Four Cases of Acute Kidney Injury Requiring Dialysis in Ultramarathoners.

Transient acute kidney injury (AKI) following ultraendurance footraces is a common biochemical diagnosis. However, severe AKI requiring renal replacement therapy is uncommon in ultramarathoners. We report 4 runners (3 men; mean age, 44 ± 3 y) who required prolonged (10-42 d) dialysis following the Western States 100 Mile Endurance Run over a 3-y span (0.38% of starters). The maximum ambient temperatures on the race day ranged from 36.6° to 38.3°C. The runners presented to local hospitals 17 to 32 h after running, with laboratories confirming rhabdomyolysis, hyponatremia (mean serum sodium concentration, 127±2 mmol⋅L-1), and AKI (mean serum creatinine concentration, 8.5±2 mg⋅dL-1). The case-cluster report highlights the potential synergistic effects of high ambient temperatures, muscle damage, and electrolyte imbalance on protracted renal dysfunction in ultramarathoners competing in a warming world.

Too Tall for the DXA Scan? Contributions of the Feet and Head to Overall Body Composition.

Accurate assessment of total body composition in tall (>1.96m) individuals using dual energy x-ray absorptiometry (DXA) scans is problematic due to current height restrictions of the scan table. The aim of this investigation was to quantify absolute and relative contributions of fat, bone and lean mass, of the feet and head regions, to whole-body composition DXA scan totals. Whole-body DXA scans were performed in collegiate athletes. Athlete DXA scans were included in data analyses if the entire body fit within the confines of scan table area. The feet region of interest (ROI) was delineated at the ankle joint mortise, marked superiorly by the inferior margin of the tibial plafond and encompassing all inferior anatomical structures. The head region was calculated by the DXA scan software. Both absolute (kg) and relative (feet/whole-body x 100 = feet mass %) contributions to body composition were calculated. Data presented as mean±SD. 132 National Collegiate Athletic Association (NCAA) athletes (85 female) underwent DXA scans which met the inclusion criteria. The feet region represented: 1.9±0.3kg (2.6±0.3%) of total mass; 0.4±0.3kg (2.6±0.5%) of fat mass; 1.3±0.3kg (2.5±0.3%) of lean mass; and 0.14±0.0kg (5.4±0.6%) of bone mineral content (BMC). The head region represented: 4.8±0.5kg (6.9±0.8%) of total mass; 1.2±0.2kg (8.2±3.0%) of fat mass; 3.2±0.5kg (6.1±0.9%) of lean mass; and 0.48±0.07kg (18.7±2.7%) of BMC. Significant negative relationships were found between head% versus whole-body BMC (r=-0.54;p < 0.0001), lean mass (r=-0.57;p<0.0001), and fat mass (r=-0.81;p<0.0001) and between feet% versus fat mass (r=-0.68;p<0.0001). A significant positive relationship was noted between feet% versus whole-body BMC (r=0.18;p=0.04) but not versus lean mass (r=0.15;p=0.09). Removing the feet from whole-body composition analyses reduces lean, fat and bone mass compartment totals by 3%-5%. Removing the head region reduces body composition compartments by 6%-19%, from whole-body DXA scan totals.

Muscle Damage, Soreness, and Stress During Preseason Training in Collegiate Swimmers.

