On September 3, 2008, a previously healthy 47-year-old woman from London, England, hiked for approximately 10 km on the South Kaibab Trail in Grand Canyon National Park, descending and then ascending roughly 900 m in elevation over a 5-hour period. The day was clear and sunny. Temperatures were near 10°C at the start of the hike at approximately 0800 hours, and 26.6°C at the end of the hike near 1300 hours. During the hike, her husband reported she “drank a large amount of water and ate very little,” but actual amounts are unknown. On arrival at the rim, she took a shuttle bus ride of approximately 15 minutes from the trailhead to Grand Canyon Village. Shortly thereafter, at 1400 hours, she had a syncopal episode, falling face forward onto a concrete sidewalk. According to her husband, she quickly regained consciousness, with no apparent head trauma. Grand Canyon National Park Service emergency medical service (EMS) responders were notified and arrived on the scene within 8 minutes of the call.

The patient was found sitting upright, awake but slow to respond to questions and complaining of a headache. She had no obvious signs of trauma to her head or elsewhere, and other than appearing lethargic, she had an unremarkable examination. An initial Glasgow Coma Score (GCS) was 15. Initial vital signs were stable, with blood pressure of 110/74 mm Hg, pulse of 70 beats/min, and respiratory rate of 16 breaths/min. Pulse oximetry was normal at 96%, and finger stick glucose was 82 mg/dL. An intravenous (IV) line was started, and the patient was placed in cervical spine precautions. At 1430 hours, 30 minutes after her syncopal episode, as ground ambulance transport began to the nearest hospital emergency department (128 km and 1.5 hours away), she abruptly sat upright, pulling out her IV line in the process. She then vomited a large amount of clear fluid (estimated 500 to 1000 mL) and immediately became unresponsive with a GCS of 8. She was noted to have sinus bradycardia immediately after the emesis, with a heart rate of 42 beats/min and blood pressure of 124/75 mm Hg. An electrocardiogram was unremarkable other than the bradycardia. An IV line was reestablished, and she was given 0.5 mg of IV atropine. The decision was made to expedite her transport by changing from ground to air ambulance, with the ground ambulance meeting an EMS helicopter at a highway location 48 km south of Grand Canyon Village where the transfer would be made. Over the next 30 minutes while in route to the transfer location, she received 600 mL IV normal saline. A nasopharyngeal airway was placed, and pulse oximetry was 99% on supplemental oxygen. At approximately 1540 hours, the patient and her care were transferred to the air ambulance EMS team. Her blood pressure and pulse remained stable, but her neurologic status had deteriorated to a GCS of 7. Her nasopharyngeal airway was replaced with an endotracheal tube. At approximately 1600 hours, she was on a life flight to the hospital 80 km away. An additional 400 mL IV normal saline was given before arrival at the hospital. Prehospital serum sodium testing was not done at any point because neither EMS crew was equipped with point-of-care blood analyzers at the time.

On arrival in the hospital emergency department at 1645 hours, the patient’s blood pressure was 161/108 mm Hg, heart rate 76 beats/min, respiratory rate 16 breaths/min, temperature 33.3°C (method not recorded), and oxygen saturation 100% on ventilator. On physical examination, her head was found to be normocephalic and atraumatic. Her eyes showed fixed and dilated pupils at 5 mm. Lungs were clear, heart tones were normal, and no extremity edema was noted. A comprehensive metabolic profile showed the following: low serum sodium at 127 mmol/L (normal range 135–145 mmol/L), low potassium at 2.5 mmol/L, chloride 91 mmol/L, bicarbonate 22 mmol/L, glucose 204 mmol/L, anion gap 17, calcium 8.4 mg/dL, albumin 4.7 g/dL, total bilirubin 0.5 mg/dL, alanine aminotransferase 21 U/L, aspartate aminotransferase 33 U/L, alkaline phosphatase 60 U/L, blood urea nitrogen 13 mg/dL, creatinine 0.6 mg/dL, and slightly low calculated serum osmolality of 275 mOsm/kg. Creatinine kinase was 361 IU/L; complete blood count and cardiac enzymes and coagulation studies were normal. A Foley catheter was placed, and 2000 mL clear urine was obtained with specific gravity of 1.007. Urinalysis and urine toxicology were negative. Urine osmolality was not done. Severe closed head injury was considered part of the differential diagnosis, and a head computed tomography scan was obtained. It showed severe cerebral edema and impending herniation, but no evidence of trauma or intracranial hemorrhage. Cervical spine radiographs were normal.

During the 2 hours of treatment in the emergency department before transfer to the intensive care unit, an intensivist and neurosurgeon were consulted. The patient received 60 g IV mannitol and 40 mg IV furosemide, and was started on a 3% hypertonic saline drip at 40 mL/h. She was also provided IV normal saline at 125 mL/h. She was hyperventilated to a Pco₂ of 34 mm Hg, and the head of her bed was elevated to 25 degrees. Her neurologic status never improved. Although her serum sodium eventually corrected to 143 mmol/L a little more than 4 hours after admission, a cerebral flow study obtained early the next morning showed the absence of blood flow to the brain, confirming brain death. She was pronounced dead at 0838 hours from “severe cerebral edema from water intoxication resulting in uncal herniation and brain death,” less than 19 hours after her syncopal episode.

