2012全身性感染与感染性休克

全身性感染与感染性休克 What is New? 严重全身性感染与感染性休克 非特异性损伤引 起的临床反应 , 满足 2条标准 : T 38C or 90 bpm RR 20 bpm WCC 12,000/mm3 or 10%杆状核 SIRS = systemic inflammatory response syndrome SIRS及可疑或 明确的感染 Chest 1992;101:1644. 全身性感染 伴器官衰竭 顽固性低血压 SIRS Sepsis Severe Sepsis Septic Shock 全身性感染 (sepsis): 流行病学 Martin GS, Mannino DM, Stephanie Eaton S, et al. The Epidemiology of Sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348: 1546-54. 全身性感染发病率的推算 平均每年增加 1.5%; 相当于年增新发病例约 22,875例 Angus DC, et al. The epidemiology of severe sepsis in the United States: Analysis of incidence, outcome and associated costs of care. 全身性感染临床试验对照组的病死率 全身性感染的医疗费用 2000年 ICU医疗费用的 40% 欧洲每年花费 7,600,000,0001 美国每年花费 $16,700,000,0002 1. Davies A et al. Abstract 581. 14th Annual Congress of the European Society of Intensive Care Medicine, Geneva, Switzerland, 30 September-3 October 2001 2. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29:13031310 Surviving Sepsis Campaign: Why? 过去 5年间阳性结果的干预措施 n 严重全身性感染与感染性休克 u EGDT u 激素 u APC u 小潮气量通气策略 n 危重病患者的一般治疗 u 镇静 u 严格血糖控制 u 脱机方案 Surviving Sepsis Campaign (SSC) Guidelines for Management of Severe Sepsis and Septic Shock Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM and the SSC Management Guidelines Committee Crit Care Med 2004; 32: 858-873 Intensive Care Med 2004; 30: 536-555 available online at The guidelines were published in both Critical Care Medicine and in Intensive care Medicine, and are available on-line Surviving Sepsis Campaign Guideline 最初复苏 (initial resuscitation) 诊断 (diagnosis) 抗生素治疗 (antibiotic therapy) 感染源控制 (source control) 液体治疗 (fluid therapy) 升压药物 (vasopressors) 强心药物 (inotropic therapy) 激素 (steroids) 活化蛋白 C (recombinant human activated protein C) 血液制品 (blood product administration) ARDS机械通气 (mechanical ventilation of sepsis-induced ALI/ARDS) 镇静 (sedation, analgesia, and NMB in sepsis) 血糖控制 (glucose control) 肾脏替代 (renal replacement) 碳酸氢钠 (bicarbonate therapy) DVT预防 (DVT prophylaxis) 应激性溃疡预防 (stress ulcer prophylaxis) 考虑限制支持治疗水平 (consideration for limitation of support) Surviving Sepsis Campaign Guideline 最初复苏 (initial resuscitation) 诊断 (diagnosis) 抗生素治疗 (antibiotic therapy) 感染源控制 (source control) 液体治疗 (fluid therapy) 升压药物 (vasopressors) 强心药物 (inotropic therapy) 激素 (steroids) 活化蛋白 C (recombinant human activated protein C) 血液制品 (blood product administration) ARDS机械通气 (mechanical ventilation of sepsis-induced ALI/ARDS) 镇静 (sedation, analgesia, and NMB in sepsis) 血糖控制 (glucose control) 肾脏替代 (renal replacement) 碳酸氢钠 (bicarbonate therapy) DVT预防 (DVT prophylaxis) 应激性溃疡预防 (stress ulcer prophylaxis) 考虑限制支持治疗水平 (consideration for limitation of support) 严重全身性感染与感染性休克的治疗 SIRS Sepsis Severe Sepsis Septic Shock 血糖控制非常重要 : 最初病情稳定后 静脉输注胰岛素 1B 目标范围 ? 血糖 215 mg/dL 110 mg/dL 胰 岛 素治 疗维 持葡萄 糖水平 180 200 mg/dL (10.0 11.1 mmol/L) 80 110 mg/dL (4.4 6.1 mmol/L) 39%应 用胰 岛 素 99%应 用胰 岛 素 Van Den Berghe G, Wouters P, Weekers F, et al.: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001, 345:1359-1367 外科患者的强化胰岛素治疗 至 随访第 12个月 , 强化 胰岛素治疗可以降低 病死率 3.4% (p 24小时 n ISS 20 n 血流动力学稳定 u SBP 100 u HR 1 mL/kg/h n 乳酸 2.5 mmol/L或其他灌注不足表现 Blow O, Magliore L, Claridge J, Butler K, Young J. The Golden Hour and the Silver Day: Detection and Correction