Efficacy of Acetazolamide for the Prophylaxis of Acute Mountain Sickness: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials

Gao, Daiquan; Wang, Yuan; Zhang, Rujiang; Zhang, Yunzhou

doi:10.1016/j.amjms.2020.12.022

Cited by 8 publications

(10 citation statements)

References 42 publications

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“…Acetazolamide elicits dose‐dependent side effects, including polyuria, paraesthesia, fatigue, and dysgeusia (Schmickl et al, 2020 ), and thus there is a desire to find the lowest prophylactic dose that minimizes both drug side effects and reported AMS symptoms. Although it has been well‐established that a prophylactic dose is superior to placebo in limiting AMS symptoms (Gao et al, 2021 ; Kayser et al, 2012 ; Low et al, 2012 ), the findings in the present study suggest no difference in AMS scores between NAz and Az groups using identical incremental ascent profiles, which was contrary to our initial hypothesis. The similarity in AMS scores between our NAz and Az groups with ascent may be attributed in part to the fact that (a) the two groups were different groups across different expeditions (i.e., not randomized or within‐individual comparisons) and/or (b) both groups had a low risk for developing AMS given the slow, incremental ascent profile we utilized (e.g., Imray, 2012 ; Kayser et al, 2012 ; Luks et al, 2019 ).…”

Section: Discussioncontrasting

confidence: 99%

“…In the present study, we established that SSCD is augmented with 7 days of incremental ascent to 4240 m (i.e., it captures VA), which is further augmented when superimposed with oral acetazolamide. Many experimental studies and reviews have assessed the efficacy of a prophylactic oral dose of acetazolamide in preventing and/or reducing AMS symptoms Gao et al, 2021;Kayser et al, 2012;Lipman et al, 2020;Low et al, 2012;McIntosh et al, 2019;Nieto Estrada et al, 2017;van Patot et al, 2008) with mixed results. There are several limitations with drawing conclusions from these studies, in part due to the subjective nature of AMS reporting, the site of recruitment (e.g., low vs. high altitude), and different ascent profiles (e.g., rapid vs. incremental ascent).…”

Section: Steady-state Chemoreflex Drive (Sscd) With Ascent: Effect Of...mentioning

confidence: 99%

“…Aside from oral acetazolamide administration to treat AMS at altitude (250 mg BID; 29), lower doses are routinely administered prophylactically to prevent AMS (e.g., 125 mg BID), particularly during rapid ascent and/or higher ascent profiles (Kayser et al, 2012 ; Luks et al, 2019 ; van Patot et al, 2008 ). Despite this, the lowest recommended acetazolamide dose that limits side effects and prevents AMS has been inconsistent, ranging from 750 mg/day (Dumont et al, 2000 ) to the current recommended 250 mg/day (Gao et al, 2021 ; Kayser et al, 2012 ; Low et al, 2012 ; Luks et al, 2019 ; Nieto Estrada et al, 2017 ). However, more recent reports indicate that an even lower dose of 62.5 mg BID can be as effective as the standard 125 mg BID (Lipman et al, 2020 ; McIntosh et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Steady‐state chemoreflex drive captures ventilatory acclimatization during incremental ascent to high altitude: Effect of acetazolamide

Cates

Bruce

Marullo

et al. 2022

Physiological Reports

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Ventilatory acclimatization (VA) is important to maintain adequate oxygenation with ascent to high altitude (HA). Transient hypoxic ventilatory response tests lack feasibility and fail to capture the integrated steady‐state responses to chronic hypoxic exposure in HA fieldwork. We recently characterized a novel index of steady‐state respiratory chemoreflex drive (SSCD), accounting for integrated contributions from central and peripheral respiratory chemoreceptors during steady‐state breathing at prevailing chemostimuli. Acetazolamide is often utilized during ascent for prevention or treatment of altitude‐related illnesses, eliciting metabolic acidosis and stimulating respiratory chemoreceptors. To determine if SSCD reflects VA during ascent to HA, we characterized SSCD in 25 lowlanders during incremental ascent to 4240 m over 7 days. We subsequently compared two separate subgroups: no acetazolamide (NAz; n = 14) and those taking an oral prophylactic dose of acetazolamide (Az; 125 mg BID; n = 11). At 1130/1400 m (day zero) and 4240 m (day seven), steady‐state measurements of resting ventilation (V̇ I ; L/min), pressure of end‐tidal (P ET )CO 2 (Torr), and peripheral oxygen saturation (SpO 2 ; %) were measured. A stimulus index (SI; P ET CO 2 /SpO 2 ) was calculated, and SSCD was calculated by indexing V̇ I against SI. We found that (a) both V̇ I and SSCD increased with ascent to 4240 m (day seven; V̇ I : +39%, p < 0.0001, Hedges' g = 1.52; SSCD: +56.%, p < 0.0001, Hedges' g = 1.65), (b) and these responses were larger in the Az versus NAz subgroup (V̇ I : p = 0.02, Hedges' g = 1.04; SSCD: p = 0.02, Hedges' g = 1.05). The SSCD metric may have utility in assessing VA during prolonged stays at altitude, providing a feasible alternative to transient chemoreflex tests.

