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- Introduction and Scientific Foundations
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5
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6
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- 3 year old girl
- Mom: mild toxemia, fet=
al
distress, C-section, 3 weeks premature
- Developmental delays, extensive evaluation in first year of life
- Dx: AUTISM/MILD MENTAL
RETARD.
- Walks on knees, minimal eye contact, afraid of people and crowds, no
ADL’s, self-abusive
- SPECT, one HBOT, repeat SPECT
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7
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- HBOT in two courses over four months
- Repeat SPECT
- Walks with a walker, eye contact, interactive, playful, comfortable =
with
people and in crowds, feeds self, decreased self-abusive behavior
- 7 month follow-up: full
ambulation, continued improvement in all areas
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8
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9
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10
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11
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- Can we explain this scientifically?
- Most definitely!
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- INADEQUATE DEFINITION:
- “Hyperbaric oxygen (HBO2) treatment, in which a pat=
ient
breathes 100% oxygen intermittently while inside a treatment chamber=
at
a pressure higher than sea level pressure (i.e., > 1 atmosphere
absolute: ATA), can be viewed as the new application of an old
established technology to help resolve certain recalcitrant, expensi=
ve,
or otherwise hopeless medical problems...pressurization should be at=
1.4
atmospheres or higher.”
- UHMS HBOT Committee Report, 1999
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14
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- 1. Air or Gas Embolism=
- 2. Carbon Monoxide Poi=
soning
with Smoke Inhalation
- 3. Clostridial Myonecr=
osis
(gas gangrene)
- 4. Crush Injury, Compa=
rtment
Syndrome, and other
- acu=
te
Traumatic Ischemias
- 5. Decompression Sickn=
ess
- 6. Enhancement of Heal=
ing in
Selected Problem
- Wou=
nds
(diabetic, arterial insufficiency, venous
- sta=
sis,
and other non-healing wounds.)
- UHMS HBOT Committee Report, 1999
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15
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- 7. Exceptional Blood L=
oss
(Anemia)
- 8. Necrotizing Soft Ti=
ssue
Infections (Subcutaneous
- tis=
sue,
muscle, fascia)
- 9. Osteomyelitis
(Refractory) or (Acute) in
-
Compromised Hosts
- 10. Radiation Tissue Damage (Osteoradionecrosis and
-
Soft Tissue)
- 11. Skin Grafts and Flaps (Compromised)
- 12. Thermal Burns
- 13. Intracranial Absce=
ss
- UHMS HBOT Committee Report, 1999
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16
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- “A Therapy in Search of a Disease”
- Gabb, Robin. Chest, 12/87; 92(6): 1074-82
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17
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- “For only one disorder, decompression sickness is
there.....acceptable clinical trials which demonstrate efficacy̶=
1;
- “HBO is used to decrease intravascular bubble size.”
- Gabb, Robin. Chest, 12/87; 92(6): 1074-82
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18
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- Science in Medicine
- “Only about 15% of medical interventions are supported by solid
scientific evidence.... Many treatments have never been assessed at
all.”1
- “Only an estimated 10 - 20% of the techniques that physicians =
use
are empirically proven.”2
- 1. Richard Smith, editor. BMJ, 1991; 303: 798-9
- 2. U. S. Congressional Office of Technology Assessment 1987;7
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19
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- “Oxygen must be viewed in pharmacologic terms...toxicity, ....
tolerance, ....therapeutic ratio, ..... biphasic response of
microorganisms to increasing hyperoxia...., PO2-time
relationships...., etc.”
- Gottlieb, S. Oxygen Under Pressure & Microorganisms. In: Hyperbaric Oxygen Thera=
py,
- eds. Davis, Hunt, UHMS, Bethesda, MD, 1986
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20
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- Hyperbaric Oxygen Therapy is the use of greater than atmosphere pres=
sure
oxygen as a DRUG to treat basic disease processes/states, and their
diseases.
- HBOT in Global Ischemia, Anoxia, and Coma. Chapter 18.
