多粘菌素用法及药代动力学研究进展

多粘菌素是一种阳离子多肽类抗生素,在1950年代首次用于临床,但在1970年代由于肾毒性和神经毒性而被基本弃用.最近,多重耐药革兰阴性病原体的流行,迫使多粘菌素再次成为临床治疗多重耐药革兰阴性菌的最后一线药物手段.临床证据表明,多粘菌素B由于以其活性形式给药,其药代动力学变异较小,主要通过非肾脏途径消除,因此肾功能损害患者无需调整用药剂量.而CMS可通过肾小球滤过和肾小管排泄迅速清除,20％～25％自发水解为粘菌素.但是不同患者具有其特殊的病理生理状态,药代动力学参数与健康志愿者间存在较大差异,按照健康人体的药代动力学参数指导用药,可能会导致药物剂量不足或剂量过大而增加毒副作用.     

体外膜肺氧合下先天性膈疝转运与外科治疗一例并文献复习

目的 探讨体外膜肺氧合(ECMO)下先天性膈疝治疗及转运中的重、难点.方法 回顾性分析1例严重缺氧性呼吸衰竭先天性膈疝,ECMO建立、转运及治疗等临床资料并结合Pubmed数据库截止2015年前部分文献复习讨论当前先天性膈疝ECMO置入的适应证、时机、ECMO模式、新生儿ECMO抗凝难点、转运风险及产前辅助检查的意义.结果 患儿,男,39周,3.75 kg,产前诊断左膈疝,2015年8月1日18时30分在浙江大学妇产科医院出生,5 min Apgar 7分,之后气促,发绀不断加重,紧急气管插管,状况仍不见明显改善,14h后紧急呼救浙江大学儿童医院ECMO团队,18h后建立VA-ECMO,缺氧立即改善,内环境逐渐稳定20 h后实施ECMO转运,2h完成两家医院顺利对接,并完成手术修补,术后继续ECMO辅助,于2015年8月5日17时撤离ECMO,总运行76h.撤离ECMO出现上下肢差异性紫绀,上肢SpO295％～100％,下肢SpO2 85％～90％,血压52/34mmHg,肺动脉压/血压0.7～1.0,降低肺动脉压力,提高体循环收缩压措施,差异紫绀减轻,约2周后,差异紫绀消失,撤离呼吸机后,血气PaCO2在75～55 mmHg之间,肾脏代偿,HCCg 30.8～41.7 mmol/L,pH 7.39～7.40,出生25d血气PaCO2下降接近正常水平,44d出院.ECMO间发生右髂静脉血栓,撤离后肝素溶栓成功.整个治疗过程均未发生颅内出血、栓塞性脑梗及伤口出血.随访6个月,生长发育良好,体重增长,呼吸平稳,X线胸片示左肺体积略小,膨胀良好.检索文献共有6篇文献专门就先天性膈疝ECMO置入的适应证、时机进行了相关讨论.结论 ECMO辅助可提高先天性膈疝存活率,掌握置入时机及治疗特点是成功的关键.     

蛋白质巯基亚硝基化修饰和心血管系统信号通路

一氧化氮（nitric oxide,NO）在调控氧化还原信号和细胞功能中发挥了重要的作用。NO可以由一氧化氮合酶（nitric oxide synthase,NOS）合成或由亚硝酸盐等化学复合物降解产生。在烟酰胺腺嘌呤二核苷酸磷酸（nieotinamide adenine dinucleotide phosphate,NADPH）和四氢生物蝶呤的存在下,NOS催化L-精氨酸和氧气生成L-瓜氨酸和NO。     

