Exercise-Associated Hyponatremia

Mike Kelleher, M4
Larner College of Medicine at the University of Vermont

Kathrine Dolbec, MD, FACEP, CAQSM
Associate Professor of Emergency Medicine
Larner College of Medicine at the University of Vermont

While Finishing the AM Shift
A 33 y/o female presents to your emergency department (ED) complaining of persistent nausea, fatigue, and dizziness. She tells you it has been going on for about four hours and began near the end of a 23-mile run earlier today. It does not seem to be getting any better with time, and she cannot tolerate even small sips of water or bites of food, although she has not vomited. She has been training for the Boston Marathon in sunny Arizona and denies any significant medical history. She takes no medications other than a prenatal vitamin.

She has normal vital signs and an otherwise unremarkable exam, except for some mild, diffuse abdominal tenderness on exam which she attributes to her nausea. There is no rebound or guarding.

Definition
One of the most notorious pathologies within the world of endurance sports is exercise-associated hyponatremia (EAH). EAH is defined as a serum sodium concentration of <135 mmol/L in the setting of prolonged exercise, with onset up to 24 hours following exercise.^1,2 EAH can be further categorized into hypovolemic, euvolemic, and hypervolemic EAH, with the latter two being the most common and the focus of this review.2 Early symptoms include fatigue, headache, and nausea/vomiting which can progress to altered mental status/encephalopathy.^1-3 In more severe cases, precipitous drops in sodium concentration (<110-115mmol/L) can lead to muscle fasciculations/cramps, disorientation, seizures, and coma. Early symptoms can manifest at serum concentrations < 130mmol/L and with 7-10% drops in sodium concentration within 24 hours.^1,2

Etiology in Endurance/Ultra Events
Symptomatic EAH has been associated with marathon and ultra-distance running (distances typically ranging from 50k-250 miles+). EAH has multiple contributors, with the most significant including excessive hypotonic fluid intake that outpaces overall fluid excretion/loss, as well as the potentiated effects of arginine vasopressin (AVP), often exacerbated by NSAID use during or directly preceding exercise.^1,2 Given the scope of these events, they often provide ample time for runners to over-consume fluids, and athletes competing in these races will often drink free water in excess either from fear of becoming dehydrated or in accordance with an arbitrary “drinking schedule.” A major tip-off is that these patients will have maintained or even added to their pre-race body weight, in the setting of prolonged or all-day efforts. Weight-tracking at aid stations or during required medical checks is common, which allows clinicians to cue-in on concerning weight gain or lack of expected weight loss. These objective data, while not perfect, are helpful in conjunction with the clinical presentation in an athlete suspected of having EAH.

It Happens to Non-Endurance Athletes, As Well!
While we tend to associate EAH with these classic prolonged endurance events and races, it is important not to overlook the circumstances and situations that can increase the risk of EAH in a host of other scenarios. A case study by Oh, et al, highlighted a young soldier who suffered from EAH as well as heat-stroke during a training field-exercise involving a simulated firefight on a hot day.⁴ When questioned in the hospital, the soldier reported “pounding water” the day before, in preparation, to avoid becoming dehydrated.⁴ In a similar case report by Changstrom, et al, an American college football player was taken to the emergency department with persistent nausea, vomiting, and headache following a regular season game.⁵ In the ED, the patient’s serum sodium was found to be 124mmol/L.⁵ In his efforts to avoid dehydration, the patient reported drinking 5 L of water the night before the game, and another 5 L of hypotonic sports drink the day of the game prior to the midday kickoff.⁵ He continued to drink water and hypotonic sports drinks throughout the game.⁵ These are just two examples of what could be considered “atypical” or non-classic scenarios that may not immediately raise suspicion for EAH. The table below highlights different scenarios in which EAH has been recorded.

Figure 1: Activities in which symptomatic EAH has been reported. Those activities in which known deaths have occurred are noted with an asterisk (*)²

The Typical Presentation?
There is a wide spectrum of presentations when it comes to EAH. There are those who meet criteria for EAH by serum sodium level but who remain asymptomatic. These patients are often discovered incidentally following exercise (typically for research purposes conducted at events).² Those with mild symptoms may present with non-specific symptoms such as fatigue, malaise, lightheadedness, dizziness, and nausea following an endurance activity.^1,2 These patients often present with an increased body weight over the course of the competition or activity.^1,2 Those with severe EAH may present with headache, altered mental status, seizure, or coma, in addition to any of the non-specific symptoms mentioned above.^1,2

