The 100 most-cited articles in Critical Care Medicine, 2018

OBJECTIVE: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. METHODS: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived…

OBJECTIVE: Decades-old, common ICU practices including deep sedation, immobilization, and limited family access are being challenged. We endeavoured to evaluate the relationship between ABCDEF bundle performance and patient-centered outcomes in critical care. DESIGN: Prospective, multicenter, cohort study from a national quality improvement collaborative. SETTING: 68 academic, community, and federal ICUs collected data during a 20-month period. PATIENTS: 15,226 adults with at least one ICU day. INTERVENTIONS: We defined ABCDEF bundle performance (our main exposure) in two ways: 1) complete performance (patient received every eligible bundle element on any given day) and 2) proportional performance (percentage of eligible bundle elements performed on any given day). We explored the association between complete and proportional ABCDEF bundle performance and three sets of outcomes: patient-related (mortality, ICU and hospital discharge), symptom-related (mechanical ventilation, coma, delirium, pain, restraint use), and system-related (ICU readmission, discharge destination). All models…

OBJECTIVES: To characterize the current burden, outcomes, and costs of managing sepsis patients in U.S. hospitals. DESIGN: A retrospective observational study was conducted using the Premier Healthcare Database, which represents ~20% of U.S. inpatient discharges among private and academic hospitals. Hospital costs were obtained from billing records per the cost accounting method used by each hospital. Descriptive statistics were performed on patient demographics, characteristics, and clinical and economic outcomes for the index hospitalization and 30-day readmissions. SETTING: Sepsis patient hospitalizations, including inpatient, general ward, and ICU (intermediate and/or step-down). PATIENTS: Adults over 18 years old with a hospital discharge diagnosis code of sepsis from January 1, 2010, to September 30, 2016. INTERVENTIONS: None. This was a retrospective observational study of deidentified data. MEASUREMENTS AND MAIN RESULTS: The final study cohort consisted of 2,566,689 sepsis cases, representing patients with a mean age of 65 years (50.8% female). Overall mortality was 12.5%…

INTRODUCTION The “sepsis bundle” has been central to the implementation of the Surviving Sepsis Campaign (SSC) from the first publication of its evidence-based guidelines in 2004 through subsequent editions (1–6). Developed separately from the guidelines publication by the SSC, the bundles have been the cornerstone of sepsis quality improvement since 2005 (7–11). As noted when they were introduced, the bundle elements were designed to be updated as indicated by new evidence and have evolved accordingly. In response to the publication of “Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016” (12,13), a revised “hour-1 bundle” has been developed and is presented below (Fig. 1).Figure 1.: Hour-1 Surviving Sepsis Campaign Bundle of Care.*The compelling nature of the evidence in the literature, which has demonstrated an association between compliance with bundles and improved survival in patients with sepsis and septic shock, led to the adoption of the SSC measures by the National Quality Forum (NQF) and subsequently both by the New York…

OBJECTIVES: To describe the frequency of co-occurring newly acquired cognitive impairment, disability in activities of daily livings, and depression among survivors of a critical illness and to evaluate predictors of being free of post-intensive care syndrome problems. DESIGN: Prospective cohort study. SETTING: Medical and surgical ICUs from five U.S. centers. PATIENTS: Patients with respiratory failure or shock, excluding those with preexisting cognitive impairment or disability in activities of daily livings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At 3 and 12 months after hospital discharge, we assessed patients for cognitive impairment, disability, and depression. We categorized patients into eight groups reflecting combinations of cognitive, disability, and mental health problems. Using multivariable logistic regression, we modeled the association between age, education, frailty, durations of mechanical ventilation, delirium, and severe sepsis with the odds of being post-intensive care syndrome free. We analyzed 406 patients with a median age of 61 years and an…

OBJECTIVES: Use systematic review and meta-analytic methodology to estimate the pooled incidence, prevalence, and proportion of delirium cases for each delirium subtype (hypoactive, hyperactive, and mixed) in an adult ICU population. DATA SOURCES: We conducted a search of the MEDLINE, EMBASE, CINAHL, SCOPUS, Web of Science, and PsycINFO databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards from database inception until October 22, 2017, with no restrictions. STUDY SELECTION: We included original research conducted in adults admitted to any medical, surgical, or speciality ICU that reported incidence or prevalence estimates of delirium according to delirium subtype. DATA EXTRACTION: Data were extracted on sample size, population demographics, condition information, and reported delirium estimates. DATA SYNTHESIS: Forty-eight studies (27,342 patients; 4,550 with delirium) with an overall pooled prevalence of 31% (95% CI, 24-41; I = 99%) met inclusion criteria. The pooled incidence (n = 18 studies) of delirium subtypes were hyperactive (4%…

Clinical practice guidelines are published and promoted, often by professional societies, because they provide a current and transparently analyzed review of relevant research and are written with the aim to guide clinical practice. The 2018 Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) (PADIS) guidelines (1) first 1) builds on this mission by updating the 2013 PAD guidelines (2); 2) by adding two inextricably related clinical care topics (immobility and sleep); 3) by including patients as collaborators and coauthors; and 4) by inviting panelists from high-income countries as an early step toward incorporating more diverse practices and expertise from the global critical care community. Readers will find rationales for 37 recommendations (derived from actionable Patient Intervention Comparison Outcome questions), two good practice statements, and 32 statements (derived from nonactionable, descriptive questions for which the Grading of Recommendations Assessment, Development and Evaluation methodology was not used) across the…

OBJECTIVES: To find and validate generalizable sepsis subtypes using data-driven clustering. DESIGN: We used advanced informatics techniques to pool data from 14 bacterial sepsis transcriptomic datasets from eight different countries (n = 700). SETTING: Retrospective analysis. SUBJECTS: Persons admitted to the hospital with bacterial sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A unified clustering analysis across 14 discovery datasets revealed three subtypes, which, based on functional analysis, we termed "Inflammopathic, Adaptive, and Coagulopathic." We then validated these subtypes in nine independent datasets from five different countries (n = 600). In both discovery and validation data, the Adaptive subtype is associated with a lower clinical severity and lower mortality rate, and the Coagulopathic subtype is associated with higher mortality and clinical coagulopathy. Further, these clusters are statistically associated with clusters derived by others in independent single sepsis cohorts. CONCLUSIONS: The three sepsis subtypes may represent a unifying framework…

OBJECTIVES: To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. DESIGN: Observational cohort study. SETTING: Tertiary, urban, academic medical center from November 2008 to January 2016. PATIENTS: All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine-based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted…

OBJECTIVES: We describe the importance of interprofessional care in modern critical care medicine. This review highlights the essential roles played by specific members of the interprofessional care team, including patients and family members, and discusses quality improvement initiatives that require interprofessional collaboration for success. DATA SOURCES: Studies were identified through MEDLINE search using a variety of search phrases related to interprofessional care, critical care provider types, and quality improvement initiatives. Additional articles were identified through a review of the reference lists of identified articles. STUDY SELECTION: Original articles, review articles, and systematic reviews were considered. DATA EXTRACTION: Manuscripts were selected for inclusion based on expert opinion of well-designed or key studies and review articles. DATA SYNTHESIS: "Interprofessional care" refers to care provided by a team of healthcare professionals with overlapping expertise and an appreciation for the unique contribution of other team members as partners in achieving a…

OBJECTIVES: Lung ultrasound is commonly used to evaluate lung morphology in patients with acute respiratory distress syndrome. Aim of this study was to determine lung ultrasound reliability in assessing lung aeration and positive end-expiratory pressure-induced recruitment compared with CT. DESIGN: Randomized crossover study. SETTING: University hospital ICU. PATIENTS: Twenty sedated paralyzed acute respiratory distress syndrome patients: age 56 years (43-72 yr), body mass index 25 kg/m (22-27 kg/m), and PaO2/FIO2 160 (113-218). INTERVENTIONS: Lung CT and lung ultrasound examination were performed at positive end-expiratory pressure 5 and 15 cm H2O. MEASUREMENTS AND MAIN RESULTS: Global and regional Lung Ultrasound scores were compared with CT quantitative analysis. Lung recruitment (i.e., decrease in not aerated tissue as assessed with CT) was compared with global Lung Ultrasound score variations. Global Lung Ultrasound score was strongly associated with average lung tissue density at positive end-expiratory pressure 5 (R = 0.78; p < 0.0001) and positive end-expiratory pressure 15…

OBJECTIVES: Traumatic brain injury triggers multiple cell death pathways, possibly including ferroptosis-a recently described cell death pathway that results from accumulation of 15-lipoxygenase-mediated lipid oxidation products, specifically oxidized phosphatidylethanolamine containing arachidonic or adrenic acid. This study aimed to investigate whether ferroptosis contributed to the pathogenesis of in vitro and in vivo traumatic brain injury, and whether inhibition of 15-lipoxygenase provided neuroprotection. DESIGN: Cell culture study and randomized controlled animal study. SETTING: University research laboratory. SUBJECTS: HT22 neuronal cell line and adult male C57BL/6 mice. INTERVENTIONS: HT22 cells were subjected to pharmacologic induction of ferroptosis or mechanical stretch injury with and without administration of inhibitors of ferroptosis. Mice were subjected to sham or controlled cortical impact injury. Injured mice were randomized to receive vehicle or baicalein (12/15-lipoxygenase inhibitor) at 10-15 minutes postinjury. MEASUREMENTS AND MAIN RESULTS: Pharmacologic…

OBJECTIVE: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. DESIGN: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. SETTING: ICUs. PATIENTS: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). INTERVENTIONS: IV angiotensin II or placebo. MEASUREMENTS AND MAIN RESULTS: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012),…

OBJECTIVES: To systematically assess the incidence and prevalence of pressure injuries in adult ICU patients and the most frequently occurring pressure injury sites. DATA SOURCES: MEDLINE, Embase, the Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature. STUDY SELECTION: Observational studies reporting incidence rates, cumulative incidence, and prevalence of pressure injuries. DATA EXTRACTION: Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Meta-analyses of pooled weighted estimates were calculated using random effect models with 95% CIs reported due to high heterogeneity. Sensitivity analyses included studies that used skin inspection to identify a pressure injury, studies at low risk of bias, studies that excluded stage 1 and each stage of pressure injury. DATA SYNTHESIS: Twenty-two studies, 10 reporting cumulative incidence of pressure injury irrespective of stage, one reporting incidence rate (198/1,000 hospital-days), and 12 reporting prevalence were included. The 95% CI of cumulative incidence and…

