EGDT翻译

Study Design and Oversight Our study was a pragmatic, open, multicenter,parallel-group, randomized, controlled trial. The North West London Research Ethics Committee approved the study protocol, which is available with the full text of this article at NEJM.org. The United Kingdom National Institute for Health Research (NIHR) funded the study and convened a trial steering committee and independent data monitoring and ethics committee. The Clinical Trials Unit at the United Kingdom Intensive Care National Audit and Research Centre (ICNARC)managed the study (for details, see the Supplementary Appendix, available at NEJM.org). Ed-wards Lifesciences loaned monitors and provided training and technical support but had no other role in the study. 方法

研究设计和监督我们的研究是一个务实的，开放，务实，平行组，随机，对照试验。北伦敦西部的研究伦理委员会批准研究协议，可与具体文章全文。英国国家健康研究所（NIHR）资助的研究并召开审判指导委员会和的数据监测和伦理委员会。临床试验单位在英国重症监护国家审计研究中心（ICNARC）管理研究（详情，见在NEJM。org提供附录，）。爱得华Lifesciences贷款监测和提供培训和技术支持，但有没有其他作用的研究。 Sites and Patients

The study was conducted in English NHS hospitals that did not routinely use EGDT that included continuous Scv O 2 monitoring. Adults (≥18 years of age) were eligible if within 6 hours after presentation to the emergency department they had a known or presumed infection, two or more criteria of the systemic inflammatory response syndrome, 16 and either refractory hypotension (systolic blood pressure, <90 mm Hg; or mean arterial pressure,<65 mm Hg, despite resuscitation with at least 1 liter of intravenous fluids within 60 minutes) or hyperlactatemia (blood lactate level, ≥4 mmol per liter) and did not meet any exclusion criteria(see the Methods section in the Supplementary Appendix).Randomization had to be completed within 2hours after the patient met the inclusion criteria.All patients provided written informed consent,or consent was granted through an agreement with a personal or professional consultee or in-dependent clinician. 17 Patients were assigned in a 1:1 ratio by means of 24-hour telephone randomization to receive either EGDT or usual care.Study-group assignment was performed by means of randomized permuted blocks, with variable block lengths of 4, 6, and 8, and stratified according to site. In all study patients, anti-microbial drugs were initiated before randomization.

网站和患者

这项研究是在英国NHS医院进行的，不经常使用，包括连续SCV EGDT O 2监测。成人（≥18岁）都可在6小时内报告急诊他们已知或推测感染后,全身炎症反应综合征的两个或两个以上的标准，16、顽固性低血压（（收缩压小于90毫米汞柱，；或平均动脉压，小于65毫米汞柱，尽管复苏至少1升静脉输液60分钟内）或高乳酸血症（血乳酸水平，≥4毫摩尔每升）并没有遇到任何的排除标准（见附录方法部分）。随机化之后必须符合纳入标准的门诊2小时内完成。所有患者提供书面知情同意，或同意授予通过个人或专业顾问或依赖临床医生的协议。17例患者按1:1的比例由24小时电话随机化意味着接受治疗或常规治疗分配。研究小组的任务是通过随机置换块的方式进行，以4，6和8，可变块长度，并根据现场分层。所有参与研究的患者，抗微生物药物开始在随机化之前。 Study Interventions

After randomization, the usual-care group continued to receive monitoring, investigations, and treatment as determined by the treating clinicians, whereas the EGDT group started the

resuscitation protocol (Fig. S1 in the Supplementary Appendix). For the latter, during the first hour,which was defined as the next whole hour (e.g.,if randomization was performed at 9:24, then by11 o’clock), a central venous catheter capable of continuous Scv O 2 monitoring was placed. The resuscitation protocol was followed for 6 hours (intervention period) with personnel involved and treatment location decided according to the site.At least one trained staff member was available throughout the intervention period. Key staff members were trained before the initiation of recruitment at each site. All other treatment, during the intervention period and after, was at the discretion of the treating clinicians. Blinding to study-group assignment was not possible. During the intervention period, data were collected prospectively for the EGDT group and retrospectively for the usual-care group to avoid the influence of data collection on treatment delivery.

