Oxygen is required for normal cellular processes, and it has been accepted wisdom for some time that oxygen is vital to wound healing. Mild hypoxia (low oxygen) is a normal biological response following an injury, and 97% of chronic, non-healing wounds have been shown to have low oxygen levels (Wounds UK, 2017).
Oxygen therapy was first used in the wound care field in the 1960s, following the discovery that the burns of those receiving treatment in hyperbaric chambers for carbon monoxide poisoning healed more quickly than those who did not receive hyperbaric oxygen treatment (Wada et al, 1965). More recently, the role of topical oxygen therapy, without the need for full-body hyperbaric chambers, has come to the fore (Tawfick and Sultan, 2009).
Granulox® (infirst Healthcare, London, UK) is a topical haemoglobin spray produced from sterile porcine products, which is an adjunct therapy to best practice wound management. As Granulox is sprayed on the non-healing or slow-healing wound (following appropriate debridement), the haemoglobin binds with atmospheric oxygen and carries it to the wound bed where it diffuses into the tissue. The published research on topical haemoglobin is growing and findings to date have been positive: a European Wound Management Association (EWMA) evaluation of the currently available oxygen therapies in wound care awarded Granulox a Grade 1B, indicating a positive benefit risk value with moderate quality of evidence (randomised controlled trials with limitations and very strong observational studies) (Gottrup et al, 2017).
With this in mind, clinicians for the multidisciplinary foot care team met in Edinburgh in October 2017 with the following objectives:
- To create guidelines for the use of Granulox therapy for people with diabetic foot ulcers, with the overall objective of improving patient care
- To consider where ‘oxygen’ treatment fits alongside other good wound care practice
- To consider for which patients Granulox therapy is most appropriate
- To develop recommendations for the use of Granulox therapy within hospital-based multi-disciplinary teams or foot clinics across Scotland. The group worked through questions to complete these objectives.
Which wound types are currently responding best to Granulox treatment?
Short-term (≤7 months) case and pilot studies in the UK have demonstrated an elimination of slough (Hunt, 2015), pain and wound area (Wounds UK, 2017), as well as increase granulation of epithelial tissue and improvement in patient quality of life following treatment with Granulox in non-healing and slow-healing ulcers (Green et al, 2014; Green and Mohamud, 2014; Norris, 2014; Tickle, 2015). Based on their own clinical observations and published research, the panel agreed that wounds that were slow-healing, painful and sloughy were responding best to Granulox treatment, especially in the initial 4–8 weeks of Granulox use (Arenbergova et al, 2015; Hunt and Elg, 2016; Hunt and Elg, 2017; Figure 1).
How should oxygen therapy fit into current management of diabetic foot ulcers (DFUs)?
Oxygen therapy should be an adjunct to good wound care practice and run alongside standard wound bed preparation (after cleansing and debridement) for the management of DFUs as per Best Practice Guidelines for Wound Management of Diabetic Foot Ulcers (Wounds International, 2013).
The results from the 2014–2016 National Diabetic Foot Audit for England and Wales (NHS Digital, 2017) indicate that immediate referral to a multidisciplinary foot care team when a DFU is suspected offers the best clinical outcomes at 12 weeks for patients. Quick referral and patient education are vital for good wound care practice. All new DFUs should be seen by a multidisciplinary foot care team and at this time, the specialist team can make an informed decision regarding the initiation of oxygen therapy, which should be alongside current standard practice for debridement, cleansing and offloading.
The panel designed a best practice pathway to provide guidance on DFU assessment, management and Granulox therapy within good wound care practice (Figure 2). Full holistic assessment of both the patient and wound is essential. Once Granulox is initiated, the wound and patient should be assessed every 4 weeks, using clinical judgement to determine whether wound progression is occurring. Expected markers of healing would be reduction in wound size and/or improvements to the wound bed, tissue, range of movement or exudate volume.
Which patient or wound characteristics suggest high-risk of microvascular complications, and thus may benefit from early topical oxygen therapy?
Patients with diabetes are at increased risk of microvascular complications (e.g. retinopathy, nephropathy and neuropathy). Patients with neuropathy have impaired cutaneous blood flow and can also have ischaemia, which can affect DFU healing (NICE, 2016). The group agreed that if an individual has a DFU and nephropathy, then topical oxygen therapy could be considered appropriate (Ndip et al, 2010). Measuring ischemia in people with neuropathy can be difficult, for example, the skin can continue to feel warm and other complications, such as renal calcinosis, can increase the risk of slow healing. There are a number of diagnostic tests and indicators that can be implemented to detect blood flow and peripheral arterial disease (see Figure 3).
Poorly oxygenated wounds can be suggestive of a microvascular complications, and thus may benefit from early topical oxygen therapy. Evidence shows that poorly oxygenated wounds almost never heal, while oxygenated wounds do – in one study, 97% of non-healing wounds were found to have low oxygen levels (Hauser, 1987). Non-healing wounds due to a lack of oxygen may signal underlying macrovascular problems (Sen, 2009); therefore, it is important to check for macrovascular complications, while initiating early Granulox therapy. However, wound ischaemia can often go unnoticed and this may be due to difficulty in measuring tissue oxygenation (TcPO2), absence of cardinal signs and symptoms, or lack of nursing/podiatry time and resources. The panel recommended that clinicians recognise the role of hypoxia in non-healing wounds, and that further work be done to raise awareness of the role of oxygen in non-healing wounds and the potential for interventions that can aid healing.
The panel also agreed that topical oxygen therapy wound be appropriate for individuals where arterial revascularisation had failed to perfuse the DFU sufficiently.
DFU classification system
The Texas Ulcer Classification (Laverty et al, 1996) is a tool used in Scotland and parts of England to classify all new DFUs (Box 1). Based on the Texas Ulcer Classification, the panel developed a “traffic light” system for determining when Granulox therapy is appropriate to initiate or for early use (Figure 3).
After 4 weeks of standard care, Granulox therapy can be used on ulcer grades I–III, and is indicated for use on sloughy or infected wounds. The panel also identified patient groups and wound types that may benefit for early oxygen therapy intervention: those not suitable for vascular intervention, those with severe peripheral arterial disease, ulcer pain or chronic kidney disease; and post-surgical amputation wounds or sloughy wounds.
Haemoglobin therapy should be considered after 4 weeks of standard care in patients with a non-healing wound, and could be considered earlier for patients at high risk of delayed wound healing. Full holistic assessment of both the patient and wound is vital, and any underlying causes for non-healing wounds should be treated as priority before initiation of an adjunct therapy.
The ‘traffic light’ system for the initiation of Granulox therapy based on the Texas Ulcer Classification and best practice algorithm developed by the panel provide simple tools for clinicians in day-to-day practice to know when and how to initiate Granulox.