of Occult Hypoperfusion within 24 Hours Improves Outcome from Major Trauma. J Trauma 1999; 47(5): 964 隐性低灌注与创伤预后 Blow O, Magliore L, Claridge J, Butler K, Young J. The Golden Hour and the Silver Day: Detection and Correction of Occult Hypoperfusion within 24 Hours Improves Outcome from Major Trauma. J Trauma 1999; 47(5): 964 严重创伤患者两次 LA 2.5 输注液体或血液制品 重复 LA 2.5 Swan-Ganz, 动脉插管 , 肾脏剂量多巴胺 将 PCWP提高到 12 15 将 Hct提高到 30% 重复 LA 2.5 升压药物 (多巴酚丁胺 ) 心脏超声检查 若 LA仍 2.5 隐性低灌注与创伤预后 Blow O, Magliore L, Claridge J, Butler K, Young J. The Golden Hour and the Silver Day: Detection and Correction of Occult Hypoperfusion within 24 Hours Improves Outcome from Major Trauma. J Trauma 1999; 47(5): 964 全身性感染的诊断 适当的培养 至少留取 2个血培养 n 1个外周血培养 n 每个留置 48 h的血管通路留取 1个血 培养 (Grade D) 抗生素治疗前后血培养的阳性率 139名患者 抗生素治疗前 抗生素治疗过程中 开始抗生素治疗 83名患者 (60%)血培养阴性或 分离出污染菌 0/83 (0%)分离到致病菌 56名患者 (40%)分离到致病菌 26/56 (45%)分离到致病菌 25名患者 (45%)分离到致 病的葡萄球菌 19/25 (76%)分离到葡萄球菌 14名患者 (25%)分离到致 病的链球菌 5/14 (36%)分离到链球菌 17名患者 (30%)分离到革 兰阴性杆菌 2/17 (12%)分离到革兰阴性杆菌 1/139 (0.72%)分离到新的致病菌 Grace CJ, Lieberman J, Pierce K, et al. Usefulness of Blood Culture for Hospitalized Patients Who Are Receiving Antibiotic Therapy. Clin Infect Dis 2001; 32: 1651-5 临床意义 应用抗生素前进行血培养分离到致病菌 的可能性增加 2.2倍 在开始抗生素治疗最初 72小时内 , 连续 进行血培养的结果 , 可以根据应用抗生 素前血培养的结果预测 极少分离到新的致病菌 医生可以等待应用抗生素前的血培养结 果回报后 , 再进行新的血培养 Grace CJ, Lieberman J, Pierce K, et al. Usefulness of Blood Culture for Hospitalized Patients Who Are Receiving Antibiotic Therapy. Clin Infect Dis 2001; 32: 1651-5 严重全身性感染与感染性休克的治疗 SIRS Sepsis Severe Sepsis Septic Shock 抗生素治疗与感染灶控制 确诊严重全身性感染后 1小时内 开始静脉抗生素治疗 1C 强化胰岛素治疗严格控制血糖 早期应用抗生素与感染患者病死率 Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34: 1589-1596 严重全身性感染与感染性休克的治疗 SIRS Sepsis Severe Sepsis Septic Shock 抗生素治疗与感染灶控制 早期目标指导治疗 持续低血压或乳酸 4 mmol/L 最初 6小时内达到的目标 CVP 8 12 mmHg MAP 65 mmHg UO 0.5 ml/kg/hr ScvO2 70% 1B 强化胰岛素治疗严格控制血糖 全身性感染 : 早期目标指导治疗 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377 全身性感染 : 早期目标指导治疗 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377 EGDT组患者输液更多 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377 EGDT组输血及应用多巴酚丁胺更多 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377 EGDT与 感染性休克的预后 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377 心血管猝死 21% vs. 10% P = 0.02 MODS 22% vs. 16% P = 0.27 严重全身性感染与感染性休克的治疗 SIRS Sepsis Severe Sepsis Septic Shock 抗生素治疗与感染灶控制 早期目标指导治疗 死亡高危 : APACHE II 25 感染诱发的 MOF 感染性休克 感染诱发的 ARDS 无绝对禁忌症 权衡相对禁忌症 B 活化蛋白 C治疗 强化胰岛素治疗严格控制血糖 全身性感染 : 活化蛋白 C Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699-709. 安慰剂 (n = 840) 活化蛋白 C (n = 850) 绝对病死率 下降 6.1% 主要分析 结 果 双尾 P值 0.005 校正后的相 对 危 险 度降低 19.4% 存活比数增加 38.1% 严重全身性感染与感染性休克的治疗 SIRS Sepsis Severe Sepsis Septic Shock 抗生素治疗与感染灶控制 早期目标指导治疗 应用氢化可的松 200 300 mg/d, 分为 3 4次给药或持续静脉输注 , 疗程 7天 经过液体复苏和升压药物治疗低血 压持续 1小时 1B 充分液体复苏后仍需升压药物至少 1 小时 2C 活化蛋白 C治疗 激素替代治疗 强化胰岛素治疗严格控制血糖 感染性休克的激素替代治疗 Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: 862-71. ACTH test 8 hours SEPTIC SHOCK placebo HC 50 mg/6 hours + FC 50 mcg/day p.o. N = 150 N = 149 28-day mortality7 days 感染性休克的激素替代治疗 Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: 862-71. P = 0.04 P = 0.96 严重全身性感染 循证医学指南 干 预 措施 NNT 小 潮气量通气策略 11 早期目 标 指 导 治 疗 6 8 活化蛋白 C 16 (whole trial) 8 (APACHE