No description available.

Hypothermia treatment with cooling to a body temperature of 32-34°C has been shown to be an effective way of improving neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest (CA). The method is used clinically but there are still many questions on the biological mechanisms and on how the treatment is best performed. This thesis focuses on cerebral and haemodynamic effects of hypothermia and rewarming. A porcine model of CA was used. To shorten time to reach target temperature, induction of hypothermia, by means of infusion of 4°C cold fluid, was started already during ongoing cardiopulmonary resuscitation. The temperature was satisfactorily reduced without obvious haemodynamic disturbances. Cerebral effects of hypothermia and rewarming were studied. Microdialysis monitoring showed signs of cerebral energy failure (increased lactate/pyruvate-ratio) and excitotoxicity (increased glutamate) immediately after CA. There was a risk of secondary energy failure that was reduced by hypothermia. Intracranial pressure (ICP) increased gradually after CA irrespectively of if hypothermia was used or not. There were no indications of increasing cerebral disturbances during rewarming. Haemodynamic effects of hypothermia treatment and rewarming were examined in a study of patients successfully resuscitated after CA. Hypothermia was induced by means of cold intravenous infusion. No negative effects on the cardiovascular system were revealed. There were indications of decreased intravascular volume in spite of a positive fluid balance. Cerebral microdialysis and ICP recording were performed in four patients. All patients had signs of energy failure and excitotoxicity following CA. ICP was only exceptionally above 20 mmHg. In contrast to the experimental study indications of increasing ischemia were seen during rewarming. Glycerol had a biphasic pattern, perhaps due to an overspill of metabolites from the general circulation. As most patients become extensively anti-coagulated following CA, intracranial monitoring is not suitable to be used in routine care.

This thesis comprises an investigation into the reaction of halogenated xenobiotics and anaesthetic agents, with hepatic microsomal stearate desaturase. The levels of stearate desaturase in the hepatic microsomes were routinely elevated by re-feeding the experimental animals a high carbohydrate diet. The interaction of the xenobiotics with stearate desaturase was assessed by monitoring their effects on the redox steady state of hepatic microsomal cytochrome b₅, in the presence and absence of cyanide.

No description available.

We recognise consciousness in ourselves and in those around us. Consciousness is the essence of our existence, who and what we are, but we are willing and able to let go of it daily during sleep, which we welcome and associate with rest, recovery and well being, knowing that consciousness will return reliably, when we are ready. Yet we cannot define this thing or process which makes us "us". We do not understand how it is constructed from the activity in our brains, how it is deconstructed by sleep, drugs or disease, or how it can be reconstructed by waking or recovery. Our ignorance renders us reliant on inadequate means of measuring consciousness, dependent on movement for its detection. Propofol is an intravenous anaesthetic drug with the capacity to safely, rapidly and reliably produce sedation and anaesthesia, providing an ideal model of unconsciousness for study. Functional magnetic resonance imaging (fMRI) provides a non-invasive means of measuring activity within the brain. EEG is a convenient broad measure of neuronal activity. This thesis exploits the advantages of each of these techniques, fMRI and EEG, first separately and then together, to link highly informative, spatially specific fMRI observations to convenient, reproducible electrophysiological surface measurements. A safe and reliable model of unconsciousness suitable for fMRI interrogation is first developed and explored. Changes in the spatial extent and interregional correlation of neuronal activity when subjects become unresponsive show that the functional connectivity of the striatum is specifically impaired as perception fails. Disruption of the brain’s internal temporal frame of reference impairs the synthesis of perceptions from their fragments. The second experimental chapter specifically examines the behaviour of sleep oscillations during ultraslow increases and decreases in the depth of sedation with propofol. Functional activity shows that the brain is intensely active despite loss of consciousness and reveals measurable transitions in neuronal activity. Combined simultaneous EEG/FMRI then shows that these transitions reflect stepwise changes in the processing of experience and a shift from externally modulated thalamocortical signaling to an internal dialogue.

