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Negative pressure wound therapy for serious dog bites of extremities: a prospective randomized trial
Negative pressure wound therapy for serious dog bites of extremities: A prospective randomized trial Chen Rui-feng M.M., Huang Li-song M.M., Zheng Ji-bo M.B., Jia Yiqing M.B., Liu Yu-jie M.M., Shan Yi M.M. PII: DOI: Reference:
S0735-6757(16)00123-6 doi: 10.1016/j.ajem.2016.02.043 YAJEM 55617
To appear in:
American Journal of Emergency Medicine
Received date: Revised date: Accepted date:
5 August 2015 18 January 2016 15 February 2016
Please cite this article as: Rui-feng Chen, Li-song Huang, Ji-bo Zheng, Yi-qing Jia, Yujie Liu, Yi Shan, Negative pressure wound therapy for serious dog bites of extremities: A prospective randomized trial, American Journal of Emergency Medicine (2016), doi: 10.1016/j.ajem.2016.02.043
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ACCEPTED MANUSCRIPT Negative Pressure Wound Therapy for Serious Dog Bites of extremities: a Prospective Randomized Trial
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Chen Rui-feng, M.M.; Huang Li-song, M.M.; Zheng Ji-bo, M.B.; Jia Yi-qing, M.B.;
addresses:
Chen
Rui-feng:
[email protected];
Zheng
[email protected];
Liu
[email protected]
Ji-bo:
[email protected];
Huang Jia
[email protected];
Yu-jie:
[email protected];
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Email
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Liu Yu-jie, M.M.; Shan Yi#, M.M.
Li-song: Yi-qing ：
Shan
Yi:
Department of Emergency, Naval General Hospital of China Liberation Army, Beijing
Corresponding
author:
Shan
Yi,
TEL:
+8618600310572;
Fax
number:
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#
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100048, P.R. China
+8601066951311; Email: [email protected]
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Conflicts of Interest and Source of Funding: The authors declare no conflicts of interest.
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Authors’ contributions
Chen Rui-feng was the junior author and was fully in charge of the study, involved in the design, demonstration, implementation, data collection and statistical analysis, and manuscript composition. Shan Yi was the senior author and was mainly responsible for the researchers and contributors, involved in the design, surveillance and manuscript revision for important intellectual content. Huang Li-song was involved in writing the manuscript. Huang Li-song, Zheng Ji-bo, Jia Yi-qing and Liu Yu-jie coordinated the data collection and implementation. All of the authors read and approved the final manuscript.
ACCEPTED MANUSCRIPT Abstract Objectives: To investigate the emergency treatment of serious dog bite lacerations on
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limbs and to identify whether negative pressure wound therapy (NPWT) was beneficial in these instances.
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Methods: A total of 580 cases with serious limb lacerations due to dog bites were
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randomly divided into two groups. After thorough debridement, the limb lacerations of group A (n=329) were left open. The remaining cases (n=251) were randomly divided into two subgroups, group B and group C, which were treated with 125 mmHg and 75 mmHg of continuous negative pressure, respectively. Antibiotics were
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only used in cases where there were systemic signs of wound infection, and were not
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given prophylactically. The infection rate, infection time, and healing time were
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analyzed.
Results: The wound infection rates of groups A, B, and C were 9.1%, 4.1%, and 3.9%,
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respectively. The infection times of the three groups were 26.3 ± 11.6 h, 159.8 ± 13.4 h, and 166.4 ± 16.2 h, respectively. The recovery times of the infection patients in the three groups were 19.2 ± 4.6 d, 13.2 ± 2.1 d, and 12.7 ± 2.3 d, respectively, and in the non-infection patients, the recovery times were 15.6 ± 2.7 d, 10.1 ± 2.3 d, and 10.5 ± 1.9 d, respectively. In groups B (-125 mm Hg) and C (-75 mm Hg), the infection rate, infection time and healing time showed no significant differences.
ACCEPTED MANUSCRIPT Conclusion: Patients with serious dog bite laceration on limbs could benefit from NPWT. Compared with the traditional treatment of leaving the wounds open, NPWT
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reduced the infection rate and shortened recovery time. When NPWT was performed, low negative pressure (-75 mm Hg) had the same positive effects as high pressure
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(-125 mm Hg). Prophylactic antibiotics administration is not recommended for
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treating this kind of laceration.
Level of Evidence: Therapeutic/Care Management, level II Key Words: Dog bite; laceration; Negative pressure wound therapy; Prospective
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randomized trial; Debridement; Antibiotics.
ACCEPTED MANUSCRIPT 1. Introduction
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In recent years, the incidence of dog bites has increased markedly. According to data
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from the Centers for Disease Control and Prevention (CDC) of Beijing, more than 150,000 people were attacked by dogs in 2006 in Beijing, which increased to more
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than 220,000 in 2012. Approximately 88.6% of dog bite cases involved the upper or
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lower extremity, and approximately 12% were serious lacerations. Some pertinent literature has been published about the surgical treatment of dog bite lacerations; however, prospective studies have rarely been performed. Dog bite wounds are a special kind of wound, with high infection rates and prolonged healing times, and
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their surgical treatment is controversial. Negative pressure wound therapy (NPWT) is
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a simple and efficient way to promote healing in a variety of complicated wounds.
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After packing or covering the wound with alginate foam containing polyvinyl alcohol and packing a layer of biological membrane at the surface of the foam and wound, the
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drainage tubes from the foam are connected to a negative pressure aspirator and the treatment is initiated. NPWT has emerged over the last 20 years, and is widely used in surgical fields. NPWT have achieved good results, especially in the treatment of complex wounds, and is widely recognized by surgeons. However, very few studies have examined the use of NPWT in serious dog bites lacerations. This prospective study aimed to assess whether NPWT has a positive effect on wound healing in serious dog bite lacerations.
ACCEPTED MANUSCRIPT 2. Patients and methods
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Male or female patients older than 18 years old, who presented at our Rabies
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Prophylaxis and Immunity Clinic of Beijing with dog bites to the limbs were enrolled in this prospective randomized trial. Patients with lacerated limb wounds demanding
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surgical treatment (lacerations with lengths of at least 5 cm, multiple penetrating
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lacerations of soft tissues, or lacerations accompanied by damage to at least one of the following: muscles, tendons, ligaments, nerves, articular capsules, fractures, important blood vessels, acra amputation) were enrolled. Exclusion criteria were puncture wounds (less than 2 mm), medium or small lacerations (less than 5 cm), infected
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wounds at presentation, having visited a doctor’s office more than 8 h after the injury,
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wounds with skin loss requiring plastic surgery, or patients with immune deficiency,
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using immunosuppressive agents, with autoimmune disorders or diabetes. All patients were subjected to block randomization and were assigned to a control group (group A)
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and an NPWT group. Those in the NPWT group were randomly assigned to group B (NPWT -125 mmHg pressure group) and group C (NPWT -75 mmHg pressure group) using a block random digits table. The therapeutic schedules were explained to the patients in each group, and their signatures were obtained on consent forms. Patients who refused the therapeutic strategy were excluded from the trial. Before the clinical trial started, we obtained approval for the clinical trial from our hospital ethics committee (IEC. Navy General Hospital, Permitted NO.: HZQX-PJ-2006-12).
ACCEPTED MANUSCRIPT 2.1 Debridement procedure
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All of the limbs with dog bite lacerations underwent thorough debridement as follows.
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2.1.1 Cleaning and disinfection
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To relieve the pain of the patients, local anesthetic was administered before wound cleaning and disinfection. After covering the wounds with sterilized dressing, a sterile
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cotton ball was used to scrub the area around the wounds 2-3 times with 20% liquid soap under running water. Subsequently, the wounds were alternately cleaned with ample 20% liquid soap and physiological saline, and with 3% hydrogen peroxide and
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physiological saline. The total cleaning time was at least 15 minutes for each wound. A large amount of 0.05% iso-osmia iodophors was used to disinfect the wounds for
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2.1.2 Debridement
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not less than 5 minutes.
