Dellinger R Phillip, Levy Mitchell M, Carlet Jean M, Bion Julian, Parker Margaret M, Jaeschke Roman, Reinhart Konrad, Angus Derek C, Brun-Buisson Christian, Beale Richard, Calandra Thierry, Dhainaut Jean-Francois, Gerlach Herwig, Harvey Maurene, Marini John J, Marshall John, Ranieri Marco, Ramsay Graham, Sevransky Jonathan, Thompson B Taylor, Townsend Sean, Vender Jeffrey S, Zimmerman Janice L, Vincent Jean-Louis
Cooper University Hospital, One Cooper Plaza, 393 Dorrance, Camden 08103, NJ, USA.
Intensive Care Med. 2008 Jan;34(1):17-60. doi: 10.1007/s00134-007-0934-2. Epub 2007 Dec 4.
To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004.
Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding.
We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations.
Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B).
There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.
对2004年发表的《拯救脓毒症运动严重脓毒症和脓毒性休克管理指南》这一原始指南进行更新。
采用改良德尔菲法,召开了由55名国际专家参加的共识会议,随后召开了多个小组及关键人员的会议、电话会议,并在小组之间以及整个委员会内部进行了基于电子的讨论。该过程独立于任何行业资助进行。
我们使用GRADE系统来指导对证据质量的评估,从高(A)到极低(D),并确定推荐强度。强烈推荐表明干预措施的有益效果明显超过其不良效果(风险、负担、成本),或者明显并非如此。弱推荐表明有益效果与不良效果之间的权衡不太明确。强烈或弱的等级被认为比证据质量字母等级的差异在临床重要性上更高。在未完全达成一致的领域,制定并应用了正式的解决程序。推荐分为直接针对严重脓毒症的推荐、针对重症患者一般护理且在严重脓毒症中被视为高度优先的推荐以及儿科相关考虑。
按类别列出的关键推荐包括:在识别脓毒症患者后的最初6小时内进行早期目标导向性复苏(1C);在抗生素治疗前进行血培养(1C);迅速进行影像学检查以确认潜在感染源(1C);在诊断脓毒性休克(1B)和无脓毒性休克的严重脓毒症(1D)后1小时内给予广谱抗生素治疗;根据微生物学和临床数据重新评估抗生素治疗,以在适当的时候缩小覆盖范围(1C);根据临床反应通常进行7 - 10天的抗生素治疗(1D);进行源头控制,同时关注所选方法的风险和益处平衡(1C);给予晶体液或胶体液复苏(1B);进行液体冲击以恢复平均循环充盈压(IC);随着充盈压升高且组织灌注无改善,减少液体输注速率(1D);优先选择去甲肾上腺素或多巴胺作为血管升压药,以维持平均动脉压≥65 mmHg的初始目标(1C);在液体复苏以及联合使用正性肌力药/血管升压药治疗后心输出量仍低时,使用多巴酚丁胺进行正性肌力治疗(1C);仅在确认血压对液体和血管升压药治疗反应不佳的脓毒性休克患者中给予应激剂量的类固醇治疗(2C);在严重脓毒症且临床评估死亡风险高的患者中使用重组活化蛋白C(术后患者为2C,其他为2B)。在不存在组织灌注不足、冠状动脉疾病或急性出血的情况下,将血红蛋白目标设定为7 - 9 g/dL(1B);对于急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS),采用低潮气量(1B)和限制吸气平台压策略(1C);在急性肺损伤中应用至少最小量的呼气末正压(1C);除非有禁忌,机械通气患者床头抬高(1B);在ALI/ARDS中避免常规使用肺动脉导管(1A);对于已确诊ALI/ARDS且未处于休克状态的患者,采用保守液体策略以减少机械通气天数和ICU住院时间(1C);制定撤机和镇静/镇痛方案(IB);采用间歇性推注镇静或每日中断或减浅的持续输注镇静(1B);尽可能避免使用神经肌肉阻滞剂(1B);在初始稳定后,进行血糖控制(1B),目标是血糖<150 mg/dL(2C);持续静 - 静脉血液滤过或间歇性血液透析等效(2B);预防深静脉血栓形成(1A);使用H2受体阻滞剂(1A)或质子泵抑制剂(1B)进行应激性溃疡预防以防止上消化道出血;并在适当情况下考虑限制支持治疗(1D)。针对儿童严重脓毒症的特定推荐包括:更多地使用体格检查治疗终点(2C);多巴胺作为低血压的首选药物(2C);仅在疑似或证实有肾上腺功能不全的儿童中使用类固醇(2C);不推荐在儿童中使用重组活化蛋白C(1B)。
一大批国际专家就许多针对严重脓毒症患者当前最佳治疗的1级推荐达成了强烈共识。关于脓毒症和脓毒性休克急性管理的循证推荐是改善这一重要重症患者群体预后的第一步。