Table 1-Various Indications Used for HBO Treatment

during the Past Few Decades

Radiation necrosis

Decompression sickness

Gas embolism

Soft tissue infection, due to

mixed aerobic and

anaerobic organisms

Soft tissue necrosis

Bacteroides infection

Compromised skin grafts

or flaps

Fungal infections

Mucormycosis

Anemia from exceptionalblood loss

Carbon tetrachloride

poisoning

Fractures

Lepromatous leprosy

Meningitis

Radiation myelitis, cystitis,

enteritisRetinal artery insufficiency

Chronic brain ischemia

Senility

Multi-infarct dementia

Infant cardiac surgery

Chronic ulcers

Peripheral vascular disease

Diabetic neuropathy

Acute endocarditis

Hearing loss due to acoustic

trauma

Cortical blindness

Cellulitis

Infected pacemaker

Hurler’s syndrome

Postcardiac arrest

Scleroderma

Mycobacterium tuberculosis

Abscess, intraabdominal

or intracranial

Asthma

Pneumomedjastjnum

HangingThrombophlebitis

Lyell’s syndrome*

CO poisoning

Gas gangrene

Osteomyelitis (refractory)

Crohn’s disease

Cyanide poisoning

Crush injury with

traumatic ischemia

Alzheimer’s disease

Brain edema

Thermal burns

Head and spinal injury

Bone grafts

Frostbite

Cerebrovascular accidents

Hydrogen sulfide

poisoning

Cancer therapy

Pseudomembranous

colitis

Sickle cell crisis

Multiple sclerosis

Pyoderma gangrenosum

Acute myocardial

infarction

Carotid aneurysm

Aortic aneurysm

Anaerobic infections

Postcardiac surgery

Pulmonary insufficiency

Arteriosclerosis

Causalgia

Collagen vascular diseases

Postoperative confusion

Traumatic amputation

Pulmonary emboli

Drowning

MoyamoyatSurgical empyema

Pharyngeal fistula

Brain cyst

Stenotic valvular heart

disease

Tetanus

Intestinal obstruction

Continued

*From Stanford University Medical Center, Stanford, California.

tMedical student.tProfessor of Medicine and Physiology.§We do not guarantee that the list is complete. We thought that

assembling this list might be helpful to future medical historians.Reprint requests: Dr Robin, Anatomy Bldg. Room 169, StanfordUniversity School of Medicine, Stanford 94305-5070

1074 Hyperbaric 02: A Therapy in Search ofDiseases (Gabb. Robin)

___ risk-beneift analysis in chest meilucineHyperbaric Oxygen*

A Therapy in Search of Diseases

Genevieve Gabb;t and Eugene D. Robin, M.D$

rf here appears to be a continual proliferation of hyperbaricoxygen (HBO) units in the US.’ The list of so-called

indications for its use, past and present, is overwhelming.

There is a wide spectrum of analyses cited to support the use

of HBO in given diseases. These range from serious,thoughtful attempts to rationalize a given use; other analysesborder on medical charlatanism.2 There is a striking dearth ofdata derived from acceptable clinical trials to support theserationalizations.

It is not practical to review the massive literature com-pletely. Herein we provide a historic perspective concerning

various indications for HBO use during the past several

decades; evaluate the evidence supporting its current use in

various disorders; analyze one major driving force for the

proliferation of uses and indications, money; review the

nature of patient risks associated with the use of HBO; andmake some suggestions for dealing with the issues raised byHBO.

The overall conclusion is that the world of HBO is amicrocosm reflecting many of the problems which plague themacrocosm of medicine.

PAST AND PRESENT INDICATIONS

Table 1 lists 132 past or present indications for the use ofHBO. We provide the list in its entirety* because we have not

been able to find a similar attempt in the recent literature.The list includes indications that are not exclusively Ameri-can. For example, HBO is used extensively in Eastern

Europe. No analysis of most non-American indications was

attempted. In assembling the list, several obvious conclu-

sions emerged. The broad range of conditions speaks foritself. HBO has been and continues to be regarded as a form

of near-universal treatment.Some indications arose as a result of assumed

pathophysiologic considerations, some indications were gen-

erated for pragmatic reasons, and for some indications, it was

(is) not possible to trace the reasons for the use of HBO.

