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Hyperbaric Oxygen Therapy What it is and why you should care.

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Title: Hyperbaric Oxygen Therapy What it is and why you should care.


1
Hyperbaric Oxygen Therapy What it is and why you
should care.
  • Mark Iafrati MD, FACS
  • Chief, Division of Vascular Surgery
  • Director, Center for Wound Healing

2
Overview
  • Clinical wound healing issues
  • Historical development of Hyperbaric Medicine
  • Physiologic Rationale for Therapeutic O2
    Administration in wound healing.
  • Evidence Based Medicine.

3
Background
  • Chronic wounds
  • High O2 demand/ Low O2 delivery gthypoxia!
  • TcPO2 lt30 mmHg predicts failure to heal in PVD
  • Poor vascularity based on large or small vessel
    disease
  • Local factors blocking O2 delivery.
  • Edema, lipodermatosclerosis gt diffusion blocks
  • Possible shunting
  • Systemic factors
  • Diabetes, Steroids, malnutrition, etc

4
Radiation Tissue injury
  • Tumor Kill vs Normal tissue injury
  • Fractionation, Hyperfractionation, Supervoltage,
    beam columnation, etc.
  • Radiation Sensitivity
  • tumor gt endothelium gt fibroblast gt muscle gt
    nerve.
  • Heterogenous response
  • Immediate cell death vs delayed cell death vs
    sub-lethal injury vs no injury

5
Radiation Tissue injury
  • Progressive radiation fibrosis and capillary loss
    with time.
  • Spontaneous radionecrosis of bone or soft tissue
    or as a complication of surgery.

6
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7
Radiation Tissue Injury
  • Radiation induced occlusion of inferior alveolar
    artery

8
Radiation Tissue injury
  • Radiation induced hypovascular, hypocellular,
    hypoxic tissue.

9
Radiation Tissue injury
10
Arterial Occlusive Dz
Local Diffusion Barrier
DM
How are we Doing?
11
EndovascularAtherectomy Stent Grafts
12
Arterial Bypass Results
13
Phases of healing
  • Coagulation (minutes)
  • Inflammation (hours-days)
  • Migration/proliferation (days-weeks)
  • Reorganization (weeks months)

14
Phases of healing
  • Coagulation (minutes)
  • Inflammation (hours-days)
  • Migration/proliferation (days-weeks)
  • Reorganization (weeks months)

15
HISTORY OF HBO
Compressed Air Theory Henshaw (British, 1662)
treatment of acute disease with increased
pressure The chamber was fitted with a large
pair of organ bellows, with valves placed so that
air could either be compressed into the chamber
or extracted from it. In the domicilium
increased pressures were used for the treatment
of acute disease, and reduced pressures for the
treatment of chronic diseases.
16
HISTORY OF HBO
  • Compressed Air Theory
  • Henshaw (1662) treatment of acute disease with
    increased pressure
  • In times of good health this domicilium is
    proposed as a good expedient to help digestion,
    to promote insensible respiration, to facilitate
    breathing and expectoration and consequently is
    of excellent use for prevention of most
    affections of the lungs

17
History of HBO
  • Fontaine (1879) pressurized mobile operating
    room

18
History of HBO (Air)
  • Cunningham (Lawrance Kansas, 1918) used
    compressed
  • air to combat heart disease, circulatory
    disorders, and other
  • anerobic related diseases. (10 x 88)
  • Claimed good results in influenza
  • pts who were profoundly hypoxic
  • and comatose. (tragedy)
  • Complete resolution of uremia in
  • Timkin (Ball Bearing Manufacturer)

19
History of HBO
  • Timkin (1928) gave Cunningham 1,000,000 to build
    Steel Ball Hospital to treat a variety of
    diseases (e.g. cancer, diabetes)

Censured by the AMA in 1928 in a report that
stated  Under the circumstances, it is not to
be wondered that the Medical Profession looks
askance at the tank treatment and intimates
that it seems tinctured much more strongly with
economics than with scientific medicine.  It is
the mark of the scientist that he is ready to
make available the evidence on which his claims
are based.
  • Five stories high and 64 feet in diameter.  Each
    floor had 12 bedrooms with all the amenities of a
    good hotel.

