Severe cerebral emergency : aspects of treatment and outcome in the intensive care patient

Severe Traumatic Brain Injury (TBI) and aneurysmal Subarachnoid Hemorrhage (SAH) are severe cerebral emergencies. They are common reasons for extensive morbidity and mortality in young people and adults in the western world. This thesis, based on five clinical studies in patients with severe TBI (I-IV) and SAH (V), is concentrated on examination of pathophysiological developments and of evaluation of therapeutic approaches in order to improve outcome after cerebral emergency. The treatment for severe TBI patients at Umeå University Hospital, Sweden is an intracranial pressure (ICP)-targeted therapy according to “the Lund-concept”. This therapy is based on physiological principles for cerebral volume regulation, in order to preserve a normal cerebral microcirculation and a normal ICP. The main goal is to avoid development of secondary brain injuries, thus avoiding brain oedema and worsened microcirculation. Study I is evaluating retrospectively 41 children with severe TBI, from 1993 to 2002. The boundaries of the ICP-targeted protocol were obtained in 90%. Survival rate was 93%, and favourable outcome (Glasgow Outcome Scale, score 4+5) was 80%. Study II is retrospectively analysing fluid administration and fluid balance in 93 adult patients with severe TBI, from 1998 to 2001.The ICP-targeted therapy used, have defined fluid strategies. The total fluid balance was positive day one to three, and negative day four to ten. Colloids constituted 40-60% of total fluids given/day. Severe organ failure was evident for respiratory insufficiency and observed in 29%. Mortality within 28 days was 11%. Study III is a prospective, randomised, double-blind, placebo-controlled clinical trial in 48 patients with severe TBI. In order to improve microcirculation and prevent oedema formation, prostacyclin treatment was added to the ICP-targeted therapy. Prostacyclin is endogenously produced, by the vascular endothelium, and has the ability to decrease capillary permeability and vasodilate cerebral capillaries. Prostacyclin is an inhibitor of leukocyte adhesion and platelet aggregation. There was no significant difference between prostacyclin or placebo groups in clinical outcome or in cerebral microdialysis markers such as lactatepyruvate ratio and brain glucose levels. Study IV is part of the third trial and focus on the systemic release of pro-inflammatory mediators that are rapidly activated by trauma. The systemically released pro-inflammatory mediators, interleukin-6 and CRP were significantly decreased in the prostacyclin group versus the placebo group. Study V is a prospective pilot study which analyses asymmetric dimethylarginine (ADMA) concentrations in serum from SAH patients. Acute SAH patients have cerebral vascular, systemic circulatory and inflammatory complications. ADMA is a marker in vascular diseases which is correlated to endothelial dysfunction. ADMA concentrations in serum were significantly elevated seven days after the SAH compared to admission and were still elevated at the three months follow-up. Our results show overall low mortality and high favourable outcome compared to international reports on outcome in severe TBI patients. Prostacyclin administration does not improve cerebral metabolism or outcome but significantly decreases the levels of pro-inflammatory mediators. SAH seems to induce long-lasting elevations of ADMA in serum, which indicates persistent endothelial dysfunction. Endothelial dysfunction may influence outcome after severe cerebral emergencies

Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury : a randomised clinical study

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1. CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583

Survival and growth success of russian olive (Elaeagnus angustifolia L.), salt cedar (Tamarix smyrnensis bunge) and white poplar (Populus alba l.) seedlings in salt-sodic central anatolia areas with gypsum and sulfur applications

