Download - Rhabdomyolysis
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