On Rhabdomyolysis

I have had many requests in the past, and even more recently after my Dehydration post, for information and advice on Rhabdomyolysis.

I am prompted by Ken, who left a comment here that he experienced symptoms similar to mine at the Bishop 50k race, his first ultra. Ken said he is interested in how to avoid rhabdo in the future. Well, that is an excellent question and we can all learn from others' mistakes (including my own) and from the medical and endurance running literature. I think it's an issue worth addressing.

So, to start, here's what Ken wrote:

"Lisa,
I was so relieved to read your blog. The Bishop 50k was my first ultra and experienced all the symptoms you described. I asked a couple of experienced runners at the finish and they hadn't heard of the symptoms I was having. I used to work as a wildland firefighter and worked in lots of extreme heat and shifts as long as 36 hours w/o ever having those symptoms. The only thing I could think of was that I drank too much Heed and not enough water during the event (water tasted so swampy). I still don't understand this rhabdo thing, but maybe I can find a local sports med doc to explain how to avoid it in the future. Thanks for the post."

I want to respond to him, but I think it's worth responding to everybody because this is real ultra stuff, the hazards inherent to our sport, that we want to avoid.

So, first, I say to Ken, CONGRATS on your first ultra! I hope you come back for more! And second, thanks for raising an important issue.

Now, to get to the gritty...

What is Rhabdomyolysis (aka rhabdo)?

Rhabdo is caused by damage to skeletal muscle, which then leaks its contents (myoglobin, potassium, phosphate) into the bloodstream.

Who gets it?

Rhabdo is seen in victims of crush injury, in those with prolonged immobility such as being in a coma, with seizures due to the tonic muscle activity, with certain immune disorders, even as a rare side effect of some of the popular cholesterol drugs (the "statins"). It can be caused by viral infections, metabolic disorders, some toxins like snake bites. Important to the ultrarunning community, rhabdo can be caused by excessive muscular activity (especially eccentric muscle activity, which is when a muscle is activated while lengthening such as in downhill running) and by hyperthermia.

So, why does this seem to be a problem for some ultrarunners but not others?

Muscles adapts with training. The less training (and I will include here also the less ultrarunning experience), the more muscle breakdown. Remember that first marathon or first 100-miler? Were you sore afterwards? How about after that 5th marathon or 5th 100-miler? Still sore probably, but not as bad? How about a hard workout versus an easy workout? We all know, muscle must break down in order to receives signals to build stronger. Hence, the weight lifting to "failure." There is certainly truth to "no pain, no gain."

But, NO, not every sore muscle is undergoing rhabdo. That is NOT the case. But when you are talking about long-distance running, such as marathons or ultras, yes, everybody - to some extent - gets enough muscle breakdown that there is release of the muscle contents into the blood, and that (the Creatine Phosphokinase - CPK - level) can be measured by a lab test. Technically, a CPK level of > 5x the normal level indicates a laboratory diagnosis of rhabdo. Normal levels are different depending on the lab, but in general it's safe to say that a level < 200 IU/L is normal. So, that means that CPK's > 1000 IU/L = rhabdo.

BUT, many, many of us ultrarunners have had CPK levels > 1000 IU/L. In the few years I have been reviewing CPK's drawn at the finish line of Western States, I have not seen ONE normal CPK value. All are elevated, and in 2006, they ranged from 2600 IU/L to 82,200 IU/L. The highest post-race CPK at Western States was, I believe, recorded at 220,000 IU/L. The average for 2006 was 22,092 IU/L. Now, these are not runners who presented sick at the finish line; these are runners who volunteered in advance to get their blood drawn at the finish...and that's an important point.

So, what separates the 2600 from the 82,200 or > 100,000 levels? Good question. There has not been a formal investigation on that. We do, however, know the risk factors for rhabdo, and so can speculate what that difference may be. Other than individual differences, influential factors include level of training for distance, heat training (if relevant) and training for the specific terrain, especially downhill running. Running intensity has been shown to influence CPK levels at much shorter distance races, that is, the faster the running, the higher the CPK, but this has NOT been shown to hold true for the ultradistance events (at least at the Spartathlon[1] or at Western States).

