CPK Rhabdomyolysis Diagnosis: A Comprehensive Guide for Clinicians

Introduction

Rhabdomyolysis, a serious condition characterized by skeletal muscle breakdown, poses significant risks due to potential systemic complications. These complications primarily arise from the leakage of intracellular muscle components, notably myoglobin and creatine phosphokinase (CPK), into the bloodstream. Among the various diagnostic markers, CPK elevation is paramount in confirming rhabdomyolysis. This article delves into the critical role of Cpk Rhabdomyolysis Diagnosis, exploring the etiology, pathophysiology, and clinical presentation of this condition, while emphasizing optimal diagnostic and management strategies for healthcare professionals.

Rhabdomyolysis stems from the disintegration of striated muscle, leading to the release of muscle cell contents, including myoglobin, sarcoplasmic proteins, and electrolytes, into the systemic circulation. The term itself originates from Greek roots: rhabdos (striated), mys (muscle), and lysin (dissolution). Common triggers encompass traumatic injuries, excessive physical exertion, metabolic disorders, viral infections, and electrolyte imbalances.

Patients may present with a spectrum of symptoms, from muscle weakness and pain to dark urine (myoglobinuria). Clinically, rhabdomyolysis can range from mild CPK elevations to severe, life-threatening conditions such as compartment syndrome, fluid imbalances, disseminated intravascular coagulation (DIC), acute kidney injury (AKI), and cardiac arrhythmias.

Laboratory diagnosis hinges on elevated serum creatine phosphokinase (CPK) levels. CPK is acknowledged as the most sensitive indicator of muscle injury. While there isn’t a universally defined diagnostic CPK threshold, a common clinical practice is to consider levels 3 to 5 times the upper limit of normal (ULN), approximately 1000 U/L, as suggestive of rhabdomyolysis. However, it’s crucial to recognize that the magnitude of CPK elevation doesn’t directly correlate with the severity of muscle damage or the risk of renal injury.

Rhabdomyolysis is a significant contributor to AKI. Early identification of rhabdomyolysis-induced AKI generally leads to a more favorable prognosis. It’s essential to differentiate rhabdomyolysis from other causes of AKI, such as dehydration, sepsis, and drug-induced nephrotoxicity. Factors like seizures, alcohol abuse, drug use, and prolonged immobilization are common non-traumatic causes of rhabdomyolysis. Rarer etiologies include Haff disease, mushroom poisoning, and genetic predispositions.

Historically, instances resembling rhabdomyolysis date back centuries. A notable example is described among Israelites exhibiting myolysis-like symptoms after consuming quail that had ingested poisonous plants. In modern times, crush injuries resulting from wars and natural disasters have highlighted rhabdomyolysis. In 1943, Bywaters and Stead identified myoglobin as the causative agent in brown urine acute tubular necrosis, marking a significant step in understanding the pathophysiology.

Etiology of Rhabdomyolysis and the Importance of CPK in Diagnosis

The causes of rhabdomyolysis are broadly categorized into traumatic (physical) and non-traumatic (non-physical) factors. Many cases involve a combination of factors, potentially including genetic susceptibility alongside external insults.

A thorough patient history, physical examination, and laboratory investigations are crucial for pinpointing the underlying cause of rhabdomyolysis. Epidemiological studies indicate varying frequencies of different causes depending on hospital settings and community characteristics.

Traumatic or Physical Causes

Traumatic rhabdomyolysis often results from physical compression. Subclinical CPK elevations, myoglobinemia, and myoglobinuria are frequently observed following intense physical activity.

Key traumatic etiologies include:

Crush injuries: Polytrauma, motor vehicle accidents, mining accidents, and earthquakes, especially in entrapped individuals.
Prolonged immobilization: Coma, alcohol or opioid intoxication, hip fractures, and surgeries requiring prolonged specific positioning.
Physical abuse: Torture and physical restraint, particularly in children.
Vascular compromise: Fractures, especially tibial fractures, leading to arterial occlusion from immobilization, tourniquets, or surgical clamping.
Thermal injuries: Fire accidents and explosions.
Electrical injuries: High voltage electric shock and lightning strikes, causing direct sarcoplasmic membrane damage and massive calcium influx, leading to severe rhabdomyolysis.
Excessive muscle activity: Strenuous exercise (especially in untrained individuals), heavy lifting, exertion in extreme heat, status epilepticus, tetanus, and rarely, sepsis.

