Hyperbaric Oxygen: Putting Principles into Practice Session 245 Sunday, September 11 th 2011.

Transcription

1 Session 45 Sunday, September 11 th 011 Session Overview Jeffrey A. Niezgoda, MD, FACHM, MAPWCA Statistics & Definitions Non Healing PVD Ulcer Oxygen & Wound Healing Advanced Modalities for Angiogenesis Hyperbaric Oxygen Therapy History, Mechanisms of Action, Brief Literature Review HBO DFU Algorithm Case Studies 1

2 Session 45 Sunday, September 11 th 011 Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 1994 Obesity (BMI 30 kg/m ) Diabetes Missing Data <14.0% % %.0-5.9% 6.0% Missing data <4.5% % % % 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 004 Obesity (BMI 30 kg/m ) Diabetes Missing Data <14.0% % %.0-5.9% 6.0% Missing data <4.5% % % % 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at

3 Session 45 Sunday, September 11 th 011 Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes 009 Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes Obesity (BMI 30 kg/m ) Obesity (BMI 30 kg/m ) Diabetes No Data <14.0% % %.0-5.9% >6.0% Diabetes Missing Data <14.0% % %.0-5.9% 6.0% Missing data <4.5% % % % 9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at No Data <4.5% % % % >9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at Diabetic Statistics Prevalence of Diabetes (US, All Ages, 008) 18. million people 6.3 percent of the population Direct medical costs: $9 billion Indirect costs: $40 billion disability, work loss, premature mortality Source: NIDDK - National Institute of Diabetes & Digestive & Kidney Diseases The Diabetic Foot Disease 8,000 non-traumatic lower limb amputations 00 54,000 diabetic amputations reported in 199 $43,000 for minor amputation $65,000 for major amputation Apelqvist 1995 $,000 to $36,000 per diabetic foot ulcer Bentkover & Champion, 1993 Wound Healing Compromise Tissue Hypoxia Infection Edema Mechanical Forces Cellular Dysfunction Nutrition? Common Pathophysiology? Source: *00 Theta Report Advanced Wound Care Biologics Market Analysis 3

4 Session 45 Sunday, September 11 th 011 HEMOSTASIS PHASE Platelets Fibrin Stops the flow of O INFLAMMATION PHASE Neutrophils Macrophages Lymphocytes Time PROLIFERATION PHASE Fibroblasts Collagen Consumes O Endothelium Requires O REMOLDING PHASE Collagen Crosslinking Scar Maturation Oxygen & Wound Healing Angiogenesis is oxygen dependent. Antimicrobial activity is oxygen dependent. Tissue oxygen tensions above 30mmHg are needed for collagen synthesis. The metabolic demands of healing tissue can increase by a factor of 0 or more. SKnighton DR, Oredsson S, Banda MJ, Hunt TK. Regulation of repair: Hypoxic control of macrophage mediated angiogenesis. In: (Hunt TK, Heppenstall RB, Pines E, Rovee D, Eds.) Soft and hard tissue repair. New York:Praeser;1948: Knighton DR, Hunt TK, Scheuenstuhl H. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science. 1983;1: The Role of the Wound Care Specialist is to Initiate the Diagnosis and Treatment of the Factors Compromising Wound Healing and then to Utilize Advanced Wound Care Techniques and Adjunctive Modalities to Optimize the Potential for Healing. Advanced Modalities/Therapies (Ancillary or Adjunctive Interventions) Definition Mechanical, Biological or Pharmaceutical modalities that are utilized in addition to standard basic wound care protocols with the intent to promote wound healing and/or limb salvage, via mechanisms which stimulate perfusion or enhance angiogenesis. INJURY COMPLEMENT KININS COAGULATION PLATELETS RESISTANCE TO INFECTION INFLAMMATION GRANULOCYTES MACROPHAGES LYMPHOCYTES MIGRATION PROLIFERATION FIBROBLASTS KERATINOCYTES DEBRIDEMENT ENDOTHELIAL CELLS (ANGIOGENESIS) CONTRACTION COLLAGEN LYSIS COLLAGEN SYNTHESIS PROTEOGLYCAN SYNTHESIS REMODELING HEALED WOUND Adapted from Zabel DD, Hunt TK. Perspect Colon Rectal Surg. Thieme Medical Publishers; 1993:

5 Session 45 Sunday, September 11 th 011 Advanced Modalities Mechanical Pneumatic Compression Therapy Pulsed Electromagnetic Field Therapy Ultrasonic Guided Debridement Negative Pressure Wound Therapy (NPWT) Electrical Stimulation Therapy Ultraviolet Light Therapy Vashe Wound Therapy Monochromatic Infrared Energy (MIRE) Advanced Modalities Biological Bioactive Bioengineered Skin Substitutes Autologous Platelet Grafts Biomaterials Autologous Dermal Matrix Acellular Matrices Biosynthetic Growth Factors Biotechnologies Genetic Transfer Stem Cell Therapies Advanced Modalities Pharmaceutical Platelet Aggregation Inhibitors Plavix (cilostazol) Pletal (clopidogrel) Prasugrel Glycoprotein Platelet Inhibitors Aggrastat (tirofiban) Oxygen Hyperbaric Oxygen Therapy Definition Mechanism of Action Hyperbaric Oxygen Therapy is NOT Definition Mechanism of Action 5

6 Session 45 Sunday, September 11 th 011 Definition: Inhaled 100% Oxygen delivered to the Patient Completely Enclosed in a Pressurized Environment Brief Historical Perspective D. Jourdanet Paul Bert 1880 s 6

7 Session 45 Sunday, September 11 th 011 Milwaukee: Mechanism of Action A T A Atmospheres Absolute 1 ATA = Sea Level Pressure 7

8 Session 45 Sunday, September 11 th 011 Normobaric Conditions O Hyperoxygenation 1ATA Air Total Pressure O Content w/ HBO ATA mmhg (VOL %) (0.3 in air) (0.81 in air) Hyperbaric Conditions Normobaric Conditions 3ATA Oxygen Normoxic zone 64 u Ischemic zone 64 u Hyperbaric Conditions 50 u Normoxic zone 50 u O Diffusion Overlap 64 u 8

9 Session 45 Sunday, September 11 th 011 OXYGEN RESPONSE CURVES ( 90 min tx ) A T A of O x y g e n O Blood Muscle Sub Q TIME IN HOURS Chamber Types / Oxygen Delivery Oxygen Delivery MULTIPLACE MONOPLACE Accepted Indications Emergent Indications Decompression Sickness Gas Embolism Gas Gangrene Acute Ischemia Extreme Anemia Carbon Monoxide Cyanide (Smoke Inhalation) Thermal Burns Elective Indications Radiation Injury Chronic Osteomyelitis Diabetic Wounds Problem Wounds 9

10 Session 45 Sunday, September 11 th 011 Radiation ~ 30% Diabetic ~ 30% Flaps & Grafts ~ 15% Osteomyelitis ~ 15% Anaerobic ~ 5% CO / AGE / DCS / Anemia ~ 5% Approximate distribution for outpatient program. Practice & Hospital variations are common. Side Effects Barotrauma (Otic, Pulmonary, Odontic) Oxygen Toxicity (CNS, Pulmonary, Ocular) Hypoglycemia Claustrophobia Congestive Heart Failure Contraindications ABSOLUTE Untreated Pneumothorax RELATIVE Claustrophobia Fever CHF, COPD High FiO Chemotherapeutic Agents Tissue & Cellular Effects Tissue Hyperoxygenation Salvage marginal tissue Satisfy increased demand Stimulates Angiogenesis Decreases Tissue Edema Antimicrobial Antioxidant Growth Factor Up Regulation Literature Review Basic Science, Animal & In Vitro Data 10

11 Session 45 Sunday, September 11 th 011 O Enhanced Host Resistance The killing capacity of granulocytes is normal only to the degree that oxygen is available HBO O Dermal necrosis following 10 7 E coli Knighton DR; Archives of Surgery 1986: p191 Diameter of necrosis (cm) % 1% 45% Neovascularization 1 hrs 4 hrs 36hrs 48hrs Regulation of Wound-Healing Angiogenesis The Effect of Oxygen Gradients Knighton, Silver & Hunt - Surgery, 1981 Normal Conditions Membrane Closed Central Hypoxia healing time "Central" Hyperoxia Membrane Open No oxygen gradient Becomes a "problem wound" healing time RABBIT EAR CHAMBER MODEL 11

12 Session 45 Sunday, September 11 th Knighton, Hunt 1981 O Impermeable Cover Normal Conditions Membrane Closed Central Hypoxia healing time 40 0 O Permeable Cover "Central" Hyperoxia Membrane Open No oxygen gradient Becomes a "problem wound" healing time Days after first vessels entered chamber "Peripheral" Hyperoxia Membrane Closed Supplemental O - Simulating H B O conditions healing time Conclusions Oxygen gradients govern angiogenesis Capillary growth stops when the gradient is flat Experimental Design I/R injury and HBO treatment 4 hours Hypoxia/Hypoglycemia 0 hours Normoxia/ Normoglycemia HUVECs 1.5 hours HBO at.5 ATA 18.5 hours Normoxia/ Normoglycemia Buras, et al Hyperbaric oxygen down regulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. Am. J. Physiol. Cell Physiol. 78: C9 C30,

