Mutluoglu M, Uzun G, Bennett M, Germonpré P, Smart D, Mathieu D, et al.
Diving and hyperbaric medicine. Date of publication 2016 Sep 1;volume 46(3):133-134.
1. Diving Hyperb Med. 2016 Sep;46(3):133-134.
Poorly designed research does not help clarify the role of hyperbaric oxygen in
the treatment of chronic diabetic foot ulcers.
Mutluoglu M(1), Uzun G(2), Bennett M(3), Germonpré P(4), Smart D(5), Mathieu
D(6).
Author information:
(1)Associate Professor, Department of Underwater and Hyperbaric Medicine, GATA
Haydarpasa Teaching Hospital, Istanbul, Turkey, drmutluoglu@gmail.com.
(2)Professor, Department of Underwater and Hyperbaric Medicine, GATA Ankara,
Turkey.
(3)Professor, Anaesthesia, Diving and Hyperbaric Medicine, University of New
South Wales, Australia.
(4)Centre for Hyperbaric Oxygen Therapy, Military Hospital Brussels, Belgium.
(5)Clinical Professor, Medical Co-director and Senior Visiting Specialist,
Department of Diving and Hyperbaric Medicine, Royal Hobart Hospital, Tasmania,
Australia.
(6)Professor, Centre d'oxygenotherapie hyperbare, Hopital Roger Salengro, CHU
Lille, Lille, France.
Comment on
Diabetes Care. 2016 Mar;39(3):392-9.
Diabetic foot ulcers (DFUs) are one of the most common indications for hyperbaric
oxygen treatment (HBOT). The role of HBOT in DFUs is often debated. Recent
evidence based guidelines, while recommending its use, urge further studies to
identify the patient subgroups most likely to benefit from HBOT. A recent study
in Diabetes Care aimed to assess the efficacy of HBOT in reducing the need for
major amputation and improving wound healing in patients with chronic DFUs. In
this study, patients with Wagner grade 2-4 diabetic foot lesions were randomly
assigned to have HBOT (30 sessions/90 min/244 kPa) or sham treatment (30
sessions/90 min/air/125 kPa). Six weeks after the completion of treatment (12
weeks after randomization) neither the fulfillment of major amputation criteria
(11/49 vs. 13/54, odds ratio 0.91 [95% CI 0.37, 2.28], P = 0.846) nor
wound-healing rates (20% vs. 22%, 0.90 [0.35, 2.31], P = 0.823) significantly
differed between groups. The authors concluded that HBOT does not offer any
additional advantage over comprehensive wound care. Since this paper was
published in Diabetes Care, one of the most prestigious diabetes journals, it is
likely it will have a major impact on the clinical practice of many physicians
dealing with diabetic foot problems. Although from a methodological standpoint
the conduct of the study (prospective, double-blind, randomized, controlled)
seems to be close to ideal, several significant flaws render the conclusions
weak. Firstly, there were some problems with the assessment of the primary
outcome of "meeting the criteria for amputation". In their published protocol
paper, the trial lists indicated that "At the end of the 6-week follow-up
phase……, the patient is sent to the participating vascular surgeon for an
amputation evaluation". However, in the published report in Diabetes Care, it is
evident that patients were not assessed in a face-to-face consultation, but
rather by the remote examination of wound photographs and clinical data
"Participant clinical data together with digital photographs of the study wound
progress were presented to the vascular surgeon". This departure from the
original intent undermines the primary outcome of the study significantly.
