Acetazolamide for the Prevention of Acute Mountain Sickness—A Systematic Review and Meta‐analysis

Ritchie, Neil D.; Baggott, Amy; Todd, W. T. A.

doi:10.1111/j.1708-8305.2012.00629.x

Cited by 71 publications

(52 citation statements)

References 41 publications

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“…At present, interventions in humans are extremely limited, due in part to the lack of organ specificity of candidate drugs that also affect renal function, and to the lack of molecular knowledge about the regulation of CSF formation. Parenteral administration of the carbonic anhydrase inhibitor, acetazolamide, is commonly used to reduce CSF formation in patients with idiopathic intracranial hypertension (pseudotumor cerebri), acute mountain sickness and other conditions associated with raised intracranial pressure (Fraser and Plant, 2011; Biousse, 2012; Ritchie et al, 2012). In our experiments, intraventricular infusion of acetazolamide reduced CSF formation by 57%.…”

Section: Discussionmentioning

confidence: 99%

A novel method to study cerebrospinal fluid dynamics in rats

Karimy

Kahle

Kurland

et al. 2015

Journal of Neuroscience Methods

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Background Cerebrospinal fluid (CSF) flow dynamics play critical roles in both the immature and adult brain, with implications for neurodevelopment and disease processes such as hydrocephalus and neurodegeneration. Remarkably, the only reported method to date for measuring CSF formation in laboratory rats is the indirect tracer dilution method (a.k.a., ventriculocisternal perfusion), which has limitations. New Method Anesthetized rats were mounted in a stereotaxic apparatus, both lateral ventricles were cannulated, and the Sylvian aqueduct was occluded. Fluid exited one ventricle at a rate equal to the rate of CSF formation plus the rate of infusion (if any) into the contralateral ventricle. Pharmacological agents infused at a constant known rate into the contralateral ventricle were tested for their effect on CSF formation in real-time. Results The measured rate of CSF formation was increased by blockade of the Sylvian aqueduct but was not changed by increasing the outflow pressure (0–3 cm of H2O). In male Wistar rats, CSF formation was age-dependent: 0.39±0.06, 0.74±0.05, 1.02±0.04 and 1.40±0.06 µL/min at 8, 9, 10 and 12 weeks, respectively. CSF formation was reduced 57% by intraventricular infusion of the carbonic anhydrase inhibitor, acetazolamide. Comparison with existing methods Tracer dilution methods do not permit ongoing real-time determination of the rate of CSF formation, are not readily amenable to pharmacological manipulations, and require critical assumptions. Direct measurement of CSF formation overcomes these limitations. Conclusions Direct measurement of CSF formation in rats is feasible. Our method should prove useful for studying CSF dynamics in normal physiology and disease models.

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Section: Discussionmentioning

confidence: 99%

A novel method to study cerebrospinal fluid dynamics in rats

Karimy

Kahle

Kurland

et al. 2015

Journal of Neuroscience Methods

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“…We have used this site for a number of randomized, controlled trials in the past, 2,3,11 whose results have been verified by other studies from other venues. 31 It is well known that acetazolamide can be taken episodically to hasten acclimatization even while trekkers are ascending. We reasoned that another drug that performed likewise would be a useful alternative.…”

Section: Limitations Of the Studymentioning

confidence: 99%

Altitude Sickness in Climbers and Efficacy of NSAIDs Trial (ASCENT): Randomized, Controlled Trial of Ibuprofen Versus Placebo for Prevention of Altitude Illness

Gertsch

Corbett

Holck

et al. 2012

Wilderness & Environmental Medicine

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Ibuprofen was found to be effective in preventing AMS in the intent-to-treat analysis group but not in those who completed the trial. This loss of significance in the subjects who completed the trial may be explained by persons in the placebo group having a higher burden of illness and associated decreased compliance with the protocol. An important limitation of this study may be the possibility that ibuprofen can mask headache, which is a compulsory criterion for the diagnosis of AMS.

