A randomized trial of dexamethasone and acetazolamide for acute mountain sickness prophylaxis

Ellsworth, Allan; Larson, Eric B.; Strickland, Daniel

doi:10.1016/0002-9343(87)90937-5

Cited by 108 publications

(66 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondly, the temporal development of increases in lung water in the rat, first seen after a latency of24 h, is quite similar to the development of HAPE in man, which also tends to occur after 12-24 h of hypoxic exposure. Finally, the known beneficial effects of DEX on the prevention of altitude-induced respiratory difficulties (19)(20)(21)(22)) also parallel our observations in the rat. Thus, the tendency of the rat to develop increases in lung water after hypoxic exposure, the latency of the onset of the increases in lung water after hypoxia, and the beneficial effects of glucocorticoids on this response all parallel features seen during the development of the human condition of HAPE and may have relevance to the understanding of this process.…”

Section: Methodssupporting

confidence: 84%

“…We also determined the time of onset and the relative effects of hypobaric and normobaric hypoxia on transvascular protein escape. Finally, because the synthetic glucocorticoid dexamethasone has been used for both prevention and therapy of altitude-associated illness in humans (19)(20)(21)(22), we investigated the role of exogenous and endogenous glucocorticoids in the modulation of vascular permeability in hypoxia.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia-induced increases in pulmonary transvascular protein escape in rats. Modulation by glucocorticoids.

Stelzner¹,

O'Brien²,

Sato³

et al. 1988

J. Clin. Invest.

111

View full text Add to dashboard Cite

Pulmonary edema after ascent to altitude is well recognized but its pathogenesis is poorly understood. To determine whether altitude exposure increases lung vascular permeability, we exposed rats to a simulated altitude of -14,500 feet (barometric pressure [Pbi 450 Torr) and measured the pulmonary transvascular escape of radiolabeled '25l-albumin corrected for lung blood content with 51Cr-tagged red blood cells (protein leak index = PLI). Exposures of 24 and 48 h caused significant increases in PLI (2.30±0.08 and 2.40±0.06) compared with normoxic controls (1.76±0.06), but brief hypoxic exposures of 1-13 h produced no increase in PLI, despite comparable increases in pulmonary artery pressure. There were associated increases in gravimetric estimates of lung water in the altitude-exposed groups and perivascular edema cuffs on histologic examination. Normobaric hypoxia (48 h; fractional inspired oxygen concentration [FI021 = 15%) also increased lung transvascular protein escape and lung water.Dexamethasone has been used to prevent and treat altitude-induced illnesses, but its mechanism of action is unclear. Dexamethasone (0.5 or 0.05 mg/kg per 12 h) started 12 h before and continued during 48 h of altitude exposure prevented the hypoxia-induced increases in transvascular protein escape and lung water. Hemodynamic measurements (mean pulmonary artery pressure and cardiac output) were unaffected by dexamethasone, suggesting that its effect was not due to a reduction in pulmonary artery pressure or flow. The role of endogenous glucocorticoid activity was assessed in adrenalectomized rats that showed augmented hypoxia-induced increases in transvascular protein escape, which were prevented by exogenous glucocorticoid replacement. In summary, subacute hypoxic exposures increased pulmonary transvascular protein escape and lung water in rats. Dexamethasone prevented these changes independent of reductions of mean pulmonary artery pressure or flow, whereas adrenalectomy increased pulmonary vascular permeability and edema at altitude. Increases in vascular permeability in hypoxia could contribute to the development of high-altitude pulmonary edema and endogenous glucocorticoids may have an important influence on pulmonary vascular permeability in hypoxia. Introduction Rapid ascent to high altitude may be associated with the development of pulmonary edema (HAPE)' (1,2 Despite this, attempts to demonstrate hypoxia-induced changes in permeability in the laboratory have produced conflicting results. Bland et al. (5) and Landolt et al. (6) failed to detect increases in lung lymph flow in adult sheep during hypoxia, even with the added stress of increased blood flow. In contrast, other studies have demonstrated increases in lymph flow in newborn lambs (7) and dogs (8-10) after hypoxia. Furthermore, studies in isolated perfused dog lungs have revealed increased filtration and reflection coefficients consistent with increased vascular permeability after brief exposures to anoxic gas (1 1, 12). Differences in both species and ...

show abstract

Section: Methodssupporting

confidence: 84%

mentioning

confidence: 99%

Hypoxia-induced increases in pulmonary transvascular protein escape in rats. Modulation by glucocorticoids.

