Supported by an educational grant from Novadaq Technologies Inc.

Hyperbaric Oxygen Therapy in Combination with

Fluorescence Imaging: Patient Selection and Monitoring

Presenters

Charles Andersen, MD, FACS Chief of Vascular/Endovascular Surgery

Director of Wound Care Clinic Madigan Army Medical Center

Tacoma, Washington Clinical Professor of Surgery, USUHS

Bethesda, Maryland Clinical Professor of Surgery, UW

Seattle, Washington

Stephen Guthrie, MD, PhD (Moderator) President and Chief Medical Officer

Designed Altobaric Research Foundation Livonia, Michigan

Thomas E. Serena, MD, FACS Medical Director and CEO

Serena Group Cambridge, Massachusetts

Disclosures

•  Dr. Andersen: Speaker – Acelity, Novadaq Technologies Inc., Organogenesis

•  Dr. Guthrie: Speakers’ Bureau – Novadaq Technologies, Inc

•  Dr. Serena: Grant/Research Support – Celleration, KCI, MiMedix, Redress, Systagenix; Consultant – KCI, MiMedix, Nuo Therapeutics, Smith & Nephew; Board Member – Association for the Advancement of Wound Care

•  This continuing education activity includes medication brand names for participant clarity purposes only. No product promotion or recommendations should be inferred.

Learning Objectives

After completing this activity, participants should be able to

•  Assess the science on use of fluorescence imaging in assessing tissue perfusion in diabetic foot ulcers and non-healing wounds

•  Evaluate the use of fluorescence angiography in identifying patients who would benefit from hyperbaric oxygen therapy (HBOT)

•  Employ methods to monitor perfusion of wounds undergoing HBOT

•  Review clinical cases of wounds that underwent hyperbaric oxygen treatment, fluorescence imaging solutions and application of an acellular dermal matrix

KCI

The Role of Fluorescence Imaging in Advanced Wound Care

Charles Andersen, MD, FACS, FAPWCA

Measurement of Tissue Perfusion

•  Critical to every component of advanced wound care

•  Fluorescent angiography helps answer key questions –  Is there a need for revascularization, and is revascularization

adequate?

–  Is there adequate perfusion to heal a wound?

–  Is debridement adequate?

–  Is the wound responding to advanced wound care, including HBO?

HBO = hyperbaric oxygen. Braun JD, et al. J Vasc Surg. 2013;57(5):1213-1238.

Measurement of Tissue Perfusion

•  Clinical judgment

•  ABIs, toe pressures, toe waveforms

•  Forefoot pulse volume recording

•  Duplex scan

•  Transcutaneous oximetry

•  Skin perfusion pressure

ABI = ankle-brachial index. Andersen CA. J Vasc Surg. 2010;52(125):76s-80s.

Measurement of Tissue Perfusion

•  Current methods utilized to evaluate tissue perfusion are often limited by medial calcinosis, scarring, wounds, prior amputations, and infection

•  Current methods can be technically challenging, costly, and time consuming, and don’t measure global perfusion of the foot

•  Fluorescent angiography offers an additional option to measure tissue perfusion

•  Fluorescent angiography is becoming a critical component of advanced wound care

Andersen CA. J Vasc Surg. 2010;52(125):76s-80s.

Fluorescent Angiography

Visualize and quantitate microcirculation: See what the eye can’t see

Definition

•  Fluorescent angiography is a diagnostic technique that uses fluorescent dye ICG injected IV to allow the sequential visualization of blood flow

ICG = indocyanine green. Gurtner GC, et al. Ann Surg Innov Res. 20137(1):1.

ICG

•  Strong record of safe clinical use

•  Excreted hepatically – not contraindicated in patients with compromised renal function

•  3-5 – minute half-life

•  Only contraindication – should be used with caution in patients who have a history of sensitivity to iodine

Gurtner GC, et al. Ann Surg Innov Res. 20137(1):1. Perry D, et al. J Diabetes Sci Technol. 2012;6(1):204-208.

•  ICG is injected IV

•  The injected agent lights up blood flowing through the veins and arteries in real time, and the camera captures live images of the patient’s vasculature

•  These images can be captured on a computer screen, analyzed, saved, and printed for medical reference

Gurtner GC, et al. Ann Surg Innov Res. 20137(1):1.

