Rhabdomyolysis

Contents

Definition/Description

Rhabdomyolysis is defined as a clinical and biochemical syndrome resulting from skeletal muscle injury that alters the integrity of the muscle cell membrane sufficiently to allow the release of the muscle cell content into the plasma.[1] Due to the quick breakdown of the skeletal muscle there is a big accumulation of the breakdown products which can cause renal failure.

Historical Background

The first known report of rhabdomyolysis occurred in Sicily in 1908 after an earthquake, this was also the first case of crush syndrome as well and was found in German military literature.[2][3] [4]  While this was the first report there has been some speculation that there are references in the Bible about rhabdomyolysis during the Jews exodus from Egypt. It was described as a plague that occurred after a large intake of quail.[2] [4]  A similar incident occurred in 1930 in the Baltic sea area where there was a large consumption of intoxicated fish.[3]  

Military

The focus of rhabdomyolysis really came about during World War II, especially during the bombing that occurred in London, where crush victims developed acute renal failure.[2][3]  Reports were also present during the Korean War as well as during Vietnam.  During Vietnam the incidence actually decreased which is thought to be due to the faster evacuation techniques and improved fluid resuscitation to victims.[2]

Natural Disasters
Picture of rescue attempts in Haiti after the earthquake in January 2010

As seen through history the most common incidence of rhabdomyolysis occurs during natural disasters where there are less resources available to help trapped victims, making their time under rubble longer and increasing their chances of developing rhabdomyolysis.  On August 17, 1999 in Marmara, a region of Turkey, an earthquake with a 7.4 magnitude devastated the area.  This earthquake caused 17,480 deaths.  Many victims were sent to hospitals; 9,843 patients were hospitalized with 425 of them dying.  Of those 9,843 patients, 639 patients developed renal failure, this was 12% of the patients that were hospitalized.  The victims average time spent under rubble was 11.7 hours. [2]

Collapse of World Trade Center

On September 11, 2001 in New York City the twin towers collapsed trapping many victims under rubble.  Hospitals were prepared to have dialysis ready the days following the attacks to treat the many victims to prevent renal failure.  Fortunately, very few victims had crush injuries and the only victim developed rhabdomyolysis was a 38 year-old police officer who had been trapped under rubble for 24 hours.[2]

Prevalence

Eighty-five percent of victims of traumatic injuries develop rhabdomyolysis.[2]  Of those, 10-50% of those patients will develop acute renal failure.[2]  It is also suggested that victims of severe injury that develop rhabdomyolysis and later acute renal failure have a mortality of 20%.[2] An estimated 26,000 cases of rhabdomyolysis are reported annually in the US.[5]  Men have a slightly higher incidence of developing rhabdomyolysis than women.[6]


Prevalence in Children[7]

Limited data exists on the prevalence of rhabdomyolysis in the pediatric population. The incidence of rhabdomyolysis in this population is estimated to be 0.26% (4:1,500 inpatient consultations) in a three year period at the University of California. Several small retrospective studies concluded that acute kidney injury rates in children admitted for rhabdomyolysis ranged from 42% to 50%, particularly when nongenetic chronic myopathies were evaluated. One other retrospective study included children with high CK after admission to the emergency department, excluding children with muscular disease, 5% developed acute kidney injury.

Pathophysiology

Rhabdomyolysis occurs due to injury whether it is mechanical, chemical, toxins, poisons, or burns, these injuries have a detrimental effect to the cell membranes throughout the body. When a cell membrane is damaged the breakdown or lysis releases organic and inorganic intracellular components such as potassium, myoglobin, lactic acid, purines, and phosphate which enter the circulation.  Exhaustive work of cells and stretching can increase sarcoplasmic influx of sodium, chloride, and water, which can result in swelling and auto destruction.[4]  After the restoration of blood flow after the injury these components become toxic to the body and in most cases are life threatening, making rhabdomyolysis a medical emergency. [3]  "Myoglobin levels rise within hours of muscle damage, but can return to normal in 1-6 hours if continuous muscle injury is not present."[6]
Courtesy Of: Efstratiadis G, Voulgaridou A, Nikiforou D, et al. Rhabdomyolysis updated. Hippokratia 2007; 11(3): 129-137.


Myoglobin is usually filtered through glomeruli and reabsorbed in the proximal tubules by endocytosis, however when rhabdomyolysis occurs there is an excess of myoglobin, which overloads the proximal tubule cells ability to convert iron to ferritin, which then results in intracellular ferrihemate accumulation.[6]  Since iron can donate and except electrons as well as having the ability to generate free radicals the urine’s pH can lead to metabolic acidosis.  This process puts oxidative stress and injury to the renal cells, which if untreated can lead to renal cell failure.[3]


When there is an excess of myoglobin the tubules are unable to reabsorb it.[3][4] Systemic vasoconstriction sets in which results in water reabsorption in renal tubules, which then increases myoglobin concentration in urine.  This in turn causes formation of casts that obstruct renal tubules. Another contributing factor of cast formation is apoptosis that occurs in epithelial cells.[6]  This obstruction causes formation of free radicals from iron, which can lead to renal failure.[3]


Potassium is another byproduct of muscle lysis.  If there is too much potassium in the circulation then hyperkalemia can occur which is life threatening, because of its cardiotoxicty effects, this is a medical emergency.[3]   Cardiac arrhythmias can occur due to increased levels of potassium in the blood. In some cases, early death occurs due to ventricular fibrillation.[8]