Stelzner¹,

O'Brien²,

Sato³

et al. 1988

J. Clin. Invest.

111

View full text Add to dashboard Cite

show abstract

“…The medication is typically started the night before the planned ascent and continued until descent is initiated or until the individual has been at the target elevation for 2-3 days. Dexamethasone is a well-studied alternative [120,121] for those who are intolerant of or have a contraindication to acetazolamide. Given the risk of adrenal suppression with long-term use of high-dose systemic corticosteroids, the medication should not be used for more than seven consecutive days and, if longer use is necessary, should be tapered off rather than stopped abruptly [21,102].…”

Section: Pharmacological Measuresmentioning

confidence: 99%

Acute high-altitude sickness

2017

View full text Add to dashboard Cite

At any point 1-5 days following ascent to altitudes ⩾2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly. This review provides detailed information about each of these important clinical entities. After reviewing the clinical features, epidemiology and current understanding of the pathophysiology of each disorder, we describe the current pharmacological and nonpharmacological approaches to the prevention and treatment of these diseases.

show abstract

“…189 The drug is best used with caution, however, because it may have physical side effects. 3,190,191 Tyrosine, a precursor of the neurotransmitter norepinephrine, reduces some of the adverse effects of high altitude and cold. 129,192 -194 Tyrosine improved symptoms, moods, and various performances in volunteers who showed average or greater than average adverse effects during an environmental challenge in which they had been treated with a placebo.…”

Section: Medical Strategiesmentioning

confidence: 99%

Cognitive performance, mood, and neurological status at high terrestrial elevation

Banderet¹,

Shukitt-Hale²

2002

PsycEXTRA Dataset

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. ABSTRACT (Maximum 200 words)Cognitive and psychomotor performance and mood states, including many critical behavioral functions such as sleep, memory, ■ reasoning, and vigilance, are significantly impaired by ascent to HTE higher than 3,000 m. Impairments in behavior caused by HTE can degrade military operations because the judgment and rate and accuracy of performance of military personnel can be affected. Such adverse effects have distinct and measurable time courses; onset of some effects is immediate (cognitive performance), whereas the onset of others is delayed (symptoms of AMS or adverse moods). The behavioral consequences of HTE are primarily dependent on the level of altitude, the duration of exposure the rate of ascent, an individual's state of physiological acclimation or acclimatization, characteristics of the task performed, and characteristics of the individual such as hypoxic sensitivity. Military history documents that the adverse effects induced by HTE need to be considered when military operations at altitude are planned and undertaken. Current research indicates that some performance decrements induced by ascent to extremely high mountains (e.g., Mount Everest, 8,848 m) may persist for a year or longer after return to lower elevations. Psychological, operational, and medical strategies have been employed to minimize these adverse effects. Psychological strategies often involve training and familiarization with the adverse effects that will be experienced at high altitude. Operational strategies include staging at intermediate altitudes, acclimatizing, and using supplemental oxygen from tanks of oxygen generators. Medical strategies often involve the use of medications to improve functioning at altitude and techniques to avoid complications. In most situations, multiple strategies are employed. The strategies now available and new developments to come will ensure that high-altitude military operations in the future will be less affected by adverse changes in cognitive and psychomotor performance and mood.14. SUBJECT TERMS high altitude, hypoxia, cognitive performance, moods, symptoms, time course of altitude effects, behavior NUMBER OF PAGES 3516. PRICE CODE

show abstract

A randomized trial of dexamethasone and acetazolamide for acute mountain sickness prophylaxis

Cited by 108 publications

References 17 publications

Hypoxia-induced increases in pulmonary transvascular protein escape in rats. Modulation by glucocorticoids.

Hypoxia-induced increases in pulmonary transvascular protein escape in rats. Modulation by glucocorticoids.

Acute high-altitude sickness

Cognitive performance, mood, and neurological status at high terrestrial elevation

Contact Info

Product

Resources

About