. As the unstable trauma patient is moved to the angiography suite
or hybrid OR, resuscitation should continue to maintain an acceptable perfu-
sion pressure; and survival is higher if this transition occurs within 3 hours
of presentation [25]. Management of these interventions in the OR requires
an understanding of the anatomy, physiology, and surgical considerations
involved in their use in the operative setting.
In trauma, REBOA has evolved as an alternative to a resuscitative thoracot-
omy with cross clamping of the aorta to reduce ongoing bleeding, increase cen-
tral perfusion pressure, and allow time for operative control of hemorrhage
[26]. In addition, it allows for a more localized approach to intra-aortic occlu-
sion compared with cross clamping, because the balloon can be inflated in
different zones to preferentially preserve more proximal perfusion with known
or suspected hemorrhage sites. Zone 1, used for intra-abdominal hemorrhage,
is occlusion in the thoracic aorta above the diaphragm; zone 2 is a nonocclusion
zone in the paravisceral aorta; and zone 3, used for pelvic and lower extremity
hemorrhage, is occlusion in the infrarenal aorta (Fig. 2). Although the use of
zone 3 may appear beneficial in terms of limiting visceral ischemic burden
and instability on reperfusion, animal studies suggest that this results in signif-
icantly less proximal hemodynamic support [27]. Nonetheless, multiple inves-
tigators have recommended use of zone 3 occlusion in the hemodynamically
unstable patient with pelvic fractures (Fig. 3) [24,26,28–30].
In-hospital placement of REBOA has also been shown to temporize venous
hemorrhage and change the treatment algorithm for hemorrhage due to pelvic
injury. Where pelvic packing was once the mainstay when angioembolization
was unavailable, REBOA deployment in zone 3 can reduce arterial inflow
decreasing blood loss and allowing for resuscitation and definitive treatment
with either surgery, angioembolization, or both (Fig. 4) [31]. Morrison and
6 RICHARDS, CONTI, & GRISSOM

Fig. 2. Anatomy and inflation zones for REBOA. Zone 1, origin of the left subclavian artery to
celiac artery; zone 2, from celiac artery to the most caudal renal artery; zone 3, from the most
caudal renal artery to the aortic bifurcation. (From Conti BM, Richards JE, Kundi R, et al. Resus-
citative endovascular balloon occlusion of the aorta and the anesthesiologist: a case report
and literature review. A A Case Rep 2017;9:155; with permission.)

colleagues [32] compared the use of a hemostatic dressing combined with direct
pressure in a swine model with an open pelvic wound with REBOA inflated in
zone 3 and found both interventions to be equally effective in controlling hem-
orrhage in the setting of normal coagulation status. In the setting of coagulop-
athy, REBOA results in better hemorrhage control, lower rate of bleeding,
higher mean arterial pressure, and lower mortality compared with direct pres-
sure with a hemostatic dressing. When effective at stabilizing blood pressure,
the usual next step involves embolization or control of hemorrhage within
the abdomen via a laparotomy and pelvic packing with or without external pel-
vic fixation. Embolization is 85% to 97% effective in controlling arterial
bleeding associated with pelvic fractures; however, these interventions require
significant ongoing support and patients may not be stable for transfer to an
angiography suite without extensive resources for ongoing resuscitation and
management, particularly after balloon deflation [33]. In those cases, use of a
hybrid OR with angiography and operative/anesthesia support may be the
best option.
To date, there are no reports specifically looking at REBOA deployment
solely for the control of hemorrhage related to severe pelvic trauma. Several
recent reports document the effectiveness of REBOA for noncompressible
truncal hemorrhage, including a subset of patients with pelvic hemorrhage
and associated pelvic fractures [28,31,34]. The first report from the American
SEVERELY INJURED ORTHOPEDIC TRAUMA PATIENT 7

Fig. 3. Anteroposterior radiograph of the pelvis demonstrating severe disruption of the pelvic
ring, a right iliac wing fracture that extends into the right acetabulum, and a right subtrochan-
teric femur fracture. REBOA catheter is visualized over the left hemipelvis (arrow). (From Conti
BM, Richards JE, Kundi R, et al. Resuscitative endovascular balloon occlusion of the aorta and
the anesthesiologist: a case report and literature review. A A Case Rep 2017;9:155; with
permission.)

