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High Altitude Medicine & Biology Mar 2021Toussaint, Claudia M., Robert W. Kenefick, Frank A. Petrassi, Stephen R. Muza, and Nisha Charkoudian. Altitude, acute mountain sickness, and acetazolamide:...
Toussaint, Claudia M., Robert W. Kenefick, Frank A. Petrassi, Stephen R. Muza, and Nisha Charkoudian. Altitude, acute mountain sickness, and acetazolamide: recommendations for rapid ascent. . 22:5-13, 2021. Sea level natives ascending rapidly to altitudes above 1,500 m often develop acute mountain sickness (AMS), including nausea, headaches, fatigue, and lightheadedness. Acetazolamide (AZ), a carbonic anhydrase inhibitor, is a commonly used medication for the prevention and treatment of AMS. However, there is continued debate about appropriate dosing, particularly when considering rapid and physically demanding ascents to elevations above 3,500 m by emergency medical and military personnel. Our goal in the present analysis was to evaluate and synthesize the current literature regarding the use of AZ to determine the most effective dosing for prophylaxis and treatment of AMS for rapid ascents to elevations >3,500 m. These circumstances are specifically relevant to military and emergency medical personnel who often need to ascend rapidly and perform physically demanding tasks upon arrival at altitude. We conducted a literature search from April 2018 to February 2020 using PubMed, Google Scholar, and Web of Science to identify randomized controlled trials that compared AZ with placebo or other treatment with the primary endpoint of AMS incidence and severity. We included only research articles/studies that focused on evaluation of AZ use during rapid ascent. Four doses of AZ (125, 250, 500, and 750 mg daily) were identified as efficacious in decreasing the incidence and/or severity of AMS during rapid ascents, with evidence of enhanced effectiveness with higher doses. For military, emergency medical, or other activities involving rapid ascent to altitudes >3,500 m, doses 500-750 mg/day within 24 hours of altitude exposure appear to be the most effective for minimizing symptoms of AMS.
Topics: Acetazolamide; Acute Disease; Altitude; Altitude Sickness; Carbonic Anhydrase Inhibitors; Humans; Incidence
PubMed: 32975448
DOI: 10.1089/ham.2019.0123 -
Journal of Cataract and Refractive... Jan 2023A 50-year-old ophthalmic technician was referred by her retina specialist for urgent consultation due to markedly elevated intraocular pressure (IOP) unresponsive to...
A 50-year-old ophthalmic technician was referred by her retina specialist for urgent consultation due to markedly elevated intraocular pressure (IOP) unresponsive to medical therapy. Her history included chronic polyarticular juvenile rheumatoid arthritis and chronic uveitis requiring ongoing topical steroid therapy. She had a sub-Tenon injection of Kenalog (triamcinolone) 18 months prior to referral. Chronic topical anti-inflammatory therapy included nepafenac (Ilevro) and prednisolone acetate 2 times a day. Attempts to discontinue topical steroid resulted in worsening inflammation. The patient was referred when the IOP measured 44 mm Hg in the left eye despite aggressive medical therapy, including acetazolamide. The IOP improved slightly when loteprednol was substituted for prednisolone acetate. Current medications in the left eye include brimonidine 3 times a day, loteprednol 2 times a day, nepafenac 2 times a day, and fixed combination latanoprost + netarsudil at bedtime. Her only medication in the right eye was travoprost. She is intolerant to dorzolamide. She was also taking acetazolamide 500 mg 2 times a day. She was not taking any anticoagulants. Past surgical history included cataract surgery in each eye. She has not had laser trabeculoplasty in either eye. Examination revealed uncorrected visual acuity of J1+ in the right eye (near) and 20/30 in the left eye (mini-monovision). There was no afferent pupillary defect. There was mild band keratopathy in each eye while the central cornea was clear in both eyes without keratic precipitates. Here angles were open to gonioscopy without peripheral anterior synechia. There was mild to moderate flare in each eye with trace cells. The IOP was 17 mm Hg in the right eye and 31 mm Hg in the left. Central corneal thickness measured 560 μm and 559 μm in the right and left eye respectively. There was a well-positioned intraocular lens within each capsule with a patent posterior capsulotomy. There was mild vitreous syneresis but no vitreous cell. The cup to disc ratio was 0.5 in each eye with a symmetrical neural rim. The retina was flat without macular edema. Visual field was normal in both eyes (Figures 1 and 2). Optical coherence tomography of retinal nerve fiber layer (RNFL) is shown in Figure 3 and retinal ganglion cell layer is shown in Supplemental Figure 1 (http://links.lww.com/JRS/A756).JOURNAL/jcrs/04.03/02158034-202301000-00020/figure1/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure2/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure3/v/2022-12-26T045736Z/r/image-tiff Please comment on your management of this patient's left eye.
