Topical Honey and Wounds

Honey on Sloughy Venous Ulcers

   Reference: Gethin, G, Cowman S. Manuka honey vs. hydrogel—a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers. J Clin Nurs. 2008;Aug 23. [Epub ahead of print]    Rationale: Expert opinion suggests honey may be effective as a wound desloughing and healing agent. Randomized controlled trials (RCTs) on chronic wounds remain to be conducted.    Objective: Conduct a prospective RCT to explore the effects of Manuka honey (MH) on VU desloughing and healing.    Methods: Adult patients with an ankle/brachial systolic blood pressure ratio (ABI) ≥ 0.8 recruited from vascular centers in the United Kingdom, acute care, and community leg ulcer clinics with a VU area 100 cm2 covered at least 50% in slough, were randomized to weekly treatment for 4 weeks with sustained multilayer high compression and either MH (n = 54) or an amorphous hydrogel (n = 54). The primary wound dressing was covered with secondary hydrocellular foam dressing in addition to appropriate compression. All patients were treated for 8 additional weeks according to investigator preference. Patients taking antibiotics, undergoing immunotherapy, or who had significant nonvenous conditions were excluded. Primary outcomes were percentage of the ulcer covered with slough on week 4 and percentage of patients healed at week 12. Secondary outcomes were decreases in wound size and/or epithelization. Adverse events were analyzed as a measure of safety. Subset healing analysis was performed as a function of Margolis score for VU delayed healing risk,5 which adds 1 risk unit if a VU is ≥ 6 months in duration or ≥ 5 cm2 in area, or 2 risk units if both are true.    Results: Both groups were comparable at baseline. The percentage of patients healed during 12 weeks was higher (P = 0.03) for MH patients (44%) than for hydrogel patients (33%), and 4-week median wound area was smaller (P = 0.001).    Manuka honey patients also experienced greater 4-week percentage slough reduction (P = 0.05). Percentage of VU covered with slough declined significantly in both groups from baseline to week 4: from 85% slough at baseline to 29% slough at 4 weeks for the MH group, and from 78% to 43% for the hydrogel group. A nonsignificant trend (P = 0.06) favored the MH group.    Adverse events were comparable with trends (P = 0.07) for more study VU-related withdrawals: 17 (31%) in the hydrogel group and 9 (17%) in the honey group, and for earlier infection-related study withdrawal in the hydrogel group. The main reasons for withdrawal were study VU infections (hydrogel 22%; MH, 11%) and patient request (5.5% of hydrogel patients, no MH patients).    Margolis score was strongly associated with 12-week VU healing. The difference between MH and hydrogel percentage healed at 12 weeks persisted (P = 0.025), independent of Margolis score adjustment.    Authors’ Conclusions: Manuka honey increased healing and desloughing of VUs compared to hydrogel control therapy.

