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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Exercise-induced muscle necrosis.

Pathophysiology!!navigator!!

  • Exercise-induced skeletal muscle necrosis results in release of CK and myoglobin into circulation, often with stiffness, cramping, and pain; severe myoglobinuria can result in renal tubular damage and renal insufficiency.
  • ER can occur as an acquired disorder associated with overexertion, heat exhaustion, viral infections, and other factors; however, it is most commonly associated with heritable muscular disorders including RER and PSSM

Systems Affected!!navigator!!

Genetics!!navigator!!

  • In Thoroughbreds, RER is an autosomal dominant trait potentially associated with disturbed intracellular calcium regulation. Causative genetic defect is currently unknown.
  • In Quarter Horses and related breeds, and Belgian drafts, PSSM is an autosomal dominant trait related to a mutation in the glycogen synthase 1 gene (GYS1). Homozygotes and horses that concurrently carry the malignant hyperthermia-associated mutation of the ryanodine receptor gene (RYR1) tend to have more severe clinical signs

Incidence/Prevalence!!navigator!!

  • RER affects ~5–7% of racing Thoroughbreds.
  • PSSM affects ~6–10% of Quarter Horses, higher prevalence in halter Quarter Horses (~28%). In Belgian drafts, prevalence approaches 40%

Geographic Distribution!!navigator!!

Worldwide

Signalment!!navigator!!

Breed Predilections

Thoroughbreds, Quarter Horses, Appaloosa, Paint, Belgian draft, Percheron, Arabian, Standardbred, Warmblood, many other light breeds.

Mean Age and Range

  • For PSSM, mean age of onset of signs in Quarter Horses is ~5 years (range 1 day to late maturity).
  • In Thoroughbred racehorses, 2-year-olds most frequently affected.
  • In Arabian endurance horses, clinical disease >5 years of age and often in older horses

Predominant Sex

  • In Thoroughbreds and Standardbred racehorses, 2–3-year-old females more likely to be affected. Sex bias resolves with increasing age.
  • Sex predilection not reported for the other disorders

Signs!!navigator!!

General Comments

  • Frequency and severity of rhabdomyolysis episodes can be very variable between and within individuals.
  • Clinical signs can occur any time from immediately before exercise until sometimes hours after exercise.
  • Subclinical disease (elevated CK/AST only) can occur with few clinically visible abnormalities, and may be a particular risk in endurance horses

Historical Findings

  • Possible triggering factors—training regime changes, ration changes, prior rest period.
  • Variable signs from mild stilted gait to severe sweating, stiffness, and recumbency.
  • Repeated episodes may be observed

Physical Examination Findings

  • Exercise intolerance.
  • Stiffness, stilted gait.
  • Sweating.
  • Reluctance to move.
  • Swollen and/or fasciculating muscles.
  • Tachycardia, tachypnea.
  • Distress.
  • Recumbency.
  • Pawing, stretching, discomfort.
  • Discolored (red/brown) urine.
  • Muscle atrophy.
  • Usually normal between episodes

Causes!!navigator!!

Acquired Causes

  • Exercise exceeding level of training.
  • Exhaustive exercise.
  • Dietary electrolyte and mineral imbalance.
  • Electrolyte depletion during exercise.
  • Vitamin E and/or selenium deficiency.
  • Influenza

Inherited Causes

  • In Thoroughbred RER, defective calcium regulation resulting in a low threshold for muscle contraction; ±analogous disorder in Standardbreds.
  • In PSSM, heritable defect of glycogen metabolism recognized in Quarter Horses, Paints, some drafts, and related breeds

Risk Factors!!navigator!!

