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Numerous illustrations, unique full-color SPECT scans
Internationally renowned contributors
K. K. Jain
Textbook of
Textbook of
K. K. Jain
Hyperbaric Medicine
Hyperbaric
This textbook, now appearing in its 5th, fully updated, and expanded edition, has become widely known as the
best exposition available on the topic of hyperbaric medicine and the wide range of applications of hyperbaric
oxygen (HBO) techniques. In addition to explaining the basic principles of HBO therapy and its application in
carbon monoxide poisoning, decompression sickness, and diving medicine, the textbook looks objectively
Hyperbaric Medicine
Textbook of
Medicine
and critically at its use in numerous other areas, such as stroke, CNS and neurological disorders, traumatology
and wound healing, infectious diseases, rehabilitation and sports medicine, plastic surgery, emergency
medicine, obstetrics, and cancer treatment. With over 1,700 up-to-date references and an extensive index,
the volume is not just a textbook suitable for those seeking an introduction to this expanding field, but also
an invaluable resource for specialists.
Well set out and easily readable a comprehensive book well-written, and the information is accurate.
(P. Moore, in Anaesthesia and Intensive Care)
This excellent and comprehensive text remains probably the standard work an essential reference text.
(N.K. Cooper, in Journal of the Royal Army Medical Corps)
The experts who have made such superb contributions to [this book] are the world leaders in their fields.
(Prof. James F. Toole, MD)
With contributions by
S.A. Baydin MD
K. K. Jain, MD
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Foreword by J. Toole IX
Foreword to the Third Edition by E. Teller X
Foreword
James F. Toole, MD
Teagle Professor of Neurology
Director, Cerebrovascular Research Center
Wake Forest University School of Medicine, Winston-Salem, NC
Slowly but surely, hyperbaric medicine is becoming an es- cial or toxic) a seemingly innocuous substance such as ox-
tablished treatment modality for a variety of medical dis- ygen can have in various circumstances.
orders, despite the rocky road that it has sometimes had to By and large, the experts who have made such superb
travel over the years. In some ways, I feel that the need for contributions to the Textbook of Hyperbaric Medicine are
oxygen in medical treatments is akin to mans basic re- the world leaders in their fields. With their help, Dr. Jain
quirement for water and food, and I also think it is fair to has expanded his already outstanding book into a com-
say that the logic and utility of hyperbaric oxygen treat- pendium of multi-authored chapters (containing over
ment now seem to be almost as undeniable as these basic 2,000 references) covering areas of medicine as disparate
requirements are. as wound healing, gastrointestinal disorders, trauma, and
It is certainly the case that, from time immemorial, rem- obstetrics. Of particular interest in this edition are the ex-
edies learned by trial and error have been handed down tensive discussions of cerebral circulation and its disor-
through the generations with the result that many roots, ders, as well as of stroke, diving accidents, and neurosur-
berries, fruits, and leaves, as well as special waters contain- gery.
ing minerals have been advocated throughout history for For an earlier edition, Dr. Jain enlisted a remarkable
their curative powers. More recently, however, evidence- Foreword by Professor Edward Teller (see next page), who
based medicine has come to the fore, demanding higher began by stating Hyperbaric medicine is new and con-
standards of evidence from basic and clinical/research tri- troversial and that we live in an age that has the habit
als and objective statistical results. One of the first instances of treating progress with suspicion, and then went on to
of such objective studies in my lifetime was when Austin pose the question, But what is the innovator to do? He
Bradford Hill and Richard Doll (Doll 2003) convinced col- also raised the age-old problem of the ethics of the dou-
leagues to allocate patients with pulmonary tuberculosis ble-blind trial, and cautioned us to be aware of the poten-
randomly to prove the efficacy of streptomycin, although tial danger of high-pressure treatment for too long a pe-
their trial followed a tradition started 200 years earlier by riod, in the same way that drug treatments at too high
Linde, who provided citrus fruits aboard some, but not all dosages bear clear risks. The field of hyperbaric medicine
ships in the British Navy to test whether they would prevent has indeed been subject to an at times intense debate, but
scurvy (Moberg & Chon 2000). much progress has been made since Professor Teller orig-
By means of prospective trials, it has been found that inally wrote his words (and will, I am sure, continue to be
various established therapies can be detrimental for some made in the future), on the basis of mutual respect, un-
diseases, while being clearly beneficial for others. This is derstanding, and cooperation, while also submitting be-
precisely the case with hyperbaric medicine now: while a liefs to randomized trials.
hyperoxic environment for newborn babies can lead to ret- Professor Teller wrote then: It is not entirely impossible
rolental fibroplasia with blindness, there is also convincing that, perhaps sometime in the next decade, professors of
evidence that hyperbaric treatments provide clear benefits medicine will have difficulty in explaining why treatment
in diseases such as various neurological disorders, stroke, with oxygen was not widely adopted much earlier. Reflec-
cerebral ischemia, and wound healing. And, of course, ting today on these words by an elder statesman whose sci-
those of us who have worked in high-altitude environ- entific observations went unheeded early on, we can safely
ments know the very short time window during which the conclude that the uphill battle for acceptance of hyperbaric
human brain can function in hypoxic conditions. It never oxygen as therapy now rests on a solid foundation. This
ceases to astonish me what a wide range of effects (benefi- solid foundation is described comprehensively and clearly
X
within this outstanding text, in which the assembled ex- References
perts provide a fair and balanced summary of the literature
and evidence. And it also means that the decade of HBO Doll R (2003). The evolution of the controlled trial. The Eighteenth
to which Professor Teller indirectly referred has now come. John P. McGovern Award Lecture, delivered at the Thirty-Third
Meeting of the American Osler Society, Edinburgh, Scotland, May
23.