I can say that there was one runner, who is a phenomenal ultrarunner who ran Western States one year while training a ton and running many 100-milers and just kicking butt at the races, and his finish line CPK at Western States was low...very low. He came back another year without the training (and experience) he had the previous year, and he had one of the highest CPK levels that year. So, there is certainly a training adaptation.

How can I minimze getting rhabdo?

Well, as you can see here, it's pretty safe to say that every ultrarunner has SOME degree of muscle breakdown and rhabdo. Not to worry though, this is "normal" and doesn't mean you will be sick. (Aside, rhabdo is created in research subjects in the lab by having people do repetitive eccentric weights....it's really not hard to do!)

We can and SHOULD minimize the risks of developing it though, and that is mostly done with training and experience. Eccentric loading of muscles (e.g. downhill running) is the hardest on muscle and causes the MOST muscle breakdown. Heat also adds to the stress. So, training both for distance and heat and doing some downhill running (or running down stairs or eccentric weights or squats) are all good ways to decrease the risk of rhabdo. That said, just running more ultras will likely get your body used to the beating. :)

So, if everybody gets it, what's the worry?

The worry is that with the muscle damage and subsequent release of muscle contents into the bloodstream (namely the myoglobin), the kidney tubules can be injured by several different mechanisms, one of which is a direct "clogging" of the tubules by the large myoglobin molecules. And while I'm being a bit simple when I say this, it's a useful image...when the pipes get clogged and fluids (and the muscle contents in the fluid) cannot be flushed through, then the kidney can start to fail. And THAT, my friends, is Acute Renal Failure and that is not good!

Now, this does NOT happen often, even with very high levels of CPK[1], but it HAS happened. There are a few ultrarunners with stories of hospitalizations and kidney dialysis. Stephanie Ehret, one of the nation's best ultrarunners has published her own brush with rhabdo, and I will include her entire story below for those who are interested. It's well-researched and well-written...and it's honest and personal. AND...she continues to dominate the women's field in ultrarunning.

In ultrarunning, the main thing is to make sure you don't get too dehydrated. You need that fluid running "through" you to wash out those big muscle proteins that get released when the muscle breaks down. Scant rusty dark urine is not good. If that happens, you must slow down or stop and hydrate up, or get an IV to help clear things up. It's of course, always a good thing to monitor closely and err on the side of caution. When concerned or when in doubt about what to do, seek medical attention!

There is a lot of ultrarunning scare these days about overhydrating and causing hyponatremia (low sodium) and that scare is a good scare because hyponatremia is real too, and it happens, and it can have grave consequences. And this makes it even more important to hydrate "optimally" not excessively or inadequately. Hydration, whether during or after the race, should always include electrolyte replacement as well. It doesn't matter how you get them, whether through supplements or food, but it is important to replace both when you are staying hydrated. (Remember, sports drinks like Gatorade do not prevent against hyponatremia IF you OVERDRINK!)

Moving on...Signs & Symptoms of rhabdo:

Dark (red-brown, "rusty," urine, sometimes mistaken for "bloody" urine) is the classic sign. It is often quite dramatic when you see it. Urine output is likely also to be less than normal. Often, muscle soreness is present, but this may not be a prominant sign initially; it may come later. The dark urine can be described as "coca-cola" colored urine and looks different from just concentrated urine. The color is from the myoglobin itself. If you were to test the urine in a lab, it would be "positive" for blood, but on miscroscopic exam, there would be no red blood cells. Instead it is the myoglobin that caused the test to say there is blood in the urine.

Other labs can be abnormal. CPK and AST (SGOT) will both be elevated. AST is generally thought of as a liver enzyme, but it is also found in (and released from) muscle. ALT (SGPT), which more specific to the liver is not as elevated. There are other labs abnormalities that may be present, but I won't go into them here.

That's because all those abnormal labs are "normal" for ultrarunners. I never said ultrarunning was GOOD FOR YOU! Alas, it is not. Like sweet Olga says, if we wanted to simply stay fit, we'd run 30-60 minutes a day, 3 days a week. Our sport is extreme, it taxes our bodies in an extraordinary way. Amazingly, our bodies adapt remarkably well with training and experience. There are thousands of ultrarunners running races over and over again. They get muscle breakdown too, but they don't get sick. Even with myoglobinuria (myoglobin in the urine) and a high CPK, a runner can recover just fine with PROPER rehydration.[1] BUT, there's always a risk, however small. And the risks are worth knowing about and worth minimizing.

