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High Altitude Mountain Sickness and Oral Appliance Therapy



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Original Research Paper Proposing the Altitude Mouthpiece



Michael D. Williams, DDS  




The purpose of this paper is to describe a treatment modality utilizing a specifically designed mandibular advancement device that can prevent or attenuate the symptoms of acute mountain sickness. It is estimated that there are over 20 million overnight visitors to the high altitude regions of <??> Colorado alone each year that could benefit from this application.   



There are basically three types of high altitude mountain sickness. The most common and least severe type is acute mountain sickness (AMS). AMS is an illness that can affect mountain climbers, hikers, skiers, or travelers who ascend to altitude too fast. It is most frequently seen when people rapidly reach an altitude typically above 8,000 feet (about 2,400 meters). However, the condition can occur at altitudes as low as 3,200 feet (1000 meters). Denver at 5,280 feet is around the height when hypoxic drive begins to kick in and some travelers experience AMS there. The individual susceptibility varies widely, and some people are highly resistant, it usually does NOT depend on athleticism or fitness. (1)  


The other more debilitating and sometimes lethal conditions are high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE).


The diseases of high altitude mountain sickness and AMS occur from the combination of reduced air pressure and a lower concentration of oxygen at high altitude. Symptoms can range from mild to life-threatening, and can affect the nervous system, brain, lungs, muscles, and heart. In severe cases fluid collects in the lungs resulting in pulmonary edema then causing extreme shortness of breath, which further reduces how much oxygen a person gets and may lead to High Altitude Pulmonary Edema (HAPE). Brain swelling may also occur causing High Altitude Cerebral Edema (HACE) in confusion, coma, and, if untreated, death. The severity of the symptoms depends on rate of altitude ascent and how hard the person pushes or exerts himself. People who normally live at or near sea level are more prone to acute mountain sickness.  


Prevalence and Incidence 

AMS is very common at high altitude. The incidence of AMS varies with location, depending on both absolute altitude reached and rate of ascent to altitude. It has been estimated that 15 to 40% of Colorado resort skiers depending on the altitude of the resort develop AMS. Studies have shown an incidence of 70% in Mt. Rainier climbers. Given the huge numbers of Colorado skiers alone tourists (10 million a year), this is not a trivial problem. (3) The sleeping altitude is the critical factor, with 9,000 feet being a significant threshold for illness (>20% incidence), and 8,000 to 9,000 feet less of a problem (perhaps 10 to 15% incidence), while below 8,000 feet, AMS is uncommon but still possible. 


Commercial airliners are pressurized to an altitude of 8000 feet. It is not uncommon to have headaches and other symptoms of high altitude while flying. The familiar Lear Jet crash carrying golfer Payne Stewart involved the loss of pressure and oxygen. It is likely that the pilots and occupants may have lost consciousness due to hypoxia, or a lack of oxygen. Loss of pressurization above 30,000 feet would cause occupants of the aircraft to lose consciousness from oxygen deficiency in one to two minutes. [4] 


Susceptibility to AMS is not related to physical fitness or gender, although women less frequently suffer from pulmonary edema (fluid in the lungs). Older adults may be less susceptible, while some data suggests that children probably have a higher incidence than the general adult population. 


Travel from sea level to only a 5-6000 foot elevation can cause symptoms in some people. (13) In 1991 in Summit County, Colorado, the incidence of acute mountain sickness was 22 percent at altitudes of 7000 to 9000 ft (1850 to 2750 meters) and 42 percent at altitudes of 10,000 ft (3000 meters). (3) At over 10,000 feet 75% of people will have some altitude illness symptoms.  



Many people will experience AMS but eventually there is an acclimatization process. The symptoms usually start 12 to 24 hours after arrival at altitude and begin to decrease in severity generally around the third day unless the altitude is increased. (3) Given enough time, your body will adapt to the decrease in oxygen at some of the higher altitudes. The acclimatization process is limited by the ascent rate and altitude. (4)  



During the 1991 International Hypoxia Symposium, held at Lake Louise in Alberta, Canada, the symposium consensus committee developed an AMS scoring system (the "Lake Louise score") which is widely used today to assess the severity of illness. This simple self-assessment scoring system can be used to determine whether or not an individual has AMS. A score of 3 or more (with a headache) after recent gain in altitude is consistent with a diagnosis of mild AMS. Mild AMS = 3-8 points, Moderate AMS = 9-18, Severe AMS = 19+  

Lake Louise Self Assessment Scoring for AMS



LLS Altitude




The Severe headache along with the other symptoms is diagnostic. The headache in severe AMS is often migraine like and that this type of headache occurs in 75% of mountaineers at altitudes above 000 meters. (5) In an attempt to maintain oxygenation your pulse rate and blood pressure go up sharply since your breathing rate cannot increase enough to raise the oxygen content in the blood to sea level concentrations. The body needs to compensate to having less oxygen. In addition, for reasons not entirely understood, high altitude and lower air pressure causes fluid to leak from the capillaries which can cause fluid build-up in both the lungs and the brain ultimately resulting in HAPE or HACE. Symptoms tend to be worse at night and when respiratory drive is decreased. Mild AMS may not interfere with normal activity and symptoms generally subside within two to four days as the body acclimatizes. 



