重症医学资质培训-呼吸机相关性肺炎

1、呼吸机相关性肺炎HAP/VAP: 概要流行病学诊断策略抗生素治疗预防总结HAP/VAP: 问题1呼吸机相关性肺炎指应用机械通气多长时间以后发生的肺炎?A.24小时B.48小时C.72小时D.96小时E.4872小时HAP/VAP/HCAP: 定义医院获得性肺炎（HAP）住院48小时后发生且住院时不处于潜伏期的肺炎呼吸机相关性肺炎（VAP）气管插管48小时以后发生的肺炎因重度HAP需要气管插管者应按照VAP处理医疗相关肺炎（HCAP）发生感染前90天内在急性病医院住院 2天在养护院或长期医疗机构住院近期接受静脉抗生素治疗、化疗或发生感染前30天内接受伤口治疗就诊于医院门诊或透析门诊ATS/IDS

2、A. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP: 流行病学发病率美国医院获得性感染的第二位515例/1000住院病例罹患率和病死率升高预后住院日延长79天医疗费用增加$40000HAP/VAP: 流行病学Kumpf G, et al. J Clin Epidemiol 1998; 54:

3、495-502Lizioli A, et al. J Hosp Infect 2003; 54: 141-148Richards MJ, et al. Crit Care Med 1999; 27: 887-892HAP/VAP: 流行病学Cook DJ, Walter SD, Cook RJ, Griffith LE, Guyatt GH, Leasa D, Jaeschke RZ, Brun-Buisson C. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patie

4、nts. Ann Intern Med 1998;129:440HAP/VAP: 流行病学HAP/VAP: 病死率总病死率3070%：大多数 HAP患者死于基础病 归因病死率3350%VAP的归因病死率升高与菌血症、耐药菌（如铜绿假单胞菌、不动杆菌属）感染、不恰当的抗生素治疗等因素相关。 HAP/VAP: 危险因素气管插管和机械通气平卧位缺乏感染控制措施缺乏ICU感染监测经鼻气管插管紧急插管或再次插管基础肺病肠道营养气管插管套囊压力低HAP/VAP: 危险因素H2受体拮抗剂进行应激性溃疡预防“自由”输血去白细胞输血血糖控制不佳ARDS深度镇静或肌松HAP/VAP: 病因学FagonKollef

5、PapazianRelloTimsitTorres革兰阴性杆菌 55 85%铜绿假单胞菌192927501628不动杆菌属104501224嗜麦芽窄食单胞菌073000肠杆菌属168004流感嗜血杆菌61810130其他革兰阴性杆菌24102841032革兰阳性球菌2030%金黄色葡萄球菌20302192620肺炎链球菌410744HAP/VAP: 病因学支气管远端标本培养分离出口咽部定植菌（草绿色链球菌，凝固酶阴性葡萄球菌，奈瑟氏菌属，棒状杆菌属）难以解释在免疫抑制甚至免疫正常患者可能引起感染Cabello H, Torres A, Celiss R, El-Ebiary M, de la

6、Bellacasa JP, Xaubet A, Gonzalez J, Augusti C, Soler N. Bacterial colonization of distal airways in healthy subjects and cronic lung diseases: a bronchoscopic study. Eur Respir J 1997;10:11371144HAP/VAP: 病因学金黄色葡萄球菌糖尿病，头颅创伤，住ICU厌氧菌：在VAP中的重要性尚不明确非插管患者误吸VAP罕见肺炎军团菌：发生率缺乏数据，但重要性受关注免疫抑制患者如器官移植，HIV，糖尿病，基础肺

7、病，终末期肾病HAP/VAP: 病因学真菌（包括念珠菌和曲霉菌）器官移植，免疫抑制，中性粒细胞缺乏免疫正常患者罕见病毒免疫正常者罕见流感病毒，副流感病毒，腺病毒，麻疹病毒，呼吸道合胞病毒占病毒的70%HAP/VAP: MDR危险因素既往90天应用抗生素住院5天所在社区或医院病房中抗生素耐药率高HCAP危险因素发生感染前90天内在急性病医院住院2天在养护院或长期医疗机构住院家庭输液治疗（包括抗生素）30天内接受慢性透析家庭伤口护理家人有多重耐药菌感染/定植免疫抑制疾病和（或）治疗HAP/VAP: 分类012345678Early-onset HAPLate-onset HAPTime from

