The 100 most-cited articles in Critical Care Medicine, 2017

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations…

OBJECTIVES: Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis. DESIGN: Observational cohort study. SETTING: Academic medical center from January 2013 to December 2015. PATIENTS: Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: High-resolution vital signs time…

OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine "Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock." DESIGN: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced…

OBJECTIVES: To describe, with an emphasis on clinical applications, what is known about the pathophysiology, management, and implications of septic cardiomyopathy in the adult ICU. DATA SOURCES AND STUDY SELECTION: A PubMed literature review was performed for relevant articles. Only articles in English that studied human adults with sepsis were included. DATA EXTRACTION AND DATA SYNTHESIS: Multiple competing definitions for septic cardiomyopathy hinder understanding of this entity. Although many patients with sepsis develop cardiac dysfunction, the impact of septic cardiomyopathy on prognosis and therapy remains to be demonstrated. Treatment of septic cardiomyopathy is aimed at treating the underlying sepsis and providing specific supportive care for cardiogenic shock when present. CONCLUSIONS: Septic cardiomyopathy is an important contributor to organ dysfunction in sepsis. Guided treatment of septic cardiomyopathy may affect patients' prognosis, especially when their cardiac index is substantially decreased. The implication of septic cardiomyopathy for both short- and long-term…

Over the past 20 years, critical care has matured in a myriad of ways resulting in dramatically higher survival rates for our sickest patients. For millions of new survivors comes de novo suffering and disability called "the postintensive care syndrome." Patients with postintensive care syndrome are robbed of their normal cognitive, emotional, and physical capacity and cannot resume their previous life. The ICU Liberation Collaborative is a real-world quality improvement initiative being implemented across 76 ICUs designed to engage strategically the ABCDEF bundle through team- and evidence-based care. This article explains the science and philosophy of liberating ICU patients and families from harm that is both inherent to critical illness and iatrogenic. ICU liberation is an extensive program designed to facilitate the implementation of the pain, agitation, and delirium guidelines using the evidence-based ABCDEF bundle. Participating ICU teams adapt data from hundreds of peer-reviewed studies to operationalize a systematic and reliable methodology that shifts ICU culture from the…

OBJECTIVES: A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study. DESIGN: Randomized prospective clinical trial. SETTING: Ten ICUs in the United States. PATIENTS: One hundred nineteen severe traumatic brain injury patients. INTERVENTIONS: Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the…

OBJECTIVES: Delirium occurs frequently in adults and is an independent predictor of mortality. However, the epidemiology and outcomes of pediatric delirium are not well-characterized. The primary objectives of this study were to describe the frequency of delirium in critically ill children, its duration, associated risk factors, and effect on in-hospital outcomes, including mortality. Secondary objectives included determination of delirium subtype, and effect of delirium on duration of mechanical ventilation, and length of hospital stay. DESIGN: Prospective, longitudinal cohort study. SETTING: Urban academic tertiary care PICU. PATIENTS: All consecutive admissions from September 2014 through August 2015. INTERVENTIONS: Children were screened for delirium twice daily throughout their ICU stay. MEASUREMENTS AND MAIN RESULTS: Of 1,547 consecutive patients, delirium was diagnosed in 267 (17%) and lasted a median of 2 days (interquartile range, 1-5). Seventy-eight percent of children with delirium developed it within the first 3 PICU days. Most cases of delirium were of the hypoactive…

OBJECTIVE: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients. PARTICIPANTS: A multispecialty task force of 16 international experts in critical care medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine. DESIGN/METHODS: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of…

OBJECTIVE: To determine whether patient- and family-centered care interventions in the ICU improve outcomes. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library databases from inception until December 1, 2016. STUDY SELECTION: We included articles involving patient- and family-centered care interventions and quantitative, patient- and family-important outcomes in adult ICUs. DATA EXTRACTION: We extracted the author, year of publication, study design, population, setting, primary domain investigated, intervention, and outcomes. DATA SYNTHESIS: There were 46 studies (35 observational pre/post, 11 randomized) included in the analysis. Seventy-eight percent of studies (n = 36) reported one or more positive outcome measures, whereas 22% of studies (n = 10) reported no significant changes in outcome measures. Random-effects meta-analysis of the highest quality randomized studies showed no significant difference in mortality (n = 5 studies; odds ratio = 1.07; 95% CI, 0.95-1.21; p = 0.27; I = 0%), but there was a mean decrease in ICU length of stay by 1.21…

OBJECTIVES: To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States. DESIGN: Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol. SETTING: Thirteen U.S.-based emergency departments and ICUs. PATIENTS: Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included. INTERVENTIONS: Procalcitonin was measured daily over the first 5 days. MEASUREMENTS AND MAIN RESULTS: The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The…

OBJECTIVES: To determine prevalence of delirium in critically ill children and explore associated risk factors. DESIGN: Multi-institutional point prevalence study. SETTING: Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. PATIENTS: All children admitted to the pediatric critical care units on designated study days (n = 994). INTERVENTION: Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected. MEASUREMENTS AND MAIN RESULTS: Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in…

OBJECTIVES: Swallowing disorders may be associated with adverse clinical outcomes in patients following invasive mechanical ventilation. We investigated the incidence of dysphagia, its time course, and association with clinically relevant outcomes in extubated critically ill patients. DESIGN: Prospective observational trial with systematic dysphagia screening and follow-up until 90 days or death. SETTINGS: ICU of a tertiary care academic center. PATIENTS: One thousand three-hundred four admissions of mixed adult ICU patients (median age, 66.0 yr [interquartile range, 54.0-74.0]; Acute Physiology and Chronic Health Evaluation-II score, 19.0 [interquartile range, 14.0-24.0]) were screened for postextubation dysphagia. Primary ICU admissions (n = 933) were analyzed and followed up until 90 days or death. Patients from an independent academic center served as confirmatory cohort (n = 220). INTERVENTIONS: Bedside screening for dysphagia was performed within 3 hours after extubation by trained ICU nurses. Positive screening triggered confirmatory specialist bedside swallowing examinations…

OBJECTIVES: To assess the knowledge and use of the Assessment, prevention, and management of pain; spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment; Early mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle to implement the Pain, Agitation, Delirium guidelines. DESIGN: Worldwide online survey. SETTING: Intensive care. INTERVENTION: A cross-sectional online survey using the Delphi method was administered to intensivists worldwide, to assess the knowledge and use of all aspects of the ABCDEF bundle. MEASUREMENT AND MAIN RESULTS: There were 1,521 respondents from 47 countries, 57% had implemented the ABCDEF bundle, with varying degrees of compliance across continents. Most of the respondents (83%) used a scale to evaluate pain. Spontaneous awakening trials and spontaneous breathing trials are performed in 66% and 67% of the responder ICUs, respectively. Sedation scale was used in 89% of ICUs. Delirium monitoring was implemented in 70% of ICUs, but only 42% used a validated delirium tool. Likewise, early…

OBJECTIVES: Controversy exists about the value of greater nutritional intake in critically ill patients, possibly due to varied patient nutritional risk. The objective of this study was to investigate whether clinical outcomes vary by protein or energy intake in patients with risk evaluated by the NUTrition Risk in the Critically Ill score. DESIGN: Prospective observational cohort. SETTING: A total of 202 ICUs. PATIENTS: A total of 2,853 mechanically ventilated patients in ICU greater than or equal to 4 days and a subset of 1,605 patients in ICU greater than or equal to 12 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In low-risk (NUTrition Risk in the Critically Ill, < 5) and high-risk (NUTrition Risk in the Critically Ill, ≥ 5) patients, mortality and time to discharge alive up to day 60 were assessed relative to nutritional intake over the first 12 days using logistic regression and Cox proportional hazard regression, respectively. In high-risk but not low-risk patients, mortality was lower with greater protein (4-d sample: odds ratio, 0.93; 95% CI, 0.89-0.98; p =…

OBJECTIVES: In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques. DESIGN: Post hoc analysis of a randomized clinical trial. SETTING: Twenty-three ICUs. PATIENTS: Patients with a respiratory rate greater than 25 breaths/min and a PaO2/FIO2 ratio less than or equal to 300 mm Hg. INTERVENTION: Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation. MEASUREMENT AND MAIN RESULTS: Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13-6.75; p =…

OBJECTIVES: To assess in-hospital neurologic (CNS) complications in adult patients undergoing veno-venous extracorporeal membrane oxygenation for respiratory failure. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization's data registry. SETTING: Data reported to Extracorporeal Life Support Organization from 350 international extracorporeal membrane oxygenation centers during 1992-2015. PATIENTS: Adults (≥ 18 yr old) supported with veno-venous extracorporeal membrane oxygenation for respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 4,988 adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure. Neurologic injury was defined as brain death, seizures, stroke, and intracranial hemorrhage occurring during extracorporeal membrane oxygenation support. We used multivariable logistic regression to explore patient and extracorporeal membrane oxygenation factors associated with neurologic injury. Median age of the study cohort was 46 (interquartile range, 32-58). Four hundred twenty-six neurologic…

OBJECTIVES: To determine the prevalence of and risk factors for cardiac arrest during intubation in ICU, as well as the association of ICU intubation-related cardiac arrest with 28-day mortality. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Sixty-four French ICUs. PATIENTS: Critically ill patients requiring intubation in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the 1,847 intubation procedures included, 49 cardiac arrests (2.7%) occurred, including 14 without return of spontaneous circulation (28.6%) and 35 with return of spontaneous circulation (71.4%). In multivariate analysis, the main predictors of intubation-related cardiac arrest were arterial hypotension (systolic blood pressure < 90 mm Hg) prior to intubation (odds ratio = 3.406 [1.797-6.454]; p = 0.0002), hypoxemia prior to intubation (odds ratio = 3.991 [2.101-7.583]; p < 0.0001), absence of preoxygenation (odds ratio = 3.584 [1.287-9.985]; p = 0.0146), overweight/obesity (body mass index > 25 kg/m; odds ratio = 2.005 [1.017-3.951]; p = 0.0445), and age more than 75…