Calcium accumulation in the muscles occurs in the early stages of rhabdomyolysis.  Massive calcification of necrotic muscles can occur which can lead to hypercalcemia.[6]  If hyperkalemia is present hypercalcemia can lead to cardiac arrhythmias, muscular contraction, or seizures.[4]

Causes

There are nine commonly reported categories of rhabdomyolysis. These categories include trauma, exertion, muscle hypoxia, genetic disorders, infections, body-temperature changes, metabolic and electrolyte disorders, drug and toxins, and idiopathic (sometimes recurrent) (Table 1). [9]


Causes chart.jpg

[9]

Categories


Trauma


Crush syndrome results in a characteristic syndrome of rhabdomyolysis, inducing myoglobinuric ARF, also known as traumatic rhabdomyolysis. Traumatic rhabdomyolysis results from muscle reperfusion with subsequent secondary systemic effects. These are direct and indirect consequences of prolonged compression on the limbs. The continuous compression results in destruction of the muscle tissue and subsequent compromise of cell wall integrity and leakage of cellular contents.

Crush syndrome is fundamentally based on three criteria [10]
1. Involvement of muscle mass
2. Prolonged compression (usually 4-6 hrs, but possibly <1 hr)
3. Compromised Circulation

Renal and cardiac complications are specifically sensitive to the amount of pressure and the size of the muscle masses being compressed. This prolonged compression and entrapment of the muscle complex can lead to compartment syndrome or rhabdomyolysis. Rhabdomyolysis under these circumstances is potentially fatal. The syndrome is characterized by hypovolemic shock and hyper kalemia. This is commonly seen in natural disasters and other disasters such as earthquakes, war settings, vehicular accidents, and events involving pinning under objects. [10]

Trauma Clinical Presentation [10]

The clinical presentation of crush syndrome is first based on the history of the event and a high index of suspicion. A compression of > 1 hr is likely to result in a crush syndrome, but this has been seen in as little as 20 min. The physical presence of trauma or local sign of compression (erythema, ecchymosis, bullae, abrasion, etc) on a muscle mass should be evaluated. The absence of a pulse or a weak, thread pulse to the distal limb may indicate muscle swelling or compromised circulation. Patients with crush syndrome have historically been described as presenting with muscle weakness, malaise, and fever. These symptoms may underestimate the real dangers which lie in the cardiovascular effect as a result of electrolyte imbalances and renal failure.


Exertional

Exercise-induced RM or exertional RM is the most frequent cause of RM-related hospitalization. Excessive, prolonged or repetitive exercise may overstretch the sarcoplasmic reticulum. This leads to an increase in Ca2+ leakage into muscle cells. The increase in Ca2+ activates sarcolemma (cell membrane)-degrading enzymes which cause an increase in sarcolemma permeability. With the sarcolemma more permeable, harmful proteins can escape and are released into the blood stream, potentially leading to renal failure, blood clotting and heart arrhythmias. [11]

Exertionalrhab.png

Image Courtesy of Len Kravitz, PhD.


Causes/Risk factors for developing ERM: [11]
1. Intensive exercise or high-repetition exercise
2. Low baseline fitness levels
3. Early introduction of highly repetitive exercises like squats, push-ups and sit-ups.
4. Exertion beyond the point when fatigue would compel an individual
5. Exercising in hot/humid environments
6. Repetitive bouts of eccentric exercise
7. Hypokalemia (from excessive sweating)
8. Sickle-cell trait

Landau and colleagues (2012) report examples of extreme exertion leading to ERM when exercisers attempted to do hundreds of push-ups in an afternoon or suffered from “squat jump syndrome” after being told to squat as low as possible and then jump as explosively as possible repeatedly until exhaustion. People who exercise regularly are less likely to develop the condition than their more sedentary counterparts. A sudden increase in intensity and duration of vigorous exercise, without proper training, may increase the likelihood of rhabdomyolysis. [12][13]


Vitamin D deficiency and exercise-induced rhabdomyolysis:
Speculation has been made that subjects with low levels of vitamin D are at higher risk for developing exertional rhabdomyolysis.[14]

Recurrent exercise-induced rhabdomyolysis:
-Metabolic Myopathies
Metabolic myopathies are a common cause of recurrent rhabdomyolysis post exertion. Most commonly including McArdle disease, and Carnitine palmitoyltransferase deficiency.
(See sections on risk stratification and prevention of recurrent episodes)[15]


Exertional Clinical Presentation


Most cases of acute exertional rhabdomyolysis occur in the military. AER has also been reported in firefighting and law enforcement trainees, long-distance runners, individuals participating in weight training, and football players. However, very few cases of AER occur relative to the thousands of people training [1] Patients typically present with muscle pain, weakness and cramping and discolored urine. Some patients will also experience general malaise, visceral pain, swelling, muscle stiffness and tightness, fever, tachycardia, nausea, and vomiting. [12] Patients will also present with significant loss of active range of motion. [1]

Muscle Hypoxia (Prolonged Immobilization)


Muscle hypoxia can result in rhabdomyolysis. The cause of this is secondary to limb compression by head or torso during prolonged immobilization or loss of consciousness. [9] Prolonged immobilization (anaesthesia, coma, drug or alcohol-induced unconsciousness) has been reported to cause rhabdomyolosis due to unrelieved pressure on gravity-dependent body parts. The primary mechanism is reperfusion of damaged tissue after a period of ischaemia, and the release of necrotic muscle material into the circulation after the pressure has been relieved. The most common positions leading to rhabdomyolosis were the lateral decubitis, lithotomy, sitting, knee-to-chest and prone position. [13]

The risk factors for position related rhabdomyolysis are identified as: [13]

1. Body weight more than 30% above ideal body weight
2. Duration of surgery more than five to six hours
3. Extracellular volume depletion
4. Pre-existing azotaemia
5. Diabetes
6. Hypertension


Muscle Hypoxia Clinical Presentation


Subjects at the highest risk for muscle hypoxia induced rhabdomyolysis include super obese male patients with hypertension and diabetes who have been in prolonged immobilization.[16] This is commonly seen following long surgeries where the patient is immobilized on the operating table. In addition, other etiologic factors include a family history of muscle disease and consumption of certain drugs, notably taking a cholesterol lowering agent.


