Predictors, Prevalence, and Outcomes of Early Crystalloid Responsiveness Among Initially Hypotensive Patients With Sepsis and Septic Shock.

OBJECTIVES: The prevalence of responsiveness to initial fluid challenge among hypotensive sepsis patients is unclear. To avoid fluid overload, and unnecessary treatment, it is important to differentiate these phenotypes. We aimed to 1) determine the proportion of hypotensive sepsis patients sustaining favorable hemodynamic response after initial fluid challenge, 2) determine demographic and clinical risk factors that predicted refractory hypotension, and 3) assess the association between timeliness of fluid resuscitation and refractoriness. DESIGN: Secondary analysis of a prospective, multisite, observational, consecutive-sample cohort. SETTING: Nine tertiary and community hospitals over 1.5 years. PATIENTS: Inclusion criteria 1) suspected or confirmed infection, 2) greater than or equal to two systemic inflammatory response syndrome criteria, 3) systolic blood pressure less than 90 mm Hg, greater than 40% decrease from baseline, or mean arterial pressure less than 65 mm Hg. MEASUREMENTS AND MAIN RESULTS: Sex, age, heart failure, renal failure, immunocompromise, source of infection, initial lactate, coagulopathy, temperature, altered mentation, altered gas exchange, and acute kidney injury were used to generate a risk score. The primary outcome was sustained normotension after fluid challenge without vasopressor titration. Among 3,686 patients, 2,350 (64%) were fluid responsive. Six candidate risk factors significantly predicted refractoriness in multivariable analysis: heart failure (odds ratio, 1.43; CI, 1.20-1.72), hypothermia (odds ratio, 1.37; 1.10-1.69), altered gas exchange (odds ratio, 1.33; 1.12-1.57), initial lactate greater than or equal to 4.0 mmol/L (odds ratio, 1.28; 1.08-1.52), immunocompromise (odds ratio, 1.23; 1.03-1.47), and coagulopathy (odds ratio, 1.23; 1.03-1.48). High-risk patients (≥ three risk factors) had 70% higher (CI, 48-96%) refractory risk (19% higher absolute risk; CI, 14-25%) versus low-risk (zero risk factors) patients. Initiating fluids in greater than 2 hours also predicted refractoriness (odds ratio, 1.96; CI, 1.49-2.58). Mortality was 15% higher (CI, 10-18%) for refractory patients. CONCLUSIONS: Two in three hypotensive sepsis patients were responsive to initial fluid resuscitation. Heart failure, hypothermia, immunocompromise, hyperlactemia, and coagulopathy were associated with the refractory phenotype. Fluid resuscitation initiated after the initial 2 hours more strongly predicted refractoriness than any patient factor tested.

Patterns and Outcomes Associated With Timeliness of Initial Crystalloid Resuscitation in a Prospective Sepsis and Septic Shock Cohort.

