Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial

Background: COPD may predispose to symptomatic pulmonary hypertension at high altitude. We investigated haemodynamic changes in lowlanders with COPD ascending to 3100 m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP). Methods: In this randomised, placebo-controlled, double-blind, parallel-group trial, patients with COPD Global Initiative for Chronic Obstructive Lung Disease grades 2–3 who were living 92% and arterial carbon dioxide tension <6 kPa were randomised to receive either acetazolamide (125–250 mg·day$^{−1}$) or placebo capsules, starting 24 h before ascent from 760 m and during a 2-day stay at 3100 m. Echocardiography, pulse oximetry and clinical assessments were performed at 760 m and after the first night at 3100 m. Primary outcome was PAP assessed by tricuspid regurgitation pressure gradient (TRPG). Results: 112 patients (68% men, mean±sdage 59±8 years, forced expiratory volume in 1 s (FEV$_{1}$) 61±12% pred,S$_{pO_{2}}$95±2%) were included. Mean±sdTRPG increased from 22±7 to 30±10 mmHg in 54 patients allocated to placebo and from 20±5 to 24±7 mmHg in 58 patients allocated to acetazolamide (both p<0.05) resulting in a mean (95% CI) treatment effect of −5 (−9 to −1) mmHg (p=0.015). In patients assigned to placebo at 760/3100 m, mean±sdS$_{pO_{2}}$was 95±2%/88±3%; in the acetazolamide group, the respective values were 94±2%/90±3% (both p<0.05), resulting in a treatment effect of +2 (1 to 3)% (p=0.001). Conclusions: In lowlanders with COPD travelling to 3100 m, preventive acetazolamide treatment attenuated the altitude-induced rise in PAP and improved oxygenation

Visuomotor performance at high altitude in COPD patients. Randomized placebo-controlled trial of acetazolamide

Introduction: We evaluated whether exposure to high altitude impairs visuomotor learning in lowlanders with chronic obstructive pulmonary disease (COPD) and whether this can be prevented by acetazolamide treatment.Methods: 45 patients with COPD, living &lt;800 m, FEV1 ≥40 to &lt;80%predicted, were randomized to acetazolamide (375 mg/d) or placebo, administered 24h before and during a 2-day stay in a clinic at 3100 m. Visuomotor performance was evaluated with a validated, computer-assisted test (Motor-Task-Manager) at 760 m above sea level (baseline, before starting the study drug), within 4h after arrival at 3100 m and in the morning after one night at 3100 m. Main outcome was the directional error (DE) of cursor movements controlled by the participant via mouse on a computer screen during a target tracking task. Effects of high altitude and acetazolamide on DE during an adaptation phase, immediate recall and post-sleep recall were evaluated by regression analyses. www.ClinicalTrials.gov NCT03165890.Results: In 22 patients receiving placebo, DE at 3100 m increased during adaptation by mean 2.5°, 95%CI 2.2° to 2.7° (p &lt; 0.001), during immediate recall by 5.3°, 4.6° to 6.1° (p &lt; 0.001), and post-sleep recall by 5.8°, 5.0 to 6.7° (p &lt; 0.001), vs. corresponding values at 760 m. In 23 participants receiving acetazolamide, corresponding DE were reduced by −0.3° (−0.6° to 0.1°, p = 0.120), −2.7° (−3.7° to −1.6°, p &lt; 0.001) and −3.1° (−4.3° to −2.0°, p &lt; 0.001), compared to placebo at 3100 m.Conclusion: Lowlanders with COPD travelling to 3100 m experienced altitude-induced impairments in immediate and post-sleep recall of a visuomotor task. Preventive acetazolamide treatment mitigated these undesirable effects

Effect of acetazolamide on visuomotor performance at high altitude in healthy people 40 years of age or older—RCT

