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
10.
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01760
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March 1986
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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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34. Johnson TS, Fulco CS, Trad LA, Spark RS, Maher JT: "Prevention of Acute Mountain Sickness by Dexamethasone," Engl. J. Med., 310, 683-686, 1984.
New.
35. Jones RM, Terhaard CT, Zullo J, Tenney SM: "Mechanism for reduced water intake in rats at high altitude," Am. J. Physiol.,
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36. Lassen NA, 2, 1154, 1975.
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37. McFarland RA: "Psychophysiolcgical s tudies at high altitudes in the Andes," J.,_ Comp. Pschol., 24, 189-220, 1937.
"38. Meehan RT,
Zavala DC: "The pathophysiology of acute high altitude illness," Am. J. Med., 73, 395-403, 1982. 39. Meyer-Ahrens C, cited in Houston CS, Going High. The Story of Man and Altitude. Burlington, Vt., Charles S. Houston, M.D., 1980,
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50. Severinghaus JW, Chiodi H, Eger II EJ, Branstater B, Hornbein TTF: "Cerebral blood flow in man at high altitude," Circ. Res., 19, 274-282, 1966. 51. Singh I, Kapila CC, Khanna PK, altitude pulmonary edema," Lancet,
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II
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2, 32-39,
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*
Townes BD,
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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)
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