Exercise-associated hyponatremia is a potentially serious condition that is now generally known to be due to overhydration in combination with fluid retention from nonosmotic stimulation of arginine vasopressin (AVP) secretion.^{25, 26} Nonosmotic stimuli for secretion of AVP include intense exercise, nausea or vomiting, hypoglycemia, and nonspecific stresses such as pain and emotion.^{27, 28, 29} Excessive losses of urine sodium due to secretion of brain natriuretic peptide may also contribute to the pathophysiology of EAH.^{14, 30, 31}

Early symptoms of EAH include nausea, vomiting and headache, which can rapidly progress to confusion, altered mental status, seizure, and death if untreated.²⁶ Often, there is a delay in the presentation of symptomatic EAH after exercise cessation.^{1, 17, 32} This delay is thought to be due to absorption of fluid remaining in the gastrointestinal tract once exercise has stopped and blood flow is redistributed away from skeletal muscles. The signs and symptoms of EAH encephalopathy are due to cerebral edema resulting from water following the osmotic gradient from the blood into brain tissue. Typical symptoms of EAH-related cerebral edema include an altered level of consciousness, seizures, coma, and in rare cases, death. In this patient’s case, her syncope and lethargy on presentation were probably related to cerebral edema, and her sudden collapse into an unresponsive state after her emesis was possibly related to a Valsalva-induced exacerbation of already elevated intracranial pressure from the underlying brain swelling.

Symptomatic EAH is known to occur at serum sodium concentrations that some might not consider especially low. For instance, symptomatic EAH has been reported at serum sodium concentrations above 125 mmol/L,^{17,33, 34} and an EAH-related fatality of a Marine with an admission serum sodium concentration of 128 mmol/L has been reported.² The admission serum sodium concentration of 127 mmol/L in the present EAH fatality case should serve as further evidence that treatment should be based on the extent of symptoms rather than the absolute sodium concentration. It is likely that symptom severity is related more to the rapidity at which the serum sodium changes than to the absolute value.

Appropriate management of EAH relies on early recognition. Although signs and symptoms of EAH are nonspecific and overlap with other conditions such as heat illness, acute mountain sickness, and hypoglycemia,²⁵ a history of high-volume fluid intake and seizure, or rapid mental status deterioration after exercise, should raise suspicion for EAH. When point-of-care blood sodium analysis is possible, the diagnosis of EAH can be readily confirmed. However, when blood analysis is not available, a presumed diagnosis may be necessary based on the available history, symptoms, and clinical signs.

The recommended current treatment includes fluid restriction to avoid further fluid overload, and oral or IV hypertonic saline.^{25, 26} Although the typical recommendation has been as much as three 100-mL IV boluses of 3% saline, larger volumes of hypertonic saline have been required.³⁵ Boluses of hypertonic saline are given over 1 minute by IV push. An interval of 10 minutes is recommended between boluses to observe for spontaneous improvement in symptoms. If none are seen, the total 300 mL of 3% saline should be given within 30 minutes. Even in a situation where EAH is a presumed diagnosis, a single bolus of hypertonic saline is thought to offer a favorable risk-to-benefit ratio.²⁵ Furthermore, rapid reversal of the hyponatremia when occurring acutely in EAH has not been associated with any known cases of central pontine myelinolysis.^{25, 26}

Avoiding additional fluid overload in EAH is particularly important.^{15, 25} Because dehydration is often a reflex diagnosis for a symptomatic exerciser in a hot environment, the usual treatment of oral or IV isotonic or hypotonic fluids needs be resisted if there is a strong likelihood that the underlying condition is EAH. Furthermore, it should be recognized that the presence of oliguria, which would be anticipated with dehydration, may only confound the situation because oliguria is also common with EAH owing to secretion of AVP.^{25, 26}

The case described here of a hiker shows a typical presentation of EAH. She had a suggested history of excessive fluid intake, a known stimuli for AVP secretion, and a delay in the onset of symptoms after exercise cessation followed by rapid deterioration in mental status. Her initial and subsequent treatment, which included isotonic fluids, remains common practice. In fact, there have been continued reports in recent years of EAH cases being managed with isotonic or hypotonic fluids,^{9, 13, 16, 17, 19, 20, 22, 24, 34, 36} making it evident that there is a need for further education on the proper management of EAH.

Emergency medical practitioners should be aware of current management guidelines for EAH because the persistent common treatment with high volumes of isotonic fluids has been associated with delayed recovery,^{5,9, 13, 14, 16, 17, 20, 22, 24, 32, 34} and has likely contributed to deaths.^{34, 36} Conversely, early recognition and treatment of symptomatic EAH with hypertonic saline has been demonstrated to be safe and effective, and is now the mainstay of current management guidelines.^{25, 26} Additionally, for situations or locales in which EAH is common, such as at endurance athletic events or where desert hiking takes place, it is beneficial for prehospital providers to have point-of-care serum sodium testing and IV hypertonic saline administration capabilities. Grand Canyon National Park has implemented this approach. We hope that this report of a fatal outcome from EAH and the discussion about the importance of rapid recognition and treatment will stimulate others to develop more appropriate systems for the recognition and treatment of EAH.