Objective: Altitude travel is increasingly popular also for middle-aged and older tourists and professionals. Due to the sensitivity of the central nervous system to hypoxia, altitude exposure may impair visuomotor performance although this has not been extensively studied. Therefore, we investigated whether a sojourn at moderately high altitude is associated with visuomotor performance impairments in healthy adults, 40y of age or older, and whether this adverse altitude-effect can be prevented by acetazolamide, a drug used to prevent acute mountain sickness. Methods: In this randomized placebo-controlled parallel-design trial, 59 healthy lowlanders, aged 40-75y, were assigned to acetazolamide (375 mg/day, n = 34) or placebo (n = 25), administered one day before ascent and while staying at high altitude (3100m). Visuomotor performance was assessed at 760m and 3100m after arrival and in the next morning (post-sleep) by a computer-assisted test (Motor-Task-Manager). It quantified deviation of a participant-controlled cursor affected by rotation during target tracking. Primary outcome was the directional error during post-sleep recall of adaptation to rotation estimated by multilevel linear regression modeling. Additionally, adaptation, immediate recall, and correct test execution were evaluated. Results: Compared to 760m, assessments at 3100m with placebo revealed a mean (95%CI) increase in directional error during adaptation and immediate recall by 1.9° (0.2 to 3.5, p = 0.024) and 1.1° (0.4 to 1.8, p = 0.002), respectively. Post-sleep recall remained unchanged (p = NS), however post-sleep correct test execution was 14% less likely (9 to 19, p<0.001). Acetazolamide improved directional error during post-sleep recall by 5.6° (2.6 to 8.6, p<0.001) and post-sleep probability of correct test execution by 36% (30 to 42, p<0.001) compared to placebo. Conclusion: In healthy individuals, 40y of age or older, altitude exposure impaired adaptation to and immediate recall and correct execution of a visuomotor task. Preventive acetazolamide treatment improved visuomotor performance after one night at altitude and increased the probability of correct test execution compared to placebo

Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy Adults

Background We evaluated the efficacy of acetazolamide in preventing adverse altitude effects in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and in healthy lowlanders 40 years of age or older. Methods Trial 1 was a randomized, double-blind, parallel-design trial in which 176 patients with COPD were treated with acetazolamide capsules (375 mg/day) or placebo, starting 24 hours before staying for 2 days at 3100 m. The mean (±SD) age of participants was 57±9 years, and 34% were women. At 760 m, COPD patients had oxygen saturation measured by pulse oximetry of 92% or greater, arterial partial pressure of carbon dioxide less than 45 mm Hg, and mean forced expiratory volume in 1 second of 63±11% of predicted. The primary outcome in trial 1 was the incidence of the composite end point of altitude-related adverse health effects (ARAHE) at 3100 m. Criteria for ARAHE included acute mountain sickness (AMS) and symptoms or findings relevant to well-being and safety, such as severe hypoxemia, requiring intervention. Trial 2 comprised 345 healthy lowlanders. Their mean age was 53±7 years, and 69% were women. The participants in trial 2 underwent the same protocol as did the patients with COPD in trial 1. The primary outcome in trial 2 was the incidence of AMS assessed at 3100 m by the Lake Louise questionnaire score (the scale of self-assessed symptoms ranges from 0 to 15 points, indicating absent to severe, with 3 or more points including headache, indicating AMS). Results In trial 1 of patients with COPD, 68 of 90 (76%) receiving placebo and 42 of 86 (49%) receiving acetazolamide experienced ARAHE (hazard ratio, 0.54; 95% confidence interval [CI], 0.37 to 0.79; P<0.001). The number needed to treat (NNT) to prevent one case of ARAHE was 4 (95% CI, 3 to 8). In trial 2 of healthy individuals, 54 of 170 (32%) receiving placebo and 38 of 175 (22%) receiving acetazolamide experienced AMS (hazard ratio, 0.48; 95% CI, 0.29 to 0.80; chi-square statistic P=0.035). The NNT to prevent one case of AMS was 10 (95% CI, 5 to 141). No serious adverse events occurred in these trials. Conclusions Preventive treatment with acetazolamide reduced the incidence of adverse altitude effects requiring an intervention in patients with COPD and the incidence of AMS in healthy lowlanders 40 years of age or older during a high-altitude sojourn. (Funded by the Swiss National Science Foundation [Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung], Lunge Zürich, and the Swiss Lung Foundation; ClinicalTrials.gov numbers, NCT03156231 and NCT03561675.

