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Purpose: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality., Materials and Methods: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox model., Results: Among the 1879 patients included in this analysis (1199 male [63.8%]; median age, 63 [IQR, 53-72] years), 1526 (81.2%) initiated IMV early and 353 (18.8%) initiated IMV late. A total of 644 of the 1526 patients (42.2%) in the early IMV group died, and 180 of the 353 (51.0%) in the late IMV group died (adjusted HR 0.77 [95% CI, 0.65-0.93])., Conclusions: In critically ill adults with respiratory failure from COVID-19, early compared to late initiation of IMV is associated with reduced mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Green et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Dr. Jacobi’s institution received funding from Visante and Pfizer Hospital Products Division. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Bundled Payments for Care Improvement-Advanced Program (BPCI-A) is designed to pay a single payment covering services provided during an episode of care. Sepsis is associated with increased readmissions, mortality, and health care costs. The purpose of the study was to evaluate the BPCI program patients with sepsis who were readmitted within 90 days versus not readmitted. This was a retrospective cohort study including 271 (110 readmitted) patients enrolled in the BPCI program with Diagnostic-Related Grouping codes of septicemia or severe sepsis. Skin/soft tissue infection was the most common infection. There was a significant difference between the groups for resource needs at discharge including wound care (25.45% versus 11.18%; P = 0.002) and physical therapy (74.55% versus 57.14%; P = 0.004). Mortality was higher among readmissions, 43.64% versus 26.71% no readmission ( P = 0.004). Identifying risk factors for readmission, providing appropriate resources, and follow-up may contribute to improved patient outcomes for patients with sepsis enrolled in the BPCI program., (Copyright © 2022 the American College of Medical Quality.)

Sepsis is a life-threatening illness that affects millions of people worldwide. Early recognition and timely treatment are essential for decreasing mortality from sepsis. The Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021, the fifth iteration of the guidelines, was released in October 2021 and includes 93 recommendations for the management of sepsis. The evidence-based guidelines include recommendations and rationales for screening and early treatment, initial resuscitation, mean arterial pressure targets, admission to intensive care, management of infection, hemodynamic monitoring, ventilation, and additional therapies. A new section addresses long-term outcomes and goals of care. This article presents several recommendations, changes, and updates in the 2021 guidelines and highlights the important contributions nurses have in delivering timely and evidence-based care to patients with sepsis. Recommendations may be for or against an intervention, according to the evidence. Although many recommendations are unchanged, several new recommendations directly affect nursing care and may require specialized training (eg, venovenous extracorporeal membrane oxygenation). The newest section, long-term outcomes and goals of care, is aimed at using available resources to provide care that is aligned with the patient and the patient's family through goals-of-care discussions and shared decision-making. Interventions aimed at improving recovery across the continuum of care should include attention to long-term outcomes. Nurses are essential in identifying patients with sepsis, administering and assessing response to treatment, supporting the patient and family, and limiting sequelae from sepsis. This article highlights the 2021 recommendations that influence nursing care for patients with sepsis., (©2022 American Association of Critical-Care Nurses.)

