ABSTRACT
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.
Subject(s)
Critical Illness , Rapid Sequence Induction and Intubation , Adult , Humans , Airway Management , Consensus , Critical Care , Critical Illness/therapyABSTRACT
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.
Subject(s)
Sepsis , Shock, Septic , Adult , Humans , Bayes Theorem , Polymyxin B/therapeutic use , Research Design , Sepsis/drug therapy , Shock, Septic/drug therapyABSTRACT
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.
Subject(s)
Acute Kidney Injury/blood , Acute Kidney Injury/diagnosis , Infections/diagnosis , Sepsis/diagnosis , Severity of Illness Index , Aged , Biomarkers/blood , Creatinine/blood , Critical Illness , Female , Humans , Infections/complications , Male , Middle Aged , Retrospective Studies , Sepsis/complications , Tissue Inhibitor of Metalloproteinase-2/bloodABSTRACT
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.
Subject(s)
Cardiopulmonary Resuscitation/methods , Emergency Medical Services , Out-of-Hospital Cardiac Arrest/therapy , Emergency Service, Hospital , Feasibility Studies , Female , Humans , Male , Michigan , Middle Aged , Time-to-TreatmentABSTRACT
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.
Subject(s)
Emergency Service, Hospital/organization & administration , Intensive Care Units/organization & administration , Patient Admission/statistics & numerical data , APACHE , Critical Illness/mortality , Critical Illness/therapy , Emergency Service, Hospital/statistics & numerical data , Female , Hospital Mortality , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Retrospective Studies , Survival AnalysisABSTRACT
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.
Subject(s)
Critical Care/standards , Extracorporeal Membrane Oxygenation/standards , Physician's Role , Practice Guidelines as Topic/standards , Societies, Medical/standards , Communication , Extracorporeal Membrane Oxygenation/adverse effects , Humans , Patient Care Team/organization & administration , Patient Selection , Retrospective Studies , Risk Factors , Time FactorsABSTRACT
OBJECTIVES: Emergency department boarding is the practice of caring for admitted patients in the emergency department after hospital admission, and boarding has been a growing problem in the United States. Boarding of the critically ill has achieved specific attention because of its association with poor clinical outcomes. Accordingly, the Society of Critical Care Medicine and the American College of Emergency Physicians convened a Task Force to understand the implications of emergency department boarding of the critically ill. The objective of this article is to review the U.S. literature on (1) the frequency of emergency department boarding among the critically ill, (2) the outcomes associated with critical care patient boarding, and (3) local strategies developed to mitigate the impact of emergency department critical care boarding on patient outcomes. DATA SOURCES AND STUDY SELECTION: Review article. DATA EXTRACTION AND DATA SYNTHESIS: Emergency department-based boarding of the critically ill patient is common, but no nationally representative frequency estimates has been reported. Boarding literature is limited by variation in the definitions used for boarding and variation in the facilities studied (boarding ranges from 2% to 88% of ICU admissions). Prolonged boarding in the emergency department has been associated with longer duration of mechanical ventilation, longer ICU and hospital length of stay, and higher mortality. Health systems have developed multiple mitigation strategies to address emergency department boarding of critically ill patients, including emergency department-based interventions, hospital-based interventions, and emergency department-based resuscitation care units. CONCLUSIONS: Emergency department boarding of critically ill patients was common and was associated with worse clinical outcomes. Health systems have generated a number of strategies to mitigate these effects. A definition for emergency department boarding is proposed. Future work should establish formal criteria for analysis and benchmarking of emergency department-based boarding overall, with subsequent efforts focused on developing and reporting innovative strategies that improve clinical outcomes of critically ill patients boarded in the emergency department.
Subject(s)
Critical Illness/therapy , Emergency Service, Hospital , Emergency Service, Hospital/statistics & numerical data , Humans , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data , Length of Stay , Patient Admission/statistics & numerical data , Patient Transfer/statistics & numerical data , Treatment Outcome , United StatesABSTRACT
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.
Subject(s)
Diabetic Ketoacidosis , Adult , Diabetic Ketoacidosis/therapy , Emergency Service, Hospital , Hospitals , Humans , Intensive Care Units , Length of Stay , Retrospective StudiesABSTRACT
Resuscitation lacks a place in the hospital to call its own. Specialised intensive care units, though excellent at providing longitudinal critical care, often lack the flexibility to adapt to fluctuating critical care needs. We offer the resuscitative care unit as a potential solution to ensure that patients receive appropriate care during the most critical hours of their illnesses. These units offer an infrastructure for resuscitation and can meet the changing needs of their institutions.
Subject(s)
Intensive Care Units/trends , Resuscitation/methods , Academic Medical Centers/organization & administration , Emergency Medicine/methods , Environment Design/standards , Environment Design/trends , Humans , Intensive Care Units/organization & administration , Maryland , Michigan , Pennsylvania , Resuscitation/trendsSubject(s)
Critical Illness , Rapid Sequence Induction and Intubation , Adult , Humans , Critical Illness/therapyABSTRACT
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.
Subject(s)
Diabetic Ketoacidosis/drug therapy , Glucose/administration & dosage , Administration, Intravenous , Adult , Clinical Protocols/standards , Disease Management , Emergency Service, Hospital/organization & administration , Female , Fluid Therapy/methods , Glucose/therapeutic use , Humans , MaleABSTRACT
Extracorporeal membrane oxygenation (ECMO) is a mode of extracorporeal life support that augments oxygenation, ventilation and/or cardiac output via cannulae connected to a circuit that pumps blood through an oxygenator and back into the patient. ECMO has been used for decades to support cardiopulmonary disease refractory to conventional therapy. While not robust, there are promising data for the use of ECMO in acute hypoxemic respiratory failure, cardiac arrest, and cardiogenic shock and the potential indications for ECMO continue to increase. This review discusses the existing literature on the potential use of ECMO in critically ill patients within the emergency department.
