P1249945250BIhSf

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Hyperbaric Oxygen in the Treatment of Diabetic
Foot Ulcers
The pressure is on to prove that it works.
Gerry Morrison, M.D.
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A Clinical vignette

• A 62 year old male diabetic with a Wagner Grade
  III foot ulcer on plantar surface of his left
  foot for 9 months.
• Multiple debridements, chronic antibiotics,
  mechanical stress relief.
• Good glycemic control, HgA1C 6.9
• Surgery recommending a BKA
• This patients vascularization adequate
• Patient has heard about HYPERBARIC OXYGEN THERAPY

Would YOU refer this patient for hyperbaric
oxygen therapy at Duke University Medical Center?
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What on earth is Hyperbaric Oxygen?

• Definition The intermittent administration of
  100 Oxygen at higher-than-atmospheric pressure,
  I.e. where oxygen dissolves in arterial blood
  plasma in increased amounts.
• Shah Pharos, 2000

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The Early Experiments

• Alexander the Great in 320 B.C.
• Aristotle 300 B.C.
• Henshaw, the Father of
• Built the DOMICILIUM1662

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The Early Experiments

• Junod, 1834, built first Hyperbaric Chamber in
  France 1834
• Pravez, 1837 built largest chamber in Europe
• No rationale for treatment (Jain)
• No standard for screening and pt selection

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Paul Bert The Father of Pressure Physiology
Oxygen
Toxicity

• 1878 observed convulsions and death in animals at
  a constant 3-4 atmospheres of pressure.
• Because of improvements in lung diseases, etc.,
  experiments continued.

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• Orville Cunningham modernizes
• 1921 Builds five story, 64 foot diameter chamber
  in Cleveland Ohio (largest built to date)
• Theory for using HBO is that people with the flu
  had a higher mortality at higher elevations.
• Begins to develop a standard for screening and
  treatment

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The Cunningham Chamber
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But then, all good things come to an end

• Tragedy strikes when mechanical failure causes
  all patients to die from decompression sickness.

• Cunningham persisted in weakly based experiments.

• AMA censured him in 1928

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Finally, some success!

• Behnke and Shaw, 1937- show improvements in
  animals revived with from
  decompression sickness
• L. Hendriks tested Lambertsens theory that
  alternating high and low oxygen pressures could
  increase working time at higher pressures.
• Period of oxygen inhalation doubled compared to
  previous studies of continuous exposure.
• This is the basis for how modern
  works.

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Modern day history of Hyperbaric Medicine -
Boerema

• Pioneered the application of to many
  medical problems.

• Performs first surgery with

• 1960 discovered that Hgb. wasnt
• necessary for O2 transport.

• Supersaturation of oxygen
• is theoretical basis for
• using to treat lower
• extremity wounds.

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Boeremas exp. with sickle cell and anemic
patients led to

• International Hyperbaric Conferences
• between 1963 and 1973

• 1976 Undersea and Hyperbaric
• Medical Society formed

• American College of Hyperbaric Medicine
• formed in 1983

• International Society of Hyperbaric Medicine 1988

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Gabb Calls . A Therapy in search of Diseases

• Universal uses (primarily Eastern Europe)

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Various indications for hyperbaric oxygen during
the past few decades

• Radiation necrosis, decompression sickness, gas
  embolism, soft tissue infection, soft tissue
  necrosis, bacteroides infection, compromised skin
  grafts, fungal infections, mucor mycosis, anemia
  from blood loss, carbon tetrachloride poisoning,
  fractures, leprosy, meningitis, radiation
  myelitis, cystitis and enteritis, retinal artery
  insufficiency, chronic brain ischemia, senility,
  multi-infarct dementia, infant cardiac surgery,
  chronic ulcers, peripheral vascular disease,
  diabetic neuropathy, acute endocarditis, hearing
  loss, cortical blindness, cellulitis, infected
  pacemaker, Hurlers syndrome, post-cardiac
  arrest, scleroderma, mycobacterium TB, abscesses,
  asthma, pneumomediastinum, hanging,
  thrombophlebitis, Lyells syndrome, CO poisoning,
  gas gangrene, osteomyelitis, Crohns DZ, Cyanide
  poisoning, crush injury with ischemia, Alzheimers

