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Search Results: 1 - 10 of 192446 matches for " G?ran Hedenstierna "
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Pharyngeal oxygen administration increases the time to serious desaturation at intubation in acute lung injury: an experimental study
Joakim Engstr?m, Gran Hedenstierna, Anders Larsson
Critical Care , 2010, DOI: 10.1186/cc9027
Abstract: Eight anesthetized piglets with collapse-prone lungs induced by lung lavage were ventilated with a fraction of inspired oxygen of 1.0 and a positive end-expiratory pressure of 5 cmH2O. The shunt fraction was calculated after obtaining arterial and mixed venous blood gases. The trachea was extubated, and in randomized order each animal received either 10 L oxygen per minute or no oxygen via a pharyngeal catheter, and the time to desaturation to pulse oximeter saturation (SpO2) 60% was measured. If SpO2 was maintained at over 60%, the experiment ended when 10 minutes had elapsed.Without pharyngeal oxygen, the animals desaturated after 103 (88-111) seconds (median and interquartile range), whereas with pharyngeal oxygen five animals had a SpO2 > 60% for the 10-minute experimental period, one animal desaturated after 7 minutes, and two animals desaturated within 90 seconds (P < 0.016, Wilcoxon signed rank test). The time to desaturation was related to shunt fraction (R2 = 0.81, P = 0.002, linear regression); the animals that desaturated within 90 seconds had shunt fractions >40%, whereas the others had shunt fractions <25%.In this experimental acute lung injury model, pharyngeal oxygen administration markedly prolonged the time to severe desaturation during apnea, suggesting that this technique might be useful when intubating critically ill patients with acute respiratory failure.Endotracheal intubation is one of the most hazardous procedures in the ICU. This is because the patients are usually in a compromised circulatory and pulmonary condition in which low functional residual capacity in combination with a pulmonary shunt and increased oxygen consumption contribute to rapidly developing hypoxemia during apnea [1-4]. Although complications may be reduced by rigorously following protocols, more than 20% of endotracheal intubations in patients in the ICU are associated with serious complications, usually caused by severe hypoxemia [5]. Furthermore, in more than 10% of p
Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse
G?rel Nyman, Stina Marntell, Anna Edner, Pia Funkquist, Karin Morgan, Gran Hedenstierna
Acta Veterinaria Scandinavica , 2009, DOI: 10.1186/1751-0147-51-22
Abstract: Seven Standardbred trotter horses aged 3–7 years and weighing 380–520 kg, were studied. The protocol consisted of three consecutive measurements; in the unsedated horse, after intravenous administration of detomidine (0.02 mg/kg) and after subsequent butorphanol administration (0.025 mg/kg). Pulmonary function and haemodynamic effects were investigated. The distribution of ventilation-perfusion ratios (VA/Q) was estimated with MIGET.During detomidine sedation, arterial oxygen tension (PaO2) decreased (12.8 ± 0.7 to 10.8 ± 1.2 kPa) and arterial carbon dioxide tension (PaCO2) increased (5.9 ± 0.3 to 6.1 ± 0.2 kPa) compared to measurements in the unsedated horse. Mismatch between ventilation and perfusion in the lungs was evident, but no increase in intrapulmonary shunt could be detected. Respiratory rate and minute ventilation did not change. Heart rate and cardiac output decreased, while pulmonary and systemic blood pressure and vascular resistance increased. Addition of butorphanol resulted in a significant decrease in ventilation and increase in PaCO2. Alveolar-arterial oxygen content difference P(A-a)O2 remained impaired after butorphanol administration, the VA/Q distribution improved as the decreased ventilation and persistent low blood flow was well matched. Also after subsequent butorphanol no increase in intrapulmonary shunt was evident.The results of the present study suggest that both pulmonary and cardiovascular factors contribute to the impaired pulmonary gas exchange during detomidine and butorphanol sedation in the horse.The possibility of producing potent sedation of horses by alpha-2-adrenoreceptor agonists (α2-agonists) is one of the greatest improvements in modern equine practice. The dose-dependent sedation and analgesia produced by the α2-agonists is reliable for diagnostic procedures and for treatment of various conditions. The central action of the α2-agonist is a presynaptic inhibition of noradrenaline accompanied by a decreased sympathetic tone
Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury
Sebastien Trachsel, Ginette Deby-Dupont, Edwige Maurenbrecher, Monique Nys, Maurice Lamy, Gran Hedenstierna
Critical Care , 2008, DOI: 10.1186/cc7099
Abstract: After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion.Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 ≥ 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO.ET-1 may therefore be involved in mediating the response to INO.Despite years of research and efforts for specific treatments of acute respiratory distress syndrome (ARDS), mortality remains significant [1]. A symptomatic approach aimed at fluid restriction, diuresis, reducing pulmonary hypertension and improving arterial oxygenation are the goals of therapy. The use of intravenous vasodilators to reduce pulmonary hypertension is limited because of deleterious side effects. Arterial oxygenation may worsen because of increased blood flow to nonventilated areas of the lung and systemic effects that can result in hypotension [2]. Inhaled nitric oxide (INO) allows selective pulmonary vasodilation and improves arterial oxygenation by redistribution of blood flow towards better ventilated parenchyma [3]. The clinical application of INO in ARDS and septic
Spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial
Hermann Wrigge, J?rg Zinserling, Peter Neumann, Thomas Muders, Anders Magnusson, Christian Putensen, Gran Hedenstierna
Critical Care , 2005, DOI: 10.1186/cc3908
Abstract: In this randomized controlled experimental trial, 22 pigs with oleic-acid-induced lung injury were randomly assigned to receive APRV with or without spontaneous breathing at comparable airway pressures. Four hours after randomization, dynamic computed tomography scans of the lung were obtained in an apical slice and in a juxtadiaphragmatic transverse slice. Analyses of regional attenuation were performed separately in nondependent and dependent halves of the lungs on end-expiratory scans and end-inspiratory scans. Tidal changes were assessed as differences between inspiration and expiration of the mechanical breaths.Whereas no differences were observed in the apical slices, spontaneous breathing resulted in improved tidal ventilation of dependent lung regions (P < 0.05) and less cyclic collapse (P < 0.05) in the juxtadiaphragmatic slices. In addition, with spontaneous breathing, the end-expiratory aeration increased and nonaerated tissue decreased in dependent lung regions close to the diaphragm (P < 0.05 for the interaction ventilator mode and lung region).Spontaneous breathing during APRV redistributes ventilation and aeration to dependent, usually well-perfused, lung regions close to the diaphragm, and may thereby contribute to improved arterial oxygenation. Spontaneous breathing also counters cyclic collapse, which is a risk factor for ventilation-associated lung injury.Spontaneous breathing in any phase of the mechanical ventilator cycle is possible during airway pressure release ventilation (APRV), a technique that provides ventilatory support by time-cycled switching between two continuous positive airway pressure levels [1-3]. Studies in patients with acute lung injury (ALI) suggest that spontaneous breathing with APRV not only reduces the need for sedation to adapt the patient to the ventilator [4], but also improves both systemic blood flow and arterial blood oxygenation when compared with controlled mechanical ventilation [4-6]. Mechanisms for improved ox
Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice
Sofia Jonasson, Linda Swedin, Maria Lundqvist, Gran Hedenstierna, Sven-Erik Dahlén, Josephine Hjoberg
Respiratory Research , 2008, DOI: 10.1186/1465-9921-9-23
