High Altitude Cerebral Edema – Symptoms, Treatment High Altitude Cerebral Edema (HACE) is a severe and potentially fatal manifestation of high altitude illness and is often characterized by ataxia, fatigue, and altered mental status. HACE is often thought of as an extreme form/end-stage of Acute Mountain Sickness (AMS). Although HACE represents the least common form of altitude illness, it may progress rapidly to coma and death as a result of brain herniation within 24 hours, if not promptly diagnosed and treated. [rx][rx][rx][rx] Acute mountain sickness (AMS) is a syndrome that arises in non-acclimatized individuals who ascend to high altitudes. It is a form of acute altitude illness that occurs due to a decrease in the atmospheric partial pressure of oxygen as the altitude increases, inducing hypoxia. This includes acute mountain sickness (AMS), high-altitude cerebral oedema (HACE), and high-altitude pulmonary edema (HAPE). This condition typically occurs at an altitude of >2500 meters; however, it can occur at lower elevations in high-risk individuals.[rx][rx] Types of High Altitude Sickness High altitude oxygenation is improving oxygenation or enriching the body with additional oxygen at high altitudes.[rx] According to the Society of Mountain Medicine (Effects of high altitude on humans), there are three altitude regions: High Altitude – 1500 to 3500 meters above sea level (4900-11500 ft.) Very high altitude – 3500 to 5500 meters above sea level (11500 to 18000 ft.) Extreme altitude – above 5500 meters above sea level (18000 ft.) High altitude (1500 to 3500 m) The onset of physiologic effects of diminished inspiratory oxygen pressure (PIO2) includes decreased exercise performance and increased ventilation (lowering of arterial PaCO2). Minor impairment exists in arterial oxygen transport (arterial oxygen saturation [SaO2] at least 90%, but arterial PO2 is significantly diminished). Because of the large number of people who ascend rapidly to 2500 to 3500 m, high-altitude illness is common in this range. Very high altitude (3500 to 5500 m) Maximum SaO2 falls below 90% as the arterial PO2 falls below 60 mm Hg. Extreme hypoxemia may occur during exercise, during sleep and in the presence of high-altitude pulmonary edema or other acute lung conditions. Severe altitude illness commonly occurs in this range. Extreme altitude (above 5500 m) Marked hypoxemia, hypocapnia and alkalosis are characteristic of extreme altitudes. Progressive impairment of physiologic function eventually outstrips acclimatization. As a result, no human habitation occurs above 5500 m.[rx] Most people who get altitude sickness get AMS, acute mountain sickness. Higher than 10,000 feet, 75% of people will get mild symptoms. There are three categories of AMS: Mild AMS – Symptoms, such as mild headache and fatigue, don’t interfere with your normal activity. Symptoms improve after a few days as your body acclimates. You can likely stay at your current elevation as your body adjusts. Moderate AMS – Symptoms start to interfere with your activities. You may experience severe headaches, nausea, and difficulty with coordination. You’ll need to descend to start to feel better. Severe AMS – You may feel short of breath, even at rest. It can be difficult to walk. You need to descend immediately to a lower altitude and seek medical care. HAPE (High-altitude pulmonary edema) – HAPE produces excess fluid on the lungs, causing breathlessness, even when resting. You feel very fatigued and weak and may feel like you’re suffocating. HACE (High-altitude cerebral edema) – HACE involves excess fluid on the brain, causing brain swelling. You may experience confusion, lack of coordination, and possibly violent behavior. Causes of High Altitude Cerebral Edema Acute Mountain Sickness is caused by the body’s reaction to the reduced oxygen level in respired air and resultant tissue hypoxia. At baseline metabolic levels, the brain is the most sensitive organ regarding hypoxia and oxygen stress. Thus, the symptoms of Acute Mountain Sickness (discussed below) are mediated by the central nervous system (CNS). In many travelers at altitude, respirations during sleep develop a periodic pattern that may contribute to the development of symptoms.