Role of Wearable Accelerometer Devices in Delirium Studies: A Systematic Review Objectives: We sought to determine the feasibility of using wearable accelerometer devices for determining delirium effects on patients’ physical activity patterns and detecting delirium and delirium subtype. Data Sources: PubMed, Embase, and Web of Science. Study Selection: Screening was performed using predefined search terms to identify original research studies using accelerometer devices for studying physical activity in relation to delirium. Data Extraction: Key data were extracted from the selected articles. Data Synthesis: Among the 14 studies identified, there were a total of 315 patients who wore accelerometer devices to record movements related to delirium. Eight studies (57.1%) used accelerometer devices to compare the activity of delirious and nondelirious patients. Delirious patients had lower activity levels, lower restlessness index, higher number of daytime immobility minutes, lower mean activity levels during the day, and higher mean activity levels at night. Delirious patients also had lower actual sleep time, lower sleep efficiency, fewer nighttime minutes resting, fewer minutes resting over 24 hours, and smaller change in activity from day to night. Six studies (42.9%) evaluated the feasibility of using accelerometer devices for detection of delirium and its subtype. Variables including number of postural changes during daytime, frequency of ultrashort, short, and continuous movements were significantly different among the nondelirium and the three delirium subtypes. Conclusions: The results from the studies using accelerometer devices in studying delirium demonstrate that accelerometer devices can potentially detect the differences between delirious and nondelirious patients, detect delirium, and determine delirium subtype. We suggest the following directions as the next steps for future studies using accelerometer devices for predicting delirium: benchmark studies with longer data collection, larger and more diverse population size, incorporating related factors (e.g., medications), and evaluating delirium subtype and severity.

Retrospective Observational Study of the Clinical Performance Characteristics of a Machine Learning Approach to Early Sepsis Identification Objectives: To estimate performance characteristics and impact on care processes of a machine learning, early sepsis recognition tool embedded in the electronic medical record. Design: Retrospective review of electronic medical records and outcomes to determine sepsis prevalence among patients about whom a warning was received in real time and timing of that warning compared with clinician recognition of potential sepsis as determined by actions documented in the electronic medical record. Setting: Acute care, nonteaching hospital. Patients: Patients in the emergency department, observation unit, and adult inpatient care units who had sepsis diagnosed either by clinical codes or by Center for Medicare and Medicaid Services Severe Sepsis and Septic Shock: Management Bundle (SEP-1) criteria for severe sepsis and patients who had machine learning–generated advisories about a high risk of sepsis. Interventions: Noninterventional study. Measurements and Main Results: Using two different definitions of sepsis as “true” sepsis, we measured the sensitivity and early warning clinical utility. Using coded sepsis to define true positives, we measured the positive predictive value of the early warnings. Sensitivity was 28.6% and 43.6% for coded sepsis and severe sepsis, respectively. The positive predictive value of an alert was 37.9% for coded sepsis. Clinical utility (true positive and earlier advisory than clinical recognition) was 2.2% and 1.6% for the two different definitions of sepsis. Use of the tool did not improve sepsis mortality rates. Conclusions: Performance characteristics were different than previously described in this retrospective assessment of real-time warnings. Real-world testing of retrospectively validated models is essential. The early warning clinical utility may vary depending on a hospital’s state of sepsis readiness and embrace of sepsis order bundles.

Circulating Gasdermin-D in Critically Ill Patients Objectives: The key to further improving outcomes in sepsis lies in understanding and abrogating the dysfunctional immune response that leads to organ failure. Activation of gasdermin-D, a pore-forming protein within the inflammasome cascade, has recently been recognized as the critical step in pyroptosis and organ dysfunction. In this study, we sought to investigate the presence of gasdermin-D in critically ill subjects. Design, Setting, and Patients: Prospective pilot study comparing microparticulate active gasdermin-D levels in critically ill patients admitted to the medical ICU at The Ohio State University Medical Center to healthy donors and clinical outcomes. Interventions: None. Measurements and Main Results: Plasma was collected from subjects upon consent and microparticles were isolated by ultracentrifugation. Proteins of interest were identified by immunoblot analysis of microparticle lysates. Quantification was accomplished by densitometry using ImageJ software (National Institutes of Health, Bethesda, MD). Investigators were then unblinded and compared microparticulate active gasdermin-D levels to physician adjudicated clinical diagnoses and outcomes. No appreciable levels of active gasdermin-D were observed in microparticles from healthy volunteers and nonseptic critically ill patients. However, elevated levels of gasdermin-D were noted in microparticles from the septic cohort of critically ill patients. Furthermore, a significant positive correlation by linear regression was noted when microparticulate active gasdermin-D levels were compared with microparticulate levels of CD63, an exosomal marker, CD14, a monocyte marker, and CD69, a marker of monocyte activation (R2 = 0.37, p = 0.0011, R2 = 0.85, p < 0.0001, and R2 = 0.43, p = 0.0003, respectively). Conclusions: This is the first study to demonstrate circulating active gasdermin-D in septic patients in the intensive care setting. Our findings also suggest that active gasdermin-D in septic patients is encapsulated in exosomes derived from activated monocytes. Further characterization in the clinical setting is warranted.