Certain normal physiologic changes occur in every person who goes to altitude  

Rapid pulse (heart rate)

Hyperventilation (breathing faster, deeper, or both) 

Shortness of breath during exertion, 

Changed breathing pattern at night 

Awakening frequently at night and difficulty sleeping 

Increased urination 

Dizziness or light-headedness  

Fatigue, malaise  

Headache, often severe  

Loss of appetite  

Nausea or vomiting                                                                                                    


More severe altitude symptoms include: 

Bluish discoloration of the skin  

Chest tightness or congestion wheezing 



Coughing up blood  

Decreased consciousness or withdrawal from social interaction  

Gray or pale complexion (cerebral edema)  

Inability to walk in a straight line, or to walk at all  

Shortness of breath at rest  


Pathology Physiology 

As one ascends through the atmosphere, barometric pressure decreases (though the air still contains 21% oxygen) and thus every breath contains fewer and fewer molecules of oxygen. At sea level, the concentration of oxygen is about 21% and the barometric pressure averages 760 mm Hg. As altitude increases, oxygen concentration remains the same but the number of oxygen molecules per breath is reduced due to lower barometric pressure. At 3,658 meters (12,000 feet), barometric pressure decreases to 483 mm Hg, resulting in roughly 40% fewer oxygen molecules per breath. In other words less pressure equals less oxygen concentration in the blood. In order to increase oxygen levels in the blood, your body responds by breathing faster. Although oxygen levels may increase, sea level concentrations cannot be reached. The body must adjust to having less oxygen, if possible. (2) This adjustment is called acclimatization. 


High altitude can mean anything above the height 5000 feet, but medically speaking it is more defined and based on alterations in human physiology. (7)  

Medium altitude is defined as (1500-2500m) at this altitude oxygen saturation remains above 90% but altitude illness is possible. At high altitude (2500-5300m) oxygen saturation falls below 90%. As a point of reference oxygen saturation in Boulder, Colorado (5400 ft) is approximately 94%. [8]

At an altitude of 3,000 meters (9,840 feet), commonly an altitude encountered at ski resorts, the barometric pressure and the inspired oxygen pressure are 70% of that noted at sea level.  At 5,000 meters (16,400 feet) the inspired oxygen barometric pressure is 50% that at sea level.  On the summit of Mt. Everest 8,848 meters (29,021 feet) the inspired oxygen is 29% that at sea level. (10)  


One must work harder to obtain oxygen, by breathing faster and deeper. This is particularly noticeable with exertion, such as walking uphill. Being out of breath with exertion is normal, as long as the sensation of shortness of breath resolves rapidly with rest. 


The increase in breathing is critical. It is therefore important to avoid anything that will decrease breathing, e.g. alcohol and other respiratory depressant drugs. Despite the increased breathing, attaining normal blood levels of oxygen is not possible at high altitude. Persistent increased breathing results in reduction of carbon dioxide in the blood, a metabolic waste product that is removed by the lungs. However, the build-up of carbon dioxide in the blood is the key signal to the brain that it is time to breathe, so if it is low, the drive to breathe is blunted. The lack of oxygen is a much weaker signal, and acts as an ultimate safety valve. Most of the AMS symptoms do not appear to be caused by low oxygen, but rather by the low CO2 levels causing a rise in blood pH, alkalosis. (11)  


As long as you are awake it isn't much trouble to consciously breathe, but at night an odd breathing pattern called High Altitude Periodic Breathing (HAPB) develops due to a back-and-forth balancing act between these two respiratory triggers of arterial concentration of CO2 and O2. HAPB consists of cycles of normal breathing which gradually slows, breath-holding, and a brief recovery period of accelerated breathing. The breath-holding may last up to 10-15 seconds. It may improve slightly with acclimatization, but does not usually resolve until descent. Periodic breathing can cause a lot of anxiety (4). This is a common finding at high altitude and is not considered as altitude sickness unless accompanied by the other symptoms. (6)  


Headache at altitude is diagnostic of AMS. It is an important and serious problem that often heralds the onset of acute mountain sickness. The headache can be sever and incapacitating. Brain edema and raised intracranial pressure may cause headache by compressing brain structures leading to displacement and stretching of the pain-sensitive intracranial structures. Furthermore, high altitude seems capable of decreasing the threshold of response to sensory stimulation. (11) 


The pathophysiology of moderate to severe AMS and HACE is clearly related to brain swelling. Factors contributing to brain swelling include, but are not limited to, the degree and rate of onset of hypoxemia (low oxygen content in the blood), inadequate breathing (known as hypoventilation, which can be due to low innate breathing response to hypoxemia, respiratory depressant drugs, or ascent too rapid for adequate acclimatization), poor gas exchange (oxygen for carbon dioxide) in the lungs, fluid retention, individual anatomy (such as ability to accommodate increased brain volume). (3)