OBJECTIVES: The objectives of this study were to 1) assess patterns of early crystalloid resuscitation provided to sepsis and septic shock patients at initial presentation and 2) determine the association between time to initial crystalloid resuscitation with hospital mortality, mechanical ventilation, ICU utilization, and length of stay. DESIGN: Consecutive-sample observational cohort. SETTING: Nine tertiary and community hospitals over 1.5 years. PATIENTS: Adult sepsis and septic shock patients captured in a prospective quality improvement database inclusion criteria: suspected or confirmed infection, greater than or equal to two systemic inflammatory response criteria, greater than or equal to one organ-dysfunction criteria. INTERVENTIONS: The primary exposure was crystalloid initiation within 30 minutes or lesser, 31-120 minutes, or more than 120 minutes from sepsis identification. MEASUREMENTS AND MAIN RESULTS: We identified 11,182 patients. Crystalloid initiation was faster for emergency department patients (ß, -141 min; CI, -159 to -125; p < 0.001), baseline hypotension (ß, -39 min; CI, -48 to -32; p < 0.001), fever, urinary or skin/soft-tissue source of infection. Initiation was slower with heart failure (ß, 20 min; CI, 14-25; p < 0.001), and renal failure (ß, 16 min; CI, 10-22; p < 0.001). Five thousand three hundred thirty-six patients (48%) had crystalloid initiated in 30 minutes or lesser versus 2,388 (21%) in 31-120 minutes, and 3,458 (31%) in more than 120 minutes. The patients receiving fluids within 30 minutes had lowest mortality (949 [17.8%]) versus 31-120 minutes (446 [18.7%]) and more than 120 minutes (846 [24.5%]). Compared with more than 120 minutes, the adjusted odds ratio for mortality was 0.76 (CI, 0.64-0.90; p = 0.002) for 30 minutes or lesser and 0.76 (CI, 0.62-0.92; p = 0.004) for 31-120 minutes. When assessed continuously, mortality odds increased by 1.09 with each hour to initiation (CI, 1.03-1.16; p = 0.002). We observed similar patterns for mechanical ventilation, ICU utilization, and length of stay. We did not observe significant interaction for mortality risk between initiation time and baseline heart failure, renal failure, hypotension, acute kidney injury, altered gas exchange, or emergency department (vs inpatient) presentation. CONCLUSIONS: Crystalloid was initiated significantly later with comorbid heart failure and renal failure, with absence of fever or hypotension, and in inpatient-presenting sepsis. Earlier crystalloid initiation was associated with decreased mortality. Comorbidities and severity did not modify this effect.

Survival Benefit and Cost Savings From Compliance With a Simplified 3-Hour Sepsis Bundle in a Series of Prospective, Multisite, Observational Cohorts.

OBJECTIVES: To determine mortality and costs associated with adherence to an aggressive, 3-hour sepsis bundle versus noncompliance with greater than or equal to one bundle element for severe sepsis and septic shock patients. DESIGN: Prospective, multisite, observational study following three sequential, independent cohorts, from a single U.S. health system, through their hospitalization. SETTING: Cohort 1: five tertiary and six community hospitals. Cohort 2: single tertiary, academic medical center. Cohort 3: five tertiary and four community hospitals. PATIENTS: Consecutive sample of all severe sepsis and septic shock patients (defined: infection, ≥ 2 systemic inflammatory response syndrome, and hypoperfusive organ dysfunction) identified by a quality initiative. The exposure was full 3-hour bundle compliance. Bundle elements are as follows: 1) blood cultures before antibiotics; 2) parenteral antibiotics administered less than or equal to 180 minutes from greater than or equal to two systemic inflammatory response syndrome "and" lactate ordered, or less than or equal to 60 minutes from "time-zero," whichever occurs earlier; 3) lactate result available less than or equal to 90 minutes postorder; and 4) 30 mL/kg IV crystalloid bolus initiated less than or equal to 30 minutes from "time-zero." Main outcomes were in-hospital mortality (all cohorts) and total direct costs (cohorts 2 and 3). MEASUREMENTS AND MAIN RESULTS: Cohort 1: 5,819 total patients; 1,050 (18.0%) bundle compliant. Mortality: 604 (22.6%) versus 834 (26.5%); CI, 0.9-7.1%; adjusted odds ratio, 0.72; CI, 0.61-0.86; p value is less than 0.001. Cohort 2: 1,697 total patients; 739 (43.5%) bundle compliant. Mortality: 99 (13.4%) versus 171 (17.8%), CI, 1.0-7.9%; adjusted odds ratio, 0.60; CI, 0.44-0.80; p value is equal to 0.001. Mean costs: $14,845 versus $20,056; CI, -$4,798 to -5,624; adjusted ß, -$2,851; CI, -$4,880 to -822; p value is equal to 0.006. Cohort 3: 7,239 total patients; 2,115 (29.2%) bundle compliant. Mortality: 383 (18.1%) versus 1,078 (21.0%); CI, 0.9-4.9%; adjusted odds ratio, 0.84; CI, 0.73-0.96; p value is equal to 0.013. Mean costs: $17,885 versus $22,108; CI, -$2,783 to -5,663; adjusted ß, -$1,423; CI, -$2,574 to -272; p value is equal to 0.015. CONCLUSIONS: In three independent cohorts, 3-hour bundle compliance was associated with improved survival and cost savings.

