+ DFUs Can Be Effectively Treated Without HBO Alexander Reyzelman - - PowerPoint PPT Presentation

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DFUs Can Be Effectively Treated Without HBO

Alexander Reyzelman DPM, FACFAS Co- Director, UCSF Center for Limb Preservation

+No Disclosures +

• 1. Levin ME. J Wound Ostomy Continence Nurs. 1998;25:129-146. 2. Mayfield JA et al. Diabetes Care.

1998;21:2161-2177. 3. Boulton AJM. Diabet Med. 1996;13(suppl 1):S12-S16.

PATHOPHYSIOLOGY OF DIABETIC FOOT ULCERS

Combination of peripheral neuropathy (PN), and

biomechanical abnormalities along with minor trauma are major contributory factors in the pathogenesis of foot ulceration1-3

Most important complication is loss of protective

sensation (LOPS) with PN1

PN is associated with 8- to 18-fold higher risk of

ulceration, 2- to 15-fold higher risk of amputation2

Biomechanical abnormalities that can lead to DFUs

include foot deformities and limited joint mobility2

+

• 1. Mayfield JA. Diabetes Care. 1998;21:2161-2177. 2. Boulton AJM. Diabet Med. 1996;13(suppl 1):S12-S16. 3. Gavin LA.
• Endocrinologist. 1993;3:191-203. 4. Frykberg RG. Diabetes Care. 1998;21:1714-1719.

Scans courtesy of John S. Steinberg, DPM University of Texas Health Science Center at San Antonio, San Antonio, Tex.

ELEVATED PLANTAR PRESSURES IN COMBINATION WITH OTHER FACTORS CAUSE ULCERATION

Role of ongoing mechanical

trauma1,2

Lack of innate sensory

feedback

High foot pad pressures3,4 Neuropathy-induced muscle

imbalance3

Biomechanical dysfunction3 Structural deformities

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+

Reiber et al. Diabetes Care 1999

Reiber et al. 1999

The most common causal pathway to a diabetic foot ulceration

NEUROPATHY + DEFORMITY + MINOR TRAUMA

= ULCERATION

+

Reiber et al. Diabetes Care 1999

Reiber et al. 1999

RESULTS: The most common component causes

• Neuropathy

78%

• minor trauma

77%

• foot deformity

63%

• edema

37%

• ischemia

35%

• callus

30%

+

• 1. Consensus Development Conference on Diabetic Foot Wound Care. ADA. Diabetes Care. 1999;22:1354-1360.

STANDARD TREATMENT FOR DIABETIC FOOT ULCERS

Standard treatment modalities1

Sharp debridement of nonviable tissue Treatment of infection Saline-moistened dressings Off-loading to decrease pressure on extremity Arterial revascularization if indicated

Risk Factors For Non-healing Wounds Non- healing wound

Infection Pro- inflammatory cytokines High levels of MMPs and Proteases Low mitogenic activity and senescent cells Offloading Vascular intervention

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Product Study Design % Healed Wounds Time to Heal P-Value Acellular/ Cellular Regranex Regranex Vs. SOC, 922 Patients Regranex (50%) SOC (36%) 14 Weeks

• VS. 20

Weeks P=0.007 Cellular GraftJacket GJ Vs. SOC, 86 Patients GJ (69.6%) SOC (46.2%) 5.7 Weeks

• VS. 6.8

Weeks P= Acellular Grafix Grafix Vs. SOC, 97 Patients Grafix (62%) SOC (21%) 6 Weeks Vs. 9.8 Weeks P=0.0001 Placenta- derived cellular Dermagraft Dermagraft

• Vs. SOC, 245

Patients Dermagraft (30.0%) SOC (18.3%) 1.6-1.7X more likely to heal P=0.023 Cellular Apligraf Apligraf Vs, SOC, 208 Patients Apligraf (56%) SOC (38%) 9.2 Weeks

• VS. 12.8

Weeks P=0.0042 Cellular EpiFix EpiFix Vs. SOC, 26 Patients EpiFix (92%) SOC (8%) 2.5 Weeks

• VS. 5 Weeks

P= <0.001 Placenta- derived acellular

+

To assess benefits and harms of adjunctive HBOT

for treating chronic ulcers of lower limb

Objectives Selection Criteria

Randomized Controlled Trials (RCTs) RCTs comparing benefit of wound healing using

HBOT

Kranke P, Bennett MH, Martyn-St James M, Schnabel A, Debus SE, Weibel S. Cochrane Database of Systematic Review 2015, Issue 6.