As brain volume increases, the pressure within the brain (intracranial pressure, or ICP) rises, although very little (perhaps only 20 to 30 milliliters) until a critical threshold is reached. A dehydrated brain is much more compliant than a “wet” brain. Dilation of cerebral blood vessels causes increased cerebral blood flow and increased cerebral blood volume, engorging the brain and making it stiffer and less compliant. As brain swelling continues, ICP rises beyond the ability of blood to flow into brain tissue. Eventually (and sometimes quite rapidly), cerebral blood flow stops, causing death, if allowed to progress. (3)   


In both the brain and the lungs, hypoxia elicits neurohumoral and hemodynamic responses that result in over perfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage, and consequent edema. The hypoxia-induced cerebral vasodilatation or its effectors, such as nitric oxide, most likely produce the headache. (15) The headache itself can cause other symptoms, such as nausea and malaise, and thereby account for mild acute mountain sickness. An alternative hypothesis is that early acute mountain sickness is due to mild cerebral edema. New evidence suggests that on ascent to high altitudes, all people have swelling of the brain.  


It has been postulated that acute mountain sickness might be related to a person’s ability to compensate for the swelling of the brain. Those with a greater ratio of cranial cerebrospinal fluid to brain volume are better able to compensate for swelling through the displacement of cerebrospinal fluid, and may therefore be less likely to have acute mountain sickness. (3) 



On arrival at altitude, there are a number of physiological changes that occur, which enable the body to function optimally in the low oxygen environment. This process by which individuals gradually adjust is known as acclimatization. The initial and most important adjustments are an increase in the frequency and depth of breathing. This begins to occur at altitudes of about 1500m. The heart pumps faster and blood pressure rises. Red blood cell production increases, resulting in an increased hemoglobin concentration, which is required to pick up oxygen and transport it around the body. These mechanisms are to ensure increased oxygen delivery to cells and efficiency of oxygen use. At sea level our blood is 98% saturated with oxygen and this decreases to 89% at 3000m and reaches as low as 40% on the summit of Everest. (2) At medium altitude (1500-2500m) oxygen saturation remains above 90% but altitude illness is possible. At high altitude (2500-5300m) oxygen saturation falls below 90%, altitude illness is common and acclimatization is necessary. Acclimatization in adults is possible up to about 5000-5500m but above this elevation there is a fine balance between adjustment to altitude and deterioration. Above 8000m no acclimatization occurs and prolonged exposure is incompatible with survival (15)  


A misconception of the acclimatization process is that the body returns to its sea level condition or that the hypoxia of high altitude can be nullified by acclimatization.  This is not the case.   For example, on arrival at 14,000 feet maximum physical performance is 80% that at sea level.  At two weeks of acclimatization it is just slightly above 85%. (9)  

Ventilation                                                                                                            As ventilation (volume of air breathed/minute) increases the partial pressure of carbon dioxide (Pco2) decreases in the alveoli, thereby allowing alveolar Po2 to increase. This response may begin immediately at altitudes as low as 1500 m and at 5000 m results in a resting ventilation rate approximately 60% higher than sea-level after several days at altitude. This process of acclimatization begins immediately but requires several days to be notable and requires weeks to be near complete.   Climbers at extreme altitude require over a month for the acclimatization process to be near complete.  Hyperventilation is the most important feature in the acclimatization process.  There is an increase in the depth and the rate of breathing; an extreme example is on the summit of Mt. Everest where the pressure of inspired oxygen is 29% that of sea level.  The ventilation is increased five-fold. 

It takes approximately two weeks to adapt to the changes associated with the hypobaric conditions at 2268m (7500ft), roughly that of Mexico City (1). Every 610m (2000ft) increase requires an additional week of acclimatization to altitude (1). But no matter how long an individual lives at altitude, they never fully compensate for the lack of oxygen and never regain the level of aerobic power or endurance performance they could at sea level. Sports advisor

The depth of respiration increases. Pressure in pulmonary capillaries is increased, "forcing" blood into parts of the lung which are not normally used when breathing at sea level. (14) In addition, high altitude and lower air pressure causes fluid to leak from the capillaries in both the lungs and the brain which can lead to fluid build-up. Continuing on to higher altitude without proper acclimatization can lead to the potentially serious, even life-threatening altitude sickness. 


The night time breathing patterns change at high altitude. At altitudes above 3,000 meters (10,000 feet) most people experience a periodic breathing during sleep known as Cheyne-Stokes Respirations. The pattern begins with a few shallow breaths and increases to deep sighing respirations then falls off rapidly even ceasing entirely for a few seconds. During the period when breathing stops the person often becomes restless and may wake with a sudden feeling of suffocation. This can disturb sleeping patterns exhausting the person at high altitude. (14)  



Heart Rate                                                                                                                

At high altitude the heart rate increases to increase the oxygen availability.   

Heart rate and blood pressure initially increase with exposure to altitude then slowly return towards low altitude values as acclimatization proceeds. (37) The normal sea level values are never reached. 

