Altitude Sickness Prevention with Ibuprofen Relative to Acetazolamide

Burns, Patrick R.; Lipman, Grant S.; Warner, Keiran; Jurkiewicz, Carrie; Phillips, Caleb; Sanders, Linda; Flores-Soto, M.E.; Hackett, Peter H.

doi:10.1016/j.amjmed.2018.10.021

Cited by 27 publications

(25 citation statements)

References 18 publications

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“…Sample size was based on prior high altitude trials at the study site using identical ascent profiles that found consistent AMS rates of 63%-69% in placebo (Lipman et al, 2012;Lipman et al, 2018) and 43%-51% AMS in those administered acetazolamide (Burns et al, 2018;Lipman et al, 2018). To achieve 80% power (a = 0.05, two-tailed test), assuming 45% AMS incidence with night before ascent acetazolamide, a total of 90 participants were required to detect a significant difference, defined a priori as a 26% absolute difference in AMS incidence between the dosing regimens.…”

Section: Discussionmentioning

confidence: 99%

“…These pharmacokinetics were clinically surmised when day of ascent acetazolamide significantly prevented severe AMS compared with placebo (Lipman et al, 2018). Furthermore, analysis of two recent high altitude trials showed no statistically significant difference between day of and night before ascent acetazolamide in AMS incidence ( p = 0.6) (Burns et al, 2018;Lipman et al, 2018). However, the efficacy of day of ascent acetazolamide for AMS prevention has yet to be confirmed.…”

Section: Introductionmentioning

confidence: 99%

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Day of Ascent Dosing of Acetazolamide for Prevention of Acute Mountain Sickness

Lipman

Jurkiewicz

Winstead-Derlega

et al. 2019

High Altitude Medicine & Biology

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Background: Acetazolamide is the most common medication used for prevention of acute mountain sickness (AMS), usually administered the day or night before ascent. The objective of this study was to evaluate the efficacy of day of ascent dosing of acetazolamide for AMS prevention. Methods: Double-blind, randomized, controlled noninferiority trial of acetazolamide 125 mg twice daily beginning either the night before or the morning of ascent. Healthy low altitude adults ascended from 1240 m (4100 ft) to 3810 m (12,570 ft) during summer 2018 on White Mountain, California. Primary outcome was incidence of AMS with the two different dosing patterns, assessed by the 1993 Lake Louise Questionnaire (LLQ) of ‡3 with headache and a minimum of 1 for other symptom. Results: One hundred four participants completed the study, with 54 (52%) randomized to night before acetazolamide and 50 (48%) to day of ascent dosing, without differences in baseline characteristics. There was 9% greater incidence of AMS in the day of ascent acetazolamide group (48.0% vs. 39%, 95% confidence interval [CI]-11.8 to 30, p = 0.46, number needed to treat [NNT] = 5.6 vs. 3.7), with the CI just surpassing the predetermined 26% noninferiority margin. There was a lower incidence of severe AMS (1993 LLQ >5) in the day of ascent group (n = 5, 10%, NNT = 2.3) compared with night before dosing (n = 12, 22%, NNT = 3.1) (95% CI-28 to 3.6), and lower average symptom severity in the day of ascent group (3 vs. 3.5, 95% CI-0.5 to 1.4). Conclusions: Day of ascent acetazolamide demonstrated higher rates of AMS compared with traditional dosing by a small margin. With similar rates of severe AMS and overall symptom severity, the potential for improved convenience and compliance may support day of ascent use.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Day of Ascent Dosing of Acetazolamide for Prevention of Acute Mountain Sickness

Lipman

Jurkiewicz

Winstead-Derlega

et al. 2019

High Altitude Medicine & Biology

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“…interleukin 1β (IL-1β), and interleukin 6 (IL-6) (Bouchama et al 1993) and lower concentrations of interleukin 10 (IL-10) (Welc et al 2013). Of note, individuals that develop acute mountain sickness (AMS), which is a common illness during travel to high altitude (Burns et al 2018), also exhibit elevated circulating concentrations of inflammatory cytokines (TNF-α, IL-1β, and IL-6) (Wang et al 2018) and lower levels of anti-inflammatory cytokines (IL-10 and IL-1Ra) (Liu et al 2017). In contrast, higher levels of anti-inflammatory cytokines have been shown to afford protection against AMS (Julian et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Prolonged treadmill running in normobaric hypoxia causes gastrointestinal barrier permeability and elevates circulating levels of pro- and anti-inflammatory cytokines

Hill

Gillum

Lee

et al. 2020

Appl. Physiol. Nutr. Metab.

