Dr.
Osama El-Shahat
Consultant Nephrologist
Head of Nephrology Department
New Mansoura General Hospital (international)
ISN Educational Ambassador
Definition
Destruction or disintegration of striated
muscle resulting in the leakage of the
intracellular muscle constituents into
the circulation and extracellular fluid
Causes
Etiology of rhabdomyolysis
Physical Causes
Trauma & Compression Straining muscular exercise
• Traffic or working accidents • Exercise
• Disasters • Epilepsy
• Abuse
• Psychiatric agitation
• Long term confinement to the same
position • Delirium tremens
Occlusion or hypo perfusion of • Tetanus
muscular Vs • Amphetamine overdose
• Thrombosis • Status asthmatics
• Embolism
• Vs clamping
Temperature related
• Shock • Exercise
Electric current • High ambient temperature
• High voltage electric injury • Sepsis
• Lightening • Narcoleptic malignant syndrome
• Cadioversion • Malignant hyperthermia
Critical care 2005 – 9,158-169
Non physical causes
Metabolic myopathies Endocrinolgic cause
• McArdle disease • Hyper/hypothyrodism
• Mitochondrial respiratory chain
enzyme deficiencies
• Carnitine palmitoyl transferas
deficiency Systemic effect
• Myoadenlyate deaminase • Toxic shock syndrome
deficiency
• Influenza
• Phosphofructokinase deficiency
•
• HIV
Drug & toxins • Herpes viruses
• Regular & illegal drugs
• Coxsackie virus
• Toxins Electrolyte abnormalities
• Snake & insect venom • Hypokalemia
• Hypocalcaemia
Polymyositis/dermatomyositis • Hyponatremia & hypernatremia
Infections • Hypophosphatemia
• Local and metastatic infections • Hyper osmotic conditions
Critical care 2005 – 9,158-169
Drugs that may
induce rhabdomyolysis
Statin related rhabdomyolysis
Directly or indirectly impairs the production or use of
ATP by skeletal muscle
Increases energy requirements that exceed the rate of
ATP production
Interfere with ATP production by reducing levels of
coenzyme Q, chronic myositis syndrome
Risk factors: high dosages, increasing age, female, renal
and hepatic insufficiency, DM and concomitant
therapy with drugs such as fibrates
Exertional Rhabdomyolysis
Exercise beyond physical capabilities
ATP demand outweighs supply resulting in
cellular membrane breakdown
Intense exercise in normal individuals
Grand mal seizure
Delirium tremens
Physical abuse
Contact sports
Crush injury
Compression
Factors in the development of
Exertional Rhabdomyolysis
Fitness level
Experience with the type of exercise being
Performed
Intensity of exercise
Type of exercise (eccentric vs concentric)
Ambient temperature
Hydration level
Fasting
Associated illness
o g y
s i o l
P h y
h o -
Pa t
Causes of Cellular Destruction in Rhabdomyolysis
Direct injury to cell membrane (ex. crushing,
tearing, burning..)
Severe electrolyte disturbance disrupting
sodium-potassium pump
Muscle cell hypoxia leading to
depletion of ATP
Patho-physiology
Physical injury
Compression
Ischemia Reperfusion
Excessive contractions injury
Electric injury
Hyperthermia
•Increase phospholipase A2
•Increase Ca++ dependent
Decrease phosphorylases
Sarcoplasmic •Increase nucleases
intracellular ATP
Ca++ influx •Increase proteases
•Increase free radicals
•Increase local BMN cells
Non physical injury
•Metabolic myopathies Compartment
•Drug & toxins syndrome
•Infection
•Electrolyte
•Endocrine disorder
Primary cellular injury inrcease intracellular Ca++ secondary injury Activation
Goldman: Cecil Medicine 23rd ed
Cellular Patho-physiology
Influx of extra cellular contents
(sodium, water, chloride, calcium)
Efflux from damaged muscle cells
(potassium, phosphates, lactic acid and other
organic acids, purines, myoglobin,thromboplatin,
creatinine, creatine kinase)
Influx and Efflux of Extra and Intra Cellular
Fluids During Cellular Destruction
Extracellular Intracellular
Chemical composition
( (mEq/L ( mEq/L)
Sodium 142 10
Potassium 4 140
Calcium 2.4 0.0001
Magnesium 1.2 58
Chloride 103 4
Bicarbonate 28 10
Protein ( myoglobin, CKetc) 5 40
Myocyte Injury
Tolerable-no
permanent Muscle
histological necrosis
changes
Hours of 0 2 4 6
ischemia
Irreversible
anatomic and
functional
changes
When to Suspect Rhabdo
Occurs in up to 85% of patients with traumatic
injuries.
