Table 1.

Characteristics of RCTs (n = 8) of acetazolamide effects on sleep apnea at high altitude.

Study	Participants	Intervention	Outcomes	Risk of bias assessment a
				1	2	3b	4	5	6
Sutton et al. [1979] Study design: randomized controlled, data analyzer blinded, crossover	9 healthy trekkers M/F 5/4 Age range 22–36 years	ACZ 250 mg/8 h (oral), total 5 doses Final altitude: 5360 m in North America	Oxygen saturation Breathing frequency	U	U	A	A	A	U
Hackett et al. [1987] Study design: randomized controlled, double-blind, crossover	4 healthy trekkers Male Age range 26–35 years	ACZ 250 mg/8 h (oral), total 3 doses Final altitude: 4400 m in North America	Hypoxic ventilatory response Sleep study	U	U	A	U	A	U
Fischer et al. [2004] Study design: randomized controlled, double-blind	20 healthy trekkers Male ACZ/control 10/10 BMI <25	ACZ 250 mg twice daily (oral), for 4 days Final altitude: 3454 m in Switzerland	Polysomnography Acute mountain sickness Pulse rate, Arterial blood gases Oxyhemoglobin saturation	U	U	A	A	A	U
Rodway et al. [2011] Study design: randomized Controlled	8 healthy trekkers M/F 12/3c ACZ/control 4/4 Age range 25–55 years	ACZ 125 mg/day (oral), for 1 night Final altitude: 5300 m in Nepal	Heart rate Respiratory rate Oxygen saturation Tidal volume, Minute volume AHI	A	U	A	U	A	U
Nussbaumer-Ochsner et al. [2012] Study design: randomized controlled, double-blind, crossover	45 OSA patients M/F 42/3 Median age 64 years	ACZ 250 mg twice daily (oral), for 3 nights Final altitude: 2590 m in Switzerland	Polysomnography Vigilance, Symptoms Oxygen saturation AHI	U	A	A	A	A	A
Latshang et al. [2012] Study design: randomized controlled, double-blind, crossover	51 OSA patients M/F 48/3 Median age 63 years	ACZ 250/500 mg (morning /evening, oral), for 3 nights Final altitude: 2590 m in Switzerland	Oxygen saturation AHI Sleep structure Vigilance Symptoms Adverse effects Exercise performance	U	A	A	A	A	A
Burgess et al. [2014], 2014 Study design: randomized controlled, single-blind, crossover	12 healthy trekkers M/F 8/4 Mean age 30 years	ACZ 10 mg/kg (intravenous), for 1 night Final altitude: 5050 m in Nepal	Arterial blood gas Cerebral blood flow Ventilatory response Sleep study	U	U	A	U	A	U
Caravita et al. [2015] Study design: randomized controlled, double-blind	41 healthy trekkers ACZ 20 (M/F 10/10) Control 21 (M/F 11/10) Mean age 36 years	ACZ 250 mg/day (oral), for 2 days Final altitude: 4559 m in Italy	Resting ventilation Chemoreflex Cardiorespiratory sleep study	U	U	A	U	A	A

M, male; F, female; ACZ, acetazolamide; AHI, Apnea–Hypopnea Index; BMI, body mass index; OSA, obstructive sleep apnea; U, unclear; A, adequate.

^aRisk of bias assessment determined by the Cochrane Collaboration’s tool for assessing risk of bias, including: (1) random sequence generation; (2) allocation concealment; (3) blinding of participants and personnel; (4) blinding of outcome assessment; (5) incomplete outcome data; (6) selective reporting.

^bThough six studies that included healthy participants did not provide adequate information to permit the assessment of performance bias or were not double-blinded, the outcomes were judged not likely to be influenced by lack of blinding because sleep apnea and nocturnal oxygenation were unlikely to have a placebo effect.

^cThe total 15 participants in the study that were assigned to 4 different treatment groups, of which ACZ and control group were included in this meta-analysis.