YÖK Tez No: 588825İç Anadolu'daki vadi tabanlarının önemli bir kısmı tuzlu-sodik toprak özelliği göstermektedir. Bu çalışmada jips ve kükürt uygulaması ile tuzlu-sodik topraklardan fazla sodyumun yıkanarak toprağın iyileştirilmesi amaçlanmıştır. Toprağa kimyasal işlemler uygulandıktan sonra ılgın (Tamarix smymensis Bunge), iğde (Elaeagnus angustifolia L.) ve akkavak (Populus alba L.) fidanları dikilerek yaşama oranları ve büyüme performansları takip edilmiştir. Üç yaşındaki fidanlar 2013 sonbaharında 1,5 X 1,5 m aralıklarla deneme ünitelerine dikilmiştir. 2015 Eylül sonu fidanların yaşama oranları belirlenerek boy ve çap ölçümleri gerçekleştirilmiştir. İkinci büyüme sezonu sonunda %80 'lik bir oranla en fazla yaşama yüzdesine ılgın türünün sahip olduğu belirlenmiştir. Akkavak bütün işlem alanlarında ortalama %36'lık bir yaşama yüzdesi göstermiştir. İğde jips ve kükürt uygulanan sahalarda 50 cm boy büyümesi yaparken kontrol sahalarında sadece 25 cm boy büyümesi yapabilmiştir. İğde fidanlarının çap ortalaması da jips ve kükürt uygulanan sahalarda 9.3 mm olarak ölçülürken kontrol sahalarında bu değer 5 mm olarak kaydedilmiştir. Akkavak ise jips ve kükürt uygulanan alanlarda kontrol sahalarına göre %42 daha fazla büyüme gerçekleştirmiştir. Ilgının büyümesi bakımından ise sahalar arasında istatistiki olarak önemli bir farklılık bulunamamıştır. Denenen türlerden de iğdenin bütün sahalarda en iyi yaşama oranını ve büyüme performansını gösterdiği ortaya çıkmıştır.An important part of the valley bases in Central Anatolia shows salt-sodic soil characteristics. In this study, it is aimed to improve the soil by washing more sodium than salty-sodic soils with gypsum and sulfur application. After chemical treatment was applied to the soil, tamarisk (Tamarix Smymensis Bunge), spindle (Elaeagnus angustifolia L.) and abele (Populus alba L.) seedlings were planted, and their survival rates and growth performances were followed. Three-year-old seedlings were planted in trial units in the autumn of 2013 at 1.5 X 1.5 m intervals. By the end of September 2015, height and diameter measurements of saplings were made. At the end of the second growth season, it was determined that 80% of the tamarisk had the highest percentage of life. Abele showed an average survival rate of 36% in all processing areas. While spindle was 50 cm in gypsum and sulfur were applied, it was able to grow only 25 cm in the control areas. The average diameter of the seedling saplings was measured as 9.3 mm in gypsum and sulfur treated areas and this value was recorded as 5 mm in the control areas. Abele achieved 42% more growth in gypsum and sulfur treated areas than in control areas. In terms of Tamarisk growth, no statistically significant difference was found between the sites. Among the tested species, spindle was found that the spindle showed the best survival rate and growth performance in all fields

AS Aldaris strategic governance improvement directions.

