Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension.

BACKGROUND: Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited. METHODS: In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed. RESULTS: A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups. CONCLUSIONS: Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).

Rural EMS STEMI Patients - Why the Delay to PCI?

BACKGROUND: The objective of this study is to identify patient and EMS agency factors associated with timely reperfusion of patients with ST-elevation myocardial infarction (STEMI). METHODS: We conducted a cohort study of adult patients (≥18 years old) with STEMI activations from 2016 to 2020. Data was obtained from a regional STEMI registry, which included eight rural county EMS agencies and three North Carolina percutaneous coronary intervention (PCI) centers. On each patient, prehospital and in-hospital time intervals were abstracted. The primary outcome was the ability to achieve the 90-minute EMS FMC to PCI time goal (yes vs. no). We used generalized estimating equations accounting for within-agency clustering to evaluate the association between patient and agency factors and meeting first medical contact (FMC) to PCI time goal while accounting for clustering within the agency. RESULTS: Among 365 rural STEMI patients 30.1% were female (110/365) with a mean age of 62.5 ± 12.7 years. PCI was performed within the time goal in 60.5% (221/365) of encounters. The FMC to PCI time goal was met in 45.5% (50/110) of women vs 69.8% (178/255) of men (p < 0.001). The median PCI center activation time was 12 min (IQR 7-19) in the group that received PCI within the time goal compared to 21 min (IQR 10-37) in the cohort that did not. After adjusting for loaded mileage and other clinical variables (e.g., pulse rate, hypertension etc.), the male sex was associated with an improved chance of meeting the goal of FMC to PCI (aOR: 2.94; 95% CI 2.11-4.10) compared to the female sex. CONCLUSION: Nearly 40% of rural STEMI patients transported by EMS failed to receive FMC to PCI within 90 min. Women were less likely than men to receive reperfusion within the time goal, which represents an important health care disparity.

Performance of Prehospital Use of Chest Pain Risk Stratification Tools: The RESCUE Study.

BACKGROUND: Emergency medical services (EMS) assesses millions of patients with chest pain each year. However, tools validated to risk stratify patients for acute coronary syndrome (ACS) and pulmonary embolism (PE) have not been translated to the prehospital setting. The objective of this study is to assess the prehospital performance of risk stratification scores for 30-day major adverse cardiac events (MACE) and PE. METHODS: A prospective observational cohort study of patients ≥21 years of age with acute chest pain who were transported by EMS in two North Carolina (NC) counties was conducted from 18 April 2018-2 January 2019. In this convenience sample, paramedics completed HEAR (history, electrocardiogram, age, risk factor), ED Assessment of Chest Pain Score (EDACS), Revised Geneva Score (RGS), and pulmonary embolism rule-out criteria (PERC) assessments on each patient. MACE (all-cause death, myocardial infarction, and revascularization) and PE at 30 days were determined by hospital records and NC Death Index. The positive (+LR) and negative likelihood ratios (-LR) of the risk scores for 30-day MACE and PE were calculated. RESULTS: During the study period, 82.1% (687/837) patients had all four risk score assessments. The cohort was 51.1% (351/687) female, 49.5% (340/687) African American, and had a mean age of 55.0 years (SD 16.0). At 30 days, MACE occurred in 7.4% (51/687), PE occurred in 0.9% (6/687), and the combined outcome occurred in 8.2% (56/687). The HEAR score had a - LR of 0.46 (95% CI 0.27-0.78) and + LR of 1.48 (95% CI 1.26-1.74) for 30-day MACE. EDACS had a - LR of 0.61 (95% CI 0.46-0.81) and + LR of 2.53 (95% CI 1.86-3.46) for 30-day MACE. The PERC score had a - LR of 0 (95% CI 0.0-1.4) and a + LR of 1.38 (95% CI 1.32-1.45) for 30-day PE. The RGS score had a - LR of 0 (95% CI 0.0-0.65) and a + LR of 2.36 (95% CI 2.16-2.57) for 30-day PE. The combination of a low-risk HEAR score and negative PERC evaluation had a - LR of 0.25 (95% CI 0.08-0.76) and a + LR of 1.21 (95% CI 1.21-1.30) for 30-day MACE or PE. CONCLUSION: The combination of a paramedic-obtained HEAR score and PERC evaluation performed best to exclude 30-day MACE and PE but was not sufficient for directing prehospital decision making.

