CHEST

Rhabdomyolysis

Postgraduate Education Corner
CONTEMPORARY REVIEWS IN CRITICAL CARE MEDICINE

Janice L. Zimmerman, MD, FCCP; and Michael C. Shen, MD

Rhabdomyolysis is a well-known clinical syndrome of muscle injury associated with myoglobinuria, electrolyte abnormalities, and often acute kidney injury (AKI). The pathophysiology involves injury to the myocyte membrane and/or altered energy production that results in increased intracellular calcium concentrations and initiation of destructive processes. Myoglobin has been identified as the primary muscle constituent contributing to renal damage in rhabdomyolysis. Although rhabdomyolysis was first described with crush injuries and trauma, more common causes in hospitalized patients at present include prescription and over-the-counter medications, alcohol, and illicit drugs. The diagnosis is confirmed by elevated creatine kinase levels, but additional testing is needed to evaluate for potential causes, electrolyte abnormalities, and AKI. Treatment is aimed at discontinuation of further skeletal muscle damage, prevention of acute renal failure, and rapid identification of potentially life-threatening complications. Review of existing published data reveals a lack of high-quality evidence to support many interventions that are often recommended for treating rhabdomyolysis. Early and aggressive fluid resuscitation to restore renal perfusion and increase urine flow is agreed on as the main intervention for preventing and treating AKI. There is little evidence other than from animal studies, retrospective observational studies, and case series to support the routine use of bicarbonate-containing fluids, mannitol, and loop diuretics. Hyperkalemia and compartment syndrome are additional complications of rhabdomyolysis that must be treated effectively. A definite need exists for well-designed prospective studies to determine the optimal management of rhabdomyolysis. CHEST 2013; 144 (3):1058–1065
Abbreviations: AKI 5 acute kidney injury; CK 5 creatine kinase; CRRT 5 continuous renal replacement therapy; IVF 5 IV fluid

is defined as injury of the skeletal Rhabdomyolysis muscle, which results in the release of intracel-

lular contents into the circulation. Skeletal muscle comprises 40% of body mass, and a large insult can result in the accumulation of cellular contents in the extracellular space such that elimination mechanisms are overwhelmed. The resulting effects are recognized as a clinical syndrome of muscle injury that is associated with the development of myoglobinuria, electrolyte abnormalities, and often acute kidney injury (AKI). Rhabdomyolysis has long been recognized as a primary condition or comorbidity in hospitalized and critically ill patients. The initial understanding of the syndrome originated from experiences of warfare during and following World War II, as well as from natural disasters. Rhabdomyolysis was caused primarily by crush injury or other physical trauma in these circumstances. Any form of therapy that prevented renal failure or avoided death was deemed successful because experience suggested that the out-

comes from rhabdomyolysis were generally poor.1,2 However, in the mostly civilian setting of current health care, the characteristics of rhabdomyolysis are different. Pharmaceutical agents, alcohol, and illicit drugs are now significant causes of rhabdomyolysis, in addition to trauma.3-6 This article focuses on the causes of rhabdomyolysis likely to be encountered in hospitalized patients, current diagnosis and evaluation of the syndrome and its associated complications, and treatment of rhabdomyolysis, with an emphasis on prevention of AKI. Pathophysiology The common pathway leading to muscle injury and death in rhabdomyolysis is an increase in cytoplasmic ionized calcium.7 The major mechanisms that result in increased intracellular calcium are injury to the myocyte membrane and altered energy production. Direct disruption of the muscle cell membrane results in an influx of calcium, with further release of calcium
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resulting in the release of free radical species and oxidative damage to the renal parenchyma. 2012.org vasoconstrictors and can contribute to renal arteriolar dysregulation and hypoperfusion. and sports events.25 Genetic polymorphic variations may play a role in the variable susceptibility to exertion-related muscle injury. High concentrations of muscle cell contents are absorbed into the bloodstream. Myoglobin. Common voluntary injuries causing rhabdomyolysis follow overstrenuous or prolonged exertion during military. illicit drugs. is an important factor in rhabdomyolysis.12 but acute renal failure has been described in patients without significant hypovolemia. Trauma results in overt muscle injury. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. and purine metabolites (uric acid). NY. leading to vascular occlusion and ischemia. inorganic toxins. and Weill Cornell Medical College (Dr Zimmerman) New York. e-mail: janicez@tmhs.26 Involuntary muscle overuse usually stems from some predisposing medical condition such as seizures or status asthmaticus. revision accepted January 31. and Table 1 contains a listing of some of the most relevant. leading to intracellular calcium accumulation. can result in ischemic muscle injury and rhabdomyolysis. Houston. TX 77030. and a urine concentration . Psychiatric medications (eg.org © 2013 American College of Chest Physicians. an iron-containing protein in skeletal muscle that stores oxygen for aerobic mitochondrial metabolism. FCCP.22. sickle cell trait.3. or biologic. Pressure-related muscle injury causing rhabdomyolysis is now recognized in obese patients as a complication of bariatric surgery. coexisting factors found in patients with rhabdomyolysis. other injuries. Correspondence to: Janice L.15 Studies also suggest that myoglobin can induce lipid peroxidation. quetiapine. and phosphates). Despite the significant contribution of myoglobin to AKI. Many patients have multiple factors that contribute to the development of rhabdomyolysis. and drug effects. Zimmerman. Oxidant injury can result from dissociation of the iron in myoglobin. These molecules are potent Manuscript received August 12. as well as in nonobese patients undergoing prolonged surgeries.4 Skeletal muscle is more prone to hypoxic injury and vascular compromise because of its peripheral location.9-11 Animal studies suggest that myoglobin alone may not be nephrotoxic in the absence of hypovolemia and acidosis. resulting in the generation of isoprostanes. Ste 1001. and a significant number of patients may have no cause identified. and vasoconstriction. Limbs are at increased risk of prolonged pressure during an unconscious state. lactate dehydrogenase. Myoglobin has been implicated consistently as the primary nephrotoxin in rhabdomyolysis. Houston. Myoglobin precipitation can be exacerbated by intravascular volume depletion and systemic acidosis. the latter term is preferred because it describes the pathophysiologic process more accurately. Arterial and venous thrombosis. Myoglobin can then be precipitated out of solution in the acidic environment of the renal tubules through interaction with Tamm-Horsfall protein.15-17 Homeostatic activation of the sympathetic nervous system and the renin-angiotensin system due to intravascular hypovolemia can also contribute to vasoconstriction.1378/chest. enzymes (creatine kinase [CK]. these include electrolytes (potassium. TX. use. CHEST / 144 / 3 / SEPTEMBER 2013 1059 Downloaded From: http://journal. Myoglobin is excreted by the kidneys. Internal factors can result from voluntary and involuntary injury.chestnet. resulting in the eventual lysis of the cell and release of contents. but rhabdomyolysis can also be precipitated by less obvious injury. metabolic abnormalities. Impaired metabolism (production.12-2016 journal. and electrolyte abnormalities.publications.8 The term myoglobinuria is essentially synonymous with rhabdomyolysis.from the damaged sarcoplasmic reticulum and mitochondria.14 Myoglobin is readily filtered by glomeruli in the kidneys and concentrated in the renal tubules.18-21 A higher BMI and longer operating times may increase the risk of rhabdomyolysis. See online for more details. 2013.24 Exertional rhabdomyolysis has also occurred as a result of prolonged electronic gaming. such as hypovolemia.27 Chemical causes now account for most cases of rhabdomyolysis.org/ by a St Joseph Hospital User on 09/04/2013 . but hypovolemia leading to renal hypoperfusion may be a more important factor in AKI than tubular obstruction. The insult can usually be categorized into one of four mechanisms: hypoxic. Cause Rhabdomyolysis has numerous and diverse causes. oxidant injury. also impact renal function. or consumption) of adenosine triphosphate disrupts the function of sodium-potassium and sodium-calcium ion pumps. MD.23 The physical causes of rhabdomyolysis can be due to external factors such as trauma or internal factors such as exertion. Affiliations: From The Methodist Hospital (Drs Zimmerman and Shen). vasculitis). aspartate transaminase.publications. and aldolase). calcium. DOI: 10.11.13. Table 2 lists selected drugs implicated as a cause of rhabdomyolysis. recreational. with proposed mechanisms of toxicity that include tubular obstruction. 6550 Fannin. chemical.4 This category includes prescription and over-the-counter medications. as well as diffuse occlusion of the microvasculature (eg. 100 mg/dL is responsible for the red or brown staining of urine that can occur in rhabdomyolysis. physical.3.chestnet. proteins (myoglobin). The increase in calcium activates multiple destructive processes. A useful approach is to consider the mechanisms of skeletal muscle damage.

