How Ultra-Endurance Sports Medicine Research has Changed Our Understanding of Human Physiology: Sodium Regulation, Kidney Function and Vision
Research from ultramarathon races (foot races longer than a marathon) has not just helped us to understand what happens to the human body during long distance running, but has also provided novel information about what happens to an otherwise healthy human body, when it is pushed to its physiological limits for a prolonged period of time. As physiatrists, we are also increasingly likely to care for ultramarathon runners, as their numbers are increasing exponentially. Of note, ultramarathon running is widely considered to be a safe sport, however, as with many other sports, health and life-threatening situations can occur.
Overhydration
The dangerous consequences of hyponatremia resulting from rapid and copious water ingestion have been documented in the medical literature since the 1930’s (Helwig, 1938). However, it was not until the 1980’s that ultramarathon case reports and research began to demonstrate that exercise potentiates the risk of developing hyponatremia from fluid consumption (Noakes,1985; Frizzell, 1986). This is now known as exercise-associated hyponatremia (EAH). The etiology of the increased risk of hyponatremia during exercise is non-osmotic AVP (ADH) secretion causing impaired water excretion by the kidneys (Hew-Butler, 2015). There have been at least 14 deaths from EAH since 1981 (see box below).
Pictured below is 22-year-old fitness instructor, David Rogers, who died of hyponatremia due to water intoxication after finishing the London Marathon. Photo courtesy of dailymail.com.
The highest reported incidence of asymptomatic hyponatremia post-race has been consistently noted in 161 km ultramarathons, in which the reported incidence of EAH has been up to 51% (Hew Butler, 2015). The incidence of symptomatic EAH has been reported to be as high as 23% (Speedy, 1999) in athletes seeking medical care at an Ironman triathlon and 38% among ultramarathon runners seeking care (Lee, 2011). Health care personnel should have a high index of suspicion for EAH in endurance sporting events when an athlete presents to the medical tent, especially with mental status changes, other neurological changes or nausea and vomiting.
Some participants develop cerebral edema with seizures or other symptoms, and hypertonic saline (3%) is the appropriate treatment (Hew-Butler, 2015). Oral hypertonic saline may be used in less serious cases of confirmed or suspected hyponatremia (Hew-Butler, 2015). Rapid correction of plasma sodium does not pose a risk of central pontine myelinolysis when hyponatremia develops over less than 48 hours (Hew Butler, 2015).
Risk factors for EAH include overdrinking, weight gain during exercise, exercising for longer than four hours, event inexperience, inadequate training, slow running pace, high or low body mass index and readily available fluids (Hew Butler, 2015). Of note, hyponatremia can occur despite (excessive) sodium supplementation (Hew-Butler, 2015), and excessive sodium supplementation can be harmful and should be avoided (Hew-Butler, 2015). Athletes should instead be educated about the risks of excessive fluid consumption and told to drink according to thirst (See Figure Below: Fluid intake strategy for avoiding exercise-associated hyponatremia (EAH).)
Kidneys
The blood levels of creatine kinase (CK), a byproduct of muscle breakdown, among finishers of a 100-mile race averages 20,000 (U/L), which is approximately 100 times the upper limit of normal (See Figure Below: Distribution of Blood CK levels among finishers of the Western States 100-mile Endurance Run from Hoffman, 2012.)
This would be twice as high as the amount needed to diagnose rhabdomyolysis; however, permanent kidney damage among ultramarathon finishers is exceedingly rare (Schwabe et al, 2008; Hoffman, 2013). Although 30–80% of ultramarathon runners will meet the criteria for acute kidney injury (Hoffman, 2013; Lipman, 2014), the damage does not appear to be permanent (Hoffman &Weiss, 2015). It appears that an increased glomerular filtration rate during running clears waste products at a rate sufficient to protect the kidneys from permanent damage (Irving, 1990).
Athletes need not be routinely evaluated for rhabdomyolysis or kidney damage following ultramarathons, but should seek medical care if there is limited urine output post-race or persistent cola-colored urine despite adequate hydration (Hew-Butler & Hoffman, 2013). Additionally, athletes should avoid taking NSAIDS as they are associated with renal failure secondary to rhabdomyolysis (Hew-Butler & Hoffman, 2013). If there is a concern for kidney injury following or during a race, urine dipstick tests that read positive for at least 1+ protein, 3+ blood, and specific gravity of ≥1.025 can predict those at risk for kidney injury with excellent sensitivity and specificity (Hoffman, 2013.)
