High altitude cerebral edema

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High Altitude Cerebral Edema

X

AUTHOR(@)

Allan J.

Hamilton, M.D.,

Peter McL. 9.

Black, M.D.,

l.

CONTRACT OR GRANT NUMBER(a)

Allen Cymerman,

Ph.D.,

Ph.D.

PERFORMING ORGANIZATION NAME AND ADDRESS

Neurosurgical Service, Massachusetts General Hospital, Boston, MA 02114 and Harvard Medical School, 02115, U.S. Army Research Institute of Environmental Medicine.

I I.

Natick.

MA

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March 1986

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C

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MAY1 3 S86{

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Acclimatization, acute mountain sickness, carbonic anhydrase inhibitors, cerebra: edema, cytotoxic edema, decopression sickness, diuretics, high altitude, hypoxia, pulmonary edema, steroids, vasogenic edema.

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Acute mountain sickness (AMS) is usually a benign and self-limited illness which befalls previously healthy individuals who ascend rapidly to high altitude In its more severe forms AMS can progress without sufficient acclimatization. #..D to a life-threatening condition in which pulmonary or cerebral edema can occur known High altitude cerebral edema (HACE) is a little Ssingly or in concert. clinical entity which manifests itself by a perplexing array of both generalized and localized neurological symptoms and signs. Furthermore, the development of HACE in climbers offers a unique experimental situation in which to examine the ,.• •

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PETER McL. MASSACHUSEITS

BLACK. M. D. GENERAL HOSPITAL

15 PARKMAN STRERT.ACC 212 BOSTON.

MASSACHUSETrl

02114

(617) 726-3774

NEUROLOGICAL SURGERY

March 25,

1986

Allen Cymmerman, Ph.D. Altitude Research Division United States Army Research Institute of Environmental Medicine United States Army Research and Development Command Natick, MA 01760 Dear Dr.

Cymmerman:

Here is a copy of Dr. Allan Hamilton's review of high altitude Please let me know if cerebral edema submitted to Neurosurgery today. there are any changes you feel would be necessary if it is accepted. Si ncerely,

Peter McL. PB:daa

x

Black,

M.D.,

Ph.D. ..

/

HIGH ALTITUDE

Allan J.

Hamilton,

Allen Cymmerman,

Peter McL.

Black,

M.D.

Ph.D.

M.D.,

CEREBRAL EDEMA

(1,2)

(2)

Ph.D.

(1)

(1) Neurosurgical Service, Massachusetts General Hospital, Boston, Mass 02114 and Harvard Medical School, 02115

Research Division, United States Altitude (2) United of Environmental Medicine, Institute Natick, Mass 01760 and Development Command,

Army Research Army Research States

Correspondence: McL. Black, Neurosurgical Service, Massachusetts Dr. Peter Wang Ambulatory Care Center Room 312, Fruit General Hospital, Boston, MA 02114 Street, Running Title: High Altitude

Cerebral

Edema

SI

Hamilton-2

Abstract mountain sickness

NJýcute

(AMS)

is

usually a benign and

self-limited illness which befalls previously healthy individuals who ascend rapidly to high altitude without sufficient acclimatization.

In

life-threatening

condition in

its

can occur

singly or in

(HACE)

a little

is

more severe forms AMS can progress to a which pulmonary or cerebral edema

concert.

High altitude cerebral edema

known clinical entity which manifests itself

by a perplexing array of both generalized and localized neurological HACE in

symptoms and signs.

Furthermore,

climbers offers a unique experimental

the development of situation in

which

to examine the effects of hypoxia on the central nervous sytem. The epidemiology and clinical picture of HACE are reuiewed. addition,

In

the pathology and predominant pathophysiological

mechanisms postulated to explain HACE are examined and the present recommendations

for prevention and treatment of this

dangerous and unusual form of brain swelling are discussed. KkýUCofdz$

Key Words: aihydrase

acclimatization, acute mountain sickness,-arbonic inhibitorsicerebral

decompression pulmonary

sickness,

edema,

edema,$.tytotoxic diuretics

steroids,

high altitude,

vasogenic

edema

edema, hypoxia,

Hamilton-3

S Introduction Environments at high altitude have served as one of the most important and productive settings for exploring human physiological

adaptation.

Individuals who ascend rapidly to high

"elevations without adequate acclimatization are prone to suffer from a broad range of homeostatic disturbances which have been clinically described as acute mountain sickness benign form AMS is

4•

fatigue,

(AMS).

In its

distinguished by the onset of headache,

drowsiness,

lassitude,

vomiting and sleep disturbances;

dizziness,

anorexia,

nausea,

these symptoms usually start

within 6 to 96 hours after arrival at high altitude and resolve with just rest and adequate hydratlon although occasionally the use of supplemental oxygen may be required (6,10,17,26,30,38,47,52,59). In its

more severe form S1 AMS can lead to a life-threatening

condition in

which the manifestations of high altitude pulmonary

edema (HAPE)

or high altitude cerebral edema (HACE)

singly or in

concert (6,10,12,26,28,30,36,47,51,52,59).

can occur The

clinical presentation and pathophysiology of HAPE have been previously presented and reviewed elsewhere

(16,29,31,51,53).

This review will examine the epidemiology and clinical manifestations

of HACE,

discuss the pathology and pathophysiology

of this unique form of cerebral edema as well as the methods for its prevention and treatment in visitors to high altitude. Historical Background Mankind has lived in

areas of high altitude for as long as

there exist historical records.

I I,

; ... *

4

Most of the Altiplano of South

Hamilton-4 lies

America

above

begin at 10,000 ft

11,500 ft (3000

continuously inhabitated elevations

(3500

m) and the Tibetan plateaus

a) and yet both terrains have by races well-adapted

for several millennia

(27)

above

East is .aptly *

reported

named Jesuit

17,000 ft. Marco

to have climbed

us the first

who accompanied

these

the archeological

Polo during his travels

in

the Far

over a high range of peaks,

"the headache mountains"

priest

to living at

although no permanent

habitations have been found either now or in record

been

(27).