OBJECTIVES: To systematically review the symptoms and types of laryngeal injuries resulting from endotracheal intubation in mechanically ventilated patients in the ICU. DATA SOURCES: PubMed, Embase, CINAHL, and Cochrane Library from database inception to September 2017. STUDY SELECTION: Studies of adult patients who were endotracheally intubated with mechanical ventilation in the ICU and completed postextubation laryngeal examinations with either direct or indirect visualization. DATA EXTRACTION: Independent, double-data extraction and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias assessment followed the Cochrane Collaboration's criteria. DATA SYNTHESIS: Nine studies (seven cohorts, two cross-sectional) representing 775 patients met eligibility criteria. The mean (SD; 95% CI) duration of intubation was 8.2 days (6.0 d; 7.7-8.7 d). A high prevalence (83%) of laryngeal injury was found. Many of these were mild injuries, although moderate to severe injuries occurred in 13-31% of patients across studies.…

OBJECTIVE: This systematic review and meta-analysis addresses the efficacy and safety of corticosteroids in critically ill patients with sepsis. DATA SOURCES: We updated a comprehensive search of MEDLINE, EMBASE, CENTRAL, and LILACS, and unpublished sources for randomized controlled trials that compared any corticosteroid to placebo or no corticosteroid in critically ill children and adults with sepsis. STUDY SELECTION: Reviewers conducted duplicate screening of citations, data abstraction, and, using a modified Cochrane risk of bias tool, individual study risk of bias assessment. DATA EXTRACTION: A parallel guideline committee provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. We assessed overall certainty in evidence using Grading of Recommendations Assessment, Development and Evaluation methodology and performed all analyses using random-effect models. For subgroup analyses, we performed metaregression and considered p value less than 0.05 as significant. DATA SYNTHESIS: Forty-two randomized…

OBJECTIVES: To synthesize data on outcomes related to patients, family members, and ICU professionals by comparing flexible versus restrictive visiting policies in ICUs. DATA SOURCES: Medline, Scopus, and Web of Science. STUDY SELECTION: Observational and randomized studies comparing flexible versus restrictive visiting policies in the ICU and evaluating at least one patient-, family member-, or ICU staff-related outcome. DATA EXTRACTION: Duplicate independent review and data abstraction. DATA SYNTHESIS: Of 16 studies identified for inclusion, seven were meta-analyzed. Most studies were rated as having a moderate risk of bias. Among patients, flexible visiting policies were associated with reduced frequency of delirium (odds ratio, 0.39; 95% CI, 0.22-0.69; I = 0%) and lower severity of anxiety symptoms (mean difference, -2.20; 95% CI, -3.80 to -0.61; I = 71%). Flexible visiting policies were not associated with increased risk of ICU mortality (odds ratio, 0.71; 95% CI, 0.38-1.36; I = 86%), ICU-acquired infections (odds ratio, 0.98; 95% CI, 0.68-1.42; I = 11%), or longer ICU stay…

OBJECTIVES: This study aimed to compare the prognostic value of lactate level and lactate clearance at 6 hours after septic shock recognition. And, we performed it to determine lactate kinetics in the Sepsis-3 defined septic shock. DESIGN: This retrospective study was performed from a prospective septic shock registry. SETTINGS: This study was performed at single urban tertiary center. And, all patients were treated with protocol-driven resuscitation bundle therapy between 2010 and 2016. PATIENTS: We included septic shock patients who met the Sepsis-3 definition, which involves lactate levels greater than or equal to 2 mmol/L and vasopressor use. INTERVENTIONS: Serum lactate levels were measured at initial and 6 hours from septic shock recognition. MEASUREMENTS AND MAIN RESULTS: Lactate clearance was calculated as ([initial lactate - 6-hr lactate]/initial lactate) × 100. The prognostic value of measured lactate levels and lactate clearance for 28-day mortality was analyzed and compared with that of subsequent lactate levels greater than or equal to 2 mmol/L, greater than or equal to…

OBJECTIVES: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. DESIGN: Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs. PATIENTS: Critically ill patients expected to be ventilated for longer than 24 hours. INTERVENTIONS: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. MEASUREMENTS AND MAIN RESULTS: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and…

OBJECTIVES: To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness. DESIGN: Retrospective cohort study. SETTING: Ten ICUs in the United Kingdom and Canada. PATIENTS: Adults receiving invasive mechanical ventilation for a minimum of 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07-1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater…

OBJECTIVES: To specify when delays of specific 3-hour bundle Surviving Sepsis Campaign guideline recommendations applied to severe sepsis or septic shock become harmful and impact mortality. DESIGN: Retrospective cohort study. SETTING: One health system composed of six hospitals and 45 clinics in a Midwest state from January 01, 2011, to July 31, 2015. PATIENTS: All adult patients hospitalized with billing diagnosis of severe sepsis or septic shock. INTERVENTIONS: Four 3-hour Surviving Sepsis Campaign guideline recommendations: 1) obtain blood culture before antibiotics, 2) obtain lactate level, 3) administer broad-spectrum antibiotics, and 4) administer 30 mL/kg of crystalloid fluid for hypotension (defined as "mean arterial pressure" < 65) or lactate (> 4). MEASUREMENTS AND MAIN RESULTS: To determine the effect of t minutes of delay in carrying out each intervention, propensity score matching of "baseline" characteristics compensated for differences in health status. The average treatment effect in the treated computed as the average difference in outcomes between those treated…

OBJECTIVES: To evaluate the effect of ICU diaries on posttraumatic stress disorder symptoms in ICU survivors and their relatives. Secondary objectives were to determine the effect on anxiety, depression, and health-related quality of life in patients and their relatives. DATA SOURCES: We searched online databases, trial registries, and references of relevant articles. STUDY SELECTION: Studies were included if there was an ICU diary intervention group which was compared with a group without a diary. DATA EXTRACTION: Titles, abstracts, and full-text articles were reviewed independently by two authors. Data was abstracted using a structured template. DATA SYNTHESIS: Our search identified 1,790 articles and retained eight studies for inclusion in the analysis. Pooled results found no significant reduction in patients' posttraumatic stress disorder symptoms with ICU diaries (risk ratio, 0.75 [0.3-1.73]; p = 0.5; n = 3 studies); however, there was a significant improvement in patients' anxiety (risk ratio, 0.32 [0.12, 0.86]; p = 0.02; n = 2 studies) and depression (risk ratio, 0.39…

OBJECTIVES: To evaluate the relative validity of criteria for the identification of sepsis in an ICU database. DESIGN: Retrospective cohort study of adult ICU admissions from 2008 to 2012. SETTING: Tertiary teaching hospital in Boston, MA. PATIENTS: Initial admission of all adult patients to noncardiac surgical ICUs. INTERVENTIONS: Comparison of five different algorithms for retrospectively identifying sepsis, including the Sepsis-3 criteria. MEASUREMENTS AND MAIN RESULTS: 11,791 of 23,620 ICU admissions (49.9%) met criteria for the study. Within this subgroup, 59.9% were suspected of infection on ICU admission, 75.2% of admissions had Sequential Organ Failure Assessment greater than or equal to 2, and 49.1% had both suspicion of infection and Sequential Organ Failure Assessment greater than or equal to 2 thereby meeting the Sepsis-3 criteria. The area under the receiver operator characteristic of Sequential Organ Failure Assessment (0.74) for hospital mortality was consistent with previous studies of the Sepsis-3 criteria. The Centers for Disease Control and Prevention, Angus,…

OBJECTIVES: Presenting symptoms in patients with sepsis may influence rapidity of diagnosis, time-to-antibiotics, and outcome. We tested the hypothesis that vague presenting symptoms are associated with delayed antibiotics and increased mortality. We further characterized individual presenting symptoms and their association with mortality. DESIGN: Retrospective cohort study. SETTING: Emergency department of large, urban, academic U.S. hospital. PATIENTS: All adult patients with septic shock treated in the emergency department between April 2014 and March 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 654 septic shock cases, 245 (37%) presented with vague symptoms. Time-to-antibiotics from first hypotension or elevated lactate was significantly longer for those with vague symptoms versus those with explicit symptoms of infection (1.6 vs 0.8 hr; p < 0.01), and in-hospital mortality was also substantially higher (34% vs 16%; p < 0.01). Patients with vague symptoms were older and sicker as evidenced by triage hypotension, Sequential Organ Failure Assessment score, initial…

OBJECTIVES: Previous studies have looked at National Early Warning Score performance in predicting in-hospital deterioration and death, but data are lacking with respect to patient outcomes following implementation of National Early Warning Score. We sought to determine the effectiveness of National Early Warning Score implementation on predicting and preventing patient deterioration in a clinical setting. DESIGN: Retrospective cohort study. SETTING: Tertiary care academic facility and a community hospital. PATIENTS: Patients 18 years old or older hospitalized from March 1, 2014, to February 28, 2015, during preimplementation of National Early Warning Score to August 1, 2015, to July 31, 2016, after National Early Warning Score was implemented. INTERVENTIONS: Implementation of National Early Warning Score within the electronic health record and associated best practice alert. MEASUREMENTS AND MAIN RESULTS: In this study of 85,322 patients (42,402 patients pre-National Early Warning Score and 42,920 patients post-National Early Warning Score implementation), the primary outcome of…

OBJECTIVES: Benzodiazepine use may be associated with delirium in critically ill children. However, benzodiazepines remain the first-line sedative choice in PICUs. Objectives were to determine the temporal relationship between administration of benzodiazepines and delirium development, control for time-varying covariates such as mechanical ventilation and opiates, and evaluate the association between dosage of benzodiazepines and subsequent delirium. DESIGN: Retrospective observational study. SETTING: Academic tertiary care PICU. PATIENTS: All consecutive admissions from January 2015 to June 2015. INTERVENTIONS: Retrospective assessment of benzodiazepine exposure in a population that had been prospectively screened for delirium. MEASUREMENTS AND MAIN RESULTS: All subjects were prospectively screened for delirium throughout their stay, using the Cornell Assessment for Pediatric Delirium, with daily cognitive status assigned as follows: delirium, coma, or normal. Multivariable mixed effects modeling determined predictors of delirium overall, followed by subgroup analysis to assess…

OBJECTIVES: To estimate the impact of each of six types of acute organ dysfunction (hepatic, renal, coagulation, neurologic, cardiac, and respiratory) on long-term mortality after surviving sepsis hospitalization. DESIGN: Multicenter, retrospective study. SETTINGS: Twenty-one hospitals within an integrated healthcare delivery system in Northern California. PATIENTS: Thirty thousand one hundred sixty-three sepsis patients admitted through the emergency department between 2010 and 2013, with mortality follow-up through April 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute organ dysfunction was quantified using modified Sequential Organ Failure Assessment scores. The main outcome was long-term mortality among sepsis patients who survived hospitalization. The estimates of the impact of each type of acute organ dysfunction on long-term mortality were based on adjusted Cox proportional hazards models. Sensitivity analyses were conducted based on propensity score-matching and adjusted logistic regression. Hospital mortality was 9.4% and mortality was 31.7% at 1 year. Median…