So, how to treat rhabdo?

Like I mentioned, rehydrate sensibly and monitor how you feel and monitor the color of the urine. Heck, even collect it in a clear cup(!)....this is your kidney talking, dude! Do it. Be careful. Don't decide to crash for 12 hours on your hotel bed alone. Rather, have someone wake you up a couple of times to drink some fluids. By wise. Drink sensibly. Use the bathroom, watch the recovery happen. If you start flushing and are urinating well, then there is no concern. If you are not, then there is concern. Later signs of severe rhabdo can include mild flu-like symptoms. When in doubt...check it out. Always err on the side of caution. It is our responsibility to take care of our bodies, even as we put them through so much to break them down. We have family and friends and fellow ultrarunners who want us to be healthy and stick around for a long time. So, train sensibly, run sensibly, educate yourself and others, and then by all means, have FUN on the trails and roads.

And remember the quote:

"Any idiot can run a marathon. It takes a special kind of idiot to run an ultramarathon."

Here's Stephanie's story:

Date: Mon, 4 Jan 1999 12:20:41 PST

From: stephanie ehret
Subject: Accross the Years

A fat woman in hospital pants isn't much of an anomaly in a western airport. But, it was a unique experience for me -- a normally slight, athletic girl -- as I was the one wearing the pants. Six days earlier I had driven to Phoenix with my coach, Scott Weber, and Barb Marquer, a young mother from Wyoming who finished second at the 1997 24 hour national championships at Olander Park. Our objective was the AcrossThe
Years 24/48/72 hour Run, Walk, Eat, Nap. I had planned to do the 24 hour and Barb had set her sights on the 48 hour race. We were joined, in a separate car, by 1998 Comrades winner Charl Mattheus and his short distance Olympian friend, Audrey.

The first evening in Phoenix Barb and I shared a room. I was struck by her impeccable organization and in-depth knowledge of race preparation and strategy. I felt hopelessly underprepared. I was also feeling the early signs of a cold -- slight sore throat, congestion, headache. We talked late into the night, driven by our anxiety, excitement and anticipation.

When I awoke the next morning, all I could think of was my cold. I tossed it out to Scott like a tennis ball and he tossed it back with several packs of Thera-flu. Barb took some too for good measure. The fact that the "cold" probably had psychological roots didn't eliminate the symptoms. On the positive side, the "cold" had completely
distracted me from my ongoing ankle concerns. It's always something!

The night before the race Barb and I had decided to take separate rooms to limit the sharing of germs and late night stories. I spent several hours bumbling deleriously around the room going over my supplies and my "game plan." Finally I enjoyed the luxury of simply waiting for the race to begin -- too late for last minute reparations. I imitated Barb's strategy of alternating bottles of Cytomax and
Metabolol,ultimately consuming about six bottles between the evening and the beginning of the race. I slept fitfully but deeply -- strange dreams that had nothing to do with the race. Then the alarm went off and I calmly dressed, making sure that my lucky angel pin was firmly attached to my equally lucky Fat Tire baseball cap.

The race began on Tuesday, December 29th, 9:00 a.m. How is it that I can't remember the start of the race? Suddenly I was simply running. Early on Barb and I paced each other at about 10 minute miles. I was comforted to be running with my friend, an experienced 24 hour runner and excellent companion. At about mile fifteen I began to feel very ill. Fifteen miles! How could this be happening? Fifteen miles wasn't
even a training run! For fifteen miles it was barely worth getting out of bed. All that Cytomax and Metabolol swirled in my belly. A few sips of Ensure at the 2 hour mark was all it took to expell the whole mess. I tried to puke as inconspicously as possible while several runners passed by offering condolenses and a kind of congratulatory encouragement "Get rid of it all Steph. You're going to feel so much
better!" And indeed I did.

