High Altitude: Physiology

1
High AltitudePhysiology Illness
Military Sports Medicine Fellowship
Every Warrior an Athlete

• Kevin deWeber, MD, FAAFP, FACSM
• COL, US Army
• Director, Military Sports Medicine Fellowship
• 2012

2
(No Transcript)
3
Objectives

• Outline strategies to optimize exercise
  performance at altitude
• Review pathophysiology of high altitude illness
  (HAI)
• Review the types of HAI and how they are treated
• Review factors predisposing to HAI
• Discuss factors in return-to-altitude decisions
  after HAI

4
Preview

• Acclimatization and slow ascent are powerful
  preventives for High Altitude Illness
• Acclimatize properly
• Spend 2-3 nights at 2500-3000m before ascent
• Slow ascent
• Ascend lt 500 m/day of sleeping altitude
• Rest day every 3-4 days
• Prophylactic meds advised if unable to comply
• Acetazolamide is powerful to prevent most HAI
• Dexamethasone powerfully treats serious HAI

5
Fellows on arrival to Snowbird, UT
Someone with Cerebral Edema
Someone with Acute Mountain Sickness
6
Environment at high altitude(gt1500 m or 4920 ft)

• Barometric pressure decreases
• Partial pressure of oxygen decreases
• RESULT Hypobaric Hypoxia
• Lower alveolar O2 leads to lower SaO2

7
Ft. Carson, CO, 6500 ft
Pikes Peak, 14,110 ft (4300 m)
US Air Force Academy, 7,000 ft
8
Effects of High Altitude Exposure

• Decreased exercise capacity
• /- 1 decrease in VO2max per 100m above 1500m
• Individual variability
• MECHANISMS
• Peripheral hypoxia
• Cerebral hypoxia ? peripheral inhibition
• High altitude illness
• Individual variability

9
Acclimatization bodys adaptation to hypobaric
hypoxia
10
Acclimatization

• Immediate (minutes to hours)
• ? Sympathetic tone ? ? HR CO
• ? Ventilation ? ? PaO2 and ? PaCO2 ? ? pH
• Renal bicarbonate diuresis (to balance pH)
• ? Pulmonary artery pressure ? ? O2 absorption
• Delayed (days to weeks)
• Erythropoietin ? ? RBC production,
  hemoconcentration
• Remodeling of pulmonary arterioles

11
Implications for Athletes

• Endurance performance of lowlanders is impaired
  at altitude
• Mexico City Olympics 1968, elev 2240m
• Sprint projectile performance might be enhanced
• Thinner air
• Altitude training enhances altitude performance
• Altitude training MAY affect sea-level performance

Bob Beaman shatters world high jump record by
22
12
Training Strategies to Optimize Altitude
Performance

• Live High Train High (LHTH)
• classic method
• Live High - Train Low (LHTL)
• Natural (descend for training)
• Artificial live-high
• Long-continuous low-O2
• Brief-continuous low-O2
• Brief-Intermittent low O2
• Live Low Train High in low-O2

Application of Altitude/Hypoxic Training by Elite
Athletes, Med Sci Sports Exer 2007
13
(No Transcript)
14
(No Transcript)
15
Sea-level exercise performance following
adaptation to hypoxia a meta-analysis

• Bonetti DL, Hopkins WG
• Sports Med 2009

16
Classic Live High Train High (LHTH)

• Sub-elite athletes
• LIKELY GOOD FOR VO2MAX (?placebo)
• Elite BAD
• Collegiate runners returned to SL 3-8 detrained
  in 1- and 2-mile times

17
Live High - Train Low (LHTL)

• LH Deer Valley, UT 2500m, 22 h/d
• TL SLC, UT 1250m, 2 h/d
• Logistically difficult
• Elite athletes POSSIBLE benefit (4 /- 3.7)
• Sub-elite LIKELY benefit (4.2 /- 2.9)

18
Artificial LH TLLong-continuous hypoxia, 8-18
hrs

• Live at sea level but in hypoxic environment
• Nitrogen dilution (Scandinavia)
• Oxygen filtration (OTC Chula Vista, CA)
• Train at normoxic sea level
• Unproven but assumed altitude advantage
• Results equivocal at sea level performance
• Sub-elite POSSIBLE 1.4 /- 2.0
• Elite UNCLEAR

