Controlled release ibuprofen-poloxamer gel for epidural use - A pharmacokinetic study using microdialysis in pigs

In order to avoid the risks of sideeffects of epidural local anesthetics and opioids, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) epidurally would be an interesting option of analgesic therapy. The fairly short duration of action of spinally administered NSAIDs, e.g., ibuprofen, may be prolonged by using controlled release poloxamer gel formulation. Using a microdialysis technique we studied the epidural and intrathecal pharmacokinetics of ibuprofen after its epidural administration as a poloxamer 407 formulation or a solution formulation. In addition, plasma ibuprofen concentrations were analyzed from central venous blood samples. Ibuprofen concentrations in the epidural space were significantly higher and longer lasting after the epidural gel injection compared with the epidural solution injection. The epidural AUC of ibuprofen was over threefold greater after epidural ibuprofen gel injection compared with the ibuprofen solution injection (p <0.001). The systemic absorption of ibuprofen from 25% poloxamer 407 gel was very low. The in situ forming poloxamer gel acted as a reservoir allowing targeted ibuprofen release at the epidural injection site and restricted ibuprofen molecules to a smaller spinal area. Ibuprofen diffusion from the epidural space to the intrathecal space was steady and prolonged. These results demonstrate that the use of epidurally injectable poloxamer gel can increase and prolong ibuprofen delivery from epidural space to the CSF enhancing thus ibuprofen entry into the central neuroaxis for spinal analgesia. Further toxicological and dose-finding studies are justified. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Analgesia and side effects of the addition of 10 or 20 mu g fentanyl to articaine in spinal anesthesia for knee arthroscopy : a randomized and observer-blinded study

Objectives Articaine, a popular and rapidly acting local anesthetic in dentistry, has been also found to be beneficial in ambulatory spinal anesthesia. Analgesia in the intraoperative and immediate postoperative period may be further improved by adding fentanyl to the local anesthetic solution for spinal anesthesia. The aim was to evaluate dose-dependency of analgesia and side effects associated with intrathecal fentanyl additive to articaine for spinal anesthesia in knee arthroscopy patients. Methods In this randomized, observer- and patient-blinded study, 90 adult patients scheduled for elective ambulatory knee arthroscopy under spinal anesthesia were randomized into three groups: plain articaine 60 mg with saline (group AF0), articaine 60 mg with fentanyl 10 A mu g (group AF10) or 20 A mu g (group AF20) in a total volume of 1.9 ml. The blinded observer tested the sensory and the motor block, and performed telephone interviews on the first and seventh postoperative days. Results The median (IQR) duration of sensory block at the dermatomal level of T10 was significantly longer in groups AF10, 69 min (56) and AF20, 69 min (45) than in group AF0, 41 min (35) (p = 0.013). Motor block duration was similar in all groups (median 120 min). Group AF20 patients experienced pruritus significantly more often than patients in the other groups (p = 0.039). No acute or late anesthetic side effects occurred, and satisfaction with the anesthetic technique was the same in all groups (97% satisfied). Conclusions Fentanyl 10 or 20 A mu g as additive to articaine for spinal anesthesia prolonged the duration of sensory block significantly and similarly. Fentanyl 20 A mu g was more often associated with pruritus than fentanyl 10 A mu g.Peer reviewe

Barriers and bridges for sustaining functional habitat networks: A macroecological system analysis of wet grassland landscapes

This study aims at supporting the maintenance of representative functional habitat networks as green infrastructure for biodiversity conservation through transdisciplinary macroecological analyses of wet grassland landscapes and their stewardship systems. We chose ten north European wet grassland case study landscapes from Iceland and the Netherlands in the west to Lithuania and Belarus in the east. We combine expert experiences for 20-30 years, comparative studies made 2011-2017, and longitudinal analyses spanning >70 years. Wader, or shorebird, (Charadrii) assemblages were chosen as a focal species group. We used evidence-based knowledge and practical experience generated in three steps. (1) Experts from 8 wet grassland landscapes in northern Europe's west and east mapped factors linked to patterns and processes, and management and governance, in social-ecological systems that affect states and trends of wet grasslands as green infrastructures for wader birds. (2) To understand wader conservation problems and their dynamic in wet grassland landscapes, and to identify key issues for successful conservation, we applied group modeling using causal loop diagram mapping. (3) Validation was made using the historic development in two additional wet grassland landscapes. Wader conservation was dependent on ten dynamically interacting ecological and social system factors as leverage points for management. Re-wetting and grazing were common drivers for the ecological and social system, and long-term economic support for securing farmers' interest in wader bird conservation. Financial public incentives at higher levels of governance of wetland management are needed to stimulate private income loops. Systems analysis based on contrasting landscape case studies in space and over time can support (1) understanding of complex interactions in social-ecological systems, (2) collaborative learning in individual wet grassland landscapes, and (3) formulation of priorities for conservation, management, and restoration

Estimation of Arterial Carbon Dioxide Based on End-Tidal Gas Pressure and Oxygen Saturation