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All devitalized tissue, coagulated blood, foreign material, and markedly contaminated tissue were carefully removed to expose the surrounding healthy tissue. It was essential to retain the integrity of this tissue as much as possible to repair them later and to prevent osteofascial compartment syndrome. The final procedure of debridement involved cleaning of the inside part of the laceration with 0.05% iodophors again. Sterile gloves, aseptic covers, and surgical instruments were then prepared for tissue repair. At this time, passive immunity, if necessary, was administered.
ACCEPTED MANUSCRIPT 2.1.3 Important tissue repair
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All of the important impaired organs or tissues (such as muscles, tendons, ligaments,
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important nerves, articular capsules, fractures, important blood vessels, and acra amputation) were repaired with suitable operations after debridement, and these
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surgeries were performed at least 2 hours after rabies immunoprophylaxis therapy.
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2.1.4 Wound cover
After thorough cleaning and debridement, the lacerations in group A were left open and covered with sterilized dressings. The lacerations in groups B and C were covered
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with a polyvinyl alcohol shrink formaldehyde bubble dressing (VSD Medical Science and Technology Co. Ltd., Wuhan, China) for NPWT. We used a hospital central
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vacuum aspiration system as a continuous negative pressure source, and negative
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and C.
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pressure was set at two levels: 125 mm Hg and 75 mm Hg, respectively in groups B
All of the patients were administered rabies prophylactic active immunity and/or passive immunity. Tetanus antitoxin was also administered, if necessary. Drainage was performed according to the actual condition of the lacerations. A drain was placed in the innermost part of the wound and was replaced or removed according to the drainage quantity, usually 24 –48 h after surgery. All of the wounds in groups A were covered with sterilized dressings, which were changed 24–48 h after surgery. The NPWT was removed 4-5 days after surgery in groups B and C. The stitches in all sutured lacerations were removed 10–14 d after surgery, according to the state of
ACCEPTED MANUSCRIPT wound healing. Antibiotics were administered only after wound infection occurred.
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2.2 Observation indices
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2.2.1 Infection rate
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Infection was defined as the satisfaction of one of the following three major criteria: fever (body temperature ≥ 38°C), abscess, and lymphangitis; or four of five minor
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criteria: wound-associated erythema that extended more than 3 cm from the edge of the wound, tenderness at the wound site, swelling at the site, purulent drainage, and a white blood cell count in the peripheral blood of 12,000/ml.
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2.2.2 Infection time
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The infection time was the interval from being bitten to emerging infection
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indications (calculated as the time in hours).
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2.2.3 Recovery time
The recovery time was the interval from being bitten to the wound achieving clinical healing (calculated as the time in days). 2.3 Statistical analysis Statistical analysis was performed with SPSS software, version 13.0 (Chicago, IL, USA), to compare the two groups. The chi-square test and t-test were applied. Statistical significance was set at α=0.05.
ACCEPTED MANUSCRIPT 3. Results
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Between January 2007 and September 2015, 653 patients were enrolled in this study.
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After assessment, 42 were excluded and 25 were not willing to participate in our study. A total of 586 patients were included in this study. After randomization, 335 patients
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were in group A and 251 were included in the NPWT group. All the patients in NPWT
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group and most of the patients in group A (90%, 296/329) were hospitalization. In addition, 6 patients in the group A were lost to follow up (see Fig. 1). Among the 580 valid patients, 265 were male and 315 were female. The age range was 18-94 years old. The average length of the largest wounds was 9.32±3.27 cm, and the average
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wound number was 4.6±1.7. Some patients lost or suffered serious damage to their
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organs from dog bites: 24 cases lost parts of fingers, 75 cases were accompanied by
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open fractures, and 76% of the cases were accompanied by damaged muscles, ligaments, or tendons.
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After randomization, 141 male (42.9%) patients and 188 female (57.1%) patients were enrolled in control group A (average age: 45.36±12.38 years old), 57 male patients (46.3%) and 66 female patients (53.7%) were enrolled in group B (average age: 44.79±14.26 years old), and 67 male (52.3%) and 61 female (47.7%) were enrolled in group C (average age: 49.17±11.67 years old).
ACCEPTED MANUSCRIPT None of the enrolled patients contracted rabies or died. The wound infection rates in the three groups (A, B, and C) were 9.1%, 4.1% and 3.9%, respectively. The infection
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times in the three groups were 26.3±11.6 h, 159.8 ± 13.4 h and 166.4 ± 16.2 h, respectively. The recovery times of infection of the patients in the three groups were
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19.2±4.6 d, 13.2 ± 2.1 d and 12.7 ± 2.3 d, respectively, and those of the non-infection
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patients were 15.6±2.7 d, 10.1 ± 2.3 d and 10.5 ± 1.9 d, respectively (Table 1). [Table 1] 4. Discussion
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Dog bites pose a serious public health problem in China. Every year, more than ten million people are attacked by mammals in China, most of which are dog bites. Dog
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bites can induce rabies, which is a fatal communicable disease [1,2], as well as serious
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lacerations and important organ damage. Although many experts have reached
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consensuses regarding rabies prophylaxis, immunization, and control [3,4], no consensus exists regarding surgical treatment for dog bites lacerations. In particular, the use of prophylactic antibiotics, post-debridement procedures, such as primary wound closure, and the suitability of further surgery, remain controversial [5-15]. NPWT has emerged over the last 20 years, and is widely used in surgical fields. However, whether NPWT could be used to treat serious dog bite laceration, as well as how much negative pressure would be suitable for these wounds, remains unknown.
ACCEPTED MANUSCRIPT 4.1 The characters of serious dog bites laceration and the importance of
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debridement
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Dog bite wounds are a special type of surgical wound. They can not only induce rabies but also serious lacerations. As a dog bites, it often bites and tears, which can
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induce seriously rips and tears in soft tissue. Furthermore, dog bites can induce severe
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complications, such as unmanageable complicated infections, high infection rates, organ damage, fasciitis, arthritis, erysipelas, lymphangitis, osteofascial compartment syndrome, compound open fractures, and abscesses [2,16,17]. Prompt local treatment of all bite wounds is a very important step in post-exposure prophylaxis [3]. It is
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widely accepted that dog bite wounds are accompanied by high infection rates, and
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some studies have reported that the infection rate is between 3% and 45% [12,18,19].
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Dog bite wound infection is associated with many factors [19-21], such as visiting time, type and site of the injuries, wound contamination condition, surgical
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debridement methods, effect and quality, and inherent factors in the individual. In fact, the root cause of the difference in the infection rates after visiting a physician was the surgical treatment. That is, the infection rate was affected by whether the inner wounds have been thoroughly washed, cleaned, disinfected and debrided, instead of being simply cleaned at the surface of the wounds. Only thorough debridement can remove the vast majority of viruses and bacteria inside the wounds [22,23]. Therefore, thorough debridement of the lacerations is not only the most important key measure for the prevention of rabies, but also the most effective means for the prevention of wound infection.