OBJECTIVES: To assess whether sepsis-associated coagulopathy predicts hospital mortality. DESIGN: Retrospective cohort study. SETTING: One-thousand three-hundred beds urban academic medical center. PATIENTS: Six-thousand one-hundred forty-eight consecutive patients hospitalized between January 1, 2010, and December 31, 2015. INTERVENTIONS: Mild sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.2 and less than 1.4 plus platelet count less than or equal to 150,000/µL but greater than 100,000/µL; moderate sepsis-associated coagulopathy was defined with either an international normalized ratio greater than or equal to 1.4 but less than 1.6 or platelets less than or equal to 100,000/µL but greater than 80,000/µL; severe sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.6 and platelets less than or equal to 80,000/µL. MEASUREMENTS AND MAIN RESULTS: Hospital mortality increased progressively from 25.4% in patients without sepsis-associated coagulopathy to 56.1% in patients with…

OBJECTIVES: Basic science and clinical studies suggest that sleep disturbance may be a modifiable risk factor for postoperative delirium. We aimed to assess the association between preoperative sleep disturbance and postoperative delirium. DATA SOURCES: We searched PubMed, Embase, CINAHL, Web of Science, and Cochrane from inception until May 31, 2017. STUDY SELECTION: We performed a systematic search of the literature for all studies that reported on sleep disruption and postoperative delirium excluding cross-sectional studies, case reports, and studies not reported in English language. DATA EXTRACTION: Two authors independently performed study selection and data extraction. We calculated pooled effects estimates with a random-effects model constructed in Stata and evaluated the risk of bias by formal testing (Stata Corp V.14, College Station, TX), DATA SYNTHESIS:: We included 12 studies, from 1,238 citations that met our inclusion criteria. The pooled odds ratio for the association between sleep disturbance and postoperative delirium was 5.24 (95% CI, 3.61-7.60; p < 0.001 and I =…

OBJECTIVES: Chest radiograph is considered the first-line diagnostic imaging modality for patients presenting with pulmonary symptoms in the ICU. In this meta-analysis, we aim to evaluate the diagnostic accuracy of chest radiograph, and when concomitantly studied lung ultrasound, in comparison with the gold-standard CT for adult critically ill patients with respiratory symptoms. DATA SOURCES: PubMed, EMBASE, and Gray literature. STUDY SELECTION: Studies comparing chest radiograph, and if performed lung ultrasound, with CT for adult ICU patients with respiratory symptoms. DATA EXTRACTION: Quality was scored with Quality Assessment of Diagnostic Accuracy Studies-2, and study setting, test characteristics, and study design were extracted. DATA SYNTHESIS: In the meta-analysis, we included 10 full-text studies, including 543 patients, and found that chest radiograph has an overall sensitivity of 49% (95% CI, 40-58%) and specificity of 92% (86-95%). In seven studies, where also lung ultrasound was studied, lung ultrasound had an overall sensitivity of 95% (92-96%) and specificity of 94%…

OBJECTIVES: To identify, appraise, and synthesize the most current evidence to determine whether early enteral nutrition alters patient outcomes from critical illness. DATA SOURCES: Medline and Embase were searched. The close out date was November 20, 2017. STUDY SELECTION: Early enteral nutrition was defined as a standard formula commenced within 24 hours of ICU admission. Comparators included any form of nutrition support "except" early enteral nutrition. Only randomized controlled trials conducted in adult patients requiring treatment in an ICU were eligible for inclusion. DATA EXTRACTION: The primary outcome was mortality. Secondary outcomes included pneumonia, duration of mechanical ventilation, and ICU and hospital stay. DATA SYNTHESIS: Six-hundred ninety-nine full-text articles were retrieved and screened. Sixteen randomized controlled trials enrolling 3,225 critically ill participants were included. Compared with all other types of nutrition support, commencing enteral nutrition within 24 hours of ICU admission did not result in a reduction in mortality (odds ratio, 1.01;…

OBJECTIVES: Mounting evidence has shown that critically ill patients are commonly thiamine deficient. We sought to test the hypothesis that critically ill patients with septic shock exposed to thiamine would demonstrate improved lactate clearance and more favorable clinical outcomes compared with those not receiving thiamine. DESIGN: Retrospective, single-center, matched cohort study. SETTING: Tertiary care academic medical center. PATIENTS: Adult patients admitted with an International Classification of Diseases, 9th Edition, or International Classification of Diseases, 10th Edition, diagnosis code of septic shock to either the medicine or surgery ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients who received IV thiamine supplementation within 24 hours of hospital admission were identified and compared with a matched cohort of patients not receiving thiamine. The primary objective was to determine if thiamine administration was associated with a reduced time to lactate clearance in septic shock. Secondary outcomes included 28-day mortality, acute kidney injury, and…

OBJECTIVES: We determine the frequency, risk factors, and mortality of neurologic complications in adults on extracorporeal membrane oxygenation and propose an algorithm for preventive strategies. DATA SOURCES: PubMed, Embase, and Cochrane databases. STUDY SELECTION: Screening was performed using predefined search terms to identify cohort studies reporting neurologic complications in adults during extracorporeal membrane oxygenation from 1990 to 2017. DATA EXTRACTION: The final reference list was generated on the basis of relevance to the discussed topics. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation classification of evidence scheme. DATA SYNTHESIS: In 44 studies, the median frequency of acute neurologic complications is 13% (1-78%; 5% intracranial hemorrhages, 5% ischemic strokes, 2% seizures). Neurologic complications are reported more frequently with venoarterial extracorporeal membrane oxygenation compared with venovenous extracorporeal membrane oxygenation (14 vs eight studies) with a median proportion of…

OBJECTIVES: Occurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients. DESIGN: A single-center, triple-blinded, randomized placebo-controlled trial. SETTING: ICU of an academic hospital. PATIENTS: Eligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission. INTERVENTIONS: The intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU. MEASUREMENTS AND MAIN RESULTS: A total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically…

OBJECTIVES: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. DESIGN: Randomized controlled trial. SETTING: Tertiary mixed ICU. PATIENTS: Adult patients admitted for septic shock within the first 72 hours. INTERVENTIONS: Patients were assigned randomly into two groups. The control group benefited from manual mobilization once a day. The intervention group had twice daily sessions of both manual mobilization and 30-minute passive/active cycling therapy. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle biopsies were analyzed for histology and molecular components of signaling pathways regulating protein synthesis and degradation as well as inflammation markers. Hemodynamic values and patient perception were collected during each…

OBJECTIVES: To review women's participation as faculty at five critical care conferences over 7 years. DESIGN: Retrospective analysis of five scientific programs to identify the proportion of females and each speaker's profession based on conference conveners, program documents, or internet research. SETTING: Three international (European Society of Intensive Care Medicine, International Symposium on Intensive Care and Emergency Medicine, Society of Critical Care Medicine) and two national (Critical Care Canada Forum, U.K. Intensive Care Society State of the Art Meeting) annual critical care conferences held between 2010 and 2016. SUBJECTS: Female faculty speakers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Male speakers outnumbered female speakers at all five conferences, in all 7 years. Overall, women represented 5-31% of speakers, and female physicians represented 5-26% of speakers. Nursing and allied health professional faculty represented 0-25% of speakers; in general, more than 50% of allied health professionals were women. Over the 7 years, Society of Critical Care…

OBJECTIVES: Many septic patients receive care that fails the Centers for Medicare and Medicaid Services' SEP-1 measure, but it is unclear whether this reflects meaningful lapses in care, differences in clinical characteristics, or excessive rigidity of the "all-or-nothing" measure. We compared outcomes in cases that passed versus failed SEP-1 during the first 2 years after the measure was implemented. DESIGN: Retrospective cohort study. SETTING: Seven U.S. hospitals. PATIENTS: Adult patients included in SEP-1 reporting between October 2015 and September 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 851 sepsis cases in the cohort, 281 (33%) passed SEP-1 and 570 (67%) failed. SEP-1 failures had higher rates of septic shock (20% vs 9%; p < 0.001), hospital-onset sepsis (11% vs 4%; p = 0.001), and vague presenting symptoms (46% vs 30%; p < 0.001). The most common reasons for failure were omission of 3- and 6-hour lactate measurements (228/570 failures, 40%). Only 86 of 570 failures (15.1%) had greater than 3-hour delays until broad-spectrum antibiotics. Cases that failed…

OBJECTIVES: Patients and caregivers can experience a range of physical, psychologic, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. DESIGN: We sought to identify technical, safety, and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. SUBJECTS AND SETTING: Seventeen Thrive sites from the United States, United Kingdom, and Australia were represented by a range of healthcare professionals. MEASUREMENTS AND MAIN RESULTS: Via an iterative process of in-person and email/conference calls, members of the Collaborative defined the key areas on which peer support models could be defined and compared, collected detailed self-reports from all sites, reviewed the information, and identified clusters of models. Barriers and challenges to implementation of peer support models were also…

OBJECTIVES: ICU admission delays can negatively affect patient outcomes, but emergency department volume and boarding times may also affect these decisions and associated patient outcomes. We sought to investigate the effect of emergency department and ICU capacity strain on ICU admission decisions and to examine the effect of emergency department boarding time of critically ill patients on in-hospital mortality. DESIGN: A retrospective cohort study. SETTING: Single academic tertiary care hospital. PATIENTS: Adult critically ill emergency department patients for whom a consult for medical ICU admission was requested, over a 21-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient data, including severity of illness (Mortality Probability Model III on Admission), outcomes of mortality and persistent organ dysfunction, and hourly census reports for the emergency department, for all ICUs and all adult wards were compiled. A total of 854 emergency department requests for ICU admission were logged, with 455 (53.3%) as "accept" and 399 (46.7%) as "deny" cases, with…

OBJECTIVES: Experience in the ongoing wars in Iraq and Afghanistan confirm that faster transport combined with effective prehospital interventions improves the outcomes of patients suffering hemorrhagic shock. Outcomes of patients with hemorrhagic shock and extremity bleeding have improved with widespread use of tourniquets and early balanced transfusion therapy. Conversely, civilian patients suffering truncal bleeding and shock have the same mortality (46%) over the last 20 years. To understand how to decrease this substantial mortality, one must first critically evaluate all phases of care from point of injury to definitive hemorrhage control in the operating room. DATA SOURCES: Limited literature review. DATA SYNTHESIS: The peak time to death after severe truncal injury is within 30 minutes of injury. However, when adding prehospital transport time, time spent in the emergency department, followed by the time in the operating room, it currently takes 2.1 hours to achieve definitive truncal hemorrhage control. This disparity in uncontrolled truncal bleeding and time to hemorrhage…

