Implementing Early Goal-directed Therapy in the Emergency Setting: The Challenges and Experiences of Translating Research Innovations into Clinical Reality in Academic and Community Settings

Research knowledge translation into clinical practice pathways is a complex process that is often time-consuming and resource-intensive. Recent evidence suggests that the use of early goal-directed therapy (EGDT) in the emergency department care of patients with severe sepsis and septic shock results in a substantial mortality benefit; however, EGDT is a time- and resource-intensive intervention. The feasibility with which institutions may translate EGDT from a research protocol into routine clinical care, among settings with varying resources, staff, and training, is largely unknown. The authors report the individual experiences of EGDT protocol development, as well as preimplementation and postimplementation experiences, at three institutions with different emergency department, intensive care unit, and hospital organization schemes.     

严重脓毒症和脓毒性休克的急诊集束化治疗依从性调查分析

目的 调查严重脓毒症和脓毒性休克在急诊患者中的发生率以及针对严重脓毒症和脓毒性休克早期集束化治疗的依从性.方法 选择2009年5月至6月由救护车送至上海交通大学医学院附属瑞金医院急诊科的患者为调查对象,统计严重脓毒症和脓毒性休克的发生率,对符合诊断标准的患者分别统计早期复苏集束化治疗各项指标完成的依从性.结果 共纳入急诊就诊患者917例,其中符合严重脓毒症和脓毒性休克诊断标准者96例,发生率为10.47%.在符合诊断标准的患者中,早期复苏集束化治疗、使用抗菌药物前留取病原学标本、2 h内放置深静脉导管并监测中心静脉压(CVP)与中心静脉血氧饱和度(ScvO2)、3 h内使用广谱抗菌药物、6 h内早期目标导向治疗(EGDT)达标、12 h内乳酸下降或原乳酸≤2 mmol/L的依从性分别为1.04%、3.12%、2.08%、83.33%、1.04%、23.96%,急诊内科各指标的依从性依次为1.19%、3.57%、2.38%、83.33%、1.19%、26.19%,急诊外科各指标的依从性依次为0、0、0、83.33%、0、8.33%,急诊内、外科依从性比较差异均无统计学意义(均P＞0.05).结论 严重脓毒症和脓毒性休克在急诊就诊患者中占相当比例,但医师的认识不足;早期集束化治疗依从性较低,需加大指南的教育及执行程度.

Abstract：

Objective To evaluate the occurrence of severe sepsis and septic shock and the rate of compliance with sepsis bundle in patients with severe sepsis and septic shock in emergency department.Methods A prospective study was conducted on consecutive adult patients who were sent to Emergency Department of Ruijin Hospital, Shanghai Jiaotong University School of Medicine by ambulance from May to June in 2009. The occurrence of severe sepsis and septic shock, and the number of the patients in whom who met the criteria of compliance with sepsis bundle were analyzed. Results Nine hundred and seventeen patients who were sent to the emergency department by ambulance in that period were enrolled in the study.The number of patients with severe sepsis and septic shock was 96. The incidence of severe sepsis and septic shock was 10.47%. Among these patients, the number of patients in whom the sepsis bundle was complied,i.e. sepsis bundle, appropriate cultures were taken before antimicrobial therapy, placement of central venous catheter and monitoring of central venous pressure(CVP)as well as central venous oxygen saturation (ScvO2)within 2 hours, antibiotic therapy within 3 hours, early goal-directed therapy(EGDT)within 6 hours, and lactate clearance in 12 hours reached 1.04%, 3. 12%, 2.08%, 83. 33%, 1.04%, 23.96%.The results were 1.19%, 3. 57%, 2.38%, 83.33%, 1.19%, 26.19% and 0, 0, 0, 83.33%, 0, 8. 33% in medical and surgical emergency department respectively. There was no statistical difference between the two divisions(all P＞0. 05). Conclusion The incidence of severe sepsis and septic shock was high in emergency department, but the rate of recognition of it and the compliance with sepsis bundle were inadequate. It is urgently necessary to enhance the learning and implementation of the guideline.     

