Limb Salvage: The Wound
Center Approach
Why Not?
“In the 39th year of his reign, King Asa was
afflicted with a disease in his feet. Though the
disease was severe, even in his illness, he did not
seek help from the Lord, but only from the
physicians. Then in the 41st year of his reign Asa
died and rested with his fathers.”
II Chronicles 16:12-14 Compliments of Dr. Wayne Caputo, Belleville, NJ
“He is a good surgeon who can
amputate a limb, but he is a better
surgeon who can save a limb.”
Sir Astley Cooper,
British Surgeon
Diabetics and Amputation
“Avoiding amputation is probably the
most important means of reducing
costs and achieving cost effectiveness
in the management of diabetic foot
ulcers.”
Drug Ther Perspect 1998;11(3):13-16
Diabetics and Amputation
Every 30 seconds, somewhere in the
world someone is having a major
amputation for diabetic foot problems!!!!
Every 10 minutes, someone in the
United States is having a major
amputation for diabetic foot problems.
Quote Dr. Andrew Bolton, SAWC, 2011, Dallas, Texas
Arterial Insufficiency and Chronic
Wounds
• ~20% venous ulcer patients have arterial
insufficiency(1)
• 40-55% of diabetic ulcers are ischemic(2)
• In Africa – only 36% of patients with ulcers
have peripheral vascular disease (PVD)(3)
1) Falanga V. Venous Ulceration. J Dermatol Surg Oncol. 1993;19(8):764-771
2) Kerdal FA. Inflammatory Ulcers. J Dermatol Surg Oncol. 1993;19:772-778
3) Ogbera OA, Osa E, et al. Common Clinical Features of Diabetic Foot Ulcers:
Prespectives from a Developing Nation. Int J Low Extrem Wounds 2008;7:93-98
Healing in Patients with Severe
Unreconstructable Vascular Disease
• ABI < .50 and toe pressure < 30
• Could not be revascularized
• Complete wound closure
– 37% at 6 months
– 51% at 12 months
– 66% at 16 months
Major amputation – 15% at 12 months
Wounds 2003;15(12):390-394
Ambulation following
Amputation Of patients ambulatory prior to their amputation:
• BKA
16% ambulated independently
19% required walker
65% unable to walk
• AKA
11% ambulated independently
9% required walker
80% unable to walk Cruz CP, Eidt JF, Capps C, Kirtley L, Moursi MM. Major lower extermity amputations at a
Veterans Affairs hospital. Am Jour Surg 2003;186:449-454
Prepare the Wound for Healing
Wound bed preparation is necessary
to correct the cellular imbalances
present in chronic wounds allowing
the wound to heal or be receptive to
our therapy.
Optimal Wound Bed Preparation
• Maintenance of optimal moisture balance
• Complete debridement of devitalized and poorly functioning tissue
• Restoration of bacterial balance
• Optimize cellular function
• Treatment of edema / lymphedema
Schultz GS, Falanga V, et. al., Wound Rep Reg 2003;11(Supp):1-28
Wound Environment
• Must be kept moist!
• Air-exposed wounds have increased tissue
necrosis and cell death
• Epithelialization is impaired if eschar or
scab remains in place
WOUND DEBRIDEMENT
• Surgically (Sharply)
• Mechanically
• Autolytically
• Enzymatically
• Biosurgically (Maggots)
Effect of Debridement of Chronic
Wounds
• Removes necrotic and ischemic tissues
• Removes infected tissues
• Exposes receptors so that growth factors can get to them
• Removes senescent and non-functioning cells
• Stimulates healing
Debridement
Diabetic Gangrene of Toes with
Abscess of Foot
Diabetic Gangrene of Toes and
Abscess of Foot
Diabetic Foot Ulcer and Abscess
CHRONIC WOUNDS AND
BACTERIA
“All wounds contain bacteria yet few become infected.”
