Bench-to-bedside review: Rhabdomyolysis – an overview for clinicians

Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration.     

非外伤性横纹肌溶解症的临床特点

目的了解非外伤性横纹肌溶解症(RM)的临床特点和发病机制。方法对11例非外伤性RM的病因和临床表现进行回顾性分析。结果本组病因包括药物性3例,一氧化碳中毒2例,高强度运动2例,高强度农业劳动1例,其他3例。临床表现为肌无力、肌痛、肌肿胀、茶色尿、肾功能衰竭,实验室检验包括肌酸激酶增高,各种电解质紊乱。结论药物是引起非外伤性RM的主要原因,诊断主要依据临床表现和血清肌酸激酶显著升高。急性肾功能衰竭是其严重和导致死亡的主要并发症。     

Exertional rhabdomyolysis in a body builder abusing anabolic androgenic steroids.

Rhabdomyolysis, or acute skeletal muscle destruction, may be accompanied by myoglobinaemia, myoglobinuria, and an elevated serum creatine kinase level. This disorder has many potential causes. In this article, the authors describe a case of rhabdomyolysis occurring after vigorous weight lifting by a man who was supplementing his weight-training programme with the intake of anabolic androgenic steroids dispensed to him by a colleague.     

Natural history of potassium-deficiency myopathy in the dog: role of adrenocorticosteroid in rhabdomyolysis

Potassium deficiency occurs in several conditions and is reported to cause muscle weakness and rhabdomyolysis. The mechanisms by which potassium deficiency cause muscle disease remain unknown, but the primary purpose of the present study was to determine whether abnormal muscle glycogen metabolism causes muscle weakness, as suggested by previous work. We monitored the natural history of potassium deficiency in two groups of dogs, one of which also received deoxycorticosterone acetate (DOCA), an agent commonly used in other studies to accelerate potassium loss. Group I dogs on potassium-free diet alone showed a 41% decrease in muscle potassium, no change in serum CO2, creatine kinase (CK), or muscle phosphorylase activity and only mild histopathologic abnormalities before death, after 198 +/- 42 days on the diet (mean +/- S.D.). In contrast, group II dogs on the same diet plus DOCA developed clinically similar severe weakness and died more rapidly than group I, 37 +/- 7 days (p less than 0.03). DOCA dogs showed a more rapid decrease in muscle potassium to the same level as group I, a 37% increase in serum CO2, an increase in serum CK to 1060 to 2775 IU/ml, a 23% decrease in muscle phosphorylase activity, and severe muscle histopathology, including rhabdomyolysis. Neither group showed any change in body weight, electromyogram (EMG), muscle glycogen concentration, glycogen synthetase activity, serum or muscle magnesium or phosphorus, or serum T3 or T4. In conclusion, dietary potassium deficiency in dogs causes severe weakness and death without causing rhabdomyolysis or abnormal muscle glycogen metabolism. Adding DOCA to the potassium-free diet creates a different model characterized by rapid clinical deterioration and rhabdomyolysis.     

Masseter muscle rigidity, elevated creatine kinase, and rhabdomyolysis following succinylcholine administration: a case report

This case report details the onset of masseter muscle rigidity, elevated creatine kinase levels, and rhabdomyolysis following a sevoflurane mask induction and succinylcholine administration in a 12-year-old boy. The patient had no family or personal history of neuromuscular disease or malignant hyperthermia. Hyperkalemia, metabolic acidosis, and rhabdomyolysis occurred within 75 minutes of masseter muscle rigidity. Subsequent to this event, it was recommended that the patient undergo a workup for neuromuscular disease and malignant hyperthermia with muscle biopsy. Until this workup is completed, the family should advise anesthesia providers that the patient is "malignant hyperthermia susceptible." Masseter muscle rigidity, elevated creatine kinase levels, and rhabdomyolysis will be thoroughly discussed in this article.     

