General principles of fracture management: Early and late complications

INTRODUCTION — Fractures are associated with a range of potential complications. Acute complications occur as a direct result of the trauma sustained and can include damage to vascular structures, nerves, or soft tissue. Delayed complications may occur after initial treatment or in response to treatment. Therefore, reevaluation at regular intervals during healing is prudent in most cases.

Major acute and long-term complications of fractures are described here. The management of specific fractures and some specific complications are discussed in detail separately. (See "Acute compartment syndrome of the extremities" and "Osteomyelitis associated with open fractures in adults" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

LIFE-THREATENING CONDITIONS — Certain fractures can cause severe hemorrhage or predispose to other life-threatening complications. Femur fractures that disrupt the femoral artery or its branches are potentially fatal [1]. Pelvic fractures can damage pelvic arteries or veins causing life-threatening hemorrhage; the more displaced the pelvic fracture, the greater the potential blood loss [2]. Hip fractures, particularly in older adults, may prevent ambulation, resulting in potentially life-threatening complications, such as pneumonia, thromboembolic disease, and possibly rhabdomyolysis, especially if there is a prolonged period of immobility. Patients with multiple rib fractures are at substantial risk for pulmonary contusion and related complications. (See "Midshaft femur fractures in adults" and "Pelvic trauma: Initial evaluation and management" and "Overview of common hip fractures in adults" and "Initial evaluation and management of rib fractures".)

ACUTE COMPLICATIONS

Arterial injury — Proper fracture healing requires adequate blood supply to the injured site. However, fractures can involve sharp bone fragments that injure adjacent arteries, causing hemorrhage and possibly disruption of distal blood supply to a limb, and potentially impairing bone healing. Certain fractures are associated with particular arterial injuries (table 1) [3]. In all cases, the distal and proximal pulses of any fractured extremity should be examined as early as the fracture is identified and at follow-up encounters to ensure the adequacy of arterial flow. Immediate reduction and immobilization is required for any fracture associated with neurovascular compromise. A detailed examination of the extremity should be documented at the initial presentation so that changes in the neurovascular status can be recognized.

In cases of high-velocity trauma, angiography may be needed to define vascular injury, as the presence of distal pulses does not always indicate intact proximal arteries. Signs of disrupted arterial flow may include a cool extremity, mottled skin color, and loss of sensation. (See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Clinical presentations'.)  

Arterial disruption can occur with fractures in the region of the elbow or knee. Fractures around the elbow without distal pulses but with a warm hand demonstrating good capillary refill warrant orthopedic consultation but can generally be observed. Conversely, fractures around the knee without distal palpable pulses are considered a surgical emergency and the surrounding vascular anatomy should be evaluated emergently with diagnostic imaging.

Nerve injury — Nerves are susceptible to damage from fracture fragments acutely but can also be injured during treatment from complications of casting or by excessive callus formation. (See "Overview of upper extremity peripheral nerve syndromes", section on 'Compression' and "Overview of upper extremity peripheral nerve syndromes", section on 'Transection' and "Overview of lower extremity peripheral nerve syndromes", section on 'Compression' and "Overview of lower extremity peripheral nerve syndromes", section on 'Transection'.)

Certain nerves are particularly susceptible to injury because of their proximity to common fracture sites (table 1). As an example, the median nerve is often injured in association with distal radius fractures. The reported incidence of this complication is up to 17 percent [4]. The mechanism for median nerve injury can involve stretching of the nerve due to fracture fragment displacement, or possibly swelling around the distal radius or excessive wrist flexion of the cast, both of which increase pressure within the carpal tunnel [5]. Humeral shaft fractures are commonly associated with radial nerve injury, manifested by loss of the ability to extend the wrist and fingers. This can be seen on presentation or after splinting. Most often, no intervention other than observation is necessary and the injury eventually resolves with time. (See "Distal radius fractures in adults" and "Midshaft humerus fractures in adults", section on 'Radial nerve injury'.)

With any extremity fracture, sensory and motor function should be examined at the time of presentation. Pain often limits the initial evaluation and adequate analgesia must be provided. Immediate reduction and immobilization is required for any fracture associated with neurovascular or skin compromise.

Complete or partial nerve transection, or excessive nerve stretch or compression, from fracture fragments or the force of the initial trauma can lead to chronic nerve injury. Nerve injury that is not present initially but presents after immobilization can be caused by excessive pressure from the cast or splint, or from stretching of the nerve from abnormal positioning during immobilization. Generally, such delayed injuries result in neurapraxia, in that the nerve fibers are not permanently damaged, but physiologically the nerve signal is interrupted. Transient neurapraxia generally resolves by two to three months with proper treatment, which includes ensuring that the nerve is allowed to heal without stretching or prolonged compression [6]. Reexamination following immobilization to characterize any residual deficits is essential and should be documented.

