Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force.

OBJECTIVES: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. DESIGN: Review and task force position statements with necessary guidance. SETTING: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. SUBJECTS: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. INTERVENTIONS: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. MEASUREMENTS AND MAIN RESULTS: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. CONCLUSIONS: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

Awareness with paralysis and symptoms of post-traumatic stress disorder among mechanically ventilated emergency department survivors (ED-AWARENESS-2 Trial): study protocol for a pragmatic, multicenter, stepped wedge cluster randomized trial.

BACKGROUND: Awareness with paralysis (AWP) is memory recall during neuromuscular blockade (NMB) and can cause significant psychological harm. Decades of effort and rigorous trials have been conducted to prevent AWP in the operating room, where prevalence is 0.1-0.2%. By contrast, AWP in mechanically ventilated emergency department (ED) patients is common, with estimated prevalence of 3.3-7.4% among survivors given NMB. Longer-acting NMB use is a critical risk for AWP, and we have shown an association between ED rocuronium use and increased AWP prevalence. As NMB are given to more than 90% of ED patients during tracheal intubation, this trial provides a platform to test an intervention aimed at reducing AWP. The overall objective is to test the hypothesis that limiting ED rocuronium exposure will significantly reduce the proportion of patients experiencing AWP. METHODS: This is a pragmatic, stepped wedge cluster randomized trial conducted in five academic EDs, and will enroll 3090 patients. Per the design, all sites begin in a control phase, under observational conditions. At 6-month intervals, sites sequentially enter a 2-month transition phase, during which we will implement the multifaceted intervention, which will rely on use of nudges and defaults to change clinician decisions regarding ED NMB use. During the intervention phase, succinylcholine will be the default NMB over rocuronium. The primary outcome is AWP, assessed with the modified Brice questionnaire, adjudicated by three independent, blinded experts. The secondary outcome is the proportion of patients developing clinically significant symptoms of post-traumatic stress disorder at 30 and 180 days after hospital discharge. We will also assess for symptoms of depression and anxiety, and health-related quality of life. A generalized linear model, adjusted for time and cluster interactions, will be used to compare AWP in control versus intervention phases, analyzed by intention-to-treat. DISCUSSION: The ED-AWARENESS-2 Trial will be the first ED-based trial aimed at preventing AWP, a critical threat to patient safety. Results could shape clinical use of NMB in the ED and prevent more than 10,000 annual cases of AWP related to ED care. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05534243 . Registered 06, September 2022.

Assessment of implementation methods in sepsis: study protocol for a cluster-randomized hybrid type 2 trial.

BACKGROUND: Sepsis is the leading cause of intensive care unit (ICU) admission and ICU death. In recognition of the burden of sepsis, the Surviving Sepsis Campaign (SSC) and the Institute for Healthcare Improvement developed sepsis "bundles" (goals to accomplish over a specific time period) to facilitate SSC guideline implementation in clinical practice. Using the SSC 3-h bundle as a base, the Centers for Medicare and Medicaid Services developed a 3-h sepsis bundle that has become the national standard for early management of sepsis. Emerging observational data, from an analysis conducted for the AIMS grant application, suggest there may be additional mortality benefit from even earlier implementation of the 3-h bundle, i.e., the 1-h bundle. METHOD: The primary aims of this randomized controlled trial are to: (1) examine the effect on clinical outcomes of Emergency Department initiation of the elements of the 3-h bundle within the traditional 3 h versus initiating within 1 h of sepsis recognition and (2) examine the extent to which a rigorous implementation strategy will improve implementation and compliance with both the 1-h bundle and the 3-h bundle. This study will be entirely conducted in the Emergency Department at 18 sites. A secondary aim is to identify clinical sepsis phenotypes and their impact on treatment outcomes. DISCUSSION: This cluster-randomized trial, employing implementation science methodology, is timely and important to the field. The hybrid effectiveness-implementation design is likely to have an impact on clinical practice in sepsis management by providing a rigorous evaluation of the 1- and 3-h bundles. FUNDING: NHLBI R01HL162954. TRIAL REGISTRATION: ClinicalTrials.gov NCT05491941. Registered on August 8, 2022.

Timing of invasive mechanical ventilation and death in critically ill adults with COVID-19: A multicenter cohort study.

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.

Evaluation of Adult Patients Readmitted for Severe Sepsis/Septic Shock Under the BPCI Advanced Program.

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.

Nursing Implications of the Updated 2021 Surviving Sepsis Campaign Guidelines.

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.

Effects of Compliance With the Early Management Bundle (SEP-1) on Mortality Changes Among Medicare Beneficiaries With Sepsis: A Propensity Score Matched Cohort Study.