Fluorescent Angiography

Vascular Interventions

•  Fluorescence angiography can help answer critical questions

–  Is revascularization required?

–  Did revascularization provide adequate tissue perfusion (involved angiosome)?

–  If a procedure is planned following revascularization, when is maximal perfusion established (timing of a podiatric procedure)?

Braun JD, et al. J Vasc Surg. 2013;57(5):1213-1238. Perry D, et al. J Diabetes Sci Technol. 2012;6(1):204-208.

Case 1

Assess the Need for Revascularization and the Results of Revascularization

History

•  72-year-old male with severe ischemic rest pain in the left foot and an ulcer between the 4th and 5th toes and an ulcer at the base of the 5th toe

•  8/19/14 – arteriogram with placement of 8x61 self-expanding iliac stent

•  Fluorescent angiography studies obtained prior to the intervention and in subsequent days

8/18/2014 – Rest Pain with Dependent Rubor and Pallor on Elevation

Dependent Rubor Pallor on Elevation

FOV = field of view.

Pre-Treatment and Immediate Post-Treatment: 101% Improvement in Ingress Rate

Immediate Post-Treatment Compared to 1 Day Post-Treatment

Perfusion Continued to Improve with a 35% Improvement in Ingress

Role of Fluorescent Angiography in Vascular Surgery

•  Assesses the need for revascularization –  Assess regional perfusion of the foot

•  Assesses adequacy of perfusion following revascularization (involved angiosome)

•  Assesses time of maximum perfusion (aids in timing of a secondary procedure)

Gurtner GC, et al. Ann Surg Innov Res. 2013;7(7 Suppl 1):1. Perry D, et al. J Diabetes Sci Technol. 2012;6(1):204-208.

Assessing Perfusion to

Determine Amputation Level

Case 2

Hallux Amputation for Gangrene Osteomyelitis, Cellulitis, and Abscess

History

•  79-year-old male with diabetes and multiple comorbidities admitted with gangrene, osteomyelitis, and cellulitis of the right great toe and dorsal foot

•  2-3 – week history of pain and swelling

•  Poor historian – not sure of trauma

•  History of deep vein thrombosis with chronic venous insufficiency, peripheral arterial disease, and atrial fibrillation

History

•  Positive blood cultures for MRSA

•  Started on broad-spectrum IV antibiotics with resolution of cellulitis on dorsum of foot

•  Vascular assessment

•  Fluorescent angiography

•  February 2015 – Right hallux amputation

MRSA = methicillin-resistant staphylococcus aureus.

Pre-Op

Pre-Op

Pre-Op MRI

•  Abscess surrounding the flexor hallucis longus

•  Tendon is concerning for infective tenosynovitis

•  Moderate osteoarthritis of the right foot

 

 

 

MRI = magnetic resonance imaging.

Pre-Op Vascular Assessment

•  ABIs – noncompressible vessels with ABIs greater than 1.5

•  Biphasic waveforms at right ankle

•  Right toe pressure not obtainable

Management Questions

•  Does the patient need a CTA or arteriogram?

•  If these studies are performed, does he need vascular intervention? Will vascular disease be seen?

•  Based on the arterial studies, should a BKA be performed?

CTA = computed tomography arteriography; BKA = below-knee amputation.

Pre-Op Fluorescence Angiography

Management Outcomes

•  No CTA or arteriogram

•  No BKA

•  Limited amputation under regional anesthesia

•  Intraoperative modification based on fluorescent angiography

Intra-Op Fluorescence Angiography

Amputation

Flap revision following intra-op fluorescence angiography

Amputation

Amputation following excision of ischemic distal flap

Amputation

Flap closure

Fluorescence Angiography Following Closure

Post-Op

2 days post-op 5 days post-op

Peripheral arterial disease is a critical component of morbidity and mortality related to pedal ulcerations. Non-invasive vascular testing is the first step indetermining a viable level of amputation when a patient presents with a diabetic foot ulceration compromised by arterial insufficiency. Current non-invasivevascular testing methods have significant limitations. The cases above demonstrate how non-invasive vascular studies would have prompted for a higher level ofamputation. However, the use of fluorescence angiography revealed adequate distal perfusion resulting in a more distal procedure for limb salvage. Fluorescentangiography is a useful tool to assess areas of viability and determine a level of amputation most likely to heal. The procedure is an easily reproduciblequalitative study which is minimally invasive, with minimal patient risk that can be used in patients with renal insufficiency to provide site specific assessmentof cutaneous arterial perfusion for limb salvage procedures.