Association for Surgical Trauma Aortic Occlusion for Resuscitation in Trauma

and Acute Care Surgery (AORTA) registry was published in 2016 comparing
prospective observational outcomes and procedural information for both RE-
BOA and open aortic occlusion (thoracotomy with cross clamping) [34].
This initial report from the AORTA registry included 114 patients with aortic
occlusion from 8 Level 1 trauma centers over a 15-month period. REBOA was
used in 46 patients and open aortic occlusion in 68 patients with overall sur-
vival rates of 28.2% and 16.1%, respectively. There were no significant differ-
ences in mortality, resuscitation requirements, or organ system complications
in survivors. After occlusion, REBOA patients were noted to have a higher
mean systolic blood pressure (90.0  52.9 mm Hg vs 64.6  61.1 mm Hg)
but were less likely to have an identified source of bleeding above the level
of occlusion (intrathoracic injury). There were no subgroup analyses for
zone 1 versus zone 3 deployment or for patients bleeding from pelvic fracture.
Important limitations included likely selection bias with only 5 of the 8 contrib-
uting centers having access to REBOA. The general conclusions from this
report support the continued use of REBOA over open aortic occlusion in a
subset of severely injured trauma patients.
At the same time, Moore and colleagues [28] from Houston reported on their
Level 1 trauma center experience with REBOA over a 4-year period. A total of
31 patients underwent REBOA with 14 zone 1 and 17 zone 3 deployments.
The median ISS was 34 (interquartile range ¼ 22–42) with an overall survival
rate of 32%. Pelvic bleeding accounted for 21% of the zone 1 and 53% of the
 8
RICHARDS, CONTI, & GRISSOM
Fig. 4. Pelvic trauma assessment and management algorithm showing integration of REBOA into operative planning. DRE, digital rectal examination; ER,
emergency room; EUA, examination under anesthesia; FAST, focused assessment with sonography for trauma; GI, gastrointestinal; GU, genitourinary; I&D,
incision and drainage; IR, interventional radiology; IV, intravenous; MHCP, massive hemorrhage control protocol (also known as massive transfusion pro-
tocol); RUG, retrograde urethrogram. (From Skitch S, Engels PT. Acute management of the traumatically injured pelvis. Emerg Med Clin N Am
2018;36:163; with permission.)
SEVERELY INJURED ORTHOPEDIC TRAUMA PATIENT 9

zone 3 REBOA cases. Of the zone 3 occlusion, 12 (70%) were taken to the OR
for pelvic packing with or without exploratory laparotomy for other injuries,
with the remainder going for angiography. The highest survival rate (54%)
was seen in patients undergoing zone 3 deployment with vital signs present
during REBOA placement. Nonetheless, 2 patients died in the OR attributed
to uncontrollable pelvic hemorrhage. Most recently, Brenner and colleagues
[31] have published their single-center, retrospective review including 90 pa-
tients over a 4-year period in a Level 1 trauma center. Compared with the
Houston experience, zone 1 placement was more common (81% vs 45%) likely
related to the higher incidence of traumatic arrest (63% vs 32%) as the indica-
tion for deployment. Of note, 11 patients (12%) received REBOA for nontrau-
matic hemorrhage. A total of 9 cases (82%) occurred in the OR with the
remainder in the intensive care unit or other hospital location. At the time of
REBOA placement in this subgroup, 7 patients (64%) were in arrest with 5
(45%) ultimately surviving to discharge.
Taken together, the use of REBOA appears to be on the rise as another
method for resuscitation of the patient with severe hemodynamic compromise
or potential deterioration from ongoing hemorrhage below the diaphragm,
including those with severe pelvic fractures. Concerns remain about more
broad usage since methods for controlling hemorrhage (access to angiography,
availability of a trauma surgeon, and/or OR capability) must be immediately
available. To that end, the American College of Surgeons Committee on
Trauma and the American College of Emergency Physicians have published
a joint statement regarding the clinical use of REBOA [35]. They acknowledge
the lack of high-grade evidence to guide REBOA use with a significant risk for
complications if used inappropriately. Their recommended indications for RE-
BOA use include the following:

