Life-Threatening Rhabdomyolysis Complicating Surgical Reperfusion of Peripheral Arterial Occlusive Disease — a Case Report and Literature Review

Case Report Chih-Hsuan Yen et al. Acta Cardiol Sin 2004;20:120-124

Life-threatening Rhabdomyolysis Complicating Surgical Reperfusion of Peripheral Arterial Occlusive Disease — A Case Report and Literature Review

Chih-Hsuan Yen,1 Ping-Ying Lee,1,2 Charles Jia-Yin Hou,1 Yu-San Chou,1 Cheng-Ho Tsai1

Rhabdomyolysis is a rare complication following successful reperfusion of occluded peripheral arteries. Acute renal failure frequently develops in these patients, and it carries a high mortality rate. We report a 78-year-old female with near-total occlusion of bilateral femoral arteries. After successful femoral-popliteal artery bypass, she developed rhabdomyolysis with acute renal failure. Despite intensive support and treatment, she died of multiple-organ failure.

Key Words: Rhabdomyolysis · Acute renal · Failure peripheral · Arterial occlusive disease

INTRODUCTION nal failure after successful peripheral vascular surgery.

Rhabdomyolysis, compartment syndrome, and crush syndrome represent a spectrum of the same disease,1,2 CASE REPORT which may be induced by numerous factors, including alcoholism, crush injury to a limb, overuse of skeletal A 78-year-old female suffered from right leg swell- muscle, heat, viral infections, metabolic disorder, ing, pallor, and pain and was not able to move her leg for myopathies, drugs, toxins, and hyperkalemia.1,3 2 weeks prior to admission. The patient had a history of Rhabdomyolysis is a rare complication after successful hypertension treated with amlodipine for 2 years and bypass surgery for peripheral vascular disease. Acute type 2 diabetes mellitus for 3 years. She did not smoke. myoglobinuric renal failure may further complicate the Toes of both legs were cyanotic and cold, and dorsalis situation, with catastrophic results. In a recent study of pedis pulses were weak bilaterally. crush injuries, acute renal failure developed in 16.5% of Selective angiographic examination (Figure 1) re- patients with rhabdomyolysis, and 42.3% of them died.3 vealed near-total occlusion of several segments of We report a case of severe rhabdomyolysis with acute re- bilateral femoral arteries. She underwent a femoral-popliteal bypass with 10 mm ringed vascular grafts and bilateral femoral artery endarterectomy. After sur- Received: October 24, 2003 Accepted: December 12, 2003 gery, her legs became warm and strong dorsalis pedis 1 Division of Cardiology, Department of Internal Medicine, Mackay pulses were palpable bilaterally. She was treated with in- Memorial Hospital, Mackay Junior College of Nursing, 2Graduated Institute of Medical Science, Taipei Medical University, Taipei, Taiwan travenous heparin and prostaglandin E1 postoperatively. Address correspondence and reprint requests to: Dr. Chih-Hsuan Yen, Neither hemodynamic compromise nor hypoglycemia Division of Cardiology, Department of Internal Medicine, Mackay were found during and on the first day after the surgery. Memorial Hospital, No. 92, Sec. 2, Chung-Shan North Road, Taipei 104, Taiwan. Tel: 886-2-2543-3535 ext. 2456; Fax: 886-2-2543-3535, Three days after surgery, the patient suddenly be- ext. 2459; E-mail: [email protected] came dyspneic and oliguric. Her urine was dark red in

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ing, and compartment syndrome was suspected. She therefore underwent fasciotomy. Unfortunately, the right toe was persistent in gangrene and subsequent right above-the-knee amputation was performed a few days later. The CK decreased to 938 U/L and creatinine level to 0.9 mg/dL 10 days after the amputation. However, the patient later developed pneumonia with septic shock and became comatose. She subsequently developed multiple-organ failure syndrome and died 1 month later.

