influence of debridement on chronic lower extremity ulcers...sustaining a lower extremity wound of...

Influence of Debridement on Chronic Lower Extremity Ulcers

• Wound Care | Undersea & Hyperbaric Medicine | Infectious Diseases

• Associate Chief Medical Officer

MiMedx Group

• Adjunct Assistant Professor

Duke University School of Medicine

• Adjunct Professor

Western University of Health Sciences/College of Podiatric Medicine

• Former System Medical Director of Wound & HBO2 Medicine Services

Intermountain Healthcare

• Former Program Director of Duke Hyperbaric Medicine Fellowship & Faculty of Intermountain Medical Center Podiatry Residency Program

William H Tettelbach, MD, FACP, FIDSA, FUHM, CWS

• Employee of MiMedx Group, Inc.

• All materials are confidential and may not be recorded, photographed, copied and or reproduced without written permission from MiMedx Group, Inc.

Conflict of Interest

Objectives

• Appreciate burden of hard to heal wounds.

• Review bioburden/biofilm and wound healing.

• Understand the favorable impact of appropriate wound debridement on hard to heal lower extremity diabetic wounds

Hard To Heal Wounds

• Affect both the patient’s quality of life, as well as place a significant burden on healthcare systems around the world.

• Incidence of hard to heal wounds continues to rise wherever the age of the population is increasing.

• Correct diagnosis and treatment at an early stage in the treatment course holds the potential to favorably impact the outcomes of hard-to-heal wounds.

The Problem: In 2018 Over 27 million Diagnosed with Diabetes in the U.S.

Overall Percentage of Americans Diagnosed With Diabetes in 2017

Source: CDC, Behavioral Risk Factor Surveillance System, https://www.americashealthrankings.org/explore/annual/measure/Diabetes/state/ALL

https://www.americashealthrankings.org/explore/annual/measure/Diabetes/state/CO

https://www.americashealthrankings.org/explore/annual/measure/Diabetes/state/ALL

• 18.6 million practice nurse visits

• 10.9 million community nurse visits

• 7.7 million general practitioner visits

• 3.4 million hospital outpatient visits

• Estimated cost of £5.3 billion

− Continues to rise annually

1. Guest JF, Ayoub N, McIlwraith T, Uchegbu I, Gerrish A, Weidlich D, Vowden K, Vowden P. Health economic burden that wounds impose on the National Health Service in the UK. BMJ Open 2015; 5(12).

The Burden of Wound Management in UK1

https://www.americashealthrankings.org/explore/annual/measure/Diabetes/state/CO

• The annual incidence of foot ulcers in diabetics is approximately 2% in most Western countries.1

• The annual incidence of DFUs in the diabetic Medicare population is estimated at 6%.2

• The lifetime incidence of DFUs in patients with diabetes is estimated to range from 19% to 34%.3

1. Abbott CA, Carrington AL, Ashe H, et al. The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med 2002; 19: 377-84.2. Margolis DJ et al, Incidence of Diabetic Foot Ulcer and Lower Extremity Amputation Among Medicare Beneficiaries, 2006 to 2008: Data Points #2 Data Points Publication Series [Internet]. Rockville (MD): Agency for

Healthcare Research and Quality (US); 2011 Feb 17.3. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017 Jun 15;376(24):2367-2375.

Diabetic Foot Ulcers (DFUs)

• Once a diabetic undergoes a non-traumatic lower extremity amputation their 5-year mortality rate can be as high as > 70%.1

• The optimistic perspective of these ominous statistics is the estimates that 49% to 85% of DFU related amputations may be preventable.2

1. Hambleton IR, Jonnalagadda R, Davis CR, Fraser HS, Chaturvedi N, Hennis AJ. All cause mortality after diabetes-related amputation in Barbados: a prospective case-control study. Diabetes Care. 2009 Feb;32(2):306-72. Driver VR, de Leon JM. Health economic implications for wound care and limb preservation. J Manag Care Med. 2008;11(1):13-19.

