Exertional Rhabdomyolysis

LTC Fred H. Brennan, Jr., DO Director, Tri-Service Primary Care Sports Medicine Fellowship Program Uniformed Services University of the Health Sciences Bethesda, MD

Objectives
Define rhabdomyolysis and exertional rhabdomyolysis Epidemiology Pathophysiology Risk factors Causes of rhabdomyolysis Rhabdomyolysis syndromes

Objectives
Clinical picture Diagnosis Treatment Prognosis/return to duty/medical board Prevention Summary

Case 1
27 year old male sergeant ; always healthy Push ups and weight lifting 1 week laterstill with chest soreness Physical: very tender pectoralis muscles

Case 1
Labs CK = 10,000! ESR = 30 UA = no blood or RBCs Chem 7= normal Diagnosis: Limited rhabdo Treatment: Admitted, IV fluids, observed Follow up

Definition of Rhabdomyolysis
Rhabdomyolysis is a condition or syndrome of skeletal muscle breakdown with release of myocyte contents into the circulation which may arise from a variety of stresses that cause injury to muscle tissue. It is characterized by laboratory findings of myonecrosis with clinical spectrum dependent upon amount of muscle injury and associated comorbid factors.

Definition of Exertional Rhabdomyolysis

"Exertional rhabdomyolysis" is the term applied to rhabdomyolysis arising from exercise or exertion. It is most frequently ascribed to running activity and often associated with exertional heat illness (heat stroke). However any extreme muscle overload activity may precipitate rhabdomyolysis . It is a spectrum illness ranging from insignificant asymptomatic muscle injury with minor laboratory alterations to fulminant immediate life threatening syndrome with severe metabolic alterations and cardiac dysrythmias.

Epidemiology
Subclinical rhabdo common in vigorous exercisers and collision sports (how common ?) More serious cases seen in endurance athletes and military personnel Symptoms downplayed 26,000 + per year in US

Predisposing Factors
Intrinsic/Inherited Extrinsic/Acquired

-Genetic-Muscle Diseases/Enzyme Def. (McArdles, CPT II)

-Metabolic Diseases or Disorders (Diabetes, Thyroid Disease, Chronic Electrolyte Disorders or Acidosis) -Sickle Cell Trait -Autoimmune/Inflam Disorders -Familial Recurrent Myoglobinuria

-Recent Trauma or Crush

-Excessive Muscle Overload or Exertion and/or low fitness levels

-Heat Illness (Heat Stroke)

-Infection (EBV, HIV, influenza) -Drug or Toxin Exposure (alcohol, statins, amphets, cocaine,ephedra?) -Dehydration

Pathophysiology
Muscle injury with release of myoglobin and muscle enzymes (CPK, LDH, AST, ALT) Severe states with metabolic acidosis, electrolyte issues (potassium,phos,calcium), renal failure, DIC, fluid shifts

Evolving compartment syndrome due to swelling and fluid shifts

Pathophysiology
Physical Injury Reperfusion Injury

*these all increase

-Phospho Lipase A

Decreased Intracellular ATP

Sarcoplasmic Calcium Influx

-Ca Dep Phospho

-Nucleases

Rhabdo

Non-Physical Injury

Compartment Syndrome

-Proteases
-Free radical -Local PMN

Pathophysiology and Clinical Picture

Depends on:
Volume of injured tissue Ability of body to handle the damage Other contributors like hyperthermia, muscle ischemia, dehydration, continued muscle overload

Exertional Rhabdomyolysis Syndromes

Isolated muscle injury or limited rhabdo Rhabo due to exertional heat illness Exertional rhabdo without heat illness

Limited Rhabdo
Overload of limited muscle group (quads) Symptoms 1-3 days after event Muscles tender, warm, swollen, painful with stretch CPK elevations in 10-50 K range; also urine myoglobin common Usually self limited with treatment and no sequelae

Exertional Rhabdo With Heat Stroke

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

Exertional Rhabdo With Heat Stroke

Clinically presents differently: More global and less severe muscle injury Less muscle soreness and quicker recovery Chemistries more reflective of early liver and renal injuries; also high CPK (25,000 +) Treatment goals: Restore normal body temperature and perfusion Effectively manage metabolic/electrolyte/organ sequelae
*Heat Stress Control and Heat Casualty Management. TB MED 507/AFPAM 48-152. Headquarters Department of the Army and Air Force. Washington DC, 7 March 2003. *AR 40-501

Case 2
22 year old soldier s/p Division 12 mile road march Sick call: My calves and quads are killing me PE: limping; calves and quads not tight but very tender to gentle squeeze

Case 2
Labs
CK = 50,000! UA = + blood with no RBCs

Diagnosis: Exertional rhabdo Treatment: Admitted, IV fluids, monitor labs Follow up

Exertional Rhabdo Without Heat

Intense exertional effort, typically > 5 minutes and 15 METS Setting: rapid conditioning or non-familiar exercise (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

