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Alan E Jones - One of the best experts on this subject based on the ideXlab platform.

  • the impact of emergency medical services on the ed care of severe sepsis
    American Journal of Emergency Medicine, 2012
    Co-Authors: Jonathan R Studnek, Melanie R Artho, Craymon L Garner, Alan E Jones
    Abstract:

    Abstract Objective The identification and treatment of critical illness is often initiated by emergency medical services (EMS) providers. We hypothesized that emergency department (ED) patients with severe sepsis who received EMS care had more rapid recognition and treatment compared to non-EMS patients. Methods This was a prospective observational study of ED patients with severe sepsis treated with Early Goal-Directed Therapy (EGDT).We included adults with suspected infection, evidence of systemic inflammation, and either hypotension after a fluid bolus or elevated lactate. Prehospital and ED clinical variables and outcomes data were collected. The primary outcome was time to initiation of antibiotics in the ED. Results There were 311 patients, with 160 (51.4%) transported by EMS. Emergency medical services–transported patients had more organ failure (Sequential Organ Failure Assessment score, 7.0 vs 6.1; P = .02), shorter time to first antibiotics (111 vs 146 minutes, P = .001), and shorter time from triage to EGDT initiation (119 vs 160 minutes, P = .005) compared to non–EMS-transported patients. Among EMS patients, if the EMS provider indicated a written impression of sepsis, there was a shorter time to antibiotics (70 vs 122 minutes, P = .003) and a shorter time to EGDT initiation (69 vs 131 minutes, P = .001) compared to those without an impression of sepsis. Conclusions In this prospective cohort, EMS provided initial care for half of the patients with severe sepsis requiring EGDT. Patients presented by EMS had more organ failure and a shorter time to both antibiotic and EGDT initiation in the ED.

  • multicenter study of central venous oxygen saturation scvo2 as a predictor of mortality in patients with sepsis
    Annals of Emergency Medicine, 2010
    Co-Authors: Jennifer V Pope, Alan E Jones, David F Gaieski, Stephen Trzeciak, Ryan C Arnold, Nathan I Shapiro
    Abstract:

    Study objective Abnormal (both low and high) central venous saturation (ScvO 2 ) is associated with increased mortality in emergency department (ED) patients with suspected sepsis. Methods This was a secondary analysis of 4 prospectively collected registries of ED patients treated with Early Goal-Directed Therapy–based sepsis resuscitation protocols from 4 urban tertiary care hospitals. Inclusion criteria were sepsis, hypoperfusion defined by systolic blood pressure less than 90 mm Hg or lactate level greater than or equal to 4 mmol/L, and Early Goal-Directed Therapy treatment. ScvO 2 levels were stratified into 3 groups: hypoxia (ScvO 2 2 71% to 89%); and hyperoxia (ScvO 2 90% to 100%). The primary exposures were initial ScvO 2 and maximum ScvO 2 achieved, with the primary outcome as inhospital mortality. Multivariate analysis was performed. Results There were 619 patients who met criteria and were included. For the maximum ScvO 2 , compared with the mortality rate in the normoxia group of 96 of 465 (21%; 95% confidence interval [CI] 17% to 25%), both the hypoxia mortality rate, 25 of 62 (40%; 95% CI 29% to 53%) and hyperoxia mortality rate, 31 of 92 (34%; 95% CI 25% to 44%) were significantly higher, which remained significant in a multivariate modeling. When the initial ScvO 2 measurement was analyzed in a multivariate model, only hyperoxia was significantly higher. Conclusion The maximum ScvO 2 value achieved in the ED (both abnormally low and high) was associated with increased mortality. In multivariate analysis for initial ScvO 2 , the hyperoxia group was associated with increased mortality, but not the hypoxia group. This study suggests that future research aimed at targeting methods to normalize high ScvO 2 values by therapies that improve microcirculatory flow or mitochondrial dysfunction may be warranted.

  • 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
    Critical Care, 2009
    Co-Authors: Michael A Puskarich, Jeffrey A Kline, Michael R Marchick, Michael T Steuerwald, Alan E Jones
    Abstract:

    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. Methods We performed a longitudinal analysis of a prospective before and after study conducted at a large urban ED. Adult patients were enrolled if they had suspected infection, 2 or more systemic inflammatory response criteria, and either systolic blood pressure (SBP) 4 mM. Exclusion criteria were: age <18 years, no aggressive care desired, or need for immediate surgery. Clinical and outcomes data were prospectively collected on consecutive eligible patients for 1 year before and 2 years after implementing EGDT. Patients in the pre-implementation phase received nonprotocolized care at attending physician discretion. The primary outcome was mortality at one year. Results 285 subjects, 79 in the pre- and 206 in the postimplementation phases, were enrolled. Compared to preimplementation, post-implementation subjects had a significantly lower ED SBP (72 vs. 85 mm Hg, P < 0.001) and higher sequential organ failure assessment score (7 vs. 5, P = 0.0004). The primary outcome of 1 year mortality was observed in 39/79 (49%) pre-implementation subjects and 77/206 (37%) post-implementation subjects (difference 12%; P = 0.04). Conclusions Implementation of EGDT for the treatment of ED patients with severe sepsis and septic shock was associated with significantly lower mortality at one year.

  • 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
    Academic Emergency Medicine, 2007
    Co-Authors: Alan E Jones, Nathan I Shapiro, Michael Roshon
    Abstract:

    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.

  • prospective external validation of the clinical effectiveness of an emergency department based Early goal directed Therapy protocol for severe sepsis and septic shock
    Chest, 2007
    Co-Authors: Alan E Jones, Anne Focht, James M Horton, Jeffrey A Kline
    Abstract:

    Objective To determine the clinical effectiveness of implementing Early Goal-Directed Therapy (EGDT) as a routine protocol in the emergency department (ED). Methods Prospective interventional study conducted over 2 years at an urban ED. Inclusion criteria included suspected infection, criteria for systemic inflammation, and either systolic BP Results We enrolled 79 patients in the preintervention year and 77 patients in the postintervention year. Compared with the preintervention year, patients in the postintervention year received significantly greater crystalloid volume (2.54 L vs 4.66 L, p Conclusions Implementation of EGDT in our ED was associated with a 9% absolute (33% relative) mortality reduction. Our data provide external validation of the clinical effectiveness of EGDT to treat sepsis and septic shock in the ED.

Bryant H Nguyen - One of the best experts on this subject based on the ideXlab platform.

  • comparison of predisposition insult infection response and organ dysfunction acute physiology and chronic health evaluation ii and mortality in emergency department sepsis in patients meeting criteria for Early goal directed Therapy and the severe sepsis resuscitation bundle
    Journal of Critical Care, 2012
    Co-Authors: Bryant H Nguyen, Chad Van Ginkel, Michael Batech, Jim E Banta, Stephen W Corbett
    Abstract:

    Abstract Purpose The aim of the study was to examine the performance of the Predisposition, Insult/Infection, Response, and Organ dysfunction (PIRO) model compared with the Acute Physiology and Chronic Health Evaluation (APACHE) II and Mortality in Emergency Department Sepsis (MEDS) scoring systems in predicting in-hospital mortality for patients presenting to the emergency department (ED) with severe sepsis or septic shock. Materials and Methods This study was an analysis of a prospectively maintained registry including adult patients with severe sepsis or septic shock meeting criteria for Early Goal-Directed Therapy and the severe sepsis resuscitation bundle over a 6-year period. The registry contains data on patient demographics, sepsis category, vital signs, laboratory values, ED length of stay, hospital length of stay, physiologic scores, and outcome status. The discrimination and calibration characteristics of PIRO, APACHE II, and MEDS were analyzed. Results Five-hundred forty-one patients with age 63.5 ± 18.5 years were enrolled, 61.9% in septic shock, 46.9% blood-culture positive, and 31.8% in-hospital mortality. Median (25th and 75th percentile) PIRO, APACHE II, and MEDS scores were 6 (5 and 8), 28 (22 and 34), and 12 (9 and 15), with predicted mortalities of 48.5% (40.1 and 63.9), 66.0% (42.0 and 83.0), and 16.0% (9.0 and 39.0), respectively. The area under the receiver operating characteristic curves for PIRO was 0.71 (95% confidence interval, 0.66-0.75); APACHE II, 0.71 (0.66-0.76); and MEDS, 0.63 (0.60-0.70). The standardized mortality ratio was 0.70 (0.08-1.41), 0.70 (−0.46 to 1.80), and 4.00 (−8.53 to 16.62), respectively. Actual mortality significantly increased with increasing PIRO score in patients with APACHE II 25 or more ( P Conclusions The PIRO, APACHE II, and MEDS have variable abilities to Early discriminate and estimate in-hospital mortality of patients presenting to the ED meeting criteria for Early Goal-Directed Therapy and the severe sepsis resuscitation bundle. The PIRO may provide additional risk stratification in patients with APACHE II 25 or more. More studies are required to evaluate the clinical applicability of PIRO in high-risk patients with severe sepsis and septic shock.

  • an educational course including medical simulation for Early goal directed Therapy and the severe sepsis resuscitation bundle an evaluation for medical student training
    Resuscitation, 2009
    Co-Authors: Bryant H Nguyen, Lynda Danielunderwood, Chad Van Ginkel, Melanie Wong, Anthony San Lucas, Janice Palaganas, Daryl P Banta, Kent T Denmark, Kathleen J Clem
    Abstract:

    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.

  • implementation of a bundle of quality indicators for the Early management of severe sepsis and septic shock is associated with decreased mortality
    Critical Care Medicine, 2007
    Co-Authors: Bryant H Nguyen, Jim E Banta, Stephen W Corbett, Thomas Cho, Robert Steele, Robin Clark, Sean R Hayes, Jeremy Edwards, William A Wittlake
    Abstract:

    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. (Crit Care Med 2007; 35:1105‐1112)

  • Early goal directed Therapy in severe sepsis and septic shock revisited concepts controversies and contemporary findings
    Chest, 2006
    Co-Authors: R Otero, David F Gaieski, Munish Goyal, Bryant H Nguyen, David T Huang, Kyle J Gunnerson, Stephen Trzeciak, Robert Sherwin, Christopher V Holthaus, Tiffany M Osborn
    Abstract:

    Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of Therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing Early Goal-Directed Therapy (EGDT) vs standard care was performed using specific criteria for the Early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.

  • severe sepsis and septic shock review of the literature and emergency department management guidelines
    Annals of Emergency Medicine, 2006
    Co-Authors: Bryant H Nguyen, Emanuel P Rivers, David T Huang, Stephen Trzeciak, Tiffany M Osborn, Fredrick M Abrahamian, Gregory J Moran, Edward Abraham, Dennis Stevens, David A Talan
    Abstract:

    Severe sepsis and septic shock are as common and lethal as other acute life-threatening conditions that emergency physicians routinely confront such as acute myocardial infarction, stroke, and trauma. Recent studies have led to a better understanding of the pathogenic mechanisms and the development of new or newly applied therapies. These therapies place Early and aggressive management of severe sepsis and septic shock as integral to improving outcome. This independent review of the literature examines the recent pathogenic, diagnostic, and therapeutic advances in severe sepsis and septic shock for adults, with particular relevance to emergency practice. Recommendations are provided for therapies that have been shown to improve outcomes, including Early Goal-Directed Therapy, Early and appropriate antimicrobials, source control, recombinant human activated protein C, corticosteroids, and low tidal volume mechanical ventilation.

Antonio Pesenti - One of the best experts on this subject based on the ideXlab platform.

  • persistence of central venous oxygen desaturation during Early sepsis is associated with higher mortality a retrospective analysis of the albios trial
    Chest, 2018
    Co-Authors: Alessandro Protti, Serge Masson, Roberto Latini, Roberto Fumagalli, Marilena Romero, Carla Pessina, Giovanni Stefano Pasetti, Gianni Tognoni, Antonio Pesenti
    Abstract:

    Background Relevance of low ( 2 ) during Early sepsis has been recently questioned by three negative trials (Protocol-Based Care for Early Septic Shock, Australasian Resuscitation in Sepsis Evaluation, and Protocolized Management in Sepsis) on Early Goal-Directed Therapy; however, subjects included in those trials had Scvo 2 at enrollment as high as 71 ± 13%, 73 ± 11%, and 70 ± 12%. Here we assess the association between Scvo 2 2 Methods Regardless of treatment assignment (to receive albumin or not), all subjects enrolled in the ALBIOS trial received Early Goal-Directed Therapy aiming for Scvo 2  ≥ 70% at 6 h. Using multivariable logistic regression analyses, we tested the association between Scvo 2 2 Results Scvo 2 2 P  = .007) but not in those with initial Scvo 2  ≥ 70% (OR, 1.25; 95% CI, 0.79-1.95; P  = .357). Scvo 2 Conclusions In the ALBIOS trial, persistence of low Scvo 2 was associated with higher 90-day mortality, possibly because it reflected underlying cardiac dysfunction. Subjects with Scvo 2 Trial Registry ClinicalTrials.gov; No. NCT00707122; URL: www.clinicaltrials.gov.

  • persistence of central venous oxygen desaturation during Early sepsis is associated with higher mortality a retrospective analysis of the albios trial
    Chest, 2018
    Co-Authors: Alessandro Protti, Serge Masson, Roberto Latini, Roberto Fumagalli, Marilena Romero, Carla Pessina, Giovanni Stefano Pasetti, Gianni Tognoni, Antonio Pesenti
    Abstract:

    Background Relevance of low ( Methods Regardless of treatment assignment (to receive albumin or not), all subjects enrolled in the ALBIOS trial received Early Goal-Directed Therapy aiming for Scvo2 ≥ 70% at 6 h. Using multivariable logistic regression analyses, we tested the association between Scvo2  Results Scvo2  Conclusions In the ALBIOS trial, persistence of low Scvo2 was associated with higher 90-day mortality, possibly because it reflected underlying cardiac dysfunction. Subjects with Scvo2  Trial Registry ClinicalTrials.gov; No. NCT00707122; URL: www.clinicaltrials.gov.

Stephen Trzeciak - One of the best experts on this subject based on the ideXlab platform.

  • multicenter study of central venous oxygen saturation scvo2 as a predictor of mortality in patients with sepsis
    Annals of Emergency Medicine, 2010
    Co-Authors: Jennifer V Pope, Alan E Jones, David F Gaieski, Stephen Trzeciak, Ryan C Arnold, Nathan I Shapiro
    Abstract:

    Study objective Abnormal (both low and high) central venous saturation (ScvO 2 ) is associated with increased mortality in emergency department (ED) patients with suspected sepsis. Methods This was a secondary analysis of 4 prospectively collected registries of ED patients treated with Early Goal-Directed Therapy–based sepsis resuscitation protocols from 4 urban tertiary care hospitals. Inclusion criteria were sepsis, hypoperfusion defined by systolic blood pressure less than 90 mm Hg or lactate level greater than or equal to 4 mmol/L, and Early Goal-Directed Therapy treatment. ScvO 2 levels were stratified into 3 groups: hypoxia (ScvO 2 2 71% to 89%); and hyperoxia (ScvO 2 90% to 100%). The primary exposures were initial ScvO 2 and maximum ScvO 2 achieved, with the primary outcome as inhospital mortality. Multivariate analysis was performed. Results There were 619 patients who met criteria and were included. For the maximum ScvO 2 , compared with the mortality rate in the normoxia group of 96 of 465 (21%; 95% confidence interval [CI] 17% to 25%), both the hypoxia mortality rate, 25 of 62 (40%; 95% CI 29% to 53%) and hyperoxia mortality rate, 31 of 92 (34%; 95% CI 25% to 44%) were significantly higher, which remained significant in a multivariate modeling. When the initial ScvO 2 measurement was analyzed in a multivariate model, only hyperoxia was significantly higher. Conclusion The maximum ScvO 2 value achieved in the ED (both abnormally low and high) was associated with increased mortality. In multivariate analysis for initial ScvO 2 , the hyperoxia group was associated with increased mortality, but not the hypoxia group. This study suggests that future research aimed at targeting methods to normalize high ScvO 2 values by therapies that improve microcirculatory flow or mitochondrial dysfunction may be warranted.

  • Early increases in microcirculatory perfusion during protocol directed resuscitation are associated with reduced multi organ failure at 24 h in patients with sepsis
    Intensive Care Medicine, 2008
    Co-Authors: Stephen Trzeciak, Nathan I Shapiro, Phillip R Dellinger, Nicole L Abate, Joseph E Parrillo, Ryan C Arnold, Jonathan V Mccoy, Michael Rizzuto, Steven M Hollenberg
    Abstract:

    Sepsis mortality is closely linked to multi-organ failure, and impaired microcirculatory blood flow is thought to be pivotal in the pathogenesis of sepsis-induced organ failure. We hypothesized that changes in microcirculatory flow during resuscitation are associated with changes in organ failure over the first 24 h of sepsis Therapy. Prospective observational study. Emergency Department and Intensive Care Unit. Septic patients with systolic blood pressure <90 mmHg despite intravenous fluids or lactate ≥4.0 mM/L treated with Early Goal-Directed Therapy (EGDT). We performed Sidestream Dark Field (SDF) videomicroscopy of the sublingual microcirculation <3 h from EGDT initiation and again within a 3–6 h time window after initial. We imaged five sites and determined the mean microcirculatory flow index (MFI) (0 no flow to 3 normal) blinded to all clinical data. We calculated the Sequential Organ Failure Assessment (SOFA) score at 0 and 24 h, and defined improved SOFA a priori as a decrease ≥2 points. Of 33 subjects; 48% improved SOFA over 0–24 h. Age, APACHE II, and global hemodynamics did not differ significantly between organ failure groups. Among SOFA improvers, 88% increased MFI during EGDT, compared to 47% for non-improvers (P = 0.03). Median change in MFI was 0.23 for SOFA improvers versus −0.05 for non-improvers (P = 0.04). Increased microcirculatory flow during resuscitation was associated with reduced organ failure at 24 h without substantial differences in global hemodynamics. These data support the hypothesis that targeting the microcirculation distinct from the macrocirculation could potentially improve organ failure in sepsis.

  • Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock relationship to hemodynamics oxygen transport and survival
    Annals of Emergency Medicine, 2007
    Co-Authors: Stephen Trzeciak, Phillip R Dellinger, Nicole L Abate, Sergio Zanotti, Joseph E Parrillo, Massimiliano Guglielmi, Jasmeet Bajaj, Ryan C Arnold, Susan Colilla, Steven M Hollenberg
    Abstract:

    Study objective To study Early microcirculatory perfusion indices in patients with severe sepsis/septic shock, compare Early microcirculatory indices in sepsis survivors versus nonsurvivors, and identify systemic hemodynamic/oxygen transport variables that correlate with Early microcirculatory perfusion indices. Methods This prospective observational study used orthogonal polarization spectral imaging to directly visualize the sublingual microcirculation in patients with severe sepsis/septic shock treated with Early Goal-Directed Therapy. We performed initial imaging within 6 hours of Early Goal-Directed Therapy initiation and late follow-up studies at 24-hour intervals until death or resolution of organ dysfunction. We imaged 5 sublingual sites and analyzed the data offline in a blinded fashion. We calculated 3 microcirculatory perfusion indices: flow velocity score, flow heterogeneity index, and capillary density. We analyzed Early data to compare survivors versus nonsurvivors and examine correlations with systemic hemodynamic measurements. We used a linear mixed-effects model for longitudinal analyses. Results We performed 66 orthogonal polarization spectral studies in 26 sepsis patients. Early microcirculatory indices were more markedly impaired (lower flow velocity and more heterogeneous perfusion) in nonsurvivors compared with survivors. These same Early indices, flow velocity and heterogeneity, were also more markedly impaired with increasing severity of systemic cardiovascular dysfunction (lower arterial pressure or increasing vasopressor requirement). Conclusion Early microcirculatory perfusion indices in severe sepsis and septic shock are more markedly impaired in nonsurvivors compared with survivors and with increasing severity of global cardiovascular dysfunction.

  • Early goal directed Therapy in severe sepsis and septic shock revisited concepts controversies and contemporary findings
    Chest, 2006
    Co-Authors: R Otero, David F Gaieski, Munish Goyal, Bryant H Nguyen, David T Huang, Kyle J Gunnerson, Stephen Trzeciak, Robert Sherwin, Christopher V Holthaus, Tiffany M Osborn
    Abstract:

    Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of Therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing Early Goal-Directed Therapy (EGDT) vs standard care was performed using specific criteria for the Early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.

  • severe sepsis and septic shock review of the literature and emergency department management guidelines
    Annals of Emergency Medicine, 2006
    Co-Authors: Bryant H Nguyen, Emanuel P Rivers, David T Huang, Stephen Trzeciak, Tiffany M Osborn, Fredrick M Abrahamian, Gregory J Moran, Edward Abraham, Dennis Stevens, David A Talan
    Abstract:

    Severe sepsis and septic shock are as common and lethal as other acute life-threatening conditions that emergency physicians routinely confront such as acute myocardial infarction, stroke, and trauma. Recent studies have led to a better understanding of the pathogenic mechanisms and the development of new or newly applied therapies. These therapies place Early and aggressive management of severe sepsis and septic shock as integral to improving outcome. This independent review of the literature examines the recent pathogenic, diagnostic, and therapeutic advances in severe sepsis and septic shock for adults, with particular relevance to emergency practice. Recommendations are provided for therapies that have been shown to improve outcomes, including Early Goal-Directed Therapy, Early and appropriate antimicrobials, source control, recombinant human activated protein C, corticosteroids, and low tidal volume mechanical ventilation.

Derek C Angus - One of the best experts on this subject based on the ideXlab platform.

  • adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation
    Genes and Immunity, 2019
    Co-Authors: John A Kellum, Derek C Angus, Kate F Kernan, Lina Ghaloulgonzalez, Bita Shakoory, Joseph A Carcillo
    Abstract:

    Post-hoc subgroup analysis of the negative trial of interleukin-1β receptor antagonist (IL1RA) for septic shock suggested that patients with features of macrophage activation syndrome (MAS) experienced a 50% relative risk reduction for mortality with treatment. Here we seek a genetic basis for this differential response. From 1341 patients enrolled in the ProCESS trial of Early goal directed Therapy for septic shock, we selected 6 patients with MAS features and the highest ferritin, for whole exome sequencing (mean 24,030.7 ηg/ml, ±SEM 7,411.1). In total 11 rare (minor allele frequency <5%) pathogenic or likely pathogenic variants causal for the monogenic disorders of Familial Hemophagocytic Lymphohistiocytosis, atypical Hemolytic Uremic Syndrome, Familial Mediterranean Fever, and Cryopyrin-associated Periodic Fever were identified. In these conditions, seven of the identified variants are currently targeted with IL1RA and four with anti-C5 antibody. Gene-targeted precision medicine may benefit this subgroup of patients with septic shock and pathogenic immune variation.

  • Early goal directed Therapy for septic shock a patient level meta analysis
    The New England Journal of Medicine, 2017
    Co-Authors: Prism Investigators, Rinaldo Bellomo, Anthony Delaney, Derek C Angus, Amber E Barnato, Timothy J Coats, Kathryn M Rowan, Michael Bailey, Ruth R Canter, Elizabeth Gimbel
    Abstract:

    BACKGROUND: After a single-center trial and observational studies suggesting that Early, Goal-Directed Therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-Therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS: We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS: In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158.)

  • a systematic review and meta analysis of Early goal directed Therapy for septic shock the arise process and promise investigators
    Intensive Care Medicine, 2015
    Co-Authors: Derek C Angus, Rinaldo Bellomo, Amber E Barnato, Derek Bell, Cherrin Chong, Timothy J Coats, Andrew Ross Davies
    Abstract:

    Purpose To determine whether Early Goal-Directed Therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock.

  • a systematic review and meta analysis of Early goal directed Therapy for septic shock the arise process and promise investigators
    Intensive Care Medicine, 2015
    Co-Authors: Derek C Angus, Rinaldo Bellomo, Amber E Barnato, Derek Bell, Cherrin Chong, Timothy J Coats, Andrew Ross Davies
    Abstract:

    To determine whether Early Goal-Directed Therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2 % [495/2134] versus control: 22.4 % [582/2601]; pooled OR 1.01 [95 % CI 0.88–1.16], P = 0.9, with heterogeneity [I 2 = 57 %; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95 % CI 0.86–1.15), P = 0.93] with no heterogeneity (I 2 = 0.0 %; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95 % CI 1.10–1.41]; P < 0.001) and ICU admission [OR 2.19 (95 % CI 1.82–2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I 2 = 71 %; P < 0.001) but did not change overall results [pooled OR 0.94 (95 % CI 0.82 to 1.07); P = 0.33]. EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

  • implementation of Early goal directed Therapy for severe sepsis and septic shock a decision analysis
    Critical Care Medicine, 2007
    Co-Authors: David Huang, Gilles Clermont, Tony T Dremsizov, Derek C Angus
    Abstract:

    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