Introduction

Travel to elevations above 2500 meters/8200 feet is associated with risk of developing one or more forms of acute altitude illness: acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). Although unacclimatized individuals are at risk of high altitude illness when ascending to altitudes above 2500 m/8200 ft, it is not unknown to see altitude illness present at lower elevations due to a high degree of variability in responses to high altitude between individuals.

To provide guidance to clinicians and disseminate knowledge about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute altitude illness. Preventive and therapeutic modalities are presented, and recommendations made for each form of acute altitude illness.

Full text: wemjournal.org/article/S1080-6032(19)30090-0/fulltext

Acute Mountain Sickness and High Altitude Cerebral Edema

From a clinical standpoint, HACE represents an extremely severe form of AMS; therefore, preventive and treatment measures for the two disorders can be addressed simultaneously.

Prevention

Suggested Approach: The approach to prevention of AMS and HACE should be a function of the risk profile of the individual traveling to high altitude (Table 1). The first priority should be ensuring gradual ascent to the target elevation. Travelers can lower their risk by sleeping one night at an intermediate altitude. For example, sea level residents traveling to Colorado resort areas over 2800 m/8200 ft can spend one night in Denver (1600 m/5200 ft.) If travelers are unable to ascend gradually due to various logistical factors, pharmacologic prophylaxis can be considered. Prophylactic medications are generally not necessary in low risk situations but should be considered in addition to gradual ascent for use in moderate to high-risk situations (Table 1). With travel above 3000 m/9800 ft, individuals should not increase the sleeping elevation by more than 500 m/1600 ft per day and should include a rest day (i.e. no ascent to higher sleeping elevation) every 3-4 days.

Table 1. Risk Categories for Acute Mountain Sickness

Risk Category Description

Low

• Individuals with no prior history of altitude illness and ascending to ≤ 2800 m;
• Individuals taking ≥ 2 d to arrive at 2500-3000 m with subsequent increases in sleeping elevation < 500 m•d-1and an extra day for acclimatization every 1000 m

Moderate

• Individuals with prior history of AMS and ascending to 2500-2800 m in 1 d
• No history of AMS and ascending to > 2800 m in 1 d
• All individuals ascending > 500 m•d-1 (increase in sleeping elevation) at altitudes above 3000 m but with an extra day for acclimatization every 1000 m

High

• Individuals with a history of AMS and ascending to > 2800 m in 1 d
• All individuals with a prior history of HACE or HAPE
• All individuals ascending to > 3500 m in 1 d
• All individuals ascending > 500 m•d-1 (increase in sleeping elevation) above > 3000 m without extra days for acclimatization
• Very rapid ascents (eg. < 7 d ascents of Mt. Kilimanjaro)

AMS: Acute mountain sickness; HACE: High altitude cerebral edema; HAPE: High altitude pulmonary edema

Notes:

• Altitudes listed in the table refer to the altitude at which the person sleeps
• Ascent is assumed to start from elevations < 1200 m
• The risk categories described above pertain to unacclimatized individuals

Gradual Ascent: Controlling the rate of ascent, in terms of the number of meters/feet gained per day, is a highly effective means of preventing acute altitude illness. In planning the rate of ascent, the altitude at which someone sleeps is considered more important than the altitude reached during waking hours.

Acetazolamide: Acetazolamide has an established role in prevention of AMS. There is a risk, albeit extremely low, of inciting an allergic reaction in persons with sulfonamide allergy when taking acetazolamide. Also, any prior anaphylactic reaction to a sulfonamide medication or a history of Stevens-Johnson syndrome should be considered a contraindication to acetazolamide. The recommended dosing is shown in Table 2. Acetazolamide should be started the day before ascent but will still have beneficial effects if started on the day of ascent.

Dexamethasone: Dexamethasone does not facilitate acclimatization like acetazolamide, but it has an established benefit in AMS prevention. The recommended adult doses (Table 2) may be considered in very high risk situations such as military or search and rescue personnel being airlifted to altitudes > 3500 m/11,500 ft with immediate performance of physical activity, but should not be used except in these limited circumstances. Since prolonged dexamethasone use carries a risk of adrenal suppression, if used for longer than 10 days, the medication should be tapered over a one week period rather than stopped abruptly. Dexamethasone is not recommended for AMS prevention in children. Dexamethasone should be started the day before ascent but will still have beneficial effects if started on the day of ascent.

Ibuprofen: Ibuprofen cannot be recommended over acetazolamide or dexamethasone for AMS prevention during rapid ascent (Table 2).

Staged Ascent and Preacclimatization: Because the optimal methods for preacclimatization (i.e., repeated exposures to hypoxia preceding high altitude travel) and staged ascent have not been fully determined, the panel recommends consideration of these approaches but does not endorse a particular protocol as a means of AMS prevention. And in the case of normobaric hypoxia exposure in a hypoxic tent, only sufficiently long exposures (> 8 hours per day) that can be undertaken regularly over an appropriate number of weeks are likely to offer any significant preacclimatization benefit.

