1、2008感染性休克指南解读,南京市第二医院 史东阳,概念,感染性休克(septic shock)，亦称脓毒性休克，是指由微生物及其毒素等产物所引起的脓毒性综合征（sepsis syndrome）伴休克。感染灶中的微生物及其毒素、胞壁产物等侵入血循环，激活宿主的各种细胞和体液系统；产生细胞因子和内源性介质，作用于机体各种器官、系统，影响其灌注，导致组织细胞缺血缺氧、代谢紊乱、功能障碍，甚至多器官功能衰竭。,概念,因此感染性休克是微生物因子和机体防御机制相互作用的结果，微生物的毒力数量以及机体的内环境与应答是决定感染性休克的发展的重要因素。,2004年，代表11个国际组织的诊断和治疗感染的国际专家
2、小组发布了能够帮助临床医师改善严重脓毒症和脓毒性休克治疗效果及预后的国际指南引起了全球医师的高度重视，经过2年多的临床实践，20062007年，上述专家又重新聚集，应用新的循症医学的方法，总结脓毒症临床研究的新成果，评价证据的质量和确定推荐的强度，对2004年指南进行修订和增补，并于2008年发表 。,2008年严重脓毒症和脓毒性休克治疗指南是以2001年的第一版和2004年的第二版脓毒症治疗指南为基础形成的。,2008年指南的修订采用改良的Delphi方法，采用推荐、判断、开发、评估的分级系统(GRADE)作为证据质量评判的依据，从高到低分为 AD四个级别来决定推荐力度。重点推荐“1”是指干
3、预措施的预期效果明显大于副作用(风险、负担、费用) 或没有副作用。一般推荐“2”是指干预措施的预期效果和不良作用的分解不甚明确。重点或一般推荐的确定更注重临床重要性，而不是证据质量的水平。在没有取得一致性意见的临床问题，应用正式规范的过程产生决议。推荐强度和证据质量用GRADE标准评价，附在每一条推荐后的括号内。,要点,Early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); 确诊脓毒血症的最初6小时尽快有目标性的复苏治疗 blood cultur
4、es prior to antibiotic therapy (1C); 留取血培养先于抗生素治疗 imaging studies performed promptly to confirm potential source of infection(1C); 影像学检验常规进行以确定感染的潜在病灶,administration of broad spectrum antibiotic therapy within1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D) 感染性休克和严重
5、脓毒血症而无休克的诊断后1小时内实用广谱抗生素 reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate(1C); 选择合适的时机根据微生物和临床资料重新评估抗生素疗法以缩小抗菌谱 a usual 710 days of antibiotic therapy guided by clinical response (1D) 根据临床反应使用常规7-10天抗生素疗法,source control with attention to the
6、balance of risks and benefits of the chosen method (1C) 选取针对病灶的处理方法时需注意风险和收益的平衡 administration of either crystalloid or colloid fluid resuscitation (1B) 使用晶体或胶体液进行复苏 fluid challenge to restore mean circulating filling pressure (1C) 液体冲击以回复平均循环充盈压 reduction in rate of fluid administration with rising
7、 filing pressures and no improvement in tissue perfusion (1D) 当充盈压提升而组织灌注没有提高时减少液体输注,vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure 65mm Hg(1C) 升压药物优选去甲肾上腺素或多巴胺以使平均动脉压 65mm Hgdobutamine inotropic therapy when cardiac output remains low d
8、espite fluid resuscitation and combined inotropic/vasopressor therapy(1C) 当液体复苏后心脏持续低输出时使用多巴酚丁胺收缩心脏治疗，联合实用血管加压素 stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C) 类固醇激素治疗仅用于感染性休克患者证实其血压对液体和血管加压素反应差时,
9、recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B) 对于严重脓毒血症患者和临床评估高死亡风险者使用重组活性蛋白CIn the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 79 g/dL (1B) 在没有组织灌注不足、冠心病或是急性出血的患者，血红蛋白目标为79
10、g/dL a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy(1C) for acute lung injury (ALI)/acute respiratory distress syndrome(ARDS) ALI 和ARDS患者使用低潮气量和限制吸气平台压,application of at least a minimal amount of positive endexpiratory pressure in acute lung injury (1C) ALI使用至少小量呼气末正
11、压 head of bed elevation in mechanically ventilated patients unless contraindicated (1B) 除非禁忌，机械通气患者的床头可以抬高 avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A) ALI/ARDS避免常规使用肺动脉导管 to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for pati