Compartment syndrome — The muscle groups of human limbs are divided into sections, or compartments, formed by strong, potentially unyielding, fascial membranes. Acute compartment syndrome (ACS) occurs when increased pressure within a compartment compromises the circulation and function of tissues within that space. With fractures, bleeding or swelling within a fascial compartment creates the increased pressure. ACS is discussed in detail separately. (See "Acute compartment syndrome of the extremities".)

Long bone fractures are the injuries most commonly associated with ACS, particularly fractures of the tibia, distal radius, supracondylar area of the humerus, and occasionally the femur (table 2). In addition to excessive intracompartmental fluid, ACS can also be caused by casts or bandaging that limits the space available for soft tissue swelling.

Early recognition of ACS and immediate fasciotomy may be limb sparing. Early symptoms and signs can include pain out of proportion to the apparent injury, persistent deep ache or burning pain, paresthesias, and pain with passive stretching of muscles in the affected compartment. When ACS is recognized, any circumferential cast, splint, or bandage should be loosened or cut to decrease the intracompartmental pressure, and orthopedic surgery consultation obtained immediately.

Thromboembolic disease — Major orthopedic trauma substantially increases the risk for venous thrombosis and its sequelae (eg, pulmonary embolism) (table 2). Therefore, patients hospitalized with major fractures receive prophylactic treatment to prevent the development of deep vein thrombosis (DVT). Although minor fractures are associated with an increased risk for DVT, thromboprophylaxis is typically not indicated. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients", section on 'Assess risk for thrombosis'.)

Given the increased risk for DVT associated with trauma, imaging studies are needed to assess fracture patients with suggestive clinical findings, which may include warmth, swelling, or edema of the limb, pain that may be out of proportion to the fracture findings, or pain that is distant from the fracture site. The diagnosis and management of DVT is discussed separately. (See "Overview of the causes of venous thrombosis", section on 'Trauma' and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)

Fat embolism syndrome — Fat embolism syndrome (FES) is a difficult diagnosis associated with closed long bone fractures of the lower extremity, most commonly involving the femoral shaft. FES typically manifests 24 to 72 hours after injury with dyspnea, tachypnea, and hypoxemia. Neurologic abnormalities and a petechial rash may be present. Severe respiratory distress and death can occur. FES is discussed in detail separately. (See "Fat embolism syndrome".)

Open fractures — Open fractures are those with direct communication between the fracture and the environment due to traumatic disruption of the intervening soft tissue and skin. Open fractures have a higher incidence of infection than closed fractures. Up to 10 percent of open fractures may still develop acute compartment syndrome as the open wound may not decompress all affected compartments in the limb [7]. (See "Osteomyelitis associated with open fractures in adults" and "Acute compartment syndrome of the extremities".)

Management of open fractures depends to some degree upon the extent of soft tissue damage, the degree of wound contamination, and the underlying health of the patient. All open fractures receive the following treatment [8]:

●Immobilization

●Antibiotics

●Tetanus prophylaxis as indicated (see "Tetanus")

●Analgesia as needed

●Prompt irrigation and debridement

Irrigation of an open wound using a sterile isotonic saline solution and low pressure is a sound approach. According to an international, blinded, randomized trial involving 2447 patients, no improvement in outcome was noted when either higher pressure irrigation or a soap solution was used to clean open fractures [9]. (See "Surgical management of severe lower extremity injury", section on 'Debridement and irrigation'.)

In addition, early wound closure reduces infection risk and is performed whenever possible [8]. The pathogens and antibiotics used for prophylaxis against open fracture infection are discussed separately. (See "Osteomyelitis associated with open fractures in adults".)

Classification systems have been developed to determine the risk of infection in open fractures. Risk increases in correlation with the size of the wound, severity of soft tissue and bone damage, degree of contamination, and whether wound coverage is adequate. The most commonly used classification system is described in the attached table (table 3) [8,10]:

In addition to fracture characteristics, the number and severity of patient comorbidities also increases the risk of infection. Host factors associated with infection and compromised wound healing include age ≥80 years, nicotine use, diabetes, active malignancy, pulmonary insufficiency, and immunocompromised states. The following infection rates have been reported [11]:

●Class A (no comorbid factors): 4 percent

●Class B (1 to 2 comorbid factors): 15 percent

●Class C (3 or more comorbid factors): 31 percent

Fracture blisters — Blisters can develop over the site of traumatic fractures, usually in areas where the skin is significantly swollen or the soft tissue is injured. They typically develop within the first one or two days after the acute trauma. Blisters are filled with either clear fluid (partial thickness skin injury) or blood (full thickness, hemorrhagic injury) [12]. The most common locations for fracture blisters are over the tibia, ankle, and elbow [13-15].

