Nephrology
Rhabdomyolysis
Background
- Definition
- Muscle injury that can lead to various forms of systemic insult, such as
- Acute kidney injury (AKI)
- Electrolyte imbalance
- Disseminated intravascular coagulation (DIC)
- Synopsis
- Medical management includes:
- ABCs (Airway, Breathing, Circulation)
- Identification/correction of the etiology
- Fluid resuscitation, prevention of AKI/acute renal failure (e.g., Urinary alkalization, mannitol, loop diuretics)
- Correction of electrolyte, acid-base, metabolic abnormalities
- Hemodialysis (severe cases)
Pathophysiology
- Mechanism
- Clinical syndrome of muscle injury with myoglobinuria, electrolyte abnormalities, and often associated kidney injury
- Often defined as CK > 5-10 times upper limit of normal for reference population
- Results from direct injury to myocyte membranes resulting in altered energy production, increased intracellular calcium levels, leading to release of myoglobin
- Leakage of muscle cell contents into circulation
- Myoglobin concentrates along renal tubules resulting in proximal tubular
- Cytotoxicity and distal tubular obstruction
- Etiology/Risk Factors
- Trauma
- Crush injury
- Taser (or similar device) shocks (behavior leading to the use of Taser more likely to cause rhabdomyolysis than the shock itself)
- Exertion
- Strenuous exercise, seizures
- Muscle hypoxia
- Limb compression
- Arterial occlusion (thrombosis, atherosclerosis, sickle cell, vasculitis)
- Compartment syndrome
- Genetic defects (e.g., carbohydrate metabolism disorder)
- Infections
- Sepsis
- Legionella, bacterial pyomyositis
- Viral myositis (influenza)
- Body temp dysregulation
- Heat stroke, malignant hyperthermia
- Metabolic or electrolyte disorders
- Drugs and toxins
- Lipid lowering drugs
- Statin monotherapy has lower risk than combination statin-fibrate therapy
- Severe rhabdomyolysis from statin therapy requiring hospitalization is rare
- CYP interactions may increase risk
- Alcohol
- Mushroom Tricholoma equestre
- Haff disease (after fish consumption)
- Snake envenomations, particularly Timber (canebrake) rattlesnake and Mojave rattlesnake
- Any drugs of abuse (particularly opioids such as heroin)
- That cause rapid sedation and immobility (e.g., antipsychotics, anticholinergics)
- That lead to temperature dysregulation, agitation, or neuromuscular agitation
- Cocaine, amphetamines, MDMA (ecstasy) or phenylalkylamines ("bath salts"), anti-psychotics or anticholinergics
- That lead to neuroleptic malignant syndrome (NMS) or serotonin syndrome
- Idiopathic
- Epidemiology
- Incidence/Prevalence
- Approximately. 26,000 cases annually
- Most adult cases of rhabdomyolysis are due to
- Abuse of illicit drugs or alcohol
- Muscular trauma
- Crush injuries
- Myotoxic effects of prescribed drugs
- Found in 24% of adult patients who present to emergency departments (EDs) with cocaine-related conditions
- Mortality/Morbidity
- Overall mortality: 5%
- Risk of death dependent on underlying etiology, any existing comorbid conditions, in patients with AKI, and extremely elevated CPK levels
- Rapid appropriate supportive treatment of rhabdomyolysis-related kidney injury and renal failure improves prognosis
Diagnostics
- History/Symptoms
- Classic triad
- Muscle pain (< 50%)
- Weakness (< 50%)
- Dark urine
- Malaise, fatigue, N/V
- Careful history of
- Prescription, non-prescription/OTC/herbal medications
- Look for drug interactions
- Substance abuse history
- May lead to
- Acute renal failure
- Disseminated intravascular coagulation
- Metabolic acidosis
- Physical Exam/Signs
- General Appearance, Vitals
- Fever, tachycardia
- May appear acutely ill
- Musculoskeletal/Nervous System
- Skin/Extremities
- Crush injury, bruising, blebs, tense compartments
- Labs/Tests
- CBC +Diff, CMP
- ESR, CRP
- CPK is the most sensitive indicator of muscle injury
- Rises in 12 hrs, peaks 1-3 days, declines 3-5 days
- > 5-10 x upper level of normal (~1000 U/L)
- Severe rhabdomyolysis usually defined by CPK > 5,000 U/L
- Risk for kidney injury usually occurs > 3-5,000 U/L range in previously healthy patients
- Risk occurs at lower levels if poor baseline renal function
- Myoglobinuria
- Inferred by a positive urine dip with little/no RBCs
- Myoglobin will also react with the orthotolidine test reagent
- Electrolyte abnormalities
- Increased potassium, phosphate, uric acid
- Calcium initially decreases then gradually increases
- Initially low due to precipitation with phosphates in muscle
- Later calcium is released from damaged muscles
- Urinalysis
- Other Tests/Criteria
- McMahon Score for Rhabdomyolysis (Open Calc)
- EKG
- May show
- Peaked T waves
- Prolonged PR interval
- Wide QRS interval w/ or w/o conduction blocks
- Ventricular tachycardia
- Asystole secondary to hyperkalemia
- Hypocalcemia may manifest as QTc prolongation
- Differential Diagnosis
Treatment
- Initial/Prep/Goals
- ABCs, IV access, monitor
- Goals:
- Prevent renal failure
- Manage life -threatening complications
