| 1. |
- Jacobson, Sofie, 1961-
(författare)
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Severe sepsis : epidemiology and sex-related differences in inflammatory markers
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Sepsis is a syndrome associated with high mortality rates, substantial morbidity and high costs of care. The incidents of sepsis is reported to be high and controversy exists whether gender affect severity or outcome. Little is known about factors determining susceptibility for developing the syndrome and severity of the syndrome once developed. Early detection and adequate antibiotic administration are the mainstay of treatment and means to identify patients with particular high risk of adverse outcome are desirable. There are data to suggest that the course of sepsis and outcome from the syndrome may be influenced by inherited differences in the immunological response among humansAims: Paper I: Assess incidence and outcome for ICU-treated sepsis patients in this region; Paper II: Assess if there are gender differences related to characteristics, aspects of treatment or outcome in sepsis in this region. Paper III: Assess the association of baseline levels of leptin and adiponectin and future sepsis event, and association of these adipokines in the cute phase and sepsis severity and outcome. Paper IV: Assess association of baseline levels of mannose-binding lectin (MBL) and future sepsis event, and MBL levels in the acute phase in relation to sepsis severity and outcome.Results. Paper I: Overall ICU mortality rate was 25%, while the ICU mortality for patients with septic shock was 58% in this retrospective single university hospital cohort analysis. Cardiovascular disease and diabetes were the most prevalent comorbidities among patients who died during hospital stay. Paper II: No gender-related differences in mortality or length of stay was found in this prospective single center observational study. Differences in aspects of treatment were related to differences in site of infection. Men had more often infections in skin and skin-structures, whereas women more often had abdominal infections. Early organ dysfunction assessed as SOFA score at admission was a stronger predictor for hospital mortality for women than for men. The discrepancy was related to the SOFA coagulation-sub score. Paper III: In this nested case-referent study hyperleptinemia at baseline predicted a first-ever sepsis event, even after adjustment for BMI and other cardiovascular risk factors. Hyperleptinemia in the acute sepsis phase was associated with reduced risk of in-hospital death in men, but associated with increased risk of in-hospital death in women. Paper IV: In the same matched cohort as in Paper III high baseline levels of MBL predicted a first ever sepsis event. High MBL levels in the acute phase or an increase from baseline to the acute phase associate with increased in-hospital death in women but not in men. Low MBL levels was not identified as a risk for acute sepsis or in-hospital death.Conclusions. Mortality from severe sepsis is high, equally affecting men and women. There are differences in patient characteristics and inflammatory markers, which associate with in-hospital mortality differentially in men and women. Aspects of gender should be mandatory, and genetic analysis are desired in future sepsis research.
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| 2. |
- Rydvall, Anders, 1950-
(författare)
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Withhold or withdraw futile treatment in intensive care : arguments supported by physicians and the general public
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Since the 60s and with increasing intensity a discussion have continued about balance between useful and useless/harmful treatment. Different attempts have been done to create sustainable criteria and recommendations to manage the situations of futile treatment near the end of life. Obviously, to be able to withhold (WH) or withdraw (WD) treatment which is no longer appropriate or even harmful and burdensome for the patient, other processes than strict medical (or physiological) assessments are necessary.Aim. To shed light on the arguments regarding to WH or WD futile treatment we performed two studies of physicians’ and the general populations’ choice and prioritized arguments in the treatment of a 72-year-old woman suffering from a large intra-cerebral bleeding with bad prognosis (Papers I and II) and a new born boy with postpartum anoxic brain damage (Papers III and IV).Methods. Postal questionnaires based on two cases presented above involving severely ill patients were used. Arguments for and against to WH or WD treatment, and providing treatment that might hasten death were presented. The respondents evaluated and prioritized arguments for and against withholding neurosurgery, withdrawing life-sustaining treatment and providing drugs to alleviate pain and distress. We also asked what would happen to physicians’ own trust if they took the action described, and what the physician estimated would happen to the general publics’ trust in health services (Paper IV).Results. Approximately 70% of the physicians and 46% of the general public responded in both surveys. The 