Exertional rhabdomyolysis occurs in response to strenuous physical activity where exercise places stress on the muscle causing damage to the muscle fibers (2,7,9,10,12,22). The more strenuous or prolonged the exercise, the more damage is incurred. When muscle fibers are damaged, muscle proteins such as creatine kinase (CK) and myoglobin are released into the blood. Although CK and other intramuscular proteins are cleared from the blood by the reticuloendothelial system, myoglobin is cleared by the kidneys. High blood myoglobin levels will first “spill over” into the urine, resulting in myoglobinuria (dark urine) and then can precipitate in the kidneys, resulting in renal failure (9,10). Few incidents of rhabdomyolysis, however, result in renal failure. Rhabdomyolysis can be life threatening due to several factors, including renal failure, hyperkalemia, and disseminated intravascular coagulation.
Exercises that are biased toward eccentric contractions, where the muscles are lengthening while trying to contract, are particularly effective in damaging muscle fibers because of the increased strain they place on muscle tissue (3). An example of an eccentric contraction is lowering weights in a controlled manner (often called “negatives” in the gym). Exercises with repetitive, strenuous eccentric contractions can result in rhabdomyolysis. Although numerous cases of exertional rhabdomyolysis have been reported in the literature, these cases mostly involve individuals who were inexperienced exercisers, uneducated in fitness and health principles, dehydrated or heat stressed, taking drugs, ill, or military recruits in basic training (1,5,6,13,14,19,23,24).
We report here two cases where individuals, both well educated and experienced in fitness, were encouraged by exercise leaders in a local health club to overexertion during their exercise routine leading to rhabdomyolysis.
METHODS AND RESULTS
The first case is a 22-yr-old female college senior, height 172.7 cm and weight 59.5 kg, without any underlying disease state. She agreed to the use of her clinical data for this report. She was taking Allegra (180 mg·d−1) and Flonase (one spray twice per day) for seasonal allergies and Allese oral contraceptive pills for regulation of menses. She usually exercised by running 3–5 miles daily and lifted weights 5 d·wk−1. Her typical resistance-training regimen was to exercise the legs on Tuesdays and Thursdays and the upper body on Mondays, Wednesdays, and Fridays. On the exercise day that precipitated the rhabdomyolysis event, a personal trainer at the health club encouraged the woman to increases the repetitions and weights for the exercises. She performed squats and lunges (number of repetitions not known) and worked the calf muscles to exhaustion. She was experiencing profound fatigue in her legs, which shook noticeably. The trainer had to assist the woman in walking from one exercise machine to another. She was urged on despite her statements that she wanted to quit. As reported by the subject, the room temperature was comfortable, estimated to be about 70–75°. She was drinking fluids during the workout, consuming an estimated 72 ounces of fluid within the exercise hour.
The next day the woman experienced a “normal” amount of muscle soreness. At 48 h postexercise, the soreness and pain in her legs became severe. She also experienced extreme pain in her back and under her ribs of unknown origin, and these latter complaints prompted her to seek medical attention at a local hospital emergency department. Urinalysis showed large blood in the urine by dipstick but was normal by microscopic analysis (suggesting the presence of myoglobin). The color and specific gravity were normal. Leukocyte esterase was moderate and the white blood cell/HPF ratio was 8. Her serum CK level was 234,000 U·L−1; myoglobin levels were not assessed. Blood chemistry is presented in Table 1. She was diagnosed with rhabdomyolysis and admitted to the hospital. She received 4-L intravenous normal saline in the emergency department. Upon admission, she received two additional 1-L normal saline boluses, with 1 AMP HCO3·L−1. She was then placed on continuous normal saline infusion at 200 cc·h−1. Upon release from the hospital the following day (3 d postexercise), repeat CK level was 34,400 U·L−1; urinalysis was normal. At 6 d postexercise, the CK level was 57,850 U·L−1, and again blood was noted. No further CK levels were reported. At 7 d postexercise her urinalysis was normal.
She eventually informed the trainer of what had happened. She reported that the trainer said he had never heard of this happening (exertional rhabdomyolysis) as this was not covered in his certification in health and fitness (the patient did not know the exact certification).