Early sepsis bundle compliance for non-hypotensive patients with intermediate versus severe hyperlactemia.

OBJECTIVE: To compare the association of 3-h sepsis bundle compliance with hospital mortality in non-hypotensive sepsis patients with intermediate versus severe hyperlactemia. METHODS: This was a cohort study of all non-hypotensive, hyperlactemic sepsis patients captured in a prospective quality-improvement database, treated October 2014 to September 2015 at five tertiary-care centers. We defined sepsis as 1) infection, 2) ≥2 SIRS criteria, and 3) ≥1 organ dysfunction criterion. "Time-zero" was the first time a patient met all sepsis criteria. INCLUSION CRITERIA: systolic blood pressure>90 mmHg, mean arterial pressure>65 mmHg, and serum lactate≥2.2 mmol/L. Primary exposures: 1) intermediate(2.2-3.9 mmol/L) versus severe(≥4.0 mmol/L) hyperlactemia and 2) full 3-h bundle compliance. Bundle elements: The primary outcome was 60-day in-hospital mortality. RESULTS: 2417 patients met inclusion criteria. 704(29%) had lactate≥4.0 mmol/L versus 1775 patients with lactate 2.2-3.9 mmol/L. Compliance was 75% for antibiotics and 53% for fluids. Full-compliance was comparable between lactate groups (n=200(29%) and 488(28%), respectively). We observed 424(17.5%) mortalities: intermediate/non-compliant - 182(14.9%), intermediate/compliant - 41(8.4%), severe/non-compliant - 147(29.2%), severe/compliant - 54(27.0%) [difference-of-differences=4.3%, CI=2.6-5.9%]. In multivariable regression, mortality predictors included severe hyperlactemia (OR=1.99, CI=1.51-2.63) and bundle compliance (OR=0.62, CI=0.42-0.90), and their interaction was significant: p(interaction)=0.022. CONCLUSION: We observed a significant interaction between 3-h bundle compliance and initial hyperlactemia. Bundle compliance may be associated with greater mortality benefit for non-hypotensive sepsis patients with less severe hyperlactemia.

Association of Fluid Resuscitation Initiation Within 30 Minutes of Severe Sepsis and Septic Shock Recognition With Reduced Mortality and Length of Stay.

STUDY OBJECTIVE: We evaluate the association of intravenous fluid resuscitation initiation within 30 minutes of severe sepsis or septic shock identification in the emergency department (ED) with inhospital mortality and hospital length of stay. We also compare intravenous fluid resuscitation initiated at various times from severe sepsis or septic shock identification's association with the same outcomes. METHODS: This was a review of a prospective, observational cohort of all ED severe sepsis or septic shock patients during 13 months, captured in a performance improvement database at a single, urban, tertiary care facility (90,000 ED visits/year). The primary exposure was initiation of a crystalloid bolus at 30 mL/kg within 30 minutes of severe sepsis or septic shock identification. Secondary analysis compared intravenous fluid initiated within 30, 31 to 60, or 61 to 180 minutes, or when intravenous fluid resuscitation was initiated at greater than 180 minutes or not provided. RESULTS: Of 1,866 subjects, 53.6% were men, 72.5% were white, mean age was 72 years (SD 16.6 years), and mean initial lactate level was 2.8 mmol/L. Eighty-six percent of subjects were administered intravenous antibiotics within 180 minutes; 1,193 (64%) had intravenous fluid initiated within 30 minutes. Mortality was lower in the within 30 minutes group (159 [13.3%] versus 123 [18.3%]; 95% confidence interval [CI] 1.4% to 8.5%), as was median hospital length of stay (6 days [95% CI 6 to 7] versus 7 days [95% CI 7 to 8]). In multivariate regression that included adjustment for age, lactate, hypotension, acute organ dysfunction, and Emergency Severity Index score, intravenous fluid within 30 minutes was associated with lower mortality (odds ratio 0.63; 95% CI 0.46 to 0.86) and 12% shorter length of stay (hazard ratio=1.14; 95% CI 1.02 to 1.27). In secondary analysis, mortality increased with later intravenous fluid resuscitation initiation: 13.3% (≤30 minutes) versus 16.0% (31 to 60 minutes) versus 16.9% (61 to 180 minutes) versus 19.7% (>180 minutes). Median hospital length of stay also increased with later intravenous fluid initiation: 6 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 8 days) versus 8 days (95% CI 7 to 9 days). CONCLUSION: The time of intravenous fluid resuscitation initiation was associated with improved mortality and could be used as an easier obtained alternative to intravenous fluid completion time as a performance indicator in severe sepsis and septic shock management.

