Multimodal analysis of the effects of dexamethasone on high-altitude cerebral oedema : protocol for a pilot study

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Abstract

Background
Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers.

Methods/design
D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25 mg dexamethasone or normal saline placebo intravenously after 8 h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention.

Discussion
MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Altitude, Influence of -- Research, Human beings -- Effect of environment on, Anoxemia, Cerebral edema
Journal or Publication Title: Trials
Publisher: Biomed Central
ISSN: 1745-6215
Official Date: 24 October 2019
Dates:
Date
Event
24 October 2019
Published
25 August 2019
Accepted
Volume: 20
Number: 1
Page Range: p. 604
DOI: 10.1186/s13063-019-3681-0
Status: Peer Reviewed
Publication Status: Published
Re-use Statement: ** From Europe PMC via Jisc Publications Router ** History: ppub 01-10-2019; epub 24-10-2019. ** Licence for this article: cc by
Access rights to Published version: Open Access (Creative Commons open licence)
Date of first compliant deposit: 12 December 2019
Date of first compliant Open Access: 12 December 2019
RIOXX Funder/Project Grant:
Project/Grant ID
RIOXX Funder Name
Funder ID
UNSPECIFIED
Jabbs Foundation
UNSPECIFIED
UNSPECIFIED
University Hospitals Coventry and Warwickshire NHS Trust
Related URLs:
URI: https://wrap.warwick.ac.uk/130457/

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