Cardiac output increases during rest sub maximal exercise. During the first few hours at altitude stroke volume decreases during sub maximal exercise. This is a result of the reduction in plasma volume. Heart rate increases enough to compensate for this and to actually slightly raise cardiac output. After a few days however, oxygen extraction becomes more efficient reducing the need to increase cardiac output. (13) Heart rate and blood pressure initially increase with exposure to altitude then slowly return towards low altitude values as acclimatization proceeds. 


Hemodynamics and Polycythemia  

Dramatic changes take place in the body's chemistry and fluid balance during acclimatization. The osmotic center, which detects the "concentration" of the blood, gets reset so that the blood is more concentrated. This results in an altitude diuresis as the kidneys excrete more fluid. It has the effect of increasing the hematocrit (concentration of red blood cells) and perhaps improving the blood's oxygen-carrying ability somewhat; it also counteracts the tendency for edema formation. It is normal at altitude to be urinating more than usual. If you are not, you may be dehydrated, or you may not be acclimatizing well. Initial exposure to altitude decreases plasma volume. However, this begins to increase slightly with long-term acclimatization to altitude. (13).


Blood volume decreases. Plasma volume decreases by up to 25% within the first few hours of exposure to altitude and doesn’t plateau until after a few weeks. This is partially a deliberate response by the body as reducing plasma in effect increases the density of red blood cells. While no extra red blood cells have been produced in this acute phase, the amount of hemoglobin per unit of blood (called hematocrit) is now increased – resulting in greater oxygen transport for a given cardiac output (13) 


Red blood cell count increases.Lack of oxygen stimulates the kidneys to release erythropoietin, the hormone responsible for red blood cell production, within 3 hours and reaches a peak after 24 to 48 hours (8). In sea level residents, hematocrit is about 45-48%. With 6 weeks exposure to an altitude of 4540m (14895ft) these levels can increase to 59% (2). The concentration of oxygen-carrying red blood cells is increased by the production of new red blood cells resulting in a hematocrit about 10 % or more higher than sea-level usually within a week to a month. (37) 


Since the alveolar Pco2 is reduced, carbonic acid in the blood is also reduced making the blood more alkaline. The kidneys respond by increasing bicarbonate excretion in order to return blood pH to near its normal value. This response starts within 24 hrs and lasts for several days.   (37)


There is also an increased capillarization for greater oxygen delivery to the tissues, muscles and brain (14)   



Oxygen Saturation at High Altitude

As one gains altitude, there is a drop in the barometric pressure with a corresponding drop in the oxygen pressure.  At an altitude of 3,000 meters (9,840 feet), commonly an altitude encountered at ski resorts, the barometric pressure and the inspired oxygen pressure are 70% that noted at sea level.  This compares to conditions found at Breckenridge Colorado. (33)  


In a person at sea level, the arterial oxygen partial pressure is 90-95 mmHg; oxygen saturation is 97-98%. If that same individual travels to an altitude of 14,000 feet, the figures fall to 45 mmHg and 71% prior to acclimatization. However, even with acclimatization the oxygen blood saturation level never reaches the sea level 

concentration. (32) 



Oxygen available at altitude 

Oxygen Available at Altitude as Compared to Sea Level Figure 1 




Altitude, how much oxygen there is compared to sea level, and normal average red blood cell oxygen saturation. From High Altitude Medicine Guide  




Altitude saturation


Altitude Performance 

High altitude oxygen saturation affects physical and mental performance. One measure of the amount of oxygen available for use within the body is arterial oxygen saturation Sao2, the percentage of binding sites of hemoglobin molecules that are carrying oxygen. This quantity can be easily measured using a finger or ear oximeter. Within a minute of exposure to altitude Sao2 begins to drop. Typical values for Sao2 as a function of altitude for un acclimatized individuals are shown in Figure 2. Figure 2 also indicates the general level of human performance impairment expected at high altitude, but note that the boundaries between the different levels of impairment are very approximate and vary between individuals. (31) For example at an altitude of 14,000 feet commonly hiked in Colorado the breathing air would allow about 83% oxygen saturation and result in minimal sensory and physical impairment. However, greater altitude or exertion could quickly reduce the saturation resulting in mental and physical impairment. 

Acute profound hypoxia may occur during rapid ascent, or when there is an abrupt decline in oxygenation. The latter may be due to overexertion, pulmonary edema, sleep apnea, or failure of the system used to deliver oxygen. Symptoms include fatigue, weakened sensory perceptions, vertigo, sleepiness, hallucinations, and ringing in the ears. The ultimate consequence of acute hypoxia is loss of consciousness, which occurs in the non-acclimatized person at an arterial oxygen saturation (SaO2) of 40% to 60% or an arterial PO2 of < 30 mm Hg (1). (51)

 Oxygen Saturation and Performance 

Oxygen Saturation and Tollerance at Altitude  


Figure 2 The relationship between mean arterial oxygen saturation (%) and altitude for several performance tests in un acclimatized subjects (from McFarland, 1972). (31) (17) 


Some debate persists as to the relevance of oximetry and AMS. Increase in pulse rate is positively associated with AMS. (39) (40)  


However one study showed that lowered oxygen saturation in a hypoxic environment is a predictor of AMS. SaO2 values were taken by finger pulse oximetry after 20 to 30 min of hypoxic exposure. SaO2 values after 20 to 30 min of hypoxia were on average 4.9% lower in subjects susceptible to AMS than in those who were not. AMS susceptibility was correctly predicted in 86% of the selected individuals exposed to short-term hypoxia. In conclusion, oximetry SaO2 values represent a useful tool to detect subjects highly susceptible to AMS. 

