Exertional rhabdomyolysis in a 4-year-old standardbred filly

Abstract

A young standardbred filly became stiff and uncomfortable after racing. A day later, creatine kinase, aspartate aminotransferase, and lactic dehydrogenase levels were markedly elevated. Exertional rhabdomyolysis was diagnosed. Limited exercise and a low carbohydrate, high fat diet were prescribed. Eight days later, the filly was raced again without consequences.

Equine exertional rhabdomyolysis (ER) was diagnosed in a 4-year-old standardbred filly that had raced successfully as a 3-year-old. During training, the filly often experienced mild stiffness after exercise and poor performance. This reached a peak after she won a race as a 4-year-old (day 1), when she became severely stiff and uncomfortable after finishing. A post-race urine sample was dark red and appeared bloody; later that evening, the filly again passed dark urine. The owner administered lactated Ringer's solution, IV, and contacted the veterinarian the next morning.

When examined on day 2, the filly was very bright and was eating and drinking well. Mucous membranes, capillary refill time, and hydration were normal. Body temperature, respiration, and heart rate were within normal limits. However, there was moderate hind limb stiffness, particularly in the right hind limb. Blood samples were taken for a complete blood cell (CBC) count and a biochemical profile. Urine collected after administration of furosemide (Lasix; Hoechst Roussel Vet, Regina, Saskatchewan), 0.5 mg/kg BW, IV, appeared clear and of normal color; there were no significant findings on urinalysis. Differential diagnoses included carbohydrate overloading, dietary deficiencies of selenium and vitamin E, laminitis, colic, renal disease, or ER (tying-up syndrome). On the basis of the history and clinical signs, a tentative diagnosis of ER was made.

Biochemical analysis (VetTest blood analyzer; IDEXX Laboratories, Westbrook, Maine, USA) revealed abnormalities in creatine kinase (CK) (> 2036 U/L; reference range, 10 to 350 U/L), aspartate aminotransferase (AST) (3500 U/L; reference range, 100 to 600 U/L), and lactate dehydrogenase (LDH) (> 2800 U/L; reference range, 250 to 2070 U/L), consistent with both acute and chronic muscle damage (Table 1). However, electrolyte values were within normal limits and kidney function appeared normal. The owner was instructed to limit exercise until muscle function returned to normal, as determined by further blood tests. A low carbohydrate and high fat diet was suggested, and the trainers were instructed to increase exercise gradually, ensure ample warm-up and cool-down procedures, and provide as much pasture turn-out as possible. At the owner's request, the filly was also treated with dantrolene sodium (Dantrium; Procter and Gamble Pharmaceuticals, Cincinnati, Ohio, USA), 2 mg/kg BW, PO, q24, for 10 d. Dantrolene sodium, a nonveterinary muscle relaxant, has been used commonly to treat ER, with questionable efficacy.

Table 1.

When blood tests and urinalysis were repeated on day 9, muscle function was returning to normal. The serum CK level was normal (292 U/L), while AST (809 U/L) and LDH (3055 U/L) were slightly above normal limits.

The owner had commenced training the horse for a few days prior to day 9 with no apparent problems. It was recommended that the filly continue this work schedule but not race for another 3 to 4 wk. However, she was scheduled to race that evening. The owner planned to give her ample pre-race conditioning and post-race cool down to prevent another tying-up episode. The filly was not pushed excessively in the race and placed 3rd with no recurrence of the tying-up problem. On day 129, the owner reported that the filly had not experienced another clinical recurrence and had been racing well.

Exertional rhabdomyolysis is a myopathy that has been recognized for over a century, first described in working draft horses that were exercised after being rested for 1 to 2 d and while being fed a high grain diet (1,2). It is a frequently encountered problem of unknown etiology in many breeds of domestic horses, including quarter horses, standardbreds, and Thoroughbreds, and it represents a major problem in performance horses by limiting or preventing training and inhibiting peak performance. It has been referred to as tying-up, paralytic myoglobinuria, Monday morning disease, azoturia, and myositis (2,3). Although ER has occurred in horses at rest, and after transport or anesthesia, exercise usually is the triggering factor (4).

Diagnosis may be challenging, as clinical signs vary in severity from mild stiffness after exercise to a marked reluctance to move, swollen and painful gluteal muscles, profuse sweating, elevated respiratory and heart rates, myoglobinuria and, in rare cases, recumbency and death (3,5). Some individuals appear to be particularly predisposed to ER and have repeated episodes after levels of exercise from slow walking to maximal exertion (4).