Non-traumatic or Non-physical Causes

Non-traumatic rhabdomyolysis can arise from imbalances between oxygen supply and demand, electrolyte abnormalities, and metabolic disturbances.

Medications: Statins are notorious for inducing rhabdomyolysis as a common adverse effect.
Infections: Viral myositis is prevalent, and recently, SARS-CoV-2 infection has emerged as a significant association. Sepsis and bacterial infections also contribute.
Electrolyte imbalances: Hypokalemia, hypophosphatemia, hyperosmolar states, hypo- and hypercalcemia, and severe dehydration.
Endocrine disorders: Hyperosmolar hyperglycemic state, diabetic ketoacidosis with coma, myxedema.
Congenital myopathies: Myotonic dystrophy, Duchenne muscular dystrophy, and Becker muscular dystrophy are among the most common.
Toxins: Insect bites, snake venom, hornet stings, carbon monoxide poisoning, Haff disease, and mushroom poisoning.
Autoimmune myositis: Polymyositis and dermatomyositis.
Thermoregulatory dysfunction: Neuroleptic malignant syndrome, malignant hyperthermia, near drowning, hypothermia, and frostbite.
Supplements: Over-the-counter vitamins, performance-enhancing, and weight-loss supplements.
Capillary leak syndrome: Resulting from muscle edema.
Drugs: Both drug intoxication and withdrawal can trigger rhabdomyolysis.

Statins and CPK Elevation

Statins are the most frequent pharmaceutical culprits in rhabdomyolysis. Up to 10% of statin users experience muscle pain. With increasing statin utilization, rhabdomyolysis incidence from HMG Co-A reductase inhibitors is on the rise. Statin-induced muscle toxicity ranges from myopathy and myalgia to myositis and rhabdomyolysis. Proposed mechanisms include CoQ10 depletion, mitochondrial dysfunction, impaired calcium homeostasis, apoptosis induction, and direct anti-HMG Co-A reductase effects. Statins commonly cause toxic myopathy (CPK < 1000 U/L, no necrosis) and less frequently autoimmune myopathy (CPK > 1000 U/L, muscle necrosis).

Discontinuation of statins is usually effective for statin-induced rhabdomyolysis. However, persistent CPK elevation post-discontinuation should raise suspicion for necrotizing autoimmune myopathy. Concomitant use of drugs like gemfibrozil, cyclosporine, cytochrome P450 inhibitors, and corticosteroids increases the risk. Clinically significant rhabdomyolysis requiring hospitalization occurs in approximately 0.44 per 10,000 patients on atorvastatin, simvastatin, or pravastatin monotherapy. Despite the low incidence, muscle-related side effects are a common reason for statin therapy discontinuation. Using the lowest tolerable statin dose is advised in patients with a history of drug-induced rhabdomyolysis.

Drug Intoxication and CPK Levels

Various intoxicants can induce rhabdomyolysis through different mechanisms. Cocaine is a well-known trigger, involving increased sympathetic stimulation, endothelin production, and decreased nitric oxide. Cocaine is also thrombogenic.

Heroin, particularly intravenous use, shows a high incidence of drug-induced rhabdomyolysis, possibly due to local trauma from injection and immune mechanisms. Amphetamines are also associated with high rhabdomyolysis rates, likely due to hyperthermia from effects on serotonin, dopamine, and norepinephrine. Alcohol, opiates, phenobarbital, and benzodiazepines can cause rhabdomyolysis due to prolonged immobilization and muscle compression during intoxication. Opioid and baclofen withdrawal can also lead to rhabdomyolysis. Alcohol misuse disorder is frequently linked to rhabdomyolysis due to direct muscle toxicity and electrolyte imbalances like hypophosphatemia and hypokalemia.

