Rhabdomyolysis

SHEEBA HAKAKAMNCH

DEFINITION

DEFINITION

• Rhabdomyolysis is the breakdown of muscle fibers, specifically of the sarcolemma of skeletal muscle, resulting in the release of muscle fiber contents (myoglobin) into the bloodstream.

HISTORY

• The association between rhabdomyolysis and ARF was first established during world war II.After the bombing of London,crush victims developed AKI with pigmented casts in renal tubules at autopsy.

PATHOPHYSIOLOGY

pathophysiology

pathophysiology

Mechanism of ARF

causes

What causes rhabdomyolysis?• Direct Muscle Injury

– Crush injuries, deep burns, electrical injuries, acute necrotizing myopothy of certain cancers, assaults with prolonged and vicious beating/repetitive blows

• Excessive Physical Exertion– Results in state in which ATP production can’t keep up with demand exhaustion

of cellular energy supplies & disruption of muscle cell membrane– Protracted tonic-clonic seizures, psychotic hyperactivity (mania or drug-induced

psychosis)

• Muscle Ischemia– Interference with O2 delivery to cells and therefore limiting production of ATP– Generalized ischemia from shock & hypotension, carbon monoxide poisoning,

profound systemic hypoxemia, localized compression leading to skeletal muscle ischemia, tissue compression d/t immobilization of muscle, intoxicated/comatose down for long periods, immobilization from acute SCI, compartment syndrome, arterial/venous occlusions

Causes cont.

• Temperature Extremes– Excessive Cold muscle perfusion, ischemia; freezing causes cellular destruction– Excessive Heat destroys cells & metabolic demands (every degree temp =

metabolic demand by ~ 10%) & if body can’t keep up with requirement, cellular hypoxia anaerobic environment

– Malignant hyperthermia, neuroleptic malignant syndrome (d/t psychotropic medications)

• Electrolyte & Serum Osmolality Abnormalities– Chronic hypokalemia significant total body loss of K+ disrupts Na+ K+ pump cell

membrane failure, leak of toxic intracellular contents from muscle cells– Overuse of diuretics , hyperemesis gravidarum, some drugs (amphotericin B),

hyperglycemic hyperosmolar nonketotic coma

Causes cont.

• Infections– Pneumococcal & Staphylococcus aureus sepsis, salmonella & listeria infections, gas

gangrene, NF– Can destroy large quantities of muscle tissue through generation of toxins or direct

bacterial invasion

• Drugs, Toxins, Venoms– Ethanol depresses CNS and leads to periods of immobility; alcohol also has toxic

effects on myocytes with binge drinking– -statins– Drugs that mimic or stimulate SNS (cocaine, methamphetamines, ecstasy,

pseudoephedrine, excessive caffeine)– Chemicals & toxic plants– Snake venoms, multiple stings by wasps, bees, hornets– Pharmaceutical agents – benzodiazepines, corticosteroids, narcotics,

immunosuppressants, antibiotics, antidepressants, antipsychotics

Causes cont.

• Endocrinologic Disorders– Either wasting or hypermetabolic conditions– K+ wasting diabetic ketoacidosis, hyperosmolar nonketotic coma,

hyperaldosteronism– Na+ depletion Addison disease– sympathetic stimulation & metabolic demands beyond sustainability thyroid

storm & pheochromocyoma

• Genetic & Autoimmune Disorders– Carbohydrate & lipid metabolism; muscular dystrophies, autoimmune disorders

such as polymyositis & dermatomyositis

Clinical Presentation

• Many features are nonspecific• Triad :muscle pain ,weakness and dark urine• Varies depending on underlying condition• Features– Local– Systemic

Clinical Presentation

• Local features– Muscle pain– Tenderness– Swelling– Bruising– Weakness

• Systemic features– Tea-colored urine– Fever– Malaise– Nausea– Emesis– Confusion– Agitation – Delirium– Anuria

Potential Complications

• Acute RF (myoglobinuric RF)

• Compartment syndrome (with crush injuries) decompression fasciotomy

• DIC give FFP

• Disturbances in serum & urine electrolyte levels/balance cardiac arrhythmias

• Hypovolemia

• Metabolic Acidosis

• Respiratory failure

• Acute muscle wasting

Diagnostics• serum total CK & CK-MM (CK isoenzyme in skeletal muscle)

