Complications in wound healing — coupled with increasing multidrug resistance — is an emerging threat to patient morbidity and mortality, presenting challenges to infectious disease and contemporary wound care managers.1-4  The accelerated rate at which microorganisms are becoming increasingly resistant to established pharmacotherapeutic agents is staggering, with established regimens in danger of becoming less effective to common pathogens.5 Ultimately the rise in pathogenic opposition, the burden to the healthcare community, and patient welfare could be insurmountable.6,7 While not often easy to quantify, a salient example is the rising cost of methicillin-resistant Staphylococcus aureus (MRSA), with treatment in the United States alone well in excess of $34 billion each year.5 Yet, this is not limited to financial capital, as mortality from MRSA has been attributed to 75% of inpatient burn cases alone.6,8 Therefore, it becomes evident that alternative treatments need to be entertained as potential adjuncts to contemporary pharmacotherapeutic regimens. Although complementary therapies such as acupuncture, massage, and relaxation have been proposed, these may be impractical for most clinical scenarios.3,9 With this in mind, we present treatment options (and the evidence supporting paradigm shifts) that suggest prompt adaptation into conventional practice with the greatest applicability to improve patient outcomes in wound management.9

Essential Oils

Essential oils are derived from distillation of leaves, bark, or flowers of certain organic materials that are believed to possess inherent antimicrobial properties with limited risk of progression in emerging microbial resistance. 1,5,6,10-12 Recent literature supports the use of various essential oils to decrease virulence, particularly multidrug resistance10,  Promotion of antimicrobial properties and improvement in wound healing has been linked to those oils with phenols, alcohols, and terpenic ketones.4-6

Although numerous agents have been proposed for use as potential antimicrobials, only a few have been consistently studied for their reliability and mechanism of action.5,6,10 Yet, the studies that have been performed have shown destruction of the microbial cell membrane leading to lysis and expulsion of cellular ions.9 The most common agents proposed with a propensity for wound healing effectiveness are aloe vera, echinacea, thyme, peppermint, mimosa, cinnamon, tea tree, rosemary, ginseng, jojoba, eucalyptus, lemongrass, garlic, and gingko.3,9,10


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As with existing pharmacotherapeutic agents, the efficacy of an essential oil is dependent on the target organism, its concentration, and its dispersion properties.10 For example, Foeniculum vulgare fruits are known to possess broad-spectrum antimicrobial properties — with activity against both Gram-positive and Gram-negative microbes — and antifungal properties, while other agents have proven more selective when used appropriately.10 Rosemary and clary sage oils are known to inhibit only Gram-positive bacteria, while basil oil may inhibit both Gram-positive and Gram-negative bacteria. Although evidence supports the effectiveness of rosemary, clary sage, and basil against S aureus, rosemary has also been associated with synergistic and inhibitory properties against E faecalis when added to antibiogram-directed treatments (even when the organism had proven resistant to such agents as gentamycin and ciprofloxacin).1

It is important to note that routes of administration and associated efficacy are contingent on the agent being examined, and what works for some essential oils will not apply to all agents and illnesses being considered.

Vapor

Organism-targeted therapies can be affected by the route of essential oil exposure. As a vapor, essential oils have consistently revealed an affinity for some of the most virulent organisms, such as MRSA, but also vancomycin-resistant Enterococci and Clostridium difficile.12 In vitro studies of essential oil vapor have revealed promising results in reducing numerous “antibiotic-resistant, healthcare-associated” pathogens.12 Most of the focus in this research aims to reduce air contamination during procedures and in environments where airborne pathogens pose risk. A study performed by Doran et al reported a reduction in airborne bacteria by 89% when essential oil vapor was used for as little as 15 hours.12  With limited established toxicity profiles when delivered as an aerosolized instrument, essential oils present the greatest benefit in areas where decontamination places a significant burden on medical and treatment staff. 12 The value of vapor transmission is therefore that of prophylactic management as a means of disease reduction.