Prehospital Time Disparities for Rural Patients with Suspected STEMI.

BACKGROUND: Rural patients with ST-elevation myocardial infarction (STEMI) may be less likely to receive prompt reperfusion therapy. This study's primary objective was to compare rural versus urban time intervals among a national cohort of prehospital patients with STEMI. METHODS: The ESO Data Collaborative (Austin, TX), containing records from 1,366 emergency medical services agencies, was queried for adult 9-1-1 responses with suspected STEMI from 1/1/2018-12/31/2019. The scene address for each encounter was classified as either urban or rural using the 2010 US Census Urban Area Zip Code Tabulation Area relationship. The primary outcome was total EMS interval (9-1-1 call to hospital arrival); a key secondary outcome was the proportion of responses that had EMS intervals under 60 minutes. Generalized estimating equations were used to determine whether rural versus urban differences in interval outcomes occurred when adjusting for loaded mileage (distance from scene to hospital) and patient and clinical encounter characteristics. RESULTS: Of 15,915,027 adult 9-1-1 transports, 23,655 records with suspected STEMI were included in the analysis. Most responses (91.6%, n = 21,661) occurred in urban settings. Median EMS interval was 37.6 minutes (IQR 30.0-48.0) in urban settings compared to 57.0 minutes (IQR 46.5-70.7) in rural settings (p < 0.01). Urban responses more frequently had EMS intervals <60 minutes (89.5%, n = 19,130), compared to rural responses (55.5%, n = 1,100, p < 0.01). After adjusting for loaded mileage, age, sex, race/ethnicity, abnormal vital signs, pain assessment, aspirin administration, and IV/IO attempt, rural location was associated with a 5.8 (95%CI 4.2-7.4) minute longer EMS interval than urban, and rural location was associated with a reduced chance of achieving EMS interval < 60 minutes (OR 0.40; 95%CI 0.33-0.49) as compared to urban location. CONCLUSION: In this large national sample, rural location was associated with significantly longer EMS interval for patients with suspected STEMI, even after accounting for loaded mileage.

Prehospital time for patients with acute cardiac complaints: A rural health disparity.

OBJECTIVE: Delays in care for patients with acute cardiac complaints are associated with increased morbidity and mortality. The objective of this study was to quantify rural and urban differences in prehospital time intervals for patients with cardiac complaints. METHODS: The ESO Data Collaborative dataset consisting of records from 1332 EMS agencies was queried for 9-1-1 encounters with acute cardiac problems among adults (age ≥ 18) from 1/1/2013-6/1/2018. Location was classified as rural or urban using the 2010 United States Census. The primary outcome was total prehospital time. Generalized estimating equations evaluated differences in the average times between rural and urban encounters while controlling for age, sex, race, transport mode, loaded mileage, and patient stability. RESULTS: Among 428,054 encounters, the median age was 62 (IQR 50-75) years with 50.7% female, 75.3% white, and 10.3% rural. The median total prehospital, response, scene, and transport times were 37.0 (IQR 29.0-48.0), 6.0 (IQR 4.0-9.0), 16.0 (IQR 12.0-21.0), and 13.0 (IQR 8.0-21.0) minutes. Rural patients had an average total prehospital time that was 16.76 min (95%CI 15.15-18.38) longer than urban patients. After adjusting for covariates, average total time was 5.08 (95%CI 4.37-5.78) minutes longer for rural patients. Average response and transport time were 4.36 (95%CI 3.83-4.89) and 0.62 (95%CI 0.33-0.90) minutes longer for rural patients. Scene time was similar in rural and urban patients (0.09 min, 95%CI -0.15-0.33). CONCLUSION: Rural patients with acute cardiac complaints experienced longer prehospital time than urban patients, even after accounting for other key variables, such as loaded mileage.

