The effects of hyperbaric oxygen therapy on chronic

The effects of hyperbaric oxygen therapy on chronic diabetic ulcer healing Capstone Project, MPAS 218 Spring 2019 Breann Kinsey 04/16/2019

Disclaimer • No conflicts of interest.

PICOT Question • In diabetic adults with chronic lower extremity (LE) ulcers, what is the effect of hyperbaric oxygen therapy (HBOT), compared to standard wound care alone, on the healing process up to one year after treatment? Chronic diabetic ulcer = LE wound x >1 month, failed standard wound care Standard wound care = any localized treatment (topical ointments/ solutions, dressings, or tissue debridement). 8, 9

Key Objectives • Chronic diabetic wound physiology includes persistence of inflammatory phase of the wound healing process. • No defined treatment regimen to effectively heal chronic diabetic wounds. • HBOT has the potential to play an effective role as an adjunct tool in the chronic wound repair process. • Research limitations hinder its use as a standard treatment option. • More research should be conducted in order to strongly support the use of HBOT.

Background Information

Diabetic LE Wounds • 15% of diabetic patients develop foot ulcers 14 -24% of those patients will require an amputation 1 • Average cost of healing a single non-infected ulcer = $8, 0002 • Average cost for a major amputation = $45, 000 ~50% of people with amputations develop ulcers in the opposite limb within 18 months 3 yr mortality after one amputation is 20 -50%. 2

Normal vs Chronic Wound Healing Excerpted from Schreml S, Szeimies RM, Prantl L, Karrer S, Landthaler M, Babilas P. Oxygen in acute and chronic wound healing. Br J Dermatol. 2010; 163(2): 257 -268. doi: 10. 1111/j. 1365 -2133. 2010. 09804. x

HBOT • 100% oxygen exposure at ~2 -3 atmosphere absolute (ata) pressure for several minutes QD or BID. • Performed by placing patient in a pressurized chamber and allowing them to breathe concentrated oxygen. • Role of HBOT: maintain tissue oxygen saturation break prolonged inflammatory cycle continue through the healing process. 6 -8 • Works on ischemic portion of diabetic wounds – supplementary treatment

Excerpted from https: //www. bethesdahbot. com/ Excerpted from https: //www. hyperbaricflorida. com/

Evidence

Ischemic/ Hyperglycemic States André-Lévigne, et al. • Strengths: Diabetic ulcer conditions Experimental and control groups Strong research design and statistical analysis • Limitations: Conducted on rats Small sample size Artificially created conditions Excerpted from André-Lévigne D, Modarressi A, Pignel R, Bochaton-Piallat ML, Pittet-Cuénod B. Hyperbaric oxygen therapy promotes wound repair in ischemic and hyperglycemic conditions, increasing tissue perfusion and collagen deposition. Wound Repair Regen. 2016; 24(6): 954 -965. doi: 10. 1111/wrr. 12480

Severity and Timing Fife, et al. • Strengths: Target population • Limitations: Retrospective study Lack of control group Excerpted from https: //dukimgy. pw/Wagner-Scale-for-diabetic-ulcers. Wound-care-Skin-care. html

Safety Hadanny, et al. • Strengths: Large sample size Thorough data analysis • Limitations: Retrospective study Self-reported data Excerpted from Hadanny A, Meir O, Bechor Y, Fishlev G, Bergan J, Efrati S. The safety of hyperbaric oxygen treatment – retrospective analysis in 2, 334 patients. Undersea Hyperb Med. 2016; 43(2): 113 -122. https: //www. researchgate. net/profile/Shai_Efrati 2/publication/ 303569636_The_safety_of_hyperbaric_oxygen_treatment_-_retrospective_analysis_ in_2334_patients/links/5760 cfdf 08 ae 244 d 0370 d 4 da/The-safety-of-hyperbaric-oxygentreatment-retrospective-analysis-in-2 -334 -patients. pdf. Accessed August 29, 2018.

Summary of the Evidence • HBOT has the potential to promote complete wound closure in ischemic and hyperglycemic wound environments. • More severe wounds may benefit the most. • Uninterrupted treatment courses have more favorable results. • Considered generally safe with continuous patient evaluation. • Lack in strong quality of evidence to consider HBOT as a standard treatment option. Limitations of current studies are too significant.

