Statement of the Third International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015
2015; Lippincott Williams & Wilkins; Volume: 25; Issue: 4 Linguagem: Inglês
10.1097/jsm.0000000000000221
ISSN1536-3724
AutoresTamara Hew‐Butler, Mitchell H. Rosner, Sandra Fowkes-Godek, Jonathan Dugas, Martin D. Hoffman, Douglas Lewis, Ronald J. Maughan, Kevin C. Miller, Scott J. Montain, Nancy J. Rehrer, William O. Roberts, Ian R. Rogers, Arthur J. Siegel, Kristin J. Stuempfle, James Winger, Joseph G. Verbalis,
Tópico(s)Muscle metabolism and nutrition
ResumoINTRODUCTION The third International Exercise-Associated Hyponatremia (EAH) Consensus Development Conference convened in Carlsbad, California in February 2015 with a panel of 17 international experts. The delegates represented 4 countries and 9 medical and scientific sub-specialties pertaining to athletic training, exercise physiology, sports medicine, water/sodium metabolism, and body fluid homeostasis. The primary goal of the panel was to review the existing data on EAH and update the 2008 Consensus Statement.1 This document serves to replace the second International EAH Consensus Development Conference Statement and launch an educational campaign designed to address the morbidity and mortality associated with a preventable and treatable fluid imbalance. The following statement is a summary of the data synthesized by the 2015 EAH Consensus Panel and represents an evolution of the most current knowledge on EAH. This document will summarize the most current information on the prevalence, etiology, diagnosis, treatment and prevention of EAH for medical personnel, athletes, athletic trainers, and the greater public. The EAH Consensus Panel strove to clearly articulate what we agreed upon, did not agree upon, and did not know, including minority viewpoints that were supported by clinical experience and experimental data. Further updates will be necessary to both: (1) remain current with our understanding and (2) critically assess the effectiveness of our present recommendations. Suggestions for future research and educational strategies to reduce the incidence and prevalence of EAH are provided at the end of the document as well as areas of controversy that remain in this topic. CONSENSUS METHODOLOGY The third International Exercise-Associated Hyponatremia Consensus Development Conference utilized National Institutes of Health guidelines, amended for a more holistic approach to fit the needs of both the group and the topic. Twenty-two individuals (17 accepted) were invited to participate in the consensus conference who: (1) have made scientific and/or clinical contributions to the topic of water and sodium homeostasis and/or hyponatremia and (2) represented a specific group (eg, nephrology, endurance medicine, etc.) or had unique topical expertise (eg, cystic fibrosis, muscle cramps, fluid balance, etc.). The present document is intended to serve as the scientific record of the conference with intent to widely disseminate this information to achieve maximum impact on both current health care practice and future medical research. The methodology governing the conduct of this consensus development conference is summarized below: A broad based expert panel was assembled. Panel members included researchers and clinicians in endocrinology (J.G.V.), nephrology (M.H.R.), emergency medicine (I.R.R.), family medicine (W.O.R., J.M.W., D.P.L.), internal medicine (A.J.S.), physical medicine and rehabilitation (M.D.H.), sports medicine (W.O.R., J.M.W., D.P.L.), athletic training (S.F.-G., K.C.M.) and exercise physiology (J.P.D., S.F.-G., T.H.-B., M.D.H., R.J.M., S.J.M., N.J.R., K.J.S.). These experts presented data on EAH in a day long public session, followed by open question/answer and discussion periods with the audience. The panel members met the following day in a closed session to prepare the consensus statement. Workgroups were created 3 months prior to the February 2015 meeting to update the following EAH target areas: epidemiology, etiology and pathophysiology, diagnosis, treatment, and prevention. Each workgroup was asked to present updated drafts for discussion during the closed session. A systematic, comprehensive and updated literature review was shared by the panel members prior to the February 2015 meeting, using a cloud storage service that was organized into workgroup categories (epidemiology, etiology and pathophysiology, diagnosis, treatment and prevention). All panel members had unlimited access to the cloud storage service and could