Moberg CL, Chon ZA (Eds.). (1990). Launching the antibiotic era.
Personal accounts of the discovery and use of the first antibiotics.
New York: Rockefeller University Press.
Hyperbaric medicine is new and controversial. Indeed, Perhaps the most natural use of HBO is to counteract
since it is new, it must be controversial in an age that has carbon monoxide poisoning. The best known effect of car-
the habit of treating progress with suspicion. But what is bon monoxide is to replace oxygen by being more firmly
the innovator to do? If he applies a new and safe procedure bound to hemoglobin. But, of course, high pressure oxygen
to patients, and the procedure appears to be successful, his can drive out the carbon monoxide and produce a cure in
success might well be denigrated as anecdotal. Will he be an understandable fashion.
allowed to run a double blind experiment in which half of A little harder to grasp is why pure oxygen at two atmo-
the patients are denied the benefits of what appears to be a spheres of pressure (which is ten times as concentrated as
cure? It is an age-old problem that has grown sharper in the natural occurrence) should have any general uses. In-
the course of time. deed, under normal circumstances, the hemoglobin in ar-
Hyperbaric medicine grew out of the problems encoun- terial blood is 97 percent saturated with oxygen. Are we
tered by divers exposed to high pressures. The treatment of exerting ourselves to supply the remaining 3 percent? The
disturbances due to bubbles which develop during rapid de- answer, of course, is no. Oxygen is also soluble in blood. At
compression was the natural connection between high pres- two atmospheres of pressure, oxygen can be dissolved into
sure and medicine. This limited application of a medical pro- the plasma at several times normal levels, and can signifi-
cedure is, of course, widely accepted. But its extension to cantly improve tissue oxygenation. This is important be-
counteract the damage due the air bubbles resulting from cause hemoglobin, while more eager to take up oxygen, is
other causes, such as those accidentally introduced during also more reluctant to part with it. The oxygen dissolved in
medical treatment, is less generally recognized. the plasma, having a higher chemical potential, is pushed
What is attempted in this book is a detailed and critical out from the capillaries and into the surrounding tissue.
treatment of a large subject. If thorough discussion will From there, it can spread small distances by diffusion.
lead to some consensus, the subject could grow very much Even in the blood itself, the dissolved oxygen may help
larger. Indeed, oxygen, which in the form of hyperbaric ox- the white blood cells in their phagocytic activity. Bacteria
ygen (HBO) is called a drug, is the most natural of all drugs. themselves may react in a variety of ways. It appears that
The first problem we must face is the danger of high many can use oxygen at normal pressures, but are damaged
pressure treatment used at excess pressure for too long a by oxygen at higher pressures. In the case of anaerobic bac-
period, or in conjunction with the wrong kind of drug. Ox- teria, oxygen can act in a powerful way to stop the infection.
ygen indeed has toxic effects. Furthermore, the delivery of In combination with other methods, HBO clearly appears
the pressurized gas to the patient may be mishandled. A effective in cases of gangrene.
properly extensive discussion is devoted to such dangers, But more is involved than the straightforward destruc-
which are completely avoidable. tion of the pathogen. The natural healing process may also
XI
be assisted by the presence of oxygen. This obviously to distinguish between the fight against the causes of a dis-
should be the case when hyperbaric treatment counteracts ease, and our efforts to aid toward the reassertion of overall
on oxygen deficiency. Many injuries involve the destruction health. There are good indications that HBO is helpful in
of capillaries, the means of delivering oxygen. Under such many diseases, such as multiple sclerosis and osteomyelitis.
circumstances, healing is itself tied to revascularization of One may mention these two applications because, in the
the damaged tissue. But growth of the requisite capillaries former, earlier recognition of the disease made possible by
is in turn tied to the oxygen supply. This relationship can the use of magnetic resonance imaging has made early
explain why in the case of many slow healing wounds, HBO treatment a better possibility, and seems to have given a real
seems to have a strong positive effect. Very much more can chance for help from HBO. In the latter case, osteomyelitis,
and should be done to extend the study of the speed of the location of the disease is the bone, where oxygen is usu-
healing to the more normal cases. ally not amply available.
In the human body, 20 percent of the oxygen consump- As members of the scientific community we are all nat-
tion occurs in 3 percent of the body mass: the brain. This urally tempted to theorize, as long as a glimmer of a theory
is also the region most sensitive to a deficiency of oxygen, might be perceived. This book proceeds, however, along
which can produce dramatic results. Indeed, surgical meth- strictly step by step empirical lines. Case after case, the var-
ods on the carotid artery are often used to relieve oxygen ious pathologies are reviewed. In each situation, it is care-
deficiency to the brain. It seems logical that in HBO we fully stated to what extent the evidence merely indicates a
have a tool that can serve a similar purpose. This might be conclusion, and to what extent the conclusion can be
particularly important in the case of stroke, a high-ranking proved. In the present stage of HBO, it is a certainty that
cause of death and disability. It is clearly worthwhile to ex- there will be considerable criticism. On the other hand,
plore whether and to what extent disability can be reduced those who disagree are likely at the same time to disagree
or avoided by prompt use of hyperbaric treatment. If the among themselves. I believe that the result will be not only
blood supply to a small region of the brain is reduced, relief critical reflection, but also more experimentation, more re-
might come from the diffusion of oxygen into the ischemic views, more understanding, and more progress. It is not
region from neighboring capillaries. entirely impossible that, perhaps sometimes in the next de-
For all new medical techniques, scientific evidence is de- cade, professors of medicine will have difficulty in explain-
manded. Yet medicine is still partly an art, as well as a dra- ing why the treatment with oxygen was not widely adopted
matically advancing science. Therefore in the complicated much earlier.
