Reconstruction of COVID-19–Related Compartment Syndrome With Massive Soft Tissue Necrosis

Christopher Bibbo, DO, FACS, FAAOS, FACFAS


Wounds. 2021;33(4):99-105. 

In This Article


The direct viral effects of COVID-related thrombosis have been cited secondary to increases in angiotensin II (vasoconstriction), relative decrease in angiotensin (vasodilation), release of sepsis-induced cytokines (eg, IL-6), platelet activation, and thrombocytopenia.[1–3] An increase in D-dimers, thrombin generation, and fibrin production results in both microvascular and macrovascular thrombosis.[4] In association, a disseminated consumptive coagulopathy- like state often ensues, resulting in hemorrhagic complications. Thrombotic coagulopathy has been recorded in up to 50% of patients with COVID-19.[1,4] Of the cohort of patients with COVID-19 who are diagnosed with thromboembolism, 87% will have pulmonary emboli; 4% develop massive venous thrombosis, while arterial thrombosis occurs in 2.6%;[4] cerebrovascular events may occur in 7%. The risk of cardiovascular death is elevated by 14%.[4] The presence of COVID-related coagulopathy alone is a predictor of a poor outcome.[4,5]

The effects of platelet activation[2] and thrombocytopenia[3] place both hospitalized and ambulatory patients with COVID-19 at risk for thrombotic and thromboembolic events. Clearly, the presence of a nearly temporally situated arterial and venous coagulopathy of both thrombotic and hemorrhagic natures may be present.

Infection with COVID-19 may result in 2 intertwined pathologies: COVID-19–related thromboembolic and hemorrhagic coagulopathies and COVID-19–related capillary leak syndrome (similar to COVID-19 alveolar fluid leak). These 2 phenomena can produce rapid swelling of potential third spaces and the defined spaces of the body that contain muscle and neurovascular bundles, especially the extremities. In the most basic terms, compartment syndrome develops because of abnormally elevated pressure within a "closed" anatomic space. When unrecognized, or when there is a delay in diagnosis, elevated compartment pressures may result in necrosis of muscle, nerve, or other critical organs (like that which occurs with intra-abdominal compartment syndrome). Late findings include both arterial and venous thrombosis.

Although a traumatized extremity is the most common clinical setting for compartment syndrome, the etiologies of any compartment syndrome are varied. Massive third space fluid within a muscular compartment, such massive extravasation of intravenous fluids, may result in compartment syndrome as well as hemorrhage and arterial or venous thrombosis. In this setting, compartment syndrome may develop acutely or in a slower, progressive fashion. Tissue necrosis (ie, muscle, nerve) may be limited or occur as a massive and irreversible process that may result in a functionless limb or necessitate an amputation.

Rhabdomyolysis that induces severe compartment syndrome may result in acute kidney injury, which could be severe and lead to overt renal failure requiring hemodialysis. Although commonly cited as a definitive diagnostic tool, intracompartmental pressure measurements can be misleading and are commonly forgone, such as in the present case. Additionally, compartment pressure readings are often subject to technical errors that may result in false-negative results and a "dismissed" diagnosis, when, in reality, compartment syndrome exists. With experience over time, the present author has found compartment pressure readings to be of less utility than a discerning history and physical examination. A mis-diagnosis or delayed diagnosis is supported by persistent elevations of serum CPK (as in the presented case) and the presence of urine myoglobin. In the presented patient, CPK levels were persistently elevated from 2944 U/L to 9633 U/L. In the early stages of presentation of suspected compartment syndrome, a urine sample for the detection of myoglobin is helpful to guide the early use of alkalinized diuresis.

Within a patient's acute presentation period, such as in this case, a differential diagnosis of necrotizing fasciitis (NF) should be included, especially when seropurulent discharge is present and the patient is septic and rapidly declining toward a moribund state. However, in the present case, a diagnosis of NF was excluded due to a lack of clinical or histologic features characteristic of NF. The infection was that of a secondary bacterial infection.