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Thermal burns, head and spinal injury, bone
grafts, frost bite, CVAs, Hydrogen sulfide
poisoning, cancer therapy, Pseudomembraneous
colitis, sickle cell crisis, MS, pyoderma
gangrenosum, acute MI, carotid aneurysm, aortic
aneurysm, anaerobic infections, post-cardiac
surgery, pulmonary insufficiency,
arteriosclerosis, causalgia, collagen vascular
diseases, post-op confusion, traumatic
amputation, pulmonary emboli, drowning, moyamoya,
surgical empyema, pharyngeal fistula, brain cyst,
stenotic valvular heart DZ, tetanus, intestinal
obstruction, necrotizing fasciitis,
post-epileptic headache, radiation pneumonia,
balloon aspiration, migraine, allergic reactions,
quadripelegia, dust induced bronchitis,
gastroduodenal ulcer, facial neuritis, late
pregnancy toxemia, liver failure, closed chest
trauma, emphysema, paralytic ilius, pararectal
fistula, necrobiosis lipoidic diabeticorum, black
lung DZ, allergies, myositis, colitis, cerebral
vasospasm, malignant otitis externa, acute
hearing loss, and..
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AGING.
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Dont you think that it works!!!????!!
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Speaking of famous people
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How is administered???

• Two types of hyperbaric chambers
• Monoplace vs. multiplace

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What are the differences?

• Monoplace
• Patient in lone chamber with oxygen, temp and
  humidity controlled. Most common, and can
  accommodate external mechanical vent.

• Multiplace
• Attendant is pressurized with patients
  requiring them to decompress via Navy dive
  tables.

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The process of treatment

• Initial compression for 30 minutes
• Treatment for 90 minutes with air breaks (10
  minutes every 30 minutes is standard)
• Decompression for 30 minutes

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The complications
Boyles Law a volume of gas in a closed space
will decrease as pressure increases
P1V1P2V2 - problems with air filled spaces
beneath dental fillings, middle ear and
sinuses. - Remedy is to teach valsalva maneuver
- Ventilated patients require myringotomy or
dental filling removal. - Neurologic damage
can occur - spontaneous pneumothoraces and those
associated with CV catheters occur. Sherid
an etal, 1999
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The complications

• Barotrauma from increased barometric pressure
• - Ears, sinuses, middle ear hemorrhage,
  deafness.
• Oxygen toxicity
• - convulsions and CNS manifistations
• - pulm edema, hemorrhage and resp flr
• Decompression sickness
• - pneumothorax and nitrogen emboli to CNS,
  joints, etc.
• Fire Hazard to patients and medical attendants
• Myopia, fatigue, headaches, vomiting and
  claustrophobia. Gabb Chest, 1987

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Modern Day uses of

• Category 1 Non-disputed (and reimbursable)
  uses
• Treatment of choice in decompression sickness
• Boyles Law P1V1P2V2
• Treatment of Choice in air Embolism
• Dissolving the obstructive gases back into
  solution
• Treatment for CO poisoning, Gas gangrene,
  anaerobic infections, osteomyelitis, burns and
  anemia from blood loss
• Gabb Chest, 1987

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Category 2 uses CONTROVERSIAL!!! (Not proven
and NOT reimbursable)

• CO poisoning, gas gangrene, burns, cancer and

• DIABETIC ULCERS

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Whats the rationale for the controversial uses???

• Actively healing wounds require more oxygen,
  and in areas of low circulation, proposed that
  hyperbaric oxygen is answer. Zamboni Und Hyper
  Med, 1997
• Proven to inhibit the growth of anaerobic
  bacteria Brummelkamp Lancet, 1963

• Problem Not all infections are anaerobic.

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The Evidence for using in the treatment
of Diabetic Wounds.

