1. High Altitude Illness
Terry O’Connor, MD

2. Topic Highlights: HYPOTHERMIA FROSTBITE ACUTE MOUNTAIN SICKNESS
HIGH ALTITUDE CEREBRAL EDEMA
HIGH ALTITUDE PULMONARY EDEMA

3. The Hypothermic Patient
Classically defined as a core temp below 35C
Environmental exposure = primary
Other factors – cns dysfxn, drugs, sepsis, iatrogenic
Further divided into Zones based on symptoms and clinical disease

4. The Hypothermic Patient
MILD
‘excitation phase’
32-35C
Shivering, increased muscle tone
poor judgement

5. The Hypothermic Patient
Moderate
‘metabolic slowing’
30-32 C
Stupor
Extinguished shivering
Ataxia, apathy
Paradoxical undressing

6. The Hypothermic Patient
Severe
<30 C
Decreased Vfib threshold
Loss of reflexes, including cranial nerves
Hypotension bradycardia

7. The Hypothermic Patient – Trivia!
Lowest adult accidental hypothermia survival?
13.7C or 56.8F
Lowest infant accidental hypothermia survival?
15C or 59F
Nozaki R et al. Profound accidental Hypothermia. NEJM 315; 1986

8. The Hypothermic Patient – EKG changes

9. The Hypothermic Patient
INSULATE + TRANSPORT
Dry ‘em off
Cut off wet clothing if practical
Replace with dry insulated clothing

10. The Hypothermic Patient
INSULATE + TRANSPORT
Warm ‘em up
Warm IV fluids if feasible
Insulated Hot Water bottles

11. The Hypothermic Patient
INSULATE + TRANSPORT
Wrap ‘em up
Burrito wrap – start with tarp, insulated sleeping bag, heating bottles (iv) inside, leave room for face for monitoring

12. FROSTBITE Pathophysiology 3 zones of injury
Zone of coagulation (irreversible damage)
Zone of stasis ( possibly reversible)
Zone of hyperemia (recovers in about 10d)
Burrito wrap – start with tarp, insulated sleeping bag, heating bottles (iv) inside, leave room for face for monitoring

13. FROSTBITE Pathophysiology Phase 1 Shut down of blood flow
Ice crystals in extracellular space
Osmotic pull from intracellular space
Cell membranes destroyed
Burrito wrap – start with tarp, insulated sleeping bag, heating bottles (iv) inside, leave room for face for monitoring

14. FROSTBITE Pathophysiology Phase 2 Reperfusion injury
Leakage from damaged vessels
Free radicals, inflammatory mediators
Thrombosis, ischemia, necrosis
Burrito wrap – start with tarp, insulated sleeping bag, heating bottles (iv) inside, leave room for face for monitoring

15. FROSTBITE PRINCIPLES OF TREATMENT
1. AVOID ‘RECYLING’ THROUGH THE PHASES
-- ONLY THAW IF YOU CAN KEEP EM THAW
2. DO NO MORE HARM
Burrito wrap – start with tarp, insulated sleeping bag, heating bottles (iv) inside, leave room for face for monitoring

16. FROSTBITE CLASSIFICATION
SUPERFICIAL
‘GOOD PROGNOSIS’
1ST degree: no blisters, edema, erythema
2nd degree: substantial edema, clear fluid

17. FROSTBITE CLASSIFICATION
DEEP
‘POOR PROGNOSIS’
3RD degree: blue-grey, feels like ‘block of wood’
4th degree: black, mummified

18. FROSTBITE TREATMENT Correct hypothermia Rehydrate
Remove restrictive clothing

19. FROSTBITE
TREATMENT
Thaw Bath
40-42C
10-30min
circulate
Pain control

20. FROSTBITE TREATMENT ‘post thaw’ Debride clear blisters
Leave hemorrhagic
ibuprofen
Consider abx
Daily hydrotherapy
Bulky dressing

21. WHAT IS ALTITUDE? INTERMEDIATE ALTITUDE (1500-2500M)
Physiologic changes detectable
Sp02% > 90%
Altitude illness possible, but very rare

