Hyponatremia in Marathon Runners
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《新英格兰医药杂志》
To the Editor: Almond et al. (April 14 issue)1 excluded an important variable in their assessment of hyponatremia in marathon runners. Excess fluid intake is clearly a contributor to low serum sodium concentrations,2 but numerous long-distance runners in the study population ingested high-sodium endurance gels. These popular supplements were offered by the race sponsors at mile 17 of the Boston Marathon or carried by the runners and ingested ad lib. Most of the gels contain 40 to 100 mg of sodium per packet of 32 to 41 g. The typical marathoner who completes the race in four to five hours might ingest a packet every hour, roughly equivalent to 160 to 500 mg of sodium per race. In contrast to hypotonic sports drinks and water, fluids with high sodium concentrations can counter hyponatremia if used appropriately,3 an effect not investigated in this study.
W.F. Peate, M.D., M.P.H.
University of Arizona College of Medicine
Tucson, AZ 85719
peate@email.arizona.edu
References
Almond CSD, Shin AY, Fortescue EB, et al. Hyponatremia among runners in the Boston Marathon. N Engl J Med 2005;352:1550-1556.
Noakes T. Hyponatremia in distance runners: fluid and sodium balance during exercise. Curr Sports Med Rep 2002;1:197-207.
Twerenbold R, Knechtle B, Kakebeeke TH, et al. Effects of different sodium concentrations in replacement fluids during prolonged exercise in women. Br J Sports Med 2003;37:300-303.
To the Editor: Almond et al. demonstrate that hyponatremia, a sodium concentration of less than 135 meq per liter, is a common complication in marathon runners. Symptomatic hyponatremia can be fatal if not treated with hypertonic saline. Despite the proven safety of hypertonic saline for the treatment of hyponatremic encephalopathy,1,2,3 its use has been marginalized in the literature,4 resulting in confusion with regard to therapy. We described noncardiogenic pulmonary edema due to increased intracranial pressure from cerebral edema as a presenting feature of hyponatremic encephalopathy in marathon runners.5 Six patients treated with hypertonic saline survived without neurologic sequelae, whereas one patient who was not treated died. We therefore recommend that any runner who exhibits signs of respiratory insufficiency, confusion, obtundation, nausea, and vomiting should be evaluated for hyponatremia, with a rapid method on site in a medical tent. We suggest that runners with hyponatremia be treated with 100 ml of 3 percent sodium chloride solution for 10 minutes to raise the serum sodium concentration rapidly by 2 to 3 meq per liter and to decrease brain edema. This therapy should stabilize the patient's condition before transfer to the hospital and neuroimaging studies but should not result in complications.
Juan C. Ayus, M.D.
University of Texas Health Science Center at San Antonio
San Antonio, TX 78207
Alan Arieff, M.D.
University of California, San Francisco
San Francisco, CA 94143
Michael L. Moritz, M.D.
Children's Hospital of Pittsburgh
Pittsburgh, PA 15213
References
Ayus JC, Krothapalli RK, Arieff AI. Treatment of symptomatic hyponatremia and its relation to brain damage: a prospective study. N Engl J Med 1987;317:1190-1195.
Sarnaik AP, Meert K, Hackbarth R, Fleischmann L. Management of hyponatremic seizures in children with hypertonic saline: a safe and effective strategy. Crit Care Med 1991;19:758-762.
Ayus JC, Arieff AI. Chronic hyponatremic encephalopathy in postmenopausal women: association of therapies with morbidity and mortality. JAMA 1999;281:2299-2304.
Sterns RH. Treating hyponatremia: why haste makes waste. South Med J 1994;87:1283-1287.
Ayus JC, Varon J, Arieff AI. Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners. Ann Intern Med 2000;132:711-714.
To the Editor: Almond and colleagues correctly warn that weight gain during marathons may cause acute hyponatremia. Nevertheless, the degree of water retention may be underestimated if assessed on the basis of weight gain because of the oxidation of about 0.5 kg of the fuel, glycogen plus triglyceride. Since each kilogram of glycogen associates with about 3 kg of "bound" water, this release of water can cause hyponatremia without weight gain if the water is electrolyte-free.