Topical

Although vapor is the most prevalent essential oil route, topical antimicrobial therapy is regarded as an important component of wound care to prevent wound deterioration and infection.4,8 The skin plays a significant role in protecting the internal body environment from external hazards, and any intrusion into or destruction of this barrier can disrupt the body’s essential systemic structures and biomechanical function.13

Burns from heat, chemicals, electricity, sunlight, and radiation are just a few examples of trauma that can expose the body to denaturing compromise.  Accidental thermal burns alone are considered the leading cause of mortality and disability with an estimated 2 million people afflicted each year, and wound healing is essential for barrier restoration.13,14 The aim of wound healing is to facilitate a short time for repair with few side effects and reducing incidence of infections, which is why there is a growing tendency toward pharmaceutical herb usage.15,16   The 4 phases of wound healing — hemostasis, inflammation, proliferation, and remodeling — are each influenced by the migration of specific types of cells into the wound; each phase is dependent on the acceleration or deceleration of certain components in that process, which when fostered allow for improved healing.11,14,17,18   

The primary treatment goal of topical agents is to promote multidimensional wound healing by inhibiting the proliferation of infection-causing microbes.13,15 Inhibition of microbe proliferation may lead some to entertain applying essential oils to wound dressings.6,8 Of those noted agents, tea tree oil from Melaleuca alterifolia lends itself as one of the most effective agents against prominent skin flora — especially Staphylococcal species, namely MRSA and methicillin-susceptible S aureus — when topically applied.5,9 Predominating in chronic wound management, tea tree oil has the advantage of possessing both bacteriostatic and bactericidal properties, while also increasing monocytic differentiation and decreasing inflammation and overall time spent healing.5,9 Although tree oil has been reported by Shea et al as the most efficacious essential oil monotherapy for topical wound management, geranium and citricidal oils can also be used as a combination agent with similar results.8

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Lavender has been proposed to possess similar antimicrobial, anti-inflammatory, and even analgesic properties.6 However, the evidence for its proposed benefits, including wound healing and scar reduction, remains largely anecdotal.6,12

Studies have revealed some agents with a proclivity toward improved deep tissue wound healing derived from their phytochemical ingredients. L augustifolia and L nobilis are noted for improved tensile strength of a wound following incision, which can be beneficial for those who are prone to poor wound healing and atrophy.6,19

Oral

Studies have supported the use of essential oils as oral therapies. For example, while a naturally occurring spice compound, the bioactive component of turmeric is proposed to possess anti-inflammatory, analgesic, and healing properties.3 At this time, however, the ideal dosage of the agent and route of optimal delivery remain uncertain.3 Although toxicity, allergic reactions, and complications from topical and vapor agents remain low, the safety of oral therapies cannot be substantiated reliably. Therefore, oral administration of essential oils is not endorsed.9,12

Aloe
Aloe vera extract has shown impressive effects in cutaneous injury and wound healing, especially those associated with burn and frostbite.13,17,20,21  Since antiquity, aloe has been known by many as “the healing plant,”16 and it is ultimately the most studied species of the Aloe genus.15-18,20,21 Recent research has revealed that in addition to its hypoglycemic, gastroprotective and “antimalignancy properties, it has been shown to exhibit anti-inflammatory, antifungal, and antimicrobial properties.”15-18,20,21    

It is through these essential properties that aloe is able to exert its skin protective activities, including stimulating primary epidermal keratinocyte proliferation that is crucial in the first hours of wound healing.14,20

The gel formulation of aloe is derived from the succulent leaves of the plant, whereas aloe juice is obtained from the peripheral bundle sheath cells.20 Aloe gel, the active ingredient of which is an organically active compound known as aloin, increases aloe’s stability, basic structure, and water solubility, making it attractive to study in wound healing.18 Consisting of 99% water with long-chain polysaccharides, aloe gel prevents skin dryness and bacterial growth, largely due to its high osmotic composition.15  Furthermore, aloe gel has been found to increase epithelialization, thereby shortening the duration of wound healing; this has been most prominently studied in first- and second-degree burns.17

Conventional strategies of wound management have included aloe in both simple and complex wound care regimens, including dressings. Such dressing, historically composed of pectin and gelatin with success, were recently studied using aloe vera as part of their matrix.  The results supported aloe’s strong anti-inflammatory effect, enhanced cell migration, and scar prevention, as well as orderly collagen formation and neovascularization.21

Further studies of the effect of aloe vera gel on wound healing continue to support significant acceleration in the healing process due to increased proliferation of fibroblasts and keratin, increased collagen synthesis, and reduction of inflammation.15,18 While higher-potency applications have demonstrated impressive findings in healing time, these outcomes were consistently observed across all spectra of wound management and potency of gel, including low-potency aloin vehicles.18 Overall, clinical research has supported that aloin solution, especially that of aloe gel, promotes faster rate of wound closure and inhibited scar tissue formation and should be considered an essential component within the continuum of topical wound management.