questions of life, disease, and recovery, it is sometimes hard
XII
Almost 20 years have passed since the first edition of the of hyperbaric oxygen in organ transplantation has been ad-
Textbook of Hyperbaric Medicine was written, and since the ded as well as a chapter on the treatment of chronic lyme
publication of the 4th revised edition in 2004, there has disease by William Fife and Caroline Fife.
been a considerable increase of research and development Multimodality treatment is required in some complex
in applications of hyperbaric oxygen. Of the more than disorders and hyperbaric oxygen has been combined with
1200 publications relevant to hyperbaric medicine during new advances in drug treatment and surgical procedures as
20042008, approximately 300 have been selected and ad- well as with complementary medicine techniques such as
ded to the list in this book, whilst a corresponding number acupuncture. As other new technologies such as those for
of older references have been deleted to maintain the bib- manipulating stem cells develop, their interaction with hy-
liography at 2000 entries. Several older publications have perbaric oxygen is being studied. Hyperbaric oxygen may
been retained for their historical interest, and some of these prove to be a useful adjunct to stem cell-based therapeutics
have indeed become classics. and regenerative medicine.
There is an ever increasing use of hyperbaric oxygen for I would like to thank the editorial staff at Hogrefe &
neurological disorders. Other areas of expansion include Huber Publishers, particularly the Publishing Manager,
applications in ophthalmology and the chapter on this has Robert Dimbleby, for their help and encouragement during
been rewritten and expanded by Frank Butler and Heather this revision.
Murphy-Lavoie. A new chapter by Alan Wyatt on the role
The textbook has been revised in accordance with the pro- ygen, pressure, and duration of treatment need to be deter-
gress made in hyperbaric medicine during the past four mined for each patient individually. It is difficult to reach
years. There were over 1000 publications relevant to hyper- any conclusions from clinical trials about a particular pres-
baric medicine during 19992002. Approximately 200 of sure of oxygen or even a range for a broad diagnostic cat-
these were selected and a corresponding number of older egory with many variants among patients that determine
references were deleted to keep the total number of refer- the response.
ences in the bibliography to 2000. The number of clinical Applications in neurological disorders are developing fur-
trials for various applications in hyperbaric oxygen therapy ther and space devoted to this area has been increased. A new
has increased. These are included wherever the published chapter by Neubauer and Harch has been added on the treat-
results are available. As personalized medicine is develop- ment of cerebral palsy with hyperbaric oxygenation.
ing, it will be applied to hyperbaric oxygenation as well. It I wish to thank the publishing directors of Hogrefe Pub-
is already obvious that patients require an individualized lishers and their Editor, Mr. Robert Dimbleby, for their help
approach in hyperbaric therapy protocols. The dose of ox- and encouragement throughout the period of revision.
XIII
Hyperbaric medicine continues to make progress. The tex- the technique is available for clinical application in certain
tbook has been revised and expanded with inclusion of new cases when the need arises and often a precedence in that
contributors. We are fortunate to have an article from Prof. area helps. Well-documented anecdotal reports have a
Hideyo Takahashi of Japan describing the state of develop- teaching value, and this has been utilized in the textbook.
ment of hyperbaric oxygen therapy in Japan. This is particularly so in the case of emergency medicine
As in the previous edition, objective judgment has been and treatment of hypoxemic/ischemic encephalopathies,
exercised in deciding to include various reports and studies where it would be practically impossible to conduct con-
on this subject. There are more than 200 publications every trolled studies.
year on hyperbaric medicine, and all the publications can- Much of the expansion of hyperbaric oxygen therapy is
not be included in references. The bibliography already in the area of neurological disorders, which is reflected in
contains more than 2000 entries. Most of the older refer- the increased number of chapters devoted to this area. This
ences have been retained because of their historical value. application of hyperbaric oxygen holds the greatest prom-
Much of the original material still holds its value and has ise for the future for diseases of the nervous system.
also been retained. Simply because no new work has been I wish to thank the publishing directors of Hogrefe &
done in some areas does not mean that these indications Huber and their Editor, Mr. Robert Dimbleby, for their
for HBO are no longer valid. Research in hyperbaric med- help and encouragement throughout the period of prep-
icine continues to be limited by lack of funding. However, aration.
A great deal of progress has taken place in Hyperbaric Med- neurosurgery, for which I was fortunate to have the collab-
icine since the publication of the first edition. This has ne- oration of Dr. Michael Sukoff of the United States, who has
cessitated a thorough revision of the book and inclusion of done much of the pioneer work in this field. The chapter
new contributors. Some of the outdated references were re- on pediatric surgery by Prof. Baydin from Russia is a useful
moved and new ones have been added, bringing the total new addition. With the inclusion of unpublished work on
about 1800 entries. I have tried to keep my judgment objec- the role of neuropeptides in oxygen therapy (Prof. G.T. Ni)
tive and this is helped by the fact I have no involvement in from China, the book is now truly international.
the political and financial aspects of hyperbaric medicine. I wish to thank the publishing directors of Hogrefe &
In spite of this critical revision and corrections, I am Huber Publishers for their help and encouragement
pleased to state that a great deal of the old stuff still holds throughout the period of revision. Countless other col-
its value. Use of hyperbaric oxygen therapy in neurological leagues also helped and their names are too numerous to
disorders continues to expand and required a chapter on list here.
