Evaluation of Wound Healing Efficacy of an Antimicrobial Spray Dressing at      Skin Donor Sites

 Lien-Guo Dai, MD, PhD¹; Keng-Yen Fu, PhD²; Pai-Shan Hsieh, MS²;Yu-Min Hung, MS³;Yi-Wen Wang^4,5, PhD; Li-Chuan Hsia², RN; Shun-Cheng Chang, MD, PhD²; Chih-Hsin Wang, MD²; Shou-Cheng Teng, MD²; Shyi-Gen Chen, MD²; Tim-Mo Chen,

MD²; Niann-Tzyy Dai, MD, PhD²

From the 1Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, ROC; 2Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; 3Institute of Polymer Science and Engineering, National

Taiwan University, Taipei, Taiwan, ROC; 4Department of Biology and Anatomy, Tri- Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; 5Burn Center, Tri-Service General Hospital, Taipei, Taiwan, ROC

Address correspondence to:

Niann-Tzyy Dai, MD, PhD

Division of Plastic and Reconstructive Surgery, Department of Surgery

Tri-Service General Hospital, National Defense Medical Center, Taiwan, ROC No. 325, Section 2, Cheng-Kung Road, Nei-Hu District

Taipei 114, Taiwan, ROC niantzyy_dai@hotmail.com

Disclosure: Financial support for this work was provided by the Ministry of National Defense, ROC (C-05-01, MAB101-45, MAB102-5, 103-M015), National Defense Medical Center and Tri-Service General Hospital, ROC (TSGH-C100-013-S02, TSGH-C101-008-013-S02, TSGH-C102- 006-008-013-S02, TSGH-C103-139).

Additional financial support was provided by Teh-Tzer Study Group for Human Medical Research Foundation, Taiwan, Republic of China.NMS Technologies Co Ltd, Nanjing, China, and ConvaTec, Bridgewater, NJ, provided products for the purposes of this study

Abstract: Introduction. Autologous skin transplantation is a com- mon treatment for patients with full-thickness burns. Postoperative wound care is essential for skin graft donor and recipient sites, but traditional wound dressings such as cotton and gauze do not form an effective barrier to bacteria, and patients can feel uncomfortable when replacing dressings. Materials and Methods. The goal of this study was to evaluate the use of an antimicrobial spray dressing (JUC Spray Dressing, NMS Technologies Co Ltd, Nanjing, China), with respect to its antimicrobial efficiency and the degree of pain experienced by patients. Results. The authors found the antimicro- bial spray can reduce pain during the recovery period, while pro- viding equivalent antibacterial protection to the control treatment (AQUACEL Hydrofiber Wound Dressing, ConvaTec, Bridgewater, NJ) based on skin culture tests. The spray did not adversely affect the wound site recovery. No significant side effects were present during the treatment period. Conclusion. This antimicrobial spray could potentially be used in wound dressing applications.

Key words: full-thickness burn, antimicrobial spray, wound dressing, antimicrobial efficiency, pain

The process of  wound  recovery  is  continuous, complex, dynamic, and sophisticated, and is affected  by  both  internal  factors  and the external environment. Internally, extracellular matrix (ECM) deposition and reepithelialization play an important role because they produce a barrier to resist microbial invasion. With respect to external factors, the  ability  to  control  infection  determines  whether  the  wound site will continue to deteriorate. Tissue  can  often  no  longer  regenerate after a deep injury; therefore, the wound area requires a dressing to assist recovery.¹ A temporary dressing is a useful and commonly used treatment to provide a suitable environment for wound healing.

Burns are painful  and  severe  injuries  that  have  a  radical  impact  on the human body. Grafting and excision have been the backbone of bumtreatment  for  100  years.²  Burn  wounds  often  require a skin autograft to provide a suitable environment for healing. However, procedural pain from repeated treat- ment such as skin  debridement  and  prolonged  dress- ing changes can be severe.^3,4 Conventional wound dressings such as plaster, gauze, and advanced wound dressings could protect the wound, although the ap- plication and removal of these dressing materials may cause pain.⁵