Honey

The use of honey for wounds, burns, and skin ulcers dates back many centuries. In the wake of progressive medical breakthroughs, including antibiotics and advanced surgical techniques, the use of honey as a foundational intervention has all but ceased.22 However, renewed interest has been observed, due largely to rising antibiotic resistance and desire for favorable adjuncts to topical wound therapy, of which honey has anecdotal, historical evidence of benefit.22

Beyond its low cost and availability, honey has properties that make it an attractive topical treatment option, including: improved tolerance of the patient to dressing changes, wound odor, swelling, hypertrophy, and contracture reduction, as well as prohibitive microbial growth properties.23 These properties would be particularly beneficial for burn injuries for which necrotic tissue can result in complex infections.23 As a vehicle, topical honey has proven anti-inflammatory and antimicrobial to both bacterial and fungal elements due mainly to its acidic viscosity, which not only allows a “moist healing environment that absorbs exudates [and accelerates] healing, but also improves patient tolerance and comfort.”22,23

Studies have compared honey with contemporary wound therapies with promising success. In several studies comparing the use of pure undiluted honey vs conventional silver sulfadiazine (SSD), honey was found to have superior healing effects.23 Healing time was significantly lower (18.1 vs 32.6 days), swab cultures became negative in less than 7 days whereas none in the SSD group became negative, and a majority of the honey group recovered completely (81% vs 45%).23 However, in additional clinical trials, it was demonstrated that burn severity contributed to the effectiveness of honey and SSD.  When considering superficial and partial-thickness burn wounds, it was noted that the honey group had better healing rates and properties; however, when studying mixed partial-thickness and full-thickness burn wounds, honey did not seem to improve healing. As few studies have been conducted, more trials are needed to elucidate the benefit of honey for burn wound healing. 22

Conclusion

Complications of wound healing coupled with multidrug resistance and cost effectiveness beg the idea of researching new and perhaps even past methods of care that could contribute to effective wound care.  Essential oils, aloe, and honey have demonstrated efficacy when used independently and synergistically with pharmacotherapy.  The broad availability and low risk of side effects make such alternatives an attractive solution to wound care.  Further trials to explore efficacy and consistency with specific essential oils and susceptible organisms would be beneficial, as would deeper exploration of aloe and honey for burns and more expansive wound management.

Bethany Helm, MPAS, PA-C, is a surgical PA and is employed by the Guam Seventh-day Adventist Clinic with a special passion for wound care. At the time of this writing she was a graduate student at Kettering College Master of Physician Assistant Studies program. Christopher Howell, DSc, MPAS, PA-C, MBA, is associate professor at Kettering College Master of Physician Assistant Studies, in Dayton, Ohio.  Dr Howell is also a staff clinician in the Emergency Department with Team Health; North Dayton Addiction Recovery; and East Indiana Addiction Recovery.