Fedorko et al claim this method of assessment has been validated, but neither of
their supporting citations appear to substantiate this claim. Wirthlin et al
assessed the level of agreement about a collection of wounds between surgeons who
were present at the bedside and a remote group who assessed the wounds using a
short clinical account and digital photography. There was reasonable agreement
between onsite and remote, although the specificity for particular signs ranged
from just 27% (erythema) to 100% (ischaemia). Importantly, only a subset of eight
of the 24 included patients had non-healing wounds and the proportion of those
that were associated with diabetes mellitus is unknown. Further, the need for
amputation was not among the management decisions examined. Wirthlin et al
concluded "a prospective trial of remote wound management …. is needed to further
validate this technology." The authors of the second supposedly supporting
citation were mainly interested in the assessment of pressure ulcers by digital
photography using the Photographic Wound Assessment Tool (PWAT) compared to the
Pressure Sore Status Tool (PSST). Of the 81 included lower leg ulcers, it is not
clear how many were associated with diabetes mellitus. Indications for amputation
were not considered. The authors concluded "The PWAT may be valuable when a
bedside assessment cannot be made. However, the size of circular wounds, wound
depth, undermining/tunneling, and odor cannot be assessed using photographs." In
the Fedorko paper, the decision that there was an indication for amputation was
made by the remote vascular surgeon by meeting any of the following criteria:
"persistent deep infection involving bone and tendons (antibiotics required,
hospitalization required, pathogen involved); ongoing risk of severe systemic
infection related to the wound; inability to bear weight on the affected limb; or
pain causing significant disability". We are particularly concerned that the
criteria, "persistent deep infection involving bone and tendons", is subjective.
Recent studies have demonstrated that diabetic foot osteomyelitis may not
necessarily require amputation and some cases may be cured with antibiotic
therapy alone. It is interesting to note that despite the high numbers of
participants assessed as fitting the requirements for amputation (23% overall),
no patient actually had a major amputation. The amputation outcome is
inappropriately assessed, done at the wrong time, and the study is grossly
underpowered to find any difference in the rate of true major amputation.
Finally, whether the surgeon performed a baseline assessment of amputation prior
to the randomised intervention is unknown. A comparison between the pre- and
post-study estimates of amputation rates could have contributed to the
interpretation of the results. Secondly, the authors fail to provide a clear
comparison of peripheral arterial disease (PAD) between the groups. Although
patients were randomized and those who were possible candidates for major vessel
revascularization were excluded from the study, microvascular status was not
assessed. No transcutaneous oxygen measurements were made on any of the patients.
Given that, firstly, the risk of microvascular vessel compromise increases with
diabetes duration, and secondly, transcutaneous oxygen measurements correlate
with the possibility of good response to HBOT, it is possible that clinically
significant differences between groups were undetected. As an example, patients
in the HBOT group had a markedly longer mean duration of diabetes (19.1 vs. 12.4
years) and would be likely to have more severe microvascular disease. Thirdly,
the follow-up period of six weeks after completion of treatment is very short.
The study to which the authors refer to justify this follow-up period enrolled
only patients with ulcers of Wagner grade 1 or 2 and specifically excluded
patients with infection or ischaemia. These are not representative of the patient
population treated with HBOT. The outcomes in patients with DFUs treated with
HBOT should be assessed over a longer period. One such randomized controlled
study demonstrated that patients receiving HBOT had significantly higher healing
rates than placebo at one-year follow-up (25/48 (52%) versus 12/42 (29%); P 〈
0.03), but not at 12 weeks. Fourthly, the authors also failed to describe the
experience of the vascular surgeon who adjudicated the wounds for amputation; how
many years he was involved in the management of diabetic foot wounds or how
specialized his practice was with these patients. Objective and universally
recognized indications for amputation are yet to be established. Therefore, a
multidisciplinary decision-making approach, rather than a single physician's
decision, would have increased the credibility of the conclusion the authors
reached. Notably, all previous studies of HBOT in this area have used actual
amputation rates in order to have a clear clinical endpoint. Careful patient
selection is paramount for the cost-effective use of HBOT as an adjunct to normal
wound care in diabetic wounds. As it is possible to identify wounds that have no
potential to heal despite HBOT, all studies should incorporate transcutaneous
oxygen measurements in their baseline evaluation. As the wounds in this study
tended to be small (6.1cm² and 5.8cm² on average) and had persisted for (on
average) one year despite state-of-the-art previous wound care, it is likely that
at least some of these would not meet the predictive minimal criteria for healing
potential with HBOT. The findings of this study do indeed show that the
indiscriminate treatment of all diabetic wounds with HBOT is probably not (cost-)
effective; however, the study conclusion that "HBO has no benefit in the
treatment of chronic diabetic foot wounds" is erroneous.
PMID: 27723012 [Indexed for MEDLINE]