Genetic Defects


Some genetic variations may predispose people to experience RM. Many of these variations result in a deficiency of enzymes important in ATP production or calcium handling. [11] Abnormalities in glycogen or lipid metabolism result in a block of anaerobic glycolysis that predisposes to the loss of integrity of the sarcolemmal membrane and the liberation of myoglobin following exercise.

The 3 most common inherited genetic alterations known to increase the risk of RM are: [11]

-McArdle’s disease
-Carnitine palmitoyltransferase II deficiency
-Myoadenylate deaminase deficiency

Other genetic causes


-Phosphorylase kinase
-Phosphofructokinase (Tarui’s disease)
-Phosphoglycerate mutase
-Phosphoglycerate kinase
-Lactate dehydrogenase
-Carnitine deficiency
-Myoadenylate deaminase deficiency
-Ducehnne’s muscular dystrophy
-Malignant hyperthermia

These genetic factors may leave patients at an increased risk of developing RM because of a reduced ability to utilize glycogen to make ATP, a reduced ability to produce ATP from fat, and a reduced ability to re-form ATP during intense exercise.

Genetic Clinical presentation


Patients with genetic induced rhabdomyolysis will present with signs and symptoms of their inherited disease but will also present with secondary signs and symptoms of rhabdomyolysis. These secondary signs and symptoms include: swelling, stiffness and cramping, accompanied by weakness and loss of function in the involved muscle group(s). Nonspecific systemic symptoms such as malaise, fever, abdominal pain, and nausea and vomiting, may also be seen. Occasionally changes in mental status can occur.  


Infections

Viral and bacterial infections can cause rhabdomyolysis. Influenza, HIV, and coxasackievirus are the most common viral infections that are seen in rhabdomyolysis. The most common bacterial infections include legionella, Fracisella tularensis, streptococcus, and salmonella. Overall, the most recognized infections associated with rhabdomyolysis are Inluenza A and B and HIV [13] The proposed mechanism for infection-induced rhabdomyolysis includes tissue hypoxia (caused by sepsis, hypoxia, dehydration, acidosis, electrolyte disturbances and hypophospataemia), direct bacterial invasion of the muscle, low oxidative glycolytic enzyme activity, activation of lysosomal enzymes, and mechanisms implicating endotoxins [13]

Infections Clinical Presentation

The clinical presentation of infection induced rhabdomyolysis will be nonspecific and will vary depending on the underlying condition. Systemic signs and symptoms of rhabdomyolysis include tea-colored urine, fever, malaise, nausea, emesis, confusion, agaitation, delirium, and anuria. In ambiguous cases, clinical suspicion of rhabdomyolysis is confirmed by a positive urine or serum test for myoglobin. [13]


Body-temperature changes


Excessive heat, regardless of cause, may result in muscle damage leading to Rhabdomyolysis. Although more rare, excessive cold with or without hyperthermia can lead to Rhabdomyolysis as well due to its direct effect on muscle tissue. The maximum thermal temperature the human body can withstand before experiencing cellular destruction is 107.6 degrees F. Cellular destruction can begin at this temperature between 45 minutes to 8 hours. [13]

Causes of excess heat that can induce Rhabdomyolysis[13]
1. Heat stroke
2. Neuroleptic malignant syndrome
3. Malignant hyperthermia.


Shared features of malignant hyperthermia, exercise induced heat illness, and exertional rhabdomyolysis are hypermetabolic states that include a high demand for adenosine triphosphate, accelerated oxidative, chemical, and mechanical stress of muscle, and an uncontrolled increase in intracellular calcium. These processes overwhelm the normal cellular regulatory mechanisms and severe muscle injury and death occur in certain individuals. These similarities have raised the possibility that exercise induced heat illness, exertional rhabdomyolysis, and malignant hyperthermia are related syndromes triggered by different mechanisms [17]

Body temperature changes Clinical Presentation


Rhabdomyolysis induced from exercise induced heat illness will manifest symptoms of the heat illnesses themselves as well as the following rhabdomyolysis symptoms: muscle tenderness, tea-coloured urine, swelling, stiffness and cramping, accompanied by weakness. Systemic symptoms such as malaise, fever, abdominal pain, and nausea and vomiting, may also be seen. [13]

Metabolic and Electrolyte Disorders


Rhabdomyolysis may be secondary to electrolyte abnormalities. These electrolyte abnormalities include hyponatraemia, hypernatraemia, hypokalaemia, and hypophosphataemia. The proposed mechanism for this is cell membrane disruption as a result of deranged sodium-potassium-ATPase pump function. In addition, rhabdomyolysis can be caused by endocrine abnormalities such as hyperthyroidism, hypothyroidism, diabetic ketoacidosis, and non-ketotic hyperosmolar diabetic coma.[13]

Endocrine and Electrolyte Clinical Presentation

The clinical presentation of metabolic and electrolyte induced rhabdomyolysis will be nonspecific and vary depending on the underlying condition. The clinician should monitor systemic signs and symptoms to help determine if further testing is needed.

