In May 2023, a healthy 36-year-old woman attempted a 17-mile “rim-to-river-to-rim” day hike in the Grand Canyon National Park. Several hours into the hike, she started complaining of headaches and feeling ill, with nausea and vomiting. After 12 hours of hiking and approximately two miles left, she became confused and had difficulty staying on the trail. Within an hour, her encephalopathy worsened, she sat down, and soon afterward, she lost consciousness and then stopped breathing. Cardiopulmonary resuscitation was initiated by family members, who recounted that she had been drinking copious amounts of water (6 L or more) during the hike. When Emergency Medical Services arrived, the patient was pulseless and apneic and had a point-of-care measured blood sodium level of 123 mg/dl. In total, 150 ml of 3% sodium chloride was administered, but resuscitation efforts were unsuccessful. The cause of death was later confirmed as brain herniation from severe cerebral edema related to acute hyponatremia.

This tragic case highlights an existing—but still underrecognized—public health issue for those engaged in prolonged physical activity in extreme heat: water intoxication (or clinically speaking, exercise-associated hyponatremia). Exercise-associated hyponatremia was first recognized in the early 1980s as an acute variant of hyponatremia that typically occurred during or immediately after endurance activities (i.e., Ironman triathlons, ultramarathons) with a common denominator: the ingestion of large amounts of hypotonic fluids in excess of the body's ability to excrete excess fluids.1 Another significant contributing factor to the development of exercise-associated hyponatremia is the secretion of vasopressin (arginine vasopressin) in response to blood osmolality, decreased circulating volume, or other nonosmotically driven variables (e.g., pain, nausea, fatigue, high ambient temperatures), which limits the kidney's ability to excrete any excess water load.1 On the basis of the understanding of this physiology, highly effective treatment has been developed that relies on symptom recognition, avoidance of hypotonic fluids, and, in severe cases, rapid administration of intravenous (IV) hypertonic (typically, 3%) saline to reverse the intracerebral osmotic gradient, which decreases cerebral edema and intracranial pressure.2,3 Owing to the acute development of exercise-associated hyponatremia, there have been no reported cases of central pontine myelinolysis, and IV 3% sodium chloride is considered a safe intervention.2,3 Prevention has focused on symptoms recognition, safe drinking habits, and avoidance of overhydration through simple recommendations, such as drinking to thirst. Repeatedly, this guidance for therapy and prevention has been shown to minimize the morbidity and mortality of exercise-associated hyponatremia with encephalopathy.2–4

The Emergency Medical Services branch at the Grand Canyon National Park responds to approximately 1000 calls annually, approximately 300 of which are inner Canyon Search and Rescues.5 For decades, Park Rangers have focused on heat illness (heat exhaustion and heat stroke) prevention.5 However, a 6-year study reported that exercise-associated hyponatremia, dehydration, and heat exhaustion occurred at nearly the same rate, prompting re-examination of emergency protocols.6 Most exercise-associated hyponatremia cases at the Grand Canyon occur among summer hikers to the inner Canyon and are often misdiagnosed as exertional heat illness due to overlapping signs and symptoms.7,8 The number of these cases might be expected to increase in the coming years as the effects of climate change become more evident. A diagnostic challenge exists for rapid recognition and appropriate intervention in these situations because the standards of care for treating exercise-associated hyponatremia versus heat illnesses are essentially opposite (Figure 1).2 For example, exercise-associated hyponatremia may require fluid restriction until the onset of urination, while heat illness (often associated with dehydration) necessitates fluid administration to facilitate evaporative cooling and vascular support (Figure 1). Wrongly interpreting exercise-associated hyponatremia as heat exhaustion is a common error among hikers, as their high sustained fluid intake exacerbates hyponatremia due to continued renal retention of free water in the setting of arginine vasopressin activity.

Figure 1: Clinical approach for field treatment of suspected exercise-associated hyponatremia. IV, intravenous. Reprinted from ref. 2, with permission.

The data supporting overhydration as the major mechanism involved in exercise-associated hyponatremia are largely derived from observations of weight gain seen in most individuals after endurance athletic events in which prerace and postrace weights were taken.9 However, extrapolation of these weight data in exercise-associated hyponatremia development to other endurance wilderness events, such as hiking, is limited. A common observation in many hikers who develop exercise-associated hyponatremia is that they have not eaten much food or salt during their activity. Individuals with normal kidney function who ingest a regular diet can excrete between 500 and 1000 ml/h of water. With additional nonrenal losses of water, such as sweat and insensible fluid losses with prolonged physical activity, individuals should be able to consume as much as 1000–1500 ml/h before developing water retention and dilutional hyponatremia.1 However, many individuals who develop exercise-associated hyponatremia do not drink more than 1000–1500 ml/h; thus, vasopressin, which limits renal water excretion and promotes water retention, is likely involved in lowering the threshold of water intake at which exercise-associated hyponatremia develops. This, often in combination with low solute intake, creates the “perfect storm” for the development of hyponatremia (drinking beyond thirst, nonosmotic vasopressin release, and low solute intake).