Competing Interests: Dr. Alhazzani is the Chair of the Guidelines Chapter for the Saudi Critical Care Society and is the chair of the guidelines in intensive care, development and evaluation (GUIDE) Group, McMaster University Canada. Dr. Antonelli received funding from GE, Toray-Estor, Baxter, Pfizer, Orion, Maquet, and Fisher and Paykel; he was on the board of Baxter and Pfizer, and is a member of the executive committee and past president of Società Italiana di Anestesia Rianimazione e Terapia Intensiva (SIAARTI). Dr. French contributed to the ANZICS Guidelines and the National COVID-19 Guidelines. Dr. Machado is a member of the Executive Committee for the Basics Study (for which Baxter provided the drugs and logistics) and AMIB. Dr. McIntyre is a member of the Canadian Critical Care Society and serves on the Surviving Sepsis Campaign Steering Committee. Dr. Ostermann is a council member of the Intensive Care Society UK and member of the Renal Association UK and World Sepsis Alliance. Dr. Prescott is a member of the ATS Critical Care Program Committee. Dr. Simpson is the president-elect and Chair of CHEST, is a member of the board of directors and medical director of Sepsis Alliance, and Chair of the Sepsis Institute Advisory Board. Dr. Wiersinga is a member of ISF, ESCIMID, and SWAB. Dr. Angus received funding from Ferring Pharmaceuticals, Inc and ALung Technologies, Inc. Dr. Beale provides consultancy services for Philips Healthcare with his time billed by his institution. Dr. Beilman is the president of the Surgical Infection Society. Dr. Belley-Cote received grants from Roche and Bayer and is a panel member on the Saudi Critical Care Society COVID-19 Thrombosis Guidelines. Dr. Cecconi is a consultant for Edwards Lifesciences, Cheetah Medical, and Directed Systems and is President of the European Society of Intensive Care Medicine. Dr. Coz is a board member of the American College of Chest Physicians. Dr. De Waele consulted for Accelerate, Bayer, Grifols, Pfizer, and MSD with all honoraria paid to Ghent University; he is a Senior Clinical Investigator with the Research Foundation Flanders. Dr. Dellinger serves as an expert witness on occasional medical legal case reviews. Dr. Doi is a member of the Japanese Society of Intensive Care Medicine. Dr. Du is a member of the Chinese Society of Critical Care Medicine and the Chinese College of Intensive Care Medicine. Dr. Ferrer received funding from Grifols, MSD, Pfizer, Shionogi, Toray, Jafron, and Cytosorbents; he is a member of SEMICYUC. Dr. Gomersall is a member of an educational subgroup of the International Forum of Acute Care Trialists. Dr. Hodgson is a member of the Australian National Health and Medical Research Council guidelines (COVID-19) and leading funded trials in early rehabilitation and ECMO. Dr. Møller contributed to guideline work for DASAIM, SSAI, GUIDE, and ESA. Dr. Iwashyna is a member of the ATS, the NIH, and an informal (unincorporated) organization called the Critical and Acute Illness Recovery Organization. Dr. Jacob co-directs the African Research Collaboration on Sepsis (ARCS, funded by UK National Institute for Health Research, sponsored by Liverpool School of Tropical Medicine), he is Secretary General for the African Sepsis Alliance, and is a technical expert for the World Health Organization panels. Dr. Kleinpell is a board member of the World Federation of Intensive and Critical Care, American Nurses Credentialing Center, and the Tennessee Nurses Association Political Action Committee. Dr. Klompas received funding from Up-to-Date; he is a member of the guidelines committees of the Infectious Disease Society of America (IDSA) and Society of Healthcare Epidemiologists of America (SHEA). Dr. Koh is a member of The Korean Society of Critical Care Medicine, The Korean Academy of Tuberculosis and Respiratory Diseases, The Korean Society of Medical Ethics, and the Asia Ventilation Forum. Dr. Kumar served as an expert witness regarding a lethal dose of narcotics. Dr. Kwizera is president of the Intensive Care Society of Uganda and PRO for the Association of Anesthesiologists of Uganda. Dr. Lobo received funding from Pfizer, MSD, Edwards, and Nestle; she is the principal investigator in new antibiotics research led by CROs/industry; she is a member of the AMIB Executive Board and was elected president for 2020-2021. Dr. McGloughlin is a member of ANZICS (Australian New Zealand Intensive Care Society). Dr. Mehta participated in two non-interventional studies by ISCCM-Hermes and Indicaps. Dr. Mer has been an invited speaker for educational talks in industry-sponsored symposia for which honoraria was received; he is the current Vice President of the Southern African Society of Thrombosis and Haemostasis (SASTH), and is involved in annual congress organization; he is an invited author of the Global guidelines for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Dr. Nunnally is the treasurer of SOCCA, committee member of ASA, NYSSA, IARS, AUA, and SAAAPM and serves on the American College of Critical Care Medicine Board of Regents. Dr. Oczkowski is a member of the European Respiratory Society, and contributed to the High Flow Nasal Cannula Guidelines, the Non-Invasive