traumatic life-threatening hemorrhage below the diaphragm in patients in hem-
orrhagic shock who are unresponsive or transiently responsive to resuscitation

patients arriving in arrest from injury due to presumed life-threatening hemor-
rhage below the diaphragm; no evidence exists for the recommended duration
of arrest and use of REBOA but should be used within the same time as would
resuscitative thoracotomy

patients with severe intra-abdominal or retroperitoneal hemorrhage, or those
with traumatic arrest with inflation at the distal thoracic aorta (zone 1)

patients with severe pelvic, junctional, or proximal lower extremity hemorrhage
with inflation at the distal abdominal aorta (zone 3)

Additionally, they emphasized that REBOA should be performed by an in-

dividual with training and experience. When performed by a nonsurgeon, the
individual must be able to have immediate availability of an acute care or
vascular surgeon trained in REBOA to address hemorrhage control and
removal of the device.
For patients presenting to the OR with severe pelvic trauma and hemorrhage
with a REBOA catheter in place, there should be advanced planning for
10 RICHARDS, CONTI, & GRISSOM

deflation of the balloon. Current recommendation is for slow deflation once

surgical or embolization has controlled most of the associated pelvic hemor-
rhage. Communication is key to ensure the surgical and anesthesia teams are
prepared for reperfusion because the patient may deteriorate after balloon
deflation and preplanning with volume loading and pressor management
may be necessary. Slow deflation should occur over several minutes with small
volumes being removed to allow for more gradual equilibration and reperfu-
sion. In the event of prolonged balloon occlusion in the setting of poorly
controlled hemorrhage or a delay in getting to more definitive treatment, early
partial REBOA may be used [36]. If the patient responded well to resuscitation
in combination with full occlusion, the balloon may be partially deflated after
10 minutes. In theory, this allows for a more normotensive resuscitation above
the level of balloon inflation while allowing some distal perfusion. This can best
be accomplished by monitoring the distal arterial pressure waveform from the
femoral sheath introducer and withdrawing small volumes from the REBOA
cuff (<1 mL of saline at a time) until a pulsatile arterial waveform is just
seen. If this is tolerated, deflation can continue slowly to complete or further
partial deflation while monitoring other markers of perfusion. Several recent
reviews of REBOA deployment and anesthetic considerations have been pub-
lished describing the physiologic changes associated with balloon deflation and
will not be covered in detail in this review [37–39].

OPERATIVE TIMING: NOW OR LATER?

General considerations
Timing of operative intervention in polytrauma patients with orthopedic in-
juries has been a topic of considerable academic and clinical discussion. Muscu-
loskeletal injuries represent common injury patterns seen in patients with high-
energy mechanisms of injury and are one of the more common reasons for
operative intervention in the trauma population [40,41]. Historically, injuries
to the extremities in multisystem trauma patients who were too critically
injured for definitive operative intervention were managed with traction and
prolonged immobilization. These patients experienced high rates of pulmonary
failure and prolonged mechanical ventilation, developed sepsis frequently, and
had high mortality rates [42,43]. Specifically, pulmonary complications have
been a common occurrence in this population of trauma patients with nearly
30% of patients with multiple extremity injuries experiencing pulmonary
morbidity [42,44]. Therefore, the goal of fracture management in the multi-
system trauma patient is restoring musculoskeletal anatomy that allows for
mobilization, pulmonary toilet, and adequate pain control.
In the patient with isolated extremity or hip fracture without polytrauma, the
evidence remains clear that early definitive fracture care improves outcomes. In
patients with hip fracture, current US [45] and Canadian [46] guidelines recom-
mend surgery within 48 hours. Within the United Kingdom, surgery within 36
hours is a quality of care indicator, although adherence to these guidelines is
incomplete [47]. These recommendations may require revision, as more recent
SEVERELY INJURED ORTHOPEDIC TRAUMA PATIENT 11

