Room Air for Initiating Term Newborn Resuscitation: A Systematic Review With Meta-analysis.

: media-1vid110.1542/5839981898001PEDS-VA_2018-1825Video Abstract CONTEXT: The International Liaison Committee on Resuscitation prioritized to rigorously review the initial fraction of inspired oxygen (Fio2) during resuscitation of newborns. OBJECTIVE: This systematic review and meta-analysis provides the scientific summary of initial Fio2 in term and late preterm newborns (≥35 weeks' gestation) who receive respiratory support at birth. DATA SOURCES: Medline, Embase, Evidence Based Medicine Reviews, and Cumulative Index to Nursing and Allied Health Literature were searched between January 1, 1980 and August 10, 2018. STUDY SELECTION: Studies were selected by pairs of independent reviewers in 2 stages, with a Cohen's κ of 0.8 and 1.0. DATA EXTRACTION: Pairs of independent reviewers extracted data, appraised risk of bias, and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence. RESULTS: Five randomized controlled trials (RCTs) and 5 quasi RCTs included 2164 patients. Room air (Fio2 0.21) was associated with a statistically significant benefit in short-term mortality compared with 100% oxygen (Fio2 1.0) (7 RCTs; n = 1469; risk ratio [RR] = 0.73; 95% confidence interval [CI]: 0.57 to 0.94). No significant differences were observed in neurodevelopmental impairment (2 RCTs; n = 360; RR = 1.41; 95% CI: 0.77 to 2.60) or hypoxic-ischemic encephalopathy (5 RCTs; n = 1315; RR = 0.89; 95% CI: 0.68 to 1.18). LIMITATIONS: The Grading of Recommendations Assessment, Development and Evaluation certainty of evidence was low for short-term mortality and hypoxic-ischemic encephalopathy and very low for neurodevelopmental impairment. CONCLUSIONS: Room air has a 27% relative reduction in short-term mortality compared with Fio2 1.0 for initiating neonatal resuscitation ≥35 weeks' gestation.

Initial Oxygen Use for Preterm Newborn Resuscitation: A Systematic Review With Meta-analysis.

: media-1vid110.1542/5839981895001PEDS-VA_2018-1828Video Abstract CONTEXT: The International Liaison Committee on Resuscitation prioritized to review the initial fraction of inspired oxygen (Fio2) during the resuscitation of preterm newborns. OBJECTIVES: This systematic review and meta-analysis provides the scientific summary of initial Fio2 in preterm newborns (<35 weeks' gestation) who receive respiratory support at birth. DATA SOURCES: Medline, Embase, Evidence-Based Medicine Reviews, and Cumulative Index to Nursing and Allied Health Literature were searched between January 1, 1980 and August 10, 2018. STUDY SELECTION: Studies were selected by pairs of independent reviewers in 2 stages with a Cohen's κ of 0.8 and 1.0. DATA EXTRACTION: Pairs of independent reviewers extracted data, appraised the risk of bias (RoB), and assessed Grading of Recommendations Assessment, Development and Evaluation certainty. RESULTS: Ten randomized controlled studies and 4 cohort studies included 5697 patients. There are no statistically significant benefits of or harms from starting with lower compared with higher Fio2 in short-term mortality (n = 968; risk ratio = 0.83 [95% confidence interval 0.50 to 1.37]), long-term mortality, neurodevelopmental impairment, or other key preterm morbidities. A sensitivity analysis in which 1 study with a high RoB was excluded failed to reveal a reduction in mortality with initial low Fio2 (n = 681; risk ratio = 0.63 [95% confidence interval 0.38 to 1.03]). LIMITATIONS: The Grading of Recommendations Assessment, Development and Evaluation certainty of evidence was very low for all outcomes due to RoB, inconsistency, and imprecision. CONCLUSIONS: The ideal initial Fio2 for preterm newborns is still unknown, although the majority of newborns ≤32 weeks' gestation will require oxygen supplementation.

