The use of honey in healing of multiply infected skin lesions following meningococcal septicaemia.
C. Dunford1, R. A. Cooper2 and P. C. Molan3
1Clinical Nurse Specialist in Tissue Viability, Salisbury District Hospital, Salisbury, Wiltshire
2Microbiologist, School of Applied Sciences, University of Wales Institute Cardiff, Cardiff
3Director of the Honey Research Unit, University of Waikato, New Zealand
The development of haemorrhagic skin lesions following meningococcal septicaemia is described in detail by Thomas et al. (1998). Briefly, infection with Neisseria meningitidis can cause either or both meningitis and septicaemia. The purpuric eruptions which are a characteristic of meningococcal septicaemia are caused by the bacterial endotoxin in the circulation, which has a ten times greater potency against skin tissue than against other body tissues. In clinical sepsis, endotoxin derived from cell wall lipopolysaccharide is released during the phagocytosis of invading Neisseria meningitidis. It induces a complex response in macrophages which includes the production of elevated levels of tumour necrosis factor-alpha (TNF-a). This pro-inflammatory cytokine has multiple effects which culminate in tissue and organ damage as the result of disseminated intravascular coagulation and a suppurative inflammatory response. TNF-a promotes the release of nitric oxide from endothelial cells which leads to vasodilation, increased vascular permeability and hypotension, causing inadequate blood flow to meet tissue needs. It also activates coagulation and impairs fibrinolysis, which allows the development of blood clots in small vessels throughout the body. TNF-a- mediated activation of leukocytes can additionally contribute to local tissue and organ damage during sepsis by producing reactive oxygen species and proteinases which indiscriminately attack host tissue (van der Poll & Lowry, 1995). In severe cases areas of intradermal bleeding coalesce and become necrotic, leading to extensive tissue loss. The resultant oedema causes a rise in compartment pressure that restricts circulation and increases the extent of the damage, and gangrene and amputation are common consequences in severe cases. Thomas et al. (1998) refer to reports of such lesions being managed as full thickness burn wounds, with surgical excision of necrosis and application of silver sulfadiazine.
This paper reports an extreme case in which multiple, non-healing, infected lesions were particularly difficult to manage because of the pain experienced by the patient. Previous reports of the effectiveness of honey as a soothing antibacterial dressing for burn wounds (Subrahmanyam, 1993, 1998 and 1991) and of its potent antibacterial action against Pseudomonas (Cooper & Molan, 1999) and Staphylococcus aureus (Cooper et al 1999), indicated a possible role for honey in the management of this patient. An excellent outcome was achieved.
'Bernie' was 15 years old when in January 1999 he contracted meningococcal septicaemia, and required resuscitation on admission to hospital. He presented with multiple systemic ecchymoses of both lower limbs and many fingers, which progressed to necrosis. Amputations were performed on distal and middle phalanges on both hands and also below both knees; multiple skin grafts were harvested and applied.
After 2 months in ITU, Bernie was transferred to a Regional Burns and Plastics Department, by which time a pressure ulcer had developed on his left buttock and his nutrition was found to be compromised (albumin level of 23 g/L and haemoglobin of 6.7 g/dL). A high protein, high calorie diet was commenced, supplemented by overnight naso-gastric feeding. Initially traditional dressings of paraffin gauze and bandages, with hydrocolloid to the pressure ulcer, were applied and changed under general anaesthetic to minimise trauma to Bernie. Amputation sites to all phalanges healed without incident. In the following 6 months, 6 skin graft procedures were undertaken, but the success rate was variable and failed donor sites contributed to the numerous lesions on his legs. Heavy growth of Pseudomonas, Staphylococcus aureus and Enterococcus was reported from swabs of his leg lesions. Several treatment options were tried, including multi-layered dressing (Tenderwet 24), a silicone dressing (Mepitel), and topical silver sulfadiazine. Although the lesions appeared cleaner with the multi-layered dressing, the frequency of changes made it impracticable. Despite copious amounts of analgesia (Oromorph, dihydrocodeine and diazepam), soaking in a bath was insufficient to remove all dressings, which meant that wound debris began to accumulate, and the risk of infection increased. Dressing changes became traumatic for all concerned. After 9 months in hospital, there was little evidence of healing in Bernie's leg wounds.
It was at this point that a new approach was used. Combine dressings (Smith & Nephew) impregnated with 25-35g active manuka honey (activity rating "UMF 13", as descibed in Molan, 1999) and irradiated by gamma radiation were applied to lesions on Bernie's right leg. Again general anaesthetic was used to dress the lesions at 3-day intervals. Wound swabs and photographs were taken at the start of honey treatment and at regular intervals. It became apparent within a few days that the legs showed signs of epithelialisation and corresponding reduction in wound pathogens. Both legs and the pressure ulcer were then treated with the honey dressings. Within a few weeks Pseudomonas and Enterococcus were eliminated from the wound bed, but Staphylococcus remained throughout the duration of the healing process, without appearing to hinder it. Within a few weeks of starting the honey treatment, general anaesthetic was discontinued at dressing changes; Bernie was able to manage his pain and anxiety with entinox. The honey dressings did not adhere to the wounds, and a shower trolley was used in their removal. The increased rate of epithelialisation was maintained and Bernie received his last skin graft within 6 weeks of starting the honey dressings. As new areas of epithelial tissue developed, manuka honey ointment was applied, while honey impregnated dressings continued to be applied to broken areas. Complete healing of all lesions including the pressure ulcer occurred within 10 weeks of commencing the honey treatment.