- Textbook of Hyperbaric Med., K.K. Jain (Ed.), 1999
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- “A Re-appraisal”
- The basis of HBOT:
- The Physiology and Biology of Intermittent Hyperoxia, and possibly
intermittent pressure
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- Pharmacological Principles of Dose
- 1. Absolute pressure/F=
iO2
- 2. Duration of exposur=
e
- 3. Frequency
- 4. Number of treatment=
s
- 5. Half-life
- 6. Timing of dose with
respect to evolving
- pat=
hology
- 7. Side effects
- 8. Over-dose/toxicity<=
/li>
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- Facilitated by Henry’s Law
- (A Universal Gas Law):
- [ gas] solution =3D K (PP) gas
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- On RA at 1 ATA (sea Level):
- 19.5 vol. % of O2Hb + 0.5 vol. % dissolved
- =3D 20 vol. % or 20 cc O2/100cc blood
- Average O2 extraction of tissue @ 5 vol. %
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- Consequences of Henry’s Law:
- IDEAL dissolved O2 (Vol. %)
- ATA mmHG Breat=
hing
Air Breathing O2
- 1  =
;
760  =
;
.32  =
; &n=
bsp;
2.09
- 1.5
1140  =
;
.61  =
; &n=
bsp;
3.26
- 2
 =
;
1520  =
;
.81  =
; &n=
bsp;
4.44
- 2.5
1900  =
;
1.06  =
; &n=
bsp;
5.62
- 3
 =
;
2280  =
;
1.31  =
; &n=
bsp;
6.80
- K.K. Jain. Textbook of Hyp Med., Ist Ed., p 19
- Hogrefe & Huber, Toronto, 1990
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- I. Boerema,
- Netherlands, 19=
60
- Boerema, I. J. Cardiovasc Research, 1960; 1: 133-146
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- Acute and Chronic (Trophic) Effects
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- Acute Effects:
- Reduction of Hypoxia (Haldane - 1895, Sheffield - 1985)
- Hastened Dissociation COHb (End - 1942, Pace 1950)
- Inhibition of Reperfusion Injury (Zamboni - 1993, Thom – 1993,=
and
30+ other references)
- Haldane, JS. J. Physiol (London), 1895; 18: 201-217
- Sheffield, PJ. Hyper Oxy Rev, 1985; 6(1): 18-46
- End, E. J. Ind Hyg Toxicol, 1942; 24: 302-6
- Pace, N. Science, 1950; 111: 652-4
- Zamboni, WA. Plastic Reconstr Surg, 1993; 91: 1110-1123\
- Thom, SR. Toxicol Appl Pharmacol, 1993; 123: 234-47
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- Acute Effects:
- Cessation of Clostridial alpha toxin production (Van Unnik - 1965)=
li>
- Clostridial Bacteriostasis (Kaye - 1967, Hill - 1972)
- Reduction of Cerebral Edema (Sukoff - 1968, Miller - 1970)
- Recoupling of uncoupled flow and metabolism in acute severe TBI
(Rockswold, 2001)
- Van Unnik, AJM. Antonie Leeuwenhoek Microbiol, 1965; 31: 181-86
- Kaye, D. Proc Soc Exp Biol Med, 1967; 124: 360-66
- Hill, GB. J. Infect Dis, 1972; 125: 17-35
- Sukoff, MH. J. Neurosurg, 1968; 29: 236-4
- Miller, JD. J. Neurosurg, 1970;33:287-96
- Rockswold, SB, 2001;94:403-411.
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- Acute Effects:
- Reduction in burn shock and increased survival (Bleser - 1973)
- Amelioration of Hemorrhage shock (Attar - 1962)
- Reduction of Burn Edema (Nylander - 1984)
- Normalized/Enhanced wbc - mediated bacterial killing (Mader - 1980)<=
/li>
- Bleser, F. J Chir (Paris), 1973; 106: 281-90
- Attar, S. J Thorac Cardiovasc Surg, 1962; 44: 759-70
- Nylander, G. Burns, 1984; 10: 193-196
- Mader, JT. J Infect Dis, 1980; 142: 915-22
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- Reperfusion Injury
- Definition:
- A paradoxically harmful aspect of blood flow return after local isch=
emia
which contributes to parenchymal cell loss.
- Hallenbeck, Dutka. Arch Neurol, 1990. 47: 1245-54
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- Rat Gracilis Muscle Flap Model
- 4 hrs. Warm Global Ischemia
- Zamboni, W. Plast and Reconstr. Surgery, 1993; 91: 1110-1123
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- Results:
- HBOT Decreased
- 1. Wbc venule adherence
during or
- upt=
o 1 hr
during reperfusion.
