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Caudwell Xtreme Everest: a field study of human adaptation to hypoxia.
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MedLine Citation:
PMID:  17672886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Caudwell Xtreme Everest (CXE) is a large healthy volunteer field study investigating human adaptation to environmental hypoxia. More than 200 individuals were studied at sea-level and in four laboratories on the trek to Everest Base Camp (5,300 m). Fifteen physicians climbed high on Everest and continued the studies as they ascended; eight of these individuals reached the summit of Everest and succeeded in sampling arterial blood at 8,400 m on their descent. Core measurements included cardiopulmonary exercise testing, neuropsychological assessment, near infra-red spectroscopy of brain and exercising muscle, blood markers and daily recording of simple physiological variables. The goal of CXE is to further our understanding of human adaptation to cellular hypoxia, a fundamental mechanism of injury in critical illness, with the aim of improving the care of critically ill patients.
Authors:
Mike Grocott; Alan Richardson; Hugh Montgomery; Monty Mythen
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Publication Detail:
Type:  Editorial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care (London, England)     Volume:  11     ISSN:  1466-609X     ISO Abbreviation:  Crit Care     Publication Date:  2007  
Date Detail:
Created Date:  2008-01-16     Completed Date:  2008-03-26     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  9801902     Medline TA:  Crit Care     Country:  England    
Other Details:
Languages:  eng     Pagination:  151     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / physiology*
Altitude
Anoxia / physiopathology*
Humans
Mountaineering / physiology
Nepal
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Crit Care
ISSN: 1364-8535
ISSN: 1466-609X
Publisher: BioMed Central
Article Information
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Copyright ? 2007 BioMed Central Ltd
Print publication date: Year: 2007
Electronic publication date: Day: 1 Month: 8 Year: 2007
Volume: 11 Issue: 4
First Page: 151 Last Page: 151
ID: 2206524
Publisher Id: cc5921
PubMed Id: 17672886
DOI: 10.1186/cc5921

Caudwell Xtreme Everest: a field study of human adaptation to hypoxia
Mike Grocott1
Alan Richardson2
Hugh Montgomery1
Monty Mythen1 Email: montymythen@btinternet.com
1Centre for Altitude, Space and Extreme Environment Medicine (CASE Medicine), UCL Institute of Human Health and Performance, Ground Floor, Charterhouse Building, UCL Archway Campus, Highgate Hill, London, N19 5LW, UK
2Chelsea School, University of Brighton, Hillbrow, Denton Road, Eastbourne BN20 7SR, UK

Caudwell Xtreme Everest (CXE) is a large, healthy volunteer field study investigating human adaptation to environmental hypoxia [1]. The project is organised by the Centre for Altitude Space and Extreme Environment Medicine (CASE Medicine) at University College London. During April and May 2007 more than 200 individuals were studied as they were progressively exposed to hypobaric hypoxia on the trek to Everest Base Camp at 5,300 m. Most of these individuals were volunteers who gave up their holidays to be participants in the study. The remainder was comprised of doctors and scientists, 15 of whom continued the studies as they ascended up to 8,000 m. Eight of these investigators reached the summit of Everest and on their descent took the first measurement of arterial oxygen levels above 8,000 m. So what is the relevance of CXE to intensive care medicine?

Cellular hypoxia is a fundamental mechanism of injury in the critically ill [2,3]. Indeed, it is hard to think of a critically ill patient in whom cellular hypoxia, either local or generalized, is not present. Hypoxia may occur as either a cause of or as a consequence of a variety of critical illnesses. Hypoxia mediated cell death may lead to the generation of an inflammatory response. Systemic inflammation is associated with the development of cellular hypoxia caused by decreased tissue oxygen delivery associated with microcirculatory dysfunction. Cellular hypoxia may also be caused by alterations in cellular energy pathways and mitochondrial function, resulting in decreased ability to utilize available oxygen [2,3]. Although our dominant treatment paradigm revolves around maintenance of oxygen delivery to the cells, there are few data to guide the optimal level of inspired oxygen. Moreover, in some circumstances increasing oxygen delivery confers no benefit or may even cause harm; for example, elevating haemoglobin levels or 'optimization' of oxygen delivery to specific goals in established critical illness [4-6]. Might it be that variations in the cellular efficiency of oxygen metabolism account for some of the observed differences in outcome following critical illness?