Table 1—Causes of Rhabdomyolysis Hypoxic External Carbon monoxide exposure Cyanide exposure Internal Compartment syndrome Vascular compression Immobilization Bariatric surgery Prolonged surgery Sickle cell trait Vascular thrombosis Vasculitis Physical External Crush injury Trauma Burns Electrocution Hypothermia Hyperthermia (heat stroke) Internal Prolonged and/or extreme exertion Seizures Status asthmaticus Severe agitation (delirium tremens. hornets.publications. and change in urine color or quantity.31 Few of these drugs have direct cytotoxic effects on myocytes. scorpions.31-33 Alcohol may act as a direct toxin to muscles and cause rhabdomyolysis via other effects. warfarin. the cytochrome P isoenzyme system. has also been associated with clinically significant rhabdomyolysis. and calcium channel blockers). Psychiatric patients are also considered higher risk because of use of antipsychotic and antidepressant medications. In addition. Fewer than 1% of those taking statins alone will develop rhabdomyolysis resulting in hospitalization or kidney injury. The history should elicit information on prior exertional activities. viral. and unconscious patients are at high risk of rhabdomyolysis. or arthralgias. Biologic causes make up the last category of causes of rhabdomyolysis. gram-positive organisms predominate.chestnet. Stimulants such as cocaine. appropriate treatment. and HIV. a thorough history and physical examination. multiple factors coincide to inflict muscle damage. rash.30 Daptomycin.6. Rhabdomyolysis can accompany the development of propofol-related infusion syndrome.4 Statins are also implicated frequently.39 Clinical Evaluation and Diagnosis Rapid recognition of rhabdomyolysis is important to implement timely.29 Although less common. psychotic. and parasitic myositis Organic toxins Snake venom Spider bites Insect stings (ants.14 Illicit drugs are well-described precipitants of rhabdomyolysis. a potentially fatal complication of prolonged or highdose propofol use. and enzymes of the coenzyme Q10 synthetic pathway have been associated with a higher risk of statin-associated myopathy. ants. wasps) Internal Dermatomyositis. often used to treat serious hospital-acquired infections.34 Intoxication can lead to immobilization associated with compression and ischemic injury. the diuretic 1060 effect of alcohol can lead to dehydration and increase the risk of AKI. azole antifungals. electrolyte abnormalities. and the most common viruses associated with myositis are influenza A and B.35 Organic toxins that affect skeletal muscles via stings and bites have been reported for bees. wasps. and bath salts (mephedrone. The physician should be aware that intoxicated. but the risk increases to 6% when used concomitantly with a fibrate.36-38 Genetic inborn errors of metabolism and muscular dystrophies can present with rhabdomyolysis later in life. Although almost any bacteria can cause myositis. limited energy stores. agitated. trauma.28 The risk of rhabdomyolysis is also higher when statins are combined with drugs that inhibit statin metabolism by cytochrome P450 isoenzymes (cyclosporine. prolonged immobilization. amiodarone. and additional evaluation should be considered in patients with recurrent episodes of rhabdomyolysis.org/ by a St Joseph Hospital User on 09/04/2013 . centipedes. with a portion related to neuroleptic malignant syndrome. precipitate seizures or hyperthermia. symptoms of infection.13. The variable clinical manifestations in rhabdomyolysis may result from the precipitating cause (ie. and laboratory testing. and brown recluse spiders. and enzyme deficiencies. polymyositis Endocrinopathies Adrenal insufficiency Hypothyroidism Hyperaldosteronism Diabetic ketoacidosis Hyperosmolar state aripiprazole) rank as one of the most frequent precipitants. instead. psychosis) Neuroleptic malignant syndrome Malignant hyperthermia Chemical External Alcohol Prescription medications Over-the-counter medications Illicit drugs Internal Hypokalemia Hypophosphatemia Hypocalcemia Hypo-/hypernatremia Biologic External Bacterial. enteroviruses. Chronic alcoholism also predisposes to rhabdomyolysis because of malnutrition. methamphetamines. environmental exposures. illicit drug or alcohol use. rhabdomyolysis can also result from medications administered to hospitalized patients. prescription and over-the-counter medication use. and produce ischemia from arterial vasoconstriction. Postgraduate Education Corner Downloaded From: http://journal. Evaluation requires an assessment of risk factors for rhabdomyolysis. influenza. methylenedioxypyrovalerone) can increase physical activity to deleterious levels. amphetamines. Genetic polymorphisms of transporter proteins that facilitate hepatic uptake of statins. bees.