Jose de Acosta was a

the Conquistadores

to Peru and gave

written description of acute mountain sickness

he arrived at an elevation of approximately 12,000 ft

a mountain pass between what is

when

(3700m)

in

now the city of Lima and that of

Jauga: "I therefore persuade myself that the element of air i. there subtle and delicate, as it is not proportionable with the breathing of man, which requires a more gross and temperate air, and I believe it is the cause that doth so much alter the stomach, and trouble all the disposition" (7). It

is

means

Acosta who wrote "seasickness

of the desert

come to mean altitude In

of the mareo de las punas which literally

sickness in

1760 Horace

de Saussure

first

ascent up Mt. Blanc,

hopes

that this

mountain

might

offered a monetary prize Europe,

in

encourage guides to develop a route

Balmat,

In

claimed

has

Peru.

the highest peak in

so he could climb it.

a mountain guide,

places" and the term puna

1786,

a physician,

for the the up the

Paccard,

and

the prize and the next year de

Saussure found himself on the summit where he wrote: "I was constantly forced to interrupt my work and devote myself entirely to breathing...the kind of fatigue which results from the rarity of the air is absolutely unconquerable"(8).

so

"Hamilton-5 t In

name

a member cf the Alpine Club known only by her first

1872,

of Joanne wrote in

their journal:

"The lightness and great rarity of air in the Alps...cause at certain altitudes very noticeable physiological phenomena such as...nausea, drowsiness, panting, headache, fatigue, etc..."(33). In

1862 two British balloonists ascended tc the height of

approximately 29,000 ft (8840 m) which is tie highest point on Earth,

Everest.

Mt.

virtually as high as They very nearly died

from hypoxia before they could force the balloon to lower in

altitudes

their

last

nineteenth century, in

moments of

consciousness.

In

the late

Paul Bert performed a series of experiments

a decompression chamber aimed at permitting balloonist to

conquer even loftier heights and discovered

that the administration

of

oxygen could prevent or abolish most of the symptoms of high altitude, iA

remarking in

"...the favorable effects of inhalation of oyxygen. Return of strength and appetite, decrease of headache, restoration of clear, calmness of mind .... " (2) IN 1854 Dr.

Lj

his notes:

Conrad Meyer-Ahrens

of Leipzig published a

woes and wrote:

compendium of alpinist's

"The principal symptoms (of altitude illness)...which occur oftenest in man are: discomfort, distaste for food, especially distaste for wine (however, the contrary has sometimes been noted), intense thirst..., nausea, vomiting; accelerated and panting respiration; dyspnea, acceleration of the pulse, throbbing of the large arteries and temples, violent palpitations, oppression, anxiety, asphyxia, vertigo, headache, tending to syncope, unconquerable desire for sleep, muscular of sensory perception and the intelligence, fatigue...blunting

impatience,

N.•

P

buzzing in

irritability...finally,

the ears."

Scarcely anything could be added even today

to this

constitute

an Intalian

altitude

physiologist,

sickness.

developed

Angelo Mosso,

the first

high altitude

list

research

(39) of ills

station

that

Hamilton-6

Sand'in

1898 originally

described periodic sleep disturbances

associated with high elevation (44). performed

in

barometric

his decompression

pressure

pO

of only 40 and a pCO

2

observations,

the

(equivalent

introduced

to the altitude

of

composition of expired gas had a

of 5 mm Hg.

2

he

chamber shoved that at a

of 246 mm Hg

the summit of Mt. Everest)

Other studies

Because

of these

the notion that diminished

pCOP

, or

2 "acapnia,"

as he called

it,

might play a significant

role

in

AMS

(43). IN 1913,

T.H.

mountain sickness medical officer 1

"normal

I

AMS.

puna"

in

Ravenhill described in

(47)

his observations

the Andes where he was stationed as a

one of the mining districts.

which comprises

the earliest,

He described benign

He also further identified "cardiac puna"

and symptoms were primarily cardiopulmonary in correspond to what we term today HAPE. of "nervous puna" the clinical was the

in

features of

in which the signs nature and

His last category was that

which neurological manifestations

dominated

picture and would be equivalent to HACE.

first

of

to comprehend

clinically

that

it

Ravenhill

was dysfunction

within these two organ systems which dominated the pathophysiology of severe AMS. Joseph Barcroft

England in found all

spent

in

1919 a British a "Glass House"

scientist in

named

Cambridge,

which the prcentage of oxygen was lowered to that

at 18,000 ft.

the

10 days

In

By the

symptoms of AMS.

demonstrated

sixth day,

During his

Bercroft was experiencing

"stay" at high altitude

that there existed a diminished alveolar

arterial

he

Hamilton-7 oxygen gradient by drawitig arterial specimens from his radial artery and

simultaneously determining

concentration in

the alveolar oxygen

breath samples taken at end expiration.

irrevocably refuted with this data Haldane's

He

then popular notion

that oxygen could De secreted against a concentration gradient from the alveoli into the pulmonary capillaries and that such active

secretion

altitude

constituted

the physiologic3l

basis for high

adaptation.

By the middle of the twentieth century Carlos Monge had published his classic work on chronic high altitude adaptation amongst

the native populations

of the Andes

(41,42)

to which

l urtado was to add a great wealth of physiological data on both human and animal subjects (32).

In

1960 Charles Houston,

who is

one of the modern day American fathers of high altitude physiology,

had described the first

case of HAPE (25)

English literature and Hultgren et al (3.1) more cases of HAPE within the next year. first

in

the

described four In 1960,

Chiodi (5)

reported on a Peruvian patient suffering with severe AMS

who experienced occipital headaches, paresthesias

and postulated

altered consciousness and

that these manifestations

cerebral form of high altitude illness.

In 1964,

reflected a

Fitch described a

similar form of mountain sickness with neurolkgical manifestations following year,

in

the English literature

thousand

I

The

large numbers of Indian troops were amassed along

the mountainous borders between outbreak in

(12).

hostilities

India and Pakistan during an

and Singh et al (51)

soldiers rapidly ascending

evaluated

to high altitude.

nearly They

two

'

Hamilton-8

wi4espread reported

petechial

(52)

hemorrhages

Dickinson

18,000 ft.

as opposed to pulmonary edema in

24 soldiers Houston and

1975,

cerebral

of predominantly

the course of

and coined the phrase

high elevations edema" or HACE.

In

in

12 patients with histories

suggestive

presentations

and later

two HAPE fatalities

presented a series of

(28)

and clinical

in

neurological manifestations

suffering from severe AMS at

edema and

findings of cerebral

described neuropathological

first

their

at

illness

"high altitude

cerebral

Epidemiology to be considered when

There are several limitations to arrive at an understanding true

incidence cannot

population at risk

be clearly identified

cannot

the

First,

of the incidence of AMS.

be known with certainty because

trying

the

(26)

Furthermore, until recently only small groups of exceptionally fit

individuals

acrte,

(mostly mountaineers and. soldiers) exposures

well-documented

a period of several days and this statistical

to the highest altitudes

for of any

limited the applicability

drawn from studies of such select groups

conclusions

In

to larger populations.

underwent

addition,

observations

made on

individuals stricken with AMS were often performed only once had been evacuated down

from higher altitudes and their

and signs might have already started to resolve. multi-national expeditions language

difficulties

often made

the popularity

symptoms

Finally,

with

entering high altitude regions,

and valuable epidamiological recently,

they

precise interviewing

information was missing

of mountaineering has

impossible (10).

surged in

More

Hamilton-9

conjunction with increased

air travel

numbers of individuals with lesser ascend

to high altitudes

likelihood

that

et al

Hackett 14,000 ft

severe

on

AMS at 53% and the

to

time thereby the

and increasing

•.t

examined 278 trekkers arriving the route tu

during a one month interval

within

very short periods of

fitness

AMS may occur.

