Rhabdomyolysis managment

1. Rhabdomyolysis
SHEEBA HAKAK
AMNCH

2. DEFINITION
Rhabdo = straited
myo = muscle
lysis = breakdown

3. 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.

4. 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.

5. PATHOPHYSIOLOGY
hypoxia
reperfusion
Direct injury to
membrane
integrity

6. pathophysiology
Hypoxia leads to anaerobic metabolism
Dec .ATP generation
Loss of ion gradients esp Na
Increase in intracellular ca
Leakage of intracellular protein intoECF

7. pathophysiology
Reperfusion injury generates o2 free
radicles
Vasoconstriction of pre capillary
arterioles
Lipid peroxidation of cell
membranes,formation of peroxynitrite
Self perpetuating secondary injury

8. Mechanism of ARF
Damaged muscle
cells
myoglobin
Precipitation of
casts,occlude renal
tubules
O2 free
radicles,peroxidation
of mem lipids
Release of
PAF,andothelin,PGF2
Constriction of renal
arterioles ,dec GFR

9. causes
rhabdomyolysis
Muscle
injury
Medications
& illicit
drugs
Increased
muscle
activity

10. 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

11. 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

12. 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

13. 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

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

15. Clinical Presentation
• Local features
– Muscle pain
– Tenderness
– Swelling
– Bruising
– Weakness
• Systemic features
– Tea-colored urine
– Fever
– Malaise
– Nausea
– Emesis
– Confusion
– Agitation
– Delirium
– Anuria

16. 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

17. 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

18. 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

19. Treatment
• A B C
• Fluids
• Treat hyperkalaemia

20. 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.

21. Over view of studies for fluid
management of Rhabdomyolysis
Study design No.of patients treatment conclusion
Brown et al
2004
Retrospective 1771 Bicarbonate,m
annitol&saline
VS. saline
No
improvement
over saline
alone
Homsi et al
1997
Retrospective 24 Bicarbonate,m
annitol & saline
vs.saline
No
improvement
over saline
alone
Cho et al
2007
prospective 200 Lactated ringer
vs.saline
Decreased
amount of
NAHCO3 &
diuretics given
with LR
solution

22. Mannitol

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

24. 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.

25. 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.

26. 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

27. 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.

28. Dialysis
• Despite optimal treatment ,pts may still
develop AKI with severe acidosis &
hyperkalemia (daily haemodialysis or
haemofiltration may be necessary)
• Remove urea and potassium