- 2. Adjacent arteriolar
vasoconstriction
- dur=
ing or
upto 2 hr during
-
reperfusion
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- HBOT with Respect  =
;
HBOT
- to
Ischemia Mod=
el
of  =
; &n=
bsp;
Dose
-  =
;
Study
Date
Species &nb=
sp;
Organ
Ischemia Eff=
ect (ATA)
- Pre
During Pos=
t
-  =
;
X  =
;
X
Thomas
‘90
Dog  =
;
Heart  =
;
MI  =
;
+  =
;
2.0
- X  =
;
X
Zamboni
‘93  =
;
Rat  =
;
Muscle
Global  =
;
+  =
;
2.5
- X  =
;
X  =
;
X  =
;
Thom
‘93
Rat  =
;
Brain  =
;
CO &n=
bsp;
+  =
;
.21,1,2,3
-  =
;
X  =
;
X
Yamada
‘95
Rat
Intestine &=
nbsp;
Global  =
;
+  =
;
2.0
-  =
; &n=
bsp;
X &nb=
sp;
Mink
‘95 Rab=
bit
Brain  =
;
Global
+  =
;
2.8
- X  =
; &n=
bsp;  =
;
Atochin
‘99
Rat &=
nbsp;
Brain  =
;
Stroke
+  =
;
2.8
- X  =
;
Martin &nbs=
p;
2000 Rat  =
;
Brain  =
;
DCS &=
nbsp;
+  =
;
2.8X
-  =
; &n=
bsp;
X V=
an
Meter 2001
Pig &=
nbsp;
Brain  =
;
Global
+ &nb=
sp;
4
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- Human Example:
- Cerebral
- Decompression Illness
- Harch, P.G. 45th UHMS Workshop,
- Editors Moon & Sheffield, 6/1996, UHMS & Aerospace Med Assoc=
.
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49
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- Clearance of Bubbles From Cerebral Circulation
- Bubble emboli cleared from retinal vessels so rapidly that single-fr=
ame
photography was impossible.
- Cockett. 1973, 5th Int. Hyp. Congr. Procs
- Burnaby, Canada
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- Clearance of Bubbles From Cerebral Circulation
- Animal CAGE Studies:
- Bubbles cleared within minutes of injection ( true primarily for
injections of smaller gas volumes/bubbles)
- Helps, 1991. Stroke; 22: 351-54
- Helps, 1990. Stroke; 21: 1340-45
- Gorman, 1987. 9th Int. Symp. on U&HP. 1031-49
- Gorman, 1980. UBR; 13 (3); 9/86: 317-333
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- Cerebral Pathology Post
Passage of Bubbles
- Animal CAGE Studies:
- 1-4 hrs: granulocyte accumulation in areas of
-  =
;
decreased blood flow (Hallenbeck, ‘86)
- 4 hrs: platelet accumulation in areas of
-  =
;
decreased blood flow (Obrenovitch, ‘85)
- 3/4 - 1 hrs: decreased blood flow (Helps, ‘90)
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- Animal CAGE Studies
- Granulocytopenia prevents decreased brain blood flow (1,2) and
eliminates(1) or decreases(2) inhibition of
CEP’s 1 hr(2) - 2 hrs(1) post CAGE
- (1) Helps, SC. Stroke, 1991; 22: 351-354
- (2) Dutka, AJ. Stroke, 1989; 20: 390-395
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- Greatest single treatment success for DCS occurs with delays to
treatment of £
2 hrs., ideally 1 hr.<=
/font>
- Thalmann, ED. 41st UHMS
Workshop,
- editors Bennett and Moon,12/90, UHMS
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- In cerebral DCI nearly all bubbles pass through the brain within
minutes.
- Bubble passage causes a WBC-mediated
- reperfusion injury.
- HBOT powerfully inhibits wbc-mediated R.I. if delivered within 1 hou=
r of
injury.
- >90% single HBOT cure of DCI if treat within 1-2 hours of injury.=
- Conclusion: Throughout=
the
history of HBOT in diving, HBOT has been treating R.I. in cerebral D=
CI,
not bubbles.
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- “The Emperor Has No Clothes”
- Harch, P.G. 45the UHMS Workshop, 1995. Best Pub
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- Human Examples:
- 1. Hutchison; Lancet, =
1963.
Apneic Newborns
- 2. Mathieu; JHM, 1987.=
Near
Hanging
- 3. Shn-Rong; 11th Int.
Congress Hyper. Med.,<=
/li>
- 199=
5.
