Small, Elan, Nicholas Juul, David Pomeranz, Patrick Burns, Caleb Phillips, Mary Cheffers, and Grant S. Lipman. Predictive capacity of pulmonary function tests for acute mountain sickness. High Alt Med Biol. 00:000-000, 2021. Background: Pulmonary function as measured by spirometry has been investigated at altitude with heterogenous results, though data focused on spirometry and acute mountain sickness (AMS) are limited. The objective of this study was to investigate the capacity of pulmonary function tests (PFTs) to predict the development of AMS. Materials and Methods: This study was a blinded prospective observational study run during a randomized controlled trial comparing acetazolamide, budesonide, and placebo for AMS prevention on White Mountain, CA. Spirometry measurements of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow were taken at a baseline altitude of 1,250 m, and the evening of and morning after ascent to 3,810 m. Measurements were assessed for correlation with AMS. Results: One hundred three participants were analyzed with well-matched baseline demographics and AMS incidence of 75 (73%) and severe AMS of 48 (47%). There were no statistically significant associations between changes in mean spirometry values on ascent to high altitude with incidence of AMS or severe AMS. Lake Louise Questionnaire scores were negatively correlated with FVC (r = -0.31) and FEV1 (r = -0.29) the night of ascent. Baseline PFT had a predictive accuracy of 65%-73% for AMS, with a receiver operating characteristic of 0.51-0.65. Conclusions: Spirometry did not demonstrate statistically significant changes on ascent to high altitude, nor were there significant associations with incidence of AMS or severe AMS. Low-altitude spirometry did not accurately predict development of AMS, and it should not be recommended for risk stratification.