Ventilation in COPD Guidelines. Dr. Osborn received funding from Viven Inc, Inflammatrix, Beckman, and the Foundation for Barnes Jewish Hospital; she is on the advisory board for Beckman, Inflammatix, and Viven; she is a member of the American College of Emergency Physicians, American College of Chest Physicians, American Medical Association, Society of Academic Emergency Medicine, and American Academy of Emergency Physicians; she served as an expert witness in a case related to viral as compared to bacterial sepsis. Dr. Papathanassoglou is a member of the World Federation of Critical Care Nurses (Editor of Journal) and the Canadian Association of Critical Care Nurses. Dr. Perner received a research grant from Pfizer Denmark. Dr. Puskarich is the co-inventor of a patent to assess L0carnitine drug responsiveness in sepsis (USPO 10330685); he is a member of the Society for Academic Emergency Medicine, American College of Emergency Physicians (ACEP); he was invited to a recently gathered ACEP early sepsis treatment policy task force asked to develop specialty recommendations for early sepsis treatment. Dr. Roberts received funding from MSD, The Medicines Company, Cardeas Pharma, Biomerieux, QPEX, Cipla, and Pfizer; he consulted for MSD, QPEX, Discuva Ltd, Accelerate Diagnostics, Bayer, Biomerieux, UptoDate, and Australian Therapeutic Guidelines; he is a member of the Society of Hospital Pharmacists of Australia Leadership Committees for Critical Care and Infectious Diseases and the Lead of Sepsis Working group for the International Society of Anti-infective Chemotherapy. Dr. Schweickert is a paid consultant to the American College of Physicians (last performed in Spring, 2019). Dr. Seckel volunteers for AACN and is a paid consultant to revise online Critical Care Orientation. Dr. Sevransky received funding from the Marcus Foundation- PI VICTAS Trial and serves on the American College of Critical Care Medicine Board of Regents. Dr. Welte received funding from Astellas, AstraZeneca, Boehringer, Basilea, Bayer, Berlin-Chemie, Grifols, Infectopharm, Mundipharma, MSD, Novartis, Pfizer, DFG, EU, BMBF, and Insmed; he is on the advisory board for AstraZeneca, Boehringer, Bayer, Gilead, GSK, Insmed, Novartis, Pfizer, Roche; he is a member of the European Respiratory Society, German Society of Pneumology, and Paul Ehrlich Gesellschaft. Dr. Zimmerman is a member of the ACP, AACP, and WFPICCS. Dr. Levy is a legal consultant for a few cases involving sepsis and serves as co-chair of the Surviving Sepsis Campaign Steering Committee. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: After critical illness, new or worsening impairments in physical, cognitive, and/or mental health function are common among patients who have survived. Who should be screened for long-term impairments, what tools to use, and when remain unclear., Objectives: Provide pragmatic recommendations to clinicians caring for adult survivors of critical illness related to screening for postdischarge impairments., Participants: Thirty-one international experts in risk-stratification and assessment of survivors of critical illness, including practitioners involved in the Society of Critical Care Medicine's Thrive Post-ICU Collaboratives, survivors of critical illness, and clinical researchers., Design: Society of Critical Care Medicine consensus conference on post-intensive care syndrome prediction and assessment, held in Dallas, in May 2019. A systematic search of PubMed and the Cochrane Library was conducted in 2018 and updated in 2019 to complete an original systematic review and to identify pre-existing systematic reviews., Meeting Outcomes: We concluded that existing tools are insufficient to reliably predict post-intensive care syndrome. We identified factors before (e.g., frailty, preexisting functional impairments), during (e.g., duration of delirium, sepsis, acute respiratory distress syndrome), and after (e.g., early symptoms of anxiety, depression, or post-traumatic stress disorder) critical illness that can be used to identify patients at high-risk for cognitive, mental health, and physical impairments after critical illness in whom screening is recommended. We recommend serial assessments, beginning within 2-4 weeks of hospital discharge, using the following screening tools: Montreal Cognitive Assessment test; Hospital Anxiety and Depression Scale; Impact of Event Scale-Revised (post-traumatic stress disorder); 6-minute walk; and/or the EuroQol-5D-5L, a health-related quality of life measure (physical function)., Conclusions: Beginning with an assessment of a patient's pre-ICU functional abilities at ICU admission, clinicians have a care coordination strategy to identify and manage impairments across the continuum. As hospital discharge approaches, clinicians should use brief, standardized assessments and compare these results to patient's pre-ICU functional abilities ("functional reconciliation"). We recommend serial assessments for post-intensive care syndrome-related problems continue within 2-4 weeks of hospital discharge, be prioritized among high-risk patients, using the identified screening tools to prompt referrals for services and/or more detailed assessments.