Acute Coma
- Hutchison. The Lancet, 11/16/1963; 1019-1022
- Mathieu. J. Hyper Med, 1987; 2(2): 63-67
- Shn-Rong. Procs. Of the 11th Int Congress on Hyper Med, 1995, Best P=
ub:
279-285
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- In Chronic Conditions:
- Increased Fibroblast Proliferation (Hehenberger - 1997)
- Increased Bone Mineral Density & Healing (Ueng - 1998)
- Angiogenesis (Marx - 1990, Manson - 1980)
- Epithelialization (Uhl - 1994, Manson - 1980)
- Ischemic Tissue Oxygen Capacitance (Siddiqui - 1997)
- Mobilization of Bone Marrow Stem Cells (Thom-2006)
- Immune system modulation (Chen-2003)
- Hehenberger, K. Wound Rep Regen, 1997; 5: 147-50
- Marx, RE. Am J Surg, 11/90; 160: 519-24
- Manson, PN. Surg Forum, 1980; 31: 564-66
- Uhl, E. Plast Reconstr Surg, 1994; 93: 835-41
- Siddiqui, A. Plast Reconstr Surg, 1997; 99: 148-55
- Ueng, SWN. J of Trauma; Injury , Infection & Critical Care, 1998;
44(4): 676-81
- Thom, SR. Am J Physiol Heart Circ Physiol, 2006;290:1378-86.
- Chen, SY. Clin Immunol,
2003;108(2):103-10.
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- Angiogenesis:
- Prototypic Model
- Marx External Beam
- Radionecrosis of the Mandible
- Marx, RE. Chapter 4, In Problem Wounds,
- The Role of Oxygen, eds. Davis & Hunt
- Elsevier Pub, NY, 1988
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- Mechanism of Action in Acute & Chronic Wounding:
- Signal Induction of DNA
- 1. Wu - PDGF Receptor
mRNA
‘d
- 2. Siddiqui - O=
2
Capacitance =
‘d
- 3. Bonomo - PDGF
Receptor
‘d
- 4. Reenstra - GF
Receptor
‘d
- 5. Buras - ICAM1 -
=
216;d
in acute I/RI
- 6. Sheikh - VEGF - acute w=
ound
- 7. Asano-bFGF, hep. =
GF
mRNA- ‘d in
acute wd.
- Wu, L. Surgery, 1995; 117: 570
- Siddiqui, A. Plast Reconstr Surg, 1997; 99:148-55
- Bonomo. SR. Undersea Hyper Med, 1998; 25(4): 211-16
- Reebstra, WR. Ann Emerg Med, 1999; 34(4): S2
- Buras, JA. Am J Physiol Cell Physiol, 2000; 278: C292-302
- Sheikh, AY. Arch Surg, 2000; 135: 1293-7
- Asano, T. Circ. J,
2007;71(3):405-411
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- 1. Air or Gas Embolism=
- 2. Carbon Monoxide Poi=
soning
with Smoke Inhalation
- 3. Clostridial Myonecr=
osis
(gas gangrene)
- 4. Crush Injury, Compa=
rtment
Syndrome, and other
- acu=
te
Traumatic Ischemias
- 5. Decompression Sickn=
ess
- 6. Enhancement of Heal=
ing in
Selected Problem
- Wou=
nds
(diabetic, arterial insufficiency, venous
- sta=
sis,
and other non-healing wounds.)
- UHMS HBOT Committee Report, 1999
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- 7. Exceptional Blood L=
oss
(Anemia)
- 8. Necrotizing Soft Ti=
ssue
Infections (Subcutaneous
- tis=
sue,
muscle, fascia)
- 9. Osteomyelites
(Refractory) or (acute) in
-
Compromised Hosts
- 10. Radiation Tissue Damage (Osetoradionecrosis and
-
Soft Tissue)
- 11. Skin Grafts and Flaps (Compromised)
- 12. Thermal Burns
- 13. Intracranial Absce=
ss
- UHMS HBOT Committee Report, 1999
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- What other conditions is HBOT effective for?
- How many acute neurological conditions are characterized by reperfus=
ion
injury?
- How many chronic conditions are a result of immune system dysfunctio=
n?
- How can HBOT impact the reperfusion injury of surgery?
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- 1. HBOT is a DRUG.
- 2. HBOT has drug-like effects on basic
-
pathophysiologic processes and their diseases.
- 3. One of the key mechanisms of action of HBOT:
- DNA
Signal Induction.
- 4. HBOT, through its actions on basic pathophysiologic processes, has
huge potential in applications to myriad neurological, medical, and
surgical conditions.=
li>
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- Textbook of Hyperbaric Medicine, 4th Edition, editor K.K. Jain, Hogr=
efe
& Huber Publishers, Toronto, 2004.
- HBOT Committee Report, Chairman J. J. Feldmeier, M.D., Undersea &
Hyperbaric Medicine Society, Kensington, MD, 2003.
- Hyperbaric Medicine Practice, 2nd Edition, editors: Kindwall, Whelan,
Best Publishing Co., Flagstaff, AZ, 1999
- The Oxygen Revolution, Paul G. Harch, M.D., Virginia McCullough,
Hatherleigh Press, NY, 2007.
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