work has consistently demonstrated an increasing complication rate for

surgery >24 hours after injury [48–51]. In the most recent study looking at
the association between wait time and 30-day mortality, Pincus and colleagues
[52] examined the impact of wait time in hours on mortality and other compli-
cations, including myocardial infarction, deep vein thrombosis, pulmonary em-
bolism, and pneumonia. Among adults requiring hip fracture surgery, a wait
time of 24 hours appears to be a threshold defining higher risk. The study pop-
ulation, however, did not include many patients with significant trauma (<1%
of patients had an ISS 16) or multiple fractures (4.9%), making it impossible
to directly apply these results to the polytrauma patient. Similarly, fixation of
femur fractures in patients with a lower ISS within 48 hours of injury is also
associated with improved outcomes [53].

Pathophysiologic considerations
Decision about timing of operative interventions in the polytrauma patient with
orthopedic injuries is more complex. The inflammatory response to disruption
of soft tissue structures, including muscle and bone, may produce marked
changes in the pulmonary vascular system [54]. Furthermore, the operative
intervention required to treat severe musculoskeletal injuries may further exac-
erbate the inflammatory reaction [55–57]. Fat particles released into the sys-
temic circulation after injury resulting in a fractured bone may embolize into
the pulmonary vasculature leading to activation of neutrophils and comple-
ment resulting in endothelial damage and alterations in pulmonary capillary
permeability [56]. The end result of this inflammatory reaction is the potential
for increased pulmonary vascular resistance with an abnormal and increasing
alveolar-arterial oxygen (PAO2-PaO2) gradient [54,57]. Willis and colleagues
[57] examined the impact of a femoral fracture and subsequent operative treat-
ment in a rodent model and observed that the fracture itself was associated
with an increased pulmonary vascular resistance, and that the operative inter-
vention to achieve osteosynthesis resulted in greater pulmonary microvascular
permeability and lung neutrophil counts. Husebye and colleagues [54] also
observed in human subjects with a femur fracture that before operative inter-
vention, patients demonstrated an elevated PAO2-PaO2 gradient, lower oxygen
saturation, and decreased mixed venous oxygen saturation.
The method by which traumatic orthopedic injuries are operatively
managed is a topic of importance. Intramedullary nailing is a common fixation
approach for fractures of the femoral and tibial shaft, injuries that are common
in the patient with multisystem trauma. In addition, fractures of the humerus
may also be managed with an intramedullary device. The technical process
of inserting an intramedullary nail involves opening of the intramedullary ca-
nal, mechanical reaming to increase the diameter of the intramedullary space,
and insertion of the intramedullary device itself, which allows for rigid fracture
fixation. Previous studies have investigated the impact of intramedullary ream-
ing on cardiac and pulmonary function, compared with operative fixation
achieved by open reduction and internal fixation with a plate device that is
12 RICHARDS, CONTI, & GRISSOM