OBJECTIVES: The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy. DATA SOURCES: Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched. STUDY SELECTION: Articles not in English, pediatric studies, and case reports were excluded. DATA EXTRACTION: Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3. DATA SYNTHESIS: Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The…

OBJECTIVES: Delirium severity is independently associated with longer hospital stays, nursing home placement, and death in patients outside the ICU. Delirium severity in the ICU is not routinely measured because the available instruments are difficult to complete in critically ill patients. We designed our study to assess the reliability and validity of a new ICU delirium severity tool, the Confusion Assessment Method for the ICU-7 delirium severity scale. DESIGN: Observational cohort study. SETTING: Medical, surgical, and progressive ICUs of three academic hospitals. PATIENTS: Five hundred eighteen adult (≥ 18 yr) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received the Confusion Assessment Method for the ICU, Richmond Agitation-Sedation Scale, and Delirium Rating Scale-Revised-98 assessments. A 7-point scale (0-7) was derived from responses to the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale items. Confusion Assessment Method for the ICU-7 showed high internal consistency (Cronbach's α = 0.85) and good correlation with…

OBJECTIVES: To evaluate the effect of an extended visitation model compared with a restricted visitation model on the occurrence of delirium among ICU patients. DESIGN: Prospective single-center before and after study. SETTING: Thirty-one-bed medical-surgical ICU. PATIENTS: All patients greater than or equal to 18 years old with expected length of stay greater than or equal to 24 hours consecutively admitted to the ICU from May 2015 to November 2015. INTERVENTIONS: Change of visitation policy from a restricted visitation model (4.5 hr/d) to an extended visitation model (12 hr/d). MEASUREMENTS AND MAIN RESULTS: Two hundred eighty-six patients were enrolled (141 restricted visitation model, 145 extended visitation model). The primary outcome was the cumulative incidence of delirium, assessed bid using the confusion assessment method for the ICU. Predefined secondary outcomes included duration of delirium/coma; any ICU-acquired infection; ICU-acquired bloodstream infection, pneumonia, and urinary tract infection; all-cause ICU mortality; and length of ICU stay. The median duration of…

OBJECTIVES: To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock. DESIGN: Retrospective cohort. SETTING: Six hundred fifty-six bed urban academic medical center. PATIENTS: Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded. INTERVENTIONS: Not available. MEASUREMENTS AND MAIN RESULTS: We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96-6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60-4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01-1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11-1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02-1.08), and time to first antimicrobial (odds…

OBJECTIVES: To longitudinally evaluate the association of post-ICU muscle weakness and associated trajectories of weakness over time with 5-year survival. DESIGN: Longitudinal prospective cohort study over 5 years of follow-up. SETTING: Thirteen ICUs in four hospitals in Baltimore, MD. PATIENTS: One hundred fifty-six acute respiratory distress syndrome survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Strength was evaluated with standardized manual muscle testing using the Medical Research Council sum score (range, 0-60; higher is better), with post-ICU weakness defined as sum score less than 48. Muscle strength was assessed at hospital discharge and at 3, 6, 12, 24, 36, and 48 months after acute respiratory distress syndrome. At discharge, 38% of patients had muscle weakness. Every one point increase in sum score at discharge was associated with improved survival (hazard ratio [95% CI], 0.96 [0.94-0.98]), with similar findings longitudinally (0.95 [0.93-0.98]). Having weakness at discharge was associated with worse 5-year survival (1.75 [1.01-3.03]), but the…

OBJECTIVE: Dynamic tests of fluid responsiveness have been developed and investigated in clinical trials of goal-directed therapy. The impact of this approach on clinically relevant outcomes is unknown. We performed a systematic review and meta-analysis to evaluate whether fluid therapy guided by dynamic assessment of fluid responsiveness compared with standard care improves clinically relevant outcomes in adults admitted to the ICU. DATA SOURCES: Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and the International Clinical Trials Registry Platform from inception to December 2016, conference proceedings, and reference lists of relevant articles. STUDY SELECTION: Two reviewers independently identified randomized controlled trials comparing dynamic assessment of fluid responsiveness with standard care for acute volume resuscitation in adults admitted to the ICU. DATA EXTRACTION: Two reviewers independently abstracted trial-level data including population characteristics, interventions, clinical outcomes, and source of funding. Our primary outcome was…

The definition of sepsis has been recently modified to accommodate emerging knowledge in the field, while at the same time being recognized as challenging, if not impossible, to define. Here, we seek to clarify the current understanding of sepsis as one that has been typically framed as a disorder of inflammation to one in which the competing interests of the microbiota, pathobiota, and host immune cells lead to loss of resilience and nonresolving organ dysfunction. Here, we challenge the existence of the idea of noninfectious sepsis given that critically ill humans never exist in a germ-free state. Finally, we propose a new vision of the pathophysiology of sepsis that includes the invariable loss of the host's microbiome with the emergence of a pathobiome consisting of both "healthcare-acquired and healthcare-adapted pathobiota." Under this framework, the critically ill patient is viewed as a host colonized by pathobiota dynamically expressing emergent properties which drive, and are driven by, a pathoadaptive immune response.

OBJECTIVES: To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies. DESIGN: Retrospective cohort study. SETTING: Patients admitted to ICUs in 14 Saudi Arabian hospitals. PATIENTS: Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n = 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non-Middle East respiratory syndrome etiology (non-Middle East respiratory syndrome severe acute respiratory infection) (n = 222). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non-Middle East respiratory syndrome…

OBJECTIVES: Emerging data suggest that early deep sedation may negatively impact clinical outcomes. This systematic review and meta-analysis defines and quantifies the impact of deep sedation within 48 hours of initiation of mechanical ventilation, as described in the world's literature. The primary outcome was mortality. Secondary outcomes included hospital and ICU lengths of stay, mechanical ventilation duration, and delirium and tracheostomy frequency. DATA SOURCES: The following data sources were searched: MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, Cochrane Database of Systematic Reviews databases, ClinicalTrials.gov, conference proceedings, and reference lists. STUDY SELECTION: Randomized controlled trials and nonrandomized studies were included. DATA EXTRACTION: Two reviewers independently screened abstracts of identified studies for eligibility. DATA SYNTHESIS: Nine studies (n = 4,521 patients) published between 2012 and 2017 were included. A random effects meta-analytic model revealed that early…

OBJECTIVES: In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have focused on identifying "one" autoregulation-guided cerebral perfusion pressure target-called "cerebral perfusion pressure optimal". We investigated whether a cerebral perfusion pressure autoregulation range-which uses a continuous estimation of the "lower" and "upper" cerebral perfusion pressure limits of cerebrovascular pressure autoregulation (assessed with pressure reactivity index)-has prognostic value. DESIGN: Single-center retrospective analysis of prospectively collected data. SETTING: The neurocritical care unit at a tertiary academic medical center. PATIENTS: Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol. INTERVENTIONS: None. METHODS AND MAIN RESULTS: Cerebral…

OBJECTIVE: To determine the association of new-onset atrial fibrillation with outcomes, including ICU length of stay and survival. DESIGN: Retrospective cohort of ICU admissions. We found atrial fibrillation using automated detection (≥ 90 s in 30 min) and classed as new-onset if there was no prior diagnosis of atrial fibrillation. We identified determinants of new-onset atrial fibrillation and, using propensity matching, characterized its impact on outcomes. SETTING: Tertiary care academic center. PATIENTS: A total of 8,356 consecutive adult admissions to either the medical or surgical/trauma/burn ICU with available continuous electrocardiogram data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 74 patient-years of every 15-minute observations, we detected atrial fibrillation in 1,610 admissions (19%), with median burden less than 2%. Most atrial fibrillation was paroxysmal; less than 2% of admissions were always in atrial fibrillation. New-onset atrial fibrillation was subclinical or went undocumented in 626, or 8% of all ICU admissions. Advanced age, acute respiratory…

OBJECTIVE: Alarm fatigue is a widely recognized safety and quality problem where exposure to high rates of clinical alarms results in desensitization leading to dismissal of or slowed response to alarms. Nonactionable alarms are thought to be especially problematic. Despite these concerns, the number of clinical alarm signals has been increasing as an everincreasing number of medical technologies are added to the clinical care environment. DATA SOURCES: PubMed, SCOPUS, Embase, and CINAHL. STUDY SELECTION: We performed a systematic review of the literature focused on clinical alarms. We asked a primary key question; "what interventions have been attempted and resulted in the success of reducing alarm fatigue?" and 3-secondary key questions; "what are the negative effects on patients/families; what are the balancing outcomes (unintended consequences of interventions); and what human factor approaches apply to making an effective alarm?" DATA EXTRACTION: Articles relevant to the Key Questions were selected through an iterative review process and relevant data was extracted using a…

OBJECTIVE: To study incidence, type, etiology, risk factors, and impact on outcome of nosocomial infections during extracorporeal membrane oxygenation. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Italian tertiary referral center medical-surgical ICU. PATIENTS: One hundred five consecutive patients who were treated with extracorporeal membrane oxygenation from January 2010 to November 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-two patients were included in the analysis (48.5 [37-56] years old, simplified acute physiology score II 37 [32-47]) who underwent peripheral extracorporeal membrane oxygenation (87% veno-venous) for medical indications (78% acute respiratory distress syndrome). Fifty-two patients (55%) were infected (50.4 infections/1,000 person-days of extracorporeal membrane oxygenation). We identified 32 ventilator-associated pneumonia, eight urinary tract infections, five blood stream infections, three catheter-related blood stream infections, two colitis, one extracorporeal membrane oxygenation cannula infection, and one…