Executive Summary: Usage of hospice services for patients facing life-limiting illness has steadily increased. In these services, hospitals discharge patients to various hospice settings, including the inpatient model, where a patient may remain in the discharging hospital to receive hospice services. In this discharge practice, the patient is considered a hospital survivor and subsequent hospice death. The purpose of the study was to determine if the decline of in-hospital mortality for six common high-volume admission diagnoses could be attributed in part to an increase in discharges to a hospice setting for end-of-life care. In this retrospective study using the National Inpatient Sample database from 2007 to 2011, we identified patients ≥18 years for six acute and chronic diagnoses: heart failure, chronic obstructive pulmonary disease, acute myocardial infarction, acute myocardial infarction with cardiogenic shock, septic shock, and lung neoplasm (cancer). We categorized patients according to their hospital discharge disposition as hospice or in-hospital mortality. A total of 10,458,728 patients met our criteria, of which 2.72% were discharged to hospice and 6.38% died. Compared to patients who died in the hospital, hospice patients were older, had a shorter length of stay, and experienced more comorbidities. Hospice use was more common in Medicare patients, in nonteaching hospitals, and in the South. White individuals were more likely to be discharged to hospice compared to nonwhites. Among the six selected diagnoses over the 5-year period, hospice use rose as observed mortality decreased. Our findings suggest that variability among hospitals in hospice use will affect benchmarked hospital mortality comparisons and could inappropriately reward or penalize hospitals in their public reporting.

Background and Purpose: Data regarding the incidence of seizures in patients diagnosed with fat embolism syndrome (FES) are lacking. We examined the incidence of seizures in patients with FES, and the impact of seizures on outcomes over a 10-year period., Methods: Using the National Inpatient Sample data set we identified adults (age 18 y old or above) with a diagnosis of FES (ICD-9 958.1) between 2005 and 2014, and categorized them according to the presence or absence of seizures. We excluded patients with a history of epilepsy or traumatic brain injury RESULTS:: Of the 66,227,531 discharges, we identified 1888 patients (0.003%) with FES of which 53% were male and mean age of 56 (±57.45). Seizure or epilepsy rate in patients with FES was 2.86% (1.69% with seizures and 1.16% with epilepsy), as compared with 3.6% in all hospitalized patients without FES. The Charlson Comorbidity Index for all FES patients was 2.38 (±5.28) and was similar for those with and without seizures. Hospital length of stay was higher in patients with FES and seizures versus those without seizures (14.59 vs. 10.82 d, P=0.09). No statistically significant difference in mortality was observed between the 2 groups., Conclusions: The rate of seizure and epilepsy in patients with FES is low when compared with rates in all hospitalized patients or in patients with other causes of acute neurological injury such as intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury. Further studies are needed to provide recommendations for antiepileptic medication use in FES.