Monocyte chemoattractant protein-1 is not predictive of cardiac events in patients with non-low-risk chest pain.

BACKGROUND: Prior studies suggest monocyte chemoattractant protein-1 (MCP-1) may be useful for risk stratifying ED patients with chest pain. We hypothesise that MCP-1 will be predictive of 90-day major adverse cardiovascular events (MACEs) in non-low-risk patients. METHODS: A case-control study was nested within a prospective multicentre cohort (STOP-CP), which enrolled adult patients being evaluated for acute coronary syndrome at eight US EDs from 25 January 2017 to 06 September 2018. Patients with a History, ECG, Age, and Risk factor score (HEAR score) ≥4 or coronary artery disease (CAD), a non-ischaemic ECG, and non-elevated contemporary troponins at 0 and 3 hours were included. Cases were patients with 90-day MACE (all-cause death, myocardial infarction or revascularisation). Controls were patients without MACE selected with frequency matching using age, sex, race, and HEAR score or the presence of CAD. Serum MCP-1 was measured. Sensitivity and specificity were determined for cut-off points of 194 pg/mL, 200 pg/mL, 238 pg/mL and 281 pg/mL. Logistic regression adjusting for age, sex, race, and HEAR score/presence of CAD was used to determine the association between MCP-1 and 90-day MACE. A separate logistic model also included high-sensitivity troponin (hs-cTnT). RESULTS: Among 40 cases and 179 controls, there was no difference in age (p=0.90), sex (p=1.00), race (p=0.85), or HEAR score/presence of CAD (p=0.89). MCP-1 was similar in cases (median 191.9 pg/mL, IQR: 161.8-260.1) and controls (median 196.6 pg/mL, IQR: 163.0-261.1) (p=0.48). At a cut-off point of 194 pg/mL, MCP-1 was 50.0% (95% CI 33.8% to 66.2%) sensitive and 46.9% (95% CI 39.4% to 54.5%) specific for 90-day MACE. After adjusting for covariates, MCP-1 was not associated with 90-day MACE at any cut-off point (at 194 pg/mL, OR 0.88 (95% CI 0.43 to 1.79)). When including hs-cTnT in the model, MCP-1 was not associated with 90-day MACE at any cut-off point (at 194 pg/mL, OR 0.85 (95% CI 0.42 to 1.73)). CONCLUSION: MCP-1 is not predictive of 90-day MACE in patients with non-low-risk chest pain.

Sex and race differences in safety and effectiveness of the HEART pathway accelerated diagnostic protocol for acute chest pain.

BACKGROUND: The HEART Pathway is an accelerated diagnostic protocol for Emergency Department patients with possible acute coronary syndrome. The objective was to compare the safety and effectiveness of the HEART Pathway among women vs men and whites vs non-whites. METHODS: A subgroup analysis of the HEART Pathway Implementation Study was conducted. Adults with chest pain were accrued from November 2013 to January 2016 from 3 Emergency Departments in North Carolina. The primary outcomes were death and myocardial infarction (MI) and hospitalization rates at 30 days. Logistic regression evaluated for interactions of accelerated diagnostic protocol implementation with sex or race and changes in outcomes within subgroups. RESULTS: A total of 8,474 patients were accrued, of which 53.6% were female and 34.0% were non-white. The HEART Pathway identified 32.6% of females as low-risk vs 28.5% of males (P = 002) and 35.6% of non-whites as low-risk vs 28.0% of whites (P < .0001). Among low-risk patients, death or MI at 30 days occurred in 0.4% of females vs 0.5% of males (P = .70) and 0.5% of non-whites vs 0.3% of whites (P = .69). Hospitalization at 30 days was reduced by 6.6% in females (aOR: 0.74, 95% CI: 0.64-0.85), 5.1% in males (aOR: 0.87, 95% CI: 0.75-1.02), 8.6% in non-whites (aOR: 0.72, 95% CI: 0.60-0.86), and 4.5% in whites (aOR: 0.83, 95% CI: 0.73-0.94). Interactions were not significant. CONCLUSION: Women and non-whites are more likely to be classified as low-risk by the HEART Pathway. HEART Pathway implementation is associated with decreased hospitalizations and a very low death and MI rate among low-risk patients regardless of sex or race.

