Introduction

The three illnesses associated with an ascent to altitudes 8,000 ft (high altitude) or more above sea level include:

• Acute mountain sickness (AMS)
• High-altitude cerebral edema (HACE)
• High-altitude pulmonary edema (HAPE)

These represent a spectrum of diseases with similar pathophysiology but increasing severity. Successful treatment of these conditions requires accurate recognition and prompt response.  The Wilderness Medical Society (WMS) publishes regularly updated evidence-based guidelines for treatment.[1] This article summarizes the guidelines in a way that is helpful for first responders and medical personnel responding to these high-altitude emergencies.

Issues of Concern

Diagnosis and treatment of high-altitude illnesses present several unique challenges. First, modern technology makes it possible, even for inexperienced climbers, to travel from sea level to high altitude in a short duration of time. Such rapidity of ascent generally makes acclimatization difficult. Furthermore, untrained climbers could have comorbidities that might mimic, mask, or aggravate symptoms of high-altitude illness. Moreover, common travel-related illnesses, such as dehydration and infections such as pneumonia or food poisoning, could co-exist, further confounding the clinical picture. Such challenges could be overcome by a thorough understanding of the signs, symptoms, and pathophysiology of high-altitude illnesses, as described below.[2]

Clinical Significance

At higher altitudes, there is a decrease in atmospheric pressure. This situation causes the partial pressure of inspired oxygen to decrease. Decreased partial pressures decrease the driving pressure for gaseous exchange in the lungs, leading to hypoxemia.  In response to this hypoxemia, the human body makes several physiologic changes to adapt to the new normal.  This process is known as acclimatization. Very rapid ascent, intrinsic poor hypoxic ventilatory response, and low vital capacity lead to inadequate acclimatization. The symptoms resulting from this mostly manifest at altitudes greater than 8,000 feet, which is the reason why altitudes greater than 8,000 ft are known as "high altitude."[3]  (Commercial airliners maintain cabin pressures below 8,000 ft for preventing altitude illness amongst the passengers and crew.)  

Acute Mountain Sickness (AMS) AMS is the most benign of the three altitude illnesses but must be recognized early because it has the potential to progress to life-threatening High Altitude Cerebral Edema (HACE). About 25% of all travelers ascending to above 11,500 ft will experience AMS.[4]  A previous history of AMS is a risk factor for future episodes and, therefore, an indication for precaution.

AMS Diagnosis: Headache plus one other symptom

The typical history for AMS is that of a low altitude dweller traveling to and exerting himself at high altitudes (most often above 8,000 ft).[5] It is diagnosed clinically by the presence of a headache AND at least one of the following symptoms: lack of appetite, nausea, vomiting, insomnia, dizziness, and/or fatigue.  These symptoms will range from mild to incapacitating (Severe AMS).  Symptoms usually begin 6 to 12 hours after traveling to altitude but may manifest sooner at 1 or 2 hours only.  Symptoms are generally self-limiting, lasting 24 to 48 hours.  However, in less than 1% of cases, AMS may progress to become HACE.[6]

AMS Prophylaxis: gradual ascent plus acetazolamide

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.

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[7].  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.[8][9] 

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.  

AMS Treatment: dexamethasone, with or without descent

Dexamethasone (initial 8mg PO, IM, or IV followed in 6 hours by 4mg PO, IM, or IV every 6 hours)

• Dexamethasone is the medication of choice for the treatment of both AMS and HACE. It helps by decreasing vasogenic edema. NSAIDs in appropriate dosages may be added if the headache is debilitating.  If taking dexamethasone for more than ten days, it requires tapering to prevent complications.

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. 

High-Altitude Cerebral Edema (HACE)

HACE is a medical emergency.  If untreated, the patient's condition will rapidly deteriorate, and death may occur within 12 to 24 hours.[10]  A previous history of HACE is a risk factor for future episodes and is an indication to take the proper precautions for prevention.

HACE Diagnosis: AMS plus neurologic symptoms

HACE most often occurs at altitudes above 10,000 ft and is differentiated from AMS by the presence of neurologic symptoms. Ataxia is typically the earliest finding which may progress to lethargy, alteration of mental status, or even seizures. Without treatment, symptoms will rapidly worsen and result in unconsciousness and death. 

