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Introduction. The COVID-19 virus is caused by the new coronavirus, SARS-CoV-2. COVID-19 has drastically changed the medical landscape. Although predominantly impacting the respiratory system, COVID-19 has several non-respiratory symptoms associated with its presentation and course. Among these are gastrointestinal symptoms and thromboembolic events with stroke. Increasingly recognized, but often overlooked, are the coagulopathy phenomena occurring with COVID-19. The severe respiratory symptoms are the primary focus of clinical management. However, close inspection of patients demonstrates that patients often exhibit both thromboembolic and bleeding events, ranging from simple skin lesions to overt emergencies. Case Report. The author presents a case of COVID-19–associated coagulopathy resulting in compartment syndrome of the arm with volar forearm necrosis, requiring flap reconstruction and tendon transfer to salvage the upper extremity. Conclusions. Massive rhabdomyolysis resulted in acute tubular necrosis with renal failure requiring hemodialysis. The timing of reconstruction of the sequelae of compartment syndrome in an acutely ill patient is challenging, but optimal timing can result in a successful outcome.
COVID-19 has emerged as a devastating viral illness; in addition to acute and chronic pulmonary complications, it may also result in hypercoagulable states affecting the heart, central nervous system, and peripheral vasculature. Limb involvement may be severe and can lead to limb-threatening complications. This report details severe complications in the upper extremity of a patient with severe COVID-19 disease.
A 35-year-old male rehabilitation nurse presented to the emergency department with a fever, shortness of breath, and a cough; the patient’s condition rapidly deteriorated and intubation was required. Computerized tomography of the chest revealed a ground-glass appearance in all lung fields, consistent with COVID-19 respiratory disease. Subsequent COVID test results were positive for COVID-19.
At 2 weeks post intubation, standard hematologic laboratory values (platelet, disseminated intravascular coagulation panel, prothrombin time/partial thromboplastin time) were consistent with consumptive coagulopathy. The patient developed massive soft tissue edema of the right arm. Skin ecchymoses over the forearm developed, quickly followed by clear, then hemorrhagic, skin bullae and semirigid flexion deformity of the right wrist and fingers. The arm continued to become even more edematous, with larger blue hemorrhagic blisters and skin necrosis; serial serum creatine phosphokinase (CPK) levels were persistently elevated (2944 U/L rising to a peak of 9633 U/L [normal male range, 39–308 U/L]). Nutritional indices were suboptimal (serum albumin, 2.9 g/dL [range, 3.4–5 g/dL]; serum total protein, 5.4 g/dL [range, 6.4–8.2 g/dL]). Acute renal failure ensued, and the patient required hemodialysis.
Consultation with the general musculoskeletal service was ordered, but a thorough musculoskeletal examination was not possible because the patient was intubated and obtunded. Therefore, a diagnosis of compartment syndrome was uncertain. However, due to the persistently high CPK levels, additional subspecialty consultation with the reconstructive orthopaedic-plastic surgery service was ordered, yielding a delayed diagnosis of capillary leak syndrome and hemorrhagic/thrombotic coagulopathy. This resulted in compartment syndrome of the right arm. Emergent surgical intervention was performed to prevent loss of the upper extremity.
Reconstruction
At surgery, medium-sized and small-sized venous thrombosis and massive third-spacing of fluid was evident, resulting in the necrosis of the superficial volar compartment muscles and the median nerve. The radial and ulnar arteries remained patent, and the ulnar nerve was viable. The arm required an extended volar fasciotomy crossing the antecubital fossa onto the distal brachium, and anterior over the dorsal forearm (Figure 1). Operative cultures grew Klebsiella aerogenes, and parental culture/sensitivity-specific antibiotics were initiated.
At repeat irrigation and debridement, there was continued necrosis involving the deep volar compartment (Figure 2). After secondary debridement, both the radius and ulna were exposed (Figure 3); only the flexor carpi ulnaris (FCU), brachioradialis (BR), radial and ulnar arteries, and ulnar nerve remained. The stumps of flexor digitorum longus (FDL), flexor digitorum profundus (FDP), and flexor pollicis longus (FPL) were salvaged at the wrist crease. A negative pressure dressing with fluid ingress/egress function was applied in the operating room.