There are three problems associated with the interpretation of postrace plasma sodium concentrations. First, water retained in the gastrointestinal tract contributes initially to weight gain, but later, when absorbed, the water contributes to hyponatremia if there is vasopressin activity.1 Second, when water absorption is rapid, the venous plasma sodium concentration is appreciably higher than in the arterial sodium plasma concentration (a measure of the sodium concentration to which the brain is exposed) in a simultaneously drawn sample.2 Third, if the effective osmolality in myocytes rises appreciably when L-lactic acid accumulates during a final sprint, there can be a sudden but transient rise, by about 10 mM, in the venous plasma sodium concentration.3 Therefore, physicians should recognize that the postrace venous plasma sodium concentration might appreciably underestimate the potential severity of hyponatremia in runners who have gained weight.
Mitchell L. Halperin, M.D.
Kamel S. Kamel, M.D.
St. Michael's Hospital
Toronto, ON M5B 1A6, Canada
mitchell.halperin@utoronto.ca
Richard Sterns, M.D.
Rochester General Hospital
Rochester, NY 14621
References
Cherney DZ, Davids MR, Halperin ML. Acute hyponatraemia and `ecstasy': insights from a quantitative and integrative analysis. QJM 2002;95:475-483.
Shafiee MA, Charest AF, Cheema-Dhadli S, et al. Defining conditions that lead to the retention of water: the importance of the arterial sodium concentration. Kidney Int 2005;67:613-621.
Welt LG, Orloff J, Kydd DM, Oltman JE. An example of cellular hyperosmolarity. J Clin Invest 1950;29:935-939.
The authors reply: As Dr. Peate points out, it is possible that differences in sodium intake before, during, or after the race help to explain some of the observed variation in sodium levels among runners with similar degrees of weight gain. Although Twerenbold et al. found a difference,1 other studies analyzing the effect of salt intake on plasma sodium levels during prolonged exercise have shown mixed results.2,3,4 It is unclear whether the lack of a consistent benefit can be explained by methodologic issues or by the pathophysiology of hyponatremia, which may include a component of antidiuresis, a mechanism that may be less amenable to correction with sodium. Nevertheless, these reports document a low incidence of hyponatremia among runners who did not gain weight. Although the role of salt supplementation merits further study, the available evidence indicates that the most effective way to prevent hyponatremia during marathon running is to avoid a positive fluid balance.
We agree with Dr. Ayus and colleagues that hypertonic saline is the treatment of choice for symptomatic patients with severe hyponatremia, and that treatment with hypotonic fluids for presumed hypovolemia could be detrimental. Rapid point-of-care testing to establish the serum sodium level is invaluable in determining the appropriate fluid therapy for ill marathoners, especially because the clinical presentation of dehydration can be similar to that of hyponatremia.
Dr. Halperin and colleagues point out that weight gain may underestimate the degree of free water excess in runners, if one assumes that the postrace weight should be lower than the prerace weight on the basis of glycogen and fat metabolism, irrespective of fluid balance. We agree with Dr. Halperin and colleagues, whose suggestion may account for the small group of runners in our study who had hyponatremia but did not have an appreciable weight change. Indeed, the optimal fluid balance for marathoners may involve the loss of a small percentage of body weight during the race.
Christopher S.D. Almond, M.D., M.P.H.
Andrew Y. Shin, M.D.
David S. Greenes, M.D.
Children's Hospital Boston
Boston, MA 02115
christopher.almond@childrens.harvard.edu
References
Twerenbold R, Knechtle B, Kakebeeke TH, et al. Effects of different sodium concentrations in replacement fluids during prolonged exercise in women. Br J Sports Med 2003;37:300-303.
Speedy DB, Thompson JM, Rodgers I, Collins M, Sharwood K, Noakes TD. Oral salt supplementation during ultradistance exercise. Clin J Sport Med 2002;12:279-284.