EMS blood collection from patients with acute chest pain reduces emergency department length of stay.

BACKGROUND: Expediting the measurement of serum troponin by leveraging EMS blood collection could reduce the diagnostic time for patients with acute chest pain and help address Emergency Department (ED) overcrowding. However, this practice has not been examined among an ED chest pain patient population in the United States. METHODS: A prospective observational cohort study of adults with non-traumatic chest pain without ST-segment elevation myocardial infarction was conducted in three EMS agencies between 12/2016-4/2018. During transport, paramedics obtained a patient blood sample that was sent directly to the hospital core lab for troponin measurement. On ED arrival HEART Pathway assessments were completed by ED providers as part of standard care. ED providers were blinded to troponin results from EMS blood samples. To evaluate the potential impact on length of stay (LOS), the time difference between EMS blood draw and first clinical ED draw was calculated. To determine the safety of using troponin measures from EMS blood samples, the diagnostic performance of the HEART Pathway for 30-day major adverse cardiac events (MACE: composite of cardiac death, myocardial infarction (MI), coronary revascularization) was determined using EMS troponin plus arrival ED troponin and EMS troponin plus a serial 3-h ED troponin. RESULTS: The use of EMS blood samples for troponin measures among 401 patients presenting with acute chest pain resulted in a mean potential reduction in LOS of 72.5 ± SD 35.7 min. MACE at 30 days occurred in 21.0% (84/401), with 1 cardiac death, 78 MIs, and 5 revascularizations without MI. Use of the HEART Pathway with EMS and ED arrival troponin measures yielded a NPV of 98.0% (95% CI: 89.6-100). NPV improved to 100% (95% CI: 92.9-100) when using the EMS and 3-h ED troponin measures. CONCLUSIONS: EMS blood collection used for core lab ED troponin measures could significantly reduce ED LOS and appears safe when integrated into the HEART Pathway.

HEART Pathway Implementation Safely Reduces Hospitalizations at One Year in Patients With Acute Chest Pain.

STUDY OBJECTIVE: We determine whether implementation of the HEART (History, ECG, Age, Risk Factors, Troponin) Pathway is safe and effective in emergency department (ED) patients with possible acute coronary syndrome through 1 year of follow-up. METHODS: A preplanned analysis of 1-year follow-up data from a prospective pre-post study of 8,474 adult ED patients with possible acute coronary syndrome from 3 US sites was conducted. Patients included were aged 21 years or older, evaluated for possible acute coronary syndrome, and without ST-segment elevation myocardial infarction. Accrual occurred for 12 months before and after HEART Pathway implementation, from November 2013 to January 2016. The HEART Pathway was integrated into the electronic health record at each site as an interactive clinical decision support tool. After integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or nonlow risk (appropriate for further inhospital evaluation). Safety (all-cause death and myocardial infarction) and effectiveness (hospitalization) at 1 year were determined from health records, insurance claims, and death index data. RESULTS: Preimplementation and postimplementation cohorts included 3,713 and 4,761 patients, respectively. The HEART Pathway identified 30.7% of patients as low risk; 97.5% of them were free of death and myocardial infarction within 1 year. Hospitalization at 1 year was reduced by 7.0% in the postimplementation versus preimplementation cohort (62.1% versus 69.1%; adjusted odds ratio 0.70; 95% confidence interval 0.63 to 0.78). Rates of death or myocardial infarction at 1 year were similar (11.6% versus 12.4%; adjusted odds ratio 1.00; 95% confidence interval 0.87 to 1.16). CONCLUSION: HEART Pathway implementation was associated with decreased hospitalizations and low adverse event rates among low-risk patients at 1-year follow-up.

Point-of-Care Troponin Testing during Ambulance Transport to Detect Acute Myocardial Infarction.