BACKGROUND: In 2014, 6 collegiate swimmers were hospitalized for symptomatic exertional rhabdomyolysis. OBJECTIVE: To serially monitor and assess relationships between skeletal muscle membrane disruption, upper body soreness (UBS) and lower body soreness (LBS), and stress during the first 6 weeks (timepoints) of preseason training in collegiate male and female swimmers. DESIGN: Prospective observational study. SETTING: College/university. PARTICIPANTS: Forty swimmers. INDEPENDENT VARIABLES: Upper and lower body soreness rating (0-10); testosterone (T), cortisol (C), and T/C ratio. MAIN OUTCOME MEASURES: Creatine kinase (CK) and myoglobin (over time) versus independent variables. RESULTS: Weekly training load consisted of ∼87% swimming, ∼5% running, and ∼8% weight training, which increased from 15.8 hours to 20.5 total training hours per week over the first 6 weeks of training. Muscle damage in collegiate swimmers was modest and peaked after the first week of training (week 2) for men (CK = 438 ± 259 U/L; P < 0.0001; r2 = 0.28; myoglobin = 47 ± 18 ng/mL; P = 0.001; r2 = 0.22) and women (CK = 446 ± 723 U/L; P < 0.01; r2 = 0.13; myoglobin = 63 ± 140 ng/mL, not significant) with high variability. Data were presented as peak mean ± SD, significant P value, and r2 from repeated-measures analysis of variance. A temporal disconnect was noted between muscle damage and UBS, which peaked at week 5 in both men (5 ± 2; P < 0.0001; r2 = 0.44) and women (6 ± 2; P < 0.0001; r2 = 0.57). The serum cortisol level decreased over time, which peaked at week 1 (baseline) in men (15 ± 6 µg/dL; P = 0.0004; r2 = 0.38) and women (19 ± 10 µg/dL; P < 0.0001; r2 = 0.49). The testosterone level remained unchanged, which promoted an anabolic hormonal environment that peaked at week 6 (increasing T/C ratio) in men (58 ± 32; P = 0.0003; r2 = 0.31) and women (4 ± 3; P = 0.04; r2 = 0.18) despite gradual increases in training and soreness. CONCLUSIONS: Muscle soreness does not parallel muscle membrane disruption. A 1-week "transition" period is required for muscles to adapt to intense/novel training.

Oral Hypertonic Saline Is Effective in Reversing Acute Mild-to-Moderate Symptomatic Exercise-Associated Hyponatremia.

OBJECTIVES: To determine whether oral administration of 3% hypertonic saline (HTS) is as efficacious as intravenous (IV) 3% saline in reversing symptoms of mild-to-moderate symptomatic exercise-associated hyponatremia (EAH) in athletes during and after a long-distance triathlon. DESIGN: Noninferiority, open-label, parallel-group, randomized control trial to IV or oral HTS. We used permuted block randomization with sealed envelopes, containing the word either "oral" or "IV." SETTING: Annual long-distance triathlon (3.8-km swim, 180-km bike, and 42-km run) at Mont-Tremblant, Quebec, Canada. PARTICIPANTS: Twenty race finishers with mild to moderately symptomatic EAH. INDEPENDENT VARIABLES: Age, sex, race finish time, and 9 clinical symptoms. MAIN OUTCOME MEASURES: Time from treatment to discharge. METHODS: We successfully randomized 20 participants to receive either an oral (n = 11) or IV (n = 9) bolus of HTS. We performed venipuncture to measure serum sodium (Na) at presentation to the medical clinic and at time of symptom resolution after the intervention. RESULTS: The average time from treatment to discharge was 75.8 minutes (SD 29.7) for the IV treatment group and 50.3 minutes (SD 26.8) for the oral treatment group (t test, P = 0.02). Serum Na before and after treatment was not significantly different in both groups. There was no difference on presentation between groups in age, sex, or race finish time, both groups presented with an average of 6 symptoms. CONCLUSIONS: Oral HTS is effective in reversing symptoms of mild-to-moderate hyponatremia in EAH.

Wilderness Medical Society Clinical Practice Guidelines for the Management of Exercise-Associated Hyponatremia: 2019 Update.

