Effect of Sodium Supplements and Climate on Dysnatremia During Ultramarathon Running.

OBJECTIVE: Analyze the effect of sodium supplementation, hydration, and climate on dysnatremia in ultramarathon runners. DESIGN: Prospective observational study. SETTING: The 2017 80 km (50 mile) stage of the 250 km (150 mile) 6-stage RacingThePlanet ultramarathon in 2017 Chilean, Patagonian, and 2018 Namibian, Mongolian, and Chilean deserts. PARTICIPANTS: All race entrants who could understand English were invited to participate, with 266 runners enrolled, mean age of 43 years (± 9), 61 (36%) females, average weight 74 kg (± 12.5), and average race time 14.5 (± 4.1) hours. Post-race sodium collected on 174 (74%) and 164 (62%) participants with both the blood sample and post-race questionnaire. INTERVENTION: Weight change and finish line serum sodium levels were gathered. MAIN OUTCOME MEASURES: Incidence of exercise-associated hyponatremia (EAH; <135 mmol·L-1) and hypernatremia (>145 mmol·L-1) by sodium ingestion and climate. RESULTS: Eleven (6.3%) runners developed EAH, and 30 (17.2%) developed hypernatremia. Those with EAH were 14 kg heavier at baseline, had significantly less training distances, and averaged 5 to 6 hours longer to cover 50 miles (80 km) than the other participants. Neither rate nor total ingested supplemental sodium was correlated with dysnatremia, without significant differences in drinking behaviors or type of supplement compared with normonatremic runners. Hypernatremic runners were more often dehydrated [8 (28%), -4.7 kg (± 9.8)] than EAH [4 (14%), -1.1 kg (± 3.8)] (P < 0.01), and EAH runners were more frequently overhydrated (6, 67%) than hypernatremia (1, 11%) (P < 0.01). In the 98 (56%) runners from hot races, there was EAH OR = 3.5 [95% confidence interval (CI), 0.9-25.9] and hypernatremia OR = 8.8 (95% CI, 2.9-39.5) compared with cold races. CONCLUSIONS: This was the first study to show that hot race climates are an independent risk factor for EAH and hypernatremia. Sodium supplementation did not prevent EAH nor cause hypernatremia. Longer training distances, lower body mass, and avoidance of overhydration were shown to be the most important factors to prevent EAH and avoidance of dehydration to prevent hypernatremia.

A Randomized Controlled Trial of the Lowest Effective Dose of Acetazolamide for Acute Mountain Sickness Prevention.

BACKGROUND: Acetazolamide is the most common medication used for acute mountain sickness prevention, with speculation that a reduced dose may be as efficacious as standard dosing with fewer side effects. METHODS: This double-blind, randomized, controlled noninferiority trial compared acetazolamide 62.5 mg twice daily to the standard dose acetazolamide 125 mg twice daily starting the evening prior to ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (ie, headache, Lake Louise Questionnaire ≥3, and another symptom). RESULTS: A total of 106 participants were analyzed, with 51 (48%) randomized to 125 mg and 55 (52%) to 62.5 mg, with a combined acute mountain sickness incidence of 53 (50%) and mean severity of 3 (± 2.1). The 62.5-mg group failed to fall within the prespecified 26% noninferiority margin for acute mountain sickness incidence (62.5 mg = 30 [55%] vs 125 mg = 23 [45%], 95% confidence interval [CI] -11% to 30%). Participants in the 62.5-mg group had a higher risk of acute mountain sickness (odds ratio = 1.5, 95% CI 0.7-3.2) and moderate acute mountain sickness (odds ratio = 1.8, 95% CI 0.6-5.9), with a number needed to harm (NNH) of 9, with a number needed to treat (NNT) in the 125-mg group of 4.8. Increased acute mountain sickness incidence and symptom severity corresponded to lower weight-based and body mass index dosing, with similar side effects between groups. CONCLUSION: Acetazolamide 62.5 mg twice daily failed to demonstrate equal effectiveness to 125 mg twice daily for prevention of acute mountain sickness. With increased risk and no demonstrable symptomatic or physiologic benefits, acetazolamide 62.5 mg twice daily should not be recommended for acute mountain sickness prevention.

Wilderness Medical Society Clinical Practice Guidelines for Diabetes Management.

The Wilderness Medical Society convened an expert panel in 2018 to develop a set of evidence-based guidelines for the treatment of type 1 and 2 diabetes, as well as the recognition, prevention, and treatment of complications of diabetes in wilderness athletes. We present a review of the classifications, pathophysiology, and evidence-based guidelines for planning and preventive measures, as well as best practice recommendations for both routine and urgent therapeutic management of diabetes and glycemic complications. These recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks or burdens for each recommendation.

Day of Ascent Dosing of Acetazolamide for Prevention of Acute Mountain Sickness.

Background: Acetazolamide is the most common medication used for prevention of acute mountain sickness (AMS), usually administered the day or night before ascent. The objective of this study was to evaluate the efficacy of day of ascent dosing of acetazolamide for AMS prevention. Methods: Double-blind, randomized, controlled noninferiority trial of acetazolamide 125 mg twice daily beginning either the night before or the morning of ascent. Healthy low altitude adults ascended from 1240 m (4100 ft) to 3810 m (12,570 ft) during summer 2018 on White Mountain, California. Primary outcome was incidence of AMS with the two different dosing patterns, assessed by the 1993 Lake Louise Questionnaire (LLQ) of ≥3 with headache and a minimum of 1 for other symptom. Results: One hundred four participants completed the study, with 54 (52%) randomized to night before acetazolamide and 50 (48%) to day of ascent dosing, without differences in baseline characteristics. There was 9% greater incidence of AMS in the day of ascent acetazolamide group (48.0% vs. 39%, 95% confidence interval [CI] -11.8 to 30, p = 0.46, number needed to treat [NNT] = 5.6 vs. 3.7), with the CI just surpassing the predetermined 26% noninferiority margin. There was a lower incidence of severe AMS (1993 LLQ >5) in the day of ascent group (n = 5, 10%, NNT = 2.3) compared with night before dosing (n = 12, 22%, NNT = 3.1) (95% CI -28 to 3.6), and lower average symptom severity in the day of ascent group (3 vs. 3.5, 95% CI -0.5 to 1.4). Conclusions: Day of ascent acetazolamide demonstrated higher rates of AMS compared with traditional dosing by a small margin. With similar rates of severe AMS and overall symptom severity, the potential for improved convenience and compliance may support day of ascent use.

