Introduction
Low-intensity blood flow restriction (BFR) training is routinely performed in Japan. According to the guidelines of the American College of Sports Medicine (ACSM) for resistance training, 60–70% 1 repetition maximum (1RM) is recommended to improve muscle strength during novice to intermediate levels of exercise (8). However, previous studies have reported muscle hypertrophy and increased strength after BFR training with intensity as low as 20% 1RM (16). These positive effects of resistance training are considered to be due to multiple mechanisms, such as mechanical stress, endocrine responses, and metabolite accumulation (6). Levels of growth hormone and insulin-like growth factor 1, the production of which has been reported to lead to increased protein synthesis and result in muscle hypertrophy, are significantly higher after BFR training than high-intensity training without BFR (1,27).
However, information regarding the most effective BFR training protocol with respect to exercise intensity or occlusion pressure and duration is scarce (21). In addition, a number of complications, such as subcutaneous hemorrhage or temporary numbness due to BFR training have been reported (9). Although rhabdomyolysis is a serious complication related to traditional resistance training, to our knowledge, only 1 case of rhabdomyolysis caused by BFR training has been reported (11). Here, we report a rare case of a patient presenting with severe rhabdomyolysis accompanied by acute tonsillitis the day after BFR training.
Case Description
History
The patient was a 30-year-old obese Japanese man (height, 1.82 m; weight, 92.9 kg; body mass index, 28.1) with no remarkable medical history, including muscular disorders. He had no family history of rhabdomyolysis. Although he had played football frequently throughout university, he stopped after graduation, gained weight due to physical inactivity and overeating, and subsequently joined a gym. On the first day of training, he performed squats (3 sets of 20 reps) with leg muscle BFR under the instruction of a qualified trainer. No further information regarding exercise intensity or occlusion pressure was available. Because of excess fatigue and pain after BFR training, he stopped BFR training and instead performed normal upper extremity resistance training without BFR for the rest of his exercise session. The next morning, he developed severe muscle pain in his upper and lower extremities with high fever and pharyngeal pain. He went to a local clinic and was prescribed the following medications: acetaminophen, oseltamivir, clarithromycin (CAM), carbocysteine, tranexamic acid, and levocetirizine hydrochloride. That same evening, he was admitted to our hospital with worsening muscle pain accompanied by brown urine.
Clinical Examination
Vital signs were as follows: temperature, 39.9° C; heart rate, 111 b·min−1; respiratory rate, 14 breaths·min−1; and blood pressure, 133/87 mm Hg. Physical examination was otherwise normal except for severe tenderness and mild swelling of the bilateral upper and lower extremities. No significant neurological abnormalities were noted.
Diagnosis and Management
Laboratory findings are shown in Table 1. The patient was diagnosed with acute rhabdomyolysis based on serum creatine phosphokinase (CPK) level of 56,475 U·L−1 and urine myoglobin of >3,000 ng·ml−1, accompanied by acute tonsillitis, based on a white blood cell count of 17,390·μl−1 and C-reactive protein of 10.43 mg·dl−1. Levels of other muscle enzymes (aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase) were also markedly elevated. Rapid influenza antigen detection test results were negative, and electrocardiogram showed no significant findings of ischemic cardiac disease. Fatty liver was detected by abdominal ultrasound. A number of factors were deemed potentially related to the onset and exacerbation of rhabdomyolysis, including excessive BFR training, bacterial infection, and medications. The patient was treated with rapid and aggressive infusion of intravenous fluids, and CPK levels decreased after peaking at 89,824 U·L−1 on day 2 in hospital without inducing acute renal failure. Acute tonsillitis was also improved after administration of an antibacterial drug (cefazolin). Group A β-hemolytic streptococcus (Streptococcus pyogenes) was confirmed by culture of a throat specimen, and blood culture was negative. The patient was discharged on day 10.
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Table 1.: Laboratory test results from time of admission to discharge.*†
Discussion
This is a rare case report of rhabdomyolysis after BFR training. Rhabdomyolysis is a complex medical condition involving the rapid dissolution of damaged or injured skeletal muscle (28). An elevated plasma CPK level (≥10 times the upper limit of normal) followed by a rapid decrease is the most sensitive laboratory finding pertaining to muscle injury, whereas hyperkalemia, acute renal failure, and compartment syndrome represent major life-threatening complications (12,31). Muscle pain, weakness, and brown urine are considered characteristic symptoms of rhabdomyolysis. Notably, however, more than 50% of sufferers do not experience muscle pain or weakness. Additional systemic symptoms include fever, general malaise, tachycardia, nausea, and vomiting (3).
