The 100 most-cited articles in Critical Care Medicine, 2019

OBJECTIVES: We performed a national cross-sectional survey to determine the epidemiologic characteristics of patients with sepsis in ICU in China. DESIGN: A cross-section survey study. SETTING: Forty-four hospitals in mainland China from December 1, 2015, to January 31, 2016. PATIENTS: All septic patients diagnosed according sepsis-1 criteria admitted to participating ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recorded demographic, physiologic, and microbiological data with follow-up for 90 days or death, if sooner. The frequency of sepsis and 90-day mortality rate were computed, and the relationship with gross domestic product determined. Multivariate logistic regression analysis was used to determine risk factors for 90-day mortality in patients with sepsis. Two-thousand three-hundred twenty-two patients with sepsis were included in the analysis, of whom 786 patients (33.9%) had hospital-acquired sepsis. The most common infection site was the lung (68.2%), followed by abdomen (26.6%) and bloodstream (7.8%). The frequency of sepsis in the ICU was 20.6 cases per 100…

OBJECTIVES: Sepsis is a major public health concern with significant morbidity, mortality, and healthcare expenses. Early detection and antibiotic treatment of sepsis improve outcomes. However, although professional critical care societies have proposed new clinical criteria that aid sepsis recognition, the fundamental need for early detection and treatment remains unmet. In response, researchers have proposed algorithms for early sepsis detection, but directly comparing such methods has not been possible because of different patient cohorts, clinical variables and sepsis criteria, prediction tasks, evaluation metrics, and other differences. To address these issues, the PhysioNet/Computing in Cardiology Challenge 2019 facilitated the development of automated, open-source algorithms for the early detection of sepsis from clinical data. DESIGN: Participants submitted containerized algorithms to a cloud-based testing environment, where we graded entries for their binary classification performance using a novel clinical utility-based evaluation metric. We designed this scoring function…

OBJECTIVES: Develop and implement a machine learning algorithm to predict severe sepsis and septic shock and evaluate the impact on clinical practice and patient outcomes. DESIGN: Retrospective cohort for algorithm derivation and validation, pre-post impact evaluation. SETTING: Tertiary teaching hospital system in Philadelphia, PA. PATIENTS: All non-ICU admissions; algorithm derivation July 2011 to June 2014 (n = 162,212); algorithm validation October to December 2015 (n = 10,448); silent versus alert comparison January 2016 to February 2017 (silent n = 22,280; alert n = 32,184). INTERVENTIONS: A random-forest classifier, derived and validated using electronic health record data, was deployed both silently and later with an alert to notify clinical teams of sepsis prediction. MEASUREMENT AND MAIN RESULT: Patients identified for training the algorithm were required to have International Classification of Diseases, 9th Edition codes for severe sepsis or septic shock and a positive blood culture during their hospital encounter with either a lactate greater than 2.2 mmol/L or a systolic…

OBJECTIVES: The objective of this systematic review and meta-analysis was to assess the effects of including critical care pharmacists in multidisciplinary ICU teams on clinical outcomes including mortality, ICU length of stay, and adverse drug events. DATA SOURCES: PubMed, EMBASE, and references from previous relevant systematic studies. STUDY SELECTION: We included randomized controlled trials and nonrandomized studies that reported clinical outcomes such as mortality, ICU length of stay, and adverse drug events in groups with and without critical care pharmacist interventions. DATA EXTRACTION: We extracted study details, patient characteristics, and clinical outcomes. DATA SYNTHESIS: From the 4,725 articles identified as potentially eligible, 14 were included in the analysis. Intervention of critical care pharmacists as part of the multidisciplinary ICU team care was significantly associated with the reduced likelihood of mortality (odds ratio, 0.78; 95% CI, 0.73-0.83; p < 0.00001) compared with no intervention. The mean difference in ICU length of stay was -1.33 days (95% CI,…

OBJECTIVES: To assess for the first time the safety and pharmacokinetics of an antiprogrammed cell death-ligand 1 immune checkpoint inhibitor (BMS-936559; Bristol-Myers Squibb, Princeton, NJ) and its effect on immune biomarkers in participants with sepsis-associated immunosuppression. DESIGN: Randomized, placebo-controlled, dose-escalation. SETTING: Seven U.S. hospital ICUs. STUDY POPULATION: Twenty-four participants with sepsis, organ dysfunction (hypotension, acute respiratory failure, and/or acute renal injury), and absolute lymphocyte count less than or equal to 1,100 cells/μL. INTERVENTIONS: Participants received single-dose BMS-936559 (10-900 mg; n = 20) or placebo (n = 4) infusions. Primary endpoints were death and adverse events; key secondary endpoints included receptor occupancy and monocyte human leukocyte antigen-DR levels. MEASUREMENTS AND MAIN RESULTS: The treated group was older (median 62 yr treated pooled vs 46 yr placebo), and a greater percentage had more than 2 organ dysfunctions (55% treated pooled vs 25% placebo); other baseline characteristics were comparable.…

OBJECTIVES: Corticosteroids may be beneficial in sepsis, but uncertainty remains over their effects in severe influenza. This systematic review updates the current evidence regarding corticosteroids in the treatment of influenza and examines the effect of dose on outcome. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and Web of Science) and trial registries were searched to October 2018 for randomized controlled trials, quasi-experimental designs, and observational cohort studies reporting corticosteroid versus no corticosteroid treatment in individuals with influenza. STUDY SELECTION AND DATA EXTRACTION: Two researchers independently assessed studies for inclusion. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomized controlled trials) or Newcastle-Ottawa Scale (observational studies). Where appropriate, we estimated the effect of corticosteroids by random-effects meta-analyses using the generic inverse variance method. Meta-regression analysis was used to assess the association of corticosteroid dose and mortality. DATA…

OBJECTIVES: To synthesize the literature describing compliance with World Health Organization hand hygiene guidelines in ICUs, to evaluate the quality of extant research, and to examine differences in compliance levels across geographical regions, ICU types, and healthcare worker groups, observation methods, and moments (indications) of hand hygiene. DATA SOURCES: Electronic searches were conducted in August 2018 using Medline, CINAHL, PsycInfo, Embase, and Web of Science. Reference lists of included studies and related review articles were also screened. STUDY SELECTION: English-language, peer-reviewed studies measuring hand hygiene compliance by healthcare workers in an ICU setting using direct observation guided by the World Health Organization's "Five Moments for Hand Hygiene," published since 2009, were included. DATA EXTRACTION: Information was extracted on study location, research design, type of ICU, healthcare workers, measurement procedures, and compliance levels. DATA SYNTHESIS: Sixty-one studies were included. Most were conducted in high-income countries (60.7%) and in…

OBJECTIVES: To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population. DESIGN: Prospective observational study. SETTING: Fifteen ICUs worldwide. PATIENTS: Consecutive adult ICU patients with a bladder catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28- and 90-day mortality, whereas the presence of intra-abdominal hypertension on…

OBJECTIVES: To provide a concise review of the literature and data pertaining to the use of nurse practitioners and physician assistants, collectively called advanced practice providers, in ICU and acute care settings. DATA SOURCES: Detailed search strategy using the databases PubMed, Ovid MEDLINE, and the Cumulative Index of Nursing and Allied Health Literature for the time period from January 2008 to December 2018. STUDY SELECTION: Studies addressing nurse practitioner, physician assistant, or advanced practice provider care in the ICU or acute care setting. DATA EXTRACTION: Relevant studies were reviewed, and the following aspects of each study were identified, abstracted, and analyzed: study population, study design, study aims, methods, results, and relevant implications for critical care practice. DATA SYNTHESIS: Five systematic reviews, four literature reviews, and 44 individual studies were identified, reviewed, and critiqued. Of the research studies, the majority were retrospective with others being observational, quasi-experimental, or quality improvement, along with two…

OBJECTIVES: There is growing recognition that high-quality care for patients and families in the ICU requires exemplary interprofessional collaboration and communication. One important aspect is how the ICU team makes complex decisions. However, no recommendations have been published on interprofessional shared decision-making. The aim of this project is to use systematic review and normative analysis by experts to examine existing evidence regarding interprofessional shared decision-making, describe its principles and provide ICU clinicians with recommendations regarding its implementation. DATA SOURCES: We conducted a systematic review using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases and used normative analyses to formulate recommendations regarding interprofessional shared decision-making. STUDY SELECTION: Three authors screened titles and abstracts in duplicate. DATA SYNTHESIS: Four papers assessing the effect of interprofessional shared decision-making on quality of care were identified, suggesting that interprofessional shared…

OBJECTIVES: Observational studies suggest obesity is associated with sepsis survival, but these studies are small, fail to adjust for key confounders, measure body mass index at inconsistent time points, and/or use administrative data to define sepsis. To estimate the relationship between body mass index and sepsis mortality using detailed clinical data for case detection and risk adjustment. DESIGN: Retrospective cohort analysis of a large clinical data repository. SETTING: One-hundred thirty-nine hospitals in the United States. PATIENTS: Adult inpatients with sepsis meeting Sepsis-3 criteria. EXPOSURE: Body mass index in six categories: underweight (body mass index < 18.5 kg/m), normal weight (body mass index = 18.5-24.9 kg/m), overweight (body mass index = 25.0-29.9 kg/m), obese class I (body mass index = 30.0-34.9 kg/m), obese class II (body mass index = 35.0-39.9 kg/m), and obese class III (body mass index ≥ 40 kg/m). MEASUREMENTS: Multivariate logistic regression with generalized estimating equations to estimate the effect of body mass index category on short-term mortality…

OBJECTIVES: Rapid fluid resuscitation has become standard in sepsis care, despite "low-quality" evidence and absence of guidelines for populations "at risk" for volume overload. Our objectives include as follows: 1) identify predictors of reaching a 30 mL/kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) assess the impact of 30by3 and fluid dosing on clinical outcomes; 3) examine differences in perceived "at-risk" volume-sensitive populations, including end-stage renal disease, heart failure, obesity, advanced age, or with documentation of volume "overload" by bedside examination. DESIGN: Retrospective cohort study. All outcome analyses controlled for sex, end-stage renal disease, heart failure, sepsis severity (severe sepsis vs septic shock), obesity, Mortality in Emergency Department Sepsis score, and time to antibiotics. SETTING: Urban, tertiary care center between January 1, 2014, and May 31, 2017. PATIENTS: Emergency Department treated adults (age ≥18 yr; n = 1,032) with severe sepsis or septic shock. INTERVENTIONS: Administration of IV fluids by bolus.…

