The use of silver sulfadiazine should be discouraged for burn wounds

数十年来，含银抗菌剂一向作为非全层皮肤烧伤患者的尺度部门疗法使用。尤其是磺胺嘧啶银（SSD）被普遍用于医治烧伤。然而，其疗效一向不明确。最近颁发的两篇系统评述[1, 2]文章揭示了含银敷料和部门医治药物医治烧伤不足有效证据。

Silver-containing antibiotics have been applied as standard topical therapy for patients with partial-thickness burns for decades. Silver sulfadiazine (SSD or SD-Ag) in particular is commonly used to manage burns. However, evidence of their effectiveness remains poorly defined. Two recently published systematic reviews [1, 2] suggested the lack of evidence of effectiveness for silver-containing dressings and topical agents in burns.

第一篇系统评述[1]是在英国表科杂志上颁发的，Brölmann等人筛选了Cochrane创伤与表周血管疾病组截止到2011年6月颁发的所有Cochrane系统评述文章[3]。他们甄别和审阅了蕴含109条基于证据的结论的共44篇有关评述。在其文章表2中列出了数条与烧伤有关的证据，蕴含“其他纤维敷料和含银抗菌剂可能没有成果或甚至延缓了愈合”，“与SSD相比，部门负压医治5天时烧伤伤口面积缩幼”以及“使用SSD霜增长或削减习染率证据有限，相互矛盾。没有证据批注在创伤愈合和伤口习染时部门使用银造剂有效”，同时在对急性创伤（含烧伤）的总结中得出结论“由于多个临床试验显示延缓创伤愈合和增长疼痛及习染率的趋向，磺胺嘧啶银不宜用于烧伤”。并且，在其表8中他们建议“在急性创伤中不要使用磺胺嘧啶银作为部门医治药物”。

In the first article, published on British Journal of Surgery [1], Brölmann et al. have screened all Cochrane systematic reviews [3] up to June 2011 published by the Cochrane Wounds and Peripheral Vascular Diseases Groups. They identified and reviewed 44 relevant reviews containing 109 evidence based conclusions. Several evidences regarding burns were listed in table 2 of their article, including “Other fibre dressings and antimicrobial (silver) dressings may have no effect on, or even prolong, healing”, “A reduction in burn size at day 5 was seen when TNP (topical negative pressure) was compared with SSD” and “Contradictory limited evidence of increased and decreased infection rates when using SSD cream. No evidence for effectiveness of topical silver for preventing wound infection in terms of wound healing and wound infection”, and they concluded that “For burn wounds the use of silver sulfadiazine should be discouraged, as several trials showed a trend towards wound healing delay and increased pain and infection rates” in their results for acute wounds. Furthermore, they recommended that “In acute wounds do not use silver sulfadiazine as topical agent” in table 8 of their article.

Brölmann引用的一篇系统评述[4]总结了来自医治浅表烧伤和非全层皮肤烧伤的26项随机对照临床试验的最好证据，了局显示烧伤敷料用水凝胶、硅衣敷料、生物合成敷料和抗菌敷料要迸酌SSD或洗必泰药纱敷料伤口愈合的更快。这篇评述还发现，固然在所有有关钻研中没有统计意思上的差距，但是有个一致的趋向，就是与SSD或洗必泰敷料相比，使用其他所有过问敷料时病人经受的疼痛更少。

One systematic review [4] cited by Brölmann summarized the best available evidence from a total of 26 included randomised controlled trials (RCTs) relating to the effects of dressings used to treat adults with superficial or partial thickness burns, and the results indicated that burn wounds dressed with hydrogels, silicon coated dressings, biosynthetic dressings and anti microbial dressings healed more rapidly than those dressed with SSD or chlorhexidine impregnated gauze dressings. Also in this review, there was a finding, not statistically significant in all studies but was consistent for all intervention dressings, that the pain experienced by patients appeared to be reduced with the use of the intervention dressing when compared against SSD or chlorhexidine dressings.

