Pathophysiology, classification, and causes of acute extremity compartment syndrome

INTRODUCTION — Any pathologic process that results in increased pressure within a muscular compartment exceeding the perfusion pressure of the tissue has the potential to cause extremity compartment syndrome. Most cases of acute extremity compartment syndrome are associated with trauma and/or vascular disorders, but a variety of other conditions can lead to increased compartment pressure and extremity compartment syndrome.

The pathophysiology, classification, and etiologies of acute extremity compartment syndrome are reviewed here. The clinical features, diagnosis, and treatment of acute extremity compartment syndrome, including fasciotomy techniques and management following fasciotomy, are reviewed elsewhere. Chronic compartment syndromes are reviewed separately. (See "Acute compartment syndrome of the extremities" and "Upper extremity fasciotomy techniques" and "Lower extremity fasciotomy techniques" and "Patient management following extremity fasciotomy" and "Chronic exertional compartment syndrome".)

PATHOPHYSIOLOGY — Multiple explanations for the complex pathophysiology of acute extremity compartment syndrome exist [1]. In all cases, the final common pathway is cellular anoxia [2]. Any etiology that increases the fluid volume within a muscle compartment, or restrains the external expansion of the compartment, will increase the internal pressure of the compartment because of the relatively nondistensible fascia that encloses the muscles.

The most widely accepted hypothesis for the pathophysiology of acute extremity compartment syndrome is the arteriovenous pressure gradient theory [3]. The increased compartment pressure restricts local tissue perfusion by reducing the arteriovenous pressure gradient (reduced arterial pressure, increased venous pressure) and, if prolonged, will result in cellular anoxia leading to damage to nerve and muscle tissues [3]. A vicious cycle ensues, in which capillary flow deteriorates owing to an increase in compartment pressure, which further reduces tissue perfusion, enhancing blood vessel permeability and further increasing internal pressure (figure 1) [4]. Inadequate venous drainage further increases pressure. Compartment pressures capable of compromising perfusion develop when they rise to within 10 to 30 mmHg of diastolic pressure; muscle oxygenation decreases as tissue pressure approaches mean arterial pressure [2,5,6]. Therefore, acute extremity compartment syndrome develops based on both compartment and systemic blood pressures. As an example, compared with a normotensive patient, a patient with hypotension is less likely to tolerate any given increase in tissue pressure.

Nerve conduction disturbances emerge when the difference between the compartment and diastolic pressure becomes less than 30 mmHg or compartment pressure becomes greater than 30 mmHg [7,8]. If this occurs, patients may perceive altered sensation at the affected site and exhibit decreased performance in the two-point discrimination test. However, nerve conduction studies are not sensitive enough to detect an increase in compartment pressure [9]. If the compartment pressure continues to rise beyond this point, nerve conduction eventually ceases and motor paralysis will occur [10]. In the setting of compartment syndrome, nerve conduction studies will show a decrease in both the amplitude of sensory nerve and action potential and compound muscle action potential [9]. Further progression of ischemia results in cell death and myocytolysis. The degree of muscle damage depends on the duration of extremity ischemia and the metabolic rate of the tissue, though damage typically becomes irreversible after four to eight hours [11]. Ultimately, long-term ischemia may lead to liquefactive necrosis of the muscles within the compartment.

It is important to note that chronic arterial occlusive disease more commonly affects the lower extremity, which may favor the development of collateral circulation and precondition the muscle to ischemia. These changes may increase the relative tolerance of the limb to additional ischemia and alter the clinical presentation. (See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Acute-on-chronic limb ischemia' and "Patient management following extremity fasciotomy", section on 'Ischemia-reperfusion'.)

CLASSIFICATION — Extremity compartment syndromes are described as acute or chronic. The subcategories of acute compartment syndrome as described for the upper extremity are given below, but these are equally applicable to the lower extremity as well [12,13].

Chronic extremity compartment syndrome is characterized by recurrent, transient increases in compartment pressures during exercise with transient neurologic symptoms and pain, which resolve with rest. (See "Chronic exertional compartment syndrome".)

