Hyperbaric Oxygen Therapy
for Radiation Injuries
HBO – What is it?
• 100% oxygen is administered to a patient
at higher then normal atmospheric
pressue.
• 2 -2.5 ATA is typical
• Treatments average approximately 2
hours.
Domicilium
1662
Henshaw, British clergyman built a sealed chamber called a Domicilium. (O2 discovered 1775).
Fontaine’s mobile operating
room 1879
French surgeon named J.A. Fontaine built a pressurized mobile operating room.
Cunningham’s chamber in 1921
Orville J. Cunningham, a professor at the University of Kansas built a chamber that was 10 feet in diameter and 88 feet in length
Steel Ball Hospital 1928
• .
However, one patient that Cunningham treated, Mr Timkin of the Timkin Rollerbearing Company, felt that the time he
spent in Cunningham's chamber cured his uremia. In 1928 as a show of gratitude, Timkin built a steel sphere, which
was 6 stories tall, and 64 feet in diameter, the largest hyperbaric chamber ever built. Cunningham used this hospital,
located in Cleveland, to treat patients with a number of ailments. It was well appointed, with dining rooms, private
patient rooms, plush carpets, and even a smoking room on the top floor! Without any scientific rationale for his work,
he was forced to close down by the AMA and the Cleveland Medical Society in 1930, and the steel ball hospital was
cut up for scrap during World War II. This essentially ended the era of compressed-air hyperbaric therapy
Today
Today
Today
UHMS INDICATIONS
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1. Air or Gas Embolism.
2. Carbon Monoxide Poisoning/Cyanide Poisoning.
3. Clostridial Myositis and Myonecrosis (Gas Gangrene).
4. Crush Injury, Compartment Syndrome and other Acute Traumatic
Ischemia’s.
5. Decompression Sickness.
6. Arterial Insufficiencies – Enhancement of Healing in Selected Problem
Wounds and Central Retinal Artery Occlusion.
7. Severe Anemia.
8. Intracranial Abscess.
9. Necrotizing Soft Tissue Infections.
10. Osteomyelitis (Refractory).
11. Delayed Radiation Injury (Soft Tissue and Bony Necrosis).
12. Compromised Grafts and Flaps.
13. Acute Thermal Burn Injury.
14. Idiopathic Sudden Sensorineural Hearing Loss.
Definition: Radiation Tissue Injuries
• Radiation injuries can be divided into two
categories on a time basis:
– Acute injuries are those that present shortly
after irradiation—generally within weeks1
– Osteoradionecrosis and soft tissue
radionecrosis are those conditions that
present several months or even years after
irradiation.1,2
1Feldmeier JJ. Undersea Hyperbaric Med 2004;31:133-45.
2Pasquier D, Hoelscher T, Schmutz J, et al. Radiother Oncol 2004;72:1-13.
Rads & Grays
1 rad = 1 centi Gray (cGy)
The effect causes damage to the
DNA, lipids, and proteins
Causes cell dysfunction and death
Incidence of ORN and STRN
• The incidence of osteoradionecrosis (ORN) and soft tissue
radionecrosis (STRN) is not known with any certainty
• In the U.S., approximately 1.5 million new cancer cases are
diagnosed every year1
• Data suggest that 750,000 patients with cancer receive
radiotherapy every year, and if two-thirds are long-term survivors
and 10% of these patients experience ORN or STRN in their
lifetime,2,3 this would be about 50,000 individuals per year
(0.017% of U.S. population)
• Another way of looking at the statistics: More than 200,000
patients receive abdominal or pelvic radiation therapy each year,
and there are approximately 1.7 million survivors of this
treatment who have or have had intestinal dysfunction as a
result of STRN.4
1Jemal A, Siegel R, Ward E, et al. CA Cancer J Clin 2009;59:225-49.
2Feldmeier JJ, Hampson NB. Undersea Hyperb Med 2002;29:4-30.
3Rubin P, Casarrett GW. Clinical Radiation Pathology. Vol 1. Philadelphia: WB Saunders, 1968:58-61.
