IU Indianapolis ScholarWorks :: Browsing by Author "Trzeciak, Stephen"

Browsing by Author "Trzeciak, Stephen"

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Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study
(American Heart Association, 2018-05-15) Roberts, Brian W.; Kilgannon, J. Hope; Hunter, Benton R.; Puskarich, Michael A.; Pierce, Lisa; Donnino, Michael; Leary, Marion; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Emergency Medicine, School of Medicine
BACKGROUND: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome. METHODS: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pao2) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pao2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pao2 and poor neurological outcome. To assess whether there was an association between other supranormal Pao2 levels and poor neurological outcome, we used other Pao2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg). RESULTS: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1-23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11-1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02-1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg. CONCLUSIONS: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge.
Association Between Elevated Mean Arterial Blood Pressure and Neurologic Outcome After Resuscitation From Cardiac Arrest: Results From a Multicenter Prospective Cohort Study
(Wolters Kluwer, 2019-01) Roberts, Brian W.; Kilgannon, J. Hope; Hunter, Benton R.; Puskarich, Michael A.; Shea, Lisa; Donnino, Michael; Jones, Christopher; Fuller, Brian M.; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Department of Emergency Medicine
Objective: Laboratory studies suggest elevated blood pressure after resuscitation from cardiac arrest may be protective; however, clinical data are limited. We sought to test the hypothesis that elevated post-resuscitation mean arterial blood pressure (MAP) is associated with neurological outcome. Design: Pre-planned analysis of a prospective cohort study. Setting: Six academic hospitals in the United States. Patients: Adult, non-traumatic cardiac arrest patients treated with targeted temperature management after return of spontaneous circulation (ROSC). Interventions: MAP was measured non-invasively after ROSC and every hour during the initial six hours after ROSC. Measures and Main Results: We calculated the mean MAP and a priori dichotomized subjects into two groups: mean MAP 70–90 and > 90 mmHg. The primary outcome was good neurological function, defined as a modified Rankin Scale (mRS) ≤ 3. The mRS was prospectively determined at hospital discharge. Of the 269 patients included, 159 (59%) had a mean MAP > 90 mmHg. Good neurological function at hospital discharge occurred in 30% of patients in the entire cohort, and was significantly higher in patients with a mean MAP > 90 mmHg (42%) as compared to MAP 70–90 mmHg (15%) [absolute risk difference 27% (95% CI 17%−37%)]. In a multivariable Poisson regression model adjusting for potential confounders, mean MAP > 90 mmHg was associated with good neurological function, adjusted relative risk 2.46 (95% CI 2.09–2.88). Over ascending ranges of mean MAP, there was a dose-response increase in probability of good neurological outcome, with mean MAP > 110 mmHg having the strongest association, adjusted relative risk 2.97 (95% CI 1.86 – 4.76). Conclusions: Elevated blood pressure during the initial six hours after resuscitation from cardiac arrest was independently associated with good neurological function at hospital discharge. Further investigation is warranted to determine if targeting an elevated MAP would improve neurologic outcome after cardiac arrest.
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.
Characteristics and Outcomes of Patients with Vasoplegic Versus Tissue Dysoxic Septic Shock
(2013-07) Sterling, Sarah A; Puskarich, Michael A; Shapiro, Nathan I; Trzeciak, Stephen; Kline, Jeffrey A.; Summers, Richard L; Jones, Alan E
Background: The current consensus definition of septic shock requires hypotension after adequate fluid challenge or vasopressor requirement. Some patients with septic shock present with hypotension and hyperlactatemia greater than 2 mmol/L (tissue dysoxic shock), whereas others have hypotension alone with normal lactate (vasoplegic shock). Objective: The objective of this study was to determine differences in outcomes of patients with tissue dysoxic versus vasoplegic septic shock. Methods: This was a secondary analysis of a large, multicenter randomized controlled trial. Inclusion criteria were suspected infection, two or more systemic inflammatory response criteria, and systolic blood pressure less than 90 mmHg after a fluid bolus. Patients were categorized by presence of vasoplegic or tissue dysoxic shock. Demographics and Sequential Organ Failure Assessment scores were evaluated between the groups. The primary outcome was in-hospital mortality. Results: A total of 247 patients were included, 90 patients with vasoplegic shock and 157 with tissue dysoxic shock. There were no significant differences in age, race, or sex between the vasoplegic and tissue dysoxic shock groups. The group with vasoplegic shock had a lower initial Sequential Organ Failure Assessment score than did the group with tissue dysoxic shock (5.5 vs. 7.0 points; P = 0.0002). The primary outcome of in-hospital mortality occurred in 8 (9%) of 90 patients with vasoplegic shock compared with 41 (26%) of 157 in the group with tissue dysoxic shock (proportion difference, 17%; 95% confidence interval, 7%–26%; P < 0.0001; log-rank test P = 0.02). After adjusting for confounders, tissue dysoxic shock remained an independent predictor of in-hospital mortality. Conclusions: In this analysis of patients with septic shock, we found a significant difference in in-hospital mortality between patients with vasoplegic versus tissue dysoxic septic shock. These findings suggest a need to consider these differences when designing future studies of septic shock therapies.