Diagnosis of ER can be made on the basis of history (muscle cramping and stiffness, usually after exercise), myoglobinuria, moderate to marked elevations in levels of serum CK, LDH, and AST, and, or, a muscle biopsy showing histological lesions (4,5). Although muscle was not biopsied in this case, the filly showed all clinical signs of ER. In moderate and severe cases of ER, significant amounts of myoglobin are released from injured muscles and excreted in the urine. The frequency of myoglobinuria increases as muscle damage becomes more severe. Free myoglobin may precipitate in renal tubules, causing in tubular degeneration. In severely affected patients, deterioration and blockage of the renal tubules by myoglobin casts may result in acute renal failure (3). The serum enzymes CK, LDH, and AST become increased in the listed order during an episode of ER, and are cleared in the reverse order (3). High serum CK, specifically, indicates acute muscle necrosis. The level of this enzyme peaks 6 h after muscle damage and returns to normal within 2 to 3 d after resolution of rhabdomyolysis. Serum LDH and AST are not muscle specific, and serum activities increase with both muscle and liver necrosis. However, in ER, elevated LDH and AST values reflect the time interval since the muscle was damaged. Values increase during the first 12 h to 24 h after muscle damage and remain elevated for 1 wk to 2 wk (3,6). Although it is helpful to have a blood profile when making a diagnosis of ER, elevation of serum enzymes may be variable and must be interpreted to reflect differences in horses' training schedules and fitness (6).

Histologically, degenerative lesions can be detected in the highly glycolytic, fast twitch skeletal muscle fibers of affected horses. Skeletal muscle can repair and regenerate within 4 to 8 wk after an episode of ER (5).

Causes of the ER syndrome are not completely understood, and probably involve several pathophysiologic mechanisms. Certain horse breeds appear to be predisposed, and a familial basis has been suggested (7). Other possible factors include heavy musculature, irregular exercise, high-grain diet, nervous disposition, stress, age, and female sex (4,7). Many studies have suggested that nutritional factors, such as electrolyte imbalances and vitamin and selenium deficiencies, contribute to the disorder. Viral infections, hormonal imbalances, metabolic abnormalities, and abnormal regulation of intracellular calcium concentration have also been identified as possible causes (6,7).

The therapeutic goals for ER are to control pain and anxiety, restore fluid and electrolyte balance, and prevent further muscle and kidney damage (8). Treatment depends on the severity of the episode in the individual. In acute rhabdomyolysis, exercise should be stopped immediately. Supportive care is important to make affected horses as comfortable as possible. When horses are showing signs of moderate to severe generalized muscle cramping and pain, they often become more comfortable after administration of nonsteroidal anti-inflammatory drugs (NSAIDS). Other agents, such as detomidine, butorphanol tartrate, and meperidine hydrochloride, may be used additionally for severe pain. If dehydration is evident, IV fluids are indicated before other drugs are administered (6). These restore fluid and electrolyte balance, and prevent the possibility of renal failure induced by NSAIDS in a dehydrated animal (4,8). Since renal failure is also a possibility in horses with myoglobinuria, serum creatinine and urea nitrogen levels should be evaluated. If they are increased, aggressive fluid therapy is required to prevent renal damage (4).

As many factors predispose horses to tying-up, and specific causes may not be identified, there is no definitive treatment protocol (4). As a result, many diverse treatments have been used in horses with a history of ER in an attempt to prevent further muscle damage. For example, dantrolene sodium, phenytoin, methocarbanol, low doses of tranquilizer, electrolytes, sodium bicarbonate, and vitamin E and selenium supplements have been suggested as treatments for ER, with varying degrees of success (8,9). Presently, the most effective protocol for minimizing recurrence of ER includes establishing a standardized daily routine and providing a diet that is low in soluble carbohydrates and high in fat (4), as in the case presented here.

Horses with a history of tying-up should have an individualized exercise program. The length of time a horse should rest after a tying-up incident is variable, depending on the extent of muscle damage (6). Once the initial stiffness has subsided, hand walking should be initiated. When serum CK levels return to normal, training can be gradually resumed. The exercise schedule should match the degree of exertion to the horse's underlying state of training (3,5). Once started on such a program, these horses benefit from regular or, preferably, daily exercise; daily pasture turn-out; and as little stall rest as possible. Any change in the intensity or duration of exercise should be undertaken carefully (4,5).

Feeding routines should be altered simultaneously with the change in exercise. Recurrence of rhabdomyolysis may be minimized by decreasing the amount of soluble carbohydrates in the diet. Grain, sweet feed, and molasses should be minimized. Instead, the diet should be based on high quality hay, combined with balanced vitamin, mineral, and electrolyte supplementation (5). Horses with ER must receive the minimum number of calories necessary to meet their energy needs (6). Foods high in fat, such as rice bran, corn oil, or commercially available soy bean-rice bran, may be used if additional calories are necessary. High fat diets may help to change the nervous behavior of an affected horse or stabilize muscle membrane components (4). Energy intake should be decreased for a horse that must be rested for a period of time (5).

The attainable level of exercise for horses with a history of ER varies. Some horses compete successfully in various equestrian disciplines, while others continue to have episodes of tying-up, despite carefully controlled exercise, diet, and medical management. In these situations, owners may become frustrated with the demands of constant management, and mares may be retired for breeding (4). As it is possible that susceptibility to rhabdomyolysis has a genetic component, this practice may propagate ER in subsequent generations (7). Further research into the etiology, treatment, and prevention of the tying-up syndrome is essential for improved understanding of this disorder.