000 IU/L. Additional laboratory testing is needed to determine the potential precipitating factors and complications resulting from rhabdomyolysis. Patients who do complain of myalgias or develop a change in urine color should journal. because myoglobin will also react with the orthotolidine test reagent. and therefore is less sensitive for detecting rhabdomyolysis. it is difficult to use the magnitude of the CK value to estimate the risk of kidney injury.000 IU/L and creatinine .org/ by a St Joseph Hospital User on 09/04/2013 . especially those with extensive crush injuries. Serial CK measurements should be monitored. Laboratory monitoring may be indicated in patients with risk factors such as obesity. serum should be sent for measurement of CK. tenderness. and the complications associated with rhabdomyolysis. 100 IU/L. erlotinib Narcotics Colchicine Vasopressin Amiodarone Aminocaproic acid Illicit drugs Cocaine Amphetamines/methamphetamines Hallucinogens Heroin Methylenedioxypyrovalerone.4. severe agitation. Detection of rhabdomyolysis that develops during hospitalization may be more difficult.44. especially when presentation is delayed. a positive urine dipstick test for blood without evidence of RBCs on microscopy is a clue to the presence of rhabdomyolysis. and deterioration of renal function. Red or brown urine suggests significant myoglobin excretion but its absence does not preclude the presence of rhabdomyolysis. which is more specific for the diagnosis of rhabdomyolysis than are other markers that may also be elevated.3 When initially evaluating a patient with dark-colored urine.44 Some studies suggest that patients with CK levels .chestnet. The edema and inflammation resulting from muscle damage in the limbs can secondarily increase local pressure and compromise circulatory flow.publications. 5. therefore.publications. Myoglobin is cleared more rapidly than CK. suggest ongoing muscle injury or the development of renal failure. Muscle injury may manifest as pain. and fever. especially after volume resuscitation.5 mg/dL. propofol use. Significant limb pain in the setting of trauma should raise the suspicion for compartment syndrome. nausea. The CK level for clinical concern is uncertain. atypical antipsychotics) Selective serotonin reuptake inhibitors Lithium Valproic acid Antimicrobial agents Antiretroviral medications (protease inhibitors) Trimethoprim-sulfamethoxazole Daptomycin Macrolide antibiotics Quinolones Amphotericin B Anesthetics/paralytics Succinylcholine Propofol Antihistamines Doxylamine Diphenhydramine Appetite suppressants Phentermine Ephedra Others Sunitinib. nor is it specific for the development of AKI. because it may not be suspected and patients may not be able to communicate complaints. alcohol abuse. swelling. mephedrone (bath salts) Phencyclidine trauma). may present with arrhythmias or sudden death resulting from hyperkalemia.chestnet. Serum myoglobin levels are not needed for the diagnosis or management of rhabdomyolysis. A metabolic CHEST / 144 / 3 / SEPTEMBER 2013 1061 Downloaded From: http://journal. patients may present with manifestations due to complications of rhabdomyolysis.3. the muscle injury (direct or indirect). but such findings may be absent or may be overshadowed by other conditions. Normal CK levels are usually . or failure of levels to decline despite therapy. or weakness. prolonged surgery.000 IU/L are not at risk of developing AKI42.org have medications reviewed and diagnostic testing initiated. Urine output may be decreased on presentation if AKI has already developed. an arbitrary value of 500 to 1. prolonged seizure activity. otherwise. Diagnostic laboratory testing for rhabdomyolysis is straightforward (Table 3).Table 2—Selected Drugs Associated With Rhabdomyolysis Drugs Medications Lipid-lowering agents Statins Fibrates Psychiatric medications Neuroleptics/antipsychotics (including haloperidol. or five to 10 times the upper limit of normal is frequently used to define rhabdomyolysis. resulting in compartment syndrome. Urine myoglobin is not a sensitive test for rhabdomyolysis.40-43 A reasonable consensus recommendation suggests close monitoring of renal function in patients with CK levels . vomiting. but levels correlate marginally with the development of AKI or mortality. 5. Nonspecific symptoms may include fatigue. Higher CK levels correlate with a greater degree of muscle injury.6. it is not necessary for routine testing. unexplained hyperkalemia. 1. statin use. Less commonly. Circulation should be evaluated periodically in any severely affected limb. increasing levels. Some patients.