secured with screws to the outside of the bone. Schemitsch and colleagues [56]
examined pulmonary function in a canine model. Fat emboli were generated
with pressurization of the intramedullary canal; a femur fracture was created,
and subsequently fixed with reamed intramedullary nailing, undreamed, intra-
medullary nailing, or plate fixation via open reduction and internal fixation.
The investigators observed that the PAO2-PaO2 gradient was increased in all
animals after the initial insult of fat emboli, but that the method of fracture fix-
ation did not impact the pulmonary artery pressure or fat emboli content in the
lungs, kidney, or brain postmortem. Similarly, Bosse and colleagues [58] retro-
spectively examined 453 patients with femur fractures and an ISS >16 from 2
Level 1 trauma centers. They reported that there was no difference in the
occurrence of acute respiratory distress syndrome, pulmonary emboli, pneu-
monia, multiple organ failure, or death when fixation of the fracture was
with an intramedullary nail compared with open reduction and internal fixa-
tion with a plate. Considering the large amount of evidence suggesting no dif-
ference in pulmonary outcomes in patients with multisystem trauma treated
with reamed intramedullary nailing, and the considerable success of the intra-
medullary device at achieving fracture healing, this is the preferred method of
operative treatment for these trauma patients with a femur fracture at most
centers.
Invariably, many trauma patients with musculoskeletal injuries will require
an operative intervention, and although the method of that intervention has
been discussed, there remains an inherent risk of a ‘‘second hit’’ related to
that intervention [59]. The 2-hit theory describes the initial traumatic injury
as the ‘‘first hit’’ in a cascade of pathophysiologic events that are affected by
the degree of soft tissue destruction and systemic inflammation. In many clin-
ical scenarios, the pathophysiologic response to the ‘‘first hit’’ may resolve with
minimal long-term adverse sequelae. However, when the magnitude of this
initial insult is severe, causing hematologic and microvascular derangements,
trauma patients are at an increased risk of multiple organ failure [59,60].
The ‘‘second hit’’ of this phenomenon is manifested when a second insult, often
times an operative intervention but also any potential changes in patient phys-
iologic status, such as hypoxia or hypotension, occurs before resolution of the
initial ‘‘first hit.’’ In the case of patients with multisystem orthopedic trauma,
the 2-hit theory focuses on the definitive operative intervention, which aims
to address the primary musculoskeletal injuries. Previous studies in human
subjects who sustained a high-energy mechanism of injury with a mean ISS
of 31 observed that definitive fixation of a femur fracture with reamed intrame-
dullary nailing was associated with significantly increased pulmonary artery
pressures, cardiac indices, and pulmonary vascular resistance index [54]. Of
note, some of these changes were apparent from the time of intramedullary
nailing until 3 days postoperatively. Therefore, this ‘‘second hit,’’ when per-
formed at an inappropriate time, may further exacerbate the inflammatory
response and place the patient at greater risk of systemic complications, such
as multiple organ failure or acute respiratory distress syndrome.
SEVERELY INJURED ORTHOPEDIC TRAUMA PATIENT 13

Timing
Early definitive fixation of lower extremity fractures in multiply injured trauma
patients has become a standard treatment approach in most patients. Bone and
colleagues [44] solidified the basis for this practice in a prospective, randomized
controlled trial that demonstrated reduced pulmonary complications, decreased
hospital length of stay, and overall lower cost of care in patients treated with
definitive fixation within 24 hours of admission, compared with 48 hours or
later. These findings have also been corroborated by numerous other retrospec-
tive studies, such that recent practice management guidelines from the Eastern
Association for the Surgery of Trauma conditionally recommends early defini-
tive fixation [61]. However, the idea that definitive fracture care may represent
a ‘‘second hit’’ in severely injured patients with multisystem orthopedic trauma
tempered enthusiasm for early definitive care. Following the examples in the gen-
eral trauma literature and the practice of damage control resuscitation (DCR) [5],
whereby life-threatening hemorrhage is controlled in conjunction with hemody-
namic resuscitation and correction of coagulopathy followed by later definitive
repair of injuries, the concept of damage control orthopedics has evolved to mini-
mize the ‘‘second hit’’ of long-bone fracture care in patients deemed at significant
risk for pulmonary complications and multisystem organ failure. Pape and col-
leagues [62] have observed in those patients with profound shock or serious
concomitant injuries to other organ systems are at increased risk of complica-
tions after early definitive fracture fixation. Therefore, it is hypothesized by
the 2-hit theory that initial serious metabolic disturbances in the form of hemor-
rhagic shock and endothelial dysfunction may prime an inflammatory response
that is further exacerbated by definitive fracture care if the ‘‘second hit’’ occurs
during a period of underresuscitation and systemic hypoperfusion [63].
Pape and colleagues [64] proposed a grading scale to risk-stratify patients
into stable, borderline, unstable, and in-extremis categories to determine
optimal time of fracture fixation. The grading scheme and subsequent algo-
rithm incorporates various measurements of depth of clinical shock and resus-
citation requirements, such as blood pressure, units of blood transfused, serum
lactate, base deficit, platelet count, and fibrinogen level. All of these measure-
ments have demonstrated a significant association with the subsequent develop-
ment of multiple organ failure [65,66]. Serum lactate represents an easily
obtainable and readily available marker of hemodynamic resuscitation in
trauma patients. Crowl and colleagues [67] suggested that failure to clear
elevated lactate levels to normal (defined as <2.5 mmol/L) before definitive fix-
ation of a femur fracture was associated with increased complications. Howev-
er, only 2 patients in the study cohort were admitted with an elevated lactate
that subsequently normalized before definitive operative intervention. Further-
more, Pape and colleagues [64] advocated for delayed fixation in patients who
are categorized as borderline, with among other factors having a lactate of
approximately 2.5 mmol/L, to allow for adequate preoperative resuscitation.
Similarly, Morshed and colleagues [68] demonstrated that fixation of femoral
shaft fractures within 12 hours of injury was associated with increased
14 RICHARDS, CONTI, & GRISSOM

