High Altitude Illness (HAI)
Objectives
• What is it?
• Who gets it?
• How common is it?
• What can be done to prevent it?
Source: Wilson MH, Newman S, Imray CH. Lancet Neurol. 2009 Feb;8(2):175-91.
• Case Studies: High altitude travel & pre-existing
medical conditions
Definition of High Altitude
High Altitude: 1500 - 3500 m (5000-11,500 ft)
skiing vacations in Banff (usually < 2500 m)
Cusco (Peru) 3300-3500 m (sleeping)
Very High Altitude: 3500 - 5500 m (11,500-18,000 ft)
Mt. Robson (Canada) 3954 m
Lhasa (Tibet) 3685 m
La Paz (Bolivia) 3658 m
Puno/Lake Titicaca (Peru) 3810 m
Mt. Everest base camp (Nepal) 5150 m
Definition of High Altitude
Extreme Altitude: > 5500 m (>18,000 ft)
Mt. McKinley (Alaska, USA) 6138 m
Mt. Everest (Nepal) 8848 m (29029 ft)
• Two non-technical climbing mountains:
Mt. Kilimanjaro (Tanzania) 5895 m
- Marangu route 4-5 days/temp -20C
Mt. Aconcagua (Argentina) 6962 m
High Altitude = Hypoxic
Altitude
Ascending to high altitude is accompanied
by a series of physiologic changes elicited by
a fall in the partial pressure of oxygen (O2)
These changes help to maintain oxygen delivery
to tissues relatively preserved
despite the hypoxic environment
Acclimatization
High degree of individual variability
At a given altitude,
one individual may thrive quite readily
another may develop life-threatening condition
Difficult to predict without past exposure history
HAI: Primary Risk Factor
HYPOXIA = pathological condition in which the body
is deprived of adequate oxygen supply
Fraction of oxygen (O2) is 0.21 at any elevation
altitude - barometric pressure falls leading to
fall in partial pressure of oxygen inhaled
In given volume of air, decrease in total number of
molecules = less oxygen available absolutely.
Partial Pressure Drop in O2
Sea Level
Altitude 350o m
21% Oxygen
21% Oxygen
Acclimatization Physiology
Key changes to hypoxia:
Oxygen Delivery = Cardiac Output x Arterial O2 Content
DO2
=
Q
x
CaO2
1. Hyperventilation:
CaO2 maintained by involuntary increase in
ventilation
Leads to respiratory alkalosis (PaCO2 falls) …
… at sea level, would reduce respirations
… causing PaCO2 and blood pH to return to normal
Acclimatization Physiology
You can’t stop hyperventilating at altitude, so …
2. Kidney Excretion of Bicarbonate (HCO3):
CSF is acidified by renal excretion of HCO3)
continued stimulation of central medullary chemoreceptors
CMC continue to drive high ventilation rates
Renal response fully manifest over 2-3 days*
Acclimatization Physiology
In addition:
3. Affinity of hemoglobin (Hb) for O2:
At extreme altitude, PaO2 on steep slope of
… oxygen-dissociation curve
PaO2, oxygen saturation (in Hb)
limits fall of PaO2 to ≈ 35 mm Hg in extreme hypoxia
Acclimatization Physiology
Key changes to hypoxia:
Oxygen Delivery = Cardiac Output x Arterial O2 Content
DO2
=
Q
x
CaO2
4. Cardiac Output & Heart Rate:
within 24 hours after arrival to altitude
due to hypoxia-induced sympathetic nerve activity
Source: Palmer BF. Am J Med Sci (2010)
Altitude Illness: What is it?