19
Artificial LH - TLBrief-continuous hypoxia,
1.5-5 hrs

• Sub-elite UNCLEAR
• Elite UNCLEAR

20
Artificial LH TLBrief-Intermittent, lt 1.5 hrs
ea

• Sub-elite VERY LIKELY (2.6 /- 1.2)
• Elite UNCLEAR

21
Live Low Train High

• UNCLEAR

22
Live Low - Train High Methods

• - IHE intermittent hypoxic exposure
• - IHT intermittent hypoxic training
• Dosing variation (hrs/day, weeks)
• Ventilatory benefits gtgt hematologic
• Effective for pre-acclimatization, not
  performance
• ? Tissue effect (increased skeletal muscle
  mitochondrial density, capillary to fiber ratio,
  fiber area)

23
How long do benefits of altitude training last
after cessation?

• 3-6 weeks upon return to sea level

24
Altitude Illnesses (Failure to Acclimatize)
25

• Cerebral Syndromes
• Acute Mountain Sickness (AMS)
• High Altitude Cerebral Edema (HACE)
• mild AMS moderate AMS HACE
• Pulmonary Syndrome
• High Altitude Pulmonary Edema (HAPE)
• Importance
• HACE and HAPE can be fatal

26
Acute Mountain Sickness (AMS)

• Occurs above 1500 m (4920 ft)
• More common above 2500 m
• Defined as HEADACHE plus one or more symptom
• Anorexia, nausea or vomiting
• Fatigue or weakness
• Dizziness or lightheadedness
• Difficulty sleeping
• Headache alone High-Altitude Headache
• Gabapentin, Acetazolamide, or Ibuprofen
  preventative
• J Neurol Neurosurg Psychiat 2008
• Cephalgia 2007
• Wilderness Environ Med 2010

27
Effects of AMS on performance

• Mild annoyance only
• Moderate impaired concentration, memory,
  speech, and physical performance
• Can be disabling
• Subtle abnormalities visible on MRI
• Effects can last weeks

28
High Altitude Cerebral Edema(HACE)

• AMS symptoms plus ALTERED L.O.C. and ATAXIA
• Other neuro findings possible
• Coma develops
• Death results if untreated
• Pathophysiology
• altered cerebral vascular permeability
• leads to brain swelling
• MRI cerebral edema,
• lesions of corpus callosum

29
High Altitude Pulmonary Edema(HAPE)

• Defined by two pulmonary symptoms
• Cough, dyspnea at rest, exercise intolerance,
  chest tightness/congestion
• and two pulmonary signs
• Crackles, wheezing, cyanosis, tachypnea,
  tachycardia
• Most common cause of death among HAI
• 50 mortality rate if not treated quickly

30
High Altitude Pulmonary Edema(HAPE)

• CXR findings
• Blotchy fluffy infiltrates
• Pathophysiology
• Hypoxia
• ? pulmonary artery hypertension
• alveolar damage
• ? edema and hemorrhage into alveoli

31
Risk factors for HAI

• Rapid gain in altitude
• Prior history of HAI
• genetic factors involved
• Alcohol, sedatives
• Strenuous exercise
• HAPE cold ambient temperature, resp. infxn

32
HAI Protective Factors

• Residence at elevation gt900 m (2950 ft)
• Slow gain in elevation
• lt500 m (1640 ft) per day in sleeping elevation
• Genetic factors
• Physical fitness NOT protective

33
Treating HAIGeneral Principles

• Rest, halt ascent
• Descend
• Moderate AMS gt500 m (1640 ft)
• HACE/HAPE gt 1000 m (3280 ft)
• Oxygen if available (keep Pox gt90)
• Keep warm (esp. for HAPE)

34
Treating HAIMedications

• Acetazolamide
• Speeds acclimatization
• Treats moderate AMS HACE
• Dose 125-250 mg BID
• Anti-emetics
• Non-narcotic analgesics

35
Meds (cont.)

• Dexamethasone
• Decreases cerebral edema
• Treats moderate AMS and HACE
• Prevents AMS, HACE, HAPE
• Dose
• 8-16 mg/d in div doses

36
Meds (cont.)

• Nifedipine
• Decreases pulmonary artery pressure
• Prevents HAPE
• Dose 30 mg SR BID (one study)
• NOT EFFECTIVE FOR TREATMENT (one study)

37
Meds (cont.)

• Salmeterol
• Decreases alveolar fluid transport
• May prevent HAPE
• Dose 125 mcg inhaled BID