Formulation of local anaesthetics in different dosage forms, including those for oral, parenteral, and topical application have being widely investigated. All of these formulations include local anaesthetics in their salt forms. The lipophilic nature of the bases of local anaesthetics may influence the rate of the pharmacological effect. There has been very little research done towards this aspect of local anaesthetics. Prilocaine base and lignocaine base possess greater lipophilicity than their salts. The salt forms undergo dissociation in the body. To maximise the absorption rate lipophilicity plays an important role. The aim of the present study is to evaluate the potential of using prilocaine and lignocaine individually and in combination as bases for parenteral formulations using cyclodextrins as complexing agents. Cyclodextrins are widely used as complexing agents to increase the solubility of poorly soluble drugs. Hydroxypropyl-β-cyclodextrin (HPβCD) was the first choice amongst the different cyclodextrins to be evaluated as a solubility enhancer as it does not show nephrotoxicity and is more bio-available compared to other cyclodextrins. / Method: Prilocaine base was prepared from its salt and lignocaine base was obtained from Sigma Pharmaceuticals. Solubilities were examined individually and in combination by the phase solubility method and complex formation investigated. The mobile phase used was methanol:water (55:45) with phosphate buffer at pH 5.5. An AL type solubility isotherm was obtained for the influence of HPβCD on the solubilities of prilocaine and lignocaine. Complexation was investigated for both prilocaine and lignocaine to HPβCD by NMR. Results: The measured solubilities of prilocaine and lignocaine individually at 30% HPβCD from 25°C to 42°C were 1.96-7.91 moles/L and 1.69-4.55 moles/L respectively. The solubilities in combination were 0.91-3.68 moles/L for prilocaine and 1.03-8.35 moles/L for lignocaine respectively. The NMR data suggested that complexation involves the aromatic ring for both prilocaine and lignocaine apart from methene and methyl groups for prilocaine and ethyl amide and aromatic methyl groups for lignocaine.

Bakgrund: Anestesisjuksköterskor i Sverige har en unik roll i och med att de har ett eget yrkesansvar som ger behörighet att utföra anestesiarbetet självständigt. Det finns många utmaningar som en anestesisjuksköterska ställs inför vid sövning av barn, både ur fysiologisk och psykologisk synvinkel. Få studier finns gjorda kring anestesisjuksköterskors erfarenheter av barninduktion. Syfte: Studiens syfte var att belysa anestesisjuksköterskors erfarenheter vid barninduktion. Metod: Studien genomfördes på ett sjukhus i mellersta Sverige under våren 2011. En kvalitativ intervjumetod användes med innehållsanalys av materialet. Sammanlagt intervjuades 14 anestesisjuksköterskor med varierande yrkeserfarenhet. Resultat: Alla studiedeltagare ansåg att det är en utmaning att söva barn. Med ökad erfarenhet upplevde anestesisjuksköterskorna att de blev tryggare i sin yrkesroll och att de lättare kunde hantera de små marginaler som barns fysiologi innebär. De betonade vikten av en god kommunikation med barnet och dess familj. Ibland uppkom situationer som ställde anestesisjuksköterskan inför etiska dilemman. Diskussion: I studien framkom hur anestesisjuksköterskor utvecklas från att vara noviser till att bli experter på sitt område. En tydlig känsla av yrkesstolthet kunde utläsas av intervjuerna. Anestesisjuksköterskorna befann sig på ett kontinuum mellan att vara uppgifts- eller relationsfokuserad.   Nyckelord: Anestesisjuksköterskor, barninduktion, erfarenheter, omvårdnad, samspel / Background: Nurse Anesthetists in Sweden have a unique role due to the responsibilities required of the profession and due to the fact that NA´s often work alone. There are many challenges a nurse anesthetist meets when performing a child induction, both from a physiological and a psychological aspect. There are only a few studies conducted concerning nurse anesthetists´ experiences of child induction. Aim: The aim of this study was to describe nurse anesthetists´ experiences of child induction. Method: The study was conducted in a hospital in Norrland in the spring of 2011. A qualitative interview method was used with a content analysis of the material. A total of 14 NA´s were interviewed, with a varied amount of years in the profession. Result: All interviewees thought that it was a challenge to perform a child induction. With increasing experience, the NA´s became more comfortable in their professional role and could cope with the small margins that a child´s physiology brings. They all emphasized the importance of a good communication with the child and its family. NA´s sometimes found themselves in situations wherein ethical dilemmas arose. Discussion: The study showed that NA´s evolved from being a novice to becoming an expert in their field. A clear sense of pride of the profession could be read between the lines during the interviews. The NA´s could be found in a continuum between being relationship-oriented and being task-oriented.   Key words: Child induction, experience, interaction,  Nurse anesthetist, Nursing