(22)

(4,243m)

larger

degrees of physical

the extent of acclimatization

re.2ucing

*'

in

permitting ever

the Mr.

and placed

that of severe,

this particular

group.

It

Everest

Base Camp

the overall

incidence of

life-threatening

AMS at 4.3%

also important

to distinguish

is

between those individuals suffering primarily from pulmonary as As mentioned earlier,

opposed to cerebral manifestaions of AMS. Singh et al (52)

examined 1925 Indian soldiers at high altitude

between 11,000 (3350 m) and 18,000 ft (5500 m) in

their clascic

paper and found that the incidence of AilS varied widely from 1.01 to 83.3 per 1000. of HACE within

Furthermore,

this

group and three

died from neurological

4]•

of severe AMS Kathmandu,

between

Nepal,

HAPE alone,

they identified 24 '1.2%) patients within this

complications. 1969 and

In

1978 at

his analysis

suffering with HACE alone

26 (66%)

have

features

severely

stricken patients,

of both forms (10). 5 (12.8%)

group

of 39 cases

the general hospital

Dickinson found only 3 (7.5%)

10 (26%)

cases

suffering and

from their

from

the remaining

Within this

died

in

series

of

illness.

In

a separate review of 12 cases of AMS in which Lhe manifestations of HACE were two fatalities

predominant reported

features

in

the clinical presentation,

(28).

-A

11: ., .•..

.. u A

a s

. .- .

.' a'

'

. -,

.-

~---

e

,

l I S4

. 0

..

Hamilton-i0 Dickinson from

found his patients with severe AMS were derived

15 different

sherpas) (10).

nationalitles

and ranged

(including

from the second to seventh decades in

Hackett and his colleagues

younger

trekkers

ones even if

was found; et al;

In

(21,22)

in

in

rate of ascent

however,

a preponderance

in

that

to AMS than

in

older

of males

thaL of Hackett

undoubtedly reflects

presently involved

age

were taken into

Dickinson's paper and 71%

sex distribution

of males

found,

to be more susceptible

both studies of AMS,

84.5%

this

numbers

tended

difterences

consideration.

two native Nepalese

the larger

trekking and

mountaineering.

44?

Altitude

of onset of AM4S

the rate of ascent. (2000

AMS is

m) but becomes

is,

to a large extent,

(2500

m)

(26);

increasingly common after

Dickinson (14)

a), which is a! (52)

87Z of

occured

9,840 ft

at altitudes

(3000

m)

as low as 8200

the cases of severe AMS that were seen by

between

10,000 ft

(3050

(5500

m) and 18,000 ft

roughly the same range of altitude in

reported

on

rarely experienced below 6,560 ft

and death from HACE has been reported ft

dependent

which Singh et

their 24 cases of HACE.

Clinical Manifestations A variety of schemes

have been proposed to classify

and

categorize the wide spectrum of clinical manifestations of AMS (10,47,52,60).

For

the purposes

classification

adapced

by Dickinson (10)

Clinical manifestations subdivided generalized

S,

W,

• I

I

II

Into

those

versus

of discussion in

grouped

features

IVi

I9

I

review,

term AMS

are

benign and

which are clinically

which are malignant

nN

the

will be employed.

under the general

those features

this

m

and organ

AI

%bm

Hamilton-il specific.

These maligant fe'tures are then subdivided into those

attributable

to

HAPE or HACE

The earliest anorexia,

signs

and

(see

Table

signs of AMS are sleep

disturbances

I).

headache,

(60);

other

of AMS which might be attributable

are loss of memory,

tinnitus,

nausea and vomiting, early

and

benign

to early cerebral

irritability,

edema

emotional lability

and mood disturbances as well as dilatation of retinal veins and retinal

hemorrhages.

retinal

vein morphology were

in

decompression

pressure

(40).

incapacitated did not

chambers

Of

840

with receive

of decreasing

insomnia, giddiness,

Similar disturbances described

symptoms

any medical

frequency:

human studies intracranial judged

of early,

treatment,

the

nausea,

lethargy,

thirst,

couhh and peripheral edema (52).

benign

symptoms anorexia,

fullness or pain in

AMS

were

but

in

order

dyspnea,

the chest,

indigestion,

outburst o: other behavior disturbances, fever,

earlier

who were

and signs

headache,

mentation and

to increased

soldiers

muscular weakness, vomiting,

in

and ascribed

Indian

in

hysterical

decreased concentration, The onset of symptoms is

usually between one and three days after arrival at high altitude (12,17,26,28,51,52,59).

Singh et al (52)

showed that only 38% of

patients were free of the symptoms and signs of AMS within 3 days of their arrival;

furthermore,

remained incapacitated and 1% were still Estimates

12.5% of affected soldiers still

after 2 weeks of attempted acclimatization

not acclimatized at the end of 6 months. as to the incidence

of severe or malignant HACE

amongst those affected by high altitude sickness are quite

variable

as discussed

earlier.

clinical

picture

the mechanisms

(10).

which may be

HACE are numerous and on the central enormous

in

Observations deterioration

As will be discussed in involved in

system.

of alpinists

of sensory,

subsequently

at 11,480

alpha-wave

activity

Reductions

in

arterial

judgement,

motor and higher cognitive

brain syndromes

recordings ft (3500

underwent

that of

(37,57).

of subjects at sea level and

m)

showed increased

levels of

blood saturation down to 45%

(such

with exertion at extreme altitudes)

the administration tests

immediately

after,

and one year after

The results

of this

2 months

study (57)

was accompanied

motor coordination, abilities

(as

spelling); members was

in

(48). as have

lead to

behavioral changes and impaired motor function

neuropsychological

altitvtes

functions

and that at extreme altitude,

Members of the 1981 American Medical Research

Everest

an

of RACE itself.

suggesting diffuse cortical depression

been shown to occur

(57).

there is

of mountain-ers might closely parallel

Electroencephalographic

effects

had suggested that severe

patients with acute organic

faulty

of this,

manifestations

occurred with increasing altitude the behavior

section,

the pathophysiology of

As a result

the clinical

of

a later

can have multiple and overlapping

nervous

diversity

Dickinson

92% had evidence of RACE as part

studied with severe AMS, their

Of the 39 patients

within days

their ascent

showed that ascent

on Everest. to extreme

deterioration of fine

short-term and long-term memory,

determined addition,

significantly

of a battery of cognitive and

prior to,

by significant

Expedition. to

by errors in the altitude related

reading,

and language

writing and

attained by individual to the increase

in

so called

Hamilton-13 "aphasia

errors."

of

cognitive

these

over

a

year

eleven

deficits

after

Houston which the

Furthermore,

out

of

the

emotional

of

twelve

complained

half

of

the

during

and

extension while

in

diplopia

administered commented

that

sensitive

in

from

others

particularly studied neurological particular

displayed

(59)

climbers,

sign).

