JVD 9/02

RHABDOMYOLYSIS
WHAT IS THE DDX?
! Physical causes: Trauma; compression- torture, abuse, long-term confinement (surgical procedures),
coma; occlusion of muscular vessels: thrombosis, embolic, sickle cell, vessel clamping; strainful
exercise- untrained athletes, hot humid conditions, epilepsy, psychiatric agitation, delirium tremens,
tetanus, amphetamine overdose, status asthmaticus; electrical current- high voltage electrical injury,
lightening strikes, cardioversion; hyperthermia- NMS, malignant hyperthermia, sepsis, exercise.
! Nonphysical causes: metabolic myopathies- McCardle disease, mitochondrial enzyme deficiencies,
phosphofructokinase deficiency; drug and toxins- alcohol, speed, cocaine, colchicines, steroids,
fibrates, statins, heroin, INH, PCP, AZT, snake venom, quail ingestion, buffalo fish ingestion;
infections- legionella, tularemia, salmonella, F. malaria, toxic shock, HIV, herpes, cocksakie, toxic
shock syndromes, pyomysotis (local infection); electrolyte abnormalities- hypocalcemia,
hypokalemia, hypophosphatemia, hyponatremia, hyperosmotic conditions; endocrine- hypothyroid and
DM; CVD- poylmyositis ad dermatomyositis
FASCINATING CELL BIOLOGY
! Rhabdomyolysis is defined as the as the disintegration of striated muscle (myolysis) which results in
the release of muscular cell components due to both changes in cellular metabolism and reperfusion
injury. Stretching or exhaustive work of muscle cells increases the sarcoplasmic influx of sodium,
chloride and water resulting in cell swelling and death. At the same time, there is a huge increase of
intracellular calcium which triggers persistent muscle contraction, energy depletion, phospholipase
activation and cell death. The milieu is topped off with the release of vasoactive molecules, creating
hypoxic conditions. Once blood flow is restored, inflammation ensues by the invasion of leukocytes
and production of free radicals.
METABOLIC DERANGEMENTS: ELECTROLYTE MESS
! Release of large amounts intracellular muscle enzymes is diagnostic: CK, AST, LDH and aldolase.
CK is the most sensitive (100%), correlates with severity of injured muscle, actual level is
controversial (some suggest >1000 U/L), noted to peak within 24-48 hours post injury with aggressive
hydration, declines at a rate of 40 % a day (compared to previous day value), if persistently elevated
look for ongoing myocyte damage or renal failure.
! Myoglobinuria: myoglobin is a unique muscle cell protein (18 Kdalton) that contains a heme moiety,
oxygen carrier. In serum, bound to plasma protein and reaches the kidney in very small amounts,
freely filtered and not reabsorbed. The urine orthotoluidine dipstick test is positive for both heme and
myoglobin pigments, if dip is positive and micro with no RBCs, think rhabdo. Useful as an early
marker, but 18 % patients may not have positive dipstick. Myoglobin is cleared from the plasma
within 1-6 hours by renal excretion and hepatic metabolism.
! Hypocalcemia: calcium accumulates intracellularly, sometimes resulting in massive calcifications of
necrotic muscles or heterotropic ossification and may be so severe to cause tetany, seizures and cardiac
arrhythmias. In later stages, hypercalcemia can be seen as calcium is released from muscle storage,
parathyroid has kicked in and renal Vit D production is increased. Watch out with calcium
replacement therapy.
! Metabolic acidosis with elevated anion gap: due to lactate and other organic anions.
! Hyperphosphatemia: enhances hypocalcemia.
! Hyperkalemia: life threatening cardiac arrhythmias
! Elevated uric acid: degradation of nucleosides, may cause additional tubular damage.
! Severe intravascular volume depletion: net fluid shift into affected muscles of about 10 liters of fluid
per limb may result in shock with end organ dysfunction and hypernatremia. As muscles recover,
fluid is shifted back into circulation, if kidney are working there will be a net diuresis, if anuric watch
out for massive third spacing.

WHAT ABOUT THE KIDNEY DAMAGE: three pathways that lead to ATN, myoglobin is main
player, increased incidence if CK> 15, 000.
! Tubular obstruction: as water is being avidly reabsorbed in the tubules, the concentration of
myoglobin rises and ultimately precipitates to cause obstructive cast formation. This binding is
enhanced by acidic conditions.
! Tubular necrosis with lipid peroxidation: the heme moiety seems to be a direct and indirect cause (via
release of free iron with its degradation) of free radical production and tubular epithelial cell membrane
injury.
! Renal vasoconstriction: massive intravascular depletion results in a decrease of EABV and
consequently activates the sympathetic and rennin-angiotensin systems, leading to renal
vasoconstriction and increased Na and water reabsorption.
WHAT CAN WE DO TO FIX IT? Goal is to prevent ARF
! Treat muscle injury: may worsen reperfusion injury, get fluids started early.
o Dantrolene or bromocriptine for NMS or malignant hyperthermia,
o Fasciotomy to release pressure, watch for infection
! Volume expansion: single most important treatment to prevent ARF.
o Patients need at least 10 liters a day, start with NS at rates of 500cc/hour to restore
intravascular volume to optimize GFR. Goal UO is 200/hour.
o Alkalinisation is recommended: D5 W with 2 amps HCO3, infuse at rates of 100-200 cc/hour
to maintain urine pH of at least 7. This increases the solubility of myoglobin in the tubules,
allows tubular washout of casts, inhibits lipid peroxidation and improves renal
vasoconstriction.
o Mannitol: controversial, as an osmotic diuretic it promotes diuresis and theoretically with
pull water out of edematous muscles to restore intravascular volume. No clinical benefit has
been proven.
! Plasmapheresis: MAY increase myoglobin clearance, but no clear clinical benefit.
! Renal replacement therapy: call renal early if refractory hyperkalemia, acidosis, volume expansion or
uremia.
PROGNOSIS
! Early volume resuscitation is key to avoiding ARF.
! Rhabdomyolyis induce ARF carries a 20% mortality (early death due to hyperkalemia and shock).
! If patient survives, renal function almost always recovers within three months.

References:
Vanholder et al. Rhabdomyolyis. J Am Soc Nephrology. Vol. 11: 1553-1561. 2000.
Holt et al. Pathogenesis and Treatment of Renal Dysfunction in Rhabdomyolysis. Intensive Care
Medicine. vol. 27: 803-811. 2001.
Richards et al. Rhabdomyolysis and Drugs of Abuse. The Journal of Emergency Medicine: 19:51-56.
2000.