Clinical chemistry score versus high-sensitivity cardiac troponin I and T tests alone to identify patients at low or high risk for myocardial infarction or death at presentation to the emergency department.

BACKGROUND: Testing for high-sensitivity cardiac troponin (hs-cTn) may assist triage and clinical decision-making in patients presenting to the emergency department with symptoms of acute coronary syndrome; however, this could result in the misclassification of risk because of analytical variation or laboratory error. We sought to evaluate a new laboratory-based risk-stratification tool that incorporates tests for hs-cTn, glucose level and estimated glomerular filtration rate to identify patients at risk of myocardial infarction or death when presenting to the emergency department. METHODS: We constructed the clinical chemistry score (CCS) (range 0-5 points) and validated it as a predictor of 30-day myocardial infarction (MI) or death using data from 4 cohort studies involving patients who presented to the emergency department with symptoms suggestive of acute coronary syndrome. We calculated diagnostic parameters for the CCS score separately using high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: For the combined cohorts (n = 4245), 17.1% of participants had an MI or died within 30 days. A CCS score of 0 points best identified low-risk participants: the hs-cTnI CCS had a sensitivity of 100% (95% confidence interval [CI] 99.5%-100%), with 8.9% (95% CI 8.1%-9.8%) of the population classified as being at low risk of MI or death within 30 days; the hs-cTnT CCS had a sensitivity of 99.9% (95% CI 99.2%-100%), with 10.5% (95% CI 9.6%-11.4%) of the population classified as being at low risk. The CCS had better sensitivity than hs-cTn alone (hs-cTnI < 5 ng/L: 96.6%, 95% CI 95.0%-97.8%; hs-cTnT < 6 ng/L: 98.2%, 95% CI 97.0%-99.0%). A CCS score of 5 points best identified patients at high risk (hs-cTnI CCS: specificity 96.6%, 95% CI 96.0%-97.2%; 11.2% [95% CI 10.3%-12.2%] of the population classified as being at high risk; hs-cTnT CCS: specificity 94.0%, 95% CI 93.1%-94.7%; 13.1% [95% CI 12.1%-14.1%] of the population classified as being at high risk) compared with using the overall 99th percentiles for the hs-cTn assays (specificity of hs-cTnI 93.2%, 95% CI 92.3-94.0; specificity of hs-cTnT 73.8%, 95% CI 72.3-75.2). INTERPRETATION: The CCS score at the chosen cut-offs was more sensitive and specific than hs-cTn alone for risk stratification of patients presenting to the emergency department with suspected acute coronary syndrome. Study registration: ClinicalTrials.gov, nos. NCT01994577; NCT02355457.

Performance of high-sensitivity cardiac troponin in the emergency department for myocardial infarction and a composite cardiac outcome across different estimated glomerular filtration rates.

BACKGROUND: Clinicians regularly observe increased high-sensitivity cardiac troponin (hs-cTn) concentrations in patients with low estimated glomerular filtration rate (eGFR). The challenge is to differentiate acute coronary syndrome (ACS) from increased hs-cTn results across a range of eGFR. The objective of this study was to determined the optimal hs-cTn concentrations for acute myocardial infarction (MI) and a composite cardiovascular outcome across different eGFR ranges and to assess the utility of a low hs-cTn cutoff to rule-out events. METHODS: We undertook an observational study in the emergency department of patients (n = 1212) with symptoms suggestive of ACS who had an eGFR and at least one Roche hs-cTnT and one Abbott hs-cTnI result. The 7-day outcomes were MI or a composite of MI, unstable angina, congestive heart failure, serious ventricular cardiac arrhythmia, or death. The maximum hs-cTn concentration was assessed across different eGFR ranges (<30,30-59,60-89,≥90 ml/min/1.73m2) by spearman correlation, ROC-curve analyses, and sensitivity and negative predictive value (NPV) for the proposed rule-out hs-cTn cutoffs (hs-cTnI<5 ng/l and hs-cTnT<6 ng/l) for the outcomes. RESULTS: Both hs-cTnI and hs-cTnT concentrations were negatively correlated with eGFR. The lower the eGFR, the lower the AUC and the higher the optimal hs-cTn cutoffs for both MI and the composite outcome. The highest combined sensitivity (100%), NPV (100%) and proportion of low-risk for MI (45% of group) was observed for patients with hs-cTnT<6 ng/l with an eGFR≥90. CONCLUSION: The test performance for hs-cTn for diagnosing or ruling-out an acute cardiac event varies per the eGFR. Accurate risk stratification requires knowledge of the eGFR.

