rhabdomyolysis .-dr.-osama-2017
TRANSCRIPT
Rhabdomyolysis
Dr. Osama El-Shahat Head of Nephrology Department
New Mansoura General Hospital (international)ISN Educational Ambassador
WEEKLY SCIENTIFIC MEETING
Nephrology Department New Mansoura General Hospital
(international)
Definition
Destruction or disintegration of striated
muscle resulting in the leakage of the
intracellular muscle constituents into the
circulation and extracellular fluid
Causes
Exertional & Traumatic
Inherited metabolic
Miscellaneous Acquired metabolic
Hypoxia / Ischemia
Drugs
Etiology of rhabdomyolysisPhysical Causes
Trauma & Compression• Traffic or working accidents• Disasters• Torture• Abuse• Long term confinement to the same
position Occlusion or hypo perfusion of muscular
Vs• Thrombosis• Embolism• Vs clamping • Shock
Electric current• High voltage electric injury• Lightening• Cadioversion
Straining muscular exercise• Exercise• Epilepsy• Psychiatric agitation• Delirium tremens• Tetanus• Amphetamine overdose• Ecstasy• Status asthmatics
Temperature related• Exercise• High ambient temperature• Sepsis• Narcoleptic malignant syndrome• Malignant hyperthermia
Critical care 2005 – 9,158-169
Non physical causes
Metabolic myopathies• McArdle disease• Mitochondrial respiratory chain
enzyme deficiencies• Carnitine palmitoyl transferas
deficiency• Myoadenlyate deaminase
deficiency• Phosphofructokinase deficiency•
Drug & toxins• Regular & illegal drugs• Toxins• Snake & insect venom
Polymyositis/dermatomyositis Infections
• Local and metastatic infections
Endocrinolgic cause• Hyper/hypothyrodism
Systemic effect• Toxic shock syndrome• Influenza• HIV• Herpes viruses• Coxsackie virus
Electrolyte abnormalities• Hypokalemia• Hypocalcaemia• Hyponatremia &
hypernatremia• Hypophosphatemia• 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 capabilitiesATP 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 ofExertional Rhabdomyolysis
Fitness levelExperience with the type of exercise being
PerformedIntensity of exerciseType of exercise (eccentric vs concentric)Ambient temperatureHydration levelFastingAssociated illness
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 Excessive contractions Electric injury Hyperthermia
Non physical injury• Metabolic myopathies• Drug & toxins• Infection • Electrolyte• Endocrine disorder
Decrease intracellular
ATPSarcoplasmic Ca++ influx
Reperfusion injury
Compartment syndrome
• Increase phospholipase A2
• Increase Ca++ dependent phosphorylases
• Increase nucleases• Increase proteases• Increase free radicals• Increase local BMN
cells
Rhabdomyolysis
Primary cellular injury inrcease intracellular Ca++ secondary injury Activation Goldman: Cecil Medicine 23rd ed
Patho-physiology
Etiology of acute renal injury with rhabdomyolysis
Acute kidney injury
Direct toxicity of myoglobin in tubular cells
Hypovolemia and decrease renal
perfusion
Cast formation decreasing
tubular flow
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 CellularFluids During Cellular Destruction
Chemical composition
Extracellular (mEq/L)
Intracellular (mEq/L)
Sodium 142 10Potassium 4 140Calcium 2.4 0.0001Magnesium 1.2 58Chloride 103 4Bicarbonate 28 10Protein ( myoglobin, CKetc) 5 40
Myocyte Injury
zHours of ischemia
0 2 4 6
Tolerable-no permanent histological
changes
Irreversible anatomic and
functional changes
Muscle necrosis
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 surgeryBrown urine
AXIOM
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)
Early Signs and Symptoms
weaknessfatigueheadacheslowed
mentation
thirstmuscle
crampsnausea,
vomitingdiarrhea
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
Rhabdomyolysis
Haemolysis
Hematuria
Red discoloration
plasmaPositive benzidine dipstick
Presence of erythrocyte by
urine microscopyElevated CK
concentration in the blood
Approach to the patient with red or brown urine
Diagnosis Serum CKMM
Correlates w/severity of rhabdoNormally 145-260 U/L100,000’s not uncommonhigh t(1/2): 1.5 daysRises within 12 hours of the onsetPeaks in 1–3 days, and declines 3–
5 days5000 U/l or greater is related to
renal failure
Serum myoglobint(1/2) 2-3 hExcreted in bile
sample UA
uric acid crystals
Creatine kinase(CK);CPK ( 38-174U/L for M
26-140 U/L for F )
CPK can be divided to 3 isoenzymes:
1-MM or CK3 96-100%(Skletal muscle and cardiac)
is the isoenzyme that constitutes almost all the
circulatory enz. In the healthy person
2-BB or CK1 0%(brain,GIT,Genitourinary)
3MB or CK2 0-6%
Creatine kinase(CK);CPK CK levels rise within 12 hours of muscle injury,
peak in 24-36 hours, and decrease at a rate of 30-40% per day.The serum half-life is 36 hours. CK levels decline 3-5 days after resolution of muscle injury ; failure of CK levels to decrease suggests ongoing muscle injury or development of a compartment syndrome. The peak CK level, especially when it is higher than 15,000 U/L, may be predictive of renal failure.
Myoglobin(5-70ng/ml)
Plasma myoglobin measurements are not
reliable, because myoglobin has a half-life
of 1-3 hours and is cleared from plasma in
the urine within 6 hours. Urine myoglobin
measurements are therefore preferable.
UA-myoglobinuriadipstick will be (+) for
hemoglobin, RBC’s and myoglobin
Microscopy: no RBC’s, brown casts, uric acid crystals
Other measures: carbonic anhydrase III, aldolase
Serum creatinine : disproportionate to BUN
Uric acid
Leucocytosis
Hypoalbuminemia
Haematocrite
Urine Na +
K +
Ca + +
Po4 Gluc.in urine Pigment casts
(+) for blood
Clinical Manifestations & Complications
Early signs:ɚ Hyperkalemia, ɚ Hypocalcemia,ɚ Hyperphosphatemia, ɚ Hyperuricemia ,
ɚ AcidosisEarly complications:
ɚ Cardiac arrhythmia
up to cardiac arrest & deathɚ HypovolemiaLate complications:ɚ Acute renal failure ɚ DICɚ Compartment syndrome ɚ Hypercalcemiaɚ Infection ɚ MOSF ɚ ARDSɚ 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, mannitol, 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 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
Dirutics Remains controversial, but it is clear that it should be
restricted to patients in whom the fluid repletion has been achieved.Mannitol may have several benefits: as an osmotic diuretic, it increases urinary flow and the flushing of nephrotoxic agents through the renal tubules; as an osmotic agent, it creates a gradient that extracts fluid that has accumulated in injured muscles and thus improves hypovolemia; finally,it is a free-radical scavenger
During the time mannitol is being administered, plasma osmolality and the osmolal gap (i.e., the difference between the measured and calculated serum osmolality) should be monitored frequently and therapy discontinued if adequate diuresis is not achieved or if the osmolal gap rises above 55 mOsm per kilogram
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
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 ARF), initial detection of myglobolin.
Management: Aggressive hydration, diuresis, urine alkalinzation, free-radical scavengers, dialysis.
Do not treat hypocalcemia unless symptom developed.
Conditioning by regular exercise to prevent ″white-collar rhabdomyolysis ″ .
بسم الله الرحمن الرحيم
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