Comprise of at least three syndromes:
A. Effects on the Brain:
• Acute Mountain Sickness (AMS)
• High Altitude Cerebral Edema (HACE)
AMS  HACE are different ends of same spectrum
B. Effects on the Lungs:
• High Altitude Pulmonary Edema (HAPE)
HAPE is a separate independent entity
AMS - Definition
• Recent gain in altitude
• Symptoms (resemble an alcohol hangover):
•
•
Headache (≈ 2-12 hrs after arrival at high altitude)
Plus one or more other symptoms:
•
Fatigue, weakness, lassitude
Loss of appetite, nausea/vomitting
Dizziness, lightheaded
Difficulty sleeping, insomnia
No signs
4.
AMS – Formal Definition
Lake Louise Consensus Committee
definition of acute mountain sickness:
To diagnose AMS, all of criteria 1. to 3. and
one of symptoms a. to d. are required:
Criteria:
1. a recent gain in altitude
2. at least several hours at the new altitude, and
3. the presence of headache
Symptoms:
a. gastrointestinal upset (anorexia, nausea or vomiting)
b. fatigue or weakness
c. dizziness or lightheadedness
d. difficulty sleeping
How common is AMS?
Uncommon < 2500 m
30% > 3000 m
75% > 4500 m
Case Fatality Rate (CFR) 1/30,000 trekkers
AMS - Clinical
• Common with travel sea level to > 3000 m gain
• Often subsides in 2-3 days at same altitude
• Clinically associated with:
Relative
hypoventilation
Early fluid retention (and
weight gain)
AMS - Pathophysiology
Not known for certainty
Hypoxia-induced cerebral vasodilation
Alter permeability of blood brain barrier
= vasogenic form of cerebral edema
Higher CSF to brain volume may be protective
= AMS risk in persons over 50 years old
… “small brains in big skulls”?
• Worsening of moderate to severe AMS
• With Signs such as:
Ataxia (i.e., gross lack of coordination of muscle movements)
Severe lassitude (i.e., lack of energy)
Altered mental status (e.g., hallucinations)
Encephalopathy (i.e., global brain dysfunction)
HACE - Clinical
Rarely occurs below 4000 m
Prevalence (@ 4000-5000 m): about 0.5 to 1.5%
Severe AMS with onset of signs (i.e. physical abnormalities)
Progressive truncal ataxia, staggering, trouble sitting
Increasing confusion, mood changes, hallucinations
Papilledema, retinal hemorrhage, 6th nerve palsy
Coma, death due to brain herniation within 1-2 days
Often associated with pulmonary edema
Source: Wilson MH, Newman S, Imray CH. Lancet Neurol. 2009 Feb;8(2):175-91.
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HACE - Definition
HACE - Pathophysiology
Not know for certainty
Vasogenic form of cerebral edema
overperfusion and pressure in microvascular beds
capillary leakage and consequental edema
In absence of treatment:
intracranial pressure increases leading to
herniation of brain causing death …
… in 1 -2 days
HAPE – Definition
No formal definition, and difficult to diagnose early
Noncardiogenic form of pulmonary edema …
… causing most deaths at altitude
Presents within 1-5 days after arrival at high altitude
Risk related to rate of ascent and absolute altitude:
Gradual rate to 4500 m, < 1% develop HAPE
Rapid rate of ascent to 4500 m, 6% incidence
At altitude of 5500 m, rate varies 2 – 15%
HAPE - Definition
Early signs and symptoms (usually in the first 48 hours):
Exertional dyspnea (i.e., shortness of breath)
Decreased performance (“falling behind”)*
Insidious progressive dry cough (many other causes also)
AMS symptoms usually present as well
Unfortunately, HAPE may occur explosively
… without warning
HAPE - Definition
Late signs and symptoms:
Obvious breathlessness @ rest – can’t finish a sentence
Orthopnea (SOB lying down)
Gurgling in the chest
Worsening cough with pink frothy sputum
Rales over the middle lung fields (unlike pneumonia)
Chest X-ray (usually not available) – patchy infiltrates
HAPE - Pathophysiology
Noncardiogenic form of pulmonary edema
Exaggerated hypoxic pulmonary vasoconstriction
causes pulmonary capillary pressure (HTN)
leads to mechanical disruption of capillaries
leads to extravasation of fluid into …
… interstitial and alveolar spaces without inflammation
Periodic Breathing of High Altitude
Also called “Cheynes Stokes Breathing”
Breathing pattern with apnea causing waking:
decreases over several
nights at moderate altitudes
4500 m)
may persist at very high altitudes (>
Pros to PB:
Ventilation and oxygenation are
Associated with
better!
lower risk of AMS!
