Sundeep Dhillon

Children at High Altitude: An International Consensus Statement by an Ad Hoc Committee of the International Society for Mountain Medicine, March 12, 2001

Peter Barry (ISMM and MedicalExpeditions, UK), Peter Ba rtsch (ISMM, Ger-many), Franz Berghold (ISMM and ASMAM,Austria), Rachel A. Bishop (ISMM and WMS,Nepal), Charles Clarke (UIAA Mountain Med-icine Data Centre and the British Moun-taineering Council, UK), Sundeep Dhillon (theMedical Cell of the Royal Geographical Soci-ety, UK), Thomas E. Dietz (WMS and ISMM,USA), Anthony Durmowicz (USA), Bruno Dur-rer (ISMM and UIAA Medical Commission,Switzerland), Marlowe Eldridge (USA), PeterHackett (ISMM and WMS, USA), DominiqueJean (France), Susi Kriemler (ISMM, Switzer-land), James A. Litch (ISMM and WMS, Nepal),David Murdoch (ISMM, New Zealand),Annabel Nickol (ISMM, Medical Expeditionsand the Medical Cell of the Royal Geographi-cal Society, UK), Jean-Paul Richalet (ISMM andARPE, France), Rob Roach (ISMM, USA),David R. Shlim (CIWEC clinic, Nepal), UrsWiget (IKAR, Switzerland), Michael Yaron(ISMM, USA), Gustavo Zubieta-Castillo, Sr.,Gustavo R. Zubieta-Calleja, Jr. (ISMM andHigh Altitude Pathology Institute, IPPA Clinic,Bolivia).

Design and conduct of Caudwell Xtreme Everest: an observational cohort study of variation in human adaptation to progressive environmental hypoxia

BackgroundThe physiological responses to hypoxaemia and cellular hypoxia are poorly understood, and inter-individual differences in performance at altitude and outcome in critical illness remain unexplained. We propose a model for exploring adaptation to hypoxia in the critically ill: the study of healthy humans, progressively exposed to environmental hypobaric hypoxia (EHH). The aim of this study was to describe the spectrum of adaptive responses in humans exposed to graded EHH and identify factors (physiological and genetic) associated with inter-individual variation in these responses.MethodsDesign: Observational cohort study of progressive incremental exposure to EHH.SettingUniversity human physiology laboratory in London, UK (75 m) and 7 field laboratories in Nepal at 1300 m, 3500 m, 4250 m, 5300 m, 6400 m, 7950 m and 8400 m.Participants198 healthy volunteers and 24 investigators trekking to Everest Base Camp (EBC) (5300 m). A subgroup of 14 investigators studied at altitudes up to 8400 m on Everest.Main outcome measuresExercise capacity, exercise efficiency and economy, brain and muscle Near Infrared Spectroscopy, plasma biomarkers (including markers of inflammation), allele frequencies of known or suspected hypoxia responsive genes, spirometry, neurocognitive testing, retinal imaging, pupilometry. In nested subgroups: microcirculatory imaging, muscle biopsies with proteomic and transcriptomic tissue analysis, continuous cardiac output measurement, arterial blood gas measurement, trans-cranial Doppler, gastrointestinal tonometry, thromboelastography and ocular saccadometry.ResultsOf 198 healthy volunteers leaving Kathmandu, 190 reached EBC (5300 m). All 24 investigators reached EBC. The completion rate for planned testing was more than 99% in the investigator group and more than 95% in the trekkers. Unique measurements were safely performed at extreme altitude, including the highest (altitude) field measurements of exercise capacity, cerebral blood flow velocity and microvascular blood flow at 7950 m and arterial blood gas measurement at 8400 m.ConclusionsThis study demonstrates the feasibility and safety of conducting a large healthy volunteer cohort study of human adaptation to hypoxia in this difficult environment. Systematic measurements of a large set of variables were achieved in 222 subjects and at altitudes up to 8400 m. The resulting dataset is a unique resource for the study of genotype:phenotype interactions in relation to hypoxic adaptation.

Caudwell Xtreme Everest expedition

The Caudwell Xtreme Everest (CXE) expedition involved the detailed study of 222 subjects ascending to 5300 m or higher during the first half of 2007. Following baseline measurements at sea level, 198 trekker-subjects trekked to Everest Base Camp (EBC) following an identical ascent profile. An additional group of 24 investigator-subjects followed a similar ascent to EBC and remained there for the duration of the expedition, with a subgroup of 14 collecting data higher on Everest. This article focuses on published data obtained by the investigator-subjects at extreme altitude (>5500 m). Unique measurements of peak oxygen consumption, middle cerebral artery diameter and blood velocity, and microcirculatory blood flow were made on the South Col (7950 m). Unique arterial blood gas values were obtained from 4 subjects at 8400 m during descent from the summit of Everest. Arterial blood gas and microcirculatory blood flow data are discussed in detail.