Eyes
Three years ago, essentially nothing was known about ultramarathon-related visual impairment, except that it happened to approximately 3% of 100-mile race entrants (Hoffman & Fogard, 2011). This type of vision loss also happened to the director of research at the Western States 100 mile run, Dr. Marty Hoffman. He, Dr. Corrigan and myself set out to learn more about ultramarathon-related vision loss using web-based survey, including 173 ultrarunners that had experienced ultramarathon-related vision loss. We learned that it was self-limited (tended to resolve within a few hours and never lasted more than 48 hours), it occurred over the full range of ambient temperatures and altitudes and is significantly associated with a history of refractive surgery (Høeg, 2015).
Table 1. Studied characteristics and their relations to the development of ultramarathon-related visual impairment.
The increased risk among those with a history of refractive surgery may suggest that these corneas do not respond as well to prolonged environmental irritation. Of note, approximately three quarters of the participants with vision loss had never had refractive surgery. But those who had also experienced vision loss more frequently. It was also significantly linked to being female, but that may be because females are more likely to take surveys than males (Høeg, 2015),
This type of vision loss does not appear to have any long-term visual consequences. Exercise-related corneal edema has also been documented in cyclists (Ettl, 1992). Athletes who have recurrent running or cycling related vision loss can be counseled to compete with protective eyewear and/or use artificial tears intermittently while racing. If vision loss is associated with pain or darkness (not simply described as foggy or blurry vision), or persists for over 48 hours, athletes should be advised to seek fundoscopic evaluation by an ophthalmologist.
References
1. Ettl AR, Felber SR, Rainer J. Corneal edema induced by cold. Ophthalmologica 1992;204:113–114.
2. Frizzell RT, Lang GH, Lowance DC, Lathan SR. Hyponatremia and ultramarathon running. Med Sci Sports Exerc. 1990 Oct;22(5):581–7.
3. Hew-Butler T, Hoffman T. Running, Rhabdomyolysis and Renal Failure — Who’s at Risk? Ultrarunning Magazine. 2013. Nov 24.
4. Helwig FC, Schutz B & Kuhn H. Water Intoxication: Moriburnd Patient Cured by Administration of Hypertonic Salt Soluation. JAMA 1938;110:644–5.
5. Hew-Butler T, Rosner MH, Fowkes-Godek S, et al. Statement of the 3rd International Exercise-Associated Hyponatremia Concensus Development Conference, Carlasbad, California, 2015. Br J Sports Med 2015;49.1432–1446.
6. Hoffman MD, Fogard K. Factors related to successful completion of a 161-km ultramarathon. Int J Sports Physiol Perform 2011; 6:25–37.
7. Hoffman MD, Ingwerson JL, Rogers IA, Hew-Butler T, Stuempfle KJ. Increasing creatine kinase concentrations at the 161-km Western States Endurance Run. Wilderness Environ Med. 2012.23, 56–60.
8. Hoffman MD, Stuempfle KJ, Fogard K, Hew-Butler T, Winger J, Weiss RH. J Sports Sci. 2013;31(1):20–31.
9. Høeg T, Corrigan G, Hoffman M. ”An Investigation of Ultramarathon Associated Visual Impairment.” Wilderness Environ Med. 2015 Jun;26(2):200–4. doi: 10.1016/j.wem.2014.10.003. Epub 2015 Feb 26.
10. Irving RA, Noakes TD, Burger SC, Myburgh KH, Querido, van Zyl Smit R. Plasma volume and renal function during and after ultramarathon running. Med Sci Sports Exerc. 1990 Oct;22(5):581–7.
11. Lee JK, Nio AQ, Ang WH, et al. First reported cases of exercise-associated hyponatremia in Asia. Int J Sports Med. 2011;32–297–302.
12. Lipman GS, Krabak BJ, Waite BL, et al. A prospective cohort study of acute kidney injury in multi-stage ultramarathon runners: the Biochemistry in Endunce Runner Study (BIERS). Res Sports Med. 2014
13. Noakes TD, Goodwin N, Rayner BL, Branken T, Taylor RK. Water intoxication: a possible complication of endurance exercise. 1985 Jun;17(3):370–5.
14. Speedy DB, Noakes TD, Rogers IR, et al. Hyponatremia in ultradistance triathletes. Med Sci Sports Exerc 1999;31:809–15.
About the Author
Tracy Beth Høeg, MD, PhD is a PGY3 in PM&R at the University of California-Davis. Before moving to the United States last year, she spent seven years working in Ophthalmology in Denmark. She has been an ultramarathon runner since 2008 and was a member of Team USA in the World Championships in Ultra Trail Running in 2013. She is also the owner and head coach at My Little Physiology. She can be contacted at tracybethhoeg@gmail.com. If you are interested in volunteering as a physician at an ultramarathon event, you may want to consider going through http://ultramedicalteam.org/.
Article originally published in April 2016 in Physiatry in Motion Issue #1