OBJECTIVES: To evaluate knowledge translation after publication of the target temperature management 33°C versus 36°C after out-of-hospital cardiac arrest trial and associated patient outcomes. Our primary hypothesis was that target temperature management at 36°C was rapidly adopted in Australian and New Zealand ICUs. Secondary hypotheses were that temporal reductions in mortality would be seen and would have accelerated after publication of the target temperature management trial. DESIGN: Retrospective cohort study (January 2005 to December 2016). SETTING: The Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database containing greater than 2 million admission episodes from 186 Australian and New Zealand ICUs. PATIENTS: Sixteen-thousand two-hundred fifty-two adults from 140 hospitals admitted to ICU after out-of-hospital cardiac arrest. INTERVENTIONS: The primary exposure of interest was admission before versus after publication of the target temperature management trial. MEASUREMENTS AND MAIN RESULTS: The primary outcome…

OBJECTIVES: For children, adolescents, and young adults with complex chronic conditions advance care planning may be a vital component of optimal care. Advance care planning outcomes research has previously focused on seriously ill adults and adolescents with cancer where it is correlated with high-quality end-of-life care. The impact of advance care planning on end-of-life outcomes for children, adolescents, and young adults with complex chronic conditions is unknown, thus we sought to evaluate parental preferences for advance care planning and to determine whether advance care planning and assessment of specific family considerations during advance care planning were associated with differences in parent-reported end-of-life outcomes. DESIGN: Cross-sectional survey. SETTING: Large, tertiary care children's hospital. SUBJECTS: Bereaved parents of children, adolescents, and young adults with complex chronic conditions who died between 2006 and 2015. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: One-hundred fourteen parents were enrolled (54% response rate) and all parents…

OBJECTIVES: To investigate the respective impact of ventilator-associated pneumonia and ICU-hospital-acquired pneumonia on the 30-day mortality of ICU patients. DESIGN: Longitudinal prospective studies. SETTING: French ICUs. PATIENTS: Patients at risk of ventilator-associated pneumonia and ICU-hospital-acquired pneumonia. INTERVENTIONS: The first three episodes of ventilator-associated pneumonia or ICU-hospital-acquired pneumonia were handled as time-dependent covariates in Cox models. We adjusted using the case-mix, illness severity, Simplified Acute Physiology Score II score at admission, and procedures and therapeutics used during the first 48 hours before the risk period. Baseline characteristics of patients with regard to the adequacy of antibiotic treatment were analyzed, as well as the Sequential Organ Failure Assessment score variation in the 2 days before the occurrence of ventilator-associated pneumonia or ICU-hospital-acquired pneumonia. Mortality was also analyzed for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas…

OBJECTIVES: Identifying solutions to improve recovery after critical illness is a pressing problem. We systematically evaluated studies of peer support as a potential intervention to improve recovery in critical care populations and synthesized elements important to peer support model design. DATA SOURCES: A systematic search of Medical Literature Analysis and Retrieval System Online, Cumulative Index to Nursing and Allied Health Literature, PsychINFO, and Excertpa Medica Database was undertaken May 2017. Prospective Register of Systematic Reviews identification number: CRD42017070174. STUDY SELECTION: Two independent reviewers assessed titles and abstracts against study eligibility criteria. Studies were included where 1) patients and families had experienced critical illness and 2) patients and families had participated in a peer support intervention. Discrepancies were resolved by consensus and a third independent reviewer adjudicated as necessary. DATA EXTRACTION: Two independent reviewers assessed study quality with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool,…

OBJECTIVE: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. DESIGN: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. METHODS: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (Supplemental Table 1, Supplemental Digital Content 2, http://links.lww.com/CCM/D636) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire…

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of…

OBJECTIVES: Adequate assessment of fluid responsiveness in shock necessitates correct interpretation of hemodynamic changes induced by preload challenge. This study evaluates the accuracy of point-of-care Doppler ultrasound assessment of the change in carotid corrected flow time induced by a passive leg raise maneuver as a predictor of fluid responsiveness. Noninvasive cardiac output monitoring (NICOM, Cheetah Medical, Newton Center, MA) system based on a bioreactance method was used. DESIGN: Prospective, noninterventional study. SETTING: ICU at a large academic center. PATIENTS: Patients with new, undifferentiated shock, and vasopressor requirements despite fluid resuscitation were included. Patients with significant cardiac disease and conditions that precluded adequate passive leg raising were excluded. INTERVENTIONS: Carotid corrected flow time was measured via ultrasound before and after a passive leg raise maneuver. Predicted fluid responsiveness was defined as greater than 10% increase in stroke volume on noninvasive cardiac output monitoring following passive leg raise.…

OBJECTIVES: Pressure autoregulation is an organ's intrinsic ability to maintain blood flow despite changes in perfusion pressure. The purpose of this review is to discuss autoregulation's heterogeneity among different organs and variability under different conditions, a very clinically relevant topic. DATA SOURCES: Systematic search of Ovid MEDLINE; nonsystematic search of PubMed, Google Scholar, and reference lists. STUDY SELECTION: Animal or human studies investigating the potency or variation of pressure autoregulation of any organs or the association between autoregulation and outcomes. DATA EXTRACTION: Two authors screened the identified studies independently then collectively agreed upon articles to be used as the basis for this review. DATA SYNTHESIS: Study details, including subjects, organ investigated, methods of blood pressure intervention and blood flow measurement, and values of the lower limit, upper limit, and plateau were examined. Comparative canine studies were used to demonstrate the heterogeneity of pressure autoregulation among different organs and validate the…

OBJECTIVE: Ventilator dyssynchrony is potentially harmful to patients with or at risk for the acute respiratory distress syndrome. Automated detection of ventilator dyssynchrony from ventilator waveforms has been difficult. It is unclear if certain types of ventilator dyssynchrony deliver large tidal volumes and whether levels of sedation alter the frequency of ventilator dyssynchrony. DESIGN: A prospective observational study. SETTING: A university medical ICU. PATIENTS: Patients with or at risk for acute respiratory distress syndrome. INTERVENTIONS: Continuous pressure-time, flow-time, and volume-time data were directly obtained from the ventilator. The level of sedation and the use of neuromuscular blockade was extracted from the medical record. Machine learning algorithms that incorporate clinical insight were developed and trained to detect four previously described and clinically relevant forms of ventilator dyssynchrony. The association between normalized tidal volume and ventilator dyssynchrony and the association between sedation and the frequency of ventilator dyssynchrony…

OBJECTIVES: Little is known about the experience of financial stress for patients who survive critical illness or their families. Our objective was to describe the prevalence of financial stress among critically ill patients and their families, identify clinical and demographic characteristics associated with this stress, and explore associations between financial stress and psychologic distress. DESIGN: Secondary analysis of a randomized trial comparing a coping skills training program and an education program for patients surviving acute respiratory failure and their families. SETTING: Five geographically diverse hospitals. PARTICIPANTS: Patients (n = 175) and their family members (n = 85) completed surveys within 2 weeks of arrival home and 3 and 6 months after randomization. MEASUREMENTS AND MAIN RESULTS: We used regression analyses to assess associations between patient and family characteristics at baseline and financial stress at 3 and 6 months. We used path models and mediation analyses to explore relationships between financial stress, symptoms of anxiety and depression,…

OBJECTIVES: Risk adjustment algorithms for ICU mortality are necessary for measuring and improving ICU performance. Existing risk adjustment algorithms are not widely adopted. Key barriers to adoption include licensing and implementation costs as well as labor costs associated with human-intensive data collection. Widespread adoption of electronic health records makes automated risk adjustment feasible. Using modern machine learning methods and open source tools, we developed and evaluated a retrospective risk adjustment algorithm for in-hospital mortality among ICU patients. The Risk of Inpatient Death score can be fully automated and is reliant upon data elements that are generated in the course of usual hospital processes. SETTING: One hundred thirty-one ICUs in 53 hospitals operated by Tenet Healthcare. PATIENTS: A cohort of 237,173 ICU patients discharged between January 2014 and December 2016. DESIGN: The data were randomly split into training (36 hospitals), and validation (17 hospitals) data sets. Feature selection and model training were carried out using the training set…

OBJECTIVES: The Society of Critical Care Medicine recommends routine delirium monitoring, based on data in critically ill patients without primary neurologic injury. We sought to answer whether there are valid and reliable tools to monitor delirium in neurocritically ill patients and whether delirium is associated with relevant clinical outcomes (e.g., survival, length of stay, functional independence, cognition) in this population. DATA SOURCES: We systematically reviewed Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria allowed any study design investigating delirium monitoring in neurocritically ill patients (e.g., neurotrauma, ischemic, and/or hemorrhagic stroke) of any age. We extracted data relevant to delirium tool sensitivity, specificity, negative predictive value, positive predictive value, interrater reliability, and associated clinical outcomes. DATA SYNTHESIS: Among seven prospective cohort studies and a total of 1,173 patients, delirium was assessed in neurocritically patients…

OBJECTIVES: Propofol-based sedation may increase hemodynamic instability by decreasing vascular tone and venous return. Incremental exogenous catecholamines doses may be required to counteract such effects, aggravating the deleterious effects of sympathetic overstimulation. α-2 adrenergic agonists have been reported to decrease norepinephrine requirements in experimental septic shock. The aim of the present study is to test the hypothesis that switching from sedation with propofol to the α-2 agonist dexmedetomidine may decrease norepinephrine doses in septic shock. DESIGN: Prospective open-label crossover study. SETTINGS: University hospital, ICU. PATIENTS: Thirty-eight septic shock patients requiring norepinephrine to maintain adequate mean arterial pressure and needing deep sedation with propofol and remifentanil to maintain a Richmond Agitation-Sedation Scale score between -3 and -4. INTERVENTIONS: An initial set of measurements including hemodynamics, norepinephrine doses, and depth of sedation were obtained during sedation with propofol. Propofol was then replaced by…

OBJECTIVES: A growing number of patients survive sepsis hospitalizations each year and are at high risk for readmission. However, little is known about temporal trends in hospital-based acute care (emergency department treat-and-release visits and hospital readmission) after sepsis. Our primary objective was to measure temporal trends in sepsis survivorship and hospital-based acute care use in sepsis survivors. In addition, because readmissions after pneumonia are subject to penalty under the national readmission reduction program, we examined whether readmission rates declined after sepsis hospitalizations related to pneumonia. DESIGN AND SETTING: Retrospective, observational cohort study conducted within an academic healthcare system from 2010 to 2015. PATIENTS: We used three validated, claims-based approaches to identify 17,256 sepsis or severe sepsis hospitalizations to examine trends in hospital-based acute care after sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 2010 to 2015, sepsis as a proportion of medical and surgical admissions increased from 3.9% to…