含乌司他丁肺保护液在心肺转流术中的肺保护作用

Objective To evaluate protective effects of hypothermic pulmonary protective solution with uli-nastatin on lung function during cardiopulmouary bypass (CPB) in the patients with congenital heart disease(CHD) and pulmonary hypertenion. Method Fifty-four children,who had CHD of left-to-fight shunts with moderate-se-rious pulmonary hypertension, were enrolled. They had been performed with the radical operation under CPB from September 2005 to December 2006 in the Department of Cardiovascular Surgery, Children' s Hospital of Zhejiang University. Moderate-serious pulmonary hypertension was defined as pulmonary-to-systolic pressure ratio > 0.45(Pp/Ps > 0.45). Fifty-four children were randomly divided into three groups. Patients in group A (n = 18)didn't receive pulmonary protective solution, and scrved as control; patients in group B (n = 18) were adminis-tered with pulmonary protective solution without ulinastatin;patients in group C (n = 18) were administered with pulmonary protective solution with ulinastatin. The serum concentrations of MDA and MPO were measured at five different time points:pre-operation, 0 h, 3 h, 6 h and 24 h in the intensive care unit (ICU) (T1～5). Patients'lung functions were monitored at T1 - T4. The time of mechanical ventilation was recorded. Results No one died in this study. The mean time of mechanical ventilation was shorter in the group B and group C than that in the group A. The MDA and MPO levels were lower in group B compared with group A at T4. The MDA level at T3-T5 and the MPO level at T4 was lower in group C than those in group A. There were no significant in MDA and MPO levels between group B and group C at five time point.A-aDO2 was lower in groups B and C than those in group A at T3 and T4, whereas at T4, A-aDO2 was lower in group C than that in group B. Cdyn was higher in group B at T3and group C at T3 - T4 than those in group A. Cdyn was lower in groups C than that in group B at T4.Condusions Lung perfusion with hypothermic protective solution during CPB can all lung injury and promote recovery after operation, especialy with ulinastatin.     

含乌司他丁肺保护液在心肺转流术中的肺保护作用

Objective To evaluate protective effects of hypothermic pulmonary protective solution with uli-nastatin on lung function during cardiopulmouary bypass (CPB) in the patients with congenital heart disease(CHD) and pulmonary hypertenion. Method Fifty-four children,who had CHD of left-to-fight shunts with moderate-se-rious pulmonary hypertension, were enrolled. They had been performed with the radical operation under CPB from September 2005 to December 2006 in the Department of Cardiovascular Surgery, Children' s Hospital of Zhejiang University. Moderate-serious pulmonary hypertension was defined as pulmonary-to-systolic pressure ratio > 0.45(Pp/Ps > 0.45). Fifty-four children were randomly divided into three groups. Patients in group A (n = 18)didn't receive pulmonary protective solution, and scrved as control; patients in group B (n = 18) were adminis-tered with pulmonary protective solution without ulinastatin;patients in group C (n = 18) were administered with pulmonary protective solution with ulinastatin. The serum concentrations of MDA and MPO were measured at five different time points:pre-operation, 0 h, 3 h, 6 h and 24 h in the intensive care unit (ICU) (T1～5). Patients'lung functions were monitored at T1 - T4. The time of mechanical ventilation was recorded. Results No one died in this study. The mean time of mechanical ventilation was shorter in the group B and group C than that in the group A. The MDA and MPO levels were lower in group B compared with group A at T4. The MDA level at T3-T5 and the MPO level at T4 was lower in group C than those in group A. There were no significant in MDA and MPO levels between group B and group C at five time point.A-aDO2 was lower in groups B and C than those in group A at T3 and T4, whereas at T4, A-aDO2 was lower in group C than that in group B. Cdyn was higher in group B at T3and group C at T3 - T4 than those in group A. Cdyn was lower in groups C than that in group B at T4.Condusions Lung perfusion with hypothermic protective solution during CPB can all lung injury and promote recovery after operation, especialy with ulinastatin.     