The high altitude physiology literature gives us an elegant general description of adaptation to environmental hypoxia built around the idea that maintenance of oxygen delivery to the tissues will allow normal cellular function [7]. However, to date none of these adaptations explain observed (and dramatic) differences in performance between individuals at altitude. Again, the possibility that observed differences are not accounted for by variations in elements of the dominant paradigm raises the possibility that an unmeasured factor or factors may be important. The core hypothesis that CXE is addressing is that variations in metabolic efficiency (relationship between oxygen uptake and work rate) may explain, at least in part, observed differences in individuals' abilities to adapt to hypoxia. If this is true, then it may be possible ? by examining the genotype and phenotype of the 'rapid adaptors' ? to identify mechanisms and thereby develop treatments to benefit the 'slow adaptors' [8-10].

The studies conducted in CXE involve a variety of techniques, including cardiopulmonary exercise testing on cycle ergo-meters using breath-by-breath expired gas analysis, neuropsychological assessment, near infrared spectroscopy of brain and exercising muscle, blood markers (inflammatory and neuroendocrine) and daily recording of simple physiological variables [1]. These measurements and many more were taken in London before departure, in four laboratories in Nepal on the ascent to Everest Base Camp, and in two laboratories high on Mount Everest. The next few years will see whether this new approach to investigating the pathogenesis of critical illness bears fruit.


Abbreviations

CXE = Caudwell Xtreme Everest.


Competing interests

The authors are all investigators in the CXE research group.


Authors' contributions

AR, MM, HM and MG were all involved in either (or all) of original drafting, review and redrafting of the mansucript.


Acknowledgements

The research was funded from a variety of sources, none of which are public. The entrepreneur John Caudwell, whose name the expedition carries, donated ?500,000 specifically to support the research. BOC Medical, now part of the Linde Group, generously supported the research early on and continues to do so. Ely-Lilly Critical Care, The London Clinic (a private hospital), Smiths Medical, Deltex Medical and Rolex have also donated money to support the research and logistics. All monies were given as unrestricted grants. Specific research grants were awarded by the Association of Anaesthetists of Great Britain and Ireland, and the UK Intensive Care Foundation. The CXE trekkers themselves also kindly donated to support the research [1].


References
Caudwell Xtreme Everest
Fink MP. Bench-to-bedside review: cytopathic hypoxiaCrit Care 2002;6:491–499. [pmid: 12493070] [doi: 10.1186/cc1824]
Protti A,Singer M. Bench-to-bedside review: potential strategies to protect or reverse mitochondrial dysfunction in sepsis-induced organ failureCrit Care 2006;10:228. [pmid: 16953900] [doi: 10.1186/cc5014]
Hayes MA,Yau EH,Timmins AC,Hinds CJ,Watson D. Response of critically ill patients to treatment aimed at achieving supra-normal oxygen delivery and consumption. Relationship to outcomeChest 1993;103:886–895. [pmid: 8449087]
Pearse R,Dawson D,Fawcett J,Rhodes A,Grounds RM,Bennett ED. Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trialCrit Care 2005;9:R687–R693. [pmid: 16356219] [doi: 10.1186/cc3887]
Rivers E,Nguyen B,Havstad S,Ressler J,Muzzin A,Knoblich B,Peterson E,Tomlanovich M,Early Goal-Directed Therapy Collaborative GroupEarly goal-directed therapy in the treatment of severe sepsis and septic shockN Engl J Med 2001;345:1368–1377. [pmid: 11794169] [doi: 10.1056/NEJMoa010307]
Grocott M,Montgomery H,Vercueil A. High-altitude physiology and pathophysiology: implications and relevance for intensive care medicineCrit Care 2007;11:203. [pmid: 17291330] [doi: 10.1186/cc5142]
Marshall RP,Webb S,Bellingan GJ,Montgomery HE,Chaudhari B,McAnulty RJ,Humphries SE,Hill MR,Laurent GJ. Angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndromeAm J Respir Crit Care Med 2002;166:646–650. [pmid: 12204859] [doi: 10.1164/rccm.2108086]
Montgomery H,Clarkson P,Barnard M,Bell J,Brynes A,Dollery C,Hajnal J,Hemingway H,Mercer D,Jarman P,et al. Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical trainingLancet 1999;353:541–545. [pmid: 10028982] [doi: 10.1016/S0140-6736(98)07131-1]
Tsianos G,Eleftheriou KI,Hawe E,Woolrich L,Watt M,Watt I,Peacock A,Montgomery H,Grant S. Performance at altitude and angiotensin I-converting enzyme genotypeEur J Appl Physiol 2005;93:630–633. [pmid: 15578201] [doi: 10.1007/s00421-004-1284-1]

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