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.
Effect of Glucose–Insulin–Potassium Infusion on Mortality in Critical Care Settings: A Systematic Review and Meta-Analysis
(2009-07) Puskarich, Michael A; Runyon, Michael S; Trzeciak, Stephen; Kline, Jeffrey A.; Jones, Alan E
This study seeks to measure the treatment effect of glucose—insulin—potassium (GIK) infusion on mortality in critically ill patients. A systematic review of randomized controlled trials is conducted, comparing GIK treatment with standard care or placebo in critically ill adult patients. The primary outcome variable is mortality. Two authors independently extract data and assess study quality. The primary analysis is based on the random effects model to produce pooled odds ratios (ORs) with 95% confidence intervals (CIs). The search yields 1720 potential publications; 23 studies are included in the final analysis, providing a sample of 22 525 patients. The combined results demonstrate no heterogeneity (P = .57, I2 = 0%) and no effect on mortality (OR = 1.02; 95% CI, 0.93–1.11) with GIK treatment. No experimental studies of shock or sepsis populations are identified. This meta-analysis finds that there is no mortality benefit to GIK infusion in critically ill patients; however, study populations are limited to acute myocardial infarction and cardiovascular surgery patients. No studies are identified using GIK in patients with septic shock or other forms of circulatory shock, providing an absence of evidence regarding the effect of GIK as a therapy in patients with shock.
Effect of Levocarnitine vs Placebo as an Adjunctive Treatment for Septic Shock: The Rapid Administration of Carnitine in Sepsis (RACE) Randomized Clinical Trial
(American Medical Association, 2018-12-07) Jones, Alan E.; Puskarich, Michael A.; Shapiro, Nathan I.; Guirgis, Faheem W.; Runyon, Michael; Adams, Jason Y.; Sherwin, Robert; Arnold, Ryan; Roberts, Brian W.; Kurz, Michael C.; Wang, Henry E.; Kline, Jeffrey A.; Courtney, D. Mark; Trzeciak, Stephen; Sterling, Sarah A.; Nandi, Utsav; Patki, Deepti; Viele, Kert; Emergency Medicine, School of Medicine
Importance: Sepsis induces profound metabolic derangements, while exogenous levocarnitine mitigates metabolic dysfunction by enhancing glucose and lactate oxidation and increasing fatty acid shuttling. Previous trials in sepsis suggest beneficial effects of levocarnitine on patient-centered outcomes. Objectives: To test the hypothesis that levocarnitine reduces cumulative organ failure in patients with septic shock at 48 hours and, if present, to estimate the probability that the most efficacious dose will decrease 28-day mortality in a pivotal phase 3 clinical trial. Design, Setting, and Participants: Multicenter adaptive, randomized, blinded, dose-finding, phase 2 clinical trial (Rapid Administration of Carnitine in Sepsis [RACE]). The setting was 16 urban US medical centers. Participants were patients aged 18 years or older admitted from March 5, 2013, to February 5, 2018, with septic shock and moderate organ dysfunction. Interventions: Within 24 hours of identification, patients were assigned to 1 of the following 4 treatments: low (6 g), medium (12 g), or high (18 g) doses of levocarnitine or an equivalent volume of saline placebo administered as a 12-hour infusion. Main Outcomes and Measures: The primary outcome required, first, a greater than 90% posterior probability that the most promising levocarnitine dose decreases the Sequential Organ Failure Assessment (SOFA) score at 48 hours and, second (given having met the first condition), at least a 30% predictive probability of success in reducing 28-day mortality in a subsequent traditional superiority trial to test efficacy. Results: Of the 250 enrolled participants (mean [SD] age, 61.7 [14.8] years; 56.8% male), 35, 34, and 106 patients were adaptively randomized to the low, medium, and high levocarnitine doses, respectively, while 75 patients were randomized to placebo. In the intent-to-treat analysis, the fitted mean (SD) changes in the SOFA score for the low, medium, and high levocarnitine groups were -1.27 (0.49), -1.66 (0.38), and -1.97 (0.32), respectively, vs -1.63 (0.35) in the placebo group. The posterior probability that the 18-g dose is superior to placebo was 0.78, which did not meet the a priori threshold of 0.90. Mortality at 28 days was 45.9% (34 of 74) in the placebo group compared with 43.3% (45 of 104) for the most promising levocarnitine dose (18 g). Similar findings were noted in the per-protocol analysis. Conclusions and Relevance: In this dose-finding, phase 2 adaptive randomized trial, the most efficacious dose of levocarnitine (18 g) did not meaningfully reduce cumulative organ failure at 48 hours.