  • High starch (grain) diet.
  • >24 h of stall rest in horses with underlying muscle disease.
  • Sudden interruption of exercise routine.
  • Infectious respiratory disease.
  • Nervous temperament (Thoroughbreds, polo horses).
  • Lameness (Thoroughbreds).
  • Genetic predisposition.
  • High level of fitness (Thoroughbreds, Arabians)

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Association between exercise and onset of signs in addition to physical examination and laboratory findings facilitates differentiation from other conditions.
  • Conditions causing reluctance to move, acute recumbency, and/or discolored urine, including:
    • Lameness/laminitis.
    • Colic.
    • Pleuropneumonia.
    • Tetanus.
    • Lactation tetany.
    • Diseases causing intravascular hemolysis or bilirubinuria.
    • Neurologic disease.
    • Aortoiliac thrombosis.
    • HYPP

CBC/Biochemistry/Urinalysis!!navigator!!

  • Elevated serum CK, AST, and lactate dehydrogenase.
  • Myoglobinuria.
  • ±Hypochloremia, hypocalcemia, hyponatremia, hyperkalemia (severe disease).
  • ±Metabolic alkalosis or acidosis.
  • ±Elevated serum creatinine and urea nitrogen

Other Laboratory Tests!!navigator!!

  • Urinary fractional excretion of electrolytes.
  • Blood selenium and serum/plasma vitamin E

Imaging!!navigator!!

N/A

Other Diagnostic Procedures!!navigator!!

  • PCR testing of blood or hair for GYS1 mutation in PSSM breeds.
  • Semimembranosus muscle biopsy in non-PSSM breeds (Warmbloods, Arabians).
  • Submaximal exercise test—serum CK activity before 15 min of walk and trot exercise, then 4–6 h later >2–3-fold CK increase is considered suspicious. This test has greatest utility in PSSM

Pathologic Findings!!navigator!!

  • In RER, nonspecific muscle changes (increased centrally located nuclei, myocyte degeneration and regeneration).
  • In PSSM, abnormal polysaccharide inclusions if >2 years of age, subsarcolemmal vacuolations.
  • Arabian horses with ER—abnormal cytoplasmic desmin accumulation in myocytes

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

  • Aims of treatment—reduce discomfort and anxiety, prevent further damage, normalize hydration, acid–base and electrolyte status, and restore or protect renal function.
  • Severe rhabdomyolysis is an emergency. Inpatient management recommended to facilitate fluid therapy. Further muscle damage can occur with transport; less severe cases can be managed as outpatients

Nursing Care!!navigator!!

  • IV or oral fluid therapy with balanced electrolyte solutions until myoglobinuria resolves.
  • Alkalinizing fluids in myoglobinuric horses with metabolic acidosis to protect against renal injury.
  • Deep bedding, particularly for recumbent patients.
  • ±Slinging to prevent prolonged recumbency and further muscle trauma

Activity!!navigator!!

  • After mild episode, commence gentle exercise (at reduced intensity and duration than prior to episode) in 24–48 h if clinical signs of stiffness have resolved.
  • With severe episode, remain stall confined until recovered. Low-intensity exercise (hand-walking) initiated when clinical signs and serial CK improves

Diet!!navigator!!

  • Low-starch diet (grass hay) according to caloric requirements.
  • In RER-susceptible horses, avoid >2.2 kg (5 lb) of grain per day.
  • In PSSM-susceptible horses, no grain.
  • ±Fat supplements (rice bran, vegetable oil) and soluble fibers (beat pulp) if higher caloric requirements exist.
  • Eliminate high-starch supplements (molasses)

Client Education!!navigator!!

  • Susceptible horses should not be stall rested for >24 h at a time. Frequent exercise is preventative.
  • Daily turnout or forced daily exercise (riding or lunge work) is ideal. Interruption of routine exercise is a prominent risk factor.
  • Restrict dietary starch. High caloric requirements met with supplemental fat sources.
  • Discuss breeding management when underlying hereditary muscle disorder is suspected

Surgical Considerations!!navigator!!

N/A

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • For significant distress and pain, xylazine (0.2–0.4 mg/kg) or detomidine (0.01–0.02 mg/kg IM or IV); butorphanol (0.01–0.04 mg/kg IM or IV or as a CRI at 23.7 μg/kg/h after a loading dose of 17.8 μg/kg IV); or lidocaine (CRI at 30–50 μg/kg/min after a loading dose of 1.3 mg/kg IV slowly). Flunixin meglumine (1.1 mg/kg IV or PO) or phenylbutazone (2.2–4.4 mg/kg IV or PO).
  • Muscle relaxants—methocarbamol (5–22 mg/kg IV slowly every 6–12 h) or dantrolene sodium (4–6 mg/kg PO every 12–24 h). Give dantrolene within 4 h of feeding for adequate absorption.
  • Prevention—dantrolene 60–90 min prior to exercise

Contraindications!!navigator!!