ACCEPTED MANUSCRIPT 4.2 The effects of negative pressure wound therapy on dog bite lacerations
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Fleischmann first reported vacuum sealing as a treatment of soft tissue damage and
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open fractures in 1993 [24]. Over the past 20 years, NPWT had become an accepted therapy for the treatment of chronic, subacute, and acute open wounds [25-30]. To our
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knowledge, this study was the first prospective, randomized trial in the literature in
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which NPWT was used for treatment of serious dog bite lacerations. Our study clearly showed that NPWT has positive healing effects on serious dog bite lacerations by reducing the infection rate and the healing time. Although we did not determine the underlying mechanism(s), we found that the most remarkable clinical change was that
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NPWT apparently decreased the swelling, exudation, and inflammation response of
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the wounds, compared with other therapies. Huang et al. reported that the effects of
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NPWT on wound healing included primary and secondary mechanisms [31]. The primary mechanisms included macrodeformation and microdeformation of wounds,
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tissue fluid removal, and alteration of the wound environment. The secondary mechanisms included hemostasis; modulation of inflammation; cellular responses, such as division, migration, and angiogenesis; granulation tissue formation; peripheral nerve response; and alterations in bioburden. In a study of cytokine and growth factor expression profiles under NPWT, Glass et al. reported that the promotion of wound healing occurred by the modulation of cytokines to an anti-inflammatory profile and by mechanoreceptor and chemoreceptor-mediated cell signaling, culminating in angiogenesis, extracellular matrix remodeling, and deposition of granulation tissue [32]. In our research, the most remarkably positive effects of NPWT on wounds were
ACCEPTED MANUSCRIPT decreases in edema and infection. Furthermore, we found that none of the lacerations developed infection during NPWT, whereas some wounds become infected two or
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three days after NPWT ended. Based on this, we believe that NPWT actually decreased the infection rate, primarily due to the strong removal of third-space fluid
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and debris from the wounds. Therefore, we recommend that NPWT is suitable for treatment of serious dog bite lacerations of the limbs after thorough debridement.
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Particularly in complicated wounds with extensive contamination, NPWT is a useful and versatile procedure that accelerates granulation tissue formation and healing and reduces the need for dressing changes under general anesthetic. Moreover, it is
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acceptable to both adult and elderly patients.
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4.3 The effects of different negative pressures of NPWT on dog bite lacerations
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Although NPWT has significantly improved the treatment and outcomes of complex wounds, clinicians still have little insight into how to set the pressure or what wound
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interfaces to use to optimize the therapy [33-35]. Our results suggested that there were no differences in outcomes in wound healing between dog bite lacerations treated with low negative pressure (-75 mm Hg) and those treated with high negative pressure (-125 mm Hg). In contrast, we found clinically that high negative pressure had more suction power, while it was accompanied by more pain, which was more markedly greater in the hands and feet. Therefore, we recommend -75 mm Hg of negative pressure as a suitable level.
ACCEPTED MANUSCRIPT 4.4 Considerations for using NPWT in dog bite lacerations
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Although our study suggested that NPWT had positive effects on serious dog bite
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lacerations, NPWT is not recommended in certain situations. Many of these situations are emphasized by the manufacturer’s themselves. It is essential that any clinician
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involved in the application of NPWT devices be familiar with these contra-indications.
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Therefore, we discuss these contraindications here.
4.4.1 NPWT must be used only after thorough debridement NPWT is a follow-up therapy in the treatment of dog bite lacerations, after rabies
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immunity, prophylaxis therapy, and thorough debridement have been implemented.
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4.4.2 Contact
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NPWT should never be used to replace thorough debridement.
The NPWT foam dressing should not come into direct contact with exposed blood
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vessels, nerves, organs, or anastomotic sites. There is an increased risk of fistula formation in the presence of exposed organs or hemorrhage with exposed blood vessels. 4.4.3 Bleeding Bleeding should be well controlled prior to the application of NPWT. If bleeding occurs, then negative pressure should be disconnected and the dressing should be switched to a compression type dressing.
ACCEPTED MANUSCRIPT 4.4.4 Allergy
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Allergies to adhesive dressings or alcohol should be considered.
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4.4.5 Peripheral circulation
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Particularly when NPWT is ready to be applied to the hands and feet, the acra should
4.4.6 Preservation and douche
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be exposed to observe appropriate peripheral circulation.
The semi-permeable membrane of NPWT is very thin and frangible. Exact preservation interventions should be applied to prevent the membrane from being
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covered by bandages or dressings. Cleaning must be performed at least three times per
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day with 50–100 ml of sterile physiological saline. Cleaning has two purposes: one is
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to prevent negative pressure system blockage, and the other is to keep the foam moist. The best method is continuous irrigation with 250–500 ml of sterile physiological
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saline two or three times per day.
ACCEPTED MANUSCRIPT 4.5 Antibiotic use
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The routine use of prophylactic antibiotics in dog bite lacerations is a controversial
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issue. Much of the literature suggests that prophylactic antibiotics should be given to all patients because of the risk of infection [1,3-5,36-38]. Infection of mammalian bite
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wounds is associated with many factors, such as visiting time, type and site of the
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injuries, animal species involved, wound contamination condition, surgical debridement methods, effect and quality, and inherent factors in the individual. Cat and human bite wounds; puncture wounds; wounds untreated for >6-8 hours; full thickness wounds involving tendons, ligaments and joints, and devitalised tissue; and
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the presence of alcoholism, cirrhosis, asplenia, steroid therapy, rheumatoid arthritis,
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diabetes mellitus, and lymphedema are risk factors for infection [19-21,39]. In order
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to eliminate the effects of confounding factors on the infection rate, and to minimize the risk of wound infection, we set strict inclusion and exclusion criteria. Our study
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results revealed that, without prophylactic antibiotics, the infection rates were 9.1%, 4.1%, and 3.9% in the groups A, B, and C, respectively. Therefore, we believe that it is not necessary to use antibiotics preventively, and thorough debridement of the lacerations is the most important key measure for preventing wound infection. We endorse the viewpoint of the Cochrane Wounds Group, who reviewed the correlative literature and concluded that prophylactic antibiotics did not appear to reduce the rate of infection after dog bites [39]. However, in patients at high risk for infection, we recommend the usage of prophylactic antibiotics.
ACCEPTED MANUSCRIPT 4.6 Limitations
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This study had some limitations. Owning to financial and laboratory conditions, we
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did not perform bacterial culture or drug sensitive tests on the infected wounds or use further indices to assess the effects of different negative pressures. Thus, we had to
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use antibiotics empirically based on previous reports in the literature.
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5. Conclusion
Our study results support the following conclusions. First, dog bite wounds to the limb should be immediately treated with thorough debridement. Second, NPWT can
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decrease the wound infection rate and promote wound healing. Furthermore, a 75-mmHg negative pressure level was suitable for NPWT in treating dog bite
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laceration. Finally, prophylactic antibiotics administration should not be routinely
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administered in patients with no risk factors for infections.
Acknowledgments
ACCEPTED MANUSCRIPT References 1.
Talan DA, Citron DM, Abrahamian FM, Moran GJ, Goldstein EJ. Bacteriologic
RI P
T
analysis of infected dog and cat bites. Emergency Medicine Animal Bite Infection Study Group. N Engl J Med. 1999;340:85–92.
Anderson PJ, Zafar I, Nizam M, Berry RB. Compartment syndrome in victims of
SC
2.
3.
MA NU
dog bites. Injury. 1997;28:717.
World Health Organization. WHO Expert Consultation on Rabies. Second
Report. World Health Organ Tech Rep Ser. 2013;982:1–139. World Health Organization. Rabies vaccines: WHO position paper. Wkly
ED
4.
5.
PT
Epidemiol Rec. 2010;85(32):309–20.
Taplitz RA. Managing bite wounds. Currently recommended antibiotics for
Paschos NK, Makris EA, Gantsos A, Georgoulis AD. Primary closure versus
AC
6.
CE
treatment and prophylaxis. Postgrad Med. 2004;116:49–52.
non-closure of dog bite wounds. A randomised controlled trial. Injury. 2014;45:237–40. 7.
Abrahamian FM. Dog bites: bacteriology, management, and prevention. Curr
Infect Dis Rep. 2000;2:446–53. 8.