OBJECTIVES: This study sought to examine mortality, health-related quality of life, and physical function among sepsis survivors who developed chronic critical illness. DESIGN: Single-institution, prospective, longitudinal, observational cohort study assessing 12-month outcomes. SETTING: Two surgical/trauma ICUs at an academic tertiary medical and level 1 trauma center. PATIENTS: Adult critically ill patients that survived 14 days or longer after sepsis onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline patient characteristics and function, sepsis severity, and clinical outcomes of the index hospitalization were collected. Follow-up physical function (short physical performance battery; Zubrod; hand grip strength) and health-related quality of life (EuroQol-5D-3L, Short Form-36) were measured at 3, 6, and 12 months. Hospital-free days and mortality were determined at 12 months. We compared differences in long-term outcomes between subjects who developed chronic critical illness (≥ 14 ICU days with persistent organ dysfunction) versus those with rapid recovery. The…

OBJECTIVES: To assess-by literature review and expert consensus-workforce, workload, and burnout considerations among intensivists and advanced practice providers. DESIGN: Data were synthesized from monthly expert consensus and literature review. SETTING: Workforce and Workload section workgroup of the Academic Leaders in Critical Care Medicine Task Force. MEASUREMENTS AND MAIN RESULTS: Multidisciplinary care teams led by intensivists are an essential component of critical care delivery. Advanced practice providers (nurse practitioners and physician assistants) are progressively being integrated into ICU practice models. The ever-increasing number of patients with complex, life-threatening diseases, concentration of ICU beds in few centralized hospitals, expansion of specialty ICU services, and desire for 24/7 availability have contributed to growing intensivist staffing concerns. Such staffing challenges may negatively impact practitioner wellness, team perception of care quality, time available for teaching, and length of stay when the patient to intensivist ratio is greater than…

OBJECTIVES: To measure the impact of staged implementation of full versus partial ABCDE bundle on mechanical ventilation duration, ICU and hospital lengths of stay, and cost. DESIGN: Prospective cohort study. SETTING: Two medical ICUs within Montefiore Healthcare Center (Bronx, NY). PATIENTS: One thousand eight hundred fifty-five mechanically ventilated patients admitted to ICUs between July 2011 and July 2014. INTERVENTIONS: At baseline, spontaneous (B)reathing trials (B) were ongoing in both ICUs; in period 1, (A)wakening and (D)elirium (AD) were implemented in both full and partial bundle ICUs; in period 2, (E)arly mobilization and structured bundle (C)oordination (EC) were implemented in the full bundle (B-AD-EC) but not the partial bundle ICU (B-AD). MEASUREMENTS AND MAIN RESULTS: In the full bundle ICU, 95% patient days were spent in bed before EC (period 1). After EC was implemented (period 2), 65% of patients stood, 54% walked at least once during their ICU stay, and ICU-acquired pressure ulcers and physical restraint use decreased (period 1 vs 2: 39% vs 23% of patients; 30%…

OBJECTIVES: Most septic patients are initially encountered in the emergency department where sepsis recognition is often delayed, in part due to the lack of effective biomarkers. This study evaluated the diagnostic accuracy of peripheral blood monocyte distribution width alone and in combination with WBC count for early sepsis detection in the emergency department. DESIGN: An Institutional Review Board approved, blinded, observational, prospective cohort study conducted between April 2017 and January 2018. SETTING: Subjects were enrolled from emergency departments at three U.S. academic centers. PATIENTS: Adult patients, 18-89 years, with complete blood count performed upon presentation to the emergency department, and who remained hospitalized for at least 12 hours. A total of 2,212 patients were screened, of whom 2,158 subjects were enrolled and categorized per Sepsis-2 criteria, such as controls (n = 1,088), systemic inflammatory response syndrome (n = 441), infection (n = 244), and sepsis (n = 385), and Sepsis-3 criteria, such as control (n = 1,529), infection (n = 386), and…

OBJECTIVES: To assess the impact of early triggered palliative care consultation on the outcomes of high-risk ICU patients. DESIGN: Single-center cluster randomized crossover trial. SETTING: Two medical ICUs at Barnes Jewish Hospital. PATIENTS: Patients (n = 199) admitted to the medical ICUs from August 2017 to May 2018 with a positive palliative care screen indicating high risk for morbidity or mortality. INTERVENTIONS: The medical ICUs were randomized to intervention or usual care followed by washout and crossover, with independent assignment of patients to each ICU at admission. Intervention arm patients received a palliative care consultation from an interprofessional team led by board-certified palliative care providers within 48 hours of ICU admission. MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients (48.7%) were assigned to the intervention and 102 (51.3%) to usual care. Transition to do-not-resuscitate/do-not-intubate occurred earlier and significantly more often in the intervention group than the control group (50.5% vs 23.4%; p < 0.0001). The intervention group had…

OBJECTIVES: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, randomized, controlled study. SETTING: Thirty-three hospitals in China. PATIENTS: A total of 710 adults 18-75 years old with severe community-acquired pneumonia. INTERVENTIONS: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p =…

OBJECTIVE: To assess clinician perceptions of a machine learning-based early warning system to predict severe sepsis and septic shock (Early Warning System 2.0). DESIGN: Prospective observational study. SETTING: Tertiary teaching hospital in Philadelphia, PA. PATIENTS: Non-ICU admissions November-December 2016. INTERVENTIONS: During a 6-week study period conducted 5 months after Early Warning System 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert's helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours after the alert. MEASUREMENTS AND MAIN RESULTS: For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the first survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed the second survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The…

OBJECTIVES: Upper airway injury is a recognized complication of prolonged endotracheal intubation, yet little attention has been paid to the consequences of laryngeal injury and functional impact. The purpose of our study was to prospectively define the incidence of acute laryngeal injury and investigate the impact of injury on breathing and voice outcomes. DESIGN: Prospective cohort study. SETTING: Tertiary referral critical care center. PATIENTS: Consecutive adult patients intubated greater than 12 hours in the medical ICU from August 2017 to May 2018 who underwent laryngoscopy within 36 hours of extubation. INTERVENTIONS: Laryngoscopy following endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: One hundred consecutive patients (62% male; median age, 58.5 yr) underwent endoscopic examination after extubation. Acute laryngeal injury (i.e., mucosal ulceration or granulation tissue in the larynx) was present in 57 patients (57%). Patients with laryngeal injury had significantly worse patient-reported breathing (Clinical Chronic Obstructive Pulmonary Disease Questionnaire:…

OBJECTIVES: In patients at risk of hypoxic ischemic brain injury following cardiac arrest, we sought to: 1) characterize brain oxygenation and determine the prevalence of brain hypoxia, 2) characterize autoregulation using the pressure reactivity index and identify the optimal mean arterial pressure, and 3) assess the relationship between optimal mean arterial pressure and brain tissue oxygenation. DESIGN: Prospective interventional study. SETTING: Quaternary ICU. PATIENTS: Adult patients with return of spontaneous circulation greater than 10 minutes and a postresuscitation Glasgow Coma Scale score under 9 within 72 hours of cardiac arrest. INTERVENTIONS: All patients underwent multimodal neuromonitoring which included: 1) brain tissue oxygenation, 2) intracranial pressure, 3) jugular venous continuous oximetry, 4) regional saturation of oxygen using near-infrared spectroscopy, and 5) pressure reactivity index-based determination of optimal mean arterial pressure, lower and upper limit of autoregulation. We additionally collected mean arterial pressure, end-tidal CO2, and…

OBJECTIVES: To determine which multicenter randomized controlled trials in critically ill patients have shown that the study intervention was associated with a statistically significant reduction in mortality. Our analysis provides an update to a report published 10 years ago. DATA SOURCES: MEDLINE database and PubMed interface from inception until April 30, 2019. STUDY SELECTION: All adult multicenter randomized controlled trials that evaluated the effects of any intervention or monitoring system in critically ill patients and reported mortality as a primary or secondary outcome were included. DATA EXTRACTION: Numbers of centers and patients, type of intervention, reported mortality outcome, and rate and level of significance were extracted into predefined tables. Included randomized controlled trials were classified as reporting reduced, increased, or no effect of the intervention on mortality. Methodologic quality of trials was evaluated using the updated Consolidated Standards of Reporting Trials statement. DATA SYNTHESIS: A total of 212 trials met the inclusion criteria: 27…

OBJECTIVES: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. DESIGN: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. SETTING: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. SUBJECTS: Clinicians from 21 sites. MEASUREMENT AND MAIN RESULTS: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were…

INTRODUCTION: Ventilator settings for patients with severe acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation are currently set arbitrarily. The impact on serum and pulmonary biotrauma markers of the transition to ultra-protective ventilation settings following extracorporeal membrane oxygenation implantation, and different mechanical ventilation strategies while on extracorporeal membrane oxygenation were investigated. DESIGN: Randomized clinical trial. SETTINGS: Nine-month monocentric study. PATIENTS: Severe acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation. INTERVENTIONS: After starting extracorporeal membrane oxygenation, patients were switched to the bi-level positive airway pressure mode with 1 second of 24 cm H2O high pressure and 2 seconds of 12 cm H2O low pressure for 24 hours. A computer-generated allocation sequence randomized patients to receive each of the following three experimental steps: 1) high pressure 24 cm H2O and low pressure 20 cm H2O (very high positive end-expiratory…

OBJECTIVES: We examined the association between fluid overload and major adverse kidney events in critically ill patients requiring continuous renal replacement therapy for acute kidney injury. DESIGN: Retrospective cohort study. SETTING: ICU in a tertiary medical center. PATIENTS: Four-hundred eighty-one critically ill adults requiring continuous renal replacement therapy for acute kidney injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fluid overload was assessed as fluid balance from admission to continuous renal replacement therapy initiation, adjusted for body weight. Major adverse kidney events were defined as a composite of mortality, renal replacement therapy-dependence or inability to recover 50% of baseline estimated glomerular filtration rate (if not on renal replacement therapy) evaluated up to 90 days after discharge. Patients with fluid overload less than or equal to 10% were less likely to experience major adverse kidney events than those with fluid overload greater than 10% (71.6% vs 79.4%; p = 0.047). Multivariable logistic regression showed that fluid…

OBJECTIVES: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality. DESIGN: Observational study. SETTING: Three Indianapolis hospitals. PATIENTS: Three-hundred twenty-one critically ill delirious patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study…

