The Role of Hyperbaric Oxygen Therapy and Wound Healing Brian G. Halloran, MD Medical Director, Center for Wound Care and Hyperbaric Medicine St. Joseph Mercy Hospital Ann Arbor, Michigan

Objectives Provide background on role of hyperbaric oxygen treatment for chronic wounds and other FDA-approved conditions Inform how evidence-based practice and a multi-disciplinary wound team can optimize treatment and healing for ORL/HN disease

Disclosures Commercial Interest-St Joseph Mercy Health System Financial Relationship-Physician Purchased Services and Medical Director Conflict of Interest-Exempt, given the non-profit status of SJMHS

What is a Wound Center? A Wound Center Treats Chronic Wounds Chronic wounds have prolonged pro- inflammatory stimulus One time or repeated injury → fail to proceed through normal phases of wound healing Present for at least 4 weeks, to months, to years

Types of Chronic Wounds Infectious wounds Ischemic wounds Radiation wounds Surgical wounds Arterial ulcers Venous ulcers Diabetic ulcers Pressure ulcers Chronic wounds are not defined by size, complexity or failure to heal with your initial therapy

What is Hyperbaric Oxygen Therapy? HBOT is breathing 100% oxygen while under increased atmospheric pressure What is Hyperbaric Oxygen Therapy?

Have You Ever Been in a Hyperbaric Chamber? Elevation Air Pressure Sea Level 14.7 psi Denver 12.1 psi Mount Everest 4.6 psi 34,000 feet 3.6 psi Airplane cabin at 33,000 feet 10.9 psi

Oxygen Physiology Atmospheric Pressure Breathing Gas Measured PaO2 1.0 Room air (21% oxygen) 90-95 mmHg 100% oxygen 507 mmHg 3.0 1721 mmHg Since more oxygen is in solution in plasma while under pressure, it can reach areas where RBCs may not be able to pass

HBO Mechanisms of Action HBOT increases the generation of oxygen free radicals, which have bacteriostatic/bactericidal actions HBOT stimulates stem cells to produce and release growth factors Vasculogenic stem cells are mobilized to areas of wounding Since fibroblast proliferation and collagen synthesis are oxygen-dependent, angiogenesis can occur in ischemic tissue

Effects of Hyperoxygenation Plasma quickly becomes saturated with O2 Elevated O2 levels in blood stream return to normal within 10 minutes after completing hyperbaric exposure O2 tension in muscle tissue remains elevated for 1- 2 hours post-exposure O2 tension in subcutaneous tissue remains elevated up to 4 hours post-exposure

3 Main Effects of HBOT Delivery of O2 to hypoperfused tissue Limits ischemic damage Promotes collagen synthesis Generation of Oxygen Free Radicals Helps kill bacteria Vasoconstriction Decreases tissue edema

FDA-Approved Indication for HBOT Air/Gas embolism Carbon monoxide poisoning Cyanide poisoning Gas gangrene Crush injury Decompression sickness Diabetic foot wounds Necrotizing soft tissue infections Osteoradionecrosis Delayed radiation injury Compromised skin graft/flaps Central retinal artery occlusion Refractory osteomyelitis Intracranial abscess

Off-label Uses of HBOT AIDS/HIV Autism Alzheimer’s disease Asthma Bell’s palsy Brain injury Cerebral palsy Hepatitis Migraine Multiple sclerosis Parkinson’s disease Spinal cord injury Sports injury Stroke

Applications Proposed or Studied for ORL-HNS Osteoradionecrosis Chondroradionecrosis Enhancement of graft/flap viability Tracheocutaneous fistula Skull base osteomyelitis Sudden SNHL Bells’s Palsy Radiation sensitization

Radiation Injury Marx Triad Hypocellularity, Hypovascularity, Hypoxia Endarteritis Obliterans From progressive capillary loss and tissue fibrosis Manifests as: Pigmentary skin changes, tissue induration, loss of elasticity, local erythema, tenderness/pain, osteo- avascular necrosis, tissue ulcers

HBOT for Radiation Injury Hyperoxygenation Increased oxygen gradient to central hypoxic area Angiogenesis Is oxygen-dependent Increased Capillary Density Occurs after multiple HBOT treatment sessions

HBOT and Cancer Growth Theoretical Cellular turnover/division is oxygen-dependent Does HBOT enhance tumor growth? Current Experiments Cell culture and mouse models of SCCa showed no difference between HBOT and normal O2 Systematic Reviews Have failed to support any concern Malignant neoplasm may follow a different pathway of angiogenesis than wound healing

Summary HBOT is breathing 100% oxygen while under increased atmospheric pressure Most benefits derived from 30-40 treatments of 90- minutes at 2.4 atm Supported ORL-HNS indications for ORN, CRN, radiation-soft tissue injury and flap/graft survival Cost are significant ($15K), but savings likely in proven indications

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