Capillary leak syndrome, as described in the literature, has been associated with an abnormally elevated inflammatory response that results in endothelial dysfunction, causing extravasation of fluid from the vascular space to the interstitial space (third space).[6] Capillary leak syndrome alone may be severe enough to result in extremity compartment syndrome, at times affecting all 4 extremities.[6–10] Although capillary leak syndrome is often associated with hypotension, elevated hematocrit, leukocytosis, and thrombocytosis, not all of these abnormal parameters may be present. When capillary leak syndrome is associated with COVID-19, the afore-mentioned laboratory abnormalities may be overshadowed by those abnormalities associated with COVID-19. Thus, the diagnosis is favored by the clinical setting and manifestations thereof, rather than strict reliance on laboratory values. To the author's knowledge, only 1 case report has been published describing compartment syndrome resulting from capillary leak syndrome in a patient with COVID-19.[6] In the presented case, to the author's knowledge, this is the first report of a patient with COVID-19 infection who developed both thrombotic and hemorrhagic coagulopathies accompanied by capillary leak syndrome, resulting in forearm compartment syndrome that progressed to massive soft tissue necrosis. This constellation of findings is akin to a "triple hit" phenomenon (hemorrhage, thrombosis, and capillary leak) affecting the musculoskeletal system compartfirsments with attendant necrosis of all soft tissues and nerve; secondary infection also occurred. This constellation of pathologies resulted in renal failure and placed the patient at high risk for loss of the upper extremity. Loss of the upper extremities can be catastrophic and has greater implications than loss of the lower extremity. Additionally, upper extremity limb salvage is more complicated, but reconstruction can yield greater benefits than salvage of the lower extremity.

The reconstruction of severe wounds with underlying tissue destruction is a significant challenge in patients who are critically ill. The reported patient had pneumonia, sepsis, renal failure, and hemodynamic instability, requiring prolonged intubation and hemodialysis. A secondary bacterial soft tissue infection of the forearm further elevated the complexity of limb salvage. In this setting, the threat of amputation becomes a major concern. When major nerves, muscles, tendons, and large areas of skin are lost to necrosis with infection, upper extremity limb salvage becomes an extremely complicated undertaking. Aggressive debridement contributes to the resuscitation and physiologic stabilization of patients. In this patient, repeat debridements were required, ultimately yielding a barren volar forearm muscle and a nonviable median nerve. Fortunately, the radial and ulnar arteries and nerves were salvaged. To achieve a functional arm, reconstruction consisted of re-establishing the soft tissue envelope and restoration of wrist and finger flexion. Techniques to restore large areas of full thickness of the soft tissue envelope (ie, skin, fat, fascia) often require a free flap procedure. However, in this patient, hemodynamic instability and fluid shifts associated with hemodialysis made the patient a poor candidate for free tissue transfer coverage. Local (arm) and regional trunk flaps, such as the latissimus dorsi muscle flap, are insufficient when large defects exist below the elbow. Prolonged negative pressure dressings in the described soft tissue environment (vide supra) typically result in a deep, thick, neovascularized cicatrix, making functional reconstruction very difficult. Thus, given that this patient was physiologically unsuitable for a free flap technique and had no realistic local flaps, the abdominal thoracoepigastric adipofasciocutaneous "tubed" flap provided a reconstructive solution with effective soft tissue coverage that allows for immediate tendon transfers.

In this patient, thumb flexion was restored by transfer of the BR to the FPL tendon. Finger flexion was restored by transferring the ECRL to the FPD tendons. In the setting of severe inflammation, tendon integrity and tensile strength is often compromised. The author has discovered through experience with treating massive lower extremity tendon defects that tendon augmentation with the studied product herein (human decellularized dermis) can improve the mechanical and biological security of tendon reconstructions. Decellularized dermis has excellent tensile strength, providing additional strength to tendon reconstructions. In situ, the skin substitute has been shown to decrease local fibrosis proven by serial in-situ optical coherence tomography during human implant-host healing phase, as well as by histologic evaluation at day 28 of healing incorporation into host native tissue.[11] Additionally, a prospective analysis of wounds treated with decellularized dermis has been proven by CD31 staining and cytokine mRNA upregulation assays to promote angiogenesis, and its extracellular matrix metalloproteinase profile is extremely favorable to local native tissue healing.[12] The author has observed these benefits in even the most difficult soft tissue reconstructions.

It must be noted that suboptimal nutritional states, such as those seen in the reported patient (hypoalbuminemia, decreased total protein levels), pose a significant challenge to the overall recovery of patients who are critically ill with COVID-19, but they also present a challenge for soft tissue healing. Thus, early nutritional protocols must be initiated early in this patient population to facilitate both soft tissue healing and overall recovery from COVID-19.[13] Moreover, states of severe inflammation, as measured by C-reactive protein (which fluctuated from 18 mg/L FEU to 113 mg/L FEU [normal high, <9.9 mg/L FEU] in the presented patient), is a major impediment to proper tissue healing, and the "cytokine storm" seen in patients with COVID-19 will lend to a more heightened tissue healing dilemma. Additionally, the inflammation of compartment syndrome–induced myonecrosis adds further fuel to the fire of inflammation.