Drugs and Toxins


Rhabdomyolysis may result from substance abuse, toxins, prescription and nonprescription medications. Substances that are commonly abused include ethanol, methanol, ethylene glycol, heroin, methadone, barbiturates, cocaine, caffeine, amphetamine, lysergic acid diethylamid, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), phencyclidine, benzodiasepines, and toluene (from glue sniffing).[13] Rhabdomyolysis is a frequent consequence of illicit drug consumption that is not promoted by a single factor, but by a combination of several factors.[18] In acute poisoning, RM can be the result of multiple causing mechanisms. For instance, alcohol, cocaine, and possibly heroin act directly myotoxically. This mechanism should be distinguished from RM that develops secondarily, due to muscle ischemia during seizures or local muscle compression in comatose states. An increasing energy consumption can contribute to RM in some cases like hyperpyrexia in cocaine-induced RM. [19]

Main drugs and substances inducing Rhabdomyolysis[13]
-Statins
-Alcohol
-Barbiturates, benzodiazepines, and other sedatives and hypnotics
-Cocaine
-Heroin
-Ecstasy
-Stimulants used to treat ADHA (ie. Adderall, Ritalin, Vyvanse)[20]


Rhabdomyolysis from alcohol is induced from a combination of immobilization, direct myotoxicity and electrolyte abnormalities (hypokalemia and hypophosphatemia). Cocaine induced rhabdomyolysis can occur through vasospasm with muscular ischemia, seizures, hyperpyrexia, coma with muscle compression, and direct myofibrilar damage. Statin-induced rhabdomyolysis may result from an unstable skeletal muscle cell membrane, the presence of abnormal prenylated protein causing an imbalance in intracellular protein messenger, and abnormal mitochondrial respiratory function caused by a coenzyme Q10 deficiency.[13]

Drugs and Toxins Clnical Presentation

The clinical presentation of drug and toxin induced rhabdomyolysis can vary due to the nature and side effects of the drugs and toxins themselves. Clinicians must take note of the signs and symptoms of the drugs themselves as well as monitor for additional signs and symptoms of rhabdomyolysis. As previously mentioned, typical signs and symptoms of rhabdomyolysis include: tea-coloured urine, muscle tenderness, swelling, stiffness and cramping, accompanied by weakness and loss of function in the involved muscle group(s).[13]

Idiopathic


In many cases the etiology of rhabdomyolysis cannot be identified. Some cases present with recurrent myoglobinuria and are termed idiopathic paroxysmal myoglbinuria (Meyer-Betz disease). Further studes are need to determine if these effects are from a genetic disease. [13]


Other possible Causes[21]

• Status asthmaticus
• Non-depolarizing muscle blocking agents to critically ill intensive care unit patients requiring mechanical ventilation
• Capillary leak syndrome
• Baclofen withdrawal
• Inflammatory myopathies – polymyositis, dermatomyositis

Risk Factors For Postoperative Rhabdomyolysis[22]


Bodyweight >30% of ideal
Surgical Time > 4 hours
Intravascular Volume Depletion (Hematocrit >50, Na >150 mEq/l, orthostatism, pulmonary wedge pressure <5 mm Hg, FENa <1%)
Preexistent azotemia
Diabetes Mellitus
Systemic Arterial Hypertension
CPK peak >6,000 IU/l
Sepsis
Hyperkalemia or Hypophosphatemia
Hypoalbminemia



Characteristics/Clinical Presentation

The signs and symptoms of rhabdomyolyis vary from person to person. The three most common signs and symptoms are muscle pain, weakness, and dark urine.[2][3] Muscle pain as well as weakness and tenderness may be general or specific to muscle groups. The calves and low back are the most general muscle groups that are affected.[2] According to the author Efstratiadis, back pain and limb pain are the most frequent sites in patients with rhabdomyolysis.[3] However, over 50% of the patients with rhabdomyolysis may not complain of muscle pain or weakness.[2] The initial sign of rhabdomyolysis is discolored urine which can range from pink to dark black.[2][3] Other signs and symptoms include, local edema, cramps, hypotension, malaise, fever, tachycardia, nausea and vomiting.[2][3] Often during the early stages of rhabdomyolysis the following conditions may also be present: hyperkalemia, hypocalcemia, elevated liver enzymes, cardiac dysrrhythmias and cardiac arrest.[2] Some late complications include acute renal failure and disseminated intravascular coagulation.[2]

Complications of Rhabdomyolysis [13]

Hypovolemia

Compartment syndrome

Arrhythmias and cardiac arrest

Disseminated intravascular coagulation

Hepatic dysfunction

Acidosis

Acute renal failure

Death

Diagnostic Tests/Lab Tests/Lab Values

Blood samples are taken from the patient to look at various serum values, one of the most important serum indicators of myocyte injury is creatinine kinase.[3]

Creatinine Kinase
Courtesy Of: Efstratiadis G, Voulgaridou A, Nikiforou D, et al. Rhabdomyolysis updated. Hippokratia 2007; 11(3): 129-13

"Under normal conditions, CK levels are 45-260 U/L. After rhabdomyolysis, the levels of CK can be raised to 10.000-200.000 U/L or even 3.000.000.000 U/L.  No other condition except rhabdomyolysis can cause such extreme CK elevation.”[3]  

Creatine Kinase has several forms that include the muscles, heart, brain and kidneys, as well as mitochndria so it is important to look at all values.

Uric Acid

Uric Acid is important to check due to the fact that rhabdomyolysis breaks down skeletal muscle creating more creatinine, which then becomes creatinine which can then lead to acute renal failure, therefore causing the levels of uric acid to rise.