Intensive Care Unit (ICU) Admissions and CPK Monitoring

ICU admission is strongly correlated with rhabdomyolysis. Critically ill ICU patients often receive multiple medications and are prone to electrolyte disturbances, predisposing them to rhabdomyolysis. Propofol infusion syndrome (PRIS), a manifestation of propofol toxicity, is a significant concern in ventilated patients. PRIS results from uncoupled oxidative phosphorylation, leading to metabolic acidosis, rhabdomyolysis, arrhythmias, AKI, and cardiovascular collapse. Regular CPK monitoring is vital in ICU settings, especially in patients receiving propofol or with risk factors for rhabdomyolysis.

Congenital Myopathies and Genetic Predisposition

Numerous congenital myopathies can cause rhabdomyolysis. Common examples include:

Glycogenolysis disorders: McArdle disease (myophosphorylase deficiency) and phosphorylase kinase deficiency.
Glycolysis disorders: Phosphofructokinase, phosphoglycerate kinase, mutase, and lactate dehydrogenase deficiencies.
Purine metabolism disorders: Myoadenylate deaminase deficiency.
Lipid metabolism disorders: Carnitine and carnitine palmitoyltransferase deficiencies, acyl-CoA dehydrogenase deficiencies, lipin-1 deficiency, and Brody myopathy (CAT deficiency).

Genetic susceptibility plays a role, even without baseline CPK elevations. Mutations in genes like ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, and RYR1 are associated with increased risk. Sickle cell trait, affecting millions globally, also increases rhabdomyolysis risk, especially with exertional dyspnea. Patients with sickle cell disease are prone to rhabdomyolysis during crises, necessitating trigger avoidance.

Sepsis and Bacterial Infections

Sepsis can induce rhabdomyolysis via multiple mechanisms: direct muscle invasion by pathogens, muscle ischemia from hypoxia, toxin production, and cytokine-mediated muscle toxicity. Staphylococcus aureus is known to cause rhabdomyolysis through direct invasion and toxin production. Streptococci, salmonellae, and S. aureus have been identified in muscle biopsies of rhabdomyolysis patients. Other implicated pathogens include Staphylococcus epidermidis, Francisella tularensis, Streptococcus faecalis, meningococci, Hemophilus influenzae, Escherichia coli, pseudomonads, Klebsiella, Enterococcus faecalis, and Bacteroides. In sepsis, CPK levels can be an indicator of disease severity and muscle involvement.

Epidemiology of Rhabdomyolysis and Risk Factors

Approximately 26,000 rhabdomyolysis cases are reported annually in the United States. AKI incidence in rhabdomyolysis varies widely due to inconsistent definitions and variable rhabdomyolysis severity. Rhabdomyolysis can occur at any age, but adults are predominantly affected. Men, Black individuals, those over 60, and obese individuals are at higher risk. Infections are the most common cause in children (30%).

Crush syndrome incidence in traumatic rhabdomyolysis ranges from 30% to 50%. Children have a lower crush syndrome risk and mortality rate compared to adults. During natural disasters like earthquakes, early fluid resuscitation, extrication, and prompt hospitalization with a multidisciplinary approach reduce AKI, morbidity, and mortality.

In 2002, the American College of Cardiology (ACC), AHA, and NHLBI defined statin-associated rhabdomyolysis as muscle symptoms with elevated creatine kinase, typically >11 times ULN (myonecrosis), with elevated serum creatinine and myoglobinuria. About 0.5% of statin users may develop clinically significant myonecrosis.

The incidence of rhabdomyolysis from immobilization, alcohol intoxication, fractures, strenuous exercise, and insect bites is less precisely defined but represents a significant portion of non-traumatic cases.

Pathophysiology: How CPK is Released in Rhabdomyolysis

While rhabdomyolysis has diverse causes, the ultimate pathway involves direct myocyte injury or energy failure in muscle cells. The sarcoplasmic membrane’s sodium-potassium pump and sodium-calcium exchanger maintain low intracellular sodium and calcium and high potassium concentrations in resting muscle. Calcium is stored in the sarcoplasmic reticulum at rest. Muscle contraction requires ATP and calcium. Disruptions to ATP, ion channels, and the plasma membrane lead to electrolyte imbalance.