OBJECTIVES: Laboratory studies suggest elevated blood pressure after resuscitation from cardiac arrest may be protective; however, clinical data are limited. We sought to test the hypothesis that elevated postresuscitation mean arterial blood pressure is associated with neurologic outcome. DESIGN: Preplanned analysis of a prospective cohort study. SETTING: Six academic hospitals in the United States. PATIENTS: Adult, nontraumatic cardiac arrest patients treated with targeted temperature management after return of spontaneous circulation. INTERVENTIONS: Mean arterial blood pressure was measured noninvasively after return of spontaneous circulation and every hour during the initial 6 hours after return of spontaneous circulation. MEASURES AND MAIN RESULTS: We calculated the mean arterial blood pressure and a priori dichotomized subjects into two groups: mean arterial blood pressure 70-90 and greater than 90 mm Hg. The primary outcome was good neurologic function, defined as a modified Rankin Scale less than or equal to 3. The modified Rankin Scale was prospectively determined at…

OBJECTIVES: We developed quantitative methods to analyze microbubble kinetics based on renal contrast-enhanced ultrasound imaging combined with measurements of sublingual microcirculation on a fixed area to quantify early microvascular alterations in sepsis-induced acute kidney injury. DESIGN: Prospective controlled animal experiment study. SETTING: Hospital-affiliated animal research institution. SUBJECTS: Fifteen female pigs. INTERVENTIONS: The animals were instrumented with a renal artery flow probe after surgically exposing the kidney. Nine animals were given IV infusion of lipopolysaccharide to induce septic shock, and six were used as controls. MEASUREMENTS AND MAIN RESULTS: Contrast-enhanced ultrasound imaging was performed on the kidney before, during, and after having induced shock. Sublingual microcirculation was measured continuously using the Cytocam on the same spot. Contrast-enhanced ultrasound effectively allowed us to develop new analytical methods to measure dynamic variations in renal microvascular perfusion during shock and resuscitation. Renal microvascular…

OBJECTIVES: Double cycling generates larger than expected tidal volumes that contribute to lung injury. We analyzed the incidence, mechanisms, and physiologic implications of double cycling during volume- and pressure-targeted mechanical ventilation in critically ill patients. DESIGN: Prospective, observational study. SETTING: Three general ICUs in Spain. PATIENTS: Sixty-seven continuously monitored adult patients undergoing volume control-continuous mandatory ventilation with constant flow, volume control-continuous mandatory ventilation with decelerated flow, or pressure control-continuous mandatory mechanical ventilation for longer than 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 9,251 hours of mechanical ventilation corresponding to 9,694,573 breaths. Double cycling occurred in 0.6%. All patients had double cycling; however, the distribution of double cycling varied over time. The mean percentage (95% CI) of double cycling was higher in pressure control-continuous mandatory ventilation 0.54 (0.34-0.87) than in volume control-continuous mandatory…

OBJECTIVES: Critical illness can have a significant psychological impact on patients and their families. To inform the design of a larger trial, we assessed feasibility of ICU diaries and psychoeducation to prevent posttraumatic stress disorder, depression, and anxiety following ICU stays. DESIGN: Four-arm pilot randomized controlled trial. SETTING: A 10-bed tertiary ICU in Winnipeg, MB, Canada. PATIENTS: Critically ill patients greater than 17 years old with predicted ICU stays greater than 72 hours and mechanical ventilation duration greater than 24 hours. INTERVENTIONS: Patients were randomized to usual care, ICU diary, psychoeducation, or both ICU diary and psychoeducation. MEASUREMENTS AND MAIN RESULTS: Our primary objective was to determine feasibility measured by enrollment/mo. Secondary outcomes included acceptability of the ICU diary intervention and psychological distress, including patients' memories 1 week post ICU using the ICU Memory Tool, posttraumatic stress disorder (Impact of Events Scale-Revised), depression, and anxiety symptoms (Hospital Anxiety and Depression…

OBJECTIVES: Early prediction of undesired outcomes among newly hospitalized patients could improve patient triage and prompt conversations about patients' goals of care. We evaluated the performance of logistic regression, gradient boosting machine, random forest, and elastic net regression models, with and without unstructured clinical text data, to predict a binary composite outcome of in-hospital death or ICU length of stay greater than or equal to 7 days using data from the first 48 hours of hospitalization. DESIGN: Retrospective cohort study with split sampling for model training and testing. SETTING: A single urban academic hospital. PATIENTS: All hospitalized patients who required ICU care at the Beth Israel Deaconess Medical Center in Boston, MA, from 2001 to 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among eligible 25,947 hospital admissions, we observed 5,504 (21.2%) in which patients died or had ICU length of stay greater than or equal to 7 days. The gradient boosting machine model had the highest discrimination without (area under the receiver operating…

OBJECTIVES: To examine the proportion and rate of central venous access device failure and complications across central venous access device types in adult intensive care. DATA SOURCES: A systematic search was undertaken in the electronic databases Cochrane Central Register of Controlled Trials, Embase, U.S. National Library of Medicine National Institutes of Health, and Cumulative Index to Nursing and Allied Health in September 2017. STUDY SELECTION: Included studies were of observational (prospective and retrospective) or interventional design and reported central venous access device failure and complications in adult ICU settings. Studies were excluded if they were published prior to November 2006 or not reported in English. Two reviewers independently screened articles, assessed eligibility, extracted data, and assessed risk of bias. DATA EXTRACTION: Data were extracted on the primary outcome, central venous access device failure, and secondary outcomes: central venous access device complications (central line-associated bloodstream infection, catheter-related bloodstream…

OBJECTIVES: A systematic assessment of the role of benzodiazepine use during ICU stay as a risk factor for neuropsychiatric outcomes during and after ICU admission. DATA SOURCES: PubMed/Medline, EMBASE, The Cochrane Library, CINAHL, and PsychINFO. STUDY SELECTION: Databases were searched independently by two reviewers for studies in adult (former) ICU patients, reporting benzodiazepine use, and neuropsychiatric outcomes of delirium, posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction. DATA EXTRACTION: Data were extracted using a piloted extraction form; methodological quality of eligible studies was assessed by applying the Quality Index checklist. DATA SYNTHESIS: Forty-nine of 3,066 unique studies identified were included. Thirty-five studies reported on neuropsychiatric outcome during hospitalization, 12 after discharge, and two at both time points. Twenty-four studies identified benzodiazepine use as a risk factor for delirium, whereas seven studies on delirium or related outcomes did not; six studies reported mixed findings. Studies with high…

OBJECTIVES: Recent metabolomic studies of sepsis showed that increased circulatory acylcarnitines were associated with worse survival. However, it is unknown whether plasma carnitine and acylcarnitines can reflect the severity of sepsis, and the role of specific acylcarnitines in prognostic assessment need further confirmation. This study aimed to clarify these questions. DESIGN: Prospective multicenter cohort studies with derivation and validation cohort design. SETTING: ICUs at two medical centers and three regional hospitals in Taiwan. PATIENTS: Patients with sepsis and acute organ dysfunction were enrolled. Recruitment of the derivation (n = 90) and validation cohorts (n = 120) occurred from October 2010 through March 2012 and January 2013 through November 2014, respectively. INTERVENTIONS: Plasma samples were collected immediately after admission, and the levels of carnitine and acylcarnitines were measured by ultra-high performance liquid chromatography-mass spectrometry. MEASUREMENTS AND MAIN RESULTS: In the derivation cohort, increased plasma levels of short- and…

OBJECTIVES: The Sepsis-3 task force recommended the quick Sequential (Sepsis-Related) Organ Failure Assessment score for identifying patients with suspected infection who are at greater risk of poor outcomes, but many hospitals already use the National Early Warning Score to identify high-risk patients, irrespective of diagnosis. We sought to compare the performance of quick Sequential (Sepsis-Related) Organ Failure Assessment and National Early Warning Score in hospitalized, non-ICU patients with and without an infection. DESIGN: Retrospective cohort study. SETTING: Large U.K. General Hospital. PATIENTS: Adults hospitalized between January 1, 2010, and February 1, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied the quick Sequential (Sepsis-Related) Organ Failure Assessment score and National Early Warning Score to 5,435,344 vital signs sets (241,996 hospital admissions). Patients were categorized as having no infection, primary infection, or secondary infection using International Classification of Diseases, 10th Edition codes. National Early Warning Score was…

OBJECTIVES: To describe novel guideline development strategies created and implemented as part of the Society of Critical Care Medicine's 2018 clinical practice guidelines for pain, agitation (sedation), delirium, immobility (rehabilitation/mobility), and sleep (disruption) in critically ill adults. DESIGN: We involved critical illness survivors from start to finish, used and expanded upon Grading of Recommendations, Assessment, Development and Evaluation methodology for making recommendations, identified evidence gaps, and developed communication strategies to mitigate challenges. SETTING/SUBJECTS: Thirty-two experts from five countries, across five topic-specific sections; four methodologists, two medical librarians, four critical illness survivors, and two Society of Critical Care Medicine support staff. INTERVENTIONS: Unique approaches included the following: 1) critical illness survivor involvement to help ensure patient-centered questions and recommendations; 2) qualitative and semiquantitative approaches for developing descriptive statements; 3) operationalizing a three-step…

OBJECTIVES: To determine whether Telemedicine intervention can affect hospital mortality, length of stay, and direct costs for progressive care unit patients. DESIGN: Retrospective observational. SETTING: Large healthcare system in Florida. PATIENTS: Adult patients admitted to progressive care unit (PCU) as their primary admission between December 2011 and August 2016 (n = 16,091). INTERVENTIONS: Progressive care unit patients with telemedicine intervention (telemedicine PCU [TPCU]; n = 8091) and without telemedicine control (nontelemedicine PCU [NTPCU]; n = 8000) were compared concurrently during study period. MEASUREMENTS AND MAIN RESULTS: Primary outcome was progressive care unit and hospital mortality. Secondary outcomes were hospital length of stay, progressive care unit length of stay, and mean direct costs. The mean age NTPCU and TPCU patients were 63.4 years (95% CI, 62.9-63.8 yr) and 71.1 years (95% CI, 70.7-71.4 yr), respectively. All Patient Refined-Diagnosis Related Group Disease Severity (p < 0.0001) and All Patient Refined-Diagnosis Related Group patient Risk of…