干预的研究

随机分组后，他平时的护理组继续接受监控，调查和处理，由临床医生决定治疗，而EGDT组开始复苏协议（图S1在补充附录）。对于后者，在第一个小时，这被定义为下一整个小时（例如，如果进行随机化在9:24，然后11点），中心静脉导管可连续监测被SCV O 2。他复苏协议之后6小时（干预）与人员和处理根据现场决定位置。在干预期间至少有一个训练的人员可。关键员工进行培训，在每一个现场招聘开始前。所有其他的治疗，在干预期间和之后，在治疗医生的自由裁量权。盲法研究组的任务是不可能的。在干预期间，数据收集和回顾性分析EGDT组为常规护理组为避免数据采集对治疗的影响。 Outcome Measures

The primary clinical outcome was all-cause mortality at 90 days. Secondary outcomes were the score on the Sequential Organ Failure Assessment (SOFA) 18 at 6 hours and 72 hours; receipt of advanced cardiovascular, advanced respiratory,or renal support and the number of days in the first 28 days after randomization that were free from such support 19 ; length of stay in the emergency department, intensive care unit (ICU), and hospital; duration of survival; all-cause mortality at 28 days, at hospital discharge, and at 1 year; and health-related quality of life (as measured on the European Quality of Life–5 Dimensions [EQ-5D]five-level questionnaire), resource use, and costs at 90 days and 1 year. Adverse events were monitored up to 30 days. All definitions are provided in the Supplementary Appendix. 结果措施

主要临床终点为全因死亡率在90天。次要终点是在序贯器官衰竭评分（SOFA）18在6小时和72小时；先进的心血管，先进的呼吸的收据，或肾的支持和随机化，没有这样的支持19后的第一个28天的天数；在急诊科住院，ICU（ICU），和医院；生存时间；28天所有原因死亡率，出院时，在1年；与健康相关的生活质量（在5个维度的生活–[ ]五级欧洲EQ-5D问卷质量测量），资源的使用成本，并在90天和1年。不良事件监测了30天。所有的定义在附录中。 Statistical Analysis

Using the ICNARC Case Mix Program Data-base, 20 we estimated that 90-day mortality would be 40% in the usual-care group. On the basis of this estimation, we calculated that an enrollment of 1260 patients would have a power of 80% to detect a relative reduction of 20% in risk (abso- lute risk reduction, 8 percentage points) in the EGDT group, allowing for a loss to follow-up or withdrawal of 6%. 21 All analyses were performed according to the intention-to-treat principle and were prespecified in the statistical analysis plan. 22 A P value of less than 0.05 was considered to indicate statistical significance. All tests were two-sided with no adjustment for

multiple comparisons. Continuous variables are reported as means and standard deviations or medians and interquartile ranges.Categorical variables are reported as proportions.We used Fisher’s exact test to compare between-group differences in the primary outcome. Relative and absolute reductions in risk are reported with 95% confidence intervals without adjustment. Secondary analyses of the primary outcome included odds ratio with adjustment for Mortality in Emergency Department Sepsis (MEDS) score components, sensitivity analyses for missing data, learning-curve analysis, and adherence-adjusted analysis. We conducted prespecified subgroup analyses by testing interactions between the effect of EGDT and the degree of protocolized care (in the usual-care group), age, MEDS score, 23 SOFA score, and the time from presentation at the emergency department to randomization.In the cost-effectiveness analysis, we reported quality-adjusted life-years (QALYs) by combining survival data with quality-of-life scores at 90 days and estimated incremental net benefits by valuing incremental QALYs at the recommended thresh-old for a QALY gain (£20,000 [U.S. $28,430]) and then subtracting the incremental costs from this value. 24 Stata/SE software, version 13.0, was used for all analyses. (Details about methods are provided in the Statistical Analysis section in the Supplementary Appendix.) 统计分析