add digital versions of published manuscripts to the EAH manuscript section at any time. The panel chairperson (MHR) was responsible for monitoring the progress of each work group, directing the closed session and guiding the panel's deliberations. Using the previous 2 EAH consensus statements as a starting point, each work-group was asked to: (1) incorporate new data into each assigned section and (2) update any outdated information. All recommendations were graded based on clinical strength, using the grading scale described by the American College of Chest Physicians (Table 1).2 Particular emphasis was placed on creating more generalized recommendations so as to prevent and treat EAH across a wider variety of athletic events, rather than the endurance sports focus of the 2 prior EAH Consensus Statements.TABLE 1: American College of Chest Physicians Classification Scheme for Grading Evidence and Recommendations Utilized in This Statement2Sponsorship The travel (except R.J.M. and I.R.R., who supported their own travel), hotel and meal expenses for the participants were funded by CrossFit, Inc (Solana Beach, CA). The open conference was also sponsored by CrossFit, Inc. However, no members from CrossFit, Inc participated in any of the closed discussions or contributed to the development of the consensus guidelines. Furthermore, no members from CrossFit, Inc had access to the consensus document prior to publication. RESULTS AND DISCUSSION Definition EAH is used to describe hyponatremia occurring during or up to 24 hours after physical activity. It is defined by a serum, plasma or blood sodium concentration ([Na+]) below the normal reference range of the laboratory performing the test. For most laboratories, this is a [Na+] less than 135 mmol/L.1 The main determinants of the serum [Na+] are the total content of exchangeable body sodium and potassium relative to total body water and thus hyponatremia can result from loss of solutes (sodium, potassium), a relative excess of total body water or a combination of both.3,4 However, in most clinical scenarios, the driving force for the development of hyponatremia is a relative excess of total body water.5,6 The symptoms associated with EAH depend on both the magnitude of the serum sodium decrease from baseline level along with the rate at which this decrease occurs. Symptomatic EAH can occur if the rate of fall approaches 7% to 10% within 24 hours.7 Thus, more severe degrees of hyponatremia (typically <125 mmol/L) as well as more modest serum sodium values (in the range of 125-130 mmol/L), that develop over a short period of time, can both be associated with signs and symptoms.8 Epidemiology The vast majority of recreationally active individuals begin endurance races with a blood [Na+] above 135 mmol/L. Based on data pooled from 27 separate studies, encompassing 2262 participants with a verifiable pre-race blood [Na+] measurement, only 0.8% (19/2262) presented with hyponatremia prior to race start.9–35 These pooled data represent blood [Na+] measurements collected in 7 countries and between 5 minutes to 72 hours pre-competition. This 0.8% also includes 16 questionable below-normal [Na+] values possibly confounded by fingerstick hemolysis29 and/or outdated techniques.25 Thus, baseline (pre-event) hyponatremia in recreational exercisers appears to fall within the expected range for a normal population distribution (1%-2%), and at a frequency well below what has been observed in individuals presenting for non-hyponatremia related clinical treatment situations36 or in hospitalized patients.37 We thereby believe that EAH largely develops during or immediately following exercise. Exercise-associated hyponatremia can present in 2 forms: asymptomatic or symptomatic. Asymptomatic athletes with [Na+] <135 mmol/L have largely been detected by blood samples taken post-exercise from athletes participating in research protocols or obtained for reasons other than suspicion of EAH. Athletes with the symptomatic form of EAH can present with mild, non-specific symptoms (eg, lightheadedness, nausea) but typically present with headache, vomiting, and/or altered mental status (eg, confusion, seizure) resulting from cerebral edema (termed exercise-associated hyponatremic encephalopathy or EAHE) that may38–48 or may not49–52 be associated with non-cardiogenic pulmonary edema. EAHE is a life-threatening condition that has been observed across a wide variety of activities (Table 2). The incidence of asymptomatic and symptomatic cases of EAH varies widely with regard to