[rx][rx] Along with other illnesses related to altitude, HAPE occurs above 2500 meters but can occur at altitudes as low as 2000 meters. Risk factors include individual susceptibility due to low hypoxic ventilatory response (HVR), the altitude attained, a rapid rate of ascent, male sex, use of sleep medication, excessive salt ingestion, ambient cold temperature, and heavy physical exertion. Preexisting conditions such as those leading to increased pulmonary blood flow, pulmonary hypertension, increased pulmonary vascular reactivity, or patent foramen ovale may have a higher predisposition towards the development of HAPE. [rx][rx][rx] Asthma Bronchitis Mucous plugging Myocardial infarction Pneumonia Pneumothorax Pulmonary embolism Upper respiratory tract infection Acute psychosis Brain tumour Carbon monoxide poisoning Central nervous system infection Cerebrovascular bleed or infarct Cerebrovascular spasm Diabetic ketoacidosis Hypoglycemia Hyponatremia Ingestion of drugs Seizure disorder Coronary artery bypass Eisenmenger syndrome Severe symptomatic valvular heart disease Severe decompensated congestive heart disease Uncontrolled ventricular and supraventricular tachycardia Uncontrolled hypertension Unstable angina History of altitude illness The rate of ascent The ultimate altitude reached Other medical conditions such as pulmonary hypertension, chronic obstructive pulmonary disease, restrictive lung disease, pulmonary fibrosis, and congenital heart disease The degree of cold The amount of physical exertion Use of alcohol and sleeping pills Symptoms of High Altitude Cerebral Edema Some symptoms of low oxygen saturation levels include: Shortness of breath Cyanosis Extreme fatigue and weakness Mental confusion Headaches Symptoms of mild, short-term altitude sickness usually begin 12 to 24 hours after arriving at high altitude. They lessen in a day or two as your body adjusts. These symptoms include: Dizziness. Fatigue and loss of energy. Shortness of breath. Loss of appetite. Sleep problems. Symptoms of moderate altitude sickness are more intense and worsen instead of improving over time: Worsening fatigue, weakness, and shortness of breath. Coordination problems and difficulty walking. Severe headache, nausea, and vomiting. Chest tightness or congestion. Difficulty doing regular activities, though you may still be able to walk independently. Severe altitude sickness is an emergency. The symptoms are similar to moderate AMS but more severe and intense. If you start experiencing these symptoms, you must be taken to a lower altitude immediately for medical care: Shortness of breath, even when resting. Inability to walk. Confusion. Fluid buildup in the lungs or brain. HAPE, when fluid builds up in the lungs, prevents oxygen from moving around your body. You need medical treatment for HAPE. Symptoms include: Cyanosis, when your skin, nails or whites of your eyes start to turn blue. Confusion and irrational behavior. Shortness of breath even when resting. Tightness in the chest. Extreme fatigue and weakness. Feeling like you’re suffocating at night. Persistent cough, bringing up white, watery fluid. HACE happens when the brain tissue starts to swell from the leaking fluid. You need medical treatment for HACE. Symptoms include: Headache Loss of coordination. Weakness. Disorientation, memory loss, hallucinations. Psychotic behavior. Coma. Acute high altitude illness summary Condition Symptoms and Signs Treatment Prophylaxis Acute mountain sickness Headache, anorexia, nausea, vomiting, dizziness, fatigue, weakness, insomnia Descent, acetazolamide, dexamethasone, supplemental oxygen Slow ascent, acetazolamide, dexamethasone High altitude pulmonary edema Dyspnea at rest, cough, decreased exercise performance, chest pain/tightness, low pulse oximetry, central cyanosis, tachypnea, tachycardia, rales, wheezing Descent, supplemental oxygen, nifedipine, phosphodiesterase-5 inhibitors, salmeterol, portable hyperbaric chambers Slow ascent, nifedipine, phosphodiesterase-5 inhibitors, salmeterol High altitude cerebral edema Change in mental status or ataxia in a person with AMS or HAPE Descent, dexamethasone, acetazolamide, supplemental oxygen, portable hyperbaric chambers Slow ascent, dexamethasone, acetazolamide Diagnosis of High Altitude Cerebral Edema History and Physical The hallmark of Acute Mountain Sickness is a headache, with other symptoms including nausea, vomiting, loss of appetite, fatigue/malaise (particularly at rest), sleep disturbance, and dizziness/lightheadedness. Acute Mountain Sickness symptoms can begin after only a few hours and typically present the first day at a given altitude, resolving after one to three days, even without treatment, as the body adjusts physiologically (acclimates) to the lower oxygen levels. The presence of facial or extremity edema can be present with or without Acute Mountain Sickness symptoms and is felt to be a marker for not yet being acclimated to the altitude. Rarely, retinal hemorrhages can occur and affect visual fields. The onset of neurological findings such as a progressive decline in cognitive/mental function, the declining level of consciousness, impaired coordination, slurred speech, and/or lassitude signify the transition from AMS to HACE. A typical evaluation consists of an abnormal neurological exam, with ataxia often being the earliest finding. Early symptoms may be misinterpreted as exhaustion and it is important to exclude these, as well as other disorders such as dehydration, hypoglycemia, hypothermia, or hyponatremia which all may have signs and symptoms that overlap with that of HACE. Though rarely available, laboratory testing may show an elevated white blood cell count in the setting of HACE, whereas any number of metabolic abnormalities may be present with the aforementioned others within the differential diagnosis. Lumbar puncture may have an increased opening pressure with otherwise normal laboratory findings. CT may show cerebral edema, but MRI is a better study to evaluate for more subtle signs of edema and can remain abnormal for days up to weeks. To date, there has been no direct correlation between the severity of edema with clinical outcome.