Internal Medicine Review Acute Compartment Syndrome Feb.2017

Update and Review of Acute Compartment Syndrome and Necrotizing Fasciitis

Authors Abstract: 1 Paul Johnson, MD This is a brief review of the etiology, diagnosis, treatment and 2 outcome for patients with either acute compartment syndrome Justin Ocksrider, MS or necrotizing fasciitis. Both can be devastating to the 3 Selina R. Silva, MD extremities and can result in permanent impairment or amputation. Early diagnosis and treatment is the key to Affiliations prevent permanent damage. Both can also affect the head or 1 Orthopaedic Surgery trunk of the body, but this review will focus primarily on the Resident, University of involvement of the extremities. Acute compartment New Mexico Hospital syndrome (ACS) is a condition where osseofascial compartment pressures rise to a point that overcomes 2 4th year medical student capillary perfusion pressure. The lack of tissue perfusion in at the University of New ACS results in tissue ischemia and necrosis, which can lead to Mexico Medical School. permanent loss of muscle function, nerve damage, limb amputation, and multisystem organ failure. Necrotizing 3 Pediatric Orthopaedic fasciitis is a severe form of subcutaneous cellular infection Surgeon at the University with spread to and along the subcutaneous and fascial layers. of New Mexico Hospital. Because of its location along the fascial plane and it is often University of New Mexico polymicrobial nature, it can quickly progress in severity and Hospital become a life-threatening disease. Correspondence

3 Selina R. Silva, MD

Email: [email protected]

Internal Medicine Review Acute Compartment Syndrome Feb.2017

Introduction Etiology & Epidemiology Acute compartment syndrome (ACS) is a ACS is a common, yet difficult condition to condition where osseofascial compartment diagnose. Effective diagnosis requires a pressures rise to a point that overcomes thorough understanding of the etiology, capillary perfusion pressure. The lack of epidemiology and risk factors. Two broad tissue perfusion in ACS results in tissue categories of etiology for ACS are :(1) ischemia and necrosis, which can lead to increase compartment contents or -decrease permanent loss of muscle function, nerve compartment space [2]. damage, limb amputation, and multisystem organ failure. Early diagnosis is essential for successful outcomes and is based on clinical Fractures are the most common cause of findings and compartmental pressure ACS, resulting in about 69% of all ACS measurements. Common etiologies of ACS cases and 76% of pediatric cases [3]. Not all include fracture, traumatic soft tissue injury, fractures, however, impart the same level of and non-traumatic increases in risk. Tibial diaphyseal fractures comprise compartmental pressure. ACS most the leading cause of fracture-induced ACS at commonly occurs in the anterior 40% of cases [1]. The next most common compartment of the lower extremity cause of ACS is soft tissue injury in the following a tibial fracture, but can occur in absence of a fracture, accounting 23% of all the foot, thigh, forearm or hand [1]. ACS cases [4]. Table 1 is a brief list of other Treatment consists of emergent surgical causes: decompressive fasciotomy.

Table 1: Brief List of Causes INCREASED COMPARTMENTAL DECREASED COMPARTMENTAL CONTENTS [2,5,6] SPACE [2,5] Crush syndrome Burns (circumferential) Revascularization Muscle hernia repair Infiltrated fluid infusion Casts Arterial puncture Circumferential dressings Gunshot wound Pneumatic antishock garments Snake / venomous bite Lithotomy surgical positioning Nephrotic Syndrome MEDICAL COMORBIDITIES [2] Hematogenous osteomyelitis Diabetes Exercise (chronic compartment syndrome) Coagulopathies

Age is one of the strongest predictors for Patients younger than 35-years-old with ACS, where young males comprise the tibial diaphyseal fractures are three times greatest risk [7]. The incidence of ACS is more likely to develop ACS than those over 3.1/100,000 people annually, but men are 35-years-old [3]. ACS is thought to be more ten times more likely to develop ACS with common in younger patients due to presence an incidence of 7.3/100,000 [3]. The average of stronger fascia, increased muscle age for ACS diagnosis is 32-years-old [3].