OBJECTIVES: Recent evidence suggests that half-dose thrombolysis for pulmonary embolism may provide similar efficacy with reduced bleeding risk compared with full-dose therapy, but comparative studies are lacking. We aimed to evaluate the effectiveness and safety of half-dose versus full-dose alteplase for treatment of pulmonary embolism. DESIGN: A retrospective cohort study comparing outcomes in patients receiving half-dose (50 mg) versus full-dose (100 mg) alteplase for pulmonary embolism. We used propensity score matching and sensitivity analyses to address confounding and hospital-level clustering. SETTING: Data from 420 hospitals obtained from the Premier Healthcare Database between January 2010 and December 2014. SUBJECTS: Adult critically ill patients with acute pulmonary embolism treated with IV alteplase therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study included 3,768 patients: 699 (18.6%) in the half-dose and 3,069 (81.4%) in the full-dose group. At baseline, patients receiving half-dose alteplase required vasopressor therapy (23.3% vs 39.4%; p <…

OBJECTIVES: Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices for sepsis and organ dysfunction may confound efforts to estimate sepsis rates, compare outcomes, and perform risk adjustment. We evaluated hospital variation in the sensitivity of claims data relative to clinical data from electronic health records and its impact on outcome comparisons. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 4.3 million adult encounters at 193 U.S. hospitals in 2013-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was defined using electronic health record-derived clinical indicators of presumed infection (blood culture draws and antibiotic administrations) and concurrent organ dysfunction (vasopressors, mechanical ventilation, doubling in creatinine, doubling in bilirubin to ≥ 2.0 mg/dL, decrease in platelets to < 100 cells/µL, or lactate ≥ 2.0 mmol/L). We compared claims for sepsis prevalence and mortality rates between both methods. All…

OBJECTIVES: To evaluate the performance of transcranial Doppler and transcranial color-coded duplex Doppler in patients with cerebral vasospasm due to aneurysm rupture. Angiography was considered as the gold standard comparator. DATA SOURCES: Search in MEDLINE, Embase, and Central from January 2001 to October 2017, without language restriction. Bibliographies of retrieved articles were screened for additional studies. STUDY SELECTION: Randomized studies comparing transcranial Doppler or transcranial color-coded duplex Doppler with angiography in adults. DATA EXTRACTION: Data were extracted independently by several investigators. Sensitivity and specificity were combined across studies using a bivariate model. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used for reporting and Quality Assessment of Diagnostic Accuracy Studies-2 for quality assessment. DATA SYNTHESIS: We included 18 studies. Fifteen tested transcranial Doppler. For the middle cerebral artery (10 studies, 1,408 tests), the pooled sensitivity was 66.7% (95% CI, 55.9-75.9) and specificity was…

OBJECTIVES: Little is known about platelet transfusions in pediatric critical illness. We sought to describe the epidemiology, indications, and outcomes of platelet transfusions among critically ill children. DESIGN: Prospective cohort study. SETTING: Multicenter (82 PICUs), international (16 countries) from September 2016 to April 2017. PATIENTS: Children ages 3 days to 16 years prescribed a platelet transfusion in the ICU during screening days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over 6 weeks, 16,934 patients were eligible, and 559 received at least one platelet transfusion (prevalence, 3.3%). The indications for transfusion included prophylaxis (67%), minor bleeding (21%), and major bleeding (12%). Thirty-four percent of prophylactic platelet transfusions were prescribed when the platelet count was greater than or equal to 50 × 10 cells/L. The median (interquartile range) change in platelet count post transfusion was 48 × 10 cells/L (17-82 × 10 cells/L) for major bleeding, 42 × 10 cells/L (16-80 × 10 cells/L) for prophylactic transfusions to meet a defined…

OBJECTIVES: To assess the effectiveness of noninvasive ventilation in patients with acute respiratory failure and do-not-intubate or comfort-measures-only orders. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to January 1, 2017. STUDY SELECTION: Studies of all design types that enrolled patients in the ICU or hospital ward who received noninvasive ventilation and had preset do-not-intubate or comfort-measures-only orders. DATA EXTRACTION: Data abstraction followed Meta-analysis of Observational Studies in Epidemiology guidelines. Data quality was assessed using a modified Newcastle-Ottawa Scale. DATA SYNTHESIS: Twenty-seven studies evaluating 2,020 patients with do-not-intubate orders and three studies evaluating 200 patients with comfort-measures-only orders were included. In patients with do-not-intubate orders, the pooled survival was 56% (95% CI, 49-64%) at hospital discharge and 32% (95% CI, 21-45%) at 1 year. Hospital survival was 68% for chronic obstructive pulmonary disease, 68% for pulmonary edema, 41% for pneumonia, and 37% for patients…

OBJECTIVE: The objective was to compare the resolution of organ dysfunction, 28-day mortality, and biochemical markers in children with thrombocytopenia-associated multiple organ failure who received therapeutic plasma exchange versus no therapeutic plasma exchange. DESIGN: Observational longitudinal cohort study. SETTING: Nine U.S. PICUs. PATIENTS: Eighty-one children with sepsis-induced thrombocytopenia-associated multiple organ failure. INTERVENTIONS: Therapeutic plasma exchange. MEASUREMENTS AND MAIN RESULTS: Adjusted relative risk for 28-day mortality was modeled using standard multivariate regression with propensity score weighting to reduce covariate confounding. Change from baseline Pediatric Logistic Organ Dysfunction scores between therapeutic plasma exchange and no therapeutic plasma exchange differed in temporal pattern during the first week (p = 0.009). By day 4, mean Pediatric Logistic Organ Dysfunction score declined by 7.9 points (95% CI, -10.8 to -5.1) in the therapeutic plasma exchange-treated group compared with no change with no therapeutic plasma exchange. Use…

OBJECTIVES: Lactate promotes cerebral blood flow and is an efficient substrate for the brain, particularly at times of glucose shortage. Hypertonic lactate is neuroprotective after experimental brain injury; however, human data are limited. DESIGN: Prospective study (clinicaltrials.gov NCT01573507). SETTING: Academic ICU. PATIENTS: Twenty-three brain-injured subjects (13 traumatic brain injury/10 subarachnoid hemorrhage; median age, 59 yr [41-65 yr]; median Glasgow Coma Scale, 6 [3-7]). INTERVENTIONS: Three-hour IV infusion of hypertonic lactate (sodium lactate, 1,000 mmol/L; concentration, 30 µmol/kg/min) administered 39 hours (26-49 hr) from injury. MEASUREMENTS AND MAIN RESULTS: We examined the effect of hypertonic lactate on cerebral perfusion (using transcranial Doppler) and brain energy metabolism (using cerebral microdialysis). The majority of subjects (13/23 = 57%) had reduced brain glucose availability (baseline pretreatment cerebral microdialysis glucose, < 1 mmol/L) despite normal baseline intracranial pressure (10 [7-15] mm Hg). Hypertonic lactate was associated with…

OBJECTIVES: To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. DESIGN: Retrospective case series. SETTING: Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical ICU) between July 1, 2004, and October 31, 2015. PATIENTS: Adult critically ill patients with hyperammonemia not related to acute or chronic liver failure. We excluded patients with diagnosis of moderate or severe liver disease, hyperbilirubinemia, and patients who denied the use of their medical records. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,908 ICU patients with hyperammonemia, 167 (4.5%) had no evidence of acute or chronic liver failure. One-hundred one patients (60.5%) were male with median age of 65.7 years (interquartile range, 50-74.5 yr) and median serum ammonia level of 68 µg/dL (interquartile range, 58-87 µg/dL). Acute encephalopathy was present in 119 patients (71%). Predisposing conditions included malnutrition 27 (16%), gastric bypass…

OBJECTIVE: To assess the epidemiology and outcome of patients with cirrhosis following critical care unit admission. DESIGN: Retrospective cohort study. SETTING: Critical care units in England, Wales, and Northern Ireland participating in the U.K. Intensive Care National Audit and Research Centre Case Mix Programme. PATIENTS: Thirty-one thousand three hundred sixty-three patients with cirrhosis identified of 1,168,650 total critical care unit admissions (2.7%) admitted to U.K. critical care units between 1998 and 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ten thousand nine hundred thirty-six patients had alcohol-related liver disease (35%). In total, 1.6% of critical care unit admissions in 1998 had cirrhosis rising to 3.1% in 2012. The crude critical care unit mortality of patients with cirrhosis was 41% in 1998 falling to 31% in 2012 (p < 0.001). Crude hospital mortality fell from 58% to 46% over the study period (p < 0.001). Mean(SD) Acute Physiology and Chronic Health Evaluation II score in 1998 was 20.3 (8.5) and 19.5 (7.1) in 2012. Mean Acute Physiology and…

OBJECTIVES: To assess the relationship between microcirculatory perfusion and multiple organ dysfunction syndrome in patients following traumatic hemorrhagic shock. DESIGN: Multicenter prospective longitudinal observational study. SETTING: Three U.K. major trauma centers. PATIENTS: Fifty-eight intubated and ventilated patients with traumatic hemorrhagic shock. INTERVENTIONS: Sublingual incident dark field microscopy was performed within 12 hours of ICU admission (D0) and repeated 24 and 48 hours later. Cardiac output was assessed using oesophageal Doppler. Multiple organ dysfunction syndrome was defined as Serial Organ Failure Assessment score greater than or equal to 6 at day 7 post injury. MEASUREMENTS AND MAIN RESULTS: Data from 58 patients were analyzed. Patients had a mean age of 43 ± 19 years, Injury Severity Score of 29 ± 14, and initial lactate of 7.3 ± 6.1 mmol/L and received 6 U (interquartile range, 4-11 U) of packed RBCs during initial resuscitation. Compared with patients without multiple organ dysfunction syndrome at day 7, patients with multiple organ dysfunction…

OBJECTIVES: To evaluate the effect of probiotics on cytokines in children with severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: ICU of a tertiary care teaching hospital in North India. PATIENTS: Children 3 months to 12 years old with severe sepsis. INTERVENTIONS: Enrolled children were randomized to probiotic (n = 50) and placebo (n = 50) groups. Probiotic group received VSL#3 (Danisco-Dupont USA, Madison, WI) (Lactobacillus paracasei, L. plantarum, L. acidophilus, L. delbrueckii, Bifidobacterium longum, B. infantis, B. breve, Streptococcus salivarius; maltose and silicon dioxide), and placebo group received maltose and silicon dioxide. Dose was 1 sachet twice daily for 7 days. Blood was collected on days 1 and 7 for estimation of interleukin-6, interleukin-12p70, interleukin-17, tumor necrosis factor-α, interleukin-10, and transforming growth factor -β1. "Primary outcome": Change in cytokine levels in probiotic and placebo groups from day 1 to 7. "Secondary outcomes": Sequential Organ Failure Assessment score, healthcare-associated infections, ICU…

