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新生儿坏死性小肠结肠炎课件_7

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新生儿坏死性小肠结肠炎ppt 新生儿坏死性小肠结肠炎 新生儿坏死性小肠结肠炎课件 新生儿坏死性小肠结肠炎ppt课件新生儿
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With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 从先进科室到卓越科 室 新生儿坏死性小肠结肠炎新生儿坏死性小肠结肠炎 治疗的矛盾与对策治疗的矛盾与对策 儿科儿科 崔其亮崔其亮 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 概 述 l新生儿常见而严重的胃肠道急症,也是肠穿孔和 SIRS的主要原因之一 l以胃肠道缺血坏死及常见并发症——肠穿孔为其 特征,是新生儿期死亡的主要原因之一 l90%-95%发生在胎龄 34 wks 足月儿 诊断日龄: 20 days 11 days 5.5 days 3 days Ø发病日龄与胎龄、体重相关 Ø通常发生在7d的早产儿(多发生在生后2~3周) Ø有约25%病例发生在生后1个月 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 危险因素 l早产(脐血管置管、Apgar评分低、PDA) l肠道喂养与细菌定植 l缺血后再灌注损伤 l炎症介质作用 l缩血管药物、换血治疗 l其他疾病:红细胞增多症、多胎、先天性 心脏病、心律失常等 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 病理学??? 低氧, 酸中毒, 心输出量下降 内脏缺血 高渗喂养 粘膜水肿/溃疡 肠道免疫力异常细菌定植 肠壁感染扩散 门脉系统、淋巴系统 气肿、门脉积气内毒素释放 肠道透壁坏死 败血症、DIC、休克 穿孔 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 临床表现 突然发病: 足月儿或早产儿 急性灾难性病情恶化 呼吸困难 休克/酸中毒 腹胀明显 血培养阳性 潜在发病: 通常为早产儿 病情变化在1-2d 喂养不耐受 大便性状改变 间歇性腹胀 大便潜血(+) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society NEC的BELL分期 Bell分期(不同时期采取不同治疗措施) ØⅠ期(可疑NEC):体温不升,轻度腹胀,胃潴留,绿色 或血性胃内容物,呕吐,大便潜血或直肠有鲜红血。X 线见肠管扩张,轻度肠梗阻征(内科治疗、排查败血症) ØⅡ期(确诊NEC):除I期表现外,可有血便、呕血、腹胀 加剧,肠鸣消失,腹部或有压痛,轻度代酸,血小板 减少。X线可见肠管僵直固定,肠壁积气,甚或门静脉 积气(内科治疗) ØⅢ 期(重症NEC):全身情况进行性恶化,频发呼吸暂停 ,持续酸中毒,低血压,腹膜炎,或有DIC、肠穿孔。 X线可见腹水或气腹(外科手术治疗) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society NEC基本诊治方案 l禁食 l胃肠减压 l抗生素使用 l对症治疗 l拔除脐血管置管 l监测:生命体征、腹围、出入液量、胃肠道出血 l实验室:生化、败血症指标等 l影像学检查 l手术治疗 √ √ √ With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——禁食与喂养 NEC一般处理常规 禁食与胃肠减压: Ø可疑病例2-3d Ø轻症10-14d Ø重症14-20d 待腹胀消失,肠鸣恢复,大便潜血阴转,临 床一般症状好转,开始恢复饮食 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——禁食与喂养 问题—— 禁食多久? 禁食后如何喂养? With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——禁食与喂养 可能降低发生NEC 风险 延长肠外营养 肠管萎缩 院内感染 迟出院 经肠喂养 延迟经肠和经口喂养 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——禁食与喂养 Brotschi等多中心回顾性研究 Ø对象:Bell分期Ⅱ期的保守治疗NEC患儿 Ø分组:禁食5d组(n=17) Ø观察:并发症发生率 Ø结果:急性期过后,短期禁食组有较低的并发 症发生率,导管相关性败血症发生率明显降低 Barbara Brotschi1, Oskar Baenziger1, Bernhard Frey,et al. Early enteral feeding in conservatively managed stage II necrotizing enterocolitis is associated with a reduced risk of catheter-related sepsis. J. Perinat. Med.2009, 37:701-705 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——禁食与喂养 不同禁食期的并发症 Barbara Brotschi1, Oskar Baenziger1, Bernhard Frey,et