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This study examined the impact of treadmill running in normobaric hypoxia on gastrointestinal barrier permeability and the systemic inflammatory response. Ten recreationally active participants completed two 1-h bouts of matched-workload treadmill exercise (65% normoxic maximal oxygen consumption) in counterbalanced order. One bout was performed in normoxia (NORM: fraction of inspired oxygen (FIO2) = 20.9%) and the other in normobaric hypoxia (HYP: FIO2 = 13.5%). Minute ventilation, respiratory rate (RR), tidal volume (VT), oxygen consumption, carbon dioxide production, respiratory exchange ratio (RER), and heart rate (HR) were measured with a metabolic cart. Peripheral oxygen saturation (SpO2) was measured with pulse oximetry. Absolute tissue saturation (StO2) was measured with near-infrared spectroscopy. Fatty acid-binding protein (I-FABP) and circulating cytokine concentrations (interleukin (IL)-1Ra, IL-6, IL-10) were assayed from plasma samples that were collected pre-exercise, postexercise, 1 h-postexercise, and 4 h-postexercise. Data were analyzed with 2-way (condition × time) repeated-measures ANOVAs. Newman–Keuls post hoc tests were run where appropriate (p < 0.05). As compared with NORM, 1 h of treadmill exercise in HYP caused greater (p < 0.05) changes in minute ventilation (+30%), RR (+16%), VT (+10%), carbon dioxide production (+18%), RER (+16%), HR (+4%), SpO2 (–16%), and StO2 (–10%). Gut barrier permeability and circulating cytokine concentrations were also greater (p < 0.05) following HYP exercise, where I-FABP was shown increased at postexercise (+68%) and IL-1Ra at 1 h-postexercise (+266%). I-FABP and IL-1Ra did not change (p > 0.05) following NORM exercise. IL-6 and IL-10 increased with exercise in both study conditions but were increased more (p < 0.05) following HYP at postexercise (+705% and +127%, respectively) and 1 h-postexercise (+400% and +128%, respectively). Novelty Normobaric hypoxia caused significant desaturation and increased most cardiopulmonary responses by 10%–30%. Significant gut barrier permeability and increased pro- and anti-inflammatory cytokine concentrations could promote an “open window” in the hours following HYP exercise.

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“…Recent studies showed that ibuprofen may be a good alternative for AMS prevention. Although the study results revealed that ibuprofen was effective when compared to placebo, the result of the ones comparing to acetazolamide are contradictory 30, 31, 32, 33. Considering the serious side effects such as gastrointestinal bleeding, it makes sense to use ibuprofen (1800 mg daily) when the individual cannot tolerate both acetazolamide and dexamethasone.…”

Section: Preventionmentioning

confidence: 99%

High-altitude illness: Management approach

Aksel

Çorbacıoğlu

Özen

2019

Turkish Journal of Emergency Medicine

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In high altitudes, usually above 2500 m, travelers are faced with decreased partial pressure of oxygen along with decreased barometric pressure. High-altitude illness, a syndrome of acute mountain sickness, high-altitude cerebral edema and high-altitude pulmonary edema, occurs due to the hypobaric hypoxia when there is inadequate acclimatization.This review provides detailed information about pathophysiology, clinical features, prevention and treatment strategies for high-altitude illness according to the current literature.

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Altitude Sickness Prevention with Ibuprofen Relative to Acetazolamide

Cited by 27 publications

References 18 publications

Day of Ascent Dosing of Acetazolamide for Prevention of Acute Mountain Sickness

Day of Ascent Dosing of Acetazolamide for Prevention of Acute Mountain Sickness

Prolonged treadmill running in normobaric hypoxia causes gastrointestinal barrier permeability and elevates circulating levels of pro- and anti-inflammatory cytokines

High-altitude illness: Management approach

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