Exercise-associated hyponatremia (EAH) is defined by a serum or plasma sodium concentration below the normal reference range of 135 mmol·L-1 that occurs during or up to 24 h after prolonged physical activity. It is reported to occur in individual physical activities or during organized endurance events conducted in environments in which medical care is limited and often not available, and patient evacuation to definitive care is often greatly delayed. Rapid recognition and appropriate treatment are essential in the severe form to increase the likelihood of a positive outcome. To mitigate the risk of EAH mismanagement, care providers in the prehospital and in hospital settings must differentiate from other causes that present with similar signs and symptoms. EAH most commonly has overlapping signs and symptoms with heat exhaustion and exertional heat stroke. Failure in this regard is a recognized cause of worsened morbidity and mortality. In an effort to produce best practice guidelines for EAH management, the Wilderness Medical Society convened an expert panel in May 2018. The panel was charged with updating the WMS Practice Guidelines for Treatment of Exercise-Associated Hyponatremia published in 2014 using evidence-based guidelines for the prevention, recognition, and treatment of EAH. Recommendations are made based on presenting with symptomatic EAH, particularly when point-of-care blood sodium testing is unavailable in the field. These recommendations are graded on the basis of the quality of supporting evidence and balanced between the benefits and risks/burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians.

Sodium loading, treadmill walking, and the acute redistribution of bone mineral content on dual energy X-ray absorptiometry scans.

The purpose of this study was to assess relationships between plasma sodium concentration ([Na+]) and bone mineral content (BMC) after an acute sodium load plus treadmill walking and then quantify the amount of sodium the dual energy X-ray absorptiometry (DXA) scan could detect. The primary study was a single-blind randomized control crossover trial under two conditions: ingestion of six flour tablets (placebo trial) or six 1-g NaCl tablets (salt intervention trial). The tablets were ingested after baseline blood and urine collection followed immediately by the DXA scan. After 60 min of rest, a 45-min treadmill walk was conducted. Immediately postexercise, blood and urine were collected and the DXA scan was repeated. Main outcomes included changes (∆: post minus pre) in plasma [Na+] and BMC. Additionally, six 1-g NaCl tablets were superimposed over a DXA spine phantom for separate quantification of sodium as BMC. Fourteen subjects completed the primary study. Two-way repeated measures ANOVA tests revealed significant interaction ( F = 13.06; P = 0.0007), condition ( F = 21.88; P < 0.001), and time ( F = 6.51; P = 0.014) effects in plasma [Na+]. A significant condition ( F = 6.46; P = 0.014) effect was also noted in urine [Na+]. Total body BMC∆ was negatively correlated with plasma [Na+]∆ ( r = -0.43; P = 0.02) and urine [Na+]∆ ( r = -0.47; P = 0.01). Total body BMC∆ in the salt intervention trial [-5.5 (27) g] closely approximated the amount of NaCl ingested and subsequently absorbed into the bloodstream. The DXA scan quantified 67% of NaCl tablets as BMC in spine phantom analyses. Total body BMC∆ was negatively related to plasma and urine [Na+]∆ after treadmill walking. Reductions in total body BMC closely approximated the amount of NaCl ingested (~6 g). The DXA scan quantified NaCl as BMC.

Exercise-Associated Hyponatremia in a Lactating Female.

A 37-year-old woman presented to the emergency department with severe headache, which quickly progressed to altered mental status and seizure activity in hospital. Her initial serum sodium concentration ([Na]) was 126 mmol/L. In the 24 hours before admission, she exercised vigorously for 120 minutes (interval training plus yoga) and also consumed more than 4 liters of fluid during that time to both stay hydrated and facilitate milk production because she was actively nursing 2 children. Her serum [Na] and altered mental status corrected slowly over the next 48 hours with furosemide, hypertonic saline, and fluid restriction. This case is unique because it discusses the possible pathogenic role that lactation-induced oxytocin release may have on sustained antidiuresis and dilutional exercise-associated hyponatremia (EAH). This would be the first report documenting EAH in a lactating woman, which may highlight an underrecognized risk factor for physically active women who are concurrently breast-feeding.

Risk Factors for Collegiate Swimmers Hospitalized With Exertional Rhabdomyolysis.