Rhabdomyolysis in a patient treated with colchicine and atorvastatin

OBJECTIVE: To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment. CASE SUMMARY: A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50-fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis. DISCUSSION: Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatin's proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities. CONCLUSIONS: We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.     

酒精中毒合并横纹肌溶解症的诊治体会

目的：探讨酒精中毒合并横纹肌溶解症（RM）的临床特点、病因及诊治方法。方法：总结分析15例酒精中毒合并横纹肌溶解症患者的临床资料及治疗、预后情况。结果：15例患者均为重度酒精中毒,并发急性肾衰竭（ARF）6例,昏迷时间及饮酒至入院时间长,酗酒合并挤压伤、吸入性肺炎、血糖代谢紊乱是主要原因,行连续性肾脏替代治疗（CRRT）2例,血液透析（HD）1例。痊愈14例（93.3%）,死亡1例（6.7%）,为挤压伤并发尿毒症、多器官功能障碍综合征（MODS）。结论：酒精中毒合并横纹肌溶解症常见于酗酒者,早期都为昏迷患者,酗酒合并挤压伤、感染、血糖异常、电解质紊乱是其主要诱因,血肌酸激酶（CK）是反映RM肌肉损害程度和范围最敏感的指标,RM常并发ARF,MODS是其主要死亡原因。早期诊断,及时去除病因、补液、碱化尿液及合理应用血液净化技术是降低病死率的关键。CRRT可清除细胞破坏崩解产物,对预防和减轻肾功能不全疗效确切。     

Elimination kinetics of myoglobin and creatine kinase in rhabdomyolysis: implications for follow-up

OBJECTIVE: Creatine kinase and myoglobin are markers of muscular damage in rhabdomyolysis. Whereas myoglobin is considered to be the principal compound causing tubular damage, serum creatine kinase level is presently guiding therapeutic interventions in clinical practice to prevent acute renal failure. Because differences in elimination kinetics of these two compounds may influence therapeutic decisions, we studied elimination kinetics of myoglobin and creatine kinase in patients with rhabdomyolysis. DESIGN: Open, noncomparative study. SETTING: Intensive and intermediary care units in a university hospital. PATIENTS: A total of 13 consecutive patients with rhabdomyolysis whose baseline serum creatine kinase exceeded 5000 IU/L. Ten of 13 patients were treated with forced alkaline diuresis, and none were dialyzed. RESULTS: Myoglobin had faster elimination kinetics than creatine kinase (p <.01), and the average times to reach the 50% level of initial values were 12 hrs for myoglobin and 42 hrs for creatine kinase. Elimination of myoglobin was not affected by glomerular filtration rate. Compared with creatinine clearance (mean, 102 mL/min), myoglobin clearance was low (mean, 3 mL/min), both in patients with preserved renal function (n = 11) and in those with acute renal failure (n = 2). CONCLUSION: Serum myoglobin has faster elimination kinetics than creatine kinase in patients treated with forced alkaline diuresis for rhabdomyolysis. Considering the etiologic role of myoglobin, our data suggest that serum myoglobin level, rather than that of creatine kinase, should be used to guide therapy in patients with rhabdomyolysis.     

Corticosteroids in the treatment of alcohol-induced rhabdomyolysis

Rhabdomyolysis is a common condition with potentially devastating complications, including acute renal failure, arrhythmias, and death. The standard of care is to use supportive measures such as aggressive fluid repletion to prevent kidney injury and attenuate clinical symptoms. Besides fluid management, few therapeutic options are available for the treatment of acute rhabdomyolysis. As a result, acute and refractory cases remain difficult to manage. We report a case of alcohol-induced rhabdomyolysis that responded dramatically to high-dose corticosteroids. A 55-year-old man presented to the emergency department for evaluation of diffuse muscle pain, weakness, and darkening urine. On admission, his creatine kinase (CK) level was 50,022 U/L. Despite aggressive fluid repletion, his CK level continued to increase, peaking at 401,280 U/L with a concomitant increase in muscle pain and urine darkening. On administration of high-dose corticosteroids, clinical symptoms and CK levels improved dramatically, and the patient was discharged 36 hours later with complete resolution of muscle pain and weakness. Given their low toxicity profile, short-term high-dose corticosteroids may be a valid treatment option for recurrent rhabdomyolysis unresponsive to fluid repletion.     

