History of the Use of Honey in Wound Care

Large, contaminated wounds are difficult and expensive to treat. Honey contains many nutrients and minerals and has a bactericidal effect due to hydrogen peroxide liberation and a phytochemical constituent. The use of honey in the management of wounds enhances healing and eliminates invading bacteria without the use of systemic antibiotics. Honey also decreases inflammatory edema. Thus the use of honey can be an effective and economical approach to managing large wounds. Contaminated wounds, especially large wounds (e.g., major degloving injuries, burns), and conditions such as necrotizing fasciitis acquired through infections with Pseudomonas species, Escherichia coli, or streptococci, can be difficult and expensive to treat using conventional methods. As a result, owners whose pets have extensive wounds often opt to have the affected limb amputated or the animal euthanized. Honey has been shown to be effective against the growth of bacteria, and its use enhances wound healing. Thus it is an inexpensive topical treatment that is extremely effective in wound management and its use makes management of large, open wounds financially feasible. HISTORY OF THE USE OF HONEY IN WOUND CARE The use of honey to treat wounds dates back to 2000 BC. Numerous reports document the efficacy of honey in wound healing, and several studies even indicate that honey appears to be superior to many modern methods of treatment. Honey has been used for cleansing and accelerating the healing of wounds for centuries; however, the scientific basis for its success was not elucidated until the twentieth century. Honey is currently used worldwide to treat human patients with contaminated wounds or infected body cavities. The use of honey to treat wounds on animals has been slow to come into acceptance. HEALING PROPERTIES OF HONEY Mechanisms associated with wound cleansing and healing properties of honey include decreased inflammatory edema, attraction of macrophages to further cleanse the wound, accelerated sloughing of devitalized tissue, provision of a local cellular energy source, and formation of a protective layer of protein over the wound and a healthy granulation bed. Honey also has a deodorizing CE Vol. 24, No. 1 January 2002 53 V n Antibiotics are not required when treating wounds with honey due to its bactericidal effect of hydrogen peroxide liberation and a phytochemical constituent, which enhances sterilization. n When used as a topical dressing, honey decreases inflammatory edema, accelerates sloughing of devitalized tissue, and nourishes the wound; these factors contribute to enhanced granulation and epithelialization. *A companion article entitled “Wound Management Using Sugar” appears on page 41. action; this may be due to its rich supply of glucose, which would be used by the infecting bacteria in preference to amino acids, resulting in the production of lactic acid instead of malodorous compounds. The cleansing and healing properties of honey are not widely known in veterinary medicine. Honey also has antibacterial properties that have been attributed to its high osmolarity, acidity, and hydrogen peroxide (H2O2) content. The effects of osmolarity in contaminated wounds is based on the low water content (or high osmolality) created in the wound. As the high osmolarity of honey draws lymph from a wound, dissolved nutrients within the lymph provide nutrition for regenerating tissue.6, The antibacterial factor inhibine has been isolated from honey produced from several different plant sources. Inhibine, which was determined to be H2O2, is produced by the natural glucose oxidase in honey. Glucose oxidase produces gluconic acid (which is the principal acid in honey) and H2O2 from glucose. Although H2O2 is primarily responsible for the antibacterial properties of honey, it is present at harmlessly low levels. H2O2 is continuously produced by the activity of the glucose oxidase enzyme, which is only activated when diluted. The concentration of H2O2 that accumulates in 1 hour is approximately 1000 times less than that found in the H2O2 solution (3%) that is commonly used as an antiseptic. In addition to its inhibine component, pure, unpasteurized, commercial honey is composed of approximately 40% glucose; 40% fructose; 20% water; and trace amounts of amino acids, vitamins (i.e., biotin, nicotinic acid, folic acid, pentotenic acid, pyridoxine, and thiamine), enzymes (i.e., diastase, invertase, glucose oxidase, and catalase), and minerals (i.e., potassium, iron, magnesium, phosphorus, copper, and calcium). The rate of granulation tissue formation and epithelialization of wounds may be enhanced by the various constituents of honey. Honey is an excellent cellular energy source, provides a viscous barrier to wound invasion, and has a hygroscopic effect, which reduces edema. Honey also has high levels of antioxidants, which protect wound tissues from oxygen radicals that may be produced by the H2O2. H2O2 has been shown to be more effective against bacteria when it is continuously generated. The generation of low levels of H2O2 stimulates angiogenesis and the growth of fibroblasts. This increased angiogenesis increases oxygen delivery to tissues, which is a limiting factor for tissue generation. Topical acidification of wounds has been shown to promote healing; therefore, honey’s low pH (3.6 to 3.7) will accelerate healing as well as increase antibacterial effects. VARIATIONS IN THE ANTIBACTERIAL ACTIVITY OF DIFFERENT HONEYS Two millennia ago, it was recommended that honey be collected in specific regions