A topical haemoglobin spray for oxygenating chronic venous leg ulcers: a pilot study Ray Norris
Key words: Topical oxygen therapy study ■ Wound-size reduction
■
Chronic venous leg ulcers
■
Pilot
O
xygen is a prerequisite for successful wound healing due to the increased demand for it in reparative processes such as cell proliferation, the defence against bacteria, angiogenesis and collagen synthesis (Schreml et al, 2010). Damage or destruction of the blood supply to a region of living tissue can quickly compromise oxygen levels in wounded tissue. Problems such as vascular disease or oedema can also reduce the supply of oxygen to wounded tissue. It is vital, therefore, to ensure oxygen reaches the wound rapidly in order to effect repair. Hypoxia (a deficiency of oxygen reaching the tissues of the body) is generally viewed as angiogenic. This is certainly true when hypoxia is acute and mild or modest (Sen, 2009).
Ray Norris Bsc (Hons) PG Dip (Skin integrity) Clinical Nurse Specialist, Tissue Viability, South West Essex Community Services, North East London NHS Foundation Trust Accepted for publication: October 2014
S48
Delivery of oxygen to the wound Oxygen helps drive all of the processes of wound healing; indeed, cellular respiration and the prevention of infection are responsible for more than 90% of oxygen consumption. Cells use oxygen as the final electron acceptor in the aerobic metabolism of glucose to generate adenosine triphosphate (ATP), which fuels most active cellular processes, including those occurring during wound healing (Ichioka et al, 2008). The healing tissues will increase the demand for energy, which will in turn increase the demand for oxygen in order to repair the tissue (Gupta and Raghubir, 2005). Any means that will assist this process of oxygen delivery will therefore increase the potential for wound healing. Since the tissues have no storage capacity for oxygen, a continuous supply at a rate that matches changing metabolic requirements is necessary to maintain aerobic metabolism and normal cellular function. In some patients with wounds, the lack of a sufficient oxygen supply to meet their metabolic needs would result in delayed healing (Fries et al, 2005). These patients may benefit from either increased systemic oxygen or topical oxygen. Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy are treatments that can be used to facilitate wound healing. At present, the main method of oxygen therapy in wound care is HBOT (Winfeld, 2014), particularly in US wound-care centres, where this treatment is eligible for reimbursement. Few centres in the UK offer HBOT treatment, greatly limiting its availability. HBOT uses a special chamber, sometimes called a pressure chamber, to increase the amount of oxygen in the blood.The patient will be breathing 100% oxygen while under increased atmospheric pressure, with the air pressure inside the chamber being approximately two-and-a-half times greater
© 2014 MA Healthcare Ltd
Abstract
Acute wounds will generally heal independently of any interventions, whereas chronic wounds are chronic for a reason and are unlikely to successfully heal without intervention. In the treatment of venous leg ulcers, the gold standard will always be compression therapy. However, many wounds still do not heal despite best practice. Therefore, the use of adjunct therapies alongside standard care become the priority for healing. This article describes a small evaluation, involving 17 patients with chronic venous leg ulcers, that set out to determine the effect of a topical oxygen therapy on wound size. The therapy comprises a canister that sprays pure haemoglobin in a water solution into the wound. The haemoglobin spray needs to be used at least once every 3 days, and no training is required on its use. Results showed the device helped promote wound healing in 14 out of 17 wounds treated for more than 2 weeks. These patients had previously been shown to be non-healing during a 4-week run-in period where they received standard care, including compression therapy.
However, severe hypoxia, as commonly noted in problem wounds such as venous leg ulcers (VLUs), is not compatible with tissue repair (Sen, 2009). Depending on the magnitude of the hypoxia, cells will either induce an adaptive response that promotes glycolysis (the first step in the breakdown of glucose to extract energy for cellular metabolism) and conservation of the energy, or will undergo cell death (Taylor and Pouyssegur, 2007). Another complication of lack of oxygen to the wound is clinical infection as cells fighting infection require oxygen to function (Wattel and Mathieu, 2005). In hypoxic tissues, therefore, lack of oxygen can weaken the immune system, increasing the risk of infection.
British Journal of Nursing, 2014 (Tissue Viability Supplement), Vol 23, No 20
British Journal of Nursing. Downloaded from magonlinelibrary.com by 147.188.128.074 on August 20, 2015. For personal use only. No other uses without permission. . All rights reserved.