Thus began a period of effortless, joy-filled running that would take me through about mile 70. I began to become aware of the drama around me, of the incredible feats of the other runners -- the ultra endurance giant, Al Howie (who eventually ran an incredible 250 miles in 72 hours!), Andrew Lovy, whose jolly stride kept a smile on my face, John Surdyk in his mustard yellow shorts and Charl Mattheus, averaging an impressive 8 minute mile pace and still finding enough energy to flash
me a moon every few miles as he passed.

I watched Barb in her struggles with sickness just as she had watched mine. I wanted to share with her my big blue magic ball of energy, but I knew she had to find her own. During that time the sun set, a bright pink-yellow, deepening to rose. The air cooled and stars came out. The music playing on my walkman became part of the life force, propelling me, mingling love, sadness, joy, renewal, loss with the simple act of running. Other runners were in good spirits and we exchanged light banter as we passed one another. Running was extasy. My heart could have burst.

Sometime after mile 70, I began to slow. I discarded my walkman feeling the need to focus. Running became an effort, and Scott's role became primary. "You just finished your 100K" says Scott "now focus on 100 miles." I began to run three laps then walk the fourth, later shifting to running the straights and walking the curves. At some point I began to cry -- not from pain, anger or pity -- but a simple sadness that had welled up and with the release of tears, left calmness in its wake. At 100 miles, 2:14 a.m., Scott has a surprise for me -- Peter was on the phone. Under the surreal lighting of the Arizona Boys Track,I listened to the voice of my paramour -- the voice that brought me to a Leadville finish, the voice that has lived in my head for 20 years along with my own, the voice that is home to me. "Happy Anniversary,
Sweetie." It was the emotional jolt I needed. I began to run with deliberation.

At mile 111 Scott had another surprise for me. I had broken a course record that had stood for 10 years, that had been set by his wife, Theresa. And, she was on the phone. I was being congratulated by one of the all time great ultra runners, Theresa Daus-Weber! Another emotional jolt. That Scott's a smart one!

But, running was getting harder. It was all I could do to keep running the straight-aways. Scott's coaching was becoming very focused. Every lap he had a word of encouragement or something to be eaten or drunk. "Give me three good laps" he would say "then take a rest lap." At some point a new person, who would become increasingly important to my well being, entered the picture. "Hey, I'm going to run a lap with you," he said. "I'm Jordan." Jordan ran several laps with me, offering
encouragement and bits of humor. I can't remember a single thing he said, but I remember smiling ... smiling at mile 122.

When I still had about an hour to go, Scott asked me what my running strategy had been. When I told him, he said that it wasn't going to be fast enough to come close to 130 miles. From now to the finish, I would have to run, and I would have to run faster than I had been. So I ran with big tears of anger running down my face. "That bastard", I thought, "how can he ask me to run now? No one else is running. I can
barely walk. I want to die." But I ran. Scott said "now give me three more laps, then take a rest lap." With the completion of each series of four laps Scott would say "Okay, now you have the sixth fastest time in the world this year" or "four more laps and you'll have the seventh all time fastest North American 24 hour time." And I would do as he said, cursing and crying all the while. With about 15 minutes to go, Scott said "Okay, no more walking, give me a final four laps. Run." I let
out an infamous Steph growl and ran and cryed and sobbed and people cheered and my legs screamed and... I did it. On December 30th, 9:00 a.m., the race was over. I had just completed 128.99 miles in 24 hours, the 4th best in the world by a woman in 1998.

That should be the end of the story but my ordeal had really just begun. As I lay in the tent I was overcome with nausea. I threw up into a bucket something resembling thick, dark, water logged mushrooms. I had not eaten any mushrooms. A hot flash quaked my body. Something was wrong. And Jordan was back like a guardian angel -- actually an ultrarunning, Mickey Mouse loving, Doctor. He suspected that I had thrown up the sloughed-off lining between my stomach and esophogus. Meanwhile, Barb was still running -- something that seemed incomprehensible to me in my semi-delirious state. I could overhear some discussion about taking me to the hospital. I sensed that I was becoming a distraction and it would be best to get me out of there so that Barb could focus on the race. Plus, I was pretty sure I was dying.

