ALTITUDE ILLNESS

ALTITUDE ILLNESS - Robert Hyde, MD, MA, EMT-P
BASICS
DESCRIPTION
A spectrum of medical problems ranging from mild discomfort to fatal illness that may occur on ascent to higher altitude (elevations above 1,500 meters [4,921 feet]); is divided into 3 categories: High 1,500-3,500 m, very high 3,500-5,500 m, and extreme 5,500-8,850 m. (1) It can affect anyone, including the most experienced and fit individual. For most, is an unpleasant but self-limiting syndrome that will not require physician intervention.
• Acute mountain sickness (AMS): Symptoms associated with a physiologic response to a hypobaric, hypoxic environment. Onset occurs within 24 hours of arrival at altitude; often within 1-4 hours. Neurologic symptoms are predominant, and range from mild to moderate headache and malaise to severe impairment.
• High-altitude pulmonary edema (HAPE): Noncardiogenic pulmonary edema. Onset within 1-4 days at altitude. Rare below 8,000 feet (2,438 m).
• High-altitude cerebral edema (HACE): A potentially fatal neurologic syndrome; considered the end stage of AMS. Onset within 3-5 days at elevation as low as 2,750 m (9,022 feet), but may be more abrupt at higher altitudes. Death results from brain herniation.
• System(s) Affected: Nervous; Pulmonary
• Synonym(s): Mountain sickness
ALERT
Geriatric Considerations
• Risk does not increase with age.
• Age alone should not preclude travel to high altitude; allow extra time to acclimate.
• Pre-existing medical problems made worse are referred to as altitude-exacerbated conditions.
Pediatric Considerations
• Altitude illness seems to have the same incidence in children as in adults, but diagnosis may be delayed in younger children.
• Any child who experiences behavioral symptoms after recent ascent should be presumed to be suffering from altitude illness.
Pregnancy Considerations
• The risk during pregnancy is unknown.
• No evidence that exposure to high altitude (1,500-3,500 m) poses a risk to a pregnancy
• It may be prudent to advise a low-altitude dwelling to any pregnant woman experiencing complications.
GENERAL PREVENTION
• General guidelines
- Preacclimatization affords some protection against altitude illness.
- Staged or graded ascent (rest day every 600-1,200 m) and a slow ascent rate (maximum 600 m/day) should allow adequate time for acclimatization.
- Sleeping elevation: "Climb high and sleep low" is a prudent practice for anyone going above 3,500 m
- Avoid heavy exertion for the 1st 1-3 days.
- Avoid respiratory depressants such as alcohol and soporifics.
- Pre-ascent physical conditioning is not preventive.
• Drug prophylaxis
- Acetazolamide (if patient has a history of problems at altitude and/or plans to ascend >500 m/d). Dosage is usually 125-500 mg PO b.i.d. starting 2 days before ascent and continued for 3 days at maximum altitude. Patients with a drug allergy to sulfonamides should avoid acetazolamide.
- Dexamethasone may significantly reduce the incidence and severity of acute mountain sickness. Dosage is 2-4 mg PO q6h, begun the day of ascent, continued for 3 days at the higher altitude, then tapered over 5 days. Adverse side effects are rare.
- For HAPE only
 Consider nifedipine 30 mg extended-release PO b.i.d. start prior to ascent and continue for 2 days at maximum altitude.
 Consider beta-agonists (salmeterol, albuterol) 125 mcg inhaled b.i.d. starting 1 day before ascent and 2 days at maximum altitude.
EPIDEMIOLOGY
Most epidemiologic studies are limited to relatively homogenous populations of men.
Incidence
• AMS: 10-90% globally
• HAPE/HACE: 0.01-1% of sojourner ascents at typical mountain resorts, although incidence increases with rapid and higher ascents (2)
Prevalence
Unknown
RISK FACTORS
• Rapid rate of ascent
• Maximum altitude attained
• Increased duration at high altitude
• Failure to acclimatize at lower altitude
• Increased sleeping altitude
• Prior history of altitude illness
• Cardiac congenital abnormalities
PATHOPHYSIOLOGY
• Not completely understood
• Hypobaric hypoxia and hypoxemia are the pathogenetic precursors to altitude illness.