Investigative evidence indicates that acute mountain sickness (AMS) after rapid ascent to high altitude is associated with sleep and breathing disturbances during night. It was concluded that subjects with AMS, compared to controls, have a lower SpO2, this despite increased but unstable ventilation, which may reduce sleep efficiency. (36) 

Sleep at Altitude                                                                                                          Sleep disturbed breathing is a major characteristic of Acute Mountain Sickness (AMS). Most people don’t sleep well at altitude. Climbers commonly report vivid dreams, feelings of being suffocated and wake feeling un refreshed. Disturbed sleep forms one category of the Lake Louise self-assessment score sheet that is used to diagnose acute mountain sickness. However, there are important changes in the way we sleep at altitude that makes sleep quality poor. The stages of sleep can be divided into stages that are defined by the pattern of electrical activity in the brain and eye movement. The deeper stages of sleep and rapid eye movement (REM) sleep are reduced at altitude, therefore more of the night will be spent as light sleep and sleep quality will not be as good as at sea level. (35)

High altitude periodic breathing while sleeping (HAPB) is a common phenomenon and becomes more frequent with increasing altitude. This breathing pattern also called Cheyne-Stokes respiration (CSR) is found in central sleep apnea (CSA).  HAPB typically occurs during non-REM sleep.  This form of breathing consists of a period of hyperventilation followed by a period of apnea or not breathing.  Typically, three to five deep breaths will be followed by a couple of very shallow breaths or even a complete pause in breathing. A pause in breathing like this usually lasts around 5 to 15 seconds and is called an apnea. Apneas may end with a gasp that sometimes wakes the individual or their sleeping companions! People may breathe this way for most of the night. During apneic phases, oxygen levels drop and heart rate slows. Oxygen levels and heart rate rise again when breathing resumes resulting in cyclical variations in heart rate and the amount of oxygen in the blood. Low oxygen levels overnight are likely to disturb sleep but HAPB may also contribute to arousals. Arousals are more frequent at altitude. It is felt that this periodic breathing of sleep may significantly alter sleep patterns and the quality of sleep at night at altitude. (35) Many people develop HAPB at moderate altitudes. The HAPB cycle length is shorter than in CSR. (31) CSR has classically been associated with severe decompensated heart failure (6). 


A leading hypothesis relates altitude central sleep apnea to be caused by a sleep-related apnea threshold triggered by hypocapnia following ascent to high altitude where this central sleep apnea commonly develops in otherwise healthy humans. The breathing pattern and brain blood flow are closely linked by partial pressure of arterial CO2 (PaCO2) (35, 39). The effects of CO2 on cerebral blood flow (CBF) provide an important counter regulatory mechanism, which serves to minimize changes in brain. (39). 


Changes in CBF may, therefore, play an important role in etiology of central sleep apnea at high altitude.(19)At sea level the build up of the waste gas, carbon dioxide, in the blood controls breathing. If you hold your breath, carbon dioxide levels rise and create the urge to breathe. At high altitude, the body senses low oxygen levels and this becomes the main drive to breathe. Breathing faster and deeper at high altitude leads to a profound reduction in the carbon dioxide levels in the blood. During sleep at high altitude, the levels of carbon dioxide in the blood can drop very low and this can switch off the drive to breathe. Only after the body senses a further drop in oxygen levels do you start breathing again. During the apnea carbon dioxide levels rise but levels fall again when ventilation resumes, continuing the cycle.(35) 


Treatment of High Altitude Mountain Sickness 


If you begin to show symptoms of increasing altitude sickness, don't go higher until symptoms decrease. If symptoms increase go to a lower altitude immediately. 


Stay properly hydrated. Acclimatization is often accompanied by fluid loss, so you need to drink lots of fluids to remain properly hydrated (at least four to six liters per day). Urine output should be copious and clear to pale yellow. 

Take it easy and don't overexert yourself when you first get up to altitude. But, light activity during the day is better than sleeping because respiration decreases during sleep, exacerbating the symptoms. (22)  

Avoid respiratory depressants 

Avoid tobacco, alcohol and other depressant drugs including, barbiturates, tranquillizers, sleeping pills and opiates. These further decrease the respiratory drive during sleep resulting in a worsening of symptoms.   