在另一篇Brölmann引用的系统评述[5]中，甄别出26项随机对照临床试验（共计2066患者）。由于医治步骤和成效的异质性，没有做荟萃分析，而是按创伤类型和银造剂将了局分组总结。而在习染率、伤口愈合率、疼痛和用度方面的比力钻研都得出显著不利于SSD的了局，其有关结论为“没有证据支持使用SSD预防非全层皮肤烧伤患者的伤口习染。与其他含银及非银敷料相比，没有临床试验批注SSD在其他疗效上有益。并且，有证据批注SSD可能延缓伤口愈合，破费更贵以及用于烧伤时病人更疼痛”。

In another systematic review [5] cited by Brölmann, 26 RCTs (2066 patients) were identified. Due to the heterogeneity of treatments and outcomes precluded meta-analysis, they grouped results according to wound type and silver preparation. The comparisons in terms of infection rate, wound healing rate, pain, and costs showed statistically significant differences in favour of non-silver dressing against SSD with conclusions that “ there was no evidence to support the use of silver sulphadiazine (SSD) for prevention of wound infection in patients with partial-thickness burns. None of the trials indicated a beneficial effect for SSD for other outcomes when compared with other silver-containing or non-silver dressings. Furthermore, there was evidence that SSD may delay wound healing, may be more expensive, and may be more painful when applied to burns.”

第二篇系统评述是Aziz等人[2]在国际烧伤学会的烧伤杂志上颁发的，他们想通过对已有证据的荟萃分析，评价在烧伤中含银的敷料和部门药物对于预防习染和推进愈合的作用成效。他们甄别出14项随机对照临床试验，涉及877名患者。其了局批注“与非银组相比，部门银造剂显示出显著更差的愈应功夫，并且没有显示出有效预防伤口习染的证据”。他们的评述揭示了“含银敷料和部门银造剂比对照敷料在预防烧伤习染和推进烧伤愈合上更差或者不会更好”。

In the second systematic review article, published on Burns[2], Aziz et al. aimed to evaluate the effectiveness of silver containing dressings and topical silver for preventing infection and promoting healing in burns wounds through a meta-analysis of the available evidence. They identified 14 RCTs involving 877 participants. Their results indicated that “topical silver showed significantly worse healing time compared to the non-silver group and showed no evidence of effectiveness in preventing wounds infection”. Their review suggests that “silver-containing dressings and topical silver were either no better or worse than control dressings in preventing wound infection and promoting healing of burn wounds”. 

另表，SSD对皮肤细胞有毒[6]，偏差于粘附在伤口批注并且必要经；灰┮蚨Ｏ招律掀ぱ踊荷丝谟蟍6]。有确凿证据批注，利用了含银药物造剂后银离子被吸收入体循环并从尿中渗出。钻研批注磺胺嘧啶银中开释的银离子在角化细胞、肝细胞、中性粒细胞、白细胞以及成纤维细胞中是有毒性的并与细胞特点的失落有关[8, 9]。受损的人角化细胞阐发出的退行性病变可能导致创伤处上皮再生的延长。并且，持久露出于银离子的细菌产生了对银的抗药性。凭据细菌匹敌菌剂的性质，在选择压力下增殖的细菌可能出现固有的和获得性的抗药机造。临床证据已发现死于习染的患者的烧伤部位拥有银抵抗的菌株。

In addition, SSD has toxic effect on skin cells [6] and tends to adhere to wound surface and requires frequent dressing changes which would hurt newly generated epithelium and delayed wound healing [7]. Irrefutable evidence has shown that silver is absorbed into the systemic circulation and excreted in urine after application of silver-containing pharmaceutical preparation. Study has shown that silver released from SSD was toxic in keratinocyte, hepatocyte, neutrophils, leucocyte and fibroblast and was association with a loss in cellular identity [8, 9]. One of the possible outcome of human keratiocytes is degenerative changes which lead to actual "delay" of wound re-epithelialisation. Furthermore, one consideration has been implicated in bacteria after long time exposure to silver, the consequential bacterial resistance to silver [10] .
According to the nature of bacteria toward antimicrobial agent, intrinsic and acquired mechanism may emerge as bacteria proliferate under selective pressure. Clinical evidence has found patients who died from infection contained silver resistant strain of bacteria at their burn wound.

对PubMed就“磺胺嘧啶银对烧伤之成效的系统评述”进行急剧搜索，获得两篇有关的文章，了局都不利于SSD。 其中Wasiak等人[11]的评述概想是“SSD霜可能无效或有害”以及“相迸宗其他医治，SSD霜可能耽搁愈应功夫并增长疼痛”。另一篇Andrew等人[12]的文章只甄别出了7个动物尝试且了局相互矛盾。

A quick search in PubMed for “systematic review on the effectiveness of silver sulphadiazine on burns” retrieved two relevant articles, both of which are not in favor of SSD. The review by Wasiak et al. [11] got the view of “ likely to be ineffective or harmful” for SSD cream and that “Silver sulfadiazine cream may prolong healing times and increase pain compared with other treatments”. The other article by Andrew et al. [12] identified only 7 animal studies providing conflicting results.