使用ICNARC病例组合方案的数据基础，20我们估计，90天的死亡率是40%在常规护理组。基于这个估计，我们计算1260例招生会80%的功率检测相对减少20%的风险（绝对风险减少，8个百分点）在EGDT组，允许损失6%跟进或退出。21所有分析根据意向治疗原则进行了预先设定的统计分析计划。22，P值小于0.05被认为具有统计学意义。所有检验均为双侧没有调整的多重比较。连续变量的均值和标准偏差报告或中位数和四分位数。分类变量的报告比例。我们用Fisher精确检验比较组间差异的主要结果。相对和绝对减少风险报告，95%的置信区间不调整。主要结果的次级分析包括比值与死亡率急诊脓毒症的调整（MEDS）评分组件，缺失数据的敏感性分析，学习曲线分析，并坚持调整分析。我们进行了亚组分析和实施EGDT护理程度的影响之间的相互作用（试验组在常规护理），年龄，MEDS评分，23 SOFA评分，和时间的报告紧急情况部随机化。在成本效益分析，我们报告的质量调整生命年（QALY）结合的生存数据与生活质量分数在90天内，估计增量净效益价值增量QALY在推荐的阈值为一个QALY增益（£20000 [ 28430美元]）然后减去这个值的增量成本。24 Stata / SE软件，版本13，被用于所有的分析。（具体方法在附录。在统计分析部分提供） Results Study Patients

From February 16, 2011, to July 24, 2014, we screened 6192 patients at 56 sites (including 29% that are teaching hospitals), which resulted in the enrollment of 1260 patients (Tables S1 andS2 and Fig. S2 and S3 in the Supplementary Appendix). Four patients requested complete withdrawal and five were ineligible, which left 1251patients in the initial analysis (625 in the EGDT group and 626 in the usual-care group). Eight patients withdrew before 90 days, which left 1243 patients in the analysis of outcomes (623 in the EGDT group and 620 in the usual-care group) (Fig. 1, and Table S3 in the Supplementary Appendix). The two study groups were well matched at baseline (Table 1, and Table S4 in the Supplementary Appendix).The criterion for refractory hypotension was met in 338 patients (54.1%) in the EGDT group and 348 patients (55.6%) in the usual-care group,and the criterion for hyperlactatemia was met in 409 patients (65.4%) and 399 patients (63.7%),respectively. The intravenous-fluid volume before randomization was similar in the two groups, as were median times from presentation at the emergency department until inclusion

criteria were met and until randomization. Only about two thirds of patients in either group were deemed likely to be admitted to the ICU from the emergency department if they were not enrolled in the study; those deemed unlikely to be admitted were less severely ill. The sites of infection (most commonly lung) were well balanced in the two groups. All patients received antimicrobial drugs before randomization. 结果 研究的患者

从2011年2月16日，到2014年7月24日，我们筛选了6192例在56个站点（包括29%所教学医院），这导致1260例（表S1招生ands2 S2和S3和图在附录）。四患者要求完全撤出，五是不合格的，这让1251patients在初步分析（625在EGDT在常规护理组，626）。八患者退出前90天，造成1243患者疗效分析（623在EGDT组和620组在常规护理）（图1，表S3的附录）。两个研究组在基线相匹配（附表1，表S4）。两个研究组在基线相匹配（附表1，表S4）。对于顽固性低血压的标准的338例患者（54.1%）在治疗组和348例（55.6%）在常规治疗组，和高乳酸血症的标准的409例患者（65.4%）和399例（63.7%），分别为。在随机化之前是在两组相似的静脉补液量，如在急诊科从演示中位时间直到符合纳入标准，直到随机化。只有在两组中，三分之二例被认为很可能是承认他从急诊ICU如果他们没有被纳入研究；那些被认为不太可能承认不太严重的病。感染部位（最常见的肺癌）进行了很好的平衡在两组。所有患者在随机分组前接受抗菌药物。

