Exertional Rhabdomyolysis

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Exertional Rhabdomyolysis

• Liz Delasobera, MD
• (some slides c/o USU database)

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3 Things To Remember

• Know how to risk stratify rhabdo patients
• Low risk treat like concussion (step-wise
  return to play/duty)
• High risk more tests and experts, restrict play
• Heat illnessrhado until proven otherwise
• Admit for CK gt 5-10K for IVF, to check serial
  labs (CK, DIC, lytes), and to eval for
  compartment syndrome

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Our Roadmap

• The Basics Definitions, Epidemiology,
  Pathophysiology, Risk Factors
• Diagnosis Differentiating Subtypes of Rhabdo,
  Signs, Symptoms, Differential
• Treatment Short and Long-Term, Prognosis/Return
  to Play, Prevention
• Cases Test your knowledge

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Definition of Rhabdomyolysis

• Skeletal muscle breakdown with release of myocyte
  contents into the circulation caused by a variety
  of stresses
• Characterized by laboratory findings of
  myonecrosis with clinical spectrum dependent upon
  amount of muscle injury and associated co-morbid
  factors

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Definition of Exertional Rhabdomyolysis

• Most frequently ascribed to running activity and
  often associated with exertional heat illness
• Ranges from asymptomatic muscle injury with minor
  laboratory alterations to immediate life
  threatening syndrome with severe metabolic
  alterations and cardiac dysrythmias

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Definition of Exertional Rhabdomyolysis

• Not always pathologic can be a normal response
  to strenous exercise (physiologic
  rhabdomyolysis)
• Becomes more serious (clinically relevant
  rhabdomyolysis) when coupled with dehydration,
  SC trait, certain drugs, dietary supplements,
  caffeine/alcohol, exertional heat illness, and
  other poorly understood factors
• Devastating consequences
• Renal failure
• DIC
• Compartment syndrome
• Death

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Epidemiology

• Subclinical rhabdo common in vigorous exercisers
  and collision sports
• More serious cases seen mostly in endurance
  athletes and military personnel
• 26,000 per year in US
• 30 develop renal involvement

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Pathophysiology

• Intense exercise -gt hypoxia of tissues -gt failure
  of Na/K pump (K out of cell, Na/Ca into cell)
  anaerobic glycolysis and lactic acidosis -gt cell
  death
• Muscle injury causes release of myoglobin and
  muscle enzymes (CPK, LDH, AST, ALT)
• Evolving compartment syndrome due to swelling
  (muscle damage) and fluid shifts
• Renal failure due to myoglobin and uric acid in
  tubules dehydration nephrotoxic metabolites
  of myoglobin

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Risk Factors
Intrinsic/Inherited Extrinsic/Acquired
Genetic-Muscle Diseases/Enzyme Deficiency (McArdles, CPT II) Metabolic disorders (DM, Thyroid, Chronic electrolyte disorders, Acidosis) Sickle Cell Trait Autoimmune/Inflam Disorders Familial Recurrent Myoglobinuria Recent trauma or Crush Injury Excessive Muscle Overload Low Fitness Level Heat stroke Infection (EBV, HIV, flu) Drugs or Toxins (alcohol, statins, amphetamines, cocaine) Dehydration
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Our Roadmap

• The Basics Definitions, Epidemiology,
  Pathophysiology, Risk Factors
• Diagnosis Differentiating Subtypes of Rhabdo,
  Signs, Symptoms, Differential
• Treatment Short and Long-Term Treatment of
  Rhabdo, Prognosis/Return to Play, Prevention
• Cases Test your knowledge

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Subtypes of Rhabdo

• Exertional limited rhabdo
• Exertional rhabdo with heat stroke
• Exertional rhabdo without heat stroke
• Non-exertional rhabdo
• Trauma
• Medications

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Limited Exertional Rhabdo

• Overload of limited muscle group (ex, quads)
• Symptoms 1-3 days after event (delayed muscle
  soreness) and persists gt5 days after event
• Muscles tender, warm, swollen, painful with
  stretch and flex/extension
• CPK elevations in 10-50 K range
• Cola colored urine (urine myoglobin) can be
  only symptom
• Usually self limited

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Exertional Rhabdo With Heat Stroke