总的来说，鉴于没有强有效的临床证据支持SSD在烧伤的利用以及“业界的利润增长通常来自加强告白宣传而非更强的疗效证据” [13]，Brölmann等人在英国表科杂志上的系统评述里做出的结论“磺胺嘧啶银不宜用于医治烧伤”和建议“在急性创伤中不要使用磺胺嘧啶银作为部门医治药物”是的确可信的。他们的钻研
援手阐了然没有证据批注含银敷料和造剂，尤其是SSD，对类似烧伤的某些类型创伤的医治有效，这暗示着目前的临床实际不是基于证据的，为了获得最佳医治成效必要扭转。正如Palfreyman对Brölmann等人所做的评论[13]，“他们的评述会援手临床医生和决策者们在做决按时是凭据临床证据，而不是凭据传统或专家定见。这在创伤治理领域尤其沉要，由于这个领域时时短缺高质量的临床证据，而系统评述可能仅是一种借以合理揣度和削减选择的蹊径”。

In summary, since there is no strong clinical evidence supporting the use of SSD in burns and that “The explosion in profits for industry has more often than not been based on high levels of advertising rather than high levels of evidence of effectiveness” [13], the conclusion “For burn wounds the use of silver sulfadiazine should be discouraged ” and recommendation “In acute wounds do not use silver sulfadiazine as topical agent”, made by Brölmann et al. in their newly published systematic review on British Journal of Surgery, are reliable. Their study helps to illuminate the lack of evidence for silver containing dressings and agents, in particular SSD, for certain types of wound like burns, which may imply that current practice is not evidence-based and needs to change in order to ensure best quality care. As stated by Palfreyman [13], “Their review will help clinicians and policy-makers to make decisions regarding treatment based on evidence rather than tradition or expert opinion. This can be especially important within the area of wound care where high-quality evidence is often lacking and systematic reviews may be portrayed as merely a means of rationing access and reducing choice”.

北京荣祥再生医学钻研所，北京 100020
Beijing Rongxiang Institute of Regenerative Medicine, Beijing 100020

Corresponding email:tao_939@usc.edu

References

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[2] Aziz Z, Abu SF, Chong NJ.  A systematic review of silver-containing dressings and topical silver agents (used with dressings) for burn wounds. Burns. 2012, 38(3):307-18.

[3] Petticrew M, Wilson P, Wright K, Song F. Quality of Cochrane reviews. Quality of Cochrane reviews is better than that of non-Cochrane reviews. Brit Med Journal, 2002, 324: 545.

[4] Wasiak J, Cleland H, Campell F. Dressings for superficial and partial thickness burns. Cochrane Database Syst Rev, 2008, article (4)CD002106.

[5] Storm-Versloot MN, Vos CG, Ubbink DT, et al. Topical silver for preventing wound infection. Cochrane Database Syst Rev, 2010, (3)CD006478.

[6] Hussain S, Ferguson C. Silver sulphadiazine cream in burns. Emerg Med J. 2006, 23:929–32.

[7] Thomas S, Lawrence J, Thomas A. Evaluation of hydrocolloids and topical medication in minor burns. J Wound Care, 1995, 4:218–20.

[8] Lansdown AB, Silver. 2: Toxicity in mammals and how its products aid wound repair. J Wound Care, 2002, 11(5):173-7.

[9] Atiyeh BS, Costagliola M, Hayek SN, et al.  Effect of silver on burn wound infection control and healing: review of the literature. Burns, 2007, 3(2):139-48.

[10] Percival SL, Bowler PG, Russell D. Bacterial resistance to silver in wound care.
J Hosp Infect. 2005, 60(1):1-7.

[11] Wasiak J, Cleland H., Burns (minor thermal). Clin Evid (Online). 2009 Oct 27; 2009. pii: 1903.

[12] Miller AC, Rashid RM, Falzon L, et al. Silver sulfadiazine for the treatment of partial-thickness burns and venous stasis ulcers. J Am Acad Dermatol. 2012, 66(5):e159-65. 

[13] (S. Palfreyman, Evidence-based decisions for local and systemic wound care (Br J Surg 2012; 99: 1172–1183).  British Journal of Surgery 2012; 99: 1184