12、ents with established ALI/ARDS who are not in shock (1C) 为了减少呼吸机使用天数和ICU住院天数，对于确诊ALI/ARDS而没有休克的患者，要采用保守的补液目标,using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B) 使用间歇镇静或者持续静脉镇静，每日减量并且唤醒 avoidance of neuromuscular blockers,if at all poss
13、ible (1B) 尽量避免使用神经肌肉接头阻滞剂institution of glycemic control (1B) 血糖控制 targeting a blood glucose 150 mg/dL after initial stabilization ( 2C ) 在初期情况稳定后血糖控制目标为 150 mg/dL（8.3mmol/L）,equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis(2B) 持续静脉-静脉血滤和间断血透的效果是相当的 prophylaxis for dee
14、p vein thrombosis (1A) 预防深静脉血栓 use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B) 应激性溃疡者者使用H2受体阻滞剂或质子泵抑制剂防止消化道出血,Begin resuscitation immediately in patients with hypotension or elevated serum lactate 4mmol/L; do not delay pending ICU ad
15、mission (1C) 对低血压或血乳酸升高4mmolL的脓毒症患者应立即复苏，而不是延迟至ICU收住后才进行(1C),Resuscitation goals (1C) CVP 812 mmHg Mean arterial pressure65mmHg Urine output 0.5mL/(kgh) Central venous (superior vena cava) oxygen saturation 70% or mixed venous65%复苏目标：中心静脉压( CVP )812 mmHg ； 平均动脉压65mmHg； 尿量05mL/(kgh)； 中心静脉( 或上腔静脉) 氧饱和
16、度70，或混合静脉氧饱和度65。,If venous oxygen saturation target is notachieved (2C)：Consider further uid Transfuse packed red blood cells ifrequired to hematocrit of 30%and/or start dobutamine infusion, maximum 20g/（kgmin）如果静脉血氧饱和度未达到上述目标，则继续补液；必要时输注压积红细胞使血细胞比容30；和(或)给予多巴胺静脉输注，最大剂量为20g/（kgmin）,Diagnosis,Obtain
17、appropriate cultures before starting antibioticsprovided this doenst signicantly delay antimicrobial administration (1C).Obtain two or more BCs.One or more BCs should be percutaneous.One BC from each vascular access device in place 48 hrs.Culture other sites as clinically indicated.Perform imaging s
18、tudies promptly to conrm and sample any source of infection, if safe to do so (1C).,诊断,在不耽搁抗生素应用的前提下，应用抗生素前进行微生物培养.至少要做2次血培养.至少有1次血培养经皮肤取标本. 48h的静脉输液导管部位取 1次血培养. 临床提示可能存在感染的其他部位培养. 在确保患者安全的情况下，为了查找感染源或方便在感染部位取标本应及时行影像学检查.,Antibiotic therapyBegin intravenous antibiotics as early as possible and alway
19、s within the rst hour of recognizing severe sepsis (1D) and septic shock (1B).Broad-spectrum: one or more agents active against likely bacterial/fungal pathogens and with good penetration into presumed source (1B).Reassess antimicrobial regimen daily to optimize efcacy, prevent resistance, avoid tox
20、icity,and minimize costs. (1C)Consider combination therapy in Pseudomonas infections .(2D)Consider combination empiric therapy in neutropenic patients (2D).Combination therapy35 days and deescalation following susceptibilities (2D).,在诊断严重脓毒症(1D)和脓毒症休克(1B)的1h以内，尽早开始静脉应用抗生素。 抗菌谱广：选择一种或多种对可能的细菌真菌有效且能够渗
21、透到感染部位的抗生素。(1B ) 每天再次评估抗生素治疗效果，以达到理想的抗菌效果，防止耐药，减少毒性反应和降低费用。(1C) 对假单胞菌属的感染考虑联合用药。(2D) 中性粒细胞减少的患者经验性选择联合用药。( 2 D) 联合治疗不超过35d，然后根据细菌敏感情况降阶梯使用抗生素。(2D),Duration of therapy typically limited to 710 days; longer if response is slow or there areundrainable foci of infection or immunologic deciencies (1D)Sto