Importance: Polymyxin B hemoperfusion reduces blood endotoxin levels in sepsis. Endotoxin activity can be measured in blood with a rapid assay. Treating patients with septic shock and elevated endotoxin activity using polymyxin B hemoperfusion may improve clinical outcomes., Objective: To test whether adding polymyxin B hemoperfusion to conventional medical therapy improves survival compared with conventional therapy alone among patients with septic shock and high endotoxin activity., Design, Setting, and Participants: Multicenter, randomized clinical trial involving 450 adult critically ill patients with septic shock and an endotoxin activity assay level of 0.60 or higher enrolled between September 2010 and June 2016 at 55 tertiary hospitals in North America. Last follow-up was June 2017., Interventions: Two polymyxin B hemoperfusion treatments (90-120 minutes) plus standard therapy completed within 24 hours of enrollment (n = 224 patients) or sham hemoperfusion plus standard therapy (n = 226 patients)., Main Outcomes and Measures: The primary outcome was mortality at 28 days among all patients randomized (all participants) and among patients randomized with a multiple organ dysfunction score (MODS) of more than 9., Results: Among 450 eligible enrolled patients (mean age, 59.8 years; 177 [39.3%] women; mean APACHE II score 29.4 [range, 0-71 with higher scores indicating greater severity), 449 (99.8%) completed the study. Polymyxin B hemoperfusion was not associated with a significant difference in mortality at 28 days among all participants (treatment group, 84 of 223 [37.7%] vs sham group 78 of 226 [34.5%]; risk difference [RD], 3.2%; 95% CI, -5.7% to 12.0%; relative risk [RR], 1.09; 95% CI, 0.85-1.39; P = .49) or in the population with a MODS of more than 9 (treatment group, 65 of 146 [44.5%] vs sham, 65 of 148 [43.9%]; RD, 0.6%; 95% CI, -10.8% to 11.9%; RR, 1.01; 95% CI, 0.78-1.31; P = .92). Overall, 264 serious adverse events were reported (65.1% treatment group vs 57.3% sham group). The most frequent serious adverse events were worsening of sepsis (10.8% treatment group vs 9.1% sham group) and worsening of septic shock (6.6% treatment group vs 7.7% sham group)., Conclusions and Relevance: Among patients with septic shock and high endotoxin activity, polymyxin B hemoperfusion treatment plus conventional medical therapy compared with sham treatment plus conventional medical therapy did not reduce mortality at 28 days., Trial Registration: ClinicalTrials.gov Identifier: NCT01046669.

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012"., Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development., Methods: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable., Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions., Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Sepsis is the body's systemic response to infection that can be complicated by acute organ dysfunction and is associated with high mortality rates and adverse outcomes for acute and critically ill patients. The 2012 Surviving Sepsis Campaign guidelines advocated for implementation of evidence-based practice care for sepsis, with a focus on quality improvement. Nurses are directly involved in identification and management of sepsis. Implementing performance improvement strategies aimed at early recognition and targeted treatment can further improve sepsis care and patient outcomes. This article presents an overview of the process of implementing performance improvement initiatives for sepsis care, highlighting the significant contribution of nursing care.

Sepsis is a serious worldwide health care condition that is associated with high mortality rates, despite improvements in the ability to manage infection. New guidelines for the management of sepsis were recently released that advocate for implementation of care based on evidence-based practice for both adult and pediatric patients. Critical care nurses are directly involved in the assessment of patients at risk for developing sepsis and in the treatment of patients with sepsis and can, therefore, affect outcomes for critically ill patients. Nurses' knowledge of the recommendations in the new guidelines can help to ensure that patients with sepsis receive therapies that are based on the latest scientific evidence. This article presents an overview of new evidence-based recommendations for the treatment of adult patients with sepsis, highlighting the role of critical care nurses.