  • Avoid NSAIDs in azotemic or significantly myoglobinuric horses.
  • Avoid dantrolene in horses with hyperkalemia or HYPP

Precautions!!navigator!!

  • Use caution with drugs that depress blood pressure in horses with myoglobinuria or azotemia, and correct dehydration prior to use

Possible Interactions!!navigator!!

None

Alternative Drugs!!navigator!!

Diazepam (0.05–0.5 mg/kg slow IV).

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • After mild to moderate ER, resume exercise after stiffness resolves.
  • Severe ER requires longer recuperation. Resume exercise after substantial CK and AST reduction.
  • In PSSM, mild elevations of CK and AST can persist; resume exercise when clinical signs resolve

Prevention/Avoidance!!navigator!!

  • Daily exercise and avoiding stall rest are critically important for prevention in susceptible horses.
  • Eliminate/reduce high-starch feeds. Grass hay (1.5–2.0% body weight) with supplemental fat sources (rice bran, oil, commercial high-fat feeds) to meet higher caloric needs. Susceptible horses fed minimal grain.
  • Young anxious Thoroughbreds may benefit from stress-reducing management changes, such as feeding and exercising them before others and low-dose sedatives before training.
  • In sporadic ER, appropriate training regimes that prepare them for their intended athletic use

Possible Complications!!navigator!!

  • Acute or chronic renal insufficiency from myoglobinuria.
  • ±Atrophy of affected muscles weeks to months after severe episode

Expected Course and Prognosis!!navigator!!

  • Horses with sporadic acquired ER have good prognosis with appropriate management.
  • Horses with mild to moderate signs of PSSM or RER usually respond to a disciplined routine of daily exercise and appropriate dietary changes.
  • PSSM horses with late onset of signs have good prognosis if the triggering management changes are identified and addressed.
  • PSSM horses developing signs early (<1 year of age) may have a less favorable prognosis for athletic function.
  • Horses with repeated and severe episodes of muscle necrosis have poor prognosis for athletic function if they display limited response to appropriate dietary and training changes.
  • Horses with acute or chronic renal insufficiency due to rhabdomyolysis have a good to guarded prognosis depending on severity and response to treatment

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

Renal insufficiency.

Age-Related Factors!!navigator!!

Different disorders can vary in likely age of presentation.

Zoonotic Potential!!navigator!!

None

Pregnancy/Fertility/Breeding!!navigator!!

Avoid breeding horses with heritable disorders of muscle function.

Abbreviations!!navigator!!

  • AST = aspartate aminotransferase
  • CK = creatine kinase
  • CRI = constant rate infusion
  • ER = exertional rhabdomyolysis
  • HYPP = hyperkalemic periodic paralysis
  • NSAID = nonsteroidal anti-inflammatory drug
  • PCR = polymerase chain reaction
  • PSSM = polysaccharide storage myopathy
  • RER = recurrent exertional rhabdomyolysis

Suggested Reading ⬆ ⬇

Piercy RJ, Rivero JL. Muscle disorders of equine athletes. In: Hinchcliff KW, Kaneps AJ, Geor RJ, eds. Equine Sports Medicine and Surgery, 2e. Edinburgh, UK: Saunders Elsevier, 2014:109–143.

Valberg SJ. Muscling in on the cause of tying-up. Proc Am Assoc Equine Pract 2012;58:85–123.

Valberg SJ. Diseases of muscle. In: Smith BP, ed. Large Animal Internal Medicine, 5e. St. Louis, MO: Elsevier Mosby, 2015:1276–1308.

Author(s) ⬆

Author: Erica C. McKenzie

Consulting Editor: Elizabeth J. Davidson