Serum Amyloid A Stimulates PKR Expression and HMGB1 Release Possibly through TLR4/RAGE Receptors.

Serum amyloid A (SAA) proteins are known to be surrogate markers of sepsis, but their pathogenic roles remain poorly elucidated. Here we provide evidence to support a possible role of SAA as a pathogenic mediator of lethal sepsis. In a subset of septic patients for which serum high mobility group box 1 (HMGB1) levels paralleled the clinical scores, some anti-HMGB1 antibodies detected a 12-kDa protein belonging to the SAA family. In contrast to the most abundant SAA1, human SAA induced double-stranded RNA-activated protein kinase R (PKR) expression and HMGB1 release in the wild-type, but not toll-like receptor 4/receptor for advanced glycation end products (TLR4/RAGE)-deficient, macrophages. Pharmacological inhibition of PKR phosphorylation blocked SAA-induced HMGB1 release, suggesting an important role of PKR in SAA-induced HMGB1 release. In animal models of lethal endotoxemia and sepsis, recombinant SAA exacerbated endotoxemic lethality, whereas SAA-neutralizing immunoglobulins G (IgGs) significantly improved animal survival. Collectively, these findings have suggested SAA as an important mediator of inflammatory diseases. Highlights of this study include: human SAA is possibly only expressed in a subset of septic patients; SAA induces HMGB1 release via TLR4 and RAGE receptors; SAA supplementation worsens the outcome of lethal endotoxemia; whereas SAA-neutralizing antibodies confer protection against lethal endotoxemia and sepsis.

Combining transtracheal catheter oxygenation and needle-based Seldinger cricothyrotomy into a single, sequential procedure.

BACKGROUND: Needle-based cricothyrotomy is a common procedure for emergency department patients requiring an emergent surgical airway. Percutaneous transtracheal jet ventilation is well studied to provide oxygenation. We propose to combine these procedures into a novel, single, and sequential procedure. METHODS: This study was a prospective manikin/human cadaver procedural feasibility study performed at a medical education center. Forty-eight emergency medicine attending physicians and fellows performed the procedure on a single TraumaMan (Simulab Corporation, Seattle, WA), and 26 were randomly selected to perform the procedure on fresh, unfixed human cadavers. The procedure is as follows: 15 gauge/6F catheter-over-needle punctures cricothyroid membrane, needle is removed, and Enk oxygen flow modulator is attached to the catheter (start to oxygenation). The Enk set is detached, a guide wire introduced, and Seldinger cricothyrotomy is performed (oxygenation to cricothyrotomy). Start-to-oxygenation, oxygenation-to-cricothyrotomy, and start-to-cricothyrotomy times were recorded. Manikin procedures were verified by direct visualization, and cadaver procedures were verified by video laryngoscopy. RESULTS: All attempts were included in data analysis, and there was a 100% first-pass success rate. For the manikin trials, median start-to-oxygenation, oxygenation-to-cricothyrotomy, and start-to-cricothyrotomy times with interquartile ranges were 11 (8.5-13), 48 (42-57), and 59 (53-69) seconds, respectively. For the cadaver trials, median start-to-oxygenation, oxygenation-to-cricothyrotomy, and start-to-cricothyrotomy times with interquartile ranges were 12 (10-15), 59 (47-76), and 71 (61-94) seconds, respectively. Student t tests showed significant differences in start-to-oxygenation and oxygenation-to-cricothyrotomy times (P < .01) within the manikin and cadaver groups. CONCLUSION: Percutaneous transtracheal jet ventilation and needle-based Seldinger cricothyrotomy can be performed by emergency medicine physicians, and a single, sequential procedure may significantly reduce time to oxygenation for patients already undergoing surgical cricothyrotomy.