Therapy There are no randomized. HIV infection.3 Hyperuricemia resulting from the release of muscle purines is common. 6:1 Increased Elevated Positive Positive Comments Diagnostic for rhabdomyolysis. Serial trends of laboratory markers may be more appropriate than single results to assess the risk of AKI. discontinuation of medications. and creatinine levels at presentation have been evaluated.000 IU/L Marker of severity of muscle injury and renal dysfunction Potential cause of rhabdomyolysis Marker of severity of muscle injury and renal dysfunction Potential cause of rhabdomyolysis Deposition in damaged muscle Marker of decreased renal function Increased conversion of muscle creatine to creatinine Increased organic acids due to muscle injury or renal dysfunction Potential cause of rhabdomyolysis Detects myoglobinuria in absence of RBCs in urine Potential drug-related cause of rhabdomyolysis BUN 5 blood urea nitrogen. Although CK.45 Calcium mobilization from damaged muscles in the recovery phase of rhabdomyolysis and AKI may subsequently result in hypercalcemia. Calcium levels are often low initially. and opinion.Table 3—Selected Laboratory Testing for Initial Evaluation Test CK Potassium Phosphorous Calcium Creatinine BUN:creatinine Anion gap Blood alcohol level Urine blood dipstick Urine drug screen Abnormal Value for Rhabdomyolysis . The results screen for hypokalemia and hypophosphatemia as potential causes and identify potentially life-threatening hyperkalemia. The treatment of rhabdomyolysis usu1062 ally involves three components: discontinuation of further skeletal muscle damage. potassium.46 and 10% of AKI has been attributed to rhabdomyolysis. case reports or series. 6. There is complete agreement that early and aggressive volume resuscitation to restore adequate renal Postgraduate Education Corner Downloaded From: http://journal. Patients with elevated CK levels secondary to chronic myositis due to statins.0 mg/dL Decreased (. Most recommendations are based on retrospective observational studies with small numbers of patients. The major effort in the treatment of rhabdomyolysis is directed toward prevention of renal failure.40. 5. An ECG can be obtained quickly to screen for conduction abnormalities and evidence of hyperkalemia (P-R interval prolongation.4.42.43.0 mmol/L . correction of metabolic abnormalities. peaked T waves. The lack of high-quality evidence must be acknowledged and considered when reviewing recommendations for interventions. CK 5 creatine kinase. myoglobin.3. patient comorbidities. and the heterogeneity in the causes of rhabdomyolysis.publications. secondary to precipitation of calcium with phosphates in damaged muscles. often . and widened QRS complex). and initial laboratory results may be helpful in determining the risk of progression to AKI.3 The disproportionate increase in creatinine early in rhabdomyolysis is possibly due to metabolism of released muscle creatine. phosphorous) and renal function should be obtained routinely. albumin. and others. calcium.org/ by a St Joseph Hospital User on 09/04/2013 . A urine drug screen may be indicated to confirm exposure to specific drugs. and rapid identification of potentially life-threatening complications. A coagulation panel should be assessed for evidence of the disseminated intravascular coagulation that can occur with rhabdomyolysis. cooling or warming. increased risk of kidney injury if . 10:1.0 mg/dL) Increased .4 Patients with exertional rhabdomyolysis also appear to be at a much lower risk of AKI. 2. Suggested markers and models of AKI are derived from the results of singlecenter retrospective studies and are difficult to generalize. AKI has been observed in 10% to 60% of patients presenting with rhabdomyolysis. 2. 500 IU/L . panel that includes electrolytes (potassium.3. Specific measures to stop ongoing muscle injury will vary with the cause of the rhabdomyolysis. lactate dehydrogenase.10 The cause of muscle injury. with rhabdomyolysis being only one of the contributing factors.6.0 mg/dL . Only a few interventional clinical trials in rhabdomyolysis have been reported in the past 10 years. 