Hyponatremia, Cerebral Edema, and Noncardiogenic Pulmonary Edema in Marathon Runners

In a recent prospective study, 18% of 605 marathon runners developed hyponatremia; women with hyponatremia had lower plasma sodium levels and were more symptomatic than men (1). Hyponatremia in these patients resulted from substantial retention of ingested water (1). We recently reported that patients with hyponatremic encephalopathy can present with noncardiogenic pulmonary edema (2). In the present report, we describe seven marathon runners who presented with hyponatremic encephalopathy and pulmonary edema. Case Findings Demographic Characteristics Seven patients were studied, six of whom survived. Five were directly cared for by one of the authors, and the authors were consulted for the other two patients. All seven had completed marathons from 1993 to 1999 in Texas, California, and Canada and had taken nonsteroidal anti-inflammatory drugs. The clinical and laboratory characteristics are given in the Table. Table. Clinical and Laboratory Characteristics of Patients Hospital Course All seven patients were admitted to the emergency department with nausea, emesis, copious pink frothy sputum, and pulmonary edema (Figure, part A). No abnormalities were seen on electrocardiography, and echocardiography showed normal ejection fractions and wall motion. The pulmonary wedge pressure was below normal in all five patients in whom this variable was measured. All seven patients had normal calcium and phosphorus levels. Figure. Radiographs and scans obtained from patient 3, a 44-year-old woman who was admitted to the emergency department with a plasma sodium level of 121 mmol/L and oxygen saturation of 66%. A. B. C. D. Magnetic resonance imaging or computed tomography of the brain showed cerebral edema in the six patients who underwent either of these tests (Figure, part C). In patient 7, hyponatremic encephalopathy was not suspected, and the patient died of cardiopulmonary arrest. The autopsy showed cerebral edema with brainstem herniation, pulmonary edema, and a normal heart. Therapy All seven patients were intubated in the emergency department. All seven patients were supported with mechanical ventilation, and six were treated with intravenous NaCl. In these six patients, the plasma sodium level increased by 10 mmol/L in less than 12 hours (3, 4). As the plasma sodium level increased, cerebral (Figure, part D) and pulmonary (Figure, part B) edema resolved. All treated patients recovered. No sequelae have developed after follow-up of 3 to 24 months. Magnetic resonance imaging scans obtained after 1 year of follow-up in five patients were normal. Discussion Our study demonstrates that in healthy marathon runners, noncardiogenic pulmonary edema can be a clinical manifestation of hyponatremic encephalopathy. The association between noncardiogenic pulmonary edema and hyponatremic encephalopathy was suspected in six patients. Hypertonic NaCl treatment of cerebral edema and hyponatremic encephalopathy was successful and curative in these six patients. The patient in whom the diagnosis was unsuspected died of cardiopulmonary arrest caused by brainstem herniation (Table). All five patients in whom pulmonary capillary wedge pressure was measured had low pressure, indicating that pulmonary edema was noncardiogenic. Furthermore, through alleviation of cytotoxic cerebral edema with hypertonic NaCl, pulmonary edema also resolved (Figure, part D); this finding suggests a possible association between cerebral edema and noncardiogenic pulmonary edema. Previous reports have described pulmonary edema developing in marathon runners (5-7). However, we report resolution of both cerebral and pulmonary edema with the use of hypertonic NaCl. Although most marathon runners are male, a recent study shows that women are more prone to develop hyponatremia and are more symptomatic (1). Five of seven patients in our study were menstruant women, suggesting that, as in other forms of hyponatremic encephalopathy, sex may be a predisposing factor (8). Our study has some limitations. For example, the small sample precludes statistical comparisons, and we have no information on the incidence or prevalence of hyponatremic encephalopathy among marathon runners. During heavy exercise, blood flow is diverted from the gastrointestinal tract to skeletal muscle, and ingested water is sequestered in the gut (9). Diffuse loss of sodium and water due to sweating leads to volume contraction with stimulation of antidiuretic hormone (1, 9, 10). Vasopressin, in turn, increases retention of ingested water. When exercise ceases, blood flow may be partially redistributed to the gastrointestinal tract, leading to abrupt absorption of water into the bloodstream and resultant hyponatremia (9, 11, 12). The acute hyponatremia leads to increased intracranial pressure, with hypoxia and noncardiogenic pulmonary edema (2). Marathon runners are also likely to use nonsteroidal anti-inflammatory drugs, which can impair water excretion (13). When people collapse in apparent shock after strenuous exercise, heat injury is usually the presumptive diagnosis (14). Some have been treated with oral administration of water or diuretics, and some have died (15, 16). The initial hospital evaluation of a marathon runner who collapses should include measurement of the plasma sodium level and chest radiography. Although counterintuitive, administration of hypertonic NaCl should be considered if pulmonary edema and hyponatremia are present. Successful therapy in such patients depends on recognition of the association between noncardiogenic pulmonary edema and hyponatremic encephalopathy. Note added in proof: After this manuscript was accepted for publication, Dr. Sterling Huff, Director of Emergency Services at St. Joseph's Hospital, Houston, Texas, informed us of four female marathon runners who were hospitalized after completing the Houston Marathon on 16 January 2000. These women were 32 to 48 years of age and presented to the emergency department with symptoms ranging from nausea, vomiting, and headache to grand mal seizures. All had hyponatremia (plasma sodium level, 114 to 128 mmol/L). None suffered respiratory arrest. It was certain that one of the runners had been taking nonsteroidal anti-inflammatory drugs; the history of use of these drugs was unclear in the other three. All were successfully treated with intravenous NaCl (two received hypertonic NaCl and two received normal NaCl), and all were subsequently discharged without neurologic sequelae.