Impending compartment syndrome — With acute impending (incipient) compartment syndrome, tissue pressure has begun to increase and tissue perfusion is reduced, but is not sufficient to cause muscle or nerve damage. Compartment pressure is usually at or below a critical pressure threshold.

Impending compartment syndrome can arise from swelling following trauma or systemic inflammatory response syndrome (SIRS). In addition, extremity reperfusion following prolonged ischemia can be included in this category because reperfusion injury can lead to swelling and increased compartment pressures.

In these clinical settings, careful serial clinical examination is required, and sometimes a prophylactic fasciotomy is performed. (See "Upper extremity fasciotomy techniques", section on 'Impending' and "Surgical management of severe lower extremity injury", section on 'Extremity fasciotomy' and "Lower extremity fasciotomy techniques", section on 'Impending'.)

Established compartment syndrome — Acute compartment syndrome (ACS) occurs when the pressure in the compartment rises sufficiently to cause tissue ischemia. When pathologic tissue pressure elevation has been present for less than four hours, ACS has been defined as in the early stage, and if more than four hours, in the late stage. The designation of early versus late ACS relates to the probability of muscle injury; the likelihood of irreversible myonecrosis increases in proportion to the duration and intensity of ischemia. Muscle damage generally starts after four hours of muscle ischemia [11], recognizing that the tolerance to ischemia may vary between patients based on the severity of ischemia and the presence of collateral flow. In critically ill patients, intermittent/repetitive bouts of hypotension can cause or exacerbate compartment syndrome. Partial limb ischemia may lead to greater cell membrane dysfunction compared with total limb ischemia [14,15]. Late ACS does not necessarily preclude fasciotomy, and the decision to perform fasciotomy must be made on a case-by-case basis. With timely compartment decompression ischemic changes may be reversible, but the likelihood that they will be irreversible is much greater after eight hours.

Extremity fasciotomy is the only recognized treatment for acute compartment syndrome; however, some irreversible changes from ischemia may have occurred. Depending on the duration, necrotic muscle will require debridement to decrease the severity of subsequent muscle fibrosis and joint contracture. Fasciotomy for late compartment syndrome is controversial. A decision to perform fasciotomy without amputation obliges the clinician to perform surgical debridement and to monitor the wound and patient carefully for infection and other systemic problems. (See "Upper extremity fasciotomy techniques", section on 'Established' and "Lower extremity fasciotomy techniques", section on 'Established'.)

Irreversible ischemic endpoints — In addition to myonecrosis leading to fibrosis, nerve damage resulting from delayed recognition of extremity compartment syndrome can lead to irreversible nerve injury. In the upper extremity, this most commonly occurs with forearm compartment syndrome leading to Volkmann contracture, and in the lower extremity, to foot drop from compartment syndrome in the calf.

Upper extremity (Volkmann contracture) — Volkmann ischemic contracture is the final and irreversible state of acute forearm compartment syndrome in the upper extremity [16].

Fractures around the elbow, particularly supracondylar humeral fractures, can lead to Volkmann contractures. In these cases, swelling caused by a fracture leads to acute compartment syndrome. Supracondylar humeral fractures accompanied by vascular injury, nerve injury, or ipsilateral fracture increase the incidence of compartment syndrome [17]. Compression of the accompanying brachial artery exacerbates muscle ischemia and neuropathy in the forearm flexor muscles. The clinical demonstration of the ensuing contracture varies [18], but the contracture typically presents with the fingers and wrist flexed, and passive extension of the finger is difficult or impossible. In severe cases, the metacarpophalangeal joints are overextended and interphalangeal joints are flexed in what is called the "intrinsic minus deformation." While acute compartment syndrome is painful, a complete contracture is not. Deformation progresses over several months, and, in children, the deformation progresses even further because ischemic muscle does not extend during growth.

Lower extremity (foot drop) — In the lower extremity, nerve injury most frequently involves the deep peroneal nerve, leading to numbness in the area of the first dorsal web space of the foot, and injury to the superficial peroneal nerve, which leads to sensory changes at skin over the anterolateral aspect of the leg and the dorsum of the foot (except for the first dorsal web space), foot drop palsy, and fibrotic contractures with deformity and pain.