In a retrospective series of 53 fracture blisters associated with trauma, patients who had surgery within four hours after their acute injury had the lowest incidence of blister formation (2 percent), while the highest incidence was reported among those whose surgery was delayed over 24 hours (8 percent) [15]. When fracture blisters were present before surgery, wound complications (eg, post-operative wound infections) developed at a higher rate. Fifteen of the blisters in this series were found to have sterile, transudative fluid in subepidermal vesicles. When blisters ruptured, the wound was contaminated by skin flora in all 11 cases.

Fracture blisters should not be disrupted if at all possible. Once disrupted, they can become infected with skin flora. Disrupted blisters may do better if an ointment such as silver sulfadiazine is applied to promote re-epithelialization and to prevent infection or by leaving the blistered skin on as a biologic dressing after the blister has drained.

NON-ACUTE COMPLICATIONS

Osteomyelitis — Osteomyelitis is infection localized to bone. Trauma, including fractures, is one of several possible causes. Osteomyelitis is discussed in detail separately; aspects of particular relevance to fractures are described here. (See "Osteomyelitis associated with open fractures in adults" and "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis".)

Post-traumatic osteomyelitis accounts for up to 47 percent of cases [16]. Open fractures are at greater risk, with infection rates reported to range from 2 to 50 percent [8,10,17]. The extent of soft tissue injury at presentation appears to be the most significant risk factor. With open fractures, copious irrigation and fracture stabilization are important for reducing the risk of infection [8].

Acute osteomyelitis usually presents with gradual progression of dull localized pain over several days. Local findings (tenderness, warmth, erythema, swelling) and systemic symptoms (fever, rigors) may be present. Decreased range of motion, point tenderness, and joint effusions may be seen but are also present with uninfected fractures, making clinical diagnosis potentially difficult.

In some cases, osteomyelitis presents with few symptoms or signs. This is more common with subacute or chronic infections, with infections of the hip, pelvis, or vertebrae, and in young patients. Chronic osteomyelitis may present with pain, erythema, or swelling, sometimes in association with a draining sinus tract. Fractures that are healing slower than expected or that remain extremely painful despite adequate immobilization may be complicated by osteomyelitis. Intravenous antibiotics and surgical debridement are the mainstays of therapy.

Nonunion and malunion — Incomplete healing of a fracture where the cortices of the bone fragments do not reconnect is called a nonunion. When a fracture heals with a deformity (eg, angulation, rotation, incongruent joint surface), this is called a malunion. A subset of fractures is more susceptible to these complications (table 2).

Nonunions commonly present with persistent pain, swelling, or instability beyond the time when healing should normally have occurred. In most cases, symptomatic nonunions are treated with open reduction and fixation. Some nonunions are asymptomatic and treatment is unnecessary. An example of such a nonunion is spondylolysis of the lumbar pars interarticularis, where a fibrous union can provide sufficient stability and often forms without causing persistent symptoms.

Common reasons for nonunion and malunion include a tenuous blood supply to the fractured bone (eg, scaphoid, proximal fifth metatarsal, talar neck), behaviors that interfere with bone healing (eg, smoking, chronic alcohol abuse), poor bone fixation (ie, excessive movement at the fracture site), poor apposition of bone fragments (ie, fragment ends too far from one another), and infection [18]. Fractures sustained during high energy trauma, particularly open fractures and those associated with severe soft tissue injury, are at increased risk for nonunion. Patients whose baseline risk for nonunion is elevated due to chronic disease, such as those with diabetes, osteoporosis, obesity, malnutrition, or neuropathy, must be reevaluated frequently (usually weekly or every other week) during the course of fracture healing. Immunosuppression, malignancy, and local infection may also impair fracture healing. (See 'Osteomyelitis' above.)

Some medications may inhibit bone healing and should be used cautiously after a fracture occurs. However, many studies of the effect of medications upon bone healing use animal models and should be interpreted conservatively when considering the effect on humans. The following table lists some of the agents known to adversely affect bone healing after a fracture (table 4). Drugs that affect bone metabolism generally are discussed in detail separately. (See "Drugs that affect bone metabolism".)

Drugs that may impair fracture healing include the following:

●Nonsteroidal anti-inflammatory drugs (NSAIDs): The effect of these drugs on bone healing is discussed separately. (See "Nonselective NSAIDs: Overview of adverse effects", section on 'Healing of musculoskeletal injury'.)

●Glucocorticoids: Glucocorticoids are known to impair bone metabolism and reduce bone density, but animal studies of their effect on fracture healing have shown inconsistent results. Effects may be dose dependent [19]. (See "Clinical features and evaluation of glucocorticoid-induced osteoporosis", section on 'Pathogenesis'.)

●Select antibiotics: Multiple fluoroquinolones have been implicated in impaired fracture healing [20]. The mechanism is thought to involve effects on cartilage growth and production. Studies of gentamicin and tetracycline report mixed results in effects on bone healing [21,22].

