Bayesian methods: a potential path forward for sepsis trials.

BACKGROUND: Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods. METHODS: We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60-0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment. RESULTS: In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored. CONCLUSIONS: Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.

Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Performance of a Standardized Clinical Assay for Urinary C-C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury.

Background: Clinical use of biomarkers requires the development of standardized assays and establishment of cutoffs. Urinary C-C motif chemokine ligand 14 (CCL14) has been validated to predict persistent severe AKI in critically ill patients with established AKI. We now report on the performance of standardized cutoffs using a clinical assay. Methods: A second aim of the multicenter RUBY Study was to establish two cutoffs for the prediction of persistent severe AKI (defined as KDIGO stage 3 AKI for at least 72 consecutive hours). Patients who received renal replacement therapy (RRT) or died before achieving 72 hours in stage 3 AKI were also considered to have reached the end point. Results: A cutoff value for urinary CCL14 of 1.3 ng/ml was determined to achieve high sensitivity (91%; 95% CI, 84% to 96%), and 13 ng/ml achieved high specificity (93%; 95% CI, 89% to 96%). The cutoff of 1.3 ng/ml identifies the majority (91%) of patients who developed persistent severe AKI with a negative predictive value of 92%. The cutoff at 13 ng/ml had a positive predictive value of 72% (with a negative predictive value of 75%). In multivariable adjusted analyses, a CCL14 concentration between 1.3 and 13 ng/ml had an adjusted odds ratio (aOR) of 3.82 (95% CI, 1.73 to 9.12; P=0.001) for the development of persistent severe AKI compared with those with a CCL14 ≤1.3 ng/ml, whereas a CCL14 >13 ng/ml had an aOR of 10.4 (95% CI, 3.89 to 29.9; P<0.001). Conclusions: Using a clinical assay, these standardized cutoffs (1.3 and 13 ng/ml) allow for the identification of patients at high risk for the development of persistent severe AKI. These results have immediate utility in helping to guide AKI patient care and may facilitate future clinical trials.Clinical Trial registry name and registration number: Identification and Validation of Biomarkers of Acute Kidney Injury Recovery, NCT01868724.

Effect of an emergency department intensive care unit on medical intensive unit admissions and care: A retrospective cohort study.

OBJECTIVE: Evaluate the impact of an emergency critical care center (EC3) on the admissions of critically ill patients to a critical care medicine unit (CCMU) and their outcomes. METHODS: This was a retrospective before/after cohort study in a tertiary university teaching hospital. To improve the care of critically ill patients in the emergency department (ED), a 9-bed EC3 was opened in the ED in February 2015. All critically ill patients in the emergency department must receive intensive support in EC3 before being considered for admission to the CCMU for further treatment. Patients from the emergency department account for a significant proportion of the patients admitted to the CCMU. The proportions of patients admitted to the CCMU from the ED were analyzed 1 year before and 1 year after the opening of the EC3. We also compared the admission data, demographic data, APACHE III scores and patient outcomes among patients admitted from ED to the CCMU in the year before and the year after the opening of the EC3. RESULT: The establishment of the EC3 was associated with a decreased proportion of patients admitted to the CCMU from the ED (OR 0.73 95% CI 0.63-0.84, p < 0.01), a decrease in the proportion of patients with sepsis admitted from the ED (OR 0.68, 95% CI, 0.54-0.87, p < 0.01) and a decrease in the proportion of patients with gastrointestinal bleeding admitted from the ED (OR 0.49, 95% CI 0.28-0.84, p < 0.05). Following the establishment of the EC3, patients admitted to the CCMU had a higher APACHE III score in 2015 (74.85 ± 30.42 vs 72.39 ± 29.64, p = 0.015). Fewer low-risk patients were admitted to the CCMU for monitoring following the opening of the EC3 (112 [6.8%] vs. 181 [9.3%], p < 0.01). Propensity score matching analysis showed that the opening of the EC3 was associated with improved 60-day survival (HR 0.84, 95% CI 0.70-0.99, p = 0.046). CONCLUSION: Following the opening of the EC3, the proportion of CCMU admissions from the ED decreased. The EC3 may be most effective at reducing the admission of lower-acuity patients with GI bleeding and possibly sepsis. The EC3 may be associated with improved survival in ED patients.

Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest (EROCA): Results of a Randomized Feasibility Trial of Expedited Out-of-Hospital Transport.

STUDY OBJECTIVE: Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency department (ED) arrival interval, and for emergency physicians to rapidly initiate ECPR in eligible patients. METHODS: In a 2-tiered emergency medical service with an ECPR-capable primary destination hospital, adults with refractory shockable or witnessed out-of-hospital cardiac arrest were randomized 4:1 to expedited transport or standard care if the predicted 911 call to ED arrival interval was less than or equal to 30 minutes. The primary outcomes were the proportion of subjects with 911 call to ED arrival less than or equal to 30 minutes and ED arrival to ECPR flow less than or equal to 30 minutes. RESULTS: Of 151 out-of-hospital cardiac arrest 911 calls, 15 subjects (10%) were enrolled. Five of 12 subjects randomized to expedited transport had an ED arrival time of less than or equal to 30 minutes (overall mean 32.5 minutes [SD 7.1]), and 5 were eligible for and treated with ECPR. Three of 5 ECPR-treated subjects had flow initiated in less than or equal to 30 minutes of ED arrival (overall mean 32.4 minutes [SD 10.9]). No subject in either group survived with a good neurologic outcome. CONCLUSION: The Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest trial did not meet predefined feasibility outcomes for selecting out-of-hospital cardiac arrest patients for expedited transport and initiating ECPR in the ED. Additional research is needed to improve the accuracy of predicting the 911 call to ED arrival interval, optimize patient selection, and reduce the ED arrival to ECPR flow interval.

Use of Biomarkers to Identify Acute Kidney Injury to Help Detect Sepsis in Patients With Infection.

OBJECTIVES: Although early recognition of sepsis is vital to improving outcomes, the diagnosis may be missed or delayed in many patients. Acute kidney injury is one of the most common organ failures in patients with sepsis but may not be apparent on presentation. Novel biomarkers for acute kidney injury might improve organ failure recognition and facilitate earlier sepsis care. DESIGN: Retrospective, international, Sapphire study. SETTING: Academic Medical Center. PATIENTS: Adults admitted to the ICU without evidence of acute kidney injury at time of enrollment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We stratified patients enrolled in the Sapphire study into three groups-those with a clinical diagnosis of sepsis (n = 216), those with infection without sepsis (n = 120), and those without infection (n = 387) at enrollment. We then examined 30-day mortality stratified by acute kidney injury within each group. Finally, we determined the operating characteristics for kidney stress markers (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) for prediction of acute kidney injury as a sepsis-defining organ failure in patients with infection without a clinical diagnosis of sepsis at enrollment. Combining all groups, 30-day mortality was 23% for patients who developed stage 2-3 acute kidney injury within the first 3 days compared with 14% without stage 2-3 acute kidney injury. However, this difference was greatest in the infection without sepsis group (34% vs 11%; odds ratio, 4.09; 95% CI, 1.53-11.12; p = 0.005). Using a (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) cutoff of 2.0 units, 14 patients (11.7%), in the infection/no sepsis group, tested positive of which 10 (71.4%) developed stage 2-3 acute kidney injury. The positive test result occurred a median of 19 hours (interquartile range, 0.8-34.0 hr) before acute kidney injury manifested by serum creatinine or urine output. Similar results were obtained using a cutoff of 1.0 for any stage of acute kidney injury. CONCLUSIONS: Use of the urinary (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) test could identify acute kidney injury in patients with infection, possibly helping to detect sepsis, nearly a day before acute kidney injury is apparent by clinical criteria.

Angiotensin II Infusion for Shock: A Multicenter Study of Postmarketing Use.

