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Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running (strength of recommendation [SOR]: C, small observational studies). The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven’t been observed.
Be vigilant, but not hypervigilant
Tim Mott, MD
US Naval Hospital, Sigonella, Italy
Elevated CK noted on incidental testing can be vexing for physicians who treat athletes. Because asymptomatic exertional rhabdomyolysis is historically underdiagnosed and underappreciated, one may feel compelled to test all such patients for renal function, electrolytes, and myoglobinuria.1
Vigilance is mandatory—especially for symptoms of myalgia, generalized weakness, and dark urine—but this Clinical Inquiry also supports using a sound patient history and clinical judgment to avoid extensive laboratory testing or hospital admission. Indeed, patients who participate in moderate intensity, eccentric muscle contraction activities can be followed as outpatients because a correlation between CK elevation and renal dysfunction has not been detected in this group.
Evidence summary
Rhabdomyolysis is a well-described clinical syndrome resulting from injury to skeletal muscle and subsequent release of cellular contents into the extracellular fluid and circulation. It can lead to many complications, including renal failure, disseminated intravascular coagulation, and even death in 5% of cases.2 The leading causes of rhabdomyolysis include trauma, soft tissue compression, alcohol, drugs, infections, seizures, and exercise.3
Only half of patients experience muscle pain.2 Elevations occur in multiple serum markers, including CK, myoglobin, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, in either plasma or urine.4,5
Variable elevations, ranging from mild to extreme, that are discovered incidentally after exercise may cause clinical uncertainty.
No clear consensus defines CK levels in rhabdomyolysis
CK is the primary serum marker for rhabdomyolysis. It’s highly sensitive, but not specific. No clear consensus exists on what threshold of CK elevation correlates with clinically relevant disease.6 A relationship between CK elevation and the severity of disease has been established (>6000 IU/L predicts renal failure), but patients can have significant morbidity with only moderately elevated CK levels.7,8 Normal reference ranges for serum CK are 55 to 170 IU/L for males, and 30 to 135 IU/L for females.9
Recent definitions of rhabdomyolysis have been established to address muscle toxicity from lipid-lowering medications. The United States Food and Drug Administration specifies a CK level of more than 50 times the upper limit of normal (ULN)—or 10,000 IU/L—accompanied by organ damage, usually renal compromise.6 The National Lipid Association’s Muscle Safety Expert Panel has defined rhabdomyolysis as any evidence of muscle cell destruction regardless of the CK level and a causal relationship to a change in renal function. The panel further subdivides CK elevations into categories of mild (<10 times ULN), moderate (10-49 times ULN), and marked (≥50 times ULN).6
Exercise elevates CK level, but consider other factors, too
Although exercise is known to elevate CK, it produces a wide range of levels, based on a host of variables.3,10 Increases in CK are more pronounced in males, blacks, and untrained people; age doesn’t seem to be a factor.10,11 Higher-intensity, longer-duration, and weight-bearing exercise (eccentric muscular contractions and downhill running) cause the greatest rises in CK.10 Other influences include temperature, altitude, gravitational forces, noise, and vibration.
No studies firmly establish a normal range of CK elevation from moderate exercise; better data are available for extreme athletes, such as long-distance runners and triathletes. One study found that mean total CK elevations 24 hours after a marathon were 3322 IU/L (22.3 times baseline) for men and 946 IU/L (8.6 times baseline) for women.4 Another study showed that triathletes had a 12-fold mean increase in CK levels as long as 24 hours after the race.12
Eccentric exercises significantly raise CK
Exercise programs that include eccentric muscle contractions can result in significant serum CK elevations. One study followed 203 participants to evaluate the magnitude of CK elevation and the effect on renal function produced by exercise.3 After performing 50 maximal eccentric elbow flexor contractions, 55% of participants had CK elevations >2000 IU/L at 4 days after exercise; 25% had CK elevations >10,000 IU/L; 13% had levels >20,000 IU/L. None showed any evidence of renal compromise on clinical follow-up. Another study found significant increases in CK (approximate mean of 15,000 IU/L) after repetitive eccentric elbow flexor contractions in college-age males.13
Eccentric weight lifting and similar activities, like downhill running, may result in an increase in serum CK levels of 10 to 20 times normal, whereas other nonweight-bearing exercises and exercise involving no or minimal eccentric contractions, such as swimming and cycling, cause only nominal increases in serum CK.10
Recommendations
No formal guidelines from authoritative sources are available.