Maģistra darba tēma ir A/S „ALDARIS” stratēģiskās vadīšanas pilnveidošanas virzieni. Savukārt darba mērķis ir izpētīt un analizēt A/S „ALDARIS” uzņēmuma darbību, tās stratēģiskās vadīšanas virzienus, jo A/S „ALDARIS” ir viena no senākajām un lielākajām alus darītavām Latvijā, turklāt uzņēmuma zīmols mūsdienās kļuvis atpazīstams arī ārpus valsts robežām. A/S „ALDARIS” ir viens no vadošajiem alus ražotājiem Latvijas alus nozarē. Maģistra darba pirmajā nodaļā tiek pētīta alus nozare Latvijas tautsaimniecībā, alus kultūra, tradicionālā pieeja un attīstības gaita. Otrajā nodaļā tiek pētīta pirmā saskarsme ar Carlsberg Grupu, uzņēmuma pievienošanās vienam no pasaules līderiem alus ražošanas nozarē, kā arī tiek aplūkotas valsts likumdošanas izmaiņas saistībā ar akcīzes nodokļa maiņām, kas būtiski ietekmē alus nozares uzņēmumus. Trešajā nodaļā tiek pētītas vadības stratēģijas, izveidota SVID analīze, kā arī veikta aptauja, lai noskaidrotu patērētāju viedokli par uzņēmuma darbību. Ceturtajā nodaļā tiek pētīta nākotnes vīzija par uzņēmuma attīstību, jaunu produktu ieviešana tirgū, papildus motivācijas sistēma, kā arī izvērtēta vadītāja un līderu loma uzņēmumā. A/S „ALDARIS” uzņēmuma analizējamais periods ir no 2008. - 2018.gadam. Maģistra darbs uzrakstīts latviešu valodā un tas sastāv no 93 lappuses, 2 pielikumiem, 14 tabulām, 25 attēliem un darbā tika izmantoti 77 literatūras avotiem.The theme of the master degree work is AS Aldaris strategic governance improvement directions. In turn, the aim of the work ir explore and analyze AS Aldaris the activities of the company, it’s strategic directions of management, because company is one of the oldest and largest breweries in Latvia, besides, the company’s brand has no become recognizable also abroad. AS Aldaris is one of the leading breweries in the Latvian beer industry. The first chapter of the master’s paper investigates the beer industry in the national economy of Latvia, the culture of beer, the tradiciocal approach and the course of development. The second chapter examines the first contact with the Carlsberg Group, the company's accession to one of the world's leaders in the beer industry, and examines changes in national legislation regarding excise tax changes that have a significant impact on beer industry companies. The third chapter examines management strategies, develops SWOT analysis, and conducts a survey to find out the views of consumers about the company's operations. The fourth chapter examines the future vision of the company's development, the introduction of new products on the market, an additional motivation system, and assesses the role of manager and leaders in the company. The analyzing period of the AS Aldaris is from 2008 to 2018. The Master job is written in Latvian and ir consist of 93 pages, 2 supplements, 14 appendixes, 25 pictures, 77 literature resources were used in the wor

P E D I A T R I C O R I G I N A L Severe traumatic brain injury in pediatric patients: treatment and outcome using an intracranial pressure targeted therapy- the Lund concept Springer-Verlag 2005

Abstract Objective: This study evaluated the outcome of treatment according to the Lund concept in children with severe traumatic brain injury and investigated whether the preset goals of the protocol were achieved. Design and setting: A twocenter retrospective study in neurointensive care units at university hospitals. Patients: Forty-one children with severe traumatic brain injury from blunt trauma and arriving at hospital within 24 h after injury. Median age was 8.8 years (range 3 months-14.2 years), Glasgow Coma Scale 7 (3-8), and Injury Severity Score 25 (16-75). All children had pathological findings on initial computed tomography. All developed intracranial hypertension, and survivors required intensive care longer than 72 h. Interventions: Treatment according to the principles of the Lund concept. Measurements and results: Neurosurgery was required in 46% of the children. Survival rate was 93% and favorable outcome (Glasgow Outcome Score 4 or 5) was 80% at long-term follow-up (median 12 months postinjury, range 2.5-26). The preset physiological and biochemical goals were achieved in over 90% of observations. Conclusions: Treating pediatric patients with severe traumatic brain injury, according to the Lund concept, results in a favorable outcome when the protocol is followed

Prostacyclin treatment in severe traumatic brain injury : a microdialysis and outcome study

Prostacyclin (PGI2) is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation. In trauma the balance between PGI2 and thromboxane A2 (TXA2) is shifted towards TXA2. External provided PGI2 would, from a theoretical and experimental point of view, improve the microcirculation in injured brain tissue. This study is a prospective consecutive double blinded randomised study on the effect of PGI2 versus placebo in severe traumatic brain injury (sTBI). All patients with sTBI were eligible. Inclusion criteria: verified sTBI, Glasgow Coma Score (GCS) at intubation and sedation ≤8, age 15 - 70 years, a first recorded cerebral perfusion pressure (CPP) of ≥ 10mmHg, and arrival within 24h of trauma. All subjects received an intra-cranial pressure (ICP) measuring device, bilateral intracerebral microdialysis catheters, and a microdialysis catheter in the abdominal subcutaneous adipose tissue. Subjects were treated according to an ICP targeted therapy based on the Lund concept. 48 patients, mean age of 35.5 years, and a median GCS 6 (3-8) were included. We found no significant effect of epoprostenol on either the lactate pyruvate ratio (L/P) at 24 hours or the brain glucose levels. There was no significant difference in clinical outcome between the two groups. The median Glasgow Outcome Score (GOS) at 3 months was 4, and mortality was 12.5%. The favourable outcome (GOS 4-5) was 52%. The initial L/P did not prognosticate for outcome. Thus our results indicate that there is no effect of PGI2 at a dose of 0.5 ng/kg/min on brain L/P, brain glucose levels or outcome at 3 months. The treatment seemed to yield a high number of favourable outcome and low mortalit