Rhabdomyolosis and its pathogenesis

BACKGROUND:

Rhabdomyolysis may cause severe damage to the human body because of acute renal failure, fatal heart rhythm disturbances, hypovolemic shock, disturbances of electrolyte balance, metabolic acidosis, hyperthermia, disseminated intravascular coagulation, etc. Drugs and toxins are the most common factors for the disease. This article aimed to review the prognosis of rhabdomyolysis.DATA SOURCES: Based on the reported studies of cell and molecular biology, we reviewed the clinical presentations, laboratory findings, and mechanisms of rhabdomyolysis in the Pubmed.

RESULTS:

The clinical symptoms of rhabdomyolysis were dependent on the severity of the condition and whether kidney failure develops. Since the necrosis and dissolution of muscle cells, entocytes such as myoglobin, creatine phosphokinase (CPK), electrolytes, proteins and non-protein substances were released into the plasma, the detection of the entocytes may contribute to the early diagnosis of rhabdomyolysis.

CONCLUSION:

Despite the etiology of the disease is multifactorial, the potential causes of rhabdomyolysis share the same pathophysiological pathway involving an increase in intracellular calcium.KEY WORDS: Rhabdomyolysis, Etiology, Pathophysiological pathway     

Rhabdomyolysis in the intensive care unit

Rhabdomyolysis is a clinical syndrome defined by muscle breakdown and subsequent release of intracellular contents. There are many etiologies of rhabdomyolysis, classified here as congenital and acquired; compartment syndrome secondary to trauma with reperfusion injury is one common precipitating factor. Regardless of the underlying etiology, the pathophysiology follows a similar pathway via myocyte destruction and release of myoglobin into the systemic circulation. Rhabdomyolysis-induced renal failure is caused by the precipitation of myoglobin in the renal tubules which is enhanced under acidic conditions. A high index of clinical suspicion is required to promptly recognize rhabdomyolysis, especially in the unconscious patient. Presenting symptoms include tea-colored urine and muscle weakness or fatigue. The diagnosis is confirmed most reliably with the finding of elevated serum creatine kinase levels. Early, aggressive resuscitation with either normal saline or lactated Ringer's solution to maintain an adequate urine output is the most important intervention in preventing the development of acute renal failure. There is insufficient clinical evidence supporting the routine administration of diuretics and bicarbonate to protect against the development of acute renal failure.     

McArdle disease presenting as acute renal failure

In 1951, McArdle described a glycogen storage disorder which presents primarily as a myopathy. It is characterized by muscle pain, weakness and exercise intolerance with elevated creatine kinase from rhabdomyolysis. The pathophysiology involves a deficiency of myophosphorylase enzyme resulting in an inability to degrade glycogen stores. We present a novel case of McArdle disease (glycogen storage disease V [GSDV]) in a patient who had sickle cell trait and bulimia. The disease went unrecognized despite several admissions to the hospital with increased creatine kinase and muscle myopathy until the patient's initial presentation with acute renal failure.     

Rhabdomyolysis associated with compartment syndrome resulting in acute renal failure.

Compartment syndrome has rarely been reported associated with acute rhabdomyolysis. In the case described, the rhabdomyolysis was severe enough to cause compartment syndrome and acute renal failure after moderate exercise and alcohol intake and had the appearance of a myositis. The case emphasizes the importance of early recognition of compartment syndrome, as loss of pulses is a very late sign, and the examination of the urine to detect myoglobinuria in rhabdomyolysis. Measurement of creatine kinase is predictive of the extent of muscle damage and the development of renal failure.     

