Ultrasound Assessment of the Change in Carotid Corrected Flow Time in Fluid Responsiveness in Undifferentiated Shock.

OBJECTIVES: Adequate assessment of fluid responsiveness in shock necessitates correct interpretation of hemodynamic changes induced by preload challenge. This study evaluates the accuracy of point-of-care Doppler ultrasound assessment of the change in carotid corrected flow time induced by a passive leg raise maneuver as a predictor of fluid responsiveness. Noninvasive cardiac output monitoring (NICOM, Cheetah Medical, Newton Center, MA) system based on a bioreactance method was used. DESIGN: Prospective, noninterventional study. SETTING: ICU at a large academic center. PATIENTS: Patients with new, undifferentiated shock, and vasopressor requirements despite fluid resuscitation were included. Patients with significant cardiac disease and conditions that precluded adequate passive leg raising were excluded. INTERVENTIONS: Carotid corrected flow time was measured via ultrasound before and after a passive leg raise maneuver. Predicted fluid responsiveness was defined as greater than 10% increase in stroke volume on noninvasive cardiac output monitoring following passive leg raise. Images and measurements were reanalyzed by a second, blinded physician. The accuracy of change in carotid corrected flow time to predict fluid responsiveness was evaluated using receiver operating characteristic analysis. MEASUREMENTS AND MAIN RESULTS: Seventy-seven subjects were enrolled with 54 (70.1%) classified as fluid responders by noninvasive cardiac output monitoring. The average change in carotid corrected flow time after passive leg raise for fluid responders was 14.1 ± 18.7 ms versus -4.0 ± 8 ms for nonresponders (p < 0.001). Receiver operating characteristic analysis demonstrated that change in carotid corrected flow time is an accurate predictor of fluid responsiveness status (area under the curve, 0.88; 95% CI, 0.80-0.96) and a 7 ms increase in carotid corrected flow time post passive leg raise was shown to have a 97% positive predictive value and 82% accuracy in detecting fluid responsiveness using noninvasive cardiac output monitoring as a reference standard. Mechanical ventilation, respiratory rate, and high positive end-expiratory pressure had no significant impact on test performance. Post hoc blinded evaluation of bedside acquired measurements demonstrated agreement between evaluators. CONCLUSIONS: Change in carotid corrected flow time can predict fluid responsiveness status after a passive leg raise maneuver. Using point-of-care ultrasound to assess change in carotid corrected flow time is an acceptable and reproducible method for noninvasive identification of fluid responsiveness in critically ill patients with undifferentiated shock.

When host defense goes awry: Modeling sepsis-induced immunosuppression.

Sepsis is associated with an initial hyperinflammatory state; however, therapeutic trials targeting the inflammatory response have yielded disappointing results. It is now appreciated that septic patients often undergo a period of relative immunosuppression, rendering them susceptible to secondary infections. Interest in this phenomenon has led to the development of animal models to study the immune dysfunction of sepsis. In this review, we analyze the available models of sepsis-induced immunosuppression.

Development of secondary bacterial pneumonia in adults presenting with influenza versus noninfluenza viral respiratory infection.

BACKGROUND: Respiratory viral infections, particularly influenza, are known to cause significant morbidity and mortality, often due to secondary infections. Our aim was to comparatively analyze the incidence, epidemiology, and outcomes of secondary pneumonia in adult patients hospitalized with influenza versus noninfluenza viral infections and determine whether influenza particularly predisposes to secondary infections. METHODS: This was a retrospective analysis from a single tertiary medical center of adult patients admitted to the hospital between 2008 and 2010 with respiratory viral infections. Microbiological patterns and clinical outcomes were compared between those with influenza (VI, n = 57) and those with noninfluenza (NI, n = 77) respiratory viral infections. RESULTS: The NI group was older (60.6 ± 14.0 versus 53.3 ± 19.7 years, p = 0.019) with higher rates of lung transplantation (29% versus 9%, p = 0.009) than VI. Overall, 35% developed secondary pneumonia, higher among NI (44%) than VI (23%, p = 0.017). Staphylococcus aureus was the most common cause of pneumonia in VI, whereas Gram-negative rods were most frequently identified in NI. The NI group had longer hospital [median 10 (interquartile range (IQR) 6-19) versus 6 (IQR 4-15) days, p = 0.019] and intensive care unit [median 4 (IQR 0-12) versus 0 (IQR 0-8) days, p = 0.029] stays compared with VI. Further, the NI group was more likely to be admitted to the intensive care unit compared with VI (62% versus 39%, p = 0.011). A trend towards increased mortality was observed in viral infections complicated by secondary pneumonia than primary viral infections (28% versus 15%, p = 0.122). CONCLUSION: Secondary pneumonia is common among adults hospitalized with viral respiratory infections. Within our population, NI results in more frequent secondary pneumonia and longer hospital stays than those with VI. Given the high number of infections caused by Gram-negative rods, monitoring local epidemiology is critical for guiding initial antibiotic selection in empirical treatment of secondary infections.The reviews of this paper are available via the supplemental material section.

Reference Values for Chronotropic Index from 1280 Incremental Cycle Ergometry Tests.

