Frailty, Outcomes, Recovery and Care Steps of Critically Ill Patients (FORECAST): a prospective, multi-centre, cohort study.

PURPOSE: Frailty is common in critically ill patients but the timing and optimal method of frailty ascertainment, trajectory and relationship with care processes remain uncertain. We sought to elucidate the trajectory and care processes of frailty in critically ill patients as measured by the Clinical Frailty Scale (CFS) and Frailty Index (FI). METHODS: This is a multi-centre prospective cohort study enrolling patients ≥ 50 years old receiving life support > 24 h. Frailty severity was assessed with a CFS, and a FI based on the elements of a comprehensive geriatric assessment (CGA) at intensive care unit (ICU) admission, hospital discharge and 6 months. For the primary outcome of frailty prevalence, it was a priori dichotomously defined as a CFS ≥ 5 or FI ≥ 0.2. Processes of care, adverse events were collected during ICU and ward stays while outcomes were determined for ICU, hospital, and 6 months. RESULTS: In 687 patients, whose age (mean ± standard deviation) was 68.8 ± 9.2 years, frailty prevalence was higher when measured with the FI (CFS, FI %): ICU admission (29.8, 44.8), hospital discharge (54.6, 67.9), 6 months (34.1, 42.6). Compared to ICU admission, aggregate frailty severity increased to hospital discharge but improved by 6 months; individually, CFS and FI were higher in 45.3% and 50.6% patients, respectively at 6 months. Compared to hospital discharge, 18.7% (CFS) and 20% (FI) were higher at 6 months. Mortality was higher in frail patients. Processes of care and adverse events were similar except for worse ICU/ward mobility and more frequent delirium in frail patients. CONCLUSIONS: Frailty severity was dynamic, can be measured during recovery from critical illness using the CFS and FI which were both associated with worse outcomes. Although the CFS is a global measure, a CGA FI based may have advantages of being able to measure frailty levels, identify deficits, and potential targets for intervention.

Improving appropriate use of intravenous albumin: results of a single-centre audit and multifaceted intervention.

BACKGROUND: Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence. AIM: To reduce unnecessary transfusion of albumin. INTERVENTIONS: Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage. IMPLEMENTATION AND EVALUATION: Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures. RESULTS: Appropriate albumin usage based on indication increased from 30% to 50% (p<0.0001). There was significantly less overall albumin usage in the post-intervention period compared with the pre-intervention period (negative coefficient, p<0.0001), driven by a major reduction in the utilisation of the 5% formulation (p<0.0001). Overall albumin usage was significantly lower in the post-intervention period, decreasing from 800 to 450 vials per month. The intervention resulted in significantly less wastage (negative coefficient, p=0.017). Mortality, length of stay and new starts on kidney replacement therapy remained constant throughout the study period. CONCLUSION: Improved prescribing of albumin was achieved with a multifaceted approach. Substantial and sustained reductions in usage were achieved without negatively impacting patient-important outcomes. The estimated annual savings for the purchase cost of albumin was CAN $300 000. We provide a structured process for other organisations to optimise their use of albumin.

An International Survey of the Management of Atrial Fibrillation in Critically Unwell Patients.

OBJECTIVES: To evaluate the current management of new-onset atrial fibrillation and compare differences in practice regionally. DESIGN: Cross-sectional survey. SETTING: United States, Canada, United Kingdom, Europe, Australia, and New Zealand. SUBJECTS: Critical care attending physicians/consultants and fellows. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 386 surveys were included in our analysis. Rate control was the preferred treatment approach for hemodynamically stable patients (69.1%), and amiodarone was the most used antiarrhythmic medication (70.9%). For hemodynamically unstable patients, a strategy of electrolyte supplementation and antiarrhythmic therapy was most common (54.7%). Physicians responding to the survey distributed by the Society of Critical Care Medicine were more likely to prescribe beta-blockers as a first-line antiarrhythmic medication (38.4%), use more transthoracic echocardiography than respondents from other regions (82.4%), and more likely to refer patients who survive their ICU stay for cardiology follow-up if they had new-onset atrial fibrillation (57.2%). The majority of survey respondents (83.0%) were interested in participating in future studies of atrial fibrillation in critically ill patients. CONCLUSIONS: Significant variation exists in the management of new-onset atrial fibrillation in critically ill patients, as well as geographic variation. Further research is necessary to inform guidelines in this population and establish if differences in practice impact long-term outcomes.

Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study.

OBJECTIVES: Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Multicenter ICU study. PATIENTS: Adults requiring invasive mechanical ventilation secondary to COVID-19. INTERVENTION: Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events. CONCLUSIONS: In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology.

Ceragenin-coated endotracheal tubes for the reduction of ventilator-associated pneumonia: a prospective, longitudinal, cross-over, interrupted time, implementation study protocol (CEASE VAP study).

BACKGROUND: Critically ill patients are at high risk of acquiring ventilator-associated pneumonia (VAP), which occurs in approximately 20% of mechanically ventilated patients. VAP results either from aspiration of pathogen-contaminated oropharyngeal secretions or contaminated biofilms that form on endotracheal tubes (ETTs) after intubation. VAP results in increased duration of mechanical ventilation, increased intensive care unit and hospital length of stay, increased risk of death and increased healthcare costs. Because of its impact on patient outcomes and the healthcare system, VAP is regarded as an important patient safety issue and there is an urgent need for better evidence on the efficacy of prevention strategies. Modified ETTs that reduce aspiration of oropharyngeal secretions with subglottic secretion drainage or reduce the occurrence of biofilm with a coating of ceragenins (CSAs) are available for clinical use in Canada. In this implementation study, we will evaluate the efficacy of these two types of Health Canada-licensed ETTs on the occurrence of VAP, and impact on patient-centred outcomes. METHODS: In this ongoing, pragmatic, prospective, longitudinal, interrupted time, cross-over implementation study, we will compare the efficacy of a CSA-coated ETT (CeraShield N8 Pharma) with an ETT with subglottic secretion drainage (Taper Guard, Covidien). The study periods consist of four alternating time periods of 11 or 12 weeks or a total of 23 weeks for each ETT. All patients intubated with the study ETT in each time period will be included in an intention-to-treat analysis. Outcomes will include VAP incidence, mortality and health services utilisation including antibiotic use and length of stay. ETHICS AND DISSEMINATION: This study has been approved by the Health Sciences Research Ethics Board at Queen's University. The results of this study will be actively disseminated through manuscript publication and conference presentations. TRIAL REGISTRATION NUMBER: NCT05761613.

Magnesium prophylaxis of new-onset atrial fibrillation: A systematic review and meta-analysis.

PURPOSE: Atrial fibrillation (AF) is the most common cardiac arrhythmia in intensive care units (ICU) and is associated with increased morbidity and mortality. Magnesium prophylaxis has been shown to reduce incidence of AF in cardiac surgery patients, however, evidence outside this population is limited. The objective of this study is to summarize studies examining magnesium versus placebo in the prevention of NOAF outside the setting of cardiac surgery. SOURCE: We performed a comprehensive search of MEDLINE, EMBASE, and Cochrane Library (CENTRAL) from inception until January 3rd, 2023. We included all interventional research studies that compared magnesium to placebo and excluded case reports and post cardiac surgery patients. We conducted meta-analysis using the inverse variance method with random effects modelling. PRINCIPAL FINDINGS: Of the 1493 studies imported for screening, 87 full texts were assessed for eligibility and six citations, representing five randomized controlled trials (n = 4713), were included in the review, with four studies (n = 4654) included in the pooled analysis. Administration of magnesium did not significantly reduce the incidence of NOAF compared to placebo (OR 0.72, [95% CI 0.48 to 1.09]). CONCLUSION: Use of magnesium did not reduce the incidence of NOAF, however these studies represent diverse groups and are hindered by significant bias. Further studies are necessary to determine if there is benefit to magnesium prophylaxis for NOAF in non-cardiac surgery patients.

