Notes

Outline

Diabetes, PAD, and Wound Care: Protocols for Best Outcomes Peter Sheehan, M.D. Director,  Diabetes Center of Greater New York Cabrini Medical Center Senior Faculty Mount Sinai School of Medicine New York, NY psheehan@cabrininy.org

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Protocol for Treatment of Diabetic Foot Ulcers Harold Brem, MD Columbia University College of Physicians and Surgeons, New York, NY Peter Sheehan, MD Hospital for Joint Diseases, New York University School of Medicine New York, NY Andrew JM Boulton, MD University of Manchester Manchester, UK

American Diabetes Association Consensus Development Conference On Diabetic Foot Wound Care 7-8 April 1999 Boston, Massachusetts Diabetes Care 1999, 22: 1354-1360

Consensus Panel Peter Cavanagh, Chair John Buse Robert Frykberg Gary Gibbons Benjamin Lipsky Leonard Pogach Gayle Reiber Peter Sheehan

Treatment Protocol for Diabetic Foot Ulcers Evidence-based Sound surgical and/or biomechanical principles Clinical experience Importance of multidisciplinary team Expectation of healing ulcers in the absence of infection or ischemia

ADA Consensus Established Treatment Modalities Off-Loading Debridement Wound Dressings Treatment of Infection Vascular Reconstruction Amputation

UT Classification of Diabetic Foot Ulcers Neuropathic Infected Mild Moderate Severe Neuroischemic Infected and Ischemic Grade A Grade B Grade C Grade D

FDA Approved Treatments PDGF-BB (Regranex) Grafskin (Apligraf) Dermagraft

Platelet-Derived Growth Factor (PDGF)  Potent chemotactic factor for macrophages  PDGF-BB isoform the most efficient in stimulating fibroblasts and promote wound healing  Becaplermin (rhPDGF-BB) has similar properties to natural PDGF-BB and is currently commercially available

Becaplermin (rhPDGF-BB)

Graftskin

Histologic Comparison

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FREQUENCY OF COMPLETE WOUND CLOSURE BY 12 WEEKS

TIME TO COMPLETE WOUND CLOSURE BY 12 WEEKS

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Clinical Study Results

Wound Healing Trajectories

Proportion of Healed Wounds  With a Duration <6 Months

12-Week Healing Rates in Patients Above and Below the Median Change in Ulcer Area at 4 Weeks

Mean Change in Wound Area  at 4 Weeks with  95% Confidence Intervals

Proposed Foot Ulcer Algorithm

IDSA Classification Uninfected No purulence or inflammation Mild 2 or more manifestations of inflammation Superficial; < 2cm. of cellulitis Moderate > 2cm. of cellulitis Deep, involving abscess, gangrene, tendon, bone Severe Systemic toxicity or metabolic instability

Evaluation of Osteomyelitis “Probes to Bone” test in 75 patients:      Sensitivity    66%               Specificity    85% Positive Predictive Value    89%

MRI in Osteomyelitis Primary signs         Abnormal marrow signal intensity Secondary Signs         Cutaneous ulcer      Sinus tract      Cortical interruption

Magnetic Resonance Imaging

MRI and Osteomyelitis: Location, Location, Location Contrast-enhanced MRI in 161 feet Osteomyelitis most common in forefoot 5th metatarsal (24 feet), 1st metatarsal (21 feet) 1st distal phalanx (15 feet) Osteomyelitis was directly adjacent to foot ulcers in all cases but one Spread to adjacent bones in 26 (16%) Septic arthritis in 53 feet (33%)

Microbiology Bone vs. Soft Tissue Polymicrobial ( 70 – 85%) Aerobic gram-positive Staph Aureus ~ 45% Aerobic gram-negative Anaerobic “Contaminants” Staph Epi, Corynebacterium sp.

Relative Distribution of  Micro-Organisms in Diabetic Foot Ulcers Using Wagner Classification

IDSA Guidelines: Diabetic Foot Infections: Suggested empirical antibiotic regimens, based on clinical severity

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Treatment of Osteomyelitis Medical Prolonged antibiotics Conservative Surgery               Limited resection with antibiotics Aggressive Surgery Ablative resection; short-course tx

Conservative Treatment of Foot Infections   5-Year Retrospective Cohort Study, with Prospective Long-term Follow-up       Patients          Success Amputation 14 N/A Ulcer 26 21 (81) Osteomyelitis 50 35 (70) Gangrene 15 1  (7) Total 91                 57 (63)

Early Surgical Intervention                       Patients            Osteo            Amp No Surgery      87     21(24)       24(28) Surgery      77     44(57)       10(13)* Early                 46     23(50)        4(8.7)* Late                   31     21(68)             6(19)* *p<0.01 v. No Surg

Osteomyelitis Outcomes             Initial Procedure: 58 Patients

Osteomyelitis Outcomes             One-Year Results: 58 Patients

Treatment Strategies Early limited surgical intervention Empiric broad-spectrum antibiotics Procedure guided by soft-tissue and           functional considerations Post-operative adherence to principles of  advanced wound-care, off-loading