4Hauer-Jensen M, Wang J, Boerma M, et al. Curr Opin Support Palliat Care 2007;1:23-9.
ORN/STRN Tissue Injury Sites
Where can ORN or STRN occur?
Any tissue that has been irradiated!
• Jaw (osteoradionecrosis; inadequate bone repair)1
• Neck area (e.g., chondroradionecrosis of the larynx)2
• Chest wall radionecrosis (result of treatment for breast, lung, or
esophageal cancers)1
• Hemorrhagic radiation-induced cystitis1
• Chronic radiation-induced proctitis/enteritis1
• Spinal cord, brain, optic nerve, brachial plexus (myelitis or radiationinduced necrosis/injury).1
1Feldmeier JJ. Undersea Hyperbaric Med 2004;31:133-45.
2Hunter SE, Scher RL. Curr Opin Otolaryngol Head Neck Surg 2003;11:103-6.
Risk Factors for ORN/STRN
Radiation
dose1
Trauma or
surgery in
irradiated area1
Location and
size of original
tumor1
Risk Factors
Patient age2
Infection in
irradiated area1
Prior ischemia
(local hypoxia)3
Immunodeficiency1
• Diabetes
• Steroids
• Immune
suppression
1Chrcanovic BR, Reher P, Sousa AA, et al. Oral Maxillofac Surg 2010;14:3-16.
2Lye KW, Wee J, Gao F, et al. Int J Oral Maxillofac Surg 2007 36:315-20.
3Hoffman KE, Horowitz NS, Russell AH. Gynecol Oncol 2007;106:262-4.
Tissues require oxygen to survive
We can measure tissue oxygenation levels with a TcPo2
A minimum of 20 mmhg partial pressure of oxygen is
required for cells that aide in wound healing (fibroblast
proliferation and collagen production) to function
Levels are far below this 20 mmhg in tissue that has received
radiation
HBO stimulates collagen
synthesis, vascular
networking, metabolism of
bone, and may increase
stem cells.
1.0 ATA
Air
In normal tissue in
normobaric (room air or 1
ata) conditions, the tension
of oxygen in the tissues is
only 30 microns away from
the
damaged
capillary wall
5 10 15 20 35 40 55
HBO - 2.5 ATA
In hyperbaric conditions,
the oxygen tension in the
tissues can be up to 280
microns away allowing
for a rich collagen matrix
to form
50 50 90 120-350 350
Capillary buds
invade and form
a new vascular
network
(angiogenesis)-Oxygen tension
returns to
normal. Wounds
can HEAL!
Plateau
Phase
Typically after 20
treatments, the new
vascular network is
laid.
280 300 320 350
Increased
oxygen tension
allows cells to
function
normally and
aide in healing
General Causes of ORN/STRN
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ORN or STRN actually begins when radiation is first given1
• Levels of pro-inflammatory cytokines rise (e.g., IL-1, IL-6, TNF-alpha)
• In some cases, the levels of cytokines associated with inflammatory actions
stay elevated leading to further injury
• The levels of these same cytokines may subside but the cytokines may be
affected later by another surgery, trauma, or infection years later.
Radiation causes the lining of small blood vessels to become inflamed and then
occluded, leading to tissue ischemia2
Some researchers postulate increased thrombin levels and vascular
permeability with subsequent fibrin and collagen deposition between cells.
Fibrosis, dysfunction, and even obliteration of the local vasculature (especially
capillaries) then follow.3
1Brush J, Lipnick SL, Phillips T, et al. Semin Radiat Oncol 2007;17:121-30.
2American College of Hyperbaric Medicine. Osteoradionecrosis. 2010.
3Wang J, Boerma M, Fu Q, et al. World J Gastroenterol 2007;13:3047-55.