Study protocol for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study.

BACKGROUND: Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient's effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient's respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand. METHODS: The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured. DISCUSSION: Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447692 . Prospectively registered on May 19, 2015.

A deep learning model for the classification of atrial fibrillation in critically ill patients.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the intensive care unit and is associated with increased morbidity and mortality. New-onset atrial fibrillation (NOAF) is often initially paroxysmal and fleeting, making it difficult to diagnose, and therefore difficult to understand the true burden of disease. Automated algorithms to detect AF in the ICU have been advocated as a means to better quantify its true burden. RESULTS: We used a publicly available 12-lead ECG dataset to train a deep learning model for the classification of AF. We then conducted an external independent validation of the model using continuous telemetry data from 984 critically ill patients collected in our institutional database. Performance metrics were stratified by signal quality, classified as either clean or noisy. The deep learning model was able to classify AF with an overall sensitivity of 84%, specificity of 89%, positive predictive value (PPV) of 55%, and negative predictive value of 97%. Performance was improved in clean data as compared to noisy data, most notably with respect to PPV and specificity. CONCLUSIONS: This model demonstrates that computational detection of AF is currently feasible and effective. This approach stands to improve the efficiency of retrospective and prospective research into AF in the ICU by automating AF detection, and enabling precise quantification of overall AF burden.

Quantifying deep neural network uncertainty for atrial fibrillation detection with limited labels.

Atrial fibrillation (AF) is the most common arrhythmia found in the intensive care unit (ICU), and is associated with many adverse outcomes. Effective handling of AF and similar arrhythmias is a vital part of modern critical care, but obtaining knowledge about both disease burden and effective interventions often requires costly clinical trials. A wealth of continuous, high frequency physiological data such as the waveforms derived from electrocardiogram telemetry are promising sources for enriching clinical research. Automated detection using machine learning and in particular deep learning has been explored as a solution for processing these data. However, a lack of labels, increased presence of noise, and inability to assess the quality and trustworthiness of many machine learning model predictions pose challenges to interpretation. In this work, we propose an approach for training deep AF models on limited, noisy data and report uncertainty in their predictions. Using techniques from the fields of weakly supervised learning, we leverage a surrogate model trained on non-ICU data to create imperfect labels for a large ICU telemetry dataset. We combine these weak labels with techniques to estimate model uncertainty without the need for extensive human data annotation. AF detection models trained using this process demonstrated higher classification performance (0.64-0.67 F1 score) and improved calibration (0.05-0.07 expected calibration error).

Airway injury from the presence of endotracheal tubes and the association with subglottic secretion drainage: a prospective observational study.

PURPOSE: Laryngeal and tracheal injuries are known complications of endotracheal intubation. Endotracheal tubes (ETTs) with subglottic suction devices (SSDs) are commonly used in the critical care setting. There is concern that herniation of tissue into the suction port of these devices may lead to tracheal injury resulting in serious clinical consequences such as tracheal stenosis. We aimed to describe the type and location of tracheal injuries seen in intubated critically ill patients and assess injuries at the suction port as well as in-hospital complications associated with those injuries. METHODS: We conducted a prospective observational study of 57 critically ill patients admitted to a level 3 intensive care unit who were endotracheally intubated and underwent percutaneous tracheostomy. Investigators performed bronchoscopy and photographic evaluation of the airway during the percutaneous tracheostomy procedure to evaluate tracheal and laryngeal injury. RESULTS: Forty-one (72%) patients intubated with ETT with SSD and sixteen (28%) patients with standard ETT were included in the study. Forty-seven (83%) patients had a documented airway injury ranging from hyperemia to deep ulceration of the mucosa. A common tracheal injury was at the site of the tracheal cuff. Injury at the site of the subglottic suction device was seen in 5/41 (12%) patients. There were no in-hospital complications. CONCLUSIONS: Airway injury was common in critically ill patients following endotracheal intubation, and tracheal injury commonly occurred at the site of the endotracheal cuff. Injury occurred at the site of the subglottic suction port in some patients although the clinical consequences of these injuries remain unclear.

