RHABDOMYOLYSIS

    DEFINITION

    Rhabdomyolysis is a syndrome caused by injury to skeletal muscles and
    the resultant leakage of muscle cell contents (myoglobin, potassium,
    phosphate, etc.) into the plasma.

    TOXIC CAUSES

    Rhabdomyolysis has been associated with a variety of toxins and drugs.
    They can either exert a direct toxic effect on muscles (metabolic
    poisons) or indirectly predispose to rhabdomyolysis.

    Direct toxic effect:     Amatoxins
                             Carbon monoxide
                             Colchicine
                             Ethylene glycol
                             Snakebite

    Indirect effect:         Excessive muscular hyperactivity or rigidity
                             (dystonia)
                             Prolonged seizures
                             Hyperthermia
                             Muscular compression from prolonged
                             immobility (coma)

    NON-TOXIC CAUSES

    Coma or prolonged immobility from any cause
    Direct Muscle Injury
    Excessive muscular activity
         Endurance sporting activities 
         Seizures
    Immunological
         Dermatomyosits
         Polymyositis
    Ischaemic Muscle injury
         Crush injury
         Vascular occlusion
    Metabolic
         Hypokalaemia
         Hypophophataemia
    Viral Infections
         Coxsackie 
         Influenza

    CLINICAL FEATURES

    The clinical presentation is extremely variable. In conscious
    patients, the main complaint may be muscle tenderness, stiffness and
    cramping, accompanied by weakness and loss of function.  However,
    myalgia may be absent or minimal initially (upon admission). In

    comatose patients, the finding of limb induration should suggest
    rhabdomyolysis. Skin changes due to ischaemic tissue injury
    (discoloration, blisters) may be present on the affected area.
    Physical examination may reveal a "woody" muscle swelling which may
    worsen after parenteral rehydration. Severe muscle swelling can result
    in a compartment syndrome, with absent pulses.  

    Dark (red-brown) urine is a classical manifestation of rhabdomyolysis.
    Signs of dehydration (due to sequestration of fluid in damaged
    muscles) may be present along with oliguria. In rhabdomyolysis due to
    severe poisoning, muscle signs can be overlooked if signs indicative
    of the underlying disorder (e.g., extreme agitation, seizures,
    hyperthermia) dominate the clinical picture.  Signs related to
    complications of rhabdomyolysis (e.g., hyperkalaemia, acute renal
    failure, metabolic acidosis, disseminated intravascular coagulation
    and, rarely, respiratory failure) can also constitute the main
    clinical findings.

    RELEVANT INVESTIGATIONS

    A serum creatine phosphokinase activity greater than five times the
    normal value (in the absence of heart and brain disease) is the most
    sensitive indicator of rhabdomyolysis.

    Myoglobinaemia may result from the leakage of myocyte contents into
    the plasma.  When muscle destruction is acute, extensive myoglobinuria
    can occur and may cause a visible discoloration of the urine
    (red-brown). A positive orthotoluidine reaction (Hematest),in the
    absence of red blood cells in the urine, confirms the presence of
    myoglobinuria.

    The following laboratory findings can be present: hyperkalaemia,
    hypocalcaemia, hyperphosphataemia, hyperuricaemia, elevated blood urea
    and serum creatinine, elevated AST (SGOT) and LDH activities. The
    creatinine may be disproportionately elevated in relation to renal
    insufficiency because of the release of preformed creatine from
    damaged muscles.

    TREATMENT

    The first aim of treatment is to support vital functions.

     Diazepam 
    In case of excessive muscular activity (e.g. combativeness, seizures),
    initiate treatment with  Diazepam (5 to 10 mg slowly IV, up to a
    maximum of 30 mg). 

     Fluids
    Crystalloid infusion should be given to maintain a high urine output
    (> 3 - 4 mLs/hr). 

     Furosemide/Mannitol
    Diuretics:  Furosemide or  Mannitol may be used when administration
    of fluids alone is inadequate. 

     Sodium Bicarbonate
    Urine alkalinization has been proposed for the prevention of myoglobin
    nephrotoxicity, but its effectiveness has not been demonstrated
    conclusively.

     Calcium Salts
    Hypocalcaemia, a common finding in rhabdomyolysis, is rarely
    symptomatic when present alone, and therefore does not necessitate
    treatment.  

     Haemodialysis
    Dialysis is indicated whenever acute renal failure occurs and/or
    life-threatening complications (e.g. hyperkalaemia) are present.

     Fasciotomy
    Fasciotomy is rarely indicated and may be associated with serious
    complications.

    CLINICAL COURSE AND MONITORING 

    Careful clinical monitoring of vital signs
    Urine output
    Cardiac rhythm
    Serum sodium, potassium, and calcium  
    Haematocrit/Haemoglobin
    Arterial blood gases
    Creatine phosphokinase activity
    Serum creatinine and blood urea 
    AST (SGOT) and LDH
    Hematest (orthotoluidine reaction): if Hematest is positive,
    haematuria must be ruled out by microscopic examination of the urine.
    Platelet count, fibrinogen level, partial thromboplastin and
    prothrombin times to detect either thrombocytopenia or disseminated
    intravascular coagulation.

    POTENTIAL COMPLICATIONS/SEQUELAE 

    Prolonged muscle weakness is the most frequent complaint following
    rhabdomyolysis.  Peripheral neuropathy with permanent neurologic
    deficits can result from neuronal ischaemia due to a compartment
    syndrome.  The acute renal failure secondary to rhabdomyolysis has a
    good prognosis when early treatment is performed.

    AUTHOR(S)/REVIEWERS

    Author:        Dr T. Della Puppa, Centro Antiveleni, Milano, Italy.

    Peer Review:   Sao Paulo 9/94, Cardiff 3/95, Berlin 10/95: A. Wong,
                   T. Meredith, V. Danel.