Internal Medicine Review Acute Compartment Syndrome Feb.2017

volumes, and increased frequency of high- Pain is recognized as the most prominent, energy trauma [2]. reliable indicator of early ACS [1,2,5]. Pain in ACS is progressive and typically resistant to analgesic medications [2,8]. Patients may Other risk factors for development of ACS present early with paresthesia, or pressure include high-energy trauma and polytrauma on palpation [5] . More commonly, [3]. Although it would seem like open paresthesia and paresis are both late signs fractures should decrease the risk of ACS, that only occur after a significant decrease in studies have shown no difference in the arterial blood flow [2]. Paresis is the result incidence of ACS in open versus closed of longstanding nerve compression or fractures [2]. ACS can be iatrogenic during irreversible muscle damage [5]. surgical procedure due to limb placement, Pulselessness, pallor and slow capillary refill traction, or intramedullary pinning [2,7]. times are rare and more indicative of a vascular injury, although present as late signs in ACS [2,5]. It is therefore important Diagnosis to note that while the “6 P’s” have a correlation with compartment syndrome, ACS can be difficult to diagnose and have these signs and symptoms often present after poor outcomes when not recognized early in cell death has already begun to occur. its course. The approach to diagnosing ACS Making the diagnosis before the is most frequently based on history and presentation of these late signs is much more physical exam [1-3,5,6,8]. Some institutions ideal. also utilize intra-compartmental pressure (ICP) measurement techniques to aid in The clinical diagnosis to ACS has its diagnosis. Regardless of approach, early limitations. Although pain is the most diagnosis is necessary for successful early reliable indicator used by clinicians, it may intervention [6]. The symptoms of ACS are occasionally be absent, especially in patients progressive and therefore should be presenting with fully established ACS [5]. monitored over time in patients most at risk Pain can be masked by associated nerve [5,8]. injury, fracture, or the use of local or epidural anesthetics [2,3,8]. The utility of pain measurement is further limited by its subjectivity and variability among the The “6 P’s” represent a helpful mnemonic population [3]. Obtaining information for remembering the indicators associated regarding pain can be especially challenging with ACS: pain out of proportion to injury in certain patient populations: intoxicated and pain with passive stretch, paresthesia , patients, obtunded patients, patients with pressure on palpation, pallor , paresis , and learning disabilities, or young children [1- pulselessness [1,2,5]. Collectively, these 3,5]. The variability of patient presentation, indicators have modest sensitivities, but high pain perception and the low positive negative predictive values [2,3,8]. Patients predictive-values of the “6 P’s” can with two positive indicators have a 25% sometimes make clinical diagnosis difficult probability of ACS, whereas patients with or impossible. three positive indicators have a 93% of ACS [1].

Internal Medicine Review Acute Compartment Syndrome Feb.2017

Intra-compartmental pressure (ICP) monitoring offers a helpful alternative when clinical diagnosis is uncertain. As ACS Attempts have been made to incorporate develops, the pressure inside the imaging and biomarkers into the diagnostic compartment progressively increases. There workup for ACS. Near-InfraRed (NIR) is a critical point when the increased spectroscopy is an imaging technique, based pressure inside the compartment inhibits on the same principle as pulse oximetry, vascular supply to the tissue causing currently being developed and studied for necrosis. Therefore, when compartment determining muscle tissue oxygenation in syndrome is suspected, intra-compartmental ACS progression [1-4,8]. More large scale pressures should be measured early and trials are needed before the efficacy of NIR continued over time [5]. Pressure spectroscopy can be determined [8]. Other measurements allow clinicians to monitor imaging modalities such as MRI and possible progression to ACS and allow for Scintigraphy have shown limited diagnostic early intervention. efficacy [2]. Biomarkers such as serum creatinine phosphokinase, erythrocyte sedimentation rate, white blood cells, and myoglobin can be elevated in ACS, but are Controversy exists regarding the minimum not specific [2,5]. ICP for diagnosing ACS, ranging anywhere from 30 mmHg to 45 mmHg [1,2]. Symptoms of ACS begin to appear around ICP of 20-30 mmHg [2], and most sources The key to successful treatment of ACS is define ACS at ICP measurements of greater early diagnosis [6]. The differential than 30 mmHg [2]. Similarly, ACS is diagnoses include cellulitis, deep venous diagnosed when ICP measurements are thrombosis, fracture, gas gangrene, within 30 mmHg (delta pressure) of the necrotizing fasciitis, peripheral vascular diastolic blood pressure [3-5]. injury rhabdomyolysis. The diagnostic approach to ACS utilizes information from patient history and physical exam, intra- compartmental pressure (ICP) Common techniques to measuring pressure measurements, or both. Currently, the use of within the compartment include slit catheter, imaging and laboratory biomarkers is slide port needle, fluid-filled catheter inadequate for diagnosis. Clinicians should attached to an extracorporal transducer, understand mechanism of injury, potential simple needle manometry, or the infusion risk factors and maintain a high index of technique [1,5]. Pressure measurements suspicion for at-risk patients [1,5]. should occur as close to the injury site as possible, and should be obtained in all compartments [6,8]. Some sources recommend both clinical and pressure Pathogenesis monitoring during the first 48-hours after a Extremity compartments are finite anatomic fracture or surgical fixation [2]. Continuous spaces formed by fascia, epimysium and pressure monitoring has been recommended skin [5,8]. Fascia is a low-compliance tissue by some to monitor for compartment that encases and separates muscle groups syndrome in all tibial diaphyseal fractures and their respective neurovascular supply. It [9]. provides sites for muscle attachment, and