al. Early enteral feeding in conservatively managed stage II necrotizing enterocolitis is associated with a reduced risk of catheter-related sepsis. J. Perinat. Med.2009, 37:701-705 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society M Chauhan, G Henderson, W McGuire.Enteral feeding for very low birth weight infants:reducing the risk of necrotising enterocolitis . Arch. Dis. Child. Fetal Neonatal Ed. 2008;93;162-166 不同方法经肠喂养和发生NEC的风险 治疗矛盾与对策 ——禁食与喂养 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society M Chauhan, G Henderson, W McGuire.Enteral feeding for very low birth weight infants:reducing the risk of necrotising enterocolitis . Arch. Dis. Child. Fetal Neonatal Ed. 2008;93;162-166 VLBW喂配方奶与人乳发生NEC的风险比较 治疗矛盾与对策 ——禁食与喂养 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——禁食与喂养 策略—— Ø 禁食时间尽可能缩短 Ø 母乳喂养为佳 Ø 适量喂养 Ø 缓慢加奶:增加量5d Ø方法 ü接受初始经验性抗生素治疗,疗程中位数5d(1-36d) ü2147例(53%)接受延长经验性抗生素治疗 Ø结果 ü生后3d内初次培养结果为无菌 ü延长经验性应用抗生素治疗可能增加NEC或死亡的 风险(校正多变量分析) Ø建议:谨慎使用延迟疗法 Cotton, et al. Pediatrics 2009;123:58–66 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 抗菌素应用 初始经验性抗生素治疗天数 Cotton, et al. Pediatrics 2009;123:58–66 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 抗菌素应用 初始抗生素疗程及接受延迟经验治疗的婴儿比例与NEC或死亡的结果 Cotton, et al. Pediatrics 2009;123:58–66 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 抗菌素应用 抗生素疗程与NEC或死亡的关系 Cotton, et al. Pediatrics 2009;123:58–66 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 抗菌素应用 生后7d内气管插管婴儿抗菌素疗程与NEC或死亡的多元回归分析 Cotton, et al. Pediatrics 2009;123:58–66 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 院内细菌流行分布[1] 中国院内 细菌流行/ 耐药监测( NPRS)协 作组 (2004) G-杆菌构成(1958株) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 院内细菌流行分布[2] 中国 NPRS 协作组 (2004) G-杆菌构成(1958株) 呼吸道标本菌种构成(1274株) 血液标本菌种构成(147株) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 院内细菌耐药监测[1] 中国 NPRS 协作组 (2004) G-杆菌构成(1958株) 呼吸道标本菌种构成(1274株) 血液标本菌种构成(147株) GG - - 菌总敏感率菌总敏感率(1994-2004)(1994-2004) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 院内细菌耐药监测[2] 中国 NPRS 协作组 (2004) G-杆菌构成(1958株) 呼吸道标本菌种构成(1274株) 血液标本菌种构成(147株) 血培养血培养GG - - 菌总敏感率菌总敏感率(1994-2004)(1994-2004) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 院内细菌耐药监测[4] 中国 NPRS协作组ESBL检出率(2004) ü 大肠埃希菌53.0% 血液标本菌种构成(147株) ESBLESBL阳性大肠杆菌耐药率阳性大肠杆菌耐药率(228(228株株) ) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 院内细菌耐药监测[5] 血液标本菌种构成(147株) ESBLESBL阳性肺炎克雷伯菌耐药率阳性肺炎克雷伯菌耐药率(134(134株株) ) 中国 NPRS协作组ESBL检出率(2004) ü 