The Role of Hyperbaric Therapy in Wound Management

Transcription

1 No Conflicts to declare No off label use discussed Define the role of oxygen as a signal molecule Understand the difference between oxygen pressure versus oxygen content Define the role of oxygen and the clearance of bacteria from tissue Identify the relationship between HBO, stems cells, and wound The Role of Hyperbaric Therapy in Wound Management How is HBO administered? How does it work? What is used for? When do you use it? 1

2 A T A Atmospheres Absolute 1 ATA = Sea Level Pressure O2 Hyperoxygenation Total Pressure Normoxic zone 64 u O2 Content w/ HBO ATA mmhg (VOL %) (0.32 in air) (0.81 in air) Normoxic zone 250 u Ischemic zone 250 u O2 Diffusion Overlap 64 u 64 u 2

3 OXYGEN RESPONSE CURVES ( 90 min tx ) 2.0 A T A of O x y g e n 1.8 Blood Muscle Sub Q O TIME IN HOURS The killing capacity of granulocytes is normal O2 Enhanced Host Resistance only to the degree that oxygen is available HBO O2 Dermal necrosis following 107 E coli Diameter of necrosis (cm) Knighton DR; Archives of Surgery 1986: p % 4 21% O2 Neovascularization % 1 12 hrs 24 hrs 36hrs 48hrs 3

4 Normal Conditions Membrane Closed Central Hypoxia Regulation of Wound-Healing Angiogenesis The Effect of Oxygen Gradients "Central" Hyperoxia Membrane Open No oxygen gradient Becomes a "problem wound" RABBIT EAR CHAMBER MODEL Normal Conditions Knighton, Hunt 1981 Membrane Closed Central Hypoxia 60 O2 Impermeable Cover 40 Membrane Open No oxygen gradient Becomes a "problem wound" 20 "Central" Hyperoxia O2 Permeable Cover "Peripheral" Hyperoxia Days after first vessels entered chamber Conclusions Oxygen gradients govern angiogenesis Membrane Closed Supplemental O2 Simulating H B O conditions 80 Hunt TK- Surgery, 1981 Is oxygen pressure ( po2 ) more important than oxygen content? Capillary growth stops when the gradient is flat 4

5 Tissue Oxygenation, Anemia & Perfusion In Relation to Wound Healing Tissue Oxygenation, Anemia & Perfusion In Relation to Wound Healing Jonsson 1991 Jonsson 1991 Unfortunately the anemia question diverts attention Post-op wounds were created using a std porous extruded polytetraflouroethylene (eptfe) tubing model from the significance of data that link closely to arterial & tissue oxygen pressure Measurements: & far less closely to arterial oxygen content Wound O2 pressure Collagen deposition Collagen g/cm vs oxygen pressure Jonsson 1991 Collagen g/cm vs hematocrit Jonsson Max po2 mmhg Conclusions Jonsson 1991 C ollagen deposition was proportional to wound oxygen tension (pressure) and measures of perfusion Post op hct % Inspired O2 vs Tensile Strength Do we know what the ideal po2 should be for maximum collagen production? A nemia, (blood loss) had no effect A lthough oxygen is essential to many aspects of & must be delivered at adequate partial pressures, reparative tissue consumes a relatively small amount. 5

6 Effect of Varying Ambient Oxygen Tensions on Wound Metabolism & Collagen Synthesis Oxygen tension vs Collagen production Increasing po2 from 80 to 200 mm raises the transported oxygen by 1%. The corresponding increase in collagen accumulation is 50%! Hunt and Pai, 1972 Hydroxyproline (mg) 20 Dorsal wire mesh cylinder in rats Varied FIO2 14%, 20%, 45% 10 Per Wound Total tissue growth & collagen content Dry Weight 5 Wet Weight Total Hydroxyproline 0 Arterial po Conclusions Rate of collagen synthesis is more closely related to po2 than oxygen carrying capacity. Adequate O2 is essential for cross-linking of collagen (tensile strength) Tissue oxygenation depends on perfusion or increased FI02 More than a Metabolite Upregulation of Platelet Derived Growth Factor (PDGF) receptor gene expression Bonomo SR Undersea & Hyperbaric Med 1998; 25:

7 Dose dependent O2 effect on angiogensis mediated by Vascular Endothelial Growth Factor (VEGF) Serial HBO increases NO production in vascular endothelial cells which appears to be gene up regulation of Nitric Oxide Synthase Gibson JJ, Surgical Forum 1997; 48: Angeles AP. Wound Rep & Regeneration 1997; 5: A104 Siddiqui A, Plastic & Recon Surg 1997; 99: A single HBO tx (2.5 ATA) increases human fibroblast proliferation and is associated w/ increased expression of: A single HBO tx (2.4 ATA) stimulated human fibroblast proliferation for 72 hrs after exposure A second exposure on the same day did not increase or prolong the effect Epidermal Growth Factor Receptors Platelet Derived Growth Factor Receptors Tompach PC, Int J Oral Maxillofac Surg 1997;26:82-86 Reenstra WR UHMS :53 & 25:54 In a murine model, we found HBO augments stem cell mobilization, recruitment to ischemic wounds, & hastens ischemic wound Thom S, Am J Physiol Heart Circ Physiol 2005 % CD34+ Gated Cell Population Stem cell mobilization by HBO * * 1.0 p < * 0 Pre Post HBO #1 * * Pre Post HBO #10 Pre Post HBO #20 7