Acetazolamide (Diamox)  

Diamox is a drug used to stimulate breathing and reduce mild symptoms of mountain sickness. This drug can cause increased urination. Make sure you drink plenty of fluids. Do not drink alcohol while taking this drug. Acetazolamide is the most tried and tested drug for altitude sickness prevention and treatment. This drug does not mask the symptoms but actually treats the problem. It seems to works by increasing the amount of alkali (bicarbonate) the base form of carbon dioxide, excreted in the urine, making the blood more acidic. This re-acidifies the blood, balancing the effects of the hyperventilation that occurs at altitude in an attempt to get oxygen. These re-acidification acts as a respiratory stimulant, particularly at night, thus reducing or eliminating the periodic breathing pattern common at altitude. Its net effect is to accelerate acclimatization.  (25) For prevention, 125 to 250mg twice daily starting one or two days before and continuing for three days once the highest altitude is reached is effective. Blood concentrations of acetazolamide peak between one to four hours after administration of the tablets. (26)

Diamox Side Effects

Some side effects include these: an uncomfortable tingling of the fingers, toes and face, carbonated drinks tasting flat; excessive urination; and rarely, blurring of vision. (26) Some studies have shown a large intolerance to the side effects of Acetazolamide. In a study initiated in France for migraine research 53 patients had been enrolled when the study was prematurely stopped because of a high number of withdrawals (68 %), primarily linked to acetazolamide related side effects. (43)   

Dexamethasone (Decadron)

The steroid drug dexamethasone (Decadron) may help reduce swelling in the brain (cerebral edema). Dexamethasone prevents the inflammatory response to hypoxia in the mesenteric microcirculation and suggests that its effect on AMS may be due to its anti-inflammatory properties. (27) 


100% Oxygen also reduces the effects of altitude sickness. Supplemental oxygen is thought to work by decreasing the hypoxic drive and thus attenuating the hyperventilatory response to a change in PaCO2. (49) Oxygen is effective against high-altitude periodic breathing and improves the sleep architecture. Any patient with central sleep apnea and significant hypoxemia is a potential candidate for a trial with supplemental oxygen. 50) 

Hyperbaric Chambers 

The Gamow Bag has revolutionized field treatment of altitude sickness. The bag is composed of a sealed chamber with a pump. The casualty is placed inside the bag and it is inflated by pumping it full of air effectively increasing the concentration of oxygen and therefore simulating a descent to lower altitude. 

In as little as 10 minutes the bag can create an "atmosphere" that corresponds to that at (3,000 to 5,000 feet) lower.  (28)

High Altitude CPAP 

In one study continuous positive air pressure (CPAP) was used at high altitude in the wilderness environment. CPAP was effectively delivered. Peripheral oxygen saturation (SpO2) was significantly increased. The subject with HAPE improved dramatically with CPAP. This device may offer a practical, drug-free solution for treating high altitude illness.  (45)

Ibuprofen which is effective in relieving altitude induced headache. (600mg three times a day). 

Nifedipine: This drug is usually used to treat high blood pressure. It rapidly decreases pulmonary artery pressure and also seems able to decrease the narrowing in the pulmonary artery caused by low oxygen levels, thereby improving oxygen transfer. The dosage is 20mg of long acting Nifedipine, six to eight hourly. Nifedipine can cause a sudden lowering of blood pressure so the patient has to be warned to get up slowly from a sitting or reclining position. 

Viagra. Sildenafil (Viagra) and other phosphodiesterase-5 inhibitors prevent the breakdown of nitric oxide and cause a marked rise in nitric oxide concentrations in the lungs. Sildenafil (40mg every eight hours) reduces pulmonary artery pressures and increases arterial oxygen saturation in healthy volunteers. Pulmonary artery pressure seen in HAPE may be directly connected to the sharp fall in nitric oxide production that is commonly seen in HAPE susceptible volunteers. At high altitude, levels of nitric oxide fall in all of us. (29)  

Ginkgo biloba was used in three studies, and shown to reduce AMS from 35 to 100%. It may be more effective during a moderate rate of ascent. The dose is 100 mg by mouth twice a day starting 2 to 3 days before and while at altitude. It is safe and inexpensive, but it has not been proven effective in all studies. (3)

Hypobaric Preventative Treatment: 

Colorado Altitude Training Institute (CAT) (30) CAT's systems duplicate the lower oxygen pressure found at high altitude by lowering the % of oxygen in the air. For example, a CAT system will reduce the oxygen content to 15.2% to simulate 9,000 feet at sea level. Whether up a mountain, in a hypobaric chamber, or in a CAT system, the number of oxygen molecules inspired per breath, and consequently the physiological effects, are the same. Effectively a person can acclimatize at lower altitudes before entering the high country.



Most cases are mild, and symptoms improve promptly with a return to lower altitude. Severe cases may result in death due to respiratory distress or brain swelling. In remote locations, emergency evacuation may not be possible, or treatment may be delayed. These conditions could adversely affect the outcome. 

