Early Goal-directed Therapy Group Research Articles

The Effect of Implementing the Sepsis Early Goal-Directed Therapy (EGDT) Protocol on Patient Mortality in the Hospital ICU in Cairo, Egypt

Introduction: Sepsis is a life-threatening systemic inflammatory syndrome with a high mortality rate. Early goal-directed therapy (EGDT) is a structured therapy protocol that aims to improve tissue perfusion and oxygenation in sepsis patients.
 Methods: This retrospective observational study analyzed data on sepsis patients in the ICU of a Cairo hospital, Egypt (2020-2023). Patient mortality was compared before and after the implementation of the EGDT protocol.
 Results: Of the 220 sepsis patients, 120 were treated before and 100 after EGDT implementation. Patient mortality in the EGDT group was significantly lower (12% vs 25%, p<0.05).
 Conclusion: Implementation of the EGDT protocol can reduce the mortality of sepsis patients in the hospital ICU in Cairo, Egypt.

Early Goal-Directed Therapy Using FloTrac/EV1000 Platform for Hemodynamic Optimization to Improve Perioperative Outcomes in Patients Undergoing Major Abdominal Surgery: A Randomized Controlled Trial

Objective: To compare the efficacy of early goal-directed therapy (EGDT) based on the FloTrac/EV1000 platform versus standard care to improve perioperative outcomes in patients undergoing major abdominal surgery. Materials and Methods: Forty patients undergoing major abdominal surgery were randomized to the Control or EGDT group. The Control group was managed to achieve a mean arterial pressure (MAP) of 65 to 90 mmHg, a central venous pressure of 8 to 12 mmHg, a urine output of 0.5 mL/kg/h or more, and an SpO₂ of more than 95%. The EGDT group was managed to achieve similar goals using information from the FloTrac/ EV1000 platform by receiving fluid to maintain stroke volume variation (SVV) of less than 13%, inotropic drugs to achieve a cardiac index (CI) of 2.2 to 4.0 L/min/m⁻², and/or vasoactive drugs to achieve a systemic vascular resistance index (SVRI) of 1,600 to 2,500 dynes·s/cm⁻⁵/m². Results: There were 20 patients in each group. The EGDT group received more colloid (p=0.035). The MAP and SVRI of both groups were comparable. The SVV of the Control group was higher (p=0.002), while the CI of the EGDT group was higher (p<0.001). The EGDT group had a shorter intubated time and a shorter stay in the ICU, with a mean difference of –3.95 h (95% CI –7.85 to –0.05, p=0.047) and –14.75 h (95% CI –25.38 to –4.12, p=0.008), respectively. The EGDT group had shorter hospital stays, albeit without significance (p=0.273). No postoperative complication was detected. Conclusion: Implementation of EGDT using FloTrac/EV1000, compared to conventional care, in patients undergoing major abdominal surgery results in shorter intubated time and shorter stay in the ICU. The shorter hospital stay did not achieve statistical significance. Keywords: Early goal-directed therapy; Major abdominal surgery; Perioperative outcome; Intubation time; ICU stay; Hospital stay

Early goal directed therapy versus a protocolized resuscitation care in early management of septic shock

ABSTRACT Objective Multicenter studies showed that early goal directed therapy (EGDT) did not improve outcome in patients with septic shock compared with undefined usual care. The aim of this study was to evaluate the efficacy of a protocolized resuscitation care compared to traditional EGDT in early management of septic shock on short-term mortality. Design A randomized controlled trail. Setting Emergency Department and Critical Care Units of Alexandria main university hospital. Patients 100 adult patients of both genders with septic shock. Methods All patients received early fluid resuscitation, empirical broad-spectrum antibiotic therapy and mechanical ventilation if indicated. Then, they were randomly assigned into two groups: Early goal directed therapy (EGDT) group (n = 50) and Protocolized resuscitation care (PRC) group (n = 50). Results EGDT group showed 20% reduction in need for vasopressor than PRC group with significant difference (p = 0.001). PRC group showed lower mortality rate than EGDT group but with no significant difference (p = 0.405). There were no differences in ICU stay, mechanical ventilation days and duration of vasopressor (p= 0.091, 0.243, 0.372 respectively). Conclusion A Protocolized resuscitation care may be beneficial as compared to EGDT in early management of septic shock with a non-significant trend to decrease mortality.

Echocardiography-guided hemodynamic management of severe sepsis and septic shock in adults: a randomized controlled trial

Background: Echocardiography (ECHO) is used to guide septic shock resuscitation, but without evidence for efficacy. Therefore, we compared the outcome of early goal-directed therapy (EGDT) and ECHO-guided management of hemodynamics in severe sepsis and septic shock.
 Methodology: This was a single center, randomized controlled trial conducted on 100 adult patients with severe sepsis or septic shock. Patients were assessed and treated with either EGDT protocol (Group I - EGDT group) or ECHO-guided resuscitation protocol (Group II - ECHO group). 
 Results: Only 87 patients (45 in Group I and 42 in Group II) were analyzed. There was a significant increase of mean norepinephrine and dobutamine use and a significant decrease in total fluids needed in the first 24 h, time to normalization, time to weaning of vasopressors, total mechanical ventilation (MV) days, MV free days and ICU and hospital stay in ECHO group. At 30 days, the mortality rate in EGDT group was 35.6% which was significantly higher compared to 14.3% in the ECHO group. At 90 days, the overall mortality was significantly higher in EGDT group compared to ECHO group (40.0% vs 16.7% respectively). Hazardous ratio of mortality was 1.630 [95% confidence interval (CI): 1.123 - 2.366] and 1.653 (95% CI: 1.137 - 2.404) at 30 and 90 days respectively in EGDT group compared to ECHO group.
 Conclusions: In severe sepsis and septic shock, ECHO-guided management of hemodynamics resulted in a decrease in mortality, lower total fluid intake, higher vasopressor and inotrope support, earlier weaning of vasopressors; and reduced mechanical ventilation days, as well as ICU and hospital stay.
 Keywords: Echocardiography; EGDT; Severe sepsis; Septic Shock; Adults
 Citation: Alhabashy WS, Shalaby OM, Elgebaly AS, Abd El Ghafar MS. Echocardiography-guided hemodynamic management of severe sepsis and septic shock in adults: a randomized controlled trial. Anaesth. pain intensive care 2021;25(6):722–732;
 DOI: 10.35975/apic.v25i6.1694
 Received: June 20, 2021, Reviewed: August 10, 2021, Accepted: August 13, 2021

The cost-effectiveness of early goal-directed therapy: an economic evaluation alongside the ARISE trial

Objective: To determine the cost-effectiveness of early goal-directed therapy (EGDT) for patients with early septic shock.Design: Within-trial cost-effectiveness evaluation.Setting: Nineteen hospitals in Australia and New Zealand.Participants and interventions: Patients with early septic shock enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial were randomly assigned to EGDT versus usual care. A subgroup of patients participated in a nested economic evaluation study in which detailed resource use data were collected until 12 months after randomisation.Outcome measures: Clinical outcomes included lives saved, life-years gained and quality-adjusted life-years (QALYs), with mortality collected until 12 months and health-related quality of life assessed at baseline, 6 and 12 months using the 3-level EuroQol five dimensions questionnaire (EQ-5D-3L). Economic outcomes included health care resource use, costs and cost-effectiveness from the Australian health care payer perspective.Results: A total of 205 patients (100 EGDT, 105 usual care) participated in the nested economic evaluation study, of which 203 had complete resource use data. Unadjusted mean health care costs to 12 months were $67 223 (standard deviation [SD], $72 397) in the EGDT group and $54 179 (SD, $61 980) in the usual care group, with a mean difference of $13 044 (95% CI, –$5791 to $31 878). There was no difference between groups with regards to lives saved (EGDT, 69.4% v usual care, 68.6%; P = 1.0), life-years gained (mean EGDT, 0.746 [SD, 0.406] v usual care, 0.725 [SD, 0.417]; P = 0.72) or QALYs (mean EGDT, 0.318 [SD, 0.291] v usual care, 0.367 [SD, 0.295]; P = 0.24). EGDT was dominated (higher costs, lower effectiveness) by usual care in 80.4% of bootstrap replications. For a willingness-to-pay threshold of $50 000 per QALY, the probability of EGDT being cost-effective was only 6.4%.Conclusions: In patients presenting to the emergency department with early septic shock, EGDT compared with usual care was not cost-effective.Clinical trial registration:ClinicalTrials.gov number NCT00975793.

Efficacy of Intraoperative Hemodynamic Optimization Using FloTrac/EV1000 Platform for Early Goal-Directed Therapy to Improve Postoperative Outcomes in Patients Undergoing Coronary Artery Bypass Graft with Cardiopulmonary Bypass: A Randomized Controlled Trial.

PurposeEarly goal-directed therapy (EGDT) using the FloTrac system reportedly improved postoperative outcomes among high-risk patients undergoing non-cardiac surgery. This study’s objective was to evaluate the FloTrac/EV1000 platform’s efficacy for improving postoperative outcomes in cardiac surgery.Patients and MethodsEighty-six adults undergoing coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB) in 2 tertiary referral centers were randomized to the EGDT or Control group. The Control group was managed with standard care to achieve the following goals: mean arterial pressure 65–90 mmHg; central venous pressure 8–12 mmHg; urine output ≥0.5 mL·kg−1·h−1; oxygen saturation >95%; and hematocrit 26–30%. The EGDT group was managed to reach similar goals using information from the FloTrac/EV1000 monitor. The targets were stroke volume variation <13%; stroke volume index 33–65 mL·beat−1·m−2; cardiac index 2.2–4.0 L·min−1·m−2; and systemic vascular resistance index 1600–2500 dynes·s·cm-5·m-2.ResultsThe intensive care unit (ICU) stay of the EGDT group was significantly shorter (mean difference −29.5 h; 95% CI −17.2 to −41.8, P < 0.001). The mechanical ventilation time was also shorter in the EGDT group (mean difference −11.3 h; 95% CI −2.7 to −19.9, P = 0.011). The hospital LOS was shorter in the EGDT group (mean difference −1.1 d; 95% CI −0.1 to −2.1, P = 0.038).ConclusionEGDT using FloTrac/EV1000 can be applied in CABG with CPB to improve postoperative outcomes.

Feasibility and beneficial effects of an early goal directed therapy after cardiac arrest: evaluation by conductance method

Although beneficial effects of an early goal directed therapy (EGDT) after cardiac arrest and successful return of spontaneous circulation (ROSC) have been described, clinical implementation in this period seems rather difficult. The aim of the present study was to investigate the feasibility and the impact of EGDT on myocardial damage and function after cardiac resuscitation. A translational pig model which has been carefully adapted to the clinical setting was employed. After 8 min of cardiac arrest and successful ROSC, pigs were randomized to receive either EGDT (EGDT group) or therapy by random computer-controlled hemodynamic thresholds (noEGDT group). Therapeutic algorithms included blood gas analysis, conductance catheter method, thermodilution cardiac output and transesophageal echocardiography. Twenty-one animals achieved successful ROSC of which 13 pigs survived the whole experimental period and could be included into final analysis. cTnT and LDH concentrations were lower in the EGDT group without reaching statistical significance. Comparison of lactate concentrations between 1 and 8 h after ROSC exhibited a decrease to nearly baseline levels within the EGDT group (1 h vs 8 h: 7.9 vs. 1.7 mmol/l, P < 0.01), while in the noEGDT group lactate concentrations did not significantly decrease. The EGDT group revealed a higher initial need for fluids (P < 0.05) and less epinephrine administration (P < 0.05) post ROSC. Conductance method determined significant higher values for preload recruitable stroke work, ejection fraction and maximum rate of pressure change in the ventricle for the EGDT group. EGDT after cardiac arrest is associated with a significant decrease of lactate levels to nearly baseline and is able to improve systolic myocardial function. Although the results of our study suggest that implementation of an EGDT algorithm for post cardiac arrest care seems feasible, the impact and implementation of EGDT algorithms after cardiac arrest need to be further investigated.

Inferior vena cava diameter combined with lung ultrasound B-line score to guide fluid resuscitation in patients with septic shock

To compare the effect of goal-directed fluid resuscitation and bedside ultrasound-guided fluid resuscitation in patients with septic shock, and to evaluate the application value of bedside ultrasound in fluid resuscitation of patients with septic shock. Forty patients with septic shock admitted to department of critical care medicine of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2018 to October 2019 were enrolled, and they were divided into early goal-directed therapy (EGDT) group and ultrasound group according to random number table, with 20 patients in each group. Bacterial cultures were routinely performed, and all patients received conventional treatments, such as anti-infection, nutritional support and organ support. All patients were given initial fluid resuscitation (30 mL/kg). The patients in the EGDT group continued to be given fluid resuscitation according to the guidelines (EGDT 6-hour target) after the initial fluid resuscitation. The patients in the ultrasound group were given follow-up fluid resuscitation based on bedside ultrasound inferior vena cava diameter and lung ultrasound B-line score after initial fluid resuscitation. The general data, main laboratory indexes and efficacy indexes of the two groups were compared, including 6-hour blood pressure achieved rate [mean arterial pressure (MAP) ≥ 65 mmHg (1 mmHg = 0.133 kPa) was defined as blood pressure reaching standard], 24-hour resuscitation fluid volume, 24-hour norepinephrine (NE) consumption, 24-hour oxygenation index (PaO2/FiO2) and 24-hour clearance of lactic acid (LCR) were compared between the two groups. The survival curve of intensive care unit (ICU) was drawn by Kaplan-Meier analysis. There was no significant difference in the gender, age, heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), underlying diseases, sequential organ failure assessment (SOFA) score, PaO2/FiO2, blood lactic acid (Lac), D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), total bilirubin (TBil) and serum creatinine (SCr) baselines at admission between the two groups. There was also no significant difference in the 6-hour target blood pressure achieved rate [65.0% (13/20) vs. 70.0% (14/20)], 24-hour total NE dosage [mg: 20.0 (10.0, 66.5) vs. 30.0 (10.5, 85.0)], 24-hour PaO2/FiO2 (mmHg: 274.6±123.8 vs. 243.1±124.0) or 24-hour LCR [9.1% (-34.5%, 58.0%) vs. 44.0% (-24.1%, 81.3%)] between the EGDT group and ultrasound group (all P > 0.05), but the 24-hour total fluid infusion in the ultrasound group was significantly less than that in the EGDT group (mL: 2 783.1±704.2 vs. 3 692.0±1 433.1, P < 0.05). The Kaplan-Meier survival curve showed that the cumulative survival rate of ICU between the two groups was not statistically significant (Log-Rank test: χ2 = 0.088, P = 0.767). Bedside ultrasound protocol combined inferior vena cava diameter with lung ultrasound B-line score can be used to guide fluid resuscitation in patients with septic shock, the total fluid infusion is decreased and the risk of oxygenation deterioration is reduced.

Effect of different fluid resuscitation strategies on renal function in patients with septic shock induced acute kidney injury

To compare the therapeutic effect of fluid resuscitation strategy guided by pulse-indicated continuous cardiac output (PiCCO) monitoring and early goal-directed therapy (EGDT) on renal function of acute kidney injury (AKI) patients caused by septic shock. Septic shock patients with AKI admitted to the intensive care unit (ICU) of Tianjin Fifth Central Hospital and Teda International Cardiovascular Hospital from March 2017 to February 2020 were enrolled. All patients were given fluid resuscitation. Patients were divided into PiCCO-guided fluid resuscitation group [PiCCO group, intrathoracic blood volume index (ITBVI) was maintained between 850-1 000 mL/m2] and EGDT-guided fluid resuscitation group [EGDT group, central venous pressure (CVP) was maintained between 8-12 mmHg (1 mmHg = 0.133 kPa) or CVP ≤ 15 mmHg when patients received mechanical ventilation (MV)] according to both the patient's condition and the informed consent of the patient's family. The changes of heart rate (HR), mean arterial pressure (MAP), CVP, blood lactic acid (Lac), fluid balance, urine volume and serum creatinine (SCr) at 6, 24, and 48 hours after fluid resuscitation in the two groups were observed, and the renal replacement therapy (RRT), duration of MV, length of ICU stay and 28-day mortality between the two group were compared. (1) A total of 94 patients were enrolled, including 51 in the EGDT group and 43 in the PiCCO group. There was no significant difference in gender, age, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, procalcitonin (PCT), HR, MAP, CVP, Lac or SCr at ICU admission between the two groups. (2) The parameters of hemodynamics, fluid balance, urine volume and SCr were improved with the time of resuscitation in the two groups, and there was no significant difference in HR, MAP or Lac between the two groups. Compared with the EGDT group, the CVP decreased significantly at 24 hours and 48 hours after fluid resuscitation in the PiCCO group (mmHg: 9.1±0.9 vs. 12.0±1.3 at 24 hours, 8.0±1.0 vs. 10.2±1.3 at 48 hours), the fluid balance significantly decreased (mL: 2 929.8±936.3 vs. 3 898.4±923.5 at 24 hours, 3 143.5±1 325.4 vs. 4 843.8±1 326.7 at 48 hours), and the condition of urine volume and SCr were better in the PiCCO group [urine volume (mL×kg-1×h-1): 1.02±0.21 vs. 0.79±0.14 at 24 hours, 1.28±0.18 vs. 0.94±0.22 at 48 hours; SCr (μmol/L): 145.7±37.6 vs. 164.3±46.4 at 24 hours, 128.4±33.6 vs. 143.5±37.7 at 48 hours), with significant differences (all P < 0.05). (3) Compared with the EGDT group, the rate of RRT in the PiCCO group was lower [11.6% (5/43) vs. 17.6% (9/51)], the duration of MV and the length of ICU stay were shorter [duration of MV (days): 4.64±1.31 vs. 6.50±2.19, length of ICU stay (days): 10.35±3.50 vs. 14.50±5.78), with significant differences (all P < 0.05). There was no significant difference in the 28-day mortality between the PiCCO group and EGDT group [14.0% (6/43) vs. 15.7% (8/51), P > 0.05]. Fluid resuscitation strategy guided by PiCCO in septic shock patients with AKI can reduce the amount of fluid load, improve renal function, shorten the MV duration and length of ICU stay, and shows clinical significance.

Transthoracic echocardiographic versus cardiometry derived indices in management of septic patients

ABSTRACT Background: Sepsis and sepsis shock are leading causes of mortality around the world. Early identification, proper management and close monitoring are associated with improved patient outcomes. Echocardiography allows proper monitoring of fluid-guided therapy and early identification of patients requiring vasopressors and inotropic drugs, although it requires special training and has some limitations. This study aims to compare echocardiography (echo) derived indices to cardiometry-derived indices in management of septic patients. Methods: This prospective, randomized study was carried out on 90 patients with sepsis. The patients were divided into three groups: cardiometry group, which included those who underwent evaluation by the electrical cardiometry monitor; echo group, which included patients who underwent resting transthoracic echocardiography; and early goal-directed therapy (EGDT) group, which included those who received intravenous fluid. Thirty-day mortality was recorded, in addition to total infused fluid, total dose of vasopressor and inotrope, mechanical ventilation (MV) duration, and the intensive care unit (ICU) and hospital stay period. Results: Mortality in echo and cardiometry-guided therapy was significantly lower than in the EGDT group. There was significantly higher norepinephrine and dobutamine doses, prolonged time to weaning of vasopressors, MV, longer ICU and hospital stay duration in echo and cardiometry groups compared to the EGDT group. On the other hand, all measurements were comparable in echo and cardiometry groups. Conclusion: Evidence supports the usefulness of echocardiogram-guided treatment, similar to cardiometry hemodynamic management. However, cardiometry showed the advantage of being a simple and noninvasive technique that does not require a trained cardiologist. Trial registration: Pan African clinical trial registry on 08/05/2019 with unique identification number: PACTR201911842779294.

Comparative study on the outcome of Early Goal Directed Therapy (EGDT) versus standard care in pediatric septic shock patients: A prospective open labeled randomized controlled trial

Background : Sepsis in children is a noteworthy cause of morbidity and mortality all over the world. Given the crucial need to reduce the mortality from sepsis, conflicting results from adult studies and lack of high quality pediatric controlled study warrant a trial to examine the effectiveness of early goal directed therapy (EGDT) versus standard care in Indian patients. Methods : The trial was a prospective open labeled randomized controlled trial conducted from 1st July 2015 to 30th June 2017. All children from one month of age to 12 years with septic shock fulfilling the inclusion criteria were enrolled in the study. Eligible patients were randomized and allocated one of the two study groups (EGDT Group and standard care group). If the patient was assigned to EGDT, the EGDT protocol adapted from Rivers et al. was commenced by the treating team within one hour of enrollment. If the patient was assigned to standard care, no changes were made to the plan of the treating team. Results : The 110 patients were recruited from July 2015 to June 2017. Out of 110 patients, 54 patients were randomized to the EGDT group and 56 randomized to the standard care group. The trial had to be stopped after an interim analysis by the independent data monitoring committee indicated the futility of the study. The overall all-cause mortality at 28 days of the study population was 53.6%. Children in the EGDT group had 46.3% mortality while children in the standard care group had 60.7% mortality (p=0.13). There was 14.4% absolute risk reduction of mortality in the EGDT group. There was no difference in any secondary outcome regarding the proportion of patients achieving therapeutic end points at 6 hours, use and duration of organ support, SOFA and PeLOD score and length of PICU and hospital stay. Conclusion : Our study suggests that the implementation of the early goal directed therapy (EGDT) by the addition of intermittent ScvO2 monitoring and protocolized management did not improve mortality in the EGDT group compared to standard care group. The implementation of EGDT needed the greater intensity of treatment in the form of inotrope and packed RBCs transfusion requirement.

Early outcome of early-goal directed therapy for patients with sepsis or septic shock: a systematic review and meta-analysis of randomized controlled trials.

Various trials and meta-analyses have reported conflicting results concerning the application of early goal-directed therapy (EGDT) for sepsis and septic shock. The aim of this study was to update the evidence by performing a systematic review and meta-analysis. Multiple databases were searched from initial through August, 2016 for randomized controlled trials (RCTs) which investigated the associations between the use of EGDT and mortality in patients with sepsis or septic shock. Meta-analysis was performed using random-effects model and heterogeneity was examined through subgroup analyses. The primary outcome of interest was patient all-cause mortality including hospital or ICU mortality. Seventeen RCTs including 6207 participants with 3234 in the EGDT group and 2973 in the control group were eligible for this study. Meta-analysis showed that EGDT did not significantly reduce hospital or intensive care unit (ICU) mortality (relative risk [RR] 0.89, 95% CI 0.78 to 1.02) compared with control group for patients with sepsis or septic shock. The findings of subgroup analyses stratified by study region, number of research center, year of enrollment, clinical setting, sample size, timing of EGDT almost remained constant with that of the primary analysis. Our findings provide evidence that EGDT offers neutral survival effects for patients with sepsis or septic shock. Further meta-analyses based on larger well-designed RCTs or individual patient data meta-analysis are required to explore the survival benefits of EDGT in patients with sepsis or septic shock.

The effect of early goal-directed therapy for treatment of severe sepsis or septic shock: A systemic review and meta-analysis

PurposeTo assess the effects of early goal-directed therapy (EGDT) on reducing mortality compared with conventional management of severe sepsis or septic shock. Materials and methodsWe included a systemic review, using the Medline and EMBASE. Seventeen randomized trials with 5765 patients comparing EGDT with usual care were included. ResultsThere were no significant differences in mortality between EGDT and control groups (relative risk [RR], 0.89; 95% confidence interval [CI], 0.79-1.00), with moderate heterogeneity (I2=56%). The EGDT was associated with lower mortality rates when the mortality rate of the usual care group was greater than 30% (12 trials; RR, 0.83; 95% CI, 0.72-0.96), but not when the mortality rate in the usual care group was less than 30% (5 trials; RR, 1.03; 95% CI, 0.92-1.16). The mortality benefit was seen only in subgroup of population analyzed between publication of the 2004 and 2012 Surviving Sepsis Campaign guidelines, but not before and after these publications. ConclusionThis meta-analysis was heavily influenced by the recent addition of the trio of trials published after 2014. The results of the recent trio of trials may be biased due to methodological issues. This includes lack of blinding by incorporating similar diagnostic and therapeutic interventions as the original EGDT trial.

The Effect of Early Goal-Directed Therapy on Outcome in Adult Severe Sepsis and Septic Shock Patients: A Meta-Analysis of Randomized Clinical Trials.

Whether early goal-directed therapy (EGDT) improves outcome in severe sepsis and septic shock remains unclear. We performed a meta-analysis of existing clinical trials to examine whether EGDT improved outcome in the resuscitation of adult sepsis patients compared with control care. We searched for eligible studies using MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials, and Web of Science databases. Studies were eligible if they compared the effects of EGDT versus control care on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Data including mortality, sample size of the patients with severe sepsis and septic shock, and resuscitation end points were extracted. Data were analyzed using methods recommended by the Cochrane Collaboration Review Manager 4.2 software. Random errors were evaluated by trial sequential analysis (TSA). Nine studies compared EGDT with control care, and 5202 severe sepsis and septic shock patients were included. A nonsignificant trend toward reduction in the longest all-cause mortality was observed in the EGDT group compared with control care (relative risk, 0.89; 99% confidence interval, 0.74-1.07; P = 0.10). However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients (relative risk, 0.72; 99% confidence interval, 0.57-0.90; P = 0.0002). TSA indicated lack of firm evidence for a beneficial effect. In this meta-analysis, a nonsignificant trend toward reduction in the longest all-cause mortality in patients resuscitated with EGDT was noted. However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients. TSA indicated a lack of firm evidence for the results. More powered, randomized controlled trials are needed to determine the effects.

Early goal-directed resuscitation for patients with severe sepsis and septic shock: a meta-analysis and trial sequential analysis.

BackgroundThe aim of this study was to explore whether early goal-directed therapy (EGDT) was associated with a lower mortality rate in comparison to usual care in patients with severe sepsis and septic shock.MethodsPubMed, EMBASE, Cochrane library and a Chinese database (SinoMed) were searched systematically to identify randomized controlled trials (RCTs) comparing standard EGDT with usual care in resuscitation of patients with severe sepsis and septic shock and the search time could date back to the publication of the study by Rivers in 2001. The study selection, data extraction and methodological evaluation were performed by two investigators independently. The primary outcome was all-cause mortality. The present meta-analysis had been registered in PROSPERO (CRD42015017667).ResultsOur meta-analysis identified 6 studies and enrolling 4336 patients. There was no significant difference in mortality between the two groups, and the pooled odds ratio (OR) was 0.83 (95 % confident interval, CI, 0.64–1.08) with significant heterogeneity (p = 0.02, I2 = 64 %). However, the pooled OR of 3 multicenter RCTs was 1.03 (95 % CI, 0.89–1.21) with no heterogeneity (p = 0.78, I2 = 0 %). The effects of EGDT on length of stay in the emergency department and intensive care unit were uncertain, and there was no effect of EGDT on hospital length of stay. There were no differences of mechanical ventilation rate and renal replacement therapy rate between the two groups, and patients in the EGDT group were more admitted in ICU than patients in the control group. During the early 6-h intervention period, patients in the EGDT group received more intravenous fluids, had a higher vasopressor usage rate, higher dobutamine usage rate and higher blood transfusion rate, than patients in the control group. Finally, there was no difference in the incidence of adverse events between the two groups, and the pooled OR was 1.06 (95%CI 0.80–1.39) with moderate heterogeneity (I2 = 62 %, p = 0.07).DiscussionOur meta-analysis showed that the application of EGDT was not associated with lower mortality rate currently. However it does not mean that it is useless of EGDT in patients with sever sepsis and septic shock. On the contrary, there was no difference in mortality rate between the two groups may be due to the improvement of therapeutic strategies in these patients. And the results may be related to the different compliance rate of EGDT resuscitation bundle.ConclusionsThe current evidence does not support the significant advantage of Early goal-directed therapy (EGDT) in the resuscitation of patients with severe sepsis and septic shock.Electronic supplementary materialThe online version of this article (doi:10.1186/s13049-016-0214-7) contains supplementary material, which is available to authorized users.

Effect of early goal-directed therapy on mortality in patients with severe sepsis or septic shock: a meta-analysis of randomised controlled trials

ObjectiveTo determine whether patients with severe sepsis or septic shock could benefit from a strict and early goal-directed therapy (EGDT) protocol recommended by Surviving Sepsis Campaign (SSC) Guidelines.MethodsMEDLINE/PubMed, EMBASE/OVID and...

The effect of early goal-directed therapy on mortality in patients with severe sepsis and septic shock: a meta-analysis

BackgroundThe Surviving Sepsis Campaign has recommended early goal-directed therapy (EGDT) as an essential strategy to decrease mortality among patients with severe sepsis and septic shock. However, three latest multicenter trials failed to show its benefit in the patients with severe sepsis and septic shock. This article was to evaluate the effect of EGDT on the mortality of patients with severe sepsis and septic shock. MethodsRelevant studies from PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were identified from January 1, 2001 to June 13, 2015. With both randomized controlled trials (RCTs) and non-RCTs selected, a meta-analysis on the effects of EGDT on all identified trials was performed. The primary outcome was the inhospital mortality. In subgroup, RCTs and non-RCTs were analyzed, respectively. ResultsA total of five RCTs and 10 non-RCTs involving 3285 patients in EGDT group and 3233 patients in the control group were identified. Pooled analyses of all studies showed significant difference in the inhospital mortality between the EGDT group and the control group (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.74–0.94; P = 0.003) with substantial heterogeneity (χ2 = 24.93, P = 0.04, I2 = 44%). In subgroup analysis, there were no significant difference in inhospital mortality between the EGDT group and the control group (RR, 0.95; 95% CI, 0.83–1.10; P = 0.51) with no significant difference in heterogeneity (χ2 = 6.62, P = 0.16, I2 = 40%) in RCTs. In non-RCTs, EGDT significantly reduced inhospital mortality (RR, 0.75; 95% CI, 0.65–0.88; P = 0.0003) with no significant difference in heterogeneity (χ2 = 11.96, P = 0.22, I2 = 25%). ConclusionsThis meta-analysis suggests that EGDT can significantly reduce the mortality among patients with severe sepsis and septic shock.

Management of septic shock: a protocol-less approach.

Expanded abstractCitationProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014; 370:1683–93.BackgroundIn a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-h protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets including central venous pressure, central venous oxygen saturation, and indirect estimates of cardiac output, than among those receiving usual care.MethodsObjective: The objective was to determine whether these EGDT findings were generalizable and whether all aspects of the EGDT protocol were necessary to achieve those outcomes.Design: A multicenter randomized three-arm controlled trial.Setting: Thirty-one academic emergency departments in the United States.Subjects: Patients older than 18 years of age presenting to the emergency department with septic shock.Intervention: Patients were assigned to one of three groups for 6 h of resuscitation: protocol-based EGDT as defined by River and colleagues; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; and usual care which mandated no specific monitoring or management approaches.Outcomes: The primary end point was 60-day in-hospital mortality. Also tested sequentially was whether protocol-based care (EGDT and standard therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support.ResultsA total of 1,351 patients were enrolled, of whom 1,341 were evaluable due to patient/family request: 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and central venous oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0 %), 81 in the protocol-based standard therapy group (18.2 %), and 86 in the usual care group (18.9 %) (relative risk with protocol-based therapy versus usual care, 1.04; 95 % confidence interval, 0.82 to 1.31; P = 0.83; relative risk with protocol-based EGDT versus protocol-based standard therapy, 1.15; 95 % CI, 0.88 to 1.51; P = 0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support.ConclusionsIn a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes.

Improvement effect of early goal-directed therapy on the prognosis in patients with septic shock

Improvement effect of early goal-directed therapy on the prognosis in patients with septic shock

Clinical Outcomes of Early Goal-Directed Therapy vs Usual Care for Patients With Early Septic Shock: A Meta-analysis of Randomized Controlled Trials

SESSION TITLE: Sepsis and Shock Posters SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: Early goal-directed therapy (EGDT) has been endorsed as a key therapeutic strategy in the management of early septic shock aiming to improve survival and reduce length of hospitalization. However; evidence is conflicting regarding the efficacy of EGDT compared to usual care. METHODS: A systematic literature review identified publications of randomized controlled trials (RCT) evaluating EGDT in early septic shock were used to obtain data. Odds ratios (OR) and 95% confidence intervals (CI) computed using the Mantel-Haenszel method. Random effect model was used in the analysis of all variables as they were heterogeneous. Publication bias was tested by funnel plot and Egger's regression. RESULTS: Four RCT involving 3999 patients were included in the meta-analysis. Compared to usual-care group, patients who assigned to the EGDT group showed no significant difference in the rate of in-hospital mortality (OR 0.92; 95% CI, 0.72 - 1.19, P = 0.53, I2 = 59.11), 28 days mortality (OR 0.84; 95% CI, 0.62 - 1.15, P = 0.28, I2 = 62.07), 90 days mortality (OR 0.91; 95% CI, 0.76- 1.10, P = 0.34, I2 = 36.54), respiratory support (OR 1.05; 95% CI, 0.88-1.26, P = 0.59, I2 = 37.72), and the rate of renal support (OR 1.04; 95% CI, 0.84- 1.28, P = 0.7433, I2 = 0.00). However; there is significant difference in the rate of cardiovascular support as more support was needed in EGDT group (OR 1.41; 95% CI, 1.170-1.691, P = 0.00029, I2 = 43.57). CONCLUSIONS: In patients presented with early septic shock, the implementation of EGDT was not superior to usual care in improving in-hospital mortality, 28 days mortality, 90 days mortality, respiratory and renal support. Patients in the EGDT group required more cardiovascular support. CLINICAL IMPLICATIONS: This analysis demonstrated that EGDT has not reduced mortality as compared to usual care in patients with early septic shock. This raise the question on whether EGDT implementation will remain the base of treatment for severe sepsis. DISCLOSURE: The following authors have nothing to disclose: Mohsin Salih, Mohamed Ayan, Mlatoum Hamza, Moataz Gaddor, Mohamed Gashouta, Erika Leung, George Mansour, Haitham AlAshry, Mahmoud Traina No Product/Research Disclosure Information