38
Meds (cont.)

• Tadalafil
• Dilates pulmonary vessels, prevents pulmonary
  hypertension
• May prevent HAPE
• Dose 10 mg po BID

39
Treatment of AMS

• Descend gt 500 m (1640 ft) OR
• Rest 1-2 days at same altitude
• Oxygen 12-24 hours, if available
• Symptomatic treatment with analgesics,
  anti-emetics
• Consider acetazolamide 125-250 mg po BID

40
Treatment of HACE

• Immediate descent gt 1000 m and hospitalize
• Oxygen to maintain SaO2 gt90
• Dexamethasone8 mg PO/IM/IV initially followed by
  4 mg QID
• Consider adding acetazolamide
• Portable hyperbaric therapy if descent impossible

41
Portable Hyperbaric Chambers
42
Treatment of HACE (cont.)

• Management of coma
• Bladder catheterization
• Airway control
• Diagnostic studies
• CXR to rule out concurrent HAPE
• MRI to rule out other conditions

43
Recovery from HACEhighly variable

• 1-3 days for symptoms to resolve
• Days to 12 weeks for neuropsychological function
  to normalize
• 3-4 weeks for papilledema to resolve
• Days to 5 weeks for MRI to normalize

44
Treatment of HAPE

• Immediate descent gt1000 m
• Oxygen to keep SaO2 gt90.
• If descent/O2 not immediately available
• Portable hyperbaric therapy
• Nifedipine 30 mg extended release BID (avoid if
  concomitant HACE) and
• Salmeterol 125 mcg inhaled

45
Treatment of HAPE (cont.)

• Admit if
• gt4L/min O2 requirement
• Elderly, very young
• Concomitant HACE or co-morbid cardio-pulmonary
  disease
• Dexamethasone if concomitant HACE
• Low-flow outpatient O2 for others check daily

46
Recovery from HAPE

• Variable little evidence in literature
• May take 2 weeks to recover strength
• Resume some activity when SaO2 gt 90 without
  supplemental O2
• Remaining at some altitude fosters
  acclimatization via pulmonary arteriolar
  remodeling

47
PREVENTION OFHAI
48
Prevention of HAIGeneral Principles

• Proper acclimatization protocols are paramount
• Avoid abrupt ascent to gt3000 m (9843 ft)
• Spend 2-3 nights at 2500-3000 m before ascending
  further
• Ascend no more than 500 m (1640 ft) per day in
  sleeping altitude when gt2500 m (8200 ft)
• Rest day every 3-4 days

49
Effect of ascent protocol on AMS and success at
Muztagh Ata, 7546 mBloch KE at al, High Alt Med
Biol 2009

• Randomized, controlled trial, 48 climbers
• 15 day vs 19 day ascent
• 15 day 3d at 3000, 500m/d x 2d, then rest day
• 19 day 4d at 3000, 500m/d x 3d, then rest day
• Slow (19d)
• OddsRatio 9.5 for reaching high camp w/o AMS
• Fewer days of AMS (plt.04)
• Lower AMS scores (plt.008)

50
Prevention of HAIOther protective factors

• Living at altitude gt2200 m days to weeks
• gt5days above 3000m last 2 months --gt less AMS
  (Schneider et al, MSSE 2002)
• Intermittent Hypoxic Exposure (IHE) 4hr/d x15d ?
  less AMS _at_4300 m
• Beidleman et al, Clin Sci 2004

51
Acute mountain sickness influence of
susceptibility, preexposure, and ascent rate
Schneider M et al. Med Sci Sports Exerc 2002
52
Prevention of HAIFIRST DETERMINE RISK

• Low risk
• No prior h/o HAI and ascent to lt2800m (9180 ft)
• Taking gt 2 days to ascend to 2500-3000m
  (8200-9840 ft) AND sleeping altitude increases
  lt500m/d

Luks et al. Wilderness Medicine Society
consensus guidelines for prevention and
Treatment of acute altitude illness. Wilderness
Envir Med 2010.
53

• Moderate risk of HAI
• Prior h/o AMS and ascending to 2500-2800m in 1
  day
• NO prior h/o AMS but ascending to gt2800m in 1
  day
• ALL ascending gt500m/d (sleep elev.) at gt3000m

54

• High risk of HAI
• Prior h/o AMS and ascending to gt2800m in 1 day
• ALL with prior h/o HACE or HAPE
• ALL ascending to gt3500m (11480 ft) in 1 day
• ALL ascending gt500m/d (sleep elev.) at gt3500m
• Very rapid ascents (e.g. Mt. Kilamanjaro)