OBJECTIVES: High-flow nasal cannula is increasingly used in the management of respiratory failure. However, little is known about its impact on respiratory effort, which could explain part of the benefits in terms of comfort and efficiency. This study was designed to assess the effects of high-flow nasal cannula on indexes of respiratory effort (i.e., esophageal pressure variations, esophageal pressure-time product/min, and work of breathing/min) in adults. DESIGN: A randomized controlled crossover study was conducted in 12 patients with moderate respiratory distress (i.e., after partial recovery from an acute episode, allowing physiologic measurements). SETTING: Institut Universitaire de Cardiologie et de Pneumologie de Québec, QC, Canada. SUBJECTS: Twelve adult patients with respiratory distress symptoms were enrolled in this study. INTERVENTIONS: Four experimental conditions were evaluated: baseline with conventional oxygen therapy and high-flow nasal cannula at 20, 40, and 60 L/min. The primary outcomes were the indexes of respiratory effort (i.e., esophageal pressure…

OBJECTIVES: The "Pneumonia Zero" project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ventilator-associated pneumonia in critically ill patients admitted to the ICU. DESIGN: Prospective, interventional, and multicenter study. SETTING: A total of 181 ICUs throughout Spain. PATIENTS: All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012. INTERVENTION: Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April-June 2010) as the baseline period.…

OBJECTIVE: To evaluate the association between total medical contact, prehospital, and emergency department delays in antibiotic administration and in-hospital mortality among patient encounters with community-acquired sepsis. DESIGN: Retrospective cohort study. SETTING: Nine hospitals served by 21 emergency medical services agencies in southwestern Pennsylvania from 2010 through 2012. PATIENTS: All emergency medical services encounters with community acquired sepsis transported to the hospital. MEASUREMENTS AND MAIN RESULTS: Among 58,934 prehospital encounters, 2,683 had community-acquired sepsis, with an in-hospital mortality of 11%. Median time from first medical contact to antibiotic administration (total medical contact delay) was 4.2 hours (interquartile range, 2.7-8.0 hr), divided into a median prehospital delay of 0.52 hours (interquartile range, 0.40-0.66 hr) and a median emergency department delay of 3.6 hours (interquartile range, 2.1-7.5 hr). In a multivariable analysis controlling for other risk factors, total medical contact delay was associated with increased…

OBJECTIVES: Delirium is prevalent among critically ill children, yet associated outcomes and modifiable risk factors are not well defined. The objective of this study was to determine associations between pediatric delirium and modifiable risk factors such as benzodiazepine exposure and short-term outcomes. DESIGN: Secondary analysis of collected data from the prospective validation study of the Preschool Confusion Assessment Method for the ICU. SETTING: Tertiary-level PICU. PATIENTS: Critically ill patients 6 months to 5 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily delirium assessments were completed using the Preschool Confusion Assessment Method for the ICU. Associations between baseline and in-hospital risk factors were analyzed for likelihood of ICU discharge using Cox proportional hazards regression and delirium duration using negative binomial regression. Multinomial logistic regression was used to determine associations between daily risk factors and delirium presence the following day. Our 300-patient cohort had a median (interquartile range) age of…

OBJECTIVE: The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors. DESIGN: Cohort study (April 2009 to March 2016). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN). PATIENTS: Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries. INTERVENTIONS: All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations. MEASUREMENTS AND MAIN RESULTS: We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based…

OBJECTIVES: Among critically ill patients with acute kidney injury, exposure to positive fluid balance, compared with negative fluid balance, has been associated with mortality and impaired renal recovery. However, it is unclear whether positive and negative fluid balances are associated with poor outcome compared to patients with even fluid balance (euvolemia). In this study, we examined the association between exposure to positive or negative fluid balance, compared with even fluid balance, on 1-year mortality and renal recovery. DESIGN: Retrospective cohort study. SETTING: Eight medical-surgical ICUs at the University of Pittsburgh Medical Center, Pittsburgh, PA. PATIENTS: Critically ill patients admitted between July 2000 and October 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 18,084 patients, fluid balance was categorized as negative (< 0%), even (0% to < 5%), or positive (≥ 5%). Following propensity matching, positive fluid balance, compared with even or negative fluid balance, was associated with increased mortality (30.3% vs 21.1% vs 22%, respectively; p…

OBJECTIVES: A recent post hoc analysis suggested that driving pressure may be more important than traditional ventilatory variables in determining outcome in mechanically ventilated patients with acute respiratory distress syndrome. We conducted a systematic review and meta-analysis to summarize the risk of mortality for higher versus lower driving pressure. DATA SOURCES: MEDLINE, EMBASE, PubMed, CINAHL, and Cochrane CENTRAL from inception to February 10, 2017. STUDY SELECTION: Studies including mechanically ventilated adult patients with acute respiratory distress syndrome, reporting driving pressure and mortality. DATA EXTRACTION: Seven studies including five secondary analysis of previous randomized controlled trials and two observational studies (6,062 patients) were eligible for study. All studies were judged as having a low risk of bias. Median (interquartile range) driving pressure between higher and lower driving pressure groups was 15 cm H2O (14-16 cm H2O). Median (interquartile range) mortality of all included studies was 34% (32-38%). DATA SYNTHESIS: In the meta-analyses…

OBJECTIVES: The emergency department is an important venue for initial sepsis recognition and care. We sought to determine contemporary estimates of the epidemiology of U.S. emergency department visits for sepsis. DESIGN: Analysis of data from the National Hospital Ambulatory Medical Care Survey. SETTING: U.S. emergency department visits, 2009-2011. PATIENTS: Adult (age, ≥ 18 yr) emergency department sepsis patients. We defined serious infection as an emergency department diagnosis of a serious infection or a triage temperature greater than 38°C or less than 36°C. We defined three emergency department sepsis classifications: 1) original emergency department sepsis-serious infection plus emergency department diagnosis of organ dysfunction, endotracheal intubation, or systolic blood pressure less than or equal to 90 mm Hg or explicit sepsis emergency department diagnoses; 2) quick Sequential Organ Failure Assessment emergency department sepsis-serious infection plus presence of at least two "quick" Sequential Organ Failure Assessment criteria (Glasgow Coma Scale ≤ 14, respiratory rate…

OBJECTIVES: ICU survivors frequently report reduced health-related quality of life, but the relative importance of preillness versus acute illness factors in survivor populations is not well understood. We aimed to explore health-related quality of life trajectories over 12 months following ICU discharge, patterns of improvement, or deterioration over this period, and the relative importance of demographics (age, gender, social deprivation), preexisting health (Functional Comorbidity Index), and acute illness severity (Acute Physiology and Chronic Health Evaluation II score, ventilation days) as determinants of health-related quality of life and relevant patient-reported symptoms during the year following ICU discharge. DESIGN: Nested cohort study within a previously published randomized controlled trial. SETTING: Two ICUs in Edinburgh, Scotland. PATIENTS: Adult ICU survivors (n = 240) who required more than 48 hours of mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We prospectively collected data for age, gender, social deprivation (Scottish index of…

OBJECTIVES: Early goal-directed therapy has shown discordant survival outcomes in sepsis studies. We aim to find the reasons for this discordance. DESIGN: Random-effects and Bayesian hierarchical analyses. SETTING: Studies that evaluated early goal-directed therapy. SUBJECTS: Patients with severe sepsis and/or septic shock. INTERVENTIONS: Early goal-directed therapy. MEASUREMENTS AND MAIN RESULTS: A total of 19,998 patients were included in the main analysis: 31 observational (n = 15,656) and six randomized (n = 4,342) studies. The analysis from 37 studies showed that early goal-directed therapy was associated with a 23% reduction in the risk of death: relative risk = 0.77 (95% CI, 0.71-0.83); p value of less than 0.0001. Mortality reduction was seen with observational studies: relative risk = 0.73 (0.67-0.80); p value of less than 0.0001 but not with randomized studies: relative risk = 0.92 (0.78-1.07); p = 0.268. Meta-regression analysis showed lower risk of death in observational compared with randomized studies: relative risk = 0.81 (0.68-0.95); p = 0.01. Differences in age,…

OBJECTIVES: Catatonia, a condition characterized by motor, behavioral, and emotional changes, can occur during critical illness and appear as clinically similar to delirium, yet its management differs from delirium. Traditional criteria for medical catatonia preclude its diagnosis in delirium. Our objective in this investigation was to understand the overlap and relationship between delirium and catatonia in ICU patients and determine diagnostic thresholds for catatonia. DESIGN: Convenience cohort, nested within two ongoing randomized trials. SETTING: Single academic medical center in Nashville, TN. PATIENTS: We enrolled 136 critically ill patients on mechanical ventilation and/or vasopressors, randomized to two usual care sedation regimens. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for delirium and catatonia by independent and masked personnel using Confusion Assessment Method for the ICU and the Bush Francis Catatonia Rating Scale mapped to Diagnostic Statistical Manual 5 criterion A for catatonia. Of 136 patients, 58 patients (43%) had only delirium, four (3%) had…

OBJECTIVE: To evaluate the acquisition rate, identify risk factors, and estimate the risk for subsequent infection, associated with the colonization of the digestive tract with extended-spectrum beta-lactamase-producing Enterobacteriaceae during ICU-hospitalization. DATA SOURCES: PubMed, EMBASE, and reference lists of all eligible articles. STUDY SELECTION: Included studies provided data on ICU-acquired colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae in previously noncolonized and noninfected patients and used the double disk synergy test for extended-spectrum beta-lactamase-producing Enterobacteriaceae phenotypic confirmation. Studies reporting extended-spectrum beta-lactamase-producing Enterobacteriaceae outbreaks or data on pediatric population were excluded. DATA EXTRACTION: Two authors independently assessed study eligibility and performed data extraction. DATA SYNTHESIS: Thirteen studies (with 15,045 ICUs-patients) were evaluated using a random-effect model and a meta-regression analysis. The acquisition rate of digestive tract colonization…