OBJECTIVES: To assess the effectiveness of the ventilator bundle in the reduction of mortality in ICU patients. DATA SOURCES: PubMed, Scopus, Web of Science, Cochrane Library for studies published until June 2017. STUDY SELECTION: Included studies: randomized controlled trials or any kind of nonrandomized intervention studies, made reference to a ventilator bundle approach, assessed mortality in ICU-ventilated adult patients. DATA EXTRACTION: Items extracted: study characteristics, description of the bundle approach, number of patients in the comparison groups, hospital/ICU mortality, ventilator-associated pneumonia-related mortality, assessment of compliance to ventilator bundle and its score. DATA SYNTHESIS: Thirteen articles were included. The implementation of a ventilator bundle significantly reduced mortality (odds ratio, 0.90; 95% CI, 0.84-0.97), with a stronger effect with a restriction to studies that reported mortality in ventilator-associated pneumonia patients (odds ratio, 0.71; 95% CI, 0.52-0.97), to studies that provided active educational activities was analyzed (odds…

OBJECTIVES: To determine the prevalence of intra-abdominal hypertension in mixed medical-surgical critically ill patients using modern definitions and measurement techniques. Secondarily to determine variables associated with intra-abdominal hypertension and ICU mortality. DESIGN: A prospective observational study. SETTING: Single institution trauma, medical and surgical ICU in Canada. PATIENTS: Consecutive adult patients admitted to the ICU (n = 285). INTERVENTION: Intra-abdominal pressure measurements twice a day during admission to the ICU. MEASUREMENTS AND MAIN RESULTS: In 285 patients who met inclusion criteria, 30% were diagnosed with intra-abdominal hypertension at admission and a further 15% developed intra-abdominal hypertension during admission. The prevalence of abdominal compartment syndrome was 3%. Obesity, sepsis, mechanical ventilation, and 24-hour fluid balance (> 3 L) were all independent predictors for intra-abdominal hypertension. Intra-abdominal hypertension occurred in 28% of nonventilated patients. Admission type (medical vs surgical vs trauma) was not a…

OBJECTIVES: Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group. DESIGN: Population-based data linkage study using the Secure Anonymised Information Linkage databank. SETTING: All ICUs between 2006 and 2013 in Wales, United Kingdom. PATIENTS: We identified 40,631 patients discharged alive from Welsh adult ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was 365-day survival. The secondary outcomes were 30- and 90-day survival and hospital utilization in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. Seven-thousand eight-hundred eighty-three patients (19.4%) died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality.…

Balas, Michele C. PhD, RN, CCRN-K, FCCM, FAAN1,2; Weinhouse, Gerald L. MD3,4; Denehy, Linda PT, PhD5; Chanques, Gerald MD, PhD6; Rochwerg, Bram MD, MSc7; Misak, Cheryl J. DPhil8; Skrobik, Yoanna MD, FRCP(c), MSc, FCCM9; Devlin, John W. PharmD, FCCM10,11; Fraser, Gilles L. PharmD, MCCM12,13 Author Information

OBJECTIVES: Clinical ethics consultation as a mechanism for supporting patients, family, and staff during ethically challenging situations has become standard of care. Despite this, there is a lack of consensus about the effectiveness of clinical ethics consultation consultation in the ICU. We performed a systematic review of outcomes associated with clinical ethics consultation within adult ICUs. DATA SOURCES: We searched MEDLINE, PubMed, Cochrane CENTRAL, Embase, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature from 1984 to May 2017. STUDY SELECTION: Two reviewers independently screened articles, assessed eligibility, extracted data, and assessed risk of bias using the Cochrane Collaboration Risk of Bias tool and the Newcastle-Ottawa Scale. Pooled estimates of effect were calculated where possible. We screened 3,970 abstracts and reviewed 325 full-text articles of which 16 met all eligibility criteria. DATA EXTRACTION: We examined changes in processes and outcomes as a result of clinical ethics consultation in the ICU. Categories of outcomes included user…

OBJECTIVES: Pressure reactivity index and oxygen reactivity index are used to assess cerebral autoregulation after acute brain injury. The value of autoregulation indices in the prediction of delayed cerebral ischemia and outcome in patients with subarachnoid hemorrhage is still inconclusive. In this study, we aimed to focus on the predictive value of the first 72 hours commonly referred to as "early brain injury" in comparison to the overall monitoring period. DESIGN: Retrospective observational cohort study. SETTING: Neurocritical care unit at a tertiary academic medical center. PATIENTS: Forty-three consecutive poor-grade patients with nontraumatic subarachnoid hemorrhage admitted between 2012 and 2016 undergoing continuous high-frequency monitoring. INTERVENTIONS: High-frequency monitoring includes arterial blood pressure, intracranial pressure, and brain tissue oxygen tension. Pressure reactivity index and oxygen reactivity index were evaluated as moving correlation coefficient between mean arterial pressure/intracranial pressure and cerebral perfusion pressure/brain tissue…

OBJECTIVES: Intracranial pressure in traumatic brain injury is dynamic and influenced by factors like injury patterns, treatments, and genetics. Existing studies use time invariant summary intracranial pressure measures thus potentially losing critical information about temporal trends. We identified longitudinal intracranial pressure trajectories in severe traumatic brain injury and evaluated whether they predicted outcome. We further interrogated the model to explore whether ABCC8 polymorphisms (a known cerebraledema regulator) differed across trajectory groups. DESIGN: Prospective observational cohort. SETTING: Single-center academic medical center. PATIENTS: Four-hundred four severe traumatic brain injury patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used group-based trajectory modeling to identify hourly intracranial pressure trajectories in days 0-5 post traumatic brain injury incorporating risk factor adjustment (age, sex, Glasgow Coma Scale 6score, craniectomy, primary hemorrhage pattern). We compared 6-month outcomes (Glasgow Outcome Scale, Disability…

OBJECTIVES: Chimeric antigen receptor T-cell therapy, a type of immune effector therapy for cancer, has demonstrated encouraging results in clinical trials for the treatment of patients with refractory hematologic malignancies. Nevertheless, there are toxicities specific to these treatments that, if not recognized and treated appropriately, can lead to multiple organ failure and death. This article is a comprehensive review of the available literature and provides, from a critical care perspective, recommendations by experienced intensivists in the care of critically ill adult chimeric antigen receptor T-cell patients. DATA SOURCES: PubMed and Medline search of articles published from 2006 to date. STUDY SELECTION: Clinical studies, reviews, or guidelines were selected and reviewed by the authors. DATA EXTRACTION: Not available. DATA SYNTHESIS: Not available. CONCLUSIONS: Until modifications in chimeric antigen receptor T-cell therapy decrease their toxicities, the intensivist will play a leading role in the management of critically ill chimeric antigen receptor T-cell patients. As…

OBJECTIVES: Rapid muscle wasting occurs during acute respiratory failure, resulting in muscle weakness and functional impairments. This study examines survivors' body composition in the year after acute respiratory distress syndrome and tests associations of patient characteristics, hospital exposures, and survivors' strength and physical functioning with whole body percent lean mass. DESIGN: Prospective cohort study with 6- and 12-month follow-up. SETTING: National study enrolling patients from five study centers. PATIENTS: Acute respiratory distress syndrome survivors (n = 120). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Lean and fat mass from dual energy x-ray absorptiometry. On average, survivors gained whole body total mass (+1.4 kg; 0.1-2.7) and fat mass (+1.2 kg; 0.2-2.2) and maintained lean mass (+0.2 kg; -0.4 to 0.8) between 6 and 12 months. Proportionally, percent fat mass increased and percent lean mass decreased for the whole body, trunk, and legs (p < 0.05). Greater whole body percent lean mass was associated with younger age, male sex, and lower baseline body…

OBJECTIVES: To characterize admission patterns, treatments, and outcomes among patients with moderate traumatic brain injury. DESIGN: Retrospective cohort study. SETTING: National Trauma Data Bank. PATIENTS: Adults (age > 18 yr) with moderate traumatic brain injury (International Classification of Diseases, Ninth revision codes and admission Glasgow Coma Scale score of 9-13) in the National Trauma Data Bank between 2007 and 2014. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Demographics, mechanism of injury, hospital course, and facility characteristics were examined. Admission characteristics associated with discharge outcomes were analyzed using multivariable Poisson regression models. Of 114,066 patients, most were white (62%), male (69%), and had median admission Glasgow Coma Scale score of 12 (interquartile range, 10-13). Seventy-seven percent had isolated traumatic brain injury. Concussion, which accounted for 25% of moderate traumatic brain injury, was the most frequent traumatic brain injury diagnosis. Fourteen percent received mechanical ventilation, and 66% were…

OBJECTIVES: To assess the variability in short-term sepsis mortality by hospital among Centers for Medicare and Medicaid Services beneficiaries in the United States during 2013-2014. DESIGN: A retrospective cohort design. SETTING: Hospitalizations from 3,068 acute care hospitals that participated in the Centers for Medicare and Medicaid Services inpatient prospective payment system in 2013 and 2014. PATIENTS: Medicare fee-for-service beneficiaries greater than or equal to 65 years old who had an inpatient hospitalization coded with present at admission severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Individual level mortality was assessed as death at or within 7 days of hospital discharge and aggregated to calculate hospital-level mortality rates. We used a logistic hierarchal linear model to calculate mortality risk-adjusted for patient characteristics. We quantified variability among hospitals using the median odds ratio and calculated risk-standardized mortality rates for each hospital. The overall crude mortality rate was 34.7%. We found…

OBJECTIVES: Tight glycemic control using intermittent blood glucose measurements is associated with a risk of hypoglycemia. Glucose concentrations can now be measured near continuously (every 5-15 min). We assessed the quality and safety of glycemic control guided by a near-continuous glucose monitoring system in ICU patients. DESIGN: Prospective, cluster-randomized, crossover study. SETTING: Thirty-five-bed medico-surgical department of intensive care with four separate ICUs. PATIENTS: Adult patients admitted to the department and expected to stay for at least 3 days were considered for inclusion if they had persistent hyperglycemia (blood glucose > 150 mg/dL) up to 6 hours after admission and/or were receiving insulin therapy. INTERVENTIONS: A peripheral venous catheter was inserted in all patients and connected to a continuous glucose monitoring sensor (GlucoClear; Edwards Lifesciences, Irvine, CA). The four ICUs were randomized in pairs in a crossover design to glycemic control using unblinded or blinded continuous glucose monitoring monitors. The insulin infusion rate was…