XIV
This book goes considerably beyond the scope of the Hand- discussed elsewhere in a 1989 title by K.K. Jain, Oxygen in
book of Hyperbaric Oxygen Therapy, which was written by Physiology and Medicine.
me, and published by Springer Verlag in 1988. In addition, I have written this current work in a textbook style, and
with the many rapid developments in this field, the Hand- there is more discussion on the pathophysiology of diseases
book has already become remarkably outdated. Our use of and the rational basis of hyperbaric oxygen than in the
the word textbook in the title of the present work is in Handbook. Extensive and up-to-date references have been
keeping with the increasing worldwide recognition of this assembled as an integral part of this project, and these total
branch of medicine, and the need for a definite and inclu- about 1,500.
sive source covering this body of knowledge, as it exists to- The highlights of this present effort are the newly docu-
day. mented effectiveness of hyperbaric oxygen therapy in the
In practice hyperbaric medicine of course involves mo- rehabilitation of stroke patients, and the validation of these
stly the use of hyperbaric oxygen, i.e., oxygen under pres- gains via the iofetamine scan technique. This same method
sure greater than atmospheric. As a result, this field over- has also been used to document the improvement in mul-
laps with diving medicine in the areas of tiple sclerosis patients undergoing hyperbaric oxygen ther-
apy.
the effect of high pressure on the human body In the preparation of this work I was considerably aided
physical exercise under hyperbaric environments by the capable and cooperative management effort provid-
air embolism ed by the two directors of the Hogrefe & Huber publishing
decompression sickness company. The execution of a project involving this degree
of both scope and detail is certainly an exercise in team-
I have made no attempt to intrude any further into diving work between author and publisher, and it was a pleasure
medicine, as there are several excellent textbooks on that to have shaped the production in a creative and timely
subject. In addition, the use of normobaric oxygen has been manner.
The History of Hyperbaric Chapter
Medicine1
PART I:
BASIC ASPECTS
1 The History of
Hyperbaric Medicine
K.K. Jain
This chapter reviews the historical relationship between hyperbaric therapy and diving medicine,
recounting the important stages in the development of compressed gas technology and a few of the
more interesting early attempts to utilize it for medical purposes. The sections involved are:
Hyperbaric Therapy and Diving method of replenishing the air supply using weighted bar-
rels (Smith, 1986). This was followed in the next two cen-
Medicine turies by the development of compressed-air diving hel-
mets and suits which made it possible to remain under
As is well known, the origins and development of hyper- water for an hour or more.
baric medicine are closely tied to the history of diving med- Even though the duration of dives had been extended,
icine. While the attractions of the deep are easily under- divers were still limited to the same shallow waters as be-
stood, it was the various unpleasant physical consequences fore. Undersea pioneers had quickly discovered the ear-
of venturing beneath the surface of the worlds oceans that drum-rupturing effects of increasing water pressure. Those
led directly to the many applications of compressed-gas attempting to venture even deeper in diving bells also
therapy in modern medicine. Although scientifically based
applications of hyperbaric technology are a relatively re-
cent development, the use of compressed gas in medicine
actually has ancient roots.
The origin of diving is not known, but it was recognized
as a distinct occupation as far back as 4500 B. C. However,
since humans can only hold their breath for a few minutes,
unaided dives are limited to depths of less than about 30
meters. The first use of actual diving equipment to extend
the limits of underwater activity is attributed in legend to
none other than Alexander the Great, who, in 320 B. C., is
said to have been lowered into the Bosphorus Straits in a
glass barrel (see Figure 1.1), which purportedly gave him a
secret weapon in the siege of Tyre.
Around the year 1500, Leonardo Da Vinci made sketches
of a variety of diving appliances, without developing any
for practical use. It was not until 1620 that the Dutch in-
ventor Cornelius Drebbel developed the first true diving
bell. His device was extremely limited, especially by its sim- Figure 1.1
Alexander the Great was said to have been lowered into the Bospho-
ple air supply that delivered air pressurized at only one at-
rus Straits in a glass barrel. Note that the candles are lighted and if,
mosphere, but it was certainly the forerunner of all sub- indeed, Alexander went into this barrel, he was lucky to survive. The
mersible vehicles. illustration is redrawn from a thirteenth century manuscript in the
In 1691 Edmund Halley, after whom the comet is Burgundy Library in Brussels, and is reproduced courtesy of Dr. E.
named, advanced diving bell technology by devising a B. Smith (1986).
Table 1.1
Some Important Benchmarks in the History of Diving Medicine in Relation to Hyperbaric Medicine
Figure 1.2
Fontaines mobile operating room of
1877. Note the manual nature of the
compressor apparatus and the anesthe-
sia gas container and mask in the cham-
ber. (Photo courtesy of Dr. Baixe, Tou-
lon, France.)
6 Chapter 1
During the second half of the nineteenth century, hyper- literature on hyperbaric medicine up to 1887 was reviewed
baric centers were advertised as being comparable to health by Arntzenius and contains a remarkable 300 references.
spas. Junod referred to his treatment as Le Bain dair com- The first hyperbaric chamber on the North American con-
prim (the compressed-air bath). In 1855 Bertin wrote a tinent was constructed in 1860 in Oshawa, Ontario, Canada,
book on this topic (the title page is shown in Figure 1.3) and just east of Toronto. The first such chamber in the United
constructed his own hyperbaric chamber (Figure 1.4). The States was built by Corning a year later in New York to treat
nervous disorders. The chamber that received the most pub-
licity, however, and was the most actively used, was that of
Cunningham in Kansas City in the 1920s (Sellers, 1965). He
first used his chamber to treat the victims of the Spanish in-
fluenza epidemic that swept the USA during the closing days
of the First World War. Cunningham had observed that mor-
tality from this disease was higher in areas of higher elevation,
and he reasoned that a barometric factor was therefore in-
volved. Cunningham claimed to have achieved remarkable
improvement in patients who were cyanotic and comatose.