Does Early Coronary Angiography Improve Survival After out-of-Hospital Cardiac Arrest? A Systematic Review With Meta-Analysis.

BACKGROUND: In patients with out-of-hospital cardiac arrest who achieve return of spontaneous circulation, coronary angiography (CAG) might improve outcomes. We conducted a systematic review and meta-analysis to elucidate the benefit and optimal timing of early CAG in comatose out-of-hospital cardiac arrest patients with return of spontaneous circulation. METHODS: We searched MEDLINE, EMBASE, and Cochrane from 1990 to May 2017. Studies reporting survival and/or neurological survival in early (< 24-hour) vs late/no CAG were selected. We used the Clinical Advances Through Research and Information Translation (CLARITY) risk of bias in cohort studies tool and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria to assess risk of bias and quality of evidence, respectively. Results were pooled using random effects and presented as risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: After screening 9185 titles/abstracts and 631 full-text articles, we included 23 nonrandomized studies. Short (to discharge or 30 days) and long-term (1-5 years) survival were significantly improved (52% and 56%, respectively) in the early < 24-hour CAG group compared with the late/no CAG group (RR, 1.52; 95% CI, 1.32-1.74; P < 0.00001; I2, 94% and RR, 1.56; 95% CI, 1.14-2.14; P = 0.006; I2, 86%). Survival with good neurological outcome was also improved by 69% in the < 24-hour CAG group at short- (RR, 1.69; 95% CI, 1.40-2.04; P < 0.00001; I2, 93%) and intermediate-term (3-11 months; RR, 1.49; 95% CI, 1.27-1.76; P < 0.00001; I2, 67%). We found consistent benefits in the < 2-hour and < 6-hour subgroups. Early CAG was associated with significantly better outcomes in studies of patients without ST-elevation, but the results did not reach statistical significance in studies of patients with ST-elevation. CONCLUSIONS: On the basis of very low quality, but consistent evidence, early CAG (< 24 hours) was associated with significantly higher survival and better neurologic outcomes.

High-sensitivity cardiac troponin concentrations at emergency department presentation in females and males with an acute cardiac outcome.

Background There is interest in utilizing different cut-offs per sex for high-sensitivity cardiac troponin I (hs-cTnI) but less so for high-sensitivity cardiac troponin T (hs-cTnT) for patient management in the acute setting. Our objective was to assess if differences in hs-cTn concentrations exist between males and females for an acute cardiac outcome following the presentation measurement in the emergency department. Methods An observational emergency department population with hs-cTn measurements (Roche Diagnostics and Abbott Diagnostics) at presentation with seven-day outcomes for a composite acute cardiac outcome (i.e. myocardial infarction, unstable angina, ventricular arrhythmia, heart failure or cardiovascular death) (ClinicalTrials.gov: NCT01994577). Receiver operating characteristic curve analyses were performed for each sex with both hs-cTn assays. Results In those patients who had a composite acute cardiac outcome ( n = 128 females; n = 145 males), there was no difference in hs-cTn concentrations between the sexes (median [IQR] female hs-cTnT = 35 ng/L [21-69] vs. male hs-cTnT = 38 ng/L [19-77], P = 0.95; and median [IQR] female hs-cTnI = 27 ng/L [12-75] vs. male hs-cTnI = 26 ng/L [12-85], P = 0.97]. There was also no difference in the area under the curve between the hs-cTn assays and between the sexes ( P > 0.10). Comparing hs-cTn concentrations in those patients with the composite outcome between the sexes <60 years and ≥60 years of age also did not yield significant differences ( P > 0.70). Conclusions The concentrations and area under the curves of hs-cTnT and hs-cTnI at patient presentation in the emergency department for an acute composite cardiac outcome were similar between the sexes in this exploratory study.