OBJECTIVE: To identify midseason risk factors for symptomatic exertional rhabdomyolysis (sER) in swimmers after a novel upper body workout. DESIGN: Retrospective (1) survey and (2) analyses of observational laboratory data conducted over a 16-week training period, 2 months before sER. SETTING: Midwest University. PARTICIPANTS: Thirty-four collegiate swimmers. INDEPENDENT VARIABLES: (1) Motivation, symptoms, and supplements for survey variables. (2) Changes (midseason minus preseason) in body composition, blood pressure (BP), urinary measures, and protein shake ingestion for laboratory variables. MAIN OUTCOME MEASURES: Swimmers were categorized in hospitalized (H), treated and released from hospital (RH), and nonhospitalized (NH) groups for analyses. RESULTS: (1) Six swimmers were in the H group (17.6%; 3 male/3 female) and 7 in the RH group (20.6%; 3 male/4 female). Nonsignificant trend toward H swimmers relating more upper body soreness (≥9/10) than RH (8/10) and NH (6/10) swimmers (P > 0.05) while reporting "felt bad and workout went poorly" (P = 0.009). H and RH swimmers reported more arm locking during the workout (P = 0.04) and brown urine after arm competition compared with NH-group swimmers (P = 0.03). (2) Increases in right systolic (P = 0.01) and left diastolic (P = 0.02) BP, with trends toward decreased left arm lean mass (P = 0.06) in H compared with RH and NH swimmers. Female H swimmers had more acidic urine (pH = 5.50 vs 6.9; P = 0.004), less volume, and higher specific gravity than RH + NH swimmers. All H swimmers regularly ingested protein shakes after workouts. CONCLUSIONS: Risk factors for sER included exceptional motivation, extreme soreness, increased resting BP, acidic urine (females), and regular ingestion of protein shakes.

Special Communication of a Case of Hypovolemic-Associated EAH: Lessons Learned During Recovery.

Severe exercise-associated hyponatremia (EAH) is largely dilutional, whereas contributions of sodium loss remain equivocal. We present a case of EAH with encephalopathy involving an experienced male cyclist with no recollection of the event. We thereby conducted a retrospective analysis of biochemical trajectories during hospital recovery. The normalization of serum [Na], in context with changes in other variables, offered a 'reverse' perspective of the underlying pathophysiology. The following biochemical changes were temporally observed, with the return of normonatremia: 1) a decrease in serum potassium and calcium concentrations (absence of extracellular fluid dilution); 2) a decrease in total protein, blood urea nitrogen, hematocrit and hemoglobin (plasma volume expansion); and 3) an increase in mean platelet and red cell corpuscular volumes (cellular expansion after total body water and sodium deficits). Collectively, these temporal changes provide biochemical evidence suggesting that this patient's severe symptomatic EAH was associated with volume depletion from underreplaced sodium losses.

Proof of concept: hypovolemic hyponatremia may precede and augment creatine kinase elevations during an ultramarathon.

PURPOSE: It is not known if exercise-associated hyponatremia (EAH) is a cause or consequence of exertional rhabdomyolysis (ER).We hypothesized that osmotic stress (EAH) coupled with mechanical stress (running) potentiated muscle cell breakdown (ER). This concept would be supported if a nadir in serum sodium concentration ([Na(+)]) temporally preceded peak creatine kinase levels (CK) during an ultramarathon run. METHODS: Fifteen participants ran ≥104 km and had blood drawn: prior to start; 53; 104 km; and 24-h post run. Serum [Na(+)], CK, urea, creatinine and estimated glomerular filtration rate (eGFR) were measured from serial blood samples. Two-way repeated-measures ANOVA was used to examine differences regarding both race distance and natremia status. RESULTS: Ten of 15 participants demonstrated EAH (serum [Na(+)] <135 mmol/L) at least once during serial testing. Participants were categorized post hoc into one of three natremia groups based on lowest recorded [Na(+)]: (1) <129 mmol/L (n = 3; moderate EAH); (2) between 129 and 134 mmol/L (n = 7; mild EAH); and (3) >134 mmol/L (n = 5; normonatremia). Participants with lowest [Na(+)] demonstrated highest CK values at subsequent checkpoints. Significant natremia group differences noted at the 53 km point (p = 0.0002) for [Na(+)] while significant natremia group effect noted for CK seen at the 24-h post-finish testing point (p = 0.02). Significant natremia group effects noted for renal biomarkers, with the moderate EAH group documenting the lowest eGFR (p = 0.005), and highest serum urea (p = 0.0006) and creatinine (p < 0.0001) levels. Hyponatremic runners had lower post-race urine [Na(+)] than normonatremic runners (26 ± 15 vs. 89 ± 79 mmol/L; p = 0.03). CONCLUSIONS: Preliminary data support the possibility that transient hypovolemic EAH may precede and augment CK during an ultramarathon.