RéSUMé: OBJECTIF: Les lésions laryngées et trachéales sont des complications connues de l'intubation endotrachéale. Les sondes endotrachéales (SET) avec dispositifs d'aspiration sous-glottiques (DASG) sont couramment utilisées aux soins intensifs. On craint qu'une hernie tissulaire dans l'orifice d'aspiration de ces dispositifs n'entraîne des lésions trachéales, résultant en de graves conséquences cliniques telles qu'une sténose trachéale. Nous avons cherché à décrire le type et l'emplacement des lésions trachéales observées chez les patients gravement malades intubés et à évaluer les lésions au port d'aspiration ainsi que les complications hospitalières associées à ces lésions. MéTHODE: Nous avons mené une étude observationnelle prospective auprès de 57 patients gravement malades admis dans une unité de soins intensifs de niveau 3 qui ont été intubés par voie endotrachéale et ont subi une trachéostomie percutanée. Les chercheurs ont réalisé une bronchoscopie et une évaluation photographique des voies aériennes au cours de la trachéostomie percutanée afin d'évaluer les lésions trachéales et laryngées. RéSULTATS: Quarante et un (72 %) intubés par SET avec DASG et seize (28 %) patients avec SET standard ont été inclus dans l'étude. Quarante-sept (83 %) patients ont présenté une lésion documentée des voies aériennes allant de l'hyperémie à l'ulcération profonde de la muqueuse. Une lésion trachéale commune était localisée sur le site du ballonnet trachéal. Une lésion au site du dispositif d'aspiration sous-glottique a été observée chez 5/41 (12 %) patients. Il n'y a pas eu de complications à l'hôpital. CONCLUSION: Les lésions des voies aériennes étaient fréquentes chez les patients gravement malades après une intubation endotrachéale, et les lésions trachéales se produisaient généralement au site du ballonnet endotrachéal. Des lésions se sont produites au site de l'orifice d'aspiration sous-glottique chez certains patients, bien que les conséquences cliniques de ces lésions restent incertaines.

The frailty, outcomes, recovery and care steps of critically ill patients (FORECAST) study: pilot study results.

INTRODUCTION: Frailty is common in critically ill patients and is associated with increased morbidity and mortality. There remains uncertainty as to the optimal method/timing of frailty assessment and the impact of care processes and adverse events on outcomes is unknown. We conducted a pilot study to inform on the conduct, design and feasibility of a multicenter study measuring frailty longitudinally during critical illness, care processes, occurrence of adverse events, and resultant outcomes. METHODS: Single-center pilot study enrolling patients over the age of 55 admitted to an Intensive Care Unit (ICU) for life-support interventions including mechanical ventilation, vasopressor therapy and/or renal replacement therapy. Frailty was measured on ICU admission and hospital discharge with the Clinical Frailty Scale (CFS), the Frailty Index (FI) and CFS at 6-month follow-up. Frailty was defined as CFS ≥ 5 and a FI ≥ 0.20. Processes of care and adverse events were measured during their ICU and hospital stay including nutritional support, mobility, nosocomial infections and delirium. ICU, hospital and 6 months were determined. RESULTS: In 49 patients enrolled, the mean (SD) age was 68.7 ± 7.9 with a 6-month mortality of 29%. Enrollment was 1 patient/per week. Frailty was successfully measured at different time points during the patients stay/follow-up and varied by method/timing of assessment; by CFS and FI, respectively, in 17/49 (36%), 23/49 (47%) on admission, 22/33 (67%), 21/33 (63%) on hospital discharge and 11/30 (37%) had a CFS ≥ 5 at 6 months. Processes of care and adverse events were readily captured during the ICU and ward stay with the exception of ward nutritional data. ICU, hospital outcomes and follow-up outcomes were worse in those who were frail irrespective of ascertainment method. Pre-existing frailty remained static in survivors, but progressed in non-frail survivors. DISCUSSION: In this pilot study, we demonstrate that frailty measurement in critically ill patients over the course and recovery of their illness is feasible, that processes of care and adverse events are readily captured, have developed the tools and obtained data necessary for the planning and conduct of a large multicenter trial studying the interaction between frailty and critical illness.