BACKGROUND: Vasodilatory shock refractory to catecholamine vasopressors and arginine vasopressin is highly morbid and responsible for significant mortality. Synthetic angiotensin II is a potent vasoconstrictor that may be suitable for use in these patients. RESEARCH QUESTION: What is the safety and effectiveness of angiotensin II and what variables are associated with a favorable hemodynamic response? STUDY DESIGN AND METHODS: We performed a multicenter, retrospective study at five tertiary medical centers in the United States. The primary end point of hemodynamic responsiveness to angiotensin II was defined as attainment of mean arterial pressure (MAP) of ≥ 65 mm Hg with a stable or reduced total vasopressor dosage 3 h after drug initiation. RESULTS: Of 270 included patients, 181 (67%) demonstrated hemodynamic responsiveness to angiotensin II. Responders showed a greater increase in MAP (+10.3 mm Hg vs +1.6 mm Hg, P < .001) and reduction in vasopressor dosage (-0.20 µg/kg/min vs +0.04 µg/kg/min; P < .001) compared with nonresponders at 3 h. Variables associated with favorable hemodynamic response included lower lactate concentration (OR 1.11; 95% CI, 1.05-1.17, P < .001) and receipt of vasopressin (OR, 6.05; 95% CI, 1.98-18.6; P = .002). In severity-adjusted multivariate analysis, hemodynamic responsiveness to angiotensin II was associated with reduced likelihood of 30-day mortality (hazard ratio, 0.50; 95% CI, 0.35-0.71; P < .001). Arrhythmias occurred in 28 patients (10%) and VTE was identified in 4 patients. INTERPRETATION: In postmarketing use for vasopressor-refractory shock, 67% of angiotensin II recipients demonstrated a favorable hemodynamic response. Patients with lower lactate concentrations and those receiving vasopressin were more likely to respond to angiotensin II. Patients who responded to angiotensin II experienced reduced mortality.

Resonance Raman Spectroscopy Derived Tissue Hemoglobin Oxygen Saturation in Critically Ill and Injured Patients.

BACKGROUND: In this study, we examined the ability of resonance Raman spectroscopy to measure tissue hemoglobin oxygenation (R-StO2) noninvasively in critically ill patients and compared its performance with conventional central venous hemoglobin oxygen saturation (ScvO2). METHODS: Critically ill patients (n = 138) with an indwelling central venous or pulmonary artery catheter in place were consented and recruited. R-StO2 measurements were obtained by placing a sensor inside the mouth on the buccal mucosa. R-StO2 was measured continuously for 5 min. Blood samples were drawn from the distal port of the indwelling central venous catheter or proximal port of the pulmonary artery catheter at the end of the test period to measure ScvO2 using standard co-oximetry analyzer. A regression algorithm was used to calculate the R-StO2 based on the observed spectra. RESULTS: Mean (SD) of pooled R-StO2 and ScvO2 were 64(7.6) % and 65(9.2) % respectively. A paired t test showed no significant difference between R-StO2 and ScvO2 with a mean(SD) difference of -1(7.5) % (95% CI: -2.2, 0.3%) with a Clarke Error Grid demonstrating 84.8% of the data residing within the accurate and acceptable grids. Area under the receiver operator curve for R-StO2's was 0.8(0.029) (95% CI: 0.7, 0.9 P < 0.0001) at different thresholds of ScvO2 (≤60%, ≤65%, and ≤70%). Clinical adjudication by five clinicians to assess the utility of R-StO2 and ScvO2 yielded Fleiss' Kappa agreement of 0.45 (P < 0.00001). CONCLUSIONS: R-StO2 has the potential to predict ScvO2 with high precision and might serve as a faster, safer, and noninvasive surrogate to these measures.

Emergency Department-based Intensive Care Unit Use Peaks Near Emergency Department Shift Turnover.