Topics: Humans; Female; Middle Aged; Intraocular Pressure; Iritis; Acetazolamide; Loteprednol Etabonate; Triamcinolone Acetonide; Latanoprost
PubMed: 36573765
DOI: 10.1097/j.jcrs.0000000000001104 -
Sleep Apr 2023To assess altitude-induced sleep and nocturnal breathing disturbances in healthy lowlanders 40 y of age or older and the effects of preventive acetazolamide treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVES
To assess altitude-induced sleep and nocturnal breathing disturbances in healthy lowlanders 40 y of age or older and the effects of preventive acetazolamide treatment.
METHODS
Clinical examinations and polysomnography were performed at 760 m and in the first night after ascent to 3100 m in a subsample of participants of a larger trial evaluating altitude illness. Participants were randomized 1:1 to treatment with acetazolamide (375 mg/day) or placebo, starting 24 h before and while staying at 3100 m. The main outcomes were indices of sleep structure, oxygenation, and apnea/hypopnea index (AHI).
RESULTS
Per protocol analysis included 86 participants (mean ± SE 53 ± 7 y old, 66% female). In 43 individuals randomized to placebo, mean nocturnal pulse oximetry (SpO2) was 94.0 ± 0.4% at 760 m and 86.7 ± 0.4% at 3100 m, with mean change (95%CI) -7.3% (-8.0 to -6.5); oxygen desaturation index (ODI) was 5.0 ± 2.3 at 760 m and 29.2 ± 2.3 at 3100 m, change 24.2/h (18.8 to 24.5); AHI was 11.3 ± 2.4/h at 760 m and 23.5 ± 2.4/h at 3100 m, change 12.2/h (7.3 to 17.0). In 43 individuals randomized to acetazolamide, altitude-induced changes were mitigated. Mean differences (Δ, 95%CI) in altitude-induced changes were: ΔSpO2 2.3% (1.3 to 3.4), ΔODI -15.0/h (-22.6 to -7.4), ΔAHI -11.4/h (-18.3 to -4.6). Total sleep time, sleep efficiency, and N3-sleep fraction decreased with an ascent to 3100 m under placebo by 40 min (17 to 60), 5% (2 to 8), and 6% (2 to 11), respectively. Acetazolamide did not significantly change these outcomes.
CONCLUSIONS
During a night at 3100 m, healthy lowlanders aged 40 y or older revealed hypoxemia, sleep apnea, and disturbed sleep. Preventive acetazolamide treatment improved oxygenation and nocturnal breathing but had no effect on sleep duration and structure.
TRIAL REGISTRATION
The trial is registered at Clinical Trials, https://clinicaltrials.gov, NCT03561675.
Topics: Humans; Female; Male; Acetazolamide; Altitude; Sleep; Respiration
PubMed: 36356042
DOI: 10.1093/sleep/zsac269 -
Polish Archives of Internal Medicine Dec 2023Decongestion is a therapeutic target in acute heart failure (AHF). Acetazolamide is a diuretic that decreases proximal tubular sodium reabsorption, and may also reverse... (Randomized Controlled Trial)
Randomized Controlled Trial
Diuretic, natriuretic, and chloride-regaining effects of oral acetazolamide as an add-on therapy for acute heart failure with volume overload: a single-center, prospective, randomized study.
