The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis.
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ABSTRACT: Background
Acetazolamide has been investigated for treating sleep apnea in newcomers ascending to high altitude. This study aimed to assess the effect of acetazolamide on sleep apnea at high altitude, determine the optimal therapeutic dose, and compare its effectiveness in healthy trekkers and obstructive sleep apnea (OSA) patients.Methods
PubMed, Embase, Scopus, Cochrane Library, and Airiti Library databases were searched up to July 2015 for randomized controlled trials (RCTs) performed above 2500 m in lowlanders and that used acetazolamide as intervention in sleep studies. Studies including participants with medical conditions other than OSA were excluded.Results
Eight studies of 190 adults were included. In healthy participants, the pooled mean effect sizes of acetazolamide on Apnea-Hypopnea Index (AHI), percentage of periodic breathing time, and nocturnal oxygenation were 34.66 [95% confidence interval (CI) 25.01-44.30] with low heterogeneity ( p = 0.7, I2 = 0%), 38.56% (95% CI 18.92-58.19%) with low heterogeneity ( p = 0.24, I2 = 28%), and 4.75% (95% CI 1.35-8.15%) with high heterogeneity ( p < 0.01, I2 = 87%), respectively. In OSA patients, the pooled mean effect sizes of acetazolamide on AHI and nocturnal oxygenation were 13.18 (95% CI 9.25-17.1) with low heterogeneity ( p = 0.33, I2 = 0%) and 1.85% (95% CI 1.08-2.62%) with low heterogeneity ( P = 0.56, I2 = 0%).Conclusions
Acetazolamide improves sleep apnea at high altitude by decreasing AHI and percentage of periodic breathing time and increasing nocturnal oxygenation. Acetazolamide is more beneficial in healthy participants than in OSA patients, and a 250 mg daily dose may be as effective as higher daily doses for healthy trekkers.
SUBMITTER: Liu HM
PROVIDER: S-EPMC5941979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTherapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however, given overlapping pathophysiologic properties of OSA and CSA, we hypothesized that acetazolamide is equally effective for both types. Prior reviews focused on specific subtypes of sleep apnea, study designs, and languages, thus including few studies (typically ≤3) limiting insights.Research questionHow efficacious is acetazolamide for sleep apnea, and is its effect modified by sleep apnea type or acetazolamide dose?Study design and methodsWe queried MEDLINE, EMBASE, and ClinicalTrials.gov from inception until March 11, 2019. Any study in which adults with OSA/CSA received oral acetazolamide vs no acetazolamide (control) that reported sleep apnea-related outcomes was eligible, independent of study design or language. Two reviewers independently assessed eligibility and abstracted data. Primary outcomes were apnea-hypopnea index (AHI) and oxygen saturation nadir. Quality of evidence (QoE) was rated with the use of Grades of Recommendation Assessment, Development and Evaluation methods.ResultsWe included 28 studies (13 OSA/15 CSA; NSubjects,Acetazolamide = 542; NSubjects,Control = 553) that enabled meta-analyses for 24 outcomes. Acetazolamide doses ranged from 36 to 1000 mg/d and treatment duration from 1 to 90 d (median, 6 d). Overall, acetazolamide vs control lowered the AHI by -0.7 effect sizes (95% CI, -0.83 to -0.58; I2 = 0%; moderate QoE) that corresponded to a reduction of 37.7% (95% CI, -44.7 to -31.3) or 13.8/h (95% CI, -16.3 to -11.4; AHIControl = 36.5/h). The AHI reduction was similar in OSA vs CSA, but significantly greater with higher doses (at least up to 500 mg/d). Furthermore, acetazolamide improved oxygen saturation nadir by +4.4% (95% CI, 2.3 to 6.5; I2 = 63%; no evidence of effect modification; very low QoE) and several secondary outcomes that included sleep quality measures and BP (mostly low QoE).InterpretationShort-term acetazolamide improved both OSA and CSA. Rigorous studies with long-term follow up are warranted to assess Acetazolamide's value for the chronic treatment of patients with sleep apnea.Clinical trial registrationPROSPERO (CRD42019147504).
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Project description:BackgroundObstructive sleep apnea (OSA) is associated with increased morbidity and mortality, and decreased quality of life. Treatment with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is effective for many symptoms of OSA. However, it remains controversial whether treatment with CPAP or MAD also improves depressive symptoms.Methods and findingsWe performed a systematic review and meta-analysis of randomized controlled trials that examined the effect of CPAP or MADs on depressive symptoms in patients with OSA. We searched Medline, EMBASE, the Cochrane Central Registry of Controlled Trials, and PsycINFO from the inception of the databases until August 15, 2014, for relevant articles. In a random effects meta-analysis of 19 identified trials, CPAP treatment resulted in an improvement in depressive symptoms compared to control, but with significant heterogeneity between trials (Q statistic, p<0.001; I(2) = 71.3%, 95% CI: 54%, 82%). CPAP treatment resulted in significantly greater improvement in depressive symptoms in the two trials with a higher burden of depression at baseline (meta-regression, p<0.001). The pooled standardized mean difference (SMD) in depressive symptoms with CPAP treatment in these two trial populations with baseline depression was 2.004 (95% CI: 1.387, 2.621), compared to 0.197 (95% CI: 0.059, 0.334) for 15 trials of populations without depression at baseline. Pooled estimates of the treatment effect of CPAP were greater in parallel arm trials than in crossover trials (meta-regression, p = 0.076). Random effects meta-analysis of five trials of MADs showed a significant improvement in depressive symptoms with MADs versus controls: SMD = 0.214 (95% CI: 0.026, 0.401) without significant heterogeneity (I(2) = 0%, 95% CI: 0%, 79%). Studies were limited by the use of depressive symptom scales that have not been validated specifically in people with OSA.ConclusionsCPAP and MADs may be useful components of treatment of depressive symptoms in individuals with OSA and depression. The efficacy of CPAP and MADs compared to standard therapies for depression is unknown. Please see later in the article for the Editors' Summary.