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.
Outcomes of Patients Undergoing Early Sepsis Resuscitation for Cryptic Shock Compared with Overt Shock
(2011-10) Puskarich, Michael A; Trzeciak, Stephen; Shapiro, Nathan I; Heffner, Alan C; Kline, Jeffrey A.; Jones, Alan E
Introduction We sought to compare the outcomes of patients with cryptic versus overt shock treated with an emergency department (ED) based early sepsis resuscitation protocol. Methods Pre-planned secondary analysis of a large, multicenter ED-based randomized controlled trial of early sepsis resuscitation. All subjects were treated with 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 h. Outcomes data of patients who were enrolled with a lactate ≥4 mmol/L and normotension (cryptic shock) were compared to those enrolled with sustained hypotension after fluid challenge (overt shock). The primary outcome was in-hospital mortality. Results A total of 300 subjects were enrolled, 53 in the cryptic shock group and 247 in the overt shock group. The demographics and baseline characteristics were similar between the groups. The primary endpoint of in-hospital mortality was observed in 11/53 (20%, 95% CI 11–34) in the cryptic shock group and 48/247 (19%, 95% CI 15–25) in the overt shock group, difference of 1% (95% CI −10 to 14; log rank test p = 0.81). Conclusion Severe sepsis with cryptic shock carries a mortality rate not significantly different from that of overt septic shock. These data suggest the need for early aggressive screening for and treatment of patients with an elevated serum lactate in the absence of hypotension.
Partial pressure of arterial carbon dioxide after resuscitation from cardiac arrest and neurological outcome: A prospective multi-center protocol-directed cohort study
(Elsevier, 2018) Hope Kilgannon, J.; Hunter, Benton R.; Puskarich, Michael A.; Shea, Lisa; Fuller, Brian M.; Jones, Christopher; Donnino, Michael; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Roberts, Brian W.; Emergency Medicine, School of Medicine
Aims Partial pressure of arterial carbon dioxide (PaCO2) is a regulator of cerebral blood flow after brain injury. We sought to test the association between PaCO2 after resuscitation from cardiac arrest and neurological outcome. Methods A prospective protocol-directed cohort study across six hospitals. Inclusion criteria: age ≥ 18, non-traumatic cardiac arrest, mechanically ventilated after return of spontaneous circulation (ROSC), and receipt of targeted temperature management. Per protocol, PaCO2 was measured by arterial blood gas analyses at one and six hours after ROSC. We determined the mean PaCO2 over this initial six hours after ROSC. The primary outcome was good neurological function at hospital discharge, defined a priori as a modified Rankin Scale ≤ 3. Multivariable Poisson regression analysis was used to test the association between PaCO2 and neurological outcome. Results Of the 280 patients included, the median (interquartile range) PaCO2 was 44 (37-52) mmHg and 30% had good neurological function. We found mean PaCO2 had a quadratic (inverted “U” shaped) association with good neurological outcome, with a mean PaCO2 of 68 mmHg having the highest predictive probability of good neurological outcome, and worse neurological outcome at higher and lower PaCO2. Presence of metabolic acidosis attenuated the association between PaCO2 and good neurological outcome, with a PaCO2 of 51 mmHg having the highest predictive probability of good neurological outcome among patients with metabolic acidosis. Conclusion PaCO2 has a “U” shaped association with neurological outcome, with mild to moderate hypercapnia having the highest probability of good neurological outcome.

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