Stan Reents, PharmD
05/06/2007 10:25 AM
Last Revision: 09/14/2013 08:09 PM
"Exertional rhabdomyolysis" is a rare, but serious complication of too much exercise. It can affect people of any race, age, or fitness level. Consider the following cases (by the way, these are real....I did not make them up!)
• Case #1: A 19-year old college freshman experienced 2 episodes of rhabdomyolysis while playing competitive ultimate frisbee. The first episode occurred following a 5-hr frisbee tournament (her actual playing time was estimated to be 3 hours).
At the end of the tournament, she developed severe, diffuse muscle soreness. She was unable to straighten her elbows and knees and had difficulty standing because of soreness in her back muscles. Her urine became brown-colored but she did not seek medical attention. The muscle soreness resolved after 3 days.
Her second episode of rhabdomyolysis occurred 2 weeks later. This time, she participated in a 2-hr frisbee scrimmage followed by a 2-hr karate class. Shortly thereafter, she experienced severe muscle cramping and sought medical attention.
The following day, her CK (creatine kinase, an enzyme found in muscle cells) levels peaked at 59,000 U/L. Over the following week, the CK level fell to 266.
She did not recall any illness or fever preceding these 2 episodes and was not taking any medication. Until this point in her life, this young woman had no history of rhabdomyolysis. In high school, she played tennis and ran track. She tolerated workouts of up to 2 hours without difficulty. She was a sprinter, but could run 2 miles with no problem. It was subsequently determined that she had a genetic predisposition for rhabdomyolysis (Krivickas LS. 2006).
• Case #2: A 40-year old black male developed rhabdomyolysis in his biceps after doing several sets of "negative curls". These are exercises where a spotter helps lift a heavy barbell up (concentric phase), and then the weight-lifter lowers the barbell (without assistance) until his arms are in an extended position (eccentric phase). Roughly 18 hours after doing negative curls, this athlete experienced severe biceps pain and could not fully extend his arms. His CK levels reached 76,000 U/L (normal range: 60-320 U/L) (Bolgiano EB. 1994).
• Case #3: A 21-year old inmate participated in a prison hazing ritual where he had to move 10 chess pieces on the floor. (I won't mention which part of his anatomy was used to pick up the chess pieces, but, suffice to say it wasn't his hands!) The chess pieces were lined up on the floor and the prisoner had to squat to first pick them up, then had to squat again to put them down. This required approximately 110 deep knee bends.
Within 12 hours, he was unable to leave his bed because of severe pain in his anterior thighs. Three days later, he was taken to the hospital with complaints of brown urine and nocturia.
On physical exam, his thighs were mildly swollen and his quadriceps were exquisitely tender. He was unable to flex his knees. He had protein in his urine, and his CK level was greater than 160,000 U/L. With treatment, the CK levels returned to normal after 12 days (Frucht M. 1994).
CAUSES OF EXERTIONAL RHABDOMYOLYSIS
Exertional rhabdomyolysis is largely unpredictable. It can happen to persons of either sex, and any age, and it can be caused by a variety of physical activities. When it occurs after exercise, it doesn't always require the exercise session to be extreme. In case #3 above, it occurred after only 110 deep knee bends, which were probably completed in no more than 15-20 minutes. A 29-year old man developed rhabdomyolysis after doing 30-40 sit-ups per day for 5 consecutive days (Kao PF, et al. 1998). In another report, over 100 high schoolers developed rhabdomyolysis after doing 120 push-ups in 5 minutes (Lin AC, et al. 2005).
It appears that the key factor in many cases is an abrupt increase in the intensity of exercise. Consider the following examples:
• A 22 year-old college senior whose usual exercise routine included running 3-5 miles per day and lifting weights 5 days per week, developed rhabdomyolysis when her personal trainer pushed her too hard. On the day that precipitated rhabdomyolysis, both the repetitions and the amount of weight were increased. She performed squats and lunges and worked the calf muscles to exhaustion. She experienced profound fatigue in her legs, which shook noticeably. The personal trainer had to assist the woman in walking from one exercise machine to the other and he urged her to continue despite her protests. Forty-eight hours later, she experienced severe pain in her legs and back. She went to the emergency department where it was determined that she had blood in her urine and her CK value was 234,000 U/L. She was admitted for treatment and gradually her CK levels returned to normal (Springer BL, et al. 2003).
