Can Mt. Everest Yield Clues To Critical Care at Sea Level?

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ISSUE: 7/2008 | VOLUME: 34:07

Can Mt. Everest Yield Clues To Critical Care at Sea Level?

Larry Beresford

The extreme mountain climber gasping for breath on the rarefied upper slopes of Mt. Everest has much in common with the critically ill,

ventilated patient struggling with lung disease or injury in the ICU: Both have dangerously low levels of oxygen in their blood.

An English scientific expedition that last year scaled Mt. Everest, which at 29,035 feet above sea level is the highest mountain on earth,

hopes that its research into human physiology under extreme conditions may eventually yield new treatments for patients in critical care

settings.

Michael Monty Mythen, MD, professor of anesthesia and critical care at University College London (UCL),

described the Caudwell Xtreme Everest expedition (named for its principal benefactor, British

telecommunications billionaire John Caudwell) in a session at the 2008 annual congress of the International

Anesthesia Research Society in March. Dr. Mythen was a member of the expedition, managing a research

laboratory at 11,483 feet that performed thousands of clinical tests on participants, but he did not attempt to

reach the summit. The expedition was led by Mike Grocott, MD, director of UCLs Center for Altitude, Space &Extreme Environment Medicine, which organized the project.

Some of your peers think we were just playing in the snow, Dr. Mythen told the audience in San Francisco.

They think the hypobaric chamber is good enough for answering these kinds of questions. In fact, he said, the

researchers made good use of the hypobaric chamber, but it was not feasible to ask 200 people to sit in one for

a month. Plus its the adventure element that made the project viable.

Some of the controversy generated by the research effort may also reflect its need to get quite commercial and create a story for the

media, including a BBC documentary, in order to raise approximately $5 million in private donations.

Four Facets of Research

Other medical researchers have done high-altitude studies, but the Caudwell Xtreme Everest expedition is noteworthy for its sheer size.

It included 200 trekkersall volunteers, many of them clinicians or medical students, who also contributed financiallyalong with 60

research investigators and numerous Nepalese Sherpas. Eight doctors who were experienced climbers reached the summit last May,

along with two camera operators.

An estimated 93% of planned testing was completed on the mountain, and all participants returned home safely, a significant feat for a

mountain that has claimed the lives of more than 200 climbers since Edmund Hillary and Tenzing Norgay became the first to reach the

summit in 1953.

The project, whose origins lay in the overlap between the UCL medical groups extracurricular hobbies and research interests, included

a battery of tests designed to improve understanding of human adaptation to environmentally caused hypoxia. Procedures included

arterial blood gases and cardiomuscular exercise bicycle tests, both conducted at an altitude of above 26,000 feet in the worlds highest

medical laboratory. Also included were measures of oxygen efficiency and blood flow, a variety of other blood markers, neuropsychiatric

testing, muscle biopsies40 study protocols in all. Four main areas of research are described on the projects Web site

(http://www.xtreme-everest.co.uk):

oxygen delivery and utilization at high altitude;1.

changes in blood flow to the brain and how this affects brain function;2.

processes that may lead to illnesses affecting lungs at high altitude; and3.

testing of new rebreather portable breathing systems that may someday help oxygen-dependent patients with lung disease

become more mobile.

4.

One of the pro-jects main aims is to shed more light on the variation in human adaptation to hypoxia, Dr. Mythen said. In essence, does

the oxygen efficiency of the human being fundamentally change at higher altitudes? All climbers suffer from altitude sickness to some

extent, but some adapt more quickly, some have a very hard time adapting at all and a larger group in the middle will adapt with time

but also with some struggle.

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There is an adaptive process to hypoxiawell recognized and described but unpredictable based on overall physical health, Dr.

Mythen said, suggesting the need for a genetic explanation. If researchers can identify markers and factors that contribute to this

adaptation, that information could help guide treatment approaches for patients in the ICU, as well as the search for drugs to promote

such adaptation in all patients.