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Table 1, continued

Necrotizing fasciitis

Postepileptic headaches

Radiation pneumonia

Balloon aspiration

Migraine

Allergic reaction

Quadriplegia

Dust-induced bronchitis

Gastroduodenal ulcer

Facial neuritis

Late pregnancy toxemia

Liver failure

Closed chest trauma

Emphysema

Paralytic ileus

Rendu-Osler Weber

disease

Perirectal fistula

Necrobiosis lipoidic

diabeticorumBlack lung disease

Allergies

Myositis

Colitis

Cerebral vasospasm

Malignant otitis externa

Acute hearing loss

Pneumatosis cystoides

intestinales

Maxillofacial phiegmon

Cochlear vestibular syndrome

Viral encephalitis

Bites

Buerger’s disease

Vascular headache

Precardiac surgery

Tracheal fistula

Vertigo

Rheumatoid arthritis

Preservation of

youthfulness

Viral hepatitis

Habitual abortion

Sodium nitrite poisoning

Diabetes mellitus

Fourier’s gangrenel

Acute pancreatitis

Organophosphate

poisoning

Penanal hidradenitis

supprativa

Organ preservation

Muscular dystrophy

Poor circulation

Cirrhosis of the liver

Epilepsy

Pulmonary hypertension

Lung lavage

Revascularization

Chronic coronary artery

disease

Penodontosis

CHEST I 92 I 6 / DECEMBER, 1987 1075

5Lyell� syndrome: toxic epidermal necrglysis found in lympho-

proliferative disease

tMoyamoya: sudden cerebral vascular insufficiency with a specific

arteriographic pattern

lFourier’s gangrene: idiopathic gangrene of the scrotum

Applications of HBO, not uncommonly, arise as a result of

medical adventurism, therapy in search of diseases. A unit is

available at a given facility. A patient enters with a givendisease for which treatment is unsatisfactory. Why not try

HBO?

There is also a dynamic flux involving its use for specific

indications. Most of these seem to go through a typicalevolution in which there is an initial increase in use charac-

terized by great enthusiasm and widespread use followed by,perhaps, a realization that HBO is not effective, followed by agradual decline in use. For example, in the 1960s, HBO was

touted as an effective antidote for senility which encom-

passed a spectrum of patients ranging from those with senile

dementia to benign senile forgetfulness, and HBO was used

in large numbers of older patients.34 This treatment, over thecourse of several decades, gradually fell into disrepute as a

cure for aging although, even in the early 1980s, some

patients continued to be treated for senility.’

There has been no mechanism for memory, ie, to recordprevious errors so that current HBOers can learn from the

mistakes of the past. In fact, a discredited or abandoned use

of HBO is seldom, if ever, provided wlth a decent burial.It is usually assumed that the use of HBO is scientifically

based. After all, HBO is based on the gas laws56 and uses a

variety of complex, sophisticated devices for pressurization

and monitoring.

With rare exceptions, the potential risks ofHBO have been(are) ignored or underplayed. With rare exceptions, physi-cians using the equipment have had little or no personalexperience in conducting appropriate clinical trials nor havethey demonstrated substantial interest in testing the safetyand efficacy of HBO. Increasingly, there have been formalexpressions of the desirability of controlled prospective

randomized clinical trials. These expressions almost assumethe form of a catechism (see below); the clinical trials are notconducted.

The activities of ilBOers have ranged from serious at-tempts to rationalize HBO use, by groups such as theUndersea Medical Society, to impulsive and poorly con-ceived thrusts. Risk-benefit analysis has been strikinglyabsent. In brief, the history of the use of HBO is notqualitatively different than the history of many therapeuticattempts in medicine.78 The overall point is that, with onlyrare exception, the history of the use of HBO has beencharacterized by unscientific, uncritical pragmatism.

Baromedicine has also been characterized by a spirit ofmedical adventures, a willingness to try this therapy in a

wide variety of disorders with minimal careful analysis; HBO

often is a form of treatment in search of diseases.

Table 2 lists various disease states for which HBO iscurrently recommended (with various degrees of enthusiasmby baromedical experts). In general, these conditions arethird party reimbursable which plays some role in the degreeof enthusiasm. As indicated in the table, for only onedisorder, decompression sickness, is there an overwhelmingclinical experience and acceptable clinical trials which dem-onstrate efficacy. For only a few of these conditions is the

incidence in the general population of sufficient magnitude

to represent an overwhelming health problem. For many ofthe entities there are effective alternative forms of treatment.In addition to lack of studies indicating benefits, for most ofthe entities the risks have not been carefully quantitated. Thedata do not suggest that most present uses of HBO therapy

are more clearly established now than in the past severaldecades.

