695 research outputs found
PACS: Pediatric Analgesia after Cardiac SUrgery: Intermittent intravenous paracetamol versus continuous morphine in children younger than three years undergoing cardiothoracic surgery: a multi-center randomized controlled trial.
No full textThis is a a multi-center randomized controlled trial in children aged 0-36 months after cardiac surgery.
.Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has
unwanted hemodynamic and respiratory side effects. Therefore, post–cardiac surgery patients may potentially
benefit from a non-opioid drug for pain relief.
The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement in the first 48 hours.
This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units
(ICUs) in the Netherlands and Belgium. Children who are 0–36 months old are randomly assigned to
receive either intermittent IV paracetamol or continuous IV morphine up to 48 h post-operatively. Morphine
will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be
used to monitor patients. The sample size (n = 208, 104 per arm) was calculated in order to detect a 30%
reduction in morphine dose; two-sided significance level was 5% and power was 95%
Sequestration of Voriconazole and Vancomycin Into Contemporary Extracorporeal Membrane Oxygenation Circuits: Anin vitroStudy
Get PDFBackground: Bacterial and fungal infections are common and often contribute to death
in patients undergoing extracorporeal membrane oxygenation (ECMO). Drug disposition
is altered during ECMO, and adsorption in the circuit is an established causative factor.
Vancomycin and voriconazole are widely used, despite the lack of evidence-based
prescription guidelines.
Objective: The objective of this study was to determine the extraction of voriconazole
and vancomycin by the Xenios/Novalung ECMO circuits.
Methods: We have set up nine closed-loop ECMO circuits, consisting of four different
iLAActivve® kits for neonatal, pediatric, and adult support: three iLA-ActivveMiniLung®
petite kits, two iLA-ActivveMiniLung® kits, two iLA-ActivveiLA® kits, and two iLA-Activve
X-lung® kits. The circuits were primed with whole blood and maintained at physiologic
conditions for 24 h. Voriconazole and vancomycin were injected as a single-bolus
age-related dose into the circuits. Pre-membrane (P2) blood samples were obtained at
baseline and after drug injection at 2, 10, 30, 180, 360 min, and 24 h. A control sample
at 2 min was collected for spontaneous drug degradation testing at 24 h.
Results: Seventy-two samples were analyzed in triplicate. The mean percentage of drug
recovery at 24 h was 20% for voriconazole and 62% for vancomycin.
Conclusions: The extraction of voriconazole and vancomycin by contemporary ECMO
circuits is clinically relevant across all age-related circuit sizes and may result in reduced
drug exposure in vivo
In Vitro Adsorption of Analgosedative Drugs in New Extracorporeal Membrane Oxygenation Circuits
No full textOBJECTIVE:
Evaluate drug disposition of sedatives and analgesics in the Xenios/Novalung extracorporeal membrane oxygenation circuits.
DESIGN:
In vitro experimental study.
SETTING:
Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
SUBJECTS:
Nine closed-loop extracorporeal membrane oxygenation circuits, made up of the iLA Activve console with four different iLA Activve kits: two X-lung kits, two iLA-Activve iLA kits, two MiniLung kits, and three MiniLung petite kits.
INTERVENTIONS:
The circuits were primed with fresh whole blood and maintained under physiologic conditions (pH/temperature) throughout 24 hours. Paracetamol, morphine, midazolam, fentanyl, and sufentanil were injected as standard age-related doses into nine closed-loop extracorporeal membrane oxygenation circuits.
MEASUREMENTS AND MAIN RESULTS:
Pre-membrane (P2) blood samples were obtained prior to drug injection and after injection at 2, 10, 30, 180, 360 minutes, and at 24 hours. A control sample at 2 minutes was collected for spontaneous drug degradation testing at 24 hours. Two hundred sixteen samples were analyzed. After correction for the spontaneous drug degradation, the mean drug loss at 24 hours was paracetamol 49%, morphine 51%, midazolam 40%, fentanyl 84%, sufentanil 83%. Spontaneous degradation was paracetamol 6%, morphine 0%, midazolam 11%, fentanyl 4%, and sufentanil 0%. The decline of drug concentration over time was more pronounced for the more lipophilic drugs.