[rx][rx] The Lake Louise Score for the diagnosis of acute mountain sickness.[rx] Symptoms Severity Score 1. Headache None 0 Mild 1 Moderate 2 Severe/incapacitating 3 2. Gastrointestinal None 0 Poor appetite or nausea 1 Moderate nausea or vomiting 2 Severe nausea or vomiting/incapacitating 3 3. Fatigue/weakness None 0 Mild 1 Moderate 2 Severe/incapacitating 3 4. Dizziness/lightheaded None 0 Mild 1 Moderate 2 Severe/incapacitating 3 5. Difficulty sleeping None 0 Not as well as usual 1 Poor night’s sleep 2 Unable to sleep 3 A diagnosis of acute mountain sickness (AMS) requires (a) score > 3, (b) presence of headache and (c) recent ascent. High-altitude cerebral edema With AMS Altered mental status or/and ataxia Without AMS Altered mental status and ataxia Acute mountain sickness (AMS) - In the setting of a recent gain in altitude, there is the presence of headache and at least one of the following: - Gastrointestinal (anorexia, nausea, or vomiting) - Fatigue or weakness - Dizziness or lightheadedness - Difficulty sleeping High-altitude cerebral edema (HACE) - Can be considered “end-stage” or severe AMS. In the setting of a recent gain in altitude, there is either — - the presence of a change in mental status and/ or ataxia in a person with AMS - or the presence of both mental status changes and ataxia in a person without AMS. High-altitude pulmonary edema (HAPE) In the presence of a recent gain in altitude, the presence of the following: At least two of the following symptoms — - Dyspnea at rest - Cough - Weakness or decreased exercise performance - Chest tightness or congestion At least two of the following signs: - Crackles or wheezing in at least one lung field - Central cyanosis - Tachypnea - Tachycardia Treatments of High Altitude Cerebral Edema Non-pharmacological Pure oxygen – Giving pure oxygen can help a person with severe breathing problems caused by altitude sickness. Physicians at mountain resorts commonly provide this treatment. A Gamow bag – This portable plastic hyperbaric chamber can be inflated with a foot pump and is used when a rapid descent is not possible. It can reduce the effective altitude by up to 5,000 ft (1,500 m). It is usually used as an aid to evacuate people with severe symptoms, not to treat them at high altitudes. Gradual Ascent – The recommended method for the prevention of high-altitude illness is to allow the body time to acclimatize via gradual ascent. The WMS recommends one day of travel for every 1,500 ft ascent above 10,000 ft above sea level and a day of rest every 3 to 4 days of travel. Descent – Non-severe AMS: Descent is not necessary for non-severe AMS. It responds well to rest and/or pharmacological treatment. If symptoms resolve, ascent may resume. Severe AMS is AMS with incapacitating symptoms. The appropriate and definitive treatment for severe AMS is immediate descent to a lower altitude. Supplemental Oxygen – If available, supplemental oxygen should be administered with oxygen saturation of above 90% as a goal for both severe AMS and HACE. Supplemental oxygen should only be used in conjunction with evacuation or while waiting for it. Portable Hyperbaric Chamber – These portable chambers are indicated for severe AMS and HACE when evacuation is delayed. Symptoms will recur when the patient exits the chamber. However, it may temporarily improve symptoms long enough for patients to be able to assist with their evacuation. The equipment and constant supervision make this a resource-intensive treatment, but it has the potential to save lives in remote areas where evacuation may be delayed. Medication Established drug treatments include acetazolamide, dexamethasone, and nifedipine. Acetazolamide is thought to be effective in treating AMS, creating an acidemia, increasing ventilation, and therefore, increasing the arterial oxygen content.[rx] Dexamethasone is effective at reducing edema and symptoms in HACE, just as it is in any other form of cerebral edema. Nifedipine is used in HAPE for its dilatory effect on the pulmonary vasculature; however, a recent study did not demonstrate any benefit over descent and supplemental oxygen in patients with HAPE.