Decompression Sickness

The use of hyperbaric chambers during ascent from deepdiving represents the most clearly and perhaps only vali-dated use of hyperbaric therapy. Proof of efficacy has beenestablished as a result of extensive pragmatic studies by theUS Navy as well as other organizations.9 A series of tables hasbeen developed for the estimation of safe periods of gradualdecompression. There is not only an extensive clinical ex-

perience, but the clinical experience embodies some ele-

ments of alternating single-patient clinical trials.’#{176}11Symp-toms indicating too rapid decompression are rapidly

alleviated by recompression at a higher pressure.

It should be emphasized that no similar clinical experienceor trial supports the use of HBO for the treatment of most

forms of intravascular aeroembolism, as that arising during

cardiac surgery or during scuba diving. HBO is used todecrease intravascular bubble size and to increase the driv-ing pressure for oxygen into tissue and cells. There are many

factors which determine outcome in these patients, such asthe time between embolism and the time of treatment. Thus,clain�s that aggressive HBO treatment is effective from

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would require an

No such data are

Table 2-Current ‘Strong” indications for the Use of HBO

1076 HyperbarIc 02: A Therapy in Search of Diseases (Gabb, Robin)

Adequate Extensive Incidence Alternative

Clinical Favorable in General Forms ofTrials Clinical Hospital Treatment

Available Experience Population Available

Decompression sickness + + very low 0

Intravascular gas embolism 0 0 very low ±

Carbon monoxide intoxication 0 0 moderate ifsmoke inhalation included 4.

Gas gangrene and other anaerobic infections (I ± low 4.

Osteomyelitis 0 0 moderate +

Selected mycotic infections 0 0 moderate +

Cyanide poisoning 0 0 very low +

Brain edema 0 0 moderate +

Burns 0 0 high +

Anemia from exceptional blood loss 0 0 high 4.

Enhancement of wound healing 0 0 high +

Radiation necrosis ±

Established 0 0 low +

Prophylactic 0 0 high 0

Key: + (yes) 0 (no) ± (possibly)

minutes to hours after gas embolismacceptable clinical trial for evaluation.

available.

Carbon Monoxide Poisoning

This entity is currently cited as the indication par excel-

lence for the use of HBO treatment. It has been establishedthat HBO reduces blood concentrations of carboxyhemo-globin more rapidly than is effected by breathing 100 percent

oxygen at ambient pressure (carboxyhemoglobin half-life atroom air: 5 hours and 20 minutes; carboxyhemoglobin half-life at 100 percent oxygen breathing: 90 minutes; and carbox-yhemoglobin half-life under HBO: 23 minutes).’

It is by no means established that this decrease in half-liferesults in improved outcome. It is not at all certain that HBOimproves oxygen delivery to the brain and myocardium,

which depends not only on the Pa02 but also on the rate oforgan blood flow. Nor is there evidence indicating that HBOreduces cerebral edema by brain vasoconstriction. Even ifthe latter two mechanisms operate, whether these are trans-lated into a better outcome for patients would requireindependent documentation. None has been provided. Thelack of acceptable evidence of efficacy of HBO in COpoisoning has been noted elsewhere.C

One interesting claim, unsupported by firm evidence, isthat HBO therapy may improve brain function hours to days

after the acute event when blood concentrations of CO areminuscule. The world’s record is the report of a patient whoresponded to HBO therapy nearly two months after carbon

monoxide intoxication.0 Needless to say, no firm evidence isavailable to support this claim. Perhaps the claim is accurateand HBO reverses some mysterious biochemical alterationrelated to CO poisoning, but in the absence of firm evidence,this claim cannot be accurately evaluated.

The indications for treatment have been broadened toinclude suspected CO poisoning even in the absence of de-tectable CO-Hb levels,’4 and subacute sequelae of estab-lished CO poisoning. ‘�

The most mysterious fact about the use of HBO in CO poi-soning is the failure to carry out animal trials in primates. The

organization of such trials would be relatively simple. Carbonmonoxide can be administered with great accuracy; quantita-lion of carboxyhemoglobin levels is simple; outcome as afunction of no treatment, treatment with 100 percent oxygen

and with HBO could easily be compared. It would bepossible to determine whether late application of HBO re-verses brain injury even when significant blood levels of COare no longer present. Finally, the quantitative risks associ-

ated with HBO could be determined. The total fundsrequired to carry out these studies would be substantiallyless than maintaining numerous HBO units in various com-munities.