Urinalysis
Courtesy Of: Efstratiadis G, Voulgaridou A, Nikiforou D, et al. Rhabdomyolysis updated. Hippokratia 2007; 11(3): 129-137

Urine analysis can be very helpful in diagnosing rhabdomyolysis.  Urinalysis will be able to detect changes in the body’s waste, such as increases in uric acid, albumin, as well as myoglobin.[3]  Often patients that are positive for rhabdomyolysis have brown tinted urine.  Table 3 has a description of common findings in urinalysis.

Causes of Reddish-Brown Discoloration of the Urine[4]

Myoglobinuria

        Rhabdomyolysis

              Traumatic

              Non-Traumatic 

Hemoglobinuria

        Hemolysis

              Mechanical Damage

              Immunologic Damage

              Structural Fragility of Erythrocytes

              Microangiopathy

Hematuria
Courtesy of: Vanholder R, Mehmet S, Erek E, Lameire N. Rhabdomyolysis. Journal of the American Society of Nephrology 2000; 1553-1561.

        Renal Causes

        Post Renal Causes

External Factors

        Red Beets

        Drugs

              Vitamin B12

              Rifampicin

              Phenolphthalein

              Phenytoin

        Metabolites

              Bilirubin

              Porphyrin

Systemic Involvement

Systemic involvement for rhabdomyolysis includes the muscle groups that have been directly involved such as during a crush injury or overuse.  Once the breakdown of muscle occurs the by-product will then filter into the renal system, which if gone untreated can lead to renal failure.

Medical Management (current best evidence)

The best medical management for rhabdomyolysis is stabilizing the patient and aggressive fluid replacement with saline to preserve renal function.[2][3]  It is also suggested that fluids be given to victims before extraction.  The increase in fluids helps to expand the intravascular volume, thereby inducing diuresis and clearance of toxins.[3]  It Is recommended that patients should be given 10 or more liters of fluid per day, so that they maintain a urine output of 150-300 ml/per hour.[3]  Sometimes mannitol and bicarbonate are given during the initial resuscitation.  It is believed that mannitol acts as a free-radical scavenger minimizing cell injury.  Mannitol is also a renal vasodilator to prevent renal failure.  Bicarbonate is given to help correct the effects of metabolic acidosis and enhance myoglobin.[3]  Along with the patient’s vital signs and urine output, the patient’s electrolytes should be closely monitored.


Prehospital Care[13]

  • ABC assessment
  • Intravenous access
  • Consider the importance of early fluid administration in the field
  • NS infusion at a rate of 1.5 liters/ hour, to maintain a urine output of 200-300 ml/hour
  • Avoid empirical administration of potassium and lactate-containing fluids


In hospital Care[13]

  • Aggressive intravenous rehydration
  • A careful history and physical examination
  • Closely monitor serum electrolyte and CK
  • Monitor fluid intake and urinary output (urinary catheter insertion).
  • Check limbs for compartment syndromes
  • Hemodynamic monitoring (central venous pressure measurements).
  • Administer mannitol and bicarbonate (for patients with crush injury): a 20% mannitol infusion at a dose of 0.5 g/kg an infusion at 0.1 g/kg/h. Adjustments are made to maintain urine output >200ml/h. Sodium bicarbonate, one ampoule (44 mEq) added to 1 l of 1/2 NS or two to three ampoules (88 to 132 mEq) in D5W to run at a rate of 100ml/hour, has been recommended to maintain a urinary pH of ≤6.5 to prevent the development of ARF
  • Intensive care monitoring (for critically ill patients)

Treatment of any reversible cause of muscle damage[13]

  • Correct electrolyte and metabolic abnormalities
  • Treat hyperthermia and hypothermia
  • Eliminate and detoxify drugs and toxins

Management and prevention of complications[13]

  • Hyperkalemia may be fatal and should be corrected vigorously
  • Hypocalcemia should be corrected only if it causes symptoms
  • Hypophosphatemia and hyperphosphatemia with oral phosphate binders when serum levels exceed 7 mg/dl
  • Compartment syndrome requires immediate orthopaedic consultation for fasciotomy
  • DIC usually usually resolves spontaneously after several days if the underlying cause is corrected, but if haemorrhagic compliations occur, therapy with platelets, vitamin k, and fresh frozen plasma may be necessary
  • Hyperuricaemia and hyperphophatemia are rarely of clinical significance and rarely require treatment
  • Consider dailysis as a lifesaving procedure for patients with rising or elevated potasum level, persistent acidosis, or oliguric renal failure with fluid overload
  • Consider continuing dialysis support until patients' kidney function has recovered



Dialysis

Unfortunately, patients that have rhabdomyolysis are more likely to develop acute renal failure.  A common treatment for acute renal failure is dialysis to correct fluid, electrolytes, and acid-base abnormalities.  This is a slow process to correct the fluid overload and as well as removal of potassium and urea.[2]

Medications

A patient wil rhabdomyolysis will not take medications on a regular basis, they will only take them in the emergency medical treatment.  However, patients are encouraged to drink lots of water throughout treatment.


(current best evidence)

It is important to keep in mind the cause of rhabdomyolysis. It is important to not overexert the patient to prevent them from creating more muscle breakdown.  The most important thing is for the patient to retain range of motion as well as to properly hydrate.