Abstract: Balb/c mice were sensitized to ovalbumin (OVA) and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics.DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 ± 0.3 to 2.8 ± 0.1 cmH2O·s·mL-1 in healthy mice and 5.1 ± 0.3 to 3.5 ± 0.3 cmH2O·s·mL-1 in acute airway inflammation (both P < 0.001). In healthy mice, DI reduced the maximum decrease in lung compliance from 15.9 ± 1.5% to 5.6 ± 0.6% (P < 0.0001). This protective effect was even more pronounced in mice with chronic inflammation where DI attenuated maximum decrease in compliance from 44.1 ± 6.6% to 14.3 ± 1.3% (P < 0.001). DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both P < 0.0001) and chronic allergen-treated animals (G and H both P < 0.0001).We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.Mice are increasingly being used to develop in vivo models for studying airway physiology and airway inflammation. Exposure to aerosolized antigen in animals mimics the chronic inflammatory characteristics of human asthma and prolonged exposure to allergen has been suggested to be of importance for the development of airway hyperreactivity and remodeling in asthma [1,2].Deep inspirations (DI) have been shown in human subjects to cause a decrease in airway resistance, to have bronchoprotective effects in healthy subjects, and to reverse bronchoconstriction [3-8]
Cardiorespiratory effects of spontaneous breathing in two different models of experimental lung injury: a randomized controlled trial
Dirk Varelmann, Thomas Muders, J?rg Zinserling, Ulf Guenther, Anders Magnusson, Gran Hedenstierna, Christian Putensen, Hermann Wrigge
Critical Care , 2008, DOI: 10.1186/cc7108
Abstract: Forty-four pigs were randomly assigned to ALI resulting either from hydrochloric acid aspiration (HCl-ALI) or from increased intra-abdominal pressure plus intravenous oleic acid injections (OA-ALI) and were ventilated in PCV mode either with SB (PCV + SB) or without SB (PCV – SB). Cardiorespiratory variables were measured at baseline after induction of ALI and after 4 hours of treatment (PCV + SB or PCV – SB). Finally, density distributions and end-expiratory lung volume (EELV) were assessed by thoracic spiral computed tomography.PCV + SB improved arterial partial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2) by a reduction in intrapulmonary shunt fraction in HCl-ALI from 27% ± 6% to 23% ± 13% and in OA-ALI from 33% ± 19% to 26% ± 18%, whereas during PCV – SB PaO2/FiO2 deteriorated and shunt fraction increased in the HCl group from 28% ± 8% to 37% ± 17% and in the OA group from 32% ± 12% to 47% ± 17% (P < 0.05 for interaction time and treatment, but not ALI type). PCV + SB also resulted in higher EELV (HCl-ALI: 606 ± 171 mL, OA-ALI: 439 ± 90 mL) as compared with PCV – SB (HCl-ALI: 372 ± 130 mL, OA-ALI: 192 ± 51 mL, with P < 0.05 for interaction of time, treatment, and ALI type).SB improves oxygenation, reduces shunt fraction, and increases EELV in both models of ALI.Alveolar recruitment in response to therapeutic interventions such as mechanical ventilation with positive end-expiratory pressure (PEEP) has been suggested to differ between direct (pulmonary) or indirect (extrapulmonary) acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) [1-3]. In direct ALI/ARDS, the injury originates from the alveolar epithelium and is characterized by alveolar collapse, fibrinous exudates, and alveolar wall edema [4], which might result in an increased lung elastance while chest wall elastance is often normal Computed tomography (CT) scans show equal amounts of consolidation and ground-glass opacities, with consolidated areas favoring the verte
Organ Dysfunction among Piglets Treated with Inhaled Nitric Oxide and Intravenous Hydrocortisone during Prolonged Endotoxin Infusion
Sofie Paues G?ranson, Waldemar Go?dzik, Piotr Harbut, Stanis?aw Ryniak, Stanis?aw Zielinski, Caroline Gillis Haegerstrand, Andrzej Kübler, Gran Hedenstierna, Claes Frostell, Johanna Albert
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096594
Abstract: Objective It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables. Design Randomized controlled trial. Setting University animal laboratory. Subjects Domestic piglets (n = 30). Interventions Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid. Measurements and Main Results Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups. Conclusions This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion.