Introduction: Transfer of critically ill patients from outside emergency department has the potential for delaying the admission to the intensive care unit. We sought to determine the effect of outside emergency department transfer on hospital outcomes in critically ill patients with stroke., Methods: We designed a retrospective cohort analysis using a prospectively compiled and maintained registry (Cerner Project IMPACT). Patients with acute ischemic stroke and intracerebral hemorrhage admitted to our intensive care unit from our emergency department and transfers from outside emergency department within 24 hours of stroke between January 1, 2003, and December 31, 2008, were selected for the analysis. Data collected included demographics, admission physiologic variables, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II score, and total intensive care unit and hospital length of stay. Primary (poor) outcome was a composite of death or fully dependent status at hospital discharge, and secondary outcomes were intensive care unit and hospital length of stay. To assess for the impact of outside emergency department transfer on primary and secondary outcomes, demographic and admission clinical variables were used to construct logistic regression models using the outcome measure as a dependent variable., Results: A total of 448 patients were selected for analysis. The mean age was 65 ± 14 years, of which 214 (48%) were male and 282 (65%) white, 152 (34%) were patients with acute ischemic stroke, and 296 (66%) were patients with intracerebral hemorrhage. The median hospital length of stay was 7 days (interquartile range, 4-11 days) and median intensive care unit length of stay was 2 days (interquartile range, 1-3 days). Overall hospital mortality was 30%, and outside emergency department transfer increased the odds of poor outcome by 2-fold (65% vs 34%; P = .05). Multivariate regression analysis showed that age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01-1.1), Acute Physiology and Chronic Health Evaluation II score >14 (OR, 1.9; 95% CI, 1.3-2.7), Glasgow Coma Scale <12 (OR, 2.0; 95% CI, 1.4-2.8), do-not-resuscitate status (OR, 3.5; 95% CI, 2.2-5.9), and outside emergency department transfers (OR, 1.4; 95% CI, 1.02-1.8) were independently associated with poor outcome. Outside emergency department transfer was not significantly associated with secondary outcomes., Conclusion: These data suggest that in critically ill patients with stroke, transfer from outside emergency department is independently associated with poor outcome at hospital discharge. Further research is needed as to identify the potential causes for this effect., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Although transfusion has been linked to the development of atrial fibrillation (AF) in cardiac surgical patients, this association has not been investigated in patients with acute myocardial infarction (AMI). Evidence supports an inflammatory mechanism in the development of AF, and red cell transfusions also elicit an inflammatory response. We therefore sought to evaluate whether packed red blood cell transfusion increases the risk of AF, ventricular tachycardia (VT), and other arrhythmias and conduction abnormalities in patients with AMI., Materials and Methods: This is a retrospective study on patients with AMI and no prior history of AF, admitted to a critical care area and entered in Project Impact database from 08/2003-12/2007. Primary outcome measures were new-onset cardiac arrhythmias or conduction disturbances., Results: Transfused patients had significantly higher incidences of AF (4.7% vs 1.3%, P = .008), cardiac arrest (9.5% vs 1.7%, P < .001) and heart block (3.4% vs 0.1%, P < .001), and a trend toward a higher incidence of VT (3.4% vs 1.3%, P = .058). Multivariate regression analysis confirmed transfusion as an independent risk factor for "non-lethal" cardiac events (AF/heart block; odds ratio [OR], 4.7 [1.9-11.9]; P = .001), "lethal" events (VT/cardiac arrest; OR, 2.4 [1.1-5]; P = .016), and all cardiac events (OR, 2.8 [1.5-65.1]; P = .001). Transfused patients had significantly longer length of stay (P < .0001) and significantly higher mortality rates than nontransfused patients (OR, 3 [1.7-5.5]; P < .001)., Conclusions: Packed red blood cell transfusion is independently associated with an increased risk of new-onset cardiac arrhythmias and conduction abnormalities in the setting of AMI, even after controlling for traditional risk factors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Only through adequately designed and adequately conducted clinical trials can new treatments be found for the benefit of the septic patient. Over the past 20 years, tens of thousands of patients have been enrolled in sepsis clinical trials with little success. These efforts, however, have not been without worth. Much has been learned and the knowledge gained has changed our approach to trial design in this very difficult field. Animal studies are better designed to match the clinical picture of severe sepsis. Phase II studies are more carefully engineered to answer questions about the most suitable target population and end points. Trial conduct likely benefits from use of CROs and a CCC. The future of clinical trials may include more standardization of sepsis management across investigative sites. Before the decision is made to become an investigative site in a multicenter industry-sponsored clinical trial in sepsis or severe sepsis, it is important to recognize what is required to succeed. Once these key-to-success elements are in place, members of the investigative team are more likely to realize the satisfaction and career growth