• Most of muscle injury as a result of intense
  hyperthermia (heat stroke)
• Risk factors
• Unacclimated
• Sickle cell trait
• High BMI
• Dehydrated
• Meds/supplements

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Exertional Rhabdo With Heat Stroke

• Clinically present with
• More global muscle injury
• Less muscle soreness and quicker recovery
• Chemistries more reflective of early liver and
  renal injuries
• High CPK (25,000)
• Treatment goals
• Restore normal body temperature and perfusion
• Effectively manage metabolic/electrolyte/organ
  sequelae

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Exertional Rhabdo Without Heat

• Intense exertional effort, typically gt 5 minutes
  and 15 METS
• Setting rapid conditioning or non-familiar
  exercise (ex, Basic Training)
• Pain or weakness out of proportion
• Usually involves large muscle groups
• May manifest hours after the insult
• May be additive from earlier training stress with
  fulminant end state
• Acute management is similar to extertional rhabdo
  with heat except that cooling is unnecessary

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Differential Diagnosis

• Guillan-Barre Syndrome (post viral)
• Electrolyte Abnormalities
• Periodic Paralysis
• Compartment Syndrome
• Neuroleptic Malignant Syndrome
• Polymyositis/Myopathy
• Porphyria

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Making the Diagnosis of Rhabdo

• General signs and symptoms
• Pain
• Swelling
• Tenderness
• Weakness
• Mental status changes
• Hyperthermia
• Cramping
• Discolored or brown urine

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Making the Diagnosis of Rhabdo

• Physical exam
• Swollen, tender, warm muscle groups
• Tight muscle compartments
• Objective weakness
• Intense pain with passive stretch of muscle
• Altered gait (lower extremities)

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Labs

• Initial studies
• CPK, UA with micro, Chem 7, Calcium, Phos, CBC,
  AST, ALT, LDH, Uric acid
• Serum or urine myoglobin - may not be available
  acutely
• Other studies to consider
• PT, PTT, Fibrinogen, ABG

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Labs

• CPK tends to peak 1-2 days after the insult
• Persistent elevation or increasing values
  suggests ongoing muscle ischemia/injury
  (compartment syndrome)
• Laboratory definition of rhabdo is CPK 5x normal
  and/or heme blood without RBCs
• CPK gt 16,000 U/L is threshold for renal damage

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Labs

• AST/ALT/LDH marker for more severe muscle damage
  in exertional rhabdo, and for liver injury when
  heat related
• Uric acid sensitive but not specific - normal is
  reassuring

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Labs

• Urine myoglobin
• Usually a send out lab
• This is the toxic effects on distal tubule
• Sludging and obstruction leads to muddy casts
  (frothy urine)
• Dehydration worsens toxic effects
• Load and duration of exposure toxicity

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Other Tests

• Compartment pressure testing
• MRI scan for limited rhabdo (concern for
  myopathy, abscess, etc)
• EKG (electrolyte changes)
• Muscle biopsy not acutely
• Severe, recurrent, or unusual precipitators
• Concern for neuromuscular disease
• Special stains and techniques needed (specialty
  center) to get various diagnoses

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Other Tests

• Ischemic Forearm Test
• Forearm exercise with BP cuff inflated gt 200 mm
  Hg
• Serial lactate and ammonia levels from
  antecubital vein
• Muscle enzyme deficiencies
• Low lactate production disorder of carbo
  metabolism (McArdles)
• Low ammonia production myoadenylate deficiency

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Our Roadmap

• The Basics Definitions, Epidemiology,
  Pathophysiology, Risk Factors
• ?Diagnosis Differentiating Subtypes of Rhabdo,
  Signs, Symptoms, Differential
• Treatment Short and Long-Term Treatment of
  Rhabdo, Prognosis/Return to Play, Prevention
• Cases Test your knowledge

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Short Term Treatment

• Admit for total CK gt 5-10K (literature varies on
  the exact level)
• IVF hydration for goal UOP 200 mL/hr (usually 400
  mL/hr IVF) needs up to 12 L in first 24 hours
• Treat electrolyte abnormalities except
  hypocalcemia
• Low Ca is a result of Na/K pump but also from
  deposition of calcium in muscles replete Ca
  leads to higher deposition levels, only tx if
  having EKG changes, severe hyperkalemia, tetany,
  etc

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Short Term Treatment

• Urine alkalinization (myoglobin and uric acid
  more soluble, less nephrotoxic) with bicarb
  (definitely if CKgt100K otherwise contraversial)
• If bicarb gt15 some literature suggests using oral
  acetazolamide
• Furosemide may be needed to maintain kidney fxn
• Fasciotomy as needed
• Dialysis in extreme cases
• Get ortho and renal involved early for help with
  making these decisions!