type and duration of activity, location of the event, characteristics of the participants (see risk factors) and heat or cold stress during the event.TABLE 2: Activities in Which Symptomatic EAH Has Been Reported. Those Activities in Which Known Deaths Have Occurred Are Noted With an Asterik (*)Epidemiology of Asymptomatic EAH The reported incidence of asymptomatic EAH has ranged from 0%30,53 to 51%54 immediately post-race. In a study of an ultramarathon, 67% of the participants were hyponatremic (asymptomatic) at some point during the race, but only 27% finished the with serum [Na+] <135 mmol/L (40% self-corrected prior to finishing the event).11 The highest reported incidence of asymptomatic hyponatremia post-race has been consistently noted in 161-km ultramarathons, in which the reported incidence of EAH has ranged between 5% and 51%.18,54–56 The incidence of asymptomatic EAH in Ironman triathlons in different environments has been reported to range from negligible10 to as high as 18%57 and 25%.19 In studies on endurance cyclists the incidence of asymptomatic EAH has ranged from 0% in a 720-km race30 to 12% in a 109-km race.15 In a 26.4-km swim, 17% of swimmers developed asymptomatic hyponatremia.32 The reported incidences at the standard marathon distance run (42.2 km) have ranged from 0%53 to 12% to 13% of race finishers.28,58 Additionally, asymptomatic hyponatremia was observed in 33% of premier league UK rugby players following an 80 minutes rugby competition59 and 70% of elite rowers during a 28-day training camp.60 Epidemiology of Symptomatic EAH Symptomatic EAH is rare and occurs with considerably less frequency than asymptomatic EAH, but complications associated with EAH have led to at least 14 athlete related deaths since 1981.28,38,47,50,61–69 Symptomatic EAH generally occurs as an isolated case or in small clusters during or following endurance events with participants reporting to the race medical facilities or to hospital emergency departments within 24 hours after participation. In general, participants seek treatment for a constellation of symptoms ranging from feeling unwell to convulsions. Clusters of cases have occurred in military training exercises, marathons, Ironman triathlons and ultramarathons. The incidence of symptomatic EAH has been reported to be as high as 23%57 and 38%70 of athletes seeking medical care in an Ironman Triathlon and an ultramarathon, respectively, but most endurance events report no cases of symptomatic EAH, especially at the marathon distance and below. Two studies have examined large compilations of data to help define the incidence of symptomatic and asymptomatic EAH.55,71 In the first study of 2135 athletes from 8 endurance events ranging in length from 42.2 to 161 km,71 the incidence of symptomatic EAH was 1% (compared to 6% with asymptomatic EAH) among study participants. In the second study of 669 161-km ultramarathon runners,55,72 only one case (0.1% among study participants) of symptomatic EAH presented during the 5-year sampling period (compared to 13% with asymptomatic EAH), but considering the total number of race participants over this time period, the actual incidence of symptomatic EAH was approximately 0.06%. Symptomatic EAH has also been reported in hikers73–75 and military personnel.75–77 Symptomatic EAH accounted for 16% of Grand Canyon hikers seeking medical care for exercise-associated collapse or exhaustion from May 31, 1993 through September 31, 1993 providing an estimated incidence rate between 2 and 4 per 100,000 persons.73,78 Furthermore, suspected hyponatremia was found to account for 19% of non-fatal suspected heat-related incidents in the Grand Canyon National Park from April through September during 2004 through 2009 hiking seasons.74 In the US active duty military, the annual incidence rate of hyponatremia from 1999 through 2012 has ranged from ∼4 to 13 cases per 100,000 person-years (averaged 6.7 cases per 100 000 person-years).77 However, this incidence is probably inflated as the data were derived from a medical coded database that does not have a specific designation for EAH and likely includes hyponatremia from both exercise and non-exercise related conditions. Alarmingly, symptomatic EAH is now being reported in a more diverse set of sporting activities. For instance, symptomatic EAH has been reported in shorter distance endurance competitions, such as a half marathon79 with slower finishers completing the distance in 2 to 3 hours and a sprint triathlon with slower finishers taking approximately 2 hours