One

commented

particularly either tests

for

detecting (17,59)

that

the

of HACE

exhibited

out

One

and

became

abnormal exhibited plantar

meningismus Gray et

AMS.

has

confirming to be

hypoxia.

Singh

included

the

has

the most reports

et

al

(52)

other

and seizures. of

gait

(10)

amongst

appeared

palsies

(17)

been

Dickinson

were

HACE,

al

of ataxic

furosemide

hemiparesis unilateral

Four

of patients

whose presentations

paralysis,

illness.

development

cerebellum

and

patients

including

ataxia

cases of

In

the history

exhibited

treat

to high altitude

problems patient

or

cerebellar early

sensitive 24 cases

prevent

in

Two patients

rigidity. the

(28).

displayed

patient

on

AMS

to concentrate.

reflexes,

those to whom to

their

the group

decerebrate

have

Three

patients

abnormal

(Babinski's

HACE of

disease.

other of

severe

consciousness

their

out

four exhibited

another

Wilson

Five

of of

ability

lost

two

some

demonstrable

details

on in

decreasing

of

that

to us.

early

and

12 cases was

available

course

significantly

some

eventually

responses.

ataxia

and

of

more distressing,

level.

compiled

lability

tha

still

patients

are

patients

perhaps

problem

twelve

exhibited

pupillary

sea

clinical

examination

"experienced

to

and Dickinson

physical

comatose

were

return

primary

and

One sixth

and

Hamilton-14 seventh cranial nerves and underwent craniotomy for what was suspected to be a hitherto subclinical cerebral tumor.

Biopsy

revealed only edematous brain with no evidence of tumor. Dickinson (10) gross,

coarse

seen in

has reported on a Japanese climber who developed a 'hznd

flapping'

that was indistinguishable from that

hepatic encephalopathy and resolved in

a matter of days

after descent. Retinal hemorrhages were first individuals working on Mt.

Logan at 17,500 ft

who also exhibited papilledema et al (52) blurring

had reported

described in

in

underwent

fundoscopic examination

presence

four cases of HACE.

In

1969

disk and increased

persisted

veins,

at the Mt.

(4

hemorrhages Logan research retinal

it

a scotoma.

had occured in

the region

Marked hyperemia around

diameter and tortuosity of retinal

were noted in throughout

because

their

all

stay at high altitude Fluorescein

injections

intraocular

pressure

elevated;

mean

retinal

increases

by others at high altitude

,

i

of

did not

nor was

circulacion

30Z which parallels

blood flow measured

veins

regardless

the presence of active capillary leakage

by approximately

the

subjects and these changes

demonstrate

cerebral

Singh

25 subjects

to detect retinal

level of acclimatization achieved.

decreased

(15).

only one subject was symptomatically aware of the

of the hemorrhages

and arteries

(15),

of the subjects developed

of macula and resulted in optic

one of

and frank papilledema

during the course of acclimatization

hemorrhages;

two

finding engorgement of the retinal

of the optic disk margins

Over one third

(5300 m),

and was semi-comatose

diopters)

station.

1968 in

time was in (52).

I

No

Hamilton-16 was negative seen.

in

cases and normal

CSF chemistries

Dickinson (28) on five of elevated fifth

all

their twelve

that lumbar

cases.

opening pressures

greater

opening

appearance

of the

leucocytosis

suggestive

pressure

performed

the assessment

of meningitis.

retinal

the

but had been vigorously of CSF pressure.

as "bloody"

count from a second

blurred vision and

were

five exhibited

Wilson

climber suffering with decreased mentation, dymetria,

Houston and

than 200 mm of water;

patients was reported

ant, a CSF cell

punctures

Four of the

treated with diuretics prior to CSF from one

excursions were

and cell counts were normal.

also reported

had a normal

respiratory

patient (59)

in showed a

reported

on a

ataxic gait,

hemorrhages

whose opening

pressure count.

was 340 mm H 0 with normal CSF chemistries and cell 2 After resolution of HACE over 4 days and after evacuation

to lower altitude

and treatment with steroids and diuretics,

pressure was 85 mm H 0. In

1960,

Chiodi .(5)

described

CSF

a patient

2 suffering with HACE who developed paresthesias, to develop

nucchal

was performed susbsequent

intermittent rigidity

occipital headaches,

loss of consciousness and hyperreflexia.

and who went on

A lumbar puncture

which revealed grossly hemorrhagic

CSF.

A

cerebral angiogram was reported as normal.

the only case

in

the

HACE has undergone The issue as are permanent

literature

in

which a patient

cerebral arteriography

suffering with

to date.

to whether any of these neurological

sequelae

from a vist

to high altitude

significant

issue not only for candidates

expeditions

but also in

determining

This is

deficits

is

a

of high altitude

the vigor and rapidity with

tl.Lon was

o

.

IUULIU

hemorrhages.

retinal

,rice or abs

to

symptoms attributable

in

12 reviewed cases

toheir

hemorrhages

was

papilledema

HACE while

on (28) founretinal a*. 7 out of tý

HolustO"

')e present

or

, varying degree~ in

f.

75% of

of the

dp cases.

The exact significance

observations (27)

is

debatable

over the last

hemorrhages

more

than 50X^)f all

that they are rarely'if

incidence

of papilledema

ophthalmoscopy ie

deficits.

(18,58)

resolve without

can

changes serve

deleterious

he contends

as one of

an effect

identify individuals Singh et al during and after found the

the

performed

their

recovery

to 210 mm of water during had

recovered.

,.V: "

"

'

"

to their

visual

that the more serious

lumbar

of how

to

punctures on 34 patients

pressure

all

(jugular

• .

,

•• ,.

patients

to be elevated

as compared

• " : ,

serve

on

HACE.

from AMS and in

(CSF)

test

system

hypoxia may be exerting

the illness

Queckenstedt's

j;'''

of p,.rmanent

and

permanent

brain and can therefore

(52)

fluid

leaving

a classificati•,i

at risk for severe

cerebrospinal

photographs,

the bes; indicators

high altitude

similer vascular beds in

that the

be groiped according

severity and the increasing likelhood

retinal

persons going to high

by stereo-pair

has developed

hemorrhages

Furthermore,

studies

retinal

ever symptomatic,

not confirmed

Weidman

impairment.