Acknowledgments
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.
1. Chen TC, Hsieh SS. Effects of a 7-day eccentric training period on muscle damage and inflammation. Med Sci Sports Exerc. 2001;33:1732-1738.
2. Line R, Rust G. Acute exertional rhabdomyolysis. Am Fam Physician. 1995;52:502-506.
3. Rogers MA, Stull GA, Apple FS. Creatine kinase isoenzyme activities in men and women following a marathon race. Med Sci Sports Exerc. 1985;17:679-682.
4. Craig S. Rhabdomyolysis. November 2006. Available at: www.emedicine.com/emerg/topic508.htm. Accessed September 14, 2007.
5. Clarkson PM, Kearns AK, Rouzier P, Rubin R, Thompson PD. Serum creatine kinase levels and renal function measures in exertional muscle damage. Med Sci Sports Exerc. 2006;38:623-627.
6. Visweswaran P, Guntupalli J. Rhabdomyolysis. Crit Care Clin. 1999;15:415-428.
7. Thompson PD, Clarkson PM, Rosenson RS, et al. An assessment of statin safety by muscle experts. Am J Cardiol. 2006;97:69C-76C.
8. American College of Sports Medicine Position Stand. The recommended quantity and quality of exercise for developing and maintaining cardio-respiratory and muscular fitness and flexibility in healthy adults. Med Sci Sports Exerc. 1998;30:975-991.
9. Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. 1988;148:1553-1557.
10. McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, Pa: Saunders Elsevier; 2007.
11. Noakes TD. Effect of exercise on serum enzyme activities in humans. Sports Med. 1987;4:245-267.
12. Munjal DD, McFadden JA, Matix PA, Coffman KD, Cattaneo SM. Changes in serum myoglobin, total creatine kinase, lactate dehydrogenase, and creatine kinase MB levels in runners. Clin Biochem. 1983;16:195-199.
13. Margaritis I, Tessier F, Verdera F, Bermon S, Marconnet P. Muscle enzyme release does not predict muscle function impairment after triathlon. J Sports Med Phys Fitness. 1999;39:133-139.
Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running (strength of recommendation [SOR]: C, small observational studies). The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven’t been observed.
Be vigilant, but not hypervigilant
Tim Mott, MD
US Naval Hospital, Sigonella, Italy
Elevated CK noted on incidental testing can be vexing for physicians who treat athletes. Because asymptomatic exertional rhabdomyolysis is historically underdiagnosed and underappreciated, one may feel compelled to test all such patients for renal function, electrolytes, and myoglobinuria.1
Vigilance is mandatory—especially for symptoms of myalgia, generalized weakness, and dark urine—but this Clinical Inquiry also supports using a sound patient history and clinical judgment to avoid extensive laboratory testing or hospital admission. Indeed, patients who participate in moderate intensity, eccentric muscle contraction activities can be followed as outpatients because a correlation between CK elevation and renal dysfunction has not been detected in this group.
Evidence summary
Rhabdomyolysis is a well-described clinical syndrome resulting from injury to skeletal muscle and subsequent release of cellular contents into the extracellular fluid and circulation. It can lead to many complications, including renal failure, disseminated intravascular coagulation, and even death in 5% of cases.2 The leading causes of rhabdomyolysis include trauma, soft tissue compression, alcohol, drugs, infections, seizures, and exercise.3
Only half of patients experience muscle pain.2 Elevations occur in multiple serum markers, including CK, myoglobin, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, in either plasma or urine.4,5
Variable elevations, ranging from mild to extreme, that are discovered incidentally after exercise may cause clinical uncertainty.
