Browsing by Author "Arnold, Ryan C"

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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.
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    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.
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    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%.