Airway & Respiratory

Treating Sickness & Edema Caused by High Altitude

Issue 6 and Volume 41.

LEARNING Objectives

  • Understand the body’s physiologic response to altitude.
  • Recognize which drugs to use for prevention and treatment of altitude sickness.
  • Differentiate treatments for AMS, HAPE and HACE.

KEY Terms

  • Dalton’s law: The total pressure exerted by a gas mixture is the sum of the individual pressures that created the given volume or gas mixture.
  • High altitude cerebral edema: Neurological impairment that develops during ascent to altitudes above 8,000 feet in otherwise healthy but unacclimatized subjects.
  • High altitude pulmonary edema: Respiratory difficulty that develops during ascent to altitudes above 8,000 feet in otherwise healthy but unacclimatized subjects.
  • Periodic breathing: An abnormal pattern of respiration characterized by alternating periods of apnea and deep, rapid breathing.

It’s October—a call comes in for your helicopter EMS crew for a patient with dyspnea. Per a friend’s report, the patient has had a cough and hasn’t been feeling well for the last few days, and today he seems less alert. They’re located in a remote section of a nearby national forest about 60 minutes of flight time away.

Dispatch provides more information en route: The patient is a 32-year-old male. He’s been hunting elk the last two days at an elevation of nearly 10,000 feet (3,048 m). His friend says he takes no medication daily and has no known medical conditions. He’s been complaining about gradually worsening shortness of breath since they arrived in camp. Now he has a productive cough but no fever. He has labored breathing and seems increasingly sleepy.

On arrival, you find a mid-30s-appearing male in obvious respiratory distress and altered mental status. He’s markedly cyanotic and is frequently coughing, producing a large amount of frothy pinkish sputum. Every time you try to lay him flat he becomes combative. His finger pulse oximeter reads 58% with a good waveform, he has a respiratory rate in the 40s with 2-3 word dyspnea, and his pulse is 125 at rest. He tolerates a non-rebreather face mask, so you start oxygen at 15 Lpm.

He’s confused and not oriented to place or situation, but he recognizes his friend and intermittently follows simple commands. However, he easily becomes combative and asks to be left alone. His lungs have diffuse rales with decreased aeration in the bases. His heart exam is tachycardic without murmur. Abdomen is moderately obese but soft and non-tender. Extremities show no signs of injury, infection or edema.

Additional information from the friend reveals no history of illicit drug use. He reports a shot of peppermint schnapps for breakfast the last two days and a few drinks every night. His friend says the patient was unable to hunt yesterday because he was so short of breath he couldn’t walk more than 50 feet before needing to stop and rest. He states they’re from the Midwest where the elevation is 1,000 feet (304 m). This is his friend’s first trip to the West and his first time at higher/greater elevation.

After oxygen administration, the patient is more alert and his oxygen saturation climbs to 85%. His vitals also include a pulse of 115, blood pressure of 155/90 and temp of 36.6 degrees C (97.9 degrees F). He insists on sitting upright. You immediately begin transport to the hospital and start the patient on continuous positive airway pressure (CPAP). The CPAP nearly instantaneously improves his pulse oximetry reading to normal.

Getting High

Altitude illness generally occurs at elevations above 8,000 feet.1 The condition has a genetic component as well as some degree of variable individual exposure based on underlying medical conditions and fitness level.2Acute mountain sickness (AMS) becomes more prevalent as altitude increases and is the most common form of altitude illness. AMS symptoms include headache, general malaise, decreased appetite, fatigue, nausea and vomiting.

Periodic breathing is an altitude-related condition that causes irregular breathing most noticed during periods of sleep. Periodic breathing is thought to be due to the interaction between the feedback mechanisms of the body regulating normal oxygen, carbon dioxide and acid-base balance. Irregular breathing patterns can lead to difficulty sleeping and well as causing concerns to companions due to periods of apnea followed by heavy, deep breathing. Although disconcerting, it’s felt that periodic breathing isn’t life threatening.3

Usually, AMS and periodic breathing are self-limiting as the body acclimates to altitude. However, if the body continues a maladaptive response to the altitude, then life-threatening conditions of high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE) can occur.