More recernt

as repcrted on the basis of direct

hemorrhages

whereby retinal

7,30,58).

decade seem to iadicate that

occur in

almost all

cignosis of these iundoscopic

(6,15,18•

altitude,

that

an

venous

-,

to when

by 60

they

compression)

Hamilton-17 * whibh physicians initiate

therapy for HACE and begin evacuation

of stricken individuals to lower altitudes. seen,

Townes et al (57)

dysfunction in

have demonstrated

As we have already long-lasting cognitive.

high altitude climbers and several authors have

//

commented on permanent visual deficits from retinal hemorrhages in

the macular region (18,27,58).

two climbers weeks in

Dickinson (10)

has reported on

suffering from HACE who remained unconscious

one case and 3 weeks in

another.

Pines (46)

for 6

has

described a case of a 39 year old climber who ascended rapidly to 18,500 f- (5600 m) and subsequently developed loss of consciousness,

severe HACE with

absence of pupillary reactions,

flaccidity

of all extremities and the presence of bilateral Babinski responses.

The climber was emergently evacuated

altitudes and treated with steroids;

to lower

48 hrs later the patient had

regained conscio~isaess but was left with slurred speech and ataxia.

Neurological examination a month later still

intellectual impairment,

emotional lability and ataxia causing

the author to suggest that somt neurological not resolve.

Dickinson (10)

accidents may occur in

showed

sequelae of HACE may

cautions that cerebrovascular

setting of individuals at high altitudes,

as has happened to one Sherpa and a physician on previous Everest expeditions in

the recent past,

and that such a superimposing of

pathologies may confound the picture of transient and permanent deficits.

Finally,

the recent trend in

mountaineering

towards

climbing Himalayan peaks without the al.d of supplemental has made the made it

oxygen

even more urgent that the issue of permanent

Hamilton-18 neurological

sequelae

from prolcnged

high altitude

exposure

be

resolved. Pathology Necropsy HACE are ,S

findings

rare.

(see

autopsy findings

in

from confirmed

brain parenchyma

first

cases of

reported

in

1965 on

7 fatalities

from HAPE and noted that

examinations

of the two brains available

study revealed congested,

plugged

II)

Singh and his colleagues

histopathological

"*

Table

(51).

with sludged

dilated capillaries

Many of

the capillaries

erthrocytes

for

throughout

the

appeared

to be

and there were numerous,

4qI

widespread

perivascular hemorrhages

producing a typicaJ

*

largest -j

clinical

so-called

'ring-and-ball'

study of AMS to date,

that both autopsies

in

their

1969

edema of the white matter and evidence

from the two

post-mort.em examination.

a biopsy taken

from one of their

widespread petechial

in

reported

their

series.

hemorrhages

As

patients who

reported autopsy results In

both cases multiple,

were noted throughout

the brain.

One brain was avaliable from a climber who became comatose 44

HACE at 18,000 ft evcuation

m)

and had been ill

and so had suffered

time before of several hemorrhages.

I

(5480

being evacuated. small intracerebrr'

the

signs of HACE also showed

Houston and Dickinson (28) fatalities

Singh et al (52)

In

series showed well developed

was suffering with very localizing edema.

appearance.

that both patients also had

of pulmonary edema at

mentioned earlier,

brain

at such capillaries,

for almost

from HACE for a relatively He

with

a week prior to long

subsequently died showed evidence hemorrhages

and subarachnoid

Thcre were areas of focal degeneration

noted at

Hamilton-19 sites of resolving petechial hemorrhages as well as areas of mnoderate focal edema at what were felt to be sites of more severe edema during the acute illness. Wilson (59) in

reports

that autopsy

one his reported cases of death from AMS revealed a grossly

edematous brain weighing 1610 gms and exhibiting flattened convolutions.

Microscopic examination revealed widespread edema

"with occasional petechial hemorrhages found throughout the brain but more numerous in

the regions of the thalamus and pons.

Pathophysiological mechanisms It

has long been observed that the symptoms and signs of AMS

do not manifest themselves immediately upon arrival at high

4

altitude

but take between

12 and 96 hours to be exhibited;

this time lag between arrival and onset of AMS argues against a direct,

*

immediate relationship

between AMS and hypoxia (52).

Houston (26) has also points out that oxygen uptake itself same at sea level as at high altitude and is unaffected by acclimatization; its

is

the

he argues that hypoxia must then lead to AMS by

secondary effects on tissue function.

Finally,

anecdotal

reports stata that simply providing supplemental oxygen does not pre-rent

or relieve the symptoms of AMS (28).

Hansen and Evan (24)

first

symptoms of AMS corresponded .9

"brain

cell compression"

aspects of altitude edema.

sickness

and clinical

to symptoms

and suggested

Such a notion appeared

experimental

hypothesized that many of the one might expect with

that

the neurological

could be ascribed to be supported

to early

cerebral

not only by earlier

studies which had demonstrated

that

Hamilton-20 hypoxia at high altitude elevations

in

produced

brain swelling,

CSF pressures (13,40,45)

observations

which revealed

swollen,

through burr holes during trephining

Sintracranial

pressure

in

two severe

Two pathophysiological

vasogenic In

(55,36)

their view,

vasodilatory

4

but also by intra-operative edematous brain bulging for relief

of raised

cases of HACE (28).

HACE.

contend that HACE is

type according

Lassen and his primarily an edema of the

to the classification

high altitude

brain

of Fishman (11).

swelling is

caused by a

response to hypoxia with subsequent

increased

cerebral blood flow and compromised autoregulation. evidence that cerebral

"during the first

blood flow is

There is

substantially elevated

few days after arrival at high altitude (50,52),

suggesting that the vasodilatory effect of hypoxia is over the vasoconstrictive hyperventilation.

I

and

theories contend at present as to the

nature of the swelling involved in colleagues

headache

stimulation of. hypocapnia secondary

Lassen and his coworkers

exercise,

of the blood brain barrier,

transcapilary

and

transarteriolar

multifocal cerebral

encephalopathy

hypertensive

retinal

and

then overwhelms

leading

to

leakage and a vasogenic,

edema ensues

hypertensive

exercise,

at high altitude

the integrity

to

further maintain that

moderate hypertension attendant with strenous especially isometric

predominant

(36,55).

and cite

hemorrhages

They compare HACE to

the similarity between

and those seen at high

altitudes.

This notion of vasogenic edema contrasts sharply with that of Houston and Dickinson (28)

I

who theorize that HACE is

caused by

Hamilton-21

I

massive hypoxic

cell

%

type as this is

variety generally

experimental

hypoxia

cytotoxic edema in failure

of

compromise

studies

of

edema of the. cytotoxic

seen in

(60).

the setting of

According

to Fishman

ATP-dependent within

accumulate

cellular

functions

affected brain cells.

sodium pump and soon sodium

brain cells

leading

and eventually

first

to

to death of the

Fishman also points out that endothelial

cells may be particularly affected by hypoxia, for vascular

(11),

the setting of hypoxia would result from a

the cellular

and water would

producing

damage

disturbances

superimposing

occuring at the cellular level.

setting the stage

themselves upon

those

Houston and Dickinson (28)

cite

necropsy findings of videspread edema alonj with multiple,

?I

diffuse petechial hemorrhages as evidence that such a series of hypoxia-mediated changes may be occuring in the brain during HACE.