The degree of disability is directly related to the timeliness of compartment release but may differ depending upon the type of injury. In a retrospective review, the mean time interval from onset of pain to fasciotomy was 5.4 hours for five patients with proximal tibia fracture who were discharged with foot numbness, and 7.25 hours for five patients with proximal tibia fracture discharged with foot drop [19]. The mean time interval from onset of pain to fasciotomy was 7.73 hours for three patients with tibia shaft fracture discharged with foot numbness and 10.3 hours for three patients with tibia shaft fracture discharged with foot drop.

CAUSES OF ACUTE COMPARTMENT SYNDROME — Compartment syndrome can develop as a result of any condition that increases the volume of the compartment without an increase in the diameter of the unyielding myofascial envelope. The rise in interstitial tissue pressures can be due to intrinsic factors (eg, swelling, bleeding) or from after-injury or extrinsic factors that restrict the ability of the fascial envelope to expand, or both [13]. (See 'Pathophysiology' above.)

Upper versus lower extremity — Acute extremity compartment syndrome is more common in the lower compared with the upper extremity. The calf is the most frequently affected site in the lower extremity, and the forearm is the most common site in the upper extremity. Fasciotomies are needed less often in the upper extremities, accounting for approximately 20 percent of all extremity fasciotomies [20,21]. For both the upper and the lower extremity, many cases of acute compartment syndrome are associated with fractures or vascular disorders [20,22,23].

Similar causes in the upper or lower extremities:

●Long bone fracture

●Acute extremity ischemia with reperfusion

●Burn injury

●Crush injury

●Spontaneous hemorrhage/hematoma

●Soft tissue infection

●Nontraumatic myositis/myonecrosis/rhabdomyolysis

●Systemic inflammatory response syndrome (SIRS)/massive fluid resuscitation

Causes more likely in the upper extremities:

●High-pressure injection

●Intravenous extravasation injury

●Inadvertent/intentional intra-arterial injection

●Birth injury (eg, neonatal compartment syndrome)

Causes more likely in the lower extremities:

●Prolonged immobilization

●Snakebite (due to location of most snakebites)

Intrinsic versus extrinsic causes — Intrinsic causes increase the volume within the compartment, such as from bleeding or edema, and can raise compartment pressure.

Extrinsic cases such as tightly applied casts and splints, tight dressings, anti-shock garments, and closure of fascial defects cause compartment syndrome by restraining the dilation of the compartment envelope. Intraoperative lithotomy positioning (eg, colorectal surgery, gynecologic surgery) or lateral positioning (eg, hip surgery, thoracic surgery) can also cause compartment syndrome via external compression. In this setting, arterial occlusion with peripheral ischemia may also intercede to exacerbate the compartment syndrome.

Removal of an extrinsic cause of pressure, such as casts or circumferential dressings, or repositioning, can improve symptoms dramatically and may obviate the need for fasciotomy.

Traumatic injury — Compartment syndrome is commonly associated with traumatic injuries, particularly long bone fractures. In addition, intracompartmental bleeding, crush injuries with muscle injury and swelling, and prolonged compression by an external force can also cause compartment syndrome.

While blunt trauma causes the majority of acute extremity compartment syndrome, victims of penetrating extremity trauma can also be affected [24]. Vascular injury (arterial, venous) is an important etiology [2,25].

Fractures — Fractures can cause direct soft tissue damage and bleeding in the compartment. In addition, both closed and open fracture treatment (reduction) can increase compartment pressure and the risk for acute compartment syndrome [3].

Fractures account for approximately 75 percent of cases of acute extremity compartment syndrome [3,26,27]. The risk increases with increasing severity of the fracture (eg, comminuted fractures) [27]. The tibia is involved most often, with acute compartment syndrome developing in approximately 1 to 10 percent of such fractures [3,28-30]. In a review of 515 children with tibial fractures, older age, ipsilateral fibular fracture, and comminuted/segmental fractures were more often associated with compartment syndrome [31]. (See "Overview of tibial fractures in adults" and "Overview of tibial fractures in children".)