6. The reason for this difficulty is at least twofold: the multifactorial nature of kidney injury. or inflammatory myopathies may be at a lower risk of developing AKI. treatment of infection. The anion gap in rhabdomyolysis is often increased more than expected for the degree of AKI and may be due to phosphates and organic acids released from muscle.chestnet. no single marker or predictive model has been able to reliably assess the risk of AKI. bicarbonate.45 An elevated creatinine level with a blood urea nitrogen-to-creatinine ratio . surgery. 10:1 is often noted on presentation. prevention of acute renal failure.47 Trauma patients and those with comorbidities such as chronic alcoholism or drug use may be at a higher risk. Interventions may include control of agitation. animal models.0 mmol/L . controlled trials in rhabdomyolysis that offer definitive guidance for treatment. 8. intravascular volume status.

conversely.44. If the decision is made to alkalinize urine. however.5) theoretically can decrease the deposition of myoglobin in renal tubules.42 A current consensus statement suggests that sodium bicarbonate administration is not necessary and not superior to normal saline diuresis in increasing urine pH. The same small retrospective studies of bicarbonate administered with mannitol in rhabdomyolysis are cited to suggest treatment success with mannitol.48 IVF is continued by infusion until resolution of rhabdomyolysis or until the development of oliguric AKI limits further fluid administration. use may be beneficial to treat hyperkalemia before renal recovery or hemodialysis. Use of loop diuretics has been advocated to “convert” oliguria or anuria to nonoliguria. Large amounts of IVF within the first 24 h are associated with improved outcomes.55 Laboratory studies have suggested that acetaminophen and l-carnitine may be able to ameliorate nephrotoxicity from myoglobin.org bonate and mannitol therapy vs no use of this therapy in trauma patients did not find any difference between groups in the incidence of renal failure.50 At the end of 12 h of infusion.42. Indications for hemodialysis include hyperkalemia. Forced diuresis with mannitol and loop diuretics has also been used to promote urine output and prevent AKI.9.perfusion and increase urine flow is the mainstay for preventing and treating AKI in rhabdomyolysis. along with other proposed protective mechanisms. More controversy exists regarding the type and volume of fluid and the use of diuretics.48. For the first 24 h after presentation. prompt IVF administration prior to or during extrication of crush victims may help prevent later renal complications. The concept of urine alkalinization derives from the precipitation of myoglobin in an acidic environment. Anecdotal use of corticosteroids.1.17. need for dialysis. randomized trial compared the effects of lactated Ringer’s vs 0. but these agents cannot be recommended. urinary alkalinization (pH . several other retrospective studies were not able to show that bicarbonate coadministered with mannitol was more effective than volume infusion with isotonic saline. randomized trial of intraoperative isotonic fluids in bariatric surgery patients at 15 mL/kg vs 40 mL/kg total body weight did not find any difference in the incidence of rhabdomyolysis.org/ by a St Joseph Hospital User on 09/04/2013 .53 A variety of dosing regimens using intermittent bolus and continuous infusion of mannitol have been reported. Isotonic saline is preferred because it is readily available and does not contain potassium. but with very limited published experience.44 Hyperkalemia tends to be the major indication for early renal replacement therapy because of the potassium load released from muscle. but more clinical research is needed. and two small retrospective observational case series (27 patients in total) are often cited to suggest the benefit of bicarbonate and mannitol administration in rhabdomyolysis.2 Routine use of mannitol is not recommended for rhabdomyolysis.9. Theoretically.57 If AKI develops. as little as 3 L to as much as 24 L have been administered effectively.chestnet. There