Diabetic Foot Ulcers (DFUs)

• Once healed, clinicians cannot continue to view that their objective has been reached:

− 40% of healed DFUs recur within 12 months 1

− Up to 69% of venous leg ulcers recur within the first year.2

• The race to heal hard to heal ulcers is driven by the fact that a foot ulcer precedes 85% of lower-limb amputations in patients with diabetes.3

1. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017 Jun 15;376(24):2367-2375.2. Kapp S, Sayers V. (2008) Preventing venous leg ulcer recurrence: a review. Wound Practice and Research. 16: 38-47.3. The Diabetes Council, https://www.thediabetescouncil.com/diabetes-and-amputation-everything-you-need-to-know-to-avoid-amputation/

Hard to Heal Wounds

https://www.thediabetescouncil.com/diabetes-and-amputation-everything-you-need-to-know-to-avoid-amputation/

Venous Leg Ulcers (VLUs)

Potential for healing being missed in patients with venous leg ulceration:

• Research evidence reports achievable healing rates of

− 76% at 24 weeks with compression therapy

• These figures are significantly different to real life population data

− where healing rates are as low as 47% at 12 months.1,2

1. Gohel, M. S., Heatley, F., Liu, X., Bradbury, A., Bulbulia, R., Cullum, N., Epstein, D. M., Nyamekye, I., Poskitt, K. R., Renton, S., Warwick, J. & Davies, A. H. 2018. A Randomized Trial of Early Endovenous Ablation in Venous Ulceration. New England Journal of Medicine, 378, 2105-2114.

2. Guest, J. F., Ayoub, N., Mcilwraith, T., Uchegbu, I., Gerrish, A., Weidlich, D., Vowden, K. & Vowden, P. 2017. Health economic burden that different wound types impose on the UK's National Health Service. International Wound Journal, 14, 322-330.

Unwarranted Variations

Provider Related Factors That Negatively Impact Outcomes Include:

• Poor assessment and diagnosis

• The underuse of evidence-based practices− Doppler assessment of ABI

− Compression therapy

− Endovascular intervention

• Overuse of ineffective interventions

• Variations in assigning services

• Lack of understanding of the influence of external wound healing inhibitors (e.g., Biofilm)

• Absence of standardized training in wound care techniques (e.g., wound bed debridement)

Diabetic Foot Ulcers: A High Infection Risk

Sustaining a lower extremity wound of the most common precipitating events for a foot infection1

Variables achieving independent statistical significance as risk factors for foot infection. Data from a 2-year longitudinal outcomes study of 1,666 patients enrolled in a managed care-based outpatient clinic.

For patients who develop a foot infection associated with a DFU present for > 30 days:

• 55.7 times more likely to be hospitalized

• 154.5 times more likely to have an amputation

1. Maderal AD, et al. Hosp Pract. 2012;40(3):102-115.2. Lavery LA, et al. Diabetes Care. 2006;29(6):1288-1293.

Physio-pathology of the Chronic Wound

Mechanism of Chronic Wound Pathophysiology

B.A. Mast and G.S. Schultz. Wound Rep Reg 4:411-420, 1996.

Repeated Trauma, Ischemia and Bioburden (Planktonic & Biofilms)

Protracted, Elevated Inflammation

↑ neutrophils ↑macrophages ↑ mast cells

IL-1, IL-6

TNF-

Destruction of Essential Proteins (off-target) growth factors / receptors, ECM degradation

cell proliferation, cell migration,

Imbalanced Proteases & Inhibitors Proteases (MMPs, elastase, plasmin), inhibitors (TIMPs, 1PI), ROS

Acute Wound Chronic Non-Healing Wound

Bioburden & Biofilm

▪ Exhibits high levels of antibiotic, host, pH and disinfecting resistance.

▪ 1000x greater antibiotic tolerance than planktonic cells.

Bioburden & Biofilm

Hypoxic environment inhibits:

▪ Oxidative burst

▪ ATP dependent reactions

▪ Collagen deposition

Wound Management Key Points

1. Biofilms are communities of bacteria encased in a matrix of polysaccharides, protein and DNA that provides high levels of tolerance to antibodies, antibiotics and antiseptics.

2. Biofilms identified in >80% of biopsies of chronic wounds, but only in 6% of acute wounds.1

3. Impair healing by stimulating chronic inflammation, leading to elevated levels of proteases and

ROS that degrade proteins that are essential for healing.

4. Debridement is a critical first step in Biofilm-Based Wound Care; several techniques reduced

levels of biofilm bacterial, but biofilms can reform quickly (~3 days) so combine it with targeted

treatment.