Making the Diagnosis

History Listen to your patient! Clinical setting (environment, recurrent or acute stress, other risk factors) Evolution of symptoms

Making the Diagnosis

Signs and symptoms
Pain Swelling Tenderness Weakness Mental status changes Hyperthermic Cramping Discolored or brown urine

Making the Diagnosis

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

Making the Diagnosis

Labs
Initial studies
CPK, UA with micro, Chem 7, CBC, AST, ALT, LDH, Uric acid

Serum or urine myoglobin; may not be available acutely Other studies

Ca, Phos, PT, PTT, FSP, Fibrinogen, ABG Hypo or hypercalcemia can occur

Labs
CPK tends to peak 1-2 days after the insult Persistent elevation or increasing values suggests ongoing muscle ischemia/injury (compartment syndrome)

Labs
CPK: uncertainly about what is truly normal
Moderate sensitivity but not specific May be low initially or falsely high in asymptomatic patient Greater than 5 times normal is considered + maybe! > 16,000 U/L (renal damage)

+ dipstick for blood. But no RBCs on micro exam

Labs
AST/ALT/LDH: marker for more severe muscle damage in exertional rhabdo; and for liver injury when exertional and heat related Chem 7, Phos, Calcium, ABG Uric acid: sensitive but not specific; normal is somewhat reassuring CBC PT/PTT FDP

Labs
Urine myoglobin
Toxic effects on distal tubule Sludging and obstruction with renal failure; muddy casts Dehydration worsens toxic effects on kidneys Load and duration of exposure = toxicity Urine frothy when agitated

Making the Diagnosis

Other tests
Compartment pressure testing Nuclear medicine scan for limited rhabdo

Muscle biopsy: not acutely

Severe, recurrent, or unusual precipitators Muscle enzyme or neuromuscular disease Special stains and techniques (specialty center is best)

Making the Diagnosis

Ischemic Forearm Test
Forearm exercise with BP cuff inflated > 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 Normal rise in ammonia and lactate = disorder of lipid metabolism

Differential Diagnosis
Guillan-Barre Syndrome (post viral) Periodic Paralysis (follows sleep or rest) Hemolysis Intrinisic renal disease Porphria Acute Glom Beets, phenytoin, rifampin, vitamin B 12

Algorithm for Treatment of Acute Exertional Rhabdomyolosis

Service-member presents with severe muscle pain
Screen with spot UA for blood, visualize color of urine Heat stroke panel * Screen for compartment syndrome (Also follow Exertional Heat Injury Algorithm) CPK > 5X nl Or Positive urine dipstick- blood (YES) Limited indoor duty for remainder of day Medical re-evaluation on following day Home oral re-hydration

(BOTH NO)

ACUTE EXERTIONAL RHABDOMYOLYSIS -Admit to ICU -Urine myoglobin, serum calcium, phosphate, uric acid -ABG if lactic acidosis suspected -Foley catheter -IV hydration with NS to maintain urine output >200cc/hr (consider mannitol or furosemide) - Monitor for development of compartment syndrome Positive urine myoglobin OR Metabolic acidosis Phos > 7mg/dl Or SYMPTOMATIC hypocalcemia Uric acid Or Acute Renal Failure Or Consider uricosuric Refractory hyperkalemia agents Consult nephrologist for possible dialysis

Hyperkalemia

Alkalinize urine if lactate <4 or pH < 7.2: * Moderate: Add 1 amp bicarb to 1 bag NS Severe: Add 2 amps bicarb to 1 bag NS *D/C when myoglobin negative or pH>7.2

D50 -Insulin -Inhaled B-agonist

Questions: Prognosis, Return to Duty, Medical Board ?

23 year old African American E-3 with exertional rhabdo after 12 mile road march CPK peaked at 20,000 Sickle trait positive Fully recovered after 7 days with no sequelae, now what? What are the chances that this will happen again? Further eval needed?

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

Personal or family history of malignant hyperthermia Personal or family history of sickle cell trait Drug or supplement use (statins, ephedra, creatine, steroids) Prior heat casualty CPK peak > 10,000

Risk Stratify
Low risk
Rapid recovery Physically fit No prior personal or family history Other rhabdo cases in the same training unit Involvement of other viral or infectious disease

Low Risk Soldier

Limited duty profile to exclude field duty, aerobic or anaerobic exercise Re-evaluate in 72 hours (CPK and UA) Adequate sleep in thermally controlled environment When clinically resolved then increase outdoor light-duty activity Follow up in one week and advance to full duty

High Risk Soldier

Expert consultation Consider
Muscle biopsy Ischemic forearm test Rhabdo challenge test Halothane muscle contraction test

Profile until further evaluation is done

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

Summary
Spectrum disorder Multiple factors influence susceptibility Exertional rhabdo with heat stroke- multisystem problem History and progression of symptoms is importantbeware!

Summary
Maintaining hydration is important Weakness, severe pain, and collapse are ominous signs Brown urine necessitates immediate evaluation, even if asymptomatic Risk stratify and profile/evaluate accordingly