13 Session 45 Sunday, September 11 th 011 HBO down-regulates hypoxia/hypoglycemiainduced VCAM-1 expression HBO increases PDGFR and EGFR expression human dermal fibroblasts Control + HBO.5 ATA 90 min control hypoxia/hypoglycemia hypoxia/hypoglycemia HBO.5 ATA 1.5 h = EGFR = PDGFR Buras, et al Hyperbaric oxygen down regulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. Am. J. Physiol. Cell Physiol. 78: C9 C30, 000. Buras, et al Hyperbaric oxygen down regulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. Am. J. Physiol. Cell Physiol. 78: C9 C30, 000. Thom, Stephen R., Veena M. Stem cell mobilization by hyperbaric oxygen. Am J Physiol Heart Circ Physiol 90: H1378 H1386, 006. The Effect of Hyperbaric Oxygen Therapy on a Burn Wound Model in Human Volunteers Literature Review Clinical Data and Trials Niezgoda JA, Plast Reconstr Surg 1997 May;99(6): HBO 13

14 Session 45 Sunday, September 11 th 011 HBO Therapy in a Human Burn Model Niezgoda JA, Plastic Reconstr Surg 1997 Study Type: prospective, randomized, blinded trial Methods: standardized wound model Suction cup Exposure of dermis Ultraviolet Radiation Control gp: 8.75% oxygen at.4 ATA bid x 3 days HBO gp: 100% oxygen at.4 ATA bid x 3 days Measurements: wound size hyperemia exudation epithelialization WOUND HYPEREMIA ~laser doppler flow BPM UNITS 35 Niezgoda JA, Plast Recon Surg HBO Subject Control Day WOUND SIZE MEASUREMENTS Niezgoda JA, Plast Recon Surg 1997 WOUND EXUDATION 0.4 Cm HBO Subject Control Day HBO Subject Control Day HBO Therapy in a Human Burn Model Outcome: Wound size- 35% reduction in lesion size (day ) p < 0.05 Hyperemia- 4% reduction in wound hyperemia by laser-doppler (day ) p < 0.03 Exudation- % reduction in exudate (day ) p < 0.04 Epithelialization- no difference in time to complete epithelialization NS 14

15 Session 45 Sunday, September 11 th 011 HBO in Diabetic Foot Ulcers Non randomized comparative study ٠18 patients treated with HBO ٠10 controls identical wound care only Results (p=0.001) ٠16/18 HBO treated patients healed ٠1/10 control patients healed G. Baroni et.al. Diabetes Care, 1987; 10:81-86 HBO in DFU Non randomized comparative study ٠184 consecutive patients with DFU ٠HBOT adjunctive to standard of care Results ٠115 (63%) Healed ٠31 (17%) No improvement ٠38 (0%) Amputation 9 (4.9%) Major (BKA) 9 Minor Kaya A, Aydin F, Altay T. Can major amputation rates be decreased in diabetic foot ulcers with hyperbaric oxygen therapy? International Orthopaedics. August 008 HBO in DFU Prospective randomized study of 70 patients using HBO treatment in DFU ٠35 Patients each group ٠HBOT Group 3 of 35 (8.6%) patients major amputation 1AKA, BKA ٠Control Group 11 of 33 (33.3%) patients major amputation 4AKA, 7BKA ٠P=0.016 Faglia E, Favales F, Aldeghi A. Adjunctive systemic hyperbaric oxygen therapy in the treatment of diabetic foot ulcer. A randomized study. Diabetes Care 1996;19: HBO in DFU Prospective RCT of 94 patients with DFU ٠Wagner Grade, 3, and 4 ٠Randomized to HBOT vs Placebo Control ٠HBOT (N=48) Complete Healing 5/48 (5%) ٠Placebo Control Group (N=4) 1/4 (9%) P=0.03 ٠Patients completing >35 HBOTxs HBOT Group 3/38 (61%) Control 10/37 (7%) P =0.009 Londahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen therapy facilitates Healing of chronic foot ulcers in patients with diabetes. Diabetes Care 33: ,

16 Session 45 Sunday, September 11 th 011 New CMS Coverage Indication Diabetic Foot Ulcer Lower extremity wound due to Diabetes ٠Type I or Type II DM Wagner Grade III or higher Failed standard wound care ٠no measurable signs of healing for 30 days ٠Decrease in volume or size ٠Decrease in exudate ٠Decrease in necrotic tissue Lower Extremity Diabetic Wounds Wagner III, IV or V Have the 8 elements of Standard Wound Care been met? - Vascular Status? - Correction of Vasc Problems? - Nutritional Status? - Glycemic Control? - Debridement? - Appropriate Dressing? - Appropriate Off Loading? - Resolution of Infection? NO Decrease in Wound Volume in the past 30 days? Begin HBO.0-.4 ATA QD 16