High-Sensitivity Cardiac Troponin Risk Cutoffs for Acute Cardiac Outcomes at Emergency Department Presentation.

The optimal high-sensitivity cardiac troponin (hs-cTn) cutoffs for determining risk in patients who present with acute coronary syndrome symptoms are unknown. In 1137 emergency department patients we calculated adjusted relative risks for a composite outcome (myocardial infarction, unstable angina, heart failure, ventricular arrhythmia, or cardiovascular death) within 7 days for the presentation of hs-cTnT (Roche) and hs-cTnI (Abbott) assay concentrations on the basis of literature cutoffs. Patients with hs-cTn concentrations ≥ 14 ng/L had an adjusted relative risk of 4.9 for the composite outcome, with different hs-cTnT/hs-cTnI concentration ranges yielding higher risks. A common low-risk cutoff of 14 ng/L may be used for hs-cTn with higher cutoffs identifying high-risk patients.

A laboratory score at presentation to rule-out serious cardiac outcomes or death in patients presenting with symptoms suggestive of acute coronary syndrome.

BACKGROUND: We evaluated whether a low high-sensitivity cardiac troponin (hs-cTn) cutoff combined with glucose, red cell distribution width (RDW), and the estimated glomerular filtration rate (eGFR) can be used to rule-out a serious cardiac outcome or death in patients presenting with symptoms suggestive of acute coronary syndrome (ACS). METHODS: This was a prospective observational emergency department (ED) study enrolling consecutive patients presenting with symptoms suggestive of ACS (ClinicalTrials.gov: NCT01994577). The primary outcome was a 7-day composite of myocardial infarction, unstable angina, decompensated congestive heart failure, serious ventricular cardiac arrhythmia, or death. A laboratory score combining glucose, RDW, eGFR with hs-cTnT (Roche) or hs-cTnI (Abbott) was compared to hs-cTn alone using the limit of detection (LoD; hs-cTnT<5ng/l/hs-cTnI<2ng/l) as the cutoff. A benchmark of >99% sensitivity was used to assess the laboratory panel with hs-cTn versus the LoD alone to identify low-risk patients suitable for discharge. RESULTS: A total of 1095 patients (n=267 composite-outcomes) had measurements of glucose, RDW, eGFR, hs-cTnT, and hs-cTnI at presentation. Applying the hs-cTn LoD alone as the cutoff missed 5 composite-outcomes (sensitivity=98.1%), however the addition of the laboratory panel to the hs-cTn LoD increased the sensitivity to >99% with approximately 10% of the population identified as low-risk. The percentage of low-risk patients was increased to 15% (1 composite-outcome missed) when employing a low measurable hs-cTnI cutoff with the laboratory panel (laboratory score<2 points). CONCLUSION: A laboratory score with hs-cTn may identify low-risk patients suitable for ED discharge at presentation.

Rule-In and Rule-Out of Myocardial Infarction Using Cardiac Troponin and Glycemic Biomarkers in Patients with Symptoms Suggestive of Acute Coronary Syndrome.