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“…Acetazolamide (ACZ) was one of the unequivocally effective drugs. 11,[20][21][22] But it had some side effects such as memory impairment 23) and decreased exercise capacity. 24) We chose ACZ as positive control to compare the effects of AFIM and ACZ.…”

Section: )mentioning

confidence: 99%

Anti-hypoxia Activity of the Novel NO Donor Acetyl Ferulic Isosorbide Mononitrate in Acute High-Altitude Hypoxia Mice

Fan

Jiang

et al. 2015

Biological & Pharmaceutical Bulletin

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Nitric oxide (NO) may act as either a pro-oxidant or an antioxidant in biological systems. Previous work has found inhalation of NO improved survival in a high altitude rat model. NO donor isosorbide mononitrate derivants might have a protective effect against hypoxia. We synthesized a series of isosorbide mononitrate derivant compounds to test their anti-hypoxia activities. Normobaric hypoxia and hypobaric hypoxia models were used to study the protective role of NO donor in mice. The results showed isosorbide mononitrate derivants had protective effects in hypoxia mice. Among those compounds, acetyl ferulic isosorbide mononitrate (AFIM) was the most effective. It prolonged the survival time during the normobaric hypoxia test. It decreased malondialdehyde (MDA) and H 2 O 2 in hypobaric hypoxia mice. The antioxidase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) remained in normal ranges in the AFIM group. As a sign of mitochondrial dysfunction, the activities of ATPase were down regulated in mice under hypobaric hypoxia conditions. AFIM also protected ATPase activities. The protective effects of AFIM might come from a sustained NO supply and the release of acetyl ferulic acid with anti-oxidant activity.Key words altitude; hypoxia; nitric oxide; acetyl ferulic isosorbide mononitrate More than 140 M persons lives at above 2500 m (the conventional definition of high altitude as that where arterial O 2 saturation (SaO 2 ) measurably begins to fall).1) Barometric pressure falls with increasing altitude and consequently there is a reduction in the partial pressure of oxygen resulting in a hypoxic challenge to any individual ascending to altitude. With the ever increasing number of people ascending to high altitudes, medicines to deal with potential problems are becoming increasingly relevant to non-specialists, including general practitioners.A spectrum of high altitude illnesses can occur when the hypoxic stress outstrips the subject's ability to acclimatize. Acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) strike people who travel too fast to high altitudes that lie beyond their current level of acclimatization. 2)AMS is a condition affecting otherwise healthy individuals on going rapidly to altitude. A spectrum of symptoms related to acute mountain sickness may develop at altitudes below 3000 m: commonly reported symptoms are nausea, vomiting, headache, dizziness, fatigue, and sleep disturbance. 3)Acute hypoxia induces pulmonary vascular permeability and contributes to forms of noncardiogenic pulmonary edema such as high altitude pulmonary edema and acute respiratory distress syndrome.4,5) AMS can sharply limit recreation and work at high altitude, especially in the first few days following arrival at a new, higher altitude, and if AMS worsens and HACE develops, the risk of fatality is significant. 6) Although slow ascent to altitude remained the most important measure to prevent acute mountain sickness, evidence from the literature on high altitude...

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Acetazolamide for the Prevention of Acute Mountain Sickness—A Systematic Review and Meta‐analysis

Abstract: Acetazolamide is effective prophylaxis for the prevention of symptoms of AMS in those going to high altitude. A dose of 250 mg/day has similar efficacy to higher doses and may have a favorable side-effect profile.

Cited by 71 publications

References 41 publications

A novel method to study cerebrospinal fluid dynamics in rats

A novel method to study cerebrospinal fluid dynamics in rats

Altitude Sickness in Climbers and Efficacy of NSAIDs Trial (ASCENT): Randomized, Controlled Trial of Ibuprofen Versus Placebo for Prevention of Altitude Illness

Anti-hypoxia Activity of the Novel NO Donor Acetyl Ferulic Isosorbide Mononitrate in Acute High-Altitude Hypoxia Mice

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