A 96 year-old female with a past medical history of hypothyroidism, peripheral vascular disease, and a prior amputation of 2nd digit of the left foot presentedwith dry gangrene of the plantar medial left hallux. The patient reported that the ulceration began as a callus on her left big toe. The patient was referred for non-invasive vascular studies to determine a viable level of amputation. The ABI was 0.5. The TBI was 0.38 which is just at the level that primary healing would belikely. Fluorescent angiography revealed adequate perfusion for a left hallux amputation. The patient subsequently underwent amputation of the left halluxamputation which healed uneventfully at X weeks.

A 92 year-old male with a past medical history significant for: gout, venous insufficiency, peripheral vascular disease, uncontrolled diabetes with peripheralneuropathy, and CKD Stage III presented with a left hallux full thickness wound measuring 2.5cm x 2cm x 1.5cm which probed to bone. The wound continuedto deteriorate despite advanced local wound care. Radiographs revealed osseous changes concerning for osteomyelitis. The patient was referred for non-invasivevascular studies to determine a viable level of amputation. An ABI was performed but due to non-compressible arteries viable results could not be ascertained.TcPO2 (DID TCPO2 CORRELATE TO A HALLUX AMPUTATION LEVEL?) and fluorescent angiography revealed adequate perfusion for a left halluxamputation. The patient subsequently underwent amputation of the left hallux amputation which healed uneventfully at X weeks.

The estimated risk of developing a foot ulceration among those diagnosed withdiabetes mellitus is 15%. The adverse outcome of a diabetic foot ulcer is limbamputation which occurs 10 to 30 times more often in diabetics than the generalpopulation. Many contributory factors exist to developing a foot ulcer. A criticalprecursor to amputation upon developing a foot ulcer is the presence of peripheralarterial disease. Compromised vascularity can be detrimental to healing be preventionof the ability to fight infection, inhibition of proper nutrition supply for healing andfurther tissue loss. Assessing blow flow to the lower extremity should always be doneprior to any surgical intervention. Multiple noninvasive vascular tests can beperformed to evaluate pedal blood flow. An ankle-brachial index (ABI) of 0.90 or lesssuggests the presence of peripheral vascular disease. A value >1.1 can represent afalsely elevated pressure secondary to medial arterial calcinosis. Toe brachial index(TBI) and systolic toe pressure could also be used, however, cannot be performed ifthe patient has had a prior forefoot amputation, toe ulcers or gangrenous digitsCutaneous arterial oxygen supply can be measured via transcutaneous oximetry(TcPO2). A TcPO2 tension >30 mmHg correlates with a high likelihood of primarywound healing. Although TcPo2 can be objective, inherent limitations exist. The test isdifficult to reproduce and is technician dependent. Results can only be obtained undercertain physical conditions (LIKE WHAT?) and is influenced by marked edema,hyperkeratosis, dry flaky skin, probe placement over bones and tendons, cellulitis, andother factors that can reduce thermal conductivity capillary flow and therefore oxygentransmission (Levin and O'Neal's the Diabetic Foot). We hypothesize that the ability toassess cutaneous perfusion to the foot with fluorescent angiography in addition totraditional non-invasive vascular testing may lead to a more distal level of amputationyielding a high rate of limb salvage.

Presented here are two cases in which fluorescent angiography were used to determinereal-time arterial blood flow during preoperative, intraoperative, and postoperativephases of the patient’s treatment. Fluorescence angiography uses a charge-coupleddevice camera with a laser source in conjunction with the intravenous indocyaninegreen dye to assess the peri-wound skin perfusion. After clinical assessment, eachpatient received parental administration of ____ mg of intravenous indocyanine greendye followed by a 10mg saline flush. The dye binds rapidly to plasma albumin. Oncebound to plasma albumin excitation of the molecule occurs by using the laserat____causing the molecules to fluoresce. The process can then be detected by acharge-coupled camera directed at the area of interest to record a video of maximumduration of 2:30 to assess the ingress and egress of cutaneous arterial supply. The dyeis excreted exclusively through the biliary system. The half-life of the dye is 2.5-3minutes and can be safely administered multiple times with very low risk of adversereactions.

