HACE Fast Facts

Altitude sickness, sometimes called mountain or high-altitude sickness, is a disorder that affects people who spend time at high altitudes without first becoming accustomed to the high-altitude environment.

Altitude sickness symptoms may begin in as little as one hour, but they typically set in after 6-12 hours at a high elevation.

The most severe form of altitude sickness, high-altitude cerebral edema (HACE), results when a buildup of fluid causes swelling of the brain. This condition is life-threatening.

HACE typically occurs after a person has spent 1-3 days at an altitude above 9,800 feet (2,743 meters).

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Altitude sickness symptoms may begin in as little as one hour, but they typically set in after 6-12 hours at a high elevation.

What is HACE?

High-altitude cerebral edema (HACE) is the most severe form of altitude sickness. This condition can occur when a person is exposed to high-altitude environments where the air’s oxygen content is lower than at sea level. Mild altitude sickness may cause minor symptoms and improve quickly with treatment, but HACE is a potentially fatal condition requiring emergency medical treatment.

Altitude sickness is a collection of symptoms that affect people who spend time at high elevations without first becoming accustomed to the low-oxygen environment. The disorder is also sometimes called mountain sickness or high-altitude sickness.

Altitude sickness can be relatively mild, or it can be severe and life-threatening. The term is generally applied to three different disorders with varying degrees of severity:

  • High-altitude cerebral edema (HACE) is swelling of the brain caused by an accumulation of fluid. It usually occurs after the symptoms of acute mountain sickness. If not treated immediately, HACE can be fatal.
  • Acute mountain sickness (AMS) is the least severe form of altitude sickness. It typically sets in after 12-24 hours at high altitude. Symptoms usually resolve within 1-2 days at altitude as the body adjusts to the environment.
  • High-altitude pulmonary edema (HAPE) is an accumulation of fluid in the lungs. It can occur in conjunction with AMS and/or HACE, but HAPE can also occur independently. Without treatment, HAPE can also be life-threatening.

Symptoms of High-Altitude Cerebral Edema

The symptoms of altitude sickness occur because the air’s oxygen content at high altitudes is relatively less than at low altitudes. The lack of oxygen puts stress on the body and causes a variety of symptoms. A person can become accustomed to the low-oxygen environment by climbing slowly and spending adequate time at each level before climbing higher. Altitude sickness happens when you ascend too high, too fast.

HACE affects the sufferer’s thought processes, so symptoms might only be noticed by others around them.

Symptoms of HACE include:

  • Extreme headache
  • Vomiting
  • Difficulty walking in a straight line
  • Extreme fatigue
  • Confusion
  • Difficulty concentrating or forming thoughts
  • Changes in behavior (sometimes irrational)
  • Hallucinations

If left untreated, HACE can quickly cause coma or death.

What Causes HACE?

AMS, HACE, and HAPE occur as the body tries to adjust to suddenly decreased access to oxygen. The body’s initial reaction to the oxygen deficit is to increase its breathing and heart rates to take in as much oxygen as possible and transport that oxygen more effectively around the body. As oxygen deprivation continues, the body responds by making changes to its circulatory system and other processes to protect vital organs and functions.

The body’s rapid adjustments to the new environment put stress on many organs and tissues, resulting in AMS symptoms. As the brain and lungs contend with circulatory function changes, the normal fluid flow in their tissues is disrupted, and fluid may accumulate abnormally in the organs, causing HACE and HAPE.

Is HACE Hereditary?

Scientists are currently unsure about the heritability of altitude sickness. Some people are more susceptible than others to altitude sickness, leading some scientists to suspect an inherited component that increases the risk for the disorders. Studies have attempted to find specific genetic traits associated with AMS, HACE, and HAPE.

Recent studies have been unable to find a genetic link to either AMS or HACE. Moreover, the studies’ results have been inconclusive, partly because AMS symptoms are challenging to measure objectively, and HACE is relatively rare.

How Is HACE Detected?

The first symptoms of AMS are commonly rapid breathing, rapid heart rate, and headache. These symptoms may not be dangerous on their own, but in rare cases, AMS can progress to HACE and/or HAPE, so even mild symptoms shouldn’t be ignored.

HACE progresses rapidly and can only be stopped with swift, decisive intervention. The symptoms often begin overnight while the sufferer is sleeping, and because HACE adversely affects thought processes, the sufferer might not recognize the signs on their own. It is often up to the people around the sufferer to identify the symptoms and take action.

Early signs of HACE include:

  • Difficulty walking in a straight line
  • Changes in behavior
  • Hallucinations

How Is HACE Diagnosed?

HACE should be suspected when someone at high altitude shows symptoms such as behavior changes, hallucinations, or difficulty walking in a straight line. Magnetic resonance imaging (MRI) scans can detect brain swelling consistent with HACE.


How Is HACE Treated?

Treatment for HACE typically includes:

  • Moving to a lower altitude as quickly and safely as possible
  • Administration of supplemental oxygen
  • Administration of the steroid dexamethasone to reduce brain swelling
  • Use of a hyperbaric chamber, a high-pressure environment that delivers oxygen more effectively to the patient

How Does HACE Progress?

HACE is the most immediately life-threatening type of altitude sickness, and without immediate treatment, brain swelling can quickly result in severe complications and death. Complications of severe, untreated HACE can include:

  • Permanent cognitive impairment
  • Seizures
  • Vision disruption
  • Coma
  • Death

How Is HACE Prevented?