EMS treatment of altitude sickness

If descent isn’t possible due to weather or other factors, a portable hyperbaric chamber can be used, which can simulate about 5,000 feet of descent. Photo Heather Shannon

HACE usually occurs at altitudes above 13,123 feet (4,000 m) and often has very similar symptoms to AMS initially.1 However, a lack of coordination (ataxia) is a hallmark of HACE and not usually seen in AMS. In the natural course of HACE, coma and death follow lethargy if not treated (ideally with descent). It’s possible to have both HAPE and HACE occur simultaneously. Approximately 1-3% of individuals will experience both these severe forms of altitude illness.3 As with AMS, risk for HACE and HAPE increases if there’s no acclimatization process, and as altitude increases.1,4HAPE is characterized by gradually worsening shortness of breath and increasing cough, leading to hypoxia and possibly death if not reversed. The cough often progresses from dry to wet sounding and produces usually white, then progressively more pink, frothy sputum. The associated shortness of breath severely limits the patient’s ability to carry out any activity.

Physiology

To understand altitude illness, one must have a basic understanding of the body’s physiologic response to altitude and its acid-base system. When one ascends in altitude, the amount of oxygen molecules available (partial pressure of oxygen) decreases as the total air pressure decreases, as described in physics by Dalton’s law. This leads to a conflict in the respiratory system. As the oxygen content (PaO2) and consequently the oxygen saturation (SpO2) in the arterial blood drops, the brain tells the body to breathe faster. When the body breathes faster, the carbon dioxide (PaCO2) content also decreases. As CO2 is blown off by increased minute ventilation due to increased respiratory rate, the blood becomes alkalotic within minutes. This causes the kidneys to begin to excrete bicarbonate. As bicarbonate is removed by the kidneys, the acid-base balance is restored. However, it takes the kidneys days to significantly change the amount of bicarbonate in the blood. As the body becomes acclimatized to altitude over a few days, the SpO2 and PaO2 gradually increase. Because oxygen moves into the blood by going from high concentration to lower concentration, the amount of PaO2 is always slightly less than the amount of oxygen in the alveoli of the lungs. Thus, at altitude where the partial pressure of oxygen in ambient air is less than at sea level, the PaO2 and SpO2 will not be normal.

EMS treatment of altitude sickness

Oxygen can help treat all forms of altitude sickness, but generally isn’t able to be carried in significant quantities at high altitudes. Photo WMI files

This decrease in PaO2 has another direct physiologic effect on the blood vessels of the lungs: It causes vasoconstriction. This physiologic condition is a remnant of the fetal circulatory system. The fetal alveoli are full of fluid and consequently are in an oxygen-poor environment. The vasoconstricted state of the fetal pulmonary vasculature shuts blood away from the lungs. When the newborn takes its first breaths, the alveoli are suddenly in an oxygen-rich environment and the pulmonary vasculature converts from its non-aerated, high vasoconstriction state to the aerated, low vasoconstriction state.

All humans show some degree of pulmonary vasoconstriction in low-oxygen environments, but individual sensitivity to decreased alveolar oxygen concentrations varies widely.2 The decrease in diameter of the pulmonary vasculature causes an increase in the resistance. Consequently, the right ventricle pumps at greater pressure to overcome this increased vascular resistance. Increased blood pressure results in greater pressure exerted by the blood on capillary walls (i.e., hydrostatic pressure), increasing the amount of fluid pushed out of the blood vessels. In some individuals, this vasoconstriction can occur unevenly and cause further injury in some areas.

If the increased amount of fluid pushed out of the blood vessels exceeds the pull of fluid back in by the proteins and other solids dissolved in the blood (i.e., oncotic pressure), edema results. Like edema from other causes, fluid in the alveolar space interferes with the ability of oxygen to diffuse into the blood, resulting in hypoxia.

Cerebral edema occurs by similar mechanism (i.e., hydrostatic pressure exceeds oncotic pressure), but the cause is related to low PaCO2, not low PaO2. In the brain, low amounts of CO2 in the blood cause vasoconstriction. Hypoxia from the increase in altitude leads to hyperventilation. This hyperventilation significantly lowers PaCO2. In certain individuals, this decrease in PaCO2 will result in cerebral edema. If this edema becomes severe enough, it will cause coma and then death.