OBJECTIVES: The aim was to investigate whether patients who participated in a mobility program in the ICU performed better on functional status, muscle, mobility, and respiratory assessments upon discharge than patients who received conventional physiotherapy. DESIGN: Randomized controlled trial. SETTING: Blind evaluation. PATIENTS: Adults with previous functional independence and without contraindications for mobilization were eligible. INTERVENTIONS: The intervention group participated in an early and progressive mobility program with five levels of activity. The control group underwent the conventional treatment without a preestablished routine. We evaluated functional status, level of activity, respiratory status, muscle strength, and mobility at ICU discharge. MEASUREMENTS AND MAIN RESULTS: We analyzed 49 patients in the control group and 50 patients in the intervention group. Our data showed patients with better functional status and more functionally independent patients in the intervention group compared with those in the control group (96% vs 44%; p < 0.001). The results of…

OBJECTIVES: Culture-based diagnostics represent the standard of care in septic patients, but are highly insensitive and in many cases unspecific. We recently demonstrated the general feasibility of next-generation sequencing-based diagnostics using free circulating nucleic acids (cell-free DNA) in plasma samples of septic patients. Within the presented investigation, higher performance of next-generation sequencing-based diagnostics was validated by comparison to matched blood cultures. DESIGN: A secondary analysis of a prospective, observational, single-center study. SETTING: Surgical ICU of a university hospital and research laboratory. PATIENTS: Fifty patients with septic shock, 20 uninfected patients with elective surgery as control cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 256 plasma samples of 48 septic patients at up to seven consecutive time points within the 28-day observation period, cell-free DNA was isolated and analyzed by next-generation sequencing and relevance scoring. In parallel, results from culture-based diagnostics (e.g., blood culture)…

OBJECTIVES: Sepsis-3 defines organ dysfunction as an increase in the Sequential Organ Failure Assessment score by greater than or equal to 2 points. However, some Sequential Organ Failure Assessment score components are not routinely recorded in all hospitals' electronic health record systems, limiting its utility for wide-scale sepsis surveillance. The Centers for Disease Control and Prevention recently released the Adult Sepsis Event surveillance definition that includes simplified organ dysfunction criteria optimized for electronic health records (eSOFA). We compared eSOFA versus Sequential Organ Failure Assessment with regard to sepsis prevalence, overlap, and outcomes. DESIGN: Retrospective cohort study. SETTING: One hundred eleven U.S. hospitals in the Cerner HealthFacts dataset. PATIENTS: Adults hospitalized in 2013-2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified clinical indicators of presumed infection (blood cultures and antibiotics) concurrent with either: 1) an increase in Sequential Organ Failure Assessment score by 2 or more points (Sepsis-3) or…

OBJECTIVES: Prior studies have reported that hospital-onset sepsis is associated with higher mortality rates than community-onset sepsis. Most studies, however, have used inconsistent case-finding methods and applied limited risk-adjustment for potential confounders. We used consistent sepsis criteria and detailed electronic clinical data to elucidate the epidemiology and mortality associated with hospital-onset sepsis. DESIGN: Retrospective cohort study. SETTING: 136 U.S. hospitals in the Cerner HealthFacts dataset. PATIENTS: Adults hospitalized in 2009-2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified sepsis using Centers for Disease Control and Prevention Adult Sepsis Event criteria and estimated the risk of in-hospital death for hospital-onset sepsis versus community-onset sepsis using logistic regression models. In patients admitted without community-onset sepsis, we estimated risk of death associated with hospital-onset sepsis using Cox regression models with sepsis as a time-varying covariate. Models were adjusted for baseline characteristics and…

OBJECTIVE: Cancer and its treatment are known to be important risk factors for sepsis, contributing to an estimated 12% of U.S. sepsis admissions in the 1990s. However, cancer treatment has evolved markedly over the past 2 decades. We sought to examine how cancer-related sepsis differs from non-cancer-related sepsis. DESIGN: Observational cohort. SETTING: National Readmissions Database (2013-2014), containing all-payer claims for 49% of U.S. PATIENTS: A total of 1,104,363 sepsis hospitalizations. INTERVENTIONS: We identified sepsis hospitalizations in the U.S. National Readmissions Database using explicit codes for severe sepsis, septic shock, or Dombrovskiy criteria (concomitant codes for infection and organ dysfunction). We classified hospitalizations as cancer-related versus non-cancer-related sepsis based on the presence of secondary diagnosis codes for malignancy. We compared characteristics (site of infection and organ dysfunction) and outcomes (in-hospital mortality and 30-d readmissions) of cancer-related versus non-cancer-related sepsis hospitalizations. We also completed…

OBJECTIVE: ICU survivors suffer from long-lasting physical, mental, and cognitive health impairments, also called "postintensive care syndrome". However, an overview of the effectiveness of interventions to prevent or mitigate these impairments is lacking. The aim of this study is to assess the effectiveness of nonpharmacologic interventions. DATA SOURCES: PubMed, CINAHL, PsycINFO, Embase, and Cochrane Library were systematically searched from inception until July 19, 2018. STUDY SELECTION: (Non)randomized clinical trials, controlled before-after studies, and interrupted time series were included. Outcomes of interest included patients physical, mental and cognitive outcomes, quality of life, and outcomes such as social functioning and functional status, measured after hospital discharge. DATA EXTRACTION: Two independent reviewers selected studies, extracted data, and assessed the risk of bias. Pooled mean differences and standardized mean differences were calculated using random-effect meta-analyses. DATA SYNTHESIS: After screening 17,008 articles, 36 studies, including 10 pilot…

OBJECTIVES: It is unclear if a low- or high-volume IV fluid resuscitation strategy is better for patients with severe sepsis and septic shock. DESIGN: Prospective randomized controlled trial. SETTING: Two adult acute care hospitals within a single academic system. PATIENTS: Patients with severe sepsis and septic shock admitted from the emergency department to the ICU from November 2016 to February 2018. INTERVENTIONS: Patients were randomly assigned to a restrictive IV fluid resuscitation strategy (≤ 60 mL/kg of IV fluid) or usual care for the first 72 hours of care. MEASUREMENTS AND MAIN RESULTS: We enrolled 109 patients, of whom 55 were assigned to the restrictive resuscitation group and 54 to the usual care group. The restrictive group received significantly less resuscitative IV fluid than the usual care group (47.1 vs 61.1 mL/kg; p = 0.01) over 72 hours. By 30 days, there were 12 deaths (21.8%) in the restrictive group and 12 deaths (22.2%) in the usual care group (odds ratio, 1.02; 95% CI, 0.41-2.53). There were no differences between groups in the rate of new organ failure,…

OBJECTIVES: The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure. DESIGN: Prospective cohort study. SETTING: Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital. PATIENTS: Intubated adults with acute respiratory failure having chest CT and portable chest radiograph performed within 24 hours of intubation. INTERVENTIONS: A 9-point pulmonary ultrasound examination performed at the time of intubation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients had pulmonary ultrasound, portable chest radiograph, and chest CT performed within 24 hours of intubation. Overall agreement of pulmonary ultrasound and portable chest radiograph findings with correlating lobe ("lobe-specific" agreement) on CT was 87% versus 62% (p < 0.001), respectively. Relaxing the agreement definition to a matching CT finding being present anywhere…

OBJECTIVES: Assessing gas exchange, diaphragm function, respiratory rate, and patient comfort during high-flow oxygen therapy and standard oxygen at the time of noninvasive ventilation discontinuation. DESIGN: Randomized crossover physiologic study. SETTING: Two ICUs. PATIENTS: Thirty chronic obstructive pulmonary disease patients with hypercapnic acute respiratory failure receiving noninvasive ventilation greater than 24 hours. INTERVENTIONS: All patients underwent five 30-minute trials, the first, third, and fifth trial in noninvasive ventilation, whereas the second and fourth were randomly conducted with either standard oxygen and high-flow oxygen therapy. MEASUREMENTS AND MAIN RESULTS: Diaphragm displacement and thickening fraction were determined by sonographic evaluation at the end of each trial. Arterial blood gases, respiratory rate, and patient comfort were also assessed. PaCO2 (p = 0.153) and pH (p = 0.114) were not different among trials, while PaO2 was greater in noninvasive ventilation than with both standard oxygen (p ≤ 0.005) and high-flow oxygen therapy (p ≤ 0.001).…

OBJECTIVES: Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission. DESIGN: Retrospective, multicenter, national study over an 18-year period (2000-2017). SETTING: Thirty-one French ICUs. PATIENTS: The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. MEASUREMENTS AND MAIN RESULTS: Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients…

OBJECTIVES: Classification of patients with acute respiratory distress syndrome into hyper- and hypoinflammatory subphenotypes using plasma biomarkers may facilitate more effective targeted therapy. We examined whether established subphenotypes are present not only in patients with acute respiratory distress syndrome but also in patients at risk for acute respiratory distress syndrome (ARFA) and then assessed the prognostic information of baseline subphenotyping on the evolution of host-response biomarkers and clinical outcomes. DESIGN: Prospective, observational cohort study. SETTING: Medical ICU at a tertiary academic medical center. PATIENTS: Mechanically ventilated patients with acute respiratory distress syndrome or ARFA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed longitudinal measurements of 10 plasma biomarkers of host injury and inflammation. We applied unsupervised latent class analysis methods utilizing baseline clinical and biomarker variables and demonstrated that two-class models (hyper- vs hypoinflammatory subphenotypes) offered improved fit…

OBJECTIVES: Our objective was to obtain international consensus on a set of core outcome measures that should be recorded in all clinical trials of interventions intended to modify the duration of ventilation for invasively mechanically ventilated patients in the ICU. DESIGN: A two-stage consensus process was undertaken between December 2015 and January 2018. Stage 1 included an online three-round Delphi study and three consensus meetings. Stage 2 included three consensus meetings. SETTING: The setting was international, including Europe, North and South America, Australia, Asia, and Africa. PARTICIPANTS: Organization members representing intensive care survivors and carers; nursing, allied health professionals, and critical care physicians; clinical trials groups and trial investigators; and industry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Delphi study outcomes were scored by participants from one (least important) to nine (most important). Consensus criteria for including the outcome in the core set were more than 70% of responses rating the outcome above seven and…

OBJECTIVES: To characterize renin in critically ill patients. Renin is fundamental to circulatory homeostasis and could be a useful marker of tissue-perfusion. However, diurnal variation, continuous renal replacement therapy and drug-interference could confound its use in critical care practice. DESIGN: Prospective observational study. SETTING: Single-center, mixed medical-surgical ICU in Europe. PATIENTS: Patients over 18 years old with a baseline estimated glomerular filtration rate greater than 30 mL/min/1.73 m and anticipated ICU stay greater than 24 hours. Informed consent was obtained from the patient or next-of-kin. INTERVENTIONS: Direct plasma renin was measured in samples drawn 6-hourly from arterial catheters in recumbent patients and from extracorporeal continuous renal replacement therapy circuits. Physiologic variables and use of drugs that act on the renin-angiotensin-aldosterone system were recorded prospectively. Routine lactate measurements were used for comparison. MEASUREMENTS AND MAIN RESULTS: One-hundred twelve arterial samples (n = 112) were drawn from 20…