Effect of Acetazolamide on Postural Control in Patients with COPD Travelling to 3100 m Randomized Trial

Patients with chronic obstructive pulmonary disease (COPD) may be susceptible to impairments in postural control (PC) when exposed to hypoxia at high altitude. This randomized, placebo-controlled, double-blind, parallel-design trial evaluated the effect of preventive acetazolamide treatment on PC in lowlanders with COPD traveling to 3100 m. 127 lowlanders (85 men, 42 women) with moderate to severe COPD, aged 57 &plusmn; 8 y, living below 800 m, were randomized to treatment with acetazolamide 375 mg/d starting 24 h before ascent from 760 m to 3100 m and during a 2-day sojourn in a clinic at 3100 m. PC was evaluated at both altitudes with a balance platform on which patients were standing during five tests of 30 s each. The primary outcome was the center of pressure path length (COPL). In the placebo group, COPL significantly increased from (mean &plusmn; SD) 28.8 &plusmn; 9.7 cm at 760 m to 30.0 &plusmn; 10.0 cm at 3100 m (p = 0.002). In the acetazolamide group, COPL at 760 m and 3100 m were similar with 27.6 &plusmn; 9.6 cm and 28.4 &plusmn; 9.7 cm (p = 0.069). The mean between-groups difference (acetazolamide-placebo) in altitude-induced change of COPL was &minus;0.54 cm (95%CI &minus;1.66 to 0.58, p = 0.289). Multivariable regression analysis confirmed an increase in COPL of 0.98 cm (0.39 to 1.58, p = 0.001) with ascent from 760 to 3100 m, but no significant effect of acetazolamide (0.66 cm, 95%CI &minus;0.25 to 1.57, p = 0.156) when adjusting for several confounders. In lowlanders with moderate to severe COPD, an ascent to high altitude was associated with impaired postural control and this was not prevented by acetazolamide

Effect of Acetazolamide on Postural Control in Patients with COPD Travelling to 3100 m Randomized Trial

Patients with chronic obstructive pulmonary disease (COPD) may be susceptible to impairments in postural control (PC) when exposed to hypoxia at high altitude. This randomized, placebo-controlled, double-blind, parallel-design trial evaluated the effect of preventive acetazolamide treatment on PC in lowlanders with COPD traveling to 3100 m. 127 lowlanders (85 men, 42 women) with moderate to severe COPD, aged 57 ± 8 y, living below 800 m, were randomized to treatment with acetazolamide 375 mg/d starting 24 h before ascent from 760 m to 3100 m and during a 2-day sojourn in a clinic at 3100 m. PC was evaluated at both altitudes with a balance platform on which patients were standing during five tests of 30 s each. The primary outcome was the center of pressure path length (COPL). In the placebo group, COPL significantly increased from (mean ± SD) 28.8 ± 9.7 cm at 760 m to 30.0 ± 10.0 cm at 3100 m (p = 0.002). In the acetazolamide group, COPL at 760 m and 3100 m were similar with 27.6 ± 9.6 cm and 28.4 ± 9.7 cm (p = 0.069). The mean between-groups difference (acetazolamide-placebo) in altitude-induced change of COPL was −0.54 cm (95%CI −1.66 to 0.58, p = 0.289). Multivariable regression analysis confirmed an increase in COPL of 0.98 cm (0.39 to 1.58, p = 0.001) with ascent from 760 to 3100 m, but no significant effect of acetazolamide (0.66 cm, 95%CI −0.25 to 1.57, p = 0.156) when adjusting for several confounders. In lowlanders with moderate to severe COPD, an ascent to high altitude was associated with impaired postural control and this was not prevented by acetazolamide

Validation of a Portable Blood Gas Analyzer for Use in Challenging Field Conditions at High Altitude

Background: Novel, portable blood gas analyzers (BGAs) may serve as essential point-of-care tools in remote regions, during air travel or in ambulance services but they have not been extensively validated. Research Question: We compared accuracy of a portable BGA to a validated stationary device. Methods: In healthy individuals and patients with chronic obstructive pulmonary disease participating in clinical field studies at different altitudes, arterial blood samples were obtained at rest and during exercise in a hospital at 760 m and in a high altitude clinic at 3100 m. Paired measurements by a portable BGA (EPOC, Siemens Healthcare) and a stationary BGA (Rapidpoint500, Siemens Healthcare) were performed to compute bias (mean difference) and limits of agreement (95% CI of bias). Results: Of 105 individuals, 248 arterial blood samples were analyzed, 108 at 760 m, 140 at 3100 m. Ranges of values measured by portable BGA were: pH 7.241−7.473, PaCO2 21.5−52.5 mmHg, and PaO2 45.5−107.1 mmHg. Bias (95% CI) between devices were: pH 0.007 (−0.029 to 0.044), PaCO2 −0.3 mmHg (−4.8 to 4.2), and PaO2 −0.2 mmHg (−9.1 to 4.7). For pH, agreement between devices was improved by the equation to correct pH by portable BGA = −1.37 + pHmeasured × 1.19; bias after correction −0.007 (−0.023 to 0.009). The portable BGA was easily handled and worked reliably. Interpretation: Accuracy of blood gas analysis by the portable BGA in comparison to the reference BGA was adequate for clinical use. Because of portability and ease of handling, portable BGA are valuable diagnostic tools for use in everyday practice as well as under challenging field conditions