Internal Medicine Review Acute Compartment Syndrome Feb.2017

offers mechanical support during muscle space creates a positive feedback loop, contraction by grouping muscles of similar worsening the building compartmental function [8]. As fixed compartments, these pressure and tissue hypoxia. spaces cannot accommodate large increases in fluid without a resulting increase in compartmental pressure. ACS is a situation High interstitial pressures eventually cause whereby large hydrostatic pressures within the thin-walled venules and veins to the compartment space impede adequate collapse. The ensuing elevation in venous tissue perfusion. pressure not only contributes to increased fluid extravasation, but also causes a significant decrease in the arteriovenous The basis for both primary ACS (AV) gradient and worsened perfusion. [5] (compartment syndrome caused by trauma), These pressures can ultimately reach a and secondary ACS (non-trauma related critical level whereby the thicker-walled compartment syndrome) is elevated arterioles can spasm and close [1]. Critically hydrostatic pressure [8]. Physiologic high compartmental pressures and very low conditions allow for cellular metabolism to AV gradients overcome capillary perfusion take place at an oxygen tension of 5-7 mm pressures resulting in cessation vascular Hg, achieved by a typical capillary perfusion perfusion, nerve conduction slowing and pressure of 25 mm Hg and an interstitial ischemic tissue [5]. pressure of 4-6 mm Hg [1]. Alterations in these pressures can initiate a cascade of detrimental physiologic and biochemical The central part of the muscle is the first to events resulting in ACS. The ischemic become ischemic [5]. The hypoxic cellular threshold of skeletal muscle, determined in environment favors anaerobic metabolism canine models, is related to the difference over aerobic metabolism, resulting in between the compartment and mean arterial decreased total ATP production [8]. The (<= 30) or diastolic pressure (<=20) [5]. ATP scarcity manifests in an inability to Thus, the most important variable maintain the Na/K ATPase exchange [8]. contributing to ACS is the difference Thus, membrane potential and osmotic between compartment pressure and blood balance is lost leading to cellular swelling pressure [5]. and necrosis [8]. Myocyte necrosis causes release of osmotically active particles that draws more fluid into the tissue [1]. The progression of ACS begins with an inciting event (i.e. musculoskeletal trauma) where blood flow through the Restoring blood flow to these ischemic or microvasculature does not meet the necrotic myocytes can result in a reperfusion metabolic demand of the tissue [4]. This injury. Ischemic myocytes may produce event causes both fluid extravasation into oxygen radicals, undergo lipid peroxidation the compartment and mild tissue hypoxia. and calcium influx upon blood flow The hypoxic environment in the tissues restoration [8]. Mitochondrial dysfunction in stimulates release of vasoactive substances oxidative phosphorylation and cell for precapillary vasodilation and increased membrane damage are the immediate vascular permeability [1,8]. The subsequent consequences [8]. Necrotic myocytes also increased net filtration into the interstitial

Internal Medicine Review Acute Compartment Syndrome Feb.2017

release myoglobin, potassium, and other Following fasciotomy, the wounds are inflammatory molecules [5]. Reperfusion typically placed underneath a vacuum- will introduce these harmful molecules into assisted wound device to allow ICP to circulation and cause renal failure or cardiac continue to normalize [2,5]. Primary wound arrhythmias [5]. The duration and extent of closure may be completed once swelling has the ischemia predicts the severity of decreased and may require a split-thickness systemic response upon reperfusion [5]. skin graft.