OBJECTIVES: Prolonged emergency department to ICU waiting time may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality. DESIGN, SETTING, AND PATIENTS: We conducted a retrospective observational cohort study using data from the Dutch quality registry National Intensive Care Evaluation. Adult patients admitted to the ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation IV probability) odds ratios of emergency department to ICU time on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30-day, and 90-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 14,788…

OBJECTIVES: The aim of this study was to determine cardiac arrest- and extracorporeal membrane oxygenation-related risk factors associated with unfavorable outcomes after extracorporeal cardiopulmonary resuscitation. DESIGN: We performed an analysis of merged data from the Extracorporeal Life Support Organization and the American Heart Association Get With the Guidelines-Resuscitation registries. SETTING: A total of 32 hospitals reporting to both registries between 2000 and 2014. PATIENTS: Children younger than 18 years old who suffered in-hospital cardiac arrest and underwent extracorporeal cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 593 children included in the final cohort, 240 (40.5%) died prior to decannulation from extracorporeal membrane oxygenation and 352 (59.4%) died prior to hospital discharge. A noncardiac diagnosis and preexisting renal insufficiency were associated with increased odds of death (adjusted odds ratio, 1.85 [95% CI, 1.19-2.89] and 4.74 [95% CI, 2.06-10.9], respectively). The median time from onset of the…

OBJECTIVES: In 2014, the Tele-ICU Committee of the Society of Critical Care Medicine published an article regarding the state of ICU telemedicine, one better defined today as tele-critical care. Given the rapid evolution in the field, the authors now provide an updated review. DATA SOURCES AND STUDY SELECTION: We searched PubMed and OVID for peer-reviewed literature published between 2010 and 2018 related to significant developments in tele-critical care, including its prevalence, function, activity, and technologies. Search terms included electronic ICU, tele-ICU, critical care telemedicine, and ICU telemedicine with appropriate descriptors relevant to each sub-section. Additionally, information from surveys done by the Society of Critical Care Medicine was included given the relevance to the discussion and was referenced accordingly. DATA EXTRACTION AND DATA SYNTHESIS: Tele-critical care continues to evolve in multiple domains, including organizational structure, technologies, expanded-use case scenarios, and novel applications. Insights have been gained in economic impact and…

OBJECTIVES: Hypotension thresholds that provoke renal injury, myocardial injury, and mortality in critical care patients remain unknown. We primarily sought to determine the relationship between hypotension and a composite of myocardial injury (troponin T ≥ 0.03 ng/mL without nonischemic cause) and death up to 7 postoperative days. Secondarily, we considered acute kidney injury (creatinine concentration ≥ 0.3 mg/dL or 1.5 times baseline). DESIGN: Retrospective cohort. SETTING: Surgical ICU at an academic medical center. PATIENTS: Two-thousand eight-hundred thirty-three postoperative patients admitted to the surgical ICU. INTERVENTIONS: A Cox proportional hazard survival model was used to assess the association between lowest mean arterial pressure on each intensive care day, considered as a time-varying covariate, and outcomes. In sensitivity analyses hypotension defined as pressures less than 80 mm Hg and 70 mm Hg were also considered. MEASUREMENTS AND MAIN RESULTS: There was a strong nonlinear (quadratic) association between the lowest mean arterial pressure and the primary…

OBJECTIVES: Trauma resuscitations are complex critical care events that present patient safety-related risk. Simulation-based leadership training is thought to improve trauma care; however, there is no robust evidence supporting the impact of leadership training on clinical performance. The objective of this study was to assess the clinical impact of simulation-based leadership training on team leadership and patient care during actual trauma resuscitations. DESIGN: Randomized controlled trial. SETTING: Harborview Medical Center (level 1 trauma center). SUBJECTS: Seventy-nine second- and third-year residents were randomized and 360 resuscitations were analyzed. INTERVENTIONS: Subjects were randomized to a 4-hour simulation-based leadership training (intervention) or standard orientation (control) condition. MEASUREMENTS AND MAIN RESULTS: Participant-led actual trauma resuscitations were video recorded and coded for leadership behaviors and patient care. We used random coefficient modeling to account for the nesting effect of multiple observations within residents and to test for…

OBJECTIVES: Multiple organ dysfunction syndrome is characterized by simultaneous multiple organ failure, which is the leading cause of death in acute critically ill patients. However, what mediates multiple organ dysfunction syndrome is not fully understood. The discovery of toxic effects by extracellular histones on different individual organs strongly suggests their involvement in multiple organ dysfunction syndrome. In this study, we investigate whether circulating histones are major mediators of multiple organ dysfunction syndrome in acute critical illnesses. DESIGN: Combination of retrospective clinical studies and animal models with intervention. SETTING: ICU in a tertiary hospital and research laboratories. PATIENTS: Four hundred and twenty ICU patients, including sepsis (140), severe trauma (63), severe pancreatitis (89), and other admission diagnoses (128). LABORATORY INVESTIGATION: Cells from major organs are treated with calf thymus histones or histone-containing sera. Animal models for sepsis, trauma, and acute pancreatitis are treated with antihistone reagents.…

OBJECTIVES: To review the neurocritical care aspects of patients supported by extracorporeal membrane oxygenation, including cerebral physiology, neurologic monitoring, use of sedatives and anti-seizure medications, and prevalence and management of extracorporeal membrane oxygenation associated brain injury. DATA SOURCES: PubMed database search using relevant search terms related to neurologic complications, neurocritical care management, and brain injury management in patients with extracorporeal membrane oxygenation. STUDY SELECTION: Articles included original investigations, review articles, consensus statements and guidelines. DATA EXTRACTION: A detailed review of publications performed and relevant publications were summarized. DATA SYNTHESIS: We found no practice guidelines or management strategies for the neurocritical care of extracorporeal membrane oxygenation patients. Such patients are at high risk for hypoxic-ischemic brain injury, intracranial hemorrhage, cerebral edema, and brain death. Improving clinical outcomes will depend on better defining the neurologic…

OBJECTIVES: Septic shock carries a high mortality risk. Studies have indicated that patients with septic shock may benefit from extracorporeal membrane oxygenation. In most studies, patients exhibited shock due to myocardial dysfunction rather than distributive/vasoplegic shock. One proposed theory is that venoarterial extracorporeal membrane oxygenation alleviates a failing myocardial function. DESIGN: Retrospective observational study. SETTING: Single-center, high-volume extracorporeal membrane oxygenation unit. PATIENTS: All patients treated for septic shock between 2012 and 2017 with an age greater than 18 years old, fulfilling septic shock criteria according to "Sepsis-3" at acceptance for extracorporeal membrane oxygenation, presence of cardiocirculatory failure requiring a support equivalent to a Vasoactive Inotropic Score greater than 50 to reach a mean arterial pressure greater than 65 mm Hg despite adequate fluid resuscitation, were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-seven patients, mean age 54.7 years old, were included. Median Simplified…

OBJECTIVE: Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients. DESIGN: Retrospective observational study. SETTING: Adult surgical, anesthesiologic, and medical ICUs of a university hospital. PATIENTS: Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40…

OBJECTIVE: A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial. DESIGN: Retrospective analysis of randomized controlled clinical trial. SETTING: Multicenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis. PATIENTS: Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population. INTERVENTIONS: Random assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge. MEASUREMENTS AND MAIN RESULTS: We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We…

OBJECTIVES: As part of an improvement program targeting ICU, a national collaborative was launched to help hospitals implement patient- and family-centered care engagement initiatives. DESIGN: Ten-month quality improvement collaborative. SETTING: Guided by a national patient and family advisory group, participating teams implemented an individual project including open visitation; integrating families on rounds; establishing a patient and family advisory committee; using patient and family diaries, among others. SUBJECTS: Sixty-three adult and PICU teams from both academic and community hospitals in 34 states participated. INTERVENTIONS: Monthly team calls, quarterly webinars, newsletters, an online eCommunity, and team reporting assignments were used to facilitate project implementation. MEASUREMENTS AND MAIN RESULTS: The Family Satisfaction with Care in the ICU 24 was used to assess family satisfaction. Clinician perceptions were assessed with the Institute for Patient- and Family-Centered Care Self-Assessment Inventory. Thematic analysis was used to explore narrative data…

OBJECTIVES: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. DESIGN: Randomized, controlled, unblinded study. SETTING: Two ICUs of two university hospitals. PATIENTS: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. INTERVENTIONS: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601-16,031 U] vs 20,710 U [95% CI,…

OBJECTIVES: To examine the effect of an interdisciplinary ICU recovery program on process measures and clinical outcomes. DESIGN: A prospective, single-center, randomized pilot trial. SETTING: Academic, tertiary-care medical center. PATIENTS: Adult patients admitted to the medical ICU for at least 48 hours with a predicted risk of 30-day same-hospital readmission of at least 15%. INTERVENTIONS: Patients randomized to the ICU recovery program group were offered a structured 10-intervention program, including an inpatient visit by a nurse practitioner, an informational pamphlet, a 24 hours a day, 7 days a week phone number for the recovery team, and an outpatient ICU recovery clinic visit with a critical care physician, nurse practitioner, pharmacist, psychologist, and case manager. For patients randomized to the usual care group, all aspects of care were determined by treating clinicians. MEASUREMENTS AND MAIN RESULTS: Among the primary analysis of enrolled patients who survived to hospital discharge, patients randomized to the ICU recovery program (n = 111) and usual care (n = 121)…

OBJECTIVES: To determine the point prevalence of medication errors at the time of transition of care from an ICU to non-ICU location and assess error types and risk factors for medication errors during transition of care. DESIGN: This was a multicenter, retrospective, 7-day point prevalence study. SETTING: Fifty-eight ICUs within 34 institutions in the United States and two in the Netherlands. PATIENTS: Nine-hundred eighty-five patients transferred from an ICU to non-ICU location. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 985 patients transferred, 450 (45.7%) had a medication error occur during transition of care. Among patients with a medication error, an average of 1.88 errors per patient (SD, 1.30; range, 1-9) occurred. The most common types of errors were continuation of medication with ICU-only indication (28.4%), untreated condition (19.4%), and pharmacotherapy without indication (11.9%). Seventy-five percent of errors reached the patient but did not cause harm. The occurrence of errors varied by type and size of institution and ICU. Renal replacement therapy…