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Long Term Risk Stratifying

• First step to stratify low vs high risk is
  differentiating btwn physiologic and clinically
  relevant rhabdo
• CK level 5X  normal or greater
• OR
• UA that is positive for blood in the absence of
  RBCs
• If both of these negative then rest for 24 hours
  and repeat, if UA is still negative and CK is
  normal then dx is physiologic rhabdo and can
  gradually return to play/duty
• If either of these 2 steps are abnormal then they
  have clinically relevant rhabdo, need to further
  risk stratify

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Long-Term Risk Stratifying

• Low Risk (at least one of these most be true)
• Rapid clinical and CK recovery with exercise
  restriction (lt1 week)
• History of intense training
• No personal or family history of rhabdomyolysis
  or previous reporting of exercise- induced severe
  muscle pain, muscle cramps, or heat injury
• Existence of other rhabdomyolysis cases in the
  same training unit, team, etc
• Drug or supplement use
• Concomitant viral illness or other infectious
  disease

-Quick recovery -Good reason for this (intensity,
others with same sxs, etc) -Extrinsic
predisposiing factors (virus, drugs, etc)
without intrinsic (no FHx, etc)
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Long-Term Risk Stratifying

• Suspicion for High Risk
• Delayed recover (gt 1 week)
• Complications (renal failure, metabolic problems
  etc.)
• Muscle injury with low intensity workout
• Personal or family history of rhabdo/exertional
  cramps
• History of severe muscle pains in past

• Personal or family history of malignant
  hyperthermia
• Personal or family history of sickle cell trait
• Prior heat casualty
• CPK peak gt 10,000

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Treatment of Low Risk

• Limited duty/exertion
• If CK greater than 5-10K admit for IVF (goal UOP
  200 mL/hour usually give 400 mL/hr IVF)
• Re-evaluate labs 72 hours (CPK, creatinine,
  lytes, and UA)
• Adequate sleep in thermally controlled
  environment
• When UA is nl and total CK less than 5x nl, then
  gradual return to play/duty over 2 weeks (3
  phases)
• If CK doesnt go down within 5x upper limit nl in
  1-2 week then change to high risk algorithm

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Low Risk Soldier Return to Duty

• Phase 1
• Strict light indoor duty for 72hrs
• Must sleep eight consecutive hours nightly
• Must remain in thermally controlled environment
• Must follow-up in 72 hrs for repeat CPK/UA. When
  CPK/UA has returned to normal, begin Phase 2,
  otherwise remain in Phase 1 and return every 72
  hrs for repeat CPK/UA until normal.
• If persistently abnormal at week 2, refer for
  expert consultation.
• Phase 2
• Begin light-outdoor duty
• Follow-up with care provider in one week. If no
  issues then begin Phase 3
• Phase 3
• Return to regular outdoor duty and physical
  training
• Follow-up with care provider as needed, warn of
  symptoms, pre-disposing factors, etc

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Treatment of High Risk

• Consult with a local rhabdo expert (CHAMP
  website)
• Admit for IV hydration and repeat labs including
  calcium, K, phos, uric acid
• Can not return to play or duty until further eval
  complete with expert and further testing as
  indicated
• Consider
• Muscle Myopathy Panel (McCardles, AMP deaminase,
  CPT2 Deficiency)
• EMG
• Sickle cell screen
• Genetic testing
• Ryanodine receptor
• Muscle biopsy
• Forearm contracture test
• Caffeine Halothane contracture test (biopsy
  muscle and measure force of contraction, test
  with caffeine and halothane for malignant
  hyperthemia)

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Rhabdo Tx Algorithm
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Prevention of Rhabdo

• Acclimate
• Gradual progression of training
• Careful with meds (statins, supplements etc.)
• Proper fluid intake
• Identify susceptible individuals (genetics, FHx,
  SC trait, etc)
• Role of antioxidants (glutathone and
  bioflavinoids, such as quercitin) decreasing
  myoglobinuria