Maimaris C, Quinton DN. Dog-bite lacerations: a controlled trial of primary
wound closure. Arch Emerg Med. 1988;5:156–61.
ACCEPTED MANUSCRIPT 9.
Medeiros I, Saconato H. Antibiotic prophylaxis for mammalian bites. Cochrane
Jofré Morales L, Perret P C, Abarca V K, Solari G V, Olivares C R, López Del
RI P
10.
T
Database Syst Rev. 2001;N2:CD001738.
P J. 2006. [Guidelines for management of animal bites]. Rev Chil Infectol.
Chaudhry MA, Macnamara AF, Clark S. Is the management of dog bite wounds
MA NU
11.
SC
2006;23:20–34.
evidence based? A postal survey and review of the literature. Eur J Emerg Med. 2004;11:313–7.
Capellan O, Hollander JE. Management of lacerations in the emergency
PT
13.
ED
12. Fleisher GR. The management of bite wounds. N Engl J Med. 1999;340:138–40.
14.
CE
department. Emerg Med Clin North Am. 2003;21:205–31. Garbutt F, Jenner R. Best evidence topic report. Wound closure in animal bites.
15.
AC
Emerg Med J. 2004;21:589–90. Smith MR, Walker A, Brenchley J. Barking up the wrong tree? A survey of dog
bite wound management. Emerg Med J. 2003, 20:253–5. 16. Chen RF, Wang LQ, Li-song H. Distribution and characteristics of infection in dog bite wounds. China Journal of Emergency Resuscitation and Disaster Medicine. 2011;6:21–3. 17. Chen RF, Wang LQ. The effect analysis of debridement and immunifaction after rabid dog bite. Guide of China Medicine. 2012;5:401–2.
ACCEPTED MANUSCRIPT 18. Chaudhry MA, Macnamara AF, Clark S. Is the management of dog bite wounds evidence based? A postal survey and review of the literature. Eur J Emerg Med.
RI P
T
2004;11:313–7. 19. Morgan M, Palmer J. Dog bites. BMJ 2007;334:413–7.
SC
20. Dendle C, Looke D. Management of mammalian bites. Aust Fam Physician.
MA NU
2009V38N11 :868–74.
21. Stefanopoulos P, Karabouta Z, Bisbinas I, Georgiannos D, Karabouta I. Animal and human bites: evaluation and management. Acta Orthop Belg. 2004V70N1 :1–10.
ED
22. Dean DJ, Baer GM, Thompson WR. Studies on the local treatment of
PT
rabies-infected wounds. Bull World Health Organ.1963, V28N4 :477–86.
CE
23. Armstrong JA，Froelich EJ. inactivation of viruses by benzalkonium chloride. Appl Microbiol. 1964,V12(N2) :132–7.
AC
24. Fleischmann W, Strecker W, Bombelli M, Kinzl L. [Vacuum sealing as treatment of soft tissue damage in open fractures]. Unfallchirurg. 1993;96:488e92. 25. Kim PJ, Attinger CE, Steinberg JS, Evans KK, Lehner B, Willy C, et al. Negative-pressure wound therapy with instillation: international consensus guidelines. Plast Reconstr Surg. 2013;132:1569–79. 26. Novak A, Khan WS, Palmer J. The evidence-based principles of negative pressure wound therapy in trauma & orthopedics. Open Orthop J. 2014;8:168–77.
ACCEPTED MANUSCRIPT 27. Roberts DJ, Jenne CN, Ball CG, Tiruta C, Léger C, Xiao Z, et al. Efficacy and safety of active negative pressure peritoneal therapy for reducing the systemic
RI P
T
inflammatory response after damage control laparotomy (the intra-peritoneal Vacuum Trial): study protocol for a randomized controlled trial. Trials. 2013;14:2013V14N.
SC
28. Peinemann F, Sauerland S. Negative-pressure wound therapy: systematic review
MA NU
of randomized controlled trials. Dtsch Arztebl Int. 2011;108:381–9. 29. Masden D, Goldstein J, Endara M, Xu K, Steinberg J, Attinger C. Negative pressure wound therapy for at-risk surgical closures in patients with multiple a
prospective
2012;255:1043–7.
controlled
study.
Ann
Surg.
Kaufman-Rivi D, Hazlett AC, Hardy MA, Smith JM, Seid HB. Provider
PT
30.
randomized
ED
comorbidities:
CE
experiences with negative-pressure wound therapy systems. Adv Skin Wound Care.
AC
2013;26:311–8.
31. Huang C, Leavitt T, Bayer LR, Orgill DP. Effect of negative pressure wound therapy on wound healing. Curr Probl Surg. 2014;51:301–31. 32. Glass GE, Murphy GF, Esmaeili A, Lai LM, Nanchahal J. Systematic review of molecular mechanism of action of negative-pressure wound therapy. Br J Surg. 2014;101:1627–36. 33.
Borgquist O, Ingemansson R, Malmsjö M. The influence of low and high
pressure levels during negative-pressure wound therapy on wound contraction and fluid evacuation. Plast Reconstr Surg. 2011;127:2011V127N2.
ACCEPTED MANUSCRIPT 34. Kairinos N, Voogd AM, Botha PH, Kotze T, Kahn D, Hudson DA, et al. Negative pressure wound therapy. Volume II: negative pressure wound therapy and
RI P
T
increased perfusion. Just an illusion? Plast Reconstr Surg. 2009;123:601–2. 35. Lavery LA, La Fontaine J, Thakral G, Kim PJ, Bhavan K, Davis KE.
SC
Randomized clinical trial to compare negative-pressure wound therapy approaches
MA NU
with low and high pressure, silicone-coated dressing, and polyurethane foam dressing. Plast Reconstr Surg. 2014;133:722–6. 36.
Garcia
VF.
Animal
37.
and
Pasturella
infections.
Pediatr
Rev.
ED
1997;18:127–130.
bites
Goldstein JC, Citron DM, Wield B, Blachman U, Sutter VL, Miller TA, et al.
Chaudhry MA, Macnamara AF, Clark S. Is the management of dog bite wounds
CE
38.
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Bacteriology of human and animal bite wounds. J Clin Microbiol. 1978;8:667–72.
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evidence based? A postal survey and review of the literature. Eur J Emerg Med. 2004;11:313–7.
39. Medeiros I, Saconato H. Antibiotic prophylaxis for mammalian bites. Cochrane Database Syst Rev, 2001VN2:CD001738.
ACCEPTED MANUSCRIPT Tables
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Table 1. Characteristics of the wounds in the three groups.
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# compared with the group B, P>0.05
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* compared with the control group, P<0.05
ACCEPTED MANUSCRIPT Figures
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Figure 1. Screening randomization and follow-up of the study participants.
