Oxygen in Acute and Chronic Wound Healing

S. Schreml; R.M. Szeimies; L. Prantl; S. Karrer; M. Landthaler; P. Babilas


The British Journal of Dermatology. 2010;163(2):257-268. 

In This Article

Therapeutic Wound Oxygenation

The ability of systemic oxygen therapy as well as topical oxygen therapy (TOT) to improve wound healing and prevent infection is documented in animal models and clinical trials.[107–110] Hyperbaric oxygen therapy (HBOT) delivers 100% O2 at 2–3 atmospheres of pressure over 60–120 min 5 days a week in a specialized patient chamber. Usually, 10–30 treatments are performed. HBOT has turned out to be an effective tool to increase pO2 values in wound tissue, and the effects of HBOT on chronic wound healing have been described by a mathematical model.[108,109,111] Sheikh et al.[112] demonstrated increased VEGF expression in rats treated with HBOT, and Hopf et al.[30] showed a stimulation of neovascularization in hypoxic tissue after HBOT. Moreover, oxygen administration has been shown to increase VEGF mRNA levels in endothelial cells and macrophages and VEGF protein expression in wound fluids in vivo.[112–114] Knighton et al.[16] reported accelerated vessel growth following supplemental oxygen administration. The transcutaneous pO2 in wound-surrounding tissue measured during HBOT correlated directly with the improvement in wound healing of chronic wounds.[108,109] In a randomized controlled trial in diabetic patients (n = 68) with ulcers of the lower legs, Faglia et al.[115] ascertained that treatment with HBOT and standard care vs. standard care alone resulted in a significant lower amputation rate in the HBOT group. Kranke et al.[116] assessed the benefits and harms of HBOT for treating chronic ulcers of the lower legs and found that HBOT both significantly reduced the risk of major amputation and improved the chance of healing. Abidia et al.[117] evaluated in a double-blind study the role of HBOT in the management of ischaemic lower-extremity ulcers. Patients were given 30 treatments of 100% oxygen vs. air. Healing was achieved in five of eight ulcers in the treatment group compared with one of eight ulcers in the control group. Despite the expense of HBOT, the authors stated reduced total treatment costs for every patient during the study. Another controlled study demonstrated that HBOT did not reduce hospital days of wound patients but the amount of bacterial colonization.[118] Bonomo et al.[107,119] showed that HBOT stimulates the release and activity of growth factors and their receptors. Zhao et al.[110] measured the amount of epithelial regrowth and granulation tissue production following HBOT alone and in combination with PDGF or TGF-β1 in an ischaemic rabbit ear ulcer model. They demonstrated that HBOT alone increased the production of new granulation tissue. However, the addition of growth factors to HBOT synergistically led to increased healing rates. This supports the clinical experience that, in the majority of cases, the different treatment strategies for chronic wounds are successful only if combined. In vitro experiments of Roy et al.[53] demonstrated that oxygen triggers the differentiation of fibroblasts to myofibroblasts – a possible explanation for the accelerated healing. It has also been shown in vitro that HBOT may increase the susceptibility of certain bacteria to antimicrobial agents.[120] For example, Kenward et al.[120] reported that under HBOT the zones of inhibition were reduced in Gram-negative bacterial cultures, whereas for Gram-positive bacteria a mixture of effects was found. It seems that these effects are quite strain specific and may not easily be generalized to all aerobic or anaerobic bacteria. Grief et al.[89] reported significantly fewer postoperative infections in patients who had received 80% oxygen compared with patients who had received 30% oxygen during surgery and 2 h afterwards. However, costs of therapy, the risk of systemic oxygen toxicity, and the lack of large evidence-based studies with standardized treatment protocols impede the general acceptance of oxygen therapy as a standard treatment option in wound care.

TOT is characterized by the administration of pure oxygen to the wound area using a portable inflatable device. A major advantage of TOT is its independence of the wound's microcirculation. Other advantages are lower costs, the lower risk of oxygen toxicity, and the possibility of home treatment. Fries et al.[33] studied the efficacy of TOT in excisional dermal wounds in pigs. They showed that exposure of open dermal wounds to TOT increases wound tissue pO2 and, if repetitively applied, accelerates wound closure. Kalliainen et al.[121] conducted a retrospective uncontrolled study on 58 wounds in 32 patients given TOT. They documented a complete healing of 38 wounds in 15 patients during TOT and concluded that TOT had no detrimental effects on wounds and showed beneficial indications in promoting wound healing. However, the data currently available have a restricted informative value because of small sample sizes, the inclusion of different wound types and patient ages, additionally applied wound care regimens, nonstandardized treatment protocols, or a poor evaluation of comorbidities. Therefore, additional evidence-based studies with standardized treatment protocols are required to evaluate the efficacy of oxygen therapy.