Secondary operative evaluation of the lower extremities showed continued muscular swelling. Areas of necrosis were identified in portions of the right flexor digitorum, right posterior tibialis, and right and left soleus muscles. These muscles were debrided to a margin of viable tissue.
Irrigation and debridement along with sterile dressing changes were performed on all fasciotomy wounds every 48 hours. On the ninth day in the hospital, delayed primary closure was done, and split thickness skin grafts were placed to complete skin coverage.
The patient also had acute renal failure develop secondary to rhabdomyolysis. During the first week of her hospital stay, her peak blood urea nitrogen and creatinine values were 76mg/dL and 4.5mg/dL, respectively. She required 1 month of peritoneal dialysis. Her renal status improved during her hospital course, with her blood urea nitrogen and creatinine levels returning to normal by the time of discharge.
Multiple diagnostic tests were performed to determine the cause of the rhabdomyolysis. Muscle biopsy specimens were not diagnostic but showed extensive muscle lysis with interstitial edema (Fig 3). All blood and muscle biopsy cultures were negative, and the initial tracheal aspirate was positive for the influenza A virus. She also had an influenza A antibody titer of 1:256. Rheumatologic studies included a positive antinuclear antibody titer of 1:160 and a negative rheumatoid factor. Based on these studies and her clinical course, it was concluded that the rhabdomyolysis was secondary to an influenza A infection.
Despite intensive occupational therapy, stretching casts, and ankle to foot orthoses, equinovarus contractures of both feet occurred. Three months after her discharge, posteromedial releases were done. One year 6 months after surgery, she is able to ambulate independently. She also has the ability to toe and heel walk with minimal residual weakness. Her upper extremities are functionally normal, with normal flexion, extension, grasp, and release abilities. She also has normal cognitive function for her age.
This unique case of compartment syndrome secondary to influenza A induced rhabdomyolysis is atypical because of the mechanism of rhabdomyolysis resulting in compartment syndrome, the extent of compartments involved, and the continued swelling of the muscles after fasciotomy.
Rhabdomyolysis results from injury to the cell membrane of skeletal muscle. Membrane disruption results in the release of intracellular substances into the plasma, including myoglobin and creatine phosphokinase.10Figure 4 shows how muscle breakdown ultimately can lead to compartment syndrome and how the presence of compartment syndrome can perpetuate a cycle of additional tissue damage.
There are many potential causes of rhabdomyolysis. Chronic alcohol ingestion, muscle compression, and generalized seizures are among the three most common.3 Other causes include infection, substance intoxication, hereditary enzyme defects, and metabolic disorders.3 Common orthopaedic circumstances causing rhabdomyolysis include trauma, limb ischemia, reperfusion injury, compartment syndrome, extreme muscular exertion, posterior spinal surgery, tourniquet use, and poor positioning of obese patients during surgery.10 Viral infection may cause rhabdomyolysis either by direct cell injury or indirectly by toxin release.11,13 Influenza, human immunodeficiency virus, and enteroviruses have been reported to be associated with rhabdomyolysis.13
The presentation of rhabdomyolysis is varied, and the diagnosis of rhabdomyolysis is important to suspect in a patient with a suggestive clinical history, myalgia, and myoglobinuria. Acute renal failure, which was seen in this case, is a major complication of rhabdomyolysis, affecting as many as 1/3 of patients.3 To detect myoglobin in the urine, its concentration must be at least 100 mg/dL.3,11 The orthotolidine dipstick test used to detect blood on urinalysis detects heme and cannot differentiate myoglobin from hemoglobin.3 However, this test is useful when used in conjunction with the microscopic urine analysis because few erythrocytes should be seen in patients with myoglobinuria. Thus, the positive heme test, in a clinical situation suggesting rhabdomyolysis, is indicative of myoglobin. Myoglobinuria may be diagnosed conclusively using a specific assay or visualizing pigmented granular casts of myoglobin in the urine sediment.3,11 Elevated serum creatine phosphokinase and myoglobin also suggest significant muscle injury. Creatine phosphokinase has a much slower clearance from the plasma than does myoglobin, and thus is detected for a longer duration after muscle damage.3,11 Other abnormal laboratory values in rhabdomyolysis include serum hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia.3,10,11 Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels also may be elevated.11
Typical musculoskeletal signs and symptoms of rhabdomyolysis include muscle pain, stiffness, and weakness. However, these may be present only 50% of the time.3 Muscle involvement may be diffuse or involve specific muscle groups. The myopathy of rhabdomyolysis usually is self limited, resulting in little residual muscle damage.11
Rarely, compartment syndrome may be a complication of rhabdomyolysis. Typically, it is the rhabdomyolysis associated with trauma and prolonged immobilization that results in compartment syndrome.11 Although influenza is the most common viral cause of rhabdomyolysis, influenza induced rhabdomyolysis infrequently results in compartment syndrome.11,13 The authors could locate only one other case of influenza infection associated rhabdomyolysis leading to compartment syndrome. That report involved influenza B infection leading to bilateral lower extremity compartment syndrome.9 The current authors' study is significant because of much more widespread muscle injury, resulting in the need for fasciotomy in all four extremities, and the involvement of influenza A.