含乌司他丁肺保护液在心肺转流术中的肺保护作用

Objective To evaluate protective effects of hypothermic pulmonary protective solution with uli-nastatin on lung function during cardiopulmouary bypass (CPB) in the patients with congenital heart disease(CHD) and pulmonary hypertenion. Method Fifty-four children,who had CHD of left-to-fight shunts with moderate-se-rious pulmonary hypertension, were enrolled. They had been performed with the radical operation under CPB from September 2005 to December 2006 in the Department of Cardiovascular Surgery, Children' s Hospital of Zhejiang University. Moderate-serious pulmonary hypertension was defined as pulmonary-to-systolic pressure ratio > 0.45(Pp/Ps > 0.45). Fifty-four children were randomly divided into three groups. Patients in group A (n = 18)didn't receive pulmonary protective solution, and scrved as control; patients in group B (n = 18) were adminis-tered with pulmonary protective solution without ulinastatin;patients in group C (n = 18) were administered with pulmonary protective solution with ulinastatin. The serum concentrations of MDA and MPO were measured at five different time points:pre-operation, 0 h, 3 h, 6 h and 24 h in the intensive care unit (ICU) (T1～5). Patients'lung functions were monitored at T1 - T4. The time of mechanical ventilation was recorded. Results No one died in this study. The mean time of mechanical ventilation was shorter in the group B and group C than that in the group A. The MDA and MPO levels were lower in group B compared with group A at T4. The MDA level at T3-T5 and the MPO level at T4 was lower in group C than those in group A. There were no significant in MDA and MPO levels between group B and group C at five time point.A-aDO2 was lower in groups B and C than those in group A at T3 and T4, whereas at T4, A-aDO2 was lower in group C than that in group B. Cdyn was higher in group B at T3and group C at T3 - T4 than those in group A. Cdyn was lower in groups C than that in group B at T4.Condusions Lung perfusion with hypothermic protective solution during CPB can all lung injury and promote recovery after operation, especialy with ulinastatin.     

含乌司他丁肺保护液在心肺转流术中的肺保护作用

Objective To evaluate protective effects of hypothermic pulmonary protective solution with uli-nastatin on lung function during cardiopulmouary bypass (CPB) in the patients with congenital heart disease(CHD) and pulmonary hypertenion. Method Fifty-four children,who had CHD of left-to-fight shunts with moderate-se-rious pulmonary hypertension, were enrolled. They had been performed with the radical operation under CPB from September 2005 to December 2006 in the Department of Cardiovascular Surgery, Children' s Hospital of Zhejiang University. Moderate-serious pulmonary hypertension was defined as pulmonary-to-systolic pressure ratio > 0.45(Pp/Ps > 0.45). Fifty-four children were randomly divided into three groups. Patients in group A (n = 18)didn't receive pulmonary protective solution, and scrved as control; patients in group B (n = 18) were adminis-tered with pulmonary protective solution without ulinastatin;patients in group C (n = 18) were administered with pulmonary protective solution with ulinastatin. The serum concentrations of MDA and MPO were measured at five different time points:pre-operation, 0 h, 3 h, 6 h and 24 h in the intensive care unit (ICU) (T1～5). Patients'lung functions were monitored at T1 - T4. The time of mechanical ventilation was recorded. Results No one died in this study. The mean time of mechanical ventilation was shorter in the group B and group C than that in the group A. The MDA and MPO levels were lower in group B compared with group A at T4. The MDA level at T3-T5 and the MPO level at T4 was lower in group C than those in group A. There were no significant in MDA and MPO levels between group B and group C at five time point.A-aDO2 was lower in groups B and C than those in group A at T3 and T4, whereas at T4, A-aDO2 was lower in group C than that in group B. Cdyn was higher in group B at T3and group C at T3 - T4 than those in group A. Cdyn was lower in groups C than that in group B at T4.Condusions Lung perfusion with hypothermic protective solution during CPB can all lung injury and promote recovery after operation, especialy with ulinastatin.     