Nancy Stotts, RN, Symposium on Advances in
Skin and Wound Care, 2000
CHRONC WOUNDS AND
BACTERIA
• Contamination – organisms are present on
the wound surface
• Colonization – organisms are present and
multiply on the wound surface
• Infection – organisms invade the tissue and
there is a tissue response
EFFECT OF EDEMA AND
CHRONIC WOUND FLUID 1. Normal anti-Streptococcal properties of skin are
inactivated by edema fluid.
2. Chronic wound fluid inhibits mitogenic activity and DNA synthesis.
3. Cytokine environment in chronic wound fluid is more proinflammatory.
4. Protease activity is higher in chronic wound fluid.
5. Growth factors levels are decreased in chronic wound fluid.
Compression Therapy and
Circulation
ABI Bandage Sub-bandage
pressure (mm Hg)
> 0.8 4-layer 35-40
0.7 2-3-layer 17-25
0.6 2-3-layer 17-25
<0.5 Only with medical
supervision ---
Moffatt C. www.worldwidewounds.com (accessed 1/5/06)
Control Leg Treated Leg
Before
Bandage
With
Bandage
52 47
49 74
ml/min
ml/min
Arterial Flow Pulses
Below Knee Blood Flow via Nuclear Magnetic Resonance
Increased pulses
likely augment
Lymph/venous
transport Dr. HN Mayrovitz, Univ of Miami
Proteases and Compression Therapy
Marston WA, Beider S, Davies S, Berndt DF. Protease and Cytokine Levels in Non-Healing Venous Leg
Ulcers Before and After Compression Therapy. Presented at Symposium on Advanced Wound Care/Wound
Healing Society Meeting, San Diego, CA. April 25, 2008
Inflammatory Cytokines and
Compression Therapy
Marston WA, Beider S, Davies S, Berndt DF. Protease and Cytokine Levels in Non-Healing
Venous Leg Ulcers Before and After Compression Therapy. Presented at Symposium on
Advanced Wound Care/Wound Healing Society Meeting, San Diego, CA. April 25, 2008
Need to Optimize the Wound
Environment
• Compression therapy
• Can be done with doxycycline*
• Can be done with protease modulating
matrix products, Promogran and Prisma
• Can be done with protease reducing agent,
Tegaderm Matrix
*Chin GA, Schultz GS. Wounds 2003;15(10):315-323
Wound Bed Preparation with Prisma:
Apligraf and Diabetic Foot Ulcers
66%
68%
70%
72%
74%
76%
78%
80%
No Prisma
Prisma
(Unpublished data: Institute for Advanced Wound Care, 10/05 – 3/06)
Diabetic Foot Ulcers Healed 12 Weeks Following Apligraf
OK!!!
Now What????
Falanga V, Moneta G. Vasc Surg. 1999; 33:197-210.
Falanga V, Sabolinski ML. Wounds. 2000; 12:42A-46A.
Sheehan P, et al. Diabetes Care. 2003;26(6):1879-1882.
Use of Advanced Technology in
Wound Healing
• Healing rates at 4 weeks predict
overall healing rates
• Initial healing rates of >0.1
cm/wk correlate with healing
• Rapid identification of patients
unlikely to respond to
conventional care will allow for
earlier interventions with
advanced therapies
0.0
2.0
4.0
6.0
8.0
10.0
12.0
4/2
4/8
4/1
4
4/2
0
4/2
6
5/2
5/8
Graph wound
area, length,
width, depth
DERMAGRAFT
DERMAGRAFT
APLIGRAF
APLIGRAF®
(Graftskin) Human Skin
Photomicrographs of hematoxylin-eosine-stained cross-sections of APLIGRAF® (left) and human skin (right) 250.