• Symptoms of AMS may be the result of cerebral swelling, either through vasodilatation induced by hypoxia or through cerebral edema.
• Other mechanisms include impaired cerebral autoregulation, release of vasogenic mediators, and alteration of the blood-brain barrier
• HAPE is a noncardiogenic pulmonary edema characterized by exaggerated pulmonary hypertension leading to vascular leakage through overperfusion, stress failure, or both.
ETIOLOGY
Individuals with a prior episode of HAPE have an increased risk of recurrence. (3)


DIAGNOSIS
SIGNS AND SYMPTOMS
• AMS, mild to moderate symptoms
- Headache, plus at least 1 of the following
 Anorexia
 Nausea or vomiting
 Dizziness or lightheadedness
 Insomnia
• AMS, severe symptoms
- Increased headache
- Irritability
- Marked fatigue
- Dyspnea with exertion
- Nausea and vomiting
• HAPE (Lake Louise diagnostic criteria)
- At least 2 of the following symptoms
 Dyspnea at rest
 Cough
 Weakness
 Decreased exercise performance
 Chest tightness
 Congestion
- AND at least 2 of the following signs
 Crackles or wheezing in at least 1 lung field
 Central cyanosis
 Tachycardia
 Tachypnea
- Note: Fatigue may be pulmonary edema
• HACE symptoms
- Mental status changes (irrational behavior, lethargy, obtundation, coma)
- Truncal ataxia
- Papilledema, retinal hemorrhage, cranial nerve palsies
- Focal neurologic deficits (rare)
TESTS
ECG may show sinus tachycardia, or right-sided heart strain.
Lab
• AMS: Laboratory studies are nonspecific and rarely required for diagnosis.
• HAPE: Severe hypoxemia demonstrated with oximetry or blood gas analysis.
Imaging
No radiographic feature is specific to HAPE.
DIFFERENTIAL DIAGNOSIS
Onset of symptoms >3 days at a given altitude, the absence of headache or the lack of rapid response to oxygen or descent suggest other diagnoses
• AMS/HACE
- Subarachnoid hemorrhage; central nervous system (CNS) mass; cerebrovascular accident (CVA)
- Migraine headache
- Dehydration
- Ingestion of toxins, drugs, or alcohol
- Carbon monoxide exposure
- CNS infection
- Acute psychosis
• HAPE
- Pneumonia
- Cardiogenic pulmonary edema
- Spontaneous pneumothorax
- Pulmonary embolism
- Asthma, bronchitis
- Myocardial infarction
- Hyperventilation syndrome
TREATMENT
STABILIZATION
Outpatient treatment for mild cases
GENERAL MEASURES
• Therapy must be tailored to fit disease severity
• Early recognition is critical.
• Stop ascent, acclimatize at the same altitude and/or descend if symptoms do not improve over 24 hours. Definitive treatment is to descend to a lower altitude. Dramatic improvement accompanies even modest reductions in altitude.
• Oxygen helps relieve symptoms. Give continuously by cannula or mask initially, then titrate to SaO2 >90%
• AMS
- Acetazolamide is effective in reducing mild to moderate symptoms of AMS, but the optimum dosage is unknown. Consider 125-500 mg PO b.i.d. until symptoms resolve.
- Dexamethasone may also be effective in treating moderate AMS. Consider 4 mg PO/IM/IV q6h.
- Analgesics and antiemetics as needed for symptomatic relief
• HAPE
- Oxygen therapy
- Minimize exertion and keep patient warm
- Immediate descent or evacuation to a lower altitude
- Portable hyperbaric therapy (2-15 psi), such as the Gamow bag or Chamberlite, is an effective and practical alternative when descent is not possible.
- Consider nifedipine 10 mg PO, then 20-30 mg extended release PO b.i.d.