The bones of the forearm are involved second most often. Injuries such as perilunate dislocations and forearm fractures are major causes of upper extremity compartment syndrome in adults [13]. Compartment syndrome does not occur very often in cases of isolated distal radius fractures, but the risk of forearm compartment syndrome increases with a concomitant injury of the ipsilateral elbow [32]. On the other hand, in children, distal humerus fractures and concomitant forearm fractures of both the ulna and radius are major causes of compartment syndrome [13]. (See "Acute compartment syndrome of the extremities", section on 'Pediatric considerations' and "Supracondylar humeral fractures in children".)

Crush injury — Compartment syndrome can occur with forceful direct trauma to the extremity (with or without concomitant fracture). In both upper and lower extremities, most crush injuries are associated with high-energy mechanisms such as motor vehicle accidents or industrial accidents [33]. (See "Severe lower extremity injury in the adult patient".)

Crush injuries also occur when an extremity is pinned beneath heavy equipment or building structures during a disaster event (eg, earthquake) [34]. The long duration of compression can sometimes induce compartment syndrome. The increase of the compartment pressure in a crush injury is determined by the state and duration of the crush.

Burn injury — Burn injuries, particularly full-thickness burns, can cause acute extremity compartment syndrome [2]. The large fluid shifts associated with burn resuscitation contribute to tissue edema, while burn eschar may restrict tissue swelling. With severe burns, various chemical mediators are produced, causing SIRS, which is a condition of excessive inflammatory reactions throughout the body. This inflammatory response exacerbates tissue edema. (See "Overview of the management of the severely burned patient" and 'SIRS/massive fluid resuscitation' below.)

Both thermal and electric burns can cause rapid formation of edema (picture 1). The upper extremities are particularly susceptible to electrical injury, and compartment syndrome can sometimes occur from muscle damage in extremities not obviously in the current pathway [35]. (See "Overview of the management of the severely burned patient".)

Bite and stings

Snakebite — There are approximately 20 species of venomous snakes in the United States. Certain snake venoms cause vasospasm or necrosis through the action of toxins and can cause compartment syndrome [36]. (See "Snakebites worldwide: Management" and "Snakebites worldwide: Clinical manifestations and diagnosis".)

Most snakes deposit venom into subcutaneous tissue during a strike, with swelling progressing through lymphangitic spread of venom, which rarely affects compartment pressure. However, some snakes (eg, rattlesnakes) with longer fangs can inject venom directly into the muscular compartment.

The majority of snakebites in the United States occur in the lower extremity, often on bare feet [37]. In the upper extremity, snakebite is most likely to occur on the hand or fingers [13].

In most cases of snakebite, fasciotomy is not necessary. Antivenin neutralizes the venom components and reduces compartment pressure once administered, inhibiting the development of compartment syndrome [38]. Fasciotomy is only recommended in cases when the compartment pressure continues to rise after antivenin administration [39,40]. Fasciotomy performed prophylactically may lead to worsened local myonecrosis [41].

Others — Other types of bites/stings have been reported to cause extremity compartment syndrome, mostly involving the hand/forearm [42-46]. Insects such as bees, mosquitos, and wasps have been reported as the causes, with authors suggesting that injected toxins or a localized allergic reaction was the cause of the compartment syndrome. In one case, Volkmann contracture was attributed to a wasp sting [47]. (See "Marine envenomations from corals, sea urchins, fish, or stingrays" and "Bee, yellow jacket, wasp, and other Hymenoptera stings: Reaction types and acute management" and "Jellyfish stings" and "Scorpion envenomation causing neuromuscular toxicity (United States, Mexico, Central America, and Southern Africa)".)

High-pressure injection — High-pressure injection injuries are also a cause of compartment syndrome, typically found in the nondominant hand [48]. Erroneous subcutaneous injection of a gas or liquid under high pressure elevates the internal compartment pressure from the injected material itself and edema following the injection.