Early Goal-directed Therapy, Corticosteroid, and Recombinant Human Activated Protein C for the Treatment of Severe Sepsis and Septic Shock in the Emergency Department

Objectives: To describe our experience with early goal‐directed therapy (EGDT), corticosteroid administration, and recombinant human activated protein C (rhAPC) administration in patients with severe sepsis or septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥25 in the emergency department (ED). Methods: This was a retrospective case series of a prospectively maintained ED sepsis registry. Data are presented as median (25th, 75th percentile). The setting was an academic tertiary ED with approximately 60,000 annual patient visits. Patients with severe sepsis or septic shock and an APACHE II score ≥25 entered in an ED sepsis registry over a four‐month period were included. Patients who received rhAPC in the intensive care unit were excluded. Central venous catheterization for central venous pressure and central venous oxygen saturation monitoring, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, inotropes, corticosteroids, and rhAPC were initiated by the emergency physicians and continued in the intensive care unit by intensivists. Results: Twenty‐four patients were enrolled. Patient characteristics were as follows: age, 79.5 (68.0, 83.5) years; APACHE II score, 31.5 (29.8, 36.0); ED length of stay, 6.5 (4.0, 10.5) hours; predicted mortality, 76.7% (71.9, 86.4); and in‐hospital mortality, 45.8%. All patients received broad‐spectrum antibiotics, 54.2% completed EGDT, 33.3% received corticosteroids, and 33.3% received rhAPC. Time of antibiotic administration was 1.5 (1.0, 2.0) hours, time of central venous pressure/central venous oxygen saturation monitoring was 1.0 (0.5, 2.5) hour, and time of rhAPC administration was 9.5 (6.8, 10.5) hours after patients met criteria for severe sepsis or septic shock. In‐hospital mortality of patients who received rhAPC in addition to other therapies was 25.0%. Conclusions: EGDT, corticosteroid administration, and rhAPC administration are feasible in the ED setting. While these evidence‐based therapies individually have been shown to improve outcomes for patients with severe sepsis or septic shock, further studies are needed to examine their combined effectiveness during the early stages of this disease.     

Commentary: Trzeciak S et al. (2006). Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department

Early goal‐directed therapy (EGDT) has been shown to decrease mortality in patients with severe sepsis and septic shock. Consensus guidelines now advocate EGDT for the first 6 h of sepsis resuscitation. However, EGDT has not yet been widely adopted in practice. A need for effective collaboration between emergency medicine and critical care medicine services has been identified as an obstacle to implementation. We aimed to determine if EGDT end‐points could reliably be achieved in real‐world clinical practice. EGDT was implemented as a collaborative emergency medicine/critical care quality improvement initiative. EGDT include the following: intravenous (IV) fluids (IVF) targeting central venous pressure ≥8 mmHg, vasopressors targeting mean arterial pressure ≥65 mmHg, and (if necessary) packed RBCs (PRBCs) and/or dobutamine targeting central venous oxygen saturation ≥70%. A retrospective analysis was performed of emergency department (ED) patients with persistent sepsis‐induced hypotension (systolic blood pressure <90 mmHg despite 1.5 L of IVF) treated with EGDT during the first year of the initiative. Primary outcome measures included successful achievement of EGDT end‐points and time to achievement. A secondary analysis was performed, comparing EGDT cases to historical control cases (non‐protocolized control subjects without invasive monitoring). All end‐points were achieved in 20 of 22 cases (91%). The median time to reach end‐point was ≤6 h. In the secondary analysis, patients (n = 38; EGDT, n = 22; pre‐EGDT, n = 16) had similar age, do‐not‐resuscitate status, severity scores, hypotension duration and vasopressor requirement (p = not significant). In the ED, EGDT used more IVF and included PRBC/dobutamine utilization, without any effect on the overall use of these therapies through the first 24 h in the ICU. EGDT was associated with decreased intensive care unit pulmonary artery catheter (PAC) utilization (9.1% versus 43.7%, p = 0.01). With effective emergency medicine/critical care collaboration, we demonstrate that EGDT end‐points can reliably be achieved in real‐world sepsis resuscitation. ED‐based EGDT appears to decrease ICU PAC utilization. Abstract reprinted from the Chest volume 129, Trzeciak et al., ‘Translating research to clinical practice: a 1–year experience with implementing early goal‐directed therapy for septic shock in the emergency department.’, pages 225–232. © 2006, with permission from Blackwell Publishing Ltd.     