• During a 6-month Amphibious Task Force deployment to the Mediterranean Sea, five sailors and Marines developed severe arm pain. Each patient had begun a vigorous upper-extremity work-out program in the ship's weight room 1-3 days prior to the onset of these symptoms. A medical exam revealed elevated serum muscle enzymes and the presence of blood in the urine. All subjects responded to IV fluids, alkalinization of the urine, and rest (Brown JA, et al. 1994).
In addition to strenuous exercise, a surprisingly wide variety of activities have been associated with exertional rhabdomyolysis. It has occurred after conga drumming (Furie B, et al. 1974), karate kicking (Russell SM, et al. 1975), mechanical bull riding (Powers RD, et al. 1981), hiking (Koizumi T, et al. 1996) and even cheer-leading training (Mahakkanaukrauh A, et al. 2003).
RHABDOMYOLYSIS vs. DELAYED-ONSET MUSCLE SORENESS (DOMS)
Research shows that CK levels can reach 3000 U/L in men 24 hours after a marathon (Rogers MA, et al. 1985). Running a marathon is indeed hard on the body, but that doesn't even come close to the degree of muscle injury that characterizes rhabdomyolysis where CK levels can exceed 300,000 U/L (Hamer R. 1997).
So, what's the difference between rhabdomyolysis and routine post-exercise muscle soreness? Here's an example:
Several years ago, I entered the MS-150. (For those of you unfamiliar with this event, it is a fund-raiser for multiple sclerosis and requires you to ride a bike 150 miles over 2 days.)
I had done it before, so I knew what I was in for. But, like clockwork, just as we took off on Saturday at 7AM, it began to rain. And it rained pretty much all day long. We rode 80 miles that day. Aside from being really annoyed by the weather, I felt OK at that point.
The next day, the sun was out, but now we were riding into a stiff headwind. I battled it for hours.
For several days afterwards, my thighs were pretty darn sore...probably the worst I have ever experienced. I didn't get checked out medically, but my urine never turned dark, so I don't believe I had rhabdomyolysis. Rather, what I had is called "delayed-onset muscle soreness (DOMS)".
Unlike rhabdomyolysis, DOMS is fairly predictable. It's also not nearly as serious. In some cases, rhabdomyolysis has been fatal. DOMS is discussed in greater detail in other reviews. (see "Pain Medications and the Athlete").
During rhabdomyolysis, the contents of skeletal muscle cells are dumped into the blood stream. The two most important factors are creatine kinase, CK (a muscle enzyme, sometimes abbreviated "CPK"), and myoglobin (a muscle protein). Extremely elevated concentrations of CK in the blood confirms the diagnosis, however, it is the presence of myoglobin in the urine that generally alerts the athlete that something is really wrong, causing them to seek medical attention. When myoglobin appears in the urine, the urine color changes to a dark brown.
So, the diagnosis of rhabdomyolysis focuses on 3 details:
- severe, incapacitating muscle pain
- elevated levels of creatine kinase (CK) in the blood
- myoglobin in the urine
Finally, it's possible to have elevated CK levels after strenuous exercise without any symptoms. This is called "asymptomatic rhabdomyolysis".
In Greece, there is a race called the "Spartathlon" that requires running from Athens to Sparta in under 36 hours. (The distance is 155 miles!) After one of these events, blood levels of CK were measured in 39 athletes within 15 minutes after completing the race. It was found that the average post-exercise CK level was 43,763 +/-6,764 IU/L. Although this is a very high CK value, none of the runners required medical attention during or after the race (Skenderi KP, et al. 2006).
RISK FACTORS FOR RHABDOMYOLYSIS
So, why do most athletes only experience the benign and predictable "DOMS" after strenuous exercise while others develop the very serious condition known as rhabdomyolysis?
• Genetics: One explanation is that some athletes have a genetic predisposition. Athletes with "CPT II deficiency", an inherited trait, have a higher likelihood of developing rhabdomyolysis. This genetic condition is common among Ashkenazi Jews. The college co-ed described in case #1 above was of European Jewish descent (Krivickas LS. 2006).