DISCUSSION

Rhabdomyolysis has been defined as reversible or irreversible injury of skeletal muscle in which cell membrane loses its integrity and cell contents leak out to the extracellular compartment.1 It can be triggered by any process which diminishes the production of adenosine triphosphate, such as inadequate oxygen sup- ply secondary to ischemia, hypotension or vasospasm, or increased consumption of ATP beyond the production rate of the skeletal muscle.1,4 It is generally accepted that intracompartment pressures between 30 and 50 mmHg may render muscle ischemia and under Figure 1. Angiographic examination of lower-extremity arteries shows such condition for 4 to 8 hours necrosis occurs in skele- atherosclerotic changes of both iliac arteries and femoral arteries (A, 5 thin arrowheads) and near-total occlusion in several segments of the tal muscle. In crush syndrome, a rapidly progressive femoral arteries. (B, thick arrowheads). Note that collateral circulation pressure-stretch myopathy is thought to be the earliest is more abundant in the left side, compared to the right side. predominant event.6 Besides compartment pressure-induced ischemia, another important cause of skeletal muscle damage is reperfusion injury mediated by oxy- Table 1. Patient,s serial muscle enzymes gen free radicals.5,7 In our patient, neither hemodynamic 3/16 3/17 3/17 3/17 3/19 3/21 3/22 3/24 compromise nor metabolic disorders such as CK (U/L) 3526 7011 21659 5808 3378 3299 938 730 hyperkalemia, acidosis, and hypoglycemia were found AST (U/L) 2003 1101 1805 1079 128 112 37 51 during and in the first 2 days after surgery. In addition, CK = creatine kinase; AST = aspartate aminotransferase. rhabdomyolysis secondary to anastomosis leakage and thrombosis usually occurs within 24 hours after the sur- color and her plasma creatinine increased from 0.8 to 2.0 gery,4 but in our patient after bypass, strong bilateral mg/dL, creatine kinase (CK) level was 3526 U/L on the dorsal pedis pulses persisted for 2 days, and next day, and 1 day later it reached peak (21659 U/L, rhabdomyolysis with subsequent acute renal failure did 200 times higher than normal)(Table 1). Serum myoglobin not happen until 3 days later. We therefore suspected measured several days after the acute episode was within that the cause of rhabdomyolysis in our patient was at normal limits. The patient was treated with saline infu- least in part from reperfusion injury following bypass. sion to keep adequate hydration and intravenous sodium The mechanism of reperfusion injury involves cal- bicarbonate to maintain the urine pH above 6.5. Her cium, leukocytes, and oxygen free radicals, the last of right toes subsequently developed gangrene and swell- which is thought to have major impact on the progression