No clear consensus defines CK levels in rhabdomyolysis
CK is the primary serum marker for rhabdomyolysis. It’s highly sensitive, but not specific. No clear consensus exists on what threshold of CK elevation correlates with clinically relevant disease.6 A relationship between CK elevation and the severity of disease has been established (>6000 IU/L predicts renal failure), but patients can have significant morbidity with only moderately elevated CK levels.7,8 Normal reference ranges for serum CK are 55 to 170 IU/L for males, and 30 to 135 IU/L for females.9
Recent definitions of rhabdomyolysis have been established to address muscle toxicity from lipid-lowering medications. The United States Food and Drug Administration specifies a CK level of more than 50 times the upper limit of normal (ULN)—or 10,000 IU/L—accompanied by organ damage, usually renal compromise.6 The National Lipid Association’s Muscle Safety Expert Panel has defined rhabdomyolysis as any evidence of muscle cell destruction regardless of the CK level and a causal relationship to a change in renal function. The panel further subdivides CK elevations into categories of mild (<10 times ULN), moderate (10-49 times ULN), and marked (≥50 times ULN).6
Exercise elevates CK level, but consider other factors, too
Although exercise is known to elevate CK, it produces a wide range of levels, based on a host of variables.3,10 Increases in CK are more pronounced in males, blacks, and untrained people; age doesn’t seem to be a factor.10,11 Higher-intensity, longer-duration, and weight-bearing exercise (eccentric muscular contractions and downhill running) cause the greatest rises in CK.10 Other influences include temperature, altitude, gravitational forces, noise, and vibration.
No studies firmly establish a normal range of CK elevation from moderate exercise; better data are available for extreme athletes, such as long-distance runners and triathletes. One study found that mean total CK elevations 24 hours after a marathon were 3322 IU/L (22.3 times baseline) for men and 946 IU/L (8.6 times baseline) for women.4 Another study showed that triathletes had a 12-fold mean increase in CK levels as long as 24 hours after the race.12
Eccentric exercises significantly raise CK
Exercise programs that include eccentric muscle contractions can result in significant serum CK elevations. One study followed 203 participants to evaluate the magnitude of CK elevation and the effect on renal function produced by exercise.3 After performing 50 maximal eccentric elbow flexor contractions, 55% of participants had CK elevations >2000 IU/L at 4 days after exercise; 25% had CK elevations >10,000 IU/L; 13% had levels >20,000 IU/L. None showed any evidence of renal compromise on clinical follow-up. Another study found significant increases in CK (approximate mean of 15,000 IU/L) after repetitive eccentric elbow flexor contractions in college-age males.13
Eccentric weight lifting and similar activities, like downhill running, may result in an increase in serum CK levels of 10 to 20 times normal, whereas other nonweight-bearing exercises and exercise involving no or minimal eccentric contractions, such as swimming and cycling, cause only nominal increases in serum CK.10
Recommendations
No formal guidelines from authoritative sources are available.
Acknowledgments
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.
Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running (strength of recommendation [SOR]: C, small observational studies). The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven’t been observed.
Be vigilant, but not hypervigilant
Tim Mott, MD
US Naval Hospital, Sigonella, Italy
Elevated CK noted on incidental testing can be vexing for physicians who treat athletes. Because asymptomatic exertional rhabdomyolysis is historically underdiagnosed and underappreciated, one may feel compelled to test all such patients for renal function, electrolytes, and myoglobinuria.1
Vigilance is mandatory—especially for symptoms of myalgia, generalized weakness, and dark urine—but this Clinical Inquiry also supports using a sound patient history and clinical judgment to avoid extensive laboratory testing or hospital admission. Indeed, patients who participate in moderate intensity, eccentric muscle contraction activities can be followed as outpatients because a correlation between CK elevation and renal dysfunction has not been detected in this group.