from becoming a successful site. The most professional satisfaction comes from the knowledge of contributing to original science in the field of the sepsis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Sepsis guidelines, although creating a base to allow change in health care practitioner behavior, do not, in and of themselves, effect change. Change only comes with institution of a PI program, converting a core of key goals of guideline recommendations to quality indicators, and giving feedback on performance. These quality indicators are tracked before or during (recommended approach) initiation of hospital-wide education to evaluate baseline performance. When combining multispecialty and multidisciplinary champions in the ED, hospital wards, ICU, and hospital administrative leadership with timely performance feedback, case failure analysis, and re-education, an opportunity to succeed in decreasing mortality in severe sepsis can be achieved. Sepsis bundle indicators require updating as new evidence emerges and new guidelines are published.(30,31), (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Patients with septic shock have a high mortality. This study used the Surviving Sepsis Campaign (SSC) database to compare characteristics, treatments and outcomes of septic shock patients diagnosed in the emergency department (ED) to patients developing septic shock on hospital floors (HF)., Methods: The studied population included patients admitted to the intensive care unit (ICU) of an urban tertiary care medical center over an 18-month period. Acute physiology and chronic health evaluation (APACHE II) scores, need for mechanical ventilation (MV), performance on four of the SSC resuscitation bundle indicators, ICU length of stay (LOS), hospital LOS and in-hospital mortality were ascertained., Results: Sixty-six ED and 27 HF septic shock patients were included in this study. Urinary tract infections (UTI) and pneumonia were the two most common sites of infection in the ED patients. The sources of infection for HF septic shock patients were fairly well distributed across etiologies. The time to achieve superior vena cava oxygen saturation (ScvO(2)) > 70% in HF patients ((10.8 ± 9.1) hours) was longer when compared to the ED patients ((6.6 ± 6.1) hours) (P < 0.05). Hospital mortality for the ED and HF patients were 25.8% and 59.3%, respectively (P < 0.05). Use of MV during the first 24 hours of shock was 44% in the ED patients and 70% in the HF patients (P < 0.05) and was linked to mortality., Conclusions: When compared to HF patients, ED septic shock patients have lower in-hospital mortality, there was less use of MV during the first 24 hours following onset of septic shock and the HF patients required a longer time to achieve target ScvO(2). The need for mechanical ventilation is independently associated with increased mortality.

The role of endotoxin in the genesis of sepsis has long been recognized and multiple treatments aimed at neutralizing it have been studied. Endotoxin can be bound by antibodies (whose role as a therapeutic agent is unlikely), binding proteins such as BPI or human lactoferrin (effectiveness debated and promising respectively) and phospholipid emulsion (which has not improved outcomes in a recent study). Alternatively, the action of endotoxin could be blocked by lipid A analogs (initial study showed no overall benefit and another large trial is near completion targeting a subpopulation of that study). Finally, endotoxin can be bound by polymyxin B embedded in hemoperfusion cartridges. The later treatment has been used for more than a decade in Japan. Since both pre-clinical rationale and studies support the targeting of endotoxin to ameliorate the pro-inflammatory and pro-coagulation response of severe sepsis, this therapeutic intervention is being pursued.

Performance improvement in medicine based on evidence-based guidelines is a persistent challenge for clinicians. Challenges include deficiencies in collaboration, resistance to change, complex algorithms, inadequate resources, and inability to collect data and provide feedback. In severe sepsis this is further compounded by the perceived importance of early intervention and considerable conflicting literature. The bundle concept first adopted for mechanically ventilated patients and then for central line insertion, has now been applied to care for the patient with severe sepsis. The bundle concept in severe sepsis facilitates the provision of best practice consistent care to eligible patients with a structure to measure compliance. Time sensitive bundle indicators allow for uniform data collection and reporting. Successful modification of clinical practice may require months or years. The success of the program relies upon the cross-departmental collaboration and support generated before implementation and the ability to deliver timely feedback to facilitate change in performance.

The environment for clinical trials in sepsis has long been identified as challenging and full of road blocks and land mines. Unlike many other diagnoses (ie, cancer, acute myocardial infarction) relevance of animal studies and predictive capability of phase II trials for dose generation is less clear. The members of the investigative team must realize the essentials for success in a multicenter clinical trial. It is also useful and important to understand the big picture of clinical trial development as well as properly functioning interfaces among sponsor, contract research organizations, and investigative sites. Because early enrollment into sepsis clinical trials is usually required, collaboration between emergency medicine and critical care is needed.