They also cite the findings of retinal vein engorgement

during experimental

hypoxia (13)

and simulated high altitude (40)

as evidence of a similac etiology for retinal hemorrhages in

the

setting of HACE. Wohns (60) N

classification edema and its

has reviewed Fishman's (11) of vasogenic,

cytotoxic and interstitial

relationship to HACE.

edema places little

or no role in

HACE as the clinical syndromes such as obstructive

hydrocephalus or pseudotumor cerebri,

in

brain

He argues that interstitial

associated with this kind of edema,

the picture seen with AMS.

pathophysiologic

Steroids,

bear little

resemblance

which have proven beneficial

the treatment of some cases of early AMS and severe HACE

1 .~

to

ei n.

..e tin-

1Hamilton-22 (14,52),

are of little

interstital argue

benefit

in

or cytotoxic edema that vasogenic

pathophysiology

edema is

of HACE.

the treatment

(11)

and this would s2em to

playing some role in

Wohns also cautions

(60)

experimental models of hypoxia which initially cytotoxic edema can also lead Since this of HACE,

the that

may produce

to confounding vasogenic

same phenomenon might also be occuring in

swelling.

the

one must be wary about drawing any conclusions

pathophysiological efficacy.

It

is

validity

event

of the ATP-dependent dysfunction.

in

that the initial

HACE is

compromise

patients with cerebral

event--go

on to show signs

Fishman points out

infarction--a hypoxic,

As discussed earlier,

isolated neurological

suggesting well-localized

cytotoxic

of local vasogenic edema as evidenced

"by focally positive brain scans (11). do exhibit

cytotoxic changes may

mediated events.

that most

anatoinical

investigators have also-reported

demonstrated

hypoxia-mediated

on these first

then follow vasogenically

bloody

about

sodium pump leading to brain cell

Superimposed

HACE patients

setting

that are based upon therapeutic

quite feasible

pathophysiological

exhibited

of either

CSF on lumbar

both intracerebral

deficits

disturbances.

(5,28,59)

many

Many

that their

puncture and at least and subarachnoid

patients one necropsy

hemorrhage

"(28), supporting the view that localized disruption of the blood brain barrier addition,

is

taking

necropsy

hemorrhages hemorrhages,

place in

reports cite

and the histological all

arguing

I WII

•

some instances diffuse,

of HACE.

localized

demonstration

of

In

petechial 'ring-and-ball'

that some vasogenic component,

namely

Hamilton-23 disruption of the blood brain barrier,

localized in

the setting

of HACE.

hypothalamus,

Wohns has also pointed out

gland,

pituitary

area

postrema and choroid plexus

endothelium and are

possess a fenetstrated intact blood-brain

that sirnce

the brain such as the pineal gland,

regions of

specific

must be at work

barrier

therefore

such areas may be

lacking an

predisposed

to edema

and thus rendered particularly sensitive to the effects of high % -altitude

(60).

To date,

necropsy findings

specific point although there is

"suggest that there is

(see

below).

Finally,

although the relationship

(6,28),

function at

hormone secretion

to anti-diuretic

hemorrhage remains conjectural

to retinal

the fact that such

vascular disruption occurs within the eye at high altitude as frequently as now seems apparent would make it

".

(15)

likely that

similar events may be taking place within the brain. "Hohendiurese",

tj•

this

some physiological data to

impaired hypothalamo-pituitary

with respect

high altitudes

have not addressed

or the diuresis of high altitude,

was quite

a familiar phenomenon to early alpinists and had been clearly documented in both real and simulated high altitude settings (4,52).

It

experienced upon arrival

was also noted that climbers who acclimatized well a marked diuresis for the first at high altitude

while

three or four days

those who did not accl.-matize

rapidly often exhibited oliguria auid many developed symptoms of AMS (9,19,52,). wA

Singh et al (52)

found that

118 soldiers

affected with symptoms of AMS within 6 to 96 hours after arrival at high altitude showed oral fluid intakes exceeding urine output M&

'4i5

^

Hamilton-24 by. 1100 mls

to 43 mls per day as opposed

group of

soldiers who exhibited

no symptoms of AMS and showed a urine

output exceeding

oral intake of

their

mls to 4700 mls per day. that improvement

within

similarly vigorous

In

"hohendiurese" vasopressin pituitary

study revealed

It

was postulated that such

might be reflection of dimin.shed arginine

(AVP)

secretion from the posterior lobe of the the setting

of hypoxia;

to treatment with diuretics

advanced

(52).

Several

furthermore,

the setting of AMS might then be

amenable

prevent and treat

clinical

before cerebral trials

employing

edema became

diuretics

to

AMS have been performed and the results

"discussed below.

Hackett et al

HAPE exhibited higher levels (35)

demonstrated

(20)

observed

that

reduced secretion

and serum hypertonicity in

altitude.

studici (3)

More recent

will

trekkers

of AVP than. did unaffected

setting of dehyration

American Medical

be

with

trekkers.

of AVP in

the

rats at high

performed during the 1981

Research Expedition

to Everest

showed

that

prolonged exposure of humnns to high altitude was also accompanied by impaired osmoregulation and that increases serum tonicity suggesting

failed

to induce appropriate

that hypothalamic-posterior

occur at extreme altitudes. release

plays a

and whether

N

by a

diuresis which persisted 2 to 10 days after

gland in

et al

this same

the symptomatic group was preceeded

undiminished AVP secretion in

Jones

fluids by a range of 930

addition,

the symptoms of AMS had resolved.

~

to a comparable

I

I

individuals

I

I

AVP secretion,

pituitary

dysfunction does

Whether such suppression of AVP

protective

I

in

role

in

susceptible

I

I". I

high altitude

acclimatization

to AMS demonstrate

"I I

I

l

6

IP I

k

V %A

Hamilton-25 persistent,

"sea-level" release of AVP,

aa

suugested

preliminary

data

is

a question

further

in

HAPE patients

(20),

by Hackett's that merits

investigation.

Finally,

Sutton and Ltassen

had a common underlying

increased

flows in

•55)

postulated

pathophysiological

both the cerebral

by hypertensive

pulmonic

hypertension

arterial

of hypoxic vasoconztriction

and dramatic

artery pressures are commonly seen in vasculature,

basis,

namely

and pulmonary vascular beds

both of which were damaged circuit,

that AMS and HAPE

surges.

In

the

would arise as the result elevations

HAPE (49).

In

in

pulmonary

the cerebral

arterial surges are hypothesized to arise from

both physical exertion and extreme cold at high altitudes. has suggested

that HAPE may in

Wohns

fact be a variant of neurogenic

pulmonary edema and occurs as a manifestation of hypothalamic dysfunction in

HACE (60).