OBJECTIVE: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. DESIGN: Single center, randomized, double-blind controlled trial. SETTING: Teaching hospital. PATIENTS: Adult cancer patients with septic shock in the first 6 hours of ICU admission. INTERVENTIONS: Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. MEASUREMENTS AND MAIN RESULTS: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0-3] vs 0 [0-2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53-1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90…

OBJECTIVES: To examine the feasibility and safety of mobilizing patients while on extracorporeal membranous oxygenation support. DESIGN: Retrospective cohort study. SETTING: Medical and Surgical ICUs in a large tertiary care hospital in the United States. PATIENTS: Adults supported on extracorporeal membranous oxygenation from January 2014 to December 2015. MEASUREMENTS AND MAIN RESULTS: We reviewed the medical records from physical therapy, perfusion, and intensivists to obtain the number and type of physical therapy interventions and discharge status; extracorporeal membranous oxygenation type and description of support, cannulation sites; and risk management details of adverse effects, if any. Of 254 patients supported on extracorporeal membranous oxygenation, 167 patients (66.7%) received a total of 607 physical therapy sessions while on extracorporeal membranous oxygenation support. In this cohort, 134 patients (80.2%) had at least one femoral cannula during physical therapy intervention. Sixty-six of the 167 patients (39.5%) were supported on extracorporeal membranous…

OBJECTIVE: To evaluate outcomes in patients receiving balanced fluids for resuscitation in pediatric severe sepsis. DESIGN: Observational cohort review of prospectively collected data from a large administrative database. SETTING: PICUs from 43 children's hospitals. PATIENTS: PICU patients diagnosed with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed data from the Pediatric Health Information System database from 2004 to 2012. Children with pediatric severe sepsis receiving balanced fluids for resuscitation in the first 24 and 72 hours of treatment were compared to those receiving unbalanced fluids. Thirty-six thousand nine hundred eight patients met entry criteria for analysis. Two thousand three hundred ninety-eight patients received exclusively balanced fluids at 24 hours and 1,641 at 72 hours. After propensity matching, the 72-hour balanced fluids group had lower mortality (12.5% vs 15.9%; p = 0.007; odds ratio, 0.76; 95% CI, 0.62-0.93), lower prevalence of acute kidney injury (16.0% vs 19.2%; p = 0.028; odds ratio, 0.82; 95% CI, 0.68-0.98), and…

OBJECTIVE: Sepsis is life-threatening organ dysfunction due to dysregulated host responses to infection. Current knowledge of human B-cell alterations in sepsis is sparse. We tested the hypothesis that B-cell loss in sepsis involves distinct subpopulations of B cells and investigated mechanisms of B-cell depletion. DESIGN: Prospective cohort study. SETTING: Critical care units. PATIENTS: Adult sepsis patients without any documented immune comorbidity. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: B-cell subsets were quantified by flow cytometry; annexin-V status identified apoptotic cells and phosphorylation of intracellular kinases identified activation status of B-cell subsets. B cell-specific survival ligand concentrations were measured. Gene expression in purified B cells was measured by microarray. Differences in messenger RNA abundance between sepsis and healthy controls were compared. Lymphopenia present in 74.2% of patients on admission day was associated with lower absolute B-cell counts (median [interquartile range], 0.133 [0.093-0.277] 10 cells/L) and selective…

OBJECTIVE: Respiratory muscle weakness frequently develops during mechanical ventilation, although in children there are limited data about its prevalence and whether it is associated with extubation outcomes. We sought to identify risk factors for pediatric extubation failure, with specific attention to respiratory muscle strength. DESIGN: Secondary analysis of prospectively collected data. SETTING: Tertiary care PICU. PATIENTS: Four hundred nine mechanically ventilated children. INTERVENTIONS: Respiratory measurements using esophageal manometry and respiratory inductance plethysmography were made preextubation during airway occlusion and on continuous positive airway pressure of 5 and pressure support of 10 above positive end-expiratory pressure 5 cm H2O, as well as 5 and 60 minutes postextubation. MEASUREMENTS AND MAIN RESULTS: Thirty-four patients (8.3%) were reintubated within 48 hours of extubation. Reintubation risk factors included lower maximum airway pressure during airway occlusion (aPiMax) preextubation, longer length of ventilation, postextubation upper airway…

OBJECTIVE: Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management. DESIGN, SETTING, AND PATIENTS: We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 μg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 μg/L (upper limit of normal). MEASUREMENTS AND MAIN RESULTS: A neuron-specific enolase serum concentration greater than 90 μg/L predicted Cerebral Performance Category 4-5 with a positive predictive value of 99%, false positive rate…

OBJECTIVES: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome. DESIGN: A secondary analysis of existing data from previously reported observational studies. SETTING: A network of ICUs. PATIENTS: We studied 778 patients with moderate to severe acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome…

OBJECTIVES: To study the prognostic value of fever in the emergency department in septic patients subsequently admitted to the ICU. DESIGN: Observational cohort study from the Swedish national quality register for sepsis. SETTING: Thirty ICU's in Sweden. PATIENTS: Two thousand two hundred twenty-five adults who were admitted to an ICU within 24 hours of hospital arrival with a diagnosis of severe sepsis or septic shock were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Body temperature was measured and classified according to four categories (< 37°C, 37-38.29°C, 38.3-39.5°C, ≥ 39.5°C). The main outcome was in-hospital mortality. Odds ratios for mortality according to body temperature were estimated using multivariable logistic regression. Subgroup analyses were conducted according to age, sex, underlying comorbidity, and time to given antibiotics. Overall mortality was 25%. More than half of patients had a body temperature below 38.3°C. Mortality was inversely correlated with temperature and decreased, on average, more than 5% points per °C increase, from 50% in…

OBJECTIVE: To evaluate the effectiveness of noninvasive ventilation in patients with acute hypoxemic nonhypercapnic respiratory failure unrelated to exacerbation of chronic obstructive pulmonary disease and cardiogenic pulmonary edema. DATA SOURCES: PubMed, EMBASE, Cochrane library, Web of Science, and bibliographies of articles were retrieved inception until June 2016. STUDY SELECTION: Randomized controlled trials comparing application of noninvasive ventilation with standard oxygen therapy in adults with acute hypoxemic nonhypercapnic respiratory failure were included. Chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients were excluded. The primary outcome was intubation rate; ICU mortality and hospital mortality were secondary outcomes. DATA EXTRACTION: Demographic variables, noninvasive ventilation application, and outcomes were retrieved. Internal validity was assessed using the risk of bias tool. The strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology. DATA SYNTHESIS:…

OBJECTIVES: In the contemporary ICU, mechanically ventilated patients may not have arterial blood gas measurements available at relevant timepoints. Severity criteria often depend on arterial blood gas results. Retrospective studies suggest that nonlinear imputation of PaO2/FIO2 from SpO2/FIO2 is accurate, but this has not been established prospectively among mechanically ventilated ICU patients. The objective was to validate the superiority of nonlinear imputation of PaO2/FIO2 among mechanically ventilated patients and understand what factors influence the accuracy of imputation. DESIGN: Simultaneous SpO2, oximeter characteristics, receipt of vasopressors, and skin pigmentation were recorded at the time of a clinical arterial blood gas. Acute respiratory distress syndrome criteria were recorded. For each imputation method, we calculated both imputation error and the area under the curve for patients meeting criteria for acute respiratory distress syndrome (PaO2/FIO2 ≤ 300) and moderate-severe acute respiratory distress syndrome (PaO2/FIO2 ≤ 150). SETTING: Nine hospitals within the…

OBJECTIVE: Piperacillin-tazobactam is a commonly used antibiotic in critically ill patients; however, controversy exists as to whether mortality in serious infections can be decreased through administration by prolonged infusion compared with intermittent infusion. The purpose of this systematic review and meta-analysis was to describe the impact of prolonged infusion piperacillin-tazobactam schemes on clinical endpoints in severely ill patients. DESIGN: We conducted a systematic literature review and meta-analysis searching MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to April 1, 2017, for studies. INTERVENTIONS: Mortality rates were compared between severely ill patients receiving piperacillin-tazobactam via prolonged infusion or intermittent infusion. Included studies must have reported severity of illness scores, which were transformed into average study-level mortality probabilities. MEASUREMENTS AND MAIN RESULTS: Two investigators independently screened titles, abstracts, and full texts of studies meeting inclusion…

OBJECTIVES: The mechanism(s) for septic cardiomyopathy in humans is not known. To address this, we measured messenger RNA alterations in hearts from patients who died from systemic sepsis, in comparison to changed messenger RNA expression in nonfailing and failing human hearts. DESIGN: Identification of genes with altered abundance in septic cardiomyopathy, ischemic heart disease, or dilated cardiomyopathy, in comparison to nonfailing hearts. SETTING: ICUs at Barnes-Jewish Hospital, St. Louis, MO. PATIENTS: Twenty sepsis patients, 11 ischemic heart disease, nine dilated cardiomyopathy, and 11 nonfailing donors. INTERVENTIONS: None other than those performed as part of patient care. MEASUREMENTS AND MAIN RESULTS: Messenger RNA expression levels for 198 mitochondrially localized energy production components, including Krebs cycle and electron transport genes, decreased by 43% ± 5% (mean ± SD). Messenger RNAs for nine genes responsible for sarcomere contraction and excitation-contraction coupling decreased by 43% ± 4% in septic hearts. Surprisingly, the alterations in messenger RNA…

OBJECTIVE: To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI). PARTICIPANTS: A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES: Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews. RESULTS: Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by…