Muscle injury (trauma, exercise, thermal syndromes) or ATP depletion (medications, electrolytes, hereditary/metabolic disorders, intense exercise, ischemia) causes intracellular sodium and calcium influx. Water follows sodium, causing cell swelling and structural disruption. Excess intracellular calcium activates actin-myosin, leading to contraction and ATP depletion. Calcium also activates phospholipases and proteases, dissolving cell membranes and disrupting ion channels.

Reperfusion brings leukocytes to damaged muscle, releasing cytokines, prostaglandins, and free radicals, exacerbating myolysis, necrosis, and release of potassium, myoglobin, CPK, phosphate, uric acid, and organic acids into the bloodstream. This results in hyperkalemia and hyperphosphatemia. Initially, hypocalcemia occurs as calcium enters myocytes, followed by hypercalcemia as calcium leaks out after lysis.

Myoglobinuria and Renal Injury

Myoglobin, a heme protein, carries and stores oxygen in muscle. It has a higher oxygen affinity than hemoglobin. Circulating myoglobin binds to haptoglobin, but excess free myoglobin is filtered by glomeruli. While kidneys normally filter and excrete small amounts, large myoglobin release in rhabdomyolysis can cause AKI.

Acute Kidney Injury (AKI) in Rhabdomyolysis

Kidneys are vulnerable to rhabdomyolysis-induced damage due to high oxygen consumption and mitochondrial density. Muscle damage releases contents, causing inflammation and fluid sequestration, reducing intravascular volume and activating the renin-angiotensin-aldosterone axis, further impairing renal blood flow. Sympathetic activation releases vasopressin, worsening ischemia.

Myoglobin is a primary contributor to renal injury. Overwhelmed kidneys deposit myoglobin in tubules, causing toxicity. Myoglobin binds oxygen, increasing free radicals and lipid peroxidation, causing oxidative damage and vasoconstriction. Rhabdomyolysis also increases uric acid and acidosis, facilitating myoglobin binding to uromodulin (Tamm-Horsfall protein), forming tubular casts and worsening injury. Heme depletes nitric oxide and induces vasoconstrictors like endothelin-1. Heme also activates platelets.

AKI risk is estimated at 10-50% when CPK > 1000 U/L. Predictors include dehydration, high initial serum creatinine, low bicarbonate/calcium, and high phosphate. Hypoalbuminemia and elevated BUN are also associated with AKI development.

Compartment Syndrome

Muscle trauma in compartments can cause compartment syndrome due to swelling, leading to pressure-related damage like arterial occlusion and necrosis. Pressure > 30 mm Hg causes ischemia, requiring fasciotomy. Rhabdomyolysis patients with blood loss and hypotension are more susceptible to ischemia, even at lower pressures. Crush injuries increase compartment syndrome risk.

Disseminated Intravascular Coagulation (DIC)

Heme proteins can cause inflammation and thrombosis. They activate platelets, act as damage-associated molecular patterns (DAMPs), induce apoptosis, damage mitochondria, activate inflammasomes, and produce cytokines. Heme is directly thrombogenic, promoting neutrophil extracellular traps (NETs), platelet degranulation, macrophage activation, and tissue factor expression. In inflammatory/thrombogenic states, DIC can result from thromboplastin release during muscle injury. DIC is characterized by increased prothrombin time, activated partial thromboplastin time, INR, D-dimer, and decreased platelet count and fibrinogen.

Histopathology: Muscle Biopsy and CPK Diagnosis

Muscle biopsy is essential when metabolic myopathies are suspected in rhabdomyolysis. Timing is critical; biopsy during acute injury may miss underlying myopathy due to excessive necrosis. Current recommendations suggest biopsy after rhabdomyolysis recovery. However, EFNS guidelines suggest biopsy at presentation for patients with muscle pain, weakness, CPK elevation 2-3 times normal, myoglobinuria, muscle atrophy/hypertrophy, and myopathy on electromyography.

Specific stains aid in identifying myopathy types. Glycogen storage disorders show glycogen vacuoles with PAS and H&E staining. Mitochondrial myopathies show ragged red fibers with succinate dehydrogenase, cytochrome oxidase, and Gomori trichrome staining. Immunohistochemistry identifies enzyme deficiencies like phosphokinase and myophosphorylase deficiencies.