Saline Flush Test: Can Bedside Sonography Replace Conventional Radiography for Confirmation of Above-the-Diaphragm Central Venous Catheter Placement?

OBJECTIVES: Resuscitation often requires rapid vascular access via central venous catheters. Chest radiography is the reference standard to confirm central venous catheter placement and exclude complications. However, radiographs are often untimely. The purpose of this study was to determine whether dynamic sonographic visualization of a saline flush in the right side of the heart after central venous catheter placement could serve as a more rapid confirmatory study for above-the-diaphragm catheter placement. METHODS: A consecutive prospective enrollment study was conducted in the emergency departments of 2 major tertiary care centers. Adult patients of the study investigators who required an above-the-diaphragm central venous catheter were enrolled during the study period. Patients had a catheter placed with sonographic guidance. After placement of the catheter, thoracic sonography was performed. The times for visualization of the saline flush in the right ventricle and sonographic exclusion of ipsilateral pneumothorax were recorded. Chest radiography was performed per standard practice. RESULTS: Eighty-one patients were enrolled; 13 were excluded. The mean catheter confirmation time by sonography was 8.80 minutes (95% confidence interval, 7.46-10.14 minutes). The mean catheter confirmation time by chest radiograph availability for viewing was 45.78 minutes (95% confidence interval, 37.03-54.54 minutes). Mean sonographic confirmation occurred 36.98 minutes sooner than radiography (P< .001). No discrepancy existed between sonographic and radiographic confirmation. CONCLUSIONS: Confirmation of central venous catheter placement by dynamic sonographic visualization of a saline flush with exclusion of pneumothorax is an accurate, safe, and more efficient method than confirmation by chest radiography. It allows the central line to be used immediately, expediting patient care.

The relationship between patient age and pain management of acute long-bone fracture in the ED.

OBJECTIVE: Certain patient populations may be unable to communicate their needs in the emergency department (ED) setting, and the ability to communicate varies between age groups. We aim to determine if there are differences in pain management of acute long-bone fracture (ALBF) among age groups presenting to the ED. METHODS: This study was a retrospective chart review of a consecutive sample of subjects over 13 months. Fracture site, subject age, arrival time, whether pain medication was administered, and time to initial administration were recorded. Subjects were categorized into 3 groups based on age: pediatric (<18 years), adult (≥18 and <65 years), and geriatric (≥65 years). RESULTS: A total of 1255 patients were included in analysis. One hundred seventy-seven (78.0%) pediatric, 364 (86.5%) adult, and 486 (80.1%) geriatric patients received pain medication during their ED stay. Median and average times to initial pain medication administration with 95% confidence intervals were 44 and 52.0 minutes (45.9-58.1), 39 and 53.6 minutes (48.8-58.4), and 55 and 73.2 minutes (68.1-78.3) for pediatric, adult, and geriatric groups, respectively. A single-factor analysis of variance indicated a significant difference between the groups (P<.01). Student t tests revealed significant differences between pediatric and geriatric groups (P<.01) and adult and geriatric groups (P<.01). CONCLUSIONS: Although most patients presenting to the ED with ALBF were geriatric, these patients were the least likely to have their pain addressed in a timely fashion. Subgroup analysis of pediatric and geriatric populations indicates significant delay, especially for those ages younger than 3 and 85 years and older. We believe that patients within these groups experience the greatest difficulty communicating their needs effectively due to age-related issues.