Gas Gangrene and Other Anaerobic Infections

The modern revival of the use ofHBO stemmed from a re-

port by Brummelkaxnp and colleagues’8 in the 1960s. They

treated 26 patients with clostridial infection and reportedthat 25/26 patients were cured and 21126 patients survived.Needless to say, the study was uncontrolled. Even the simpleexpedient of comparing the outcome of patients receiving 100percent oxygen with those on HBO was not considered; norhas it been since. Controlled studies or not, the use of HBOwas widely applied to patients with clostridial disease.

There may be a subgroup of patients with clostridialinfection who may have improved outcome on HBO used asan adjuvant to surgery and antibiotics. This favorable re-sponse is by no means universal.’7’8 How these patientswould respond on 100 percent oxygen at ambient pressures isnot known. One could hardly use this small group of patientsto justify the organization of HBO units in the community. Inflict, before general clinical application to the treatment ofgangrene, a controlled trial of HBO in treating clostridialinfection would be desirable.

The clinical experience with non-clostridial anaerobicinfections or mixed infections does not suggest that the use ofHBO has a favorable risk-benefit balance.’8

Osteomyelitis

The first report of the use of HBO to treat osteomyelitis

(OM) was in 1965.’8 Five cases of chronic OM were described

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CHEST I 92 I 6 I DECEMBER, 1987 1077

and all were noted to have “responded to treatment withHBO at 2 ATA given fur various periods.” The report wasremarkable as in only one of the five cases were antibiotics

used as part of the treatment. Since then, numerous studies

evaluating the use of HBO to treat chronic OM in animalsand humans have been reported.

Two separate animal experiments have compared the effect

of treatment with HBO versus nontreatment on established

OM in rats and rabbits, respectively.3’�’ Both experimentsdemonstrated that those animals treated with HBO had asignificant increase in the healing of OM compared withthose animals given no treatment. More specifically, ‘friplett

et a12’ found a significant improvement in the healing of

sinuses, reduced fracture mobility and improved histologic

appearance in their group of HBO-treated rabbits. However,these experiments did not include an antibiotic treatment

group, or antibiotic and HBO treatment group.

In 1978, Mader et al3’ compared the effect of four treat-ment programs on established OM in the long bone of a rab-

bit. Their treatment groups were: no treatment, HBO alone,

antibiotic alone, and HBO and antibiotic in combination.

They found significant differences in outcome between the

control animals and all treatment groups; however, there wasno difference between any one ofthe three treatment groups.

They concluded that HBO did not appear to be synergistic or

additive with cephalothin (the antibiotic used) in the treat-

ment of OM.

Several large series of patients with refractory OM, treated

with HBO in combination with surgery and antibiotics, havebeen reported.ZU�S�S7 These uncontrolled trials show suc-cess rates of 63 percent to 85 percent. However, important

criticisms should be made of these trials. In one study the

duration of previous infection ranged from one week to 20

years.3’ OM of one week’s duration can hardly be described aschronic.27 The studies are, without exception, lacking in

control groups, the intention being that each patient shouldact as his/her own “historic control.” It is impossible to knowif the surgical and medical aspects of the combined HBO

treatment program are identical to those employed beforeHBO was commenced. One study stated,” ... the absenceof medical records prevented precise documentation of theadequacy of previous treatment.” That being so, the ability ofa patient to stand as his or her own historic control is in doubt.Moreover, the use of historic controls are notoriously unrelia-ble.

In conclusion, the current evidence for the efficacy ofHBO as an adjuvant in the treatment of refractory OM isdrawn from animal studies where HBO-treated groups ofani-mals are compared with those given no treatment, anduncontrolled human case studies. As such, it would seem

that the claim that HBO is “rational, scientific and proventherapy for chronic refractory OM” is, at best, premature andprobably unfounded.�

Selected Mycotic Infections

The use of HBO in any mycotic infection has never beenadequately documented. In fact, with the availability ofcurrent antifungal agents, the use of HBO must be consid-ered particularly unscientific.

Cyanide Poisoning

This is a rare form of poisoning, and the death rate isestimated at between 80 to 400 cases per 10 million popula-

tion.� Presumably, HBO could compete with CN binding tocytochrome aa�#{176}Animal studies do not indicate efficacy.3’The case reports from human cases are equally unimpres-sive.3’3’ There is an excellent non-toxic therapeutic agent,hydroxycobalamine,� and it is difficult to escape the conclu-

sion that the use of HBO as a form of therapy in the case ofCN poisoning stems from the Sir Edmund Hillary dictum(who climbed Mt. Everest because “the mountain was

there”): “the HBO chamber is there.”