An antimicrobial spray dressing (JUC Spray, NMS Technologies Co. Ltd, Nanjing, China) includes quater- nary ammonium salts that have been widely used as antimicrobial agents. Their  antimicrobial  activity  may be related to the negatively charged cell surfaces of bacteria that attract the positively charged  salts  and allow them to disrupt the cell  membrane.⁶ Therefore, once the antimicrobial spray is applied to the skin sur- face, it forms a positive charge film to kill and isolate bacteria. The antimicrobial properties of  these  salts could be altered to fit different applications by chang- ing their functional groups.^7,8

Some areas of the body are difficult to protect from microbial infection using traditional wound  dressings, and  the  broad-spectrum  antimicrobial  spray  could  be a useful alternative in these cases. Unlike  chemical- based treatment, antimicrobial barriers  will  not  pro- duce bacterial resistance.This dressing spray was used in a study to control oral infection after an operation in the oral cavity, and was shown to significantly im- prove healing in all patients without any obvious side effects.⁹ In the current  study, the  authors  investigated the efficacy of the antimicrobial spray in preventing infection at a skin donor site.

Materials and Methods

The antimicrobial spray was provided by NMS Tech- nologies Co Ltd, Nanjing, China  for  the  purposes  of this study, and polyurethane film (Tegaderm, 3M, St. Paul, MN) was purchased for use as a cover film.An ad- vanced wound dressing (AQUACEL Hydrofiber Wound Dressing, ConvaTec, Bridgewater, NJ) was provided by the company for use as a control treatment.

Clinical case criteria. One hundred patients under- going skin autografting were recruited for this  study from the Tri-Service General Hospital, National De- fense Medical Center, Taiwan, Republic of China, be- tween July 30, 2012 and June 30, 2013. A skin graft donor site of both thigh areas measuring less than 10% total body surface area was tested, and the wound wastreated within 24 hours. Patients were  randomly  di- vided into an antimicrobial spray group and a control- treated group. The  patients  consisted  of  35  men  and 23 women between 34 and 50 years old. This study protocol was registered and approved by the National Defense Medical Center (TSGHIRB No.: 1-101-03-001). The inclusion criteria were patients with burns un- dergoing autologous skin surgery who had donor site exudate; no obvious signs of infection (ie, redness or fever); and were able to self-assess. The exclusion cri- teria were significant donor site infection or systemic manifestations of infection, a  dry  donor  site  or  one with very little exudate; existing skin diseases; severe cardiopulmonary dysfunction;  and  any  other  reason (eg, severe diseases such as liver and kidney dysfunc- tion that may have seriously interfered with  wound repair) determined by the study investigator. Treatment and evaluation standard. After surgery, the donor sites underwent conventional iodine disin- fection, wound tissue was taken for culture, and the color of the wound site was recorded. For the experi- mental group, the antimicrobial spray was applied uni- formly to the wound site, where it solidified immedi- ately to produce an invisible protective layer.This layer contains quaternary ammonium salts that have antibac- terial properties. The wound site was protected with polyurethane film that was replaced every 2-3 days as required. Patients in the control group were subject to routine disinfection using only hydrocolloid dressings. Pain was measured using the Visual Analogue Scale (VAS), where 0 indicated no pain and 10 indicated ex- treme pain. Samples were  taken  from  the  donor  site at 0, 4, 8, and 12 days for evaluation of infection and morphology, and the estimated time needed for  heal- ing, based on the clinician’s assessment, was recorded. Tissue  culture  at  wound  sites. A cotton  swab was used to collect bacteria from the wound area, and thendelivered to the Division of Clinical Pathology, Tri-Ser- vice General Hospital for analysis with a wound and pus culture. Microbes detected in the tissue cultures included diptheroids, Staphylcoccus epidermidis, and Proionbacterium acnes. If no colonies, or very few colonies, were present on the culture plate, the result was recorded as negative; otherwise, the result was re- corded as positive.

Statistical analysis. Except for tissue culture results expressed  as  a  percentage  of  the  population, results are presented as the mean ± standard deviation. Statis- tical differences were analyzed using Student’s  t  test, and  differences  were  considered  to  be  significant  for P values < 0.05.

Results

Wound healing time and morphology. A visual re- spresentation of the wound sites is presented in Figure

1. Compared  with  the  control  dressing, the  antimicro-

bial spray allowed a clear view of the wound site at the beginning of treatment (Figure 1a).Three days later, the control dressing had absorbed a great quantity of exu- date, but because the antimicrobial spray forms only a thin film, the exudate could evaporate. In addition, the wound was easier to clean, so the wound surface was drier than when using the control (Figure 1b). After 15 days, the wound pictured had almost healed, and the wound sites of both groups showed no significant dif- ferences (Figure 1c).