This case presents a 37-yr-old male, height 177.8 cm and weight 77.3 kg, who was a multiple sport athlete in college who had participated on an Olympic Handball Team (10 yr ago). His only experience with weight training was in 1998 that was self-guided (no trainer). He agreed to the use of his clinical data for this report. He had been relatively sedentary except for his active job as an emergency physician. He had no underlying disease and took no medications except for nutritional supplements. He went to a local health club (the same national chain as reported in case 1) where the personal trainer, instructed him to perform three sets of four types of exercises on a rowing machine to stress the upper-back muscles, three sets of biceps curls, three sets of dumbbell curls, and several types of lower back/abdominal muscle exercises. His trainer reduced the amount of weight used during subsequent sets, to allow for the completion of 10–12 repetitions. He vomited after the session. There appeared to be no heat stress or dehydration. The next day he experienced extreme soreness and canceled the following day’s training. One week after that exposure, he returned to the health club, where chest and triceps muscle exercises were performed in the same manner as on session 1. These muscle groups may have been less fit than the muscle groups exercised in the previous session and therefore more susceptible to damage. The following day, he could not bend his arms. Forty-eight hours after the exercise, he noted dark urine. Suspecting rhabdomyolysis, he started to force fluids. His urine output decreased, and his urine at 96 h postexercise was very dark. He submitted his blood sample to the laboratory, and the CK was 19,746 U·L−1. Blood chemistries are presented in Table 2. The urinalysis showed large blood with a normal microscopic exam (suggesting the presence of myoglobin). He sought the help of a nephrologist at the hospital, who recommended fluids and bicarbonate to maintain the pigment in a soluble state. After 24 h, he sent a repeat blood sample with the resulting CK value of 70,158 U·L−1. The next day the CK value was 45,461 U·L−1, and the pain had subsided. Although this individual was taking no medication, he had recently started to take the dietary supplement creatine on a loading dosage. He took 20 g·d−1 for 5 d and then 5 g·d−1 for 2 d before the onset of symptoms and discontinued use after developing symptoms.
In both cases, the patient presented with classic signs of rhabdomyolysis. These cases involved otherwise healthy individuals where the primary factor precipitating the event was overexertion encouraged by a trainer. There are secondary factors that can exacerbate exercise muscle damage such as dehydration, genetic conditions such as sickle cell trait and malignant hyperthermia (4,24), metabolic defects in the muscle (15), existing bacterial or viral infections (13), heat stress (11), and nutritional supplement and drug use (1,18). In case 1, there were no apparent risk factors. It is unlikely that the oral contraceptive or allergy medication was a factor.
In case 2, the man admitted using creatine supplements. A recent study showed that creatine supplementation did not alter thermoregulatory responses during exercise (25) and did not exacerbate exercise-induced muscle to damage (16). Although there has been suggestion that creatine can increase dehydration, this has not been proven. Commercially available creatine products do not have to meet the same quality control standards of pharmaceuticals. Thus, there is concern (8) that these products, intentionally or otherwise, contain impurities, higher or lower doses than stated on the label, or other active ingredients, including stimulants, not stated on the label that might be a factor contributing to rhabdomyolysis. Kamber et al. (8) analyzed 75 different nutritional supplements and found that although many were contaminated with other ingredients including the drugs ephedrine and caffeine, the seven creatine supplements were not found to be contaminated. Although Sandhu et al. (19) reported three cases where rhabdomyolysis was associated with creatine supplements, the subjects were also using amino acids and ephedrine. There is one report of compartment syndrome and rhabdomyolysis in a weight lifter who had been taking the loading dose (five times the maintenance dose) for 1 yr before the incident (18). Thus , it is unlikely that creatine played a major role in the development of rhabdomyolysis, but it cannot be ruled out as a secondary factor.
Some individuals may be particularly susceptible to exercised-induced rhabdomyolysis. About 3% of subjects in research studies of exercise-induced muscle damage of the elbow flexors show dramatic increases in CK, with some subjects as high as 40,000 U·L−1 after eccentric exercise (the average response is about 4000 U·L−1 (20)). Only one limb and one muscle group is exercised in these studies so that the amount of myoglobin in the blood will never reach levels that will result in acute renal failure. In addition to the high CK, these subjects generally present with profound arm swelling and prolonged strength loss lasting up to 2 months or more. For most of these subjects, it is unknown why they are “high responders,” as no accompanying secondary factors have been observed. The authors suggest that some individuals may have a genetic predisposition making their muscles more susceptible to damage and that this trait is unmasked only under extreme exercise stress, like performance of maximal eccentric contractions or under the direction of an overzealous trainer, as in these case reports.
The incidence of rhabdomyolysis is less in women than men (9). However, Schimpf et al. (21) also reported a case of rhabdomyolysis in a woman who had consulted a personal trainer. This 25-yr-old woman had previously been an athlete and wanted to improve her condition and lose weight. The trainer encouraged her to push herself through several types of exercise routines. Forty-eight hours after the exercise session, she was admitted to the hospital with a diagnosis of rhabdomyolysis. Rinard et al. (17) found that women and men experienced the same amount of muscle damage in response to a standard exercise. Thus, it is tempting to suggest that the higher incidence of rhabdomyolysis in men is due to the fact that more men may be in situations of being “pushed” to overexert themselves.
It is of interest to note that one of the reported cases is a physician and the other is a very fit young college woman. Fortunately, the physician recognized the symptoms of rhabdomyolysis early and sought diagnosis and treatment. The woman, being a regular exerciser, also recognized a problem and sought help early. Their quick action likely prevented acute renal failure and possibly a more devastating outcome. Both individuals followed the directions and encouragement of the personal exercise trainers at local health clubs, who may have pushed them to overexertion. Although this may be a rare situation, it should serve as a warning. We urge those involved with the education and certification of exercise trainers to include rhabdomyolysis in their syllabus. Prospective exercise leaders must be informed of this potentially dangerous outcome from overexertion.
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