Possible Complications:           


High altitude cerebral edema (brain swelling)  

Pulmonary edema  



High Altitude Periodic Breathing and Central Sleep Apnea 

The sleep conditions of central sleep apnea and high altitude periodic breathing are similar. Sleep disorders at high altitude are common and well-known for centuries. High altitude periodic breathing while sleeping (HAPB) has a similar breathing pattern to Cheyne-Stokes Respiration (CSR) which occurs in central sleep apnea (CSA). At higher altitudes frequent arousals cause total sleep deprivation and mental and physical impairment of the victim. (41) 


Central sleep apnea is caused by a problem with the control of breathing in the brain stem. Normally, the brain stem is very sensitive to changes in the blood level of carbon dioxide (a by-product of metabolism). When levels are high, the brain stem signals the respiratory muscles to breathe harder and faster to remove carbon dioxide through exhalation, and vice versa. In central sleep apnea, the brain stem is less sensitive to changes in the carbon dioxide level. The brain stem responds slowly to the removal of carbon dioxide from the blood, the body's response—a pause in breathing—is prolonged. People who have heart failure or severe brain disease, such as a stroke that affects the brain stem, may have CSR during central sleep apnea. (41)


If a reversible cause is present, treatment improves central sleep apnea. For example, descending to a low altitude is effective in treating high-altitude periodic breathing in AMS.   Lateral position attenuates severity of CSA-CSR. This effect is independent of postural effects on the upper airway and is likely to be due to changes in pulmonary oxygen stores. (41)


Treatment for Central Sleep Apnea at Sea Level 


Acetazolamide has some benefit for central sleep apnea, at sea level as well as high altitude. 

Continuous Positive Air Pressure (CPAP) 

Some people with central sleep apnea may benefit from Positive Air Pressure (PAP): Both CPAP and bi-level PAP have been used to treat central sleep apnea syndrome. Bi-level PAP: This is effective for treating patients with hypercapnic central sleep apnea (associated with hypoventilation syndrome). The inspiratory positive airway pressure (IPAP) is higher than the expiratory positive airway pressure (EPAP). The degree of IPAP-to-EPAP differential provides pressure support to augment ventilation. Bi-level PAP: (48) 


Supplemental oxygen is thought to work by decreasing the hypoxic drive and thus attenuating the hyperventilatory response to a change in PaCO2. Oxygen may be effective in some patients with Cheyene Stokes Breathing Central Apnea CSB-CSA due to heart failure. Oxygen is effective against high-altitude periodic breathing and improves the sleep architecture.  (43) The treatment modalities for both HAPB and CSA appear to be similar.  

Oral Appliance Therapy  

Oral appliance therapy utilizing a mandibular advancement device has been shown to successfully treat sleep disordered breathing in patients with congestive heart failure (CHF) [and central sleep apnea]. (47)  


Oral Appliance Therapy for Sleep Breathing Disorders  

Oral appliances have been shown to alleviate the severity of respiratory disturbances during sleep by about 60 percent, with an overall acceptance rate of 75 percent. The long-term complications generally are minor and are related to occlusal changes and temporomandibular joint discomfort.   


With the advent of oral appliances, dentists are increasingly involved in managing the care of patients with sleep-related breathing disorders. Breathing disorders during sleep can cause significant health problems that are associated with a high morbidity and a high risk of mortality. 


In a Swedish study a mandibular advancement device reduces sleep disordered breathing (SDB) in patients with congestive heart failure (CHF) [and central sleep apnea]. the MAD intervention may be a feasible method for reducing SDB in patients with stable, mild to moderate CHF. However, because the treatment of SDB is important in the management of CHF, the MAD intervention seems to be a valuable method in the treatment arsenal of SDB. In patients with stable CHF who are experiencing problems with sleep breathing disorders, MAD intervention appears to reduce the severity of SBD, sleep apnea-related symptoms. (47)  


Oral mandibular advancement devices (MAD) have been shown to be effective in the treatment of CSA and CSB and therefore should be also effective in treating HAPB during sleep and attenuate or eliminate AMS. Furthermore, the condition of Obstructive Sleep Apnea (OSA) leads to arousals, which leads to hyperventilation, which leads to hypocapnia, which leads to a decreased respiratory drive, which leads to CSA. So, if the airway can be opened more, especially at high altitude, any airway obstructive effect will be lessened with a MAD, and you can then lessen the likelihood of CSA manifestation. This should help with AMS symptoms. More oxygen equals fewer problems. (19) Any airway increase should help with AMS and a MAD does that.


Clinical Trail Use of Oral Appliance Therapy for AMS  

Limited non clinical trails have shown a modified mandibular advancement oral appliance (MAD) to be effective in the prevention and treatment of AMS. The appliance was used only for night time sleeping. 

This author and the subject using the trial appliance had a 10 year plus experience of AMS treated with acetazolamide successfully. However, the drug’s many side effects and sometimes short stay at high altitude mad an alternative very desirable. Some of the side effects of Diamox included the following: numbness, tingling, or vibrating sensations in hands, feet, and lips. Paresthesia and other taste alterations, increased urination and ringing in the ears. (51). Other less frequent side effects include: dizziness, nausea and vomiting, drowsiness, sulfonamide allergy, and headache. Confusion and rashes have all been reported but are unusual. It makes many people feel a little "off color". Exceptionally the drug has caused more serious problems with blood formation and/or the kidney. A few trekkers have had extreme visual blurring after taking only one or two doses of acetazolamide (49) Carbonated drinks including sodas and beer taste very strange when you are taking Diamox

In the study mentioned earlier 68% of the test subject withdrew due to the side effects of acetazolamide. So any treatment to avoid medication is desirable. For those spending only a short time at altitude you want to enjoy the mountains as soon as possible without the annoying Diamox side effects.  