72-year-old woman: A majority of doctors (82.3%) stated that they would withhold treatment, whereas a minority of the general public (40.2%) would do so; the arguments forwarded and considerations regarding quality of life differed significantly between the two groups. Quality-of-life aspects were stressed as an important argument by the majority of both neurosurgeons and ICU-physicians (76.8% vs. 54.0%); however, significantly more neurosurgeons regarded this argument as the most important. A minority in both groups, although more ICU-physicians, supported a patient’s previously expressed wish of not ending in a persistent vegetative state as the most important argument. As the case clinically progressed, a consensus evolved regarding the arguments for decision making.The new born child: A majority of both physicians [56 % (CI 50–62)] and the general population [53 % (CI 49–58)] supported arguments for withdrawing ventilator treatment. A large majority in both groups supported arguments for alleviating the patient’s symptoms even if the treatment hastened death, but the two groups display significantly different views on whether or not to provide drugs with the additional intention of hastening death, although the difference disappeared when we compared subgroups of those who were for or against euthanasia-like actions.Conclusions. There are indeed considerable differences in how physicians and the general public assess and reason in critical care situations, but the more hopelessly ill the patient became the more the groups' assessments tended to converge, although they prioritized different arguments. In order to avoid unnecessary dispute and miscommunication, it is important that health care providers are aware of the public's views, expectations, and preferences. Our hypothesis—physicians’ estimations of others’ opinions are influenced by their own opinions—was corroborated. This might have implications in research as well as in clinical decision-making.
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| 3. |
- Abrahamsson, Pernilla, 1972-
(författare)
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Methodological aspects on microdialysis sampling and measurements
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The microdialysis (MD) technique is widely spread and used both experimentally and in clinical practice. The MD technique allows continuous collection of small molecules such as glucose, lactate, pyruvate and glycerol. Samples are often analysed using the CMA 600 analyser, an enzymatic and colorimetric analyser. Data evaluating the performance of the CMA 600 analysis system and associated sample handling are sparse. The aim of this work was to identify sources of variability related to handling of microdialysis samples and sources of error associated with use of the CMA 600 analyser. Further, to develop and compare different application techniques of the microdialysis probes both within an organ and on the surface of an organ. Material and Methods: Papers I and II are mainly in vitro studies with the exception of the No Net Flux calibration method in paper I where a pig model (n=7) was used to examine the true concentration of glucose and urea in subcutaneous tissue. Flow rate, sampling time, vial and caps material and performance of the analyser device (CMA 600) were examined. In papers III and IV normoventilated anaesthetised pigs (n=33) were used. In paper III, heart ischemia was used as intervention to compare microdialysis measurements in the myocardium with corresponding measurements on the heart surface. In paper IV, microdialysis measurements in the liver parenchyma were compared with measurements on the liver surface in association with induced liver ischemia. All animal studies were approved by the Animal Experimental Ethics Committee at Umeå University Sweden. Results: In paper I we succeeded to measure true concentrations of glucose (4.4 mmol/L) and Urea (4.1 mmol/L) in subcutaneous tissue. Paper II showed that for a batch analyse of 24 samples it is preferred to store microdialysis samples in glass vials with crimp caps. For reliable results, samples should be centrifuged before analysis. Paper III showed a new application area for microdialysis sampling from the heart, i.e. surface sampling. The surface probe and myocardial probe (in the myocardium) showed a similar pattern for glucose, lactate and glycerol during baseline, short ischemic and long ischemic interventions. In paper IV, a similar pattern was observed as in paper III, i.e. data obtained from the probe on the liver surface showed no differences compared with data from the probe in liver parenchyma for glucose, lactate and glycerol concentrations during baseline, ischemic and reperfusion interventions. Conclusion: The MD technique is adequate for local metabolic monitoring, but requires methodological considerations before starting a new experimental serie. It is important to consider factors such as flow rate, sampling time and handling of samples in association with the analysis device chosen. The main finding in this thesis is that analyses of glucose, lactate and glycerol in samples from the heart surface and liver surface reflect concentrations sampled from the myocardium and liver parenchyma, respectively.