to complete.80 In addition, EAH has been reported in US professional and college American rules football players40,41 and has led to the deaths of 3 US high school football players between 2008 and 2014.63,64,69 Symptomatic hyponatremia has also been reported in a 48 year old lawn bowler who was heterozygous for the Delta F508 cystic fibrosis (CF) mutation, although it is unclear if complete genetic analysis for all possible CF mutations was performed,81 a 34 year old woman following a Bikram Yoga session82 and in a 39 year old woman following a 2 hour workout including tennis and weightlifting.83 Cases of symptomatic EAH have also been induced in 2 separate laboratory studies involving low intensity exercise conducted in high ambient temperatures.84,85 Deaths from symptomatic EAH have occurred in a 25 year old male police officer participating in a 19-km bicycle training ride68 and at least partially contributed to a case of fraternity hazing involving a male pledge performing calisthenics.67 It is likely that other cases of symptomatic hyponatremia have either not been recognized or reported. Risk Factors The major risk factors for developing EAH are listed in Table 3. The single most important risk factor is sustained, excessive fluid (water, sports drinks or other hypotonic fluids) intake in volumes greater than loss through sweat, respiratory and renal water excretion so that a positive fluid balance accrues over time.86,87 Almost all cases of symptomatic EAH have occurred in individuals who have gained or maintained weight during activities in which some weight loss would represent fluid balance and euhydration.71,72 Body weight losses of <0.75 kg after a standard marathon35 and 20 hours),11,54–56 and/or in hotter11,19,20,55,108,109 environments and/or with higher sweat sodium losses.99,101 Clinical confirmation of the hypovolemic form of hyponatremia is supported by a spot urine sodium concentration (U[Na+]) below 30 mmol/L136,137,144 in conjunction with a serum or plasma [Na+] below 135 mmol/L. A spot U[Na+] 5 mmol/L) in serum [Na+] following isotonic saline administration136 in clinical patients. Elevated blood urea nitrogen levels (>20 mg/dL)136,139 and weight loss19,20,55 may also suggest volume depletion as a pathogenic contributor to EAH. However, these biochemical tests are not always available at the point of care and thus clinical assessment (vital signs, weight change, and physical examination) may be the only indication of volume depletion.TABLE 4: Comparisons of Sodium and fluid Balance Measured During the Recovery Period After Exercise Demonstrating Race Characteristics and Biochemical Differences Between Fluid Overload Hyponatremia (Irving et al,123 Speedy et al,140 and Speedy et al141) Versus Suspected Hypovolemic Hyponatremia (Owen et al139)SUMMARY STATEMENT Under-replaced sodium losses contribute to serum [Na+] independent of distance (Grade 1A). However, there is paucity of data supporting sodium loss as the primary mechanism of symptomatic EAH even in those who exercise for prolonged periods of time and in warm weather (Grade 2C). In these cases, relative over-drinking of hypotonic fluids with sustained non-osmotic AVP secretion is likely involved in the development of symptomatic EAH. The Role of Thirst Since drinking fluid volume above sweat and urinary losses during and after activity is the main pathophysiological mechanism underlying asymptomatic, symptomatic and fatal cases of EAH, prevention is dependent on drinking less. Thirst should provide adequate stimulus for preventing excess dehydration and markedly reduce the risk of developing EAH in all sports. Physiologically-driven thirst has been defined as a “generalized, deep seated feeling of desire for water”145 and is an evolutionarily conserved, finely tuned, regulatory mechanism serving to protect both plasma osmolality and circulating plasma volume.146 Osmoreceptors located within the circumventricular organs of the brain (highly vascularized structures located around the third and fourth ventricles and characterized by the lack of a blood–brain barrier that are points of communication between the blood, the brain parenchyma, and the cerebral spinal fluid) and baroreceptors located within the aortic arch, carotid sinus and great veins provide “real-time” neural input to higher centers of the brain which continuously and simultaneously coordinate the regulation of both thirst and AVP secretion. Thus, there are physiological sensing mechanisms in place to prompt when to drink and therefore guard