22、p antimicrobial therapy if cause is found to be noninfectious (1D),抗生素使用时间一般为710d，如临床效果不佳、 感染灶未清除或免疫缺陷患者可适当延长。(1D) 如确定是非感染性病因， 应停止使用抗生素。(1D),A specic anatomic site of infection should be established as rapidly as possible (1C) and within rst 6 hrs of presentation (1D) Formally evaluate patient for a
23、 focus of infection amenable to source control measures (e.g.abscess drainage, tissue debridement) (1C) Implement source control measures as soon as possible following successful initial resuscitation (1C) (exception: infected pancreatic necrosis, where surgical intervention is best delayed) (2B)Cho
24、ose source control measure with maximum efcacy and minimal physiologic upset (1D)Remove intravascular access devices if potentially infected (1C),尽早确定特异性的感染解剖部位(1C)；在就诊6h之内明确感染部位。(1D) 进行临床评价，寻找感染部位，控制感染源(如脓肿或局部感染灶的引流，感染坏死组织的清除)。(1C) 成功的初期复苏后，尽早采取控制感染源措施。 (1C)除感染引起的坏死性胰腺炎，这类患者应延迟手术。(2 B) 选择最大临床效果和最小生
25、理紊乱的手段来控制感染源。(1D) 如发现介入性血管内器械是潜在的感染源，去除这些器械。(1C),Fluid therapy,Fluid-resuscitate using crystalloids or colloids (1B) Target a CVP of 8mmHg(12 mmHg if mechanically ventilated).(1C) Use a fluid challenge technique while associated with a hemodynamic improvement (1D) Give uid challenges of 1000 mL of c
26、rystalloids or 300500 mL of colloids over 30 mins. More rapid and larger volumes may be required in sepsis-induced tissue hypoperfusion (1D) Rate of uid administration should be reduced if cardiac lling pressures increase without concurrent hemodynamic improvement (1D),液体复苏,用晶体液或胶体液进行液体复苏 。(1B) 使中心静
27、脉压8 mmHg ( 在机械通气时12 mmHg )。(1C) 应用补液试验，改善血流动力学状态。(1B) 选用1000mL晶体液或300500mL胶体液，补液不少于30min，对脓毒症导致的低灌注情况需要更快和更大量的补液。(1D) 如果心室充盈压升高，而同时血流动力学状况未改善，应减缓补液速度。(1D),Vasopressors,Maintain MAP 65 mm Hg (1C) Norepinephrine and dopamine centrally administered are the initial vasopressors of choice (1C) Epinephrin
28、e, phenylephrine, or vasopressin should not be administered as the initial vasopressor in septic shock (2C). Vasopressin 0.03 units/min may be subsequently added to norepinephrine with anticipation of an effect equivalent to norepinephrine alone Use epinephrine as the rst alternative agent in septic
29、 shock when blood pressure is poorly responsive to norepinephrine or dopamine (2B). Do not use low-dose dopamine for renal protection (1A) In patients requiring vasopressors, insert an arterial catheter as soon as practical (1D),维持平均动脉压65 mmHg。(1C) 中心静脉给予去甲肾上腺素和多巴胺是首选升压药。(1C) 在脓毒症休克中，肾上腺素、去氧肾上腺素或升压素
30、不应作为首选药物(2C)，去甲肾上腺素加用0.03U/mi n升压素与单独使用去甲肾上腺素效果相似。 对于脓毒性休克，当去甲肾上腺素和多巴胺不能升高血压时，选择肾上腺素。(2B) 不使用小剂量多巴胺保护肾功能。( 1A) 对需要升压药患者而言， 情况允许时应置入动脉导管。(1D),Inotropic therapy,Use dobutamine in patients with myocardial dysfunction as supported by elevated cardiac lling pressures and low cardiac output (1C) 对心功能障碍患者使
31、用多巴胺，可提高心脏充盈压和降低心脏输出。(1C) Do not increase cardiac index to predetermined supranormal levels (1B) 不推荐应用药物把心脏指数增加到高于正常值的预设水平。(1B),Steroids,Consider intravenous hydrocortisone for adult septic shock when hypotension responds to adequate uid resuscitation and vasopressors (2C) ACTH stimulation test is n
