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diving and undersea medicine for the non-medical diver, the non-diving
physician and the specialist.
Detection of endogenous gas phase formation in humans at
by Dr. Jolie Bookspan, PhD
Bookspan, J. Detection of endogenous gas
phase formation in humans at altitude. Medicine & Science in Sports
& Exercise Suppl. Vol. 35, Num 5, May
2003 # 901, p S164.
DETECTION OF ENDOGENOUS GAS PHASE FORMATION IN HUMANS AT ALTITUDE
Jolie Bookspan, Ph.D. Research Associate, Institute for
Environmental Medicine (IFEM) University of Pennsylvania School of
G. Golden Bell Labs.
That endogenous gas bubbles form after decompression from saturation at
depth appears to be well founded. Data from preliminary work for this
study (1) suggest the decompression required to produce bubbles in 50%
of male subjects is from air saturation at only 10 fswg. Extrapolation
to altitude suggests that pressure reductions commonly attained in
commercial and military aircraft may be sufficient to form a gas phase
in humans. We examined the magnitude and duration of gas phase
production in human male volunteers at altitudes up to 10,000 feet in
an altitude chamber to establish a dose response relationship between
bubble formation and hypobaric exposures using Doppler ultrasound. This
study has the benefits of identifying potentially preventable
decompression stress during flying after diving in what is often
considered routine cabin pressures. Individual factors that predispose
to bubble formation were examined. The data may be applicable to flying
after diving schedules.
Delaying flying after recreational diving is an important issue
requiring more objective data. That gas bubbles form in the body after
decompression from saturation at depth is well founded. Recent data
from preliminary work for this study by co-investigator of previous
work Eckenhoff showed bubbles in 50% of male subjects after
decompression from saturation in an underwater habitat at only 10 feet
(fswg). Extrapolation to altitude suggests that pressure reductions
commonly attained in commercial and military aircraft may be sufficient
to form a gas phase in humans. Air travel routinely exposes passengers
to ambient pressure transients. Work in decompression during undersea
operations has established that these pressure changes may produce
small, mostly inert gas bubbles which become widespread throughout
tissues and blood. It was previously thought that bubbles would not
form unless a specific supersaturation ratio of tissue pressure to
ambient pressure was exceeded. However, detectable gas phases
develop in humans after surprisingly small decompressions (1,2).
Since this small decompression is substantially less than previously
thought required for these gas phases to evolve (3,4) it is possible
that humans have stable pre-existing gas spaces (5, 6) which with
reduced pressure, enlarge according to Boyle's Law and bud-off bubbles
into the tissues and blood stream.
Inert gas bubbles are generally accepted as the mechanism behind
decompression sickness (DCS), also called dysbarism or bends.
Manifestations of DCS range from itching to death, although more often
the gas phase is asymptomatic (silent bubbles) or noticeable only as
fatigue. Long term exposure to silent bubbles may be associated with
health risks in commercial divers such as osteobaric necrosis.
Conditions analogous to decompression from undersea are encountered in
altitude exposure. Grover et al. (7) considered bubble formation
a factor in acute altitude sickness. Significant and ongoing work done
in this area by Eckenhoff (1,2) suggests that a gas phase may form at
pressure reductions commonly attained in commercial and military
aircraft, a prediction consistent with a recent case report of DCI
occurring after decompression to 8000 feet (8), but no study has
examined if this extrapolation is valid. We examined the magnitude,
duration, and latency of gas phase production in human male volunteers
at (chamber) altitudes of 2000 to 14,000 feet to establish a dose
response relationship between hypobaric exposure and bubble formation.
STATEMENT OF PROBLEM
No study to date has examined gas phase formation at routine flight
altitudes. The purpose of the study is to identify the magnitude
and duration of gas phase production at altitude to establish a dose
response relationship between bubble formation and hypobaric exposures
using Doppler ultrasound.
- To establish if tissue bubbles form in humans at
altitude, and gather information toward developing a dose-response
- To gather information toward developing a
dose-response curve. This curve can be applied to information regarding
flying after diving schedules.
- To identify individual factors which predispose to
tissue bubble formation at altitude
- Elimination or modification of bubble production, a
known health risk, using a physical or pharmacologic approach is a long
range goal of this research.
SIGNIFICANCE OF THE PROJECT
The expected dose response curve will help identify acceptable
schedules of flying after recreational diving, as well as potentially
preventable decompression stresses during flying after diving for all
divers. This study was the first to investigate gas phase formation
with exposure to routine flight altitude.
DESCRIPTION OF EXPERIMENTAL WORK
Human subject approval was obtained. Subjects were recruited from the
general population with no restriction on age or physical
stature. Physical examination by a physician familiar with diving
medicine was required before exposures. Subjects were free of
hyper or hypobaric exposures for three days prior to exposure.