Objective: Use of point-of-care (POC) troponin (cTn) testing in the Emergency Department (ED) is well established. However, data examining POC cTn measurement in the prehospital setting, during ambulance transport, are limited. The objective of this study was to prospectively test the performance of POC cTn measurement by paramedics to detect myocardial infarction (MI) among patients transported to the ED for acute chest pain. Methods: A prospective cohort study of adults with non-traumatic chest pain was conducted in three Emergency Medical Services agencies (December 2016 to January 2018). Patients with ST-elevation MI on ECG were excluded. During ambulance transport paramedics initiated intravenous access, collected blood, and used a POC device (i-STAT; Abbott Laboratories) to measure cTn. Following ED arrival, participants received standard evaluations including clinical blood draws for cTn measurement in the hospital central lab (AccuTnI +3 assay; Beckman Coulter, or cTnI-Ultra assay; Siemens). Blood collected during ambulance transport was also analyzed for cTn in the central lab. Index visit MI was adjudicated by 3 experts using central lab cTn measures from the patient's clinical blood draws. Test characteristics (sensitivity, specificity, and predictive values) for detection of MI were calculated for POC and central lab cTn measurement of prehospital blood and compared with McNemar's test. Results: During the study period prehospital POC cTn results were obtained on 421 patients, of which 5.0% (21/421) had results >99th percentile upper reference limit. MI was adjudicated in 16.2% (68/421) during the index visit. The specificity and positive predictive value of the POC cTn measurement were 99.2% (95% CI 97.5-99.8%) and 85.7% (95% CI 63.7-97.0%) for MI. However, the sensitivity and NPV of prehospital POC cTn were 26.5% (95% CI 16.5-38.6%) and 87.5% (95% CI 83.9-90.6%). Compared to POC cTn, the central lab cTn measurement of prehospital blood resulted in a higher sensitivity of 67.9% (95% CI 53.7-80.1%, p < 0.0001), but lower specificity of 92.4% (95% CI 88.4-95.4%, p = 0.0001). Conclusions: Prehospital POC i-STAT cTn measurement in patients transported with acute chest pain was highly specific for MI but had low sensitivity. This suggests that prehospital i-STAT POC cTn could be useful to rule-in MI, but should not be used to exclude MI.

Identification of very low-risk acute chest pain patients without troponin testing.

BACKGROUND: The HEART Pathway combines a History ECG Age Risk factor (HEAR) score and serial troponins to risk stratify patients with acute chest pain. However, it is unclear whether patients with HEAR scores of <1 require troponin testing. The objective of this study is to measure the major adverse cardiac event (MACE) rate among patients with <1 HEAR scores and determine whether serial troponin testing is needed to achieve a miss rate <1%. METHODS: A secondary analysis of the HEART Pathway Implementation Study was conducted. HEART Pathway risk assessments (HEAR scores and serial troponin testing at 0 and 3 hours) were completed by the providers on adult patients with chest pain from three US sites between November 2014 and January 2016. MACE (composite of death, myocardial infarction (MI) and coronary revascularisation) at 30 days was determined. The proportion of patients with HEAR scores of <1 diagnosed with MACE within 30 days was calculated. The impact of troponin testing on patients with HEAR scores of <1 was determined using Net Reclassification Improvement Index (NRI). RESULTS: Providers completed HEAR assessments on 4979 patients and HEAR scores<1 occurred in 9.0% (447/4979) of patients. Among these patients, MACE at 30 days occurred in 0.9% (4/447; 95% CI 0.2% to 2.3%) with two deaths, two MIs and 0 revascularisations. The sensitivity and negative predictive value for MACE in the HEAR <1 was 97.8% (95%CI 94.5% to 99.4%) and 99.1% (95% CI 97.7% to 99.8%), respectively, and were not improved by troponin testing. Troponin testing in patients with HEAR <1 correctly reclassified two patients diagnosed with MACE, and was elevated among seven patients without MACE yielding an NRI of 0.9% (95%CI -0.7 to 2.4%). CONCLUSION: These data suggest that patients with HEAR scores of 0 and 1 represent a very low-risk group that may not require troponin testing to achieve a missed MACE rate <1%. Trial registration number NCT02056964.