The degree of damage tends to be underestimated because injection wounds are small. Delay of adequate treatment can lead to a need for amputation. One review reported that the amputation rate after injection injuries was 30 percent and recommended surgical fasciotomy within six hours to reduce the amputation risk [49]. The injected gas or liquid can sometimes induce infection or dissolution of the soft tissue. If the injection is oil based, it can cause severe dysfunction of the hands if initial treatment is delayed, so early exploration, fasciotomy, and debridement are required [50]. (See "Overview of hand infections".)

Birth injury — Neonatal compartment syndrome is caused by ischemia (typically of the forearm) before, during, and after birth (picture 2). This condition is usually present in only one upper limb, particularly on the dorsal forearm, wrist, or hand [51]. The combined effects of fetal posture and oligohydramnios [52], birth trauma [53], or hypercoagulability have been assumed as causes of neonatal compartment syndrome. (See "Compound fetal presentation".)

Skin lesions and open wounds on the forearm are regarded as important indicators of neonatal compartment syndrome and unusual tissue ischemia [54]. The lesions present as local ulcerations and bullae.

Despite the risks of surgery on neonates, some authors recommend emergency fasciotomies for neonatal compartment syndrome [55,56]. Early diagnosis and fasciotomy may salvage the limb and prevent neonatal Volkmann contracture, but the disease condition has not been well recognized, and fasciotomy was rarely performed even when indicated [54,57,58]. Although immobilization with a splint and local treatment for the skin lesions with topical agents have been the mainstay of treatment, emergency fasciotomy is being performed more aggressively to avoid irreversible damage to nerves and muscles [59]. However, early detection and intervention of neonatal compartment syndrome do not always guarantee complete functional recovery. Despite the use of urgent fasciotomy, amputation of the fingers, shortening of the radius caused by damage to the epiphysis, and progressive medial deformity have been reported [60,61].

Extremity ischemia — Muscle tissue deprived of arterial blood flow becomes ischemic, which causes progressive interstitial edema by increasing capillary permeability. The acutely ischemic muscle is prone to injury once flow is restored (ie, reperfusion) and is easily injured further if tissue pressure is elevated [62]. Reperfusion causes microvascular obstruction and increases capillary permeability by free radical production, exacerbating the edema [63]. The incidence of reperfusion injury after prolonged acute limb ischemia, such as after arterial repair for injury or embolectomy in the absence of concomitant chronic vascular disease, is reported to be high. The incidence of compartment syndrome after vascular trauma may be as high as 20 percent [64,65]. Prolonged tourniquet use to control hemorrhage can also cause compartment syndrome by this mechanism due to increased permeability of the capillaries and external compression (picture 3). (See "Overview of thoracic outlet syndromes", section on 'Arterial TOS' and "Popliteal artery aneurysm", section on 'Acute ischemia' and "Severe lower extremity injury in the adult patient", section on 'Hard signs of arterial injury' and "Embolism to the lower extremities" and "Embolism to the upper extremities".)

Spontaneous hemorrhage/hematoma — Hemorrhage/hematomas located beneath the fascia can cause compartment syndrome in the absence of trauma [66-68]. The use of anticoagulants or antiplatelet drugs is often implicated as the likely cause of such bleeding with minor trauma (picture 4).

Anticoagulation following surgery, such as prophylaxis against deep vein thrombosis, may contribute to the development of acute extremity compartment syndrome [69]. Symptoms can mimic postoperative pain, making the diagnosis difficult.

Patients with hemophilia can have acute compartment syndrome caused by idiopathic bleeding into a muscle compartment [70,71]. Appropriate coagulation factor supplementation is required when fasciotomy is performed, and without it, uncontrollable persistent bleeding may occur. Several authors have reported that compartment syndrome associated with hemophilia can be controlled with coagulation factor supplementation alone without fasciotomy and that emergency fasciotomy is not absolutely necessary [70,71]. However, in patients with hemophilia, bleeding of the lesion sometimes persists for several days, and one should not hesitate to perform a fasciotomy to reduce intracompartmental pressure if there is a persistent increase in this pressure [72].