In 1923, the first recorded hyperbaric chamber fire occurred
at Cunninghams sanatorium. He had installed open gas
burners under the tank to keep it warm in winter and some-
one turned the flame the flame too high so that it scorched
the interior insulation. The patients were evacuated safely.
However, one night a mechanical failure resulted in a com-
plete loss of compression and all his patients died. This trag-
edy was a sobering lesson but ultimately did not deter Dr
Cunningham. His enthusiasm for hyperbaric air continued,
and he started to treat diseases such as syphilis, hypertension,
diabetes mellitus, and cancer. His reasoning was based on the
assumption that anaerobic infections play a role in the etiol-
ogy of all such diseases. In 1928, in Cleveland, Cunningham
constructed the largest chamber ever built five stories high
and 64 feet in diameter (Figure 1.5). Each floor had 12 bed-
rooms with all the amenities of a good hotel. At that time it
was the only functioning hyperbaric chamber in the world.
As the publicity surrounding his treatments grew, Dr
Cunningham was repeatedly requested by the Bureau of
Investigations of the American Medical Association (AMA)
to document his claims regarding the effectiveness of hy-
perbaric therapy. Apart from a short article in 1927, how-
Figure 1.4 ever, Cunningham made no efforts to describe or discuss
Hyperbaric chamber constructed by Bertin in 1874. his technique in the medical literature. He was eventually
Table 1.2
Landmarks in the History of Hyperbaric (Compressed) Air Therapy
1662 Henshaw used compressed air for the treatment of a variety of diseases
1834 Junod of France constructed a hyperbaric chamber and used pressures of 24 ATA to treat pulmonary disease
1837 Pravaz of France constructed the largest hyperbaric chamber of that time and used it to treat a variety of ailments
18371877 Construction of pneumatic centers in various European cities, e.g., Berlin, Amsterdam, Brussels, London, Vienna, Milan
1860 First hyperbaric chamber on the North American continent in Oshawa, Canada
1870 Fontaine of France used the first mobile hyperbaric operating theater
1891 Corning used the first hyperbaric chamber in the USA to treat nervous disorders
1921 Cunningham (USA) used hyperbaric air to treat a variety of ailments
1925 Cunningham tank was the only functional hyperbaric chamber in the world
1928 Cunningham constructs the largest hyperbaric chamber in the world; American Medical Association condemns Cun-
ninghams hyperbaric therapy
1937 The Cunningham chamber is dismantled for scrap metal
The History of Hyperbaric Medicine 7
Figure 1.5
Cunningham's giant steel ball hyper-
baric chamber built in 1928 in Cleve-
land, Ohio. It was six stories high and
contained 72 rooms. (Photo courtesy of
Dr. K.P. Fasecke.)
Table 1.3
Landmarks in the Development of Hyperbaric Oxygen (HBO) Therapy
Figure 1.6
Sketch of the 1917 Drger 2 ATA system
for diving accidents, including oxygen
breathing system. (Photo courtesy of
Dr. Baixe, Toulon, France.)
censured by the AMA in 1928, in a report that stated: Un- ticated air. A more detailed history of the applications of
der the circumstances, it is not to be wondered that the oxygen since that time can be found in Jain (1989b). Al-
Medical Profession looks askance at the tank treatment though hyperbaric air had been used as early as 1662, oxygen
and intimates that it seems tinctured much more strongly was not specifically added to early hyperbaric chambers. The
with economics than with scientific medicine. It is the mark toxic effects of concentrated oxygen reported by Lavoisier
of the scientist that he is ready to make available the evi- and Seguin in 1789 were reason enough for hesitation to use
dence on which his claims are based. it under pressure. Beddoes and Watt, who wrote the first
Dr Cunningham was given repeated opportunities to book on oxygen therapy in 1796, completely refrained from
present such evidence but never did so. A more detailed mentioning the use of oxygen under pressure. Paul Bert, the
account of Cunninghams story and the history of hyper- father of pressure physiology, discovered the scientific basis
baric medicine is to be found in Trimble (1974). The Cun- of oxygen toxicity in 1878 and recommended normobaric,
ningham chamber was dismantled for scrap in 1937, which but not hyperbaric, oxygen for decompression sickness.
brought to a temporary end the era of hyperbaric air ther- The potential benefits of using oxygen under pressure
apy for medical disorders. for the treatment of decompression sickness were first
realized by Drger, who in 1917 devised a system for treat-
ing diving accidents (Figure 1.6). For some unknown
reason, however, Drgers system never went into produc-
The Development of Hyperbaric tion. It was not until 1937 the very year that Cunning-
Oxygen Therapy hams air chamber hotel was demolished that Behnke
and Shaw actually used hyperbaric oxygen for the treat-
Oxygen was not discovered until 1775, when the English ment of decompression sickness. The age of Hyperbaric
scientist Joseph Priestley isolated what he called dephlogis- Oxygen (HBO) therapy had finally arrived.
HB O Therapy in Global Cerebral Ischemia/Anoxia Chapter
and Coma19
Hyperbaric oxygen therapy has been used in a number of conditions characterized by global ischemia
(as opposed to focal ischemia of stroke), and anoxia, and leading to impairment of consciousness.