Kidney biopsy in rhabdomyolysis-induced AKI shows varied findings. Early tubular changes are visible by light microscopy within 1-12 hours. Early findings include dilated Bowman’s spaces, ruptured glomerular membrane, reduced glomerular tufts, and flattened podocytes. Proximal tubules show necrosis and microvilli loss. Electron microscopy reveals electron-dense casts in distal tubules.

History and Physical Examination in CPK Rhabdomyolysis Diagnosis

While muscle pain, weakness, and dark urine are classic rhabdomyolysis symptoms, they are present in less than half of patients. Muscle pain is the most common symptom (around 50% of adults), and dark urine in 30-40%. Weakness typically affects proximal muscles. Non-specific symptoms include cramps, stiffness, swelling, malaise, abdominal pain, nausea, palpitations, and fever. Weakness is the main complaint in adults with myopathies but less so in children. History may reveal illicit drug use, insect bites, heat exposure, surgery, accidents, medication changes, or supplements. High suspicion is sometimes necessary for diagnosis.

Patients with myopathies may have muscle atrophy or hypertrophy. Rhabdomyolysis has local (bruising, swelling, tenderness) and systemic features (fever, malaise, nausea, confusion, dark urine, anuria). Trauma patients need distal pulse and nerve evaluation for ischemia, compartment syndrome, and neuropathy. Dehydration signs should be noted. Early recognition is crucial to prevent complications.

Evaluation and Diagnostic Role of CPK in Rhabdomyolysis

After vital signs, basic labs are essential, including complete blood count, metabolic panel, CRP, ESR, serum CPK, and urinalysis. Chest X-ray and ECG are also recommended. Besides CPK, muscle enzymes like LDH, aldolase, ALT, and AST are released but are non-specific. Elevated inflammatory markers and leukocytosis are also non-specific.

Elevated serum CPK is the hallmark of rhabdomyolysis diagnosis. Reddish-brown urine from myoglobinuria occurs in about 50% of cases. Urine dipstick tests for blood react with myoglobin. Microscopic urinalysis differentiates myoglobinuria (no RBCs) from hemoglobinuria.

Normal CPK range is 20-200 U/L. Typically, a CPK elevation >5 times ULN is needed for rhabdomyolysis diagnosis. CPK has isoenzymes: CK-MM (skeletal muscle), CK-MB (cardiac), and CK-BB (brain). CPK half-life is 36 hours; levels rise in 2-12 hours post-injury, peak in 1-5 days, and decline after 3-5 days without further injury. CPK > 5000 IU/L suggests significant muscle injury and higher AKI risk.

Myoglobin’s half-life is 2-4 hours, metabolized to bilirubin. Serum myoglobin can be detected earlier than CPK but is less consistently detectable due to its short half-life. Proteinuria may occur due to released proteins and glomerular changes. Biomarkers for heme-induced AKI are under investigation.

Electrolyte imbalances in rhabdomyolysis include hyperkalemia and hyperphosphatemia. AKI can cause resistant hyperkalemia. Calcium influx causes initial hypocalcemia, followed by hypercalcemia. Uric acid levels increase. Organic acids like lactic acid can cause metabolic acidosis.

ECG may show hyperkalemia signs (peaked T waves, prolonged PR/QRS, arrhythmias, asystole) and hypocalcemia signs (QTc prolongation). Plain radiographs detect fractures, dislocations, and soft tissue swelling. CT may identify compartment syndrome. Acute compartment syndrome diagnosis is primarily clinical, confirmed by compartment pressure measurement or near-infrared spectroscopy. MRI, muscle biopsy, or EMG are not needed for rhabdomyolysis diagnosis itself, but are useful for underlying myopathy investigations.

Muscle biopsy is usually performed after recovery to identify inflammatory myopathies if suspected. Inflammatory and metabolic myopathies are considered in recurrent rhabdomyolysis, exercise intolerance, cramps, fatigue, and family history.

Treatment and Management Strategies for Rhabdomyolysis

Rhabdomyolysis management aims to maintain hydration and prevent AKI. The first step is identifying and removing the underlying cause. Active management includes airway, breathing, and circulation assessment, frequent exams, hydration, urine output monitoring, electrolyte correction, and compartment syndrome/DIC identification.