The pathophysiology of ACS is important There is no successful alternative to for understanding the approach to diagnosis decompressive fasciotomy. Adjunctive and the goals for treatment. The exact therapy may include blood pressure mechanism for the progression of ACS is management and hydration to increase tissue debated, but the common final pathway of perfusion pressure [1]. Oxygen all compartment syndromes is tissue anoxia supplementation has also been [5]. Many factors contribute to the recommended to maximize saturation and development and severity of compartment oxygen delivery to ischemic tissue [6]. syndrome including vascular tone, blood pressure, duration of elevated pressure, and the tissue metabolic demand [5]. Outcomes & Complications Untreated, ACS leads to muscle necrosis, Treatment fibrosis and contracture [5]. A late presentation may result in total loss of ACS is a surgical emergency that requires muscle function and require amputation [5]. immediate decompressive fasciotomy of all Muscle necrosis will cause release of affected compartments upon diagnosis [2,5]. myoglobin and potassium, which can lead to Prior to surgery, attempts to decrease ICP renal failure or cardiac arrhythmias, should include prompt removal of casts and respectively [5]. Multisystem organ failure any other occlusive dressings [5]. The and death are other possible sequelae [5]. muscles affected should be placed at the level of the heart, but no higher as to maximize perfusion to the ischemic tissue Early fasciotomy, on the other hand, can [5]. Fasciotomy should be performed as allow for complete limb recovery if the early as possible following diagnosis. diagnosis occurs within six hours of Fasciotomy is contraindicated if the symptom onset [1]. Irreversible nerve diagnosis is suspected to be delayed over damage occurs after 12 hours [1]. eight hours and if the patient has no apparent Fasciotomy that occurs in a delayed fashion muscle function in any segment of the will cause an increased risk of infection, affected limb [5]. sepsis, amputation, renal failure and death [1]. The use of vacuum-assisted wound devices and prophylactic antibiotics have During surgery, the goal is to decompress decreased post-operative complication rates the compartments to allow reestablished [1]. blood flow to the tissues [5]. All visibly necrotic tissue must be debrided [2].

Internal Medicine Review Acute Compartment Syndrome Feb.2017

Although the consequences of untreated disease, necrotizing fasciitis in children may ACS are devastating, decompressive be found in otherwise healthy patients fasciotomy is not risk-free. Potential adverse without any known susceptibilities for postoperative outcomes include infection, infection [12]. Moss et al . reported that 95% need for split-thickness skin grafting, and of 20 children with necrotizing fasciitis were poor cosmetic appearance [1,5]. Only 68% previously healthy, and Fustes-Morales et of fasciotomies performed within 12 hours al. reported half of their 39 children with of symptom onset resulted in complete necrotizing fasciitis had no predilection for recovery of muscle function, and only 8% if infection, though there was a strong performed after 12 hours [7]. association with malnutrition [12][13].

The process of deep bacterial seeding within ACS is a condition that causes significant the fascia is not thought to be different from morbidity and potential mortality if that of adults. Minor and major trauma undiagnosed or untreated. Even if the creating an entry-way for bacteria seems to diagnosis is made early and decompressive be a common etiology. Excoriations during fasciotomy is performed, some patients courses of varicella infection have been the sustain significant morbidity from the most common cause among small children surgical procedure. Patients must be [13]. In newborns, cases of omphalitis and educated on both the complications of ACS infected surgical wounds from circumcision and the potential complications of surgery. have led to several cases [13]. Another common initiating factor is the infection of wounds from surgery or trauma, but in some cases the etiology cannot be determined Necrotizing Fasciitis [14]. Over 50% of pediatric cases present in the extremities, though other common Incidence and Etiology locations include the trunk and neck [13]. Necrotizing fasciitis is a severe form of subcutaneous cellular infection with spread Clinical Presentation and Diagnosis to and along the subcutaneous and fascial Delayed diagnosis is one reason for high layers. Because of its location along the mortality rates among patients with fascial plane and it is often polymicrobial necrotizing fasciitis [15]. Early in its course, nature, it can quickly progress in severity necrotizing fasciitis may appear clinically and become a life-threatening disease [10]. indistinguishable from cellulitis or other Prompt diagnosis is essential, and emergent more mild dermal infections. For one to surgery is indicated in the case of two days patients may have no indication of progressive disease. severe disease, presenting with only dermal induration and erythema accompanied by a The development of necrotizing fasciitis in fever [16]. On days 3 to 4, hemorrhagic children is rare, with an incidence of blisters or bullae may develop, and the skin approximately 0.8 in every one million will typically start to appear shiny, and the children [11]. The clinical picture of the fulminant infectious process leads to severe disease is distinct from the usual localized pain [12]. In the following days, presentation of necrotizing fasciitis in adults. thrombosis of superficial nutrient vessels in While typically presenting in adults that are the subcutaneous tissue leads to devitalized immunocompromised have a chronic and friable subcutaneous tissue as well as