ACCEPTED MANUSCRIPT Table 1. Characteristics of the wounds in the three groups. Group A
Group B
Group C
p-Value
Topography 29.2%(96)
37.4%(46)
32.8%(42)
The lower limb
23.1%(76)
28.5%(35)
30.5%(39)
Hand
23.7%(78)
19.5%(24)
Foot
8.8%(29)
7.3%(9)
Muti-location
15.2%(50)
7.3%(9)
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The upper limb
p>0.05 p>0.05
17.2%(22)
p>0.05
8.6%(11)
p>0.05
10.9%(12)
P<0.05
45.36±12.38
44.79±14.26
49.17±11.67
-
Gender(♂/♀)
141/188
57/66
67/61
-
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Mean age(years), (SD)
9.31±3.49
9.58±2.94
9.23±3.37
p>0.05
Total
329
123
128
-
Infection rate (%)
9.1%(30)
Infection time(h) Recovery time(d)
Infection
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Mean wound size(cm)(SD)
4.1%(5)*
3.9%(5)*#
26.3 ± 11.6
159.8 ± 13.4*
166.4 ± 16.2*#
19.2 ± 4.6
13.2 ± 2.1*
12.7 ± 2.3*#
10.1 ± 2.3*
10.5 ± 1.9*#
No infenction 15.6 ± 2.7
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* compared with the control group (group A), P<0.05 # compared with the group B, P>0.05
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ACCEPTED MANUSCRIPT
S0735-6757(16)00123-6 doi: 10.1016/j.ajem.2016.02.043 YAJEM 55617
To appear in:
American Journal of Emergency Medicine
Received date: Revised date: Accepted date:
5 August 2015 18 January 2016 15 February 2016
Please cite this article as: Rui-feng Chen, Li-song Huang, Ji-bo Zheng, Yi-qing Jia, Yujie Liu, Yi Shan, Negative pressure wound therapy for serious dog bites of extremities: A prospective randomized trial, American Journal of Emergency Medicine (2016), doi: 10.1016/j.ajem.2016.02.043
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Negative Pressure Wound Therapy for Serious Dog Bites of extremities: a Prospective Randomized Trial
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Chen Rui-feng, M.M.; Huang Li-song, M.M.; Zheng Ji-bo, M.B.; Jia Yi-qing, M.B.;
addresses:
Chen
Rui-feng:
[email protected];
Zheng
[email protected];
Liu
[email protected]
Ji-bo:
[email protected];
Huang Jia
[email protected];
Yu-jie:
[email protected];
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Liu Yu-jie, M.M.; Shan Yi#, M.M.
Li-song: Yi-qing ：
Shan
Yi:
Department of Emergency, Naval General Hospital of China Liberation Army, Beijing
Corresponding
author:
Shan
Yi,
TEL:
+8618600310572;
Fax
number:
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#
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100048, P.R. China
+8601066951311; Email: [email protected]
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Conflicts of Interest and Source of Funding: The authors declare no conflicts of interest.
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Authors’ contributions
Chen Rui-feng was the junior author and was fully in charge of the study, involved in the design, demonstration, implementation, data collection and statistical analysis, and manuscript composition. Shan Yi was the senior author and was mainly responsible for the researchers and contributors, involved in the design, surveillance and manuscript revision for important intellectual content. Huang Li-song was involved in writing the manuscript. Huang Li-song, Zheng Ji-bo, Jia Yi-qing and Liu Yu-jie coordinated the data collection and implementation. All of the authors read and approved the final manuscript.
ACCEPTED MANUSCRIPT Abstract Objectives: To investigate the emergency treatment of serious dog bite lacerations on
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limbs and to identify whether negative pressure wound therapy (NPWT) was beneficial in these instances.
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Methods: A total of 580 cases with serious limb lacerations due to dog bites were
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randomly divided into two groups. After thorough debridement, the limb lacerations of group A (n=329) were left open. The remaining cases (n=251) were randomly divided into two subgroups, group B and group C, which were treated with 125 mmHg and 75 mmHg of continuous negative pressure, respectively. Antibiotics were
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only used in cases where there were systemic signs of wound infection, and were not
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given prophylactically. The infection rate, infection time, and healing time were
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analyzed.
Results: The wound infection rates of groups A, B, and C were 9.1%, 4.1%, and 3.9%,
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respectively. The infection times of the three groups were 26.3 ± 11.6 h, 159.8 ± 13.4 h, and 166.4 ± 16.2 h, respectively. The recovery times of the infection patients in the three groups were 19.2 ± 4.6 d, 13.2 ± 2.1 d, and 12.7 ± 2.3 d, respectively, and in the non-infection patients, the recovery times were 15.6 ± 2.7 d, 10.1 ± 2.3 d, and 10.5 ± 1.9 d, respectively. In groups B (-125 mm Hg) and C (-75 mm Hg), the infection rate, infection time and healing time showed no significant differences.
ACCEPTED MANUSCRIPT Conclusion: Patients with serious dog bite laceration on limbs could benefit from NPWT. Compared with the traditional treatment of leaving the wounds open, NPWT
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reduced the infection rate and shortened recovery time. When NPWT was performed, low negative pressure (-75 mm Hg) had the same positive effects as high pressure
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(-125 mm Hg). Prophylactic antibiotics administration is not recommended for
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treating this kind of laceration.
Level of Evidence: Therapeutic/Care Management, level II Key Words: Dog bite; laceration; Negative pressure wound therapy; Prospective
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randomized trial; Debridement; Antibiotics.
ACCEPTED MANUSCRIPT 1. Introduction
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In recent years, the incidence of dog bites has increased markedly. According to data
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from the Centers for Disease Control and Prevention (CDC) of Beijing, more than 150,000 people were attacked by dogs in 2006 in Beijing, which increased to more
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than 220,000 in 2012. Approximately 88.6% of dog bite cases involved the upper or
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lower extremity, and approximately 12% were serious lacerations. Some pertinent literature has been published about the surgical treatment of dog bite lacerations; however, prospective studies have rarely been performed. Dog bite wounds are a special kind of wound, with high infection rates and prolonged healing times, and
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their surgical treatment is controversial. Negative pressure wound therapy (NPWT) is
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a simple and efficient way to promote healing in a variety of complicated wounds.
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After packing or covering the wound with alginate foam containing polyvinyl alcohol and packing a layer of biological membrane at the surface of the foam and wound, the
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drainage tubes from the foam are connected to a negative pressure aspirator and the treatment is initiated. NPWT has emerged over the last 20 years, and is widely used in surgical fields. NPWT have achieved good results, especially in the treatment of complex wounds, and is widely recognized by surgeons. However, very few studies have examined the use of NPWT in serious dog bites lacerations. This prospective study aimed to assess whether NPWT has a positive effect on wound healing in serious dog bite lacerations.
ACCEPTED MANUSCRIPT 2. Patients and methods
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Male or female patients older than 18 years old, who presented at our Rabies
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Prophylaxis and Immunity Clinic of Beijing with dog bites to the limbs were enrolled in this prospective randomized trial. Patients with lacerated limb wounds demanding
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surgical treatment (lacerations with lengths of at least 5 cm, multiple penetrating
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lacerations of soft tissues, or lacerations accompanied by damage to at least one of the following: muscles, tendons, ligaments, nerves, articular capsules, fractures, important blood vessels, acra amputation) were enrolled. Exclusion criteria were puncture wounds (less than 2 mm), medium or small lacerations (less than 5 cm), infected
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wounds at presentation, having visited a doctor’s office more than 8 h after the injury,
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wounds with skin loss requiring plastic surgery, or patients with immune deficiency,
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using immunosuppressive agents, with autoimmune disorders or diabetes. All patients were subjected to block randomization and were assigned to a control group (group A)
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and an NPWT group. Those in the NPWT group were randomly assigned to group B (NPWT -125 mmHg pressure group) and group C (NPWT -75 mmHg pressure group) using a block random digits table. The therapeutic schedules were explained to the patients in each group, and their signatures were obtained on consent forms. Patients who refused the therapeutic strategy were excluded from the trial. Before the clinical trial started, we obtained approval for the clinical trial from our hospital ethics committee (IEC. Navy General Hospital, Permitted NO.: HZQX-PJ-2006-12).
ACCEPTED MANUSCRIPT 2.1 Debridement procedure
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All of the limbs with dog bite lacerations underwent thorough debridement as follows.
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2.1.1 Cleaning and disinfection
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To relieve the pain of the patients, local anesthetic was administered before wound cleaning and disinfection. After covering the wounds with sterilized dressing, a sterile
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cotton ball was used to scrub the area around the wounds 2-3 times with 20% liquid soap under running water. Subsequently, the wounds were alternately cleaned with ample 20% liquid soap and physiological saline, and with 3% hydrogen peroxide and
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physiological saline. The total cleaning time was at least 15 minutes for each wound. A large amount of 0.05% iso-osmia iodophors was used to disinfect the wounds for
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2.1.2 Debridement
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not less than 5 minutes.