8 Hyperbaric Oxygen Therapy: A new physiologic concept A single 60 min HBO treatment produces cellular mitosis for 24 hrs A dose dependent effect was present through 2.5 ATA Hehenberger K, Wound Rep Reg 1997; 5: Thomas Mustoe Plast Reconstr Surg 1997; 99: Cells in a wound view oxygen pressure as a trigger signaling that enough oxygen is present to proceed with normal Hyperbaric Oxygen Therapy: A new physiologic concept Thomas Mustoe Plast Reconstr Surg 1997; 99: Regular exposure to the What are the commonly accepted indications for HBO? threshold level reinforces the signal and supplies an important factor for repair Approximate distribution for outpatient program. Practice & Hospital variations are common. Radiation ~ 30% Diabetic ~ 30% Flaps & Grafts ~ 15% Osteomyelitis ~ 15% Hyperbaric oxygen treatment in chronic wounds in general, diabetic foot ulcers in particular, has been recommended by 7 independent evidenced-based reviews: Blue Cross/Blue Shield Technology Assessment 1999 American Diabetes Association Foot Council 1999 Wound Healing Society 1999 British Journal of Medicine 2000, 2001, 2002 Medical Services Advisory Committee, Australia AHRQ Report to CMS 2001 CMS Coverage Decision for HBO in DFU 2002 Anaerobic ~ 5% CO / AGE / DCS / Anemia ~ 5% 8

9 1999 Consensus Conference on Diabetic Foot Wound Care BCBS Technology Assessment Program Vol 14 (13), August 1999 Hyperbaric Oxygen Therapy for Wound Healing-Part I American Diabetes Association There is sufficient evidence to support the use of HBO in the treatment of adequately perfused chronic non wounds of the lower extremity in combination with std wound care. Pts who have received std wound care plus HBO have shown better wound rates & fewer amputations in comparison to similar pts treated with std wound care. It is reasonable to use this modality to treat severe & limb- or life threatening wounds that have not responded to other treatments, particularly if ischemia that cannot be corrected by vascular procedures is present. Diabetes Care 1999;22: Wound Healing Society - Guidelines for Chronic Wound Care, June 21, 1999, Arterial Subcommittee British Journal of Medicine, Clinical Evidence co-chaired by Drs. Harriet Hopf & Judith West For diabetic foot ulcer, likely to be beneficial...in communities where accessible, HBO should be considered std of care for wounds that are hypoxic (due to ischemia), and the hypoxia is reversible by hyperbaric oxygenation. The tissue hypoxia, reversibility, & responsiveness to oxygen challenge are measurable by TCOMs. Two small RCTs have found that, compared with routine care, systemic HBO reduces the risk of foot amputation in people with severe infected foot ulcers. June, 2001 Issue 5 Major Amputation Rates HBO Therapy and the treatment of Ischemic (Grade 4/5) Diabetic Foot Ulcers Faglia, Diabetes Care 1996;19:1338 HBO Non-HBO After revascularization 2/13 (15.4) 4/13 (30.8) No revascularization 1/22 (4.5) 7/20 (35.0) All major amputations 3/35 (8.6)* 11/33 (33.3) Prospective Randomized Surgical Blinding Faglia Diabetes Care 1996;19:1338 * p=

10 HBO therapy in ischemic, diabetic, lower-extremity ulcers: a double-blind randomized controlled trial % Healing Abidia A. British Journal of Surgery 2001; 88: % HBO p = % Control 20 Abidia A et al British Journal of Surgery 2001; 88:744 Randomized, double-blinded, placebo-controlled trial Wagner grade 2, 3, or 4 ulcers present for >3 months Unresponsive to comprehensive care for >2 months Vascular assessment / interventions on all pts (55%) Multiplace chamber 2.5 ATA x 85 min, QD, M-F n = 94 Londahl M, Diabetes Care Per protocol analysis (35 tx) at 12 months: HBO group: 61% Placebo: 27% P < All patient analysis for at 12 months: HBO group: 52% P < 0.03 Placebo: 29% Londahl M, Diabetes Care 2010 Journal of Diabetes and its Complications 2002, Vol 16: Hyperbaric oxygen therapy for diabetic foot ulcers; Double blind PRCT design Long-term (3 yr) follow-up The results provides additional support for the use of HBO to enhance in patients with diabetes. HBO doubled the rate compared to placebo. Londahl M, Diabetes Care 2010 Majid Kalani, Gun Jörneskog, Nazanin Naderi, Folke Lind & Kerstin Brismar 10