The wound healing times in the antimicrobial spray group were 16.74 ± 4.76 days, and 16.13 ± 4.84 days in the control group (Table 1), but the difference was not statistically significant. This indicates  the  protec- tive film from the antimicrobial spray did not adversely affect the wound site recovery. None of the patients showed any side effects during the study period. Wound culture.  Before  wound  treatment,  culture tests showed no obvious bacteria from the donor area in either group. After 3 days  of  treatment, 0.03%  of the antimicrobial spray group, but none in the control group, had a positive culture test. The number of cul- tures positive for bacteria increased to 0.18% in the control group and 0.17% in the antimicrobial spray group after 7 to 8 days of treatment (Table 1); however, none of these differences were statistically significant. Visual analog score. The VAS score exponentially decreased during treatment for both  groups; however, the pain scores of the antimicrobial spray group at any of the time intervals were less than those of the control group (Table 1). No patient in either treatment arm re- ported a VAS score greater than 4, and before treatment and 3 days postoperation there were statistical differ- ences (P < 0.05) between the antimicrobial spray and

control groups with respect to the VAS score.

Discussion

Burn treatment and healing are complex processes. Burn wounds are prone to bacterial infections that may delay healing. Thus, good autograft wound recovery is essential to prevent fluid and  nutrient  loss  and  pro- mote healing.¹⁰

The main  ingredients  of  the  antimicrobial  spray used in this study are water and quaternary ammonium salts, which act as cation particles. As an aerosol, the antimicrobial spray can uniformly  cover  wound  sites and form a thin antimicrobial layer. This layer provides a barrier between the wound and the external envi- ronment, thus preventing disease transmission. Unlike conventional dressings, this  method  can  be  used  for any part of the body and can reduce the risk of wound- dressing detachment, which results from physical ac- tivity. Microorganisms such as bacteria carry a net neg- ative charge. When bacteria are close  to  wound  sites, the electrostatic force leads the  cation  particles  to absorb negatively charged bacteria. This disrupts bac- terial cell membranes and leads to a loss of structure and cellular activity.¹¹ In this clinical study, the spray showed efficient antimicrobial activity. There  were  a few infections after treatment with the antimicrobial spray, but this may have been caused by sweat from physical activity that could have caused a loss of the protective film.To enable widespread use of the antimi- crobial spray, the timing of changing wound dressings that have been placed over skin treated with the anti- microbial spray should be researched and discussed to test for limits of adherence.

Autograft is a common and useful way to treat burn

wounds, but recovery depends  heavily  on  postopera- tive care; for most patients, this is a huge challenge. Pruritus and pain at the wound site is a serious prob- lem,  especially  for  burn  patients  with   comorbities, and represents both a psychological and physiological burden during treatment. Pain control is essential to improve the patient’s quality of  life. Currently, long- term pain control  using  medications  like  methadone or morphine reduces background pain and promotes recovery,¹² but the associated side effects such as re- spiratory depression, sedation, nausea, or constipation could prove problematic. Antimicrobial spray can re- duce pain at the donor site by forming a physical bar- rier and can reduce pain significantly (P < 0.05), espe- cially in the initial recovery period. The authors found that, even when the donor site had almost healed, the VAS score of the antimicrobial spray group was lower than that of  the  control  group, suggesting  antimicro- bial spray is useful for reducing pain throughout re- covery. In addition, no significant side effects were ob- served during the treatment period, indicating that the antimicrobial spray can be used as a treatment tool to improve the quality of life of burn patients.

Conclusion

The objective of this study was to determine wheth- er an antimicrobial spray is superior to conventional wound dressings. Burns are an  accidental  injury  that can result in long-term pain during recovery. The an- timicrobial spray  is  an  ideal  wound  dressing, because it could effectively  reduce  pain  while  being  suitable for wounds in areas difficult to fit with a conventional dressing. The wound healing times are comparable be- tween the control dressing and the antimicrobial spray. In addition, none of the patients had any side effects af- ter surgery. Therefore, antimicrobial spray may be use- ful in a variety of postoperative applications.

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10.evaluation of wound healing efficacy of an antimicrobial spray dressing at skin donor sites.pdf