Nausea is associated with endotoxemia during a 161-km ultramarathon.

This study explored possible contributing factors to gastrointestinal distress, including endotoxemia, hyperthermia, dehydration and nutrition, during a 161-km ultramarathon. Thirty runners participated in the study and 20 finished the race. At three checkpoints and the finish, runners were interviewed to assess the incidence and severity of 12 gastrointestinal symptoms and to determine dietary intake. Core temperature was measured at the same locations. Runners were weighed pre-race, at the three checkpoints and the finish to monitor hydration status. Blood markers for endotoxemia (sCD14) and inflammation (interleukin-6 and C-reactive protein) were measured pre- and post-race. Gastrointestinal symptoms were experienced by most runners (80%), with nausea being the most common complaint (60%). Runners with nausea experienced significantly greater (P = 0.02) endotoxemia than those without nausea (sCD14 mean increase 0.7 versus 0.5 µg · mL(-1)). There was a significant positive correlation (r = 0.652, P = 0.005) between nausea severity and endotoxemia level. Inflammatory response, core temperature, hydration level and race diet were similar between runners with and without nausea. This study links endotoxemia to nausea in ultramarathon runners. Other possible contributing factors to nausea such as hyperthermia, dehydration and nutrition did not appear to play a role in the symptomatic runners in this study.

Incidence of Exercise-Associated Hyponatremia and Its Association With Nonosmotic Stimuli of Arginine Vasopressin in the GNW100s Ultra-endurance Marathon.

OBJECTIVES: (1) To examine the incidence of exercise-associated hyponatremia (EAH) during and after an ultramarathon and (2) to evaluate hypothesized nonosmotic stimuli [interleukin-6 (IL-6), hypoglycemia, ambient temperature] with arginine vasopressin (AVP) concentrations in hyponatremic versus normonatremic runners. DESIGN: Prospective cohort study. SETTING: The Great North Walk 100s ultramarathons. PARTICIPANTS: Fifteen runners participated in either 103.7- or 173.7-km ultramarathons. MAIN OUTCOME MEASURES: Serum sodium concentration ([Na]) and AVP concentration. Secondary outcome measures included IL-6, blood glucose, ambient temperature, weight change, fluid consumption, and use of nonsteroidal anti-inflammatory drugs (NSAIDs). RESULTS: Postrace EAH incidence was 4 of 15 runners, whereas EAH incidence at any point during the race was in 10 of 15 runners. A significant positive correlation was noted between AVP and IL-6 (r = 0.31, P < 0.05) but not between AVP and blood glucose (r = 0.09, nonsignificant) or ambient temperature (r = -0.12, NS). Subgroup analysis revealed that the correlation between AVP and IL-6 was significant in hyponatremic (r = 0.37, P < 0.05) but not normonatremic runners (r = 0.31, NS). Hyponatremic runners lost less weight than normonatremic runners (2.5 vs. 3.7 kg, P < 0.05, respectively) despite similar fluid consumption. Seven of 10 hyponatremic runners consumed NSAIDs versus 0 of 5 normonatremic runners. CONCLUSIONS: Exercise-associated hyponatremia incidence mid-race is higher than postrace, suggesting that 40% of runners are able to self-correct low serum [Na] status during an ultramarathon. Interleukin-6 seems to be the main nonosmotic stimulus associated with AVP in hyponatremic runners. Nonsteroidal anti-inflammatory ingestion is more common in hyponatremic versus normonatremic runners. CLINICAL RELEVANCE: Exercise-associated hyponatremia associated with nonosmotic AVP secretion may be more common during ultramarathon races without discriminatory clinical symptomatology.