OBJECTIVE: To provide ICU clinicians with evidence-based guidance on tested interventions that reduce or prevent alert fatigue within clinical decision support systems. DESIGN: Systematic review of PubMed, Embase, SCOPUS, and CINAHL for relevant literature from 1966 to February 2017. PATIENTS: Focus on critically ill patients and included evaluations in other patient care settings, as well. INTERVENTIONS: Identified interventions designed to reduce or prevent alert fatigue within clinical decision support systems. MEASUREMENTS AND MAIN RESULTS: Study selection was based on one primary key question to identify effective interventions that attempted to reduce alert fatigue and three secondary key questions that covered the negative effects of alert fatigue, potential unintended consequences of efforts to reduce alert fatigue, and ideal alert quantity. Data were abstracted by two reviewers independently using a standardized abstraction tool. Surveys, meeting abstracts, "gray" literature, studies not available in English, and studies with non-original data were excluded. For the primary…

OBJECTIVES: To estimate the prevalence of physician burnout, psychological distress, and its association with selected personal and practice characteristics among pediatric critical care physicians and to evaluate the relationship between burnout and psychological distress. DESIGN: Cross-sectional, online survey. SETTING: Pediatric critical care practices in the United States. SUBJECTS: Pediatric critical care physicians. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: A nonrandom sample of 253 physicians completed an online survey consisting of personal and practice characteristics, the Maslach Burnout Inventory, and the General Health Questionnaire. Nearly half of the participants (49%; 95% CI, 43-55%; n = 124) scored high burnout in at least one of the three subscales of the Maslach Burnout Inventory and 21% reported severe burnout. The risk of any burnout was about two times more in women physicians (odds ratio, 1.97; 95% CI, 1.2-3.4). Association between other personal or practice characteristics and burnout was not evident in this study, while regular physical exercise…

OBJECTIVE: To investigate if postoperative delirium was associated with the development of dementia within 5 years after cardiac surgery. DESIGN: Longitudinal cohort study. SETTING: Cardiothoracic Division, Umeå University Hospital, Sweden. PATIENTS: Patients aged 70 years old or older (n = 114) scheduled for routine cardiac procedures with cardiopulmonary bypass without documented dementia were enrolled in 2009. INTERVENTION: Structured assessments were performed preoperatively, 1 and 4 days after extubation, and 1, 3, and 5 years postoperatively. MEASUREMENTS AND MAIN RESULTS: Patients were assessed comprehensively, including cognitive and physical function, coexisting medical conditions, demographic characteristics, and medications. Diagnoses of delirium, depression, and dementia were made according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. During the 5-year period, 30 of 114 participants (26.3%) developed dementia. Postoperative delirium had occurred in 87% of those who later developed dementia. A multivariable logistic…

OBJECTIVES: Angiotensin II is an emerging therapy for septic acute kidney injury, but it is unknown if its vasoconstrictor action induces renal hypoxia. We therefore examined the effects of angiotensin II on intrarenal PO2 in ovine sepsis. We also assessed the validity of urinary PO2 as a surrogate measure of medullary PO2. DESIGN: Interventional study. SETTING: Research Institute. SUBJECTS: Sixteen adult Merino ewes (n = 8/group). INTERVENTIONS: Sheep were instrumented with fiber-optic probes in the renal cortex, medulla, and within a bladder catheter to measure PO2. Conscious sheep were infused with Escherichia coli for 32 hours. At 24-30 hours, angiotensin II (0.5-33.0 ng/kg/min) or saline vehicle was infused. MEASUREMENTS AND MAIN RESULTS: Septic acute kidney injury was characterized by hypotension and a 60% ± 6% decrease in creatinine clearance. During sepsis, medullary PO2 decreased from 36 ± 1 to 30 ± 3 mm Hg after 1 hour and to 20 ± 2 mm Hg after 24 hours; at these times, urinary PO2 was 42 ± 2, 34 ± 2, and 23 ± 2 mm Hg. Increases in urinary neutrophil gelatinase-associated…

OBJECTIVE: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill. DATA SOURCES: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015. STUDY SELECTION: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system. The committee collectively developed Population, Intervention, Comparator, Outcome questions and quality of evidence statements pertaining to medication errors and adverse drug events addressing the key components. A total of 34 Population, Intervention, Comparator, Outcome questions, five quality of evidence statements, and one commentary on disclosure was developed. DATA EXTRACTION: Subcommittee members were assigned selected Population, Intervention, Comparator, Outcome questions or quality of evidence statements. Subcommittee members completed their Grading of Recommendations Assessment, Development, and Evaluation of…

INTRODUCTION: A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the feasibility of undertaking a larger trial investigating the efficacy and safety of withholding proton pump inhibitors in critically ill patients. METHODS: In 10 ICUs, we randomized adult ICU patients anticipated to be mechanically ventilated for greater than or equal to 48 hours to receive 40 mg of IV pantoprazole daily or placebo. We excluded patients who had acute or recent gastrointestinal bleed, used dual antiplatelet agents, had a medical condition requiring proton pump inhibitor treatment, or had already received more than one dose of acid suppression daily. Patients, families, clinicians, and research staff were blinded. We conducted a systematic review and meta-analysis of similar trials. MAIN RESULTS: Ninety-one patients (49 pantoprazole and 42 placebo) from 10 centers in Canada,…

OBJECTIVE: To determine the incidence and risk factors of chronic critical illness after severe blunt trauma. DESIGN: Prospective observational cohort study (NCT01810328). SETTING: Two level-one trauma centers in the United States. PATIENTS: One hundred thirty-five adult blunt trauma patients with hemorrhagic shock who survived beyond 48 hours after injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Chronic critical illness was defined as an ICU stay lasting 14 days or more with evidence of persistent organ dysfunction. Three subjects (2%) died within the first 7 days, 107 (79%) exhibited rapid recovery and 25 (19%) progressed to chronic critical illness. Patients who developed chronic critical illness were older (55 vs 44-year-old; p = 0.01), had more severe shock (base deficit, -9.2 vs -5.5; p = 0.005), greater organ failure severity (Denver multiple organ failure score, 3.5 ± 2.4 vs 0.8 ± 1.1; p < 0.0001) and developed more infectious complications (84% vs 35%; p < 0.0001). Chronic critical illness patients were more likely to be discharged to a long-term care setting…

OBJECTIVE: To describe trends in outcomes of cancer patients with an unplanned admission to the ICU between 1997 and 2013 and to identify risk factors for mortality of those admitted between 2009 and 2013. DESIGN: Retrospective analysis. SETTING: Intensive Care National Audit & Research Centre Case Mix Programme Database including data of ICUs in England, Wales, and Northern Ireland. PATIENTS: Patients (99,590) with a solid tumor and 13,538 patients with a hematological malignancy with an unplanned ICU admission between 1997 and 2013; 39,734 solid tumor patients and 6,652 patients with a hematological malignancy who were admitted between 2009 and 2013 were analyzed in depth. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In solid tumor patients admitted between 2009 and 2013, hospital mortality was 26.4%. Independent risk factors for hospital mortality were metastatic disease (odds ratio, 1.99), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.63), Intensive Care National Audit & Research Centre Physiology score (odds ratio, 1.14), admission for…

OBJECTIVES: Atelectasis develops in critically ill obese patients when undergoing mechanical ventilation due to increased pleural pressure. The current study aimed to determine the relationship between transpulmonary pressure, lung mechanics, and lung morphology and to quantify the benefits of a decremental positive end-expiratory pressure trial preceded by a recruitment maneuver. DESIGN: Prospective, crossover, nonrandomized interventional study. SETTING: Medical and Surgical Intensive Care Units at Massachusetts General Hospital (Boston, MA) and University Animal Research Laboratory (São Paulo, Brazil). PATIENTS/SUBJECTS: Critically ill obese patients with acute respiratory failure and anesthetized swine. INTERVENTIONS: Clinical data from 16 mechanically ventilated critically ill obese patients were analyzed. An animal model of obesity with reversible atelectasis was developed by placing fluid filled bags on the abdomen to describe changes of lung mechanics, lung morphology, and pulmonary hemodynamics in 10 swine. MEASUREMENTS AND MAIN RESULTS: In obese patients (body mass index,…

OBJECTIVE: Sepsis is a leading cause of mortality in noncoronary ICUs. Although immediate start of antibiotics reduces sepsis-related mortality, antibiotics are often administered for too long, leading to suboptimal treatment and, importantly, contributes to antimicrobial resistance. Prior literature suggests that procalcitonin correlates with infection and thus may help to guide the decision on when to stop antibiotic treatment. This study was conducted as part of a regulatory submission to the U.S. Food and Drug Administration and aimed to summarize the evidence of procalcitonin guidance on efficacy and safety outcomes in adult patients with sepsis. DATA SOURCES: PubMed and the Cochrane Database of Systematic Reviews. STUDY SELECTION: English-language randomized controlled trials evaluating procalcitonin use among adult patients with suspected or confirmed sepsis published between January 2004 and May 2016. DATA EXTRACTION: Inverse-variance weighting fixed and random effects meta-analyses were performed on the following efficacy and safety endpoints: antibiotic duration, all-cause…

OBJECTIVES: First, we aimed at assessing whether fluid responsiveness is predicted by the effects of an end-expiratory occlusion on the velocity-time integral of the left ventricular outflow tract. Second, we investigated whether adding the effects of an end-inspiratory occlusion and of an end-expiratory occlusion on velocity-time integral can predict fluid responsiveness with similar reliability than end-expiratory occlusion alone but with a higher threshold, which might be more compatible with the precision of echocardiography. DESIGN: Diagnostic study. SETTING: Medical ICU. PATIENTS: Thirty mechanically ventilated patients in whom fluid administration was planned. INTERVENTIONS: A 15-second end-expiratory occlusion and end-inspiratory occlusion, separated by 1 minute, followed by a 500-mL saline administration. MEASUREMENTS AND MAIN RESULTS: Pulse contour analysis-derived cardiac index and velocity-time integral were measured during the last 5 seconds of 15-second end-inspiratory occlusion and end-expiratory occlusion and after fluid administration. End-expiratory occlusion…