Introduction Exercise-associated hyponatremia (EAH) is a well-recognized potential complication of endurance runners. It is a syndrome of hypervolemic hyponatremia and occurs secondary to a relative increase in total body water primarily caused by water intake exceeding urinary and sweat losses. Symptomatic EAH has been found in up to 23% to 38% in those seeking medical care in triathalons, marathons, and ultramarathons (1,2). Mild EAH is likely underdiagnosed, as symptoms of nausea, vomiting, headache, and dizziness are often ascribed to dehydration or heat-related illness (3–5). Severe EAH symptoms are mainly neurologic due to the osmotic gradient between plasma and brain cells that induces cerebral edema. Symptoms are related to both rapidity and amount of change in plasma sodium, not necessarily the absolute level (6,7). EAH can be fatal, (8–12) and has led to a dozen confirmed deaths (13). Consensus guidelines recommend immediate testing with a point-of-care device when severe EAH is suspected, and when diagnosed, to treat with 100-mL boluses of 3% sodium chloride (hypertonic saline, HTS) until neurologic symptoms resolve (5,14). Small volume HTS (200 mL) has been given empirically in the field for severe EAH with rapid improvement, (15) and volumes as large as 0.95 L given over 7 h have successfully treated severe EAH in a hospital setting (16). However, in the absence of on-site sodium testing some consensus guidelines recommend small amounts of HTS that may be clinically insufficient, or algorithms that direct fluid avoidance until confirmatory serum testing is available (5). Because ultramarathons are often held in wilderness environments where testing is usually unavailable, (17) medical providers need to have an empiric treatment protocol for suspected severe EAH (18). Case Presentation In June 2016, a previously healthy 31-yr-old female with no medical problems, drug use, or issues with prior endurance running participated in an 80-km (50 miles) ultramarathon foot race with the hottest ambient temperatures ranging from 46°C to 50°C (115°F to 122°F). Competitors had 2 L of water provided at a checkpoint every 10 km (6 miles). The runner had been performing well and consumed one electrolyte tablet every other liter of water, with an additional salt tablet every 2 h throughout the day. At the fifth checkpoint at 50 km (30 miles), the racer was nauseous and vomited once. She was given ondansetron 4-mg oral dissolving tablet (ODT), observed for 1 h while tolerating fluids, and continued racing. She finished the next 10 km (6 miles) in 2 to 3 h while ingesting 3 to 4 L more water and arrived at approximately 10 p.m. the ambient temperature was 32°C (90°F). The runner consumed 1 L of electrolyte mix and then vomited. Over the next hour, she was unable to tolerate fluids or food, so ondansetron 4 mg ODT was given. She consumed a 250-mL soda and a salt tablet and was feeling well. She ambulated without difficulty to the optional sleeping area of the checkpoint and slept for 2 h when she had a generalized tonic-clonic seizure that resolved spontaneously after 2 min. The patient was obtunded, withdrawing from pain, eyes opening spontaneously, and normal vital signs. Intravenous access was rapidly obtained and given the recent caloric ingestion and several hours of rest preceding the seizure, it was unlikely hypoglycemia or heat stroke; 100 mL of HTS was given within minutes of seizure cessation for presumed severe EAH. Evacuation was initiated via an off-road truck. Ten minutes after the first HTS bolus, there was no neurologic improvement, and a second bolus was given, which was repeated every 10 to 15 min. During this evacuation, a total of 600 mL of HTS was given with no change in the patient's mental status. The patient was transferred to an ambulance and transported 3 h to the nearest hospital with critical care facilities. En route, local paramedics repeatedly attempted to start a 0.9% sodium chloride (normal saline [NS]) intravenous drip, but were dissuaded by the race physician coordinating care. Upon arrival in the emergency department at approximately 6 a.m. (4 h postseizure), the patient had normal vital signs, was afebrile, and continued her postictal state (Glasgow Coma Scale of 10). A noncontrast head computed tomography (CT) scan was negative for acute intracranial process, and she had a serum sodium of 121 mmol·L−1, chloride of 79 mmol·L−1, and potassium of 2.8 mmol·L−1. The patient was admitted to the intensive care unit ICU at 8 a.m. on a HTS drip at 30 mL·h−1 for 11 h until 7 p.m. at which time the serum sodium was 128 mmol·L−1, and the drip was discontinued. The next morning, the patient was found awake, without complaints, and mentating normally. Repeat serum electrolyte testing revealed normal values. Within 6 h, she was discharged from the hospital. The patient was monitored for the following 36 h without any neurologic events and remained asymptomatic. She reported no neurologic sequelae at 6, 12, and 18 months after the event. Discussion This case is the largest known volume of HTS given for severe EAH in the absence of confirmatory serum testing. Treatment of severe EAH with HTS (513 mEq·L−1) is known to result in typically rapid correction of sodium levels, (16) and highly efficacious and more rapid than that of NS (154 mEq·L−1) (7). NS should be avoided in severe EAH, (5,14) and there have been numerous grievous examples of worsened morbidity and mortality when given isotonic fluids (8,12,19). This is due to the urinary excretion of all the sodium in isotonic fluids with a proportion of water to equal the high urine osmolality, leaving a net positive of serum-free water which can worsen the osmotic gradient and cerebral edema. There have been no reported cases of central pontine myelinolysis (osmotic demyelination) with the rapid correction of severe EAH. The successful outcome of this case highlights the safety of this intervention. The patient's prolonged encephalopathy while unusual in severe EAH, is not unprecedented (8,20). Nor was a negative head CT, which was seen in a runner with severe EAH who received 650 mL of HTS for persistent altered mental status (16). Although the lack of information regarding weight changes, urinary output, sand race sodium, and dietary intake limit pathophysiologic insight. This case clearly illustrates the potential need for larger volumes of HTS for event medical management than the often recommended three 100-mL boluses, (5,14) and supports the sideline medical provider to pursue treatment until “neurologic symptoms subside” (14). Delay of empiric treatment can lead to worsened hyponatremia (21). The etiology of EAH is likely multifactorial, thought to be due to several proposed mechanisms. A combination of overhydration from excessive hypotonic fluid intake (i.e., water or sports drinks); (22,23) impaired excretion of water due to inadequate suppression of arginine vasopressin (AVP), (14,22) and sodium and/or fluid losses through sweating to form a hypovolemic stimulus of ADH. These mechanisms have been proposed to coexist and present as a “continuum” that can range from pure overhydration to excessive sweat sodium losses and overhydration (24). Increased consumption of hypotonic solutions can lead to a dilutional hyponatremia, and intake overwhelms the rate of renal water excretion. In the setting of hypervolemia and/or hyponatremia, plasma AVP that presents at “normal levels” is actually abnormal, as AVP should be maximally suppressed (22,25) resulting in a syndrome of inappropriate antidiuretic hormone secretion. Also, hypovolemia from insensible losses, such as sweating, will stimulate ADH secretion and contribute to the hyponatremia (24). While the symptoms of EAH may be acute, delay of symptomatic EAH may occur several hours after the end of exercise (26,27). During heavy exercise, blood flow is diverted from the gastrointestinal tract to skeletal muscle, and ingested water is sequestered in the gut (28). When exercise ceases, partial redistribution of blood to the mesentery may lead to abrupt absorption of water into the bloodstream and resultant symptomatic EAH. Upon arrival in the emergency room, the diagnosis of EAH was confirmed with the serum sodium level of 121 mmol·L−1. This is consistent with severe EAH, as 121 mmol·L−1 was the average sodium level in seven cases of marathon runners intubated with severe EAH (8). It is unknown what the initial sodium level in this patient was, but reasonable to assume it was less than 110 mmol·L−1 when she seized, as 100 mL of 3% sodium chloride is estimated to increase the serum sodium concentration 2 to 5 mmol·L−1 (6,29). The patient's nausea and vomiting earlier were likely insidious symptoms of mild EAH, and nausea is known as a potent trigger for ADH secretion. As gastrointestinal distress is very common in ultramarathoners (30), holding a participant until symptom cessation and able to tolerate fluids and food by mouth is a reasonable safety measure. The nausea likely contributed to poor food ingestion which could have contributed to inadequate dietary sodium intake. The 3-L to 4-L water ingested during the 10 km (6 miles) preceding the runner's final stop with minimal sodium supplementation was a recipe for hypervolemic hyponatremia, as excess water ingestion and weight gain are well-recognized independent risk factors for EAH (22,31,32). The high ambient temperatures during the 60-km (37 miles) run and vomiting likely contributed to hypovolemia and a mixed mechanism. It is unknown the exact amount of sodium ingested by the runner during the race, but the reported rates in the setting of aggressive hydration were likely inadequate to maintain isotonicity. Exercise in hot environments has been shown to increase the need for hydration as well as medical consults in endurance runners (31,33,34). While challenging in hot conditions, avoidance of overhydration has been found to be more protective of EAH than sodium supplementation (35). Event planners and medical providers at endurance race events should be aware of severe heat as a potential risk factor for EAH, and although empiric large volume HTS has not been rigorously tested, it should be considered a safe and effective treatment modality for severe EAH. Conclusions Medical support staff of endurance activities particularly in hot environments should be aware of the risks of overhydration, symptom recognition of severe EAH, and preparedness to deliver large volumes of HTS. The rapid treatment of severe EAH is essential to prevent fatal outcomes. This case highlights the potential need for larger volumes of HTS than often recommended, and neurologic presentation should dictate treatment rather than a set amount of fluid. An empiric treatment algorithm that is based on presenting symptoms rather than serum blood testing can enhance survival and outcomes of endurance runners.