Adherence to the Protocol

Most patients in the EGDT group underwent timely insertion of a central venous catheter capable of continuous ScvO 2 monitoring. Two catheters that were inserted in error in the usual-care group were not used for monitoring ScvO 2 (Table 2,and Table S5 in the Supplementary Appendix). In the EGDT group, reasons for failure of insertion were as follows: patient no longer met inclusion criteria or met exclusion criteria (22 patients),there was a lapse in the process of care (lack of equipment, staff, beds, communication, or error)(20 patients), there were technical difficulties or problems with a patient (18 patients), there was a decision by a clinician (9 patients), or the patient declined to have a catheter inserted but did not withdraw from the trial (5 patients); in 4 patients,no reason was provided, and 2 patients died before catheter insertion. The mean (±SD) first ScvO 2 value recorded (at hour 1) was 70±12%(Fig. S4 in the Supplementary Appendix). Standard central venous catheters were not mandated but were placed in 50.9% of the patients in the usual-care group, and ScvO 2 was measured from aspirated blood samples in 6 patients. Arterial catheters were also not mandated but were placed in most patients. EGDT was stopped prematurely in 21 patients(median time to cessation, 3 hours) because active treatment was withdrawn (9 patients), the patient was no longer considered to have sepsis (5 patients), or EGDT was terminated in error(3 patients); in addition, 1 patient was transferred to an operating room, 1 patient declined treatment, and no reason was provided for 2 patients. Among the 35 patients who died within 6 hours(17 in the EGDT group and 18 in the usual-care group), 5 in the EGDT group and 6 in the usual-care group had withdrawal of active treatment. Adherence to EGDT ranged from 86 to 95%,depending on the method of assessment (Fig. S5 in the Supplementary Appendix). 遵守协议

在EGDT组多数患者及时插入中心静脉导管可连续ScvO 2监测。两导管分别插在常规护理组的错误并非用

于监测ScvO 2（表2，表S5的附录）。在EGDT组，失败的原因如下：插入患者不再符合纳入标准或符合排除标准（22例），有一个在照顾过程中的失误（缺乏设备，人员，床位，通信，或错误）（20例），有技术困难或病人的问题（18例），均由临床医生决定（9例），或患者拒绝导管插入但没有退出试验（5例患者）；在4例患者中，没有提供理由，前死亡2例导管插入。平均（±SD）第一次ScvO 2价值记录（1小时）为70±12%（图S4的附录）。标准的静脉导管没有授权，但被放置在常规护理组患者的50.9%，并从吸气ScvO 2血液样本测定6例。动脉导管还没有授权，但被放置在大多数患者。EGDT被提前停止（停止21例，中位时间3小时）因为积极治疗被撤回（9例），病人不再认为有脓毒症（5例），或终止错误治疗（3例）；此外，1的患者被转移到一个营业厅，1病人拒绝治疗，没有理由为2例。35例患者在6小时内死亡（17间EGDT组和常规护理18组），5和6的EGDT组在常规护理组积极治疗戒断。坚持治疗的范围从86到95%，取决于评估方法（图S5在补充附录）。 Intervention Period

During the 6-hour intervention period, patients in the EGDT group received more intravenous fluids than did patients in the usual-care group(Table 2). Hourly fluid volume decreased over the 6 hours, but patients in the usual-care group received a larger initial volume (Fig. S6 in the Supplementary Appendix). Crystalloids were administered more frequently than colloids in the two groups. More patients in the EGDT group than in the usual-care group received vasopressors and dobutamine. Although more patients in the EGDT group received red-cell transfusions, larger volumes were transfused in the usual-care group.During the 6-hour intervention period, administration of platelets and fresh-frozen plasma was similar in the two groups, although the volume of each was higher in the EGDT group (Table 2). At 6 hours, values for central venous pressure, mean arterial pressure, systolic blood pressure, and hemoglobin were similar in the two groups among patients in whom they were measured, which happened with greater frequency in the EGDT group (Table S6 in the Supplementary Appendix).