OBJECTIVES: Less than half of the thousands of children who suffer in-hospital cardiac arrests annually survive, and neurologic injury is common among survivors. Hemodynamic-directed cardiopulmonary resuscitation improves short-term survival, but its impact on longer term survival and mitochondrial respiration-a potential neurotherapeutic target-remains unknown. The primary objectives of this study were to compare rates of 24-hour survival with favorable neurologic outcome after cardiac arrest treated with hemodynamic-directed cardiopulmonary resuscitation versus standard depth-guided cardiopulmonary resuscitation and to compare brain and heart mitochondrial respiration between groups 24 hours after resuscitation. DESIGN: Randomized preclinical large animal trial. SETTING: A large animal resuscitation laboratory at a large academic children's hospital. SUBJECTS: Twenty-eight 4-week-old female piglets (8-11 kg). INTERVENTIONS: Twenty-two swine underwent 7 minutes of asphyxia followed by ventricular fibrillation and randomized treatment with either hemodynamic-directed cardiopulmonary…

OBJECTIVES: The Centers for Medicare and Medicaid Services requires hospitals to report compliance with a sepsis treatment bundle as part of its Inpatient Quality Reporting Program. We used recently released data from this program to characterize national performance on the sepsis measure, known as SEP-1. DESIGN: Cross-sectional study of United States hospitals participating in the Centers for Medicare and Medicaid Services Hospital Inpatient Quality Reporting Program linked to Centers for Medicare and Medicaid Services' Healthcare Cost Reporting Information System. SETTING: General, short-stay, acute-care hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: We examined the hospital factors associated with reporting SEP-1 data, the hospital factors associated with performance on the SEP-1 measure, and the relationship between SEP-1 performance and performance on other quality measures related to time-sensitive medical conditions. A total of 3,283 hospitals were eligible for the analysis, of which 2,851 (86.8%) reported SEP-1 performance data. SEP-1 reporting was more…

OBJECTIVES: Suspected infection and sepsis are common conditions seen among older ICU patients. Frailty has prognostic importance among critically ill patients, but its impact on outcomes and resource utilization in older patients with suspected infection is unknown. We sought to evaluate the association between patient frailty (defined as a Clinical Frailty Scale ≥ 5) and outcomes of critically ill patients with suspected infection. We also evaluated the association between frailty and the quick Sequential Organ Failure Assessment score. DESIGN: Analysis of a prospectively collected registry. SETTING: Two hospitals within a single tertiary care level hospital system between 2011 and 2016. PATIENTS: We analyzed 1,510 patients 65 years old or older (at the time of ICU admission) and with suspected infection at the time of ICU admission. Of these, 507 (33.6%) were categorized as "frail" (Clinical Frailty Scale ≥ 5). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in-hospital mortality. A total of 558 patients (37.0%) died in-hospital. Frailty was associated…

OBJECTIVES: We assessed the growth, distribution, and characteristics of pediatric intensive care in 2016. DESIGN: Hospitals with PICUs were identified from prior surveys, databases, online searching, and clinician networking. A structured web-based survey was distributed in 2016 and compared with responses in a 2001 survey. SETTING: PICUs were defined as a separate unit, specifically for the treatment of children with life-threatening conditions. PICU hospitals contained greater than or equal to 1 PICU. SUBJECTS: Physician medical directors and nurse managers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PICU beds per pediatric population (< 18 yr), PICU bed distribution by state and region, and PICU characteristics and their relationship with PICU beds were measured. Between 2001 and 2016, the U.S. pediatric population grew 1.9% to greater than 73.6 million children, and PICU hospitals decreased 0.9% from 347 to 344 (58 closed, 55 opened). In contrast, PICU bed numbers increased 43% (4,135 to 5,908 beds); the median PICU beds per PICU hospital rose from 9 to 12…

OBJECTIVES: To describe the most common serious adverse effects and organ toxicities associated with emerging therapies for cancer that may necessitate admission to the ICU. DATA SOURCES AND STUDY SELECTION: PubMed and Medline search of relevant articles in English on the management of adverse effects of immunotherapy for cancer. DATA EXTRACTION AND DATA SYNTHESIS: Targeted therapies including tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors, and immune effector cell therapy have improved the outcome and quality of life of patients with cancer. However, severe and life-threatening side effects can occur. These toxicities include infusion or hypersensitivity reactions, cytokine release syndrome, pulmonary, cardiac, renal, hepatic, and neurologic toxicities, hemophagocytic lymphohistiocytosis, opportunistic infections, and endocrinopathies. Cytokine release syndrome is the most common serious toxicity after administration of monoclonal antibodies and immune effector cell therapies. Most of the adverse events from immunotherapy results from an exaggerated T-cell…

OBJECTIVES: Studies have shown contradicting results on the association of nursing workload and mortality. Most of these studies expressed workload as patients per nurse ratios; however, this does not take into account that some patients require more nursing time than others. Nursing time can be quantified by tools like the Nursing Activities Score. We investigated the association of the Nursing Activities Score per nurse ratio, respectively, the patients per nurse ratio with in-hospital mortality in ICUs. DESIGN: Retrospective analysis of the National Intensive Care Evaluation database. SETTING: Fifteen Dutch ICUs. PATIENTS: All ICU patients admitted to and registered ICU nurses working at 15 Dutch ICUs between January 1, 2016, and January 1, 2018, were included. The association of mean or day 1 patients per nurse ratio and Nursing Activities Score per nurse ratio with in-hospital mortality was analyzed using logistic regression models. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nursing Activities Score per nurse ratio greater than 41 for both mean Nursing Activities Score…

OBJECTIVES: To evaluate the effects on quality and efficiency of implementation of the advanced practice provider in critical care. DATA SOURCES: PubMed, Embase, The Cochrane Library, and CINAHL were used to extract articles regarding advanced practice providers in critical care. STUDY SELECTION: Articles were selected when reporting a comparison between advanced practice providers and physician resident/fellows regarding the outcome measures of mortality, length of stay, or specific tasks. Descriptive studies without comparison were excluded. The methodological quality of the included studies was rated using the Newcastle-Ottawa scale. The agreement between the reviewers was assessed with Cohen's kappa. A meta-analysis was constructed on mortality and length of stay. DATA EXTRACTION AND SYNTHESIS: One-hundred fifty-six studies were assessed by full text. Thirty comparative cohort studies were selected and analyzed. These compared advanced practice providers with physician resident/fellows. All studies comprised adult intensive care. Most of the included studies showed a moderate to…

OBJECTIVES: Lung CT is the reference imaging technique for acute respiratory distress syndrome, but requires transportation outside the intensive care and x-ray exposure. Lung ultrasound is a promising, inexpensive, radiation-free, tool for bedside imaging. Aim of the present study was to compare the global and regional diagnostic accuracy of lung ultrasound and CT scan. DESIGN: A prospective, observational study. SETTING: Intensive care and radiology departments of a University hospital. PATIENTS: Thirty-two sedated, paralyzed acute respiratory distress syndrome patients (age 65 ± 14 yr, body mass index 25.9 ± 6.5 kg/m, and PaO2/FIO2 139 ± 47). INTERVENTIONS: Lung CT scan and lung ultrasound were performed at positive end-expiratory pressure 5 cm H2O. A standardized assessment of six regions per hemithorax was used; each region was classified for the presence of normal aeration, alveolar-interstitial syndrome, consolidation, and pleural effusion. Agreement between the two techniques was calculated, and diagnostic variables were assessed for lung ultrasound using lung CT as a…

OBJECTIVES: The objective of this study was to associate ventilation rates during in-hospital cardiopulmonary resuscitation with 1) arterial blood pressure during cardiopulmonary resuscitation and 2) survival outcomes. DESIGN: Prospective, multicenter observational study. SETTING: Pediatric and pediatric cardiac ICUs of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Intubated children (≥ 37 wk gestation and < 19 yr old) who received at least 1 minute of cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure and ventilation rate (breaths/min) were manually extracted from arterial line and capnogram waveforms. Guideline rate was defined as 10 ± 2 breaths/min; high ventilation rate as greater than or equal to 30 breaths/min in children less than 1 year old, and greater than or equal to 25 breaths/min in older children. The primary outcome was survival to hospital discharge. Regression models using Firth penalized likelihood assessed the association between ventilation rates and outcomes. Ventilation rates were…

OBJECTIVES: To determine if higher fresh frozen plasma and platelet to packed RBC ratios are associated with lower 24-hour mortality in bleeding pediatric trauma patients. DESIGN: Retrospective cohort study using the Pediatric Trauma Quality Improvement Program Database from 2014 to 2016. SETTING: Level I and II pediatric trauma centers participating in the Trauma Quality Improvement Program PATIENTS:: Injured children (≤ 14 yr old) who received massive transfusion (≥ 40 mL/kg total blood products in 24 hr). Of 123,836 patients, 590 underwent massive transfusion, of which 583 met inclusion criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ratios of fresh frozen plasma:packed RBC and platelet:packed RBC. Of the 583 patients, 60% were male and the median age was 5 years (interquartile range, 2-10 yr). Overall mortality was 19.7% (95% CI, 16.6-23.2%) at 24 hours. There was 51% (adjusted relative risk, 0.49; 95% CI, 0.27-0.87; p = 0.02) and 40% (adjusted relative risk, 0.60; 95% CI, 0.39-0.92; p = 0.02) lower risk of death at 24 hours for the high (≥ 1:1) and medium (≥ 1:2…

OBJECTIVES: The effects of vitamin C administration on clinical outcome in critically ill patients remain controversial. DATA SOURCES: Online databases were searched up to October 1, 2018. STUDY SELECTION: We included randomized controlled trials on the use of vitamin C (any regimen) in adult critically ill patients versus placebo or no therapy. DATA EXTRACTION: Risk ratio for dichotomous outcome and standardized mean difference for continuous outcome with 95% CI were calculated using random-effects model meta-analysis. DATA SYNTHESIS: Forty-four randomized studies, 16 performed in ICU setting (2,857 patients) and 28 in cardiac surgery (3,598 patients), published between 1995 and 2018, were included in the analysis. In ICU patients, vitamin C administration was not associated with a difference in mortality (risk ratio, 0.90; 95% CI, 0.74-1.10; p = 0.31), acute kidney injury, ICU or hospital length of stay compared with control. In cardiac surgery, vitamin C was associated to a reduction in postoperative atrial fibrillation (risk ratio, 0.64; 95% CI, 0.52-0.78; p < 0.0001), ICU stay…