8、hospitalization （days）012345678Early-onset VAPLate-onset VAPTime from Intubation （days）ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP: 病因学早发性HAP/VAP迟发性HAP/VAP细菌学

9、肺炎链球菌铜绿假单胞菌流感嗜血杆菌不动杆菌MSSAMRSA敏感GNB耐药肠杆菌科大肠杆菌肠杆菌属肺炎克氏菌ESBL +ve菌变形杆菌属克雷伯菌属肠杆菌属嗜肺军团菌粘质沙雷氏菌洋葱伯克霍尔德菌曲霉菌属预后病情较轻，对预后影响小归因病死率高病死率低罹患率高ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388

10、-416HAP/VAP: 概要流行病学诊断策略抗生素治疗预防总结HAP/VAP: 问题2以下哪个不是呼吸机相关性肺炎确切的发病机制A.误吸B.直接吸入C.血行性播散D.胃肠道细菌移位E.以上答案均不对HAP/VAP: 发病机制改变胃排空及胃液pH值的药物有生物膜的装置（气管插管，鼻胃管）既往应用抗生素宿主因素（免疫抑制，烧伤）消化道细菌定植细菌误吸细菌吸入医院获得性肺炎水, 药物溶液及呼吸治疗装置污染经胸种植原发性菌血症胃肠道细菌移位感染控制措施不够（洗手，隔离衣，手套）医务人员不足HAP/VAP: 影像学诊断对于可疑肺炎患者，如果根据其他临床表现不能确诊，影像学判断也不能提高诊断的正确性若胸

11、片显示明显浸润影，则鉴别心源性肺水肿、非心源性肺水肿、肺挫伤和肺不张将非常困难各种影像学表现的敏感性和特异性差异很大，诊断准确性均不超过70%支气管气像诊断肺炎的准确性最高（64%）HAP/VAP: 影像学诊断CXR vs. CT手术后肺实变：敏感性0.331.00，特异性 0.79不同医生判读的一致性放射科医生：kappa 0.27ICU医生：1239%Wunderink RG, Woldenberg LS, Zeiss J, et al. The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia.

12、Chest 1992; 101: 458-63.Fagon J, Chastre J, Hance A. Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients. Chest 1993; 103: 547-53.Beydon L, Saada M, Liu N, et al. Can portable chest x-ray examination accurately diagnose lung consolidatio

13、n after major abdominal surgery?: a comparison with computed tomography scan. Chest 1992; 102: 1698-703.HAP/VAP: 临床诊断胸片新出现浸润影或原有浸润性加重以下临床表现中两条：T38白细胞增多或白细胞缺乏脓性气道分泌物敏感性69%，特异性75%HAP/VAP: 细菌学诊断下呼吸道标本的半定量培养特异性低：培养结果阳性可能仅提示定植敏感性高：培养结果阴性有助于除外感染除非刚刚应用或更换抗生素常导致过度应用抗生素革兰染色结果结合培养结果有助于指导抗生素治疗HAP/VAP: 细菌学诊断PSB

14、ETABAL诊断阈值103 cfu/mL105106 cfu/mL104105 cfu/mL敏感性667673特异性907582特异敏感准确采样部位越远，特异性越高，敏感性越低，诊断阈值越低HAP/VAP: 细菌学诊断试验设计：多中心随机临床试验入选标准：免疫功能正常的成年患者住ICU超过4天后怀疑呼吸机相关性肺炎排除标准：假单胞菌属或MRSA定植或感染分组：诊断：BALF定量培养 vs. ETA的非定量培养治疗：美罗培南 + 环丙沙星 vs. 美罗培南The Canadian Critical Care Trials Group. A randomized trial of diagnost

15、ic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630HAP/VAP: 细菌学诊断ETA（n=374）BAL（n=365）合计（n=739）明确VAP01（0.3）1（0.1）高度可疑VAP0180（49.3）180（24.4）可能VAP310（82.9）134（36.7）444（60.1）无VAP64（17.1）50（13.7）114（15.4）高度可疑VA =临床诊断+BALF104cfu/ml；可能VAP=临床诊断The Canadian Critical Care Tria

16、ls Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630HAP/VAP: 细菌学诊断ETABALP值28天病死率18.4%18.9%0.946天时针对性治疗74.6%74.2%0.90无抗生素存活天数10.67.910.47.50.86最高MODS评分8.64.08.33.60.26The Canadian Critical Care Trials Group. A randomized trial of