Complications of Critical COVID-19: Diagnostic and Therapeutic Considerations for the Mechanically Ventilated Patient.

Patients admitted to the ICU with critical COVID-19 often require prolonged periods of mechanical ventilation. Difficulty weaning, lack of progress, and clinical deterioration are commonly encountered. These conditions should prompt a thorough evaluation for persistent or untreated manifestations of COVID-19, as well as complications from COVID-19 and its various treatments. Inflammation may persist and lead to fibroproliferative changes in the lungs. Infectious complications may arise including bacterial superinfection in the earlier stages of disease. Use of immunosuppressants may lead to the dissemination of latent infections, and to opportunistic infections. Venous thromboembolic disease is common, as are certain neurologic manifestations of COVID-19 including delirium and stroke. High levels of ventilatory support may lead to ventilator-induced injury to the lungs and diaphragm. We present diagnostic and therapeutic considerations for the mechanically ventilated patient with COVID-19 who shows persistent or worsening signs of critical illness, and we offer an approach to treating this complex but common scenario.

Providing Evidence-Based Care, Day and Night: A Quality Improvement Initiative to Improve Intensive Care Unit Patient Sleep Quality.

OBJECTIVE: Evidence-based guidelines recommend promoting sleep in the Intensive Care Unit (ICU), yet many patients experience poor sleep quality. We sought to engage allied health staff and patient families to determine barriers to sleep promotion, to measure sleep quality for ICU patients, and to evaluate the improvement in sleep quality after implementation of nursing morning report protocol and a doorway poster. DESIGN: The study followed an interrupted time-series framework of quality improvement. Qualitative diagnostics included focus groups and interviews with patients, families, and allied health care workers, analyzed by qualitative descriptive analysis. Quantitative diagnostics included direct observation of nurses and patients overnight. Analysis of primary outcome data used statistical process control methodology. PATIENTS: Patients included were >18 years old, admitted overnight to a Canadian tertiary academic ICU, with a Richards Agitation Sedation Scale (RASS) ≥-2. INTERVENTIONS: Sleep quality was measured using the Richards Campbell Sleep Questionnaire (RCSQ). Two interventions were developed: sleep quality in morning nursing report, and a doorway poster. MAIN RESULTS: A total of 2332 patient nights across 7 consecutive months were included for analysis. Baseline sleep in the ICU was poor (mean RCSQ 53.7/100). Root cause-analysis identified the most prominent sleep barriers as nurse stigma associated with less active management of patients and lack of physician engagement. No significant improvement occurred over the sleep quality improvement initiative (mean RCSQ 59.5/100). Sleep quality was better among non-delirious patients compared with delirious patients (mean RCSQ 62.7 vs 53.3). CONCLUSION: The intervention of a nursing morning report protocol and sleep posters did not improve the quality of ICU patient sleep in this study. Structured interviews revealed potential sleep barriers to be addressed such as nursing stigma and inappropriate awakenings. Nursing stigma has not been previously linked to sleep quality.

The relationship between immune status as measured by stimulated ex-vivo tumour necrosis factor alpha levels and the acquisition of nosocomial infections in critically ill mechanically ventilated patients.