Characterization of the effects of the vasopressin V2 receptor on sweating, fluid balance, and performance during exercise.

A regulatory effect of arginine vasopressin (AVP) on sweat water conservation has been hypothesized but not definitively evaluated. AVP-mediated insertion of sweat and salivary gland aquaporin-5 (AQP5) water channels through activation of the vasopressin type 2 receptor (V2R) remains an attractive, yet unexplored, mechanism that could result in a more concentrated sweat with resultant decreased water loss. Ten runners participated in a double-blind randomized control treadmill trial under three separate pharmacological conditions: a placebo, V2R agonist (0.2 mg desmopressin), or V2R antagonist (30 mg tolvaptan). After a familiarization trial, runners ran for 60 min at 60% of peak speed followed by a performance trial to volitional exhaustion. Outcome variables were collected at three exercise time points: baseline, after the steady-state run, and after the performance run. Body weight losses were <2% across all three trials. Significant pharmacological condition effects were noted for urine osmolality [F = 84.98; P < 0.0001] and urine sodium concentration ([Na(+)]) [F = 38.9; P < 0.0001], which verified both pharmacological activation and inhibition of the V2R at the kidney collecting duct. Plasma osmolality and [Na(+)] demonstrated significant exercise (F = 26.0 and F = 11.1; P < 0.0001) and condition (F = 5.1 and F = 3.8; P < 0.05) effects (osmolality and [Na(+)], respectively). No significant exercise or condition effects were noted for either sweat or salivary [Na(+)]. Significant exercise effects were noted for plasma [AVP] (F = 22.3; P < 0.0001), peak core temperature (F = 103.3; P < 0.0001), percent body weight change (F = 6.3; P = 0.02), plasma volume change (F = 21.8; P < 0.0001), and thirst rating (F = 78.2; P < 0.0001). Performance time was not altered between conditions (P = 0.80). In summary, AVP acting at V2R does not appear to regulate water losses from body fluids other than renal excretion during exercise.

Effect of compression stockings on physiological responses and running performance in division III collegiate cross-country runners during a maximal treadmill test.

There is a growing trend for runners to use compression stockings (CS) to improve performance. The purpose of this study was to determine the effect of CS on physiological variables associated with running performance. Participants were 10 NCAA division III cross-country runners. The study used a randomized, crossover design with 2 conditions (with CS and without CS). Both conditions consisted of a maximal treadmill test that involved 3-minute stages of increasing speed and incline, separated by a minute and one-half walking recovery stage. Seven days later, the participants repeated the maximal test but switched CS condition. Heart rate, blood lactate (BLa), blood lactate threshold, maximal oxygen consumption (VO2max), respiratory exchange ratio, rating of perceived exertion, and time to fatigue were measured. Before and during the maximal treadmill tests, the variables showed no significant difference (p ≤ 0.05) between the CS conditions. Blood lactate was lower while wearing CS when measured during recovery at the 1-minute (CS = 13.3 ± 2.9 mmol · L(-1), non-CS = 14.8 ± 2.8 mmol · L(-1), p = 0.03) and the 5-minute (CS = 11.0 ± 2.7 mmol · L(-1), non-CS = 12.8 ± 2.8 mmol · L(-1), p = 0.02) periods. Time to fatigue was longer without CS (CS = 23.570 ± 2.39 minutes, non-CS = 23.93 ± 2.49 minutes, p = 0.04). These findings suggest that CS may not improve running performance, but could lend credence to certain manufacturers' claims of improved recovery through lower BLa values after exercise.

The need for salt: does a relationship exist between cystic fibrosis and exercise-associated hyponatremia?

