Rhabdomyolysis
Uptodate – Rhabdomyolysis
o Rhabdomyolysis = syndrome of muscle necrosis and release of intracellular muscle
contents into the circulation
o Can range from asymptomatic elevations in serum muscle enzymes to life
threatening
o Clinical Manifestations
o Myalgias, red to brown urine, elevated serum muscle enzymes
o Objective muscle weakness occurs in those with severe muscle damage
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Muscle enzymes
 Hallmark = CK> 100,000 (MM fraction although there may be a
small MB fraction))
Urine Color
 Myoglobin is a monomer that is not protein bound and is therefore
rapidly excreted in the urine, often resulting in the production of red
to brown urine
 Pigmenturia will be missed in rhabdomyolysis if the filtered load of
myoglobin is insufficient or has largely resolved before the patient
seeks medical attention. Myoglobin is cleared from the plasma more
rapidly than creatine kinase (CK). Thus, it is not unusual for CK
levels to remain elevated in the absence of myoglobinuria
Renal Failure
 Volume depletion resulting in renal ischemia, tubular obstruction due
to heme pigment casts, and tubular injury from free chelatable iron all
contribute to the development of renal dysfunction
Electrolyte Abnormalities
 Hyperkalemia and hyperphosphatemia result from the release of
potassium and phosphorus from damaged muscle cells
 Hypocalcemia, which can be extreme, occurs in the first few days
because of both deposition of calcium salts in damaged muscle and
decreased bone responsiveness to parathyroid hormone
 Severe hyperuricemia may develop because of the release of purines
from damaged muscle cells
Compartment syndrome
 exists when increased pressure in a closed anatomic space threatens
the viability of the muscles and nerves within the compartment
 lower extremity compartment syndrome can be the cause of
rhabdomyolysis
 normal tissue pressure = 0mmHg
 ischemic threshold reached when the pressure in the compartment
rises to within 20 mmHg of the diastolic pressure or within 30 mmHg
of the systolic pressure
o Causes
o Traumatic/Muscle Compression
 Multi-Trauma
 Struggling against restraints/Torture victims
 Immobilization (coma, overdose, elderly hip fracture)
 Surgical procedures where there is prolonged muscle compression
(tourniquets, compression due to positioning)
 Lower extremity compartment syndrome (most commonly associated
with tibial fracture)
o Non-traumatic Exertional
 Massive rhabdomyolysis may arise with marked physical exertion,
particularly when one of more of the following risk factors are present
 The individual is physically untrained
 Exertion occurs in extremely hot, humid conditions
 Normal heat loss through sweating is impaired, as with the use
of anticholinergic medications or heavy athletic equipment
 Sickle cell trait in an individual who exercises at high altitude
 Hypokalemia caused by potassium loss from sweating
 Release of K from muscle cells promotes local
vasodilatation increasing the O2 and nutrient delivery to
working muscle groups
o Metabolic Myopathies
 Very rare
 In cases of repeat episodes of rhabdomyolysis after exertion should
suspect Carnitine palmitoyltransferase (CPT) (most common of these
disorders) followed by muscle phosphorylase deficiency (McArdle
disease)
o Malignant Hyperthermia
 AD inheritance
 Characterized by hyperkalemia, metabolic acidosis, muscle rigidity,
hyperthermia
 Look for triggering agents in the anesthetic
 Succinylcholine, volatile anesthetics (Gas)
 Treatment = dantrolene 2.5mg/kg repeated q5min
 After initial response continue drug 4-8mg/kg/day divided q6h
orally or continue IV doses for 3 days
o Neuroleptic Malignant syndrome
 Idiosyncratic reaction to antipsychotics
 In addition to hyperthermia, NMS is also characterized by "lead pipe"
muscle rigidity, altered mental status, choreoathetosis, tremors, and
evidence of autonomic dysfunction, such as diaphoresis, labile blood
pressure, and dysrhythmias
 Treatment = dantrolese, ECT, D/C antipsychotics
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Time to complete recovery was reduced from a mean of 15 days (with
supportive care alone) to nine days (with dantrolene) and 10 days
(with bromocriptine). Another analysis found reduced mortality: 8.6
percent in patients treated with dantrolene, 7.8 percent in patients
treated with bromocriptine, and 5.9 percent in patients treated with
amantadine compared with 21 percent in those receiving supportive
care alone
 ECT is generally reserved for patients not responding to other
treatments or in whom nonpharmacologic psychotropic treatment is
needed
Near Drowning
 Rhabdomyolysis with myoglobinuric acute renal failure can occur
after prolonged immersion. The mechanism of rhabdomyolysis in this
setting may involve hypothermia with muscle injury from marked
vasoconstriction or from excessive shivering and/or generalized
hypoxia.