Compartment syndrome leads to muscle and nerve damage by the pathway of increased tissue pressure. As the tissue pressure approaches terminal arteriolar pressure, the nutrients in the circulation cannot reach the capillary bed, and tissue ischemia results. Terminal arteriolar pressure has been shown to be equal to diastolic blood pressure.14 Blood flow in the microcirculation ceases when tissue pressure approaches diastolic blood pressure.1 Initially, the surrounding tissues are able to compensate for the decrease in blood flow by autoregulation of the microcirculation, enhanced venous oxygen extraction, and oxygen tension normally in excess of critical levels.4 However, with increasing or prolonged elevation of tissue pressures, compensatory mechanisms fail.4 In the current report, the increase in tissue pressure was caused by primary muscle destruction and resulting edema.
Another interesting aspect of this study was the continued muscle swelling after the release of the lower extremity compartments. This progressive swelling likely is related to the directly toxic effects of influenza infection on muscle. Whether the virus directly invades the muscle or releases a muscle damaging toxin has not been established.11,13 Histologic examination of muscle associated with influenza infection reveals clusters of necrotic muscle mixed with normal muscle, sometimes associated with a lymphocytic infiltrate, as was seen in this patient.13 Identification of the viral particles within the tissue sometimes is possible, although it was not done in this case.13 Normally in compartment syndrome, once the compartments are released, external pressure is released and blood flow increases, resulting in an end to the injury. Progressive swelling is a unique finding of this case and may be unique to influenza associated rhabdomyolysis. Continued swelling may suggest a primary muscle pathologic process, or myositis, as opposed to other more common causes of compartment syndrome.
There is no exact value of compartment pressure that is accepted universally as an indication for fasciotomy. Normal compartment pressure ranges from 0 to 8 mm Hg.12 Some authors recommend decompression at an absolute compartment pressure in the clinical setting of compartment syndrome. Mabee and Bostwick5 and Matsen et al7 recommended using 45 mm Hg, and Mubarak and Hargens recommended using 30 mm Hg as the critical decompression pressure.8 Other authors suggested there is no absolute tissue pressure defining compartment syndrome. Heppenstall et al4 recommended evaluating the difference between the mean arterial blood pressure and the compartment pressure to define compartment syndrome. They suggested the lowest pressure difference allowing muscle to remain viable is 30 mm Hg in atraumatic muscle and 40 mm Hg in traumatized muscle.4
In the patient reported here, continued deterioration of physical examination and tissue pressure measurement were important diagnostic tools. At the authors' institution, the criteria suggested by Matava et al6 and Whitesides and Heckman15 for compartment decompression is preferred. They recommended decompression when intracompartmental pressures approach 20 mm Hg below diastolic blood pressure. Clinicians should maintain careful observation of these difficult wounds to ensure adequate debridement of necrotic muscle and adequate compartment decompression and should anticipate additional swelling attributable to progressive muscle injury.
Compartment pressures should be measured intraoperatively to ensure adequate decompression. After surgery, limbs should be monitored closely for signs of progressive swelling, as was seen in the patient reported here. Serial debridements and secondary procedures for coverage and reconstruction often are necessary. Range of motion exercises and intensive occupational therapy should be started early to limit the severity of postoperative stiffness and facilitate muscle tendon and nerve excursion.7
Although rare, compartment syndrome must be considered in the evaluation of a patient with influenza and severe myalgia. Standard physical examination methods and diagnostic assessment strategies are useful in diagnosis. The outcome in patients with compartment syndrome caused by influenza infection may be guarded because of numerous factors, including the potential involvement and compromise of multiple organ systems and the severity of the myositis and duration of pressure elevation.
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© 2000 Lippincott Williams & Wilkins, Inc.
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