Risk factor identification and predictive models for central line requirements for patients on vasopressors.

Vasopressors are ubiquitous in intensive care units. While central venous catheters are the preferred route of infusion, recent evidence suggests peripheral administration may be safe for short, single-agent courses. Here, we identify risk factors and develop a predictive model for patient central venous catheter requirement using the Medical Information Mart for Intensive Care, a single-centre dataset of patients admitted to an intensive care unit between 2008 and 2019. Using prior literature, a composite endpoint of prolonged single-agent courses (>24 hours) or multi-agent courses of any duration was used to identify likely central venous catheter requirement. From a cohort of 69,619 intensive care unit stays, there were 17,053 vasopressor courses involving one or more vasopressors that met study inclusion criteria. In total, 3807 (22.3%) vasopressor courses involved a single vasopressor for less than six hours, 7952 (46.6%) courses for less than 24 hours and 5757 (33.8%) involved multiple vasopressors of any duration. Of these, 3047 (80.0%) less than six-hour and 6423 (80.8%) less than 24-hour single vasopressor courses used a central venous catheter. Logistic regression models identified associations between the composite endpoint and intubation (odds ratio (OR) 2.36, 95% confidence intervals (CI) 2.16 to 2.58), cardiac diagnosis (OR 0.72, CI 0.65 to 0.80), renal impairment (OR 1.61, CI 1.50 to 1.74), older age (OR 1.002, Cl 1.000 to 1.005) and vital signs in the hour before initiation (heart rate, OR 1.006, CI 1.003 to 1.009; oxygen saturation, OR 0.996, CI 0.993 to 0.999). A logistic regression model predicting the composite endpoint had an area under the receiver operating characteristic curve (standard deviation) of 0.747 (0.013) and an accuracy of 0.691 (0.012). This retrospective study reveals a high prevalence of short vasopressor courses in intensive care unit settings, a majority of which were administered using central venous catheters. We identify several important risk factors that may help guide clinicians deciding between peripheral and central venous catheter administration, and present a predictive model that may inform future prospective trials.

F-Actin is associated with a worsening qSOFA score and intensive care unit admission in emergency department patients at risk for sepsis.

Objective: We previously demonstrated that plasma levels of F-actin and Thymosin Beta 4 differs among patients with septic shock, non-infectious systemic inflammatory syndrome and healthy controls and may serve as biomarkers for the diagnosis of sepsis. The current study aims to determine if these proteins are associated with or predictive of illness severity in patients at risk for sepsis in the Emergency Department (ED).Methods: Prospective, biomarker study enrolling patients (>18 years) who met the Shock Precautions on Triage Sepsis rule placing them at-risk for sepsis.Results: In this study of 203 ED patients, F-actin plasma levels had a linear trend of increase when the quick Sequential Organ Failure Assessment (qSOFA) score increased. F-actin was also increased in patients who were admitted to the Intensive Care Unit (ICU) from the ED, and in those with positive urine cultures. Thymosin Beta 4 was not associated with or predictive of any significant outcome measures.Conclusion: Increased levels of plasma F-actin measured in the ED were associated with incremental illness severity as measured by the qSOFA score and need for ICU admission. F-actin may have utility in risk stratification of undifferentiated patients in the ED presenting with signs and symptoms of sepsis.

Antibiotic Delays and Feasibility of a 1-Hour-From-Triage Antibiotic Requirement: Analysis of an Emergency Department Sepsis Quality Improvement Database.

STUDY OBJECTIVE: We identify factors associated with delayed emergency department (ED) antibiotics and determine feasibility of a 1-hour-from-triage antibiotic requirement in sepsis. METHODS: We studied all ED adult septic patients in accordance with Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock National Quality Measures in 2 consecutive 12-month intervals. During the second interval, a quality improvement intervention was conducted: a sepsis screening protocol plus case-specific feedback to clinicians. Data were abstracted retrospectively through electronic query and chart review. Primary outcomes were antibiotic delay greater than 3 hours from documented onset of hypoperfusion (per Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock National Quality Measures) and antibiotic delay greater than 1 hour from triage (per 2018 Surviving Sepsis Campaign recommendations). RESULTS: We identified 297 and 357 septic patients before and during the quality improvement intervention, respectively. Before and during quality improvement intervention, antibiotic delay in accordance with Centers for Medicare & Medicaid Services measures occurred in 30% and 21% of cases (-9% [95% confidence interval -16% to -2%]); and in accordance with 2018 Surviving Sepsis Campaign recommendations, 85% and 71% (-14% [95% confidence interval -20% to -8%]). Four factors were independently associated with both definitions of antibiotic delay: vague (ie, nonexplicitly infectious) presenting symptoms, triage location to nonacute areas, care before the quality improvement intervention, and lower Sequential [Sepsis-related] Organ Failure Assessment scores. Most patients did not receive antibiotics within 1 hour of triage, with the exception of a small subset post-quality improvement intervention who presented with explicit infectious symptoms and triage hypotension. CONCLUSION: The quality improvement intervention significantly reduced antibiotic delays, yet most septic patients did not receive antibiotics within 1 hour of triage. Compliance with the 2018 Surviving Sepsis Campaign would require a wholesale alteration in the management of ED patients with either vague symptoms or absence of triage hypotension.