Barr SI, Costill DL, Fink WJ. Fluid replacement during prolonged exercise: effects of water, saline, or no fluid. Med Sci Sports Exerc 1991;23:811-817.
Irving RA, Noakes TD, Buck R, et al. Evaluation of renal function and fluid homeostasis during recovery from exercise-induced hyponatremia. J Appl Physiol 1991;70:342-348.
W.F. Peate, M.D., M.P.H.
University of Arizona College of Medicine
Tucson, AZ 85719
peate@email.arizona.edu
References
Almond CSD, Shin AY, Fortescue EB, et al. Hyponatremia among runners in the Boston Marathon. N Engl J Med 2005;352:1550-1556.
Noakes T. Hyponatremia in distance runners: fluid and sodium balance during exercise. Curr Sports Med Rep 2002;1:197-207.
Twerenbold R, Knechtle B, Kakebeeke TH, et al. Effects of different sodium concentrations in replacement fluids during prolonged exercise in women. Br J Sports Med 2003;37:300-303.
To the Editor: Almond et al. demonstrate that hyponatremia, a sodium concentration of less than 135 meq per liter, is a common complication in marathon runners. Symptomatic hyponatremia can be fatal if not treated with hypertonic saline. Despite the proven safety of hypertonic saline for the treatment of hyponatremic encephalopathy,1,2,3 its use has been marginalized in the literature,4 resulting in confusion with regard to therapy. We described noncardiogenic pulmonary edema due to increased intracranial pressure from cerebral edema as a presenting feature of hyponatremic encephalopathy in marathon runners.5 Six patients treated with hypertonic saline survived without neurologic sequelae, whereas one patient who was not treated died. We therefore recommend that any runner who exhibits signs of respiratory insufficiency, confusion, obtundation, nausea, and vomiting should be evaluated for hyponatremia, with a rapid method on site in a medical tent. We suggest that runners with hyponatremia be treated with 100 ml of 3 percent sodium chloride solution for 10 minutes to raise the serum sodium concentration rapidly by 2 to 3 meq per liter and to decrease brain edema. This therapy should stabilize the patient's condition before transfer to the hospital and neuroimaging studies but should not result in complications.
Juan C. Ayus, M.D.
University of Texas Health Science Center at San Antonio
San Antonio, TX 78207
Alan Arieff, M.D.
University of California, San Francisco
San Francisco, CA 94143
Michael L. Moritz, M.D.
Children's Hospital of Pittsburgh
Pittsburgh, PA 15213
References
Ayus JC, Krothapalli RK, Arieff AI. Treatment of symptomatic hyponatremia and its relation to brain damage: a prospective study. N Engl J Med 1987;317:1190-1195.
Sarnaik AP, Meert K, Hackbarth R, Fleischmann L. Management of hyponatremic seizures in children with hypertonic saline: a safe and effective strategy. Crit Care Med 1991;19:758-762.
Ayus JC, Arieff AI. Chronic hyponatremic encephalopathy in postmenopausal women: association of therapies with morbidity and mortality. JAMA 1999;281:2299-2304.
Sterns RH. Treating hyponatremia: why haste makes waste. South Med J 1994;87:1283-1287.
Ayus JC, Varon J, Arieff AI. Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners. Ann Intern Med 2000;132:711-714.
To the Editor: Almond and colleagues correctly warn that weight gain during marathons may cause acute hyponatremia. Nevertheless, the degree of water retention may be underestimated if assessed on the basis of weight gain because of the oxidation of about 0.5 kg of the fuel, glycogen plus triglyceride. Since each kilogram of glycogen associates with about 3 kg of "bound" water, this release of water can cause hyponatremia without weight gain if the water is electrolyte-free.
