To the Editor:
The incidence of exercise-associated hyponatremia (EAH) is common in endurance and ultraendurance events, in which both athletes and medical providers need to be aware of risk factors, symptom presentation, and management. The recently published Wilderness Medical Society (WMS) practice guidelines for EAH 1 present a thorough review of the pathophysiology: a combination of excessive water intake and an endocrine-axis–focused dilutional state characteristic of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Symptomatic EAH is a diagnostic challenge when point-of-care (POC) testing of serum sodium is unavailable—a regular occurrence in the wilderness environments where many ultraendurance events are undertaken. Treatment options are usually based on clinical symptom recognition, complicated by similar presentations of heat-induced illness, dehydration, or altitude illness. There is concern that the published practice guidelines do not provide ample evidence to support several of their recommendations, or a sufficient treatment algorithm to benefit the medical provider without POC testing when treating suspected EAH in a remote area. The aim is to review the available evidence supporting the current treatment paradigm, and to deliver clinical practice guidelines for the treatment of EAH based on the available evidence.
Symptomatic EAH should be defined qualitatively as with most diseases: either “mild” or “severe,” differentiated by the presence or absence of neurologic manifestations. This classification of disease is more than semantics, as EAH may be progressive with severe disease associated with cerebral edema, brainstem compression, pulmonary edema, respiratory failure, and death. As symptomatic EAH in the endurance athlete may be confounded by profound dehydration necessitating intravenous (IV) rehydration, severity of EAH dictates fluid choices, with the 2 categories having different IV fluid treatment options. Bennett et al 1 reasonably point out that dehydration may be misdiagnosed as EAH, as delayed urination caused by inappropriate secretion of arginine vasopressin can lead to an oliguric state. However their example of “unstable blood pressure” as an indication for administration of IV fluids in the dehydrated athlete implies an inappropriately high threshold. Hypotension becomes evident during stage III of hypovolemic shock, in which there is loss of more than 30% of circulating volume. In the athlete with excellent cardiovascular reserve, hypotension is a late occurrence, and this physiologic finding signals impending circulatory collapse. So the question is raised, if a medical provider is concerned about treating severe dehydration and desires to rehydrate intravenously in the setting of symptoms that may represent mild EAH, why must one be so cautious about giving isotonic IV fluids?
The WMS practice guidelines state that administration of isotonic fluids could be “disastrous” for an athlete with EAH, may worsen hyponatremia, and may have potentially “devastating” consequences. 1 The theory is that low sodium avidity and the expanded plasma volume seen in EAH may decrease serum sodium concentrations in response to isotonic saline. As with SIADH, the excretion of all of the sodium will be with a proportion of the water to equal the higher urine osmolality (which is greater than the serum)—resulting in a worsened dilutional state. However, the EAH literature does not support these conclusions (or 1A recommendation grade). As these references are cited to support these alarmist quotations and recommendations in the practice group, the quoted literature was revisited to shed light on this debatable issue—which has clinical and potentially medical and legal ramifications. The literature was examined with attention to differentiating mild from severe EAH, type and amount of IV hydration, and effect on patient outcome.
The first paper described 7 patients with severe EAH who were comatose and intubated in the emergency room with evidence of cerebral edema on computed tomography. The 6 patients who were treated with hypertonic saline (HTS; 3% saline solution, 514 mmol/L of sodium) made a full neurologic recovery. There was 1 fatality, which occurred in 1 individual who was not treated with HTS. However, the paper does not describe what, if any, IV solution was administered. As an added note, after publication there were 4 reported cases of mild EAH (with no neurologic involvement); 2 were treated with HTS and 2 with normal saline (NS; 154 mmol/L of sodium)—all 4 made an uneventful recovery. 2 Conclusion: HTS is beneficial for critical EAH, and mild EAH can be treated with either HTS or NS.
The next case series details 2 runners with severe EAH (encephalopathic but not intubated). One person received NS, had a seizure, but eventually had a full neurologic recovery without intensive care. The second person initially received lactated Ringer’s solution (LR; 130 mmol/L of sodium), which was changed to HTS. He went on to receive 2.1 L of “intravenous fluid” during the next 8 hours and was discharged. There was also brief mention of 3 hospitalized ultramarathon runners who were hospitalized with EAH and responded well to undifferentiated “treatment.” 3 Conclusion: Severe EAH resolves with both NS and HTS, and extremely high-rate HTS results in rapid recovery. Also, “treatment” of some sort appears to be efficacious.
The study by Siegel et al 4 was a case series encapsulated within an observational study. Two cases of severe EAH presented to the emergency department in a coma with respiratory failure necessitating intubation. After intubation, 150 mL of NS was infused, and the patients eventually died. Another 2 cases of severe EAH (encephalopathic) received HTS and made a full recovery. The figures depicting time vs serum sodium concentrations show both of the latter 2 patients had resolution of central nervous system symptoms several hours before HTS infusion. 4 Conclusion: Severe EAH requiring intubation has a dismal prognosis. No subsequent sodium levels were provided in the first 2 cases, so it is unknown what effect 150 mL of NS had on the hyponatremic state or clinical condition, but caution may be warranted to avoid NS in severe EAH.
The most robust of the references was a retrospective chart review combined with a small prospective case series, comparing 2 years of different EAH treatments. The retrospective analysis was of 16 marathon runners who received NS in the emergency department for EAH. Of the 5 admissions, 3 had severe EAH on arrival and were intubated before receiving NS, and 2 eventually received HTS in the intensive care unit, but there was no description of the fluids the third patient received. All 3 were discharged with full recovery several days later. The other 2 runners with mild EAH who received NS were admitted, but not to critical care. A year later, a prospective analysis of 5 runners, 4 with mild and 1 with severe EAH (encephalopathic) received HTS as the initial emergency department infusion, and all were discharged. The article contains a Figure showing correction rates from a sample of the 2 groups: the NS group had 2 of 8 (25%) patients’ serum sodium concentration initially decrease before increasing; the HTS group had 1 of 4 (25%) with the same trend. 5 Conclusion: In critical EAH, NS had the same outcome as HTS therapy; in mild EAH, NS may worsen outcome requiring hospital admission but not to critical care levels. EAH patients may experience a transient decrease in serum sodium with both isotonic and hypertonic IV therapy.
Algorithm for field treatment of exercise-associated hyponatremia without point-of-care serum sodium testing. (D5NS, 5% dextrose in normal saline solution; EAH, exercise-associated hyponatremia; LOC, level of consciousness; NS, normal saline solution; PO, per os [orally].)
The above cases describe the clinical spectrum of EAH. It is a potentially fatal disease that requires medical providers at endurance and ultraendurance events to be comfortable with airway management and critical care. Although caution is warranted in treating any patient with symptomatic EAH, IV rehydration with isotonic fluids has not been causally related to worsening outcomes necessitating intensive level care. However, delay in treating an athlete’s hypovolemia with anything other than a few milliliters of hypertonic saline when transportation to a care facility is many hours away may have grave consequences. If there is any question or concern of neurologic impairment, HTS is the most efficacious agent and NS should be avoided. With a qualified definition of EAH, an IV fluid treatment approach is possible that is evidence-based and clinically oriented to assist the medical provider when there is no available POC serum sodium testing. The Figure shows a treatment algorithm emphasizing symptom recognition rather than serum sodium testing to provide guidelines for clinical assistance when technological support is unavailable.