The physical therapist treating a patient with rhabdomyolysis must make sure that the patient is not having any urinary problems which includes urine color.[23] Some interventions would include range of motion exercises both active and passive, aerobic training, and gradual resistance training.[23]


Exertional Rhabdomyolysis and Return to Sport


A client’s fitness level is extremely important when considering the development of a workout program. Exertional rhabdomyolysis may occur when a client is not accustomed to the mode or intensity of the exercise prescribed. Fitness professionals must understand the importance of initial fitness level and progressional overload so that the exercise stress challenges the client appropriately. Fitness specialists should also consider the risks when providing eccentric training in a hot environment or if the client has any genetic risk factors for rhabdomyolysis.


Physical Therapy Management Return to Sport [24]

There is currently no evidence based guidelines for return to play after an episode of exertional rhabdomyolysis. However, a conservative return to sport protocol has been described by Consortium for Health and Military Performance (CHAMP) and is listed below.


Returntosport.png [24]
Image Courtesy of David C. Tietze, M.D.

Schleich et al, outlined a phased reintegration program for safe and effective return to play post exertional rhabdomyolysis (table 1 below). Following phase IV, athletes in the study continued with agility work, speed development, and resistance training under the supervision of strength and conditioning staff. Each athletes return-to-play time will vary depending on severity of rhabdomyolysis, previous fitness level, training experience and maturation.

Table 1. Overview of Phased Return [25]
Phase 1: Activities  
Return to activities of daily living for 2 wk
Regular monitoring by athletic training staff
Screening for symptoms consistent with exertional rhabdomyolysis, sleep patterns, hydration, urine color, and class attendance
Monitoring of creatinine kinase and serum creatinine by primary care physician
Phase 2: Activities
Daily monitoring of hydration status, muscle soreness, and swelling
Initiation of physical activity: foam rolling, dynamic warm-up, aquatic jogging, and stretching
Phase 3: Activities
Daily monitoring of hydration status, muscle soreness, and swelling
Progression of physical activity: body-weight resistance movements, resistance training with elastic band, core training, stationary bicycling, and stretching
Phase 4: Activities
Daily monitoring of hydration status, muscle soreness, and swelling
Initiation of resistance training at 20%–25% of estimated 1-repetition maximum, agility exercises, and running
Risk stratification for recurrent rhabdomyolysis [26]
According to O’Connor et al., an athlete who experiences clinically relevant exertional rhabdomyolysis (ER) should first be risk-stratified as either low or high risk for a recurrence.
To be considered "suspicious for high risk,' at least one of the following conditions must exist or be present:
a. Delayed recovery (more than 1 wk) when activities have been restricted
b. Persistent elevation of CK (greater than five times the upper limit of the normal lab range) despite rest for at least 2 wk
c. ER complicated by acute renal injury of any degree
d. Personal or family history of ER
e. Personal or family history of recurrent muscle cramps or severe muscle pain that interferes with activities of daily living or sports performance
f. Personal or family history of malignant hyperthermia, or family history of unexplained complications or death following general anesthesia
g. Personal or family history of sickle cell disease or trait
h. Muscle injury after low to moderate work or activity
i. Personal history of significant heat injury (heat stroke)
j. Serum CK peak ≥ 100,000 U·L−1.
To be considered a "low risk" athlete, none of the high-risk conditions should exist, and at least one of the following conditions must exist or be present:
a. Rapid clinical recovery and CK normalization after exercise restrictions
b. Sufficiently fit or well trained athlete with a history of very intense training/exercise bout
c. No personal or family history of rhabdomyolysis or previous reporting of debilitating exercise-induced muscle pain, cramps, or heat injury
d. Existence of other group or team-related cases of ER during the same exercise sessions
e. Suspected or documented concomitant viral illness or infectious disease
f. Taking a drug or dietary supplement that could contribute to the development of ER
Complete history and physical examination should be completed and referral to experts for consideration of myopathic disorders before return to sport for any individual at high risk.
Prevention of recurrent episodes in pre-disposed individuals [27]
Regardless of cause:
• Avoid triggers
• Hydrate
• Warm-up before exercise
Fatty acid beta-oxidation:
• Low fat diet
• Replacement of essential fatty acids with walnut or soy oils
Vitamin D deficiency:
• Monitoring and normalization of vitamin D levels

Brief video regarding physical therapy management[28][29]

https://www.youtube.com/watch?v=NDdoiNNaMKI





Differential Diagnosis

Most Common Differential Diagnoses[30]

  • Burns, Electrical
  • Carnitine Deficiency
  • Child Abuse and Neglect, physical abuse
  • Dermatomyositis
  • Multisystem Organ Failure of Sepsis
  • Myoglobinuria[4]
  • Neuroleptic Malignant Syndrome
  • Sepsis
  • Systemic Inflammatory Response Syndrome
  • Systemic Lupus Erythmatosus
  • Thromboembolism
  • Toxic Shock Syndrome
  • Toxicity, Ethanol

Other Problems to Consider[30]

Traumatic injuries
, Viral infections, 
Myalgias from other etiologies, 
Bacterial infections, 
Pyomyositis, 
Heatstroke
, Cold exposure, 
Snakebite, 
Malignant hyperthermia, 
Muscle phosphorylase deficiency, 
Phosphofructokinase deficiency, 
Carnitine palmityl transferase deficiency, 
Phosphoglycerate mutase deficiency, 
Other inborn errors of metabolism, 
Hyperosmotic conditions, 
Guillain-Barré syndrome, 
Inflammatory myositis.


Rhabdomyolysis Case Study

Case Report (Diagnosis and Treatment of Acute Exertional Rhabdomyolysis)[31]

Subjective Findings

Patient  was a walk in to the US Military Academy Cadet Physical Therapy Clinic complaining of bilateral shoulder pain and weakness.  The patient reported performing hundreds of push up of varying types 36 hours earlier.  The patient reported being in pain and that he had noticed dark colored urine 24 hours after his push up session.