Management of Traumatic Rhabdomyolysis

In crush injuries, IV hydration should begin immediately, ideally pre-hospital and before stimulus relief. Continue hydration during transport. Delaying fluids worsens hypovolemia. Liberal fluid administration (10-20L) is needed to maintain intravascular volume and diuresis.

Large-volume resuscitation in crush injuries prevents AKI and reduces dialysis needs. Patients trapped longer may have AKI upon arrival, making fluid management challenging due to volume overload risk. No studies directly compare fluid types/rates. ISN Renal Disaster Relief Task Force recommends isotonic saline over alkaline fluids for field resuscitation. Dextrose in saline can provide calories and minimize hyperkalemia. Initial rate: 1L/h for 2 hours, then 500 mL/h in adults. Adjust rate based on age, gender, body habitus, bleeding risk, and trauma type. Avoid potassium-containing fluids like Ringer’s lactate.

Hospitalized patients need urine output monitoring. After confirming output and no alkalosis, consider urine alkalinization to prevent myoglobin precipitation in distal tubules. Alkalinization also reduces uric acid precipitation, corrects acidosis, and reduces hyperkalemia risk. Most data on alkalinization are from case series. Sodium bicarbonate (50 mEq in half-normal saline) is traditional method. Alkalinization can cause hypocalcemia and tetany/seizures. Aim for serum pH ≤ 7.5 and urine pH > 6.5. Discontinue bicarbonate when serum pH reaches 7.5.

Mannitol can improve urine output in crush injury patients with adequate output (>20 mL/h). No specific guidelines exist. A 60 mL 20% mannitol IV trial over 5 minutes can assess urine output increase. If output increases 30-50 mL/h, continue mannitol. Avoid mannitol in AKI, oliguria, or anuria. Mannitol risks include volume overload and hyperosmolality. Current literature doesn’t support combined mannitol and bicarbonate for AKI prevention.

Prevent hyperkalemia. Avoid potassium-containing IV fluids. Sodium polystyrene sulfate and sorbitol are common for hyperkalemia. New potassium binders’ role is unclear. Use point-of-care devices and ECG for suspected hyperkalemia.

Crush syndrome patients need Foley catheters. IV fluids should maintain urine output at 200-300 mL/h until myoglobinuria resolves and CPK decreases. Minimize Foley catheter duration to prevent infection. Consider loop diuretics for volume overload. Hemodialysis is used for anuric AKI, hyperkalemia, and volume overload after conservative measures fail. Peritoneal dialysis is less preferred in trauma.

Management of Non-traumatic Rhabdomyolysis

Non-traumatic rhabdomyolysis management is similar to traumatic cases. Use isotonic saline for hydration, adjusting based on cause. Remove offending agent upon diagnosis. Titrate IV fluids to maintain urine output at 200-300 mL/h. Monitor daily CPK to track trends. For CPK < 5000 U/L, aggressive hydration is discouraged as AKI risk is lower. Alkaline diuresis can be considered in severe cases (CPK > 30,000 U/L) without oliguria/AKI. Mannitol is less common in non-traumatic rhabdomyolysis. Loop diuretics can manage volume overload from aggressive fluids. Hemodialysis is needed for persistent oliguria/anuria and AKI. Dialysis’s role in myoglobin removal is not proven.

Electrolyte Management in Rhabdomyolysis

Rhabdomyolysis causes hyperkalemia, hypocalcemia, hyperuricemia, and hyperphosphatemia. Hyperkalemia (< 6 mEq/L, no ECG changes) is managed with potassium binders and bicarbonate in fluids. Hyperkalemia (≥ 6 mEq/L or with ECG changes) requires D50, regular insulin, and IV sodium bicarbonate. Calcium gluconate/chloride is commonly used in emergencies, but use cautiously in rhabdomyolysis due to late hypercalcemia risk.

Symptomatic hypocalcemia (tetany, seizures, arrhythmias) is treated with IV calcium gluconate. Avoid excessive calcium to prevent recovery-phase hypercalcemia. Manage hyperuricemia (> 8 mg/dL) with allopurinol. Hemodialysis is needed for volume overload, severe acidosis, uremia, and refractory hyperkalemia. Peritoneal dialysis may be insufficient for electrolyte correction.