OBJECTIVES: Daily ICU interprofessional team rounds, which incorporate the ICU Liberation ("A" for Assessment, Prevention, and Manage Pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, support both the care coordination and regular provider communication necessary for Bundle execution. This article describes evidence-based practices for conducting effective interprofessional team rounds in the ICU to improve Bundle performance. DESIGN: Best practice synthesis. METHODS: The authors, each extensively involved in the Society of Critical Care Medicine's ICU Liberation Campaign, reviewed the pertinent literature to identify how ICU interprofessional team rounds can be optimized to increase ICU Liberation adherence. RESULTS: Daily ICU interprofessional team rounds that foster ICU Liberation Bundle use support both care coordination and regular provider communication within and…

OBJECTIVES: Visual assessment of the electroencephalogram by experienced clinical neurophysiologists allows reliable outcome prediction of approximately half of all comatose patients after cardiac arrest. Deep neural networks hold promise to achieve similar or even better performance, being more objective and consistent. DESIGN: Prospective cohort study. SETTING: Medical ICU of five teaching hospitals in the Netherlands. PATIENTS: Eight-hundred ninety-five consecutive comatose patients after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Continuous electroencephalogram was recorded during the first 3 days after cardiac arrest. Functional outcome at 6 months was classified as good (Cerebral Performance Category 1-2) or poor (Cerebral Performance Category 3-5). We trained a convolutional neural network, with a VGG architecture (introduced by the Oxford Visual Geometry Group), to predict neurologic outcome at 12 and 24 hours after cardiac arrest using electroencephalogram epochs and outcome labels as inputs. Output of the network was the probability of good…

OBJECTIVES: To compare the passive leg raising test ability to predict fluid responsiveness in patients with and without intra-abdominal hypertension. DESIGN: Observational study. SETTING: Medical ICU. PATIENTS: Mechanically ventilated patients monitored with a PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany) in whom fluid expansion was planned, with (intra-abdominal hypertension+) and without (intra-abdominal hypertension-) intra-abdominal hypertension, defined by an intra-abdominal pressure greater than or equal to 12 mm Hg (bladder pressure). INTERVENTIONS: We measured the changes in cardiac index during passive leg raising and after volume expansion. The passive leg raising test was defined as positive if it increased cardiac index greater than or equal to 10%. Fluid responsiveness was defined by a fluid-induced increase in cardiac index greater than or equal to 15%. MEASUREMENTS AND MAIN RESULTS: We included 60 patients, 30 without intra-abdominal hypertension (15 fluid responders and 15 fluid nonresponders) and 30 with intra-abdominal hypertension (21 fluid…

OBJECTIVES: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. "Flow-controlled ventilation", providing a constant expiratory flow, has been suggested as a new lung-protective ventilation strategy. The aim of this study was to test whether flow-controlled ventilation attenuates lung injury in an animal model of acute respiratory distress syndrome. DESIGN: Preclinical, randomized controlled animal study. SETTING: Animal research facility. SUBJECTS: Nineteen German landrace hybrid pigs. INTERVENTION: Flow-controlled ventilation (intervention group) or volume-controlled ventilation (control group) with identical tidal volume (7 mL/kg) and positive end-expiratory pressure (9 cm H2O) after inducing acute respiratory distress syndrome with oleic acid. MEASUREMENTS AND MAIN RESULTS: PaO2 and PaCO2, minute volume, tracheal pressure, lung aeration measured via CT, alveolar wall thickness, cell infiltration, and surfactant protein A…

OBJECTIVES: Venovenous extracorporeal membrane oxygenation is indicated in patients with severe refractory acute respiratory failure. Venous thrombosis due to indwelling catheters is a frequent complication. The aim of this study was to analyze the incidence of cannula-related thrombosis and its risk factors after venovenous extracorporeal membrane oxygenation. DESIGN: Retrospective observational study. SETTING: A medical ICU at the University Hospital Regensburg. PATIENTS: We analyzed consecutive patients with severe respiratory failure (PaO2/FIO2 < 85 mm Hg and/or respiratory acidosis with pH < 7.25) who were successfully treated with venovenous extracorporeal membrane oxygenation in a medical ICU between 2010 and 2017. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: After extracorporeal membrane oxygenation weaning, duplex sonography or CT was conducted to detect cannula-related thrombosis. Thrombosis was classified as a large thrombosis by vein occlusion of greater than 50%. The incidence of thrombosis was correlated with risk factors such as coagulation variables (mean…

OBJECTIVES: To critically assess available high-level clinical studies regarding RBC transfusion strategies, with a focus on hemoglobin transfusion thresholds in the ICU. DATA SOURCES: Source data were obtained from a PubMed literature review. STUDY SELECTION: English language studies addressing RBC transfusions in the ICU with a focus on the most recent relevant studies. DATA EXTRACTION: Relevant studies were reviewed and the following aspects of each study were identified, abstracted, and analyzed: study design, methods, results, and implications for critical care practice. DATA SYNTHESIS: Approximately 30-50% of ICU patients receive a transfusion during their hospitalization with anemia being the indication for 75% of transfusions. A significant body of clinical research evidence supports using a restrictive transfusion strategy (e.g., hemoglobin threshold < 7 g/dL) compared with a more liberal approach (e.g., hemoglobin threshold < 10 g/dL). A restrictive strategy (hemoglobin < 7 g/dL) is recommended in patients with sepsis and gastrointestinal bleeds. A slightly higher…

OBJECTIVES: Assess patient outcomes in patients with suspected infection and the cost-effectiveness of implementing a quality improvement program. DESIGN, SETTING, AND PARTICIPANTS: We conducted an observational single-center study of 13,877 adults with suspected infection between March 1, 2014, and July 31, 2017. The 18-month period before and after the effective date for mandated reporting of the sepsis bundle was examined. The Sequential Organ Failure Assessment score and culture and antibiotic orders were used to identify patients meeting Sepsis-3 criteria from the electronic health record. INTERVENTIONS: The following interventions were performed as follows: 1) multidisciplinary sepsis committee with sepsis coordinator and data abstractor; 2) education campaign; 3) electronic health record tools; and 4) a Modified Early Warning System. MAIN OUTCOMES AND MEASURES: Primary health outcomes were in-hospital death and length of stay. The incremental cost-effectiveness ratio was calculated and the empirical 95% CI for the incremental cost-effectiveness ratio was estimated from 5,000…

OBJECTIVES: To understand the impact of mild-moderate and severe acute kidney injury in patients with acute respiratory distress syndrome. DESIGN: Secondary analysis of the "Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure", an international prospective cohort study of patients with severe respiratory failure. SETTING: Four-hundred fifty-nine ICUs from 50 countries across five continents. SUBJECTS: Patients with a glomerular filtration rate greater than 60 mL/min/1.73 m prior to admission who fulfilled criteria of acute respiratory distress syndrome on day 1 and day 2 of acute hypoxemic respiratory failure. INTERVENTIONS: Patients were categorized based on worst serum creatinine or urine output into: 1) no acute kidney injury (serum creatinine < 132 µmol/L or urine output ≥ 0.5 mL/kg/hr), 2) mild-moderate acute kidney injury (serum creatinine 132-354 µmol/L or minimum urine output between 0.3 and 0.5mL/kg/hr), or 3) severe acute kidney injury (serum creatinine > 354 µmol/L or renal replacement therapy or minimum urine output < 0.3…

OBJECTIVES: Cellular Immunotherapy for Septic Shock is the first-in-human clinical trial evaluating allogeneic mesenchymal stem/stromal cells in septic shock patients. Here, we sought to determine whether plasma cytokine profiles may provide further information into the safety and biological effects of mesenchymal stem/stromal cell treatment, as no previous study has conducted a comprehensive analysis of circulating cytokine levels in critically ill patients treated with mesenchymal stem/stromal cells. DESIGN: Phase 1 dose-escalation trial. PATIENTS: The interventional cohort (n = 9) of septic shock patients received a single dose of 0.3, 1.0, or 3.0 million mesenchymal stem/stromal cells/kg body weight (n = 3 per dose). The observational cohort received no mesenchymal stem/stromal cells (n = 21). INTERVENTIONS: Allogeneic bone marrow-derived mesenchymal stem/stromal cells. MEASUREMENTS AND MAIN RESULTS: Serial plasma samples were collected at study baseline prior to mesenchymal stem/stromal cell infusion (0 hr), 1 hour, 4 hours, 12 hours, 24 hours, and 72 hours after mesenchymal…

OBJECTIVES: To assess the feasibility and efficacy of implementing "Family Care Rituals" as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members. DESIGN: Prospective, before-and-after intervention evaluation. SETTING: Two U.S. academic medical ICU's, and one Italian academic medical/surgical ICU. SUBJECTS: Family members of patients who had an attending predicted ICU mortality of greater than 30% within the first 24 hours of admission. INTERVENTIONS: A novel intervention titled "Family Care Rituals" during which, following a baseline observation period, family members enrolled in the intervention phase were given an informational booklet outlining opportunities for engagement in care of the patient during their ICU stay. MEASUREMENTS AND MAIN RESULTS: Primary outcome was symptoms of post-traumatic stress disorder in family members 90 days after patient death or ICU discharge. Secondary outcomes included symptoms of depression, anxiety, and family satisfaction.…

OBJECTIVES: After traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome. DESIGN: Post hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID study (ClinicalTrials.gov: NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as "ictal-interictal continuum"; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta…

OBJECTIVES: We sought to characterize 1) the difference in the diffusion gradient of cellular oxygen delivery and 2) the presence of diffusion limitation physiology in hypoxic-ischemic brain injury patients with brain hypoxia, as defined by parenchymal brain tissue oxygen tension less than 20 mm Hg versus normoxia (brain tissue oxygen tension > 20 mm Hg). DESIGN: Post hoc subanalysis of a prospective study in hypoxic-ischemic brain injury patients dichotomized into those with brain hypoxia versus normoxia. SETTING: Quaternary ICU. PATIENTS: Fourteen adult hypoxic-ischemic brain injury patients after cardiac arrest. INTERVENTIONS: Patients underwent monitoring with brain oxygen tension, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and jugular venous bulb oxygen saturation. Data were recorded in real time at 300Hz into the ICM+ monitoring software (Cambridge University Enterprises, Cambridge, United Kingdom). Simultaneous arterial and jugular venous bulb blood gas samples were recorded prospectively. MEASUREMENTS AND MAIN RESULTS: Both the normoxia and…