Evidence summary
Rhabdomyolysis is a well-described clinical syndrome resulting from injury to skeletal muscle and subsequent release of cellular contents into the extracellular fluid and circulation. It can lead to many complications, including renal failure, disseminated intravascular coagulation, and even death in 5% of cases.2 The leading causes of rhabdomyolysis include trauma, soft tissue compression, alcohol, drugs, infections, seizures, and exercise.3
Only half of patients experience muscle pain.2 Elevations occur in multiple serum markers, including CK, myoglobin, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, in either plasma or urine.4,5
Variable elevations, ranging from mild to extreme, that are discovered incidentally after exercise may cause clinical uncertainty.
No clear consensus defines CK levels in rhabdomyolysis
CK is the primary serum marker for rhabdomyolysis. It’s highly sensitive, but not specific. No clear consensus exists on what threshold of CK elevation correlates with clinically relevant disease.6 A relationship between CK elevation and the severity of disease has been established (>6000 IU/L predicts renal failure), but patients can have significant morbidity with only moderately elevated CK levels.7,8 Normal reference ranges for serum CK are 55 to 170 IU/L for males, and 30 to 135 IU/L for females.9
Recent definitions of rhabdomyolysis have been established to address muscle toxicity from lipid-lowering medications. The United States Food and Drug Administration specifies a CK level of more than 50 times the upper limit of normal (ULN)—or 10,000 IU/L—accompanied by organ damage, usually renal compromise.6 The National Lipid Association’s Muscle Safety Expert Panel has defined rhabdomyolysis as any evidence of muscle cell destruction regardless of the CK level and a causal relationship to a change in renal function. The panel further subdivides CK elevations into categories of mild (<10 times ULN), moderate (10-49 times ULN), and marked (≥50 times ULN).6
Exercise elevates CK level, but consider other factors, too
Although exercise is known to elevate CK, it produces a wide range of levels, based on a host of variables.3,10 Increases in CK are more pronounced in males, blacks, and untrained people; age doesn’t seem to be a factor.10,11 Higher-intensity, longer-duration, and weight-bearing exercise (eccentric muscular contractions and downhill running) cause the greatest rises in CK.10 Other influences include temperature, altitude, gravitational forces, noise, and vibration.
No studies firmly establish a normal range of CK elevation from moderate exercise; better data are available for extreme athletes, such as long-distance runners and triathletes. One study found that mean total CK elevations 24 hours after a marathon were 3322 IU/L (22.3 times baseline) for men and 946 IU/L (8.6 times baseline) for women.4 Another study showed that triathletes had a 12-fold mean increase in CK levels as long as 24 hours after the race.12
Eccentric exercises significantly raise CK
Exercise programs that include eccentric muscle contractions can result in significant serum CK elevations. One study followed 203 participants to evaluate the magnitude of CK elevation and the effect on renal function produced by exercise.3 After performing 50 maximal eccentric elbow flexor contractions, 55% of participants had CK elevations >2000 IU/L at 4 days after exercise; 25% had CK elevations >10,000 IU/L; 13% had levels >20,000 IU/L. None showed any evidence of renal compromise on clinical follow-up. Another study found significant increases in CK (approximate mean of 15,000 IU/L) after repetitive eccentric elbow flexor contractions in college-age males.13
Eccentric weight lifting and similar activities, like downhill running, may result in an increase in serum CK levels of 10 to 20 times normal, whereas other nonweight-bearing exercises and exercise involving no or minimal eccentric contractions, such as swimming and cycling, cause only nominal increases in serum CK.10
Recommendations
No formal guidelines from authoritative sources are available.
Acknowledgments
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.
1. Chen TC, Hsieh SS. Effects of a 7-day eccentric training period on muscle damage and inflammation. Med Sci Sports Exerc. 2001;33:1732-1738.