HISTOLOGIC COMPARISON
Stem Cells
• Master cells of the body
• Can divide an infinite number of times
Human Skin and Related Structures
Stem Cells in Apligraf
• Epidermal stem cells present in
Apligraf after manufacturing
• Epidermal stem cells detected in
wounds 8 weeks post application of
Apligraf
Carlson M, Faria K, Leman J, et al. Epidermal Stem Cells Are Preserved During
Commercial Scale Manufacturing of a Bilayered, Living Skin Substitute (Apligraf)
Utilized for Chronic Wound Repair, Wound Rep Reg 2009:17(2):A27. Data presented
at Wound Healing Society Meeting, Dallas, Texas, 2009
What Evidence Is There That
These Products Work?
FDA Product Indications
Apligraf Dermagraft Regranex Oasis Integra
DFU Yes Yes Yes
VLU Yes
Other
WOUND BED PREPARATION
Wound Bed Preparation with
Apligraf
1 month of hydrogen peroxide,
Bactroban, and whirlpool
71 y/o man who
dropped a tree
limb on his leg 1
month prior
Apligraf applied 4 weeks prior
to stimulate wound bed
Wound Bed Preparation with
Apligraf
Wound
Healed 10
Weeks Post
Application
of Apligraf
DIABETIC FOOT ULCER
Pre Apligraf
DIABETIC FOOT ULCER POST APLIGRAF
First Dressing Change 28 days post Apligraf
at 5 days post Apligraf
DIABETIC FOOT ULCER
3 MONTHS POST APLIGRAF
DIABETIC HEEL ULCER
Heel ulcer before Heel after debridement
debridement
DIABETIC HEEL ULCER
APPLICATION OF APLIGRAF
DIABETIC HEEL ULCER
16 WEEKS POST APLIGRAF
IV Infiltration Injury of Foot
IV Infiltration Injury of Foot
6 Weeks Post Apligraf 16 Weeks Post Apligraf
IV Infiltration Injury of Foot
Wound Healed – 20 weeks Post Application of Apligrf
Venous Ulcer
Venous Ulcer
8 weeks post application Healed at 33 weeks
Venous Ulcer
99 year old lady
with ulcer for 8
months. Started
as a scratch on
ankle. ABI-.45
Informed that BK
amputation was
the only therapy.
Venous Ulcer
Wound healed after
47 weeks.
Required 2
applications of
Apligraf. Patient is
now 100 years old
and happy to have
a leg with no ulcer!
“REAL WORLD” USES of
Bilayered Tissue Engineered Skin
for Limb Salvage
Wound of Ischemic Foot
77 y/o gentleman with
severe limiting
claudication of left foot.
No history of diabetes.
Had attempted dorsalis
pedis bypass graft 5 mo.
prior to being seen. Distal
surgical incision broke
down. Was referred for
amputation.
Wound of Ischemic Foot
After treating infection
and debriding
8 weeks after
application of Apligraf
Wound of Ischemic Foot
Wound healed
32 weeks after
1st application
of Apligraf.
2 applications
required
Pressure Ulcer of Ankle Due to Cast
88 y/o lady with fracture of ankle treated with cast
Pressure Ulcer of Ankle
Open Joint
8 Weeks Post Debridement
Apligraf applied
Pressure Ulcer of Ankle
2 Weeks Post Application of Apligraf
Pressure Ulcer of Ankle
9 Months Post First Application
7 Months Post Second Application
Limb Salvage:
The Wound Center Perspective
Comments we DO NOT
want to hear
I normally wouldn’t
recommend an
amputation but that
wound will never heal
anyway.
I normally wouldn’t
recommend an
amputation but you are
going to lose your leg
someday anyway so we
might as well do it now.
I normally wouldn’t
recommend an
amputation but that is all
I know to do for your
wound.
I normally wouldn’t
recommend an
amputation but I don’t
want to mess with your
problem any more.
“It’s what you learn
after you know it all
that counts.”
John Wooden,
Legendary basketball coach at UCLA
“It’s kind of fun to do
the impossible.”
Walt Disney