OBJECTIVES: To compare physicians' perceptions and practice of end-of-life care in the ICU in three East Asian countries cultures similarly rooted in Confucianism. DESIGN: A structured and scenario-based survey of physicians who managed ICU patients from May 2012 to December 2012. SETTING: ICUs in China, Korea, and Japan. SUBJECTS: Specialists who are either intensivists or nonintensivist primary attending physicians in charge of patients (195 in China, 186 in Korea, 224 in Japan). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Country was independently associated with differences in the practice of limiting multiple forms of life-sustaining treatments on multivariable generalized linear model analysis. Chinese respondents were least likely to apply do-not-resuscitate orders, even if they existed (p < 0.001). Japanese respondents were most likely to practice do not resuscitate for terminally ill patients during cardiac arrest, even when no such prior order existed (p < 0.001). Korean respondents' attitudes were in between those of Chinese and Japanese respondents as far as…

OBJECTIVES: Soluble urokinase plasminogen activator receptor is a prognostic biomarker associated with critical illness, disease progression, and risk of mortality. We aimed to evaluate whether soluble urokinase plasminogen activator receptor adds prognostic value to a vital sign-based score for clinical monitoring of patient risk (National Early Warning Score) in acute medical patients. DESIGN: Registry-based observational cohort study of consecutively admitted acute medical patients. SETTING: The Acute Medical Unit, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. PATIENTS: Acute medical patients admitted between November 18, 2013, and September 30, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 17,312 included patients, admission National Early Warning Score was available for 16,244 (93.8%). During follow-up, 587 patients (3.4%) died in-hospital, 859 (5.0%) within 30 days, and 1,367 (7.9%) within 90 days. High soluble urokinase plasminogen activator receptor was significantly associated with in-hospital-, 30-day-, and 90-day mortality within…

OBJECTIVES: To identify, appraise, and synthesize current evidence to determine whether early enteral nutrition alters patient outcomes from major burn injury. DATA SOURCES: Medline, Embase, and the China National Knowledge Infrastructure were searched. The close out date was May 1, 2018. STUDY SELECTION: Early enteral nutrition was defined as a standard formula commenced within 24 hours of injury or admission to ICU or burn unit. Comparators included any form of nutrition support "except" early enteral nutrition. Only randomized controlled trials reporting patient-centered outcomes were eligible for inclusion. DATA EXTRACTION: The primary outcome was mortality. Gastrointestinal hemorrhage, sepsis, pneumonia, renal failure, and hospital stay were evaluated as secondary outcomes. DATA SYNTHESIS: Nine-hundred fifty-eight full-text articles were retrieved and screened. Seven randomized controlled trials enrolling 527 participants with major burn injury were included. Compared with all other types of nutrition support, early enteral nutrition significantly reduced mortality (odds ratio,…

OBJECTIVES: Cardiac arrest etiology may be an important source of between-patient heterogeneity, but the impact of etiology on organ injury is unknown. We tested the hypothesis that asphyxial cardiac arrest results in greater neurologic injury than cardiac etiology cardiac arrest (ventricular fibrillation cardiac arrest), whereas ventricular fibrillation cardiac arrest results in greater cardiovascular dysfunction after return of spontaneous circulation. DESIGN: Prospective observational human and randomized animal study. SETTING: University laboratory and ICUs. PATIENTS: Five-hundred forty-three cardiac arrest patients admitted to ICU. SUBJECTS: Seventy-five male Sprague-Dawley rats. INTERVENTIONS: We examined neurologic and cardiovascular injury in Isoflurane-anesthetized rat cardiac arrest models matched by ischemic time. Hemodynamic and neurologic outcomes were assessed after 5 minutes no flow asphyxial cardiac arrest or ventricular fibrillation cardiac arrest. Comparison was made to injury patterns observed after human asphyxial cardiac arrest or ventricular fibrillation…

OBJECTIVES: Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. DESIGN: Case-control study. SETTING: Four tertiary care hospitals. PATIENTS: We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery,…

OBJECTIVES: Absence of somatosensory evoked potentials is considered a nearly perfect predictor of poor outcome after cardiac arrest. However, reports of good outcomes despite absent somatosensory evoked potentials and high rates of withdrawal of life-sustaining therapies have raised concerns that estimates of the prognostic value of absent somatosensory evoked potentials may be biased by self-fulfilling prophecies. We aimed to develop an unbiased estimate of the false positive rate of absent somatosensory evoked potentials as a predictor of poor outcome after cardiac arrest. DATA SOURCES: PubMed. STUDY SELECTION: We selected 35 studies in cardiac arrest prognostication that reported somatosensory evoked potentials. DATA EXTRACTION: In each study, we identified rates of withdrawal of life-sustaining therapies and good outcomes despite absent somatosensory evoked potentials. We appraised studies for potential biases using the Quality in Prognosis Studies tool. Using these data, we developed a statistical model to estimate the false positive rate of absent somatosensory evoked…

OBJECTIVES: To evaluate the Chronic Liver Failure-Consortium Acute on Chronic Liver Failure score in acute on chronic liver failure patients admitted to ICUs from different global regions and compare discrimination ability with previously published scores. DESIGN: Retrospective pooled analysis. SETTING: Academic ICUs in Canada (Edmonton, Vancouver) and Europe (Paris, Barcelona, Chronic liver failure/Acute-on-Chronic Liver Failure in Cirrhosis [CANONIC] study). PATIENTS: Sample of analysis of 867 cirrhotic patients with acute on chronic liver failure admitted to ICU. Cumulative incidence functions of death were estimated by acute on chronic liver failure grade at admission and at day 3. Survival discrimination abilities of Chronic Liver Failure-Consortium Acute on Chronic Liver Failure, Model for End-Stage Liver Disease, Acute Physiology and Chronic Health Evaluation II, and Child-Turcotte-Pugh scores were compared. INTERVENTIONS: ICU admission for organ support. MEASUREMENTS AND MAIN RESULTS: At admission 169 subjects (19%) had acute on chronic liver failure 1, 302 (35%) acute on…

OBJECTIVES: To examine neurophysiologic predictors and outcomes of patients with late awakening following cardiac arrest. DESIGN: Observational cohort study. SETTING: Academic ICU. PATIENTS: Adult comatose cardiac arrest patients treated with targeted temperature management and sedation. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Time to awakening was calculated starting from initial sedation stop following targeted temperature management and rewarming (median 34 hr from ICU admission). Two-hundred twenty-eight of 402 patients (57%) awoke: late awakening (> 48 hr from sedation stop; median time to awakening 5 days [range, 3-23 d]) was observed in 78 subjects (34%). When considering single neurophysiologic tests, late awakening was associated with a higher proportion of discontinuous electroencephalography (21% vs 6% of early awakeners), absent motor and brainstem responses (38% vs 11%; 23 vs 4%, respectively), and serum neuron specific enolase greater than 33 ng/mL (23% vs 8%; all p < 0.01): no patient had greater than 2 unfavorable tests. By multivariable analysis-adjusting…

OBJECTIVES: Investigations of acute respiratory distress syndrome in adults suggest hypoxemia is an uncommon cause of death. However, the epidemiology of death in pediatric acute respiratory distress syndrome is not well characterized. We aimed to describe the cause, mode, and timing of death in pediatric acute respiratory distress syndrome nonsurvivors. We hypothesized that most deaths would be due to nonpulmonary factors, rather than hypoxemia. DESIGN: Retrospective, decedent-only analysis. SETTING: Two large, academic PICUs. PATIENTS: Nonsurvivors with pediatric acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 798 subjects with pediatric acute respiratory distress syndrome, there were 153 nonsurvivors (19% mortality). Median time to death was 6 days (interquartile range, 3-13 d) after pediatric acute respiratory distress syndrome onset. Patients dying less than 7 days after pediatric acute respiratory distress syndrome onset had greater illness severity and worse oxygenation. Patients dying less than 7 days were more likely to die of a…

OBJECTIVE: We aimed to compare the sepsis incidence, mortality rates, and primary sites of infection among adult, elderly, and octogenarian patients with sepsis. DESIGN: Population-based cohort study. SETTING: The entire health insurance claims data of Taiwan, which enrolled 99.8% of the 23 million Taiwanese population. PATIENTS: Sepsis patients were identified by International Classification of Diseases, 9th Edition, Clinical Modification codes for both infection and organ dysfunction from January 1, 2002, to December 31, 2012. Patients were categorized into three age groups: 1) adults (18-64 yr); 2) elderly (65-84 yr); and 3) oldest old (≥ 85 yr). The 30-day all-cause mortality was verified by a linked national death certificate database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 2002 to 2012, we identified 1,259,578 patients with sepsis, of which 417,328 (33.1%) were adults, 652,618 (51.8%) were elderly, and 189,632 (15.1%) were oldest old. We determined that the incidence of sepsis in the oldest old was 9,414 cases per 100,000 population on 2012, which was 31-fold…

OBJECTIVES: Transfusion-related acute lung injury is characterized by the onset of respiratory distress and acute lung injury following blood transfusion, but its pathogenesis remains poorly understood. Generally, a two-hit model is presumed to underlie transfusion-related acute lung injury with the first hit being risk factors present in the transfused patient (such as inflammation), whereas the second hit is conveyed by factors in the transfused donor blood (such as antileukocyte antibodies). At least 80% of transfusion-related acute lung injury cases are related to the presence of donor antibodies such as antihuman leukocyte or antihuman neutrophil antibodies. The remaining cases may be related to nonantibody-mediated factors such as biolipids or components related to storage and ageing of the transfused blood cells. At present, transfusion-related acute lung injury is the leading cause of transfusion-related fatalities and no specific therapy is clinically available. In this article, we critically appraise and discuss recent preclinical (bench) insights related to…

OBJECTIVES: Music intervention has been shown to reduce anxiety and sedative exposure among mechanically ventilated patients. Whether music intervention reduces ICU costs is not known. The aim of this study was to examine ICU costs for patients receiving a patient-directed music intervention compared with patients who received usual ICU care. DESIGN: A cost-effectiveness analysis from the hospital perspective was conducted to determine if patient-directed music intervention was cost-effective in improving patient-reported anxiety. Cost savings were also evaluated. One-way and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. SETTING: Midwestern ICUs. PATIENTS: Adult ICU patients from a parent clinical trial receiving mechanical ventilatory support. INTERVENTIONS: Patients receiving the experimental patient-directed music intervention received a MP3 player, noise-canceling headphones, and music tailored to individual preferences by a music therapist. MEASUREMENTS AND MAIN RESULTS: The base case cost-effectiveness analysis…