肺炎克雷伯菌43.0% With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society NPRS研究结论(2004) l15290株G-菌(35个ICU):铜绿大肠肺炎克雷伯不动 杆菌肠杆菌 l产酶是G-菌主要耐药问题:产酶率不断升高 •ESBL:大肠埃希菌53.0%、肺炎克雷伯菌43.9% •AmpC酶:17% l亚胺培南 •对所有G-菌敏感率最高和稳定性最好 •对大肠埃希、肺炎克雷伯菌保持高度敏感,而其他 抗菌药物敏感率逐年下降 •对AmpC酶稳定,对阴沟肠杆菌等产AmpC酶菌保持高 度敏感 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 新生儿NI病原学特点 lG-杆菌多见,最常见克雷伯菌,其次大肠菌、铜绿菌、不动杆菌等 ØHoexter等(2002):总结一组新生儿感染病原菌12年资料,克雷 伯菌占NI病原菌15.2% Ø深圳市人民医院(2003):81例NI肺炎患儿,31例(38.27%)检出 产ESBL菌34株,其中克雷伯菌58.82%(20/34);对亚胺培南普遍 敏感,对三代头孢等普遍耐药 Ø中山一院(2004):22例培养阳性患儿检出病原菌107株,G-杆菌 97株(87.9%),G+球菌13株(12.1%)。G-杆菌以克雷伯菌最常见; 产ESBL菌株60%(24/40);G-杆菌对青霉素类、头孢类耐药率均高 (44.6%-79.5%) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 新生儿败血症细菌学特点 n药物敏感率70%:万古 (96.18%)、利福平(75.19%)、 阿米卡星(75.17%)、亚胺培南 .(7513%)、环丙沙星(7313%) nG-菌对亚胺培南最敏感 (92.19%),G+菌对万古最敏感 (96.18%) nESBL菌共602株(70.19%),产 酶率依次为肺炎克雷伯75.17% 、大肠埃希65.16%、产酸克雷 伯63.16% 古锐:中国实用儿科杂志,2007,22(1) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 细菌耐药问题 n超广谱β-内酰胺酶 (extend spectrumβ- lactamase,ESBLs) n头孢菌素酶 (AmpC酶) n其他酶机制 吴茜:中华妇幼保健临床医学杂志,2008,4:(2). With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ESBL与产ESBL菌[1] lESBL:对β-内酰胺酶类抗生素(三代头孢、氨曲南等) 具较强水解作用的酶,主要由肠杆菌科细菌产生 l产ESBL菌多重耐药:质粒中ESBL基因编码与其他耐 药基因联结,或除携带ESBL耐药基因质粒外还带有其他 耐药基因 l耐药性传播与扩散:在同种或异种菌通过质粒的介导( 接合、转化、转导)而致细菌耐药性传播与扩散 l广谱抗菌药滥用→细菌间质粒介导耐药→产ESBLs菌 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ESBL与产ESBL菌[2] l产ESBL菌:携带耐药质粒菌种 l常见产ESBL菌:克雷伯菌、阴沟杆菌、大肠埃希菌等 •复旦儿科医院(2002):分别为70%、66.7%、64.3% •中山一院(2003):早产儿(73.1%),呼吸道(61.5%) lPaterson等(2004):既往使用头孢类与使用碳青霉烯类 抗生素出现ESBL肺炎克雷伯菌感染危险之比为3.9:1.5 l克雷伯菌对大部分头孢、青霉素类耐药,产ESBL菌多 为多重耐药 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ESBL与产ESBL菌[3] ESBL: lG-需氧菌产生 l多为质粒介导 l灭活青霉素、头孢、单环β-内酰 胺类 l可被克拉维酸、舒巴坦、三唑巴 坦抑制 l通常不灭活碳青霉烯、头霉素类 l同一菌株中可产不同型质粒酶 易感ESBL阳性菌因素: lICU l儿科:特别是早产儿 l血液科 l应用广谱抗生素:尤其是三代头孢 l侵入性操作:机械通气等 l长期或预防性使用抗生素史 l长期住院 临床研究证明ESBL死亡率更高:40% vs 18% With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ESBL与产ESBL菌[4] lESBL(+)菌株的治疗建议 n加酶抑制剂复合药:头孢哌酮/舒巴坦、哌拉西林/三唑巴坦 n头霉素类:头孢美唑、头孢米诺 n严重感染碳青霉烯类:美罗培南、亚胺培南 头孢吡肟、头孢他啶体外显示敏感 国外证明头孢吡肟疗效和细菌清除率80% n喹诺酮类:环丙沙星、左氧氟沙星 n联合氨基糖苷类:阿米卡星 62 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society AmpC酶与产AmpC酶菌[1] lAmpC酶水解:青霉素、头霉素、1-3代头孢、单环类、 加酶抑制剂(克拉维酸、舒巴坦等) l分类: • 按产生方式:诱导高产酶、持续高产酶、持续低产酶 • 按作用原理:诱导型、结构型、质粒型 l发生率:有结果显示30-50%肠杆菌属产AmpC酶 •国内监测(2004):17% •常见于G-杆菌:阴沟、枸橼酸杆菌占的比例越来越高 ,有的医院排名在第6、7位 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society AmpC酶与产AmpC酶菌[2] l产AmpC酶肠杆菌感染死亡率更高 死亡率死亡率% % 15%15% 