References

  1. Sienkiewicz M, Łysakowska M, Kowalcyzk E, et al. The ability of selected plant essential oils to enhance the action of recommended antibiotics against pathogenic wound bacteria. Burns. 2017;43(2):310-317.
  2. Beitz JM, Goldberg E, Yoder LH. The lived experience of having a chronic wound: a phenomenologic study. Medsurg Nurs. 2005;14(1):51-82. 
  3. Levine, J. The effect of oral medication on wound healing. Adv Skin Wound Care. 2017;30(3):137-142.
  4. Barreto RS, Albuquerque-Júnior RL, Araújo AA, et al. A systematic review of the wound-healing effects of monoterpens and iridoid derivatives. Molecules. 2014;19(1):846-862.
  5. Chin K, Cordell B. The effect of tea tree oil (Melaleuca alternifolia) on wound healing using a dressing model. J Altern Complement Med. 2013;19(12):942-945.
  6. Süntar I, Akkol EK, Tosun A, and Keleş H. Comparative pharmacological and phytochemical investigation on the wound healing effects of the frequently used essential oils. J Essential Oil Res. 2014;26(1):41-49.
  7. Andreau V, Mendoza G, Arruebo M, Irusta, S. Smart dressings based on nanostructured fibers containing natural origin antimicrobial, anti-inflammatory, and regenerative compounds. Materials. 2015;8(8):5154-5193.
  8.  Edwards-Jones V, Buck R, Shawcross SG, Dawson MM, Dunn K. The effect of essential oils on methicillin-resistant Staphylococcus aureus using a dressing model. Burns. 2004;30(8):772-777.
  9. Stea S, Beraudi A, De Pasquale D. Essential oils for complementary treatment of surgical patients: state of the art. Evid Based Complement Alternat Med. 2014;2014:726341.
  10. Liakos I, Rizzello L, Scurr DJ, Pompa PP, Bayer IS, Athanassiou A. All-natural composite wound dressing films of essential oils encapsulated in sodium alginate with antimicrobial properties. Int J of Pharm. 2014;463(2):137-145.
  11. Wu JG, Ma L, Zhang SY, Zhu ZZ, Zhang H, Qin LP, Wei YJ. Essential oil from rhizomes of Ligusticum chuanxiong induces apoptosis in hypertrophic scar fibroblasts. Pharm Biol. 2011;49(1):86-93. 
  12. Doran AL, Morden WE, Dunn K, Edwards-Jones V. Vapour-phase activities of essential oils against antibiotic sensitive and resistant bacteria including MRSA. Lett Appl Microbiol. 2009;48(4):387-392.
  13. Hashemi SA, Madani SA, Abediankenari S. The review on properties of aloe vera in healing of cutaneous wounds. BioMed Res Int. 2015;2015:714216.
  14. Moriyama M, Moriyama H, Uda J, et al. Beneficial effects of the genus aloe on wound healing, cell proliferation, and differentiation of epidermal keratinocytesPLoS ONE. 2016;11(10):e0164799.
  15. Takzare N, Hosseini M-J, Hasanzadeh G, Mortazavi H, Takzare A, Habibi P. Influence of aloe vera gel on dermal wound healing process in rat. Toxicol Mech Methods. 2009;19(1):73-77.
  16. Jahandideh M, Hajimehdipoor H, Mortazavi SA, Dehpour A, Hassanzadeh G. Evaluation of the wound healing activity of a traditional compound herbal product using rat excision wound modelIranian J Pharm Res. 2017;16(Suppl):153-163.
  17. Fox LT, Mazumder A, Dwivedi A, Gerber M, du Plessis J, Hamman JH. In vitro wound healing and cytotoxic activity of the gel and whole-leaf materials from selected aloe species. J Ethnopharmacol. 2017;200:1-7.
  18. Li L-J, Gao S-Q, Peng L-H, et al. Evaluation of efficacy of aloin in treating acute trauma in vitra and in vivo.  Biomed & Pharmacother. 2017; 88:1211-1219
  19. Cheung C. Older adults, falls, and skin integrity. Adv Skin Wound Care. 2017;30(1):40-46.
  20. Akaberi M, Sobhani Z, Javadi B, Sahebkar A, Emami SA. Therapeutic effects of Aloe spp. in traditional and modern medicine: a review. Biomed Pharmacother. 2016;84:759-772. 
  21. Tummalapalli M, Berthet M, Verrier B, Deopura BL, Alam MS, Gupta B.  Composite wound dressings of pectin and gelatin with aloe vera and curcumin as bioactive agents. Int J Biol Macromol. 2016;82:104-113.
  22. Dorai AA. Wound care with traditional, complementary and alternative medicine.  Indian J Plast Surg. 2012;45(2):418-424. 
  23. Gupta SS, Singh O, Bhagel PS, Moses S, Shukla S, Mathur RK. Honey dressing versus silver sulfadiazene dressing for wound healing in burn patients: a retrospective study. J Cutan Aesthetic Surgery. 2011;4(3);183-187.

This article originally appeared on Clinical Advisor