32、ot recommended to identify the subset of adults with septic shock who should receive hydrocortisone (2B) Hydrocortisone is preferred to dexamethasone (2B) Steroid therapy may be weaned once vasopressors are no longer required (2D) Fludrocortisone (50g orally once a day) may be included if an alterna
33、tive to hydrocortis is being used that lacks signicant mineralocorticoid activity. Fludrocortisone if optional hydrocortisone is used (2C) Hydrocortisone dose should be 300 mg/day (1A) Do not use corticosteroids to treat sepsis in the absence of shock unless the patients endocrine or corticosteroid
34、history warrants it (1D),对于成人脓毒性休克，当充分补液和升压药应用后血压仍不稳定，考虑静脉给予氢化可的松。(2C) 不推荐使用ATCH刺激试验筛选成人脓毒症休克中应接受氢化可的松治疗的患者亚组。(2B) 氢化可的松优于地塞米松。(2B) 当不需要应用血管升压药物时，应停用类固醇药物治疗。(2D) 如果使用氢化可的松缺乏显著的盐皮质激素活性，可应加用氟氢可的松50g，1次d口服。在应用氢化可的松的情况下，是否加用氟氢可的松可自行选择。( 2 C) 氢化可的松剂量应300mgd 。(1C) 除非患者有内分泌疾病或皮质类固醇缺乏病史，不使用皮质类固醇治疗没有休克的脓毒症。(
35、1D),Recombinant human activated protein C,Consider rhAPC in adult patients with sepsis-induced organ dysfunction with clinical assessment of high risk of death (typically APACHE II 25 or multiple organ failure) if there are no contraindications (2B, 2C for postoperative patients). Adult patients wit
36、h severe sepsis and low risk of death (typically, APACHE II 20 or one organ failure) should not receive rhAPC (1A),如无其他禁忌，对脓毒症致器官功能障碍伴临床评估具有高死亡风险的成人患者使用rh APC(一般APACHEII评分2 5分或多器官功能衰竭)(2B)，对术后脓毒症患者。(2C) 有严重脓毒症而低死亡风险(一般APACHE评分20分或单个器官功能衰竭) 的患者不应用rhAPC治疗。( 1 A),Blood product administration,Give red b
37、lood cells when hemoglobin decreases to7.0 g/dL (70 g/L) to target a hemoglobin of 7.09.0 g/dL in adults (1B). A higher hemoglobin level may be required in special circumstances (e.g., myocardial ischaemia, severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis) Do not use er
38、ythropoietin to treat sepsis-related anemia. Erythropoietin may be used for other accepted reasons (1B) Do not use fresh frozen plasma to correct laboratory clotting abnormalities unless there is bleeding or planned invasive procedures (2D),当血红蛋白7.0g/dl (70g/L )时，应输注红细胞使血红蛋白达7.09.0 g/dl。(1B) 在特殊情况下(
39、如心肌缺血、严重缺氧、急性出血、紫绀性心脏病或乳酸酸中毒)需要达到更高的血色素水平。 不使用促红细胞生成素治疗脓毒症相关性贫血，促红细胞生成素可应用于其他原因的贫血。(1B) 除非有出血或计划行侵入性操作，不用新鲜冰冻血浆纠正凝血异常。(2D),Do not use antithrombin therapy (1B) Administer platelets when (2D)Counts are50109 /L are required for surgery or invasive procedures.,不使用溶栓治疗。(1B) 输注血小板：(2D) 当血小板计数5109/L时，不管有无
40、出血；当血小板计数5109/L-30109/L ，有明显的出血风险时；当行外科手术和侵入性操作时， 需要使血小板总计数50000mm3(50109L ) 。,Mechanical ventilation of sepsis-induced ALI/ARDS,Target a tidal volume of 6 mL/kg (predicted) body weight in patients with ALI/ARDS (1B) Target an initial upper limit plateau pressure30cmH2O. Consider chest wall complian
41、ce when assessing plateau pressure (1C) Allow PaCO2 to increase above normal, if needed, to minimize plateau pressures and tidal volumes.(1C) Set PEEP to avoid extensive lung collapse at end-expiration.(1C),ALI/ARDS患者应设定6 mL/kg的潮气量(1B) 设定初始平台压上限30cmH2O，评估气道压力时应考虑胸壁顺应性因素。(1C) 允许PaCO2高于正常水平，如需要，可减少平台压