Safely Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge.

BACKGROUND: The HEART Pathway (history, ECG, age, risk factors, and initial troponin) is an accelerated diagnostic protocol designed to identify low-risk emergency department patients with chest pain for early discharge without stress testing or angiography. The objective of this study was to determine whether implementation of the HEART Pathway is safe (30-day death and myocardial infarction rate <1% in low-risk patients) and effective (reduces 30-day hospitalizations) in emergency department patients with possible acute coronary syndrome. METHODS: A prospective pre-post study was conducted at 3 US sites among 8474 adult emergency department patients with possible acute coronary syndrome. Patients included were ≥21 years old, investigated for possible acute coronary syndrome, and had no evidence of ST-segment-elevation myocardial infarction on ECG. Accrual occurred for 12 months before and after HEART Pathway implementation from November 2013 to January 2016. The HEART Pathway accelerated diagnostic protocol was integrated into the electronic health record at each site as an interactive clinical decision support tool. After accelerated diagnostic protocol integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or non-low risk (appropriate for further in-hospital evaluation). The primary safety and effectiveness outcomes, death, and myocardial infarction (MI) and hospitalization rates at 30 days were determined from health records, insurance claims, and death index data. RESULTS: Preimplementation and postimplementation cohorts included 3713 and 4761 patients, respectively. The HEART Pathway identified 30.7% as low risk; 0.4% of these patients experienced death or MI within 30 days. Hospitalization at 30 days was reduced by 6% in the postimplementation versus preimplementation cohort (55.6% versus 61.6%; adjusted odds ratio, 0.79; 95% CI, 0.71-0.87). During the index visit, more MIs were detected in the postimplementation cohort (6.6% versus 5.7%; adjusted odds ratio, 1.36; 95% CI, 1.12-1.65). Rates of death or MI during follow-up were similar (1.1% versus 1.3%; adjusted odds ratio, 0.88; 95% CI, 0.58-1.33). CONCLUSIONS: HEART Pathway implementation was associated with decreased hospitalizations, increased identification of index visit MIs, and a very low death and MI rate among low-risk patients. These findings support use of the HEART Pathway to identify low-risk patients who can be safely discharged without stress testing or angiography. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02056964.

Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial.

Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.

Cost analysis of the History, ECG, Age, Risk factors, and initial Troponin (HEART) Pathway randomized control trial.

INTRODUCTION: The HEART Pathway is a diagnostic protocol designed to identify low-risk patients presenting to the emergency department with chest pain that are safe for early discharge. This protocol has been shown to significantly decrease health care resource utilization compared with usual care. However, the impact of the HEART Pathway on the cost of care has yet to be reported. METHODS AND RESULTS: We performed a cost analysis of patients enrolled in the HEART Pathway trial, which randomized participants to either usual care or the HEART Pathway protocol. For low-risk patients, the HEART Pathway recommended early discharge from the emergency department without further testing. We compared index visit cost, cost at 30 days, and cardiac-related health care cost at 30 days between the 2 treatment arms. Costs for each patient included facility and professional costs. Cost at 30 days included total inpatient and outpatient costs, including the index encounter, regardless of etiology. Cardiac-related health care cost at 30 days included the index encounter and costs adjudicated to be cardiac-related within that period. Two hundred seventy of the 282 patients enrolled in the trial had cost data available for analysis. There was a significant reduction in cost for the HEART Pathway group at 30 days (median cost savings of $216 per individual), which was most evident in low-risk (Thrombolysis In Myocardial Infarction score of 0-1) patients (median savings of $253 per patient) and driven primarily by lower cardiac diagnostic costs in the HEART Pathway group. CONCLUSIONS: Using the HEART Pathway as a decision aid for patients with undifferentiated chest pain resulted in significant cost savings.

Coronary Computed Tomography Angiography Versus Traditional Care: Comparison of One-Year Outcomes and Resource Use.