No description available.

Knowledge of the absorption of inhalation anaesthetic agents is essential if one is to safely administer them. Despite many years of research in linear science, no model has been described that can reliably predict inhalation agent uptake. To date no published investigation has looked for non¬linearity in the absorption process. The aim if this research project was to determine if the absorption of anaesthetic agents is non-linear, using isoflurane and enflurane as examples. To detect non-linearity, four conditions must be met: <ul> <li>Sensitivity to initial conditions, </li> <li>Fractal Dimension of the attract or, </li> <li>Invariant probability distribution of the attractor, and</li> <li>Detection of an underlying dynamical process. <br></li></ul> Ten measured time series for both isoflurane and enflurane absorption were measured. These were then compared with ten noise signals, with similar standard deviations, means and number of points in the series. Calculated Lyapunov exponents tested sensitivity to initial conditions. The dimension of the attractor was calculated using the following statistics, each giving an approximation of the fractal dimension. Approximate entropy, information entropy, correlation dimension and fractal dimension (box counting method). The Invariant probability distribution of the attractor was tested for using non-linear forecasting. Detection of an underlying dynamical process was determined by the method of surrogate data. Each of the four conditions required have been met with statistical significance ( p< 0.05) and acceptable statistical power (>0.8). It is therefore concluded that the absorption of both isoflurane and enflurane are non-linear processes. The implications and implementations in anaesthesia practice are discussed. / Thesis (PhD (Anaesthesiology))--University of Pretoria, 2005. / Anaesthesiology / unrestricted

After two decades of liberal prescribing of opioids, there has been an increasing recognition of problems connected to the prolonged use of opioids for chronic pain. The aim of my thesis was to explore some consequences of long-term opioid treatment for chronic pain such as problematic opioid use, endocrine disorders, tolerance and genetic variations in pain and opioid response. Sixty patients with severe pain and problematic opioid use were treated with a structured methadone programme. Risk factors were musculoskeletal pain, psychiatric co-morbidity and previous addiction. Treatment resulted in good pain relief and improved quality of life, but function was impaired by side effects indicating endocrine dysregulation. The possibility of opioid-induced endocrine dysfunction was explored in the second paper, where 40 pain patients treated with strong opioids and 20 pain patients without treatment of strong opioids were investigated. The opioid-treated patients had significantly higher incidence of endocrine disturbance affecting gonadal and adrenal function and prolactin levels. The functionality of the μ-receptor after long-term treatment with morphine, saline and naloxone was explored in a cell-line expressing the μ-receptor. After one and four weeks of treatment the binding was tested with morphine, methadone, fentanyl and DAMGO and function measured by GTP γ-assay. The binding of DAMGO was significantly diminished after 4 weeks in cells treated with morphine compared with saline and naloxone. Genetic variation in three genes with functional impact on opioid response and pain sensitivity was investigated in 80 patients with chronic low-back pain and differential opioid sensitivity and in 56 healthy controls. The results indicated a higher incidence of opioid-related side effects and gender differences in patients with the minor allele of the ABCB1 gene, a correlation between increased opioid sensitivity and the major CACNA2D2 allele and a possible relationship between intrinsic protection against chronic pain and the minor allele of OPRM1.