5. Step-down-step-up (SD-SU) therapy is based on starting with the therapies that most

effectively reduce biofilms, inflammation, and proteases, (Step-Down) then shifting to

advanced therapies (Step-Up) that enhance repair of the wound bed including dHACM

(growth factors, protease inhibitors, intact collagen).

1. Malone M, Bjarnsholt T, McBain AJ, James GA, Stoodley P, Leaper D, Tachi M, Schultz G, Swanson T, Wolcott RD. The prevalence of biofilms in chronic wounds: a systematic review and

meta-analysis of published data. J Wound Care. 2017 Jan 2;26(1):20-25.

Step-down Step-up

Modified from Schultz, G., Bjarnsholt, T., James, G.A., Leaper, D.L., McBain, A. J., Malone, M., Stoodley, P., Swanson, T., Tachi, M., Wolcott, R.D.; for the Global Wound Biofilm Expert Panel. Wound Repair and Regeneration: 2017.

Significance of Sharp Debridement

• Wound debridement is a vital element in the treatment of diabetic foot ulcers (DFUs), yet even today:

− Wound care clinicians receive little hands-on standardizedtraining in surgical debridement

− Wide variance in opinion among clinicians as to what constitutes adequate debridement.1

• A large 2013 retrospective study revealed that a higher frequency of debridement improves healing outcomes with shorter healing rates.2

1. Tettelbach W, Cazzell S, Reyzelman AM, Sigal F, Caporusso JM, Agnew PS. A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: A prospective, multicentre,

randomised, controlled study of 110 patients from 14 wound clinics. Int Wound J. 2019 Feb;16(1):19-29.

2. Wilcox JR, Carter MJ, Covington S. Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds. JAMA Dermatol. 2013 Sep;149(9):1050-8.

Wilcox – Frequency of Debridements & Time to Heal

Purpose, Design & Methods:

▪ Investigate healing outcomes and debridement frequency in a large wound data set.

▪ Retrospective cohort study.

▪ Data collected from 525 wound care centers from June 1, 2008, through June 31, 2012.

▪ Referred sample of 154,644 patients with 312,744 wounds.

▪ Advanced therapeutic treatment was ineligible.

Wilcox JR, Carter MJ, Covington S. Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds. JAMA Dermatol. 2013 Sep;149(9):1050-8.


Intervention:

▪ Debridement (removal of necrotic tissue and foreign bodies from the wound) at different frequencies.

Main Outcome & Measure:

▪ Wound healing (completely epithelialized with dimensions at 0 × 0 × 0 cm).



Results:

▪ A total of 70.8% of wounds healed.

▪ The median number of debridements was 2 (range, 1-138).

▪ In regression analysis, significant variables included:− male sex− physician category− wound type− increased patient age− increased wound age − area − depth

▪ The odds ratio varied considerably for each variable

▪ Frequent debridement healed more wounds in a shorter time (P < .001). Wilcox JR, Carter MJ, Covington S. Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds. JAMA Dermatol. 2013 Sep;149(9):1050-8.

Conclusion:

▪ The more frequent the debridements, the better the healing outcome.

− Remember: Study protocols not designed to evaluate debridement, but only frequency of debridement.



Tettelbach - Influence of Adequate Debridement on Healing of Chronic LE DFUs

Purpose:

• To evaluate the incidence of adequate debridement on wounds treated with:

− Advanced therapeutic treatment (ATT)

− ATT = sharp debridement, placental derived tissue allograft, absorbent non-adhesive hydropolymer secondary dressings and gauze alone

− Standard of care (SOC)− SOC = sharp debridement, standard wound dressings with alginate dressings, absorbent

non-adhesive hydropolymer secondary dressings and gauze alone with offloading when indicated

• Examine the influence of adequate debridement on rates of complete healing within 12 weeks across all groups.