Rhabdomyolysis

Rhabdomyolysis is a severe clinical symptom of variable etiology. Acquired factors of exogenous origin such as traumata and endogenous metabolic disturbances have to be separated from hereditary disease as causative mechanism. Most frequently, exertional stress during hyperthermia, traumatic damage or ethanol abuse are observed. Almost independent of the diverse initial events, the pathogenesis follows a common final pathway with intracellular calcium accumulation and ATP depletion. Clinical symptoms vary. Seldom, the classical triad of muscle pain, weakness, and dark urine is observed. Recurrent episodes should raise suspicion of an inherited disorder. Severe complications are hypovolemia, electrolyte disorders with hyperkalemia and hypocalcemia resulting in life threatening arrhythmias, a compartment syndrome, disseminated intravascular coagulation and acute renal failure, which is frequently oligo-anuric. In combination with often severe underlying disease, renal failure causes death in 1/5 of the patients. The diagnosis is made with the determination of serum creatine kinase and the myoglobin levels in plasma and urine. Therapeutic options are to correct the hypovolemia with sufficient fluid supply, the prevention of oliguria using loop diuretics, alkalinization of the urine, normalization of serum electrolytes with reduction of hyperkaemia, and decompression of compartment syndromes. An underlying disease should be evaluated to initiate specific therapeutical and preventative steps. Avoiding pre-disposing factors by identifying the mechanisms of disease will reduce the occurrence of rhabdomyolysis with its still high mortality.     

Rhabdomyolysis: two pediatric case reports

We report two pediatric cases of rhabdomyolysis. This disease involves the destruction of skeletal muscle, which can present with myalgia and a brown-pigmented urine. The first patient presented with acute renal failure, hypertension, and hyponatremia. The second patient was pyrexic, hypernatremic, and hypokalemic, and later developed hypertension. Evidence of rhabdomyolysis in both patients included dark, o-tolidine-positive urine, granular casts in the urinary sediment, and grossly increased activities of creatine kinase (greater than 60 000 U/L) in serum. An uncommonly recognized entity in the pediatric age group, rhabdomyolysis often presents as an acute disease with severe onset but can be diagnosed with relatively simple laboratory tests.     

A Study on the Effects of Severe Repetitive Exercise on Serum Myoglobin, Creatine Kinase, Transaminases and Lactate Dehydrogenase

Two groups of young men taking part in a 24-day training courseinvolving increasingly severe exercise were studied. Serum myoglobin,creatine kinase, creatine kinase-MB, transaminases, lactatedehydrogenase, urea, creatinine, calcium and uric acid wereestimated at intervals. During the first few days, increasesin myoglobin and muscle enzymes correlated with the severityof the preceding exercise. Increases in myoglobin and muscleenzymes after the final most severe exercising were less thanwith the initial exercising, demonstrating the effect of physicaltraining. The changes in myoglobin and the muscle enzymes correlatedclosely. Elevated myoglobin levels persisted for over 24 hours.There was no consistent correlation between changes in myoglobinand uric acid, both of which have been considered responsiblefor the renal failure which may occur with rhabdomyolysis.     

The role of mitochondrial uncoupling in 3,4-methylenedioxymethamphetamine-mediated skeletal muscle hyperthermia and rhabdomyolysis