Harmonizing international trials of early goal-directed resuscitation for severe sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe

Purpose

To describe and compare the design of three independent but collaborating multicenter trials of early goal-directed resuscitation for severe sepsis and septic shock.

Methods

We reviewed the three current trials, one each in the USA (ProCESS: protocolized care for early septic shock), Australasia (ARISE: Australasian resuscitation in sepsis evaluation), and the UK (ProMISe: protocolised management in sepsis). We used the 2010 CONSORT (consolidated standards of reporting trials) statement and the 2008 CONSORT extension for trials assessing non-pharmacologic treatments to describe and compare the underlying rationale, commonalities, and differences.

Results

All three trials conform to CONSORT guidelines, address the same fundamental questions, and share key design elements. Each trial is a patient-level, equal-randomized, parallel-group superiority trial that seeks to enroll emergency department patients with inclusion criteria that are consistent with the original early goal-directed therapy (EGDT) trial (suspected or confirmed infection, two or more systemic inflammatory response syndrome criteria, and refractory hypotension or elevated lactate), is powered to detect a 6–8 % absolute mortality reduction (hospital or 90-day), and uses trained teams to deliver EGDT. Design differences appear to primarily be driven by between-country variation in health care context. The main difference between the trials is the inclusion of a third, alternative resuscitation strategy arm in ProCESS.

Conclusions

Harmonization of study design and methods between severe sepsis trials is feasible and may facilitate pooling of data on completion of the trials.     

Severe sepsis in A&E.

In this article, the author clarifies the definition of sepsis, severe sepsis and septic shock, describes the physiological changes that occur and the initial treatment used to improve patient outcome, and examines the concept of early goal directed therapy (EGDT).     

Implementation of early goal-directed therapy for severe sepsis and septic shock: A decision analysis

OBJECTIVE: Early goal-directed therapy (EGDT) reduced mortality from septic shock in a single-center trial. However, implementation of EGDT faces several barriers, including perceived costs and logistic difficulties. We conducted a decision analysis to explore the potential costs and consequences of EGDT implementation. DESIGN: Estimates of effectiveness and resource use were based on data from the original trial and published sources. Implementation costs and lifetime projections were modeled from published sources and tested in sensitivity analyses. We generated incremental cost-effectiveness ratios from the hospital (short-term) and U.S. societal (lifetime) perspectives, excluding nonhealthcare costs, and applying a 3% annual discount. SETTING: Simulation of an average U.S. emergency department. PATIENTS: Total of 1,000 simulation cohorts (n = 263 for each cohort) of adult patients with severe sepsis/septic shock. INTERVENTIONS: EGDT under three alternative implementation strategies: emergency department-based, mobile intensive care unit team, and intensive care unit-based (after emergency department transfer). MEASUREMENTS AND MAIN RESULTS: For an average emergency department, we estimated 91 cases per yr, start-up costs from $12,973 (intensive care unit-based) to $26,952 (emergency department-based), and annual outlay of $100,113. EGDT reduced length of stay such that net hospital costs fell approximately 22.9% ($8,413-$8,978). EGDT implementation had a 99.4% to 99.8% probability of being dominant (saved lives and costs) from the hospital perspective, and cost from $2,749 (intensive care unit-based) to $7019 (emergency department-based) per quality-adjusted life-yr with 96.7% to 97.7% probability of being <$20,000 per quality-adjusted life-yr from the societal perspective. The intensive care unit-based strategy was the least expensive, because of lower start-up costs, but also least effective, because of implementation delay, and all three strategies had similar cost-effectiveness ratios. Sensitivity analyses showed these estimates to be particularly sensitive to EGDT's effect on mortality and intensive care unit length of stay, but insensitive to other variables. CONCLUSIONS: EGDT has important start-up costs, and modest delivery costs, but assuming LOS and mortality are reduced, EGDT can be cost-saving to the hospital and associated with favorable lifetime cost-effectiveness projections.     