17、 diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630HAP/VAP: 细菌学诊断呼吸道分泌物分离出念珠菌，很少提示深部念珠菌感染，不应进行抗真菌治疗。（A-III）Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society

18、of America. 2009; 48: 503-535HAP/VAP: 综合诊断CPIS评分012气管吸取物无无脓性分泌物脓性分泌物CXR浸润影无浸润影弥漫性浸润影局灶性浸润影肺部浸润影进展无进展有进展体温，36.5且38.438.5且38.939或36WCC，109/L4.0且11.011.0 11.0 + 杆状核0.5PaO2/FiO2，mmHg240或ARDS240且无ARDS的证据微生物学阴性或少量中等量或大量+革兰染色发现同样微生物Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis o

19、f ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and non-bronchoscopic blind bronchoalveolar lavage fluid. Am Rev Respir Dis 1991;143:1121-1129 肺部感染评分 HAP/VAP: 综合诊断CPIS评分012气管吸取物无无脓性分泌物脓性分泌物CXR浸润影无浸润影弥漫性浸润影局灶性浸润影肺部浸润影进展无进展有进展体温，36.5且38.438.5且38.939或36WCC，109/L4.0且11.011.0

20、11.0 + 杆状核0.5PaO2/FiO2，mmHg240或ARDS240且无ARDS的证据微生物学阴性或少量中等量或大量+革兰染色发现同样微生物Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and non-bronchoscopic blind bronchoalveolar lavage fluid. Am Rev Respir Di

21、s 1991;143:1121-1129 CPIS超过6分即诊断HAP HAP/VAP: 鉴别诊断肿瘤结缔组织疾病血管炎综合征肺泡出血药物诱发肺泡炎肺不张血栓栓塞性疾病胃内容物误吸未治愈社区获得性肺炎充血性心力衰竭HAP/VAP: 概要流行病学诊断策略抗生素治疗预防总结HAP/VAP: 治疗Luna CM, Vujacich P, Niederman MS, et al. Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997; 111: 676-685不充分的抗生

22、素治疗2000名连续收治的MICU/SICU患者655（25.8%）罹患感染169（8.5%）抗生素治疗不充分Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections. A risk factor for hospital mortality among critically ill patients. Chest 1999; 115: 462-474因此，临床高度怀疑VAP时，立即开始正确的经验性抗生素治疗至关重要HAP/VAP: 经验性抗生素无MDR致病菌危险因素、任何严重程度

23、、早发性HAP/VAP的初始抗生素可能致病菌推荐抗生素肺炎链球菌头孢曲松流感嗜血杆菌或MSSA左旋氧氟沙星，莫西沙星或环丙沙星敏感的肠道革兰阴性杆菌或大肠杆菌氨苄青霉素/舒巴坦肺炎克雷伯菌或肠杆菌属厄他培南变形杆菌属粘质沙雷氏菌ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP:

24、 经验性抗生素有MDR致病菌危险因素、任何严重程度、迟发性HAP/VAP的初始抗生素可能致病菌推荐抗生素上表中致病菌及抗假单胞菌头孢菌素（头孢吡肟，头孢他啶）MDR致病菌或铜绿假单胞菌抗假单胞菌碳青霉烯（亚胺培南或美罗培南）肺炎克雷伯菌（ESBL+）或不动杆菌属-内酰胺/-内酰胺酶抑制剂（哌拉西林/他唑巴坦）加抗假单胞菌喹诺酮（环丙沙星或左旋氧氟沙星）或氨基糖甙（阿米卡星，庆大霉素或妥布霉素）加MRSA利奈唑烷或万古霉素嗜肺军团菌ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilato

25、r-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP: 抗生素剂量抗生素剂量抗假单胞菌头孢菌素头孢吡肟12 g，q812 h头孢他啶2 g q8h抗假单胞菌碳青霉烯亚胺培南500 mg q6h，1 g q8h或美罗培南1 g q8h-内酰胺/-内酰胺酶抑制剂哌拉西林/他唑巴坦4.5 q6h氨基糖甙阿米卡星20 mg/kg/d庆大霉素7 mg/kg/d妥布霉素7 mg/kg/d抗假单胞菌喹诺酮左旋氧氟沙星750 mg qd环丙沙星400 mg q

26、8h万古霉素15 mg/kg q12h利奈唑烷600 mg q12hATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP: 治疗ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ven

27、tilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416怀疑HAP/VAP迟发性HAP/VAP或MDR危险因素否是使用窄谱抗生素治疗使用广谱抗生素治疗HAP/VAP: 治疗ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Re