Current Treatment Recommendations

On Site Management

• Asymptomatic: Found to have EAH incidentally following a serum sodium assessment drawn for other reasons
  • The athlete should be fluid restricted from any PO/IV hypotonic or isotonic fluids until urination has resumed.²
  • Asymptomatic patients with a [Na] < 130mmol/L may be given PO hypertonic fluids in efforts to prevent progression to severe EAH.²
• Mild EAH:
  • Observe while restricting PO/IV hypotonic/isotonic fluids until urinating freely. OR
  • Administration of intravenous hypertonic saline (HTS): 100 mL bolus of 3% NaCl, repeated twice if there is no clinical improvement (10 min intervals have been recommended, but this should be determined by the clinical judgment of the treating physician. OR
  • Oral HT solutions such as concentrated bouillon (4 bouillon cubes in 125 mL, ½ cup of water) or 100ml 3% NaCl with flavoring agent (Kool aid/crystal light etc.) OR
  • Equivalent PO volumes of other high sodium concentrations (3-9%).²
• Severe EAH:
  • Administration of intravenous hypertonic saline (HTS): 100 mL bolus of 3% NaCl, repeated twice if there is no clinical improvement (10 min intervals have been recommended in the literature, but this should be determined by the clinical judgment of the treating physician.²)
  • In some situations (ie, more severe encephalopathic symptomatology such as seizures, coma, or signs of impending brain herniation), it may be appropriate to administer larger HTS boluses initially rather than waiting to assess clinical improvement after repeated smaller boluses.²

Hospital Treatment

• Patients initially presenting to the ED or as a transfer from an event should be treated as they would on site.²
• In general, do not start intravenous fluid infusions until the sodium level has been confirmed, as this may precipitate worsening hyponatremia and turn a mild case of EAH into a severe one.²
• While confirming/continuing to trend lab values is critical, it should not delay potentially life-saving therapy with hypertonic saline. Be judicious about administration of IV fluids while awaiting sodium levels, however.²

Case Conclusion and Summary
Having just provided medical support at your local Ironman event, you astutely dive into more specific aspects of your patient’s HPI. It turns out she was weary of the 92-degree heat that was forecasted for her training run and decided to “get ahead” of her hydration by consuming three 2L bottles of water the evening before her run. During the run, she was also vigilant to refill her 2L Camelbak “a few times” over the course of the five-hour run. She reported last urinating this morning before her run, which was now almost nine hours ago. You give her some Zofran while waiting for her chemistry panel to result. However, you correctly resist the urge to unleash 1,000ml of NS through her IV … which is good as the panel returns with a sodium of 128mg/dL. You decide to treat her nausea and keep her for a few hours of observation. A few hours later, your patient has reported urinating two times in “large quantities'' and is feeling much better. A repeat sodium shows improvement to 132mg/dL. After a couple more hours, the patient is indulging on saltines and graham crackers, and her sodium improves to 134mg/dL. She is discharged with follow-up with her PCP the next day.

In the last decade, there has been an increase in the number of people participating in long-distance and ultra-endurance events, with a peak of 1.1 million people participating in a marathon in 2018 world-wide (data via The State of Running 2019 report). This increase in participation is accompanied by an increased risk of EAH to both recreational and elite endurance athletes. What is equally concerning is that symptoms can overlap with other commonly occurring problems, such as fatigue, hypoglycemia, heat stroke, altitude sickness, or even dehydration, making the etiology of these symptoms more difficult to unmask. Therefore, it is critical that providers, both in the ED and onsite at these events, are careful to consider EAH in their differential when working up non-specific symptoms in endurance athletes within 24 hours of prolonged exertion. This means being wary of initiating reflex IV fluids until a serum sodium concentration has been established. Furthermore, when considering volunteering as medical support for endurance events, it is important to, in advance of the event, make participants aware of current hydration recommendations, including drinking only to thirst and avoiding the use of NSAIDS directly before or during endurance events.

References

1. Hew-Butler T, Loi V, Pani A, Rosner MH. Exercise-Associated Hyponatremia: 2017 Update. Front Med (Lausanne). 2017;4:21. doi:10.3389/fmed.2017.00021
2. Hew-Butler T, Rosner MH, Fowkes-Godek S, et al. Statement of the 3rd International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015. Br J Sports Med. Nov 2015;49(22):1432-46. doi:10.1136/bjsports-2015-095004
3. Knechtle B, Chlíbková D, Papadopoulou S, Mantzorou M, Rosemann T, Nikolaidis PT. Exercise-Associated Hyponatremia in Endurance and Ultra-Endurance Performance-Aspects of Sex, Race Location, Ambient Temperature, Sports Discipline, and Length of Performance: A Narrative Review. Medicina (Kaunas). Aug 26 2019;55(9)doi:10.3390/medicina55090537
4. Oh RC, Galer M, Bursey MM. Found in the Field - A Soldier With Heat Stroke, Exercise-Associated Hyponatremia, and Kidney Injury. Curr Sports Med Rep. Apr 2018;17(4):123-125. doi:10.1249/jsr.0000000000000471
5. Changstrom B, Brill J, Hecht S. Severe Exercise-Associated Hyponatremia in a Collegiate American Football Player. Curr Sports Med Rep. Sep/Oct 2017;16(5):343-345. doi:10.1249/jsr.0000000000000399
6. Andersen, JJ. (2021, September 21). The State of Running 2019. Runrepeat.com. Retrieved August 1, 2022.