Honey in Wound Care: A Cochrane Review

   Reference: Jull AB, Rodgers A, Walker N. Honey as a topical treatment for wounds. Cochrane Database Syst Rev. 2008;(4):CD005083.    Rationale: Honey has been used since ancient times in wound care. Preclinical studies and some clinical trials suggest honey may accelerate healing.    Objective: Conduct a systematic review to determine whether honey accelerates acute and/or chronic wound healing.    Methods: The authors searched Cochrane, EMBASE, MEDLINE, and CINAHL databases for RCTs and quasi-experimental controlled studies using any source of honey on acute or chronic clinical wounds with primary outcomes of time to complete healing or proportion of participants with completely healed wounds. Secondary outcomes included length of hospital stay, change in wound size, cost of care, quality of life, and incidence of infections or adverse events. Manufacturers were contacted for unpublished trials. Combined analyses were performed if data were homogeneous. Treatment effects were deemed significant if P ≤ 0.05.    Results: Nineteen trials on 2554 patients were included in the analysis. Homogeneity was insufficient for a combined healing analysis of acute and chronic wound studies. Topical honey reduced healing time compared to conventional dressings for partial-thickness burns (2 studies; 496 honey patients; P 0.00001) and compared to silver sulfadiazine (1 study; 50 acute or chronic wound patients managed with honey; P 0.00001). Three small studies on chronic wounds reported significantly shorter healing time in honey-treated pressure ulcers (compared to saline gauze), infected postoperative gynecologic wounds (honey applied twice daily compared to washes with 70% ethanol with povidone iodine), and Fournier’s gangrene (compared to Eusol-soaked gauze). Combined analysis of 2 VU studies (241 receiving honey) reported that the 12-week percentage healed favored honey, but lacked statistical significance (combined P = 0.12).    Adverse event reporting varied across studies. Analyses generally showed honey groups comparable to controls. Exceptions were infected postoperative gynecology wounds, which reported fewer adverse events when treated with honey (P = 0.019), and VU in which more events (P = 0.016) were reported in the MH group, although these rarely caused study withdrawal and were estimated by the authors to be “short-lived and tolerable.” Manuka honey use was associated with a total of 10 study days of VU-related hospitalization compared to 40 days for “usual care,” a result not addressed in the adverse event analysis.6    Authors’ Conclusions: Honey may improve healing in superficial burns and skin graft donor sites, but when used with compression does not significantly increase leg ulcer healing at 12 weeks though the “possibility of a modest effect cannot be ruled out.” Other wound types have insufficient evidence to guide clinical practice.

Clinical Perspective

   The RCT by Gethin et al suggests that honey matches or exceeds the recognized capacity of hydrogel for autolytic debridement of sloughy VUs, and facilitates healing for VUs independent of risk factors for delayed healing. The robust association between Margolis scores and 12-week percentage healed in both groups suggests research exploring predictive validity of Margolis score for 12-week VU healing. Simply put, larger VUs with longer duration take longer to heal.    Another hypothesis to explore is that the larger, longer duration of the VUs, the more difference MH makes.7 Gethin et al studied patients with more recalcitrant, larger, more slough-covered VU with mean duration 29–39 weeks compared to 16- to 20-week duration VUs studied by Jull et al6—the second VU study in the Jull et al Cochrane review summarized above. Variability in “usual care” control treatments may also explain lack of consistency of the reported favorable MH healing effect.6 The Cochrane reviewers conclude that a possible healing effect of MH as an adjuvant to compression cannot be ruled out inviting further RCTs on VUs and other chronic wounds. The overall effect of honey on adverse events remains to be clarified in future studies with more consistent reporting of both severity and frequency of adverse events.    The Cochrane review conclusion that honey is safe and may improve healing in burns and skin graft donor sites is useful information to support acute wound care decisions. Future RCTs are needed on chronic wounds comparing outcomes using topical honey from different sources.

References

1. Breasted JH. The Edwin Smith Papyrus, Published in Facsimile and Hieroglyphic Transliteration. Chicago, IL: University of Chicago Press; 1930. 2. Molan PC. The evidence supporting the use of honey as a wound dressing. Int J Low Extrem Wounds. 2006;5(1):40–54. 3. Cooper RA, Molan PC, Harding KG. The sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds. J Appl Microbiol. 2002;93(5):857–863. 4. Tonks AJ, Dudley E, Porter NG, et al. A 5.8-kDa component of manuka honey stimulates immune cells via TLR4. J Leukoc Biol. 2007;82(5):1147-1155. 5. Margolis DJ, Berlin JA, Strom BL. Which venous leg ulcers will heal with limb compression bandages? Am J Med. 2000;109(1):15–19. 6. Jull A, Walker N, Parag V, Molan P, Rodgers A. Honey as adjuvant leg ulcer therapy trial collaborators. Randomized clinical trial of honey-impregnated dressings for venous leg ulcers. Br J Surg. 2008;95(2):175–182. 7. Bolton LL. Leg ulcers and honey: a review of recent controlled trials. In: Cooper RA, Molan P, White RJ, eds. Honey: A Modern Wound Management Product. Shaftesbury, Dorset, UK: Wounds UK Books; 2008:16–29.