Figure 1. Sufficient oxygen is available in air, but it cannot get to the base of the wound, due to the diffusion barrier of exudate
angiogenesis), greater blood vessel density, and almost four times higher oxygen partial pressure (pO2) levels. Kalliainen et al (2003) suggested that brief exposures to pure oxygen not only help chronic and other hard-to-heal wounds to heal completely, but that this also occurs at a faster rate. Advocates of topical oxygen claim it has several advantages over systemic hyperbaric oxygen, including decreased cost, increased safety, and decreased complications. Physiological benefits include reduced free-radical formation and more efficient delivery of oxygen to the wound surface (Feldmeier et al, 2005; Gordillo and Sen, 2009; Winfeld, 2014). The ideal topical oxygen agent designed to accelerate healing would provide sufficient quantities of oxygen to a wound several hours after application and be non-toxic to the skin (Davis et al, 2007). A chronic wound is one that does not heal in the orderly set of stages and in an orderly and timely manner (Troxler et al, 2009). Topical oxygen is a potential treatment for the chronic wound, as the wound: ■■ Is originally caused by depletion of oxygen to the tissues ■■ Worsens due to resultant chronicity, causing a further reduction in oxygen levels. It is a ‘Catch 22’ situation.
Granulox
than the normal pressure in the atmosphere. This helps blood carry more oxygen to organs and tissues. Topical oxygen is simply a low-pressure delivery of pure oxygen to the surface of the wound. It is safe and simple to use. Since oxygen is applied directly to the wound site at normal pressure and there is no additional inspiration of oxygen; the decreased oxygen penetration of the targeted tissue, when compared with HBOT, makes it a safer delivery (Winfeld, 2014). Another advantage is, of course, the possibility of home treatment (Sen et al, 2002). In a randomised study, Gordillo and Sen (2009) found that, compared with wounds treated with room air only, wounds treated with topical oxygen therapy had higher levels of VEGF protein expression (which helps promote
S50
Clinical and cost-effectiveness of Granulox Granulox can stimulate wound healing and have a potent adjunctive effect on the healing process with a marked increase in granulation tissue (75%) and epithelialisation
© 2014 MA Healthcare Ltd
Figure 2. Haemoglobin acts as transport molecule and takes oxygen to the base of the wound
Granulox, which presents as a haemoglobin spray, is a topical oxygen therapy for the treatment of chronic wounds. The device is applied topically onto the wound as a spray. Its mechanism of action is based on the premise that haemoglobin, the natural oxygen carrier, will carry oxygen from the normal atmosphere and deliver it directly into the wound bed. It is proposed this will improve the oxygen supply to a chronic wound through facilitated diffusion, in turn promoting and accelerating healing (Figures 1 and 2). Little training is required on its use. Granulox is officially licensed as a class III medical device. It contains: 10% carbonylated haemoglobin; 0.7% phenoxyethanol; 0.9% sodium chloride; 0.05% N-acetylcysteine; and water to 100%. The spray can be applied easily without contact with the wound and is approved for multi-use. It should be applied at every dressing change, but at least every 3 days. No negative side-effects have been reported. Contraindications are the use with locally-acting drugs such as antibiotics. In addition, some disinfectants and proteolytic or mechanical debridement will impair its mechanism of action. For safety reasons, Granulox should not be used on infected wounds or during pregnancy, as sufficient data are not yet available to evaluate these cases. If the wound is filled with necrotic tissue or slough, it is advisable to debride the wound before application. This can easily be achieved with autolytic or mechanical debridement, if the health professional has not been trained in sharp debridement with a curette.
British Journal of Nursing, 2014 (Tissue Viability Supplement), Vol 23, No 20
British Journal of Nursing. Downloaded from magonlinelibrary.com by 147.188.128.074 on August 20, 2015. For personal use only. No other uses without permission. . All rights reserved.