Hyperbaric Oxygen therapy for chronic wounds (Review) + Results

12 included (577 participants) 10 trials (531 participants) Enrolled people with DFU Pooled data of 5 trials (205 participants) Results Showed increase rate of ulcer healing, 95%

confidence ratio, HBOT at 6 wks

Benefit not evident at long term 1 yr follow-up No significant evidence in major amputation

rate

+ Final Conclusion

DFU HBOT beneficial in short term NOT

long term

Trials had various flaws in

design/reporting

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+ Lack of Effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation:

A Cohort Study

David J. Margolis, MD, PHD, Jayanta Gupta, MD, PHD, Ole Hoffstad, M. Maryte Papdopoulos, BA, Henry A. Glick, PHD, Stephen R. Thom, MD, PHD, and Nandita Mitra, PHD2 Diabetes Care, Volume 36, July 2013

Objective Endpoints

Compare effectiveness

• f HBO with other

conventional therapies for treatment of Plantar DFUs

• healed wound
• LE amputation
• assessed at 16 weeks

after eligibility

+ Results

N= 6,259 individuals Patient Criteria Adequate Lower limb perfusion Diabetics Wagner Grade 2 or greater Wound Healing less likely 1.2-3 times less likely

Treatment w/HBO

Amputation more likely 1.5-3 times more likely

+ Hyperbaric Oxygen Therapy Does Not Reduce Indications for Amputation in Patients with Diabetes with Non-healing Ulcers of the Lower Limb: A Prospective, Double-Blind, Randomized Controlled

Clinical Trial

Fedorko, L., Bowen, J.M., Jones, W ., Oreopoulos, G., Goeree, R., Hopkins, R.B. and O’Reilly, D.J.Diabetes care (2016): dc152001.

• Assess efficacy of HBOT in reducing

amputation need

• Efficacy in improving wound healing of

Chronic DFU

Objective

• Double Blind, Placebo Controlled
• Diabetics, Wagner 2-4 with >4 wks study

duration

• Received comprehensive wound care
• 30 day sessions, 90 min of HBOT at 244 kPa

Research Design

+Results

N=157 assessed for eligibility 107 randomly assigned Criteria for major amputation met (Primary Endpoint) 13/54 patients in sham group 11/49 in HBOT group

Healed Wounds (Secondary Endpoint)

12 (22%) in sham group healed 10 (20%) in HBOT group healed

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+ to Heal DFUs? Conclusion: Do We Need HBOT to Heal DFUs?

HBOT does NOT offer additional advantage to

comprehensive wound care in reducing the indication for amputation or facilitating wound healing in patients with chronic DFUs

HBOT provided NO incremental benefit in

measures of wound healing

Many RCTs evaluating effectiveness of other

therapies (total contact cast, and substitutes) are available and have been extensively studied.

Thank You

+ Results Continued..

1 trial (16 participants) Considered venous ulcers Reported Data at 6 wks (wound

reduction size)

Reported Data at 18 weeks (wound

reduction size & number of ulcers healed)

Benefit suggested of HBOT in terms of

reduction of ulcer area in 6 wks

+ Results Continued..

1 trial (30 participants) 30 day treatment Pts with “mixed ulcer types” Pts with venous ulcers and DM ulcers Significant benefit in size reduction No trials found that considered arterial or

pressure ulcers

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+Wagner Classification

Stage 0- pre-ulcerative lesion Stage I- superficial with exposed sub Q Stage II- down to tendon, ligament or

bone, not infected

Stage III- infected Stage IV- localized gangrene of forefoot Stage V - extensive gangrene

+

• 1. Steed DL et al. J Am Coll Surg. 1996;183:61-64. 2. Consensus Development Conference on Diabetic Foot

Wound Care. ADA Diabetes Care. 1999;22:1354-1360. 3. Robson MC et al. Clin Plast Surg. 1990;17:485-492. 4. Levin ME. J Wound Ostomy Continence Nurs. 1998;25:129-146. 5. Levin ME. J ET Nurs. 1993;20:191-198.

ROLE OF AGGRESSIVE DEBRIDEMENT

Removes necrotic tissue, senescent cells,

foreign bodies1,2

Decreases bacterial load, restores bacterial

balance1,3

Stimulates the wound healing cascade to

increase the healing rate1

Allows better visual assessment of ulcer area

(eg, sinus tracts or tunneling)4,5

+Debridement

1) Debridement reduces the bio-burden 2) potentially prevents an infection 3) allows for better visualization and inspection of the wound. Steed and coworkers reported in their multi-center study that the patients that underwent debridement showed an improved healing response compared to the patients who did not undergo debridement.