Acetazolamide in the Treatment of Acute Mountain Sickness: Clinical Efficacy and Effect on Gas Exchange

Grissom, Colin K.; Roach, Robert C.; Sarnquist, Frank H.; Hackett, Peter H.

doi:10.7326/0003-4819-116-6-461

Cited by 150 publications

(66 citation statements)

References 13 publications

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“…Since the Pa,CO 2 values measured in the current study (table 3) are lower than values observed previously under similar circumstances [31,32] it is conceiveable that the subjects were hyperventilating to some degree, which might have increased their respiratory exchange ratio. Nevertheless, an association of a widened AaD,O 2 with AMS has been observed in several previous investigations [8,31,33]. In a study by BARTSCH et al [8], subjects with AMS revealed a transient decrease in isocapnic hypoxic ventilatory response (but neither in poikilocapnic hypoxic nor hypercapnic ventilatory response) within 4 h after arrival at 4,559 m, whereas this was not observed in controls.…”

Section: Discussionmentioning

confidence: 92%

Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation

Pa¹,

Anastasi²,

Senn³

et al. 2004

Eur Respir J

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Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation. P. Erba, S. Anastasi, O. Senn, M. Maggiorini, K.E. Bloch. #ERS Journals Ltd 2004. ABSTRACT: The purpose of the study was to investigate determinants of acute mountain sickness after rapid ascent to high altitude.A total of 21 climbers were studied ascending from v1,200 m to Capanna Regina Margherita, a hut in the Alps at 4,559 m, within v24 h. During their overnight stay at 4,559 m, breathing patterns and ventilation were recorded by calibrated respiratory inductive plethysmography along with pulse oximetry. In the following morning, acute mountain sickness was assessed.Altogether, 11 mountaineers developed pronounced symptoms of acute mountain sickness (Lake Louise score o5) and 10 did not (controls). Compared to controls, subjects with acute mountain sickness had lower nocturnal oxygen saturation (mean¡SD 59¡13% versus 73¡6%), higher minute ventilation (7.94¡2.35 versus 6.06¡ 1.34 L?min -1 ), and greater mean inspiratory flow, a measure of respiratory centre drive (0.29¡0.09 versus 0.22¡0.05 L?s -1 ). Periodic respiration was prevalent but not significantly different among the two groups (apnoea/hypopnea index 60.1¡34.6 versus 47.1¡42.6 events per h).The data suggest that pronounced nocturnal hypoxemia, which was not related to hypoventilation, may have promoted acute mountain sickness. Periodic breathing seems not to play a predominant role in the pathogenesis of acute mountain sickness. Otherwise healthy subjects ascending rapidly to altitudes w2,500 m often develop acute mountain sickness (AMS), a condition characterised by insomnia, headache, dizziness, loss of appetite, nausea and vomiting [1]. In the Alps, symptoms and signs of AMS sufficiently severe to force a reduction in activity were found in 6-8% of climbers examined at altitudes between 2,850 and 3,650 m, and in 30% of climbers at 4,559 m [2]. AMS is promoted by a rapid ascent rate, depends on the altitude reached, and on acclimatisation [3]. It occurs in both sexes, at all ages, and athletic fitness does not protect against it [1,4,5].Despite its high prevalence, the pathophysiology of AMS is incompletely understood. Hypoxia seems to play an important role [3,6,7]. A reduced ventilatory response to hypoxia, and impaired pulmonary gas exchange related to pulmonary fluid accumulation, and water and salt retention have been implicated in development of exaggerated hypoxemia in subjects with AMS [8][9][10]. As AMS often develops or worsens over the night, when periodic breathing and repetitive oxygen desaturation are also prevalent, a causal relationship or a common pathophysiological pathway have been evaluated [11,12]. However, the results of these earlier studies were inconclusive due to the small number of subjects with AMS enrolled, and the lack of quantitative estimation of ventilation during sleep.Therefore, the purpose of the current study was to further explore the potential role of periodic respiration, and other characteristics of breathing patterns, in p...

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Section: Discussionmentioning

confidence: 92%

Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation

Pa¹,

Anastasi²,

Senn³

et al. 2004

Eur Respir J

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“…Currently there are two other substances which may be effective in the prevention and treatment of AMS: acetazolamide and dexamethasone [6,26,28]. Therefore, the question arises as to whether there is a need for additional medication.…”

Section: Discussionmentioning

confidence: 99%

Theophylline improves acute mountain sickness

et al. 2000

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A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m.Fourteen healthy male subjects participated in a randomized single-blind placebocontrolled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if <70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed.Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean SD 1.2 0.9) with placebo versus 3.6 0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study.In conclusion, oral slow-release theophylline improves acute mountain sickness. Eur Respir J 2000; 15: 123±127. This study was supported, in part, by Byk Gulden, Constance, Germany.Acute mountain sickness (AMS) is a frequent medical disorder in travellers who rapidly ascend to altitudes >2,500 m [1]. When altitudes >4,000 m are reached within hours, only few do not have at least mild symptoms. The symptoms of mild AMS include headache, dizziness, fatigue, gastrointestinal symptoms and sleep disturbance. During prolonged stay at high altitude, symptoms improve usually within 24±48 h.The pathogenesis of AMS is not fully understood, but it is generally agreed that the main underlying cause is hypoxia, which initiates the pathogenetic processes leading to AMS. Hypoxia is thought to cause water retention or a shift of water from intracellular to extracellular compartments [2], increase microvascular permeability [3] and increase cerebral blood flow [4]. All of these factors may contribute to AMS, although the role of enhanced cerebral blood flow remains controversial [5].AMS is normally best prevented by ascending slowly to high altitude. However, when rapid ascent is necessary (i.e. during rescue operations or passive transportation to high altitude), medical prophylaxis may be indicated. Acetazolamide at a dose of 250 mg twice daily and dexamethasone at doses of >4 mg twice daily have been reported effective in the preventive treatment of AMS [6,7].The effects of theophylline on AMS have not been studied, although its pharmacological profile would seem to predispose this substance to the treatment of AMS. The multiple pharmacological effects of theophylline (a phosphodiesterase inhibitor) are well cha...

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“…Rehydration does not treat AMS per se, but does address any dehydration, the symptoms of which can mimic those of AMS. Acetazolamide [129] and dexamethasone [121,130] can be added for those individuals with more severe AMS symptoms or those who fail to respond to conservative measures. Individuals who remain ill despite several days of these conservative measures should descend 500-1000 m or until symptoms resolve.…”

Section: Amsmentioning

confidence: 99%

Acute high-altitude sickness

2017

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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.

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Acetazolamide in the Treatment of Acute Mountain Sickness: Clinical Efficacy and Effect on Gas Exchange

Abstract: In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange.

Cited by 150 publications

References 13 publications

Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation

Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation

Theophylline improves acute mountain sickness

Acute high-altitude sickness

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