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Section: Discussioncontrasting

confidence: 99%

Section: Steady-state Chemoreflex Drive (Sscd) With Ascent: Effect Of...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Steady‐state chemoreflex drive captures ventilatory acclimatization during incremental ascent to high altitude: Effect of acetazolamide

Cates

Bruce

Marullo

et al. 2022

Physiological Reports

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“…Administration of acetazolamide and dexamethasone can also be effective in prophylaxis of AMS and HACE [43,45]. Acetazolamide can be used in doses 125, 250, and 375 mg/bid [46]. Ibuprofen may be applied in the prevention of AMS in case of allergy or intolerance to acetzolamide or dexamethasone or in persons who do not wish to take those drugs [45].…”

Section: Clinical Recommendationsmentioning

confidence: 99%

The Impact of Temporary Stay at High Altitude on the Circulatory System

Mikołajczak

Czerwińska

Pilecki

et al. 2021

JCM

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In recent times many people stay temporarily at high altitudes. It is mainly associated with the growing popularity of regular air travel, as well as temporary trips to mountain regions. Variable environmental conditions, including pressure and temperature changes, have an impact on the human body. This paper analyses the physiological changes that may occur while staying at high altitude in healthy people and in people with cardiovascular diseases, such as arterial hypertension, pulmonary hypertension, heart failure, ischemic heart disease, or arrhythmias. Possible unfavourable changes were underlined. Currently recognized treatment recommendations or possible treatment modifications for patients planning to stay at high altitudes were also discussed.

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“…The heart frequency increases, the stroke volume decreases, and the vasoconstriction of the vessels was followed by an increase of the pressure in the pulmonary circulation. However, since the preventive effect of acetazolamide is obviously independent of a wide range of its dosage [ 18 , 19 ], but the diuretic side effect is dose-dependent, perhaps this specific hypothesis can be investigated in the future.…”

Section: Discussionmentioning

confidence: 99%

Variables Influencing the Pressure and Volume of the Pulmonary Circulation as Risk Factors for Developing High Altitude Pulmonary Edema (HAPE)

Hundt

Apel

Bertsch³

et al. 2022

IJERPH

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Background: At altitudes above 2500 m, the risk of developing high altitude pulmonary edema (HAPE) grows with the increases in pulmonary arterial pressure. HAPE is characterized by severe pulmonary hypertension, though the incidence and relevance of individual risk factors are not yet predictable. However, the systolic pulmonary pressure (SPAP) and peak in tricuspid regurgitation velocity (TVR) are crucial factors when diagnosing pulmonary hypertension by echocardiography. Methods: The SPAP and TVR of 27 trekkers aged 20–65 years en route to the Solu Khumbu region of Nepal were assessed. Echocardiograph measurements were performed at Lukla (2860 m), Gorak Shep (5170 m), and the summit of Kala Patthar (5675 m). The altitude profile and the participants’ characteristics were also compiled for correlation with the measured data. Results: The results showed a highly significant increase in SPAP and TVR after ascending Kala Patthar. The study revealed a lower increase of SPAP and TVR in the group of older participants, although the respective initial measurements at Gorak Shep were significantly higher for this group. A similar finding occurred in those using Diamox® as prophylaxis. There was an inverse relationship between TVR and SPAP, the peripheral capillary oxygen saturation, and heart rate. Conclusions: The echocardiograph results indicated that older people are an at-risk group for developing HAPE. A conservative interpretation of the basic tactical rules for altitudes should be followed for older trekkers or trekkers with known problems of altitude acclimatization (“slow acclimatizer”) as SPAP elevates with age. The prophylactic use of Acetazolamide (Diamox®) should be avoided where not necessary for acute medical reasons. Acetazolamide leads to an increase of SPAP, and this may potentially enhance the risk of developing HAPE. Arterial oxygen saturation measurements can provide an indicator for the self-assessment for the risk of developing HAPE and a rule of thumb for the altitude profile, but does not replace a HAPE diagnosis. Backpack weight, sex, workload (actual ascent speed), and pre-existing diseases were not statistically significant factors related to SPAP and TVR (p ≤ 0.05).

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Efficacy of Acetazolamide for the Prophylaxis of Acute Mountain Sickness: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials

Cited by 8 publications

References 42 publications

Steady‐state chemoreflex drive captures ventilatory acclimatization during incremental ascent to high altitude: Effect of acetazolamide

Steady‐state chemoreflex drive captures ventilatory acclimatization during incremental ascent to high altitude: Effect of acetazolamide

The Impact of Temporary Stay at High Altitude on the Circulatory System

Variables Influencing the Pressure and Volume of the Pulmonary Circulation as Risk Factors for Developing High Altitude Pulmonary Edema (HAPE)

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