Con to PB:
Reduced sleep
= reduced daytime intellectual function
Periodic Breathing of High Altitude
Hypoxia:
Stimulates hyperventilation leading
to:
CO2 and O2 both trigger apnea during sleep
Apnea:
Restores ventilatory stimuli
by CO2 and O2
• Periodic respiratory cycle generated
Periodic Breathing of High Altitude
Periodic breathing in
a sleeping subject at
an altitude of 5360 m.
AMS Prevention
Practical Advice:
Go slowly; avoid overexertion
allow ~ 2 d/1000 m gained
Spend 1-2 nights at intermediate elevation before
ascent
climb high, sleep low
Avoid alcohol, sedatives
Fluids
AMS Prevention
Gradual Ascent:
controlling rate of ascent if highly effective:
Above 3000 m, do not sleeping elevation by
more than 500 m per day
rest day (no ascent to higher sleeping elevation)
Consider prophylaxis if unable to ascend gradually
Golden Rules
1.
If you feel unwell at altitude, it is altitude illness
unless proven otherwise.
2.
If AMS symptoms, go no higher
3.
If AMS symptoms worsening (or HACE/HAPE),
descend immediately!
AMS Chemoprophylaxis
Acetazolomide (Diamox®)
Primarily works to speed up acclimatization:
Dosing:
Adults (250 mg tabs): 125 mg BID
(24 hrs. before ascent & for 48 hrs. after arrival at highest altitude)
*1/4 - 1/2 tab qhs prn for period breathing
Pediatric (25mg/mL Oral Suspension):
2.5 mg/kg body weight BID up to 125 mg/dose
*High altitude travel not recommended for kids < 5-8 yrs (opinion)
Acetazolomide - Indications:
Previous AMS and/or sleep apnea at altitude
First time travelers to altitudes (>3000m)
Continuous climbers >3000m
- including emergency responders
Rapid ascent of >500m/day (e.g. Mt. Kilimajaro)
- every route is too fast, pay by day incentive
Acetazolomide - Indications:
Direct from sea level to > 3000 m (e.g., air flight)
(e.g., Cusco, Puno, La Paz, Lhasa, Shangri La, etc.)
Lack of rest day for every 1000m gain above 3000m
(e.g., quick ascent to Everest Base Camp)
Chronic cardio-pulmonary or renal disease
or recent respiratory infection
(but client needs to be cleared by doctor as well)
Acetazolomide - Contraindications
Allergy to sulfa-based non-antibiotics
do not use, as likely cross-reaction
cross-reaction is not known with sulfa antibiotics
If sulfa reaction was “anaphylactic”, use alternative
Allergy to other carbonic anhydrase inhibitor (CAI)
Pregnancy (category C) * CHF risk
Depressed sodium and/or potassium levels (marked
kidney/liver disease)
Acetazolomide (Diamox®)
Benefit is high – helps to acclimatize
Risk is low – paresthesia are annoy if at all
Can be taken stopped without fear of
recurrent of AMS if not continuing to climb
Long safety record in use against HAI:
- first studied in 1966, and all studies show effective
- only controversy is what the optimum dose to use
Acetazolomide (Diamox®)
Adverse effects:
• Parasthesiae
• urination (also occurs with acclimatization)
• Altered taste of carbonated beverages
• Gas producing
WMS (2010) does recommend as DOC
-
for adults and children
cannot be used in pregnancy
AMS Prevention
Dexamethasone (*not prescribed @ CITC)
Rapidly reverses symptoms but does not improve
acclimatization – if stopped, can lead to rebound
DOC for treating HACE
Dosing:
Adults (4 mg tablets): ½ tablet (2 mg) q 6h or 1 tablet q 12h
(start on day of ascent & until 2-3 days at maximum altitude)
Pediatric:
though used in croup – not recommended for AMS Px
WMS (2010) does recommend as alternative
AMS Prevention
Ginkgo biloba
• Several studies with opposing results as of 2010
• Cannot replace acetazolamide or dexamethasone
WMS (2010) does NOT recommend its use
AMS Prevention
Coca-leaf tea (popular in S. America)
• Never been studied for prevention
• May be mild stimulant and improve well-being,
while experiencing AMS
Garlic
• No studies to support – may prevent tick bites?