INTRODUCTION
Decongestion is a therapeutic target in acute heart failure (AHF). Acetazolamide is a diuretic that decreases proximal tubular sodium reabsorption, and may also reverse hypochloremia Objectives: We assessed the decongestive, natriuretic, and chloride‑regaining effects as well as the renal safety profile of oral acetazolamide (250 mg) used as an add‑on therapy in patients with AHF.
PATIENTS AND METHODS
This prospective, randomized study was conducted at the Institute of Heart Diseases in Wrocław, Poland. It involved patients with AHF who were randomly assigned to receive either 250 mg of oral acetazolamide or standard care, and who underwent clinical and laboratory follow‑up for 3 consecutive days since the beginning of the treatment and at discharge.
RESULTS
The study population comprised 61 patients (71% men), of whom 31 (51%) were included in the acetazolamide group. The mean (SD) age of the patients was 68 (13) years. In comparison with the controls, the acetazolamide group demonstrated significantly higher cumulative diuresis after 48 and 72 hours since treatment implementation, negative fluid balance, weight loss after 48 hours of treatment, weight loss throughout the hospitalization, natriuresis, and serum chloride concentration. In terms of the renal safety profile, no increase in the creatinine concentration and urinary renal biomarker levels was noted.
CONCLUSIONS
Oral acetazolamide seems to be a valuable add‑on therapy that helps achieve comprehensive decongestion in patients with AHF.
Topics: Male; Humans; Aged; Female; Diuretics; Acetazolamide; Chlorides; Prospective Studies; Heart Failure; Weight Loss
PubMed: 37415505
DOI: 10.20452/pamw.16526 -
Journal of Travel Medicine Jun 2023Altitude sojourns increasingly attract individuals of all ages and different health statuses due to the appeal of high-altitude destinations worldwide and easy access to... (Review)
Review
BACKGROUND
Altitude sojourns increasingly attract individuals of all ages and different health statuses due to the appeal of high-altitude destinations worldwide and easy access to air travel. The risk of acute mountain sickness (AMS) when flying to high-altitude destinations remains underemphasized. Thus, this review aims to evaluate the altitude-dependent AMS incidence depending on the mode of ascending, e.g. by air vs terrestrial travel.
METHODS
A literature search was performed to identify the observational studies assessing AMS incidence after acute ascent of primarily healthy adults to real high altitude. In addition, placebo arms of interventional trials evaluating the prophylactic efficacy of various drugs have been separately analysed to confirm or refute the findings from the observational studies. Linear regression analyses were used to evaluate the altitude-dependent AMS incidence.
RESULTS
Findings of 12 observational studies, in which the AMS incidence in 11 021 individuals ascending to 19 different altitudes (2200-4559 m) was evaluated, revealed an impressive 4.5-fold steeper increase in the AMS incidence for air travel as compared with slower ascent modes, i.e. hiking or combined car and/or air travel and hiking. The higher AMS incidence following transportation by flight vs slower means was also confirmed in placebo-treated participants in 10 studies of drug prophylaxis against AMS.
CONCLUSIONS
Due to the short time span in going from low to high altitude, reduced acclimatization likely is the main reason for a higher AMS risk when travelling to high-altitude destinations by flight. To avoid frustrating travel experiences and health risks, appropriate and timely medical advice on how to prepare for air travel to high altitude is of vital importance. Effective preparation options include the use of modern pre-acclimatization strategies and pharmacological prophylaxis by acetazolamide or dexamethasone, or even considering alternate itineraries with more gradual ascent.