Those with severe injury who develop
rhabdomyolysis-induced renal failure have a 20%
mortality rate
Multiple orthopedic injuries
Crush injury to any part of the body (eg: hand)
Laying on limb for long period of time –patient “found
down”
Long surgery
Brown urine
Sudden collapse during physical exertion
carried out under warm climatic conditions
should be primarily diagnosed as
rhabdomyolysis
(unless and until proven otherwise)
What to Watch for if you suspect Rhabdo:
Clinical: Ms pain, weakness, dark urine
Hypovolemia, shock
Electrolyte abnormalities : ↑K+, ↓ Ca++
(sequestered in injured tissues)
Causes of reddish-brown discoloration
of the urine
Characteristics of urine and plasma in the different
conditions that may cause red discoloration of the urine
Characteristic Rhabdomyolysi Haemolysis Hematuria
s
Red discoloration
plasma
Positive benzidine
dipstick
Presence of
erythrocyte by
urine microscopy
Elevated CK
concentration in
the blood
Diagnosis
Serum CKMM sample UA
Correlates w/severity of rhabdo
Normally 145-260 U/L
100,000’s not uncommon
high t(1/2): 1.5 days
Rises within 12 hours of the onset
Peaks in 1–3 days, and declines 3–5
days
Serum myoglobin uric acid
t(1/2) 2-3 h crystals
Excreted in bile
UA-myoglobinuria
(+) for
dipstick will be (+) for blood
hemoglobin, RBC’s and
myoglobin
Microscopy: no RBC’s, brown
casts, uric acid crystals
Other measures:
measures carbonic
anhydrase III, aldolase
Serum creatinine : Urine Na +
disproportionate to BUN
K+
Uric acid
Leucocytosis Ca + +
Hypoalbuminemia Po4
Gluc.in urine
Haematocrite Pigment casts
Clinical Manifestations & Complications
Early signs:
ɚ Hyperkalemia, ɚ Hypocalcemia,
ɚ Hyperphosphatemia, ɚ Hyperuricemia,
ɚ Acidosis
Early complications:
ɚ Cardiac arrhythmia
up to cardiac arrest & death
ɚ Hypovolemia
Late complications:
ɚ Acute kidney injury ɚ DIC
ɚ Compartment syndrome ɚ Hypercalcemia
ɚ Infection ɚ MOSF ɚ ARDS
ɚ Fascial compartment compression syndrome
American Family Physician (2002) 65:907-912
TREATMENT
Fluid Resuscitation
Is the cornerstone of treatment and must be
initiated as soon as possible. No
randomized trials of fluid repletion
regimens in any age group have been done.
Patients with a CK elevation in excess of 2-3 times
the reference range, appropriate clinical history,
and risk factors should be suspected of having
rhabdomyolysis. For adults, administer isotonic
fluids at a rate of approximately 400 mL/h (may
be up to 1000 mL/h based on type of condition
and severity) and then titrate to maintain a
urine output of at least 200 mL/h or 3 ml per
kilogram
Because injured myocytes can sequester large
volumes of ECF, crystalloid requirements may be
surprisingly large. Consider central venous pressure
measurement or Swan-Ganz catheterization in
patients with cardiac or renal disease. Repeat the CK
assay every 6-12 hours to determine the peak CK level.
The composition of repletion fluid is
controversial and may also include sodium
bicarbonate, esp. in NS is used.
To prevent renal failure, many authorities
advocate urinary alkalization and loop diuretics.
Check urine pH. If it is less than 6.5, alternate
each liter of normal saline with 1 liter of 5%
dextrose or 0.45% saline plus 100 mmol of
bicarbonate.
Alkalinization of urine benefits:-
1-Decrease precipitationof the Tamm–Horsfall
protein–myoglobin complex
2- Inhibits reduction–oxidation (redox)cycling of
myoglobin and lipid peroxidation , thus
ameliorating tubule injury.
3- Counteract VC
Urinary alkalization should be considered earlier in
patients with acidemia, dehydration, or underlying
renal disease. A suggested regimen for adult patients
is 0.9% NaCl with 1 ampule of sodium bicarbonate
administered at 100 mL/h. Sodium bicarbonate is
used with care because it may potentiate
hypocalcemia.
If sodium bicarbonateis used, urine pH and serum
bicarbonate,calcium, and potassium levels should be
monitored, and if the urine pH does not rise after
4 to 6 hours of treatment or if symptomatic
hypocalcemia develops, alkalinization should be
discontinued and hydration continued with NS
Diuretics
furosemide may be used to enhance urinary
output in patients who are oliguric despite
adequate intravascular volume. It is recommended
that aggressive volume expansion is to be
maintained until myoglobinuria is cleared.
Consider renal-replacement therapy if there is
resistant hyperkalemia of more than 6.5 mmol per
liter that is symptomatic (as assessed by
electrocardiography), rapidly rising serum potassium,
oliguria (<0.5 ml of urine per kilogram per hour for 12
hours), anuria, volume overload, or resistant
metabolic acidosis (pH <7.1).
Late Treatment
Dialysis –
intermitted preferred to
continuous
Reduce use of
anticoagulants in
trauma patients
Peritoneal dialysis is
inadequate
The removal of
myoglobin by plasma
exchange has not
demonstrated any benefit
Administration of calcium should be avoided
during the renal failure phase, unless the
patient has symptomatic hypocalcemia or
severe hyperkalemia(Grade IB)
IB
Take Home Message
Impairment of the production or use of ATP is the basic
cause.
Most useful laboratory findings are elevated CK(>
5000U/L related to AKI ), initial detection of
myglobolin.
Management: Aggressive hydration, diuresis, urine
alkalinzation, and dialysis.
Do not treat hypocalcemia unless symptom developed.