20
Hyperbaric Oxygen Therapy
  • Modern scientific use of hyperbaric chamber in
    clinical medicine began in 1955 by
    Church-Davidson
  • HBO potentiates XRT
  • Boerma (1955-Univ Amsterdam)
  • Life without Blood
  • HBO in cardiac surgery

21
Boerma Life without blood.
3 ATA
22
  • HBO and Surgery
  • Brummelkamp (Amsterdam) found HBO could inhibit
    anerobic infections and was very useful in
    treating Clostridial gas gangrene. First paper
    published in 1961.
  • In 1960, Duke University built its first clinical
    chamber and NY Mt. Sinai Hospital acquired a
    surgical HBO chamber which was directed by Julius
    Jacobson
  • Likewise, many other prestigious hospitals
    installed surgical and non-surgical chambers

23
  • Decline of the Field
  • Through 1960s, extensive application into a
    multitude of unrelated chronic ailments and a
    lack of objective data again resulted in great
    skepticism in HBO.
  • By early 1970s, many of the chambers were either
    closing or not used due to lack of
    clinically/scientifically proven indications.
  • There was no general textbook available regarding
    successful HBO indications
  • Insurance companies had few, if any, guidelines
    to follow regarding reimbursement of HBO
    treatment
  • In 1972, a Medicare list of covered services was
    still sadly out of date
  • In 1977 only 37 HBO chambers were operating in
    the US.

24
Show me the data!
Who Cares?
HBO RIP
25
HBO Physiological Effects
  • Pressure effects
  • Oxygen effects

26
Hyperbaric Terminology
  • Atmosphere (atm)

27
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28
Oxygen Effects on Blood
  • Reduces Hct
  • Decreased Plt aggregation
  • Inc RBC deformability
  • Improved perfusion in narrowed vessels
  • Improved Neutrophil Function
  • oxidative burst after phagocytosis increases O2
    consumption 10-15x
  • O2 is captured by leukocytes and converted to ROS
    (hydroxyl radicals, peroxides, superoxides). The
    rate of this process is dependent on conc of O2
    available.

29
Oxygen Effects on Infection
  • Enhances PMN killing
  • Inhibits C. Perfringens
  • Inhibits alpha toxin production
  • Directly bacteriostatic

30
Oxygen as an Antibiotic
  • Knighton. Arch Surg 1986121191-195.

31
Oxygen Effects on blood and vessels
  • Fully saturate hemoglobin
  • Enhanced angiogenesis (VEGF, etc)
  • Vasoconstriction in normal BVs
  • Reduction in tissue edema

32
Oxygen Effects on Blood Flow
  • Blood flow
  • Reduced in normals
  • 20 reduction in limb flow with O2 (Bird 1965)
  • Decreased CBF with HBO.(Ohta 1987)
  • HBO decreases Cardiac Output (24-35) and
    increases afterload 30-60 (Villanuci 1990)
  • Preserved in ischemic tissues
  • No chg in laser Doppler flow in CVI but again
    decreased after ulcer healing. (Hammarlund 1988)
  • Improved perfusion in acute wounds (Hammarlund)
  • Improved flow in ischemic flaps (Zamboni 1992)

33
Oxygen Effects on tissues.
  • Increased hyaluronic acid and proteoglycans by
    fibroblasts
  • Inc Endothelial cell proliferation
  • Restoration of fibroblast growth and collagen
    production
  • Preservation of cell membrane ATP
  • Enhanced osteoblast/osteoclast function

34
Phases of Healing (Effects of Oxygen)
  • Inflammation
  • PMNs and Macrophages Respiratory burst
    producing (02-), NADPH oxidase limited by O2
    availability.

35
  • Migration/proliferation
  • Hypoxia will induce VEGF mRNA via (HIF) however
    translation is limited.
  • Modulation of oxidant species has a major impact
    on growth factorsVEGF, TGF-B, EGF
  • -_at_ mM conc H2O2 induces VGEF independent of
    Hypoxia inducible factor (HIF).

36
Oxygen Gradient
  • Normal wound healing (Room air)
  • Hypoxic gradient

Macrophage derived angiogenesis factor
Macrophage derived growth factor
0-5 mmHg
50-60 mmHg
Capillary Budding, Collagen Synthesis
45-65 mmHg
37
Oxygen Gradient
  • Radiated wound
  • Diminished Hypoxic gradient

Macrophage derived angiogenesis factor
Macrophage derived growth factor
0,5, 10, 15, 20, 30, 40 mmHg
Capillary Budding, Collagen Synthesis
10-20 mmHg
38
Oxygen Gradient
  • Wound healing-Irradiated
  • (2.4 ATA- HBO2)
  • Hypoxic gradient

