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Objective: To determine if the addition of lactate to Quick Sequential Organ Failure Assessment (qSOFA) scoring improves emergency department (ED) screening of septic patients for critical illness., Methods: This was a multicenter retrospective cohort study of consecutive adult patients admitted to the hospital from the ED with infectious disease-related illnesses. We recorded qSOFA criteria and initial lactate levels in the first 6 h of ED stay. Our primary outcome was a composite of hospital death, vasopressor use, and intensive care unit stay ≤72 h of presentation. Diagnostic test characteristics were determined for: 1) lactate levels ≥2 and ≥4; 2) qSOFA scores ≥1, ≥2, and =3; and 3) combinations of these., Results: Of 3743 patients, 2584 had a lactate drawn ≤6 h of ED stay and 18% met the primary outcome. The qSOFA scores were ≥1, ≥2, and =3 in 59.2%, 22.0%, and 5.3% of patients, respectively, and 34.4% had a lactate level ≥2 and 7.9% had a lactate level ≥4. The combination of qSOFA ≥1 OR Lactate ≥2 had the highest sensitivity, 94.0% (95% CI: 91.3-95.9)., Conclusions: The combination of qSOFA ≥1 OR Lactate ≥2 provides substantially improved sensitivity for the screening of critical illness compared to isolated lactate and qSOFA thresholds., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Mitochondrial dysfunction has been implicated as a key cellular event leading to organ dysfunction in sepsis. Our objective is to measure changes in mitochondrial bioenergetics in subjects with early presentation of sepsis to provide insight into the incompletely understood pathophysiology of the dysregulated host response in sepsis., Design: Prospective observational study., Setting: Single site tertiary academic emergency department., Subjects: We enrolled a total of 48 subjects in the study, 10 with sepsis or septic shock, 10 with infection without sepsis, 14 older and 14 younger healthy controls., Interventions: Peripheral blood mononuclear cells were measured with high-resolution respirometry (OROBOROS O2K)., Measurements and Main Results: The median age in patients with sepsis, infection only, older control and younger controls were 63, 34, 61, and 29 years old, respectively. In the Sepsis group, the median 1st 24-h SOFA score was 8, and the initial median lactate was 4.2 mmol/dL, compared with 1.1 in the Infection Group. The 30-day mortality of the sepsis/septic shock group was 50%, with a median length of stay of 7-days. The Sepsis Group had significantly lower routine and Max respiration when compared with the other groups as well as uncoupled Complex I respiration. There was also a significant decrease in ATP-linked respiration along with the Spare Reserve Capacity in the Sepsis Group when compared with the other group. There were no age-related differences in respiration between the Older and Younger control group., Conclusions: Bedside measurement of mitochondrial respiration can be minimally invasive and performed in a timely manner. Mitochondrial dysfunction, detected by decreased oxygen consumption utilized for energy production and depleted cellular bioenergetics reserve.

Mitochondria are dynamic organelles that adapt in response to environmental stresses or mutations. Dynamic processes involving mitochondria include their locomotion within cells and fusion and fission events in which mitochondrial join together or split apart. Various imaging strategies have been utilized to track mitochondrial dynamics. One common limitation of most of the methods available is that the time required to perform the technique and analyze the results prohibits application to clinical diagnosis and therapy. We recently demonstrated "whole-cell" mitochondrial analysis in a two-dimensional fashion with fluorescence microscopy. Our developed technique allows evaluation of whole-cell mitochondrial networking, including assessment of mitochondrial motility and rates of fission and fusion events using human blood cells (peripheral blood mononuclear cells (PBMCs)) on a clinically relevant timescale. We demonstrate this methodology in a cohort of healthy subjects as well as a cohort of hospitalized subjects having sepsis, an acute care illness. As there is increasing use of human blood cells as a proxy of organ mitochondrial function with respiration in various disease states, the addition of mitochondrial dynamics will now allow for more thorough clinical evaluation of mitochondrial networking in human disease with potential exploration of therapeutics., (Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Objective: We sought to compare the quick sequential organ failure assessment (qSOFA) to systemic inflammatory response syndrome (SIRS), severe sepsis criteria and lactate levels for their ability to identify ED patients with sepsis with critical illness., Methods: We conducted this multicenter retrospective cohort study at five US hospitals, enrolling all adult patients admitted to these hospitals from their EDs with infectious disease-related illnesses from 1 January 2016 to 30 April 2016. We abstracted clinical variables for SIRS, severe sepsis and qSOFA scores, using values in the first 6 hours of ED stay. Our primary outcome was critical illness, defined as one or more of the composite outcomes of death, vasopressor use or intensive care unit (ICU) admission within 72 hours of presentation. We determined diagnostic test characteristics for qSOFA scores, SIRS, severe sepsis criteria and lactate level thresholds., Main Results: Of 3743 enrolled patients, 512 (13.7%) had the primary composite outcome. The qSOFA scores were ≥1, >2 and 3 in 1839 (49.1%), 626 (16.7%) and 146 (3.9%) patients, respectively; 2202 (58.8%) met SIRS criteria and 1085 (29.0%) met severe sepsis criteria. qSOFA ≥ 1 and SIRS had similarly high sensitivity [86.1% (95% CI 82.8% to 89.0%) vs 86.7% (95% CI 83.5% to 89.5%)], but qSOFA ≥1 had higher specificity [56.7% (95% CI 55.0% to 