In particular, the group is looking at the angiotensin-converting enzyme genotype, discovered to have a connection to human fitness by

Hugh Montgomery, MD, and colleagues at UCLs Center for Cardiovascular Genetics in 1998. Dr. Montgomery is also a member of the

Xtreme Everest research group.

Richard Moon, MD, medical director of the Center for Hyperbaric Medicine and Environmental Physiology at Duke University MedicalCenter in Durham, N.C., said he was intrigued with the potential of high-altitude research to aid clinicians dealing with hypoxia in

acutely ill patients.

One very practical reason for doing experiments on mountains is that the degree of hypoxia to which one may be exposed during

high-altitude mountaineering may significantly exceed the limit to which a human experimentation committee would allow in a university

laboratory, Dr. Moon said.

Other implications for anesthesiologists, Dr. Mythen said, include the potential to better identify risk in ischemic surgical candidates.

What distinguishes survivors from nonsurvivors? If part of the answer is an adaptive mechanism, how can we help the poorly toned

quarter of the population? Might depriving them of oxygen presurgically actually draw out this adaptive mechanism?

The extreme altitude research could have applications to recent research in ischemic preconditioning, an

experimental technique for producing cardioprotective resistance to the loss of blood supply and oxygen to the

tissue by exposing the patient to brief periods of sublethal ischemia, Dr. Moon said. If we were to gain better

understanding of adaptation to hypoxia, Im sure wed gain insights into ischemic preconditioning. Im lookingforward to seeing results from the Everest studies.

Hypoxia may also trigger inflammatory pathways in established critical illness, which could be compared to a kind of

hibernation or change in physiologic functioning. In some patients, might it be a mistake to push too much oxygen

too soon after major surgery? Dr. Mythen posed.

A Family Holiday Trek

The biggest controversy generated by Xtreme Everest involved its affiliated Smiths Medical Young Everest Study, sponsored by

medical device maker Smiths Medical and staffed by a separate research team and sponsored by the Institute of Child Health at UCL.

When it was revealed that nine children between the ages of 6 and 13, including Dr. Mythens own children, nephews and nieces, would

be participating, accompanied by parents and grandparents, this was decried as tantamount to child abuse, he reported in San

Francisco. Some of the media, who had not been given all of the facts, attacked the study on the basis that it would not be safe for the

children.

In fact, Dr. Mythen said, the children were only expected to climb to about 13,000 feet, the level of many ski resorts and family holiday

treks. Anecdotally, children dont seem to get altitude sickness to the same degree as adults, an important part of the puzzle Xtreme

Everest is trying to unravel.

The human response to hypoxia is also comparable to the physiology of diving mammals and to the human fetus in utero, drawing

oxygen from its mother at saturation levels roughly comparable to an Everest climber. As we adapt to hypoxic conditions, do we

essentially return to the womb? Dr. Mythen asked. This also raises interesting theoretical questions relative to the treatment of

premature infants in the neonatal ICU.

Initial results from Caudwell Xtreme Everest have been submitted to peer-reviewed medical journals, and newsworthy results will be

announced later this summer. A follow-up Everest expedition is planned for 2011.

Worlds Highest Mountain

Mt. Everest, on the border between Nepal and Tibet, was confirmed as the worlds highest point in 1852. Its summit was

reached for the first time in 1953 by Edmund Hillary of New Zealand and Nepalese Sherpa Tenzing Norgay. It was long

believed that the summit could not be reached without supplemental oxygen until Reinhold Messner and Peter Habeler did

so in 1978.

A total of 2,436 people had ascended Everest by the end of 2007, and roughly 350 of them climbed it that year; 210

climbers have died trying. Even during optimal climbing season, temperatures can plunge to 40 F, with high winds and




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fluctuating oxygen levels. At the summit, atmospheric pressure is about one-third that at sea level.

L.B.

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Can Mt. Everest Yield Clues To Critical Care at Sea Level?