Bernie was discharged from hospital before Christmas and is now attending a limb fitting centre and undergoing rehabilitation prior to starting college in 2000.
Honey, the most ancient wound dressing, has been "rediscovered" in recent times (Zumla, 1989). The numerous reports of its effectiveness have been reviewed (Molan, 1998, 1999), and include randomised controlled trials and controlled studies of experimental wounds in animal models. These reports include both clinical observation and experimental studies that have established that honey has an effective antibacterial action, a debriding action, an anti-inflammatory action that is not secondary to the removal of bacteria, and a stimulatory effect on the growth of new blood capillaries, fibroblasts, and epithelial cells. The rapid clearance of infection and achievement of clean healthy granulating tissue are the most noted features of the use of honey as a wound dressing. Randomised controlled trials have demonstrated that honey is more effective than silver sulfadiazine in controlling infection in burn wounds (Subrahmanyam, 1991 and 1998), and there are several reports of honey achieving healing of chronic infected wounds not responding to conventional treatment. This is the first reported case where honey is used on multiple meningococcal skin lesions.
The antibacterial action of the honey was evident in this case; the mixed infection of Pseudomonas, Enterococcus and Staphylococuss aureus was cleared from the lesions, leaving reduced numbers of colonising staphylococci. Thomas et al. (1998) refer to cases where skin grafting of meningococcal lesions was problematic, and cite one case where contamination was blamed. The initial failure of some skin grafts in this patient may be attributable to the presence of Pseudomonas, and the use of honey to inhibit these bacteria is thought to have contributed to the successful outcome with this patient.
There is another explanation of why honey promoted successful skin grafting in this case. The poor blood supply, the basic cause of the necrosis in meningococcal skin lesions, would normally limit the availability of oxygen and nutrients to the cells of the skin graft. Honey immediately alleviates this limitation, because it contains a mixture of vitamins, minerals and amino acids at similar levels to those in serum, as well as large amounts of glucose. Further to this, its high osmolarity induces an outflow of lymph which enhances nutrification and oxygenation, and its acidity favours release of oxygen from haemoglobin in the capillaries of adjacent tissues. Stimulation of angiogenesis also improves oxygenation, and decreased local oedema in turn increases blood flow and oxygenation. Further, the anti-inflammatory action of honey, coupled with the action of the antioxidants that are present in honey, decreases the formation of destructive free radicals which may be responsible for the problems normally experienced with getting skin grafts to take on meningococcal skin lesions.
Reduction of swelling also contributes to pain relief. One of the most immediately noticed effects on switching to honey dressings in the case reported here, was the diminution of pain at dressing changes. This would also be expected to be due to the anti-inflammatory action of honey, and an additional factor in the comfort of using honey is its non-adherence to the wound tissue - a layer of liquid forms between the wound and the dressing.
Thomas et al. (1998) have pointed out the lack of documented practical advice on conservative treatment of meningococcal skin lesions, and scarcity of evidence to support the use of modern dressing materials for moist wound healing. Hydrogel and hydrocolloid dressings were used successfully on their patient, and the advantages of preventing desiccation and of encouraging autolytic debridement, compared to the usual practice of demarcating purpural areas by drying prior to surgery were emphasised. They recognised that more extensive tissue damage could result from the development of an increased compartment pressure following wound desiccation. Because honey has a high osmolarity, it may be expected to cause desiccation of wound tissue, but in practice the osmotic flow of fluid out from the wound tissue is balanced by an inward flow from underlying tissues. Thus a layer of honey on the surface of a wound creates a moist environment for the wound tissues.
The case reported by Thomas et al. (1998) was less severe than Bernie, and in that patient the lesions produced slough. The rapid achievement of clean healthy granulating surfaces on lesions without slough observed in Bernie's case is typical of the observations reported by others dressing wounds with honey. Although no conclusions on the relative effectiveness of two different treatments can be drawn from comparison of two single cases, the results reported here are sufficiently encouraging to indicate further investigation into the usefulness of honey in managing meningococcal skin lesions. Whenever an antibacterial dressing is required, a honey of high antibacterial activity must be selected, as honeys can differ as much as 100-fold in their antibacterial potency. Other than in Australia and New Zealand, commercial brands of honey are currently neither irradiated nor assessed for antibacterial potency, and their suitability for topical wound therapy is not recommended.
Deterioration of purpuric skin lesions into necrotic areas is increased by oedema; honey is known to reduce oedema, therefore, it may be particularly advantageous to apply honey at an early stage in the development of meningococcal skin lesions. Additionally, reports of honey being effective in the treatment of gangrene suggest a role in reducing the number of amputations in meningococcal septicaemia. The disfigurement that results from meningococcal skin lesions may also be reduced by the use of honey at an early stage; when used on burns honey reduces the amount of scarring. Thomas et al. (1998) refer to the poor cosmetic results achieved with conventional dressing including silver sulfadiazine. As with burn wounds, contracture and hypertrophication are a problem in meningococcal skin lesions. However, even when used at such a late stage in the case reported here, the cosmetic results were good.
The authors would like to thank the staff of Sarum ward and the Burns Unit for their help in treating this patient.
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