This study has revealed a significant increase in the number of hospitalisations due to exercise-induced rhabdomyolysis since 2008. From 2011 to 2014, the number of admissions almost quadrupled. One reason for this may be the increasing popularity of new forms of exercise, as confirmed by the fact that 80 % of patients had engaged in strength training at fitness centres. Most of those who had practised weight training had symptoms in the arm muscles, but other major muscle groups may also be affected.
While earlier studies most commonly described exercise-induced rhabdomyolysis after endurance exercise, such as long-distance running, recent studies have shown that strength training is more likely to trigger the condition. The increase in the incidence of exercise-induced rhabdomyolysis was also confirmed by a US military study, which recorded a 30 % increase in exercise-induced cases from 2008 to 2012 (13).
Exercise-induced rhabdomyolysis has been described in connection with various forms of endurance and strength training (11). Eccentric training, as seen in CrossFit, is the form of exercise most strongly associated with the development of muscular injuries and rhabdomyolysis (14, 15). Poor fitness is a risk factor, but physically fit individuals can also be affected (16). Low fluid intake and high temperatures are considered precipitating factors (17).
Exercise combined with the use of narcotics and banned muscle-building substances, or with the use of non-steroidal anti-inflammatory drugs, statins or dietary supplements such as creatine and ephedra/ephedrine, has been associated with rhabdomyolysis (16, 18). Genetic polymorphisms may also increase risk (9). Information came to light on the use of various narcotic and performance-enhancing drugs by five persons in this study, but the relationship between rhabdomyolysis and drug use was not examined systematically and the numbers are therefore very uncertain.
In recent years there has been extensive media coverage of exercise-induced rhabdomyolysis, with stories about how the condition may be highly dangerous accompanied by information on symptoms and advice on when to seek medical attention. This may lead to more frequent diagnoses as patients visit their doctor with symptoms that they would not previously have sought advice over. On the other hand, there are probably many others who do not consult their doctor and therefore many cases that go unreported. In this study we tentatively estimated the incidence of rhabdomyolysis to be 4.5 per 100 000 population in 2014. We were unable to find any other such calculations, but a study in military personnel measured the incidence at 29.9 per 100 000 person-years (19).
It is common for some muscle damage to occur with intense physical activity. A study of 499 US military recruits revealed that after seven days of basic training, 88.5 % had elevated creatine kinase levels and 11.3 % had levels > 10 times the upper reference limit. Levels ranged from 34 IU/l to 35 056 IU/l, and the average was 1 226 IU/l after seven days. None of the recruits had symptoms or signs of rhabdomyolysis (6). Another study showed that 25 of 44 participants who completed an ultramarathon of 99 km had markedly elevated serum creatine kinase and that five of these developed myoglobinuria, although none developed renal failure (20).
The aim of rhabdomyolysis treatment is to prevent kidney injury. A retrospective analysis found that 19 % of those with exercise-induced rhabdomyolysis developed acute kidney injury, defined as a creatinine level >114.9 μmol/l, as did 34.2 % of those with rhabdomyolysis due to other causes (21). The proportion with acute kidney injury requiring dialysis was 1.6 % and 9.7 % respectively. In another study of 35 patients with exercise-induced rhabdomyolysis, none of those affected developed acute kidney injury (22).
However, serious complications of exercise-induced rhabdomyolysis have been described in several case reports (23, 24). In our study, 6 % of patients with exercise-induced disease had transient mild kidney injury but none required dialysis. Fewer of those with exercise-induced rhabdomyolysis developed renal failure compared to those with other forms of rhabdomyolysis. This may be because the causal factors in the latter group can themselves give rise to kidney injury (e.g., hypovolaemia and sepsis) and also because these patients often have considerable comorbidity, which again increases the risk of kidney injury.
Previous studies have shown that 10 – 50 % of patients with rhabdomyolysis develop renal failure (25). Although the definition of acute kidney injury varies between studies, this is reasonably consistent with our figure for the non-exercise-induced rhabdomyolysis group. A relatively large proportion of patients had electrolyte imbalance, either as a result of the rhabdomyolysis itself or its treatment. The clinical significance of this is uncertain, especially in patients with exercise-induced rhabdomyolysis.
Patients with exercise-induced rhabdomyolysis probably have a better renal prognosis than others with the same disorder, and should perhaps be treated as a separate group with distinct therapeutic criteria. Rhabdomyolysis treatment is intensive and relatively prolonged.
There have been no randomised studies comparing treatment regimes. The efficacy of urinary alkalinisation is subject to debate (7, 8, 26). The treatment involves administering large volumes of fluid intravenously, which entails a risk of complications due to overhydration. In this study none of those with exercise-induced rhabdomyolysis developed symptoms of severe hypervolaemia, whereas some of those with rhabdomyolysis due to other causes displayed symptomatic fluid retention. We did not systematically record the volume of fluid administered and the amount excreted by patients, but we did observe major electrolyte imbalance in some cases, with much of this probably due to treatment.
The current study used serum creatinine alone as an index of kidney injury and renal function. However, creatinine is an imprecise index, especially for low-grade kidney injury. Additional measures of kidney injury and previous creatinine levels were not used because patients were hospitalised with the disease. We therefore used the creatinine level at discharge as an index of kidney injury instead. However, patients with exercise-induced rhabdomyolysis had normal creatinine levels at discharge and it is thus unlikely that premorbid measurements would have revealed those with kidney injury, especially in view of the limitations related to creatinine quantification.
This study is based on a retrospective review of medical records. Patients who fulfilled the diagnostic criteria for rhabdomyolysis but who were assigned the wrong diagnostic code may have been omitted. This is most likely to apply to rhabdomyolysis as a complication of surgery. In patients with symptoms suggesting overuse of muscles in the shoulders and upper arms, the condition may for example have been coded as tendonitis.
This study is not compatible with comparing treatment strategies, but the evidence base for existing treatments is relatively limited. There is a need for studies comparing different forms of treatment, particularly for exercise-induced rhabdomyolysis, where patients have normal creatinine levels upon admission to hospital. Serum creatinine kinase levels increase approximately 12 hours after an injury and remain elevated for 2 – 3 days before gradually decreasing.
Myoglobin has a short half-life (10 – 15 min. in plasma). It may be possible to use urinary myoglobin to guide treatment: when urine dipsticks test negative for blood, treatment can be scaled down. This algorithm requires validation in a clinical trial. There is also a need for long term follow-up of rhabdomyolysis patients to determine whether they are at increased risk of renal failure in the future.
This study has revealed a clear increase in the number of hospitalisations due to exercise-induced rhabdomyolysis. We believe that new types of exercise and increased societal pressure to exercise may be contributing to the increased incidence of the condition. Renal prognosis is good, but whether the disorder leads to continued muscle weakness is unknown. Treatment is extensive and demanding, with a risk of complications, and comparative efficacy studies are required.