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All devitalized tissue, coagulated blood, foreign material, and markedly contaminated tissue were carefully removed to expose the surrounding healthy tissue. It was essential to retain the integrity of this tissue as much as possible to repair them later and to prevent osteofascial compartment syndrome. The final procedure of debridement involved cleaning of the inside part of the laceration with 0.05% iodophors again. Sterile gloves, aseptic covers, and surgical instruments were then prepared for tissue repair. At this time, passive immunity, if necessary, was administered.
ACCEPTED MANUSCRIPT 2.1.3 Important tissue repair
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All of the important impaired organs or tissues (such as muscles, tendons, ligaments,
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important nerves, articular capsules, fractures, important blood vessels, and acra amputation) were repaired with suitable operations after debridement, and these
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surgeries were performed at least 2 hours after rabies immunoprophylaxis therapy.
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2.1.4 Wound cover
After thorough cleaning and debridement, the lacerations in group A were left open and covered with sterilized dressings. The lacerations in groups B and C were covered
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with a polyvinyl alcohol shrink formaldehyde bubble dressing (VSD Medical Science and Technology Co. Ltd., Wuhan, China) for NPWT. We used a hospital central
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vacuum aspiration system as a continuous negative pressure source, and negative
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and C.
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pressure was set at two levels: 125 mm Hg and 75 mm Hg, respectively in groups B
All of the patients were administered rabies prophylactic active immunity and/or passive immunity. Tetanus antitoxin was also administered, if necessary. Drainage was performed according to the actual condition of the lacerations. A drain was placed in the innermost part of the wound and was replaced or removed according to the drainage quantity, usually 24 –48 h after surgery. All of the wounds in groups A were covered with sterilized dressings, which were changed 24–48 h after surgery. The NPWT was removed 4-5 days after surgery in groups B and C. The stitches in all sutured lacerations were removed 10–14 d after surgery, according to the state of
ACCEPTED MANUSCRIPT wound healing. Antibiotics were administered only after wound infection occurred.
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2.2 Observation indices
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2.2.1 Infection rate
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Infection was defined as the satisfaction of one of the following three major criteria: fever (body temperature ≥ 38°C), abscess, and lymphangitis; or four of five minor
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criteria: wound-associated erythema that extended more than 3 cm from the edge of the wound, tenderness at the wound site, swelling at the site, purulent drainage, and a white blood cell count in the peripheral blood of 12,000/ml.
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2.2.2 Infection time
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The infection time was the interval from being bitten to emerging infection
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indications (calculated as the time in hours).
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2.2.3 Recovery time
The recovery time was the interval from being bitten to the wound achieving clinical healing (calculated as the time in days). 2.3 Statistical analysis Statistical analysis was performed with SPSS software, version 13.0 (Chicago, IL, USA), to compare the two groups. The chi-square test and t-test were applied. Statistical significance was set at α=0.05.
ACCEPTED MANUSCRIPT 3. Results
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Between January 2007 and September 2015, 653 patients were enrolled in this study.
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After assessment, 42 were excluded and 25 were not willing to participate in our study. A total of 586 patients were included in this study. After randomization, 335 patients
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were in group A and 251 were included in the NPWT group. All the patients in NPWT
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group and most of the patients in group A (90%, 296/329) were hospitalization. In addition, 6 patients in the group A were lost to follow up (see Fig. 1). Among the 580 valid patients, 265 were male and 315 were female. The age range was 18-94 years old. The average length of the largest wounds was 9.32±3.27 cm, and the average
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wound number was 4.6±1.7. Some patients lost or suffered serious damage to their
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organs from dog bites: 24 cases lost parts of fingers, 75 cases were accompanied by
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open fractures, and 76% of the cases were accompanied by damaged muscles, ligaments, or tendons.
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After randomization, 141 male (42.9%) patients and 188 female (57.1%) patients were enrolled in control group A (average age: 45.36±12.38 years old), 57 male patients (46.3%) and 66 female patients (53.7%) were enrolled in group B (average age: 44.79±14.26 years old), and 67 male (52.3%) and 61 female (47.7%) were enrolled in group C (average age: 49.17±11.67 years old).
ACCEPTED MANUSCRIPT None of the enrolled patients contracted rabies or died. The wound infection rates in the three groups (A, B, and C) were 9.1%, 4.1% and 3.9%, respectively. The infection
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times in the three groups were 26.3±11.6 h, 159.8 ± 13.4 h and 166.4 ± 16.2 h, respectively. The recovery times of infection of the patients in the three groups were
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19.2±4.6 d, 13.2 ± 2.1 d and 12.7 ± 2.3 d, respectively, and those of the non-infection
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patients were 15.6±2.7 d, 10.1 ± 2.3 d and 10.5 ± 1.9 d, respectively (Table 1). [Table 1] 4. Discussion
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Dog bites pose a serious public health problem in China. Every year, more than ten million people are attacked by mammals in China, most of which are dog bites. Dog
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bites can induce rabies, which is a fatal communicable disease [1,2], as well as serious
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lacerations and important organ damage. Although many experts have reached
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consensuses regarding rabies prophylaxis, immunization, and control [3,4], no consensus exists regarding surgical treatment for dog bites lacerations. In particular, the use of prophylactic antibiotics, post-debridement procedures, such as primary wound closure, and the suitability of further surgery, remain controversial [5-15]. NPWT has emerged over the last 20 years, and is widely used in surgical fields. However, whether NPWT could be used to treat serious dog bite laceration, as well as how much negative pressure would be suitable for these wounds, remains unknown.
ACCEPTED MANUSCRIPT 4.1 The characters of serious dog bites laceration and the importance of
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debridement
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Dog bite wounds are a special type of surgical wound. They can not only induce rabies but also serious lacerations. As a dog bites, it often bites and tears, which can
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induce seriously rips and tears in soft tissue. Furthermore, dog bites can induce severe
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complications, such as unmanageable complicated infections, high infection rates, organ damage, fasciitis, arthritis, erysipelas, lymphangitis, osteofascial compartment syndrome, compound open fractures, and abscesses [2,16,17]. Prompt local treatment of all bite wounds is a very important step in post-exposure prophylaxis [3]. It is
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widely accepted that dog bite wounds are accompanied by high infection rates, and
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some studies have reported that the infection rate is between 3% and 45% [12,18,19].
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Dog bite wound infection is associated with many factors [19-21], such as visiting time, type and site of the injuries, wound contamination condition, surgical
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debridement methods, effect and quality, and inherent factors in the individual. In fact, the root cause of the difference in the infection rates after visiting a physician was the surgical treatment. That is, the infection rate was affected by whether the inner wounds have been thoroughly washed, cleaned, disinfected and debrided, instead of being simply cleaned at the surface of the wounds. Only thorough debridement can remove the vast majority of viruses and bacteria inside the wounds [22,23]. Therefore, thorough debridement of the lacerations is not only the most important key measure for the prevention of rabies, but also the most effective means for the prevention of wound infection.