28、spir Crit Care Med 2005; 171: 388-416第2/3天：培养结果并评价临床疗效（体温，WCC，CXR，氧合，脓痰，循环改变及器官功能）除非肺炎的临床概率低且LRT镜检阴性，否则应根据当地细菌流行病资料应用经验性抗生素采取下呼吸道（LRT）进行培养（定量或半定量）和显微镜检怀疑HAP/VAP/HCAPHAP/VAP: 治疗ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated p

29、neumonia. Am J Respir Crit Care Med 2005; 171: 388-4164872小时临床改善寻找其他致病菌，并发症，其他诊断或其他感染灶调整抗生素，寻找其他致病菌，并发症，其他诊断或其他感染灶考虑停用抗生素如可能抗生素降阶梯，治疗78天后再次评估否是培养阴性培养阳性培养阴性培养阳性培养阴性培养阳性培养阴性培养阳性培养阴性培养阳性培养阴性培养阳性培养阴性HAP/VAP: 局部抗生素局部注射氨基糖甙局部用药提高细菌学清除率，但不改变临床预后雾化吸入氨基糖甙或多粘菌素B治疗MDR致病菌副作用耐药率?诱发支气管痉挛Hamer DH. Treatment of nos

30、ocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin. Am J Respir Crit Care Med 2000;162:328-330.Brown RB, Kruse JA, Counts GW, Russell JA, Christou NV, Sands ML, Endotracheal Tobramycin Study Group. Double-blind study of endotracheal

31、 tobramycin in the treatment of gram-negative bacterial pneumonia. Antimicrob Agents Chemother 1990;34:269-272Klick JM, du Moulin GC, Hedley-Whyte J, Teres D, Bushnell LS, Feingold DS. Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence

32、 of pneumonia in seriously ill patients. J Clin Invest 1975;55:514-519HAP/VAP: 联合用药抗生素的协同效应体外试验证实有效中性粒细胞缺乏或血行性感染患者预防耐药发生增加抗菌谱-内酰胺+氨基糖甙-内酰胺+喹诺酮?HAP/VAP: 联合用药美罗培南+环丙沙星（n=369）vs. 美罗培南（n=371）RR 1.05，95%CI 0.781.42MDR革兰阴性杆菌感染（n=56）28天细菌学清除：64.1% vs. 29.4%机械通气时间：10.7（3.3）vs. 15.0（9.3）ICU住院日：14.2（8.1）vs. 2

33、1.2（14.1）ICU病死率：23.1% vs. 29.4%住院病死率：33.3% vs. 41.2%Heyland D, Dodek P, Muscedere J, et al. Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med 2008; 36(3): 737-744HAP/VAP: 联合用药Paul M, Benuri-Silbiger I, Soares-Weis

34、er K, et al. -lactam monotherapy versus -lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 2004; 328: 668总病死率RR 0.9095%CI 0.771.06临床失败率RR 0.8795%CI 0.780.97细菌学失败率RR 0.86 95%CI 0.721.02HAP/VAP: 联合用药Paul M, B

35、enuri-Silbiger I, Soares-Weiser K, et al. -lactam monotherapy versus -lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 2004; 328: 668针对VAP经验性治疗时，应根据当地细菌耐药情况，选择适当的抗生素进行单药治疗HAP/VAP: 问题3呼吸机相关性肺炎的抗生素疗程应为A.8天B.

36、15天C.肺部感染评分 CPIS评分 6D.血清降钙素原 PCT 6CPIS6可疑HAP/VAP3天后重新评估CPISCPIS 6：按照肺炎治疗CPIS 6：停用环丙沙星Singh N, Rogers P, Atwood CW, et al. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. Am J Respir Crit Care Med 2000; 162(2): 505-511HAP/VAP: 抗生素疗程PCT指导抗生素治

37、疗社区获得性下呼吸道感染不良预后相似（15.4%vs.18.9%），抗生素疗程缩短（5.7 dvs.8.7d）AECOPD减少抗生素使用（40%vs.72%）减少6个月内抗生素使用（RR 0.76，95%CI 0.640.92）社区获得性肺炎减少抗生素使用（RR 0.52，95%CI 0.480.58）Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: The ProHOSP randomized controlled trial. JAMA 2009; 302(10): 1059-1066Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerbations of COPD. Chest 2007; 131: 9-19Christ-Crain M, Stolz D, Bingisser R, et