• HACE
- Immediate descent
- Supplemental oxygen (highest flow available; maintain SaO2 >90%)
- Dexamethsone 8 mg IV/IM/PO initially, then 4 mg q6h
- Hyperbaric therapy if unable to descend
Activity
Rest until symptoms clear
MEDICATION (DRUGS)
First Line (4-6)[B]
• Oxygen: 2-15 L/min to maintain SaO2 >90% until symptoms improve
• Acetozolamide:
- Prevention of AMS: 125-500 mg PO b.i.d. starting 1 day before ascent and continued for 2 days at maximum altitude
- Treatment of AMS: 125-500 mg PO b.i.d. until symptoms resolve
• Dexamethasone:
- Prevention of AMS: 2 mg PO q6h or 4 mg PO q12h, starting 1 day before ascent and discontinued cautiously after 2 days at maximum altitude
- Treatment of AMS: 4 mg PO/IV/IM q6h
- Treatment of HACE: 8 mg PO/IV/IM initially, then 4 mg q6h
• Nifedipine (reduces pulmonary artery pressure):
- Prevention of HAPE: 20-30 mg extended-release PO b.i.d. starting 1 day prior to ascent and continued for 2 days at maximum altitude
- Treatment of HAPE: 10 mg, then 20-30 mg extended-release PO b.i.d.
• Salmeterol:
- Prevention and possible treatment of HAPE: 125 mcg inhaled b.i.d. starting 1 day before ascent and continued for 2 days at maximum altitude
• NSAIDs:
- Prevention and treatment of headache
- Aspirin 325 mg PO q4h for total 3 doses
- Ibuprofren 400-600 mg PO
- Prevention of AMS: Dose unknown. Begin 1-5 days before ascent.
• Antiemetics:
- Prochlorperazine 10 mg PO/IM q6-8h
- Promethazine 25-50 mg PO/IM/PR q6h
• Contraindications: Refer to manufacturer's profile for each drug.
• Precautions: Refer to manufacturer's profile for each drug.
• Significant possible interactions: Refer to manufacturer's profile of each drug.
Second Line
Furosemide:  Consider for treatment of AMS or HACE, 20-80 mg PO/IV q12h for total 2 doses. Currently out of favor; not recommended for prophylaxis; not established for use in HAPE
FOLLOW-UP
DISPOSITION
Admission Criteria
Severe cases
PROGNOSIS
Most cases of mild to moderate AMS are self-limiting and do not require physician intervention. Patients may resume ascent once symptoms subside. HAPE and HACE respond well to descent, evacuation, and/or pharmacologic treatment if identified early.
COMPLICATIONS
Patient may experience high-altitude retinal hemorrhage (HARH), which can cause visual changes, but is usually asymptomatic.
PATIENT MONITORING
• For mild cases, no follow-up needed.
• For more severe cases, follow until symptoms subside.
REFERENCES
1. Gallagher SA, Hackett PH. High-altitude Illness. Emerg Med Clin N Am. 2004;22:329-355.
2. Maloney JP, Broeckel U. Epidemiology, risk factors, and genetics of high-altitude-related pulmonary disease. Clin Chest Med. 2005;26:395-404.
3. Basnyat B, Murdoch DR. High-altitude Illness. The Lancet. 2003;361:1967-1973.
4. Hackett PH, Roach RC. High-Altitude Illness. NEJM. 2001;345(pt 2):107-114.
5. Barry PW, Pollard AJ. Altitude Illness. BMJ. 2003;326:915-919.
6. Dumont L, Mardirosoff C, Tramer MR. Efficacy and harm of pharmacological prevention of acute mountain sickness: quantitative systematic review. BMJ. 2000;321:267-272.
7. Rodway GW et al. High-altitude-related disorders, Part I: Pathophysiology, differential diagnosis and treatment. Heart and Lung. 2003;32(6):353-359.
8. Rodway GW, et al. High-altitude-related disorders, part II: Prevention, special populations and chronic medical conditions. Heart and Lung. 2003;33(1): 3-12.
ADDITIONAL READING
For further information about hyperbaric therapies, oxygen systems, and protocols, visit http://www.ismmed.org and www.high-altitude-medicine.com.