重症医学资质培训呼吸机相关性肺炎

1、HAP/VAP: 概要概要 流行病学流行病学 诊断策略诊断策略 抗生素治疗抗生素治疗 HAP/VAP: 问题问题1 呼吸机相关性肺炎指应用机械通气多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长时间以后发生的肺炎? 1. 24小时小时 2. 48小时小时 3. 72小时小时 4. 96小时小时 5. 48-72小时小时 HAP/VAP/HCAP: 定义定义 医院获得性肺炎医院获得性肺炎(HAP) 住院住院48小时后发生且住院时不处于潜伏期的肺炎小时后发生且住院时不处于潜伏期的肺炎 呼吸机相关性肺炎呼吸机相关性肺炎(VAP) 气管插管气管插管48小时以后发生的肺炎小时以后发生的肺炎 因

2、重度因重度HAP需要气管插管者应按照需要气管插管者应按照VAP处理处理 医疗相关肺炎医疗相关肺炎(HCAP) 发生感染前发生感染前90天内在急性病医院住院天内在急性病医院住院 2天天 在养护院或长期医疗机构住院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天内接受伤口治疗天内接受伤口治疗 就诊于医院门诊或透析门诊就诊于医院门诊或透析门诊 ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated,

3、and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416 发病率发病率 美国医院获得性感染的第二位美国医院获得性感染的第二位 5-15例例/1,000住院病例住院病例 罹患率和病死率升高罹患率和病死率升高 预后预后 住院日延长住院日延长7-9天天 医疗费用增加医疗费用增加$40,000 Kumpf G, et al. J Clin Epidemiol 1998; 54: 495-502 Lizioli A, et al. J Hosp Infect 2003; 54: 141-148 Ri

4、chards MJ, et al. Crit Care Med 1999; 27: 887-892 2%/d 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 patients. Ann Intern Med 1998;129:440 迟发性迟发性HAP 50% 早发性早发性HAP 50% 510

5、d 总病死率总病死率30-70% : 归因病死率归因病死率33-50% H2H2受体拮抗剂进行应激性溃疡预防受体拮抗剂进行应激性溃疡预防 “自由自由”输血输血 去白细胞输血去白细胞输血 血糖控制不佳血糖控制不佳 ARDSARDS 深度镇静或肌松深度镇静或肌松 FagonKollefPapazianRelloTimsitTorres 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 金黄色葡萄球菌20302192620 肺炎链球菌410744 支气管远端标本

6、培养分离出口咽部定植菌（草绿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，色链球菌，凝固酶阴性葡萄球菌，奈瑟氏菌属， 棒状杆菌属）棒状杆菌属） 难以解释难以解释 在免疫抑制甚至免疫正常患者可能引起感染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 Bellacasa JP, Xaubet A, Gonzalez J, Augusti C, Soler N. Bacterial colonization of distal airways in healthy su

7、bjects and cronic lung diseases: a bronchoscopic study. Eur Respir J 1997;10:11371144 金黄色葡萄球菌金黄色葡萄球菌 糖尿病，头颅创伤，住糖尿病，头颅创伤，住ICU 厌氧菌：在厌氧菌：在VAP中的重要性尚不明确中的重要性尚不明确 非插管患者误吸非插管患者误吸 VAP罕见罕见 肺炎军团菌：发生率缺乏数据，但重要性受关注肺炎军团菌：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，免疫抑制患者如器官移植，HIV，糖尿病，基础肺病，糖尿病，基础肺病， 终末期肾病终末期肾病 012345678 Early-ons

8、et HAP Late-onset HAP Time from hospitalization (days) 012345678 Early-onset VAPLate-onset VAP Time 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: 388-41

9、6 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: 388-416 HAP/VAP: 问题问题2 以下哪个不是呼吸机相关性肺炎确切的发病机制以下哪个不是呼吸机相关性肺炎确切的发病机制 1. 误吸误吸 2. 直接吸入直接吸入 3. 血行性播散血行性播散 5. 以上答案均不对以上答案均不对 改变胃排空及胃 液

10、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 感染控制措施不够 (洗手, 隔离衣, 手套) 医务人员不足 经胸种植 原发性菌血症 胃肠道细菌移位 CXR vs. CT 手术后肺实变：敏感性手术后肺实变：敏感性0.33 1.00，特异性，特异性 0.79 不同医生判读的一致性不同医生判读的一致性 放射科医生：放射科医生：kappa 0.27 ICU医生：医生：12 39% Wunderink RG, Woldenberg LS, Zeiss J, et a

11、l. The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia. 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,

12、et al. Can portable chest x-ray examination accurately diagnose lung consolidation after major abdominal surgery?: a comparison with computed tomography scan. Chest 1992; 102: 1698-703. 胸片新出现浸润影或原有浸润性加重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：以下临床表现中两条： T 38C 白细胞增多或白细胞缺乏白细胞增多或白细胞缺乏 脓性气道分泌物脓性气道分泌物 敏感性敏感性69%，特异性特异性