EVALUATION
© 2014 MA Healthcare Ltd
A multicentre pilot study was undertaken to examine the efficacy (defined as reduction in wound size) of Granulox in the treatment of recalcitrant VLUs. Inclusion criteria were age > 18 years of age and ABPI ≥ 0.8. Exclusion criteria were leg ulcers with clinical signs of infection, history of poor adherence with compression therapy, immobility/limited ankle joint flexibility and pregnancy/lactation. A four-week run-in period was used to determine if the wounds were ‘non-healing’, despite receiving local best practice. ‘Non-healing’ was defined as wounds that decreased in size by
Key words: Topical oxygen therapy study ■ Wound-size reduction
■
Chronic venous leg ulcers
■
Pilot
O
xygen is a prerequisite for successful wound healing due to the increased demand for it in reparative processes such as cell proliferation, the defence against bacteria, angiogenesis and collagen synthesis (Schreml et al, 2010). Damage or destruction of the blood supply to a region of living tissue can quickly compromise oxygen levels in wounded tissue. Problems such as vascular disease or oedema can also reduce the supply of oxygen to wounded tissue. It is vital, therefore, to ensure oxygen reaches the wound rapidly in order to effect repair. Hypoxia (a deficiency of oxygen reaching the tissues of the body) is generally viewed as angiogenic. This is certainly true when hypoxia is acute and mild or modest (Sen, 2009).
Ray Norris Bsc (Hons) PG Dip (Skin integrity) Clinical Nurse Specialist, Tissue Viability, South West Essex Community Services, North East London NHS Foundation Trust Accepted for publication: October 2014
S48
Delivery of oxygen to the wound Oxygen helps drive all of the processes of wound healing; indeed, cellular respiration and the prevention of infection are responsible for more than 90% of oxygen consumption. Cells use oxygen as the final electron acceptor in the aerobic metabolism of glucose to generate adenosine triphosphate (ATP), which fuels most active cellular processes, including those occurring during wound healing (Ichioka et al, 2008). The healing tissues will increase the demand for energy, which will in turn increase the demand for oxygen in order to repair the tissue (Gupta and Raghubir, 2005). Any means that will assist this process of oxygen delivery will therefore increase the potential for wound healing. Since the tissues have no storage capacity for oxygen, a continuous supply at a rate that matches changing metabolic requirements is necessary to maintain aerobic metabolism and normal cellular function. In some patients with wounds, the lack of a sufficient oxygen supply to meet their metabolic needs would result in delayed healing (Fries et al, 2005). These patients may benefit from either increased systemic oxygen or topical oxygen. Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy are treatments that can be used to facilitate wound healing. At present, the main method of oxygen therapy in wound care is HBOT (Winfeld, 2014), particularly in US wound-care centres, where this treatment is eligible for reimbursement. Few centres in the UK offer HBOT treatment, greatly limiting its availability. HBOT uses a special chamber, sometimes called a pressure chamber, to increase the amount of oxygen in the blood.The patient will be breathing 100% oxygen while under increased atmospheric pressure, with the air pressure inside the chamber being approximately two-and-a-half times greater
© 2014 MA Healthcare Ltd
Abstract
Acute wounds will generally heal independently of any interventions, whereas chronic wounds are chronic for a reason and are unlikely to successfully heal without intervention. In the treatment of venous leg ulcers, the gold standard will always be compression therapy. However, many wounds still do not heal despite best practice. Therefore, the use of adjunct therapies alongside standard care become the priority for healing. This article describes a small evaluation, involving 17 patients with chronic venous leg ulcers, that set out to determine the effect of a topical oxygen therapy on wound size. The therapy comprises a canister that sprays pure haemoglobin in a water solution into the wound. The haemoglobin spray needs to be used at least once every 3 days, and no training is required on its use. Results showed the device helped promote wound healing in 14 out of 17 wounds treated for more than 2 weeks. These patients had previously been shown to be non-healing during a 4-week run-in period where they received standard care, including compression therapy.
However, severe hypoxia, as commonly noted in problem wounds such as venous leg ulcers (VLUs), is not compatible with tissue repair (Sen, 2009). Depending on the magnitude of the hypoxia, cells will either induce an adaptive response that promotes glycolysis (the first step in the breakdown of glucose to extract energy for cellular metabolism) and conservation of the energy, or will undergo cell death (Taylor and Pouyssegur, 2007). Another complication of lack of oxygen to the wound is clinical infection as cells fighting infection require oxygen to function (Wattel and Mathieu, 2005). In hypoxic tissues, therefore, lack of oxygen can weaken the immune system, increasing the risk of infection.
British Journal of Nursing, 2014 (Tissue Viability Supplement), Vol 23, No 20
British Journal of Nursing. Downloaded from magonlinelibrary.com by 147.188.128.074 on August 20, 2015. For personal use only. No other uses without permission. . All rights reserved.