Disclaimer: The opinions or assertions contained hereinare the private view of the author and are not to beconstrued as official or reflecting the views of theDepartment of the Army or the Department of Defense.

REFERENCES: Available upon request

INTRODUCTION

METHODS

CASE 2

The use of fluorescent angiography in limb salvageRebecca Omana-Daniels, DPM: PGY-3, Podiatric Medicine and Surgery Service, Madigan Army Medical Center, Tacoma, WA

Valerie L Schade, DPM: Chief, Limb Preservation Service, Madigan Army Medical Center, Tacoma WACharles A Andersen, MD: Chief, Vascular/Endovascular Surgery Service, Madigan Army Medical Center, Tacoma WA

CASE 1

DISCUSSION

ANGIOGRAPHY PICTURES HERE

PREOP PICTURES ANGIOGRAPHY PICTURES POSTOP PICTURES HERE

Desert Foot 2014

Case 3

Debridement and Assessment of Acellular Dermal Matrix

History

•  12/9/14: 81-year-old admitted with congestive heart failure and recurrent venous ulcer with cellulitis

•  History of recurrent venous ulcers treated with perforator ligation and compression

•  12/11/14: debridement in wound care clinic followed by fluorescent angiography with additional debridement

Pre-Debridement

Fluorescent-Assisted Debridement

Post-Debridement

Baseline Fluorescent Study

•  Baseline fluorescent study documenting good arterial inflow but low egress rate, consistent with venous disease

•  Inflammatory response around the wound

1 Week Post-Debridement

Application of DermaMatrix

1 Week Post-Application

2 Weeks Post-Application

Increased Perfusion in Wound

Preoperative Perfusion Study at Level of Planned Amputation

Monitoring Response to Advanced Wound Care Treatment

•  Negative pressure wound therapy

•  Provant® Therapy System

•  Biologic tissues

•  HBO

•  ArtAssist

Conclusions – Fluorescent Angiography

•  Faster and more accurate evaluation of tissue perfusion than any other available technology

•  Assess the need for and the results of revascularization

•  Facilitate more aggressive treatment in more challenging patients

•  Aid to debridement and use of advanced wound care products, including HBO

THANK YOU !

Dr. Charles Andersen – cande98752@aol.com

Mt. Rainier at Sunrise

Indocyanine Green Fluorescent Angiography for the Wound and

Hyperbaric Physician

Thomas E. Serena, MD, FACS

Introduction

Monitoring Perfusion

Angiogenesis Dependent on Oxygen Gradient

•  In irradiated tissue: oxygen gradient 10-20 mm Hg

•  Under hyperbaric conditions: increases to 230 mm Hg

Problem Wounds: The Role of Oxygen. New York, NY: Elsevier; 1988.

SDF-1a = stromal cell-derived factor 1a; VEGF = vascular endothelial growth factor; EPCs = endothelial progenitor cells; NOS = nitric oxide synthase; eNOS = endothelial nitric oxide synthase; HBO = hyperbaric oxygen. Gallagher KA, et al. J Clin Invest. 2007;117(5):1249-1259.

Healthy Wound Diabetic Wound

VEGF Expression During the Course of Healing

Johnson KE, et al. Adv Wound Care. 2014;3(10):647-661.

1000

0

VEG

F (p

g/m

g)

500

Time (days) 14 1 3 Control

1500

5 7

750

250

1250

Serena, TE. Presented at: SAWC Spring 2014; April 24, 2014; Orlando, Florida. Oral Presentation. https://www.softconference.com/LWW/sessionDetail.asp?SID=365292. Accessed March 3, 2015.

Patient Compliance

IWCHM: Flourescence Vascular Angiography and HBOT Efficacy

•  86 patients scanned a total of 378 times over 7 months

•  Scans were performed both before and after treatment

–  HBOT

–  Ambient pressure oxygen breathing

–  Debridement

IWCHM = Institute for Wound Healing and Hyperbaric Medicine. Guthrie SD, et al. Undersea Hyperbaric Med. 2014;41(5):468.