Subject(s)
Critical Illness/therapy , Emergency Service, Hospital/trends , Extracorporeal Membrane Oxygenation/trends , Extracorporeal Membrane Oxygenation/methods , Heart Arrest/therapy , Humans , Respiratory Insufficiency/therapy , Treatment OutcomeABSTRACT
RATIONALE: We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest. OBJECTIVES: We now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients. METHODS: We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test. MEASUREMENTS AND MAIN RESULTS: Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]). CONCLUSIONS: Urinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).
Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/urine , Critical Illness , Insulin-Like Growth Factor Binding Proteins/urine , Protease Inhibitors/urine , Tissue Inhibitor of Metalloproteinase-2/urine , Aged , Aged, 80 and over , Biomarkers/urine , Cell Death , Cohort Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Severity of Illness Index , Time Factors , United StatesABSTRACT
Boarding of critically ill patients in the Emergency Department (ED) has increased over the past 20 years, leading hospital systems to explore ED-focused models of critical care delivery. ED-critical care delivery models vary between health systems due to differences in hospital resources and the needs of the critically ill patients boarding in the ED. Three published systems include an ED critical care intensivist consultation model, a hybrid model, and an ED-intensive care unit model. Paraphrasing the Greek philosopher, Plato, "necessity is the mother of invention." This proverb rings true as EDs are facing an increasing challenge of caring for boarding patients, especially those who are critically ill.
Subject(s)
Critical Care , Emergency Service, Hospital , Intensive Care Units , Humans , Emergency Service, Hospital/organization & administration , Intensive Care Units/organization & administration , Critical Care/organization & administration , Critical Care/standards , Critical Illness/therapy , Models, OrganizationalSubject(s)
Angiotensins/metabolism , Extracorporeal Membrane Oxygenation/trends , Shock/physiopathology , Adult , Angiotensin II/metabolism , Angiotensin II/pharmacology , Angiotensins/pharmacology , Extracorporeal Membrane Oxygenation/methods , Female , Humans , Male , Middle Aged , Shock/metabolism , Shock, Cardiogenic/metabolism , Shock, Cardiogenic/physiopathology , Shock, Septic/metabolism , Shock, Septic/physiopathology , Vasoconstrictor Agents/pharmacology , Vasoconstrictor Agents/therapeutic useABSTRACT
INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.
Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/urine , Cell Cycle Checkpoints/physiology , Insulin-Like Growth Factor Binding Proteins/urine , Tissue Inhibitor of Metalloproteinase-2/urine , Aged , Biomarkers/urine , Cohort Studies , Female , Humans , Male , Middle AgedABSTRACT
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.
Subject(s)
Acute Kidney Injury , Biological Assay , Chemokines, CC , Acute Kidney Injury/diagnosis , Biological Assay/standards , Chemokines, CC/analysis , Humans , Ligands , Renal Replacement TherapyABSTRACT
Importance: Value in health care is quality per unit cost (V = Q/C), and an emergency department-based intensive care unit (ED-ICU) model has been associated with improved quality. To assess the value of this care delivery model, it is essential to determine the incremental direct cost of care. Objective: To determine the association of an ED-ICU with inflation-adjusted change in mean direct cost of care, net revenue, and direct margin per ED patient encounter. Design, Setting, and Participants: This retrospective economic analysis evaluated the cost of care delivery to patients in the ED before and after deployment of the Joyce and Don Massey Family Foundation Emergency Critical Care Center, an ED-ICU, on February 16, 2015, at a large academic medical center in the US with approximately 75â¯000 adult ED visits per year. The pre-ED-ICU cohort was defined as all documented ED visits by patients 18 years or older with a complete financial record from September 8, 2012, through June 30, 2014 (660 days); the post-ED-ICU cohort, all visits from July 1, 2015, through April 21, 2017 (660 days). Fiscal year 2015 was excluded from analysis to phase in the new care model. Statistical analysis was performed March 1 through December 30, 2021. Exposures: Implementation of an ED-ICU. Main Outcomes and Measures: Inflation-adjusted direct cost of care, net revenue, and direct margin per patient encounter in the ED. Results: A total of 234â¯884 ED visits during the study period were analyzed, with 115â¯052 patients (54.7% women) in the pre-ED-ICU cohort and 119â¯832 patients (54.5% women) in the post-ED-ICU cohort. The post-ED-ICU cohort was older (mean [SD] age, 49.1 [19.9] vs 47.8 [19.6] years; P < .001), required more intensive respiratory support (2.2% vs 1.1%; P < .001) and more vasopressor use (0.5% vs 0.2%; P < .001), and had a higher overall case mix index (mean [SD], 1.7 [2.0] vs 1.5 [1.7]; P < .001). Implementation of the ED-ICU was associated with similar inflation-adjusted total direct cost per ED encounter (pre-ED-ICU, mean [SD], $4875 [$15 175]; post-ED-ICU, $4877 [$17 400]; P = .98). Inflation-adjusted net revenue per encounter increased by 7.0% (95% CI, 3.4%-10.6%; P < .001), and inflation-adjusted direct margin per encounter increased by 46.6% (95% CI, 32.1%-61.2%; P < .001). Conclusions and Relevance: Implementation of an ED-ICU was associated with no significant change in inflation-adjusted total direct cost per ED encounter. Holding delivery costs constant while improving quality demonstrates improved value via the ED-ICU model of care.
Subject(s)
Emergency Service, Hospital , Intensive Care Units , Adult , Cost-Benefit Analysis , Critical Care , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
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 (nâ=â138) 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 Pâ<â0.0001) 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 (Pâ<â0.00001). 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.