Date Published: December 01, 2018
Publisher: Mary Ann Liebert, Inc., publishers
Author(s): William J. Ennis, Enoch T. Huang, Hanna Gordon.
Objective: The goal of this research was to identify a population of diabetic foot ulcer patients who demonstrate a significant response to hyperbaric oxygen therapy (HBOT) using a large sample size to provide guidance for clinicians when treating these complicated patients.
There has been much debate in the literature surrounding the overall benefits of hyperbaric oxygen therapy (HBOT) in wound care.1,2 Many of the initial studies that resulted in positive outcomes, payment policies, and physician adoption were performed in hospital settings ensuring compliance and thereby, not surprisingly, the results did not translate to an outpatient clinic reality. Studies also reported various primary outcome objectives making comparisons difficult while confusing clinicians when confronted with an individual case.3–5 Even when outcomes were assessed for wounds of a single etiology, there was little effort to risk stratify the patients either for their overall clinical condition or for the complexity of their specific wound. Although population level wound-healing rates have been reported, stratified outcomes data are needed based on specific wound etiology to provide insight when making individual treatment decisions. A modified intent-to-treat (mITT) healing rate for >1 million wounds was recently reported at 74.6%.6 This article did not, however, describe the granular healing rates for individual wound etiologies. When diabetic wound-healing rates are reported, they can be an aggregate of diabetic wounds of the leg or diabetic foot ulcers of various Wagner grades. In many of these studies, when HBOT is given, the total number of treatments completed is rarely considered, making the impact of the therapy difficult to assess.
There has been much debate in the literature surrounding the overall benefits of HBOT in wound care.1,2 Many of the initial studies that resulted in positive outcomes, payment policies, and physician adoption were performed in hospital settings ensuring compliance and thereby, not surprisingly, the results did not translate to an outpatient clinic reality. Studies also reported various primary outcome objectives, making comparisons difficult while confusing clinicians when confronted with an individual case.3–5 This observational study discusses the importance of reporting at the population level, specific wound etiology level, a risk-stratified level, and to then overlay the effect of treatment adherence on those outcomes to provide clinicians with a comprehensive understanding of when to prescribe an advanced modality such as hyperbaric oxygen.
The initial phase of this study was to review and update the retrospective data on wounds, HBOT, and the final clinical disposition from 682 outpatient wound care centers nationwide between January 1, 2014, and April 28, 2018. The time frame for data inclusion was determined by the availability of aggregate data at the time of analysis. The data were obtained from a proprietary clinical database and collected using a specialized wound data capture system that tracks wound-related treatments and patient outcomes. Nurses and physicians document visits at the point of care. A subset of centers document using paper-based forms, which were then entered into a central system at the end of each work day. Other centers document visits on a fully electronic medical record basis. The data used for the study were compiled into a deidentified research database table distinct from the enterprise data warehouse, before the beginning of the analysis. All patient identifiers were removed from the research file. Deidentified data were extracted using SQL software and analyzed using Stata 14.1. The study was exempt from IRB review by Quorum Review IRB (QR no. 33110).
During the study time frame, a total of 2,651,878 wounds were evaluated (Table 1). The population level mITT healing rate was 74.2%, which is consistent with the previously reported 74.6% based on 1,006,690 wounds at the time of that publication. There was variability in the specific wound mITT healing rates from 55.3% to 80.6%. Not surprisingly, arterial wounds demonstrated the lowest healing rates and venous leg ulcers healed at the highest level. The overall healing rate for all wounds classified as diabetic was 70.9% (328,158/462,888) at the population level. At this level of stratification, there does not seem to be a major difference in the overall healing rate for the aggregated overall population of wounds and the rate of healing specifically diabetic wounds using the mITT method previously described. Only patients with a single wound of Wagner grades 3 and 4 located on the foot or toe were included for additional study. The healing and amputation rates for the full sample of Wagner grades 3 and 4 diabetic foot ulcers are reported in Table 2. Once the mITT exclusions are applied, the sample is reduced to 19,057 ulcers with a 56.04% healing rate and a 4.09% amputation rate. This rate is comparable with the mITT population level healing rate for arterial ulcers. By comparison, the mITT healing rate for all wound etiologies previously published by Ennis et al. was 74.6%.6 The lower healing rate for Wagner grades 3 and 4 is an indication of the difficulty in healing these patients who often have confounding medical comorbid conditions and emphasizes the importance of risk stratification when reporting outcomes. The mITT subpopulation represents 75% of the total population of diabetic foot ulcer patients with the largest group excluded being those still in treatment at the end of the study time frame, which accounted for 18.1% of the total.
This retrospective study suggests that HBOT can be effective for hard-to-heal Wagner grades 3 and 4 diabetic foot ulcers and demonstrates the complexities of studying the therapy using observational real-world data. Specifically, the results underscore the importance of treatment adherence when analyzing the effectiveness of HBOT. Furthermore, using the mITT framework to report healing outcomes allows for both transparency of results and the ability to compare programs, individual centers, and ultimately providers. Although the population level healing rate provides an overall picture of the effectiveness of wound care centers in general, we also need to analyze results on more granular levels. Venous ulcer healing rates, for example, are frequently reported without segregation into various clinical, etiology, anatomy, and pathophysiology (CEAP) classifications, making it difficult to project an individual patients potential for healing.7 Arterial ulcer healing rates rarely describe the level and extent of peripheral arterial disease when reporting healing rates. In addition, the methods of establishing revascularization are often not a variable that is considered in the final analysis. Given the fact that HBOT is approved for DWLE, a highly heterogeneous group, separating wounds by anatomic location and Wagner grade may provide different results. Variations in diabetic foot ulcer healing rates have been reported based on hospital designation, that is, community versus tertiary academic center, further complicating how results are interpreted.8 In that study, the same clinical team provided care using the same protocols at two very different hospital settings. The first, a small community 200-bed hospital and the second, a 700-bed level one trauma tertiary setting. The noted difference in healing rates at these two centers (73.7% vs. 59.5%) achieved by the same clinicians sheds light on patient referral patterns and risk stratification.
This retrospective study has clinical relevance because it suggests HBOT can be effective for hard-to-heal Wagner grades 3 and 4 diabetic foot ulcers and demonstrates the complexities of studying the therapy using observational real-world data. Specifically, the results underscore the importance of treatment adherence when analyzing the effectiveness of HBOT. Furthermore, using the mITT framework to report healing outcomes allows for both transparency of results and the ability to compare programs, individual centers, and ultimately providers.