Abstract
To the Editor
Acetazolamide is a carbonic anhydrase inhibitor that is a well-studied, proven agent for both the prevention and treatment of acute mountain sickness (AMS). 1 –4 Although this medication is well known to the mountaineering community, there has been no mention of its use in the ultramarathon race setting. Frequently these races occur at altitudes greater than 2500 m, and AMS could potentially affect a runner’s performance. Use of this well-studied agent could potentially be adapted to the race medicine setting.
One such ultramarathon that occurs at a high altitude setting is The Last Secret, a 200-km footrace that occurs in early spring in the mountainous country of Bhutan. Runners travel on forest footpaths, crossing 3 separate 3500-m passes. The race profile includes an altitude gain of 10,000 m with a maximum altitude reached of 3600 m. In the 2015 race, a total of 4 of the 36 racers approached the race physicians with symptoms consistent with AMS. After shared decision making with the athletes, 2 of the runners elected treatment with dexamethasone, 1 runner with minimal symptoms underwent watchful waiting, and the fourth runner consented to a regimen of acetazolamide. The latter was a male in his 50s who had completed several ultramarathons as well as multiday staged races. His complaints were dizziness, nausea, shortness of breath, fatigue, and headache. There was neither altered mental state nor any physical evidence of pulmonary edema on examination. The symptoms occurred after a night of sleeping at 1750 m followed by a 29-km stage run with a maximum altitude of 3500 m achieved while traversing over a mountain pass. The course then descended to 2500 m, where the night was spent. The runner was treated the evening of presentation of symptoms with a 250-mg dose of acetazolamide, with 3 additional doses administered every 12 hours of 125 mg of acetazolamide. A departure from the recommended treatment regimen was made secondary to the concern of diuresis leading to dehydration given the strenuous demands of this race. The following day the course climbed to 3600 m over a distance of 28 km. The runner experienced no further symptoms of AMS the following day while running or while at rest. He denied any untoward side effects of the medication such as paresthesias or polyuria. This runner went on to complete the entire 6-day course without any adverse events.
This is a single case in which acetazolamide was used to treat AMS in an ultramarathon setting. There are both potential risks and potential benefits to using acetazolamide in the race environment. The increase in minute ventilation after acetazolamide administration should not have any detrimental effects on the athlete. The improvement to sleep quality as a result of reductions in periodic breathing would also be of benefit.
An area of controversy regarding acetazolamide use involves its potential to affect exercise capacity under hypoxic conditions. Numerous studies have been performed since the 1980s trying to elucidate the affect acetazolamide has on both muscle performance and pulmonary gas exchange. Most sample sizes have been quite small, and unfortunately there is as much data purporting that acetazolamide can enhance the athlete’s performance at altitude as there are conclusions that acetazolamide may be detrimental to maximal athletic capability. The most recent research by Bradwell et al. 5 concluded that despite a higher resting peripheral oxygen saturation, individuals taking acetazolamide may have exhibited compromised performance at 3459 m. Any potential reduction in exercise capacity would certainly be of concern to endurance athletes; therefore, further studies of acetazolamide on exercise performance are required until definitive conclusions can be made.
A potential limitation of the use of this drug while under extreme and prolonged exertion would be the drug’s promotion of sodium and water losses by inhibition of renal carbonic anhydrase. Although it has been cited that there is a protective role of diuresis in the development of AMS, 4 significant diuresis in the race setting could be detrimental to the runner’s overall fluid and electrolyte homeostasis. No protective effects against exercise-associated hyponatremia are known to occur with this diuresis because both aquaresis and natriuresis occur with proximal tubule diuretics such as acetazolamide. Although runners can withstand substantial levels of dehydration while under exertion, precautions should be taken with any interventions that may increase the amount of water and salt losses.
Given the myriad of physiologic effects, further research of acetazolamide use during endurance events is needed before any recommendations can be made.