Decompression to altitude from one atmosphere was studied at the
Institute For Environmental Medicine (IFEM) altitude chambers at the
University of Penn School of Medicine. Subjects were divided randomly
into groups and exposed to hypobaric conditions from 4000 to 10,000 ft.
(1000 ft increments). At each altitude Doppler ultrasound (9,10) was
used to detect a mobile gas phase at several venous sites over each
twelve hour run. Dose response relationships were constructed and
contrasted to results from simpler systems (in vivo and in vitro IFEM
counter diffusion model) and differences will be used as the basis for
future studies. Data from many human subjects will allow correlations
between outcome of the Doppler monitoring and age, gender, height,
weight, body fat, previous injuries, etc. Preliminary data from
Eckenhoff (11) on 170 subjects showed a significant correlation between
age and bubbles but not between weight, body fat or gender and bubbles.
Individual factors that may predispose to bubble formation (age,
gender, height, weight, body fat, previous injuries, etc.) will be
examined. The chamber system is certified for safety by the Naval
Facilities Engineering Command under NAVMAT P-9290 and has been under
continuous certification since 1975.
CONSTRAINTS AND RISKS
Potential hazards to investigative staff and subjects are those
ordinarily encountered in work involving reduced ambient pressures
including decompression sickness and ear and other air space
equalization problems. Risk of air embolism from lung barotrauma is
greatly reduced by breathing normally and continuously at all times.
Although decompression sickness is possible the relatively low pressure
reduction makes the likelihood remote.
We found bubbling in 75% of male subjects at 10,000 feet which is
sometimes reached as an equivalent cabin pressure in commercial air
flights, and is routinely achieved in unpressurized passenger flights
and some military aircraft. The rate of ascent was found to relate to
diving decompression stops. The data may be applicable to flying after
diving schedules and may contribute to understanding of a bubble
component to altitude sickness.
MORE STILL TO DO
From this preliminary work we make the tentative conclusion that
civilian airline cabin pressure may be sufficient to form a gas phase
in humans, even with no prior diving. It is hoped to continue this
study with additional runs from 2,000 to 12,000 to establish a dose
response relationship between altitude exposure at airplane cabin
pressures and bubble formation.
In a previous study we did with 170 subjects coming up from saturation
underwater we found a relationship between age and bubbles. That may
not mean that getting older causes more bubbles, but that older
subjects tended to bubble more than younger subjects for reasons we
don¹t yet know. The dividing age for 'older¹ was age thirty.
We didn¹t find any trends between weight, body fat, or gender and
bubbles. That means we didn¹t find any bubble difference between
larger or smaller subjects, fatter or thinner, or between females and
males. Another question is why some people are more likely to form
bubbles than others. Are things like age, gender, height, weight,
body fat, and previous injuries really predisposing factors?
Predisposing factors are important to know about, but little is yet
This work will add important information to the flying after diving
Thanks to Dr. Peter Bennett and 'The Recreational Diving Research
Foundation' for funding this work.
1. Eckenhoff RG, Olstad CE, Carrod GE. Human dose
response relationship for decompression and endogenous bubble
formation. J Appl Physiol
2. Eckenhoff RG, Osborne SF, Parker JW, Bondi KR.
Direct ascent from shallow air saturation exposures. Undersea Biomed
Res 13:305-316, 1986.
3. Weathersby PK, Homer LD, Flynn ET Homogeneous
nucleation of gas bubbles in vivo. J Appl Physiol 53:940-956,
4. Yount DE & Kunkle DE. Gas nucleation in the
vicinity of solid hydrophobic spheres. J Appl Physiol
5. Evans A & Walder DN. Significance of gas
micronuclei in the aetiology of decompression sickness. Nature
6. Tikusis P. Modeling the observations of in vivo
bubble formation with hydrophobic crevices. Undersea Biomed Res
7. Grover RF. Tucker A & Reeves JT.
Hypobaria: an etiologic factor in acute mountain sickness?
in: Loeppky JA & M.L. Riedesl (eds.) Oxygen Transport to Human
Tissues. New York: Elsevier/North Holland, 1982.
8. Rudge FW. A case of decompression sickness at 2437
meters (8000 feet). Aviat Space Environ Med 1990; 61:1026-7.
9. Kisman KE & Masurel G. Bubble evaluation code
for Doppler Ultrasonic decompression data. Undersea Biomed Res
10. Spencer MP. Decompression limits for
compressed air determined by ultrasonically detected blood bubbles. J
Appl Physiol 40: 229-235,1976.
11. Eckenhoff RG, Olstad CE. Gender effect on venous
bubble formation after decompression from prolonged 16 fswg exposures.
Undersea Biomed Res
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