Recent animal studies (61)

demonstrated that pre-treatment anticonvulsant,

prevented

setting of cerebral edema, origin.

have

with diphenylhydantoin,

the occurence

an

of pulmonary edema in

the

supporting the notion of a neurogenic

While numerous cases of HAPE have occured without

clinical evidence of HACE being present such overt neurological manifestations

may only occur in a small majority of the most

severely affected patients.

On the other hand,

nearly every

necropsy to date of patients with ueuropathological cerebral edema has demonstrate 4

evidence of

concomitant pulmonary edema.

Prevention and Treatment of PACE Given the abundance and divergence of pathophysiological

Hamilton-26 mechanisms

postulated

to play a role in

the development,

it

is

not suprising that a equally wide variety of preventive measures and

therapies have Since

been proposed

the deleterious

and examined,

effects of exposure

can be prevented or dramatically acclimatization,

most protocols

reduced

to high altitude

by proper

aimed at lessening the incidence

and severity of AMS have been directed at determining the most effective respect

zate of ascent to allow adequate acclimatization.

to mobilizing

Singh et al m),

(52)

recommended

a second week at

14,000

ft

subjects

(4270

to provide

above

1000 ft

warns against

(5500

(300

sudden

m).

Hackett and Rennie

recommends

(21)

m) and setting

information

of ascent

one's

they also showed

related deaths amongst Himalayan

rate of

He also

greater

than

in

1975,

about a statistically

time could be demonstrated

at Everest

in

of

have shown that after

of clinical

protocols had proven effective

1977 and reducing

(lO00m)

to an altitude

climbing circles

prolongation

Furthermore,

(3000

for most

m) per day upward, from 10,000 ft.

amongst trekkers arriving

in

(19)

Base Camp at Pheriche, that such acclimatization

lowering

the Incidence of AMS-

trekkers from 5 in

1974 to zero

the number of emergent helicopter evacua

of AMS stricken climbers

(2400

week at

acclimatizetion

Hackett

transportation

acclimatization within

Nepal.

m) and a final

adequate

10,000 ft

widespread dissemination

significant

(3350

at 8,000 ft

for one extra day for every 3300 ft

elevation gained

10,000 ft.

m)

safely to high altitudes,

a one week stay first

11,000 ft

up to 18,000 ft

acclimatizing

ascent at

Indian soldiers

With

from 15 down to a single one over the

ion

Hamilton-27 same period. Because inducing AMS,

promising data reviewpd

of the

"Hohendiurese"

might

prevent

above suggesting

the onset of symptoms of

Singh et al undertook a study wherein 100 soldiers furosemide

treated with 80 ag of oral

controls.

were

twice a day for two days

and compared

at high altitude

after arrival

that

to comparable

They found that the incidence of subjective symptoms of by over half and the incidence of severe

AMS was diminished

dyspnea was completely abolished.

From furosemide,

a milder diuretic which also had several

to acetazolamide, theoretical First,

other investigators turned their attention

benefits for high altitude acclimatization

acetazolamide is

(1).

a carbonic anhydrase inhibitor and such

enzyme inhibition would favor the creation of a metabolic acidosis to offset the hypoxic respiratory alkalosis of high altitude hyperventilation.

In addition,

acetazolamide is

known to

reduce the rate of cerebrospinal fluid formation and this might alleviate In

rises in

intracranial pressure asociated with HACE.

1968 Forwand et al (14)

undertook a double-blind study in

which 43 subjects received either placebo or acetazolamide hours prior to airlift

to Mt. Evans,

for 32

Colorado at an altitude

of 12,800 ft (3900 m) and found that treated subjects experienced significantly fewer symptoms of AMS and exhibited a greater increase in

ventilation and alveolar oxygen tension than the

placebo-treated

counterparts.

similar but smaller trial

in

Later,

Gray et al (17)

undertook a

which 6 subjects were given 250 mg

Hamilton-28 of acetazolamide twice a day for two days prior to ascent to 17,500 ft (5400 m) and four subjects were given placebo. subjects who recieved

placebo were

incapacitated with

although none had any evidence of pulmonary the subjects Five of

pretreated with acetazolamide

the six had mild symptoms of AMS,

headache while the sixth became to have a fever. pulmonary

of HAPE.

and was later showed

by recent

arrivals

signs of

to occur

the insomnia

that is

at high altitudes

desaturation

than

often

and accompanies

thereby making AMS more

(56).

Because many believe

double-blind

because

may depress ventilatory drives during sleep and

actually worsen arterial

manifestations

found

acetazolamide seems to be more effective

experienced

sedatives

contrast,

mostly nocturnal

congestion and one was subsequently evacuated

sedatives at relieving

likely

In

fared much better.

Two of the acetazolamide-treated

Finally,

/

severe AMS

congestion.

incapacitated

traditional

AMS;

All four

that

the earliest

o: vasogenic cerebral

crossover

study was

symptoms of AMS are

edema (see

above),

recently performed

a small

(34)

in

which

"subjects were pretreated with dexamethasone and then remained in a hypobaric chamber examined

for

significant

outpat,

symptoms and signs of AMS. decrease

exhibited serial

for 42 hours while they were queried

significantly

in

and cerebral

narrower

artery

retinal

administration

in

a

symptomsI

diameters on

and demonstrated a higher urine

supporting some of earlier

Singh's group (52)

reported

both respiratory

fundoscopic examinations thus

Subjects

and

anecdotal

of improved diuresis after

reports

from

steroid

AMS patients.

MM

Hamilton-29 Treatment of HACE in

the setting of AMS has involved a wide

variety of therapeutic agents. colleagues stand unequaled therapeutic

trails

(52).

In this regard,

Singh and his

for the breadth and scope of their

Aspirin was administered at a dose of 0.6

gm three times a day for two days to 250 subjects with symptoms of AMS. sleep,

While aspirin did relieve headache it

pain and promote

had no other significant effects on any of the other

symptoms of AMS and produced a number of side-effects treated group,

namely increased dyspnea,

in

the

abdominal pain and

hematemesis. As early as 1919,

Haldane and his colleagues had suggested

that the symptoms seen in

AMS might be related to the

ventilatory alkalosis and that adminiitration of ammonium chloride might prove beneficial in (23).

hastening acclimatization

Barron et al (1) administered ammonium chloride to 6 out of

12 climbers ascending to 15,500 ft (4725

i)

and found that

although the treated subjects exhibited lower carbon dioxide and increased oxygen concentration in no significant

difference in

either group.

More recently,

expired alveolar air there was

the symptoms of AMS experienced by Singh's group (52)

administered

2

gms ammonium chloride orally for 3 days to 30 subjects with AMiS in

the hopes that some of their symptoms might be due to the

early respiratory alkalosis seen upon arrival at high altitude. Unfortunately 23 out of the 30 subjects felt worse after treatment.