Postoperatively, serial CPK levels measured daily trended downward over 2 weeks but never normalized; however, the patient still required hemodialysis and remained intubated. The patient’s pulmonary and mental status improved, and he was ultimately extubated. A bedside examination demonstrated intact sensation and intrinsic motor function to the distribution of the radial and ulnar nerves. Wrist flexion was 4-/5 (Medical Research Counsel Scale Manual Muscle Testing Scale) with activity of the FCU. Wrist and finger extension and BR functions remained. Finger flexion (deep and superficial; FDP), radial wrist flexion, and thumb flexion functions (FPL) were absent. Thenar eminence function also was absent. Thus, hand grasp via finger flexion and thumb flexion/pinch, thenar function, and partial wrist flexion were lost.
Because the stumps of the FDP and FPL were salvaged at the level of the volar wrist crease, tendon transfers remained an option to restore hand grasp. To restore finger flexion, the extensor carpi radialis longus (ECRL) tendon was transferred to the combined tendons of the FDP (Figure 4A, 4B). To restore thumb flexion-pinch, the BR was transferred to the stump of the FPL tendon (Figure 4C). A human decellularized dermal allograft with vascular-like channels (DermaPure; Tissue Regenix) was utilized to reinforce the tendon transfers (Figure 5). To achieve soft tissue coverage of the tendon transfer reconstruction and the volar forearm soft tissue defect, an adipofasciocutanious abdominal thoracoepigastric tube flap was elevated, maintaining a wide proximal skin bridge (Figure 6A, 6B). The forearm was banked under the flap, completely covering the tendon transfers and volar soft tissue defect (Figure 6C). The dorsal fasciotomy brachial wounds were skin grafted. Decellularized dermis also was used to repair an incidental defect of the transversalis abdominal fascia discovered at flap elevation.
The forearm was banked under the abdominal flap for 3 weeks, after which division of the flap skin bridge commenced. Partial skin division was performed, maintaining a smaller tubed skin bridge (Figure 7). One week later, the residual skin bridge was divided, and the forearm elevated from the abdominal wall. The orthoptic abdominal adipofasciocutaneous tissue was completely inset onto the native volar margins of the forearm (Figure 8A–8C). The abdominal wall was closed (Figure 8D). After repair of the abdominal wall fascial defect with the decellularized dermal allograft, the umbilicus was reassigned to a midline position.
After both arm banking and flap inset, the patient’s shoulder, elbow, finger, and thumb motion resumed immediately; a tendon transfer rehabilitation and retraining program was also initiated. Hand therapy was continued throughout the postoperative course.
At 6 weeks postoperatively, there was complete healing of the flap and skin grafts (Figure 9A). At the 3-month follow-up, the patient had full shoulder and elbow motion. The initial stages of self-directed thumb-index pinch and finger flexion were demonstrated (Figure 9B). Sensation to the distribution of the ulnar and radial nerve remained intact, with 3 mm static 2-point discrimination to the distribution of the ulnar and radial nerves.
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 activation2 and thrombocytopenia3 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 misdiagnosis 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 aforementioned 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.
Fulminant respiratory failure with alveolar leak can result from COVID-19. Coagulopathies also develop in large numbers of patients. These 2 pathologic processes may have serious systemic implications, such as thrombosis or hemorrhage, resulting in dysfunction of multiple organ systems. The combination of a systemic capillary leak syndrome, coupled with a thrombotic/hemorrhagic coagulopathy (“triple hit”) may also impart serious complications, such as compartment syndrome of the extremities. Although infrequently reported, vigilance must be employed with a high level of suspicion for compartment syndrome in patients with COVID-19 infection who develop tense limb edema and soft tissue changes, such as blisters and discolored bullae. In the obtunded patient, there must be a low threshold to evaluate for compartment syndrome of an extremity. In order to achieve limb salvage, surgical intervention should be performed as soon as the patient is rendered physiologically stable to tolerate an operative setting. The timing of reconstruction of the sequelae of compartment syndrome in the patient who is acutely ill is challenging, but optimal timing can result in a successful outcome.
Author: Christopher Bibbo, DO, FACS, FAAOS, FACFAS
Affiliation: Rubin Institute for Advanced Orthopedics, Baltimore, MD
Correspondence: Dr. Christopher Bibbo, International Center for Limb Lengthening, Rubin Institute for Advanced Orthopedics, Sinai Hospital of Baltimore, 2401 W Belvedere Avenue, Baltimore, MD 21215; drchrisbibbo@gmail.com
Disclosure: The author discloses no financial or other conflicts of interest.
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