Tumor - treated as a mass of cells
A boost dose of radiation is given to the center
of this mass of cells
The further away from the center of that mass, the
less the dose of radiation
Additional injury can occur to tissues around the
mass of cells (called a “diffusion injury”)
Radiation effect on tissues
(highest effect to lowest)
Tumor
Endothelium
Fibroblasts
Muscle
Nerve
Continues to cause damage to tissues ev
after therapy stops
Basically obliterates the vessels
Destroys the blood supply to the
tissues
Leaves tissue hypoxic and very fibrotic
(hard, woody tissue)
Early (acute) Effects to the skin
Redness (erythema)
Changes in the pigment of the skin
Hair loss
Skin erosion
Supportive care
Antibiotics if skin tissues
become infected (cellulitis)
Delayed Effects of Radiation
Typically seen after 6 months and up to years later
Endarteritis (inflammation of the lining of the
artery is what causes the problem)
It is difficult to provide adequate nutrients &
oxygen to tissues without a good blood supply.
This leads to delayed healing.
There is no satisfactory treatment of radiation
necrosis using conventional therapies. HBO is the
only intervention that has shown to increase the
number of blood vessels in irradiated tissue.
Bone is 1.8 x more denes than soft tissues so
it absorbs more of the radiation energy
Radiation affects both the vascular & cellular
components of bone.
Mandible (jaw) is very susceptible
– greater bone density & lower vascularity
Blood flow in bone that has NOT received radiation
Granstrom G 1993 XIXth Annual EUBS Meeting
ml/mg x 100g tissue
14
12
10
8
6
4
2
0
Frontal
Zygoma
Maxilla
Mandible
Blood flow in bone that HAS received radiation
Granstrom G 1993 XIXth Annual EUBS Meeting
ml/mg x 100g tissue
14
12
10
8
6
4
2
0
Frontal
Zygoma
Maxilla
Mandible
Clinical Damage
Clinical
Threshold
Acute
Surgical
Trauma
Mechanical
Trauma
Subclinical
Damage
Years
Rubin P, Casarett GW 1968
Nutrition
Infection
OSTEORADIONECROSIS of the mandible
(ORN)
• Incidence 0% below 6,000 cGy,1.8% 6,000-7,000 cGy, and 9%
>7,000 cGy.
• Pathophysiology – hypoxia, hypovascularity, and hypocellularity.
• Marx Protocol – prophylaxis, stages 1-111R all at 2.5 ATA for 90
minutes.
• Evidence – 1975-2001(14 case series using HBO and surgery) –
13/14 found benefit and 86% patients improved.
• Cost saving in 2006 – $168,000 without HBO and $53,000 with
HBO.
•
Feldmeier JJ, Hampson NB: Undersea Hyperbaric Med 2002, Marx RE, 1999 www.westegg.com/inflation.
MARX PROTOCOL
2.
Osteoradionecrosis is defined as the presence of exposed bone without healing.
Marx creating staging according to wound healing treatment and hyperbaric oxygen
response.
Stage I (A): Chronically exposed bone or rapidly progressive ORN without any
serious manifestations found in stage III. 30 HBO presurgical treatments
followed by minor bony debridement followed by 10 HBO postsurgical
treatments.
1Marx RE. J Oral Maxillofac Surg .
1983;41:352-7.
2American College of Hyperbaric Medicine. Osteoradionecrosis. 2010
MARX PROTOCOL
2.
Stage II – If patients are not progressing appropriately at 30 HBO at Stage I or if they are
needing more major debridement, they are advanced to this stage and receive a more
radical surgical debridement in the OR followed by 10 post-surgical HBO treatments.
Surgery must maintain mandibular continuity. If mandibular resection is required they are
advanced to Stage III.
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1Marx RE. J Oral Maxillofac Surg .
1983;41:352-7.
2American College of Hyperbaric Medicine. Osteoradionecrosis. 2010
MARX PROTOCOL
2.
In addition to those failing treatment in Stage I and II, grave prognostic signs such as
pathologic fracture, orocutaneous fistulae or lytic involvement extending to the inferior
mandibular border. Mandibular resection is part of the treatment plan. Patients receive
30 HBO pre-surgical treatments and 10 HBO post-surgical treatments.
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1Marx RE. J Oral Maxillofac Surg .
1983;41:352-7.