OBJECTIVE: Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration. DESIGN: Retrospective subgroup analysis of randomized controlled trial. SETTING: Multicenter North American and European clinical trial. PATIENTS: Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population. INTERVENTIONS: Random assignment of placebo or recombinant human interleukin-1 receptor antagonist × 72 hours. MEASUREMENTS AND MAIN RESULTS: We measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day…

OBJECTIVES: Citrate accumulation is a major complication of regional citrate anticoagulation during continuous renal replacement therapy. We studied the prediction of citrate accumulation during continuous veno-venous hemodialysis with regional citrate anticoagulation by initial lactate concentrations and lactate kinetics. DESIGN: A retrospective follow-up analysis from a cohort of critically ill patients. SETTING: Mixed medical-surgical ICUs at a university hospital. PATIENTS: All adult patients with acute kidney injury and treated with regional citrate anticoagulation-continuous veno-venous hemodialysis during a 3-year period (n = 1,070) were included in this retrospective study and screened for metabolic signs of citrate accumulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The frequency of citrate accumulation during the first 48 hours of therapy was 2.26%. In patients with initial normal lactate (< 2.2 mmol/L), elevated lactate (≥ 2.2 to < 4 mmol/L), or severe hyperlactatemia (≥ 4 mmol/L), the frequency of citrate accumulation was 0.77%, 2.70%, and 6.33%,…

OBJECTIVE: Although extracorporeal membrane oxygenation volume has increased, proficiency in the technology requires extensive training. We compared traditional water-drill-based extracorporeal membrane oxygenation training with simulation-based extracorporeal membrane oxygenation training with the hypothesis that simulation-based training is superior. DESIGN: Randomized controlled trial. SETTING: Academic medical center. SUBJECTS: Pulmonary/critical care fellows. INTERVENTIONS: Participants had a preintervention simulated extracorporeal membrane oxygenation emergency (Sim1-recirculation) then randomized into simulation and traditional groups. Each group participated in three teaching scenarios, via high-fidelity simulation or via water-drills. After 6 weeks and after 1 year, participants returned for two simulated extracorporeal membrane oxygenation emergencies (Sim2-pump failure and Sim3-access insufficiency). Sim2 was a case encountered during teaching, whereas Sim3 was novel. A critical action, necessary for resolution of each scenario, was preidentified for timing. MEASUREMENTS…

OBJECTIVES: To identify the "core domains" (i.e., patient outcomes, health-related conditions, or aspects of health) that relevant stakeholders agree are essential to assess in all clinical research studies evaluating the outcomes of acute respiratory failure survivors after hospital discharge. DESIGN: A two-round consensus process, using a modified Delphi methodology, with participants from 16 countries, including patient and caregiver representatives. Prior to voting, participants were asked to review 1) results from surveys of clinical researchers, acute respiratory failure survivors, and caregivers that rated the importance of 19 preliminary outcome domains and 2) results from a qualitative study of acute respiratory failure survivors' outcomes after hospital discharge, as related to the 19 preliminary outcome domains. Participants also were asked to suggest any additional potential domains for evaluation in the first Delphi survey. SETTING: Web-based surveys of participants representing four stakeholder groups relevant to clinical research evaluating postdischarge outcomes of…

OBJECTIVES: Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. DATA SOURCES: We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. STUDY SELECTION: All identified studies were screened for eligibility by two independent reviewers. DATA EXTRACTION: Key data were extracted using standardized data collection forms. DATA SYNTHESIS: Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized…

OBJECTIVES: Surgical and medical ICU patients are at high risk of mortality and provide a significant cost to the healthcare system. The aim of this study is to describe the effect of pharmacist-led interventions on drug therapy and clinical strategies on ICU patient outcome and hospital costs. DESIGN: Before and after study in two French ICUs (16 and 10 beds). PATIENTS: ICU patients. INTERVENTION: From January 1, 2013, to June 30, 2015, a pharmacist observation period was compared with an intervention period in which a critical care pharmacist provided recommendations to clinicians regarding sedative drugs and doses, choice of mechanical ventilation mode and related settings, antimicrobial de-escalation, and central venous and urinary catheters removal. Differences in ICU and hospital length of stay, duration of mechanical ventilation, mortality rate, and hospital costs per patient were quantified between groups with patients matched for severity of illness (Simplified Acute Physiology Score II) at admission. MEASUREMENTS AND MAIN RESULTS: From the 1,519 and 1,268 admitted patients…

OBJECTIVES: For patients supported with veno-venous extracorporeal membrane oxygenation, the occurrence of intracranial hemorrhage is associated with a high mortality. It is unclear whether intracranial hemorrhage is a consequence of the extracorporeal intervention or of the underlying severe respiratory pathology. In a cohort of patients transferred to a regional severe respiratory failure center that routinely employs admission brain imaging, we sought 1) the prevalence of intracranial hemorrhage; 2) survival and neurologic outcomes; and 3) factors associated with intracranial hemorrhage. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center, university teaching hospital. PATIENTS: Patients admitted between December 2011 and February 2016. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Three hundred forty-two patients were identified: 250 managed with extracorporeal support and 92 managed using conventional ventilation. The prevalence of intracranial hemorrhage was 16.4% in extracorporeal membrane…

OBJECTIVE: To identify, classify, and describe safety hazards during the process of intrahospital transport of critically ill patients. DESIGN: A prospective observational study. Data from participant observations of the intrahospital transport process were collected over a period of 3 months. SETTING: The study was undertaken at two ICUs in one university hospital. PATIENTS: Critically ill patients transported within the hospital by critical care nurses, unlicensed nurses, and physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Content analysis was performed using deductive and inductive approaches. We detected a total of 365 safety hazards (median, 7; interquartile range, 4-10) during 51 intrahospital transports of critically ill patients, 80% of whom were mechanically ventilated. The majority of detected safety hazards were assessed as increasing the risk of harm, compromising patient safety (n = 204). Using the System Engineering Initiative for Patient Safety, we identified safety hazards related to the work system, as follows: team (n = 61), tasks (n = 83), tools…

OBJECTIVES: Extracorporeal life support can lead to rapid reversal of hypoxemia and shock; however, it can also result in varying degrees of hyperoxia. Recent data have suggested an association between hyperoxia and mortality; however, this conclusion has not been consistent across the literature. We evaluated the association between oxygenation thresholds and mortality in three cohorts of extracorporeal life support patients. DESIGN: We performed a retrospective cohort study using the Extracorporeal Life Support Organization Registry. SETTING: We evaluated the relationship between oxygenation measured 24 hours after extracorporeal membrane oxygenation onset and mortality (2010-2015). PATIENTS: The extracorporeal life support cohorts were as follows: 1) veno-venous extracorporeal membrane oxygenation for respiratory failure, 2) veno-arterial extracorporeal membrane oxygenation for cardiogenic shock, and 3) extracorporeal cardiopulmonary resuscitation. INTERVENTIONS: The relationships between hypoxemia (PaO2 < 60mm Hg), normoxia (PaO2 60-100mm Hg), moderate hyperoxia (PaO2 101-300mm…

OBJECTIVE: To assess the prevalence of acute kidney injury in patients with subarachnoid hemorrhage patients. DESIGN: Retrospective analysis of all subarachnoid hemorrhage admissions. SETTINGS: Neurocritical care unit. PATIENTS: All patients with a diagnosis of subarachnoid hemorrhage between 2009 and 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,267 patients included in this cohort, 16.7% developed acute kidney injury, as defined by Kidney Disease Improving Global Outcome criteria (changes in creatinine only). Compared to patients without acute kidney injury, patients with acute kidney injury had a higher prevalence of diabetes mellitus (21.2% vs 9.8%; p < 0.001) and hypertension (70.3% vs 50.5%; p < 0.001) and presented with higher admission creatinine concentrations (1.21 ± 0.09 vs 0.81 ± 0.01 mg/dL [mean ± SD], respectively; p < 0.001). Patients with acute kidney injury also had higher mean serum chloride and sodium concentrations during their ICU stay (113.4 ± 0.6 vs 107.1 ± 0.2 mmol/L and 143.3 ± 0.4 vs 138.8 ± 0.1 mmol/L, respectively; p < 0.001 for both),…

OBJECTIVE: To compare cerebral autoregulation indices as predictors of patient outcome and their dependence on duration of monitoring. DATA SOURCES: Systematic literature search and meta-analysis using PubMed, EMBASE, and the Cochrane Library from January 1990 to October 2015. STUDY SELECTION: We chose articles that assessed the association between cerebral autoregulation indices and dichotomized or continuous outcomes reported as standardized mean differences or correlation coefficients (R), respectively. Animal and validation studies were excluded. DATA EXTRACTION: Two authors collected and assessed the data independently. The studies were grouped into two sets according to the type of analysis used to assess the relationship between cerebral autoregulation indices and predictors of outcome (standardized mean differences or R). DATA SYNTHESIS: Thirty-three studies compared cerebral autoregulation indices and patient outcomes using standardized mean differences, and 20 used Rs. The only data available for meta-analysis were from patients with traumatic brain injury or subarachnoid…