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Project description:PurposeThe objective of this study is to systematically review the international literature for dynamic sleep magnetic resonance imaging (MRI) as a diagnostic tool in obstructive sleep apnea (OSA), to perform meta-analysis on the quantitative data from the review, and to discuss its implications in future research and potential clinical applications.Study designA comprehensive review of the literature was performed, followed by a detailed analysis of the relevant data that has been published on the topic.MethodsClinical key, Uptodate, Ovid, Ebscohost, Pubmed/MEDLINE, Scopus, Dynamed, Web of Science and The Cochrane Library were systematically searched. Once the search was completed, dynamic sleep MRI data were analyzed.ResultsNineteen articles reported on 410 OSA patients and 79 controls that underwent dynamic sleep MRI and were included in this review. For meta-analysis of dynamic sleep MRI data, eight articles presented relevant data on 160 OSA patients. Obstruction was reported as follows: retropalatal (RP) 98%, retroglossal (RG) 41% and hypopharyngeal (HP) in 5%. Lateral pharyngeal wall (LPW) collapse was found in 35/73 (48%) patients. The combinations of RP + RG were observed in 24% and RP + RG + LPW in 16%. If sedation was used, 98% of study participants fell asleep compared to 66% of unsedated participants.ConclusionsDynamic sleep MRI has demonstrated that nearly all patients have retropalatal obstruction, retroglossal obstruction is common and hypopharyngeal obstruction is rare. Nearly all patients (98%) who are sedated are able to fall asleep during the MRI. There is significant heterogeneity in the literature and standardization is needed.
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Project description:This study is the first comparative trial of sleep medications at high altitude. We performed a randomized, double-blind trial of temazepam and acetazolamide at an altitude of 3540 meters. 34 healthy trekkers with self-reports of high-altitude sleep disturbance were randomized to temazepam 7.5 mg or acetazolamide 125 mg taken at bedtime for one night. The primary outcome was sleep quality on a 100 mm visual analog scale. Additional measurements were obtained with actigraphy; pulse oximetry; and questionnaire evaluation of sleep, daytime drowsiness, daytime sleepiness, and acute mountain sickness. Sixteen subjects were randomized to temazepam and 18 to acetazolamide. Sleep quality on the 100 mm visual analog scale was higher for temazepam (59.6, SD 20.1) than acetazolamide (46.2, SD 20.2; p=0.048). Temazepam also demonstrated higher subjective sleep quality on the Groningen Sleep Quality Scale (3.5 vs. 6.8, p=0.009) and sleep depth visual analog scale (60.3 vs. 41.4, p=0.028). The acetazolamide group reported significantly more awakenings to urinate (1.8 vs. 0.5, p=0.007). No difference was found with regards to mean nocturnal oxygen saturation (84.1 vs. 84.4, p=0.57), proportion of the night spent in periodic breathing, relative desaturations, sleep onset latency, awakenings, wake after sleep onset, sleep efficiency, Stanford Sleepiness Scale scores, daytime drowsiness, or change in self-reported Lake Louise Acute Mountain Sickness scores. We conclude that, at current recommended dosing, treatment of high-altitude sleep disturbance with temazepam is associated with increased subjective sleep quality compared to acetazolamide.
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Project description:Our aim was to assess the efficacy and safety of acupuncture for OSA patients with various severities of the disorder. Eight databases including PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and Chinese Biomedical Literature Database (CBM) were comprehensively searched till July 2019. Randomized controlled trials (RCTs) testing acupuncture in the treatment of OSA were eligible for inclusion. Studies were selected for inclusion, and data were extracted by two authors independently. The Cochrane Collaboration's Risk of Bias Assessment Tool and RevMan software (version 5.3) were used to evaluate the quality of studies and conduct statistical analysis. Nine RCTs with 584 participants were included. The trials covered acupuncture and electropuncture. Acupuncture caused clinically significant reductions in AHI (MD: -6.18; 95% CI: -9.58 to -2.78; Z = 3.56, P = 0.0004) as well as in ESS (MD: -2.84; 95% CI: -4.80 to -0.16, Z = 2.09, P = 0.04). AHI was reduced more in the subgroup analysis of moderate OSA patients (MD: -9.44; 95% CI: -12.44 to -6.45; Z = 6.18, P < 0.00001) and severe OSA patients (MD: -10.09; 95% CI: -12.47 to -7.71; Z = 8.31, P < 0.00001). ESS was also reduced more in the subgroup analysis of moderate OSA patients (MD: -2.40; 95% CI: -3.63 to -1.17; Z = 3.83, P = 0.0001) and severe OSA patients (MD: -4.64; 95% CI: -5.35 to -3.92; Z = 12.72, P < 0.00001). Besides, acupuncture had a beneficial effect on LSaO2 (MD: 5.29; 95% CI: 2.61 to 7.97; Z = 3.86, P = 0.0001). The outcome of AHI and LSaO2 yielded consistent results after sensitivity analysis, but the direction of the outcome of ESS was reversed. And the quality of evidence was mainly low to very low. Acupuncture therapy is effective for OSA patients in reducing AHI and ESS and in improving the LSaO2 of various severities, especially in moderate and severe OSA patients. High-quality trials are urgently needed.
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