Table 1.
Summary of clinical trials investigating the use of HBOT. CWM refers to convention wound care management and involves surgical debridement, antibiotic treatment, off-loading and wound care dressings. In all instances, HBOT was performed as an adjunctive therapy to CWM.
| Citation | Trial Type | Patient Population | Treatment | Conclusion | Limitations |
|---|---|---|---|---|---|
| Doctor, 1991 | Prospective RCT | 30 patients with chronic DFUs | Control – CWM Treatment – 4 sessions of 45 min HBOT at 3 ATA over 2 weeks |
HBOT reduced incidence of infection, rate of amputation, and need for skin grafts, but did not significantly reduce length of hospital stay | Lack of blinding |
| Faglia, 1996 | RCT | 70 patients with chronic DFUs | Control – CWM Treatment – 38 ± 8 daily, 90 min sessions of HBOT at 2.2 to 2.5 ATA |
Amputation rate in HBOT group decreased to 8.6% vs. 33.3% in control. TcPO2 increased and remained elevated for several days | Lack of blinding |
| Abidia, 2003 | Double-blind, Placebo-controlled RCT |
18 patients with 1–10 cm DFUs that did not show healing after 6+ weeks | Control – hyperbaric air at conditions of treatment Treatment – 90 min HBOT at 2.4 AT5 days per week for 30 sessions |
At 6 weeks, complete healing was seen in 5/8 patients in HBOT and 1/8 control patients. At 1 year, healing was consistence in HBOT group, but decreased to 0/8 for control. No significance difference between overall QOL | Control treatment may decrease healing |
| Kessler, 2003 | Prospective RCT | 28 patients with DFUs with Wagner grades I- III |
Control – CWM Treatment - two 90-min daily sessions of HBOT at 2.5 ATA 5 days/week for 2 weeks |
TcPO2 significantly increased during HBOT, leading to improved healing at day 15. At day 30, no difference was observed | Lack of blinding |
| Duzgun, 2008 | Prospective RCT | 100 patients with persistent DFU for 4+ weeks | Control – CWM Treatment – 90-min daily sessions of HBOT at 2 to 3 ATA alternating 1 and 2/day for 20–30 days |
0% patients healed without surgical intervention in control groups compared to 66% in HBOT. HBOT decreased the need for debridement, as well as amputation rate and severity | Statistically significant differences existed in baseline conditions between HBOT and controls |
| Londahl, 2010 | Double-blinded, Placebo-controlled RCT |
94 patients with DFUs Wagner grade II-IV persisting for 3+ months | Control – hyperbaric air at conditions of treatment Treatment – daily 90-min HBOT sessions at 2.5 ATA 5 days/wk for 8 wks |
61% of patients completing 35+ HBOT sessions had complete healing compared to only 27% in control | Control treatment may decrease healing |
| Londahl, 2010 | Double-blinded, Placebo-controlled RCT |
75 patients with DFUs Wagner grade II-IV persisting for 3+ months | Control – hyperbaric air at conditions of treatment Treatment – daily 90-min HBOT sessions at 2.5 ATA 5 days/wk for 8 wks |
Healing was correlated to TcPO2 values following HBOT | Control treatment may decrease healing |
| Londahl, 2010 | Double-blinded, Placebo-controlled RCT |
75 patients with DFUs Wagner grade II-IV persisting for 3+ months | Control – hyperbaric air at conditions of treatment Treatment – daily 90-min HBOT sessions at 2.5 ATA 5 days/wk for 8 wks |
At one year follow up, HBOT patients reported improvements to HRQOL, likely related to ulcer healing | Did not take into account benefits due to social interactions |
| Wang, 2011 | Prospective, open- label RCT | 86 patients with 93 chronic DFUs | Treatment 1–6 treatments of EWST completed over 3 weeks Treatment 2–20 treatments of HBOT at 2.5 ATA for 25 min increments with 5 min break for 90 min performed daily 5 days/ wk |
EWST led to greater improvements in blood perfusion, cell proliferation, and rate of apoptosis, resulting in improved healing overall | Lack of blinding, long term follow-up not conducted |
| Margolis, 2013 | Longitudinal observational cohort study | 6259 individuals with DFUs accounting for 767,060 person-days of wound care |
HBOT was administered to 12.7% of subjects, often on a 5 day/wk, regimen with 90 min sessions at 2 atm for a median of 29 sessions | HBOT patients were more likely to undergo lower limb amputations, but amputation time was postponed 3 wks compared to control | Lack of blinding, effect of patient compliance not accounted for, did not differentiate between treatment alternatives |
| Fedorko, 2016 | Double-blind, placebo-controlled RCT |
118 patients with DFUs Wagner grade II-IV |
Control – hyperbaric air at 1.25 ATA Treatment - 30 treatments of HBOT at 2.5 ATA for 90 min performed daily 5 days/wk |
No significant difference was found in major amputation rate or wound size | Short-term follow-up, actual amputation rates were not reported |
| Li. 2017 | Prospective, placebo-controlled, double-blind RCT | 103 patients with DFUs Wagner grade II-IV persisting for 4+ weeks | Control – hyperbaric air at 1.25 ATA Treatment - 30 treatments of HBOT at 2.5 ATA for 90 min performed daily 5 days/wk |
HBOT did not result in significant improvements to HFQOL, but participants reported fewer problems associated with mobility and pain discomfort compared to sham-treated | Small sample size, insufficient power to assess significance |
| Santema, 2018 | multi-center randomized parallel group superiority trial |
120 patients with DFUs Wagner grade II-IV persisting for 4+ weeks and limb ischemia | Control – CWM Treatment - 40 treatments of HBOT at 2.5 ATA for 25 min increments with 5 min break for 90 min performed daily 5 days/ wk |
HBOT did not significantly improve healing compared to control and resulted in one patient experiencing an oxygen- induced seizure and one had barotrauma | Significant reduction in sample size during trial, no sham treatment |