休克指数对感染性休克患者预后的预测价值

目的：研究休克指数（SI）对感染性休克患者预后的预测作用。方法：研究选入98例诊断为严重感染或感染性休克的患者,记录早期复苏开始时、复苏6h后的情况及6h后的休克指数。然后根据复苏6h后的情况分为A、B、C、D四组。A组为实现EGDT同时SI≤0.7,B组为实现EGDT但SI〉0.7,C组未能实现EGDT但SI≤0.7,D组未能实现EGDT同时SI〉0.7。比较四组之间6h乳酸清除率及预后。结果：6h乳酸清除率A组与其他3组均有差异,B、C两组间无差异,D与其他3组均有差异。A组的28d病死率低于D组,其余组间无差异。实现EDGT目标患者6h乳酸清除率及28d病死率均优于未实现EGDT目标者。SI≤0.7组患者6h乳酸清除率及28d病死率均优于SI〉0.7组患者。结论：感染性休克患者在早期复苏后,实现EGDT组预后优于未实现EGDT组,SI≤0.7组预后优于SI〉0.7组。如能同时实现EGDT目标和SI≤0.7,则预后显著优于其他组。SI能作为经早期复苏后感染性休克患者预测预后的指标。     

Evaluation of a modified early goal-directed therapy protocol

Objectives

The study aimed to determine mortality in septic patients 2 years after introduction of a modified early goal-directed therapy (EGDT) protocol and to measure compliance with the protocol.

Design

This was an observational study of prospectively identified patients treated with EGDT in our emergency department (ED) from May 2007 through May 2008 and compared with retrospectively obtained data on patients treated before protocol implementation, from May 2004 to May 2005.

Setting

This study was conducted at a large tertiary-care suburban community hospital with more than 85?000 ED visits annually and 700 inpatient beds.

Patients

Patients with severe sepsis or septic shock were included in the study.

Interventions

A modified EGDT protocol was implemented.

Measurements and Main Results

A total of 216 patients were treated with our EGDT protocol, with 32.9% mortality (95% confidence interval [CI], 26.6%-39.2%); 183 patients (84.7%) had septic shock, with a mortality of 34.4% (95% CI, 28%-41%). Our control group of 205 patients had a 27.3% mortality (95% CI, 21.2%-33.5%), of which 123 had septic shock with a mortality of 43.1% (95% CI, 34%-52%). Early goal-directed therapy protocol compliance was as follows: 99% received adequate intravenous fluids, 99% had a central line, 98% had antibiotics in the first 6 hours, 28% had central oxygen saturation measured, 3.7% received dobutamine, and 19% were transfused blood.

Conclusions

Although we found a trend toward decreased mortality in patients with septic shock treated with EGDT, with an absolute difference of 8.7%, this difference was not statistically significant. Compliance with individual elements of the protocol was variable.     

Therapeutic options to improve the microcirculation in sepsis and septic shock

The severe impairment of the microcirculation plays a substantial role in the pathogenesis of severe sepsis and septic shock, and leads to multiple organ failure and death. Therapeutic strategies to resuscitate the microcirculatory blood flow and to improve the functional capillar density are therefore essential to surmount the microcirculatory pathology and to avoid tissue hypoxia. Based on reasonable scientific evidence, early fluid resuscitation directed by defined haemodynamic and metabolic goals (EGDT) as well as the application of activated protein C (rhAPC) according to the guidelines could be recommended. Dobutamine is the first choice to improve cardiac output and to overcome myocardial depression in septic shock whereas phosphodiesterase-III-inhibitors and levosimendane are still experimental options. Furthermore selective inhibitors of iNOS, nitroglycerol, as well as vasopressin have to be investigated relating to their specific effects on the microcirculation and their influence on survival in seevere sepsis and septic shock.     

-反方观点-早期目标导向治疗：对降低病死率并无显著优势

早期目标导向治疗（early goal directed therapy,EGDT）自2001年由Rivers等提出以来,一直被用于严重脓毒症与感染性休克的早期复苏,因其可显著提高危重患者的抢救成功率和改善预后而受到重症医学界的极大关注。近年来,随着EGDT在临床的广泛应用以及多项与之相关的高质量研究的发表,人们发现EGDT在降低病死率方面并无显著优势,甚至还会对患者产生不利影响。     

Effects on management and outcome of severe sepsis and septic shock patients admitted to the intensive care unit after implementation of a sepsis program: a pilot study

Introduction  

The application in clinical practice of evidence-based guidelines for the management of patients with severe sepsis/septic shock is still poor in the emergency department, while little data are available for patients admitted to the intensive care unit (ICU). The aim of this study was to evaluate the effect of an in-hospital sepsis program on the adherence to evidence-based guidelines and outcome of patients with severe sepsis/septic shock admitted to the ICU.     

Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality

OBJECTIVE: The purpose of this study was to examine the outcome implications of implementing a severe sepsis bundle in an emergency department as a quality indicator set with feedback to modify physician behavior related to the early management of severe sepsis and septic shock. DESIGN: Two-year prospective observational cohort. SETTING: Academic tertiary care facility. PATIENTS: Patients were 330 patients presenting to the emergency department who met criteria for severe sepsis or septic shock. INTERVENTIONS: Five quality indicators comprised the bundle for severe sepsis management in the emergency department: a) initiate central venous pressure (CVP)/central venous oxygen saturation (Scvo2) monitoring within 2 hrs; b) give broad-spectrum antibiotics within 4 hrs; c) complete early goal-directed therapy at 6 hrs; d) give corticosteroid if the patient is on vasopressor or if adrenal insufficiency is suspected; and e) monitor for lactate clearance. MEASUREMENTS AND MAIN RESULTS: Patients had a mean age of 63.8 +/- 18.5 yrs, Acute Physiology and Chronic Health Evaluation II score 29.6 +/- 10.6, emergency department length of stay 8.5 +/- 4.4 hrs, hospital length of stay 11.3 +/- 12.9 days, and in-hospital mortality 35.2%. Bundle compliance increased from zero to 51.2% at the end of the study period. During the emergency department stay, patients with the bundle completed received more CVP/Scvo2 monitoring (100.0 vs. 64.8%, p < .01), more antibiotics (100.0 vs. 89.7%, p = .04), and more corticosteroid (29.9 vs. 16.2%, p = .01) compared with patients with the bundle not completed. In a multivariate regression analysis including the five quality indicators, completion of early goal-directed therapy was significantly associated with decreased mortality (odds ratio, 0.36; 95% confidence interval, 0.17-0.79; p = .01). In-hospital mortality was less in patients with the bundle completed compared with patients with the bundle not completed (20.8 vs. 39.5%, p < .01). CONCLUSIONS: Implementation of a severe sepsis bundle using a quality improvement feedback to modify physician behavior in the emergency department setting was feasible and was associated with decreased in-hospital mortality.     

A Blueprint for a Sepsis Protocol

Despite numerous advances in medicine, sepsis remains an unconquered challenge. Although outcomes have improved slightly over decades, the unacceptably high mortality rate of 30%–50% for severe sepsis and septic shock continues. However, after years of unsuccessful clinical trials, several investigations over the last few years have reported survival benefit in the treatment of sepsis. Physicians now have several proven therapies to treat sepsis, but have yet to implement them on a widespread, systematic basis. This led 11 international professional societies spanning multiple specialties and continents to come together to create the Surviving Sepsis Campaign. The product of their work is an international effort organized to improve care of patients with sepsis and includes consensus, evidence‐based guidelines for care that improves survival in septic patients, and an action plan for change. Given the clear role of early identification and treatment in stopping the sepsis cascade, therapy must start early in the emergency department (ED) and continue throughout the hospital course. The first of the recommendations by the Surviving Sepsis Campaign is the aggressive resuscitation strategy of early goal‐directed therapy (EGDT). EGDT is reported to reduce absolute mortality by a staggering 16%. The use of recombinant activated protein C was demonstrated to confer a 6% absolute survival benefit. Steroid supplementation in adrenal insufficiency produced a 10% benefit. Additionally, early and appropriate use of antibiotics remains a cornerstone of therapy. Although no randomized trial will be performed, the effects are undisputed. Finally, although predominantly intensive care unit therapies, tight glucose control and low‐tidal‐volume ventilation strategies have also led to improved survival. Armed with these new therapies, the medical community must rise to this call to action. Clinicians must change the approach to this disease, as well as the way the septic patient is viewed. Although complex and challenging, these therapies must be brought to the patient's bedside. We propose and describe the Multiple Urgent Sepsis Therapies (MUST) protocol as a practical way to implement a comprehensive treatment plan using available evidence‐based therapies.     

An educational course including medical simulation for early goal-directed therapy and the severe sepsis resuscitation bundle: An evaluation for medical student training

Objective

Widespread application of early goal-directed therapy (EGDT) and the severe sepsis resuscitation bundle is limited by clinician knowledge, skills and experience. This study evaluated use of simulation-based teaching during medical training to increase future clinician knowledge in the above therapies for severe sepsis and septic shock.

Methods

A prospective cohort study was performed with medical students at all levels of training. A 5-h course including didactic lectures, skill workshops, and a simulated case scenario of septic shock were administered to the participants. A checklist including 21 tasks was completed during the patient simulation. An 18-question pre-test, post-test and 2-week post-test were given. The participants completed a survey at the end of the course.

Results

Sixty-three students were enrolled. There was statistical difference between the pre-test and each of the post-test scores: 57.5 ± 13.0, 85.6 ± 8.8, and 80.9 ± 10.9%, respectively. 20.6% of participants thought the pre-test was too difficult, whereas all participants thought the post-test was either appropriate or too easy. The task performance during the simulated septic shock patient was 94.1 ± 6.0%. The participants noted improvements in their confidence levels at managing severe sepsis and septic shock, and agreed that the course should be a requirement during medical school training.

Conclusions

Medical simulation is an effective method of educating EGDT and the severe sepsis resuscitation bundle to medical students with limited experience in patient care. The results suggest that our course may be of further benefit at increasing clinical experience with this intensive protocol for the management of severe sepsis and septic shock.     

Early goal-directed therapy: what do we do now?

The meta-analysis of early goal-directed therapy (EGDT) by Gu and colleagues in the previous issue of Critical Care adds to the ongoing controversy about the value of EGDT for resuscitating patients with severe sepsis and septic shock. The results of the ProCESS (protocolized care for early septic shock) and ARISE (Australasian resuscitation in sepsis evaluation) trials failed to demonstrate any benefit of EGDT or protocolized resuscitation when compared with ‘usual care’. The questions are the following: What is ‘usual’ care? What is ‘real world’ care? Do the results of a robust and well-conducted randomized controlled trial - in which many patients may be excluded for a variety of reasons - reflect the care given to patients on a daily basis in our emergency departments and intensive care units? Of course, there are no obvious answers to these questions, and many clinicians look forward to managing these patients without protocols. For now, the data do seem to support the management of patients with septic shock without mandated central lines or protocols. Does this mean we should go back to the era of ‘do whatever you want’? No consensus exists among clinicians regarding optimal hemodynamic monitoring, and to date no method has been proven to be superior. Given the amount of fluids given prior to randomization in the ProCESS and ARISE trials, ‘usual care’ appears to now include aggressive, early fluid resuscitation with at least 20 mL/kg of crystalloid and rapid administration of appropriate antibiotics. Certainly, this reflects the impact of the original trial by Rivers and colleagues and the broad-based implementation of the Surviving Sepsis Campaign Guidelines and bundles. If this continues to define ‘usual care’, then perhaps it is no longer necessary to mandate specific protocols for resuscitation, as it appears that standard sepsis management has evolved to be consistent with published protocols.     