Conditions such as coma due to brain injury and anoxia associated with drowning and hanging are
discussed under the following headings:
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
Rational Basis of HBO Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Review of Animal Experimental Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
Review of Human Clinical Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Case Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
236 Chapter 19
Authors Diagnosis No. of Length of coma/ Timing of HBOT HBOT protocol Results and conclusions
and year patients neuro insult pre-
hyperbaric oxygen
therapy (HBOT)
2nd Inter- Chronic brain injury: 361 (?) Vast majority < 10 1.52 ATA oxy- Average 50% of patients with
national Great majority of pa- years of age gen/6090 min q.d. to noticeable improvements in
Sympo- tients were cerebral pal- b.i.d., 1 to > 500 treat- different tests
sium on sy or global ischemia, an- ments (rare case)
Hyperbaric oxia and coma.
Oxygen- Variety of tests per-
ation and formed including physi-
the Brain cal exam, laboratory test-
Injured ing and functional brain
Child (au- imaging with SPECT.
thors: Neu-
bauer,
Harch,
Chavdarov,
Lobov, Zer-
bini) 2001
Golden et Chronic neurological 50 (25 un- Unknown Average 51/3 HBOT Improvement in SPECT from
al 2002 disorders: CP 30%, TBI der 18 years postinsult 1.252.5 ATA/60 min b.i.d. first to last scan for both hemi-
26%, anoxic/ischemic years old (12 per week) spheres and cortex with the
encephalopathy 16%, and 25 3rd SPECT showing more im-
CVA 12%, lyme disease over 18 provement than the 2nd
6%, other 10%. Measure years old) SPECT, which was improved
SPECT pre, after at least over the 1st. Main increase in
15 HBOTs, and after a blood flow didnt occur until
course of at least 50 after 2nd SPECT scan and a
HBOTs. substantial number of treat-
ments (> 15). No change in
blood flow to the pons and
cerebellum.
Hardy et al Cerebral palsy. 75 (?) 312 years of age. Control 1.3 ATA air/60 min Better self-control and signifi-
(E) 2002 Psychometric testing pre No average age giv- at depth q.d., 5 days per cant improvements in audito-
and post treatment. en. week 40. ry attention, and visual work-
HBOT 1.75 ATA oxy- ing memory both groups. No
gen/60 min at depth q.d., 5 difference between groups.
days per week 40. Sham group significantly im-
proved on 8 dimensions of
parent rating scale vs. 1
dimension in HBO. No
change in verbal span, visual
attention, and processing
speed in either group.
Muira et al Overdose with loss of 1 (?) 50 days HBO 2.0 ATA/90 min, 5 Progressive improvement
(E) 2002 consciousness and cya- days a week 71 through 33 Rxs. Deterioration
nosis x unknown with strange behavior by 47th
amount of time. Second- Rx. 52nd Rx disoriented, rest-
ary deterioration fifteen less, and agitated with de-
days later with akinetic creased memory. Excitability
mutism. Measure EEG, by 71st Rx requiring Valium,
MRI, MRS, and SPECT. Tegretol, and Haldol. Behavior
improved post HBOT but dis-
orientation and amnesia wors-
ened. Nine months later pa-
tient better than pre-HBO.
MRI, MRS, and EEG tracked
patients course.
Waalkes et Cerebral anoxia: 8 with 9 (?) 6.4 years average 1.7 ATA oxygen/60 min 58% average improvement in
al (E) 2002 CP, 1 near-drowning. age q.d., five days a week 80 GMFM, minimal improve-
Measured GMFM, spas- ment WEEFIM, no change
ticity, WEEFIM, video spasticity. Significant reduc-
exams, parent question- tion in time spent with care-
naire, and time spent in giver in 24-h period. Patients
any 24-hr. period by still improving at end of study.
caregivers.
254 Chapter 19
Authors Diagnosis No. of Length of coma/ Timing of HBOT HBOT protocol Results and conclusions
and year patients neuro insult pre-
hyperbaric oxygen
therapy (HBOT)
Golden Chronic brain injury 21 chil- Not stated. Static level of func- Not stated, but HBOT pro- Children: significant improve-
(2006) (Children: CP 29%, TBI dren, 21 tion for at least 1 tocol well known at this ment in measures of daily liv-
26%, HIE 17%, Stroke adults, year, but many pa- clinic: 1.15(<)2.0 ATA/60 ing, socialization, communica-
12%, Lyme 7%, other each com- tients were years qd-bid. Children: avg. 28 tion, and motor skills.
9%; adults: TBI 26%, pared to 42 post insult. Adults Rxs in 28 days. Adults: avg. Adults: significant improve-
stroke 26%, anoxia 21%, untreated were at least 2y 35 Rxs in 35d. ments on all neuropsychologi-
hypoxia 7%, other 20%. brain in- post insult. cal measures, including atten-
jured and tion, motor, tactile, receptive
normal & expressive language, word
children or fluency, and immediate and
adults. Pro- delayed memory
spective,
non-ran-
domized.
Senechal Cerebral palsy Review of Not mentioned Years post insult All published HBOT stud- Significantly greater rate of
(2007) literature ies. Compared HBOT stud- GMFM improvement com-
ies using the Gross Motor pared to all but one study
Functional Measures which used dorsal rhizotomy.
(GMFM) outcome to stand- HBOT was the only therapy
ard therapies using the that also improved cognition.