Other Options: The following interventions have not been shown to be of benefit: chewed coca leaves, coca tea and other coca-derived products; “forced” or “over” hydration; short-term oxygen use in the form of either visits to oxygen bars or over-the-counter oxygen delivery systems by which individuals inhale oxygen-enriched gas from a small pre-filled canister; other over-the-counter products, such as the powdered drink mixes.

Table 2. Recommended Dosages for Medications Used in the Prevention and Treatment of Altitude Illness

Medication Indication Route Dosage

  AMS, HACE Prevention Oral -125 mg every 12 h1

  -Pediatrics: 2.5 mg•kg-1 every 12 h

Acetazolamide

  AMS Treatment2 Oral -250 mg every 12 h

-Pediatrics: 2.5 mg•kg-1 every 12 h (maximum: 125 mg per dose)

  AMS, HACE Prevention Oral -2 mg every 6 h or 4 mg every 12 h 1

-Pediatrics: Should not be used for prophylaxis

Dexamethasone AMS, HACE Treatment Oral, IV, IM -AMS: 4 mg every 6 h

-HACE: 8 mg once then 4 mg every 6 h

-Pediatrics: 0.15 mg•kg-1•dose-1 every 6 h (Maximum: 4 mg per dose)

Ibuprofen AMS Prevention Oral =600 mg every 8 h

Nifedipine HAPE Prevention Oral =30 mg ER version, every 12 h or 20 mg ER version every 8 h 3

HAPE Treatment Oral =30 mg ER version, every 12 h or 20 mg ER version every 8 h

Tadalafil HAPE Prevention Oral =10 mg every 12 h 3

Sildenafil HAPE Prevention Oral =50 mg every 8 h 3

AMS: Acute mountain sickness; HACE: High altitude cerebral edema; HAPE: High altitude pulmonary edema

1 For individuals ascending to and remaining at a given elevation, following arrival at the target elevation, the medication should be continued for 2 d in individuals adhering to the recommended ascent rate and 2-4 d in individuals ascending faster than recommended rates. Individuals who ascend to a target elevation and immediately descend can stop the medication once descent is initiated.

2 Acetazolamide can also be used at this dose as an adjunct to dexamethasone in HACE treatment, but dexamethasone remains the primary treatment for HACE.

3 For individuals ascending to and remaining at a given elevation, following arrival at the target elevation, the medication should be continued for 4 d in individuals adhering to the recommended ascent rate and 4-7 d in individuals ascending faster than recommended rates. Individuals who ascend to a target elevation and immediately descend can stop the medication once descent is initiated.

Treatment

Suggested Approach: Care should be taken to exclude disorders whose symptoms and signs resemble those seen with AMS and HACE, such as carbon monoxide poisoning, dehydration, exhaustion, hypoglycemia, hypothermia, and hyponatremia. Persons with AMS of any severity or HACE should cease ascending and may need to consider descent, depending on the severity of illness and circumstances. Individuals with AMS may resume ascending once symptoms resolve. Further ascent or reascent to a previously attained altitude should never be undertaken if there are ongoing symptoms. HACE is differentiated from severe AMS by neurological signs such as ataxia, confusion, or altered mental status in the setting of acute ascent to high altitude and may follow AMS or occur concurrently with HAPE. Descent should be initiated in any suspected HACE victim or if symptoms of AMS are worsening despite treatment with acetazolamide or dexamethasone. Dexamethasone is considered to be a more reliable pharmacological treatment for moderate to severe AMS/HACE than acetazolamide. If descent is not feasible, supplemental oxygen or a portable hyperbaric chamber should also be used.

Descent: Descent remains the single best treatment for AMS and HACE. Individuals should descend until symptoms resolve, unless terrain, weather, or injuries make descent impossible. Symptoms typically resolve following descent of 300 to 1000 m/980 to 3300 ft but the required altitude decrease varies between persons. Individuals should not descend alone, particularly if they are suffering from HACE.

Supplemental Oxygen: Oxygen, if available, delivered by nasal cannula or mask at flow rates sufficient to relieve symptoms provides a suitable alternative to descent. It should also be used when descent is recommended but not feasible or during descent in severely ill individuals. An SpO2 > 90% is usually adequate. Short-term oxygen use in the form of over-the-counter oxygen canisters should not be relied on for this purpose.

Portable Hyperbaric Chambers: Portable hyperbaric chambers are effective for treating severe altitude illness but require constant tending by care providers and are difficult to use with claustrophobic or vomiting patients. In many cases, ill individuals may improve enough that they can assist with their evacuation and descend once symptoms improve. Use of a portable hyperbaric chamber should not delay descent in situations where descent is required.

Acetazolamide: Acetazolamide should be considered for treatment of AMS. (Table 2).

Dexamethasone: Dexamethasone is very effective for treating AMS. The medication does not facilitate acclimatization, so further ascent should be delayed until the patient is asymptomatic while off the medication. Extensive clinical experience supports using dexamethasone in patients with HACE (Table 2).