General Conclusion • HBOT shows promising results and is considered safe. • More research should be conducted in order to make it a conventional treatment option.

Practice Implications • Consider HBOT as a possible treatment option for chronic LE diabetic ulcers.

Gaps in Knowledge • Established treatment protocols? • Cost effectiveness? • Availability of hyperbaric chambers? • Other implications?

Future Research • Randomized controlled trials • Larger sample sizes • Specific treatment protocols • Cost effectiveness • Other implications

References • Diabetic Wound Care. American Podiatric Medical Association. https: //www. apma. org/Patients/Foot. Health. cfm? Item. Number=981. Updated 2018. Accessed November 28, 2018. • Kruse I, Edelman S. Evaluation and Treatment of Diabetic Foot Ulcers. Clinical Diabetes. 2006; 24(2): 91 -93. https: //doi. org/10. 2337/diaclin. 24. 2. 91. • Kranke P, Bennett MH, Martyn-St James M, et al. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. 2015; 24(6): CD 004123. doi: 10. 1002/14651858. CD 004 123. pub 4. • Stoekenbroek RM, Santema TB, Legemate DA, et al. Hyperbaric oxygen for the treatment of diabetic foot ulcers: a systematic review. Eur J Vasc Endovasc Surg. 2014; 47(6): 647 -655. doi: 10. 1016/j. ejvs. 2014. 03. 005. • Löndahl M, Katzman P, Hammarlund C, Nilsson A, Landin-Olsson M. Relationship between ulcer healing after hyperbaric oxygen therapy and transcutaneous oximetry, toe blood pressure and ankle-brachial index in patients with diabetes and chronic foot ulcers. Diabetologia. 2011; 54(1): 65 -68. doi: 10. 1007/s 00125 -010 -1946 -y • Fife CE, Buyukcakir C, Otto G, et al. Factors influencing the outcome of lower-extremity diabetic ulcers treated with hyperbaric oxygen therapy. Wound Repair Regen. 2007; 15(3): 322 -31. doi: 10. 1111/j. 1524 -475 X. 2007. 00234. x • Medical Advisory Secretariat. Hyperbaric oxygen therapy for non-healing ulcers in diabetes mellitus: an evidence-based analysis. Ontario Health Technology Assessment Series 2005; 5(11): 1 -28. https: //www. ncbi. nlm. nih. gov/pmc/articles/PMC 3382405/. Accessed June 19, 2018.

References • Sureda A, Batle JM, Martorell M, et al. Antioxidant response of chronic wounds to hyperbaric oxygen therapy. PLo. S One. 2016; 11(9): e 0163371. doi: 10. 1371/journal. pone. 0163371 • Nicholas M, Yeung J. Current status and future of skin substitutes for chronic wound healing. J Cutan Med Surg. 2017; 21(1): 23 -30. doi: 10. 1177/1203475416664037. • Schreml S, Szeimies RM, Prantl L, Karrer S, Landthaler M, Babilas P. Oxygen in acute and chronic wound healing. Br J Dermatol. 2010; 163(2): 257 -268. doi: 10. 1111/j. 1365 -2133. 2010. 09804. x • de Smet GHJ, Kroese LF, Menon AG, et al. Oxygen therapies and their effects on wound healing. Wound Repair Regen. 2017; 25(4): 591 -608. doi: 10. 1111/ wrr. 12561 • André-Lévigne D, Modarressi A, Pignel R, Bochaton-Piallat ML, Pittet-Cuénod B. Hyperbaric oxygen therapy promotes wound repair in ischemic and hyperglycemic conditions, increasing tissue perfusion and collagen deposition. Wound Repair Regen. 2016; 24(6): 954 -965. doi: 10. 1111/wrr. 12480 • Hadanny A, Meir O, Bechor Y, Fishlev G, Bergan J, Efrati S. The safety of hyperbaric oxygen treatment – retrospective analysis in 2, 334 patients. Undersea Hyperb Med. 2016; 43(2): 113 -122. https: //www. researchgate. net/profile/Shai_Efrati 2/publication/ 303569636_The_safety_of_hyperbaric_oxygen_treatment_-_retrospective_analysis_ in_2334_patients/links/5760 cfdf 08 ae 244 d 0370 d 4 da/The-safety-of-hyperbaric-oxygen-treatmentretrospective-analysis-in-2 -334 -patients. pdf. Accessed August 29, 2018.