OBJECTIVES: To assess the efficacy of ramelteon in preventing delirium, an acute neuropsychiatric condition associated with increased morbidity and mortality, in the perioperative, ICU setting. DESIGN: Parallel-arm, randomized, double-blinded, placebo-controlled trial. SETTING: Academic medical center in La Jolla, California. PATIENTS: Patients greater than or equal to 18 years undergoing elective pulmonary thromboendarterectomy. INTERVENTIONS: Ramelteon 8 mg or matching placebo starting the night prior to surgery and for a maximum of six nights while in the ICU. MEASUREMENTS AND MAIN RESULTS: Incident delirium was measured twice daily using the Confusion Assessment Method-ICU. The safety outcome was coma-free days assessed by the Richmond Agitation-Sedation Scale. One-hundred twenty participants were enrolled and analysis completed in 117. Delirium occurred in 22 of 58 patients allocated to placebo versus 19 of 59 allocated to ramelteon (relative risk, 0.8; 95% CI, 0.5-1.4; p = 0.516). Delirium duration, as assessed by the number of delirium-free days was also similar in both…

OBJECTIVES: Past studies have examined numerous components of tele-ICU care to decipher which elements increase patient and institutional benefit. These factors include review of the patient chart within 1 hour, frequent collaborative data reviews, mechanisms for rapid laboratory/alert review, and interdisciplinary rounds. Previous meta-analyses have found an overall ICU mortality benefit implementing tele-ICU, however, subgroup analyses found few differences. The purpose of this systematic review and meta-analysis was to explore the effect of tele-ICU implementation with regard to ICU mortality and explore subgroup differences via observed and predicted mortality. DATA SOURCES: We searched PubMed, Cochrane Library, Embase, and European Society of Intensive Care Medicine for articles related to tele-ICU from inception to September 18, 2018. STUDY SELECTION: We included all trials meeting inclusion criteria which looked at the effect of tele-ICU implementation on ICU mortality. DATA EXTRACTION: We abstracted study characteristics, patient characteristics, severity of illness scores,…

OBJECTIVES: Critical care ultrasonography has become established within ICUs as a diagnostic tool and to guide management strategies and practical procedures. Following an international consensus statement in 2011, various national professional societies and organizations have sought to develop and deliver training program. The aim of this review was to assess the similarities and differences among these postgraduate intensive care/critical care training program. DATA SOURCES: A systematic review was performed in two steps. First, we searched medical databases and national societies' websites for documents meeting predefined inclusion criteria. If not found, professionals related to critical care ultrasonography were contacted. DATA EXTRACTION: Data were extracted independently by two authors. Analyses were conducted on general training requirements as well as specific competencies defined in the documents. DATA SYNTHESIS: Eight national program from seven countries were identified from a total of 25 countries; all identified program have defined competencies for core critical care…

OBJECTIVES: To determine the total numbers of privileged and full-time equivalent intensivists in acute care hospitals with intensivists and compare the characteristics of hospitals with and without intensivists. DESIGN: Retrospective analysis of the American Hospital Association Annual Survey Database (Fiscal Year 2015). SETTING: Two-thousand eight-hundred fourteen acute care hospitals with ICU beds. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 2,814 acute care hospitals studied, 1,469 (52%) had intensivists and 1,345 (48%) had no intensivists. There were 28,808 privileged and 19,996 full-time equivalent intensivists in the 1,469 hospitals with intensivists. In these hospitals, the median (25-75th percentile) numbers of privileged and full-time equivalent intensivists were 11 (5-24) and 7 (2-17), respectively. Compared with hospitals without intensivists, hospitals with privileged intensivists were primarily located in metropolitan areas (91% vs 50%; p < 0.001) and at the aggregate level had nearly thrice the number of hospital beds (403,522 [75%] vs…

OBJECTIVES: To determine the association between targeted temperature management goal temperature of 33°C versus 36°C and neurologic outcome after out-of-hospital cardiac arrest. DESIGN: This was a retrospective, before-and-after, cohort study. SETTING: Urban, academic, level 1 trauma center from 2010 to 2017. PATIENTS: Adults with nontraumatic out-of-hospital cardiac arrest who received targeted temperature management. INTERVENTIONS: Our primary exposure was targeted temperature management goal temperature, which was changed from 33°C to 36°C in April of 2014 at the study hospital. Primary outcome was neurologically intact survival to discharge. Secondary outcomes included hospital mortality and care processes. MEASUREMENTS AND MAIN RESULTS: Of 782 out-of-hospital cardiac arrest patients transported to the study hospital, 453 (58%) received targeted temperature management. Of these, 258 (57%) were treated during the 33°C period (targeted temperature management 33°C) and 195 (43%) were treated during the 36°C period (targeted temperature management 36°C). Patients treated during…

OBJECTIVES: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. DESIGN: Multicenter, prospective cohort study. SETTING: The emergency department and ICUs of 15 medical centers. PATIENTS: Mechanically ventilated adult emergency department patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI,…

OBJECTIVES: Combined with devices that enhance venous return out of the brain and into the thorax, preclinical outcomes are improved significantly using a synergistic bundled approach involving mild elevation of the head and chest during cardiopulmonary resuscitation. The objective here was to confirm clinical safety/feasibility of this bundled approach including use of mechanical cardiopulmonary resuscitation provided at a head-up angle. DESIGN: Quarterly tracking of the frequency of successful resuscitation before, during, and after the clinical introduction of a bundled head-up/torso-up cardiopulmonary resuscitation strategy. SETTING: 9-1-1 response system for a culturally diverse, geographically expansive, populous jurisdiction. PATIENTS: All 2,322 consecutive out-of-hospital cardiac arrest cases (all presenting cardiac rhythms) were followed over 3.5 years (January 1, 2014, to June 30, 2017). INTERVENTIONS: In 2014, 9-1-1 crews used LUCAS (Physio-Control Corporation, Redmond, WA) mechanical cardiopulmonary resuscitation and impedance threshold devices for out-of-hospital…

OBJECTIVES: To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients. DESIGN: Retrospective sub-analysis. SETTING: Fifty-nine ICUs in Japan, from January 2016 to March 2017. PATIENTS: Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature < 36°C, 36-38°C, > 38°C), using the core body temperature at ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compliance with the bundles proposed in the Surviving Sepsis Campaign Guidelines 2012, in-hospital mortality, disposition after discharge, and the number of ICU and ventilator-free days were evaluated. Of 1,143 enrolled patients, 127, 565, and 451 were categorized as having body temperature less than 36°C, 36-38°C, and greater than 38°C, respectively. Hypothermia-body temperature less than 36°C-was observed in 11.1% of patients. Patients with hypothermia were significantly older than those with a body temperature of 36-38°C or greater than 38°C and had a lower body mass index and…

OBJECTIVES: Epigenetic alterations are an important regulator of gene expression in health and disease; however, epigenetic data in sepsis are lacking. To demonstrate proof of concept and estimate effect size, we performed the first epigenome-wide methylation analysis of whole blood DNA samples from a cohort of septic and nonseptic critically ill patients. DESIGN: A nested case-control study using genomic DNA isolated from whole blood from septic (n = 66) and nonseptic (n = 68) critically ill patients on "Day 1" of ICU admission. Methylation patterns were identified using Illumina 450K arrays with percent methylation expressed as β values. After quality control, 134 participants and 414,818 autosomal cytosine-phosphate-guanine sites were used for epigenome-wide methylation analyses. SETTING: Tertiary care hospitals. SUBJECTS: Critically ill septic and nonseptic patients. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: A total of 668 differentially methylated regions corresponding to 443 genes were identified. Known sepsis-associated genes included complement…

OBJECTIVES: Tracheostomy and dysphagia often coexist during critical illness; however, given the patient's medical complexity, understanding the evidence to optimize swallowing assessment and intervention is challenging. The objective of this scoping review is to describe and explore the literature surrounding swallowing and tracheostomy in the acute care setting. DATA SOURCES: Eight electronic databases were searched from inception to May 2017 inclusive, using a search strategy designed by an information scientist. We conducted manual searching of 10 journals, nine gray literature repositories, and forward and backward citation chasing. STUDY SELECTION: Two blinded reviewers determined eligibility according to inclusion criteria: English-language studies reporting on swallowing or dysphagia in adults (≥ 17 yr old) who had undergone tracheostomy placement while in acute care. Patients with head and/or neck cancer diagnoses were excluded. DATA EXTRACTION: We extracted data using a form designed a priori and conducted descriptive analyses. DATA SYNTHESIS: We identified 6,396…

OBJECTIVES: Decreased urine output and/or increased serum creatinine may herald the development of acute kidney injury or reflect normal physiology. In this secondary analysis of the Sapphire study, we examined biomarkers of cell cycle arrest in the settings of oliguria and/or azotemia to improve risk assessment when used with conventional indices in predicting severe acute kidney injury (Kidney Disease: Improving Global Outcomes 3 defined by the need for renal replacement therapy or changes in urine output, serum creatinine or both) or death. DESIGN: Prospective, international, Sapphire study. SETTING: Academic Medical Center. PATIENTS: Patients without acute kidney injury Kidney Disease: Improving Global Outcomes stage 2 or 3. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint being development of severe acute kidney injury or death within 1 week. Secondary analysis examined the relationship between tissue inhibitor of metalloproteinases-2 ([TIMP-2]) and insulin growth factor binding protein 7 ([IGFBP7]) and 9-month death or dialysis conditioned on…

OBJECTIVES: Research indicates that the increasing population of over 25 million people in the United States who have limited English proficiency experience differences in decision-making and subsequent care at end of life in the ICU when compared with the general population. The objective of this study was to assess the perceptions of healthcare team members about the factors that influence discussions and decision-making about end of life for patients and family members with limited English proficiency in the ICU. DESIGN: Qualitative study using semistructured interviews with ICU physicians, nurses, and interpreters. SETTING: Three ICUs at Mayo Clinic Rochester. SUBJECTS: Sixteen ICU physicians, 12 ICU nurses, and 12 interpreters. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We conducted 40 semistructured interviews. We identified six key differences in end-of-life decision-making for patients with limited English proficiency compared with patients without limited English proficiency: 1) clinician communication is modified and less frequent; 2) clinician ability to assess…

OBJECTIVES: Cost-effectiveness analyses are increasingly used to aid decisions about resource allocation in healthcare; this practice is slow to translate into critical care. We sought to identify and summarize original cost-effectiveness studies presenting cost per quality-adjusted life year, incremental cost-effectiveness ratios, or cost per life-year ratios for treatments used in ICUs. DESIGN: We conducted a systematic search of the English-language literature for cost-effectiveness analyses published from 1993 to 2018 in critical care. Study quality was assessed using the Drummond checklist. SETTING: Critical care units. PATIENTS OR SUBJECTS: Critical care patients. INTERVENTIONS: Identified studies with cost-effectiveness analyses. MEASUREMENTS AND MAIN RESULTS: We identified 97 studies published through 2018 with 156 cost-effectiveness ratios. Reported incremental cost-effectiveness ratios ranged from -$119,635 (hypothetical cohort of patients requiring either intermittent or continuous renal replacement therapy) to $876,539 (data from an acute renal failure study in which…