Use of the popular club drug ecstasy (3,4-methylenedioxymethamphetamine, MDMA) can result in life-threatening hyperthermia and rhabdomyolysis. Recent studies show a link between skeletal muscle uncoupling proteins in MDMA-mediated hyperthermia. The mechanisms by which MDMA interacts with skeletal muscle mitochondria are largely unknown. The present study was designed to comprehensively evaluate the effects of MDMA on bioenergetics and toxicity of skeletal muscle. Using (31)P nuclear magnetic resonance (NMR) and serum creatine kinase levels, we demonstrate evidence for uncoupling of oxidative phosphorylation in the skeletal muscle of MDMA (40 mg/kg)-treated rats. In vivo, rats treated with MDMA had significantly elevated serum creatine kinase levels, a marker of rhabdomyolysis, 4 h post-MDMA treatment (955 +/- 132 IU/l) compared with saline-treated controls (373.2 +/- 59 IU/l). beta-ATP signal areas after MDMA treatment showed significant reductions (15%) from the baseline values with corresponding increases in inorganic phosphate (88% increases) and decreases in intracellular pH. Clark electrode experiments on isolated skeletal muscle mitochondria in vitro (1-5 mM MDMA) and ex vivo in MDMA-treated animals demonstrated no evidence of uncoupling of oxidative phosphorylation. In vitro experiments using L6 myotubules cocultured with primary hepatocytes demonstrated the presence of uncoupling protein-3 in the L6 myotubules, but no evidence of a direct effect of MDMA or its potential metabolites on cellular creatine kinase concentrations. These findings suggest that MDMA uncouples skeletal muscle mitochondria in vivo but that this uncoupling is the result of indirect mechanisms.     

A study on the effects of severe repetitive exercise on serum myoglobin, creatine kinase, transaminases and lactate dehydrogenase

Two groups of young men taking part in a 24-day training course involving increasingly severe exercise were studied. Serum myoglobin, creatine kinase, creatine kinase-MB, transaminases, lactate dehydrogenase, urea, creatinine, calcium and uric acid were estimated at intervals. During the first few days, increases in myoglobin and muscle enzymes correlated with the severity of the preceding exercise. Increases in myoglobin and muscle enzymes after the final most severe exercising were less than with the initial exercising, demonstrating the effect of physical training. The changes in myoglobin and the muscle enzymes correlated closely. Elevated myoglobin levels persisted for over 24 hours. There was no consistent correlation between changes in myoglobin and uric acid, both of which have been considered responsible for the renal failure which may occur with rhabdomyolysis.     

Rhabdomyolysis secondary to lovastatin therapy

We report a case of lovastatin-induced rhabdomyolysis and resulting life-threatening renal failure. Lovastatin, a hypocholesterolemic agent, decreases endogenous cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.88). This agent has been implicated in causing rare serious side effects in various clinical settings; however, the mechanism of these adverse reactions is not understood. The clinical course of our patient was characterized by profound muscle weakness with marked increases in serum creatine kinase and myoglobin. Light- and electron-microscopic studies of skeletal muscle of our patient demonstrated a noninflammatory myopathy suggestive of ongoing rhabdomyolysis with vacuolization and focal degeneration of myocytes. The patient's symptoms and the laboratory values referable to rhabdomyolysis resolved after discontinuation of the drug. We speculate that the rhabdomyolysis was due to mitochondrial damage secondary to inadequate synthesis of coenzyme Q and heme A, members of the electron-transport system of the inner mitochondrial membrane.     

Rhabdomyolysis of infectious and noninfectious causes

BACKGROUND: This study was done to determine variables associated with infectious rhabdomyolysis (IRM). METHODS: In this retrospective case-control study, rhabdomyolysis (RM) was defined as a fivefold or greater elevation in creatine kinase (CK) levels with a muscle/brain (MB) fraction <5%. Patients with myocardial infarction or cerebrovascular accident or a recent history of surgery, trauma, or immobilization were excluded. RESULTS: We analyzed 52 cases of RM seen at our institution between 1992 and 2000; IRM was the most frequent cause (31%), most commonly respiratory tract infections (38%). When a microorganism could be identified (50%), it was more often gram-negative (63%). Patients with IRM were elderly and had fever and lower CK levels. Infectious rhabdomyolysis was associated with a higher morbidity but not with a higher risk of death. CONCLUSIONS: Infectious rhabdomyolysis is the main cause of RM and must be suspected in elderly patients with fever and low levels of CK.