INTRODUCTION: Immunological dysfunction is common in critically ill patients but its clinical significance and the optimal method to measure it are unknown. The level of tumor necrosis factor alpha (TNF-α) after ex-vivo whole blood stimulation with lipopolysaccharide (LPS) has been proposed as a possible method to quantify immunological function. We hypothesized that in a cohort of critically ill patients, those with a lower post-stimulation TNF-α level would have increased rates of nosocomial infections (NIs) and worse clinical outcomes. METHODS: A secondary analysis of a phase 2 randomized, multi-centre, double-blinded placebo-controlled trial. As there was no difference between treatment and control arms in outcomes and NI rate, all the patients were analyzed as one cohort. On enrolment, day 4, 7, and weekly until day 28, whole blood was incubated with LPS ex-vivo and subsequent TNF-α level was measured. Patients were grouped in tertiles according to delta and peak TNF-α level. The primary outcome was the association between NIs and tertiles of TNF-α level post LPS stimulation; secondary outcomes included ICU and 90-day mortality, and ICU and hospital length of stay. RESULTS: Data was available for 201 patients. Neither the post LPS stimulation delta TNF-α group nor the peak TNF-α post-stimulation group were associated with the development of NIs or clinical outcomes. Patients in the highest tertile for post LPS stimulation delta TNF-α compared to the lowest tertile were younger [61.1 years ± 15.7 vs. 68.6 years ± 12.8 standard deviations (SD) in the lowest tertile], had lower acuity of illness (APACHE II 25.0 ± 9.7 vs. 26.7 ± 6.1) and had lower baseline TNF-α (9.9 pg/mL ± 19.0 vs. 31.0 pg/mL ± 68.5). When grouped according to peak post-stimulation TNF-α levels, patients in the highest tertile had higher serum TNF-α at baseline (21.3 pg/mL ± 66.7 compared to 6.5 pg/mL ± 9.0 in the lowest tertile). CONCLUSION: In this prospective multicenter study, ex-vivo stimulated TNF-α level was not associated with the occurrence of NIs or clinical outcomes. Further study is required to better ascertain whether TNF levels and ex-vivo stimulation can be used to characterize immune function in critical illness and if other assays might be better suited to this task.

Point-of-care ultrasound for the detection of hydronephrosis in emergency department patients with suspected renal colic.

BACKGROUND: Point-of-care ultrasound (PoCUS) by emergency physicians for renal colic has been proposed as an alternative to computed tomography (CT) to avoid ionizing radiation exposure and shorten emergency department length of stay. Previous studies have employed experienced or credentialed ultrasonographers or required advanced ultrasound skills. We sought to measure the diagnostic accuracy of PoCUS by physicians with varied experience using a simplified binary outcome of presence or absence of hydronephrosis. Secondary outcomes include assessment as to whether the presence of hydronephrosis on PoCUS is predictive of complications, and to evaluate possible causes for the reduced diagnostic accuracy such as body mass index (BMI) and time between PoCUS and formal imaging, and scanner experience. RESULTS: 413 patients were enrolled in the study. PoCUS showed a specificity of 71.8% [95% CI 65.0, 77.9] and sensitivity of 77.1% [95% CI 70.9, 82.6]. Hydronephrosis on PoCUS was predictive of complications (relative risk 3.13; [95% CI 1.30, 7.53]). The time interval between PoCUS and formal imaging, BMI, and scanner experience did not influence the accuracy of PoCUS. CONCLUSIONS: PoCUS for hydronephrosis in suspected renal colic has moderate accuracy when performed by providers with varied experience for the binary outcome of presence or absence of hydronephrosis. Hydronephrosis on PoCUS is associated with increased rates of complications. PoCUS for hydronephrosis is limited in its utility as a stand-alone test, however this inexpensive, readily available test may be useful in conjunction with clinical course to determine which patients would benefit from formal imaging or urologic consultation. ClinicalTrials.gov Identifier NCT01323842.

Prevention of Nosocomial Infections in Critically Ill Patients With Lactoferrin: A Randomized, Double-Blind, Placebo-Controlled Study.

OBJECTIVE: To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. DESIGN: Phase 2, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Medical-surgical ICUs. PATIENTS: Adult, critically ill patients receiving invasive mechanical ventilation. INTERVENTIONS: Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. MEASUREMENTS AND MAIN RESULTS: Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [SD], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups. CONCLUSIONS: Lactoferrin did not improve the primary outcome of antibiotic-free days, nor any of the secondary outcomes. Our data do not support the conduct of a larger phase 3 trial.