II 25) 强 化胰 岛 素治 疗 29 ACTH刺激 试验 无反 应 者小 剂 量激素治 疗 7 Sepsis Resuscitation Bundle (应在最初 6小时内达到 ) 测定血清乳酸水平 应用抗生素前留取血培养 入 急诊室 3小时或入 ICU1小时内应用抗生素 低 血压和 (或 )乳酸 4 mmol/L (36 mg/dl)时 : 最初应用晶体液至少 20 ml/kg(或 等量的胶体液 ) 最初液体复苏无效时应用升压药物以维持 MAP 65 mmHg 经过液体复苏后仍持续低血压 (感染性休克 )和 (或 )乳 酸 4 mmol/L (36 mg/dl): 使 CVP 8 mmHg 使 ScvO2 70% Sepsis Management Bundle (应在最初 24小时内达到 ) 对感染性休克患者根据 ICU标准化规定 应用小剂量激素 根据 ICU标准化规定应用活化蛋白 C 控制血糖水平 正常值下限 , 且 150 mg/dl (8.3 mmol/L) 维持机械通气患者吸气平台压力 30 cmH2O Surviving Sepsis Campaign Initial Results Reporting the Gap between Perception and Practice What We Think We Do vs. What We Actually Do ARDS保护性通气策略 ARDSnet The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301-1308 P = 0.007 研究结果的发表对日常工作并无影响 Rubenfeld GD, et al. Am J Respir Crit Care Med 2001; 163: A295 P = 0.11 P = 0.02 Adhere to “Best Practice”? Do you use lung protective strategy in ventilating acute lung injury patients? Brunkhorst FM, et al, for the German Competence Network Sepsis SepNet. The gap between perception and practice of sepsis therapy. (submitted) Adhere to “Best Practice”? Results of Non-Scripted Care Processes Brunkhorst FM, et al, for the German Competence Network Sepsis SepNet. The gap between perception and practice of sepsis therapy. (submitted) Supportive and Adjunctive Therapies Results of the German “Prevalence” Study Brunkhorst FM, et al, for the German Competence Network Sepsis SepNet. The gap between perception and practice of sepsis therapy. (submitted) 为何循证治疗在 ICU中应用并不普遍 缺乏相关知识 n 医疗费用报销的限制 , 繁忙的工作安排 ICU医生的怀疑 n 危重病领域众多的阴性试验结果 对证据的主观选择 临床惰性 不能正确鉴别患者 医疗资源的配置 VHA 19-ICU Sepsis Bundles 69% Reduction (p 0.001) 36% Reduction (NS) Pronovost P, 2005 EGDT in ED Mean SD Median Range Central line inserted 2.1 1.7 1.5 1 8 CVP goal achieved 6.3 3.8 6.0 1 14 MAP goal achieved 5.6 3.2 4.0 2 13 ScvO2 measured 2.4 1.8 2.0 1 8 ScvO2 goal achieved 6.4 4.0 5.0 2 16 Trzeciak S, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, Zanotti S, Parrillo JE. Translating Research to Clinical Practice: A 1- Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department. Chest 2006; 129: 225-232 EGDT in ED Before EGDT EGDT P value 输 注晶体液 ED 3509 2312 5685 3021 0.02 ICU第一个 24小 时 5548 4878 2752 1731 0.03 PAC应 用 7 (43.8) 2 (9.1) 0.01 ICU住院日 (d) 4.2 (0.5 14.3) 1.8 (0.0 34.9) 0.12 住院病死率 7 (43.8) 4 (18.2) 0.09 住院 费 用 (USD) 135,199 82,233 0.14 Trzeciak S, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, Zanotti S, Parrillo JE. Translating Research to Clinical Practice: A 1- Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department. Chest 2006; 129: 225-232 Sepsis Bundle 101名 严重全身性感染患者符合 6小时 Bundle 普通病房 : 90 (89%) 急诊科 : 11 (11%) 71名 收入 ICU 符合 24小时 Bundle: 69 (98%) 43 (61%)转出 ICU 28 (39%)死于 ICU 35 (81%)存活 8 (19%)死亡 65 (64%)存活 36 (36%)死亡 Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Critical Care 2005, 9:R764-R770 (DOI 10.1186/cc3909) Sepsis Bundle 符合 6小时 Bundle (n = 101) 符合 24小时 Bundle (n = 69) 52% (52/101) 30% (21/69) 依从率 Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Critical Care 2005, 9:R764-R770 (DOI 10.1186/cc3909) Sepsis Bundle (6 hour) RR 2.12 (1.20 3.76) P = 0.01 NNT = 3.9 Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-hour and 24-hour sepsi