Interstitial Pulmonary Edema Assessed by Lung Ultrasound on Ascent to High Altitude and Slight Association with Acute Mountain Sickness: A Prospective Observational Study.

Background: Acute mountain sickness (AMS) is a common disease that may have a pulmonary component, as suggested by interstitial pulmonary edema quantified by the B-line score (BLS) on ultrasound (US). This subclinical pulmonary edema has been shown to increase with ascent to high altitude and AMS severity, but has not been prospectively associated with AMS incidence in a large prospective study. Materials and Methods: This prospective observational study was part of a randomized controlled trial enrolling healthy adults over four weekends ascending White Mountain, California. Subjects were assessed by lung US and the Lake Louise Questionnaire at 4110 ft (1240 m), upon ascent to 12,500 ft (3810 m), and the next morning at 12,500 ft (3810 m). Results: Three hundred five USs in total were completed on 103 participants, with 73% total incidence of AMS. The mean (±standard deviation) BLS increased from baseline (1.15 ± 1.80) to high altitude (2.56 ± 2.86), a difference of 1.37 (±2.48) (p = 0.04). Overall BLS was found, on average, to be higher among those diagnosed with AMS than without (2.97 vs. 2.0, p = 0.04, 95% confidence interval [CI] -∞ to -0.04). The change in BLS (ΔBLS) from low altitude baseline was significantly associated with AMS (0.88 vs. 1.72, r2 = 0.023, 95% CI -∞ to -0.01, p = 0.048). Conclusions: Interstitial subclinical pulmonary edema by lung US was found to have a small but significant association with AMS.

Altitude Sickness Prevention with Ibuprofen Relative to Acetazolamide.

BACKGROUND: Acute mountain sickness is a common occurrence for travel to high altitudes. Although previous studies of ibuprofen have shown efficacy for the prevention of acute mountain sickness, recommendations have been limited, as ibuprofen has not been compared directly with acetazolamide until this study. METHODS: Before their ascent to 3810 m on White Mountain in California, adult volunteers were randomized to ibuprofen (600 mg, 3 times daily, started 4 hours before the ascent), or to acetazolamide (125 mg, twice daily, started the night before the ascent). The main outcome measure was acute mountain sickness incidence, using the Lake Louise Questionnaire (LLQ), with a score of >3 with headache. Sleep quality and headache severity were measured with the Groningen Sleep Quality Survey (GSQS). This trial was registered at ClinicalTrials.gov: NCT03154645 RESULTS: Ninety-two participants completed the study: 45 (49%) on ibuprofen and 47 (51%) on acetazolamide. The total incidence of acute mountain sickness was 56.5%, with the incidence for the ibuprofen group being 11% greater than that for acetazolamide, surpassing the predetermined 26% noninferiority margin (62.2% vs 51.1%; 95% confidence interval [CI], -11.1 to 33.5). No difference was found in the total LLQ scores or subgroup symptoms between drugs (P = .8). The GSQS correlated with LLQ sleep (r = 0.77; 95% CI, 0.67-0.84)=%. The acetazolamide group had higher peripheral capillary oxygen saturation than the ibuprofen group (88.5% vs 85.6%; P = .001). CONCLUSION: Ibuprofen was slightly inferior to acetazolamide for acute mountain sickness prevention and should not be recommended over acetazolamide for rapid ascent. Average symptoms and severity were similar between drugs, suggesting prevention of disease.

Budesonide Versus Acetazolamide for Prevention of Acute Mountain Sickness.

BACKGROUND: Inhaled budesonide has been suggested as a novel prevention for acute mountain sickness. However, efficacy has not been compared with the standard acute mountain sickness prevention medication acetazolamide. METHODS: This double-blind, randomized, placebo-controlled trial compared inhaled budesonide versus oral acetazolamide versus placebo, starting the morning of ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (headache and Lake Louise Questionnaire ≥3 and another symptom). RESULTS: A total of 103 participants were enrolled and completed the study; 33 (32%) received budesonide, 35 (34%) acetazolamide, and 35 (34%) placebo. Demographics were not different between the groups (P > .09). Acute mountain sickness prevalence was 73%, with severe acute mountain sickness of 47%. Fewer participants in the acetazolamide group (n = 15, 43%) developed acute mountain sickness compared with both budesonide (n = 24, 73%) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.3-10.1) and placebo (n = 22, 63%) (OR 0.5, 95% CI 0.2-1.2). Severe acute mountain sickness was reduced with acetazolamide (n = 11, 31%) compared with both budesonide (n = 18, 55%) (OR 2.6, 95% CI 1-7.2) and placebo (n = 19, 54%) (OR 0.4, 95% CI 0.1-1), with a number needed to treat of 4. CONCLUSION: Budesonide was ineffective for the prevention of acute mountain sickness, and acetazolamide was preventive of severe acute mountain sickness taken just before rapid ascent.