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| 4. |
- Claesson, Jonas, 1966-
(författare)
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Intestinal effects of lung recruitment maneuvers
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Lung recruitment maneuvers (brief episodes of high airway pressure) are a modern treatment alternative to achieve open lung conditions under mechanical ventilation of patients with acute lung injury. It is well known that positive pressure ventilation with high airway pressures cause negative circulatory effects, and that the effects on regional vascular beds can be even more pronounced than the systemic effects. Hypoperfusion of the mesenteric vascular bed can lead to tissue ischemia and local inflammation. This intestinal inflammation has been associated with subsequent development of multiple organ dysfunction syndrome, a syndrome that still carries a high mortality and is a leading cause of death for intensive care patients. The aim of this thesis was therefore to investigate whether lung recruitment maneuvers would cause negative effects on mesenteric circulation, oxygenation or metabolism. Methods and results: In an initial study on ten patients with acute lung injury, we could demonstrate a trend towards a decreased gastric mucosal perfusion during three repeated lung recruitment maneuvers. To more closely examine this finding, we set up an oleic acid lung injury model in pigs, and in our second study we established that this model was devoid of inherent intestinal effects and was adequate for subsequent studies of intestinal effects of lung recrutiment maneuvers. In the acute lung injury model, we also tested the effect of an infusion of a vasodilating agent concurrent with the recruitment maneuvers, the hypothesis being that a vasodilating agent would prevent intestinal vasoconstriction and hypoperfusion. We could show that three repeated lung recruitment maneuvers induced short term negative effects on mesenteric oxygenation and metabolism, but that these findings were transient and short lasting. Further, the effects of prostacyclin were minor and opposing. These findings of relative little impact on the intestines of lung recruitment maneuvers, lead us to investigate the hypothesis that repeated recruitment maneuvers maybe could elicite a protective intestinal preconditioning response, a phenomenon previously described both in the rat and in the dog. However, in our fourth study, using both classical ischemic preconditioning with brief periods of intestinal ischemia or repeated lung recrutiment maneuvers, we could not demonstrate the phenomenon of intestinal preconditioning in the pig. Conclusions: We conclude, that from a mesenteric point of view, lung recruitment maneuvers are safe, and only induce transient and short lasting negative effects. We also conclude that the cause of the minor effects of lung recruitment maneuvers is not dependent on intestinal preconditioning.
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| 5. |
- Lindgren, Lenita, 1966-
(författare)
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Emotional and physiological responses to touch massage
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Clinical findings indicate that touch massage has the ability to induce positive emotions and influence stress responses. However, little is known about mechanisms that can explain observed responses.Aim: To understand mechanisms behind observed emotional and physiological responses during and after touch massage.Methods: This thesis is based upon healthy volunteers in Studies I, II, IV and patients undergone aortic surgery in Study III. Study I had a crossover design, participants served as their own controls. After randomization they received TM on one occasion and the other occasion served as control. Heart rate variability (HRV), heart rate (HR) saliva cortisol concentration, glucose, insulin in serum and extracellular (ECV) levels of glucose, lactate, glycerol and pyruvat were measured before, during and after TM/control. In study II, functional magnetic resonance imaging (fMRI) was used in order to measure brain activity during TM movement. The study design included four different touch stimulations, human touch with movement (TM movement) human stationary touch and rubber glove with or without movement. Force (2.5 N) and velocity (1.5 cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale). Study III had a randomized controlled design. The intervention group received TM and the control group rested. HRV, cortisol, glucose, insulin in serum, blood pressure, oxygen saturation, respiratory frequency and anxiety levels were measured before, during and after TM/control. In study IV participants were interviewed about experiences after TM and the text was analyzed in by qualitative content analyze.Results:Study I. TM reduced the stress response as indicated by decreased heart rate and decreased activity in the sympathetic nervous system, followed by a compensatory decrease in parasympathetic nervous activity in order to maintain balance. Cortisol and insulin levels decreased significantly after intervention, while serum glucose levels remained stable. A similar, though less prominent, pattern was seen during the control session. There were no significant differences in ECV concentrations of analyzed substances.Study II. Human moving touch (TM movement) was significantly rated as the most pleasant touch stimulation. The fMRI results revealed that human moving touch (TM movement) most strongly activated the pregenual anterior cingulate cortex (pgACC).Study III. Selfrated anxiety levels significantly decreased in the patient group that received TM compared with control group. There were no significant differences in physiological stress-related outcome parameters between patients who received touch massage and controls.Study IV. In this study participants talked about the experience of TM in terms of rewards. Expressions like need, desire, pleasure and conditioning could be linked with a theoretical model of reward. Four different categories were identified as wanting, liking, learning and responding.In conclusion: Results from these studies indicate that receiving TM is experienced as rewarding. Touch massage movement activates a brain area involved in coding of rewarding pleasant stimulations. TM decreases anxiety and dampens the stress response by a decreased activation of the sympathetic nervous activity. Our results indicate that TM is a caring intervention that can be used to induce pleasure, decrease anxiety and stress in the receiver.