• Brummelkamp etal., Lancet 1963

- Diabetic patients with clostridial wounds
only - Study observational, not controlled with
100 oxygen or non-pressurized
treatment. - 25/26 treated patients cured and
21/25 survived. - All received standard wound
care (debridement), antibiotics. - Unknown
How pts would respond to normobaric oxygen or
how severe the wounds were, ie..no control group!
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Doctor, etal J Postgrad Med 1992First
prospective RCT

• Methods 30 pts with DM chronic ulcers
  randomized to tx and control groups

• All received 3 days of abx and surgical
  debridement as needed
• 15 patients received 4 HBO tx. in addition to
  traditional treatment.

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Doctor, etal.

• All wounds were cultured before and after each
  treatment.
• Need for amputation was assessed
• Length of Hospital Stay was assessed

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The results

• In HBO group, 2/15 amputations vs. 7/15 in the
  non HBO group (plt0.05)

• Confounding factor was that blood sugar was
  perfectly controlled in the treatment group and
  NOT in the control group.

• Cultures grew many bacteria, but statistical
  reductions in E.coli and Pseudomonas, proven by
  culture.

• No statistical differences in length of hospital
  stay.
• No mention of complications

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The Medical Community

• American Diabetes Association disregarded study
  calling it Poorly Done

• International Hyperbaric Society called for more
  RCTs to be performed.

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The landmark study to dateFaglia, etal.,
Adjunctive Systemic Hyperbaric Oxygen Therapy in
Treatment of Severe Prevalently Ischemic Diabetic
Foot Ulcer, 1996

• A double blinded, randomized controlled trial
• Followed 70 patients between 8/93 and 8/95
• Only published reasonable study to date

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Inclusion Criteria

• 70 patients consecutively admitted to a Diabetic
  Unit at the University of Milan.
• ONLY criteria for inclusion were
• Wagner Grade II-IV ulcers
• Diabetes Mellitus
• In Wagner Grade II ulcers, to have failed
  outpatient therapy after 30 days.

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Exclusion Criteria

• No previous HBO therapy
• No previous major amputations

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Methods

• 35 pts randomized to HBO and 35 to control groups

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35
control
HBO
1 CVA, death
1 quits, fearful
35 patients not Treated but study Reports 33
33 patients treated, But study reports 35
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Wounds classified by Wagner Grade

• Wagner Grade I Superficial erythema and
  abrasion
• Wagner Grade II Persistent, large and/or
  infected
• Wagner Grade III Abscess
• Wagner Grade IV Full thickness gangrene

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Multiple clinical characteristics assessed
without significant differences between tx and
control groups.

• Age, sex, insulin vs oral therapy, diabetes
  duration, prior minor amputation, prior lesion,
  retinopathy, microalbuminuria, proteinuria, renal
  imparment, hypertension, hyperlipidemia, obesity,
  smoking, CAD, prior CVA, infection, polymicrobial
  infection, infection recovery, bone lisis,
  osteopenia, Monckeberg sclerosis, peripheral
  angiography, HgA1C upon admission, HgA1C at
  discharge, total of days (hospital stay).

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Methods Cont

• Specimens of lesions were debrided and collected
  for aerobic and anaerobic cultures and for
  sensitivity testing.
• Sensorimotor neuropathy tested with
  electromyography
• Vibratory sense assessed with biothesiometer
• ABIs and transcutaneous oxygen tensions TcO2
  measured assessing ischemic DZ
• All pts received antibiotics, debridements and
  mechanical stress relief

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Methods cont

• PTA and BPG were performed on patients with
  severe ischemic disease.
• no significant differences between treatment and
  control groups.

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HBO treatment group received standard 2 phase
treatment

• Antibacterial phase
• 2.5 atm pressurized air breathing 100 O2
• - Believed to enhance antibacterial effects of
  oxygen and to increase tissue oxygen tensions.

• Reparative phase
• Intermittent pressurization to 2.2-2.4 atm
• Believed to stimulate fibroblastic activity

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What were the results???
Im not like other guys MJ
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Antibacterial effects

• 2 fold decrease in toxin production
• Decrease in number of colonies cultured from HBO
  group.
• Exact numbers, names of bacteria, and specifics.

NOT REPORTED! ! !
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Transcutaneous oxygen levels (mmHg)

• TcPO2 levels significant increase in HBO group
  p0.0002
• SD11.8 in HBO group and 5.4 in control group
• - small amount of overlap.

