Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude. R. Fischer, S.M. Lang, M. Leitl, M. Thiere, U. Steiner, R.M. Huber. #ERS Journals Ltd 2004. ABSTRACT: A randomised, double-blind, placebo-controlled study was conducted to evaluate the effects of theophylline and acetazolamide in the treatment of sleepdisordered breathing (SDB) after fast ascent to high altitude (3,454 m).The study was conducted at a high-altitude research laboratory and included 30 healthy male volunteers. Study medication was either oral slow release theophylline (26250 mg?day -1 ), oral acetazolamide (26250 mg?day -1 ) or a matched placebo tablet. Polysomnographic measurements were performed during two consecutive nights, and acute mountain sickness, pulse rate, oxyhaemoglobin saturation and arterial blood gases were assessed three times a day.Without active medication, the apnoea/hypopnoea index (AHI) was highly pathological ( Sleep-disordered breathing (SDB) of the Cheyne-Stokes type is commonly found during sleep at high altitude [1][2][3]. This typical breathing pattern with waxing and waning of the tidal volume is associated with profound desaturations and reduced overall oxygen saturation during sleep, but its association with an increased number of arousals is a matter of ongoing debate [4,5]. The use of acetazolamide at high altitude is known to reduce the time spent with periodic breathing, to improve overall oxygen saturation during sleep and to reduce the number of arousals [6].Acetazolamide inhibits the renal enzyme carbonic anhydrase, which leads to metabolic acidosis, and, as a result, increases ventilation and oxygenation. The beneficial effects of this drug at high altitude are thought to be due to this improved oxygenation. Although serious side-effects of acetazolamide are uncommon, an alternative treatment option would be desirable for patients with known sulphonamide intolerance. In a previous, prospective, randomised study, the authors were able to show that theophylline has a positive impact on symptoms of acute mountain sickness (AMS), compared with placebo [7]. As theophylline was shown to be effective in reducing periodic breathing in premature newborns and in patients with severe heart failure [8, 9], a similar effect in high-altitude periodic breathing could be assumed.Therefore, a randomised, double-blind, placebo-controlled study was conducted to evaluate the effect of theophylline and acetazolamide on periodic breathing and arterial oxyhaemoglobin desaturations during sleep at high altitude. The aims were to compare the efficacy of theophylline and acetazolamide in normalising high-altitude SDB and in decreasing nocturnal oxyhaemoglobin desaturation.
Methods
Study populationHealthy male volunteers (n=30) gave informed written consent to participate in the study. Of 30 subjects, 22 were engaged in regular mountaineering activities in their spare time, but none of them had experienced altitudes above 3,500 m. The study protocol was approved by the local ethics committee. Exclusion cr...