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial

Background COPD may predispose to symptomatic pulmonary hypertension at high altitude. We investigated haemodynamic changes in lowlanders with COPD ascending to 3100 m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP). Methods In this randomised, placebo-controlled, double-blind, parallel-group trial, patients with COPD Global Initiative for Chronic Obstructive Lung Disease grades 2–3 who were living 92% and arterial carbon dioxide tension <6 kPa were randomised to receive either acetazolamide (125–250 mg·day−1) or placebo capsules, starting 24 h before ascent from 760 m and during a 2-day stay at 3100 m. Echocardiography, pulse oximetry and clinical assessments were performed at 760 m and after the first night at 3100 m. Primary outcome was PAP assessed by tricuspid regurgitation pressure gradient (TRPG). Results 112 patients (68% men, mean±sd age 59±8 years, forced expiratory volume in 1 s (FEV1) 61±12% pred, SpO2 95±2%) were included. Mean±sd TRPG increased from 22±7 to 30±10 mmHg in 54 patients allocated to placebo and from 20±5 to 24±7 mmHg in 58 patients allocated to acetazolamide (both p<0.05) resulting in a mean (95% CI) treatment effect of −5 (−9 to −1) mmHg (p=0.015). In patients assigned to placebo at 760/3100 m, mean±sd SpO2 was 95±2%/88±3%; in the acetazolamide group, the respective values were 94±2%/90±3% (both p<0.05), resulting in a treatment effect of +2 (1 to 3)% (p=0.001). Conclusions In lowlanders with COPD travelling to 3100 m, preventive acetazolamide treatment attenuated the altitude-induced rise in PAP and improved oxygenation

Effect of acetazolamide on visuomotor performance at high altitude in healthy people 40 years of age or older-RCT.

ObjectiveAltitude travel is increasingly popular also for middle-aged and older tourists and professionals. Due to the sensitivity of the central nervous system to hypoxia, altitude exposure may impair visuomotor performance although this has not been extensively studied. Therefore, we investigated whether a sojourn at moderately high altitude is associated with visuomotor performance impairments in healthy adults, 40y of age or older, and whether this adverse altitude-effect can be prevented by acetazolamide, a drug used to prevent acute mountain sickness.MethodsIn this randomized placebo-controlled parallel-design trial, 59 healthy lowlanders, aged 40-75y, were assigned to acetazolamide (375 mg/day, n = 34) or placebo (n = 25), administered one day before ascent and while staying at high altitude (3100m). Visuomotor performance was assessed at 760m and 3100m after arrival and in the next morning (post-sleep) by a computer-assisted test (Motor-Task-Manager). It quantified deviation of a participant-controlled cursor affected by rotation during target tracking. Primary outcome was the directional error during post-sleep recall of adaptation to rotation estimated by multilevel linear regression modeling. Additionally, adaptation, immediate recall, and correct test execution were evaluated.ResultsCompared to 760m, assessments at 3100m with placebo revealed a mean (95%CI) increase in directional error during adaptation and immediate recall by 1.9° (0.2 to 3.5, p = 0.024) and 1.1° (0.4 to 1.8, p = 0.002), respectively. Post-sleep recall remained unchanged (p = NS), however post-sleep correct test execution was 14% less likely (9 to 19, pConclusionIn healthy individuals, 40y of age or older, altitude exposure impaired adaptation to and immediate recall and correct execution of a visuomotor task. Preventive acetazolamide treatment improved visuomotor performance after one night at altitude and increased the probability of correct test execution compared to placebo.Clinicaltrials.gov identifierClinicalTrials.gov NCT03536520