42、和潮气量。(1C) 设置PEEP防止呼气末肺泡塌陷。(1C),Consider using the prone position for ARDS patients requiring potentially injurious levels of FIO2 or plateau pressure, provided they are not put at risk from positional changes (2C) Maintain mechanically ventilated patients in a semirecumbent position (head of the bed
43、 raised to 45) unless contraindicated (1B), between 30and 45 (2C) Noninvasive ventilation may be considered in the minority of ALI/ARDS patients with mild to moderate hypoxemic respiratory failure. The patients need to be hemodynamically stable, comfortable, easily arousable, able to protect/clear t
44、heir airway, and expected to recover rapidly (2B),对需要保持可能对机体造成潜在损伤水平较高 FiO2 或气道高压的 ARDS患者，只要不存在体位改变的风险，应考虑使用侧卧体位。(2C) 除非禁忌，机械通气患者应取半卧位，床头抬高45(1B)；3045(2C) 无创性机械通气仅在少数轻中度低氧血症呼吸衰竭患者中使用，这些患者需要满足下列条件：血流动力学稳定、舒适、易唤醒、能主动保护/清洁气道，并有希望快速康复。(2B),Do not use a pulmonary artery catheter for the routine monitorin
45、g of patients with ALI/ARDS (1A) Use a conservative uid strategy for patients with established ALI who do not have evidence of tissue hypoperfusion (1C) Use a weaning protocol and an SBT regularly to evaluate the potential for discontinuing mechanical ventilation (1A) SBT options include a low level
46、 of pressure support with continuous positive airway pressure 5 cm H2O or a T piece Before the SBT, patients shouldbe arousablebe hemodynamically stable without vasopressorshave no new potentially serious conditionshave low ventilatory and end-expiratory pressure requirementrequire FIO2 levels that
47、can be safely delivered with a face mask or nasal cannula.,肺动脉导管不作为ALIARDS患者的常规监测。(1A) 对没有组织低灌注的 ALI 患者采用限制性输液策略。(1C) 应用脱机方案和自主呼吸试验(SBT) 定期评价脱机可能性。(1A) SBT包括用约5cmH2O的持续气道正压的低水平压力支持。(1A) 在行SBT之前，患者应 ：(1A) 可被唤醒； 不用升压药而血流动力学平稳； 无新的潜在的严重临床问题； 仅需低通气量和低呼气末正压； 所需的FiO2水平使用面罩或鼻导管就可安全达到。,Sedation, analgesia,
48、and neuromuscular blockade in sepsis,Use sedation protocols with a sedation goal for critically ill mechanically ventilated patients (1B) Use either intermittent bolus sedation or continuous infusion sedation to predetermined end points (sedation scales), with daily interruption/lightening to produc
49、e awakening. Retitrate if necessary (1B) Avoid neuromuscular blockers where possible. Monitor depth of block with train-of-four when using continuous infusions (1B),为使危重的机械通气的脓毒症患者安静，可使用镇静剂。(1B) 间断使用镇静剂静注或持续静脉点滴达到预定的理想镇静状态( 镇静指数)， 采用间断减量使用方案使患者每天都有清醒的时刻，如需要可重复静脉给药。(1B) 尽可能避免应用神经肌肉阻滞剂。持续静脉应用神经肌肉阻滞剂时应
50、监测阻滞深度。(1B),Glucose control,Use intravenous insulin to control hyperglycemia in patients with severe sepsis following stabilization in the ICU (1B) Aim to keep blood glucose 150 mg/dL (8.3 mmol/L) using a validated protocol for insulin dose adjustment (2C) Provide a glucose calorie source and monitor blood glucose values every 12 hrs (4 hrs when stable) in patients receiving intravenous insulin (1C) Interpret with caution low glucose levels obtained with point of care testing, as these techniques may overestimate arterial blood or plasma glucose values (1B),