22. WHAT IS ALTITUDE? HIGH ALTITUDE (2500-3500M)
Altitude illness common with rapid ascent

23. WHAT IS ALTITUDE? VERY HIGH ALTITUDE (3500-5800M)
Altitude illness common
Oxygen saturations < 90%
Marked hypoxemia with exercise

24. WHAT IS ALTITUDE? EXTREME ALTITUDE (>5800M)
Marked hypoxemia at rest
Progressive deterioration, despite maximal acclimatization
Permanent survival cannot be maintained

25. NORMAL SYMPTOMS AT ALTITUDE
HYPERVENTILATION
INCREASED URINATION
PERIODIC BREATHING ‘CHEYNE-STOKES’

26. ACUTE MOUNTAIN SICKNESS
DEFINITION:
recent gain to altitudes over 2400m / 8000ft
headache plus at least one of following:
GI upset
fatigue/weakness
dizziness/light-headedness
insomnia

27. ACUTE MOUNTAIN SICKNESS
INTERESTINGLY . . .
OXYGEN SATURATIONS UNHELPFUL IN THE DIAGNOSIS OF AMS
150 subjects surveyed at 10,000ft on Mt Rainer
No correlation between SpO2% and AMS
(O’Connor et al., 2004)

28. ACUTE MOUNTAIN SICKNESS
UNLIKELY AMS IF . . .
Onset >3d after exposure
No Headache
Rapid resolution of symptoms after fluids
Absence of response to descent or oxygen

29. ACUTE MOUNTAIN SICKNESS
RISK FACTORS:
Prior History
Low altitude of residence
High levels of exertion
Interestingly . . .
physical fitness (HVR, VO2 max) unrelated!
(Millege et al. 1991)

30. ACUTE MOUNTAIN SICKNESS
INCIDENCE
General tourist 2750m - 22%
(Honigman et al. 1993)
Climbers ascending to 3080m %
(O’Connor et al. 2004)

31. ACUTE MOUNTAIN SICKNESS
PATHOPHYSIOLOGY
Exact process unknown
Hypoxia  hemodynamic / neurohormonal changes  alteration of BBB (Vegf?, NO?, bradykinins?  increased vessel permeability leakage  edema

32. ACUTE MOUNTAIN SICKNESS
PATHOPHYSIOLOGY
Edema hypothesis supported by MRI studies (Hacket et al. JAMA 1998)
Optic nerves swollen at altitude and detectible by ultrasound (O’Connor, unpublished data)
Optic nerve sheath diameter correlates with symptoms of altitude illness (Smithson et al., 2004)

33. ACUTE MOUNTAIN SICKNESS Treatment(s)
IN ORDER OF EFFECTIVENESS
DESCENT IF POSSIBLE
AVOID ASCENT.
THEN THINK ABOUT MEDS
IF NO RESPONSE TO RX  DESCEND
DO NOT ASCEND IF TAKING RX
AND STILL SYMPTOMATIC!

34. ACUTE MOUNTAIN SICKNESS Treatment(s)
ACETAZOLAMIDE (DIAMOX)
125 mg po q 12 hours
Respiratory stimulant
Useful in qhs dosing for periodic breathing
Speeds up acclimatization
Parathesias of lips, hands, taste alterations common
Can cause blurry vision
Avoid in individuals with sulfa allergy

35. ACUTE MOUNTAIN SICKNESS Treatment(s)
ACETAZOLAMIDE (DIAMOX)- the evidence
Decrease severity sxs by 74% within 24 h
(Grissom et al. Ann Int Med. 1992)
In 487 trekkers in nepal, incidence of AMS 12% in individuals taking Diamox vs. 34% taking placebo, NNT 4
(Gertsh et al. BMJ. 2004)

36. ACUTE MOUNTAIN SICKNESS Treatment(s)
DEXAMETHAZONE
4 mg po/IM q 6 hours x 2 doses
Probably treats pathophysiology
Does not improve acclimatization
No further ascent till 18h after last dose and total resolution of symtoms
Not to be used in ascent!!!  Severe rebound illness can occur if medication abruptly discontinued with ascent