ACCEPTED MANUSCRIPT 4.2 The effects of negative pressure wound therapy on dog bite lacerations
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Fleischmann first reported vacuum sealing as a treatment of soft tissue damage and
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open fractures in 1993 [24]. Over the past 20 years, NPWT had become an accepted therapy for the treatment of chronic, subacute, and acute open wounds [25-30]. To our
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knowledge, this study was the first prospective, randomized trial in the literature in
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which NPWT was used for treatment of serious dog bite lacerations. Our study clearly showed that NPWT has positive healing effects on serious dog bite lacerations by reducing the infection rate and the healing time. Although we did not determine the underlying mechanism(s), we found that the most remarkable clinical change was that
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NPWT apparently decreased the swelling, exudation, and inflammation response of
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the wounds, compared with other therapies. Huang et al. reported that the effects of
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NPWT on wound healing included primary and secondary mechanisms [31]. The primary mechanisms included macrodeformation and microdeformation of wounds,
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tissue fluid removal, and alteration of the wound environment. The secondary mechanisms included hemostasis; modulation of inflammation; cellular responses, such as division, migration, and angiogenesis; granulation tissue formation; peripheral nerve response; and alterations in bioburden. In a study of cytokine and growth factor expression profiles under NPWT, Glass et al. reported that the promotion of wound healing occurred by the modulation of cytokines to an anti-inflammatory profile and by mechanoreceptor and chemoreceptor-mediated cell signaling, culminating in angiogenesis, extracellular matrix remodeling, and deposition of granulation tissue [32]. In our research, the most remarkably positive effects of NPWT on wounds were
ACCEPTED MANUSCRIPT decreases in edema and infection. Furthermore, we found that none of the lacerations developed infection during NPWT, whereas some wounds become infected two or
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three days after NPWT ended. Based on this, we believe that NPWT actually decreased the infection rate, primarily due to the strong removal of third-space fluid
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and debris from the wounds. Therefore, we recommend that NPWT is suitable for treatment of serious dog bite lacerations of the limbs after thorough debridement.
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Particularly in complicated wounds with extensive contamination, NPWT is a useful and versatile procedure that accelerates granulation tissue formation and healing and reduces the need for dressing changes under general anesthetic. Moreover, it is
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acceptable to both adult and elderly patients.
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4.3 The effects of different negative pressures of NPWT on dog bite lacerations
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Although NPWT has significantly improved the treatment and outcomes of complex wounds, clinicians still have little insight into how to set the pressure or what wound
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interfaces to use to optimize the therapy [33-35]. Our results suggested that there were no differences in outcomes in wound healing between dog bite lacerations treated with low negative pressure (-75 mm Hg) and those treated with high negative pressure (-125 mm Hg). In contrast, we found clinically that high negative pressure had more suction power, while it was accompanied by more pain, which was more markedly greater in the hands and feet. Therefore, we recommend -75 mm Hg of negative pressure as a suitable level.
ACCEPTED MANUSCRIPT 4.4 Considerations for using NPWT in dog bite lacerations
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Although our study suggested that NPWT had positive effects on serious dog bite
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lacerations, NPWT is not recommended in certain situations. Many of these situations are emphasized by the manufacturer’s themselves. It is essential that any clinician
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involved in the application of NPWT devices be familiar with these contra-indications.
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Therefore, we discuss these contraindications here.
4.4.1 NPWT must be used only after thorough debridement NPWT is a follow-up therapy in the treatment of dog bite lacerations, after rabies
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immunity, prophylaxis therapy, and thorough debridement have been implemented.
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4.4.2 Contact
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NPWT should never be used to replace thorough debridement.
The NPWT foam dressing should not come into direct contact with exposed blood
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vessels, nerves, organs, or anastomotic sites. There is an increased risk of fistula formation in the presence of exposed organs or hemorrhage with exposed blood vessels. 4.4.3 Bleeding Bleeding should be well controlled prior to the application of NPWT. If bleeding occurs, then negative pressure should be disconnected and the dressing should be switched to a compression type dressing.
ACCEPTED MANUSCRIPT 4.4.4 Allergy
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Allergies to adhesive dressings or alcohol should be considered.
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4.4.5 Peripheral circulation
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Particularly when NPWT is ready to be applied to the hands and feet, the acra should
4.4.6 Preservation and douche
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be exposed to observe appropriate peripheral circulation.
The semi-permeable membrane of NPWT is very thin and frangible. Exact preservation interventions should be applied to prevent the membrane from being
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covered by bandages or dressings. Cleaning must be performed at least three times per
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day with 50–100 ml of sterile physiological saline. Cleaning has two purposes: one is
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to prevent negative pressure system blockage, and the other is to keep the foam moist. The best method is continuous irrigation with 250–500 ml of sterile physiological
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saline two or three times per day.
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The routine use of prophylactic antibiotics in dog bite lacerations is a controversial
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issue. Much of the literature suggests that prophylactic antibiotics should be given to all patients because of the risk of infection [1,3-5,36-38]. Infection of mammalian bite
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wounds is associated with many factors, such as visiting time, type and site of the
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injuries, animal species involved, wound contamination condition, surgical debridement methods, effect and quality, and inherent factors in the individual. Cat and human bite wounds; puncture wounds; wounds untreated for >6-8 hours; full thickness wounds involving tendons, ligaments and joints, and devitalised tissue; and
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the presence of alcoholism, cirrhosis, asplenia, steroid therapy, rheumatoid arthritis,
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diabetes mellitus, and lymphedema are risk factors for infection [19-21,39]. In order
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to eliminate the effects of confounding factors on the infection rate, and to minimize the risk of wound infection, we set strict inclusion and exclusion criteria. Our study
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results revealed that, without prophylactic antibiotics, the infection rates were 9.1%, 4.1%, and 3.9% in the groups A, B, and C, respectively. Therefore, we believe that it is not necessary to use antibiotics preventively, and thorough debridement of the lacerations is the most important key measure for preventing wound infection. We endorse the viewpoint of the Cochrane Wounds Group, who reviewed the correlative literature and concluded that prophylactic antibiotics did not appear to reduce the rate of infection after dog bites [39]. However, in patients at high risk for infection, we recommend the usage of prophylactic antibiotics.
ACCEPTED MANUSCRIPT 4.6 Limitations
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This study had some limitations. Owning to financial and laboratory conditions, we
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did not perform bacterial culture or drug sensitive tests on the infected wounds or use further indices to assess the effects of different negative pressures. Thus, we had to
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use antibiotics empirically based on previous reports in the literature.
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5. Conclusion
Our study results support the following conclusions. First, dog bite wounds to the limb should be immediately treated with thorough debridement. Second, NPWT can
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decrease the wound infection rate and promote wound healing. Furthermore, a 75-mmHg negative pressure level was suitable for NPWT in treating dog bite
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laceration. Finally, prophylactic antibiotics administration should not be routinely
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administered in patients with no risk factors for infections.
Acknowledgments
ACCEPTED MANUSCRIPT References 1.
Talan DA, Citron DM, Abrahamian FM, Moran GJ, Goldstein EJ. Bacteriologic
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T
analysis of infected dog and cat bites. Emergency Medicine Animal Bite Infection Study Group. N Engl J Med. 1999;340:85–92.
Anderson PJ, Zafar I, Nizam M, Berry RB. Compartment syndrome in victims of
SC
2.
3.
MA NU
dog bites. Injury. 1997;28:717.
World Health Organization. WHO Expert Consultation on Rabies. Second
Report. World Health Organ Tech Rep Ser. 2013;982:1–139. World Health Organization. Rabies vaccines: WHO position paper. Wkly
ED
4.
5.
PT
Epidemiol Rec. 2010;85(32):309–20.
Taplitz RA. Managing bite wounds. Currently recommended antibiotics for
Paschos NK, Makris EA, Gantsos A, Georgoulis AD. Primary closure versus
AC
6.
CE
treatment and prophylaxis. Postgrad Med. 2004;116:49–52.
non-closure of dog bite wounds. A randomised controlled trial. Injury. 2014;45:237–40. 7.
Abrahamian FM. Dog bites: bacteriology, management, and prevention. Curr
Infect Dis Rep. 2000;2:446–53. 8.
Maimaris C, Quinton DN. Dog-bite lacerations: a controlled trial of primary
wound closure. Arch Emerg Med. 1988;5:156–61.
ACCEPTED MANUSCRIPT 9.