Alcohol - AVOID! (exaggerates hypoxemia)
Overhydration – AVOID (risk of hyponatremia)
HAPE Prevention
Nifidepine (*not prescribed @ CITC)
Reduces pulmonary hypertension, reducing HAPE
risk
Currently only recommended to people with past Hx
Dosing:
Adults (30 mg SR): 1 tablet q 12 h
(start on day prior to ascent & until 5 days at maximum altitude)
Pediatric:
not recommended
WMS (2010) does recommend as DOC
HAPE Prevention
Other options (not prescribed @ CITC)
Salmeterol 125 ug inhaler bid
Phosphodiesterase Inhibitors – not yet recommended
Dexamethasone may also work – case reports
Acetazolamide may also work – case reports
Treatment of HAPE:
Descent, descent, descent!
Do not exert on way down – carry or assist walking
Case Studies
1.
High school student on a 12 day trip to Peru.
Lima fly to Cusco (5 days working on a
project) Inka trail, Macchu Picchu (3 days) Puerto Maldonado (3 days) Lima
Med. History:
Asthma: uses Ventolin & Steroid puffers prn.
Allergy to sulfa medication (welt-like rash,
doesn‘t know if reaction to sulfa antibiotics or
sulfa based non-antibiotics – as a child)
Case Studies
2.
46 yr. old female traveling to Lima - Cusco - 12
day Inka Trail trek - Amazon (x 3 days). Bus to
Puno/Lake Titicaca/Uros Islands (3 days). Bus
to La Paz, Bolivia via Copacabana (2 days).
Return to Lima.
Medical History: hypertension (on a ACEInhibitor) & viral myocarditis (x 2 yrs ago).
Migraines. Takes Advil prn. Aspirin 80
mg/day.
Case Studies
3.
57 yr. old male travelling to Mt. Kilimanjaro,
Tanzania (x 6-7 days) Zanzibar (x 7 days).
Med. History: coronary artery bypass surgery
(2004)
Meds: Beta-blocker, ASA 81 mg, ACE-Inhibitor,
statin (Lipitor), last check-up was 1 year ago
Travel History: flown to Toronto and LAX since
2004, has been doing local day hikes in Banff
Case Studies
3.
57 yr. old male travelling to Mt. Kilimanjaro,
Tanzania (x 6-7 days) Zanzibar (x 7 days).
Med. History: coronary artery bypass surgery
(2004)
Meds: Beta-blocker, ASA 81 mg, ACE-Inhibitor,
statin (Lipitor), last check-up was 1 year ago
Travel History: flown to Toronto and LAX since
2004, has been doing local day hikes in Banff
Case Studies
4. 27 yr old hiking the Annapurna Circuit, Nepal x 16
days/max altitude = 5416 m (Thorong La), following
3 days in Kathmandu. Organized group tour.
Medical History:
IDDM (well managed) – insulin pump
Healthy. No allergies. No complications.
Case Studies
5. 25 year old woman already booked and paid for a 3
week trip to China including 1 week in Tibet,
including Lhasa to Shigatse to Rongbuk to see north
side of Mt Everest.
Medical History:
Just found out she is pregnant, will be 8-12 weeks
gestation overseas
Healthy. No allergies. No complications.