has been minimal investigation of fluid administration in high-risk patients to prevent the development of rhabdomyolysis prior to injury. but evidence of a clinical benefit is lacking. Currently.44 Urine alkalinization is generally accomplished by the administration of bicarbonate. either by direct infusion or by adding it to IVF.54. and it should not be administered to hypovolemic or anuric patients. there are no data to support the use of continuous CHEST / 144 / 3 / SEPTEMBER 2013 1063 Downloaded From: http://journal.9. the clinical significance of this outcome is unclear. A prospective. Mannitol has not been evaluated as a sole intervention in a controlled trial of rhabdomyolysis.51 Alkalinization of the urine is also a common intervention in rhabdomyolysis. diuresis may prevent the accumulation of debris in the renal tubules. urine output goals of 200 to 300 mL/h have been recommended. A target of 6 to 12 L within 24 h is a reasonable goal.publications. volume overload.9% saline administration causes a dilutional metabolic acidosis. or fails to reverse despite aggressive fluid administration. IVF should be administered rapidly as an initial bolus. Traditionally. Care must be taken not to exacerbate hypokalemia or hypocalcemia if loop diuretics are used. which may ameliorate renal injury.49 The administration of IV fluid (IVF) dilutes nephrotoxins and promotes renal tubule flow. the serum and urine pH were higher in the lactated Ringer’s group. and azotemia. and various antioxidants has been reported. Alkalinization of the urine may be difficult to achieve without causing a systemic metabolic alkalosis. 6. thereby decreasing the risk of obstruction contributing to AKI.9% saline administered at 400 mL/h in patients with mild rhabdomyolysis secondary to doxylamine. Mannitol also acts as an intravascular volume expander and vasodilator. as long as complications from volume overload can be avoided. or mortality. Conversely. Alkalinization therapy was shown to be more effective than IVF alone in animal models. care must be taken to ensure that other electrolytes remain balanced.1.56. acetazolamide. and therefore. renal replacement therapy may be required to manage the complications of rhabdomyolysis. When a patient is suspected or recognized to have rhabdomyolysis. which may prevent the accumulation of myoglobin and toxic products in the renal parenchyma.52 The largest retrospective study of bicarjournal. A prospective.2 However. some bicarbonate-containing fluids may be helpful if 0.10.chestnet.publications.1 No specific rate of infusion or target urine output has been demonstrated to be superior to another. In disaster situations. metabolic acidosis.

Postoperative rhabdomyolysis following laparoscopic gastric bypass in the morbidly obese.44 At the same time that IVF is initiated. the physician should assess the likelihood of electrolyte complications with laboratory testing and an ECG.18(2):90-100. J Antimicrob Chemother. Bar-Joseph G. Use of RIFLE criteria to predict the severity and prognosis of acute kidney injury in emergency department patients with rhabdomyolysis. 2009. 16. If compartment syndrome is suspected. and loop diuretics. Humphreys MH. Increased lipid peroxidation in patients with rhabdomyolysis. mannitol. 5. 3. Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure. Anthone GJ. Pathogenesis and treatment of renal dysfunction in rhabdomyolysis. Chatzizisis YS. Poch E.353(9160): 1241. 1982.49(2):314-326. Moore KP. Papadopoulos S. Bosch X. Giannoglou GD.27(5): 803-811. Melli G. Arch Surg. and CRRT is not advocated for myoglobin removal. coexisting conditions. Morgan EF. Michaelson M. 2006. Bostanjian D.42. 13. Rhabdomyolysis and myohemoglobinuric acute renal failure. Mortality in rhabdomyolysis also ranges from 1. 1989. Givens ML. Rabkin RA. Weiner ID. 12. Lancet. Crookes PF. 2003. Prevention of acute renal failure in traumatic rhabdomyolysis.57(3):578-579. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Elkin RB.61(3):141-152. alcohol. 