PURPOSE: Clinical cardiopulmonary exercise testing can determine causes of exercise limitation. The slope of heart rate (fC) versus oxygen uptake (V˙O2), which we call the chronotropic index (CI), can help identify cardiovascular impairment. We aimed to develop a reference equation for CI based on a large number of subjects considered to have normal exercise responses. METHODS: From a database of 13,728 incremental cycle ergometry exercise tests, we identified 1280 normal tests based on the absence of a clinical diagnosis, normal body mass index, and normal aerobic performance plus absence of cardiovascular disease, medications, or ventilatory limitation. A linear mixed-model approach was used to analyze the relationship between CI and other variables. RESULTS: Subjects were age 18-84 yr, and 693 (54.1%) were men. Mean ± SD CI in men was lower than in women, 41.2 ± 9.3 beats per liter versus 63.4 ± 15.7 L. Age (in years), sex (0, male; 1, female), height (in centimeters), and weight (in kilograms) were significant predictors for CI:CIi = 106.9 + 0.16 × agei + 14.3 × sexi - 0.31 × heighti - 0.24 × weighti. The SE of estimates ranged from 10.6 to 11.2 L (median of 10.7 L). CONCLUSIONS: We report a reference equation for CI derived from normal subjects. The CI can be used in conjunction with V˙O2max to interpret maximal cardiopulmonary exercise tests. We consider a high CI to be cardiovascular impairment and a low CI plus low V˙O2max to be chronotropic insufficiency.

Clinical Significance of Bronchodilator Responsiveness Evaluated by Forced Vital Capacity in COPD: SPIROMICS Cohort Analysis.

Objective: Bronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV1 (BDRFEV1) as a measure reflecting the change in flow and in FVC (BDRFVC) reflecting the change in volume. Methods: We analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models. Results: A majority of COPD participants exhibited BDR (52.7%). BDRFEV1 occurred more often in earlier stages of COPD, while BDRFVC occurred more frequently in more advanced disease. When defined by increases in either FEV1 or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDRFVC was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDRFVC was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV1. Conclusion: With advanced airflow obstruction in COPD, BDRFVC is more prevalent in comparison to BDRFEV1 and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV1, BDRFVC itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD. Clinical trials registration: ClinicalTrials.gov: NCT01969344T4.

Personalized Risk Scoring for Critical Care Prognosis Using Mixtures of Gaussian Processes.

OBJECTIVE: In this paper, we develop a personalized real-time risk scoring algorithm that provides timely and granular assessments for the clinical acuity of ward patients based on their (temporal) lab tests and vital signs; the proposed risk scoring system ensures timely intensive care unit admissions for clinically deteriorating patients. METHODS: The risk scoring system is based on the idea of sequential hypothesis testing under an uncertain time horizon. The system learns a set of latent patient subtypes from the offline electronic health record data, and trains a mixture of Gaussian Process experts, where each expert models the physiological data streams associated with a specific patient subtype. Transfer learning techniques are used to learn the relationship between a patient's latent subtype and her static admission information (e.g., age, gender, transfer status, ICD-9 codes, etc). RESULTS: Experiments conducted on data from a heterogeneous cohort of 6321 patients admitted to Ronald Reagan UCLA medical center show that our score significantly outperforms the currently deployed risk scores, such as the Rothman index, MEWS, APACHE, and SOFA scores, in terms of timeliness, true positive rate, and positive predictive value. CONCLUSION: Our results reflect the importance of adopting the concepts of personalized medicine in critical care settings; significant accuracy and timeliness gains can be achieved by accounting for the patients' heterogeneity. SIGNIFICANCE: The proposed risk scoring methodology can confer huge clinical and social benefits on a massive number of critically ill inpatients who exhibit adverse outcomes including, but not limited to, cardiac arrests, respiratory arrests, and septic shocks.

Prediction of Clinical Deterioration in Hospitalized Adult Patients with Hematologic Malignancies Using a Neural Network Model.

INTRODUCTION: Clinical deterioration (ICU transfer and cardiac arrest) occurs during approximately 5-10% of hospital admissions. Existing prediction models have a high false positive rate, leading to multiple false alarms and alarm fatigue. We used routine vital signs and laboratory values obtained from the electronic medical record (EMR) along with a machine learning algorithm called a neural network to develop a prediction model that would increase the predictive accuracy and decrease false alarm rates. DESIGN: Retrospective cohort study. SETTING: The hematologic malignancy unit in an academic medical center in the United States. PATIENT POPULATION: Adult patients admitted to the hematologic malignancy unit from 2009 to 2010. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Vital signs and laboratory values were obtained from the electronic medical record system and then used as predictors (features). A neural network was used to build a model to predict clinical deterioration events (ICU transfer and cardiac arrest). The performance of the neural network model was compared to the VitalPac Early Warning Score (ViEWS). Five hundred sixty five consecutive total admissions were available with 43 admissions resulting in clinical deterioration. Using simulation, the neural network outperformed the ViEWS model with a positive predictive value of 82% compared to 24%, respectively. CONCLUSION: We developed and tested a neural network-based prediction model for clinical deterioration in patients hospitalized in the hematologic malignancy unit. Our neural network model outperformed an existing model, substantially increasing the positive predictive value, allowing the clinician to be confident in the alarm raised. This system can be readily implemented in a real-time fashion in existing EMR systems.

Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells.

Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg) in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF) after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-), and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+) and CD103(-) and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+) Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+) Treg frequency and inversely with BOS. Higher frequencies of CCR7(+) CD3(+)CD4(+)CD25(hi)Foxp3(+)CD45RA(-) lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.