Positive end-expiratory pressure optimization with forced oscillation technique reduces ventilator induced lung injury: a controlled experimental study in pigs with saline lavage lung injury
Peter Kostic, Emanuela Zannin, Marie Andersson Olerud, Pasquale P Pompilio, Gran Hedenstierna, Antonio Pedotti, Anders Larsson, Peter Frykholm, Raffaele L Dellaca
Critical Care , 2011, DOI: 10.1186/cc10236
Abstract: 17 pigs, in which acute lung injury (ALI) was induced by saline lavage, were studied. Animals were randomized into two groups: in the first PEEP was titrated according to Xrs (FOT group), in the control group PEEP was set according to the ARDSNet protocol (ARDSNet group). The duration of the trial was 12 hours. In both groups recruitment maneuvers (RM) were performed every 2 hours, increasing PEEP to 20 cmH2O. In the FOT group PEEP was titrated by monitoring Xrs while PEEP was reduced from 20 cmH2O in steps of 2 cmH2O. PEEP was considered optimal at the step before which Xrs started to decrease. Ventilatory parameters, lung mechanics, blood gases and hemodynamic parameters were recorded hourly. Lung injury was evaluated by histopathological analysis.The PEEP levels set in the FOT group were significantly higher compared to those set in the ARDSNet group during the whole trial. These higher values of PEEP resulted in improved lung mechanics, reduced driving pressure, improved oxygenation, with a trend for higher PaCO2 and lower systemic and pulmonary pressure. After 12 hours of ventilation, histopathological analysis showed a significantly lower score of lung injury in the FOT group compared to the ARDSNet group.In a lavage model of lung injury a PEEP optimization strategy based on maximizing Xrs attenuated the signs of ventilator induced lung injury. The respiratory system reactance measured by FOT could thus be an important component in a strategy for delivering protective ventilation to patients with ARDS/acute lung injury.Mechanical ventilation is a mainstay of intensive care for patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A ventilation strategy based on tidal volumes of 6 ml.kg-1 and pre-defined positive end-expiratory pressure (PEEP) settings has been shown to reduce morbidity and mortality probably due to less ventilation-induced lung injury (VILI) [1-3]. Various protocols using higher levels of PEEP in combination
Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery
Sabrine NT Hemmes, Paolo Severgnini, Samir Jaber, Jaume Canet, Hermann Wrigge, Michael Hiesmayr, Edda M Tschernko, Markus W Hollmann, Jan M Binnekade, Gran Hedenstierna, Christian Putensen, Marcelo de Abreu, Paolo Pelosi, Marcus J Schultz
Trials , 2011, DOI: 10.1186/1745-6215-12-111
Abstract: The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH2O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH2O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication.The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications.ISRCTN: ISRCTN70332574Mechanical ventilation is a life-saving strategy in patients with respiratory failure. There is unequivocal evidence that mechanical ventilation in critically ill patients has the potential to aggravate or even initiate lung injury [1,2]. Patients with acute lung injury (ALI) could benefit from measures that prevent repeated collapse and re-expansion of alveoli, including the so-called open lung mechanical ventilation strategy with the use of higher levels of positive end-expiratory pressure (PEEP) and recruitment maneuvers [3]. Meta-analysis suggest this approach can waive the need for rescue therapies due to life-threatening hypoxemia [1], and even reduce mortality in patients with more severe ALI [4].Mechanical ventilation is frequently mandatory in patients who undergo surgery. The effects of short-term intra-operative mechanical ventilation on pulmonary integrity are less well defined [5]. In addition, it is uncertain whether ventilation strategies that use higher levels of PEEP and recruitment maneuvers during the intra-operative period are beneficial in these patients
Gamers versus the Index  [PDF]
Thomas Westin, Gran Lange
Creative Education (CE) , 2012, DOI: 10.4236/ce.2012.38B006
Abstract: This paper presents an ethnographic study of pupils within a trial programme (P2), aimed at developing an upper secondary education for so-called ‘gamers’ who had ‘dropped out’ of school. It was done to follow up a previous trial programme (P1), since many young persons have problems with school. The main question examined here is: When we found situations where the learning worked, by means of social responsitivity, what components were active? How were meaningful affordances created? The trials may be understood from a historical perspective on orality and literacy. Print enabled words to be embedded in space as indexes (tables, lists etc) rather than in time (as orality implies). The index is practiced at the core of traditional school today, with attendance lists and schedules (controlling time and space) and schoolbooks (finalizing the word). Digital culture challenges these structures where the word is not as finalized, and literacy may include other modalities than writing. School is a culture conservative context, which fights back this transformation with more control, through the use of indexes and constraints on digital culture. As contrast, P2 replaced the schedule with full workdays. This enabled the use of commercial off-the-shelf (COTS) computer games, especially massively multiplayer online (MMO) games, as replacement for schoolbooks (not all books). The study is based on interviews with the pupils as well as daily participatory observations for two years. Further, data about attendance over two years and grades at the start and end of P2 are presented. The results show that most of the pupils returned to school, became interested in learning again and got grades. They expressed a sense of freedom, which is closely related to the voluntary aspect of playing a game. In other words, to do things for the sake of the actitivity itself, rather than some external learning goal. The paper concludes with a comparison between P2 and traditional school, based upon the study and suggests future research. A review of related research is also included.
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