介入期 表2

6小时干预期间，在EGDT组患者接受更多的静脉输液比在常规治疗组的患者（表2）。在6小时内每小时的液量下降，但在常规护理组患者接受一个较大的初始体积（图S6在补充附录）。晶体溶液进行比两组胶体更频繁。在EGDT组患者比常规护理组给予升压药和多巴酚丁胺。虽然EGDT组更多患者的红细胞输血，大量输血组在常规护理的干预期间小时，血小板和新鲜冰冻血浆的管理是在两组相似，虽然每个量较高，EGDT组（表2）。6小时后，中心静脉压值，平均动脉压，收缩压，血红蛋白是相似的两组患者在他们之间，发生的频率更高，在EGDT组（附表S6）。 After the Intervention Period

Between 6 and 72 hours, the numbers of patients in the two groups receiving intravenous fluids were similar, but patients in the usual-care group received larger volumes. More patients in the EGDT group received intravenous colloids, but overall volumes were similar in the two groups. The number of patients receiving intravenous crystalloids was similar in the two groups, but volumes were larger in the usual-care group. The number of patients receiving red-cell transfusions was higher in the EGDT group, but volumes were larger in the usual-care group. The use of vasopressors and dobutamine remained higher in the EGDT group. Although the numbers of patients receiving platelets and fresh-fro-zen plasma were similar in the two groups, the volume of platelets was larger in the EGDT group,whereas the volume of fresh-frozen plasma was higher in the usual-care group (Table 2, and Table S7 in the Supplementary Appendix). At 72hours,

physiological, biochemical, and SOFA values were similar in the two groups (Table S8 in the Supplementary Appendix). 介入期后

6小时和72小时之间，在两组接受静脉输液的患者数量是相似的，但在常规护理组患者数量较大的。在EGDT组更多患者接受静脉胶体，但整体数量在两组相似。接受静脉晶体患者的数量是在两组相似，但在平时的护理组体积较大。接受红细胞输注的患者数量在EGDT组高，但体积较大的常规护理组。升压药和多巴酚丁胺使用保持较高的EGDT组。虽然接受血小板和新鲜冻结血浆的患者数量在两组相似，在EGDT组血小板体积增大,而新鲜冰冻血浆量明显高于常规治疗组（表2和表，S7的附录）。在72小时，生理，生化，和SOFA值在两组相似（附表S8）。 Primary Outcome

Mortality at 90 days was not significantly different in the two groups, with deaths reported in 184 of 623 patients (29.5%) in the EGDT group versus 181 of 620 patients (29.2%) in the usual- care group, with an unadjusted relative risk in the EGDT group of 1.01 (95% CI, 0.85 to 1.20; P = 0.90), for an absolute risk reduction of −0.3percentage points (95% CI, −5.4 to 4.7). After adjustment for baseline characteristics, the odds ratio was 0.95 (95% CI, 0.74 to 1.24; P = 0.73) (Table 3). Sensitivity analyses for patients with a missing primary outcome (2 in the EGDT group and 6 in the usual-care group) showed relative risks ranging from 0.99 to 1.03. There was no evidence of a learning-curve effect (P = 0.56). In the adherence-adjusted analysis, the relative risk was 1.02 (95% CI, 0.78 to 1.32; P = 0.90) (Table S9and Fig. S7 in the Supplementary Appendix).

