Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude

Abstract

A randomised, double-blind, placebo-controlled study was conducted to evaluate the effects of theophylline and acetazolamide in the treatment of sleep-disordered 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 (2×250 mg·day-1), oral acetazolamide (2×250 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 (median 16.2·h-1, range 2-92). Both theophylline and acetazolamide normalised SDB (median AHI 2.5·h-1, range 0-11; 4.2·h-1, range 0-19, respectively) and reduced oxyhaemoglobin desaturations during sleep (median desaturation index placebo 41.5·h-1 range 6-114; acetazolamide 6.5·h-1, range 3-28; theophylline 8.5·h-1, range 3-32). Compared with the high amount of central apnoeas or hypopnoeas, the number of obstructive events during sleep was very low in all groups (<4·h-1). In contrast to theophylline, acetazolamide significantly improved basal oxyhaemoglobin saturation during sleep (86.2±1.7% versus 81.0+3.0%). The authors conclude that both oral slow release theophylline and acetazolamide are effective to normalise high-altitude sleep-disordered breathing.