Pathophysiology: Hypoxemia at higher altitudes causes dilatation of cerebral vasculature; this results in cerebral edema.

HACE Prophylaxis: gradual ascent plus acetazolamide

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 gained above 10,000 ft and a day of rest every 3 or 4 days. 

Acetazolamide (125mg PO every 12 hours)

• Acetazolamide is the only medication proven to assist with acclimatization to prevent AMS and HACE.  Reference the AMS section above for contraindications and adverse effects of this medication.

HACE Treatment: descent from high altitude, plus dexamethasone, with or without supplemental oxygen, and with or without hyperbaric oxygen therapy (HBOT) by a portable chamber

Descent

• Immediate evacuation to a lower altitude is the definitive treatment for both Severe AMS and HACE. The target altitude for descent depends upon clinical severity and response, but generally, symptoms resolve after 1,000 ft to 3,000 ft drop in altitude. 

Dexamethasone (initial 8mg PO, IM, or IV followed in 6 hours by 4mg PO, IM, or IV every 6 hours)

• Dexamethasone is the medication of choice for the treatment of both AMS and HACE.  It helps by decreasing cerebral edema. In cases of Severe AMS or HACE, dexamethasone should be used in conjunction with evacuation or while waiting for it.  

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.

High-Altitude Pulmonary Edema (HAPE)

HAPE is the most common cause of fatality due to high altitude illness.[11] HAPE is a separate illness from AMS/HACE but often occurs simultaneously, confounding the clinical picture.  

HAPE Diagnosis: dyspnea at rest plus cough/rales/fever

The typical history for HAPE is that of low altitude dwellers traveling to and exerting themselves at altitudes above 8,000 ft.  Symptoms appear between 1-5 days of reaching altitude and begin with dyspnea on exertion and nonproductive cough.  Over the next 24 to 48 hours, the symptoms progress to a productive cough and dyspnea at rest.  Clinical signs include tachycardia, tachypnea, fever, decreased pulse oximeter readings as compared to fellow travelers, and crackles on auscultation of lungs. Without treatment, symptoms will progress rapidly to respiratory arrest and death.

Pathophysiology: Hypoxemia at high altitudes cause pulmonary vasculature to constrict to prevent ventilation-perfusion mismatch. This condition results in pulmonary hypertension and subsequent leakage from lung capillaries, eventually resulting in pulmonary edema. 

HAPE Prophylaxis: gradual ascent plus nifedipine

Gradual Ascent

• The WMS recommends the same ascent profile as noted above for prevention of AMS/HACE, namely: one day of travel for every 1,500 ft gained above 10,000 ft and a day of rest every 3 or 4 days.

Nifedipine (30 mg extended-release PO every 12 hours)

• Preventative treatment using nifedipine is reserved for individuals with a history of HAPE. It helps by decreasing pulmonary hypertension. Dosing begins one day before ascent and is discontinued after four days at the highest point of ascent or beginning of the descent.

HAPE Treatment: descend from high altitude, with or without supplemental oxygen, with or without HBOT using a portable chamber, with or without nifedipine

Descend Altitude

• Evacuation to a lower altitude is the definitive treatment for HAPE. Descent goal is at least 1,000 ft but may require further descent until symptoms resolve. Additional exercise will worsen HAPE, so care should be taken to assist the patient in limiting exertion during descent.

Supplemental Oxygen

• If available, supplemental oxygen should be administered with saturations of above 90% as a goal. Supplemental oxygen should be used in conjunction with evacuation or while waiting for it.

Portable Hyperbaric Chamber

• Portable chambers are indicated for the treatment of HAPE as a temporary measure 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 makes this a resource-intensive treatment but has the potential to save lives in remote areas where evacuation may be delayed.

Nifedipine (30 mg extended-release PO every 12 hours)

• Nifedipine should only be used as a treatment option when evacuation becomes delayed or unavailable.

Conclusion

Medical providers armed with the knowledge of prevention, diagnosis, and treatment of high-altitude illness shall be well-prepared for assisting with trip planning, and prevention, response, and treatment of patients who travel to high-altitudes. The guidelines referenced in this article are a subject of ongoing research. The Wilderness Medical Society provides guidance on high altitude medicine, which is updated regularly.[1]