Since it

was postulated that hypokalemic alkalosis

might occur during acclimatization,

Singh et al (52)

also treated

Hamilton-30 30 -patients with daily potassium supplements significant

but found

no

improvement.

Returning furosemide,

to the notion of inducing

Singh and his colleagues

(52)

"hohendiurese"

with

treated 446 cases

of

AMS with a usual dose of 80 mg of furosemide

every

two days or until

output occured.

an adequate

level

therapy was described as effective support of furosemide trail

of furosemide

therapeutic

trail.

predominantly furosemide

treatment

a more effective diuresis

Nineteen out of 24

if

data in

AMS with

were treated with

cases were treated with a

and furosemide

to determine

therapy.

The latter

group

although no clinical

data

one group fared better clinically.

cases of severe HACE were treated

furosemide and betamethasone.

with

Although again no quantitative

clinical

data was provided,

improved

rapidly with such combination therapy and presented

illustracive by prompt

papilledema

a fall

in

HACE received

lover altitude

of steroids was

one

followed

CSF pressure and resolution of

reports wherein patients

suffering from severe

steroid therapy and subsequently improved and

without neurologic

exceedingly

that patients

(52).

Anecdotal

recovered

Singh et al reported

case where administration diuresis,

The

rather than an actual

pulmonary mainfestations

was presented

for

was derived from a prophylactic

Forty-two cases of malignant

of morphine

demonstrated

although actual

described above

alone and forty-two

combination

of urine

12 hours

difficult

defict

to differentiate

and other

therapies

abound (10,28,46,52,59,). the effects

of descent

which were concomitant with

It to

IN

Hamilton-31 the administration severely

of steroids.

Wilson reports

affected with HACE and still

wide-based

ataxic

gait,

exhibiting slow mentation,

and dysmetria

upon his evacuation

hospital at sea level and who was treated dexamethasone

with full

recovery

on one climber

to a

solely with

within approximately a

week's

time (59). The use of furosemide

in

the treatment

potentially hazardous

since almost all

ar- volume

from dehydration,

contracted

respiratory losses, al

(17)

ataxia

of gait,

member

of this group lapsed

clinically

another

became

in

this

reported

concomitant

of furosemide ataxia

(52)

received

retinal

reported

required

Wilson

ataxic gait

however,

in

prevention by

(59)

after

also

furosemide

the largest

the treatment of HACE reported

the best

emergent

that volume depletion was

hemorrhages.

steroids concomitant

Finally,

severe

Four out of the five subjects

Singh et al,

the clinical

Gray et

suffering from

individuals developed

although many of their

have altered

remains

in

intake (59).

incapable of standing and the last

a patient who exhibited

administration.

insensible

group with two patients becoming

hypotensive and tachycardic. developed

increased

into coma and

The investigators evident

at high altitude

furosemide to five subjects

Three of the treated

evacuation.

climbers

vomiting and poor fluid

administered

severe AMS.

of HACE is

single study

no subsequent

patients with HACE also

with diuretic theripy

and this

results. treatment slow,

for AHS (see

deliberate ascent

Table

III)

still

to high altitude.

may

Hamilton-32 Acetazolamide AMS.

seems to alleviate some of the early symptoms of

In cases of severe AMS with evidence of cerebrai

oxygen therapy should be instituted. should be promptly evacuated therapy is

edema,

The stricken individual

to lower altitude and steroid

probably useful at least initially.

The use of

diuretics And morphine should probably be conservatively employed for cases where

there

is

clinical

eviderce

of pulmonary

congestion.

Acknowledgements: Dr.

Hamilton

Research

is

a recipient

Fellowship

the Medical Corps,

(N.I.H. United

.,he authors express Army for its

support

The views,

in

of a Neuzology and Neurosurgery

Grant T32 NS07170)

their

gratitude

to the Department of the

the preparation of this manus'ript.

opinions and assertions contained herein are to be construed

policy or statement of the Department

Department of the Army, Development

in

States Army (Reserve).

those of the authors and should not position,

and a Captain

or

Command unless

as official

of Defense,

the

the United States Research and so designated by other official

documentation. The author wishes to thank Drs. Carr for their and Mr. assisting

assistance with

Frank de la Vega of the author in

from mountaineering

/

Charles Houston and Daniel

the preparation of this

manuscript

the American Alpine Club for

assembling

records of medical

expedition mishaps.

histories

Hamilton-33 -References

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lip

.I

Viv

IVV

d U€w

uv vV~ UV~ Um~ I W~~ .~

gww.-

~

.we

j,

Table I:Clinical

Early,

Features of Acute Mountain [Modified from Dickinson (14)]

Benign AMS:

Systemic

Generalized

Sickness

(AMS)

Features

Headache

Chest

Nausea,vomiting Vertigo, insomnia Generalized fatigue Irritability Tinnitus

Peripheral edema Retinal hemorrhages Anorexia MLntal slowness

discomfort

or fullness

Malignant Features of AMS constituting High Altitude Pulmonary Edema (HAPE) Dyspnea at rest Cough Sputum production

SHemoptysis

(frothy)

Cyanosis Basal crepitations Tachypnea

Tachycardia

S~Malignant of AMS constituting High Altitude Cerebral Edema (HACE) features: Severe headache Vomiting Impaired sensory,

Impaired long,

motor

short

Extensor plantar

functions

term memory

Altered level of consciousness Hypo- or hyperreflexia Ataxia

Papilledema

responses

Less Common features:

I 4

I,

Hallucinations Scotoma Urinary incontinence Hemiparesis SParesthesias, dysesthesias SVisual field defects

Blurred vision Speech difficulty Cranial nerve palsies Rigidity or flaccidity Convulsions Tremor

Pupillary changes

Meningismus

Pathologic Features Of Table II: High Altitude Cerebral Edema (HACE)

Edema of white matter Widespread petchial hemorrhages (perivascular 'ring Sludging of erythrocyes in capillaries ? intracerebral hemorrhages ? preponderance of thalamic and pontine hemorrhages ? subarachnoid hemorhages

and

ball')

z

Table III:

Prevention and Management

of HACE

Prevention slow acclimatization

[adapted

from Hackett

(28)]

Rules of thumb: Start walking at 10,000 ft (3,000 m) 1000 ft (300 m) of ascent per day 1 night of aclimatization for every 3000 ft (1000m) gained above Acetazolamide

10,000ft

(3000m)

Management Early AMS: Analgesics for headache Hydration Rea t Supplemental Oxygen Acetazolamide

Severe HACE: Avoid sedatives or analgesics Emergent evacuation to lower altitude (on Supplemental oxygen Steroids ? Morphine if concomitant HAPE present ? Diuretics if HAPE present

foot if

necessary)