against excessive dehydration. Earlier published recommendations to begin drinking before thirst was largely meant for situations where sweating rates were high, above maximal rates of gastric emptying, and dehydration would rapidly accrue over time. Unfortunately, this advice has fostered the misconception that thirst is a poor guide to fluid replacement and has facilitated inadvertent overdrinking and pathological dilutional EAH. Clinical Classification and Diagnosis of EAH The diagnosis of EAH is made when the blood, serum or plasma [Na+] is below the normal reference range of the laboratory performing the test (typically <135 mmol/L) and is associated with typical clinical constellation of symptoms and signs. In our collective experience, EAH is best classified by clinical severity (symptoms) and not the absolute numerical [Na+] value to best guide treatment strategies. Characteristics of Asymptomatic EAH Asymptomatic EAH represents a biochemical finding, diagnosed by blood electrolyte testing for research or unrelated metabolic screening purposes.10,15,18,19,28,30,32,53–59 This group of subjects presents without any discernable symptoms or may have mild, generalized and transient complaints commonly experienced by other participants who do not typically seek medical care following exercise. In normally distributed populations, up to 5% of all athletes tested would fall outside of the normal range for [Na+], with half of those (2.5%) falling in the range of asymptomatic EAH values. Characteristics of Mild EAH Mildly symptomatic EAH typically presents with nonspecific signs and symptoms without clear signs of encephalopathy (Table 5). Athletes with mild EAH may have normal vital signs, may not have any orthostatic hypotension, and the symptoms do not resolve after placing athletes in the Trendelenburg position147 as would be expected with exercise associated postural hypotension.148 The clinical symptoms of mild symptomatic EAH are not specific or sensitive, but should raise the index of suspicion for EAH and necessitate a low threshold for [Na+] measurement, as athletes can rapidly progress from mild symptoms to severe and life-threatening EAHE (Table 5).TABLE 5: Signs and Symptoms of Mild and Severe (Life-threatening) EAH. Signs and Symptoms Related to Other Conditions Associated With Exercise-Associated Collapse Noted With an Asterisk (*)EAH must be differentiated from other causes of collapse that may present with similar signs and symptoms including exertional heat illness,73 acute mountain sickness,39 hypernatremia,149,150 and exercise associated postural hypotension.148 It is important for medical staff to perform a rapid history and physical examination to help determine the etiology of these nonspecific symptoms. However, any clinical suspicion of EAH should lead to prompt measurement of [Na+], if possible. It is common for athletes with EAH to maintain or gain weight during exercise.58,71,72 However, EAH in the presence of weight loss has been documented in ultra-endurance races in the heat.19,20,55,59 Thus, the presence of weight loss does not necessarily exclude EAH. Weight gain or weight maintenance associated with any symptoms listed in Table 5 is an indication to measure the athlete's [Na+] in order to confirm or exclude the diagnosis of EAH or to consider empiric treatment if on-site [Na+] cannot be measured, such as in remote settings.72,118,151 Characteristics of Severe EAH (EAHE) Severe symptomatic EAH is characterized by neurological signs and symptoms due to cerebral edema that occur when water flows along the osmotic gradient from the extracellular fluid into the intracellular compartment (Table 3).38–52,152 Severe symptomatic EAH may38–48 or may not49–52 be accompanied by the respiratory distress of CNS-triggered non-cardiogenic pulmonary edema (Table 5). EAHE is a life threatening condition that requires urgent intervention and should be evaluated with an immediate [Na+] measurement if available. SUMMARY STATEMENT EAH can present with a wide range of symptoms ranging from nonspecific mild complaints to severe encephalopathy. The severity of symptoms and not the absolute value of the [Na+] should guide the choice of therapy (Grade 1A). Rapid determination of [Na+] is critical in confirming clinical suspicion but may not always be available. Treatment of EAH Any athlete exhibiting signs or symptoms consistent with acute hyponatremia (Table 5) should be screened for EAH. The capacity for onsite [Na+] analysis
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