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Amputation rates
HBO Control P-value
N 35 33
Major amp 3/35 11/33 0.016
Wagner II 0 0 -
Wagner III 1 0 0.33
Wagner IV 2 11 0.002
Minor amp 21 12
No amp 11 10 0.61
of amputations, not people
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Risk vs. benefit

• Benefit
• No major amputation
• rr 0.26
• rrr74
• arr 25
• 95 CI (15-35 )
• NNT 4.0
• 95 CI (2.9-6.9)

• Harm
• 1 CVA death in tx grp
• 1 TM barot in tx grp
• rr ?
• ari5.8
• 95 CI (0.2-11 )
• NNTH 17
• 95 CI (9-500)

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What can we conclude?
ABC, easy as 123.or is it????
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The conclusions

• HBO, in conjunction with an aggressive
  multidisciplinary therapeutic protocol, may be
  effective in decreasing major amputations in
  diabetic patients with severe (Wagner Grade IV)
  prevalently ischemic foot ulcers.
• Data suggest a trend towards increase in
  limb-salvaging, minor amputations in treatment
  group.
• Is the decrease in major amp rate because of HBO
  or because of increased minor amp.??????
• Benefit outweighs risks in this study, but
  questions still exist!

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So, why the controversy??

• Consensus Development Conference on Diabetic Foot
  Wound Care Diabetes Care 221354-1360, 1999.
• There are no randomized controlled trials
  supporting the use of hyperbaric oxygen therapy
  to treat neuropathic foot wounds.

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Faglia sites Pecoraro paper

• Pathways to diabetic limb amputation states
  Diabetic ulcers frequently do not heal because
  of a combination of hypoxia and infection.
• Direct evidence lacking for direct cause of
  diabetic ulcers.
• Consensus statement does NOT recommend HBO in the
  treatment of diabetic foot ulcers until more RCTs
  are performed.

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The latest Consensus Development
Conference.awaiting the data.

• Dr. Carolyn Fife, Director of HBO center at
  Hermann Hospital.
• Has developed a screening protocol and treatment
  flow chart.
• 40 referred for intensive testing (ABI, Wagner
  grade, cultures)
• Then, trial of HBO with either healing or
  amputation as final outcomes.

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Fife sites problems to be addressed

• Lack of adequate screening and lack of proper
  training resulting in inappropriate use of HBO.
• Cost and cost-effectiveness are major issues.
• DUKE HBO CENTER.
• 266.00/tx X 38 tx 10,108.00
• Fifes current study looks at outcome,
  cost-effectiveness and risks for more than 1000
  pts
• Study to be completed later this year, anxiously
  awaited by DCC.

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The future of HBO, the pressure is on

• Current recs of American Podiatric Society and
  the Consensus statement on Diabetic foot wound
  care
• Patient education good glycemic control,
  compliance
• Daily monitoring and checking of feet
• Early use of mechanical stress relief to prevent
  ulcers and aid in healing.
• Traditional surgical and antimicrobial tx.

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Consensus Statement recs to Medical Community

• There are no RCTs supporting the use of HBOT to
  treat neuropathic foot wounds.
• DCC appeals to medical community
• Perform RCTs with strictly neuropathic pts
• Develop screening protocols
• Establish cost effectiveness of HBO as valid
  adjunctive therapy

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Dr. Fife sums it up-

• Current study looks at neuropathic patients vs.
  another group with multifactorial causes.
• Rec will include that traditional treatment be
  instituted first
• AFTER aggressive assessment and traditional
  treatment, HBO may be beneficial and should be
  done on a trial basis first.

• MORE STUDIES ARE NEEDED

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Would you recommend our pt. For HBO therapy????

• Our patient was referred to DUKE for HBO
  treatment. He underwent 36 HBO treatments, and
  ulcer size was reduced, but not Wagner Grade.

Pt underwent a BKA 4 months later.
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Acknowledgements

• Dr. David Miller
• Jessica Morrison
• David Suh, M.D.
• Amanda Ebright, M.D.
• Dr Carolyn Fife, Hermann Hospital

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Good luck to everyone

• Remember to have some fun along the way