STUDY OBJECTIVE: Three large, multicenter, randomized, clinical trials have shown that coronary computed tomography (CT) angiography allows efficient evaluation and safe discharge of patients with low- to intermediate-risk chest pain who present to the emergency department (ED). We report 1-year event rates and resource use from the American College of Radiology Imaging Network-Pennsylvania 4005 multicenter trial. METHODS: Patients with low- to intermediate-risk chest pain and presenting to the ED were randomized in a 2:1 ratio to a coronary CT angiography care pathway or traditional care. Subjects were contacted by telephone at least 1 year after ED presentation. Medical record review was performed for all cardiac hospitalizations, procedures and diagnostic tests, and adverse cardiac events. Our main outcome was the composite of cardiac death and myocardial infarction within 1 year. The secondary outcome was resource use. RESULTS: One thousand three hundred sixty-eight patients enrolled and 1,285 (94%) had direct participant or proxy contact at 1 year. All others had record review or death index search. From index presentation through 1 year, there was no difference between patients in the coronary CT angiography arm versus traditional care with respect to major adverse cardiac event (1.4% versus 1.1%; difference 0.3%; 95% CI -5.5% to 6.0%). From hospital discharge through 1 year, there was also no difference in ED revisits (36% versus 38%; difference -2.1%; 95% CI -7.9% to 3.7%), hospital admissions (16% versus 17%; difference -0.9%; 95% CI -6.7% to 4.9%), or subsequent cardiac testing (13% versus 13%; difference -0.4%; 95% CI -6.2% to 5.5%). One of 640 subjects with a negative coronary CT angiography result had a major adverse cardiac event within 1 year of presentation (0.16%; 95% CI 0.004% to 0.87%). CONCLUSION: A coronary CT angiography-based strategy for evaluation of patients with low- to intermediate-risk chest pain who present to the ED does not result in increased resource use during 1 year. A negative coronary CT angiography result is associated with a less than 1% major adverse cardiac event rate during the first year after testing.

CT angiography for safe discharge of patients with possible acute coronary syndromes.

BACKGROUND: Admission rates among patients presenting to emergency departments with possible acute coronary syndromes are high, although for most of these patients, the symptoms are ultimately found not to have a cardiac cause. Coronary computed tomographic angiography (CCTA) has a very high negative predictive value for the detection of coronary disease, but its usefulness in determining whether discharge of patients from the emergency department is safe is not well established. METHODS: We randomly assigned low-to-intermediate-risk patients presenting with possible acute coronary syndromes, in a 2:1 ratio, to undergo CCTA or to receive traditional care. Patients were enrolled at five centers in the United States. Patients older than 30 years of age with a Thrombolysis in Myocardial Infarction risk score of 0 to 2 and signs or symptoms warranting admission or testing were eligible. The primary outcome was safety, assessed in the subgroup of patients with a negative CCTA examination, with safety defined as the absence of myocardial infarction and cardiac death during the first 30 days after presentation. RESULTS: We enrolled 1370 subjects: 908 in the CCTA group and 462 in the group receiving traditional care. The baseline characteristics were similar in the two groups. Of 640 patients with a negative CCTA examination, none died or had a myocardial infarction within 30 days (0%; 95% confidence interval [CI], 0 to 0.57). As compared with patients receiving traditional care, patients in the CCTA group had a higher rate of discharge from the emergency department (49.6% vs. 22.7%; difference, 26.8 percentage points; 95% CI, 21.4 to 32.2), a shorter length of stay (median, 18.0 hours vs. 24.8 hours; P<0.001), and a higher rate of detection of coronary disease (9.0% vs. 3.5%; difference, 5.6 percentage points; 95% CI, 0 to 11.2). There was one serious adverse event in each group. CONCLUSIONS: A CCTA-based strategy for low-to-intermediate-risk patients presenting with a possible acute coronary syndrome appears to allow the safe, expedited discharge from the emergency department of many patients who would otherwise be admitted. (Funded by the Commonwealth of Pennsylvania Department of Health and the American College of Radiology Imaging Network Foundation; ClinicalTrials.gov number, NCT00933400.).