121 Acta Cardiol Sin 2004;20:120-124 Chih-Hsuan Yen et al. of injury. The primary source of superoxide in reperfused the duration of compression.2,7 Other inhibitors of free rad- tissue appears to be the product of xanthine oxidase, icals, such as superoxide dismutase, catalase, iron chelating which is converted from xanthine dehydrogenase by a agents and calcium channel blockers, have been shown to calcium-triggered proteolytic attack.7,8 be effective in animal models.8 However, these scavengers The diagnosis of rhabdomyolysis is based on a need to be administered as early as possible during 5-fold increase in the serum CK or the presence of reperfusion in order to prevent irreversible cell damage. myoglobinemia, with or without myoglobinuria.1,4 Amiloride, a potassium-sparing diuretic decreasing Myoglobinemia correlates poorly with myoglobinuria, intra-cellular sodium concentration and inhibiting so- since the level of myoglobin in the urine depends on a va- dium-hydrogen exchanger in many tissues, is reported to riety of factors, including the amount of myoglobin markedly improve the contractile and metabolic recovery released into plasma, the glomerular filtration rate, and during post-ischemic reperfusion.3 Benzamil, an amiloride the urine concentration.1 Thus, not all patients with analogue with a stronger ability to block sodium-calcium myoglobinemia have visibly red urine. Myoglobin is rap- exchanger, is more protective against the calcium-paradox idly cleared from the blood, usually within 1 to 6 hours. than amiloride.3 Our patient was hyperkalemic after the on- Therefore the plasma level may be within normal limits a set of rhabdomyolysis, therefore, usage of these few hours to days after the onset of rhabdomyolysis. This potassium-sparing agents seemed to be inappropriate. may explain the normal myoglobin level in our patient. Fasciotomy will be performed if compartment syndrome The pathogenesis of acute renal failure in develops.4,7 To save life from extension gangrene, amputa- rhabdomyolysis is still not clearly understood. One pos- tion is suggested if fasciotomy treatment is not effective.6 sibility is that decomposed myoglobin products, such as The lack of definitive therapy for rhabdomyolosis together ferrihemate that is usually present when urine pH < 6.5, with the numerous clinical problems in this lady prevented have direct toxic effects. In this regard, there may also us from saving her life from the lethal sequela after the by- be tubular obstruction by myoglobin itself or uric acid pass surgery. crystals. Another hypothesis is that the release of vasoconstrictive mediators (angiotensin-II, catechol- amines, vasopressin, and intrarenal thromboxane) REFERENCES secondary to renal ischemia may play a major role.3 Risk factors of acute renal failure in the setting of 1. Patricia AG, William DK, Stephen PK. The spectrum of rhabdomyolysis. Medicine 1982;61:141-52. rhabdomyolysis include hypovolemia, extreme elevation 3,9 2. Maclean JGB, Barrett DS. Rhabdomyolysis: a neglected priority of serum CK concentration, and a low urine pH. Some in the early management of severe limb trauma. Trauma injury authors suggest all acutely ischemic patients are groups 1993;24:205-7. 6 at high-risk for renal complication. 3. Majed O. The role of reperfusion-induced injury in the pathogenesis Adequate hydration and urine alkalization is essential of the crush syndrome. N Engl J Med 1991;324:1417-21. for treatment of rhabdomyolysis combined with acute renal 4. Ferreira TA, Pensado A, Dominguez L, et al. Compartment failure. In fact, under such treatment, our patient did ini- syndrome with severe rhabdomyolysis in the postoperative period following major vascular surgery. Anaesthesia 1996;51:692-4. tially recover from renal failure. Regarding treatment of 5. Charles AO, Scott JM, Alan RH, et al. Intramuscular pressure rhabdomyolysis secondary to reperfusion injury, contro- with limb compression: clarification of the pathogenesis of the versy exists. A previous report showed that inhibitors of drug-induced muscle-compartment syndrome. N Engl J Med oxygen free radicals limit the generation of arachidonic 1979;300:1169-72. acid products following ischemia.10 In addition, scavengers 6. Ori SB, Zaid A, Irith R, et al. The mechanism of muscle injury in of free radicals have been investigated. These agents in- the crush syndrome: ischemic versus pressure-stretch myopathy. clude mannitol (which also promotes osmotic diuresis and Miner Electrolyte Metab 1990;16:181-4. 7. Adiseshiah M, Round JM, Jones DA, et al. Reperfusion injury in may be appropriate for acute renal failure) and allopurinol.7 skeletal muscle: a prospective study in patients with acute limb However, effects are difficult to assess because the severity ischaemia and claudicants treated by revascularization. Br J Surg of crush syndrome is unpredictable; for example, it does 1992;79:1026-9. not appear to be related to the size of the area involved or 8. Joe MM. Oxygen-derived free radicals in post-ischemic tissue

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injury. N Engl J Med 1985;312:159-63. 10. Welbourn CRB, Goldman G, Paterson IS, et al. Pathophysiology 9. Ward MM. Factors predictive of acute renal failure in of ischemia reperfusion injury: central role of the neutrophil. Br J rhabdomyolysis. Arch lntern Med 1988;148:1553-7. Surg 1991;78:651-5.

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