BACKGROUND: Early rule-in/rule-out of myocardial infarction (MI) in patients presenting to the emergency department (ED) is important for patient care and resource allocation. Given that dysglycemia is a strong risk factor for MI, we sought to explore and compare different combinations of cardiac troponin (cTn) cutoffs with glycemic markers for the early rule-in/rule-out of MI. METHODS: We included ED patients (n = 1137) with symptoms suggestive of acute coronary syndrome (ACS) who had cTnI, high-sensitivity cTnI (hs-cTnI), hs-cTnT, glucose, and hemoglobin A1c (Hb A1c) measurements. We derived rule-in/rule-out algorithms using different combinations of ROC-derived and literature cutoffs for rule-in and rule-out of MI within 7 days after presentation. These algorithms were then tested for MI/cardiovascular death and ACS/cardiovascular death at 7 days. ROC curves, sensitivity, specificity, likelihood ratios, positive and negative predictive values (PPV and NPV), and CIs were determined for various biomarker combinations. RESULTS: MI was diagnosed in 133 patients (11.7%; 95% CI, 9.8-13.8). The algorithms that included cTn and glucose produced the greatest number of patients ruled out/ruled in for MI and yielded sensitivity ≥99%, NPV ≥99.5%, specificity ≥99%, and PPV ≥80%. This diagnostic performance was maintained for MI/cardiovascular death but not for ACS/cardiovascular death. The addition of hemoglobin A1c (Hb A1c) (≥6.5%) to these algorithms did not change these estimates; however, 50 patients with previously unknown diabetes may have been identified if Hb A1c was measured. CONCLUSIONS: Algorithms incorporating glucose with cTn may lead to an earlier MI diagnosis and rule-out for MI/cardiovascular death. Addition of Hb A1c into these algorithms allows for identification of diabetes. Future studies extending these findings are needed for ACS/cardiovascular death. ClinicalTrials.gov identifier: NCT01994577.

Economic Considerations of Early Rule-In/Rule-Out Algorithms for The Diagnosis of Myocardial Infarction in The Emergency Department Using Cardiac Troponin and Glycemic Biomarkers.

BACKGROUND: We have previously demonstrated the utility of a rule-in/rule-out strategy for myocardial infarction (MI) using glycemic biomarkers in combination with cardiac troponin in the emergency department (ED). Given that the cost of assessing patients with possible MI in the ED is increasing, we sought to compare the health services cost of our previously identified early rule-in/rule-out approaches for MI among patients who present to the ED with symptoms suggestive of acute coronary syndrome (ACS). METHODS: We compared the cost differences between different rule-in/rule-out strategies for MI using presentation cardiac troponin I (cTnI), high-sensitivity cTnI (hs-cTnI), high-sensitivity cardiac troponin T (hs-cTnT), glucose, and/or hemoglobin A1c (Hb A1c) in 1137 ED patients (7-day MI n = 133) as per our previously defined algorithms and compared them with the European Society of Cardiology (ESC) 0-h algorithm-cutoffs. Costs associated with each decision model were obtained from site-specific sources (length of stay) and provincial sources (Ontario Case Costing Initiative). RESULTS: Algorithms incorporating cardiac troponin and glucose for early rule-in/rule-out were the most cost effective and clinically safest methods (i.e., ≤1 MI missed) for early decision making, with hs-cTnI and glucose yielding lower costs compared to cTnI and glucose, despite the higher price for the hs-cTnI test. The addition of Hb A1c to the algorithms increased the cost of these algorithms but did not miss any additional patients with MI. Applying the ESC 0-h algorithm-cutoffs for hs-cTnI and hs-cTnT were the most costly. CONCLUSIONS: Rule-in/rule-out algorithms incorporating presentation glucose with high-sensitivity cardiac troponin are the safest and most cost-effective options as compared to the ESC 0-h algorithm-cutoffs.

Association of cardiac biomarkers with acute kidney injury after cardiac surgery: A multicenter cohort study.