Central versus local adjudication of myocardial infarction in a cardiac biomarker trial.

OBJECTIVES: The impact of regulatory requirements, which require central adjudication for the diagnosis of acute myocardial infarction (AMI) in cardiac biomarker studies, is unclear. We determined the impact of local (at the site of subject enrollment) versus central adjudication of AMI on final diagnosis. METHODS: This is a retrospective analysis of data from the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study, an 18-center prospective study of patients with suspected acute coronary syndromes, with enrollment from December 19, 2006, to September 20, 2007. Local adjudication of AMI was performed by a single site investigator at each center following the protocol-specified definition and according to the year 2000 definition of AMI, which based cardiac troponin (cTn) elevation on local cut points for each of the 13 different assays. After completion of the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study primary analysis and to evaluate a new troponin assay, a Food and Drug Administration-mandated central adjudication was performed by 3 investigators at different institutions. This adjudication used the 2007 Universal Definition of AMI, which differs by use of the manufacturer's 99th percentile cTn cut point. We describe the outcome of this process and compare it with the local adjudication. Central adjudicators were not blinded to local adjudications. For central adjudication, discrepant diagnoses were resolved by consensus. Local versus central cTn cut points differed for 6 assays. Both definitions required a rise and/or fall of cTn. Discrepant cases were reviewed by the lead author. Difficult cases were defined as having a difference between local and central adjudication, an elevated cTn with a temporal rise and fall, and a negative or absent risk stratification test. Statistics were by χ(2), κ, and logistic regression. RESULTS: Of 1,107 patients enrolled, 11 had indeterminate central adjudication, leaving 1,096 for analysis. In spite of high agreement across central versus local adjudicators, κ = 0.79 (95% CI [0.73, 0.85]), AMI was diagnosed more often by central adjudication, 134 (12.2%) versus 104 (9.5%), with 44 local diagnoses (4%) changed from non-AMI to AMI (n = 37) or AMI to non-AMI (n = 7) (P < .001). These 44 represented 34% (95% CI 26%-42%) of 141 cases in which either central or local adjudication was AMI. Of diagnoses changed to AMI, 3 reasons contributed approximately one-third each: the local use of a non-99th percentile cTn cutoff (32%), the possibility of human error (34%), and difficult cases (34%). CONCLUSION: Despite an acceptable κ, over a third of patients with a diagnosis of AMI were not assigned that diagnosis by both sets of adjudicators. This supports the importance of 1 standard method for diagnosis of AMI.

Isolated head injury is a cause of shock in pediatric trauma patients.

OBJECTIVES: Current trauma resuscitation protocols from the American College of Surgeons, Committee on Trauma, recommend intravascular volume expansion to treat shock after major trauma, assuming that hemorrhage is present. However, this assumption may not be correct. The purpose of this study was to identify the proportion of children with severe shock after trauma presenting with isolated head injury versus hemorrhagic injury. METHODS: A retrospective review of all pediatric trauma patients (aged 0-15 years) was conducted over a 5-year period. Severe shock was defined as the presence of both an elevated blood lactate level and low blood pressure for age. Traumatic injuries were classified as hemorrhagic injuries, head injuries, combined hemorrhagic and head injuries, or other injuries, by analyzing International Classification of Diseases, Ninth Revision diagnostic codes. RESULTS: A total of 31 (5%) of 680 pediatric trauma patients presented with severe shock. Among these 31 pediatric trauma patients, 9 (29%) had isolated head injury. Isolated head injury among children with shock was most frequently observed among children younger than 5 years (50%), and a decreased trend was noted with increasing age (23% for children 5-11 years and 0% for children 12-15 years [P = 0.03, Cochran-Armitage exact trend test]). CONCLUSIONS: Isolated head injury was observed in 29% of children 0 to 15 years of age with severe shock after trauma and in 50% of children younger than 5 years. Head injury is an important cause of severe shock in pediatric trauma, particularly among young children.