Nonexertional/Nontraumatic
 Drugs and toxins
 Coma secondary to drug overdose
 Statins and Cholchicine
 Carbon Monoxide poisioning
 nutritional supplements used in strength training caused
rhabdomyolysis in otherwise healthy individuals
 Snake bite, which is most often seen in Asia, Africa, and South
America
 Infections
 Influenza A and B, Coxsackievirus, Epstein-Barr, herpes
simplex, parainfluenza, adenovirus, echovirus, HIV, and
cytomegalovirus
 Bacterial pyomyositis
 Septicemia without direct muscle infection
 Human granulocytic anaplasmosis (ehrlichiosis)
 Falciparum malaria
 Electrolyte abnormalities
 Rhabdomyolysis has been associated with a variety of
electrolyte disorders, particularly hypokalemia
hypophosphatemia and, in a few reports, hyperosmolality due
to diabetic ketoacidosis or nonketotic hyperglycemia
 Endocrine disorders
 Pheochromocytoma and hyperthyroidism
 Inflammatory myopathies
 Dermatomyositis and polymyositis
 Miscellaneous
 Status Asthmaticus
 Mushroom poisoning
 Abrupt withdrawal of Baclofen
o Management
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Eliminate the underlying cause – d/c medications, fasciotomy
Prevention of Renal Failure
 General goals for preventive therapy in heme pigment-induced acute renal
failure are correcting volume depletion and preventing intratubular cast
formation
 Adequate fluid resuscitation is very important for preventing acute renal
failure. The goals of volume repletion are to both enhance renal perfusion
(thereby minimizing ischemic injury) and increase the urine flow rate to
wash out obstructing casts. A urine output of 200 to 300 mL/hour is
desirable while myoglobinuria (discolored urine) persists
 Initial fluid replacement is usually with isotonic saline at 1 to 2 liters per
hour. This rate is continued until the systemic blood pressure normalizes and
urine output is established, or there is evidence of fluid overload. If a
diuresis is established, fluids are titrated to maintain a urine output of 200 to
300 mL/hour
Forced alkaline diuresis
 In theory, urine alkalinization prevents heme-protein precipitation with
Tamm-Horsfall protein, and therefore intratubular pigment cast formation
 Alkalinization may also minimize the conversion of hemoglobin to the more
toxic methemoglobin, and the release of free iron from myoglobin
 However, there is no clear clinical evidence that an alkaline diuresis is more
effective than a saline diuresis, and there are potential risks to alkalinization
of the plasma, such as promoting calcium phosphate deposition, and
inducing or worsening the manifestations of hypocalcemia
 Complications of alkalinization
 worsen the symptoms of hypocalcemia
 increase calcium phosphate precipitation in the tissues
 Manifestations of severe ionized hypocalcemia include tetany,
seizures, and cardiac arrhythmias
 Mannitol
 Experimental studies suggested that mannitol might be protective
primarily by causing a diuresis, which minimizes intratubular heme
pigment deposition and cast formation. It has also been proposed that
mannitol acts as a free radical scavenger, thereby minimizing cell
injury
 However, experimental studies showed no amelioration of proximal
tubular necrosis with mannitol, and mannitol may cause
hyperosmolality and other complications
 Complications of mannitol
 volume depletion and, since free water is lost with mannitol,
hypernatremia
 in renal insufficiency volume depletion and, since free water is lost
with mannitol, hypernatremia
 Acute renal failure may occur if patients are treated with more than
200 g of mannitol per day. If mannitol is given, the plasma osmolal
gap should be measured, and mannitol discontinued if the osmolal
gap rises above 55 mosmol/kg
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Dialysis as required