Outcomes of Acute Respiratory Distress Syndrome in Mechanically Ventilated Patients With Cirrhosis Objective: To better describe the outcomes of acute respiratory distress syndrome in mechanically ventilated patients with cirrhosis. Design: Single-center, retrospective study of mechanically ventilated patients with cirrhosis between 2008 and 2015. Setting: ICU at a large academic medical and transplant center. Patients: One hundred eighty-one mechanically ventilated patients with cirrhosis. Interventions: Demographic and clinical data were reviewed, and acute respiratory distress syndrome was identified per Berlin criteria. We compared demographic and clinical characteristics on ICU admission in patients with and without acute respiratory distress syndrome. The primary endpoint was hospital mortality (including discharge to hospice). Mortality risk was stratified by Chronic Liver Failure-Sequential Organ Failure Assessment and Model for End-Stage Liver Disease. Measurements and Main Results: The mean age in 181 eligible patients was 53 ± 11 years; 67% were male; and 91% were Caucasian. In all, n = 35 (19%) of mechanically ventilated patients had acute respiratory distress syndrome. They were more frequently female (46% vs 30%; p = 0.08), with suspected infection (86% vs 53%; p < 0.001), and had higher mean Model for End-Stage Liver Disease (32 vs 24; p < 0.001) and Chronic Liver Failure-Sequential Organ Failure Assessment (15 vs 11; p < 0.001) than patients without acute respiratory distress syndrome. Hospital mortality was higher in patients with (40%) versus without (22%) acute respiratory distress syndrome (p = 0.03). In the risk-adjusted analysis (for Model for End-Stage Liver Disease, Chronic Liver Failure-Sequential Organ Failure Assessment and age), acute respiratory distress syndrome was not independently associated with hospital mortality (odds ratio, 0.80; CI, 0.3–2.5; p = 0.7). Conclusions: Acute respiratory distress syndrome is common in mechanically ventilated patients with cirrhosis but is not independently associated with increased mortality.

Staphylococcus Toxin-Mediated Motor Polyneuropathy Background: Staphylococcus aureus infection is known to cause a variety of neurologic complications, most involving the CNS, however, rarely have cases of S. aureus affecting the peripheral nervous system been reported in literature. We report a case of S. aureus toxin-mediated motor polyneuropathy in a patient presenting with acute flaccid quadriplegia. Case summary: A 64-year-old female with mantle cell lymphoma on oral chemotherapy with ibrutinib presents with malaise and progressive ascending bilateral lower extremity weakness. Blood cultures resulted positive for methicillin-sensitive S. aureus, and she was initiated on antibiotics. Imaging studies and laboratory workup were negative for other causes of acute flaccid quadriplegia. Patient had complete resolution of her neurologic deficits with antibiotic therapy. It was determined that the likely diagnosis was Staphylococcus toxin-mediated motor polyneuropathy. Conclusions: Staphylococcal-mediated motor polyneuropathy resulting in acute flaccid quadriplegia is a rare but treatable complication of bacteremia and should remain a diagnosis of exclusion.

Impact of Point-of-Care Ultrasound in Critically Ill Patients: Flawed Data and Wrong Conclusions No abstract available

A Pilot Study on Continuous Infusion of 4% Albumin in Critically Ill Patients: Impact on Nosocomial Infection via a Reduction Mechanism for Oxidized Substrates Objective: Care-related infections affect up to 11% of ICU patients. Running therapeutic albumin is sometimes associated to less infection: whether a specific method of its infusion is of any interest to modulate innate defense is unknown. Our objectives were: 1) to test whether the method for albumin infusion is important to prevent care-related infections and 2) to analyze in vitro the antioxidative role of albumin on host defense proteins during shock (using vasostatin-I as an example). Design: In a prospective, randomized, open-label trial, shock patients were allocated to receive either continuously 4% albumin or intermittently 20% albumin, as long as they were infused with norepinephrine. A translational study including in vivo and in vitro analyses of albumin-vasostatin-I interactions is reported. Setting: A tertiary ICU caring for 1,000 patients per year. Patients: Fifty shock patients with serum albumin less than 20 g/L. Interventions: In vivo colonization and nosocomial infections were recorded and time-dependent changes in serum albumin, chromogranin A, and vasostatin-I concentrations as well. In vitro, we studied biochemical albumin-vasostatin-I relationship using biochemical methods. Measurements and Main Results: Over 18 days, we recorded a decrease in colonization (four vs 12 episodes; p = 0.035) and nosocomial infection frequency (two vs 13 episodes; p = 0.002) in patients infused continuously 4% albumin versus controls. In vitro, albumin interacts with the disulfide loop vasostatin-I (residues 17–40) and continuous 4% albumin infusion restores its oxidative status required for antimicrobial activity. Conclusions: Continuous 4% albumin is effective in reducing care-related infections in shock patients by increasing the availability of antimicrobial vasostatin-I. This might guide future care of shock patients.