• Eccentric exercise: Eccentric exercise means the skeletal muscle fibers are lengthening while exerting force. It is well known that eccentric exercise causes more muscle soreness and muscle trauma than concentric exercise. Eccentric exercise was the cause in case #2 (negative curls) and may have contributed to case #3 (squats) described earlier.
• Out-of-shape: The physical conditioning of the athlete does appear to make a difference. Yet, as the cases I have described here suggest, even young healthy athletes can develop rhabdomyolysis.
• Hot weather/heat stroke: Heat stroke is associated with rhabdomyolysis. This may be an aggravating factor in some cases of exercise-induced rhabdomyolysis.
PREVENTING EXERTIONAL RHABDOMYOLYSIS
Even though exercise-induced rhabdomyolysis is rare, it is important to consider prevention strategies:
• Train properly: Research shows that when athletes and unfit subjects participated in the same amount of exercise, CK levels rose only in the unfit subjects (Karamizrak SO, et al. 1994). Thus, the intensity of exercise is not the only variable...an abrupt increase in exercise intensity relative to your current fitness level is important.
• Consume a recovery drink immediately after exercise: Several recent studies show that CK levels post-exercise are lower in athletes who consume a sports drink that contains protein (aka: "recovery" drinks) (Romano-Ely BC, et al. 2006). (See the related story "Sports Drinks and Recovery Drinks" for a list of commercially available sports drinks that contain protein.)
Q: How can I tell if I have simple post-exercise DOMS or if it is the more serious rhabdomyolysis?
ANSWER: The diagnosis of rhabdomyolysis is made by measuring CK levels and myoglobin levels in the blood. If your muscle soreness is severe, and, if your urine turns dark brown ("Coca-Cola urine"), then you should seek medical attention immediately. The release of massive amounts of muscle proteins into the circulation can lead to kidney failure, which can be very serious. Fortunately, with early and proper treatment, many athletes who develop rhabdomyolysis can make a complete recovery.
Q: Some drugs can cause myopathy and/or rhabdomyolysis. Can these drugs increase the risk of exertional (ie., exercise-induced) rhabdomyolysis?
ANSWER: Several case reports show that 2 categories of drugs have been involved in exertional rhabdomyolysis: (a) neuroleptic drugs of the phenothiazine type, and (b) "statins" (cholesterol-lowering drugs):
• Phenothiazine-type neuroleptics can interfere with the body's temperature regulation. And, heat stroke has been independently linked to rhabdomyolysis. At least 2 cases have been reported where subjects developed rhabdomyolysis during mountain hiking while taking phenothiazines. One of these cases was fatal (Koizumi T, et al. 1996).
• Cholesterol-lowering drugs of the "statin" group (Lipitor®, Zocor®, and others) have been associated with rhabdomyolysis independently of strenuous exercise (Deslypere JP, et al. 1991) (Wallace CS, et al. 1992).
Elevated CK levels occurred after strenuous exercise during therapy with a statin-type cholesterol-lowering drug. In one case, CK levels reached 21,000 U/L after weight-lifting (this subject also had severe muscle pain). Oddly, the elevated CK levels in these subjects normalized even though the statin drug was not discontinued (Thompson PD, et al. 1990) (Thompson PD, et al. 1991).
However, in another study, 10 subjects took lovastatin for a month, then walked downhill on a treadmill (eccentric exercise) for 60 minutes. Post-exercise CK levels were no higher with lovastatin than without (Reust CS, et al. 1991).
Nevertheless, it does seem that there is some sort of "drug-exercise interaction" going on here. Unfortunately, it's not possible to predict which patients taking statin drugs will develop rhabdomyolysis after exercise.
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ABOUT THE AUTHOR
Stan Reents, PharmD, is a former healthcare professional. He is a member of the American College of Sports Medicine (ACSM) and holds current certifications from ACSM (Health & Fitness Specialist), ACE (Personal Trainer, Health Coach) and has been certified as a tennis coach by USTA. He is the author of Sport and Exercise Pharmacology (published by Human Kinetics) and has written for Runner's World magazine, Training and Conditioning, Club Solutions, and other fitness publications.
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