Brain Edema with and without Head Trauma

Rationales for the use of HBO include reductions inintracranial pressure because of cerebral vasoconstrictionand enhanced brain oxygen supply.

The lack of good experimental evidence of benefit and theproblems of oxygen toxicity have made the use of this methodalmost, but not entirely, obsolete.3’ A prospective, ran-domized trial of 30 patients eliminated from considerationthe least sick patients and the most sick patients. This lefteight controls and seven HBO-treated patients to be ana-lyzed. There was no significant difference in survival in thetwo groups. These results would seem to be unpromising andat variance with the conclusions drawn by the investigators:

Based on the experience in the literature cited previously and onour own initial experience, we hope in the future to convincinglydemonstrate that the treatment of severe brain-injured patients withHBO will result in an overall beneficial response in terms of long-term functional recovery and decreased mortality rates.�

Thermal Burns

Only one hyperbaric chamber consistently uses HBO forburns, and has treated over a thousand patients. The rationalfor its use is based on enhancement of leukocyte bac-tenocidal activity and enhancement ofwound healing. Therehave been no controlled clinical trials and one is left towonder how patient or family permission was obtained totreat these patients.

Anemia from Exceptional Blood Loss

This treatment is suggested for the most part when bloodtransfusions are not acceptable for religious reasons. Thetheory is that enough oxygen can be physically dissolved inthe plasma to supply metabolic needs. Obviously, theefficacy has not been put to any type of critical scrutiny.

Enhancement of Wound Healing

The rationale is that HBO increases the bacteriocidalactivity of leukocytes and improves oxygen supply to poorlyvasculanzed tissue. Increasing tissue Po� may enhance

collagen synthesis by fibroblasts. No acceptable clinical trials

are available.

Radiation Necrosis

This area of disease may become the gas gangrene of the1980s. Progressive proliferative endoarteritis may result from

high doses of ionizing radiation. The primary tissues involvedinclude bone (osteoradionecrosis) and soft tissues. Datingback to 1973, clinical observations suggested that HBO treat-

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1078 HyperbariC 02: A Therapy In Search of Diseases (Gabb, Robin)

ment was valuable for partially ischemic, hypoxic bone andsoft tissue lesions.37 The putative mechanisms for improve-ment included the ability of HBO to stimulate fibroblasticproliferation and enhance collagen synthesis and capillaryangiogenesis.3’

The major form for treatment has been osteoradionecrosisinvolving the head. One randomized prospective clinical trialhas been reported. The issue was whether HBO could pre-vent the development of osteoradionecrosis of the mandibleafter tooth removal in a high-risk patient population. In thegroup of patients receiving HBO, there were significantlyfewer tooth socket wounds that failed to heal as compared to agroup of patients receiving penicillin without HBO.3’ No con-trols using 100 percent oxygen at ambient pressures were

studied.

The clinical trial studied a highly specialized and circum-scribed problem: the rate of resolution of tooth socket healingafter radiation. The number of such patients in the generalpopulation must be very small. For example, in one majorcenter over a 15-year period, a total of 101 patients weretreated.4#{176}

The extrapolation of these favorable results to the generalproblem of radiation necrosis is neither medically nor scien-

tifically justified. In fact, therapeutic and prophylactic at-

tempts to deal with radiation necrosis in other areas, in an

uncontrolled study fraught with polypharmacy, did not pro-vide striking evidence of efficacy. The sites which weretreated included the chest wall, the pelvis and lumbar area,the spinal cord, the brain, and the larynx.4’

This scanty data base is now being extrapolated to considerthe use of prophylactic HBO in all or most patients receivinghigh doses of therapeutic radiation. The patient population

for such treatment would be very large. What proportion ofthese patients would develop clinically significant radiationnecrosis is unknown. Whether HBO would be effective pro-phylactically is also not established. To implement such aproposal without a prior controlled, prospective randomizedclinical trial would be to repeat the errors of the past.

It is useful to describe two examples of more or lessdiscredited indications for the use of HBO.

Senility

The possibility of improving cognitive function in the

senile by HBO has been a pragmatic indication fur wide-spread use of HBO for a number of years.

This approach was provided a scientific rationale and someexperimental support by studies reported in the late 1960s.4The scientific rationale was that HBO increases oxygensupply to a brain with a deficient cerebral circulation. Theexperimental studies consisted of comparing several tests ofcognitive function in 13 aged subjects with chronic brainsyndrome subjected to hyperbaric 100 percent oxygen withfive similar subjects subjected to 2.5 atmospheres of 10

percent oxygen. Thirty treatments of 90 minutes each wereprovided for 30 days and three tests of cognitive functionwere applied before and 24 hours after the last treatmentadministered by an examiner who was blinded as to whichbreathing mixture had been used in which subject.

