Stanford Report Online

Stanford Report, May 2, 2001
High-altitude sleep study takes Stanford researcher to top of the world


The human body was not made to live at 18,000 feet. Oxygen is so scarce at that altitude that few plants or animals can live. For visiting humans the thin air fogs the mind, makes small actions arduous and keeps cuts and infections from healing. Even the most sedentary activity of all, sleeping, is severely disturbed in this alien environment.

If merely surviving in such a place is a challenge, it seems an unlikely place to conduct a clinical drug trial. But Stanford University Medical Center researcher Karen Nolan, MD, has just returned from doing precisely that at Mount Everest's base camp. Nolan journeyed to Everest to find out if low doses of a diuretic drug might lessen sleep disturbances.

"The outcome of this study may help skiers, climbers, hikers and others who spend time at high altitude," Nolan said. Eventually studies of the drug may also help those with more down-to-earth sleep problems, such as apnea, she added.

At 8,000 feet above sea level, humans can start to feel the effects of altitude sickness, which include headaches, nausea, dizziness, cognitive problems and disturbed sleep. Even at sea level, humans normally breathe more slowly while sleeping and experience mildly low levels of oxygen in the blood. This "hypoxia" worsens at high altitude because there is so much less oxygen in the air.

The result is a highly abnormal pattern of breathing during sleep at high altitude. When the brain senses low blood-oxygen levels, it forces the body to take three or four deep breaths. These deep breaths bring blood carbon-dioxide levels far below normal, which leads to a cessation of breathing altogether for a period of eight to 12 seconds. When the blood-oxygen level again falls low enough, the cycle begins anew.

This disordered breathing pattern usually disrupts sleep, making climbers fatigued and mistake-prone during the day. Nolan wondered if low doses of a drug called acetazolamide might allow climbers to sleep more deeply. Other studies had shown that high doses of acetazolamide provided some sleep relief to high-altitude climbers, but such doses produce bothersome side effects.

Acetazolamide is not a sleeping pill, but a drug designed as a diuretic. One unusual property of the drug, however, is that it increases the blood's acidity in much the same way that running can build up lactic acid in the bloodstream, sometimes causing muscles to freeze up. The higher level of acidity prompts the brain to increase the body's rate of breathing, which in turn helps the sleeper avoid the nightly cycle of deep breathing and halted breathing because blood-oxygen levels stay higher.

To test her theory, Nolan joined a climbing expedition on Mount Everest. She outfitted 22 climbers and trekkers with monitors to record their body movements and respiration during sleep. She separated them into two groups -- one that received acetazolamide before bedtime and another that received a placebo.

Nolan said there were some indications that acetazolamide may have helped climbers sleep, but she won't know for sure until she finishes analyzing the data and writes up the study in about nine months. Even with drugs like acetazolamide, however, life on the mountain will never be like a camping holiday. "Even with good sleep people still feel lousy, but what I hope is that they will be less fatigued and make fewer mistakes while climbing."

In some ways the experiment was reminiscent of an earlier era when scientists were an integral part of expeditions into deepest Africa or up the Amazon. But any envy that laboratory-bound scientists might have for Nolan's adventure evaporate when she describes the difficulties of the trip. For instance, it took her two days to fly to Nepal and then 11 days to hike up to base camp. And though "base camp" may sound like it's near the bottom of the mountain, it's almost as high as the peak of North America's highest mountain, Denali in Alaska.

The camp itself has a moonlike landscape, a field of gray boulders surrounded by icy crags. Inundated by freezing temperatures, thin air and infectious organisms, everyone was sick in one way or another, Nolan said. "Everyone had stomach problems, many people had respiratory infections, one guy had heart problems and one Sherpa had to be flown out after having seizures," she said. "A lot of people wanted to just turn around and leave as soon as they got there."

With so many expedition members sick, Nolan spent more hours being a doctor than she did being a researcher. "It was definitely a work trip," she said.