2. Line R, Rust G. Acute exertional rhabdomyolysis. Am Fam Physician. 1995;52:502-506.
3. Rogers MA, Stull GA, Apple FS. Creatine kinase isoenzyme activities in men and women following a marathon race. Med Sci Sports Exerc. 1985;17:679-682.
4. Craig S. Rhabdomyolysis. November 2006. Available at: www.emedicine.com/emerg/topic508.htm. Accessed September 14, 2007.
5. Clarkson PM, Kearns AK, Rouzier P, Rubin R, Thompson PD. Serum creatine kinase levels and renal function measures in exertional muscle damage. Med Sci Sports Exerc. 2006;38:623-627.
6. Visweswaran P, Guntupalli J. Rhabdomyolysis. Crit Care Clin. 1999;15:415-428.
7. Thompson PD, Clarkson PM, Rosenson RS, et al. An assessment of statin safety by muscle experts. Am J Cardiol. 2006;97:69C-76C.
8. American College of Sports Medicine Position Stand. The recommended quantity and quality of exercise for developing and maintaining cardio-respiratory and muscular fitness and flexibility in healthy adults. Med Sci Sports Exerc. 1998;30:975-991.
9. Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. 1988;148:1553-1557.
10. McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, Pa: Saunders Elsevier; 2007.
11. Noakes TD. Effect of exercise on serum enzyme activities in humans. Sports Med. 1987;4:245-267.
12. Munjal DD, McFadden JA, Matix PA, Coffman KD, Cattaneo SM. Changes in serum myoglobin, total creatine kinase, lactate dehydrogenase, and creatine kinase MB levels in runners. Clin Biochem. 1983;16:195-199.
13. Margaritis I, Tessier F, Verdera F, Bermon S, Marconnet P. Muscle enzyme release does not predict muscle function impairment after triathlon. J Sports Med Phys Fitness. 1999;39:133-139.
1. Chen TC, Hsieh SS. Effects of a 7-day eccentric training period on muscle damage and inflammation. Med Sci Sports Exerc. 2001;33:1732-1738.
2. Line R, Rust G. Acute exertional rhabdomyolysis. Am Fam Physician. 1995;52:502-506.
3. Rogers MA, Stull GA, Apple FS. Creatine kinase isoenzyme activities in men and women following a marathon race. Med Sci Sports Exerc. 1985;17:679-682.
4. Craig S. Rhabdomyolysis. November 2006. Available at: www.emedicine.com/emerg/topic508.htm. Accessed September 14, 2007.
5. Clarkson PM, Kearns AK, Rouzier P, Rubin R, Thompson PD. Serum creatine kinase levels and renal function measures in exertional muscle damage. Med Sci Sports Exerc. 2006;38:623-627.
6. Visweswaran P, Guntupalli J. Rhabdomyolysis. Crit Care Clin. 1999;15:415-428.
7. Thompson PD, Clarkson PM, Rosenson RS, et al. An assessment of statin safety by muscle experts. Am J Cardiol. 2006;97:69C-76C.
8. American College of Sports Medicine Position Stand. The recommended quantity and quality of exercise for developing and maintaining cardio-respiratory and muscular fitness and flexibility in healthy adults. Med Sci Sports Exerc. 1998;30:975-991.
9. Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. 1988;148:1553-1557.
10. McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, Pa: Saunders Elsevier; 2007.
11. Noakes TD. Effect of exercise on serum enzyme activities in humans. Sports Med. 1987;4:245-267.
12. Munjal DD, McFadden JA, Matix PA, Coffman KD, Cattaneo SM. Changes in serum myoglobin, total creatine kinase, lactate dehydrogenase, and creatine kinase MB levels in runners. Clin Biochem. 1983;16:195-199.
13. Margaritis I, Tessier F, Verdera F, Bermon S, Marconnet P. Muscle enzyme release does not predict muscle function impairment after triathlon. J Sports Med Phys Fitness. 1999;39:133-139.
Evidence-based answers from the Family Physicians Inquiries Network