Effective ICP reduction by decompressive craniectomy in patients with severe traumatic brain injury treated by an ICP-targeted therapy

Severe traumatic brain injury (TBI) is one of the major causes of death in younger age groups. In Umea, Sweden, an intracranial pressure (ICP) targeted therapy protocol, the Lund concept, has been used in treatment of severe TBI since 1994. Decompressive craniectomy is used as a protocol-guided treatment step. The primary aim of the investigation was to study the effect of craniectomy on ICP changes over time in patients with severe TBI treated by an ICP-targeted protocol. In this retrospective study, all patients treated for severe TBI during 1998-2001 who fulfilled the following inclusion criteria were studied: GCS <or= 8 at intubation and sedation, first recorded cerebral perfusion pressure (CPP) of >10 mm Hg, arrival within 24 h of trauma, and need of intensive care for >72 h. Craniectomy was performed when the ICP could not be controlled by evacuation of hematomas, sedation, ventriculostomy, or low-dose pentothal infusion. Ninety-three patients met the inclusion criteria. Mean age was 37.6 years. Twenty-one patients underwent craniectomy as a treatment step. We found a significant reduction of the ICP directly after craniectomy, from 36.4 mm Hg (range, 18-80 mm Hg) to 12.6 mm Hg (range, 2-51 mm Hg). During the following 72 h, we observed an increase in ICP during the first 8-12 h after craniectomy, reaching approximately 20 mm Hg, and later levelling out at approximately 25 mm Hg. The reduction of ICP was statistically significant during the 72 h. The outcome as measured by Glasgow Outcome Scale (GOS) did not significantly differ between the craniectomized group (DC) and the non-craniectomized group (NDC). The outcome was favorable (GOS 5-4) in 71% in the craniectomized group, and in 61% in the non-craniectomized group. Craniectomy is a useful tool in achieving a significant reduction of ICP overtime in TBI patients with progressive intracranial hypertension refractory to medical therapy. The procedure seems to have a satisfactory effect on the outcome, as demonstrated by a high rate of favorable outcome and low mortality in the craniectomized group, which did not significantly differ compared with the non-craniectomized group

Multilevel Intervention Mapping with sleepiness in focus

Driver fatigue is an important risk factor in traffic safety and an issue for both private and professional drivers. This report provides an analysis of risk factors related to fatigue-related road accidents, and describes intervention goals at multiple levels in order to reduce sleepy driving among drivers. Private drivers who are on their way to or from their holiday were assigned as the specific target group

Severe traumatic brain injury in pediatric patients : treatment and outcome using an intracranial pressure targeted therapy–the Lund concept

Objective: This study evaluated the outcome of treatment according to the Lund concept in children with severe traumatic brain injury and investigated whether the preset goals of the protocol were achieved. Design and setting: A two-center retrospective study in neurointensive care units at university hospitals. Patients: Forty-one children with severe traumatic brain injury from blunt trauma and arriving at hospital within 24 h after injury. Median age was 8.8 years (range 3 months–14.2 years), Glasgow Coma Scale 7 (3–8), and Injury Severity Score 25 (16–75). All children had pathological findings on initial computed tomography. All developed intracranial hypertension, and survivors required intensive care longer than 72 h. Interventions: Treatment according to the principles of the Lund concept. Measurements and results: Neurosurgery was required in 46% of the children. Survival rate was 93% and favorable outcome (Glasgow Outcome Score 4 or 5) was 80% at long-term follow-up (median 12 months postinjury, range 2.5–26). The preset physiological and biochemical goals were achieved in over 90% of observations. Conclusions: Treating pediatric patients with severe traumatic brain injury, according to the Lund concept, results in a favorable outcome when the protocol is followed