Prevention

Prevention of AMS, HAPE and HACE share some common themes and medications. Both individual predisposition and the speed of ascent can alter the risk for altitude illness.4 A slow ascent gives time for the body to acclimate. Expert consensus is an ascent in altitude of no more than 1,604 vertical feet (500 m) per day at elevations above 8,202 feet (2,500 m).1,4 The first camp should be below 9,843 feet (3,000 m).1 And, the first day at altitude for those who live below 4,921 feet (1,500 m) should be spent at rest.1

It’s best if activity takes place at higher elevations during the day and the individual goes to a lower elevation to sleep at night.1,3-5 At extreme altitude, above 18,045 feet (5,500 m), the body’s ability to acclimatize is exceeded by the demand of the environment.1

Proper nutrition may also help prevent or limit altitude illness symptoms.5 A high-carbohydrate diet is recommended over a high-protein or high-fat diet. Keeping well hydrated is also important. Fluid should be consumed to maintain a clear urine output. Forced or over-hydration isn’t recommended.1,5

Oxygen is helpful in preventing AMS, HACE and HAPE, but is usually unavailable in the quantities needed. Oxygen directly prevents or treats altitude illness by increasing alveolar oxygen concentration. This leads to a reduction in pulmonary hypertension and thus pulmonary edema. For prevention, it’s administered by nasal cannula at 0.5-2 Lpm. Low-flow long duration is more effective than high-flow short duration therapy. 1, 3-5

Medications for prevention of high altitude illness are generally only indicated for those who have had HACE or HAPE before, or those who are forced to go rapidly from low elevation to high elevation.1,4,5 Acetazolamide and dexamethasone are the mainstays, but ibuprofen, nifedipine, salmeterol, sildenafil and tadalafil are also used. (See sidebar below.)

Treatment

AMS usually requires no specific treatment. It does require that ascent is stopped until symptoms resolve. This normally takes 12-72 hours. Occasionally, descending 1,640 feet (500 m) to 3,281 feet (1,000 m) is required if symptoms continue to worsen or are severe.1,5

Ensuring proper hydration is essential. Vomiting is a clear impediment to this goal, not to mention unpleasant in and of itself. Vomiting can be treated with ondansetron (Zofran) 4-8 mg sublingual every 12 hours; promethazine 25 mg by mouth or rectal suppository every six hours; or prochlorperazine 10 mg by mouth or rectal suppository every six hours.

AMS-associated headache frequently improves with hydration and over-the-counter aspirin, acetaminophen or ibuprofen. Periodic breathing is treated with 62.5-125 mg of acetazolamide by mouth before going to sleep. 1, 3-5

Treatment for HAPE involves treating the underlying pulmonary hypertension. This is most definitively accomplished by descent. Symptomatic individuals should descend 1,640 feet (500 m) to 3,281 feet (1,000 m). Descent should continue until symptoms are gone or medical care is reached. Additional treatments for HAPE include oxygen titrated to an SpO2 of 90% (often this requires 4-6 Lpm of oxygen, which makes this treatment unrealistic in most settings outside of established health care facilities1, 3-5), nifedipine, salmeterol, sildenafil and tadalafil. (See sidebar below.)

If descent isn’t possible due to weather or other factors, a portable hyperbaric chamber can be used. Most portable hyperbaric chambers simulate about 5,000 feet of descent. Usually, they’re used for 50 minutes of treatment with a 10-minute break for 6-8 hours at a time. However, they require constant pumping to maintain pressure and to prevent CO2 build up from the breathing patient.1,3-5

As noted earlier, HACE usually occurs at higher elevations compared to AMS or HAPE.1 Some of the first symptoms, like headache or irritability, can be rather nonspecific. Changes in motor coordination or level of alertness are harbingers of more severe illness. For instance, a person who’s unable to walk a straight line heel to toe requires immediate treatment.1 HACE treatment shares some commonalities with HAPE.