INTRODUCTION: The Emergency Critical Care Center (EC3) is an emergency department-based intensive care unit (ED-ICU) designed to improve timely access to critical care for ED patients. ED patients requiring intensive care are initially evaluated and managed in the main ED prior to transfer to a separate group of ED-ICU clinicians. The timing of patient transfers to the ED-ICU may decrease the number of handoffs between main ED teams and have an impact on both patient outcomes and optimal provider staffing models, but has not previously been studied. We aimed to analyze patterns of transfer to the ED-ICU and the relationship with shift turnover times in the main ED. We hypothesized that the number of transfers to the ED-ICU increases near main ED shift turnover times. METHODS: An electronic health record search identified all patients managed in the ED and ED-ICU in 2016 and 2017. We analyzed the number of ED arrivals per hour, the number of ED-ICU consults per hour, the time interval from ED arrival to ED-ICU consult, the distribution throughout the day, and the relationship with shift turnover times in the main ED. RESULTS: A total of 160,198 ED visits were queried, of which 5308 (3.3%) were managed in the ED-ICU. ED shift turnover times were 7 am, 3 pm, and 11 pm. The mean number of ED-ICU consults placed per hour was 221 (85 standard deviation), with relative maximums occurring near ED turnover times: 10:31 pm-11:30 pm (372) and 2:31 pm-3:30 pm (365). The minimum was placed between 7:31 am - 8:30 am (88), shortly after the morning ED turnover time. The median interval from ED arrival time to ED-ICU consult order was 161 minutes (range 6-1,434; interquartile range 144-174). Relative minimums were observed for patients arriving shortly prior to ED turnover times: 4:31 am - 5:30 am (120 minutes [min]), 12:31 pm - 1:30 pm (145 min), and 9:31 pm - 10:30 pm (135 min). Relative maximums were observed for patients arriving shortly after ED turnover times: 7:31 am - 8:30 am (177 min), 4:31 pm - 5:30 pm (218 min), and 11:31 pm - 12:30 am (179 min). CONCLUSION: ED-ICU utilization was highest near ED shift turnover times, and utilization was dissimilar to overall ED arrival patterns. Patients arriving immediately prior to ED shift turnover received earlier consults to the ED-ICU, suggesting these patients may have been preferentially transferred to the ED-ICU rather than signed out to the next team of emergency clinicians. These findings may guide operational planning, staffing models, and timing of shift turnover for other institutions implementing ED-ICUs. Future studies could investigate whether an ED-ICU model improves critically ill patients' outcomes by minimizing ED provider handoffs.

Joint Society of Critical Care Medicine-Extracorporeal Life Support Organization Task Force Position Paper on the Role of the Intensivist in the Initiation and Management of Extracorporeal Membrane Oxygenation.

OBJECTIVES: To define the role of the intensivist in the initiation and management of patients on extracorporeal membrane oxygenation. DESIGN: Retrospective review of the literature and expert consensus. SETTING: Series of in-person meetings, conference calls, and emails from January 2018 to March 2019. SUBJECTS: A multidisciplinary, expert Task Force was appointed and assembled by the Society of Critical Care Medicine and the Extracorporeal Life Support Organization. Experts were identified by their respective societies based on reputation, experience, and contribution to the field. INTERVENTIONS: A MEDLINE search was performed and all members of the Task Force reviewed relevant references, summarizing high-quality evidence when available. Consensus was obtained using a modified Delphi process, with agreement determined by voting using the RAND/UCLA scale, with score ranging from 1 to 9. MEASUREMENTS AND MAIN RESULTS: The Task Force developed 18 strong and five weak recommendations in five topic areas of extracorporeal membrane oxygenation initiation and management. These recommendations were organized into five areas related to the care of patients on extracorporeal membrane oxygenation: patient selection, management, mitigation of complications, coordination of multidisciplinary care, and communication with surrogate decision-makers. A common theme of the recommendations is extracorporeal membrane oxygenation is best performed by a multidisciplinary team, which intensivists are positioned to engage and lead. CONCLUSIONS: The role of the intensivist in the care of patients on extracorporeal membrane oxygenation continues to evolve and grow, especially when knowledge and familiarity of the issues surrounding extracorporeal membrane oxygenation selection, cannulation, and management are applied.

An Emergency Department-Based Intensive Care Unit is Associated with Decreased Hospital and Intensive Care Unit Utilization for Diabetic Ketoacidosis.