On reviewing the literature, the most common causes of rhabdomyolysis were substance abuse (34%), medication (11%), trauma (9%), and epileptic seizures (7%), with less common causes of metabolic disturbance, infections, local muscle ischemia, generalized muscle ischemia, prolonged immobilization, exercise, and excessive temperature (31). Excessive physical exertion, such as weightlifting, marathon and military training (2,5,20), has been reported to cause exercise-induced rhabdomyolysis. In addition, low baseline fitness levels and early introduction of repetitive eccentric exercises (squats, push-ups, and sit-ups) are risk factors for developing exercise-induced rhabdomyolysis (13). The present case had no suspicions of inherited underlying predispositions, such as positive family history or recurrence of rhabdomyolysis or muscle cramps (31). Therefore, in our patient, excessive BFR training was considered the first factor responsible for the onset of rhabdomyolysis. Low-intensity BFR training typically yields high levels of perceived exertion and pain (30). However, rhabdomyolysis is generally considered a rare complication of BFR training. Nakajima et al. reported that the incidence of complications due to BFR training in Japan was as follows: subcutaneous hemorrhage (13.1%), numbness (1.297%), cerebral anemia (0.277%), cold sensation (0.127%), venous thrombus (0.055%), pulmonary embolism (0.008%), rhabdomyolysis (0.008%), and deterioration of ischemic heart disease (0.016%) (17). However, their report provided no further information on cases of rhabdomyolysis. Furthermore, Takarada et al. (27) reported no significant difference in CPK levels before and 24 hours after BFR training. We only found 1 case report of a 31-year-old man who played ice hockey and presented with rhabdomyolysis caused by BFR (11). Although the protocol was unspecified in the present case, intensity or occlusive pressure might have been inappropriate considering his low baseline fitness level and excessive fatigue and pain after performing BFR training. Although a number of factors—including the pressure of occlusion used, cuff location, width and type, exercise intensity, volume, and interset rest periods—can affect acute responses to BFR training (24), no guidelines have been established for BFR training. As such, BFR methodology tends to be based on the experience of individual instructors in a given facility.
Although the application of external occlusive pressure is considered sufficient for the maintenance of arterial inflow while occluding venous outflow of blood distal to the occlusion site (21), occlusive pressure has varied between reports (1,15,26,27). Although previous reports cited occlusive pressure exceeding 200 mm Hg (1,27), pressure for the lower body is now commonly based on a percentage of an individual's brachial systolic blood pressure (e.g., 130%) (15). However, Sumide et al. (26) reported that beneficial effects of BFR training have been observed even when the occlusive pressure applied was only 50 mm Hg. In the present case, when occlusive pressure was sufficiently high for the restriction of arterial blood flow, prolonged ischemia caused local muscular necrosis. In a previous case report, rhabdomyolysis was caused using occlusive pressure constantly maintained at 100 mm Hg during a knee extension exercise with BFR (11).
Although the optimum frequency and duration of BFR training remains unclear, a meta-analysis revealed that training 2–3 days per week seemed to maximize the training adaptation, and muscular strength does not significantly increase until the 10-week time point (16).
Recent recommendations for BFR training have stated that participants with complications, such as history of deep-vein thrombosis, pregnancy, and varicose veins, should avoid this training method (23). In addition, low-intensity BFR training is reported to induce greater acute hemodynamic responses than traditional resistance exercise without BFR (29). To prevent serious complications related to BFR training, guidelines for appropriate BFR training should be established.
Secondary factors that exacerbate exercise-induced muscle damage have been reported, such as dehydration, existing bacterial or viral infections, heat stress, and nutritional supplement and drug use (25). In the present case, bacterial infection was also suspected to be related to muscle damage. Although the patient displayed no symptoms of S. pyogenes infection during BFR training, he may have still been in the 24- to 72-hour incubation period of this infection (4). To our knowledge, however, only a few case reports of rhabdomyolysis related to S. pyogenes infection have been published to date (10,22).
In addition, the medications prescribed at the clinic the patient visited might have promoted rhabdomyolysis. Macrolide antibiotics such as CAM inhibit the metabolism of HMG-CoA reductase inhibitors (statins) that are metabolized by CYP3A4. This interaction might result in myopathy and rhabdomyolysis (14). Although the patient did not take statins, there are a few case reports of rhabdomyolysis related to CAM monotherapy (19). Similarly, a small number of case reports mention rhabdomyolysis associated with overdose of acetaminophen (18). In addition, influenza A virus has also been recognized as a risk factor for rhabdomyolysis (7). To our knowledge, however, rhabdomyolysis related to oseltamivir has not been reported.
Given the present findings, we consider several factors, including excessive BFR training, bacterial infection, and medication, to have contributed to the onset and exacerbation of rhabdomyolysis in the present case. Two or more causative factors have been reported in 60% of patients diagnosed with rhabdomyolysis (31). Interestingly, although BFR training was only performed for the lower extremities, the patient experienced severe muscle pain in both upper and lower extremities. Factors other than BFR training might therefore be responsible for muscle damage.
Conclusions
Although BFR training induces muscle hypertrophy and increases strength similar to traditional resistance training, guidelines have yet to be established for this new type of training. Inappropriate BFR training, particularly in cases of deconditioning—such as low fitness level, bacterial or viral infections, or medication—has a risk of rare yet severe complications such as rhabdomyolysis. BFR training should therefore be performed with careful consideration of the physical condition and strength of the individual. Adjustments to reduce the occlusion pressure or intensity are required, depending on the condition of the patient, to avoid complications related to BFR training.
Acknowledgments
The authors thank the patient for consenting to the publication of this report.
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