OBJECTIVE: Acute kidney injury is common after cardiac surgery and associated with postoperative mortality. Perioperative cardiac biomarkers may predict acute kidney injury and mortality. We evaluated whether cardiac biomarkers were associated with severe acute kidney injury, defined as a doubling in serum creatinine or requiring renal replacement therapy during hospital stay after surgery, and mortality. METHODS: In a prospective multicenter cohort of adults undergoing cardiac surgery, we measured the following biomarkers in preoperative and postoperative banked plasma: high-sensitivity troponin T, cardiac troponin I, creatine kinase-MB, and N-terminal prohormone of brain natriuretic peptide. RESULTS: In the patients who were discharged alive, severe acute kidney injury occurred in 37 of 960 (3.9%), and 43 of 960 (4.5%) died within 1 year of follow-up. N-terminal prohormone of brain natriuretic peptide was the only preoperative biomarker that was independently associated with severe acute kidney injury (with log transformation, adjusted odds ratio, 1.4; 95% confidence interval, 1.0-1.9). Biomarkers measured within 6 hours of surgery (day 1) were all associated with severe acute kidney injury. Preoperative N-terminal prohormone of brain natriuretic peptide was also independently associated with 1-year mortality (with log transformation, adjusted odds ratio, 1.7; 95% confidence interval, 1.2-2.2). Patients in the highest tertile for N-terminal prohormone of brain natriuretic peptide preoperatively (>1006.4 ng/L) had marked increases in their risk for 1-year mortality (adjusted odds ratio, 27.2; 95% confidence interval, 3.5-213.5). Day 1 N-terminal prohormone of brain natriuretic peptide was associated with mortality independently of change in serum creatinine from preoperative baseline. CONCLUSIONS: Of the studied biomarkers, N-terminal prohormone of brain natriuretic peptide was the only preoperative biomarker independently associated with severe acute kidney injury and mortality. Early increases in postoperative cardiac biomarkers were associated with severe acute kidney injury after cardiac surgery. Future research should focus on whether interventions that lower N-terminal prohormone of brain natriuretic peptide can affect postoperative outcomes.

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery.

Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n = 960). AKI was defined as a ≥ 50% or ≥ 0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P = 0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.

Perioperative heart-type fatty acid binding protein is associated with acute kidney injury after cardiac surgery.

Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with worse outcomes. Since heart fatty acid binding protein (H-FABP) is a myocardial protein that detects cardiac injury, we sought to determine whether plasma H-FABP was associated with AKI in the TRIBE-AKI cohort; a multi-center cohort of 1219 patients at high risk for AKI who underwent cardiac surgery. The primary outcomes of interest were any AKI (Acute Kidney Injury Network (AKIN) stage 1 or higher) and severe AKI (AKIN stage 2 or higher). The secondary outcome was long-term mortality after discharge. Patients who developed AKI had higher levels of H-FABP pre- and postoperatively than patients who did not have AKI. In analyses adjusted for known AKI risk factors, first postoperative log(H-FABP) was associated with severe AKI (adjusted odds ratio (OR) 5.39 (95% confidence interval (CI), 2.87-10.11) per unit increase), while preoperative log(H-FABP) was associated with any AKI (2.07 (1.48-2.89)) and mortality (1.67 (1.17-2.37)). These relationships persisted after adjustment for change in serum creatinine (for first postoperative log(H-FABP)) and biomarkers of cardiac and kidney injury, including brain natriuretic peptide, cardiac troponin-I, interleukin-18, liver fatty acid binding protein, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin. Thus, perioperative plasma H-FABP levels may be used for risk stratification of AKI and mortality following cardiac surgery.

Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery.

BACKGROUND: Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of the inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery. METHODS: This is a sub-study of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort, including 106 children ranging in age from 1 month to 18 years undergoing CPB. Plasma IL-6 and IL-10 concentrations were measured preoperatively and postoperatively [day 1 (within 6 h after surgery) and day 3]. RESULTS: Stage 2/3 AKI, defined by at least a doubling of the baseline serum creatinine concentration or dialysis, was diagnosed in 24 (23%) patients. The preoperative IL-6 concentration was significantly higher in patients with stage 2/3 AKI [median 2.6 pg/mL, interquartile range (IQR) 2.6 0.6-4.9 pg/mL] than in those without stage 2/3 AKI (median 0.6 pg/mL, IQR 0.6-2.2 pg/mL) (p = 0.03). After adjustment for clinical and demographic variables, the highest preoperative IL-6 tertile was associated with a sixfold increased risk for stage 2/3 AKI compared with the lowest tertile (adjusted odds ratio 6.41, 95 % confidence interval 1.16-35.35). IL-6 and IL-10 levels increased significantly after surgery, peaking postoperatively on day 1. First postoperative IL-6 and IL-10 measurements did not significantly differ between patients with stage 2/3 AKI and those without stage 2/3 AKI. The elevated IL-6 level on day 3 was associated with longer hospital stay (p = 0.0001). CONCLUSIONS: Preoperative plasma IL-6 concentration is associated with the development of stage 2/3 AKI and may be prognostic of resource utilization.