●Bisphosphonates: In some animal studies, bisphosphonates are found to aid in the formation of dense, strong callus following fracture. However, some research suggests that these drugs may arrest bone remodeling and weaken bone. Controlled studies of fracture healing in patients who take bisphosphonates are lacking. The fracture risks associated with bisphosphonates are discussed separately. (See "Risks of bisphosphonate therapy in patients with osteoporosis", section on 'Atypical femur fracture'.)

●Chemotherapy agents: Some chemotherapeutic medications inhibit rapidly reproducing cells, and these may impair normal bone healing following a fracture.

●Anticoagulants: Warfarin and heparin can delay fracture healing [23]. The osteoclast stimulation caused by these medications results in increased bone resorption, decreased bone formation, and less dense calcification of the fracture callus. These effects are more common with unfractionated heparin, so low-molecular-weight heparins are a safer choice for deep vein thrombosis (DVT) prophylaxis after fracture [24]. (See "Drugs that affect bone metabolism", section on 'Anticoagulants'.)

A number of environmental factors increase the risk of nonunion, including cigarette smoking and excessive alcohol use [25-30].

Certain fractures are more often associated with nonunion because of their tenuous blood supply. These include fractures of the following bones:

●Scaphoid – Scaphoid fractures have a high propensity for nonunion despite optimal care. (See "Scaphoid fractures".)

●Fifth metatarsal – Fractures of the proximal diaphysis of the fifth metatarsal (Jones fracture) are at high risk for nonunion despite optimal care. (See "Proximal fifth metatarsal fractures".)

●Hamate – Hook of the hamate fractures are commonly misdiagnosed as wrist sprains and frequently result in nonunion. (See "Hamate fractures".)

●Tibia – Open tibia fractures with significant displacement are at high risk for nonunion. (See "Overview of tibial fractures in adults".)

●Femoral neck and talar neck ‒ These fractures have a higher incidence of nonunion and avascular necrosis due to their relatively tenuous blood supply.

Complex regional pain syndrome — Complex Regional Pain Syndrome (CRPS), also known as Reflex Sympathetic Dystrophy (RSD), is a complex disorder of the extremities characterized by localized pain, swelling, limited range of motion, vasomotor instability, skin changes, and bone demineralization. Fractures, with or without a nerve injury, are a common inciting event. Early recognition and initiation of therapy is important for successful treatment. CRPS is discussed in detail separately. (See "Complex regional pain syndrome in adults: Pathogenesis, clinical manifestations, and diagnosis" and "Complex regional pain syndrome in adults: Treatment, prognosis, and prevention".)

Post-traumatic arthritis — Fractures with joint involvement can cause damage to articular cartilage, ultimately resulting in premature osteoarthritis. (See "Epidemiology and risk factors for osteoarthritis" and "Clinical manifestations and diagnosis of osteoarthritis".)

ADDITIONAL INFORMATION — Several UpToDate topics provide additional information about fractures, including the physiology of fracture healing, how to describe radiographs of fractures to consultants, acute and definitive fracture care (including how to make a cast), and the complications associated with fractures. These topics can be accessed using the links below:

●(See "General principles of fracture management: Bone healing and fracture description".)

●(See "General principles of fracture management: Fracture patterns and description in children".)

●(See "General principles of acute fracture management".)

●(See "General principles of definitive fracture management".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General fracture and stress fracture management in adults" and "Society guideline links: Acute pain management".)

SUMMARY AND RECOMMENDATIONS

●Life-threatening complications – Fractures are associated with a range of potential complications (table 2). Pelvis and femur fractures can cause severe hemorrhage; hip and multiple rib fractures predispose to other life-threatening complications, primarily deep vein thrombosis and pulmonary contusion, respectively. (See 'Life-threatening conditions' above.)

●Acute complications – Acute complications occur as a direct result of the trauma sustained and can include damage to vascular structures, nerves, or soft tissue (table 1). Long bone fractures (eg, tibia) are most often associated with acute compartment syndrome, a limb-threatening condition. (See 'Arterial injury' above and 'Nerve injury' above and 'Compartment syndrome' above.)

●Thromboembolic complications – Major orthopedic trauma substantially increases the risk for venous thrombosis and prophylactic treatment is indicated in most cases. (See 'Thromboembolic disease' above.)

●Delayed complications – Delayed complications may occur after initial treatment or in response to treatment. Examples include osteomyelitis, nonunion, and post-traumatic osteoarthritis. Open fractures are at greater risk for osteomyelitis. The particular fracture types and medications associated with fracture nonunion are described in the text. Frequent reevaluation of high risk fractures is imperative to help prevent nonunion or malunion. (See 'Osteomyelitis' above and 'Nonunion and malunion' above and 'Complex regional pain syndrome' above and 'Post-traumatic arthritis' above.)