37. ACUTE MOUNTAIN SICKNESS Treatment(s)
DEXAMETHAZONE – the evidence
Symptom scores rapidly improved in climbers with AMS at 14,000 within 12h, but symptoms returned with in 24h after discontinuation
(Hackett et al., 1988)
50% decrease in mean AMS symptom score in individuals at 2700m
(Montgomery et. al., 1989)

38. HIGH ALTITUDE CEREBRAL EDEMA (HACE)
DEFINITION
In the setting of a recent gain in altitude, either:
  - the presence of a change in mental status and/or ataxia in a person with AMS - or, the presence of both mental status changes and ataxia in a person without AMS
"The Lake Louise Consensus on the Definition and Quantification of Altitude Illness"

39. HIGH ALTITUDE CEREBRAL EDEMA (HACE)
Always begins with acute mtn sickness symptoms (therefore preventable!)
Thought to be the severe end of spectrum of acute mountain sickness
Hallmark symptoms are ataxia and altered mental status
Interestingly does not affect finger-nose testing
Ataxia may last for weeks after onset

40. HACE Treatments DESCENT, DESCENT, DESCENT!
OXYGEN 4L/MIN (titrate sats >90)
HYPERBARIC CHAMBERS
DEXAMETHASONE TO BUY TIME
8MG IM stat, then 4mg IM/PO q 6 H
DO NOT DELAY DESCENT! THIS IS THE DIFFERENCE BETWEEN HAVING AN ATAXIC PT AND A COMATOSE ONE!

41. HIGH ALTITUDE PULMONARY EDEMA (HAPE)
DEFINITION
Symptoms: at least two of:  
- dyspnea at rest - cough - weakness or decreased exercise performance - chest tightness or congestion 
Signs: at least two of:  
- crackles or wheezing in at least one lung field - central cyanosis - tachypnea - tachycardia

42. HIGH ALTITUDE PULMONARY EDEMA (HAPE)
PATHOPHYSIOLOGIC THEORY #1
MECHANICAL STRESS
HYPOXIA  increased PASP (35-55)  uneven pulmonary artery vasoconstriction  shear stress  membrane rupture  exudative alveolar edema
(Maggiorini et al. Circulation 2001)

43. HIGH ALTITUDE PULMONARY EDEMA (HAPE)
PATHOPHYSIOLOGIC THEORY #2
Decreased alveolar fluid clearance
Ion channels are “defenders” of dry alveolar space
These fluid pumps are challenged by hypoxia
Pumps may actually be augmented by B-agonists (salmeterol)
(Sartori et al. NEJM. 2002)

44. HAPE Treatment IN ORDER OF EFFECTIVENESS . . .
DESCENT, DESCENT, DESCENT!
KEEP PT WARM
OXYGEN 4L/MIN (titrate sats >90)
HYPERBARIC CHAMBERS
NIFEDIPINE TO BUY TIME
HAPE IS THE QUICKEST KILLER
AT ALTITUDE!

45. HAPE Treatment NIFEDIPINE
Nifedipine 10 mg chew + 10 mg swallow stat then either 10 mg po q 4 hours or an equivalent time-release dose
Thought to work by reversing pulm HTN
If the patient is comatose, pierce the nifedipine capsule and squirt the liquid into their mouth

46. HAPE Treatment NIFEDIPINE – the evidence Study of 21pt with hx of HAPE
Transported rapidly to 4559m
Mean PASP significantly less in nifedipine group
Decreased sxs (10% vs 70%)
(Bartsh et al., NEJM 1991)

47. HAPE Treatment SALMETEROL – the evidence
37 subjects susceptible to HAPE, rapidly transported to 4559m
Salmeterol decreased incidence of HAPE (33% vs 74%, p<0.05)
supports the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role
(Sartori et al. NEJM 2002)