High Altitude Pulmonary Edema

Prevention

Suggested Approach: Because the rates of acclimatization and physiologic responses to high altitude vary considerably among individuals, the ascent profile recommendations presented here do not guarantee HAPE prevention in all high altitude travelers. A gradual ascent profile is the primary method for preventing HAPE; the recommendations provided above for AMS and HACE prevention also apply to HAPE prevention. Pharmacologic prophylaxis should only be considered for individuals with a prior history of HAPE, especially multiple episodes; nifedipine is the preferred drug in such situations (Table 2). It should be started the day prior to ascent and continued either until descent is initiated or the individual has spent 4 days at the highest elevation, perhaps up to 7 days if the individual ascended faster than recommended ascent rates

Gradual Ascent: There is a clear relationship between rate of ascent and disease incidence. Gradual ascent is recommended to prevent HAPE.

Nifedipine: A calcium channel blocker that promotes vasodilation, nifedipine is recommended for HAPE prevention in HAPE-susceptible people because of its ability to lower pulmonary vascular pressures (Table 2).

Tadalafil: Tadalafil can be used for HAPE prevention in known susceptible individuals who are not candidates for nifedipine (Table 2).

Preacclimatization and Staged Ascent: Staged ascent and preacclimatization may offer a reasonable means of HAPE prevention. However, uncertainty remains as to the magnitude and duration of moderate altitude exposure necessary to yield benefit.

Treatment

Suggested Approach: Prior to initiating treatment, consideration should be given to other causes of respiratory symptoms at high altitude, such as asthma, bronchospasm, mucous plugging, pneumonia, pneumothorax, pulmonary embolism, viral upper respiratory tract infection, or myocardial infarction. If HAPE is suspected or diagnosed, oxygen should be started, if available, and descent initiated to lower elevation. If descent is infeasible or delayed, supplemental oxygen should be continued, or the individual should be placed in a portable hyperbaric chamber. Addition of nifedipine may not yield additional benefit in well-monitored settings. In the field setting, where resources are limited, nifedipine can be used as an adjunct to descent, supplemental oxygen or portable hyperbaric therapy. It should only be used as primary therapy if none of these other measures is available. A phosphodiesterase inhibitor may be used if nifedipine is not available, but concurrent use of multiple pulmonary vasodilators is not recommended due to concerns of provoking systemic hypotension. Individuals who develop HAPE may consider further ascent to higher altitude or reascent only when symptoms of HAPE have completely resolved and they maintain stable oxygenation at rest and with mild exercise while off supplemental oxygen and/or vasodilator therapy.

Descent: As with AMS and HACE, descent remains the single best treatment for HAPE. Individuals should try to descend at least 1000 m/3300 ft or until symptoms resolve. They should exert themselves as little as possible while descending (e.g. travel without a pack or via motor vehicle, helicopter or animal transportation) because exertion can further increase pulmonary artery pressure and exacerbate edema formation.

Supplemental Oxygen: When available, supplemental oxygen sufficient to achieve an SpO2 > 90% or relieve symptoms should be used while waiting to initiate descent, when descent is infeasible and during descent in severely ill patients.

Portable Hyperbaric Chambers: As for AMS and HACE, portable hyperbaric chambers can be used for HAPE treatment. When descent is infeasible or delayed or supplemental oxygen is unavailable, a portable hyperbaric chamber may be used to treat HAPE.

Nifedipine: Nifedipine should be used for HAPE treatment when descent is impossible or delayed and reliable access to supplemental oxygen or portable hyperbaric therapy is unavailable (Table 2).

Phosphodiesterase Inhibitors: By virtue of their ability to cause pulmonary vasodilation and decrease pulmonary artery pressure, there is a strong physiologic rationale for using phosphodiesterase inhibitors in HAPE treatment. Therefore, tadalafil or sildenafil can be used for HAPE treatment when descent is impossible or delayed, access to supplemental oxygen or portable hyperbaric therapy is impossible, and nifedipine is unavailable.

Continuous Positive Airway Pressure (CPAP): Positive airway pressure works by increasing transmural pressure across alveolar walls, thereby increasing alveolar volume and subsequent gas exchange. CPAP may be considered for treatment of HAPE when supplemental oxygen or pulmonary vasodilators are not available or as adjunctive therapy in patients not responding to supplemental oxygen alone.

Patients with Concurrent HAPE and HACE

Dexamethasone should be added to the treatment regimen at the doses described (for HACE) in Table 2 for HAPE patients with neurologic dysfunction that does not resolve rapidly with administration of supplemental oxygen and improvement in the patient’s oxygen saturation. If supplemental oxygen is not available, dexamethasone should be started in addition to the medications for HAPE in patients with altered mental status and/or suspected concurrent HACE. Nifedipine or other pulmonary vasodilators may be used in patients with concurrent HAPE and HACE, with care to avoid lowering systemic blood pressure.

1 Luks AM, Auerbach PS, Freer L, Grissom CK, Keyes LE, McIntosh SE, Rodway GW, Schoene RB, Zafren K, Hackett PH. Wilderness Medical Society Clinical Practice Guidelines for the prevention and treatment of acute altitude illness: 2019 Update. Wilderness Environ Med. 2019;30(4S):S3–18.

Full text: wemjournal.org/article/S1080-6032(19)30090-0/fulltext