Figure 1. Sufficient oxygen is available in air, but it cannot get to the base of the wound, due to the diffusion barrier of exudate
angiogenesis), greater blood vessel density, and almost four times higher oxygen partial pressure (pO2) levels. Kalliainen et al (2003) suggested that brief exposures to pure oxygen not only help chronic and other hard-to-heal wounds to heal completely, but that this also occurs at a faster rate. Advocates of topical oxygen claim it has several advantages over systemic hyperbaric oxygen, including decreased cost, increased safety, and decreased complications. Physiological benefits include reduced free-radical formation and more efficient delivery of oxygen to the wound surface (Feldmeier et al, 2005; Gordillo and Sen, 2009; Winfeld, 2014). The ideal topical oxygen agent designed to accelerate healing would provide sufficient quantities of oxygen to a wound several hours after application and be non-toxic to the skin (Davis et al, 2007). A chronic wound is one that does not heal in the orderly set of stages and in an orderly and timely manner (Troxler et al, 2009). Topical oxygen is a potential treatment for the chronic wound, as the wound: ■■ Is originally caused by depletion of oxygen to the tissues ■■ Worsens due to resultant chronicity, causing a further reduction in oxygen levels. It is a ‘Catch 22’ situation.
Granulox
than the normal pressure in the atmosphere. This helps blood carry more oxygen to organs and tissues. Topical oxygen is simply a low-pressure delivery of pure oxygen to the surface of the wound. It is safe and simple to use. Since oxygen is applied directly to the wound site at normal pressure and there is no additional inspiration of oxygen; the decreased oxygen penetration of the targeted tissue, when compared with HBOT, makes it a safer delivery (Winfeld, 2014). Another advantage is, of course, the possibility of home treatment (Sen et al, 2002). In a randomised study, Gordillo and Sen (2009) found that, compared with wounds treated with room air only, wounds treated with topical oxygen therapy had higher levels of VEGF protein expression (which helps promote
S50
Clinical and cost-effectiveness of Granulox Granulox can stimulate wound healing and have a potent adjunctive effect on the healing process with a marked increase in granulation tissue (75%) and epithelialisation
© 2014 MA Healthcare Ltd
Figure 2. Haemoglobin acts as transport molecule and takes oxygen to the base of the wound
Granulox, which presents as a haemoglobin spray, is a topical oxygen therapy for the treatment of chronic wounds. The device is applied topically onto the wound as a spray. Its mechanism of action is based on the premise that haemoglobin, the natural oxygen carrier, will carry oxygen from the normal atmosphere and deliver it directly into the wound bed. It is proposed this will improve the oxygen supply to a chronic wound through facilitated diffusion, in turn promoting and accelerating healing (Figures 1 and 2). Little training is required on its use. Granulox is officially licensed as a class III medical device. It contains: 10% carbonylated haemoglobin; 0.7% phenoxyethanol; 0.9% sodium chloride; 0.05% N-acetylcysteine; and water to 100%. The spray can be applied easily without contact with the wound and is approved for multi-use. It should be applied at every dressing change, but at least every 3 days. No negative side-effects have been reported. Contraindications are the use with locally-acting drugs such as antibiotics. In addition, some disinfectants and proteolytic or mechanical debridement will impair its mechanism of action. For safety reasons, Granulox should not be used on infected wounds or during pregnancy, as sufficient data are not yet available to evaluate these cases. If the wound is filled with necrotic tissue or slough, it is advisable to debride the wound before application. This can easily be achieved with autolytic or mechanical debridement, if the health professional has not been trained in sharp debridement with a curette.
British Journal of Nursing, 2014 (Tissue Viability Supplement), Vol 23, No 20
British Journal of Nursing. Downloaded from magonlinelibrary.com by 147.188.128.074 on August 20, 2015. For personal use only. No other uses without permission. . All rights reserved.
EVALUATION
© 2014 MA Healthcare Ltd
A multicentre pilot study was undertaken to examine the efficacy (defined as reduction in wound size) of Granulox in the treatment of recalcitrant VLUs. Inclusion criteria were age > 18 years of age and ABPI ≥ 0.8. Exclusion criteria were leg ulcers with clinical signs of infection, history of poor adherence with compression therapy, immobility/limited ankle joint flexibility and pregnancy/lactation. A four-week run-in period was used to determine if the wounds were ‘non-healing’, despite receiving local best practice. ‘Non-healing’ was defined as wounds that decreased in size by