CONCLUSIONS:
Loss of highly lipophilic drugs in the extracorporeal membrane oxygenation circuits at 24 hours was remarkable. Drug loss is comparable with other hollow fiber extracorporeal membrane oxygenation systems but less than in silicone-based membranes especially in the first hours after injection
Intermittent intravenous paracetamol versus continuous morphine in children younger than three years undergoing cardiothoracic surgery: a multi-center randomized controlled trial.
No full textThis is a a multi-center randomized controlled trial in children aged 0-36 months after cardiac surgery.
.Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has
unwanted hemodynamic and respiratory side effects. Therefore, post–cardiac surgery patients may potentially
benefit from a non-opioid drug for pain relief.
The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement in the first 48 hours.
This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units
(ICUs) in the Netherlands and Belgium. Children who are 0–36 months old are randomly assigned to
receive either intermittent IV paracetamol or continuous IV morphine up to 48 h post-operatively. Morphine
will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be
used to monitor patients. The sample size (n = 208, 104 per arm) was calculated in order to detect a 30%
reduction in morphine dose; two-sided significance level was 5% and power was 95%
Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies
No full textSubstance use among pregnant women is a major public health issue. Both prescription opioid use and illicit opioid abuse have increased dramatically in recent years. Prolonged in utero drug exposure may result in neonatal abstinence syndrome (NAS), an acute multisystemic clinical entity that occurs in the first days of life. This syndrome is caused by abrupt discontinuation of fetal exposure to licit or illicit drugs chronically consumed by the mother during pregnancy and transmitted to the fetus through the placenta. It usually requires prolonged hospitalization and may have long-term effects. The interplay of many factors contributes to its clinical heterogeneity, and its pathophysiology has not been fully unveiled. The first step in NAS management consists of nonpharmacologic interventions and includes promoting breastfeeding when not contraindicated. If withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring system supports care providers across the pharmacotherapy process from initiation through the monitoring phase, until weaning and discontinuation. However, a standardized approach to pharmacotherapy is still lacking. Morphine is usually the first-line agent to treat NAS. Methadone is a valid option, but its safety profile is not completely known. Phenobarbital, despite its lack of effect on gastrointestinal symptoms and unfavorable pharmacologic features, has been identified as a second-line agent to be used in infants unresponsive to opiates. Although buprenorphine and clonidine seem promising, their use requires further validation. Long-term developmental effects of NAS therapy call for more-comprehensive, longitudinal assessments. In this article, key points for use of recommended therapies are outlined, and directions for future research are suggested
Drug Disposition and Pharmacotherapy in Neonatal ECMO : From Fragmented Data to Integrated Knowledge
Get PDFExtracorporeal membrane oxygenation (ECMO) is a lifesaving support technology for potentially reversible neonatal cardiac and/or respiratory failure. As the survival and the overall outcome of patients rely on the treatment and reversal of the underlying disease, effective and preferentially evidence-based pharmacotherapy is crucial to target recovery. Currently limited data exist to support the clinicians in their every-day intensive care prescribing practice with the contemporary ECMO technology. Indeed, drug dosing to optimize pharmacotherapy during neonatal ECMO is a major challenge. The impact of the maturational changes of the organ function on both pharmacokinetics (PK) and pharmacodynamics (PD) has been widely established over the last decades. Next to the developmental pharmacology, additional non-maturational factors have been recognized as key-determinants of PK/PD variability. The dynamically changing state of critical illness during the ECMO course impairs the achievement of optimal drug exposure, as a result of single or multi-organ failure, capillary leak, altered protein binding, and sometimes a hyperdynamic state, with a variable effect on both the volume of distribution (Vd) and the clearance (Cl) of