2American College of Hyperbaric Medicine. Osteoradionecrosis. 2010
Timing of preoperative HBO therapy is not critical
“Delays of up to one year between HBO & surgery
have not compromised results”
- Marx 1991
National Cancer Institute Monographs 1990: No 9
"Osteoradionecrosis is best
managed
with hyperbaric oxygen alone, or
in
conjunction with surgery"
…in high-risk patients, pre-extraction
hyperbaric oxygen should be considered
HBO and ORN
• There have been 22 studies
published that show hyperbarics
is useful either alone or as an
adjunctive therapy
• Improvement has been show in
78% of these cases Hyperbarics
has also shown to be useful in
preventing or reducing
complications if done prior to
surgical intervention
Conventional Treatment of ORN
• Nutritional support is essential as many patients become
nutritionally deficient1
• Antibiotics where infection is suspected1
• Debridement to remove sequestra where identified2
• Microvascular free tissue transfer for stage III patients and jaw
resection as necessary.2
• There have been reports of treating stage I patients with
pentoxifylline (to improve blood flow), bisphosphonates, and vitamin
E, but success to date must be regarded as preliminary.3
1Blanchaert Jr RH, Harris CM. eMedicine 2010.
1Hao SP, Chen HC, Wei FC, et al. Laryngoscope 1999;109:1324-8.
3Delanian S, Depondt J, Lefaix JL. Head Neck 2005;27:114-23.
Complications of Surgery in Irradiated Tissue
DEHISCENCE
Control
HBO
38 (48%)
4 (11%)
INFECTION
Control
HBO
Total
19 (24%)
5 ( 6%)
DELAYED HEALING
Control
HBO
44 (55%)
9 (11%)
Marx RE 1993
Soft Tissue Radionecrosis
Radiation Cystitis
Radiation Proctitis
Laryngeal Radionecrosis
Chest Wall Radionecrosis
Abdominal and Pelvic
Radionecrosis
Radiation injuries of the extremities
Neurologic Injuries Secondary to
Radiation
Indication of HBO
Delayed Radiation Injuries
RADIATION CYSTITIS
• Symptoms include - hematuria, nocturia,
frequency and or urgency.
• 18/20 published reports showed significant
improvement or resolution in 76%.
Undersea and Hyperbaric Board Review course for physicians – Penn Medicine Aug 2010
.
Indication of HBO
Delayed Radiation Injuries
RADIATION PROCTITIS
• Symptoms include – rectal bleeding/pain, diarrhea, and
tenesmus.
• Combined results from trials including a total of 199
cases – complete resolution in 41% and 86% had at
least partial response.
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Clark RE et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with longterm follow-up. Int. Journal Radiation Oncology /Biology Phys 2008.
•
Undersea and Hyperbaric Board Review course for Physicians. Penn Medicine. August 2010 .
Laryngeal Necrosis
• Uncommon complication of radiation therapy for
patients with head and neck cancer – usually
<1%.
• Often present with persistent edema, fetid
breath, and or visible necrosis.
• Chandler grade 1-4 (1 and 2 usually resolve).
• 5 published reports – out of 43 patients, only 6
failed and required a laryngectomy, the other 37
maintained their voice box and good voice
quality with HBO.
Hyperbaric Oxygen Therapy Indications. 12th edition.
RADIATION INJURIES
Does HBO cause cancer or make
cancer worse?
Extensive review of clinical and
animal studies showed no
enhancement of cancer growth.
Hyperbaric Oxygen Therapy Indications 12th edition.
HBO for the late effects of radiation is
supported by Prospective Randomized Trials
Deemed to be a “Standard of Care” by the
National Cancer Institute
The weight of current evidence favors use of
HBO
Demonstrated “financial” effectiveness
No proven alternative therapies
REFERENCES
• G, LB. HYPERBARIC OXYGEN
THERAPY INDICATIONS. 12TH EDITION.
• KINDWALL, EP., WHELAN, HT.
HYPERBARIC MEDICINE PRACTICE.
3RD EDITION.
• HEALOGICS – WOUND CARE
CENTERS.