55
Prevention of AMS/HACE

• Moderate and High risk persons consider
  prophylactic meds
• PRIMARY Acetazolamide 125 mg bid
• Start 2d prior to ascent, stop 2-3d after summit
• Kids 2.5 mg/kg/d
• ALT Dexamethasone 2mg QID or 4mg BID
• Only if cant tolerate Acetazolamide
• Start day of ascent, stop 2-3d after summit
• Ibuprofen 600 mg tid (two studies)

Luks et al. Wilderness Medicine Society
consensus guidelines for prevention and
Treatment of acute altitude illness. Wilderness
Envir Med 2010.
56
Prevention of AMS/HACE SPECIAL SCENARIOS

• Military Ops requiring exertion and gt3500m
• Dexamethasone (also increases VO2max)

57
Prevention of HAPE

• ALL ascent/rest precautions
• Moderate/High risk consider meds
• PRIMARY Acetazolamide 125 mg BID
• PRIOR HAPE Nifedipine 60 mg SR daily
  Salmeterol 125 mcg BID
• ALTERNATE Tadalafil 10 mg BID or Dexamethasone
  16 mg/d divided doses

Luks et al. Wilderness Medicine Society
consensus guidelines for prevention and
Treatment of acute altitude illness. Wilderness
Envir Med 2010.
58
Prevention of recurrent HAPE

• The power of slow ascent case series
• 4 climbers with history of 2-4 prior cases of
  HAPE each
• Made a collective 7 ascents to gt 5000 m (16,400
  ft)
• Acclimatized fully
• Ascended only 330-350 m (984-1150 ft) a day
• RESULT no cases of HAPE (100 effective)

Bärtsch P et al. High altitude pulmonary edema.
Respiration 1997
59
Prevention of recurrent HAPE(cont.)

• The power of meds 1 R, DB, PC trial comparing
  prophylactic meds
• Dex 8 mg bid
• Tadalafil 10 mg bid
• Dex Tad vs placebo
• P lt 0.001 lt 0.007, resp.
• Dex vs Tad not significant
• Both Dex Tad reduced pulmonary artery pressure

Maggiorini M et al. Both tadalafil and
dexamethasone may reduce the incidence of
high-altitude pulmonary edema a randomized
trial. . Ann Intern Med 2006 Oct
3145(7)497-506.
60
Considerations for high-altitude activities in
those with prior HAI

• Risk level
• Severity and type of prior HAI
• Ascent requirements
• Feasibility of descent/extra rest days if needed
• Availability of medical treatments

61
Return to Altitude Activity after Recent HAI
additional issues

• Should the patient fully recover before returning
  to altitude/activity?
• How safe is continued activity at altitude?
• Should activities be limited?

62
Return to Altitude Activity during/after Mild AMS

• Common practice continue activity despite
  symptoms
• Risks
• Impaired cognition/performance
• Progression to moderate AMS or HACE
• Consider acetazolamide

63
To air is human altitude illness during an
expedition length adventure race

• 10-day, 238-mile race at elevations of 9,500
  13,500 ft
• No prophylaxis allowed
• 33 cases of AMS treated during race
• 88 were returned to race
• 58 finished race (compared to 74 overall)
• CONCLUSION untreated AMS probably reduces
  athletic performance

Talbot TS et al. Wilderness Environ Med 2004
64
Return to Altitude Activity after recovery from
Moderate AMS HACE

• Full recovery prior to activity
• Strict adherence to acclimatization and slow
  ascent protocols
• Ascend no more than 500 m/day
• Rest day every 3-4 days
• Consider acetazolamide (or dex)
• Counsel on recognition and rapid treatment of HAI

65
Reascent following resolution of high altitude
pulmonary edema (HAPE).

• Case reports of 3 mountaineers with HAPE
• Treated with
• descent to lower altitude
• oxygen
• rest 2-3 days
• Resumed ascent no prophylaxis
• lt 600 m/day ascent several rest days
• RESULT all reached peaks w/o HAPE
• One reached summit of Mt. Everest at 8850 m
  (29,035 ft)

Litch JA, Bishop R. High Alt Med Biol 2001
Spring2(1)53-5
66
Return to Altitude Activity after recovery from
HAPE