Other Supportive Care

Antibiotics and vasopressors are needed for sepsis. Malignant hyperthermia is treated with dantrolene sodium. Steroids are used in inflammatory myopathies. Orthopedic consultation is needed for compartment syndrome. DIC is managed with fresh frozen plasma, cryoprecipitate, and platelets.

Diet in Metabolic Myopathies

Dietary changes can improve hereditary myopathy symptoms. Glucose and fructose can reduce pain and fatigue in phosphorylase deficiency. High-carbohydrate, low-fat diets improve muscle pain and myoglobinuria in carnitine palmityl transferase deficiency. Consult dieticians specializing in these disorders for tailored dietary interventions.

Differential Diagnosis of Rhabdomyolysis

Hypothermia
Malignant hyperthermia
Neuroleptic malignant syndrome
Sepsis
Inflammatory myositis
Inherited myopathies
Guillain-Barré syndrome
Hyperosmolar conditions

Pertinent Studies and Ongoing Trials

Preclinical studies on vasodilators, antioxidants, curcumin, haptoglobin, hemopexin, hepcidin, and α1-microglobulin in rhabdomyolysis have not shown effectiveness. Gene therapy is being explored for muscular dystrophies like Duchenne and Becker, including read-through and exon skipping technologies. Edasalonexent (NF-κB inhibitor) and Vamorolone (membrane-stabilizing glucocorticoid) have shown promise in clinical trials. Many novel treatments are under investigation.

Prognosis of Rhabdomyolysis

Mortality for hospitalized patients with rhabdomyolysis-induced AKI is 30-50%. Renal injury severity and duration are the most significant prognostic factors. Crush injury severity and duration correlate with hemodialysis need.

Complications of Rhabdomyolysis

Acute kidney injury
Electrolyte abnormalities
Arrhythmias
Compartment syndrome
Disseminated intravascular coagulation
End-stage renal disease
Infections from prolonged hospitalization

Consultations

ICU admission is needed for acute rhabdomyolysis patients with AKI, hyperkalemia, compartment syndrome, hypotension, or arrhythmias, potentially requiring ventilation. Consultations may include critical care, nephrology, trauma surgery, vascular surgery, or orthopedics, depending on severity and cause.

Deterrence and Patient Education

Educate patients about rhabdomyolysis risk factors and prevention. Suspected inflammatory/metabolic myopathies require further workup and biopsy. Traumatic rhabdomyolysis survivors may need counseling and medication. Genetic metabolic abnormality diagnoses warrant family screening for heritable causes.

Pearls and Key Issues in Rhabdomyolysis Management

Rhabdomyolysis is traumatic or non-traumatic.
Elevated CPK is the most sensitive diagnostic test.
CPK > 5000 U/L often indicates systemic damage, but other factors influence this.
Crush injury patients are at compartment syndrome risk; monitor distal pulses and compartment pressures (> 30 mm Hg high risk).
DIC can occur due to activated platelets and inflammation.
Maintain high urine output and alkalinize urine to minimize kidney injury.
Recurrent rhabdomyolysis or cases with minimal trauma warrant genetic screening.
Sickle cell trait increases rhabdomyolysis risk; caution advised for sports and exertion.
Dietary changes can manage genetic myopathy symptoms.

Enhancing Healthcare Team Outcomes

Rhabdomyolysis management lacks high-quality randomized controlled trials. Education on prevention is crucial. Nurses and pharmacists educate patients and families on causes and prevention at discharge. Educate students on heat injuries and hydration importance. Rehabilitation or physical therapy may be needed for muscle mass and joint function recovery. Recovery can take months, with residual pain lasting years. Pharmacists should warn about rhabdomyolysis risks with recreational drugs, alcohol, and prescription medications.

Care coordination is vital. Physicians, advanced practitioners, nurses, pharmacists, and other professionals must collaborate from diagnosis through follow-up. This minimizes errors, delays, and enhances patient safety, improving outcomes and patient-centered care. Interprofessional teams improve outcomes and prevent long-term sequelae.

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References

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