Most of the time, altitude sickness can be prevented by following recommended climbing practices. It’s important to remember that altitude sickness does not only affect mountain climbers. It can affect anyone who spends time at a high altitude without first becoming accustomed to the elevation change.

To reduce your risk of developing altitude sickness:

  • Move slowly to a high altitude if possible. Do not drive or fly directly to a high elevation without stopping.
  • Do not exert yourself physically for the first few days after moving to a higher elevation.
  • Drink plenty of water as you move up in elevation.
  • Do not climb more than 1,000 feet per day when climbing above 10,000 feet.
  • Spend an extra night each time you ascend 3,000 feet.
  • Move to a lower altitude whenever you feel symptoms of altitude sickness.

HACE Caregiver Tips

If you’re spending time at a high altitude with other people, you may be responsible for keeping your companions safe and healthy.

  • Know the symptoms of altitude sickness. Educate yourself so that you can spot the early signs of altitude-related illnesses. Learn the difference between common symptoms of minor acute mountain sickness and the more severe signs of cerebral and pulmonary edema.
  • Be prepared to act quickly. Whenever you’re at a high altitude, have a plan for what you’ll do if you or your companions begin to suffer from altitude sickness. Know the safest, quickest way to move to a lower altitude. Don’t hesitate to descend and seek medical help at the first signs of severe altitude sickness.

Many people exposed to high altitudes also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with high-altitude exposure:

HACE Brain Science

Scientists are working to understand how high-altitude cerebral edema (HACE) develops and how this severe condition relates to less severe acute mountain sickness (AMS). Specifically, researchers want to know precisely what causes fluid accumulation in the brain and whether the accumulation is directly related to AMS’s early symptoms.

Cerebral edema is generally caused either by the accumulation of fluid within the brain cells themselves or by the leakage of water and proteins from blood vessels into the brain. Recent studies have suggested that HACE is likely caused by fluid leaking from blood vessels. However, it’s unclear how that fluid passes through the barrier that usually keeps contaminants from entering the brain. It’s also possible that after fluid accumulates from leaking blood vessels, additional fluid might accumulate within the cells as well.

Another question is whether the headaches characteristic of early AMS are related to brain swelling. Recent studies have shown that the brain tends to swell at high altitudes. Some research suggests that people with relatively little space inside their skulls to accommodate that swelling might be more susceptible to AMS.

HACE Research

Title: Breathing Training to Improve Human Performance at High Altitude

Stage: Recruiting

Contact: Robert Roach, PhD

Altitude Research Center

Aurora, CO 

Individuals traveling to altitudes above 8,000 feet may suffer from impaired exercise and cognitive performance and acute mountain sickness (AMS). Decreased barometric pressure, which leads to low blood oxygen levels, is the primary cause of these disorders. Symptoms of AMS are characterized by headache, nausea, vomiting, dizziness, fatigue, and difficulty sleeping. The goal of this research is to identify whether Respiratory Muscle Training will improve physical and cognitive performance, and reduce the symptoms of AMS at simulated high altitude.


Title: Safety and Efficacy of T89 in the Prevention and Treatment of Adults With Acute Mountain Sickness (AMS)

Stage: Recruiting

Principal investigator:  Jeffrey W Sall, Ph.D., MD  

University of California San Francisco

San Francisco, CA

Acute mountain sickness (AMS) is a common ailment in people venturing over 2,500 meters altitude. It is a pathological effect of high altitude on humans, caused by acute exposure to low partial pressure of oxygen at high altitude. It presents with a cluster of nonspecific symptoms, including headache and one of the following: gastrointestinal symptoms, fatigue and/or weakness, dizziness/ lightheadedness, or difficulty sleeping.

T89 capsule is a modernized industrialized version of a traditional Chinese herbal medicine. It is a botanical drug product for oral use. Previous clinical studies showed T89 has substantial benefits in the prevention or amelioration of symptoms associated with acute mountain sickness (AMS). This is a double-blind, randomized, placebo-controlled pivotal phase 3 study. After informed consent is obtained, eligible subjects will be randomized to one of the 3 study groups (T89 high dose, T89 low dose, and placebo control). The study drug will be given orally for 5 days (2 days at sea level and 3 days at high altitude). The clinical assessment of the Lake Louise Scoring System (LLSS), blood oxygen saturation, exercise tolerance, blood pressure, and heart rate will be performed at sea level and altitude. A total of 846 subjects will be enrolled with 282 subjects in each treatment arm, and a minimum of 756 subjects are expected to complete the study.


Title: Gut-microbiota Targeted Nutritional Intervention for Gut Barrier Integrity at High Altitude

Stage: Recruiting

Contact: J. Philip Karl, PhD

United States Army Research Institute of Environmental Medicine

Natick, MA 

This randomized, crossover clinical trial aims to determine the efficacy of a gut microbiota-targeted nutritional intervention containing a blend of fermentable fibers and polyphenols (FP) for mitigating increases in GI permeability, and decrements in immune function and neuropsychologic performance following rapid ascent to simulated high altitude. Fifteen healthy young adults will participate in each of three study phases that include a 14-day supplementation period in which participants will consume 1 of 2 supplement bars: placebo (PL, will be consumed during 2 phases) and FP supplementation (will be consumed during one phase only). During the final 2-d of each phase, participants will live in a hypobaric chamber under sea level or high altitude conditions.

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