Objective Findings

Range of Motion

Bilateral shoulder AROM restricted below 90 degrees elevation with abnormal scapulohumeral rhythm (excessive scapular elevation bilaterally)

PROM was within normal limits but caused pain in the pectoralis and triceps near end range shoulder elevation

Left elbow AROM and PROM were restricted to 90 degrees flexion due to pain and induration in the left triceps.

Strength
Patient's ROM before intervention

Shoulder ER 3+/5

All other muscle strength assessment was deferred due to the severity and irritability of the patient's symptoms

Special Tests

Shoulder impingement tests were negative (Hawkins-Kennedy and Neer)

Exquisite tenderness to palpation bilaterally in the pectoralis, triceps, and infraspinatus muscle, as well as in the bicipital groove

Laboratory Tests

Serum CK, completed blood count, and urinalysis were ordered

Serum CK was listed as 9,600 U/L (normal range 55-170 U/L)

Urinalysis noted that the urine was brown

Management

Patient was diagnosed with Acute Exertional Rhabdomyolysis and was admitted to the hospital.  He was given aggressive fluid replacement. While in inpatient he performed AAROM in shoulders and in elbows.  Patient was discharged after 4 days and then returned to the outpatient clinic.

Outpatient

Randall et al's Rehabilitation program for patients with with acute exertional rhabdomyolysis secondary to intense push-up training

Phase 1

     Active and gentle passive ROM of the shoulder and elbow within limits of pain

Phase 2

     Initiated once active ROM is normal.  Upper body ergometer at low intensity for 5 minutes progressing daily until this workload can be maintained for 15 minutes.

Phase 3

     Initiated once the patient can maintain 15 minutes, on the upper body ergometer without discomfort, change in technique, or muscle soreness 24 hours post exercise.  Progress to isotonic weight training with light weights for specific muscle weakness (ex. elbow extension for triceps), modified pushups, and bench press.  Modified pushups are performed daily on an incline (such as against a wall) and progressed as tolerated to tabletop, stool, and floor (without modification).

Phase 4

     Initiated once patient progresses to pushups without modification.  Patient is allowed to resume normal exercise routine with the restriction of only performing 1 set of pushups in any 24 hour period. This restriction in maintained until the patient is able to perform at their preinjury number of pushups without sequelae such as muscle soreness or loss of normal ROM.

Outcome

First Outpatient Visit

Shoulder AROM: 
Picture of patient's ROM after interventions

    Flexion 155 degrees

    Abduction 170 degrees

    External Rotation 55 degrees

    Internal Rotation 65 degrees

Strength

   5/5 for shoulder shrug, internal rotation, and elbow flexion

   4/5 or 4-/5 for shoulder abduction, flexion, external rotation, supraspinatus and triceps

CK level 5,721 U/L

Eight Day Post Diagnosis

Full AROM

Began Radall et al.Protocol

Thirty-Seven Days Post Diagnosis - serum CK levels normal

Seventy- One Days Post Diagnosis - patient's full strength was back and was able to perform 60 pushups in one continuous bout



Recent Related Research (from Pubmed)

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References

see adding references tutorial.