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Our Roadmap

• The Basics Definitions, Epidemiology,
  Pathophysiology, Risk Factors
• ?Diagnosis Differentiating Subtypes of Rhabdo,
  Signs, Symptoms, Differential
• ?Treatment Short and Long-Term Treatment of
  Rhabdo, Prognosis/Return to Play, Prevention
• Cases Test your knowledge

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Case 1

• 23 year old African American F with b/l arm and
  leg muscle pains after 12 mile run (longer than
  usual run)
• No meds, no illnesses
• No heat related illness (winter)
• No personal or family history of rhabdo
• Sickle trait positive
• CPK peaked at 20,000 (nllt120)
• Symptoms resolved after 7 days
• Dx? Acute tx? Long-term? Return to running?

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Case 1

• Diagnosis Rhabdo without heat illness
• High risk factors
• CPK peaked at 20,000
• Sickle trait positive
• Low risk factors
• Quick resolution of symptoms
• No FHx or personal hx

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Case 1

• Treatment?
• Short-term admit for IVF and serial labs, likely
  no need for bicarb unless CK gt100,000 (d/w
  renal), watch for signs of compartment syndrome
• Long-term consult with rhabdo expert for special
  testing and to aid with decisions on return to
  running/play

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Case 2

• 27 year old male healthy
• Push ups and weight lifting
• 1 week laterstill with chest soreness
• No prior or fhx, no meds, no medical problems
• Physical very tender pectoralis muscles

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Case 2

• Labs
• CK 8,000
• UA no blood or RBCs
• Chem 7 normal
• Diagnosis and treatment?

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Case 2

• Dx Limited rhabdo
• Tx watch for compartment syndromes, hydrate,
  repeat labs, and gradual return to play assuming
  CK normalizes in appropriate time period,
  asymptomatic, etc

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Case 3

• 18 y/o marathon runner who presents to the ER in
  the summer after being initially treated in the
  field for possible heat stroke after falling out
  of a run
• He was described as out of it and had an
  initial rectal temp of 106 F
• Others in marathon had heat illness and were
  transported to hospital
• His initial labs demonstrate a urine that dips
  positive for blood and a CK of 50,000 U/L
• Diagnosis?
• Treatment and return to play?

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Case 3

• Diagnosis Rhabdo with heat
• Low risk
• Others with same presentation
• Extrinsic risk factors (heat, extreme
  exercises/exertion)
• No known intrinsic risk factors
• High risk
• Level of CK

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Case 3

• Acute tx
• IV hydration and rapid cooling
• Repeat labs/lytes frequently
• Eval for compartment syndrome, liver injury, DIC,
  etc
• Long term tx
• Consider checking for SC trait
• If he had any high risk characteristics (prior
  heat illness, delayed recovery, complications,
  etc) or a prolonged recovery or other
  complications (renal, DIC, etc) would send to
  heat/rhabdo expert
• Otherwise educate patient and allow gradual
  return to running with close follow-up

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Case 4

• 32 y/o highly trained athlete who presents to the
  clinic with coca-cola urine and severe
  bilateral biceps pain
• Did 10 sets x 20 reps of with 50 pound hand
  weights
• His CK is 60,000 U/L and his urine dips positive
  for blood
• No prior history, no meds, no illness
• He recovered in 5 days labs and sxs
• Diagnosis? Return to sport/lifting?

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Case 4

• Dx Limited rhabdo
• High risk because of total CK, otherwise no high
  risk qualities
• Short-term hydrate, etc (always the same unless
  CKlt10K and then can consider outpt w/u)
• Long-term ensure no risk factors (i.e.
  supplements, FHx, personal hx, SC trait, etc), no
  complications, and full recovery then consider
  return to play with step-wise progression, but
  change work-out routine

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3 Things to Remember

• Know how to risk stratify rhabdo patients
• Low risk treat like concussion (step-wise
  return to play/duty)
• High risk more tests and experts, restrict play
• Heat illnessrhado until proven otherwise
• Admit for CK gt 5-10K for IVF, to check serial
  labs (CK, DIC, lytes), and to eval for
  compartment syndrome

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Thanks!