Descent is the most important. If the symptoms are mild, descending to a previous asymptotic altitude is reasonable. Often this requires at least 3,000 feet (914 m) of descent. Those with severe symptoms should descend to an altitude of 5,000 feet (1,524 m) or less.1 Definitive medical care is indicated for all patients with severe symptoms.

If available, supplemental oxygen titrated to a pulse oximetry of 90% is indicated, as well as dexamethasone or a portable hyperbaric chamber.

Conclusion

Descent is the common treatment for all altitude illness. Under no circumstance should someone suffering from altitude illness be allowed to descend alone. Some patients may be incapacitated to the point that they’re unable to evacuate themselves. These patients should be carried or otherwise moved to a lower elevation and medical care sought without delay.

References

1. Auerbach P, editor: Medicine for the outdoors: The essential guide to first aid and medical emergencies. Elsevier: Philadelphia, pp. 306-315, 2016.

2. Reeves J, Grover R, editors: Attitudes on altitude: Pioneers of medical research in Colorado’s high mountains. University Press of Colorado: Boulder, Colo., pp.161-192, 2001.

3. Hudson S, Smith W, Schlim D, et al: Expedition and wilderness medicine. In Zuckerman J, Brunette G, Leggat P (Eds.), Essential travel medicine. John Wiley & Sons, Ltd.: Chichester, U.K., pp. 257-278, 2015.

4. Luks AM, Mcintosh SE, Grissom CK, et al. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness Environ Med. 2014;25(4 Suppl):S4-S14.

5. Forgey W, editor: Wilderness Medical Society practice guidelines for wilderness emergency care. Falcon Guide: Guilford, Conn., pp. 46-53, 2006.


Drugs for Prevention & Treatment of HAPE & HACE

Acetazolamide is a diuretic medication that causes the kidneys to waste bicarbonate. This allows the body to acclimatize faster, thus achieving better oxygenation. Ideally, it’s started 24 hours prior to ascent at a dose of 125 mg by mouth every 12 hours. It should be used with caution in those with an allergy to sulfa drugs. Since it’s a diuretic, it’s that much more important to maintain appropriate fluid intake. Acetazolamide should be continued for two days after descent.1, 3-5

Dexamethasone is a steroidal anti-inflammatory drug. It’s indicated for those who must take a preventative medication and can’t take acetazolamide. For prevention, it’s dosed at 4 mg by mouth every 12 hours and should be started at least four hours, but ideally 24 hours, before ascent. It shouldn’t be taken for more than 48 hours due to its suppression of the adrenal axis, nor should it be discontinued at altitude due to the risk of rebound altitude illness. For this reason, many state that this should only be used on the summit day or for treatment once symptoms develop and immediate descent is planned. For HACE treatment, it’s used for cerebral swelling. The initial dose is 8 mg followed by 4 mg every six hours while descending.1, 3-5

Ibuprofen is a nonsteroidal anti-inflammatory drug. It’s been shown to decrease the incidence of AMS when taken 600 mg by mouth every eight hours. It’s generally started at least six hours prior to ascent. This medication is somewhat controversial because it can treat one of the symptoms of AMS- headache-which may cause an individual to continue to ascend when in fact they should stop or even descend.1,5

Nifedipine is a calcium channel-blocking antihypertensive. It’s useful in helping to prevent HAPE in those with a prior history. It works to prevent pulmonary hypertension. The recommended dose is 30-60 mg extended release by mouth per day. Because nifedipine is an antihypertensive medication, hypotension is possible but is rare with extended release formulations, and in generally healthy individuals.1, 3-5

Salmeterol is a long-acting inhaled beta-2 agonist. It causes bronchodilation and decreased pulmonary secretions and is dosed at 125 micrograms inhaled every 12 hours. As this is three times the normal dose for asthma treatment, systemic side effects like tachycardia and tremor can occur. It should only be used with other medications.1, 3-5

Sildenafil and tadalafil are both medications that enhance the vasodilatory effects of nitric oxide, which leads to decreased pulmonary artery pressure. Sildenafil is given 50 mg by mouth every eight hours and tadalafil is given 10 mg by mouth every 12 hours.1, 3-5