and during certain seasons (presumably from different floral sources) to be used for the treatment of different ailments. Today, honey is produced from many sources of plants and its antimicrobial activity varies greatly with origin and processing. Honey used to treat wounds must be unpasteurized and ideally should not be heated above 37 ̊C. However, the honeycombs have to be heated to get the honey out, and sometimes heating the honeycombs to 39 ̊C is necessary to do this (although not ideal, this temperature has not caused any problems). To assess the variation in antibacterial activity of honey, numerous varieties of New Zealand honeys were tested in vitro against Staphylococcus aureus in an agar well diffusion assay. This study demonstrated a highly significant difference in the antibacterial activity of honey from different floral sources. Kanuka, manuka, heather, and ling kamahi were shown to be sources likely to produce honey with high antibacterial activity. When antibacterial activity was assayed with catalase added to remove H2O2 liberated into the agar, most of the honeys showed no detectable antibacterial activity. However, manuka and vipers bugloss honeys retained their antibacterial activity in the catalase environment, indicating that these honeys also contained a nonperoxide component of activity. This activity stems partly from a phytochemical component. When manuka honey and pasture honey were tested against 58 strains of coagulase-positive S. aureus isolated from infected wounds, the minimum inhibitory concentrations were between 2% to 3% for manuka honey and 3% to 4% for pasture honey. This activity is beyond the point at which the osmolarity would have had an antibacterial effect; therefore, it was concluded that the previously identified phytochemical components of honey and the low pH are also active components. Another study showed that E. coli, Proteus mirabilis , Pseudomonas aeruginosa, Salmonella typhimurium, Serratia marcescens, S. aureus (including methicillin-resistant strains), and Streptococcus pyogenes were all susceptible in vitro to a manuka honey and a Knightia excelsa honey. In quite dilute solutions, both types of honey completely inhibited growth of all bacterial strains over an incubation period of 8 hours. The antimicrobial effects of honey are also effective against Candida albicans. The susceptibility of 72 isolates of C. albicans to a honey distillate fraction and several antimycotic agents showed all the isolates to be sensitive to the honey distillate, although 10% were variably resistant to nystatin, miconazole nitrate, and 54 Small Animal/Exotics Compendium January 2002 For more information, see the companion article entitled “Wound Management Using Sugar” on page 41. clotrimazole. The potency of the antibacterial activity of honey can vary by as much as 100-fold. It is believed that any locally produced honey with high levels of antibacterial activity will achieve good results when used to treat infected wounds. To assess this, the minimum inhibitory concentration or zones of inhibition in an agar diffusion assay can be used. A simpler method to assess the antibacterial activity of honey is to compare the amount of honey that has to be added to milk to prolong souring times. In practice, any unpasteurized honey would be effective in treating wounds. Compendium January 2002 Wound Management—Honey 55 An 8-month-old beagle mix presented with secondand third-degree burns to 20% of its body. The referring veterinarian debrided the third-degree burns and treated the area topically with silver sulphadiazine for 9 days prior to presentation to the Ontario Veterinary College. At this time, a healthy bed of granulation tissue had formed over the dorsum of the anterior thorax. The remainder of the dorsum of the torso and rump had an odorous, purulent discharge under a thick loose eschar. Oxymorphone, ketamine, and diazepam were administered, and the area was further debrided and lavaged with tap water (A). Although the dog appeared to be adequately anesthetized, it vocalized when the honey was applied to the granulation tissue and area under the previously removed eschar. Within 24 hours after the application of honey, the wound was no longer odoriferous and the appearance of the tissue was dramatically improved (B). Oxymorphone followed by propofol was used as an anesthetic to facilitate a bandage change. The dog was quiet until the honey was applied to both the areas of full thickness burn and the granulation bed, at which time it again started to vocalize. Within 48 hours of honey treatment, a clean, healthy appearing granulation bed of tissue was present in the area previously under the eschar, which could not be discerned from the early granulation bed. Isoflurane anesthesia was used for subsequent bandage changes and application of honey. At 72 hours, a healthy granulation bed was forming and most of the debridement was complete. Due to the potential for further discomfort with the application of honey, sugara was used to complete the debridement. Once a healthy granulation bed was formed (C), Furacin ointment was used to keep the wound clean during epithelialization. Primary closure of the wound was performed when the wound had contracted sufficiently. Because of this dog’s severe injury and inability to control its pain adequately prior to admission, the potential for a hyperalgesic state was high. This resulted in a very low threshold to pain; therefore, the painful response to the honey dressing may not be typical for the average wound. Pain has not been reported to occur