  1. 1.0 1.1 1.2 Brudvig T, Fitzgerald P. Identification of Signs and Symptoms of Acute Exertional Rhabdomyolysis in Athletes: A Guide for the Practitioner. Strength & Conditioning Journal (Allen Press) [serial online]. February 2007;29(1):10-14. Available from: SPORTDiscus with Full Text, Ipswich, MA. Accessed March 23, 2014.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 Huerta-Alardin AL, Varon J, Marik P. Bench-to-beside review: Rhabdomyolysis - an overview for clinicians. Critical Care 2005; 9: 158-169
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 Efstratiadis G, Voulgaridou A, Nikiforou D, et al. Rhabdomyolysis updated. Hippokratia 2007; 11(3): 129-137.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Vanholder R, Mehmet S, Erek E, Lameire N. Rhabdomyolysis. Journal of the American Society of Nephrology 2000; 1553-1561.
  5. Harriston S. A review of rhabdomyolysis. Dimensions Of Critical Care Nursing: DCCN [serial online]. July 2004;23(4):155-161. Available from: MEDLINE, Ipswich, MA. Accessed March 23, 2014.
  6. 6.0 6.1 6.2 6.3 6.4 Bagley WH, Yang H, Shah KH. Rhabdomyolysis. Intern Emergency Medicine 2007; 2: 210-218
  7. Al-Ismaili Z, Piccioni M, Zappitelli M. Rhabdomyolysis: pathogenesis of renal injury and management. Pediatric Nephrology (Berlin, Germany) [serial online]. October 2011;26(10):1781-1788. Available from: MEDLINE, Ipswich, MA. Accessed March 23, 2014.
  8. Savage DCL, Forbes M. Idiopathic Rhabdomyolysis. Archieves of Disease in Childhood 1971; 26: 594-607
  9. 9.0 9.1 9.2 Bosch X, Poch E, Grau J. Rhabdomyolysis and acute kidney injury. The New England Journal Of Medicine [serial online]. July 2, 2009;361(1):62-72. Available from: MEDLINE, Ipswich, MA. Accessed March 23, 2014.
  10. 10.0 10.1 10.2 Dario G. Crush syndrome. Critical Care Medicine [serial online]. January 2005;33(1):S34-S41. Available from: Academic Search Premier, Ipswich, MA. Accessed March 23, 2014.
  11. 11.0 11.1 11.2 11.3 Deyhle M, Kravitz L. research. Exertional Rhabdomyolysis: When Too Much Exercise Becomes Dangerous. IDEA Fitness Journal [serial online]. April 2013;10(4):16-18. Available from: SPORTDiscus with Full Text, Ipswich, MA. Accessed March 23, 2014.
  12. 12.0 12.1 Parmar S, Chauhan B, DuBose J, Blake L. Rhabdomyolysis after spin class?. Journal Of Family Practice [serial online]. October 2012;61(10):584-586. Available from: Academic Search Premier, Ipswich, MA. Accessed March 23, 2014.
  13. 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 13.12 13.13 13.14 13.15 13.16 13.17 13.18 13.19 Khan F. Rhabdomyolysis: a review of the literature. The Netherlands Journal Of Medicine [serial online]. October 2009;67(9):272-283. Available from: MEDLINE, Ipswich, MA. Accessed March 23, 2014.
  14. Glueck CJ, Conrad B. Severe Vitamin D Deficiency, Myopathy, and Rhabdomyolysis. North American Journal of Medical Sciences. 2013;5(8):494-495. doi:10.4103/1947-2714.117325.fckLRhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690793/
  15. Miller M, M.D. (2017). Causes of rhabdomyolysis. [online] Uptodate.com. Available at: http://www.uptodate.com/contents/causes-of-rhabdomyolysis [Accessed 10 Mar. 2017].fckLRhttp://www.uptodate.com/contents/causes-of-rhabdomyolysis
  16. Bostanjian D, M.D., Anthone GJ, M.D., Hamoui N, M.D., Crookes PF, M.D. Rhabdomyolysis of gluteal muscles leading to renal failure: A potentially fatal complication of surgery in the morbidly obese. Obesity Surg. 2003;13(2):302-5. http://search.proquest.com/docview/821093760?accountid=6741. doi: http://dx.doi.org/10.1381/096089203764467261.
  17. Capacchione J, Muldoon S. The relationship between exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia. Anesthesia And Analgesia [serial online]. October 2009;109(4):1065-1069. Available from: MEDLINE, Ipswich, MA. Accessed March 23, 2014.
  18. Welte T, Bohnert M, Pollak S. Prevalence of rhabdomyolysis in drug deaths. Forensic Science International [serial online]. January 6, 2004;139(1):21-25. Available from: MEDLINE, Ipswich, MA. Accessed March 23, 2014.
  19. Janković S, Jović Stošić J, Vučinić S, Perković Vukčević N, Vuković Ercegović G. Causes of rhabdomyolysis in acute poisonings. Vojnosanitetski Pregled: Military Medical & Pharmaceutical Journal Of Serbia & Montenegro [serial online]. November 2013;70(11):1039-1045. Available from: Academic Search Premier, Ipswich, MA. Accessed March 23, 2014.
  20. Fda.gov. (2017). Stimulants Used to Treat Attention Deficit Hyperactivity Disorder (ADHD). [online] Available at: https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm446139.htm [Accessed 12 Mar. 2017].
  21. Miller M, M.D. (2017). Causes of rhabdomyolysis. [online] Uptodate.com. Available at: http://www.uptodate.com/contents/causes-of-rhabdomyolysis [Accessed 10 Mar. 2017].
  22. Torres-villalobos G, Kimura E, M.D., Mosqueda JL, M.D., García-garcía E, MD, Domínguez-cherit G, MD, Herrera MF, M.D. Pressure-induced rhabdomyolysis after bariatric surgery. Obesity Surg. 2003;13(2):297-301. http://search.proquest.com/docview/821093761?accountid=6741. doi: http://dx.doi.org/10.1381/096089203764467252.
  23. 23.0 23.1 Brown T. Exertional Rhabdomyolysis: Early Recognition is Key. The Physician and Sports Medicine 2004; 32: 1-5
  24. 24.0 24.1 Tietze DC, Borchers J. Exertional Rhabdomyolysis in the Athlete: A Clinical Review. Sports Health: A Multidisciplinary Approach. 2014;:1941738114523544.
  25. Schleich, K., Slayman, T., West, D. and Smoot, K. (2016). Return to Play After Exertional Rhabdomyolysis. Journal of Athletic Training, 51(5), pp.406-409.
  26. O'Connor, F., Brennan, F., Campbell, W., Heled, Y. and Deuster, P. (2008). Return to Physical Activity After Exertional Rhabdomyolysis. Current Sports Medicine Reports, 7(6), pp.328-331.
  27. Hannah-Shmouni F, McLeod K, Sirrs S. Recurrent exercise-induced rhabdomyolysis. CMAJ : Canadian Medical Association Journal. 2012;184(4):426-430. doi:10.1503/cmaj.110518.
  28. Schleich, K., Slayman, T., West, D. and Smoot, K. (2016). Return to Play After Exertional Rhabdomyolysis. Journal of Athletic Training, 51(5), pp.406-409.
  29. O'Connor, F., Brennan, F., Campbell, W., Heled, Y. and Deuster, P. (2008). Return to Physical Activity After Exertional Rhabdomyolysis. Current Sports Medicine Reports, 7(6), pp.328-331.
  30. 30.0 30.1 Muscal E. Rhabdomyolysis: Differential Diagnoses and Workup. eMedicine 2009.
  31. Baxter R, Moore J. Diagnosis and Treatment of Acute Exertional Rhabdomyolysis. Journal of Orthopaedic and Sports Physical Therapy 2003; 33(3): 104-108