BACKGROUND: Many emergency department (ED) patients in diabetic ketoacidosis (DKA) are admitted to an inpatient intensive care unit (ICU), while ICU capacity is under increasing strain. The Emergency Critical Care Center (EC3), a hybrid ED-ICU setting, opened with the goal of providing rapid initiation of ICU care in the ED. OBJECTIVE: We sought to evaluate the impact of an ED-ICU on disposition and safety outcomes for adult ED patients in DKA. METHODS: This was a retrospective pre-post cohort of ED visits from 2012-2018 at a single academic medical center. Adult ED patients in DKA (pH < 7.30, HCO3 < 18 mEq/L, anion gap > 14, and glucose > 250 mg/dL) immediately before (pre-EC3) and after (post-EC3) opening of an ED-ICU were identified. ED disposition and safety data were collected and analyzed. RESULTS: We identified 631 patient encounters: 217 pre-EC3 and 414 post-EC3. Baseline demographics were similar between cohorts. Fewer patients in the post-EC3 cohort were admitted to an ICU (11.6% vs. 23.5%, p < 0.001, number needed to treat [NNT] = 8) or general floor bed (58.0% vs. 73.3%, p < 0.001, NNT = 6), and more were discharged from the ED (27.1% vs. 1.4%, p < 0.001, NNT = 4). Rates of hypokalemia (10.1% vs. 6.0%, p = 0.08) and admission to non-ICU with transfer to ICU within 24 h (0.5% vs. 0%, p = 0.30) did not differ. CONCLUSION: Management of patients with DKA in an ED-ICU was associated with decreased ICU and hospital utilization with similar safety outcomes. Managing rapidly reversible critical illnesses in an ED-ICU may help obviate increasing strain facing many health care systems.

Association of an Emergency Department-Based Intensive Care Unit With Survival and Inpatient Intensive Care Unit Admissions.

Importance: Increased patient acuity, decreased intensive care unit (ICU) bed availability, and a shortage of intensivist physicians have led to strained ICU capacity. The resulting increase in emergency department (ED) boarding time for patients requiring ICU-level care has been associated with worse outcomes. Objective: To determine the association of a novel ED-based ICU, the Emergency Critical Care Center (EC3), with 30-day mortality and inpatient ICU admission. Design, Setting, and Participants: This retrospective cohort study used electronic health records of all ED visits between September 1, 2012, and July 31, 2017, with a documented clinician encounter at a large academic medical center in the United States with approximately 75 000 adult ED visits per year. The pre-EC3 cohort included ED patients from September 2, 2012, to February 15, 2015, when the EC3 opened, and the post-EC3 cohort included ED patients from February 16, 2015, to July 31, 2017. Data analyses were conducted from March 2, 2018, to May 28, 2019. Exposures: Implementation of EC3, an ED-based ICU designed to provide rapid initiation of ICU-level care in the ED setting and seamless transition to inpatient ICUs. Main Outcomes and Measures: The main outcomes were 30-day mortality among ED patients and rate of ED to ICU admission. Results: A total of 349 310 visits from a consecutive sample of ED patients (mean [SD] age, 48.5 [19.7] years; 189 709 [54.3%] women) were examined; the pre-EC3 cohort included 168 877 visits and the post-EC3 cohort included 180 433 visits. Implementation of EC3 was associated with a statistically significant reduction in risk-adjusted 30-day mortality among all ED patients (pre-EC3, 2.13%; post-EC3, 1.83%; adjusted odds ratio, 0.85; 95% CI, 0.80-0.90; number needed to treat, 333 patient encounters; 95% CI, 256-476). The risk-adjusted rate of ED admission to ICU decreased with implementation of EC3 (pre-EC3, 3.2%; post-EC3, 2.7%; adjusted odds ratio, 0.80; 95% CI, 0.76-0.83; number needed to treat, 179 patient encounters; 95% CI, 149-217). Conclusions and Relevance: Implementation of a novel ED-based ICU was associated with improved 30-day survival and reduced inpatient ICU admission. Additional research is warranted to further explore the value of this novel care delivery model in various health care systems.

Simulation training enables emergency medicine providers to rapidly and safely initiate extracorporeal cardiopulmonary resuscitation (ECPR) in a simulated cardiac arrest scenario.