Internal Medicine Review Acute Compartment Syndrome Feb.2017

skin necrosis [12]. It is important to note Treatment that skin necrosis is a late finding, and the Early diagnosis, hemodynamic resuscitation extent of subcutaneous tissue destruction is and early extensive surgical debridement are always more extensive than that which may the keys to successful treatment of be perceived externally by the necrotic skin necrotizing fasciitis. One study showed that margins [17]. Beyond the local involvement when surgery was delayed more than 24 of the disease, the natural history of the hours the mortality rate was twice as high disease ultimately leads to multi-organ compared to those treated surgically within systemic dysfunction. Disseminated 24 hours [21]. Surgical debridement must intravascular coagulation was a major include sufficient excision of all involved contributor to mortality in one study, leading skin, subcutaneous tissue and fascia to be to 28% of the study’s deaths [13]. As effective [22]. As noted previously, the septicemia develops, fluid third-spacing and extent of necessary debridement of necessity autonomic vascular dysfunction can lead to must extend far beyond the border of the hemodynamic instability and demise [18]. skin necrosis. The excision should extend Lastly, infection can easily spread to until healthy vascularized borders are multiple organs and may result in organ achieved at the fascial, subcutaneous and failure. cutaneous layers [20]. The wounds should be examined frequently, and most cases will The LRINEC score has been proposed as require more than one operating room one potential diagnostic tool based on procedure as further necrotic tissue objective laboratory data [19]. This scoring eventually declares itself. Care should be system has not yet been validated in the taken to salvage all healthy soft tissue for pediatric population, but it has shown to coverage. In the extremities, justification for have a positive predictive value of 92% amputation may be found in patients that when the high risk score criteria are met have high anesthetic risk, vascular [19]. Not all adult data may be extrapolated insufficiency, unresolvable hemodynamic to children, but the LRINEC scoring system instability, or a significantly large infectious may have a role in diagnosing pediatric burden in the extremity [22]. necrotizing fasciitis. Negative-pressure wound vacuums may be In patients with an equivocal diagnosis of helpful in wound management until necrotizing fasciitis, the “finger test” or “cut coverage can be achieved through skin flaps down test” may be performed. This test or grafts [20]. Nutritional monitoring and involves making a small incision over the supplementation is critical during the wound suspect area under local anesthesia. If healing period. Coagulation profiles and “dishwater pus” presents, or if the basic metabolic profiles must be monitored subcutaneous tissue overlying the fascia closely as clotting factors and electrolytes lacks normal resistance to blunt dissection, are often depleted [23]. Careful then necrotizing fasciitis is diagnosed [20]. hemodynamic monitoring should continue in This test, in combination with the post-debridement period. histopathological analysis of a specimen of tissue from this cut down are the gold Concomitant antibiotic treatment is essential standard for confirming the diagnosis. with broad spectrum aerobic and anaerobic coverage. However, in isolation, pharmacologic treatment is insufficient as

Internal Medicine Review Acute Compartment Syndrome Feb.2017

there is no way for the antibiotics to children. Among survivors, scars and effectively reach to hypovascular, necrotic deformity were the primary complaints of tissue [24]. Antibiotic treatment may be survivors (72% and 56%, respectively). Skin narrowed based on the results of specimen and fascial contractures resulted in cultures and sensitivities. Other significant loss of joint range of motion in supplemental treatments may include 20% of patients [22]. hyperbaric oxygen, intravenous immunoglobulin, and kallistatin administration [25][26]. However, the Summary efficacy of these treatments is still With acute compartment syndrome or controversial. necrotizing fasciitis the most important factor in determining outcome is early Outcomes diagnosis and treatment. Patients can Outcome data in children is sparse than the present in a number of clinical settings literature describing adult outcomes. In the making it important for clinicians in all few pediatric studies looking at outcomes, specialties to be aware of the basic signs and the average mortality rate has ranged from symptoms. It is better to send a patient to 10-60%, with a mean among all studies of the emergency department for further approximately 20% [22]. In the largest evaluation and treatment even if they do not pediatric case series found in the literature, have acute compartment syndrome or mortality was 18% [22]. Most deaths were necrotizing fasciitis. Missing either due to infectious spread to vital organs or diagnosis can be devastating and limb/life hemodynamic compromise. The presence of threatening. hemodynamic instability before surgery and pre-existing immune--compromised state were significant risk factors for mortality in

Internal Medicine Review Acute Compartment Syndrome Feb.2017

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