Impact of a Novel Emergency Department Forward Treatment Area During the New York City COVID-19 Surge.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused a disproportionate number of patients to seek emergency care at hospitals in New York City (NYC) during the initial crisis. Our urban emergency department (ED), a member of the NYC public hospital system had to process the increased volume while also differentiating our patients' critical needs. We established a forward treatment area (FTA) directly in front of the ED to accomplish these goals from March 23-April 16, 2020. METHODS: A clinical greeter evaluated patients 18 years and older who presented to the walk-in entrance of the ED where they were screened for COVID-19-like complaints. If they did not appear critically ill and could ambulate they were directed into the FTA. Clinical and non-clinical staff worked in concert to register, evaluate, and process patients with either a disposition of directly home or into the ED for further care. RESULTS: A total of 634 patients were seen in the FTA from March 23-April 16, 2020. Of the 634 patients evaluated, 135 (21%) were referred into the ED for further evaluation, of whom 81 (12.7% of the total) were admitted. These patients were disproportionately male (91 into the ED and 63 admitted) and tended to have a higher heart rate (105.4 vs 93.7), a higher respiratory rate (21.5 vs 18.1), and lower oxygen saturation (93.9% vs 97.8%). CONCLUSION: A forward treatment area is an effective method to rapidly screen and process an increased volume of COVID-19 patients when resources are limited. This treatment area helped decompress the ED by being rapidly deployable and effectively screening patients for safe discharge home.

Intubation outcomes and practice trends during the initial New York SARS-COV-19 surge at an academic, level 1 trauma, urban emergency department.

OBJECTIVES: The goal of this study was to describe outcomes and associated characteristics of patients who were intubated during the initial (3/2020-4/2020) New York City surge of the severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic, during which time we were confronted by an unknown and unprecedented respiratory distress syndrome with extremely high degrees of morbidity and mortality. Our secondary aim was to analyze our physician's rapidly evolving approaches to COVID-19 airway management. METHODS: A retrospective cohort analysis of all patients intubated at two emergency departments (EDs) for COVID-19 suspected respiratory failure. In addition, a survey was done to analyze clinician airway management trends and attitudes as they evolved during that period. RESULTS: Ninety-five patients met inclusion criteria for the study. Primary outcomes looked at the spectrum of mortality outcomes ranging from died on arrival (DOA) to the ED, died in the ED (DED), died an inpatient (DIH), and survival to discharge. Overall mortalitywas 71.6% with an average age of 62.7 years. Female sex, as a demographic, was associated with higher rates of survival to discharge at 42.3% when compared to males at 23.2% (P < 0.001). Mean age was 70.8 years DOA, 65.6 years DED, 62.9 years DIH, and 60.0 years for survivors (P = 0.0037). Initial lactate levels were 8.15 mmol/L DED, 3.56 mmol/L DIH, and 2.61 mmol/L survivors (P < 0.0001). Initial creatinine levels were 3.38 mg/dL DED, 1.94 mg/dL DIH, and 1.77 mg/dL survivors (P = 0.0073). D-dimer levels were 7520.5 ng/mL DED, 5932.4 ng/mL DIH, and 1133.9 ng/mL survivors (P = 0.0045). Physician survey respondents reported high levels (69%) of laryngeal edema and prolonged post intubation hypoxia (>50% of time) and >80% remained concerned for their safety. There was a dramatic shift from early (73% of time) to late intubation strategies (67% of time) or non-invasive approaches (28% of time) as the first surge of the pandemic evolved. CONCLUSION: Our findings demonstrate that several demographic, clinical and laboratory parameters correlated with mortality in our cohort of patients intubated during the initial phase of the COVID-19 pandemic. These included male sex, advanced age, high levels of initial lactic acidosis, elevated D-dimer, and chronic kidney disease/acute kidney injury. In contrast, presenting respiratory characteristics were not correlated with mortality. In addition, our findings demonstrate that physician attitudes and strategies related to COVID-19 airway management evolved significantly and rapidly over the initial phase of the pandemic.

Sepsis Presenting in Hospitals versus Emergency Departments: Demographic, Resuscitation, and Outcome Patterns in a Multicenter Retrospective Cohort.