主要结果 表3

在90天的死亡率在两组差异不显著，与死亡的报道184的623例患者（29.5%）在治疗组与181的620例患者（29.2%）在平时—护理组，基线特征调整后，比值比为0.95（95% CI，0.74到1.24；P = 0.73）（表3）。一个失踪的主要疗效的敏感性分析（2，EGDT组和6组在常规护理）显示相对风险范围从0.99到1.03。没有证据表明一个学习曲线效应（P = 0.56）。在坚持调整分析，相对风险为1.02（95% CI，0.78到1.32；P = 0.90）（表s9and图S7的附录）。 Secondary Outcomes

The mean SOFA score at 6 hours, the proportion of patients receiving advanced cardiovascular support, and the median length of stay in the ICU were significantly greater in the EGDT group than in the usual-care group. No other secondaryoutcomes were significantly different (Table 3, and Table S10 in the Supplementary Appendix).There was no significant difference in the dura- tion of survival between the two groups (P = 0.63 by the log-rank test; adjusted hazard ratio, 0.94,95% CI, 0.79 to 1.11; P = 0.46) (Fig. 2). Mean EQ-5Dscores and QALYs were similar in the two groups.The average cost was higher in the EGDT group(£12,414 [U.S. $17,7]) than in the usual-care group (£11,424 [U.S. $16,239]), but the difference was not significant (P = 0.26) (Table 3, and Tables S11 through S16 and Fig. S8 in the Supplementary Appendix). The incremental net benefit for EGDT as compared with usual care was negative and similar across prespecified subgroups and alternative scenarios that were considered in sensitivity analyses (Tables S17 and S18 and Fig. S9 in the Supplementary Appendix). The probability that EGDT was cost-effective was below 20%(Fig. S10 in the Supplementary Appendix).

次要结局

在6小时的平均SOFA评分，接受先进的心血管支架的患者比例，和住在ICU的平均长度显著大于在EGDT组比常规治疗组。没有其他的结果有显著性差异（附表3，表S10）。两组之间的生存时间无显著性差异（P = 0.63 log-rank检验；调整后的危险比为0.79，表明CI，1.11；P = 0.46）（图2）。平均eq-5dscores QALY在两组中是相似的。平均成本高于EGDT组（£12414 [ 177美元]）比常规护理组（£11424 [ 16239美元]），但差异不显著（P = 0.26）（表3，表在附录通过S16和图S8 S11）。 Subgroup Analyses

There was no significant difference regarding the effect of EGDT according to prespecified subgroups as defined by the degree of protocolized care used in the usual-care group, age, MEDS score, SOFA score, or time from presentation at the emergency department to randomiza- tion (P = 0.39 to 0.72 for interaction) (Table S9and Fig. S11 in the Supplementary Appendix). 亚组分析

没有显着的差异EGDT的影响根据预先设定的亚组中使用的常规护理组实施护理定义的程度有,年龄，MEDS评分，SOFA评分，或从介绍在急诊科随机（P = 0.39至0.72的互动）（表s9and图S11在补充附录）。 Serious Adverse Events

At least one serious adverse event was reported in 30 patients (4.8%) in the EGDT group and 26 patients (4.2%) in the usual-care group (P = 0.58)(Table 3, and Table S19 in the Supplementary Appendix). Four serious adverse events were reported as being related to EGDT (two cases of pulmonary edema and one of arrhythmia, which were deemed to be probably related, and one case of myocardial ischemia, which was deemed to be definitely related), as compared with four events (in three patients) related to usual care (two cases of pneumothorax and one case of pulmonary edema, which were deemed to be probably related, and one case of ventricular fibrillation, which was deemed to be definitely related).

严重不良事件

至少有一个严重不良事件的报道在30例（4.8%）在EGDT组26例（4.2%）在常规治疗组（P = 0.58）（附表3，表S19）。我们的严重不良事件的报道是有关EGDT（两例肺水肿和心律失常，这被认为是相关的，和心肌缺血，这被认为是绝对相关的案例），与四事件相比（三例）常规治疗相关（气胸，1例肺水肿，这被认为是可能相关，与心室颤动，这被认为是绝对相关的两起案件）。

In conclusion, our results suggest that techniques used in usual resuscitation have evolved over the 15 years since the landmark study by Rivers et al. 9 In our study, NHS hospitals achieved levels of in-hospital survival in patients receiving usual care that were similar to those achieved with EGDT in the earlier study for patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation. The addition of continuous ScvO 2 monitoring and strict protocolization did not improve outcomes in the EGDT group. Our results complete the planned trio of studies of EGDT, all of which showed that EGDT was not superior to usual care.