It was reported that there was a remarkable and significantimprovement in the test scores of treated patients comparedto those who breathed an ambient-air-like gas mixture.

Several aspects of these studies warrant comment. Themajority of the patients almost certainly did not have cerebralarteriosclerosis as the basis of their chronic brain state. Anaccurate diagnosis of the majority of patients was almostcertainly Alzheimer’s disease, a fact which was not appreci-ated in 1969.4#{176}Thus, assuming that the treatment worked, it

was not because cerebral vascular insufficiency was beingtemporarily alleviated twice a day fur 180 minutes. Thus, atmost, the treatment “worked” fur the wrong reasons.

The putative benefit of the treatments continued fur 24hours after the HBO treatment had ceased. This would re-

quire that the cause of any benefit was a mechanism unknown

then and currently unknown.

The sensitivity and specificity and depth of resolution of

the three psychologic tests administered to test the effec-tiveness of HBO treatment are essentially unknown. It is

probable that the tests were inadequate to test cognition

accurately and quantitatively.Rather than stimulating an adequate clinical trial embrac-

ing an adequate number of patients with accurately diag-nosed cognitive disorders, the results stimulated mass use ofHBO treatment in the senile (aged). Masses of senior citizenswere lined up to have their senility treated. The complica-

tions resulting from HBO in this group of patients areessentially undescribed. By 1983 the practice had largelyfaded from use as a furm of treatment of senility in the US,although four patients with Alzheimer’s disease were treatedin 1985.’ No results are available.

It is probable that the gradual abandonment of HBO treat-ment fur senility was related to lack of effectiveness. It is, ofcourse, barely possible that some subgroup of patients wasbenefitted by the treatment to account for the results of the

early clinical trial, if so, then a potentially beneficial furm oftreatment has been abandoned because of inadequate scien-tific validation.

The point is that the existing lack of scientific rigor not only

leads to the use of ineffective treatment, but could also lead topremature abandonment of effective furms of treatment.

Thus, the use of HBO in the treatment of Alzheimer’sdisease remains an unsettled issue. While it is our opinion

that an adequate clinical trial will fail to show benefit, the useof HBO remains a furmal scientifically and medically unset-tled issue.

Multiple Sclerosis (MS)

The suggestion that HBO might be useful in the treatmentof MS originally rose in 1970 in Czechoslovakia.� Animalstudies were reported which suggested that HBO amelio-rated experimental allergic encephalomyelitis in guinea

pigs.”This was followed by a series of uncontrolled clinical trials

suggesting partial to complete remission in human subjectswith MS treated with HBO.”

The major impetus to its widespread use stemmed from

the results of a small “controlled” trial reporting benefit andpublished in a prestigious medical journal.

This study noted objective improvement in 12 of 17 pa-tients treated with HBO and in one of 20 patients treatedwith placebo (p’(O.OOl). Improvement was transient in sevenof the patients treated with oxygen and long lasting in fivepatients. The authors themselves recognized the inadequacy

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CHEST I 92 I 6 I DECEMBER, 1987 1079

of this study; however, the peer reviewers did not.”This report was greeted with enthusiasm and, fullowing

publication, numerous patients with MS in the US and UKwere placed on HBO therapy. In 1983, over 1,300 patientswith MS were treated, and in 1984, over 1,100 patients weretreated in the US alone.’

The initial clinical trial stimulated a series of randomized,prospective, controlled clinical trials. At least nine have been

published between 1985 and 1986. None has shown ef-ficacy.”3’ Simply stated, there is overwhelming scientificevidence that HBO does not work.

But that is not the end of the story. There has been a spateof letters to the editors of various medical journals byprotagonists. An organization called the Association forResearch into MS (not to be confused with the Multiple

Sclerosis Society) was (is) soliciting money in order to

establish hyperbaric chambers. The truly convinced remainconvinced, and it will be some time befure HBO use in MSsuffers the same fate as oil of evening primrose and snakevenom in the treatment of MS. At least in the US, enthusi-asm fur this form of treatment appears to be abating.

How MANY PATIENTS ARE TREATED WITH HBO?

The magnitude of usage from 1977 to 1985 may be judged

from the following figures. A total of 36,937 patients werereported being treated.’ Of these, 17,885 (49 percent) weretreated for indications fur which there is substantial current

enthusiasm and 18,912 (51 percent) were treated for indica-

tions of various degrees of dubiousness.

