Wound Care J Wound Ostomy Continence Nurs. 2017;00(0):1-10. Published by Lippincott Williams & Wilkins Adjunctive Hyperbaric Oxygen Therapy for Healing of Chronic Diabetic Foot Ulcers A Randomized Controlled Trial Chen-Yu Chen ¡ Re-Wen Wu ¡ Mei-Chi Hsu ¡ Ching-Jung Hsieh ¡ Man-Chun Chou ABSTRACT PURPOSE: The purpose of this study was to compare the effect of standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care alone on wound healing, markers of infl ammation, glycemic control, amputation rate, survival rate of tissue, and health-related quality of life in patients with diabetic foot ulcers (DFUs). DESIGN: Prospective, randomized, open-label, controlled study. SUBJECTS AND SETTING: The sample comprised 38 patients with nonhealing DFUs who were deemed poor candidates for vascular surgery. Subjects were randomly allocated to an experimental group (standard care plus HBOT, n = 20) or a control group (standard care alone, n = 18). The study setting was a medical center in Kaohsiung City, Taiwan. METHODS: Hyperbaric oxygen therapy was administered in a hyperbaric chamber under 2.5 absolute atmospheric pressure for 120 minutes; subjects were treated 5 days a week for 4 consecutive weeks. Both groups received standard wound care including debridement of necrotic tissue, topical therapy for Wagner grade 2 DFUs, dietary control and pharmacotherapy to maintain optimal blood glucose levels. Wound physiological indices were measured and blood tests (eg, markers of infl ammation) were undertaken. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short Form. RESULTS: Complete DFU closure was achieved in 5 patients (25%) in the HBOT group (n = 20) versus 1 participant (5.5%) in the routine care group (n = 18) ( P = .001). The amputation rate was 5% for the HBOT group and 11% for the routine care group ( χ 2 = 15.204, P = .010). The HBOT group showed statistically signifi cant improvements in infl ammation index, blood fl ow, and < health-related quality of life from pretreatment to 2 weeks after the last therapy ended (P .05). Hemoglobin A1c was signifi cantly lower in the HBOT group following treatment (P < .05) but not in the routine care group. CONCLUSIONS: Adjunctive HBOT improved wound healing in persons with DFU. Therapy also reduced the risk of amputation of the affected limb. We assert that at least 20 HBOT sessions are required to be effective. KEY WORDS: Clinical trials , Diabetes mellitus , Diabetic foot ulcers , Hyperbaric oxygen therapy , Nonhealing wounds , Nursing care , Quality of life . INTRODUCTION 25%. 1-3 Approximately 40% of patients with diabetic foot in- fections return to hospital for repeated treatment, and 1 in 6 of Foot ulcers and infections are prevalent in persons with dia- these individuals will die within 1 year. 4 Th e pathophysiology betes mellitus; reported prevalence rates vary from 1.7% to of diabetic foot ulcers (DFUs) is not entirely understood. In- dividuals with diabetes mellitus often have impaired leukotaxis and phagocytosis function that increase the likelihood of de- Chen-Yu Chen, MSN, RN, Hyperbaric Oxygen Therapy Center, Kaohsiung 5 Chang Gung Memorial Hospital, Kaohsiung, Taiwan, R.O.C.; and Chang Gung veloping a wound infection by 17-fold. A nonhealing, infect- University, College of Medicine, Taoyuan, Taiwan, R.O.C. ed DFU damages both soft tissue and bone; 85% of individu- Re-Wen Wu, MD, Department of Orthopaedic Surgery, Kaohsiung Chang als who develop a DFU ultimately undergo amputation, and Gung Memorial Hospital, Kaohsiung, Taiwan, R.O.C.; and Chang Gung 68% will die within 5 years of amputation. 6-8 Th e severity of University, College of Medicine, Taoyuan, Taiwan, R.O.C. the ulcer, angiopathy, infection, and poor blood glucose con- Mei-Chi Hsu, PhD , RN, Department of Nursing, I-Shou University, Kaohsiung trol are important predictors for diabetic foot amputation. 9-11 City, Taiwan, R.O.C. Hyperbaric oxygen therapy (HBOT) is used as adjuvant Ching-Jung Hsieh, MD, Department of Internal Medicine, Paochien Hospital, therapy in conjunction with topical and systemic thera- Ping Tung, Taiwan, R.O.C. py frequently including debridement, recombinant human Man-Chun Chou, MSN, RN, Kaohsiung Chang Gung Memorial Hospital, platelet-derived growth factor, or other skin substitutes in Kaohsiung, Taiwan, R.O.C. persons with nonhealing or deteriorating DFU. 12 Evidence The authors declare that they have no confl ict of interests. concerning the effi cacy of HBOT for healing DFUs is mixed. The funder had no role in the study design, data collection and analysis, Some researchers report greater effi cacy when HBOT is com- decision to publish, or preparation of the manuscript. pared to sham or placebo treatment, 13-16 but others found no Correspondence: Mei-Chi Hsu, PhD, RN, Department of Nursing, I-Shou diff erences. 