Cardiac biomarkers and acute kidney injury after cardiac surgery.

OBJECTIVES: To examine the relationship of cardiac biomarkers with postoperative acute kidney injury (AKI) among pediatric patients undergoing cardiac surgery. METHODS: Data from TRIBE-AKI, a prospective study of children undergoing cardiac surgery, were used to examine the association of cardiac biomarkers (N-type pro-B-type natriuretic peptide, creatine kinase-MB [CK-MB], heart-type fatty acid binding protein [h-FABP], and troponins I and T) with the development of postoperative AKI. Cardiac biomarkers were collected before and 0 to 6 hours after surgery. AKI was defined as a ≥ 50% or 0.3 mg/dL increase in serum creatinine, within 7 days of surgery. RESULTS: Of the 106 patients included in this study, 55 (52%) developed AKI after cardiac surgery. Patients who developed AKI had higher median levels of pre- and postoperative cardiac biomarkers compared with patients without AKI (all P < .01). Preoperatively, higher levels of CK-MB and h-FABP were associated with increased odds of developing AKI (CK-MB: adjusted odds ratio 4.58, 95% confidence interval [CI] 1.56-13.41; h-FABP: adjusted odds ratio 2.76, 95% CI 1.27-6.03). When combined with clinical models, both preoperative CK-MB and h-FABP provided good discrimination (area under the curve 0.77, 95% CI 0.68-0.87, and 0.78, 95% CI 0.68-0.87, respectively) and improved reclassification indices. Cardiac biomarkers collected postoperatively did not significantly improve the prediction of AKI beyond clinical models. CONCLUSIONS: Preoperative CK-MB and h-FABP are associated with increased risk of postoperative AKI and provide good discrimination of patients who develop AKI. These biomarkers may be useful for risk stratifying patients undergoing cardiac surgery.

An approach to rule-out an acute cardiovascular event or death in emergency department patients using outcome-based cutoffs for high-sensitivity cardiac troponin assays and glucose.

OBJECTIVES: The application of "undetectable" high-sensitivity cardiac troponin (hs-cTn) concentrations to "rule-out" myocardial infarction is appealing, but there are analytical concerns and a lack of consensus on what concentration should be used to define the lower reportable limit; i.e., limit of detection (LoD) or limit of blank. An alternative approach is to utilize a measurable hs-cTn concentration that identifies patients at low-risk for a future cardiovascular event combined with another prognostic test, such as glucose. We assessed both of these approaches in different emergency department (ED) cohorts to rule-out an event. DESIGN AND METHODS: We used cohort 1 (all-comer ED population, n=4773; derivation cohort) to determine the most appropriate approach at presentation (i.e., Dual Panel test: hs-cTn/glucose vs. LoD vs. LoD/glucose) for an early rule-out of hospital death using the Abbott ARCHITECT hs-cTnI assay. We used cohort 2 (n=144) and cohort 3 (n=127), both early chest pain onset ED populations as the verification datasets (outcome: composite cardiovascular event at 72h) with three hs-cTn assays assessed (Abbott Laboratories, Beckman Coulter, Roche Diagnostics). RESULTS: In cohort 1, the sensitivity was >99% for all three approaches; however the specificity (11%; 95% CI: 10-12%) was significantly higher for the Dual Panel as compared to the LoD approach (specificity=5%; 95% CI: 4-6%). Verification of the Dual Panel in cohort 2 and cohort 3 revealed 100% sensitivity and negative predictive values for all three hs-cTn assays. CONCLUSIONS: The combination of a "healthy" hs-cTn concentration with glucose might effectively rule-out patients for an acute cardiovascular event at ED presentation.