13、75% The Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630 高度可疑VAP = 临床诊断 + BALF 104 cfu/ml; 可能VAP = 临床诊断 The Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for vent

14、ilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630 The Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630 Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the mana

15、gement of candidiasis: 2009 update by the Infectious Diseases Society of America. 2009; 48: 503-535 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 lava

16、ge fluid. Am Rev Respir Dis 1991;143:1121-1129 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 Dis 1991;143:1121-1129 肺不张肺不张

17、 血栓栓塞性疾病血栓栓塞性疾病 胃内容物误吸胃内容物误吸 未治愈社区获得性未治愈社区获得性 肺炎肺炎 充血性心力衰竭充血性心力衰竭 HAP/VAP: 治疗治疗 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 2000名连续收治的名连续收治的MICU/SICU患者患者 655 (25.8%)罹患感染罹患感染 169 (8.5%)抗生素治疗不充分抗生素

18、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 HAP/VAP: 经验性抗生素经验性抗生素 ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associa

19、ted, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416 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: 388-416 ATS/IDSA. Guidelines for the manag

20、ement of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416 ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care

21、 Med 2005; 171: 388-416 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: 388-416 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 培养阴性 培养阳性 Hamer DH. Treatment of nosocomial pneumonia and tracheo

22、bronchitis 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 tobramycin in the treatment

23、 of gram-negative bacterial pneumonia. Antimicrob Agents Chemother 1990;34:269-272 Klick 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 of pneumonia in seriously

24、ill patients. J Clin Invest 1975;55:514-519 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): 737-744 Paul M, Benuri-Silbiger I, Soares-Weiser K, et al. -lactam

25、 monotherapy versus -lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 2004; 328: 668 Paul M, Benuri-Silbiger I, Soares-Weiser K, et al. -lactam monotherapy versus -lactam-aminoglycoside combination therapy

26、 for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 2004; 328: 668 HAP/VAP: 问题问题3 Probability of Survival 0102030405060 Days after Bronchoscopy 0.0 0.2 0.4 0.6 0.8 1.0 15-day 8-day Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of a

27、ntibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290(19): 2588-2598 结果：结果： 8天与天与15天抗生素疗程相比天抗生素疗程相比: 病死率、住院日和机械通气时间无显著差别病死率、住院日和机械通气时间无显著差别 减少了抗生素使用减少了抗生素使用 避免了细菌耐药的发生避免了细菌耐药的发生 PCT指导抗生素治疗指导抗生素治疗 社区获得性下呼吸道感染社区获得性下呼吸道感染 不良预后相似不良预后相似(15.4% vs. 18,9%)，抗生素疗程

28、缩短抗生素疗程缩短(5.7 d vs. 8.7 d) AECOPD 减少抗生素使用减少抗生素使用(40% vs. 72%)， 减少减少6个月内抗生素使用个月内抗生素使用(RR 0.76; 95%CI 0.64 0.92) 社区获得性肺炎社区获得性肺炎 减少抗生素使用减少抗生素使用(RR 0.52, 95%CI 0.48 0.58) Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in low

29、er respiratory tract infections: The ProHOSP randomized controlled trial. JAMA 2009; 302(10): 1059-1066 Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerbations of COPD. Chest 2007; 131: 9-19 Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic

30、therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2006; 174: 84-93 PCT 0.25 g/ml 推荐应用抗生素推荐应用抗生素 PCT 0.5 g/ml 强烈推荐应用抗生素强烈推荐应用抗生素 Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower

31、 respiratory tract infections: The ProHOSP randomized controlled trial. JAMA 2009; 302(10): 1059-1066 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: 388-416 床头抬高至少床头抬高至少30 经口气

32、管插管经口气管插管 经口留置胃管经口留置胃管 监测胃残余量并防止腹胀监测胃残余量并防止腹胀 减少抗生素的使用减少抗生素的使用 尽早开始适当的营养支持尽早开始适当的营养支持 严格控制血糖严格控制血糖 使用无创通气避免插管使用无创通气避免插管 缩短插管时间缩短插管时间 保持套囊压力保持套囊压力20 mmHg 间断吸引声门下分泌物间断吸引声门下分泌物 口腔护理减少耐药菌定植口腔护理减少耐药菌定植 避免深度镇静或肌松避免深度镇静或肌松 每日唤醒减少镇静药剂量每日唤醒减少镇静药剂量 支气管远端标本培养分离出口咽部定植菌（草绿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

33、菌属，色链球菌，凝固酶阴性葡萄球菌，奈瑟氏菌属， 棒状杆菌属）棒状杆菌属） 难以解释难以解释 在免疫抑制甚至免疫正常患者可能引起感染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 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

34、. Eur Respir J 1997;10:11371144 CXR vs. CT 手术后肺实变：敏感性手术后肺实变：敏感性0.33 1.00，特异性，特异性 0.79 不同医生判读的一致性不同医生判读的一致性 放射科医生：放射科医生：kappa 0.27 ICU医生：医生：12 39% Wunderink RG, Woldenberg LS, Zeiss J, et al. The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia. 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 examinat