A modified oral appliance was tested to determine if it would act in a similar fashion to that seen at sea level conditions to treat sleep apnea and simple snoring. By using a modified MAD at an altitude of 9800 feet the AMS symptoms were reduced or eliminated without the use of acetazolamide medication. The severe debilitating headache previously seen was eliminated on one occasion and minimized on the other. The only drugs used were ibuprofen 300 mg at night. The breathing difficulty on exertion was reduced. Notes were kept using the Lake Louise Scale of self analysis.                                                                                                                                                       


It is postulated herein that Oral Appliance Therapy (OAT) can be used to treat the HAPB associated with AMS and improve the symptoms. Modifying the night time breathing pattern can help eliminate or reduce the multiple symptoms of AMS and hasten acclimatization. Since the airway is opened further with the use of the modified appliance, the access to oxygen is increased and the periodic breathing cycle is modified or eliminated. OAT has been shown to be effective in treating obstructive sleep apnea and central sleep apnea and its similar night time use at altitude of 9800 feet has been effective.  


In a normal healthy person at altitude the periodic breathing conditions of AMS are not associated with congestive heart failure or severe brain disease, such as a stroke that affects the brain stem. As stated previously, oxygen is effective against high-altitude periodic breathing and improves the sleep architecture. It is further suggested that the oral appliance will increase the oxygen saturation as it does at lower altitudes and thereby decrease the AMS symptoms and pathology.  


The use of a modified mandibular advancement oral appliance to treat or attenuate the symptoms of acute mountain sickness has been shown to be successful on a limited trial basis and its use and further study is recommended.  


It is recommended that the OAT be used at night only for a period of 2-5 days during the usual acclimatization process. This minimizes the possibility of TMJ or other side effects. Other high altitude preventative measures should be included as usual. Further scientific studies should show the night time use of this appliance to be similarly effective for the periodic breathing pathology associated with AMS as the OAT is for central sleep apnea at lower altitudes. 


Epidemiology and Therapeutic implications 

The dangers or high altitude illnesses of the most sever nature can occur in the un aware traveler as evidenced from the following publications: 

DENVER (AP) - Colorado's high-country altitudes are hard on tourists' hearts, killing a disproportionate number of visitors in their 20s, 30s, 40s and 50s with undetected cardiac conditions, several coroners say.  (52)  

"People come here from low altitudes with undiagnosed heart problems - descending coronary arteries or valve problems. The altitude causes more stress on the heart," said Joanne Richardson, coroner for Summit County, home to Keystone, Breckenridge and Copper Mountain ski resorts. Since Friday, three skiers have died on Colorado slopes. Heart failure claimed a 51-year-old Illinois man and a 77-year-old Leadville man. Monday, a 22-year-old East Coast man collapsed on Copper Mountain, but cause of death is still unknown.  

In Gunnison County, home of 12,000-foot-high Mount Crested Butte, almost half the 23 deaths coroner Frank Vader investigated last year were tourists. Thirteen involved the heart and probably 10 of those were altitude-related, he said. Vader said in almost all cases there was some pre-existing heart problem, usually undetected.  

In Summit County in the past 10 years, 21 people under 40 have died of acute heart failure, said Richardson, a paramedic for 20 years before she became coroner. Last year, a 21-year-old and a 30-year-old from out of state died of heart-related  

Eagle County, home of Vail and Beaver Creek ski resorts, has had four heart attack deaths since January, three of them out-of-staters, said coroner Kara Bettis. The previous two years, 13 people from out of state had fatal heart attacks while visiting Eagle County. "These are people who didn't know they had a heart condition - skiing, hiking, getting to the top of a trail and dying of a heart attack," said Bettis. (53) 

In Chaffee County, which boasts the 14,000-foot Collegiate Peaks, coroner Randal Amettis said altitude-related deaths range from two to 10 annually. 

The risks of high altitude mountain illness are real and serious. 

There are large numbers of high altitude visitors to Colorado each year as reported by various businesses. Colorado Reports 11.2 million Ski Visitors in 2003-04, International Ski Visitors up 10% from Hotels Online (54) <javascript>New state tourism report notes record numbers as reported byHarriet Hamilton in the
summit daily news in Frisco Colorado. Overall statewide numbers broke records with 28 million Americans making overnight visits to Colorado in 2007, up from 26.9 million in 2006.Summit daily news 5



There are over 28 million visitors to Colorado alone each year. Most of those will visit the high altitude areas. Almost everyone at an altitude of 8000 feet will experience some form of altitude distress from mild to severe. It is estimated that at least 20 million high altitude visitors in Colorado alone can benefit from this oral appliance. It is postulated here that a modified mandibular advancement oral appliance can help the majority of those sufferers and minimize the use of medications. 


by  - MDW

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