BACKGROUND: Extracorporeal cardiopulmonaryresuscitation (ECPR) is emerging as a viable rescue strategy for refractory out-of-hospital cardiac arrest. In the U.S., limited training of emergency medicine providers is a barrier to widespread implementation. AIMS: Test the hypothesis that emergency medicine physicians and nurses can acquire and retain the skills to rapidly and safely initiate ECPR using high-fidelity simulation. STUDY DESIGN: Prospective interventional study. SETTING: U.S. tertiary academic medical center. SUBJECTS: Emergency medicine physicians and nurses with no prior ECPR/ECMO experience. METHODS: Teams of three physicians and three nurses underwent a two-day ECPR training course including didactics, hands-on training, and simulation. Teams were videotaped initiating ECPR in a high-fidelity simulation scenario before and after simulation training. The primary outcome was the proportion of simulations in which full ECPR support was achieved within 30 min of patient arrival. RESULTS: Five teams completed the entire study. Full ECPR support was achieved within 30 min of patient arrival in 11/15, 15/15, and 15/15 attempts at baseline (B), post-testing (PT) and 3-month post-testing (3-PT), respectively (p = 0.06). Intervals (mean ± sd) required to achieve full ECPR support at B, PT, and 3-PT were 25.8±5.3, 17.2±4.6, and 19.2±1.9 min respectively (p < 0.05 for B vs. PT and 3-PT). CONCLUSION: High fidelity simulation training is effective in preparing emergency medicine physicians and nurses to rapidly and safely initiate ECPR in a simulated cardiac arrest scenario, and should be considered when implementing an ED-based ECPR program.

The Two-Bag Method for Treatment of Diabetic Ketoacidosis in Adults.

BACKGROUND: The "two-bag method" of management of diabetic ketoacidosis (DKA) allows for titration of dextrose delivery by adjusting the infusions of two i.v. fluid bags of varying dextrose concentrations while keeping fluid, electrolyte, and insulin infusion rates constant. OBJECTIVE: We aimed to evaluate the feasibility and potential benefits of this strategy in adult emergency department (ED) patients with DKA. METHODS: This is a before-and-after comparison of a protocol using the two-bag method operationalized in our adult ED in 2015. A retrospective electronic medical record search identified adult ED patients presenting with DKA from January 1, 2013 to June 30, 2016. Clinical and laboratory data, timing of medical therapies, and safety outcomes were collected and analyzed. RESULTS: Sixty-eight patients managed with the two-bag method (2B) and 107 patients managed with the one-bag method (1B) were identified. The 2B and 1B groups were similar in demographics and baseline metabolic derangements, though significantly more patients in the 2B group received care in a hybrid ED and intensive care unit setting (94.1% vs. 51.4%; p < 0.01). 2B patients experienced a shorter interval to first serum bicarbonate ≥ 18 mEq/L (13.4 vs. 20.0 h; p < 0.05), shorter duration of insulin infusion (14.1 vs. 21.8 h; p < 0.05), and fewer fluid bags were charged to the patient (5.2 vs. 29.7; p < 0.01). Frequency of any measured hypoglycemia or hypokalemia trended in favor of the 2B group (2.9% vs. 10.3%; p = 0.07; 16.2% vs. 27.1%; p = 0.09; respectively), though did not reach significance. CONCLUSIONS: The 2B method appears feasible for management of adult ED patients with DKA, and use was associated with earlier correction of acidosis, earlier discontinuation of insulin infusion, and fewer i.v. fluid bags charged than traditional 1B methods, while no safety concerns were observed.

Physician training in critical care in the United States: Update 2018.