RISKS OF HBO

With few exceptions, the potential risks of HBO treatmenthave not received substantial emphasis. In qualitative terms,a number of risks have been described and these are sum-marized in Table 3. Briefly stated, these risks arise from highbarometric pressures during the process of compression;from responses to high oxygen tensions such as brain andlung injury; from gas embolism arising during the process ofdecompression; from chamber accidents arising from fire(several deaths, including a patient and attendants during afire in Germany); and from several forms of toxicity, themechanisms of which are unknown, including myopia andincreases in refractive error lasting for weeks to months,

anxiety, nausea and vomiting.Contraindications to the use of HBO are said to include

pneumothorax, severe obstructive pulmonary disease, pul-monary blebs and bullae, optic neuritis, acute viral infectionsand inability to equalize middle ear pressures.�

The precise quantitative extent of the risks associated withHBO will require appropriate clinical trials. Some estimate

can be derived from the literature.

In an early series of 445 patients, minor complicationsrelated to barotrauma occurred in about 30 percent of the

patients, convulsions occurred in 2 percent, and psychologicsymptoms occurred in about 20 percent.3’

In a series of 88 patients, there were eight grand malseizures and in one patient the convulsions persisted and thepatient died.’8

In another series of 87 patients, barotrauma occurred in 28

percent of the patients; anxiety was noted in 43 percent.Dyspnea and chest pain occurred in 18 percent of the pa-

tients, neurologic symptoms occurred in 10 percent, and 5percent had grand mal fits.’7

In a series of 109 patients treated over a 15-year period,major complications included 2 percent with convulsions;

one of these patients suffered a stroke and one an acutemyocardial infarction. Minor complications resulting frombarotrauma occurred in about 2 percent of the patients.”

To the extent that these data are representative, severe

CNS manifestations occur in 1 to 2 percent of treated pa-tients, symptomatic barotrauma in perhaps 15-20 percent of

patients, and optic symptoms in perhaps 20 percent of pa-tients. Death attributed to HBO (aside from deaths resultingfrom fire) is very rare.

In summary, then, HBO is not as safe or benign as might

be inferred from past and present descriptions of the proce-

dure.

EcoNoMIcs As A DIUVING PRESSURE

Evidence isabundant that increased use of HBO is closely

coupled to a desire fur increased profits. This is not a new

development. When HBO was thought to be a useful form of

treatment for multiple sclerosis, the number of private (forprofit) HBO units in the UK increased.

As aptly stated by Bates,There is, of course, the inevitable fact that the provision of these

chambers represents a significant investment in personal effort, time

and money which itwill be so hard to accept has been fruitless.�

Current classifications of the validity of the use of HBO furvarious conditions suggest that so-called category 1 diseases

are covered by third-party carriers-other categories are

not.57The importance of clinical trials is asserted to be based on

obtaining evidence which will increase insurance paymentsfur HBO:

Third party insurers who pay for major medical treatment today have

Table 3-Known Risks of HBO Therapy

Barotrauma from increased barometric pressure (Compression

manifestation)

ears

sinusesmiddle ear hemorrhagedeafness

Oxygen toxicity

brain

convulsions and sequelae other CNS manifestationlung

pulmonary edema, hemorrhage, respiratory failure

pulmonary oxygen toxicity

Decompression sickness

pneumothorax

nitrogen emboli-CNS, joints, etc.

Fire hazard

patients

medical attendants

Mechanism unknown

myopia

fatigue

headaches

vomitingclaustrophobia

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1080 HyperbarIc 02: A Therapy In Search of DIseases (Gabb, Robin)

to be convinced of scientific validity and we don’t always have

documented proof [of HBO eflicacyl.We need well-controlled ani-

mal wnrk and prospective clinical studies to document who and for

what disorders this therapy should be used.3’

Just how much money has been expended by patients on

HBO? Assuming that an average course of treatment is two

months and that the treatment cost is $1,000/month,3’ then

since 1977 about 80 million (documented) dollars have been

billed for HBO. This is not a large sum as these matters go. By

comparison, pulmonary flow catheters consumed 2 billion

dollars in direct costs in 1983, and an additional 1 billiondollars was spent treating the complications of the catheter!3’

A new element has been added recently to these pres-

sures. American hospitals are faced with a decreasing inpa-tient population along with a desire to maximize profits. One

solution to this dilemma is to have hospitals offer an increas-

ing number of modalities which are moneymakers.

