Hyperbaric Oxygen Therapy for Wound Healing and Limb Salvage: A Systematic Review

Abstract

This article is a systematic review evaluating published clinical evidence of the efficacy of hyperbaric oxygen therapy (HBOT) for wound healing and limb salvage. The data source is the Ovid/Medline database for key word "Hyperbaric Oxygenation" with search limits (human studies, 1978-2008). Results were combined by Boolean AND with 1 of the 3 following searches: (a) wound healing (10 permutations); (b) compromised flap or graft (3); and (c) osteomyelitis (1). The author evaluated 620 citations, of which 64 reported original observational studies and randomized controlled trials (RCTs) on HBOT and healing outcomes. All citations with 5 subjects were selected for full text review (44 articles) and evaluated according to GRADE criteria for high, medium, low, or very low level of evidence. A Cochrane review identified 1 additional study with a low level of evidence. This systematic review discusses and tabulates every article of high or moderate level of evidence. For patients with diabetic foot ulcers (DFU) complicated by surgical infection, HBOT reduces chance of amputation (odds ratio [OR] 0.242, 95% CI: 0.137-0.428) (7 studies) and improves chance of healing (OR 9.992, 95% CI: 3.972-25.132) (6 studies). Positive efficacy corresponds to HBOT-induced hyperoxygenation of at-risk tissue (7 studies) as measured by transcutaneous oximetry. HBOT is associated with remission of about 85% of cases of refractory lower extremity osteomyelitis, but an RCT is lacking to clarify extent of effect. There is a high level of evidence that HBOT reduces risk of amputation in the DFU population by promoting partial and full healing of problem wounds. There is a moderate level of evidence that HBOT promotes healing of arterial ulcers, calciphylactic and refractory vasculitic ulcers, as well as refractory osteomyelitis. There is a low to moderate level of evidence that HBOT promotes successful "take" of compromised flaps and grafts.

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

“…Obese individuals have been demonstrated as being predisposed to several severe pathologies including impaired wound healing [76], which might be explained by hypoperfusion and ischemic effects that occurs in subcutaneous adipose tissue. Thus, if the tissue in the vicinity of the wound is inadequately oxygenated, the oxygen strongly dependent cellular repair processes do not take place adequately [83,84]. Hypovascularity frequently observed in obese individuals, further contributes to poor perfusion and increases the risk of infections, due to a decreased infiltration of immune cells to the wound area [83,85].…”

“…Thus, if the tissue in the vicinity of the wound is inadequately oxygenated, the oxygen strongly dependent cellular repair processes do not take place adequately [83,84]. Hypovascularity frequently observed in obese individuals, further contributes to poor perfusion and increases the risk of infections, due to a decreased infiltration of immune cells to the wound area [83,85]. In addition, obese individuals frequently demonstrate increased tension on the wound edges contributing to the wound dehiscence [76,86].…”

Correction of Hypoxia, a Critical Element for Wound Bed Preparation Guidelines: TIMEO2 Principle of Wound Bed Preparation

“…62 Recently, Goldman showed a 3-fold reduction in risk of major amputation when HBO was included in the therapy of diabetic wounds. 54 L€ ondahl et al showed complete healing in 52% of patients in an HBO group, compared with 29% with placebo. 55 Multiple consensus statements recommend HBO therapy as a reasonable modality to salvage diabetic limbs.…”

“…34 This evidence-based review of the literature has shown the importance of correction of hypoxia (Figure 2) as an important intervention for wound bed preparation and healing in salvage of diabetic wounds. 32,33,48,54,60 While the majority of the wounds are possibly hypoxic and could potentially benefit from HBO therapy for wound bed preparation, at the present time most of the accumulated evidence suggests hypoxic diabetic lower extremity wounds and radiation wounds benefit from correction of hypoxia (Figure 2) (HBO therapy). Marx has demonstrated the enhanced vascularity and cellularity in heavily irradiated tissues after HBO therapy by comparing histologic specimens from patients pre and post HBO 61 and also demonstrated the serial improvement in transcutaneous oxygen measurements in patients receiving HBO as an indirect measure of vascular improvement.…”

“…Supression of synthesis of many bacterial toxins 12 occurs when tissue PO 2 values are sufficiently elevated during treatment. Blunting of systemic inflammatory responses 13 and prevention of leukocyte activation and adhesion after ischemic reperfusion [52][53][54] are effects that may persist even after completion of HBO therapy.…”