Macrophage derived angiogenesis factor
Macrophage derived growth factor
50, 50, 90
350 mmHg
Capillary Budding, Collagen Synthesis
230 mmHg
39
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40
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41
Plateau Phase
Rapid rise phase
Neovascularity Stable _at_ 4 yr f/u
42
Dermal Injury day 0, TO2 3hrs/day on days 1-7.
43
Day 15 Keratin Green
44
VEGF Day 7 SMA Day 16
45
Oxygen and Angiogenesis
BM Stem Cells
EPCs
Angiogenesis
()
VEGF
HBO
46
Oxygen Effects on Healing The Big Picture
  • Promotes Angiogenesis
  • Anti-bacterial effect---bodys bacterial
    mechanism is oxygen dependent--when pO2 low,
    effective ingestion and killing by phagocytic
    leukocytes is retarded
  • Anti-ischemic effect--dissolve extra oxygen into
    plasma relieving ischemia
  • Tissue repair -Oxygen promotes bone turnover,
    collagen matrix formation, and breakdown of toxins

47
Where is the data?
  • PRTs demonstrate benefit in
  • Diabetic foot wounds
  • Acute ischemia
  • Radiation fields
  • Bone Graft Reconstruction
  • Soft Tissue Vascular Flaps
  • Tooth Extraction

48
Supplemental Perioperative Oxygen (Mask) Reduces
the Incidenceof Surgical Wound Infection
Fi02 0.30 Fi02 0.80 P Value (n
250) (n 250) Infections 28 (11) 13
(5) 0.011 ASEPSIS score 5 9 3
7 0.010 Collagen deposition - mcg/cm 267
109 258 118 0.375 Greif et al, NEJM
342161-1677, 2000
49
Studies HBO in diabetic wounds.
  • (Doctor 1992) PRT-30 pts. AMPs 13 vs 47 in HBO
    vs conventional. Also fewer () Cultures.
  • (Faglia 1996) PRT. 70 pts. AMPs 3 vs 9 HbO VS
    control.
  • (Kalani 2002) Partially PRT. 38 pts. Amps in 12
    vs 33

50
Hemimandibular Reconstruction in Radiated Tissue.
Marx J oral maxillofacial surg 1982
51
Major complications after flaps
Marx in Kindwall Hyperbaric Medicine 2005
52
PRT of HBO in tooth extraction after XRT
Ave dose 7200 cGy
Marx JADA 1985
53
HBO for ORN
  • 30/10 _at_ 2.4 ATA
  • Cost (1992 dollars)

54
Side EffectsHyperbaric Oxygen
  • Barotrauma of the Ear
  • Sinus Squeeze
  • Claustrophobia

55
Oxygen Toxicity
  • Grand Mal Convulsions (2ATA or higher)
  • Hypoglycemia
  • Pulmonary (gt0.5 ATA)
  • Intratracheal and bronchial irritation
  • Initial cough, dysnea, tightness
  • Pulm edema and ARDS possible
  • Occular
  • Progressive myopia (20-40 incidence) recovery
    w/in 2 months post tx.
  • Cataracts- new and progression.

56
Does HBO increase tumor Growth?
  • No evidence in any animal studies.
  • Tumor cells seem more susceptible because of
    impaired SOD production.
  • Human data suggests HBO reduces recurrence but
    many confounders in data.

57
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58
CMS Covered IndicationsHBO
  • Acute peripheral arterial insufficiency
  • Diabetic Ulcers
  • Gas Gangrene
  • Crush injuries
  • Necrotizing fasciitis
  • Skin grafts (failing)
  • Osteomyelitis
  • Radiation Soft Tissue Necrosis
  • Osteoradionecrosis

59
Our Approach (Tufts-MC)
  • Fix underlying anatomic problems
  • Revascularize, venous surg
  • Improve medical issues
  • Diabetic management, nutrition, steroid taper,
    CHF, CRI, hyperlipidemia
  • Mechanical issues
  • Off loading, shave callus
  • Physical Therapy/Rehab
  • Dressing care
  • Enzymatics, hyrogels, etc
  • Debride necrotic tissues
  • Refractory wounds get high end adjuvant
  • T O2, HBO, VAC, Appligraft, skin graft, APC, etc

60
  • Center for Wound Healing
  • Tufts Medical Center
  • 185 Harrison Avenue
  • Boston, MA 02111
  • 617-636-7761
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