Salt replacement is often recommended to prevent exercise-associated hyponatremia (EAH) despite a lack of evidence to support such practice. Exercise-associated hyponatremia is known to be a complex process resulting from the interplay of hydration, arginine vasopressin, and sodium balance. Although evidence suggests overhydration is the dominant pathophysiologic factor in most cases, the contributions of sweat sodium losses remain unclear. A theoretical genetic mechanism producing exuberant sweat sodium loss in athletes is the presence of cystic fibrosis (CF) gene. Individuals with CF develop hypovolemic hyponatremia by sodium loss via sweat through a defective chloride ion transport channel, the CF transmembrane conductance regulator (CFTR). Elevated sweat sodium concentrations in CF single heterozygotes suggest that athletes developing EAH may be CFTR carriers. We targeted the 2010 and 2011 Western States Endurance Run ultramarathon, an event where athletes with EAH regularly present in a hypovolemic state, for a cohort maximizing the potential to document such a relationship. A total of 798 runners started the 2010 (n = 423) and 2011 (n = 375) races. Of the 638 finishers, 373 were screened for EAH by blood draw, 60 (16%) were found to have EAH, and 31 (alpha = 0.05 for n = 9) reported their CF result from a saliva-based genetic testing kit. Neither the 31 EAH-positive athletes nor the 25 EAH-negative comparison cohort athletes tested positive for a CF mutation. This null relationship suggests that CFTR mutations are not associated with the development of EAH and that salt supplementation is unnecessary for such a reason.

Wilderness Medical Society practice guidelines for treatment of exercise-associated hyponatremia: 2014 update.

Exercise-associated hyponatremia (EAH) is defined by a serum or plasma sodium concentration below the normal reference range of 135 mmol/L that occurs during or up to 24 hours after prolonged physical activity. It is reported to occur in individual physical activities or during organized endurance events conducted in austere environments in which medical care is limited and often not available, and patient evacuation to definitive care is often greatly delayed. Rapid recognition and appropriate treatment are essential in the severe form to ensure a positive outcome. Failure in this regard is a recognized cause of event-related fatality. In an effort to produce best practice guidelines for EAH in the austere environment, the Wilderness Medical Society convened an expert panel. The panel was charged with the development of evidence-based guidelines for management of EAH. Recommendations are made regarding the situations when sodium concentration can be assessed in the field and when these values are not known. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks/burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians. This is an updated version of the original WMS Practice Guidelines for Treatment of Exercise-Associated Hyponatremia published in Wilderness & Environmental Medicine 2013;24(3):228-240.

Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature.

We studied N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)thiophene-2-carboxamide hydrochloride (M8-B), a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. In vitro, M8-B blocked cold-induced and TRPM8-agonist-induced activation of rat, human, and murine TRPM8 channels, including those on primary sensory neurons. In vivo, M8-B decreased deep body temperature (T(b)) in Trpm8(+/+) mice and rats, but not in Trpm8(-/-) mice, thus suggesting an on-target action. Intravenous administration of M8-B was more effective in decreasing T(b) in rats than intrathecal or intracerebroventricular administration, indicating a peripheral action. M8-B attenuated cold-induced c-Fos expression in the lateral parabrachial nucleus, thus indicating a site of action within the cutaneous cooling neural pathway to thermoeffectors, presumably on sensory neurons. A low intravenous dose of M8-B did not affect T(b) at either a constantly high or a constantly low ambient temperature (T(a)), but the same dose readily decreased T(b) if rats were kept at a high T(a) during the M8-B infusion and transferred to a low T(a) immediately thereafter. These data suggest that both a successful delivery of M8-B to the skin (high cutaneous perfusion) and the activation of cutaneous TRPM8 channels (by cold) are required for the hypothermic action of M8-B. At tail-skin temperatures <23°C, the magnitude of the M8-B-induced decrease in T(b) was inversely related to skin temperature, thus suggesting that M8-B blocks thermal (cold) activation of TRPM8. M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system.