Manufacturers of HBO chambers now offer deals in which

chambers are installed in hospitals free of charge on a profit-

sharing basis. The major advantage to the hospital is that the

chamber requires little capital expenditure on the hospital’s

part while opening up a new source of income.

There are other advantages to the institution. The installa-

tion of a new HBO chamber is usually recognized in the

media with glowing commentaries. Once patients attend a

hospital for one purpose, they commonly use the facilities for

other (profitable) activities.

The major danger is that this practice will accelerate the

use of HBO for unproven disorders. There is always the hope

that a mass application for the use of HBO will increase

profits substantially. Another danger is that once HBO is

institutionalized in this fashion, it will become increasingly

difficult to implement the required careful clinical studies.

Institutions will, of course, claim that the HBO chambers

will be used for research, but at the very best, widespread

clinical application will precede careful studies of efficacy.

Judging by the past, no rigorous studies of efficacy will be

performed. For example, it is probable that we will experi-ence major uses of HBO to prevent radiation necrosis long

before the evidence is available as to whether HBO is usefuland safe for this purpose.

CLINICAL TRIALS

The medical literature involving HBO contains more than12 references during the past 15 years commenting on the de-sirability of adequate and appropriate clinical trials of one

disease or another. Despite these sentiments, little has beendone.

There are a number of problems. One is the sheer magni-tude of the various disorders for which HBO is used. Asecond problem is that, by dint of training, experts in HBO

are not trained or experienced in the organization and

implementation of appropriate clinical trials. A third prob-lem is that clinical trials, to paraphrase the immortal words ofWillie Sutton, is “not where the money is.”

A need for appropriate clinical trials can be derived by

analyzing the system of classification suggested by the

Hyperbaric Medicine Society for summarizing the status ofvarious indictions for HBO.6’

Category 1: conditions for which HBO treatment is known

to be effective (and is third-party reimbursable).

Given the lack of acceptable data showing efficacy for mostof these conditions, the word “known” is a substantial over-statement. At best, most conditions in this category repre-sent a consensus opinion by workers using HBO based onpragmatic and uncritical considerations.

Category 2: conditions for which HBO treatment is

unproved clinically or experimentally and is not reimburs-able.

This category raises even more sharp issues than category

1. If the treatment is experimental, is informed consentobtained from the patient or his surrogate to permit the use ofthe patient in an experiment? (Parenthetically, not to obtaininformed consent in most legal jurisdictions represents a

form of malpractice.)Are patients required to pay for experiments performed on

them? If so, what is the justification? Are such studies on

patients really scientific experiments? What are the hypoth-

eses which are tested? What controls are used? What quality

control measures are used to ensure high standards and uni-

formity of data collection? What mechanisms are used for

critical evaluation of the data and interpretation of the data?Or is HBO treatment usually a pragmatic, uncritical, un-structured effort?

WHAT MIGHT BE DONE

A starting point might be to select one or two conditions forappropriate clinical trials; for example, the treatment of CO

poisoning and the prophylazis of radiation necrosis might besuitable areas. While these trials are being conducted, avoluntary or mandated moratorium on the random use of

HBO could be suggested or enforced. A national conferenceon the application of risk-benefit analysis to HBO, sponsored

by the Hyperbaric Medical Committee of the UnderseaMedical Society, might be useful. Physicians referring pa-

tients for HBO therapy should be aware of the major

uncertainties.

SUMMARY

The application of HBO to the therapy of various humandiseases developed over a 300 year period. Like most of

medicine, the basis of these applications was and continues

to be pragmatic in nature, and involves uncritical and

untested judgments. The possibility of risks has been under-stated and possible benefits have been overstated.

Individual physicians offering HBO and organized groups,such as the Undersea Medical Society, advocating its use maywell be highly motivated, well meaning, and sincerely con-vinced that HBO is an important therapeutic approach. Itmay be that, buried among the host of indications, will besome disorders for which HBO is uniquely and highly ef-fective, If so, the present nonsystem for evaluating responsesto HBO will require modification, so that these potentiallyvaluable additions to therapeutics are not lost.

Because of its almost global application to a wide variety ofdiseases, HBO therapy lends itself easily to medical adven-turism (therapy in search of a disease) and economic exploita-tion. If there is some patient benefit to come from theexperience of the last 300 years, changes in approach, ini-tiated by baromedical devotees or by medicine generally, orresulting from pressures outside of medicine, will be re-quired.

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CHEST / 92 I 6 I DECEMBER, 1987 1081

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