– Begins 2-12h post-injury, peak 1-3 days, declines 3-5 days

• serum myoglobin– Until filters into urine causing characteristic coke-colored urine

• serum K+– Major cause of morbidity/mortality d/t muscle breakdown & release K+ which

further by acidosis & RF• Give calcium gluconate/chloride cautiously so as to prevent hypodynamic instability

• serum BUN & Cr– d/t escape of massive amounts Cr from damaged muscle

• Early hypocalcemia– Deposit of Ca in necrotic muscle, soft tissues calcify in necrosis

Diagnostics cont.• Later hypercalcemia & hyperphosphatemia

– Phosphate and calcium leakage from damaged muscle cells give PO calcium carbonate/hydroxide & calcium will follow being fixed when phosphate distribution fixed (inverse relationship)

• uric acid (hyperuricemia)

• ABC– To detect hypoxia and acidosis & when giving sodium bicarb therapy

• Clotting Studies– Useful in detecting DIC

• Urinalysis– Will reveal presence of protein, brown casts, uric acid crystals

• Urine Dipstick– Quick initial test– Myoglobin will react to hemoglobin reagent on stick if positive, need to

determine if Hgb or myoglobin

Treatment

• A B C• Fluids• Treat hyperkalaemia

Fluids• The treatment of rhabdomyolysis includes initial stabilization and

resusitation of the pt.

• Saline has been used as the fluid of choice for resusitation.

• A recent prospective randomized single-blind study compared saline or RL solution for initial resusitation.In addition, all pts were treated with bicarbonate & diuretics.The study found less bicarbonate & diuretics were needed for pts receiving RL.

Over view of studies for fluid management of Rhabdomyolysis

Study design No.of patients treatment conclusion

Brown et al2004

Retrospective 1771 Bicarbonate,mannitol&saline VS. saline

No improvement over saline alone

Homsi et al1997

Retrospective 24 Bicarbonate,mannitol & saline vs.saline

No improvement over saline alone

Cho et al2007

prospective 200 Lactated ringer vs.saline

Decreased amount of NAHCO3 & diuretics given with LR solution

Mannitol

Mannitol

• The diuretic effect of mannitol is controversial as it may further exacerbate hypovolumia,metabolic acidosis&pre renal AKI

Alkalinisation of urine• Alkalinization of the urine with sod bicarb has been

suggested to minimize renal damage after rhabdomyolysis.

• Although mannitol and NAHCO3 are frequently considered the standard of care in preventing AKI,little evidence exists to support the use of these agents.

• In a retrospective study of 24pts,vol expansion with saline alone prevented progression to renal failure,& the addition of mannitol&NAHCO3 had no additional benefit

• Brown and colleagues CK >5000U/L– 154(40%) received mannitol and bicarbonate – 228 (60%) didn’t– No significant difference in renal failure ,dialysis,or mortality

between the groups.

Alkalization continues..

• Use of carbonic anhydrase inhibitors has been suggested when ph >7.45 after NAHCO3 therapy or if there is continued aciduria despite alkalemia.

Free radical scavengers and antioxidants• The magnitude of muscle necrosis caused by ischemia-

reperfusion injury has been reduced in experimental models by the administration of free-radical scavengers .

• Many of these agents have been used in the early treatment of crush syndrome to minimize the amount of nephrotoxic material released from the muscle

• Pentoxyphylline is a xanthine derivative used to improve microvascular blood flow. In addition, pentoxyphylline acts to decrease neutrophil adhesion and cytokine release

• Vitamin E , vitamin C , lazaroids (21-aminosteroids) and minerals such as zinc, manganese and selenium all have antioxidant activity and may have a role in the treatment of the patient with rhabdomyolysis

HBO therapy

• HBO therapy also has been advocated for treatment of crush injuries because of its effects to increase perepheral o2transport.

• A RDBS examined the effect of HBO on wound healing.36 pts were divided into 2 groups ,one received HBO therapy & other conventional therapy.complete healing was achieved for 17 pts in HBO grp v/s 10 pts in placebo grp.

Dialysis• Despite optimal treatment ,pts may still

develop AKI with severe acidosis & hyperkalemia (daily haemodialysis or haemofiltration may be necessary)

• Remove urea and potassium