Hyperbaric Oxygen in the Treatment of Diabetic Foot Ulcers…
The pressure is on to prove that it works.
Gerry Morrison, M.D.
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 patient’s vascularization adequate – Patient has heard about HYPERBARIC OXYGEN THERAPY
Would YOU refer this patient for hyperbaric oxygen therapy at Duke University Medical Center?
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
The Early Experiments:
• Alexander the Great in 320 B.C. • Aristotle 300 B.C. • Henshaw, the “Father of • Built the DOMICILIUM…1662
“
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
Paul Bert: The Father of Pressure Physiology ~ Oxygen…………
• 1878 observed convulsions and death in animals at a constant 3-4 atmospheres of pressure. • Because of improvements in lung diseases, etc., experiments continued.
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
The Cunningham Chamber…
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…
Finally, some success!
• Behnke and Shaw, 1937- show improvements in animals revived with from decompression sickness… • L. Hendriks tested Lambertsen’s 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.
Modern day history of Hyperbaric Medicine - …………
• Pioneered the application of medical problems. • Performs first surgery with
• 1960 discovered that Hgb. wasn’t necessary for O2 transport. • Supersaturation of oxygen is theoretical basis for using to treat lower extremity wounds.
to many
Boerema’s 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
Gabb: Calls ……. “A Therapy in search of Diseases”
•Universal uses (primarily Eastern Europe)
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, multiinfarct dementia, infant cardiac surgery, chronic ulcers, peripheral vascular disease, diabetic neuropathy, acute endocarditis, hearing loss, cortical blindness, cellulitis, infected pacemaker, Hurler’s syndrome, post-cardiac arrest, scleroderma, mycobacterium TB, abscesses, asthma, pneumomediastinum, hanging, thrombophlebitis, Lyell’s syndrome, CO poisoning, gas gangrene, osteomyelitis, Crohn’s DZ, Cyanide poisoning, crush injury with ischemia, Alzheimers…
Thermal burns, head and spinal injury, bone grafts, frost bite, CVA’s, 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, postepileptic 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…..
AGING….
Don’t you think that it works!!!????!!
Speaking of famous people…
How is
administered???
•Two types of hyperbaric chambers: Monoplace vs. multiplace
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.
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
The complications:
Boyles Law: a volume of gas in a closed space will decrease as pressure increases P1V1=P2V2
- 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.
Sheridan etal, 1999
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
Modern Day uses of
• Category 1: Non-disputed (and reimbursable) uses
– Treatment of choice in decompression sickness
• Boyles Law: P1V1=P2V2
– 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
Category 2 uses: CONTROVERSIAL!!!
(Not proven and NOT reimbursable)
• CO poisoning, gas gangrene, burns, cancer and
• DIABETIC ULCERS
What’s 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.
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!
Doctor, etal: J Postgrad Med 1992 First 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.
Doctor, etal.
•All wounds were cultured before and after each treatment. •Need for amputation was assessed •Length of Hospital Stay was assessed
The results…
•In HBO group, 2/15 amputations vs. 7/15 in the non HBO group (p<0.05)
•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
The Medical Community:
• American Diabetes Association disregarded study calling it “Poorly Done”
• International Hyperbaric Society called for more RCTs to be performed.
The landmark study to date:
Faglia, 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
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.
Exclusion Criteria:
• No previous HBO therapy • No previous major amputations
Methods:
•35 pts randomized to HBO and 35 to control groups 35 HBO
1 CVA, death 1 quits, fearful 33 patients treated, But study reports 35
35 patients not Treated but study Reports 33
35
control
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
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).
Methods Con’t
• 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
Methods con’t
• PTA and BPG were performed on patients with severe ischemic disease.
– no significant differences between treatment and control groups.
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
What were the results???
“I’m not like other guys…” MJ
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! ! !
Transcutaneous oxygen levels (mmHg)
• TcPO2 levels = significant increase in HBO group p=0.0002 • SD=±11.8 in HBO group and ± 5.4 in control group - small amount of overlap.
40 35 30 25 20 15 10 5 0 HBO grp Control Admit D/C Variance
Amputation rates:
HBO N=
Major amp
Wagner II
Control 33 11/33
0
P-value 0.016
-
35 3/35
0
Wagner III Wagner IV
1 2
0 11
0.33 0.002 0.61
Minor amp
21*
11
12*
10
No amp
*=# of amputations, not people
Risk vs. benefit…
• Benefit… • No major amputation
rr= 0.26 rrr=74 %
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= ? ari=5.8 % 95% CI (0.2-11 %)
NNTH= 17 95% CI (9-500)
What can we conclude?
ABC, easy as 123….or is it????
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 limbsalvaging, 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!
So, why the controversy??
• Consensus Development Conference on Diabetic Foot Wound Care Diabetes Care 22:1354-1360, 1999.
– “There are no randomized controlled trials supporting the use of hyperbaric oxygen therapy to treat neuropathic foot wounds.”
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.
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.
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 • Fife’s current study looks at outcome, costeffectiveness and risks for more than 1000 pts • Study to be completed later this year, anxiously awaited by DCC.
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.
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
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
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.
Acknowledgements:
• Dr. David Miller • Jessica Morrison • David Suh, M.D. • Amanda Ebright, M.D. • Dr Carolyn Fife, Hermann Hospital
Good luck to everyone…
Remember to have some fun along the way…