- Stop ongoing cellular injury, prevent renal injury, treat complications
- Treat underlying cause, stop ongoing muscle injury
- Stop seizures, reduce temp (if hyperthermic) aggressively
- Treat overdose or underlying disease process
- Discontinue offending meds
- Treat compartment syndrome (fasciotomy)
- Sedate combative patients, benzodiazepines are typically used
- Chemical restraint and environmental control is preferable to physical restraints in these patients
- Consider paralysis and intubation
- Early aggressive repletion of fluids
- Volume depletion results from sequestration of water in injured muscles
- IVF admin important even if not hypovolemic
- Goal urine output of 300 ml/hr in adults (or 3 ml/kg/hr)
- Depending on severity and comorbidities
- Fluid composition is controversial
- Correct electrolyte disorder
- Hyperkalemia
- Hypocalcemia: avoid correcting early in process unless symptomatic or severe hyperkalemia
- Avoid nephrotoxic substances
- NSAIDs, IV contrast, nephrotoxic antibiotics
- Medical/Pharmaceutical
- Normal (isotonic) saline
- First-line treatment
- Total of 10-20 L often administered in the first 24 hr
- Titrate to urinary output of >300 mL/hr
- Continue until CPK is < 1000 units/L
- In disaster situations give first bolus during extrication of victims
- Lactated ringers have benefit of increasing serum and urine pH, but thus far no proven clinical advantage
- No evidence that adding bicarbonate (D5W + 2 amps HCO3/L) is superior to using normal saline alone
- Theoretically: alkalinization of urine may prevent precipitation of myoglobin in renal tubules
- Adjunctive therapies
- Mannitol:
- 1g/kg IV over 30 minutes or 25 g IV bolus followed by 5 g/hr infusion
- No more than 200 g/day; can cause an osmotic nephrosis
- Multiple studies have failed to find a benefit with mannitol administration
- Use only in conjunction with adequate fluid administration
- Monitor plasma osmolality and osmolar gap
- Discontinue if osmolar gap >55 mOsm/kg
- Furosemide: no proven benefit
- Surgical/Procedural
- Hemodialysis
- Profound refractory hyperkalemia, acidosis or volume overload
- Complications
- Compartment syndrome
- Surgical decompression with fasciotomy
- Mannitol may assist in reducing compartment pressures
- Cardiac arrhythmias
- Higher peak CPK, hypoalbuminemia, and metabolic acidosis are factors associated with a higher mortality
- Mortality more dependent on etiology or rhabdomyolysis (i.e., poly-trauma or burn patients have higher mortality)
- Acute kidney injury
- Electrolyte abnormalities
- DIC
- End-stage renal disease
- Requiring prolonged renal replacement therapy
- Infections from prolonged hospital stay
- Shock (low blood pressure)
- Prevention
- Drink plenty of fluids during strenuous exercise or damaged skeletal muscles
- Prompt treatment of underlying etiology
Disposition
- Admission Criteria
- Patients with significant or ongoing rhabdomyolysis should be admitted for IV hydration, diuresis and management of complications
- ICU for severe complications or metabolic derangements
- Mild elevations of CPK (< 1,000 U/L) likely to be well tolerated if normal renal function if etiology is discovered and treated/stopped
- CPK takes hours to peak
- Initial level may be low; need to trend levels over time
- Consult(s)
- Intensivist, nephrology, surgery (trauma, vascular or orthopedic) as needed
- Discharge/Follow-up Instructions
- Follow-up as per care team plan
- Educate pt on condition and treatment
- Many patients take months to recover the muscle mass even after recovery
- Some may even have residual pain for a few years
References
- Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009;361:62-72
- Zimmerman JL, Shen MC. Rhabdomyolysis. Chest. 2013;144(3):1058-1065
- Sutamtewagul G, Sood V, Nugent K. Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following "bath salts" injection. Clin Nephrol. 2014 Jan;81(1):63-66
- Rodríguez E, Soler MJ, Rap O, Barrios C, Orfila MA, Pascual J. Risk factors for acute kidney injury in severe rhabdomyolysis. PLoS One. 2013;8(12)
- Scharman EJ, Troutman WG. Prevention of kidney injury following rhabdomyolysis: a systematic review. Ann Pharmacother. 2013;47(1):90-105
- Brown CV, Rhee P, Chan L, Evans K, Demetriades D, Velmahos GC. Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? J Trauma. 2004;56(6):1191-1196
- Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009;361:62-72
- O'Connor FG, Deuster PA. Rhabdomyolysis. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011;Chapter 115
- Scharman EJ, Troutman WG: Prevention of kidney injury following rhabdomyolysis: a systematic review. Ann Pharmacother 47:90–105, 2013.
- Walls RM, Hockberger RS, Gausche-Hill M. Rosen's Emergency Medicine - Concepts and Clinical Practice, 9th ed, Philadelphia, PA;Elsevier-Saunders, 2018;Chapter 119
- Rhabdomyolysis. StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK448168/. [Accessed November 2023]
Contributor(s)
- Punja, Mohan, MD
- Ballarin, Daniel, MD
Updated/Reviewed: November 2023