OBJECTIVE: Thrombocytopenia is the most common hemostatic disorder during sepsis and is associated with high mortality. We examined whether fibrinolytic changes precede incident thrombocytopenia and predict outcome in patients with severe sepsis. DESIGN: Nested study from the multicenter, randomized, controlled trial on the efficacy of albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). SETTING: Forty ICUs in Italy. PATIENTS: Three groups of patients were selected: 1) patients with platelet count less than or equal to 50 × 10/L at study entry (n = 85); 2) patients with baseline platelet count greater than or equal to 100 × 10/L who developed thrombocytopenia (≤ 50 × 10/L) within 28 days (n = 100); 3) patients with platelet count always more than or equal to 100 × 10/L (n = 95). INTERVENTIONS: Fibrinolytic variables, including fibrinolysis inhibitors and in vivo markers of plasmin generation, were measured on day 1. MEASUREMENTS AND MAIN RESULTS: Patients with early thrombocytopenia (group 1) and those who developed it later (group 2) had…

OBJECTIVES: Mechanical ventilation can induce lung fibrosis. This study aimed to investigate whether ventilator-induced lung fibrosis was associated with endothelial-mesenchymal transition and to uncover the underlying mechanisms. DESIGN: Randomized, controlled animal study and cell culture study. SETTING: University research laboratory. SUBJECTS: Adult male Institute of Cancer Research, NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) knockout and wild-type mice. Primary cultured mouse lung vascular endothelial cells. INTERVENTIONS: Institute of Cancer Research, NLRP3 knockout and wild-type mice were subjected to mechanical ventilation (20 mL/kg) for 2 hours. Mouse lung vascular endothelial cells were subjected to cyclic stretch for 24 hours. MEASUREMENTS AND MAIN RESULTS: Mice subjected to mechanical ventilation exhibited increases in collagen deposition, hydroxyproline and type I collagen contents, and transforming growth factor-β1 in lung tissues. Ventilation-induced lung fibrosis was associated with increased expression of mesenchymal markers (α smooth muscle actin and…

OBJECTIVES: Traumatic brain injury is a major cause of death and disability, yet many predictors of outcome are not precise enough to guide initial clinical decision-making. Although increasingly used in the early phase following traumatic brain injury, the prognostic utility of MRI remains uncertain. We thus undertook a systematic review and meta-analysis of studies evaluating the predictive value of acute MRI lesion patterns for discriminating clinical outcome in traumatic brain injury. DATA SOURCES: MEDLINE, EMBASE, BIOSIS, and CENTRAL from inception to November 2015. STUDY SELECTION: Studies of adults who had MRI in the acute phase following moderate or severe traumatic brain injury. Our primary outcomes were all-cause mortality and the Glasgow Outcome Scale. DATA EXTRACTION: Two authors independently performed study selection and data extraction. We calculated pooled effect estimates with a random effects model, evaluated the risk of bias using a modified version of Quality in Prognostic Studies and determined the strength of evidence with the Grading of Recommendations,…

OBJECTIVE: The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. DESIGN: Secondary analysis of two clinical trials of early septic shock resuscitation. SETTING: Large academic emergency departments in the United States. PATIENTS: Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. INTERVENTIONS: Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. MEASUREMENTS AND MAIN RESULTS: Four hundred seventy patients were included in the present analysis.…

OBJECTIVES: Lung-protective ventilation is used to prevent further lung injury in patients on invasive mechanical ventilation. However, lung-protective ventilation can cause hypercapnia and hypercapnic acidosis. There are no large clinical studies evaluating the effects of hypercapnia and hypercapnic acidosis in patients requiring mechanical ventilation. DESIGN: Multicenter, binational, retrospective study aimed to assess the impact of compensated hypercapnia and hypercapnic acidosis in patients receiving mechanical ventilation. SETTINGS: Data were extracted from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database over a 14-year period where 171 ICUs contributed deidentified data. PATIENTS: Patients were classified into three groups based on a combination of pH and carbon dioxide levels (normocapnia and normal pH, compensated hypercapnia [normal pH with elevated carbon dioxide], and hypercapnic acidosis) during the first 24 hours of ICU stay. Logistic regression analysis was used to identify the independent…

This part II of the guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients is related to acute illnesses that may be complicated by CIRCI. We followed strictly the same methodology as for part I (Supplemental Digital Content 1, https://links.lww.com/CCM/C977), which summarized the guidelines related to CIRCI and sepsis/septic shock, acute respiratory distress syndrome (ARDS), and major trauma. PICOM questions were developed a priori for community-acquired pneumonia, influenza, meningitis, and non-septic systemic inflammatory response syndrome (SIRS) that may be associated with shock, namely burns, cardiac arrest and cardiopulmonary bypass surgery. For all these conditions, we formulated statements for or against the use of exogenous corticosteroids. Recommendations and their strength required the agreement of at least 80% of the task force members. During the editorial process, discussions about the burn condition resulted in the compromise of this question being left out and reconsidered in the next…

OBJECTIVE: Exosomes are small, cell-released vesicles (40-100 nm in size) with the potential to transfer proteins, lipids, small RNAs, messenger RNAs, or DNA between cells via interstitial fluids. Due to their role in tissue homeostasis, exosomes have emerged as a new type of therapeutic and diagnostic (theranostic) tool in the noninvasive assessment of organ response to injury or treatment and in the development of reliable organ-protective intensive therapy. Our review provides current insights into the role of exosomes in the personalized management of injury and repair responses in critical illness. DATA SOURCE: Data were obtained from a PubMed search of the most recent medical literature, including the PubMed "related articles" search methodology. STUDY SELECTION: Articles considered include original articles, review articles and conference proceedings. DATA EXTRACTION: A detailed review of scientific, peer-reviewed data was performed. Relevant pre-clinical and clinical studies were included and summarized. DATA SYNTHESIS: Current scientific evidence is focused on the…

OBJECTIVES: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance. DESIGN: Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the FIO2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. SETTING: Five academic centers in the United States. PATIENTS: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. INTERVENTIONS: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days. MEASUREMENTS AND MAIN RESULTS: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation…

OBJECTIVE: Numerous studies have evaluated the use of procalcitonin guidance during different phases of antibiotics management (initiation, cessation, or a combination of both) in patients admitted to ICUs. Several meta-analyses have attempted to generate an overall effect of procalcitonin-guidance on patient outcomes. However, combining studies from different phases of antibiotics management may not be appropriate due to the risk of clinical heterogeneity. The purpose of this systematic review and meta-analysis was to evaluate the effect of procalcitonin-guided strategies in different phases of antibiotics use. DATA SOURCES: We searched MEDLINE and EMBASE from inception until November 1, 2017. STUDY SELECTION: We included randomized controlled trials that evaluated procalcitonin guidance compared with usual care for management of antibiotics in critically ill adult patients. DATA EXTRACTION: We extracted study details, patient characteristics, procalcitonin algorithm, and outcomes. DATA SYNTHESIS: We included 15 studies, from 1,624 abstracts identified based on our search strategy…

OBJECTIVES: Identifying subgroups of ICU patients with similar clinical needs and trajectories may provide a framework for more efficient ICU care through the design of care platforms tailored around patients' shared needs. However, objective methods for identifying these ICU patient subgroups are lacking. We used a machine learning approach to empirically identify ICU patient subgroups through clustering analysis and evaluate whether these groups might represent appropriate targets for care redesign efforts. DESIGN: We performed clustering analysis using data from patients' hospital stays to retrospectively identify patient subgroups from a large, heterogeneous ICU population. SETTING: Kaiser Permanente Northern California, a healthcare delivery system serving 3.9 million members. PATIENTS: ICU patients 18 years old or older with an ICU admission between January 1, 2012, and December 31, 2012, at one of 21 Kaiser Permanente Northern California hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used clustering analysis to identify putative clusters among 5,000…

OBJECTIVES: The prevalence of responsiveness to initial fluid challenge among hypotensive sepsis patients is unclear. To avoid fluid overload, and unnecessary treatment, it is important to differentiate these phenotypes. We aimed to 1) determine the proportion of hypotensive sepsis patients sustaining favorable hemodynamic response after initial fluid challenge, 2) determine demographic and clinical risk factors that predicted refractory hypotension, and 3) assess the association between timeliness of fluid resuscitation and refractoriness. DESIGN: Secondary analysis of a prospective, multisite, observational, consecutive-sample cohort. SETTING: Nine tertiary and community hospitals over 1.5 years. PATIENTS: Inclusion criteria 1) suspected or confirmed infection, 2) greater than or equal to two systemic inflammatory response syndrome criteria, 3) systolic blood pressure less than 90 mm Hg, greater than 40% decrease from baseline, or mean arterial pressure less than 65 mm Hg. MEASUREMENTS AND MAIN RESULTS: Sex, age, heart failure, renal failure, immunocompromise, source of infection,…

OBJECTIVES: To review temporary percutaneous mechanical circulatory support devices for the treatment of cardiogenic shock, including current evidence, contraindications, complications, and future directions. DATA SOURCES: A MEDLINE search was conducted with MeSH terms: cardiogenic shock, percutaneous mechanical circulatory support, extracorporeal membrane oxygenation, Impella, and TandemHeart. STUDY SELECTION: Selected publications included randomized controlled trial data and observational studies describing experience with percutaneous mechanical circulatory support in cardiogenic shock. DATA EXTRACTION: Studies were chosen based on strength of association with and relevance to cardiogenic shock. DATA SYNTHESIS: Until recently, there were few options if cardiogenic shock was refractory to vasopressors or intra-aortic balloon pump counterpulsation. Now, several percutaneous mechanical circulatory support devices, including Impella (Abiomed, Danvers, MA), TandemHeart (CardiacAssist, Pittsburgh, PA), and extracorporeal membrane oxygenation, are more accessible. Compared with…