Prolonged extremity immobilization — Unconscious or obtunded patients with prolonged limb compression can develop acute extremity compartment syndrome from soft tissue injury and swelling [73-76]. This occurs most commonly in the lower extremity but has also been reported in the upper extremity. The two most common contexts in which prolonged immobilization cause acute compartment syndrome are lithotomy positioning during surgery and obtundation in the intoxicated individual. Gluteal compartment syndrome has also been reported after prolonged immobilization in patients undergoing bariatric surgery and intoxicated individuals who are immobilized for a prolonged period of time [77,78].

The most common surgical position association with acute compartment syndrome is the lithotomy position, which has been reported for general surgical, gynecologic, urologic, and orthopedic operations. Acute compartment syndrome has been associated with other surgical positions and in nonoperated limbs in association with the hemilithotomy position for hip surgery. (See "Patient positioning for surgery and anesthesia in adults", section on 'Particular concerns with lithotomy position' and "Patient positioning for surgery and anesthesia in adults", section on 'Particular concerns with lateral decubitus position'.)

A number of variables may contribute to acute compartment syndrome related to surgical positioning. Lithotomy positioning may decrease calf perfusion pressure [79]. Trendelenburg positioning may compound effects of immobilization in lithotomy position by further decreasing systolic pressure at the ankle [80]. Other factors associated with an increased risk of developing positioning-related acute compartment syndrome during surgery include prolonged operative times (especially >6 hours), systemic hypotension, and severe obesity [80,81]. Positioning of a limb against an immobile object, such as stirrups, may decrease local tissue perfusion and predispose to the development of acute compartment syndrome [82]. Each of these variables decreases local muscle perfusion, creating the potential for ischemia-reperfusion injury.

Deep vein thrombosis — Deep vein thrombosis (DVT) may compromise venous outflow from a limb, causing significant swelling. Phlegmasia cerulea dolens (PCD) is a severe presentation of massive DVT, and it is often associated with extremity compartment syndrome. In the setting of PCD, major veins and venous collaterals are occluded, and the loss of venous outflow elevates compartment pressures. While PCD mainly occurs in the lower extremity, there are several cases reported in the upper extremity [83,84]. The complete occlusion of major veins including collateral veins is associated with malignant tumor and hypercoagulable states. The patient demonstrates swelling of the extremity and pain caused by the tissue ischemia. PCD is predominantly treated with pharmacologic and/or mechanical thrombolysis. Rarely, venous thrombectomy may be necessary. Compartment syndrome that develops with PCD is treated with fasciotomy. The timing of the fasciotomy may be coordinated with any planned thrombolysis because life-threatening hemorrhage can occur with thrombolysis after recent surgery. Because the early stage of PCD is reversible, early recognition and early intervention of the disease are important.

Soft tissue infection — Local cellulitis and myositis (bacterial, viral) are suggested as causes of compartment syndrome. Local inflammation caused by infections increases vascular permeability, causing edema. Practically speaking, few of such severe soft tissue infections would be treated with fasciotomy alone [85]. Early debridement includes removal of the involved fascia (ie, fasciectomy), and occasionally amputation is required to avoid mortality. Group A streptococci, methicillin-resistant Staphylococcus aureus (MRSA), and Vibrio vulnificus have been reported as pathogen strains [85-88]. (See "Necrotizing soft tissue infections" and "Surgical management of necrotizing soft tissue infections".)

Nontraumatic muscle injury — Myositis and other processes that lead to muscle necrosis (table 1 and table 2) can cause compartment syndrome because the ensuing inflammation causes swelling, which increases pressure within the compartment. (See "Rhabdomyolysis: Epidemiology and etiology".)

●Myopathy – (See "Approach to the metabolic myopathies".)

●Drugs/toxins – (See "Strychnine poisoning".)

●Statin therapy – (See "Statin muscle-related adverse events".)

●Malignant hyperthermia – (See "Malignant hyperthermia: Diagnosis and management of acute crisis".)

Extravasation injury — Injected high-pressure contrast media, or other hydrophobic liquids, have been reported to cause compartment syndrome by the extravasation of the injected fluid [89,90]. Although extravasation from an injected contrast medium for a CT scan is rare, it can lead to critical complications [91]. (See "Extravasation injury from cytotoxic and other noncytotoxic vesicants in adults" and "Peripheral venous access in adults", section on 'Complications'.)