drugs. Extracorporeal membrane oxygenation introduces further PK/PD perturbation due to drug sequestration and hemodilution, thus increasing the Vd and clearance (sequestration). Drug disposition depends on the characteristics of the compounds (hydrophilic vs. lipophilic, protein binding), patients (age, comorbidities, surgery, co-medications, genetic variations), and circuits (roller vs. centrifugal-based systems; silicone vs. hollow-fiber oxygenators; renal replacement therapy). Based on the potential combination of the above-mentioned drug PK/PD determinants, an integrated approach in clinical drug prescription is pivotal to limit the risks of over- and under-dosing. The understanding of the dose-exposure-response relationship in critically-ill neonates on ECMO will enable the optimization of dosing strategies to ensure safety and efficacy for the individual patient. Next to in vitro and clinical PK data collection, physiologically-based pharmacokinetic modeling (PBPK) are emerging as alternative approaches to provide bedside dosing guidance. This article provides an overview of the available evidence in the field of neonatal pharmacology during ECMO. We will identify the main determinants of altered PK and PD, elaborate on evidence-based recommendations on pharmacotherapy and highlight areas for further research
Zwolse stadskrans; herstructurering door stedelijke inbreiding
No full textEen moderne stad van de 21e eeuw vraagt om nieuwe bestemmingen voor strategisch gelegen locaties in bestaand stedelijk gebied. Voor een aantal locaties rond de historische binnenstad van Zwolle zijn ruimtelijke veranderingsmogelijkheden, maar nog geen uitgekristalliseerde plannen. Nieuw bij de inbreiding is het 'krans'-denken. De stadskrans is de zone om de binnenstad, deze functioneert als overgang tussen de binnenstad en de omliggende wijken. Daarbij is het uitgangspunt dat de krans als geheel gezien wordt: een kralensnoer dat bestaat uit verschillende kralen met elk hun eigen thema, karakter en verschijningsvorm. De invulling van de gebieden is het resultaat van twee factoren: het huidige/beoogde karakter van het gebied en het schaalniveau waaraan het gebied gekoppeld is. Het karakter heeft alles te maken met het gebruik en de functionaliteit, zoals onderwijs, cultuur en bedrijvigheid e.d. Het schaalniveau is gekoppeld aan het infrastructurele netwerk, zoals de rijksweg A28, het spoor en de regionale wegen. Het centrum blijft het belangrijkste gebied van de stad, maar kan niet groeien door de fysieke barri van de singel. Aan de andere kant van de singel, op steenworp afstand van de binnenstad, liggen gebieden die door middel van herstructurering het centrum kunnen ondersteunen. Deze gebieden kunnen ruimte bieden aan centrumstedelijke woonmilieus nabij de binnenstad mogelijk gecombineerd met representatieve bedrijvigheid, detailhandel, dienstverlening, horeca, leisure, kantoren en (centrum-)parkeervoorzieningen.Architectur
RECEPTION OF THE EUROPEAN CITY IN THE PROSE BY E.D. AIPIN (CONCERNING THE URBAN CODE OF THE KHANTY LITERATURE)
Get PDFPurpose. The article is devoted to the issue of the urban text, being quite topical in the modern Finno-Ugric philology. The subject of analysis is the reception of the European topos in the works by a leading Khanty writer E.D. Aipin. The author aims to reveal the formation of the urban code in the Khanty literature as based on the example of the works by E.D. Aipin.
Method or methodology of the work. The basis of the research are the historical-cultural and comparative methods, as well as modern approaches to a selective sample analysis of a literary text.
Results. The results of the work lie in the fact that the author interprets the processes of formation of the urban code in the writer’s work of art as well as in national literature of the Khanty people. The research confirms a feature of E.D. Aipin’s idiostyle that was revealed earlier. The author claims the approach that the Khanty writer selected, i.e. the view at a European city through the eyes of a traveler, quite harmoniously represents both the topos and process of metatext formation in the literary work.
Field of practical application of the results. The results of the research can be applied in the field of literary and interdisciplinary humanitarian studies
Interpretation and the Problem of the Intention of the Author, by Burhanetir Tatar
No full textBurhanetir Tatar, Interpretation and the Problem of the Intention of the Author: H.G. Gadamer vs E.D. Hirsh, The Council for Research in Values and Philosophy, 199
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