Local Warming: Effects on Wound Infection and Healing

手术部位感染(SSI)占美国医院感染的37%，增加了发病率和成本。SSI的高发生率(10%-22%)与结直肠手术和肥胖有关。细菌耐药性需要氧气，而较高的组织氧气限制了普通手术患者的感染。控制核心和局部温度可能通过调节灌流、氧合、血管生成和免疫细胞反应来提高感染抵抗力。围手术期低温降低组织氧，而常温降低SSI发生率。局部加热受伤组织可能会带来额外的好处。在接受手术前局部加温的患者中，报告的皮下氧合(PscO2)增加和感染减少。手术后立即加温伤口，并在胃旁路手术或结肠切除术后间歇两天降低感染率，但缺乏对临床结果和潜在机制的系统研究。需要进一步的研究来确定疗效和剂量，并调查临床和细胞结果。目的1：进行一项大型(n=180)随机临床试验，以更确切地确定局部加温(术后即刻1小时，每8~10小时重复5次)在减少SSI和创面并发症方面的临床疗效。SSI和伤口并发症将在住院期间和术后6周内根据a)无菌伤口评分系统；b)CDC SSI分类标准进行评估。目的2：将随机接受局部升温的患者与随机接受常规护理的患者在各种组织和细胞变量上进行比较，以了解升温对这些变量的影响。需要测量的变量包括：2.1术后第9天获得的创面组织反应，包括：a)血管生成指标(通过流式细胞仪测定)：1.内皮祖细胞(EPC)CD133阳性，CD34和VEGFR-2共同表达的百分比)2.内皮细胞(CD31阳性)的百分比3.免疫组织化学证实内皮细胞(CD31阳性)和EPC(CD34和VEGFR-2共同表达)的存在。免疫反应指标(用流式细胞仪测定)1.巨噬细胞(CD68阳性)、T细胞(CDS阳性)和B细胞(CD20阳性)的百分比2.免疫组织化学证实巨噬细胞(CD68阳性)、T细胞(CDS阳性)和B细胞(CD20阳性)的存在c)胶原合成指标(用手动比色微量板法测定)1.羟脯氨酸含量。2.2.使用皮下血压计/微电极和热电偶系统，在术后第0、1和2天测试伤口处的PscO2和温度响应。2.3.术后第3、5、9天用激光多普勒血流仪(LDF)测定手术切口血流灌注(BF)。

Surgical site infections (SSI) account for 37% of US hospital infections and increase morbidity and cost. High rates (10-22%) of SSI are associated with colorectal surgery and obesity. Bacterial resistance requires oxygen, and higher tissue oxygen limits infection in general surgery patients. Control of core and local temperature may increase infection resistance by modulating perfusion, oxygenation, angiogenesis and immune cell responses. Perioperative hypothermia reduces tissue oxygen while normothermia lowers SSI rates. Warming injured tissues locally may offer additional benefit. Increased subcutaneous oxygen (PscO2) and fewer infections are reported in patients receiving pre-surgical local warming. Warming incisions immediately after surgery and intermittently for two days after gastric bypass or colectomy surgery reduced infection rates, but systematic study of clinical outcomes and potential mechanisms is lacking. Further study is needed to determine efficacy and dosage, and to investigate clinical and cellular outcomes. Aim 1: Conduct a large (n=180) randomized clinical trial to more definitively determine the clinical efficacy of local warming (for one hour mmediately post surgery, repeated every 8-10 hours for 5 more sessions) in reducing the incidence of SSI and wound complications. SSI and wound complications will be evaluated during hospitalization and for 6 weeks post-surgery by a) ASEPSIS Wound Scoring System; b) CDC Criteria for Classification of SSI. Aim 2: Compare patients randomized to local warming to those randomized to usual care on a variety of tissue and cellular variables, in order to understand the impact of warming on these variables. Variables to be measured include: 2.1 Wound tissue responses in test wound samples obtained on postoperative day 9, including: a) Indicators of Angiogenesis (determined by flow cytometry): 1. Percent of endothelial progenitor cells (EPC) CD133 positive, CD34 and VEGFR-2 co-expressing) 2. Percent of endothelial cells (CD31 positive) 3. Presence of endothelial cells (CD31 positive) and EPC (CD34 and VEGFR-2 co-expressing) confirmed by mmunohistochemistry. b) Indicators of Immune Response (determined by flow cytometry) 1. Percent of macrophages (CD68 positive), T cells (CDS positive), and B cells (CD20 positive) 2. Presence of macrophages (CD68 positive), T cells (CDS positive), and B cells (CD20 positive) confirmed by Immunohistochemistry c) Indicator of Collagen Synthesis (determined by manual colorimetric microtiter plate assay) 1. Hydroxyproline quantity. 2.2. PscO2 and temperature responses in test wound sites on postoperative days 0, 1 and 2 using a subcutaneous tonometer/micro-electrode and thermocouple system. 2.3. Perfusion (BF) in the surgical incision on postoperative days 3, 5 and 9 using Laser Doppler Flowmetry (LDF).