There are three problems associated with the interpretation of postrace plasma sodium concentrations. First, water retained in the gastrointestinal tract contributes initially to weight gain, but later, when absorbed, the water contributes to hyponatremia if there is vasopressin activity.1 Second, when water absorption is rapid, the venous plasma sodium concentration is appreciably higher than in the arterial sodium plasma concentration (a measure of the sodium concentration to which the brain is exposed) in a simultaneously drawn sample.2 Third, if the effective osmolality in myocytes rises appreciably when L-lactic acid accumulates during a final sprint, there can be a sudden but transient rise, by about 10 mM, in the venous plasma sodium concentration.3 Therefore, physicians should recognize that the postrace venous plasma sodium concentration might appreciably underestimate the potential severity of hyponatremia in runners who have gained weight.
Mitchell L. Halperin, M.D.
Kamel S. Kamel, M.D.
St. Michael's Hospital
Toronto, ON M5B 1A6, Canada
mitchell.halperin@utoronto.ca
Richard Sterns, M.D.
Rochester General Hospital
Rochester, NY 14621
References
Cherney DZ, Davids MR, Halperin ML. Acute hyponatraemia and `ecstasy': insights from a quantitative and integrative analysis. QJM 2002;95:475-483.
Shafiee MA, Charest AF, Cheema-Dhadli S, et al. Defining conditions that lead to the retention of water: the importance of the arterial sodium concentration. Kidney Int 2005;67:613-621.
Welt LG, Orloff J, Kydd DM, Oltman JE. An example of cellular hyperosmolarity. J Clin Invest 1950;29:935-939.
The authors reply: As Dr. Peate points out, it is possible that differences in sodium intake before, during, or after the race help to explain some of the observed variation in sodium levels among runners with similar degrees of weight gain. Although Twerenbold et al. found a difference,1 other studies analyzing the effect of salt intake on plasma sodium levels during prolonged exercise have shown mixed results.2,3,4 It is unclear whether the lack of a consistent benefit can be explained by methodologic issues or by the pathophysiology of hyponatremia, which may include a component of antidiuresis, a mechanism that may be less amenable to correction with sodium. Nevertheless, these reports document a low incidence of hyponatremia among runners who did not gain weight. Although the role of salt supplementation merits further study, the available evidence indicates that the most effective way to prevent hyponatremia during marathon running is to avoid a positive fluid balance.
We agree with Dr. Ayus and colleagues that hypertonic saline is the treatment of choice for symptomatic patients with severe hyponatremia, and that treatment with hypotonic fluids for presumed hypovolemia could be detrimental. Rapid point-of-care testing to establish the serum sodium level is invaluable in determining the appropriate fluid therapy for ill marathoners, especially because the clinical presentation of dehydration can be similar to that of hyponatremia.
Dr. Halperin and colleagues point out that weight gain may underestimate the degree of free water excess in runners, if one assumes that the postrace weight should be lower than the prerace weight on the basis of glycogen and fat metabolism, irrespective of fluid balance. We agree with Dr. Halperin and colleagues, whose suggestion may account for the small group of runners in our study who had hyponatremia but did not have an appreciable weight change. Indeed, the optimal fluid balance for marathoners may involve the loss of a small percentage of body weight during the race.
Christopher S.D. Almond, M.D., M.P.H.
Andrew Y. Shin, M.D.
David S. Greenes, M.D.
Children's Hospital Boston
Boston, MA 02115
christopher.almond@childrens.harvard.edu
References
Twerenbold R, Knechtle B, Kakebeeke TH, et al. Effects of different sodium concentrations in replacement fluids during prolonged exercise in women. Br J Sports Med 2003;37:300-303.
Speedy DB, Thompson JM, Rodgers I, Collins M, Sharwood K, Noakes TD. Oral salt supplementation during ultradistance exercise. Clin J Sport Med 2002;12:279-284.
Barr SI, Costill DL, Fink WJ. Fluid replacement during prolonged exercise: effects of water, saline, or no fluid. Med Sci Sports Exerc 1991;23:811-817.
Irving RA, Noakes TD, Buck R, et al. Evaluation of renal function and fluid homeostasis during recovery from exercise-induced hyponatremia. J Appl Physiol 1991;70:342-348.