11 Results Objective % Healing Investigate the long-term effect of HBO in treatment of hypoxic diabetic foot ulcers HBO p = % Control 40 % Amputation Control 48% 20 HBO 33% 12% 0 Conclusions A positive association of HBO with Accelerated Amputation reduction Long term success 1 million diabetics w/ wounds 60% of all amputations/yr (120,000 amputations /yr in the US) Average initial cost: $40, Higher ipsalteral amputations in 22% Contralateral amputation at 10% per yr Only 68% alive at 4 years Cost of primary amputation $1.5 billion annually Stump modification in two yrs $1.0 billion annually ~only 45% rehabilitated 60k 50k Cianci P, Hyper Med. 1988; 3: diabetic pts 42%w/ revascularization Referred for non wounds Refit Prosthesis PT 40k 90% Salvage 30k 20k Rehab Hospital Charges 10k 0k ~ 22 K Savings + 1 limb HBO Avg for SALVAGE Surgical Hospital Avg for AMPUTATION 11

12 Cianci P, J Am Podiatric Med Assoc1994; 84: diabetic pts (55% revascularized but w/ limb threatening Wagner Grade 4 wounds) Salvage rate of 78% SALVAGE - defined as bipedal ambulation if two limbs were originally present & wound coverage remaining intact for 1 yr. Hosp = $16,500 Cost of primary amputation ~ $40,000 + Charges HBO Charges = $15,900 TOTAL COST $32,000 + Additional costs of prosthesis, rehabilitation, & occasional surgical revision ~ $30,000 + Useful & Effective AHA Class I Indication is supported by PRT data Indication is supported by blinded PRT data The weight of current evidence, as derived by randomized trials, favors use of HBO The financial effectiveness of limb salvage has also been demonstrated TOTAL COST $70,000 + Approximate distribution for outpatient program. Practice & Hospital variations are common. Diabetic ~ 30% Radiation ~ 30% Radiation Injury Flaps & Grafts ~ 15% 30% Osteomyelitis ~ 15% Radiation Injury 30% Anaerobic ~ 5% CO / AGE / DCS / Anemia ~ 5% Radiation Injury - Objectives Understanding Radiation Injury How does HBO Help? Common Indications Scope Problems 1.2 million of newthe cases of invasive cancer will be diagnosed this yr in the United States. Half of these patients will receive radiation therapy as part of their management. Serious radiation complications will occur in ~ 5% of patients receiving radiation. This represents ~ 30,000 cases / year 12

13 Radiation - Late Effects Radiation Clinical Problems A progressive, proliferative, endarteritis Obliterative process Destroys tissue blood supply Hypoxic, fibrotic legacy "A shallow oxygen gradient forever commits irradiated tissue to exist at a lower tissue perfusion level " Robert Marx 1982 The Effect of Oxygen Gradients Knighton, Silver & Hunt - Surgery, 1981 Normal Conditions Membrane Closed Central Hypoxia Regulation of Wound-Healing Angiogenesis "Central" Hyperoxia Membrane Open No oxygen gradient Becomes a "problem wound" Loss of the oxygen gradient arrests RABBIT EAR CHAMBER MODEL 13

14 Radiation Injury - Objectives Understanding Radiation Injury How does HBO Help? Common Indications Normal Conditions Membrane Closed Central Hypoxia Becomes a "problem wound" "Peripheral" Hyperoxia Membrane Closed Supplemental O Membrane Open No oxygen gradient "Central" Hyperoxia Simulating H B O conditions Radiation Injury - Objectives Understanding Radiation Injury How does HBO Help? Common Indications

15 Common Indications Osteoradionecrosis Cochrane Systematic Review (ORN) Radiation Cystitis These trials suggest that for people with late radiation tissue injury affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. Radiation Proctitis Vaginal Radionecrosis Cerebral Radionecrosis Laryngeal Radionecrosis Bennett MH, Feldmeier J, Hampson N, et al Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database of Systematic Reviews 2005 Prep for Skin Graft AHA Class I Useful & Effective Indication is supported by PRT data Deemed to be a Standard of Care by NCI Compromised Grafts & Flaps Compromised Amputation Sites Chronic Refractory Osteomyelitis The weight of current evidence, as derived by these trials, favors use of HBO Demonstrated financial effectiveness No proven alternative therapies Risks Fire Ear barotrauma Pneumothorax Visual changes Oxygen overdose Contraindications Untreated Pneumothorax Spontaneous Pneumothorax Adriamycin Bleomycin Cis-Platin Sulfamylon 15

16 A chronic wound is a window to underlying disease. Each wound is a symptom of underlying infirmities that undermine the potential for. Dean Kane, MD 16