BACKGROUND: Differences between hospital-presenting sepsis (HPS) and emergency department-presenting sepsis (EDPS) are not well described. OBJECTIVES: We aimed to (1) quantify the prevalence of HPS versus EDPS cases and outcomes; (2) compare HPS versus EDPS characteristics at presentation; (3) compare HPS versus EDPS in process and patient outcomes; and (4) estimate risk differences in patient outcomes attributable to initial resuscitation disparities. DESIGN: Retrospective consecutive-sample cohort. SETTING: Nine hospitals from October 1, 2014, to March 31, 2016. PATIENTS: All hospitalized patients with sepsis or septic shock, as defined by simultaneous (1) infection, (2) ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria, and (3) ≥1 acute organ dysfunction criterion. EDPS met inclusion criteria while physically in the emergency department (ED). HPS met the criteria after leaving the ED. MEASUREMENTS: We assessed overall HPS versus EDPS contributions to case prevalence and outcomes, and then compared group differences. Process outcomes included 3-hour bundle compliance and discrete bundle elements (eg, time to antibiotics). The primary patient outcome was hospital mortality. RESULTS: Of 11,182 sepsis hospitalizations, 2,509 (22.4%) were hospital-presenting. HPS contributed 785 (35%) sepsis mortalities. HPS had more frequent heart failure (OR: 1.31, CI: 1.18-1.47), renal failure (OR: 1.62, CI: 1.38-1.91), gastrointestinal source of infection (OR: 1.84, CI: 1.48-2.29), euthermia (OR: 1.45, CI: 1.10-1.92), hypotension (OR: 1.85, CI: 1.65-2.08), or impaired gas exchange (OR: 2.46, CI: 1.43-4.24). HPS were admitted less often from skilled nursing facilities (OR: 0.44, CI: 0.32-0.60), had chronic obstructive pulmonary disease (OR: 0.53, CI: 0.36-0.78), tachypnea (OR: 0.76, CI: 0.58-0.98), or acute kidney injury (OR: 0.82, CI: 0.68-0.97). In a propensity-matched cohort (n = 3,844), HPS patients had less than half the odds of 3-hour bundle compliant care (17.0% vs 30.3%, OR: 0.47, CI: 0.40-0.57) or antibiotics within three hours (66.2% vs 83.8%, OR: 0.38, CI: 0.32-0.44) vs EDPS. HPS was associated with higher mortality (31.2% vs 19.3%, OR: 1.90, CI: 1.64-2.20); 23.3% of this association was attributable to differences in initial resuscitation (resuscitation-adjusted OR: 1.69, CI: 1.43-2.00). CONCLUSIONS: HPS differed from EDPS by admission source, comorbidities, and clinical presentation. These patients received markedly less timely initial resuscitation; this disparity explained a moderate proportion of mortality differences.

Evolution of Pararescue medicine during operation Enduring Freedom.

This article highlights recent advances made in U.S. Air Force Pararescue Medical Operations in relation to tactical evacuation procedures. Most of these changes have been adopted and adapted from civilian medicine practice, and some have come from shared experiences with partner nations. Patient assessment includes a more comprehensive evaluation for hemorrhage and indications for hemorrhagic control. Ketamine has replaced morphine and fentanyl as the primary sedative used during rapid sequence intubation and procedural sedation. There has been an increasing use of the bougie to clear an airway or nasal cavity that becomes packed with debris. Video laryngoscopy provides advantages over direct laryngoscopy, especially in situations where there are environmental constraints such as the back of a Pave Hawk helicopter. Intraosseous access has become popular to treat and control hemorrhagic shock when peripheral intravenous access is impractical or impossible. Revisions to patient treatment cards have improved the efficacy and compliance of documentation and have made patient handoff more efficient. These improvements have only been possible because of the concerted efforts of U.S. Air Force and partner platforms operating in Afghanistan.

Bench to bedside: HMGB1-a novel proinflammatory cytokine and potential therapeutic target for septic patients in the emergency department.