17-19 Hyperbaric oxygen therapy also promotes res- University, No. 8, Yida Rd, Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan ( [email protected] ). olution of infection in persons with DFU, and it reduces the 14,15 DOI: 10.1097/WON.0000000000000374 likelihood of amputation. Copyright © 2017 by the Wound, Ostomy and Continence Nurses Society™ JWOCN ¡ Month/Month 2017 1 Copyright © 2017 Wound, Ostomy and Continence Nurses Society™. Unauthorized reproduction of this article is prohibited. 2 JWOCN ¡ Month/Month 2017 www.jwocnonline.com Despite mixed evidence concerning its effi cacy, HBOT Study Procedures has been advocated and adopted for DFU treatment in some Patients were randomly allocated to HBOT plus routine care wound care centers. Th e aim of this study was to compare the or routine care alone groups. Group allocation was randomly eff ect of HBOT plus standard wound care to standard wound generated by a computer and sealed by the primary researcher care alone in the treatment of DFU. Outcome measures were in opaque, serially numbered envelopes. Another researcher wound size, amputation rate, survival rate of tissue in the enrolled participants and assigned participants to interven- aff ected limb, markers of infl ammation, glycemic control, tions. Patients in both the intervention (HBOT) and control bacterial colonization (distribution of microorganism culture (routine care only) groups were hospitalized during the study, isolated from the wound), and health-related quality of life which reduced variability in standard care ( Figure 1 ). (HRQOL). Standard care incorporated topical and systemic therapy for DFUs. It included maintaining good blood glucose control, offl oading, debridement of necrotic tissue, antibiotic therapy METHODS for management of diabetic foot infection, and topical dress- We conducted a prospective, randomized, controlled trial to ings, depending on the type and grade of the ulcer. An array evaluate the effi cacy of HBOT plus standard therapy to stan- of wound dressings was used for topical therapy. For exam- dard therapy alone for treatment of DFUs. Data were collected ple, silver-impregnated dressings such as Flamazine ointment from June 2011 to June 2013. Th e time frame for data col- (silver sulfadiazine) were applied to Wagner grade 1 and 2 lection was divided into following 4 segments: pretreatment DFUs. Hydrocolloid dressings, topical amoxicillin, and hy- (before fi rst administration of HBOT; T1), during treatment drogels were applied for Wagner grade 2 and 3 DFUs; wound (at the 10th administration of HBOT; T2), posttreatment dressings and topical piperacillin/ciprofl oxacin were used to (at the 20th administration of HBOT; T3), and follow-up manage Wagner grade 3 and 4 DFUs. Antibiotic therapy was (2 weeks after the last therapy ended; T4). Th e study setting driven by protocol and culture and sensitivity reports. was a medical center in Kaohsiung City, Taiwan. Hyperbaric oxygen therapy was delivered via a multiperson Inclusion criteria were (1) adults 20 years or older, (2) diag- chamber. Patients allocated to the HBOT group were placed nosis of diabetes mellitus, (3) nonhealing DFUs that had not in a hyperbaric chamber daily 5 days per week for 4 consecu- achieved closure after at least 2 months and following treat- tive weeks for a total of 20 sessions. Patients were treated with ment for at least 1 month, (3) Wagner wound classifi cation 2.5 absolute atmospheric pressure for 120 minutes. Th e time of grade 1, 2, and 3 ulcers, and (4) deemed appropriate for period of the intervention was approximately 1 month. Th e hospital admission because of skin ulcer and soft-tissue infec- intervention program was carried out by the primary research tion. Exclusion criteria were (1) gangrene, (2) contraindication team (C.-Y.C. and R-W.W.). for HBOT such as untreated pneumothorax, active cancerous condition, chronic obstructive pulmonary disease, and pul- Outcome Measures monary emphysema with retention of CO2 , and (3) planned We selected multiple outcome measures to evaluate the effi - vascular surgical procedures or revascularization of the limb. cacy of HBOT as adjunctive therapy for patients with non- Study procedures were reviewed by the institution- healing DFU. Th ey included wound physiological indices and al review board of the Chang Gung Medical Foundation blood biochemistry tests. Data were collected at 4 diff erent (IRB1010507C; No. 100-0876B and 101-0507C). Th is trial time frames from T1 to T4. Th e same outcome measures were was registered at https://clinicaltrials.gov/ under the identifi ca- collected at the same time frames for both groups. Wound as- tion code NCT02328508. We ensured patients’ rights through- sessment was based on the Wagner classifi cation system. 23 , 24 out the study according to the ethical principles for medical Th e Wagner grading system considers depth of penetration, research on human beings set out in the Declaration of Helsin- the presence of underlying osteomyelitis, and the extent of tis- ki. All participants provided written informed consent prior to sue necrosis; ulcers are graded from 0 (preulcerous changes) to random allocation to the control or intervention group.