[rx] In addition to these established treatments, potential novel therapies have been suggested such as ibuprofen, nitrates, and intravenous (IV) iron supplementation. Acetazolamide Acetazolamide prevents AMS when taken before ascent; it can also help speed recovery if taken after symptoms have developed. The drug works by acidifying the blood and reducing the respiratory alkalosis associated with high elevations, thus increasing respiration and arterial oxygenation and speeding acclimatization. An effective dose that minimizes the common side effects of increased urination and paresthesias of the fingers and toes is 125 mg every 12 hours, beginning the day before ascent and continuing the first 2 days at elevation, or longer if ascent continues. Acetazolamide (125mg PO every 12 hours) Acetazolamide is the only medication proven to speed acclimatization. It induces metabolic acidosis by bicarbonate diuresis. This acidosis triggers compensatory hyperventilation helping acclimatization. There are two adverse effects of this medication worth considering. First, acetazolamide increases urination frequency and therefore increases the risk of dehydration, which is a concern during high altitude travel[rx]. Secondly, acetazolamide has a similar molecular structure to sulfa medications and should be used cautiously in patients with sulfa allergy. Although the risk of cross-reactivity is low, travelers with sulfa allergies are recommended to undergo a trial of acetazolamide before travel.[rx][rx] Allergic reactions to acetazolamide are uncommon. As a nonantimicrobial sulfonamide, it does not cross-react with antimicrobial sulfonamides. However, it is best avoided by people with a history of anaphylaxis to any sulfa. People with a history of severe penicillin allergy have occasionally had allergic reactions to acetazolamide. The pediatric dose is 5 mg/kg/day in divided doses, up to 125 mg twice a day. Dexamethasone Dexamethasone (initial 8mg PO, IM, or IV followed in 6 hours by 4mg PO, IM, or IV every 6 hours). Dexamethasone is effective for preventing and treating AMS and HACE and prevents HAPE as well. Unlike acetazolamide, if the drug is discontinued at elevation before acclimatization, the mild rebound can occur. Acetazolamide is preferable to prevent AMS while ascending, with dexamethasone reserved as an adjunct treatment for the descent. The adult dose is 4 mg every 6 hours. An increasing trend is to use dexamethasone for “summit day” on high peaks such as Kilimanjaro and Aconcagua, in order to prevent abrupt altitude illness. Dexamethasone (4mg PO, IM, or IV every 12 hours) For those unable to take acetazolamide, dexamethasone may be used as a preventive agent. It also may be considered for individuals involved in an unusually high-risk situation (i.e., search and rescue personnel airlifted to above 11,000 ft). Dosages for dexamethasone is the same for PO, IM, and IV routes of administration. If used for longer than ten days, it must be tapered slowly to prevent withdrawal symptoms. Nifedipine Nifedipine both prevents and ameliorates HAPE. For prevention, it is generally reserved for people who are particularly susceptible to the condition. The adult dose for prevention or treatment is 30 mg of extended-release every 12 hours or 20 mg every 8 hours. Painkillers or Ibuprofen Acetaminophens, such as Tylenol, can be taken for headaches. Ibuprofen, an anti-inflammatory medicine, can also help. Other than the tight-fit hypothesis previously discussed, other possible mechanisms causing high-altitude headaches include activation of the trigeminovascular system by vasodilatation or inflammatory mediators[rx,rx] or alteration in the blood–brain barrier by inflammatory mediators causing vasogenic edema.]rx] The central role of inflammation in these mechanisms has led to an interest in nonsteroidal anti-inflammatory medications such as ibuprofen. Nitrates Nitric oxide (NO) regulates physiological processes in the human body, including vasodilation, immune function, platelet aggregation, glucose homeostasis, muscle contraction, and mitochondrial function. One possible means of eliciting this effect is via dietary nitrate supplementation (ie, nitrate-rich beetroot juice). Nitrate ingestion has been shown to increase plasma concentrations of NO metabolites (nitrate and nitrite),[rx] reduce steady-state oxygen consumption,[rx] improve arterial and tissue oxygenation,[rx] enhance exercise tolerance,[rx–rx] and improve performance,[rx] during acute normobaric hypoxia. Interestingly, under hypoxic conditions, nitrate supplementation in the form of beetroot juice resulted in faster muscle recovery and restored maximal oxidative ATP resynthesis and exercise tolerance to normoxic values, when compared to placebo.[rx,rx] Both sildenafil (a selective phosphodiesterase type 5 [PDE-5] inhibitor) and bosentan (a nonselective endothelin-receptor antagonist) have been mooted as potential treatments for AMS, due to their effect on prolonging the effect of NO. Sildenafil has been demonstrated to reduce PASP, increase oxygen delivery, and minimize the decrease in exercise capacity in both normobaric hypoxia and actual high altitude.