OBJECTIVES: Systematically review evidence examining association between preadmission socioeconomic position and physical function, health-related quality of life and survival following critical illness. DATA SOURCES: Four electronic databases (MEDLINE, Embase, CINAHL, CENTRAL) and personal libraries were searched. Reference lists of eligible articles were cross-checked. STUDY SELECTION: Primary quantitative studies reporting association between socioeconomic position and physical function, health-related quality of life, or survival of adults admitted to the ICU were included. DATA EXTRACTION: Performed by two reviewers independently in duplicate using a prepiloted data extraction form. Quality appraisal was completed by two reviewers independently in duplicate using standardized algorithms and checklists. The Preferred Reporting Items for Systematic Reviews guidelines were followed. DATA SYNTHESIS: From 1,799 records, 10 studies were included, one examining association of socioeconomic position with health-related quality of life and five with survival. Four studies accounted for…

OBJECTIVES: To characterize the prevalence, incidence, and temporal evolution of thrombocytopenia (platelets < 100 × 10/L) in septic shock and to investigate the independent association of thrombocytopenia on clinical outcomes. DESIGN: Retrospective, propensity-matched, cohort study. SETTING: Two academic ICUs in Winnipeg, Canada. PATIENTS: Nine-hundred eighty adult patients diagnosed with septic shock between 2007 and 2012. INTERVENTIONS: Propensity-matched cohort analysis and Cox proportional hazard model evaluating thrombocytopenia over time. MEASUREMENTS AND MAIN RESULTS: Of 980 adults, 165 patients (16.8%) had thrombocytopenia at ICU admission (prevalent), whereas 271 (27.7%) developed thrombocytopenia during ICU admission (incident). Among patients with incident thrombocytopenia, the median time from ICU admission to thrombocytopenia was 2 days (interquartile range, 1-3 d). Among survivors, the median time from incident thrombocytopenia to platelet recovery was 6 days (interquartile range, 4-8 d). The median time from liberation of vasopressors to recovery of platelets…

OBJECTIVES: Elevated intracranial pressure and inadequate cerebral perfusion pressure may contribute to poor outcomes in hypertensive intraventricular hemorrhage. We characterized the occurrence of elevated intracranial pressure and low cerebral perfusion pressure in obstructive intraventricular hemorrhage requiring extraventricular drainage. DESIGN: Prospective observational cohort. SETTING: ICUs of 73 academic hospitals. PATIENTS: Four hundred ninety-nine patients enrolled in the CLEAR III trial, a multicenter, randomized study to determine if extraventricular drainage plus intraventricular alteplase improved outcome versus extraventricular drainage plus saline. INTERVENTIONS: Intracranial pressure and cerebral perfusion pressure were recorded every 4 hours, analyzed over a range of thresholds, as single readings or spans (≥ 2) of readings after adjustment for intracerebral hemorrhage severity. Impact on 30- and 180-days modified Rankin Scale scores was assessed, and receiver operating curves were analyzed to identify optimal thresholds. MEASUREMENTS AND MAIN RESULTS: Of 21,954…

OBJECTIVES: To assess the attitudes of practitioners with respect to net ultrafiltration prescription and practice among critically ill patients with acute kidney injury treated with renal replacement therapy. DESIGN: Multinational internet-assisted survey. SETTING: Critical care practitioners involved with 14 societies in 80 countries. SUBJECTS: Intervention: MEASUREMENT AND MAIN RESULTS:: Of 2,567 practitioners who initiated the survey, 1,569 (61.1%) completed the survey. Most practitioners were intensivists (72.7%) with a median duration of 13.2 years of practice (interquartile range, 7.2-22.0 yr). Two third of practitioners (71.0%; regional range, 55.0-95.5%) reported using continuous renal replacement therapy with a net ultrafiltration rate prescription of median 80.0 mL/hr (interquartile range, 49.0-111.0 mL/hr) for hemodynamically unstable and a maximal rate of 299.0 mL/hr (interquartile range, 200.0-365.0 mL/hr) for hemodynamically stable patients, with regional variation. Only a third of practitioners (31.5%; range, 13.7-47.8%) assessed hourly net fluid balance during…

OBJECTIVES: Increasingly, patients admitted to an ICU survive to hospital discharge; many with ongoing medical needs. The full impact of an ICU admission on an individual's resource utilization and survivorship trajectory in the United States is not clear. We sought to compare healthcare utilization among ICU survivors in each year surrounding an ICU admission. DESIGN: Retrospective cohort of patients admitted to an ICU during one calendar year (2012) in a multipayer healthcare system. We assessed mortality, hospital readmissions (categorized by ambulatory care sensitive conditions and emergency department), and outpatient visits. We compared the proportion of patients with visits during the pre-ICU year versus the post-ICU year. PATIENTS: People admitted to an Intermountain healthcare ICU for greater than 48 hours in the year 2012 INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: Among 4,074 ICU survivors, 45% had increased resource utilization. Readmission rates at 30-day, 90-day, and 1-year were 15%, 26%, and 43%. The proportion of patients with a hospital admission increased…

OBJECTIVES: Acute kidney injury is a common complication of major surgery. However, acute kidney injury occurring within the first 48 hours after surgery (early acute kidney injury) and therefore likely related to the surgery itself is possibly different from acute kidney injury occurring after 48 hours (late acute kidney injury). The aim of this study was to describe the epidemiology and identify differences in risk factors and outcomes between early and late acute kidney injury following major surgery. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center. PATIENTS: Patients admitted to ICU following noncardiac major surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data from 3,499 patients and defined acute kidney injury according to full Kidney Disease: Improving Global Outcomes criteria and classified as early (48 hr or less) or late (> 48 hr to 7 d) based on time from surgery. Separate multivariable logistic regression models were fit to identify risk factors of early acute kidney injury compared with no acute kidney injury and risk…

OBJECTIVES: There has been multiple advances in the management of acute respiratory distress syndrome, but the temporal trends in acute respiratory distress syndrome-related mortality are not well known. This study aimed to investigate the trends in mortality in acute respiratory distress syndrome patients over time and to explore the roles of daily fluid balance and ventilation variables in those patients. DESIGN: Secondary analysis of randomized controlled trials conducted by the Acute Respiratory Distress Syndrome Network from 1996 to 2013. SETTING: Multicenter study involving Acute Respiratory Distress Syndrome Network trials. PATIENTS: Patients with acute respiratory distress syndrome. INTERVENTIONS: None. MEASURES AND MAIN RESULTS: Individual patient data from 5,159 acute respiratory distress syndrome patients (excluding the Late Steroid Rescue Study trial) were enrolled in this study. The crude mortality rate decreased from 35.4% (95% CI, 29.9-40.8%) in 1996 to 28.3% (95% CI, 22.0-34.7%) in 2013. By adjusting for the baseline Acute Physiology and Chronic Health Evaluation…

OBJECTIVES: The purpose of this position paper is two-fold: first, to describe the state of extracorporeal membrane oxygenation education worldwide, noting current limitations and challenges; and second, to put forth an educational agenda regarding opportunities for an international collaborative approach toward standardization. DESIGN: Relevant medical literature was reviewed through literature search, and materials from national organizations were accessed through the Internet. Taskforce members generated a consensus statement using an iterative consensus process through teleconferences and electronic communication. SETTING: In 2018, the Extracorporeal Life Support Organization convened the ECMOed Taskforce at two structured, face-to-face meetings of 40 healthcare practitioners and educators with expertise in caring for the extracorporeal membrane oxygenation patient and in extracorporeal membrane oxygenation education. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ECMOed Taskforce identified seven educational domains that would benefit from international…

OBJECTIVES: Occupational therapists have specialized expertise to enable people to perform meaningful "occupations" that support health, well-being, and participation in life roles. Given the physical, cognitive, and psychologic disability experienced by ICU survivors, occupational therapists could play an important role in their recovery. We conducted a scoping review to determine the state of knowledge of interventions delivered by occupational therapists in adult ICU patients. DATA SOURCES: Eight electronic databases from inception to 05/2018. STUDY SELECTION: We included reports of adult patients receiving direct patient care from an occupational therapist in the ICU, all study designs, and quantitative and qualitative traditions. DATA EXTRACTION: Independently in duplicate, interprofessional team members screened titles, abstracts, and full texts and extracted report and intervention characteristics. From original research articles, we also extracted study design, number of patients, and primary outcomes. We resolved disagreements by consensus. DATA SYNTHESIS: Of 50,700…

OBJECTIVES: The relationship between the timing of antibiotics and mortality among septic shock patients has not been examined among patients specifically with Staphylococcus aureus bacteremia. DESIGN: Retrospective analysis of a Veterans Affairs S. aureus bacteremia database. SETTING: One-hundred twenty-two hospitals in the Veterans Affairs Health System. PATIENTS: Patients with septic shock and S. aureus bacteremia admitted directly from the emergency department to the ICU from January 1, 2003, to October 1, 2015, were evaluated. INTERVENTIONS: Time to appropriate antibiotic administration and 30-day mortality. MEASUREMENTS AND MAIN RESULTS: A total of 506 patients with S. aureus bacteremia and septic shock were included in the analysis. Thirty-day mortality was 78.1% for the entire cohort and was similar for those participants with methicillin-resistant S. aureus and methicillin-sensitive S. aureus bacteremia. Our multivariate analysis revealed that, as compared with those who received appropriate antibiotics within 1 hour after emergency department presentation, each additional…

OBJECTIVES: Previous trials suggest that vasopressin may improve outcomes in patients with vasodilatory shock. The aim of this study was to evaluate whether vasopressin could be superior to norepinephrine to improve outcomes in cancer patients with septic shock. DESIGN: Single-center, randomized, double-blind clinical trial, and meta-analysis of randomized trials. SETTING: ICU of a tertiary care hospital. PATIENTS: Two-hundred fifty patients 18 years old or older with cancer and septic shock. INTERVENTIONS: Patients were assigned to either vasopressin or norepinephrine as first-line vasopressor therapy. An updated meta-analysis was also conducted including randomized trials published until October 2018. MEASUREMENTS AND MAIN RESULTS: The primary outcome was all-cause mortality at 28 days after randomization. Prespecified secondary outcomes included 90-days all-cause mortality rate; number of days alive and free of advanced organ support at day 28; and Sequential Organ Failure Assessment score 24 hours and 96 hours after randomization. We also measure the prevalence of adverse…