The location of the intravenous catheter may impact the likelihood of extravasation and compartment syndrome. Injection through the hand veins is believed to result in more extravasations compared with injection at the antecubital fossa [92]. The majority of reported cases of compartment syndrome following a high pressure injection are associated with an intravenous catheter in the dorsum of the hand [91]. Unconscious patients are at additional risk for extravasation and compartment syndrome because of their inability to express their concerns of pain during the injection [92].

Intra-arterial injection — Compartment syndrome can result from inadvertent intra-arterial injection of drugs, which can occur in the upper or lower extremity. Iatrogenic injection may result from a line erroneously placed into an artery instead of a vein (eg, brachial artery rather than median cubital vein, subclavian artery rather than subclavian vein) or injection into a preexisting arterial line (eg, radial arterial line, femoral arterial line) that was mistaken for a venous one, particularly in the critical care setting [93]. Drugs associated with severe reactions that can lead to extremity necrosis, compartment syndrome, and even amputation include benzodiazepines, phenothiazines, barbiturates, amphetamines, phenytoin, narcotics, and some antibiotics. In the past, intra-arterial injection was most commonly associated with the administration of anesthesia; however, drug abuse accounts for more cases [94-96].

SIRS/massive fluid resuscitation — Secondary extremity compartment syndrome (SECS), which is caused by severe edema after resuscitation, burns, or sepsis, is a rare complication of systemic inflammatory response syndrome (SIRS) [97]. In these cases, vascular permeability is enhanced by secretion of various cytokines, which induces an increase in compartment pressure. When administering large amounts of intravenous fluid or transfusing the patient, edema worsens further, exacerbating the compartment syndrome. It is important to be aware that extremities without any direct trauma can be affected, and to check for this condition in all critically ill patients with extremity edema [98].

Overall, the incidence of SECS is low, affecting approximately 0.1 to 0.2 percent of trauma patients. The lower extremities may be more often affected, but SECS can occur in the upper limbs, multiple limbs, or all limbs at the same time [97,99]. Risk factors for SECS include severe hypotension, a high injury severity score, and massive transfusion [100].

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: Extremity compartment syndrome" and "Society guideline links: Acute extremity ischemia".)

SUMMARY AND RECOMMENDATIONS

●Pathophysiology – Any pathologic process that results in increased pressure within a muscular compartment exceeding the perfusion pressure of the tissue has the potential to cause compartment syndrome. Compartment pressures capable of compromising perfusion develop when they rise to within 10 to 30 mmHg of diastolic pressure. (See 'Introduction' above and 'Pathophysiology' above.)

●Classification – Acute extremity compartment syndrome is classified as impending or established based on clinical features supported by measurement of compartment pressures. With impending compartment syndrome, tissue pressure has begun to increase and tissue perfusion is reduced, but is not sufficiently to cause muscle or nerve damage. Acute compartment syndrome is established when pressure in the compartment rises enough to cause tissue damage. It is considered to be in the early stage if the increased compartment pressure has been present for less than four hours, and in the late stage if increased compartment pressure has been present for a longer duration. (See 'Classification' above.)

●Causes – Acute extremity compartment syndrome can be due to a variety of causes. Acute extremity compartment syndrome is more common in the lower compared with the upper extremities. For both the upper and the lower extremity, many cases of acute upper extremity compartment syndrome are associated with traumatic injury, particularly fractures, or ischemia/reperfusion. Other causes are listed and discussed above. (See 'Causes of acute compartment syndrome' above.)

●Morbidity – Extremity fasciotomy is the only recognized treatment for acute compartment syndrome. Failure to recognize acute extremity compartment syndrome and decompress the muscular compartments in a timely fashion can result in significant functional morbidity, either the result of muscle ischemia (eg, Volkmann contracture, foot drop) or due to the need to perform amputation. (See 'Classification' above and "Upper extremity fasciotomy techniques" and "Lower extremity fasciotomy techniques".)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Jennifer M Sterbenz, BS, and You Jeong Kim, BS, who contributed to an earlier version of this topic review.