Topics: Adult; Humans; Altitude Sickness; Altitude; Acute Disease; Acetazolamide; Air Travel
PubMed: 36694981
DOI: 10.1093/jtm/taad011 -
Thorax Feb 2024Acetazolamide and atomoxetine-plus-oxybutynin ('AtoOxy') can improve obstructive sleep apnoea (OSA) by stabilising ventilatory control and improving dilator muscle... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
Acetazolamide and atomoxetine-plus-oxybutynin ('AtoOxy') can improve obstructive sleep apnoea (OSA) by stabilising ventilatory control and improving dilator muscle responsiveness respectively. Given the different pathophysiological mechanisms targeted by each intervention, we tested whether AtoOxy-plus-acetazolamide would be more efficacious than AtoOxy alone.
METHODS
In a multicentre randomised crossover trial, 19 patients with moderate-to-severe OSA received AtoOxy (80/5 mg), acetazolamide (500 mg), combined AtoOxy-plus-acetazolamide or placebo at bedtime for three nights (half doses on first night) with a 4-day washout between conditions. Outcomes were assessed at baseline and night 3 of each treatment period. Mixed model analysis compared the reduction in Apnoea-Hypopnoea Index (AHI) from baseline between AtoOxy-plus-acetazolamide and AtoOxy (primary outcome). Secondary outcomes included hypoxic burden and arousal index.
RESULTS
Although AtoOxy lowered AHI by 49 (33, 62)% (estimate (95% CI)) vs placebo, and acetazolamide lowered AHI by+34 (14, 50)% vs placebo, AtoOxy-plus-acetazolamide was not superior to AtoOxy alone (difference: -2 (-18, 11)%, primary outcome p=0.8). Likewise, the hypoxic burden was lowered with AtoOxy (+58 (37, 71)%) and acetazolamide (+37 (5, 58)%), but no added benefit versus AtoOxy occurred when combined (difference: -13 (-5, 39)%). Arousal index was also modestly reduced with each intervention (11%-16%). Mechanistic analyses revealed that similar traits (ie, higher baseline compensation, lower loop gain) were associated with both AtoOxy and acetazolamide efficacy.
CONCLUSIONS
While AtoOxy halved AHI, and acetazolamide lowered AHI by a third, the combination of these leading experimental interventions provided no greater efficacy than AtoOxy alone. Failure of acetazolamide to further increase efficacy suggests overlapping physiological mechanisms.
TRIAL REGISTRATION NUMBER
NCT03892772.
Topics: Humans; Cross-Over Studies; Acetazolamide; Sleep Apnea, Obstructive; Drug Therapy, Combination; Atomoxetine Hydrochloride
PubMed: 38286618
DOI: 10.1136/thorax-2023-220184 -
Cureus Nov 2022Acetazolamide, a carbonic anhydrase inhibitor, is primarily used in the treatment of glaucoma, due to its role in decreasing intraocular pressure by lowering the...
Acetazolamide, a carbonic anhydrase inhibitor, is primarily used in the treatment of glaucoma, due to its role in decreasing intraocular pressure by lowering the production of aqueous humor. Additionally, by lowering cerebrospinal fluid (CSF) production, it is also used in the treatment of raised intracranial pressure. Drug-induced myokymia has rarely been reported, with known triggers being clozapine, gabapentin and flunarizine, and topiramate. Acetazolamide-induced myokymia itself has only been reported once before, to the best of our knowledge, and the exact mechanism behind this occurrence remains unknown. We, therefore, report a rare case of periorbital myokymia induced by the use of acetazolamide in a patient diagnosed with idiopathic intracranial hypertension. The nature of her symptoms was significant, as they caused her considerable distress, and subsided almost immediately upon discontinuation of the drug.
PubMed: 36579233
DOI: 10.7759/cureus.31920 -
Frontiers in Endocrinology 2022Exposure to hypobaric hypoxia at high altitude puts mountaineers at risk of acute mountain sickness. The carbonic anhydrase inhibitor acetazolamide is used to accelerate...