17. Rhabdomyolysis of gluteal muscles leading to renal failure: a potentially fatal complication of surgery in the morbidly obese. Am J Med Sci. Schoenfeld PY. Studies of mechanisms and protective maneuvers in myoglobinuric acute renal injury.59 Treatment of hypocalcemia is not recommended because of the high intracellular concentrations in injured muscle and the potential for precipitation. 6. Intensive Care Med. and experimental super-high-flux filters may be even more effective. 2004. Lab Invest.139(7):801-805. The other medical causes of rhabdomyolysis. Kazory A. 2005. 2012. Rhabdomyolysis during therapy with daptomycin. 2. 49(3):741-751. Kidney Int. The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. There is little evidence to support the routine use other interventions with bicarbonate. Aggressive fluid resuscitation with isotonic fluids is probably sufficient to prevent AKI in the majority of patients with rhabdomyolysis. Rhabdomyolysis and acute kidney injury. 7. The effect of infusion of mannitol-sodium bicarbonate on the clinical course of myoglobinuria. Grau JM. Better OS. Khurana RN. Ron D. 19. Annu Rev Med. 8. 2006.139(1):73-76. 1984. 18. Holt S. 2011. Clin Infect Dis. and the variability is likely due to differing causes. N Engl J Med.144(2):277-280.6 Most patients with acute renal failure from rhabdomyolysis recover function within a few months.84(6):377-385.13(2):302-305. Kelleher SP. Arch Intern Med.org/ by a St Joseph Hospital User on 09/04/2013 . Oral phosphate binders can be considered for significant hyperphosphatemia.43. References 1. Mitochondrial free radical production induces lipid peroxidation during myohemoglobinuria. Eneas JF. but CRRT may be better tolerated in patients with hypotension or in those at risk of hypotension.1. Allison RC. Zager RA. Exceptions are concomitant hyperkalemia with significant ECG changes and symptomatic hypocalcemia (tetany).publications. Aalami OO. Winstead PS. and comorbidities. 1979. Dibadj K. surgical consultation should be obtained for measurement of intracompartment pressures and/or fasciotomy.chestnet. 4. Kaehny WD. 14. Kidney Int.renal replacement therapy (CRRT) over intermittent hemodialysis in rhabdomyolysis. Zager RA. The prominent role of medications. Arch Intern Med. Roberts LJ II. 1996. J Emerg Med.361(1):62-72. 10. Knochel JP. Boutaud O. 15. 9. cause.7% to 46%. Gabow PA.42(12):e108-e110. Significant hyperkalemia should be treated according to standard management principles. Delaney KA. Calcium levels should be monitored throughout the hospital course to detect later development of hypercalcemia. Hamoui N. 1999. Baudendistel TE. Murphy BS. Medicine (Baltimore). Wilson M.51(5):1062-1067. Liewer SE. Rhabdomyolysis and acute renal failure in a patient treated with daptomycin. Misirli G. Taitelman U. Medicine (Baltimore).60 Outcome Outcomes from rhabdomyolysis vary considerably with the type of patient population. 1982. The spectrum of rhabdomyolysis. Cornblath DR. 11. A consistent finding is that the mortality of patients with rhabdomyolysis and acute renal failure is higher than in patients with no renal failure. Holt SG.2. Rhabdomyolysis and myoglobinuria.33:435-443. Postgraduate Education Corner Downloaded From: http://journal.42 It is not surprising that hospital length of stay is noted to be longer in patients with significant renal compromise. Obes Surg.6. Eur J Intern Med. and improved treatment over time (especially for trauma patients). it is not clear that removal of myoglobin prevents or alters the clinical course of AKI.47 Conclusions Rhabdomyolysis continues to be a significant syndrome leading to hospitalization or developing in hospitalized patients. 2003. and illicit drugs as causes of rhabdomyolysis requires careful consideration when evaluating patients. Reeder B. Bedsole DL. Martin CA.9.1. 2001. 1996. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Prospective well-designed trials in rhabdomyolysis 1064 are sorely needed to provide more definitive guidance on treatment interventions. CRRT using conventional high-flux filters has been found to remove myoglobin despite its large molecular weight.42(5):521-528.58 However. 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