Acute Mountain Sickness HACE and HAPE ?????????????????

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Acute Mountain Sickness HACE and
HAPE?????????????????

• Dr Jim Milledge
• Hon Prof. University College London

Lecture to conference on Mountain Medicine,
Taiwan March 2008
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AMADABLAM 6812m
??? 8848m
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Acute Mountain Sickness
?????

• Simple AMS
  ????????
• High Altitude Cerebral Edema (HACE)
  ?????
• High Altitude Pulmonary Edema (HAPE)
  ?????
• Mixed HAPE HACE
  ????????????

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AMS (simple) symptoms
?????(???)??

• Headache
  ??
• Anorexia vomiting
  ????-??
• Malaise misery
  ??-??
• Poor sleep
  ????

5
??????????
But many wish they could ?????????
(??????)
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AMS, von Humbolt, 1802?????
We all felt a malaise, a weakness, a wish
to vomit which came from the lack of oxygen in
these regions.
?????????????????????

• Letter to Delambre after
• Expedition to Chimborazo

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AMS (Simple) Features 1?????(???)??1

• Rapid altitude gain.????????
• A latent period of 6-24 hours before symptoms
  start.????????? 6-24??
• Great individual variation of susceptibility
  regardless of fitness level.
  ????????,?????????
• Only predictor is past altitude history.
  ?????????
• All ages, races, both sexes at risk.
  ????????????????????

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AMS (Simple) Features 2?????(???)??2

• AMS is self-limiting and clears after 3-5 days.
  
  ???????????,??3-5???????
• Does not recur at that altitude
  ???????,??????
• May recur if the subject goes higher
  ?????????,?????

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Incidence of AMS various altitudes?????????????
A study in Swiss mountain huts
????????? Sleeping altitude ????? Alt. of huts
V AMS n466 subjects
????????
??
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HACE Symptoms, Signs ??????????

• Initially symptoms of simple AMS. Then
  ???????????,??
• Ataxia on walking or standing.
  ??????,??????
• Ataxia on sitting up. ?????????
• Hallucinations. ????
• Neurological signs - plantars up, ocular palsies,
  papilledema.
  ?????-?????,????????????
• Coma death if untreated.
  ??-????????

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HAPE first report (in English)??????????(??)
Houston CS (1960) N. Engl. J. Med. 263, 470
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My first case of HAPE (1961)
????????????
Advanced BC, Makalu 6300m
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• Climber with HAPE

• ???????????

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HAPE, symptoms signs 1.??????????1

• Breathlessness more than others at same altitude
  ????????????,?????????????
• Poor physical performance, fatigue ???????
• Chest pain (sometimes) ??(???)
• Cough, dry, then frothy white sputum, later
  blood-tinged.
  
  ????????????,???????????
• Crackles at lung bases, bubbly breathing
  ?????????,???????????

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HAPE, symptoms signs 2.
??????????2

• Cyanosis ??
• Mild fever, 38-9C ????,3839C
• Tachycardia, tachypnoea
  ????,????
• Progresses to more severe dyspnoea, coma and
  death if not treated .
  ?????????,??,????????

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Incidence of HACE, HAPE ??????????????

• HAPE, 1 3 depending on altitude gained
  ??????1 3 ???????
• HACE, 1 - 2
  ??????1 2
  ???????
• Often mixed HACE plus HAPE
  ?????????????????????

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Mechanisms of AMS, HACE??????????????

• Symptoms suggestive of raised intracranial
  pressure due to cerebral edema.
  
  ????????????
• Evidence for this good in HACE ????????Post
  mortem evidence of edema ?????????MRI evidence
  (Hackett et al. 1998) ?????????
  but lacking in simple AMS (so far),
  
  ?????????????????
  MRI studies show small increase in brain
  volume but poor correlation with AMS scores.
  (Roach et al. 2003)
  ??????????????????????????????????????????

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Mechanisms of AMS, HACE cont.??????????????(?)Ho
w does hypoxia produce cerebral edema?
??????????

• Cerebral blood flow increased by
  hypoxia decreased by reduced PCO2Net result
  1st days at alt. CBF increased
• But no good correlation with AMS
• ???-
• ???????????????????????,?????????????
• ?????????????????

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Mechanisms of AMS, HACE cont.??????????????(?)
How does hypoxia produce cerebral
edema???????????

• Fluid Balance?
  ?????
  Some
  evidence that exercise in getting to altitude
  causes fluid sodium retention. Some evidence of
  correlation with AMS
  ?????????????????????,??????????????
• But weak and no evidence in non-exercising
  subjects.
  ?????????????????????