GMFM
Gunther (2004) experiment the results were interesting be- of HBO was generated with one treatment, in 2 studies with
cause they suggested equal sensitivity of pathological tar- 3 treatments, and in the remaining two studies with 7 treat-
gets to both HBO and NBO very early after ischemia (5 ments. No consensus emerges for the ideal dose of HBO
minutes), but only HBO had a positive effect after 30 min- after complete global ischemia, but the Van Meter dose-re-
utes of ischemia. In addition, only the HBO dosage had any sponse study suggests that HBO at 4 to 6 ATA was effective
effect on morphology regardless of early or later initiation. in resuscitating animals with cardiac arrest. More impor-
These results reinforce the points made in the introduction tantly, in the sixteen studies, a beneficial effect on global
to this chapter about hyperbaric dosage differences with ischemia, anoxia, and coma was demonstrated even when
evolving pathology and the possible difference in efficacy the ischemic insult was as long as one hour (two studies)
of HBO depending on the route of delivery. The dose by and the delay to treatment as long as six hours after the
aviator mask is lower than by oxygen hood or in a pure ischemic insult. When metabolic parameters only are con-
oxygen environment. Similarly, the dose of HBO in tissue sidered the delay to treatment can be as long as 24 h (Zhou
slices is markedly different when 1 ATA and 3 ATA oxygen 2003).
are used. Lastly, the study by Mink and Dutka (1995b) had The results are similarly impressive and uniformly positive
conflicting results with a simultaneous decrease in brain in the group of incomplete global ischemia/anoxia experi-
vascular permeability and blood flow while somatosensory ments. As in the complete models no consensus emerges as
evoked potentials were unchanged. This implies concomi- to best HBO pressure, duration, frequency, or number of
tant beneficial and detrimental effects which are difficult treatments, but there maybe an intervention time limit of 6h
to explain without more data. for improvement in behavioral/neurological outcomes.
The five Van Meter et al studies (1988, 1999, 2001a, Shiokawa et al (1986) demonstrated an improvement in sur-
2001b, and 2008) are unique in that they showed resusci- vival with 2 ATA HBO for only 30 min, with best results at
tation of animals using HBO, rather than delivering HBO three hours post-insult as opposed to one hour. Weinstein et
after resuscitation as in the Rosenthal article. These com- al (1986) achieved an 84% reduction in mortality with a
bined experiments were dose-response evaluations of HBO 15 min 1.5 ATA treatment and Grigoryeva (1992) demon-
at 1.0, 2.0, 2.8, 4.0, and 6.0 ATA. The swine study proved strated a superior effect of 1.2 ATA/30 min over
the ability of 4 ATA HBO to resuscitate animals after 2 ATA/60 min on survival and preservation of neuronal tran-
25 min of cardiac arrest, simultaneously truncating white scription. Yaxi et al (1995) and Yiqun et al (1995) both
blood cell-independent brain lipid peroxidation. This is the showed improvements in brain enzymatic function from a
longest successful arrest/resuscitation reported in the med- single HBO treatment at 2.5 ATA with the Yaxi article sug-
ical literature and has profound implications for applica- gesting a minimum 2040 min duration of HBO exposure
tion to human cardiac arrest (see Chapter 39, HBO in for efficacy. Kondo et al (1996), meanwhile, showed that re-
Emergency Medicine). In 12 of the 16 studies the benefit petitive HBO at 2 ATA/60 preserves hippocampal neurons
HBO Therapy in Global Cerebral Ischemia/Anoxia and Coma 259
detail in the chapter on cerebral palsy. In short, improve- region of the skull. Within one-half hour Glascow coma
ments in gross motor functional measures were the high- scale was 67 and the patient was ventilator dependent. CT
est, fastest, and most durable in HBOT studies compared of the brain revealed diffuse edema, midline shift, petechial
to studies using the GMFM for other types of therapies hemorrhages, subarachnoid hemorrhage, small subdural
with the exception of two dorsal rhizotomy studies. The hematoma, and basilar skull fracture. HBO was given 19 h
second important addition is the Golden study (2006), a post injury at 1.75 ATA/90 bid. On the first treatment the
controlled nonrandomized study of HBOT in a group of patient began to fight the ventilator. Initial SPECT brain
children and adults with chronic stable brain injury. Both imaging obtained five days post injury on a single-head
groups showed significant improvements in nearly all low-resolution scanner was normal. Repeat SPECT
measures after 2835 HBO treatments at low pressure. imaging on a triple-head high -resolution scanner occurred
In conclusion, additional experience with HBO in chronic 30 days post injury (Figure 19.1, A and B) and now clearly
global ischemia, anoxia and coma that was supported by demonstrated the significant injury to the left frontal area
SPECT, standardized motor, and psychometric testing has as well as the contra coup injury to the right parietal/oc-
accumulated in the past five years, strongly suggesting a pos- cipital area characterized by luxury perfusion. Nine days
itive trophic effect of HBO. These results are underpinned by later and two hours after a fifth additional HBO, SPECT
the addition of the sole animal study in the literature that was repeated (Figure 19.2, A and B) and showed a dramatic
demonstrated a highly correlated improvement in vascular filling in of the injured areas thus giving functional neu-
density and cognition using an HBO protocol originally de- rophysiological support to the clinical decision to continue
signed for humans and used in many of the human studies HBO. The patient, meanwhile, progressed rapidly on twice
above (Harch 2007). This animal study strongly reinforces daily HBO for four weeks with often new neurological or
the human studies, especially in TBI, and argues for further cognitive findings occurring in the chamber and then con-
application of HBO to other chronic forms of brain injury. tinued on HBO 4 times a day for seven weeks, at which time
he was conversant and independently ambulatory with
slight spasticity. At 11 weeks the patient was transferred to