mortality, presumably due to inadequate resuscitation before definitive fracture

care. Unfortunately, lactate and resuscitation data were not provided in the
study results. The idea that underresuscitation before early definitive fracture
fixation posed a greater risk of multiple organ failure was further clinically sup-
ported by the 2-hit theory.
However, more recent advances in the assessment of clinical shock and resus-
citation of the patient with multisystem orthopedic trauma have potentially
offered greater insight into determining the optimal time of definitive operative
fixation. A retrospective, multicenter study of 294 patients with multisystem
trauma with a femur fracture and an elevated lactate at admission observed
that neither preoperative lactate nor a categorical lactate value <2.5 mmol/L
before definitive operative fixation were associated with the subsequent develop-
ment of pulmonary morbidity [69]. Even higher thresholds of preoperative
lactate, such as less than 3.5 mmol/L and less than 4.0 mmol/L, were not associ-
ated with the primary outcome of pulmonary complications. Furthermore, Nahm
and colleagues [70] developed a simpler grading system based on metabolic pa-
rameters to risk-stratify patients for safe and early definitive fixation. The inves-
tigators compared this modified clinical grading system to that proposed by Pape
and colleagues [64] and concluded that low-risk patients, defined at a pH 7.25,
base excess 5.5, and a lactate less than 4.0, were easily defined and at lower risk
of adverse outcomes if treated with a protocol for early appropriate care. In the
context of the tw2o-hit theory, an improvement toward normalization of basic
markers of resuscitation and anaerobic metabolism appears to allow sufficient re-
covery from the initial first hit of traumatic injury [71,72].
Despite these recent results that offer more precise guidance to determine
physiologic optimization before early definitive fracture care, there remain
certain patients with concomitant injuries that generate a cause for concern
before proceeding for operative intervention of an orthopedic injury. Patients
with multisystem trauma with TBI may often have significant extremity in-
juries. However, the impact of a prolonged operation in patients with intracra-
nial hypertension may predispose this population to lower cerebral perfusion
pressure and worse neurologic outcomes [73,74]. Furthermore, evidence
from patients with a femur fracture and a TBI demonstrates that intramedul-
lary reaming is associated with a significant decline in cerebral perfusion pres-
sure. Although previous studies have suggested that early definitive care may
be acceptable in patients with a head injury, it should be considered that these
patients be resolved of any intracranial hypertension, and aggressively moni-
tored and resuscitated in the perioperative period. In addition to intracranial
pathology, trauma patients who sustain a blunt mechanism of injury may
have various degrees of thoracic injuries. Numerous studies have evaluated
the impact of timing of operative intervention in patients with multisystem or-
thopedic trauma with long-bone fractures who have also sustained severe chest
trauma [75,76]. The degree of chest injury is most predictive of pulmonary
outcome and early definitive fixation is associated with reduced pulmonary
complications even in patients with thoracic trauma [69,76]. Unfortunately,
SEVERELY INJURED ORTHOPEDIC TRAUMA PATIENT 15

the optimal ventilator strategy for these patients is unknown; however, in clin-
ical practice the most reasonable approach is likely reflective of the patients’
pulmonary compliance, with attention toward maintaining functional residual
capacity, an open lung strategy, and optimal oxygenation. Last, there has
been much discussion regarding definitive fracture fixation once all intra-
abdominal injuries have been addressed and resuscitation completed. Although
Morshed and colleagues [68] noted that there was an increase in mortality in
patients with severe abdominal injuries who underwent early femur fracture
fixation, more recent data suggest that early definitive fracture care may be
safely performed in patients with an open abdomen [77], while simultaneously
correcting metabolic derangements and continuing hemodynamic resuscitation.