Consensus guidelines for the recognition, treatment, and prevention of exercise-associated hyponatremia in various setting have been published and have led to an approach to this condition that has largely been adopted at the Grand Canyon National Park (Figure 1).2 Optimal prevention relies on education of both hikers and first responders to the risks of overhydration, and recognition of the presenting signs and symptoms may be consistent with exercise-associated hyponatremia, especially in the context of excessive fluid intake. In settings where the incidence of exercise-associated hyponatremia may be high, availability of point-of-care serum sodium analysis by first responders makes the diagnosis straightforward. However, the expense and narrow operating ambient temperature range of these devices makes diagnoses of exercise-associated hyponatremia in most outdoor environments predicated on obtaining an accurate history of total fluid intake. Once exercise-associated hyponatremia is suspected, fluid restriction, foods with high sodium content, and the rapid administration of either oral hypertonic fluids or, in severe cases, IV 3% sodium chloride can be life-saving.2,3 Once hypertonic therapy is administered on site and the patient's neurologic status becomes stabilized, patients should be evacuated for definitive care with effective communication between first responders and medical personnel, followed by appropriate management of hyponatremia and any associated comorbid conditions.2,3

Unfortunately, neither accurate data on the exact incidence of exercise-associated hyponatremia nor on outcomes associated with this condition are available to date. However, case reports suggest that this empiric approach is effective and safe and saves lives.10 We strongly encourage participants in endurance activities (especially in environmental extremes) to familiarize themselves with presenting symptoms of exercise-associated hyponatremia and safe drinking and eating habits, as detailed in these consensus documents.2,3 We highly recommend specific educational efforts for participants at high risk for exercise-associated hyponatremia. This may take the form of clear warning signage or education that occurs with the issue of backcountry “passports.” Obviously, these educational efforts should be tailored to the specific activity and site but should be direct in defining the risks and preventative measures. First responders need to become educated about recognition of exercise-associated hyponatremia and have the means to effectively treat the condition on site. In this manner, we believe that fatalities due to this preventable and treatable condition can be avoided.

Disclosures

B. Bennett reports employment with Riverside Health System, ownership interest in TD Ameritrade, honoraria from Riverside Health System, and speakers bureau for Riverside Health System. T. Hew-Butler reports royalties from UpToDate for the topic “Exercise-Associated Hyponatremia,” coauthored by M.H. Rosner. G. Lipman reports employment with, ownership interest in, and advisory or leadership role for GOES Health. T. Myers reports employment with Grand Canyon Clinic/North Country Healthcare. M.H. Rosner reports honoraria from American Society of Nephrology, advisory or leadership role for American Society of Nephrology and as an Editor-at-Large for CJASN, and role on data safety monitoring boards for Reata and Retrophin.

Funding

None.

Acknowledgments

The authors want to recognize the dedicated and brave members of the Emergency Services program of the Grand Canyon National Park. These individuals work to ensure that visitors have a safe experience in one of America's most beautiful but also dangerous environments. The content of this article reflects the personal experience and views of the authors and should not be considered medical advice or recommendation. The content does not reflect the views or opinions of the American Society of Nephrology (ASN) or CJASN. Responsibility for the information and views expressed herein lies entirely with the authors. Because Dr. Mitchell H. Rosner is an Editor-at-Large of CJASN, he was not involved in the peer-review process for this manuscript. Another editor oversaw the peer-review and decision-making process for this manuscript.

Author Contributions

Conceptualization: Brad Bennett, Tom Myers.

Data curation: Mitchell H. Rosner.

Formal analysis: Brad Bennett, Tamara Hew-Butler, Grant Lipman, Tom Myers, Mitchell H. Rosner.

Investigation: Mitchell H. Rosner.

Methodology: Brad Bennett, Tamara Hew-Butler, Grant Lipman, Tom Myers, Mitchell H. Rosner.

Writing – original draft: Brad Bennett, Tamara Hew-Butler, Grant Lipman, Tom Myers, Mitchell H. Rosner.

Writing – review & editing: Brad Bennett, Tamara Hew-Butler, Grant Lipman, Tom Myers, Mitchell H. Rosner.

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