Stroke at High Altitude Diagnosed in the Field Using Portable Ultrasound

A tool that can differentiate ischemic stroke from other neurological conditions (eg, hemorrhagic stroke, high-altitude cerebral edema) in the field could enable more rapid thrombolysis when appropriate. The resources (eg, an MRI or CT scanner) to investigate stroke at high altitude may be limited, and hence a portable tool would be of benefit. Such a tool may also be of benefit in emergency departments when CT scanning is not available. We report a case of a 49-year-old man who, while climbing at 5900 m, suffered a left middle cerebral infarct. The clinical diagnosis was supported using 2D Power Doppler. The patient received aspirin and continuous transcranial Doppler was used for its potential therapeutic effects for 12 hours. The patient was then evacuated to a hospital in Kathmandu over the next 48 hours. This case report suggests that portable ultrasound could be used in the prehospital arena to enable early diagnosis of thrombotic stroke.

Environmental Hazards, Hot, Cold, Altitude, and Sun

There has been an increase in both recreational and adventure travel to extreme environments. Humans can successfully acclimatize to and perform reasonably well in extreme environments, provided that sufficient time is given for acclimatization (where possible) and that they use appropriate behavior. This is aided by a knowledge of the problems likely to be encountered and their prevention, recognition, and treatment.

Oral Coenzyme Q10 supplementation does not prevent cardiac alterations during a high altitude trek to everest base cAMP.

Exposure to high altitude is associated with sustained, but reversible, changes in cardiac mass, diastolic function, and high-energy phosphate metabolism. Whilst the underlying mechanisms remain elusive, tissue hypoxia increases generation of reactive oxygen species (ROS), which can stabilize hypoxia-inducible factor (HIF) transcription factors, bringing about transcriptional changes that suppress oxidative phosphorylation and activate autophagy. We therefore investigated whether oral supplementation with an antioxidant, Coenzyme Q10, prevented the cardiac perturbations associated with altitude exposure. Twenty-three volunteers (10 male, 13 female, 46±3 years) were recruited from the 2009 Caudwell Xtreme Everest Research Treks and studied before, and within 48 h of return from, a 17-day trek to Everest Base Camp, with subjects receiving either no intervention (controls) or 300 mg Coenzyme Q10 per day throughout altitude exposure. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac morphology and function. Following altitude exposure, body mass fell by 3 kg in all subjects (p<0.001), associated with a loss of body fat and a fall in BMI. Post-trek, left ventricular mass had decreased by 11% in controls (p<0.05) and by 16% in Coenzyme Q10-treated subjects (p<0.001), whereas mitral inflow E/A had decreased by 18% in controls (p<0.05) and by 21% in Coenzyme Q10-treated subjects (p<0.05). Coenzyme Q10 supplementation did not, therefore, prevent the loss of left ventricular mass or change in diastolic function that occurred following a trek to Everest Base Camp.

Surviving in a crevasse

We read with interest the case report by Peter Paal and colleagues (Feb 9, p 506)1 of a 70-year-old man surviving 6 days in a crevasse after a fall while crossing a glacier alone. Unlike the Case Report of successful resuscitation from 13·7°C,2 this climbers core temperature was 33·5°C. The authors speculate that the rescue foil used by the individual might have been a key factor in maintaining body temperature. We concur that heat loss occurs by different mechanisms,3 and that airtight foil will reduce convective and evaporative heat losses from the skin—the most important physical routes of heat loss in a cold environment.

Caudwell Xtreme Everest: An Overview

The Caudwell Xtreme Everest (CXE) expedition in the spring of 2007 systematically studied 222 healthy volunteers as they ascended from sea level to Everest Base Camp (5300 m). A subgroup of climbing investigators ascended higher on Everest and obtained physiological measurements up to an altitude of 8400 m. The aim of the study was to explore inter-individual variation in response to environmental hypobaric hypoxia in order to understand better the pathophysiology of critically ill patients and other patients in whom hypoxaemia and cellular hypoxia are prevalent. This paper describes the aims, study characteristics, organization and management of the CXE expedition.

Medicine at High Altitudes

Humans evolved at sea level and with the exception of the high-altitude populations of Central Asia and South America (who have adapted over many generations to the rarefied air) are poorly suited to high altitude. The most significant problem is hypobaric hypoxia (low oxygen levels as a result of a reduced barometric pressure), but cold, wind, reduced humidity, increased ultraviolet radiation and a paucity of flora, fauna and readily available drinking water make this a challenging environment.