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Mechanisms of AMS, HACE cont.??????????????(?)
How does hypoxia produce cerebral
edema???????????

• ? Hypoxia causes blood-brain barrier to become
  leaky
  ?????????????
• Hypoxia results in increase in oxygen free
  radicals which damage BBB
  
  ?????????????????
• Some evidence of protective effect of
  antioxidants in AMS (Bailey et al. 2001)But an
  unpublished study found no effect
  
  ????????????????????????

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Mechanisms of AMS, HACE cont.??????????????(?)
Hypoxic Ventilatory Response and AMS????????????

1. Subjects susceptible to HAPE have low HVR on
   average (overlap)
   
   ??????????????????(????)
2. Subjects with AMS have low SaO2 but not high PCO2
   
   
   ?????????????????,???????????
3. No correlation between SL HVR and subsequent AMS
   scores
   ??????????????????????????
   ????

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HVR V AMS ?????? vs.
?????
?????????
Milledge et al. 1988
??????
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Hypoxic Ventilatory Response and AMS????????????

• HVR increases during acclimatisation
  
  ???????????????
• One study suggests AMS subjects fail to increase
  HVR. (Bartsch et al. 2002)
  
  ????????????????????????
  ??

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Mechanisms in HAPE
????????

• Susceptibility a strong feature in HAPE
  
  ?????????????
• Hypoxia causes rise in Pulmonary artery pressure
  ??????????
• In susceptible subjects this response in
  exaggerated even in absence of HAPE
  
  ???????????,????????
• Patients with HAPE have very high pulmonary
  arterial pressure (normal wedge pressure)
  
  ????????????????

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Mechanisms in HAPE
????????

• It is suggested that in susceptible subjects the
  constriction is non-uniform
  
  ??????????,???????????????
• so some lung areas are protected, others have
  increased flow and thus raised capillary
  pressure.????????????,??????????????????
• These areas become oedematous.
  ???????????

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Mechanisms in HAPE cont.????????(?)

• High capillary pressure results in stress failure
  of the cap. walls and leakage of fluid, proteins,
  and eventually red cells. ????????????????????,???
  ??????
• Later inflammatory mediators are released which
  add to the progress of the condition.
  
  ????????(?cytokin),????????

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Management, simple AMS
??????????

• Go no higher until symptoms remit
  ???????????????
• If symptoms persist, go down
  ????????
• Analgesics if required, NSAIAs
  ????,??????????
• Acetazolamide (better as prophylactic but helpful
  even after symptoms start) 500mg stat then 250mg
  bd. ???????Acetazolamide (Diamox)
  500??(??????,????,????????) ????????250??

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Management of HAPE and HACE ??????????????

• GET PATIENT DOWN as soon as diagnosis is
  made???????????
• HACE (?????)- Dexamethasone (???)
  (????8mg,???4-6??,?? 4mg???? )
• HAPE(?????) Nifedipine ( ??????)
  ( ?4-6??,??20mg???? )
• Portable compression chamber (Gamow bag)Useful
  for temporary improvement of patient only
  
  ??????(????????????)

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Gamow Bag ??????
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Prevention of AMS 1????????1

• Plan time for acclimatisation ??????
• Above 3000m height gain lt 300m per day, with a
  rest day every 3 days (ideal)
  ??3000??????????????300
  ??,?3?????????(??)
• Climb high, sleep low
  ????,????????
• If symptoms go no higher
  ?????-????????(????)
• If symptoms get worse GO DOWN
  ?????-??

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Prevention of AMS 2????????2

• Consider acetazolamide (Diamox) (125-250mg bd.
  Start 24 h before ascent)
  
  ??????acetazolamide (Diamox) ???
  (???24??????,??????125-250mg )
• For subjects who know they are slow acclimatisers
  
  ?????????????
• When a major altitude gain is unavoidable (flying
  into, 3700m or no camp site at reasonable alt.
  gain)
  
  ??????????????(????????3700?? La
  Paz??????????????????,????????)

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Further reading

• Travel at High Altitude, Medex. Avail on
  www.medex.org.uk
• Relevant Chapters in The High Altitude Medicine
  Handbook, Pollard and Murdock, 3rd edition.
  Radcliffe Medical Press, Oxford
• Ditto, in High Altitude Medicine and Physiology,
  West, Schoene and Milledge 4th edition, Hodder
  Arnold, London
• Barry PW and Pollard (2003) AJ Altitude Illness
  BMJ 326 915-919
• Hackett PH and Roach RC (2004) High Altitude
  Cerebral Edema High Altitude Medicine Biology,
  5, 136-146