[rx] By dilating the pulmonary vascular bed, these drugs reduce the degree of hypoxic pulmonary vasoconstriction and consequent pulmonary hypertension, and therefore, the risk of HAPE. IV iron supplementation In hypoxic conditions, oxygen-dependent hydroxylase enzymes are unable to degrade HIF, so iron supplementation encourages the breakdown of HIF, as in normoxic conditions. This is significant as HIF is believed to coordinate the cellular inflammatory response to hypoxia.[rx] IV iron supplementation immediately prior to ascent to high altitude resulted in a significantly lower rise in AMS score from sea level to altitude, compared to IV saline. However, there was no significant difference in absolute AMS score at altitude between the two groups.[rx] Iron supplementation is an intriguing prospect in the prophylactic management of AMS; however, its feasibility on field expeditions is questionable. Oral iron supplemental is a possible alternative that needs more investigation. Exercise and AMS While the exact mechanism underlying high-altitude illness remains hotly debated, exercise has been suggested as an independent risk factor for the development of AMS.[rx] High-intensity intermittent exercise on a trekking expedition was associated with increased interstitial lung fluid at 4,090 m,rx] suggesting that exercise increases the risk of HAPE. Corroborating this, AMS scores were significantly higher in trekkers with a higher rating of perceived exertion.[rx] Conversely, several recent chamber studies have failed to demonstrate a statistical difference in the development of AMS between rest and exercise at simulated altitude.[rx–rx] Of note, in comparing the change in interstitial fluid between exercise in hypoxia at 4,090 m and exercise in simulated hypoxia, there was no significant increase in simulated hypoxia, while there was an increase in actual hypoxia.[rx] This suggests that chamber studies are possibly underestimating the effect of exercise on the development of AMS and HAPE and that this may be due to the difference between the normobaric hypoxia experienced in chamber studies and hypobaric hypoxia experienced at altitude.[rx] Nutrition There are a few nutritional concerns for athletes at high altitudes. First, there is an association between chronic high altitude exposure and significant weight loss.[rx] This seems to be primarily due to loss of fat-free mass, which may have significant negative effects on physical performance.[rx] Factors possibly contributing to this weight loss are decreased physical activity, hypoxia, irregular sleep pattern, cold exposure, and nutritional imbalance related to protein metabolism.[rx,rx] Inspiratory muscle training In addition to IHE and IHT, there are other potential techniques such as dietary nitrate supplementation (which has been discussed earlier) and inspiratory muscle training (IMT), which may attenuate arterial oxygen desaturation and a reduction in exercise performance during high-altitude exposure. Acute exposure to hypoxia and the associated reduction in the arterial partial pressure of oxygen increases minute ventilation, in an attempt to normalize arterial oxygen saturation. However, this hyperventilation increases the work of breathing and in turn the demand for respiratory blood flow,[rx] making the respiratory muscles more susceptible to fatigue. Already abroad and need to see a doctor? The following list of resources can help international travelers identify health care providers and facilities around the world. CDC does not endorse any particular provider or medical insurance company, and accreditation does not ensure a good outcome. The nearest US embassy or consulate can help travelers locate medical services and notify friends, family, or employers of an emergency. They are available for emergencies 24 hours a day, 7 days a week, overseas. The Department of State maintains a list of travel medical and evacuation insurance providers. The International Society of Travel Medicine maintains a directory of health care professionals with expertise in travel medicine in more than 80 countries. The International Association for Medical Assistance to Travelers maintains a network of physicians, hospitals, and clinics that have agreed to provide care to members. Travel agencies, hotels, and credit card companies (especially those with special privileges) may also provide information. A number of countries or national travel medicine societies have websites related to travel medicine that provide access to clinicians, including the following: Australia: Travel Medicine Alliance Canada: Health Canada (www.phac-aspc.gc.ca and https://travel.gc.ca) China: International Travel