ONGOING RESUSCITATION
General considerations
The ideal resuscitation strategy in the polytrauma orthopedic patient has not
been completely elucidated. Whether or not a massive transfusion strategy
based on a resuscitation ratio (ie, 1:1:1 of blood:plasma:platelets) is appropriate
during the intraoperative period for definitive fracture care is unknown; how-
ever, it is clinically prudent to maintain a balanced resuscitation that corrects
underlying metabolic disturbances and adjust the serum pH toward more
normal parameters [72]. It is becoming more clearly understood that severe
trauma and soft tissue injury degrades the microvascular endothelial glycoca-
lyx and is represented by elevations in inflammatory markers, such as serum
lactate [78]. This predisposes patients to alterations in coagulation function
and ultimately multiple organ failure. Future work is being conducted to eval-
uate the role of plasma resuscitation and restoration of the endothelial glycoca-
lyx and will provide valuable data that may be useful in the intraoperative and
perioperative management of polytrauma orthopedic patients [79]. Although it
may be commonly expected that such patients are at risk for coagulation dis-
turbances and may present for definitive fracture fixation demonstrating hypo-
coagulability [80], there is likely also an underappreciation for patients who are
hypercoagulable. The emergence of viscoelastic testing allows for real-time
evaluation of coagulation and identification of specific components of the clot-
ting pathway that are deficient, or even potentially expressed in excess. Ortho-
pedic trauma patients are known to be at greater risk of thromboembolic
complications during hospitalization, and viscoelastic tests have demonstrated
value in identifying these events in patients with severe extremity injuries
[81]. In addition, intramedullary reaming may generate a prothrombotic state
via activation of platelets and inhibition of fibrinolytic activity [54]. Ultimately,
continuous assessment of coagulation and a balanced, goal-based resuscitation
is of significant value in the severely injured orthopedic trauma population.

Role of antifibrinolytic therapy

A full review of resuscitation strategies for the severely injured orthopedic pa-
tient is beyond the scope of this review and can be found in multiple recent
16 RICHARDS, CONTI, & GRISSOM

reviews [82,83]. One element found in many of these strategies, however, does
deserve specific discussion relative to severe orthopedic trauma, the use of tra-
nexamic acid (TXA). The publication of results from the Clinical Randomiza-
tion of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) trial in 2010
showing a reduction in death due to bleeding in trauma for patients allocated to
receive the antifibrinolytic TXA compared with individuals receiving placebo
has resulted in the inclusion of TXA in multiple guidelines and resuscitation
strategies for the trauma patient population [84]. Early TXA administration ap-
pears to decrease mortality in both civilian [85] and military populations [86],
but a later analysis of the CRASH-2 trial suggested that late administration, af-
ter 3 hours, may be less effective and potentially harmful [87]. The need for
early administration was confirmed in a mixed population study of TXA
used in the setting of ongoing or potential hemorrhage. Gayet-Ageron and col-
leagues [88]. conducted a meta-analysis of individual-level patent data on the
effect of treatment delay on the effectiveness of TXA in acute severe bleeding
(traumatic and postpartum hemorrhage). Using results from the CRASH-2 and
World Maternal Antifibrinolytic (WOMAN) trials [89], the investigators
concluded that even a short delay in treatment reduces the benefit of TXA
administration with no impact on vascular occlusive events. Overall, survival
benefit decreased by 10% for every 15 minutes of treatment delay up to 3 hours
after injury at which point no benefit could be identified.
Concern remains, however, for the potential to increase thromboembolic
complications with the use of TXA. As noted previously, there are multiple fac-
tors in the orthopedic trauma patient that already create a prothrombotic state.
In addition, Moore and colleagues [90] have identified a subset of trauma pa-
tients who appear to have fibrinolytic shutdown manifested by increased circu-
lating plasminogen activator activity and decreased evidence of fibrinolysis on
viscoelastic monitoring. The addition of TXA to this subgroup of trauma pa-
tients with fibrinolytic shutdown and a heightened prothrombotic state has
been theorized to increase the incidence of vascular occlusive events. To
date, the only study examining the effect of TXA on different patterns of fibri-
nolysis (shutdown, physiologic, systemic) found that TXA administered to pa-
tients in fibrinolytic shutdown did not increase mortality; however, TXA use
was associated with increased mortality in patients showing a physiologic
(normal) level of fibrinolysis on admission [91]. With regard to thromboem-
bolic complications, Johnston and colleagues [92] completed a review of
TXA use by US military medical personnel and noted an overall increased
risk of venous thromboembolism (VTE) with the use of TXA, although this
has not been consistently reported in other studies.
The questions of TXA with respect to timing and VTE are particularly perti-
nent to the patient with severe orthopedic trauma. Based on the extensive work
done on the use of TXA in an elective orthopedic surgical population looking
at blood loss and transfusion requirements [93–95], there has been a natural
extension of this literature to the orthopedic trauma population requiring sur-
gical interventions. In the elective orthopedic surgical population, TXA
SEVERELY INJURED ORTHOPEDIC TRAUMA PATIENT 17