Scott accompanied me to the hospital, leaving Barb in the capable hands of race Director, Paul Bonnet-Castillo. Scott and I waited in the emergency room for countless hours. I felt very hot and nauseated and all my muscles had frozen up. I practiced my best ultra technique -- counting to eight over and over, making it through one hour at a time. When the nurse finally arrived she shoved a tube up my nose to pump my stomach. "I think I still have my camera," said Scott. More tubes were inserted to collect urine, to deliver an IV and medication, to take blood. The doctors detected very high CPK, an enzyme that breaks down skeletal muscle. A normal count is under 100, mine was 35,000. While this figure was very distressing to Dr. Tans, my Phoenix physician, Jordan explained to me, and eventually, to Dr. Tans, that it is not uncommon for an ultrarunner after a big race.

The CPK figures led Dr. Tans to diagnose my condition as Rhabdomyolysis, "an acute, sometimes fatal disease characterized by destruction of skeletal muscle." The photocopied explanation given to me by the nurse continues "Rarely, this (disease) may occur following strenuous excercise... renal damage manifested by acute tubular necrosis may result if myoglobinuria is accompanied with acute dehydration or
anoxia." As if that weren't enough, they didn't tell me that it was going to make me fat!

Treatment consisted of pumping several gallons of water into my tissues-- water that my kidneys were not able to process effectively. The result was about 25 extra water pounds on my small 5'1", 100 lb, frame. When I got home, I would tell Peter that I had actually skipped the race and spent several days hanging out at an all
night buffet.

In the meantime, Barb had dropped from her race. Her concern for me, the absense of her coach, the incredible mileage of the day before had taken their toll. She packed up the tent, organized all my belongings and came to the hospital for a visit. She was still smiling and joking and being the consumate caretaker. She had a card for me signed by everyone at the race. I was overwhelmed. I hugged Barb goodbye and she
drove back home to be with her son, Madison and her husband, Constant.

People everywhere were rallying to get information and to ensure my best possible care and comfort. Back in Boulder, Peter became a full time phone receptionist, communicating with Barb, Scott, my very concerned parents and family. Scott Weber had stayed in town to ensure my safe departure. Jordan Ross had called every few hours (in the middle of his 48 hour race!) to check on my status, to confer with my doctors, to answer my questions, and to facilitate my release.

On Friday afternoon, at 1:00 p.m., I was released from Valley Lutheran Hospital in Phoenix. I was picked up by a cheerful entourage of Jordan, Andy Lovy and John Surdyk. They took me to Jordan's Mickey Mansion to decompress and then to the airport where I waddled onto my flight back to Colorado.

So, now I'm back in Boulder, slimming down -- losing about 5 pounds/day. I've been on the web researching rhabdomyolosis in order to gain a better understanding of what happened to me. I have learned that this disease is normally seen in patients with multiple systems failure, such as heart conditions resulting from poorly controlled diabetes, emphysema, etc. It's clear to me now why Jordan made such an effort to educate the doctors in Phoenix about "exercise induced rhabdo." While
the condition is serious,it is also somewhat common and a healthy athlete is expected to recover fully and rapidly with proper treatment. As part of that treatment, I sent in my Leadville application today. I would be interested in hearing from other athletes who have been diagnosed with "rhabdo."

What's left to say? Thank you. Thank you Jordan for your medical intervention and caretaking. Thank you Barb for serving as an incredible inspiration and teaching me the secrets of the 24 hour run. Scott, I could never have gone the distance without you! Andy, just thinking of you makes me smile. Thanks for hauling all my luggage and
withholding the fat jokes, John. Thank you Paul for a well organized race in a beautiful setting. Thank you Audrey for your masterful crewing (Scott had to sleep sometime!). Thanks to everyone on the track for their support and the great card. Hey Charl... nice ass!

Ultrarunning is a microcosm of our lives -- it contains the drama, the struggle, the joy and the redemption that makes life worth living. It brings about the best in the human spirit. It contains all of life's lessons. It brings us closer to the essential meaning of our lives. AtAcross the Years I learned that it sure as hell isn't a good way to lose weight!

* * * * * * * * * * *

Medical references that back up my at least some of my claims:

[1]Skenderi, K., Kavouras, S., et al. Exertional rhabdomyolysis during a 246-km continuous running race. Med. Sci. Sports Exerc. 38(6):1054-1057, June 2006.

[2]http://www.pediatrics.org/cgi/content/full/105/2/433