Overwhelming gram-negative bacterial infection and life-threatening systemic inflammation are widespread problems in critically ill emergency department patients. Currently, the treatment of these patients is largely supportive, focusing on antibiotics, fluids, hemodynamic and ventilatory support, and intensive monitoring. The only Food and Drug Administration-approved pharmaceutical agent for the treatment of sepsis is activated protein C, with its use largely relegated to the intensive care unit. The subject thus remains an active area of exploration for emergency medicine research. During sepsis and inflammation, innate immune cells release excessive amounts of proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1beta. If delivered early enough, anti-TNF antibodies can be an effective therapy in experimental models of septic shock. Anti-TNF antibodies have been developed for clinical use in rheumatoid arthritis and Crohn's disease. However, anti-TNF treatment for sepsis has been difficult to achieve in the clinical setting, perhaps because TNF's early release and transient appearance in the serum create a narrow therapeutic window. An alternative strategy would be to identify "late" mediators that may be clinically more accessible. High mobility group box 1 (HMGB1), a protein previously known only as a nuclear transcription factor, is now implicated as a late mediator of sepsis. Targeting late mediators of lethal systemic inflammation represents a novel approach that may widen the therapeutic window and lead to new strategies for inhibiting the deleterious effects of the inflammatory cascade. Here the authors review the studies that led to the discovery of HMGB1 as a late mediator of systemic inflammation and discuss the possibility of HMGB1 as a therapeutic target for septic patients in the emergency department.

A review of the evolution of intraosseous access in tactical settings and a feasibility study of a human cadaver model for a humeral head approach.

In the tactical setting, intraosseous (IO) access has become popular to treat hemorrhagic shock when peripheral intravenous access is difficult or impractical. The traditional sites most commonly used by combat medics, corpsmen, and Pararescuemen (PJs) include the sternum and tibial tuberosity. Recent studies have shown that the humeral head (HH) is an appropriate and effective access site for IO infusion and fluid resuscitation in the clinical setting. In this procedural feasibility study, we assessed the ability of 26 U.S. Air Force PJs to perform HH IO placement on fresh, unfixed human cadavers over two consecutive cadaver lab training sessions. Following a formal didactic session, which highlighted proper patient positioning and technique, the PJs were instructed to attempt to place an IO needle using both a drill and manual driver. Once performed, correct placement was reviewed by a physician and confirmed by aspiration of bone marrow. Rates of success were calculated on first and second pass. First pass success rates were 96% and 90.5% for the drill and driver, respectively. Both devices achieved 100% success by the second pass. Military field personnel would benefit from a HH approach, especially in the care and management of patients of explosive injuries.

Peripheral administration of fetuin-A attenuates early cerebral ischemic injury in rats.

Cerebral ischemia-elicited inflammatory responses are driven by inflammatory mediators produced both by central (e.g., neurons and microglia) and infiltrating peripheral immune cells (e.g., macrophage/monocyte), and contribute to the evolution of tissue injury. A ubiquitous molecule, spermine, is released from injured cells, and counter-regulates release of various proinflammatory cytokines. However, the spermine-mediated anti-inflammatory activities are dependent on the availability of fetuin-A, a liver-derived negative acute-phase protein. Using an animal model of focal cerebral ischemia (i.e., permanent middle cerebral artery occlusion, MCAo), we found that levels of fetuin-A in the ischemic brain tissue were elevated in a time-dependent manner, starting between 2 and 6 h, peaking around 24 to 48 h, and returning to baseline 72 h after MCAo. When administered peripherally, exogenous fetuin-A gained entry across the BBB into the ischemic brain tissue, and dose dependently reduced brain infarct volume at 24 h after MCAo. Meanwhile, fetuin-A effectively attenuated (i) ischemia-induced HMGB1 depletion from the ischemic core; (ii) activation of centrally (e.g., microglia) and peripherally derived immune cells (e.g., macrophage/monocytes); and (iii) TNF production in ischemic brain tissue. Taken together, these experimental data suggest that fetuin-A protects against early cerebral ischemic injury partly by attenuating the brain inflammatory response.