Objective: To evaluate the impact of the source of patients transferred to a tertiary care intensive care unit (ICU) (referring hospital ICU vs referring hospital emergency department [ED]) on outcomes of transferred patients., Design and Setting: We performed a retrospective review of data contained in the Project Impact database of a medical-surgical ICU at a university hospital., Patients and Participants: A total of 503 patients transferred from local community hospitals, 283 from EDs and 220 from ICUs, were identified and included. In addition to comparing all ED transfers with all ICU transfers, comparisons between the 2 populations were made for the subgroups of patients with intracranial hemorrhage (group 1), nonhemorrhagic stroke (group 2), and all other patients (group 3)., Measurements and Results: Patients were evaluated for a variety of outcome parameters, including mortality and ICU and hospital length of stay (LOS) according to their location at the referring hospital at the time of transfer: ICU (ICUtx) or ED (EDtx). Mortality was significantly lower among EDtx in all transferred patients as well as in groups 2 and 3 with no difference in mortality identified in group 1. Intensive care unit LOS was shorter for EDtx and the 3 groups, and hospital LOS was shorter among all EDtx and those in group 3. Group 3 EDtx also had lower than predicted mortality., Conclusions: Transfer of patients to a tertiary care ICU from the ED of a referring hospital is associated with significantly better outcomes than transfers from referring hospital ICUs.

Purpose: No studies have specifically evaluated the incidence or clinical characteristics of atrial fibrillation (AF) in a mixed medical-surgical population of patients with sepsis. We undertook to determine the incidence and clinical course of critically ill septic patients in the intensive care unit (ICU) who developed new-onset AF., Methods: Retrospective analysis of data collected from the Project IMPACT database on 274 septic patients from July 2003 to December 2004., Results: Sixteen evaluable septic patients with new-onset AF were identified. Mortality was higher (P = .034) and ICU length of stay (LOS) longer (P = .003) in patients with AF vs those without. Intensive care unit LOS was also longer in the subset of survivors with AF (P = .0001). Hospital LOS was longer among survivors with AF than in survivors without AF (P = .047). Patients with AF had a greater need for mechanical ventilation (P = .0007). Survivors with AF had longer duration of mechanical ventilation than those without AF (P = .006)., Conclusions: Statistically significantly higher mortality was observed in critically ill septic patients with new-onset AF, as were longer duration of mechanical ventilation, ICU, and hospital LOS. Whether the higher incidence of AF in septic patients is a specific risk factor for outcome or an indication of severity of illness remains to be determined.

Background: Mechanical ventilation increases risk for bleeding in the upper part of the gastrointestinal tract. Proton pump inhibitors, although they are more potent and longer acting inhibitors of gastric acid production than are histamine(2) antagonists, also are generally more expensive. Data comparing the 2 types of agents for preventing gastrointestinal bleeding in critically ill patients are limited., Objectives: To compare the effectiveness of famotidine (a histamine(2) antagonist) and pantoprazole (a proton pump inhibitor) in preventing stress ulcers in critically ill patients receiving mechanical ventilation., Methods: Data were collected from the Project Impact database. All patients who received mechanical ventilation for more than 48 hours from November 2002 to June 2006 and were treated with either drug were included. Patients receiving other drugs or with known bleeding in the upper part of the gastrointestinal tract, thrombocytopenia, or coagulopathy were excluded., Results: A total of 522 patients who received famotidine and 95 who received pantoprazole were included. Bleeding in the upper part of the gastrointestinal tract was more common in patients receiving pantoprazole than in patients receiving famotidine (0.38% vs 3.2%, P= .03). Although scores on the Acute Physiology and Chronic Health Evaluation II were higher in patients who received pantoprazole (P= .01), other outcome measures did not differ significantly between groups. Bleeding in the upper part of the gastrointestinal tract was more frequent among dialysis patients receiving pantoprazole than among those receiving famotidine., Conclusions: Famotidine and pantoprazole are similarly effective for preventing bleeding in the upper part of the gastrointestinal tract in patients receiving mechanical ventilation.