总之，我们的研究结果表明，在通常的复苏技术已经发展了15年以来的河流等具有里程碑意义的研究。 9在我们的研究中，NHS医院接受常规护理，类似于那些在早期的研究为治疗感染性休克患者的早期发现和

接受静脉注射抗生素和充分的液体复苏取得患者达到住院生存水平。连续监测和严格的protocolization ScvO 2并不能改善在EGDT组的结果。我们的结果完成三研究EGDT，所有这些表明EGDT并不优于常规护理。 The level of adherence to EGDT was good and was equivalent to adherence levels in the ProCESS and ARISE trials and higher than reported rates of compliance with the SSC guidelines. 26 Most outcomes were similar to those reported in the ProCESS and ARISE trials, although the rate of death at 90 days that was reported in our study was lower than that in the ProCESS trial but higher than that in the ARISE trial. Of note, a higher proportion of patients in our study than in the ProCESS and ARISE trials met both of the two inclusion criteria — refractory hypotension and hyperlactatemia (Table S21 in the Supplementary Appendix)— a factor that is associated in our national ICU database with a doubling of hospital mortality(Table S22 in the Supplementary Appendix).

坚持治疗水平很好，相当于在过程控制水平和产生试验和高于报道的SSC指南依从率。26大多数的结果是类似于那些在报道过程而产生的试验，尽管速度在90天，在我们的研究中报道的死亡明显低于审判过程中但高于中出现的审判。值得注意的是，高比例的病人在我们的研究过程中出现的比和试验符合入选标准的2 -顽固性低血压和高乳酸血症（附表S21）-一种在我国ICU数据库与住院死亡率加倍相关因子（附表二）。 Unlike Rivers et al., in their 2001 study, we did not observe a significant reduction in hospital mortality with the use of EGDT. Many aspects of initial sepsis management have changed during the past 15 years, as can be seen in comparing the usual-care groups. In our study, as com- pared with the study by Rivers et al., mortality was substantially reduced, randomization oc- curred later, patients appeared to be less sick at baseline (with lower blood lactate levels and Acute Physiology and Chronic Health Evaluation[APACHE] II scores), and all patients received antibiotics before randomization. In addition,our patients received much lower volumes of intravenous fluids and more vasoactive drugs(Table S20 in the Supplementary Appendix).

不像河流等人。，在2001项研究中，我们没有观察到与EGDT的使用医院的死亡率显著降低。初始感染管理的许多方面有近15年的变化，可以看到在比较常规治疗组。在我们的研究中，与江河等人的研究相比。，死亡率大大降低，随机化发生后，患者出现不舒服的基线（低血乳酸水平和急性生理和慢性健康评估[阿帕奇] II评分），所有患者接受抗生素在随机化之前。此外，我们的患者接受低得多的静脉补液和血管活性药物（附表S20）。

Our study has several limitations. As in all studies that enroll patients presenting to emer- gency departments, recruitment was more challenging on weekends and during out-of-office hours; overall, only one third of eligible patients were recruited, although exclusion from the study by a clinician was rare. The intervention could not be blinded, but the risk of bias was minimized through central randomization to ensure the concealment of study-group assignments and the use of a primary outcome that was not subject to observer bias. Since the rate of death was lower than anticipated, our study data may not apply to settings with higher mortality.

我们的研究有一些局限性。在所有的研究招募患者的紧急部门，招聘是更具挑战性的周末和下班后在；总体而言，只有三分之一的符合条件的患者，虽然由临床医生，研究排除是罕见的。干预不能被蒙蔽，但偏倚风险最小化，通过随机保证研究小组作业的隐蔽性与原结果不是主体观察者偏见的使用。由于死亡率低于预期，我们的研究数据可能不适用于高死亡率的设置。