Urine dipstick analysis for identification of runners susceptible to acute kidney injury following an ultramarathon.

This study examined whether urine dipstick testing might be useful to predict the development of acute kidney injury after an ultramarathon. Participants in the 2011 161-km Western States Endurance Run underwent post-race blood and urine dipstick analyses. Of the 310 race finishers, post-race urine dipstick testing was completed on 152 (49%) and post-race blood also was obtained from 150 of those runners. Based on "injury" and "risk" criteria for acute kidney injury of blood creatinine 2.0 and 1.5 times estimated baseline, respectively, 4% met the criteria for injury and an additional 29-30% met the criteria for risk of injury. Those meeting the injury criteria had higher creatine kinase concentrations (P < 0.001) than those not meeting the criteria. Urine dipstick tests that read positive for at least 1+ protein, 3+ blood, and specific gravity ≥ 1.025 predicted those meeting the injury criteria with sensitivity of 1.00 (95% confidence interval [CI] 0.54-1.00), specificity of 0.76 (95% CI 0.69-0.83), positive predictive value of 0.15 (95% CI 0.06-0.30), negative predictive value of 1.00 (95% CI 0.97-1.00), and likelihood ratio for a positive test of 4.2. We conclude that urine dipstick testing was successfully able to identify those individuals meeting injury criteria for acute kidney injury with excellent sensitivity and specificity.

Association of gastrointestinal distress in ultramarathoners with race diet.

CONTEXT: Gastrointestinal (GI) distress is common during ultrarunning. PURPOSE: To determine if race diet is related to GI distress in a 161-km ultramarathon. METHODS: Fifteen (10 male, 5 female) consenting runners in the Javelina Jundred (6.5 loops on a desert trail) participated. Body mass was measured immediately prerace and after each loop. Runners reported if they had nausea, vomiting, abdominal cramps, and/or diarrhea after each loop. Subjects were interviewed after each loop to record food, fluid, and electrolyte consumption. Race diets were analyzed using Nutritionist Pro. RESULTS: Nine (8 male, 1 female) of 15 runners experienced GI distress including nausea (89%), abdominal cramps (44%), diarrhea (44%), and vomiting (22%). Fluid consumption rate was higher (p = .001) in runners without GI distress (10.9 ± 3.2 ml · kg-1 · hr-1) than in those with GI distress (5.9 ± 1.6 ml · kg-1 · hr-1). Runners without GI distress consumed a higher percentage fat (p = .03) than runners with GI distress (16.5 ± 2.6 vs. 11.1 ± 5.0). In addition, fat intake rate was higher (p = .01) in runners without GI distress (0.06 ± 0.03 g · kg-1 · hr-1) than in runners with GI distress (0.03 ± 0.01 g · kg-1 ·hr-1). Lower fluid and fat intake rates were evident in those developing GI distress before the onset of symptoms. CONCLUSIONS: A race diet with higher percentage fat and higher intake rates of fat and fluid may protect ultramarathoners from GI distress. However, these associations do not indicate cause and effect, and factors other than race diet may have contributed to GI distress.

Wilderness Medical Society practice guidelines for treatment of exercise-associated hyponatremia.

Exercise-associated hyponatremia (EAH) typically occurs during or up to 24 hours after prolonged physical activity, and is defined by a serum or plasma sodium concentration below the normal reference range of 135 mEq/L. It is also reported to occur in individual physical activities or during organized endurance events conducted in austere environments in which medical care is limited or often not available, and patient evacuation to definitive care is often greatly delayed. Rapid recognition and appropriate treatment are essential in the severe form to ensure a positive outcome. Failure in this regard is a recognized cause of event-related fatality. In an effort to produce best practice guidelines for EAH in the austere environment, the Wilderness Medical Society convened an expert panel. The panel was charged with the development of evidence-based guidelines for management of EAH. Recommendations are made regarding the situations when sodium concentration can be assessed in the field and when these values are not known. These recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians.