IU Indianapolis ScholarWorks :: Browsing by Subject "sepsis"

Browsing by Subject "sepsis"

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Association Between Timing of Antibiotic Administration and Mortality from Septic Shock in Patients Treated with a Quantitative Resuscitation Protocol
(2011-09) Puskarich, Michael A; Trzeciak, Stephen; Shapiro, Nathan I; Arnold, Ryan C; Horton, James M; Studnek, Jonathan R; Kline, Jeffrey A.; Jones, Alan E
Objective We sought to determine the association between time to initial antibiotics and mortality of septic shock patients treated with an emergency department (ED) based early resuscitation protocol. Design Pre-planned analysis of a multicenter randomized controlled trial of early sepsis resuscitation. Setting 3 urban US EDs. Patients Adult septic shock patients. Interventions A quantitative resuscitation protocol in the ED targeting 3 physiological variables: central venous pressure, mean arterial pressure and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all endpoints were achieved or a maximum of 6 hours. Measurements Data on patients who received an initial dose of antibiotics after presentation to the ED were categorized based on both time from triage and time from shock recognition to initiation of antibiotics. The primary outcome was in-hospital mortality. Main Results Of 291 included patients, mortality did not change with hourly delays in antibiotic administration up to 6 hours after triage: 1 hour (OR 1.2, 0.6–2.5), 2 hours (OR 0.71, 0.4–1.3), 3 hours (OR 0.59, 0.3–1.3). Mortality was significantly increased patients who received initial antibiotics after shock recognition (N=172, 59%) compared with before shock recognition (OR 2.4, 1.1–4.5); however, among patients who received antibiotics after shock recognition, mortality did not change with hourly delays in antibiotic administration. Conclusion In this large, prospective study of ED patients with septic shock, we found no increase in mortality with each hour delay to administration of antibiotics after triage. However, delay in antibiotics until after shock recognition was associated with increased mortality.
Cost-Effectiveness of an Emergency Department Based Early Sepsis Resuscitation Protocol
(2011-06) Jones, Alan E; Troyer, Jennifer L; Kline, Jeffrey A.
Background Guidelines recommend that sepsis be treated with an early resuscitation protocol, such as early goal directed therapy (EGDT). Our objective was to assess the cost-effectiveness of implementing EGDT as a routine protocol. Design Prospective before and after study. Setting Large urban hospital ED with >110,000 visits/year. Patients The target population was patients with consensus criteria for septic shock. We excluded those with age <18 yrs, no aggressive care desired, or need for immediate surgery. Interventions Clinical and cost data were prospectively collected on two groups: 1) patients from 1 yr before and 2) 2 yrs after implementing EGDT as standard-of-care. Before phase patients received nonprotocolized care at attending discretion. The primary outcomes were one year mortality, discounted life expectancy, and quality adjusted life years (QALYs). Using costs and QALYs, we constructed an incremental cost-effectiveness ratio and performed a net monetary benefit (NMB) analysis, producing the probability that the intervention was cost-effective given different values for the willingness to pay for a QALY. Results 285 subjects, 79 in the before and 206 in the after phases, were enrolled. Treatment with EGDT was associated with an increased hospital cost of $7028 and an increase in both discounted sepsis-adjusted life expectancy and QALYs of 1.5 and 1.3 yrs, respectively. EGDT use was associated with a cost of $5397 per QALY gained and the NMB analysis indicates a 98% probability (p = .038) that EGDT is cost-effective at a willingness to pay of $50,000 per QALY. Conclusion Implementation of EGDT in the ED care of severe sepsis patients is cost effective.
Disparities in the risk of septic events in patients undergoing splenectomy for hematological malignancies (D‐ROSE‐PUSH): A study based on ACS‐NSQIP database
(Wiley, 2019) Saliba, Antoine N.; Tamim, Hani; Mailhac, Aurelie; Jamali, Faek R.; Taher, Ali T.; Medicine, School of Medicine
The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis
(2008-10) Jones, Alan E; Brown, Michael D; Trzeciak, Stephen; Shapiro, Nathan I; Garrett, John S; Heffner, Alan C; Kline, Jeffrey A.
Objective Quantitative resuscitation consists of structured cardiovascular intervention targeting predefined hemodynamic end points. We sought to measure the treatment effect of quantitative resuscitation on mortality from sepsis. Data Sources We conducted a systematic review of the Cochrane Library, MEDLINE, EMBASE, CINAHL, conference proceedings, clinical practice guidelines, and other sources using a comprehensive strategy. Study Selection We identified randomized control trials comparing quantitative resuscitation with standard resuscitation in adult patients who were diagnosed with sepsis using standard criteria. The primary outcome variable was mortality. Data Abstraction Three authors independently extracted data and assessed study quality using standardized instruments; consensus was reached by conference. Preplanned subgroup analysis required studies to be categorized based on early (at the time of diagnosis) vs. late resuscitation implementation. We used the chi-square test and I2 to assess for statistical heterogeneity (p < 0.10, I2 > 25%). The primary analysis was based on the random effects model to produce pooled odds ratios with 95% confidence intervals. Results The search yielded 29 potential publications; nine studies were included in the final analysis, providing a sample of 1001 patients. The combined results demonstrate a decrease in mortality (odds ratio 0.64, 95% confidence interval 0.43–0.96); however, there was statistically significant heterogeneity (p = 0.07, I2 = 45%). Among the early quantitative resuscitation studies (n = 6) there was minimal heterogeneity (p = 0.40, I2 = 2.4%) and a significant decrease in mortality (odds ratio 0.50, 95% confidence interval 0.37–0.69). The late quantitative resuscitation studies (n = 3) demonstrated no significant effect on mortality (odds ratio 1.16, 95% confidence interval 0.60–2.22). Conclusion This meta-analysis found that applying an early quantitative resuscitation strategy to patients with sepsis imparts a significant reduction in mortality.
Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial
(2010-02) Jones, Alan E; Shapiro, Nathan I; Trzeciak, Stephen; Arnold, Ryan C; Claremont, Heather A; Kline, Jeffrey A.
Context Goal-directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department. Objective To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation (ScvO2) as goals of early sepsis resuscitation. Design, Setting, and Patients Multicenter randomized, noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals. Interventions We randomly assigned patients to 1 of 2 resuscitation protocols. The ScvO2 group was resuscitated to normalize central venous pressure, mean arterial pressure, and ScvO2 of at least 70%; and the lactate clearance group was resuscitated to normalize central venous pressure, mean arterial pressure, and lactate clearance of at least 10%. The study protocol was continued until all goals were achieved or for up to 6 hours. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. Main Outcome Measure The primary outcome was absolute in-hospital mortality rate; the noninferiority threshold was set at Δ equal to −10%. Results Of the 300 patients enrolled, 150 were assigned to each group and patients were well matched by demographic, comorbidities, and physiological features. There were no differences in treatments administered during the initial 72 hours of hospitalization. Thirty-four patients (23%) in the ScvO2 group died while in the hospital (95% confidence interval [CI], 17%-30%) compared with 25 (17%; 95% CI, 11%-24%) in the lactate clearance group. This observed difference between mortality rates did not reach the predefined −10% threshold (intent-to-treat analysis: 95% CI for the 6% difference, −3% to 15%). There were no differences in treatment-related adverse events between the groups. Conclusion Among patients with septic shock who were treated to normalize central venous and mean arterial pressure, additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality.
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
(2009-10) Puskarich, Michael A; Marchick, Michael R; Kline, Jeffrey A.; Steuerwald, Michael T; Jones, Alan E
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) <90 mmHg after a fluid bolus or lactate >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.
Performance of the Mortality in emergency department Sepsis score for predicting hospital mortality among patients with severe sepsis and septic shock
(2008-07) Jones, Alan E; Saak, Kristen; Kline, Jeffrey A.
Objective The aim of the study was to test if the Mortality in Emergency Department Sepsis (MEDS) score accurately predicts death among emergency department (ED) patients with severe sepsis and septic shock. Methods This study was a preplanned secondary analysis of a before-and-after interventional study conducted at a large urban ED. Inclusion criteria were suspected infection, 2 or more criteria for systemic inflammation, and either systolic blood pressure of less than 90 mm Hg after a fluid bolus or lactate 4 mmol/L or higher. Exclusion criteria were: age of less than 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 1 year after implementing early goal-directed therapy (EGDT). The MEDS scores and probabilities of in-hospital death were calculated. The main outcome was in-hospital mortality. The area under the receiver operating characteristic curve was used to evaluate score performance. Results One hundred forty-three patients, 79 pre-EGDT and 64 post-EGDT, were included. The mean age was 58 ± 17 years, and pneumonia was the source of infection in 37%. The in-hospital mortality rate was 23%. The area under the receiver operating characteristic curve for MEDS to predict mortality was 0.61 (95% confidence interval [CI], 0.50-0.72) overall, 0.69 (95% CI, 0.56-0.82) in pre-EGDT patients, and 0.53 (95% CI, 0.33-0.74) in post-EGDT patients. Conclusions The MEDS score performed with poor accuracy for predicting mortality in ED patients with sepsis. These results suggest the need for further validation of the MEDS score before widespread clinical use.
Plasma Levels of Mitochondrial DNA in Patients Presenting to the Emergency Department with Sepsis
(2012-10) Puskarich, Michael A; Shapiro, Nathan I; Trzeciak, Stephen; Kline, Jeffrey A.; Jones, Alan E
Introduction Elevated levels of plasma mitochondrial DNA (mtDNA) have been reported in trauma patients, and may contribute to the systemic immune response. We sought to determine the plasma levels of mtDNA in emergency department (ED) patients with and without sepsis and evaluate their association with severity of illness. Methods Prospective observational study of patients presenting to one of three large, urban, tertiary care EDs. Patients were enrolled into one of three cohorts: 1) sepsis defined as suspected infection and two or more SIRS criteria without hypotension; 2) septic shock defined as sepsis plus hypotension despite an adequate fluid challenge; and 3) control defined as non-infected ED patients without SIRS/hypotension. Plasma levels of three mtDNAs were measured using real-time quantitative PCR. Levels of mtDNAs were compared between the three cohorts and linear regression was used to assess the association between mtDNAs, IL-6, IL-10, and sequential organ failure assessment (SOFA) scores in patients with sepsis. Results We enrolled 93 patients: 24 controls, 29 with sepsis, and 40 with septic shock. As expected, co-morbidities and SOFA score increased across categories. We found no difference in mtDNA levels between the three groups (p = 0.14-0.30). Among patients with sepsis, we found a small but significant negative association between mtDNA level and SOFA score, most clearly with cytochrome b (p=0.03). Conclusions We found no difference in mtDNA levels between controls and patients with sepsis. mtDNA levels were negatively associated with organ dysfunction, suggesting that plasma mtDNA does not significantly contribute to the pathophysiology of sepsis.
Prognostic Value and Agreement of Achieving Lactate Clearance or Central Venous Oxygen Saturation Goals During Early Sepsis Resuscitation
(2012-03) Puskarich, Michael A; Trzeciak, Stephen; Shapiro, Nathan I; Arnold, Ryan C; Heffner, Alan C; Kline, Jeffrey A.; Jones, Alan E
Objectives: Lactate clearance (LC) and central venous oxygen saturation (ScvO2) have been proposed as goals of early sepsis resuscitation. The authors sought to determine the agreement and prognostic value of achieving ScvO2 or LC goals in septic shock patients undergoing emergency department (ED)-based early resuscitation. Methods: This was a preplanned analysis of a multicenter ED randomized controlled trial of early sepsis resuscitation targeting three variables: central venous pressure, mean arterial pressure, and either ScvO2 or LC. Inclusion criteria included suspected infection, two or more systemic inflammation criteria, and either systolic blood pressure of <90 mm Hg after intravenous fluid bolus or lactate level of >4 mmol/L. Both ScvO2 and LC were measured simultaneously. The ScvO2 goal was defined as ≥70%. Lactate was measured at enrollment and every 2 hours until the goal was reached or up to 6 hours. LC goal was defined as a decrease of ≥10% from initial measurement. The primary outcome was in-hospital mortality. Results: A total of 203 subjects were included, with an overall mortality of 19.7%. Achievement of the ScvO2 goal only was associated with a mortality rate of 41% (9/22), while achievement of the LC goal only was associated with a mortality rate of 8% (2/25; proportion difference = 33%; 95% confidence interval [CI] = 9% to 55%). No agreement was found between goal achievement (κ = –0.02), and exact test for matched pairs demonstrated no significant difference between discordant pairs (p = 0.78). Conclusions: No agreement was found between LC and ScvO2 goal achievement in early sepsis resuscitation. Achievement of a ScvO2≥ 70% without LC ≥ 10% was more strongly associated with mortality than achievement of LC ≥ 10% with failure to achieve ScvO2≥ 70%.
Prospective External Validation of the Clinical Effectiveness of an Emergency Department-Based Early Goal-Directed Therapy Protocol for Severe Sepsis and Septic Shock
(2007-08) Jones, Alan E; Focht, Anne; Horton, James M; Kline, Jeffrey A.
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 < 90 mm Hg after a fluid bolus or lactate concentration ≥ 4 mol/L. Exclusion criteria were age < 18 years, contraindication to a chest central venous catheter, and need for immediate surgery. We prospectively recorded preintervention clinical and mortality data on consecutive, eligible patients for 1 year when treatment was at the discretion of board-certified emergency physicians. We then implemented an EGDT protocol (the intervention) and recorded clinical data and mortality rates for 1 year. Prior to the first year, we defined a 33% relative reduction in mortality (relative mortality reduction that was found in the original EGDT trial) to indicate clinical effectiveness of the intervention. 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 < 0.001) and frequency of vasopressor infusion (34% vs 69%, p < 0.001) during the initial resuscitation. In-hospital mortality was 21 of 79 patients (27%) before intervention, compared with 14 of 77 patients (18%) after intervention (absolute difference, − 9%; 95% confidence interval, + 5 to − 21%). 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.

Browsing by Subject "sepsis"

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