Alsup, Carl, Grant S. Lipman, David Pomeranz, Rwo-Wen Huang, Patrick Burns, Nicholas Juul, Caleb Phillips, Carrie Jurkiewicz, Mary Cheffers, Christina Evans, Anirudh Saraswathula, Peter Baumeister, Lucinda Lai, Jessica Rainey, and Viveta Lobo. Interstitial pulmonary edema assessed by lung ultrasound on ascent to high altitude and slight association with acute mountain sickness: A prospective observational study. High Alt Med Biol. 00:000-000, 2019. 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] -infinity to -0.04). The change in BLS (Delta BLS) from low altitude baseline was significantly associated with AMS (0.88 vs. 1.72, r(2) = 0.023, 95% CI -infinity 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.

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. (c) 2018 Elsevier Inc. All rights reserved.

was 0.966 for the 125 mg BID dose group and 1.014 for the 62.5 mg BID dose group (CI,.Side effects experienced by the 62.5 mg BID group were, curiously, slightly higher than those of 125 mg BID dose group, but these differences diminished when controlling for participant weight.Conclusions.-Areduced dose of acetazolamide 62.5 mg BID is as effective as the currently recommended dose of 125 mg BID for the prevention of AMS.These results could influence future recommendations for climbers and trekkers with ascent profiles similar to those seen in our study.

CaseA 30-year-old man without prior respiratory illness presented with coughing, wheezing, dyspnea on exertion, and decreased exercise tolerance after a 7-hour overnight exposure to yak-dung smoke.This episode took place at 4,240 m elevation in Pheriche village, along the Everest Base Camp trekking route within the Khumbu region of the Nepali Himalayas.Prior to going to bed that evening, the group of five cohabitants had a difficult time igniting the potbelly heating stove filled with yak-dung biomass fuel in the common room.Each time they tried to light it, the fire would smolder and go out within a few minutes, despite the group's attempts at adjusting the flue and air intake.Eventually, they abandoned A 30-year-old man presented with coughing, wheezing, dyspnea on exertion, and decreased exercise tolerance following an overnight exposure to biomass fuel smoke.