Patterns of Medication Exposure in Children on Extracorporeal Membrane Oxygenation: A Step in Prioritizing Future Pharmacologic Studies Objectives: To identify medications administered to pediatric patients on extracorporeal membrane oxygenation and to review the available pharmacokinetics and pharmacodynamics literature for the most commonly administered medications. Design: Retrospective single-center study. Setting: ICUs at Children’s Hospital of Philadelphia. Patients: Pediatric patients supported by extracorporeal membrane oxygenation between October 1, 2014, and September 30, 2018. Interventions: None. Measurements and Main Results: Drug exposure was described according to age group (< 1 mo, 1 mo to < 2 yr, 2 to < 12 yr, and > 12 yr) and ICU (cardiac, neonatal, pediatric). The association of drug exposure with patient’s characteristics was examined using one-way analysis of variance for categorical variables and linear regression for continuous variables. All pharmacokinetics and pharmacodynamics literature for the 50 most commonly administered medications on extracorporeal membrane oxygenation was reviewed, with inclusion of studies that reported dosing regimens in conjunction with pharmacokinetics or pharmacodynamics data. A total of 179 different medications were administered to 254 children. Cumulative drug exposure increased with the duration of extracorporeal membrane oxygenation from a median (interquartile) of 10 drugs (6–14) at 1 week to 31 drugs (21–45) at 5 weeks following cannulation. There were significant differences in total drug exposure between age groups and ICUs. With exclusion of in vitro studies, published literature was available to support the use of 40% (20/50) of the most commonly administered medications. Dosing guidance was available for 20% (10/50) of medications and was primarily based on simulations and retrospective studies focusing on neonates and infants. Conclusions: This study highlights specific needs for future pharmacokinetics and pharmacodynamics studies. Dosing guidelines are essential to optimize the care of critically ill children supported by extracorporeal membrane oxygenation.

Accuracy of Quick Sequential Organ Failure Assessment Score to Predict Sepsis Mortality in 121 Studies Including 1,716,017 Individuals: A Systematic Review and Meta-Analysis Objectives: We performed a meta-analysis to assess whether the newly introduced quick Sequential Organ Failure Assessment score could predict sepsis outcomes and compared its performance to systematic inflammatory response syndrome, the previously widely used screening criteria for sepsis. Data Sources: We searched multiple electronic databases including MEDLINE, the Cochrane Library, Embase, Web of Science, and Google Scholar (up to March 1, 2019) that evaluated quick Sequential Organ Failure Assessment score, systemic inflammatory response syndrome, or both (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42018103327). Study Selection: Studies were included if the outcome was mortality, organ dysfunction, admission to ICU, ventilatory support, or prolonged ICU stay and if prediction performance was reported as either area under the curve, odds ratio, sensitivity, or specificity. Data Extraction: The criterion validity of the quick Sequential Organ Failure Assessment score and systemic inflammatory response syndrome criteria were assessed by measuring its predictive validity for primary (mortality) and secondary outcomes in pooled metrics as mentioned. The data were analyzed using random effects model, and heterogeneity was explored using prespecified subgroups analyses. Data Synthesis: We screened 1,340 studies, of which 121 studies (including data for 1,716,017 individuals) were analyzed. For mortality prediction, the pooled area under the curve was higher for quick Sequential Organ Failure Assessment score (0.702; 95% CI, 0.685–0.718; I2 = 99.41%; p < 0.001) than for systemic inflammatory response syndrome (0.607; 95% CI, 0.589–0.624; I2 = 96.49%; p < 0.001). Quick Sequential Organ Failure Assessment score consistently outperformed systemic inflammatory response syndrome across all subgroup analyses (area under the curve of quick Sequential Organ Failure Assessment vs. area under the curve of systemic inflammatory response syndrome p < 0.001), including patient populations (emergency department vs ICU), study design (retrospective vs prospective), and countries (developed vs resource-limited). Quick Sequential Organ Failure Assessment score was more specific (specificity, 74.58%; 95% CI, 73.55–75.61%) than systemic inflammatory response syndrome (specificity, 35.24%; 95% CI, 22.80–47.69%) but less sensitive (56.39%; 95% CI, 50.52–62.27%) than systemic inflammatory response syndrome (78.84%; 95% CI, 74.48–83.19%). Conclusions: Overall, quick Sequential Organ Failure Assessment score outperforms systemic inflammatory response syndrome in predicting sepsis outcome, but quick Sequential Organ Failure Assessment score has relative strengths/weaknesses (more specific but less sensitive) compared with systemic inflammatory response syndrome.