administration either intravenously or topically, is associated with fewer trans-

fusions, decreased blood loss, and no increase in VTE complications. Overall,
TXA appears to have an acceptable safety profile in the elective surgical pop-
ulation. The data are not as clear with orthopedic trauma procedures. A recent
meta-analysis identified 12 studies with use of TXA in patients undergoing or-
thopedic trauma surgery for fractures (3 femoral neck, 3 hip, 3 intertrochan-
teric, 1 calcaneus, 1 acetabular, 1 femoral shaft) [96]. Patients in this analysis
were not stratified by ISS or other markers of severity of injury with most pa-
tients presenting with single system injury from a low-energy mechanism.
Overall, the findings were similar to those for the elective surgical population.
In each of these studies, TXA was administered at the time of surgery. As
noted previously, the general resuscitative approach in the orthopedic poly-
trauma patient with ongoing hemorrhage and/or hemodynamic instability
would be early administration of TXA at time of initial assessment to optimize
benefit. It is unclear if this would have an impact on blood loss and intraoper-
ative transfusion requirements. Additionally, it is not known if multiple admin-
istration of TXA (at admission and in the OR) is beneficial or more likely to
result in thromboembolic complications. Additionally, the CRASH-2 trial sec-
ondary analysis did find that late administration, such as would typically occur
with an orthopedic surgical procedure, may be potentially harmful [87].
In summary, current data suggest that intraoperative administration of
TXA in orthopedic trauma patients presenting with single-system injury
from a low-energy mechanism is safe and can reduce blood loss and transfu-
sion requirements. In the setting of polytrauma with physiologic disturbance,
TXA is most likely beneficial if administered early as part of a DCR strategy
[97,98]. The impact of later administration of TXA in the orthopedic
polytrauma patient presenting to the OR is unknown, although clear
evidence of fibrinolysis on laboratory or viscoelastic monitoring would sup-
port its use.

SUMMARY
Perioperative management of the orthopedic polytrauma patient requiring
operative intervention can be extremely challenging. An understanding of pre-
hospital and initial management of hemorrhage control, including the
increasing use of tourniquets and REBOA, will affect operative planning. De-
cisions regarding operative timing for non–life-saving orthopedic surgical inter-
vention requires consultation among anesthesiologists, surgeons, and other
specialists to determine whether a definitive repair is appropriate given the
overall patient condition. Most patients, however, will be appropriate for early
definitive care and likely to benefit from this approach. Intraoperative resusci-
tation of these patients starts at the point of initial contact and will frequently
continue into the operative setting. Use of antifibrinolytic therapy has a role
in the management of orthopedic trauma, although additional study is required
to assess the impact on the subpopulation with fibrinolytic shutdown on arrival
to the hospital.
18 RICHARDS, CONTI, & GRISSOM

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