Healthcare Association Great Britain: National Travel Health Network and Centre and British Global and Travel Health Association South Africa: South African Society of Travel Medicine Tips for acclimatization Be sure you are in good shape before you travel – If you have significant medical problems, check with your doctor before you go; even with his approval, be sure to go slowly and listen to your body for warning symptoms. Travel is usually safe for men with mild to moderate heart or lung disease and for most with well-controlled high blood pressure or diabetes, but high altitudes are very dangerous for people with sickle cell anemia. Ascend gradually – You can fly to Denver or Mexico City in one hop, but if you’re going higher, a few days of acclimation are worth your time. Above 8,000 feet, don’t go up more than 1,000 feet a day. Travel high, sleep low – For example, if you ski at 9,000 feet, you’ll do best if your lodge is 1,000–1,500 feet lower. If you’re hiking, ascend in stages, and sleep at altitudes below your daily peak. Limit your exercise during your first days at altitude — and take it easy throughout your trip if you have medical problems or you feel sick in any way. Drink plenty of fluids – Dehydration is sneaky at altitude because you will lose lots of water through your lungs even if you don’t perspire. Drink enough to keep your urine clear and copious. Avoid alcohol or minimize your consumption, particularly for the first 48 hours at altitude. Avoid sedatives. Be alert for symptoms – You can manage mild mountain sickness yourself (see “Treatment” below), but you’ll need help for anything more serious. Don’t ignore symptoms; instead, return to a lower elevation and get help. Ascend gradually, if possible. Avoid going directly from low elevation to more than 9,000 ft (2,750 m) sleeping elevation in 1 day. Once above 9,000 ft (2,750 m), move sleeping elevation no higher than 1,600 ft (500 m) per day, and plan an extra day for acclimatization every 3,300 ft (1,000 m). Consider using acetazolamide to speed acclimatization if abrupt ascent is unavoidable. Avoid alcohol for the first 48 hours; continue caffeine if a regular user. Participate in only mild exercise for the first 48 hours. Having a high-elevation exposure (greater than 9,000 ft [2,750 m]) for 2 nights or more, within 30 days before the trip, is useful, but closer to the trip departure is better. Dress warmly. Wear sunglasses. These steps can help your body acclimate: Walk-up – Start below 10,000 feet and walk to a high altitude instead of driving or flying. If you drive or fly to an elevation higher than 10,000 feet, stay at your first stop for at least 24 hours before going higher. Go slow – Once above 10,000 feet, don’t increase your altitude more than 1,000 feet a day. Rest – Build a rest day into your schedule for every 3,000 feet you climb. “Climb high and sleep low” – If you climb more than 1,000 feet in a day, come down to sleep at a lower altitude. Know your body – Recognize the signs and symptoms of altitude sickness. Move to a lower altitude (or avoid climbing higher) if you notice any symptoms. Stay hydrated – Drink 3-4 quarts of water per day. Avoid alcohol – Alcohol can dehydrate your body. It also has stronger effects at higher elevations, which can impair judgment. Eat carbs – Eat a diet that’s more than 70% carbohydrates. Know the “don’ts – Avoid tobacco and depressant drugs, such as sleeping pills and tranquilizers. What should I ask my doctor? If you’re planning to travel to high altitudes, ask your healthcare provider: Should I take preventive medication to avoid altitude sickness? Do I have any risk factors that would prevent me from visiting high elevations? What other steps can I take to prevent altitude sickness? What steps should I take if I start to feel symptoms during my climb? References https://www.ncbi.nlm.nih.gov/books/NBK232874/ https://www.ncbi.nlm.nih.gov/books/NBK430916/ https://www.ncbi.nlm.nih.gov/books/NBK442011/ https://www.ncbi.nlm.nih.gov/books/NBK430819/ https://www.ncbi.nlm.nih.gov/books/NBK232877/ https://www.ncbi.nlm.nih.gov/books/NBK539701/ https://www.ncbi.nlm.nih.gov/books/NBK430716/ https://www.ncbi.nlm.nih.gov/books/NBK232881/ https://www.ncbi.nlm.nih.gov/books/NBK539874/ https://www.ncbi.nlm.nih.gov/books/NBK560677/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678789/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789936/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590130/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114067/ https://www.ncbi.nlm.nih.gov/books/NBK557466/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590685/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923424/ https://wwwnc.cdc.gov/travel/page/find-clinic https://wwwnc.cdc.gov/travel/page/travel-to-high-altitudes https://en.wikipedia.org/wiki/Effects_of_high_altitude_on_humans Show More