Medeiros I, Saconato H. Antibiotic prophylaxis for mammalian bites. Cochrane
Jofré Morales L, Perret P C, Abarca V K, Solari G V, Olivares C R, López Del
RI P
10.
T
Database Syst Rev. 2001;N2:CD001738.
P J. 2006. [Guidelines for management of animal bites]. Rev Chil Infectol.
Chaudhry MA, Macnamara AF, Clark S. Is the management of dog bite wounds
MA NU
11.
SC
2006;23:20–34.
evidence based? A postal survey and review of the literature. Eur J Emerg Med. 2004;11:313–7.
Capellan O, Hollander JE. Management of lacerations in the emergency
PT
13.
ED
12. Fleisher GR. The management of bite wounds. N Engl J Med. 1999;340:138–40.
14.
CE
department. Emerg Med Clin North Am. 2003;21:205–31. Garbutt F, Jenner R. Best evidence topic report. Wound closure in animal bites.
15.
AC
Emerg Med J. 2004;21:589–90. Smith MR, Walker A, Brenchley J. Barking up the wrong tree? A survey of dog
bite wound management. Emerg Med J. 2003, 20:253–5. 16. Chen RF, Wang LQ, Li-song H. Distribution and characteristics of infection in dog bite wounds. China Journal of Emergency Resuscitation and Disaster Medicine. 2011;6:21–3. 17. Chen RF, Wang LQ. The effect analysis of debridement and immunifaction after rabid dog bite. Guide of China Medicine. 2012;5:401–2.
ACCEPTED MANUSCRIPT 18. Chaudhry MA, Macnamara AF, Clark S. Is the management of dog bite wounds evidence based? A postal survey and review of the literature. Eur J Emerg Med.
RI P
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2004;11:313–7. 19. Morgan M, Palmer J. Dog bites. BMJ 2007;334:413–7.
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20. Dendle C, Looke D. Management of mammalian bites. Aust Fam Physician.
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2009V38N11 :868–74.
21. Stefanopoulos P, Karabouta Z, Bisbinas I, Georgiannos D, Karabouta I. Animal and human bites: evaluation and management. Acta Orthop Belg. 2004V70N1 :1–10.
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22. Dean DJ, Baer GM, Thompson WR. Studies on the local treatment of
PT
rabies-infected wounds. Bull World Health Organ.1963, V28N4 :477–86.
CE
23. Armstrong JA，Froelich EJ. inactivation of viruses by benzalkonium chloride. Appl Microbiol. 1964,V12(N2) :132–7.
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24. Fleischmann W, Strecker W, Bombelli M, Kinzl L. [Vacuum sealing as treatment of soft tissue damage in open fractures]. Unfallchirurg. 1993;96:488e92. 25. Kim PJ, Attinger CE, Steinberg JS, Evans KK, Lehner B, Willy C, et al. Negative-pressure wound therapy with instillation: international consensus guidelines. Plast Reconstr Surg. 2013;132:1569–79. 26. Novak A, Khan WS, Palmer J. The evidence-based principles of negative pressure wound therapy in trauma & orthopedics. Open Orthop J. 2014;8:168–77.
ACCEPTED MANUSCRIPT 27. Roberts DJ, Jenne CN, Ball CG, Tiruta C, Léger C, Xiao Z, et al. Efficacy and safety of active negative pressure peritoneal therapy for reducing the systemic
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inflammatory response after damage control laparotomy (the intra-peritoneal Vacuum Trial): study protocol for a randomized controlled trial. Trials. 2013;14:2013V14N.
SC
28. Peinemann F, Sauerland S. Negative-pressure wound therapy: systematic review
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of randomized controlled trials. Dtsch Arztebl Int. 2011;108:381–9. 29. Masden D, Goldstein J, Endara M, Xu K, Steinberg J, Attinger C. Negative pressure wound therapy for at-risk surgical closures in patients with multiple a
prospective
2012;255:1043–7.
controlled
study.
Ann
Surg.
Kaufman-Rivi D, Hazlett AC, Hardy MA, Smith JM, Seid HB. Provider
PT
30.
randomized
ED
comorbidities:
CE
experiences with negative-pressure wound therapy systems. Adv Skin Wound Care.
AC
2013;26:311–8.
31. Huang C, Leavitt T, Bayer LR, Orgill DP. Effect of negative pressure wound therapy on wound healing. Curr Probl Surg. 2014;51:301–31. 32. Glass GE, Murphy GF, Esmaeili A, Lai LM, Nanchahal J. Systematic review of molecular mechanism of action of negative-pressure wound therapy. Br J Surg. 2014;101:1627–36. 33.
Borgquist O, Ingemansson R, Malmsjö M. The influence of low and high
pressure levels during negative-pressure wound therapy on wound contraction and fluid evacuation. Plast Reconstr Surg. 2011;127:2011V127N2.
ACCEPTED MANUSCRIPT 34. Kairinos N, Voogd AM, Botha PH, Kotze T, Kahn D, Hudson DA, et al. Negative pressure wound therapy. Volume II: negative pressure wound therapy and
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increased perfusion. Just an illusion? Plast Reconstr Surg. 2009;123:601–2. 35. Lavery LA, La Fontaine J, Thakral G, Kim PJ, Bhavan K, Davis KE.
SC
Randomized clinical trial to compare negative-pressure wound therapy approaches
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with low and high pressure, silicone-coated dressing, and polyurethane foam dressing. Plast Reconstr Surg. 2014;133:722–6. 36.
Garcia
VF.
Animal
37.
and
Pasturella
infections.
Pediatr
Rev.
ED
1997;18:127–130.
bites
Goldstein JC, Citron DM, Wield B, Blachman U, Sutter VL, Miller TA, et al.
Chaudhry MA, Macnamara AF, Clark S. Is the management of dog bite wounds
CE
38.
PT
Bacteriology of human and animal bite wounds. J Clin Microbiol. 1978;8:667–72.
AC
evidence based? A postal survey and review of the literature. Eur J Emerg Med. 2004;11:313–7.
39. Medeiros I, Saconato H. Antibiotic prophylaxis for mammalian bites. Cochrane Database Syst Rev, 2001VN2:CD001738.
ACCEPTED MANUSCRIPT Tables
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Table 1. Characteristics of the wounds in the three groups.
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# compared with the group B, P>0.05
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* compared with the control group, P<0.05
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Figure 1. Screening randomization and follow-up of the study participants.
ACCEPTED MANUSCRIPT Table 1. Characteristics of the wounds in the three groups. Group A
Group B
Group C
p-Value
Topography 29.2%(96)
37.4%(46)
32.8%(42)
The lower limb
23.1%(76)
28.5%(35)
30.5%(39)
Hand
23.7%(78)
19.5%(24)
Foot
8.8%(29)
7.3%(9)
Muti-location
15.2%(50)
7.3%(9)
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The upper limb
p>0.05 p>0.05
17.2%(22)
p>0.05
8.6%(11)
p>0.05
10.9%(12)
P<0.05
45.36±12.38
44.79±14.26
49.17±11.67
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Gender(♂/♀)
141/188
57/66
67/61
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Mean age(years), (SD)
9.31±3.49
9.58±2.94
9.23±3.37
p>0.05
Total
329
123
128
-
Infection rate (%)
9.1%(30)
Infection time(h) Recovery time(d)
Infection
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Mean wound size(cm)(SD)
4.1%(5)*
3.9%(5)*#
26.3 ± 11.6
159.8 ± 13.4*
166.4 ± 16.2*#
19.2 ± 4.6
13.2 ± 2.1*
12.7 ± 2.3*#
10.1 ± 2.3*
10.5 ± 1.9*#
No infenction 15.6 ± 2.7
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* compared with the control group (group A), P<0.05 # compared with the group B, P>0.05
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