Exposure to hypobaric hypoxia at high altitude puts mountaineers at risk of acute mountain sickness. The carbonic anhydrase inhibitor acetazolamide is used to accelerate acclimatization, when it is not feasible to make a controlled and slow ascend. Studies in rodents have suggested that exposure to hypobaric hypoxia deteriorates bone integrity and reduces bone strength. The study investigated the effect of treatment with acetazolamide and the bisphosphonate, zoledronate, on the skeletal effects of exposure to hypobaric hypoxia. Eighty 16-week-old female RjOrl : SWISS mice were divided into five groups: 1. Baseline; 2. Normobaric; 3. Hypobaric hypoxia; 4. Hypobaric hypoxia + acetazolamide, and 5. Hypobaric hypoxia + zoledronate. Acetazolamide was administered in the drinking water (62 mg/kg/day) for four weeks, and zoledronate (100 μg/kg) was administered as a single subcutaneous injection at study start. Exposure to hypobaric hypoxia significantly increased lung wet weight and decreased femoral cortical thickness. Trabecular bone was spared from the detrimental effects of hypobaric hypoxia, although a trend towards reduced bone volume fraction was found at the L4 vertebral body. Treatment with acetazolamide did not have any negative skeletal effects, but could not mitigate the altitude-induced bone loss. Zoledronate was able to prevent the altitude-induced reduction in cortical thickness. In conclusion, simulated high altitude affected primarily cortical bone, whereas trabecular bone was spared. Only treatment with zoledronate prevented the altitude-induced cortical bone loss. The study provides preclinical support for future studies of zoledronate as a potential pharmacological countermeasure for altitude-related bone loss.
Topics: Absorptiometry, Photon; Acetazolamide; Altitude; Altitude Sickness; Animals; Bone Density; Cancellous Bone; Cortical Bone; Female; Mice; Quadriceps Muscle; Zoledronic Acid
PubMed: 35222286
DOI: 10.3389/fendo.2022.831369 -
Annals of the American Thoracic Society Aug 2020Amid efforts to care for the large number of patients with coronavirus disease (COVID-19), there has been considerable speculation about whether the lung injury seen in... (Review)
Review
Amid efforts to care for the large number of patients with coronavirus disease (COVID-19), there has been considerable speculation about whether the lung injury seen in these patients is different than acute respiratory distress syndrome from other causes. One idea that has garnered considerable attention, particularly on social media and in free open-access medicine, is the notion that lung injury due to COVID-19 is more similar to high-altitude pulmonary edema (HAPE). Drawing on this concept, it has also been proposed that treatments typically employed in the management of HAPE and other forms of acute altitude illness-pulmonary vasodilators and acetazolamide-should be considered for COVID-19. Despite some similarities in clinical features between the two entities, such as hypoxemia, radiographic opacities, and altered lung compliance, the pathophysiological mechanisms of HAPE and lung injury due to COVID-19 are fundamentally different, and the entities cannot be viewed as equivalent. Although of high utility in the management of HAPE and acute mountain sickness, systemically delivered pulmonary vasodilators and acetazolamide should not be used in the treatment of COVID-19, as they carry the risk of multiple adverse consequences, including worsened ventilation-perfusion matching, impaired carbon dioxide transport, systemic hypotension, and increased work of breathing.
Topics: Acetazolamide; Altitude Sickness; Betacoronavirus; COVID-19; Carbonic Anhydrase Inhibitors; Coronavirus Infections; Humans; Hypertension, Pulmonary; Lung Injury; Nifedipine; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2; Vasodilator Agents; COVID-19 Drug Treatment
PubMed: 32735170
DOI: 10.1513/AnnalsATS.202004-327CME -
NEJM Evidence Jan 2022BACKGROUND: We evaluated the efficacy of acetazolamide in preventing adverse altitude effects in patients with moderate to severe chronic obstructive pulmonary disease... (Randomized Controlled Trial)
Randomized Controlled Trial
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.)
Topics: Adult; Humans; Acetazolamide; Altitude; Altitude Sickness; Carbonic Anhydrase Inhibitors; Hypoxia; Pulmonary Disease, Chronic Obstructive
PubMed: 38296630
DOI: 10.1056/EVIDoa2100006