Selective modulation of monocyte and neutrophil responses with activated protein C in preterm infants.

BACKGROUND: Inflammation is associated with many disorders of preterm infants including periventricular leukomalacia, chronic lung disease, and necrotizing enterocolitis. Activated protein c (APC) has shown positive immunomodulatory effects. OBJECTIVES: We aimed to study neutrophil and monocyte function in response to lipopolysaccharide (LPS) and APC stimulation ex vivo in preterm infants <32 weeks gestation over the first week of life compared to neonatal and adult controls. METHODS: Peripheral blood was taken on day 1, 3, and 7 and stimulated with LPS in the absence or presence of APC. Expression of toll-like receptor 4 (TLR4) and CD11b and reactive oxygen intermediate (ROI) release from neutrophils and monocytes was examined by flow cytometry. RESULTS: LPS induced neutrophil ROI in adults and preterm infants and was significantly reduced by APC. Baseline and LPS-induced monocyte ROI production in preterm neonates was increased compared to adult and term controls. Neutrophil TLR4 baseline expression was higher in term controls compared to preterm infants. CONCLUSION: Increased systemic ROI release in preterm infants may mediate tissue damage, ROI was reduced by APC. However, due to the high risk of hemorrhage further examination of APC mutant forms with anti-inflammatory but decreased anticoagulant properties is merited.

Pediatric Intensive Care: Immunomodulation With Activated Protein C ex vivo.

Objective: Sepsis is major cause of morbidity and mortality in the Pediatric Intensive Care Unit (PICU). PICU patients may develop transient immune deficiency during sepsis. Activated Protein C (APC) has significant anti-inflammatory and cytoprotective effects. Clinical trials of APC in adult sepsis initially showed improved outcome but recent trials showed no benefit in adults or children. We aimed to assess the effects of APC treatment on innate immune responses in children. Design and Subjects: We compared neutrophil and monocyte responses to lipopolysaccharide (LPS) with and without APC treatment in PICU patients at the time of evaluation for sepsis compared with healthy adults and age-matched pediatric controls. We used flow cytometry to examine cell activation (CD11b expression), function [intracellular reactive oxygen intermediate (ROI) release] and LPS recognition [Toll like Receptor 4 (TLR4) expression]. Results: PICU patients had significantly decreased protein c levels and LPS responses compared with adult and pediatric controls for all parameters. APC reduced LPS-induced neutrophil PICU TLR4 and adult ROI (p < 0.05). PICU non-survivors had increased LPS induced neutrophil and monocyte ROI production vs. survivors which was significantly reduced by APC. Conclusion: PICU patients demonstrate significantly reduced endotoxin reactivity which may predispose them to sepsis and alter effective antibacterial responses. APC reduces LPS-induced ROI production in adults and may have a role in treating severely compromised PICU patients especially given that newer APC forms are associated with decreased bleeding risk and enhanced anti-inflammatory effects.

An Educational Intervention Optimizes the Use of Arterial Blood Gas Determinations Across ICUs From Different Specialties: A Quality-Improvement Study.

BACKGROUND: Overuse of arterial blood gas (ABG) determinations leads to increased costs, inefficient use of staff work hours, and patient discomfort and blood loss. We developed guidelines to optimize ABG use in the ICU. METHODS: ABG use guidelines were implemented in all adult ICUs in our institution: three medical, two trauma-surgery, one cardiovascular, and one neurosurgical ICU. Although relying on pulse oximetry, we encouraged the use of ABG determination after an acute respiratory event or for a rational clinical concern and discouraged obtaining ABG measurements for routine surveillance, after planned changes of positive end-expiratory pressure or Fio2 on the mechanical ventilator, for spontaneous breathing trials, or when a disorder was not suspected. ABG measurements and global ICU metrics were collected before (year 2014) and after (year 2015) the intervention. RESULTS: We saw a reduction of 821.5 ± 257.4 ABG determinations per month (41.5%), or approximately one ABG determination per patient per mechanical ventilation (MV) day for each month (43.1%), after introducing the guidelines (P < .001). This represented 49 L of saved blood, a reduction of $39,432 in the costs of ICU care, and 1,643 staff work hours freed for other tasks. Appropriately indicated tests rose to 83.4% from a baseline 67.5% (P = .002). Less than 5% of inappropriately indicated ABG determinations changed patient management in the postintervention period. There were no significant differences in MV days, severity of illness, or ICU mortality between the two periods. CONCLUSIONS: The large scale implementation of guidelines for ABG use reduced the number of inappropriately ordered ABG determinations over seven different multidisciplinary ICUs, without negatively impacting patient care.

Evaluation of the uptake of the Australian standardized terminology and definitions for texture modified foods and fluids.

This paper discusses the uptake of standardized terminology and definitions for texture modified foods and fluids. The Australian dietetic and speech-language pathology associations endorsed national standards in 2007. This project sought to determine the barriers and enablers for use of the national standards in clinical practice. Cross-sectional online surveys were developed, including open- and closed-response questions. The surveys targeted different professional groups in Australia including speech-language pathologists, dietitians, nurses, and food service personnel. Australian accredited universities were contacted to determine penetration of the standards. A total of 574 surveys were received. Sixty-five per cent of respondents indicated full implementation, 23% partial implementation, and 10% no implementation of the standards in their workplace. Speech-language pathologists and dietitians were most likely to have championed implementation of the standards. Barriers to implementation included: lack of knowledge about the standards, time, and resistance to change. Enablers included: encouragement to use the standards and 'buy-in' from stakeholders. Benefits of implementation included: consistent terminology and perceived improvements in patient safety. It was concluded that the standards have been successfully implemented in a majority of facilities and Australian universities. This study provides insight into the complexity of introducing and managing change in healthcare environments.

Electrochemical impedance spectroscopy-a simple method for the characterization of polymer inclusion membranes containing aliquat 336.

Electrochemical impedance spectroscopy (EIS) has been used to estimate the non-frequency dependent (static) dielectric constants of base polymers such as poly(vinyl chloride) (PVC), cellulose triacetate (CTA) and polystyrene (PS). Polymer inclusion membranes (PIMs) containing different amounts of PVC or CTA, along with the room temperature ionic liquid Aliquat 336 and plasticizers such as trisbutoxyethyl phosphate (TBEP), dioctyl sebecate (DOS) and 2-nitrophenyloctyl ether (NPOE) have been investigated. In this study, the complex and abstract method of EIS has been applied in a simple and easy to use way, so as to make the method accessible to membrane scientists and engineers who may not possess the detailed knowledge of electrochemistry and interfacial science needed for a rigorous interpretation of EIS results. The EIS data reported herein are internally consistent with a percolation threshold in the dielectric constant at high concentrations of Aliquat 336, which illustrates the suitability of the EIS technique since membrane percolation with ion exchangers is a well-known phenomenon.