Beginning in 2004, Xtreme Everest has been a juggernaut in the altitude research world, helping to bridge the gap between sea level critical care, and field work up high. The Xtreme Everest team have just returned from an anniversary trek to Everest Basecamp and are hosting a conference in London from 23-24 May. We caught up with Xtreme Everest Senior Research Manager Kay Mitchell to tell us more.
How did Xtreme Everest start?
Xtreme Everest was developed by a group of healthcare workers including anaesthetists, intensivists, trainees, a physician, a nurse, and a GP. As well as working with sick people, they also had a love of the outdoors, and in particular, mountains. Xtreme Everest was set up to carry out research into improving outcomes for critically ill patients. Low oxygen levels are a critical factor for this group of patients, whether in intensive care, accident and emergency, or undergoing major surgery. Similarly low oxygen levels are experienced by individuals visiting extreme environments, such as those found at altitude. Research results from critically ill patients can be difficult to interpret because of the multitude of underlying issues that cause someone to become critically ill in the first place. These issues are not likely to be present in healthy volunteers. Although it has been possible to simulate low oxygen environments in chambers, the studies are expensive to run, and can only accommodate small numbers at a time. Therefore, Xtreme Everest has used the exposure of healthy volunteers to environmental hypoxia as a model for the majority of its critical care research to date.
The Xtreme Everest Oxygen Research Consortium grew out of a research project conceived by members of CASE Medicine. The first official meeting of Xtreme Everest took place in March 2004. The number of people involved has grown to include investigators from a variety of health related disciplines; sponsors from commercial companies, third sector grant giving bodies, and governmental organisations, as well as individuals; members of the media; and our healthy volunteer subjects.
The work has been funded from a number of sources including individuals, companies, charities, and public institutions. It has resulted a large number of scientific publications, with additional related articles, and countless ‘opportunities to view’ via television, radio, print and electronic media coverage, as well as a growing exposure via other modems of social media.
Can you tell us more about the resarch?
Xtreme Everest has carried out nine research expeditions at altitude in environmental hypoxia, involving highland and lowland adults, and lowland children, and 2 research studies in chambers. Caudwell Xtreme Everest, our largest expedition to date in 2007, involved 222 lowland subjects trekking to Everest Base Camp (EBC), with a subgroup of 14 investigators studied at altitudes of up to 8400m. Baseline studies were carried out at sea level (75m) on all subjects, and then repeated in dedicated field laboratories in Kathmandu (1300m), Namche Bazaar (3500m), Pheriche (4250m), and EBC (5300m). Members of the subgroup underwent additional testing in the Western Cwm (6400m), the South Col (7950m), and the Balcony (8400m).
Repeated measurements included core physiological data such as daily blood pressure, heart rate, respiratory rate, and the Lake Louise score. Researchers also investigated maximum exercise capacity, how efficiently the body uses oxygen and fuel, brain function, lung function tests, and blood and body oxygen levels. All protocols and equipment were tested by members of the investigator team in chambers, laboratories and/or the field prior to the start of the expedition to ensure they would produce reliable data.
Three further research expeditions, including Xtreme Everest 2, have followed an identical ascent profile, with data collected up to EBC. One of the chamber studies replicated this same ascent profile up to the equivalent of Namche Bazaar (3500m). Xtreme Everest 2 included a mixture of highland and lowland subjects, including identical twins and ‘repeaters’ – healthy volunteers that had participated in at least one of our previous research expeditions in Nepal.
Whilst some of the research themes investigated over the various expeditions have been identical, some have changed as earlier results have directed the research team in new directions, for example related to epigenetic markers. Some members of the team have returned from Nepal within the last two weeks after completing a tenth anniversary trek with a similar ascent profile. It included an extra day at Namche Bazaar to enable the team to hold an event for the Sherpa community, organised with the assistance of the Namche Youth Group and the Namche Women’s group. This included presentations of research findings and demonstrations of Xtreme Everest’s gratitude for the support this community has given the team over the previous decade.
And what did you find?
Perhaps the most well-known results so far have been the arterial blood oxygen levels obtained from our climbing investigators close to the summit of Everest. The lowest arterial oxygen level recorded was 2.55 kPa. This was from one of four subjects who had just summited Everest. The subjects took the samples from each others’ femoral arteries, (average PaO2 was 3.28 kPa), and each sample was obtained at the first attempt, demonstrating the investigators’ fine motor skills despite profound low oxygen levels. These results have driven the team to investigate whether patients need to be treated so aggressively when their oxygen levels drop when critically ill. This is being done through the development of clinical feasibility studies. Some of these aggressive treatments, currently used on patients, can in themselves be harmful.
Highlights from the brain research group have included a better understanding of blood flow to the brain, and its contribution to raised pressures in the brain and high altitude headache in the presence of extremely low oxygen levels. Investigators interested in oxygen delivery have presented data related to changes at the cellular level and blood flow and muscle oxygenation in the presence of low oxygen levels, and the role of nitrogen oxide. Studies investigating the body’s use of oxygen have highlighted changes in muscle energetics, mitochondria (cell batteries) in skeletal muscle, heart function and energy metabolism. Work is on-going to publish a wealth of additional data related to these and other topics including exercise capacity, metabolic function, genetics, and epigenetics.
What are the next steps for Xtreme Everest?
The research has generated a comprehensive data set related to more than 300 adults undertaking the same ascent profile to Everest Base Camp, generating exposure at the same rate of reduction in environmental oxygen levels. The results from the analysis of some of this data are still awaiting publication, and this is expected in coming months. Work is also on-going to future proof the data as developments in software and hardware since Xtreme Everest started collecting data have been significant, and it is important that the raw data remains in a format that can be interrogated down the line. This will also enable the team to use developing data handling and management techniques to ensure that complex patterns are identified that are associated with good and poor adaptation to low oxygen levels. The long-term intention of the team is to make this fully anonymised data set available for interrogation by other research teams, once we have exhausted our own research questions.
Finally, we aim to develop a cohort study from our subjects, approaching them at ten year intervals to secure repeat measurements of some research data sets, and to catalogue significant health related events amongst this group. This will give us information regarding the impact exposure to a profoundly hypoxic environment has had on individuals’ health long term.
As the tenth anniversary of the Caudwell Xtreme Everest expedition approaches next year, the Xtreme Everest Executive team are putting on two events. The first, Knowledge 10: Oxygen, will be on 23-24 May 2017 at the Royal Society of Medicine (RSM) in conjunction with the RSM Critical Care section. Day 1 focuses on the history of research related to oxygen and altitude, and Day 2 on research results from Xtreme Everest to date. The second event will be a lecture at the Royal Geographical Society on the evening of 23 May 2017, the tenth anniversary of Xtreme Everest’s successful summit which culminated in the arterial blood sampling on Everest’s Balcony, highlighted above.