A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D.

Sepsis is defined as the dysregulated host response to an infection resulting in life-threatening organ dysfunction. The metabolic demand from inefficiencies in anaerobic metabolism, mitochondrial and cellular dysfunction, increased cellular turnover, and free-radical damage result in the increased focus of micronutrients in sepsis as they play a pivotal role in these processes. In the present review, we will evaluate the potential role of micronutrients in sepsis, specifically, thiamine, l-carnitine, vitamin C, Se and vitamin D. Each micronutrient will be reviewed in a similar fashion, discussing its major role in normal physiology, suspected role in sepsis, use as a biomarker, discussion of the major basic science and human studies, and conclusion statement. Based on the current available data, we conclude that thiamine may be considered in all septic patients at risk for thiamine deficiency and l-carnitine and vitamin C to those in septic shock. Clinical trials are currently underway which may provide greater insight into the role of micronutrients in sepsis and validate standard utilisation.

Thymosin beta 4 regulation of actin in sepsis.

INTRODUCTION: Sepsis is the dysregulated host response to an infection resulting in life-threatening organ damage. Thymosin Beta 4 is an actin binding protein that inhibits the polymerization of G-actin into F-actin and improves mortality when administered intravenously to septic rats. Thymosin Beta 4 decreases inflammatory mediators, lowers reactive oxygen species, up-regulates anti-oxidative enzymes, anti-inflammatory genes, and anti-apoptotic enzymes making it an interesting protein to study in sepsis. AREAS COVERED: The authors summarize the current knowledge of actin and Thymosin Beta 4 as it relates to sepsis via a comprehensive literature search. EXPERT OPINION: Sepsis results in measurable levels of F-actin in the circulation as well as a decreased concentration of Thymosin Beta 4. It is speculated that F-actinemia contributes to microcirculatory perturbations present in patients with sepsis by disturbing laminar flow. Given that Thymosin Beta 4 inhibits the polymerization of F-actin, it is possible that Thymosin Beta 4 decreases mortality in sepsis via the regulation of actin as well as its other anti-inflammatory properties and should be further pursued as a clinical trial in humans with sepsis.

Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE.

Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.

Survey of Emergency Department Chemical Hazard Preparedness in Michigan, USA: A Seven Year Comparison.

OBJECTIVE: To compare the state of chemical hazard preparedness in emergency departments (EDs) in Michigan, USA between 2005 and 2012. METHODS: This was a longitudinal study involving a 30 question survey sent to ED directors at each hospital listed in the Michigan College of Emergency Physician (MCEP) Directory in 2005 and in 2012. The surveys contained questions relating to chemical, biological, radiological, nuclear, and explosive events with a focus on hazardous material capabilities. RESULTS: One hundred twelve of 139 EDs responded to the 2005 survey compared to 99/136 in 2012. Ten of 27 responses were statistically significant, all favoring an enhancement in disaster preparedness in 2012 when compared to 2005. Questions with improvement included: EDs with employees participating in the Michigan voluntary registry; EDs with decontamination rooms; MARK 1 and cyanide kits available; those planning to use dry decontamination, powered air purifiers, surgical masks, chemical gloves, and surgical gowns; and those wishing for better coordination with local and regional resources. Forty-two percent of EDs in 2012 had greater than one-half of their staff trained in decontamination and 81% of respondents wished for more training opportunities in disaster preparedness. Eighty-four percent of respondents believed that they were more prepared in disaster preparedness in 2012 versus seven years prior. CONCLUSIONS: Emergency departments in Michigan have made significant advances in chemical hazard preparedness between 2005 and 2012 based on survey responses. Despite these improvements, staff training in decontamination and hazardous material events remains a weakness among EDs in the state of Michigan.

Plasma levels of F-actin and F:G-actin ratio as potential new biomarkers in patients with septic shock.

OBJECTIVE: To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls. RESULTS: F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay's lowest detection range (78 ng/ml). CONCLUSIONS: F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.