BACKGROUND: US hospitals have reported compliance with the SEP-1 quality measure to Medicare since 2015. Finding an association between compliance and outcomes is essential to gauge measure effectiveness. RESEARCH QUESTION: What is the association between compliance with SEP-1 and 30-day mortality among Medicare beneficiaries? STUDY DESIGN AND METHODS: Studying patient-level data reported to Medicare by 3,241 hospitals from October 1, 2015, to March 31, 2017, we used propensity score matching and a hierarchical general linear model (HGLM) to estimate the treatment effects associated with compliance with SEP-1. Compliance was defined as completion of all qualifying SEP-1 elements including lactate measurements, blood culture collection, broad-spectrum antibiotic administration, 30 mL/kg crystalloid fluid administration, application of vasopressors, and patient reassessment. The primary outcome was a change in 30-day mortality. Secondary outcomes included changes in length of stay. RESULTS: We completed two matches to evaluate population-level treatment effects. In standard match, 122,870 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (21.81% vs 27.48%, respectively), yielding an absolute risk reduction (ARR) of 5.67% (95% CI, 5.33-6.00; P < .001). In stringent match, 107,016 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (22.22% vs 26.28%, respectively), yielding an ARR of 4.06% (95% CI, 3.70-4.41; P < .001). At the subject level, our HGLM found compliance associated with lower 30-day risk-adjusted mortality (adjusted conditional OR, 0.829; 95% CI, 0.812-0.846; P < .001). Multiple elements correlated with lower mortality. Median length of stay was shorter among cases whose care was compliant (5 vs 6 days; interquartile range, 3-9 vs 4-10, respectively; P < .001). INTERPRETATION: Compliance with SEP-1 was associated with lower 30-day mortality. Rendering SEP-1 compliant care may reduce the incidence of avoidable deaths.

Rapid Development and Deployment of an Intensivist-Led Venovenous Extracorporeal Membrane Oxygenation Cannulation Program.

OBJECTIVES: To determine the safety and efficacy of a rapidly deployed intensivist-led venovenous extracorporeal membrane oxygenation cannulation program in a preexisting extracorporeal membrane oxygenation program. DESIGN: A retrospective observational before-and-after study of 40 patients undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation in an established cannulation program by cardiothoracic surgeons versus a rapidly deployed medical intensivist cannulation program. SETTING: An adult ICU in a tertiary academic medical center in Camden, NJ. PATIENTS: Critically ill adult subjects with severe respiratory failure undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation. INTERVENTIONS: Percutaneous cannulation for venovenous extracorporeal membrane oxygenation performed by cardiothoracic surgeons compared with cannulations performed by medical intensivists. MEASUREMENTS AND MAIN RESULTS: Venovenous extracorporeal membrane oxygenation cannulation site attempts were retrospectively reviewed. Subject demographics, specialty of physician performing cannulation, type of support, cannulation configuration, cannula size, imaging guidance, success rate, and complications were recorded and summarized. Twenty-two cannulations were performed by three cardiothoracic surgeons in 11 subjects between September 2019 and February 2020. The cannulation program rapidly transitioned to an intensivist-led and performed program in March 2020. Fifty-seven cannulations were performed by eight intensivists in 29 subjects between March 2020 and December 2020. Mean body mass index for subjects did not differ between groups (33.86 vs 35.89; p = 0.775). There was no difference in days on mechanical ventilation prior to cannulation, configuration, cannula size, or discharge condition. There was no difference in success rate of cannulation on first attempt per cannulation site (95.5 vs 96.7; p = 0.483) or major complication rate per cannulation site (4.5 vs 3.5; p = 1). CONCLUSIONS: There is no difference between success and complication rates of percutaneous venovenous extracorporeal membrane oxygenation canulation when performed by cardiothoracic surgeons versus medical intensivist in an already established extracorporeal membrane oxygenation program. A rapidly deployed cannulation program by intensivists for venovenous extracorporeal membrane oxygenation can be performed with high success and low complication rates.

Skill retention with ultrasound curricula.

BACKGROUND: Implementation of a point of care ultrasound curricula is valuable, but optimal integration for internal medicine residency is unclear. The purpose of this study was to evaluate if a structured ultrasound curriculum vs. structured ultrasound curriculum plus supervised thoracic ultrasounds would improve internal medicine residents' skill and retention 6 and 12 months from baseline. METHODS: We conducted a randomized controlled study evaluating internal medical residents' skill retention of thoracic ultrasound using a structured curriculum (control, n = 14) vs. structured curriculum plus 20 supervised bedside thoracic ultrasounds (intervention, n = 14). We used a stratified randomization based on program year. All subjects attended a half-day course that included 5 lectures and hands-on sessions at baseline. Assessments included written and practical exams at baseline, immediately post-course and at 6 and 12 months. Scores are reported as a percentage for the number of correct responses/number of questions (range 0-100%). The Mann Whitney U and the Friedman tests were used for analyses. RESULTS: Twenty-eight residents were enrolled. Two subjects withdrew prior to the 6-month exams. Written exam scores for all subjects improved, baseline median (IQR) 60 (46.47 to 66.67) post-course 80 (65 to 86.67), 6-month 80 (66.67 to 86.67) and 12-month 86.67 (80 to 88.34), p = <0.001. All subjects practical exam scores median (IQR) significantly improved, baseline 18.18 (7.95 to 32.95), post-course 59.09 (45.45 to 70.45), 6 month 71.74 (60.87 to 82.61) and 12-month 76.09 (65.22 to 88.05), p = <0.001. Comparing the control group to the intervention group, there were statistically significant higher scores, median (IQR), in the intervention group on the practical exam at 6 months 63.05 (48.92 to 69.57) vs. 82.61(72.83 to89.13), p = <0.001. CONCLUSION: In this cohort, internal medicine residents participating in a structured thoracic ultrasound course plus 20-supervised ultrasounds achieved higher practical exam scores long-term compared to controls.

Society of Critical Care Medicine's International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness.

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.