Influence of Adequate Debridement on Healing of Chronic LE DFUs

Methods:

• Retrospective evaluation of prospectively collected data from patients

enrolled in IRB approved randomized controlled trials:

− dehydrated human amnion/chorion membrane (dHACM, n=54)1

− dehydrated human umbilical cord (dHUC, n=101)2

− standard of care (SOC, n=110)1,2

− Total of wounds treated (n=265)1,2

1. Tettelbach W, Cazzell S, Reyzelman AM, Sigal F, Caporusso JM, Agnew PS. A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: A prospective, multicentre, randomised, controlled study of 110 patients from 14 wound clinics. Int Wound J. 2019 Feb;16(1):19-29. https://onlinelibrary.wiley.com/doi/full/10.1111/iwj.12976

2. Tettelbach W, Cazzell S, Sigal F, Caporusso JM, Agnew PS, Hanft J, Dove C. A multicentre prospective randomised controlled comparative parallel study of dehydrated human umbilical cord (EpiCord) allograft for the treatment of diabetic foot ulcers. Int Wound J. 2018 Sep 24. https://onlinelibrary.wiley.com/doi/full/10.1111/iwj.13001

https://onlinelibrary.wiley.com/doi/full/10.1111/iwj.12976


dHACM Multicenter DFU RTC

Design:

• 12 week, multicenter, randomized, and controlled study

• 14 clinical sites

• 218 subject entered screening

• 110 subjects Intent-to-Treat Cohort randomized (1:1 ratio)

− 54 dHACM and 56 Standard of Care (SOC) group

• 98 subjects met the inclusion and exclusion criteria (Per-Protocol Cohort)

− 47 dHACM and 51 received SOC

• Primary Endpoint: The percentage of subjects with complete closure of the study ulcer at week 12

1. Tettelbach W, Cazzell S, Reyzelman AM, Sigal F, Caporusso JM, Agnew PS. A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: A prospective, multicentre, randomised, controlled study of 110 patients from 14 wound clinics. Int Wound J. 2019 Feb;16(1):19-29. https://onlinelibrary.wiley.com/doi/full/10.1111/iwj.12976


dHUC Multicenter DFU RTC

Design:• 12 week, multicenter, randomized, and controlled study

• 11 clinical sites

• 202 subject entered screening

• 155 subjects Intent-to-Treat Cohort randomized (ratio 2:1)

− 101 dHUC and 54 Control

• 134 subjects met the inclusion and exclusion criteria (Per-Protocol Cohort)

− 86 dHUC and 48 Control

• Overall Study Population (155) show no statistical difference between groups:

− 43% smokers, 63 % obese, and 17.4 % prior amputation, Average A1c = 8.2

• Primary Endpoint: The percentage of subjects with complete closure of the study ulcer at week 12

1. Tettelbach W, Cazzell S, Sigal F, Caporusso JM, Agnew PS, Hanft J, Dove C. A multicentre prospective randomised controlled comparative parallel study of dehydrated human umbilical cord (EpiCord) allograft for the treatment of diabetic foot ulcers. Int Wound J. 2018 Sep 24. https://onlinelibrary.wiley.com/doi/full/10.1111/iwj.13001



Methods:

• Images taken pre-and-post debridement were adjudicated after the study

completion by three wound care specialists blinded to cohort assignment.

• Adequate debridement was defined as evidence of a concerted attempt to:

− excise devitalized tissue from the ulcer bed

− pare down peri-wound callous

− excise/disrupt epibole or sclerosed margins

− remove foreign material present in or around the wound.

Debridement Study Patient (Cohort Blinded)

Adjudication:

Debridement Inadequate


Adjudication:

Debridement Adequate

Healed



Results:

Adequate debridement occurred in:

• 45/54 (83%) of dHACM-treated ulcers,

• 67/101 (66%) of dHUC-treated ulcers and

• 90/110 (82%) of SOC.

• 202/265 (76%) of the overall sample

Patient Demographics & Ulcer Characteristics

dHACM dHUC SOCdHACM - dHUC - SOC

Combined(n=54) (n=101) (n=110) (n=265)

Mean Age, years (SD) 57.4 (10.6) 58.3 (10.9) 56.7 (10.3) 57.5 (10.6)Age ≥ 65 years (n, %) 12 (22.2%) 28 (27.7%) 23 (20.9%) 63 (23.8%)Male Gender (n, %) 40 (74.1%) 82 (81.2%) 84 (76.4%) 206 (77.7%)Race (n, %)

Caucasian 46 (86.8%) 81 (80.2%) 90 (81.8%) 217 (82.2%)African-American 6 (11.3%) 12 (11.9%) 16 (14.6%) 34 (12.9%)