58.5%) vs 45.6% (43.9% to 47.3%); mean difference 11.1% (95% CI 8.7% to 13.6%)]. qSOFA ≥ 2 had higher specificity than severe sepsis criteria [89.1% (88.0% to 90.2%) vs 77.5% (76.0% to 78.9%); mean difference 11.6% (9.8% to 13.4%)]. qSOFA ≥ 1 had greater sensitivity than a lactate level ≥2 (mean difference 24.6% (19.2% to 29.9%))., Conclusion: For patients admitted from the ED with infectious disease diagnoses, qSOFA criteria performed as well or better than SIRS criteria, severe sepsis criteria and lactate levels in predicting critical illness., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Resuscitation goals for the patient with sepsis and septic shock are to return the patient to a physiologic state that promotes adequate end-organ perfusion along with matching metabolic supply and demand. Ideal resuscitation end points should assess the adequacy of tissue oxygen delivery and oxygen consumption, and be quantifiable and reproducible. Despite years of research, a single resuscitation end point to assess adequacy of resuscitation has yet to be found. Thus, the clinician must rely on multiple end points to assess the patient's overall response to therapy. This review will discuss the role and limitations of central venous pressure (CVP), mean arterial pressure (MAP), and cardiac output/index as macrocirculatory resuscitation targets along with lactate, central venous oxygen saturation (ScvO 2 ), central venous-arterial CO 2 gradient, urine output, and capillary refill time as microcirculatory resuscitation endpoints in patients with sepsis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Metabolic biomarkers have potentially wider use in disease diagnosis and prognosis as well as in monitoring disease response to treatment. While biomarkers such as interleukins, microRNA, and lactate have been proposed for disease surveillance, there are still conflicting results regarding their clinical utility. Treatment of commonly encountered disease of acute care such as sepsis, trauma, and poisoning often relies on clinical diagnosis and therapy guided by use of surrogate markers of illness severity. The measurement of mitochondrial function, including respiration and motility, may offer superior alternatives to such markers. Assessing mitochondrial function in a clinical context has the potential to impact the area of acute care in terms of diagnosis, prognosis, and treatment. The study of mitochondrial bioenergetics has become critical in understanding the pathophysiology and treatment of complex diseases such as diabetes and cardiovascular disorders., (© The Author(s) 2016.)

Rationale: A small but growing number of hospitals are experimenting with emergency department-embedded critical care units (CCUs) in an effort to improve the quality of care for critically ill patients with sepsis and acute respiratory failure (ARF).Objectives: To evaluate the potential impact of an emergency department-embedded CCU at the Hospital of the University of Pennsylvania among patients with sepsis and ARF admitted from the emergency department to a medical ward or intensive care unit (ICU) from January 2016 to December 2017.Methods: The exposure was eligibility for admission to the emergency department-embedded CCU, which was defined as meeting a clinical definition for sepsis or ARF and admission to the emergency department during the intervention period on a weekday. The primary outcome was hospital length of stay (LOS); secondary outcomes included total emergency department plus ICU LOS, hospital survival, direct admission to the ICU, and unplanned ICU admission. Primary interrupted time series analyses were performed using ordinary least squares regression comparing monthly means. Secondary retrospective cohort and before-after analyses used multivariable Cox proportional hazard and logistic regression.Results: In the baseline and intervention periods, 3,897 patients met the inclusion criteria for sepsis and 1,865 patients met the criteria for ARF. Among patients admitted with sepsis, opening of the emergency department-embedded CCU was not associated with hospital LOS (β = -1.82 d; 95% confidence interval [CI], -4.50 to 0.87; P = 0.17 for the first month after emergency department-embedded CCU opening compared with baseline; β = -0.26 d; 95% CI, -0.58 to 0.06; P = 0.10 for subsequent months). Among patients admitted with ARF, the emergency department-embedded CCU was not associated with a significant change in hospital LOS for the first month after emergency department-embedded CCU opening (β = -3.25 d; 95% CI, -7.86 to 1.36; P = 0.15) but was associated with a 0.64 d/mo shorter hospital LOS for subsequent months (β = -0.64 d; 95% CI, -1.12 to -0.17; P = 0.01). This result persisted among higher acuity patients requiring ventilatory support but was not supported by alternative analytic approaches. Among patients admitted with sepsis who did not require mechanical ventilation or vasopressors in the emergency department, the emergency department-embedded CCU was associated with an initial 9.9% reduction in direct ICU admissions in the first month (β = -0.099; 95% CI, -0.153 to -0.044; P = 0.002), followed by a 1.1% per month increase back toward baseline in subsequent months (β = 0.011; 95% CI, 0.003-0.019; P = 0.009). This relationship was supported by alternative analytic approaches and was not seen in ARF. No associations with emergency department plus ICU LOS, hospital survival, or unplanned ICU admission were observed among patients with sepsis or ARF.Conclusions: The emergency department-embedded CCU was not associated with clinical outcomes among patients admitted with sepsis or ARF. Among less sick patients with sepsis, the emergency department-embedded CCU was initially associated with reduced rates of direct ICU admission from the emergency department. Additional research is necessary to further evaluate the impact and utility of the emergency department-embedded CCU model. [ABSTRACT FROM AUTHOR]