IWCHM: Flourescence Vascular Angiography and HBOT Efficacy

•  Use of FVA scanning allowed clinicians to:

–  Define wound types

–  Demonstrate the impact of HBOT

–  Document when HBOT had restored CUSH

–  Illustrate the benefits of HBOT in patients failing TCOM

CUSH = capacity for unaided secondary healing; TCOM = transcutaneous oxygen measurement. Guthrie SD, et al. Undersea Hyperbaric Med. 2014;41(5):468.

FVA for Guiding Clinical Decisions

•  Introduced in outpatient wound/HBOT clinic

•  In first 3 months, 68 patients received a total of 345 FVA studies

•  In initial review, useful clinical decisions were made in >80% of patients using FVA results

Guthrie SD, et al. Today’s Wound Clinic. 2014;8:8.

FVA and HBOT Assessment

Guthrie SD, et al. Today’s Wound Clinic. 2014;8:8.

Standard ICG Imaging prior to HBOT

Post-HBOT Imaging demonstrates

lower pixel density

FVA Future Applications

•  Analysis of wound pathophysiology

•  Precise measurement of HBOT effects, allowing for more tailored therapy

•  Device registry

•  Clinical trials

Guthrie SD, et al. Today’s Wound Clinic. 2014;8:8.

Fluorescence Vascular Angiography

in the Selection and Management of HBOT Patients

Stephen D. Guthrie, MD, PhD

If This Presentation on FVA Has Succeeded, You Will Answer “YES” to These Questions:

•  Are you convinced that indocyanine green fluorescence angiography visualizes the actual microcirculation of the wound and peri-wound tissue?

•  Do the FVA examples shown illustrate the differences between normal tissue, ischemic tissue, and wounded tissue?

•  Is it clear that FVA imaging illustrates how a therapeutic intervention is reflected?

FVA = fluorescence vascular angiography. Alander JT, et al. Int J Biomed Imaging. 2012; epub ahead of print. Braun JD, et al. J Vasc Surg. 2013; 57(5):1213-1218. Guthrie SD, Guthrie BR. Today’s Wound Clinic. 2014;8(8):19-22. Marshall MV, et al. Open Surg Oncol J. 2010;2(2):12-25.

If You Answered “YES” to Those Questions:

•  Quantification of the FVA images will reinforce your intuitive impression of the level of perfusion

•  Quantification of the FVA images will allow you to grade the severity of the wound

•  Quantification of the FVA images will allow you to grade the effectiveness of your treatment

Alander JT, et al. Int J Biomed Imaging. 2012; epub ahead of print. Braun JD, et al. J Vasc Surg. 2013; 57(5):1213-1218. Guthrie SD, Guthrie BR. Today’s Wound Clinic. 2014;8(8):19-22. Marshall MV, et al. Open Surg Oncol J. 2010;2(2):12-25.

Roger P. Contour Map

Non-healing L2 amputation site before and after tibial bypass

221

vs

533

FVA Is a Reality

For FVA to be accepted and to be effective requires:

•  Demonstration that patient will respond to HBOT

•  Demonstration that HBOT is moving the FVA metric towards the “normal” profile

•  Demonstration that HBOT has restored the wound to the state of CUSH

•  Assessment of recidivism risk

Subjective assessment and quantitative analysis of FVA data can reflect the effects of a series of

hyperbaric oxygen treatments

Peter G. Contour Map

Before HBO2Rx Chamber Session #1

After 29 HBO2Rx treatments

Peter G. Contour Map

Before HBO2Rx Chamber Session #1

After 29 HBO2Rx but at

ambient pressure this day

Quantitative Analysis of FVA Data Can Assess HBOT Candidacy in “Failed” tCOM Patients

@ 17 seconds

@ 40 seconds

Donald P. Contour Map

tCOM in single digits and no O2 response

Donald P. Transcutaneous Oximetry

FVA before HBO2Rx

FVA following HBO2Rx

Angelo A. Contour Map

To contact Dr. Guthrie with questions:

Stephen_Guthrie@icloud.com