Hispanic Ethnicity (n, %) 22 (40.7%) 28 (27.7%) 38 (34.6%) 88 (33.2%)BMI (SD) 35.8 (8.9) 33.8 (7.3) 33.7 (8.3) 34.2 (8.1)Obese BMI ≥ 30 (n, %) 39 (72.2%) 68 (67.3%) 65 (59.1%) 172 (64.9%)A1c (%, SD) 7.8 (1.4) 8.0 (1.8) 8.7 (1.9) 8.3 (1.8)Smoker (n, %) 22 (40.7%) 38 (37.6%) 45 (42.5%) 105 (40.2%)Alcohol Use (n, %) 21 (39.6%) 50 (49.5%) 46 (43.4%) 117 (45.0%)History of Recurring Ulcers (n, %) 12 (22.6%) 26 (25.7%) 24 (23.1%) 62 (24.0%)History of Cardiovascular Abnormalities (n, %)

23 (43.4%) 39 (38.6%) 44 (41.5%) 106 (40.8%)

Prior Amputation (n, %) 11 (20.4%) 17 (16.8%) 26 (23.9%) 54 (20.5%)Ulcer Position (n, %)

Plantar 25 (48.1%) 77 (76.2%) 82 (79.6%) 184 (71.9%)Ulcer Location (n, %)

Toe 7 (13.7%) 12 (11.9%) 16 (15.5%) 35 (13.7%)Forefoot 27 (52.9%) 58 (57.4%) 57 (55.3%) 142 (55.7%)Midfoot 8 (15.7%) 20 (19.8%) 17 (16.5%) 45 (17.6%)Hindfoot 8 (15.7%) 9 (8.9%) 10 (9.7%) 27 (10.6%)

Ulcer Size (cm2, SD) 3.2 (2.8) 2.6 (2.2) 3.3 (3.3) 3.0 (2.8)Ulcer Duration, weeks (SD) 20.8 (18.5) 20.5 (13.7) 20.9 (14.5) 20.7 (15.1)

Cox Regression Model Results

VariablesParameter Estimate

Standard Error

Chi-Square P-ValueHazard Ratio

95% CI for HR

Lower Upper

Debridement - Adequate vs Inadequate

1.82 0.30 37.71 <.0001 6.19 3.46 11.07

BMI (< 30) 0.36 0.16 4.68 0.031 1.43 1.03 1.97

Baseline Wound Size (<= 2.8 cm2) 0.69 0.20 12.32 0.000 1.99 1.36 2.93

DFU Position - Non-Plantar 0.48 0.17 7.73 0.005 1.62 1.15 2.27

DFU Location (Toe) vs. Hindfoot 0.81 0.33 6.16 0.013 2.25 1.19 4.28

DFU Location (Forefoot) vs.Hindfoot

0.60 0.28 4.71 0.030 1.82 1.06 3.12

DFU Location (Midfoot) vs. Hindfoot

0.39 0.31 1.51 0.219 1.47 0.80 2.72

Factors Influencing Healing Within 12 Weeks of Receiving dHACM, dHUC, SOC


N=155

Rates of Complete Healing For Wounds Treated With dHACM or dHUC by Debridement Status


Rates of Complete Healing For Wounds Treated With dHACM or dHUC or SOC by Debridement Status


N=265


Conclusion:

• Adequate wound debridement is an essential component of

wound care and influences rates of healing achieved when

using either advanced therapies such as dHACM or dHUC

allografts as well as with SOC alone.

DFU Limb Salvage Case Report

Neuropathic Diabetic Foot Ulcer

February 27th

• Diabetic Male with peripheral neuropathy

• Ulcer worsening over 3 months

• Started empiric oral antibiotics

• Referred by orthopedist


March 2nd

• Aggressive sharp excisional debridement

• Immediate mechanical NPWT initiated

• Obtained culture post debridement

• Continued oral antibiotics for suspected osteomyelitis


March 7th

Continued :

• Oral antibiotics

• Offloading with knee scooter

• Mechanical NPWT


May 2nd

• Mechanical NPWT discontinued

• Continued oral antibiotics


• Applied first placental derived allograft


May 23rd

• Wound continues to reduce in size

• Tolerating oral antibiotics


• Applied 4th (final) placental derived allograft

June 20th

Celebration!


Amanaki Fo’ou

Thank you

influence of debridement on chronic lower extremity ulcers...sustaining a lower extremity wound of...

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