32%32% P=P=0.030.03 非耐药菌非耐药菌产产AmpCAmpC霉耐药菌霉耐药菌 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 耐药细菌用药 产ESBL菌 l避免用: •青霉素 •头孢菌素 •氨曲南 l可以用: • 碳青酶烯类 • β-内酰胺酶抑制剂 • 头霉素类 • 氨基糖苷类 产AmpC菌 l避免用: •青霉素 •1-3代头孢 •氨曲南、头霉素、β-内酰胺酶抑制剂 l可以用: •碳青酶烯类 •四代头孢菌 (合并ESBL用碳青酶烯类) •喹诺酮/氨基糖苷类:辅助/联合用药 65 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 抗生素治疗原则 重度脓毒症和脓毒性休克治疗指南(2008) l尽早开始静脉抗生素治疗 •重度脓毒症和脓毒性休克:1h内 (1D,1B) l初始经验性治疗应覆盖所有可能病原菌并对感染部位有良好的组织 穿透力 (1B) l抗感染方案应每日进行评价以保证疗效、防止耐药、减少毒性、节 约费用 (1C) l铜绿假单胞菌感染应联合治疗 (2D) l经验性联合治疗不超过 3-5d,应尽快按药敏选择单药治疗 (2D) l抗感染疗程 7-10d,临床反应差、无法引流的局部感染、免疫力低 下者疗程适当延长 (1D) Crit Care Med. 2008,36(1):296-327 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——抗生素与益生菌 益生菌在NEC中的应用 Ø口服益生菌可抑制肠内致病菌的 过度繁殖,使异常的肠通透性、 失衡的肠微生态系统恢复正常 Ø有研究发现,双歧杆菌可通过减少肠道致病菌 、减少内毒素生成、降低肠上皮细胞磷脂酶A2 表达及减轻细菌移位等作用而减少NEC发生 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——抗生素与益生菌 Venkatesh等国外学者随机对照研究 Ø对象:意大利11个NICU的VLBWI(2007-2008) Ø随机分组:口服牛乳铁蛋白组(n=153)、牛乳铁蛋白加 鼠李糖乳杆菌组(n=151)、口服安慰剂组(n=168) Ø结果: ü口服乳铁蛋白者与安慰剂组比较未有明显减少NEC 发生(3例 vs 10 例, RR 0.33, 95% CI 0.09 to 1.17; RD -0.04, 95% CI -0.08 to 0.00) ü联合服用乳铁蛋白/鼠李糖乳杆菌者与安慰剂组比较 明显减少NEC发生(0例 vs 10 例, RR 0.05, 95% CI 0.00 to 0.90; RD -0.06, 95% CI -0.10 to -0.02; NNT 17, 95% CI 10 to 50) Venkatesh MP, Abrams SA. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants:a Cochrane review. Cochrane Database of Systematic Reviews 2010, Issue 5. With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——抗生素与益生菌 AlFaleh等德国学者Meta分析 Ø 对象:9个NICU中心1425名早产儿 Ø 结果:经肠道补充益生菌可显著减少严重NEC(Ⅱ期或 以上)的发生[RR 0.32(95%CI0.17,0.60)]及降低死亡率 [RR 0.43(95%CI0.25,0.75)] AlFaleh KM,Bassler D.Probiotics for prevention of necrotizing enterocolitis in preterm infants(Review).The CocbraneLibrary, 2009,Issue 1. With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society AlFaleh KM,Bassler D.Probiotics for prevention of necrotizing enterocolitis in preterm infants(Review).The CocbraneLibrary, 2009,Issue 1. With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society AlFaleh KM,Bassler D.Probiotics for prevention of necrotizing enterocolitis in preterm infants(Review).The CocbraneLibrary, 2009,Issue 1. With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society AlFaleh KM,Bassler D.Probiotics for prevention of necrotizing enterocolitis in preterm infants(Review).The CocbraneLibrary, 2009,Issue 1. With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 治疗矛盾与对策 ——抗生素与益生菌
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