• Complete rest until fully recovered
• Strict adherence to acclimatization and slow
  ascent protocols
• Ascend lt 300 - 500 m/day
• Rest day every 3-4 days
• Consider prophylaxis
• Dex, tadalafil, acetazolamide, nifedipine/salmeter
  ol
• (especially if ascent will be gt 500 m/day)

67
HAI in Children

• Risk of HAI in kids same as adults
• Prevention and treatment largely SAME
• Strict acclimatization/ascent adherence
• If meds needed
• Acetazolamide 2.5 mg/kd/d divided
• Dexamethasone 0.15 mg/kg/dose q6

68
Review

• Acclimatization and slow ascent are powerful
  preventives for High Altitude Illness
• Acclimatize properly
• Spend 2-3 nights at 2500-3000m before ascent
• Slow ascent
• Ascend lt 500 m/day of sleeping altitude
• Rest day every 3-4 days
• Prophylactic meds advised if unable to comply
• Acetazolamide is powerful to prevent most HAI
• Dexamethasone powerfully treats serious HAI

69
ITE Questions

• 2 nights after a rapid ascent from sea level to
  an elevation of 3500 meters (11500 feet), a
  non-acclimatized climber is experiencing symptoms
  of headache, dry cough, decreased exercise
  performance, tachypnea and tachycardia at rest.
  In addition to descent, what is the most
  appropriate treatment for this climber?
• A. Dexamethasone
• B. High-flow oxygen
• C. Ibuprofen
• D. Furosemide
• E. IV fluids

70

• In order to improve athletic performance,
  endurance athletes may train at altitude. Which
  of the following is true about this technique?
• A. Sleeping and training at altitude provide the
  best performance improvement
• B. Altitude training only improves performance
  for athletes of lower fitness levels
• C. The altitude required to create benefit is
  2500 meters (8200 feet) or greater
• D. Athletes with iron-deficiency status can gain
  significant benefit from this training technique
• E. The training effect can persist for 3 weeks
  after returning to previous living altitude

71

• A climber in the Himalayas crests 2500 meters
  (approximately 8,200 feet) and experiences
  headache, nausea, fatigue, significant confusion
  and ataxia. The most appropriate treatment option
  for this condition is
• A. Rapid descent
• B. Corticosteroid (prednisone)
• C. Calcium channel blockers
• D. Non-steroidal anti-inflammatories

72

• A 21 year old elite male athlete plans on taking
  a hiking trip in the French Alps during his next
  vacation, and he visits you 2 weeks prior to his
  trip for preventative information on altitude
  sickness. Which of the following is true
  regarding acute mountain sickness (AMS)?
• A. Acute mountain sickness often occurs at an
  altitude of 2,500 feet (762 m)
• B. High level of physical fitness alone can
  prevent the occurrence of AMS
• C. Acetazolamide has not been proven to help
  prevent AMS, but it is often used off label for
  its ergogenic effects
• D. Oxygen therapy and descent of at least 2,000
  feet is an effective way to treat AMS
• E. Dexamethasone is often used to treat high
  altitude cerebral edema (HACE), but its efficacy
  has yet to be proven in the treatment of AMS

73

• You are traveling from San Diego to Colorado for
  a backcountry ski trip with friends. The day
  after you arrive at the ski cabin at 10,000 feet,
  your friend stumbles into your room slurring his
  words and complaining of a headache and blurred
  vision. What is the most reliable initial
  intervention?
• A. acetazolamide
• B. oxygen
• C. dexamethasone
• D. return to Denver immediately (elev. 5,200 ft)
• E. acetaminophen

74

• An athlete travels from sea level to a city at
  3000 meters altitude in anticipation of a
  competition. Which is a true physiological
  adaptation that occurs in this setting?
• A. Mild hyperventilation induces respiratory
  alkalosis
• B. Mild hypoxia increases stage 3 and 4 sleep
• C. Decreased diuresis and increased plasma volume
• D. Increased red blood cell mass in 2-4 days due
  to increased erythropoietin secretion
• E. Pulmonary arterial vasodilation to increase
  PAO2 (alveolar partial pressure of oxygen)

75

• Which of the following therapies is advised for
  the initial treatment of Acute Mountain Sickness?
• A. Rest, ibuprofen and magnesium sulfate
• B. Increased fluids and acetazolamide
• C. Alcohol in small amounts, hydrochlorothiazide,
  propoxyphene
• D. Loop diuretics, beta-blockers, and calcium
  antagonists
• E. Oxygen, acetaminophen, and IV fluids

76
Questions?