婴幼儿心内直视术后呼吸机相关性肺炎高危因素分析

目的探讨婴幼儿先天性心脏病（先心病）心内直视术后呼吸机相关性肺炎（VAP）的高危因素。方法回顾性分析2006年1月至2008年12月间入住浙江大学医学院儿童医院SICU的143例心内直视术后机械通气时间≥48h的先心病婴幼儿的病历资料。将143例婴幼儿分为两组：发生VAP的59例为VAP组,未发生VAP的84例为对照组。以性别、疾病类型、生长发育情况、贫血、血清球蛋白水平、术前抗生素应用情况、生长发育、机械通气时间、再插管、H2受体抑制剂或制酸剂应用等为预想危险因素进行单因素及多因素分析,明确婴幼儿心内直视术后与VAP相关的危险因素。结果婴幼儿先心病心内直视术后VAP的发生率为41．3％。单因素分析发现术前抗生素使用、体外循环（CPB）时间、机械通气时间、再插管、H2受体抑制剂或制酸剂应用、术后低心排、术后合并败血症这7个因素与VAP有关（P〈0．05）。多因素logistic回归分析显示术前抗生素使用、机械通气时间、再插管、H2受体抑制剂或制酸剂应用是婴幼儿先心病心内直视术后VAP的独立危险因素（P〈0．05）。结论婴幼儿先心病心内直视术后VAP发生率高,术前抗生素使用、机械通气时间、再插管、H2受体抑制剂或制酸剂应用是婴幼儿先心病心内直视术后VAP的独立危险因素,采取综合防治措施是控制VAP的最佳策略。     

婴儿先天性心脏病术后呼吸机相关性肺炎致病菌及耐药性分析

目的　研究婴儿先天性心脏病 (先心病 )术后呼吸机相关性肺炎 (ventilator -associatedpneumonia ,VAP)的致病菌分布和耐药性及变化趋势 ,为正确选择抗生素提供依据。方法　回顾性分析 1999年 6月至 2 0 0 2年 6月本院 311例婴儿先心病 (根据病情分为复杂先心病组和单纯先心病组 )术后下呼吸道分泌物所有分离的细菌、真菌菌株及其耐药性。结果　 (1) 6 7例 (2 1 5 % )婴儿术后发生VAP ,复杂先心病组VAP的发生率比单纯先心病组高 (χ2 =2 2 4 7,P <0 0 0 0 1) ,且以迟发VAP较多 (χ2 =6 0 2 ,P =0 0 14 )。 (2 )分离出致病菌 79株 ,革兰阴性 (G-)菌为主 ,其次为真菌和革兰阳性 (G+ )菌。G-菌中多见鲍曼不动杆菌、铜绿假单胞菌、脑膜炎败血黄色杆菌等 ;G+ 菌常见金黄色葡萄球菌和表皮葡萄球菌。真菌以白色念珠菌为主。 (3)G-菌对亚胺培南 /西司他丁、头孢哌酮 /舒巴坦、哌拉西林 /他唑巴坦、环丙沙星、阿米卡星、头孢他啶较敏感 ,但其中的嗜麦芽黄单胞菌、脑膜炎败血黄色杆菌对亚胺培南 /西司他丁耐药率高。产超广谱 β -内酰胺酶菌主要为肺炎克雷伯菌和大肠埃希菌 ,对一代、二代、三代、四代头孢菌素及青霉素类抗生素耐药 ,但对亚胺培南 /西司他丁的敏感率为 10 0 %。G+ 菌对万古霉素敏感率为 10 0 %     

法洛四联症术后毛细血管渗漏综合征的危险因素及治疗

目的：探讨法洛四联症术后发生毛细血管渗漏综合征（capillary leak syndrome，CLS）的相关危险因素及治疗转归。方法：回顾性分析2002年10月至2006年12月本院32例法洛四联症根治术后发生CLS患儿的临床资料，对照组为随机抽取同期50例法洛四联症根治术后未发生CLS的患儿，对可能引起CLS发生的因素采用二分类进行单因素和多因素非条件Logistic逐步回归分析，确定与CLS发病相关的独立危险因素，并对两组患儿术后恢复经过进行总结。结果：①Logistic回归分析显示，法洛四联症根治术后发生CLS的独立危险因素按OR值大小排序分别是：年龄≤3岁（OR=6．783）、体外循环时间≥120min（OR=4．756）、MGoon指数≤1．6（OR=3．826）；②CLS组术后3天内胶体用量和血管活性药物应用时间及呼吸机支持时间，与对照组比较均有统计学差异（P〈0．01）；CLS组行腹膜透析8例，死亡3例。结论：法洛四联症患儿的年龄、体外循环时间、MGoon指数是术后发生CLS的独立危险因素。发生CLS后早期需用大量胶体维持有效循环血容量，渗漏好转后应加强利尿，同时应积极进行心肺功能支持治疗。