48. HAPE Treatment phosphodiesterase-5 inhibitors? – the evidence
Thought to work by reversing pulmonary vasoconstriction
sildenafil reduced systolic PASP (P = 0.003) and increased maximum workload (P = 0.002) at Everest basecamp
High-altitude pulmonary edema developed in 7 of 9 participants receiving placebo and 1 of the remaining 8 participants receiving tadalafil (P = for tadalafil vs. placebo)
(Ghofrani et al., ann int med, 2004)

49. SOME PASSING PEARLS 3 AXIOMS OF TREATMENT:
DESCENT, DESCENT, DESCENT
AVOID ASCENT UNTIL SYMPTOMS RESOLVE
IF NO RESPONSE TO MEDS  DESCEND
DENIAL OF SYMPTOMS IS COMMON
SYMPTOMS TYPICALLY OCCUR AT NIGHT  ‘EYEBALL’ PTS AT DINNERTIME

50. REFERENCES
Austin D, Sleigh J. Prediction of acute mountain sickness. BMJ. 1995;311:989–990.
Bärtsch P, Maggiorini M, Ritter M, et al.: Prevention of high altitude pulmonary edema by nifedipine. N Engl J Med 1991; 325:
Dumont L, Mardirosoff C, Tramer MR. Efficacy and harm of pharmacological prevention of acute mountain sickness: quantitative systemic review. BMJ. 2000;321:267–272.
Gertsch JH, Basnyat B, Johnson EW, Onopa J, Holck PS Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT).
Ghofrani HA, Reichenberger F, Kohstall MG, Mrosek EH, Seeger T, Olschewski H, Seeger W, Grimminger F. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med Aug 3;141(3):

51. REFERENCES
Hackett PH, Roach RC, Wood RA, Foutch RG, Meehan RT, Rennie D, Mills WJ Jr.R Dexamethasone for prevention and treatment of acute mountain sickness. Aviat Space Environ Med Oct;59(10):950-4.
Hackett PH. High altitude cerebral oedema and acute mountain sickness: a pathophysiology update. Adv Exper Med Biol. 1999;474:23–45.
Hackett PH, Roach RC: High altitude pulmonary edema. J Wilderness Med 1990; 1:3-26
Maggiorini M, Melot C, Pierre S, Pfeiffer F, Greve I, Sartori C, Lepori M, Hauser M, Scherrer U, Naeije R. High-altitude pulmonary edema is initially caused by an increase in capillary pressure. Circulation Apr 24;103(16):
Milledge JS, Beeley JM, Broome J, Luff N, Pelling M, Smith D. Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response. Eur Respir J. 1991;4:1000–1003.
Montgomery AB, Mills J, Luce JM: Incidence of Acute Mountain Sickness at Intermediate Altitude. JAMA 1989; 261:

52. REFERENCES
Montgomery AB, Luce JM, Michael P, Mills J. Effects of dexamethasone on the incidence of acute mountain sickness at two intermediate altitudes. JAMA Feb 3;261(5):734-6
O'Connor T, Dubowitz G, Bickler PE Pulse oximetry in the diagnosis of acute mountain sickness. High Alt Med Biol Fall;5(3):341-8.
Roach, RC.;Bärtsch, P.;Hackett, PH.; Oelz, O. The Lake Louise acute mountain sickness scoring system. In: Sutton JR, Coates G, Houston CS. , editors. Hypoxia and molecular medicine. Burlington, VT: Queen City Printers; pp. 272–274.
Sartori C, Allerman Y, Duplain H, Lepori M, Egli M, Lipp E, et al. Salmeterol for the prevention of high altitude pulmonary oedema. N Engl J Med. 2002;346:1631–1636.
Schoene RB, Hackett PH, Henderson WR, et al.: High-altitude pulmonary edema: characteristics of lung lavage fluid. JAMA 1986; 256:63-69
Ward, MP.;Milledge, JS.; West, JB. High altitude medicine and physiology. 3rd ed. London: Arnold; 2000.
Wohns RN: Transient ischemic attacks at high altitude. Crit Care Med 14(5):517, 1986