a rehabilitation center and his HBO discontinued by the
Case Studies new medical team. SPECT imaging at this time (Figure
19.3, A, B, and C) registers the patients clinical progress
To illustrate the effect of HBO in both acute and chronic with a persistent increase in flow to the left frontal region
global cerebral ischemia/anoxia and coma several cases while some deterioration occurs to the area of previous
treated by these authors are presented below. In each case luxury perfusion on the posterior right. The patient made
the visual medium of SPECT brain blood flow imaging transient limited initial progress at the rehabilitation center
on a high resolution scanner (7 mm; Picker Prism 3000) then quickly leveled off cognitively while his spasticity and
registers in a global fashion the neurocognitive clinical balance worsened. Three months after discontinuance of
improvement experienced by the patients and witnessed HBO the patients father requested further HBO and repeat
by the authors. The SPECT brain scans presented below SPECT brain scan (Figure 19.4, A and B), psychometric,
are CT technology with the patients left brain on the and motor testing were obtained. SPECT now demon-
readers right and vice versa, with the 30 frame images reg- strates a significant deterioration in the right frontal and
istering transverse slices from the top of the brain in the posterior areas, while the left frontal normalization per-
left upper corner to the base of the brain in the lower right sists. The right posterior area has infarcted on simulta-
corner. Images are approximately 4 mm thick. Brain neous MRI. To assess recoverable brain tissue the patient
blood flow is color coded from white-yellow to yellow to underwent a single 1.75 ATA/90 min HBO followed by
orange to purple, blue and black from highest brain blood SPECT imaging (Figure 19.5, A and B); SPECT showed im-
flow to lowest. Normal human brain shows predominant- provement in the right frontal and parietal/occipital lesions
ly yellows and oranges, but, more importantly, has a fairly along the ischemic penumbral margins. HBO was resumed
smooth, homogeneous appearance. The companion for an additional 80 treatments, once/day at 1.75 ATA/
image (B) to the 30 slice transverse set of images is a 90 min. The patient made a noticeable improvement in
three-dimensional surface reconstruction of the trans- cognition (40 percentile gain in written computational
verse images. Abnormalities in perfusion are registered as mathematics), insight (the patient now verbalized for the
defects and as coarseness of the brains surface. first time the understanding that he had sustained a brain
injury and could no longer aspire to be a surgeon), and
Patient 1: HBO Treatment for Coma Due to Traumatic balance (improvement in gait and progression from a 3-
Brain Injury wheel tricycle to a 2-wheel bicycle). HBO (188 treatments
total) was discontinued when the patient desired enroll-
A 19-year-old male was inadvertently ejected from a motor ment in remedial courses at a community college. SPECT
vehicle at 65 mph with impact on the left frontal/parietal imaging at this time (Figure 19.6, A and B) shows improve-
260 Chapter 19
balance (improvement in gait and progression from a 3- relapse after discontinuation of HBO, prevented further
wheel tricycle to a 2-wheel bicycle). HBO (188 treatments deterioration and improved SPECT image as well as neu-
total) was discontinued when the patient desired enroll- rocognitive function in TBI, demonstrating the benefit of
ment in remedial courses at a community college. SPECT HBO in the chronic stage of TBI
imaging at this time (Figure 19.6, A and B) shows improve-
ment in perfusion in the ischemic penumbral areas of the Patient 2: Near Drowning, Chronic Phase
right-sided lesions. The left hemisphere remains intact. In
The patient is a 4-year-old male who was found at the bot-
summary, HBO, when reinstituted following SPECT and
tom of a swimming pool after an estimated 5 min of sub-
Figure 19.1A
HMPAO SPECT brain imaging, trans-
verse slices, one month post injury. Note
severe reduction in left frontal, parietal,
and temporal brain blood flow with lux-
ury perfusion in the right occipital pa-
rietal region.
Figure 19.1B
Frontal projection three-dimensional
surface reconstruction of Figure 19.1A.
Non cerebral uptake is shown in scalp
and neck soft tissues.
HBO Therapy in Global Cerebral Ischemia/Anoxia and Coma 265
Figure 19.5A
HMPAO SPECT brain imaging, trans-
verse slices, 2 hours following single
HBO at 1.75 ATA/90min. Note im-
provement in the right frontal and pos-
terior defects.
Figure 19.5B
Right lateral projection three dimen-
sional surface reconstruction of Figure
19.5A.
n Thorough, comprehensive, objective
n The essential reference for all who use HBO
n
n
Numerous illustrations, unique full-color SPECT scans
Internationally renowned contributors
K. K. Jain
Textbook of
Textbook of
K. K. Jain
Hyperbaric Medicine
Hyperbaric
This textbook, now appearing in its 5th, fully updated, and expanded edition, has become widely known as the
best exposition available on the topic of hyperbaric medicine and the wide range of applications of hyperbaric
oxygen (HBO) techniques. In addition to explaining the basic principles of HBO therapy and its application in
carbon monoxide poisoning, decompression sickness, and diving medicine, the textbook looks objectively
Hyperbaric Medicine
Textbook of
Medicine
and critically at its use in numerous other areas, such as stroke, CNS and neurological disorders, traumatology
and wound healing, infectious diseases, rehabilitation and sports medicine, plastic surgery, emergency
medicine, obstetrics, and cancer treatment. With over 1,700 up-to-date references and an extensive index,
the volume is not just a textbook suitable for those seeking an introduction to this expanding field, but also
an invaluable resource for specialists.
Well set out and easily readable a comprehensive book well-written, and the information is accurate.
(P. Moore, in Anaesthesia and Intensive Care)
This excellent and comprehensive text remains probably the standard work an essential reference text.
(N.K. Cooper, in Journal of the Royal Army Medical Corps)
The experts who have made such superb contributions to [this book] are the world leaders in their fields.
(Prof. James F. Toole, MD)