OBJECTIVES: The objectives of this study were to 1) assess patterns of early crystalloid resuscitation provided to sepsis and septic shock patients at initial presentation and 2) determine the association between time to initial crystalloid resuscitation with hospital mortality, mechanical ventilation, ICU utilization, and length of stay. DESIGN: Consecutive-sample observational cohort. SETTING: Nine tertiary and community hospitals over 1.5 years. PATIENTS: Adult sepsis and septic shock patients captured in a prospective quality improvement database inclusion criteria: suspected or confirmed infection, greater than or equal to two systemic inflammatory response criteria, greater than or equal to one organ-dysfunction criteria. INTERVENTIONS: The primary exposure was crystalloid initiation within 30 minutes or lesser, 31-120 minutes, or more than 120 minutes from sepsis identification. MEASUREMENTS AND MAIN RESULTS: We identified 11,182 patients. Crystalloid initiation was faster for emergency department patients (β, -141 min; CI, -159 to -125; p < 0.001), baseline hypotension (β,…

OBJECTIVE: Several studies have reported a survival benefit for polymyxin B hemoperfusion treatment in patients with severe sepsis and septic shock. However, recently, a propensity-matched analysis and a randomized controlled trial reported no survival benefit for polymyxin B hemoperfusion treatment. We performed an up-to-date meta-analysis to determine the effect of polymyxin B hemoperfusion treatment on mortality in patients with severe sepsis and septic shock. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched from inception to May 2016. STUDY SELECTION: Studies investigating the effect of polymyxin B hemoperfusion on mortality were considered eligible. We searched for terms related to severe sepsis and septic shock and terms related to polymyxin B hemoperfusion. DATA EXTRACTION: The following data were extracted from the original articles: the name of the first author and publication year, subjects and setting, inclusion and exclusion criteria, mean age and size of the study population, male percentage, mortality, blood pressure, Sequential Organ Failure Assessment…

OBJECTIVES: The acute respiratory distress syndrome is a frequent condition following allogeneic hematopoietic stem cell transplantation. Extracorporeal membrane oxygenation may serve as rescue therapy in refractory acute respiratory distress syndrome but has not been assessed in allogeneic hematopoietic stem cell transplantation recipients. DESIGN: Multicenter, retrospective, observational study. SETTING: ICUs in 12 European tertiary care centers (Austria, Germany, France, and Belgium). PATIENTS: All allogeneic hematopoietic stem cell transplantation recipients treated with venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome between 2010 and 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-seven patients, nine of whom underwent noninvasive ventilation at the time of extracorporeal membrane oxygenation initiation, were analyzed. ICU admission occurred at a median of 146 (interquartile range, 27-321) days after allogeneic hematopoietic stem cell transplantation. The main reason for acute respiratory distress syndrome was pneumonia in…

OBJECTIVE: Recent preclinical and clinical data suggest that thoracic epidural analgesia, a technique primarily aimed at decreasing pain, might exert anti-inflammatory effects, enhance splanchnic and pancreatic blood flow during acute pancreatitis; however, the influence of epidural analgesia on mortality remains under investigated in this setting. This study was therefore designed to assess the impact of epidural analgesia on mortality in ICU patients with acute pancreatitis. DESIGN: Multicenter retrospective, observational, cohort study. SETTING: Seventeen French and Belgian ICUs. PATIENTS: All patients admitted to with acute pancreatitis between June 2009 and March 2014. INTERVENTIONS: The primary exposure was thoracic epidural analgesia versus standard care without epidural analgesia. The primary outcome was 30-day mortality. Propensity analyses were used to control for bias in treatment assignment and prognostic imbalances. MEASUREMENTS AND MAIN RESULTS: One thousand three ICU patients with acute pancreatitis were enrolled, of whom 212 died within 30 days. Epidural analgesia…

OBJECTIVE: Information about the epidemiology of sepsis in community residents in China remains scarce and incomplete. The purpose of this study was to describe the occurrence rate and outcome of sepsis in Yuetan Subdistrict of Beijing and to estimate the occurrence rate of sepsis in China. DESIGN: Retrospective cohort study. SETTING: All public hospitals serving residents in Yuetan Subdistrict, Beijing. PATIENTS: All patients (n = 1,716) meeting criteria for sepsis based on American College of Chest Physicians/Society of Critical Care Medicine consensus definition. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We screened all adult residents in Yuetan Subdistrict who were hospitalized from July 1, 2012, to June 30, 2014, and reviewed medical records. Patients with sepsis were included in the analysis. We enrolled 1,716 patients with sepsis out of 21,191 hospitalized adults screened, among whom severe sepsis developed in 256 patients, and septic shock developed in 233 patients. The crude annual occurrence rates of sepsis, severe sepsis, and septic shock in Yuetan Subdistrict…

OBJECTIVE: Reintubation after liberation from mechanical ventilation is viewed as an adverse event in ICUs. We sought to describe the frequency of reintubations across U.S. ICUs and to propose a standard, appropriate time cutoff for reporting of reintubation events. DESIGN AND SETTING: We conducted a cohort study using data from the Project IMPACT database of 185 diverse ICUs in the United States. PATIENTS: We included patients who received mechanical ventilation and excluded patients who received a tracheostomy, had a do-not-resuscitate order placed, or died prior to first extubation. MEASUREMENTS AND MAIN RESULTS: We assessed the percentage of patients extubated who were reintubated; the cumulative probability of reintubation, with death and do-not-resuscitate orders after extubation modeled as competing risks, and time to reintubation. Among 98,367 patients who received mechanical ventilation without death or tracheostomy prior to extubation, 9,907 (10.1%) were reintubated, with a cumulative probability of 10.0%. Median time to reintubation was 15 hours (interquartile range, 2-45…

OBJECTIVE: Long-term outcomes of patients treated with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure (i.e., cardiogenic shock complicating chronic cardiomyopathy) have not yet been reported. This study was undertaken to describe their outcomes and determine mortality-associated factors. DESIGN: Retrospective analysis of data prospectively collected. SETTING: Twenty-six-bed tertiary hospital ICU. PATIENTS: One hundred five patients implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: From March 2007 to January 2015, 105 patients were implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure in our ICU (67% of them had an intraaortic balloon pump to unload the left ventricle). Their 1-year survival rate was 42%; most of the survivors were transplanted either directly or after switching to central bilateral centrifugal pump, ventricular-assist device, or total artificial heart. Most deaths occurred…

OBJECTIVES: High fractions of inspired oxygen may augment lung damage to exacerbate lung injury in patients with acute respiratory distress syndrome. Participants enrolled in Acute Respiratory Distress Syndrome Network trials had a goal partial pressure of oxygen in arterial blood range of 55-80 mm Hg, yet the effect of oxygen exposure above this arterial oxygen tension range on clinical outcomes is unknown. We sought to determine if oxygen exposure that resulted in a partial pressure of oxygen in arterial blood above goal (> 80 mm Hg) was associated with worse outcomes in patients with acute respiratory distress syndrome. DESIGN: Longitudinal analysis of data collected in these trials. SETTING: Ten clinical trials conducted at Acute Respiratory Distress Syndrome Network hospitals between 1996 and 2013. SUBJECTS: Critically ill patients with acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined above goal oxygen exposure as the difference between the fraction of inspired oxygen and 0.5 whenever the fraction of inspired oxygen was above…

OBJECTIVES: To characterize sedation, analgesia, delirium, and mobilization practices in patients supported with venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. DESIGN: Cross-sectional electronic survey administered January 2016 to March 2016. SETTING: Three-hundred ninety-four extracorporeal membrane oxygenation centers registered with the Extracorporeal Life Support Organization. SUBJECTS: Extracorporeal membrane oxygenation medical directors and program coordinators. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed responses from 209 respondents (53%), mostly from academic centers (63%); 41% respondents provide venovenous extracorporeal membrane oxygenation to adults exclusively. Following venovenous extracorporeal membrane oxygenation initiation, 97% respondents administer sedative/analgesic infusions, and the sedation target was "sedated" or "very sedated" for 59%, "calm and cooperative" for 25%, and "unarousable" for 16%. Use of daily sedation interruption and a sedation/analgesia protocol was reported by 51% and 39%,…

OBJECTIVES: To determine whether contemporary β-lactam anti-infective dosing recommendations in critically ill children achieve concentrations associated with maximal anti-infective activity. The secondary objective was to describe the microbiological and clinical outcomes associated with β-lactam therapeutic drug management. DESIGN: Electronic Medical Record Review. SETTING: A 189-bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA. PATIENTS: Patients admitted to the PICU from September 1, 2014, to May 31, 2017, with sepsis and those receiving extracorporal therapy with either extracorporeal membrane oxygenation or continuous renal replacement therapy that had routine β-lactam therapeutic drug management. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-two patients were in the total cohort and 23 patients in the infected cohort accounting for 248 samples for therapeutic drug management analysis. The median age was 1 year (range, 4 d to 18 yr) with a mean weight of 19.7 ± 22.3 kg (range, 2.7-116 kg). Twenty-three patients (28%) had growth of…

OBJECTIVE: Systemic capillary-leak syndrome is a very rare cause of recurrent hypovolemic shock. Few data are available on its clinical manifestations, laboratory findings, and outcomes of those patients requiring ICU admission. This study was undertaken to describe the clinical pictures and ICU management of severe systemic capillary-leak syndrome episodes. DESIGN, SETTING, PATIENTS: This multicenter retrospective analysis concerned patients entered in the European Clarkson's disease (EurêClark) Registry and admitted to ICUs between May 1992 and February 2016. MEASUREMENTS AND MAIN RESULTS: Fifty-nine attacks occurring in 37 patients (male-to-female sex ratio, 1.05; mean ± SD age, 51 ± 11.4 yr) were included. Among 34 patients (91.9%) with monoclonal immunoglobulin G gammopathy, 20 (58.8%) had kappa light chains. ICU-admission hemoglobin and proteinemia were respectively median (interquartile range) 20.2 g/dL (17.9-22 g/dL) and 50 g/L (36.5-58.5 g/L). IV immunoglobulins were infused (IV immunoglobulin) during 15 episodes (25.4%). A compartment syndrome developed during 12 episodes…