Arterial blood gas (ABG) analysis is the traditional method for measuring the partial pressure of carbon dioxide. In mechanically ventilated patients a continuous noninvasive monitoring of carbon dioxide would obviously be attractive. In the current study, we present a novel formula for noninvasive estimation of arterial carbon dioxide. Eighty-one datasets were collected from 19 anesthetized and mechanically ventilated pigs. Eleven animals were mechanically ventilated without interventions. In the remaining eight pigs the partial pressure of carbon dioxide was manipulated. The new formula (Formula 1) is PaCO2 = PETCO2 + k(PETO2 - PaO2) where PaO2 was calculated from the oxygen saturation. We tested the agreements of this novel formula and compared it to a traditional method using the baseline PaCO2 - ETCO2 gap added to subsequently measured, end-tidal carbon dioxide levels (Formula 2). The mean difference between PaCO2 and calculated carbon dioxide (Formula 1) was 0.16 kPa (+/- SE 1.17). The mean difference between PaCO2 and carbon dioxide with Formula 2 was 0.66 kPa (+/- SE 0.18). With a mixed linear model excluding cases with cardiorespiratory collapse, there was a significant difference between formulae (p <0.001), as well as significant interaction between formulae and time (p <0.001). In this preliminary animal study, this novel formula appears to have a reasonable agreement with PaCO2 values measured with ABG analysis, but needs further validation in human patients.Peer reviewe

Barriers and bridges for sustaining functional habitat networks: A macroecological system analysis of wet grassland landscapes

This study aims at supporting the maintenance of representative functional habitat networks as green infrastructure for biodiversity conservation through transdisciplinary macroecological analyses of wet grassland landscapes and their stewardship systems. We chose ten north European wet grassland case study landscapes from Iceland and the Netherlands in the west to Lithuania and Belarus in the east. We combine expert experiences for 20–30 years, comparative studies made 2011–2017, and longitudinal analyses spanning >70 years. Wader, or shorebird, (Charadrii) assemblages were chosen as a focal species group. We used evidence-based knowledge and practical experience generated in three steps. (1) Experts from 8 wet grassland landscapes in northern Europe's west and east mapped factors linked to patterns and processes, and management and governance, in social-ecological systems that affect states and trends of wet grasslands as green infrastructures for wader birds. (2) To understand wader conservation problems and their dynamic in wet grassland landscapes, and to identify key issues for successful conservation, we applied group modeling using causal loop diagram mapping. (3) Validation was made using the historic development in two additional wet grassland landscapes. Wader conservation was dependent on ten dynamically interacting ecological and social system factors as leverage points for management. Re-wetting and grazing were common drivers for the ecological and social system, and long-term economic support for securing farmers’ interest in wader bird conservation. Financial public incentives at higher levels of governance of wetland management are needed to stimulate private income loops. Systems analysis based on contrasting landscape case studies in space and over time can support (1) understanding of complex interactions in social-ecological systems, (2) collaborative learning in individual wet grassland landscapes, and (3) formulation of priorities for conservation, management, and restoration.publishedVersio

Laparoscopic Lavage Is Feasible and Safe for the Treatment of Perforated Diverticulitis With Purulent Peritonitis:The First Results From the Randomized Controlled Trial DILALA

To evaluate short-term outcomes of a new treatment for perforated diverticulitis with purulent peritonitis in a randomized controlled trial. BACKGROUND: Perforated diverticulitis with purulent peritonitis (Hinchey III) has traditionally been treated with surgery including colon resection and stoma (Hartmann procedure) with considerable postoperative morbidity and mortality. Laparoscopic lavage has been suggested as a less invasive surgical treatment. METHODS: Laparoscopic lavage was compared with colon resection and stoma in a randomized controlled multicenter trial, DILALA (ISRCTN82208287). Initial diagnostic laparoscopy showing Hinchey III was followed by randomization. Clinical data was collected up to 12 weeks postoperatively. Results: Eighty-three patients were randomized, out of whom 39 patients in laparoscopic lavage and 36 patients in the Hartmann procedure groups were available for analysis. Morbidity and mortality after laparoscopic lavage did not differ when compared with the Hartmann procedure. Laparoscopic lavage resulted in shorter operating time, shorter time in the recovery unit, and shorter hospital stay. CONCLUSIONS: In this trial, laparoscopic lavage as treatment for patients with perforated diverticulitis Hinchey III was feasible and safe in the short-term

Pesticide leaching in Danish groundwater: identification of vulnerable areas

In Denmark the supply of drinking water is based almost solely on groundwater. During the past few decades Danish groundwater monitoring has encountered numerous instances of pollution with pesticides and their metabolites (GEUS 2003a). As a result, some hundreds of abstraction wells out of about 8000 in general water supply have been closed. With this background, there is a particular concern for reducing the leaching of pesticides into the groundwater. In the present study an approach for identification of areas potentially prone to pesticide leaching is described. The potential risk of leaching of pesticides from agricultural areas into groundwater is minimised through a procedure of approval; however, some leaching still occurs (GEUS 2003b). The Danish counties are therefore obliged to identify areas where there is a particular risk of pesticide leaching, and where restrictions in use of pesticides may be introduced to reduce the risk (Miljøstyrelsen 2000). The Geological Survey of Denmark and Greenland (GEUS) and the Danish Institute of Agricultural Sciences (DJF) have carried out a project, focusing on sandy agricultural areas, that attempts to establish the necessary background knowledge for identifying areas particularly prone to pesticide leaching. The project aims to distinguish vulnerable and less vulnerable areas, both locally and nationwide, in a cost-effective way