Prompt antibiotic administration and goal-directed hemodynamic support in patients with severe sepsis and septic shock

PURPOSE OF REVIEW: Treatment protocols targeting the rapid administration of appropriate antibiotics and hemodynamic support are now recognized as a key measure in the initial care of patients presenting with severe sepsis and septic shock. Strong evidence exists showing that time parameters, particularly in the emergency department, are as important as the nature of the treatment administered. The concept of sepsis bundles integrates evidence-based and time-sensitive issues, derived from international sepsis guidelines, to ensure that all eligible patients receive the right treatment as early as possible. RECENT FINDINGS: Several studies have demonstrated that patients resuscitated according to sepsis bundles had a significantly lower mortality. SUMMARY: It seems logical that timely and protocolized treatment for patients presenting with severe sepsis and septic shock will impact on outcome. It remains to be shown, however, whether translating evidence into clinical practice will increase adherence to the bundles and positively impact on survival.     

Disease Progression in Hemodynamically Stable Patients Presenting to the Emergency Department With Sepsis

Background: Aggressive diagnosis and treatment of patients presenting to the emergency department (ED) with septic shock has been shown to reduce mortality. To enhance the ability to intervene in patients with lesser illness severity, a better understanding of the natural history of the early progression from simple infection to more severe illness is needed. Objectives: The objectives were to 1) describe the clinical presentation of ED sepsis, including types of infection and causative microorganisms, and 2) determine the incidence, patient characteristics, and mortality associated with early progression to septic shock among ED patients with infection. Methods: This was a multicenter study of adult ED patients with sepsis but no evidence of shock. Multivariable logistic regression was used to identify patient factors for early progression to shock and its association with 30‐day mortality. Results: Of 472 patients not in shock at ED presentation (systolic blood pressure > 90 mm Hg and lactate < 4 mmol/L), 84 (17.8%) progressed to shock within 72 hours. Independent factors associated with early progression to shock included older age, female sex, hyperthermia, anemia, comorbid lung disease, and vascular access device infection. Early progression to shock (vs. no progression) was associated with higher 30‐day mortality (13.1% vs. 3.1%, odds ratio [OR] = 4.72, 95% confidence interval [CI] = 2.01 to 11.1; p ≤ 0.001). Among 379 patients with uncomplicated sepsis (i.e., no evidence of shock or any end‐organ dysfunction), 86 (22.7%) progressed to severe sepsis or shock within 72 hours of hospital admission. Conclusions: A significant portion of ED patients with less severe sepsis progress to severe sepsis or shock within 72 hours. Additional diagnostic approaches are needed to risk stratify and more effectively treat ED patients with sepsis. ACADEMIC EMERGENCY MEDICINE 2010; 17:383–390 © 2010 by the Society for Academic Emergency Medicine     

Early goal-directed therapy: on terminal life support?

Early goal-directed therapy (EGDT) has become regarded as the standard of care for the management of patients with severe sepsis and septic shock. The elements of EGDT have been bundled together as the “Sepsis Bundle,” and compliance with the elements of the bundle is frequently used as an indicator of the quality of care delivered. The major elements of EGDT include fluid resuscitation to achieve a central venous pressure of 8 to 12 cm of water, followed by the transfusion of packed red cells or an inotropic agent to maintain the central venous oxygen saturation higher than 70%. Although the concept of early resuscitation is a scientifically sound concept, we believe that the major elements of the sepsis bundle are fatally flawed.     

One year mortality of patients treated with an emergency department based early goal directed therapy protocol for severe sepsis and septic shock: a before and after study

Introduction  

Early structured resuscitation of severe sepsis has been suggested to improve short term mortality; however, no previous study has examined the long-term effect of this therapy. We sought to determine one year outcomes associated with implementation of early goal directed therapy (EGDT) in the emergency department (ED) care of sepsis.