IDSA Guidelines Diabetic Foot Infections  Suggested route, setting, and duration of antibiotic therapy

IDSA Osteomyelitis Guidelines No residual infected tissue                         Parenteral or oral                                   2–5 Days (e.g., post-amputation) Residual infected soft tissue                       Parenteral or oral                                   2–4 Weeks (but not bone) Residual infected (but viable) bone          Initial parenteral, then                                                                       consider oral switch                               4–6 Weeks No surgery, or residual dead                    Initial parenteral, then  bone postoperatively                                 Consider oral switch                              >3 Months

The Consensus Development Conference on Peripheral Arterial Disease in People with Diabetes

Peripheral Arterial Disease Atherosclerotic occlusive disease of the lower extremities Risk factor for amputation Marker of cardiovascular and cerebrovascular disease No established guidelines for PAD and diabetes

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The “Neuroischemic Foot” Ulcers at margins Associated with trauma, or a “pivotal event” Conservative treatment principles: Debridement Off-loading pressure and shear Appropriate dressings Treatment of infection

Treatment: Revascularization for Critical Limb Ischemia Endovascular Interventions Focal, stenotic lesions Larger, proximal vessels Open Surgical Procedures All lesions, including occlusions of small vessels Greater durability and patency

Endovascular Reconstruction in Critical Limb Ischemia Improved devices, techniques, and experience have resulted in substantial improvements in outcomes Endovascular techniques include: PTA Atherectomy Stents Thrombolytic therapy

New Devices for Intervention in Infrainguinal PAD

Endovascular Interventions Aortoiliac disease Angioplasty and stenting preferred Superficial femoral artery Selected in short-segment stenoses Tibial disease Poor long-term patency May serve as a “buy time” intervention

Atherectomy Devices

TASC Recommendations

Vascular Bypass in Diabetes 75%  are below the knee Preferred conduit: greater saphenous vein Anterior tibial/ dorsalis pedis artery the preferred target vessel Excellent patency and limb salvage outcomes

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Tibial Bypass to Foot

Femoropopliteal Disease: 5-Year Graft Patency Rates Reversed GSV Above knee popliteal 65%–90% Below knee popliteal 60%–80% Tibial 60%–70% In situ vein Below knee popliteal 60%–80% Tibial 50%–75%

Vascular Bypass in Diabetes Decreased morbidty and mortality Patency rates similar to non-diabetics Limb salvage rate greater than patency Pre-op cardiovascular assessment of risk and use of beta-blocker Combined risk of 2 procedures usually exceeds risk of leg bypass

Indications for Amputation Uncontrolled, overwhelming infection Rest pain not manageable with analgesics Extensive necrosis of the foot that prohibits adequate function

Limb-Salvage Gangrene or tissue necrosis Fundamental treatments include: Broad-spectrum antibiotics Debridement of all necrotic tissue Revascularization Staged surgical closure Adjunctive therapies, e.g.        subatmospheric pressure device

V.A.C.      Therapy System

How does the V.A.C. work? Helps promote granulation tissue formation by aiding in the wound healing process Applies localized negative pressure to help uniformly draw wounds closed Helps remove interstitial fluid and infectious material Provides a closed, moist wound healing environment Helps promote flap and graft survival

Limb Salvage: The Georgetown Approach Debride all non-viable tissue Leave all that is alive Allow exposed structures, i.e. tendon, capsule, bone Patience and vigilance, often with VAC Serial debridement Staged surgical closure

“Don’t just do something… stand there !  “ Lewis Carrol

Limb Salvage vs. Amputation Limb salvage often possible using staged approach Amputation in selected patients when a long treatment course is anticipated, risk of failure Decision considerations: Quality of life Rehabilitation

After Discharge: Outpatient Management Select the definitive antibiotic regimen Based on culture, investigations and clinical response Re-evaluate the wound Infection, healing and need for surgery Review the off-loading and wound care regimens Effectiveness and compliance Evaluate glycemic control

Therapeutic Angiogenesis Definitions

Therapeutic Angiogenesis

Molecular control of blood vessel formation

Gene Therapy for PAD Vascular Endothelial Growth Factor (VEGF) Phase 2: claudication Hepatocyte Growth Factor (HGF, Scatter       Factor) Phase 1: critical limb ischemia Hypoxia Inducible Factor (HIF-1α) Phase 1: critical limb ischemia

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Ischemia - HIF 1a for PAD Ad2/ HIF-1a/VP16 Syringe delivery 20 intramuscular injections Site specific gene delivery

The Master Switch for Hypoxic Stress

The WALK Study

Final Thoughts Importance of interdisciplinary teams Endocrinologist Radiologist Orthopedist Vascular Surgeon Podiatrist Plastic Surgeon Cardiologist Nephrologist Vascular Technologist Pedorthist “The best should not fight with the good.” Voltaire