Critical care fellowship training in the United States differs based on specific specialty and includes medicine, surgery, anesthesiology, pediatrics, emergency medicine, and neurocritical care training pathways. We provide an update regarding the number and growth of US critical care fellowship training programs, on-duty residents and certified diplomates, and review the different critical care physician training pathways available to residents interested in pursuing a fellowship in critical care. Data were obtained from the Accreditation Council for Graduate Medical Education and specialty boards (American Board of Internal Medicine, American Board of Surgery, American Board of Anesthesiology, American Board of Pediatrics American Board of Emergency Medicine) and the United Council for Neurologic Subspecialties for the last 16 years (2001-2017). The number of critical care fellowship training programs has increased 22.6%, with a 49.4% increase in the number of on-duty residents annually, over the last 16 years. This is in contrast to the period of 1995 to 2000 when the number of physicians enrolled in critical care fellowship programs had decreased or remained unchanged. Although more than 80% of intensivists in the US train in internal medicine critical care Accreditation Council for Graduate Medical Education-approved fellowships, there has been a significant increase in the number of residents from surgery, anesthesiology, pediatrics, emergency medicine, and other specialties who complete specialty fellowship training and certification in critical care. Matriculation in neurocritical care fellowships is rapidly rising with 60 programs and over 1,200 neurocritical care diplomates. Critical care is now an increasingly popular fellowship in all specialties. This rapid growth of all critical care specialties highlights the magnitude of the heterogeneity that will exist between intensivists in the future.

Practice characteristics of Emergency Department extracorporeal cardiopulmonary resuscitation (eCPR) programs in the United States: The current state of the art of Emergency Department extracorporeal membrane oxygenation (ED ECMO).

PURPOSE: To characterize the current scope and practices of centers performing extracorporeal cardiopulmonary resuscitation (eCPR) on the undifferentiated patient with cardiac arrest in the emergency department. METHODS: We contacted all US centers in January 2016 that had submitted adult eCPR cases to the Extracorporeal Life Support Organization (ELSO) registry and surveyed them, querying for programs that had performed eCPR in the Emergency Department (ED ECMO). Our objective was to characterize the following domains of ED ECMO practice: program characteristics, patient selection, devices and techniques, and personnel. RESULTS: Among 99 centers queried, 70 responded. Among these, 36 centers performed ED ECMO. Nearly 93% of programs are based at academic/teaching hospitals. 65% of programs are less than 5 years old, and 60% of programs perform ≤3 cases per year. Most programs (90%) had inpatient eCPR or salvage ECMO programs prior to starting ED ECMO programs. The majority of programs do not have formal inclusion and exclusion criteria. Most programs preferentially obtain vascular access via the percutaneous route (70%) and many (40%) use mechanical CPR during cannulation. The most commonly used console is the Maquet Rotaflow(®). Cannulation is most often performed by cardiothoracic (CT) surgery, and nearly all programs (>85%) involve CT surgeons, perfusionists, and pharmacists. CONCLUSIONS: Over a third of centers that submitted adult eCPR cases to ELSO have performed ED ECMO. These programs are largely based at academic hospitals, new, and have low volumes. They do not have many formal inclusion or exclusion criteria, and devices and techniques are variable.

TIMP2•IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients.

BACKGROUND: Acute kidney injury (AKI) is an important complication in surgical patients. Existing biomarkers and clinical prediction models underestimate the risk for developing AKI. We recently reported data from two trials of 728 and 408 critically ill adult patients in whom urinary TIMP2•IGFBP7 (NephroCheck, Astute Medical) was used to identify patients at risk of developing AKI. Here we report a preplanned analysis of surgical patients from both trials to assess whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) accurately identify surgical patients at risk of developing AKI. STUDY DESIGN: We enrolled adult surgical patients at risk for AKI who were admitted to one of 39 intensive care units across Europe and North America. The primary end point was moderate-severe AKI (equivalent to KDIGO [Kidney Disease Improving Global Outcomes] stages 2-3) within 12 hours of enrollment. Biomarker performance was assessed using the area under the receiver operating characteristic curve, integrated discrimination improvement, and category-free net reclassification improvement. RESULTS: A total of 375 patients were included in the final analysis of whom 35 (9%) developed moderate-severe AKI within 12 hours. The area under the receiver operating characteristic curve for [TIMP-2]•[IGFBP7] alone was 0.84 (95% confidence interval, 0.76-0.90; p < 0.0001). Biomarker performance was robust in sensitivity analysis across predefined subgroups (urgency and type of surgery). CONCLUSION: For postoperative surgical intensive care unit patients, a single urinary TIMP2•IGFBP7 test accurately identified patients at risk for developing AKI within the ensuing 12 hours and its inclusion in clinical risk prediction models significantly enhances their performance. LEVEL OF EVIDENCE: Prognostic study, level I.