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| 6. |
- Samuelsson, Anders, 1960-
(författare)
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Effects of burns and vasoactive drugs on human skin : Clinical and Experimental studies using microdialysis
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients who require critical care, including those with burns, are affected by a systemic inflammatory reaction, which at times has consequences such as multiple organ dysfunction and failure. It has become increasingly evident that other factors important in the development of organ dysfunction are disturbances at the tissue level, in the microcirculation. Such disturbances activate cascade systems including stress hormones, all of which have local effects on organ function.Despite this knowledge, monitoring and treatment in critical illness today relies mainly on central haemodynamics and blood sampling.Microdialysis is a minimally invasive technique that enables us to study the chemical composition and changes in biochemistry in the extracellular, extravascular space in living tissues. Most of our current experience is from animal models, but the technique has also been used in humans and has become routine in many neurosurgical intensive care units to monitor brain biochemistry after severe injury. In skin, this experience is limited. During the first half of this thesis we studied the injured and uninjured skin of severely burned patients. The results show that there are severe local metabolic disturbances in both injured and uninjured skin. Most interesting is a sustained tissue acidosis, which is not detectable in systemic (blood) sampling. We also recorded considerable alterations in the glucose homeostasis locally in the skin, suggesting a cellular or mitochondrial dysfunction. In parallel, we noted increased tissue glycerol concentrations, which indicated appreciable traumainduced lipolysis.We also examined serotonin kinetics in the same group of patients, as serotonin has been claimed to be a key mediator of the vasoplegia and permeability disturbances found in patients with burns. We have shown, for the first time in humans to our knowledge, that concentrations of serotonin in skin are increased tenfold, whereas blood and urine concentrations are just above normal. The findings support the need for local monitoring of substances with rapid local reabsorption, or degradation, or both. The results also indicate that serotonin may be important for the systemic response that characterises burn injuries.In the second half of the thesis we evaluated the effects of microdosing in skin on metabolism and blood flow of vasoactive, mainly stress-response-related, drugs by the microdialysis system. The objectives were to isolate the local effects of the drugs to enable a better understanding of the complex relation between metabolic effects and effects induced by changes in local blood flow. In the first of these two studies we showed that by giving noradrenaline and nitroglycerine into the skin of healthy subjects we induced anticipated changes in skin metabolism and blood flow. The results suggest that the model may be used to examine vascular and metabolic effects induced locally by vasoactive compounds. Data from the last study indicate that conventional pharmacodynamic models (Emax) for time and dose response modelling may be successfully used to measure the vascular and metabolic response in this microdosing model.We conclude that the microdialysis technique can be successfully used to monitor skin metabolism and iso late a mediator (serotonin) of the local skin response in burned patients. It was also feasible to develop a vascular model in skin based on microdialysis to deliver vasoactive substances locally to the skin of healthy volunteers. This model provided a framework in which the metabolic effects of hypoperfusion and reperfusion in skin tissues could be examined further.
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| 7. |
- Bergmann, Astrid, 1972-
(författare)
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Remote Ischemic Preconditioning and its Effects on the Respiratory System
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mechanical ventilation in itself can lead to pulmonary damage, and one-lung ventilation (OLV), necessary for thoracic surgery, accentuates this injury. Remote ischemic preconditioning (RIP) is a potential tool to reduce lung injury after mechanical ventilation, including OLV. However, current data on pulmonary RIP-effects are contradictory. Therefore, the overall purpose of this Ph.D. project was to assess the effects of RIP on the respiratory system. In Study I, in healthy spontaneously breathing volunteers, oxygenation was impaired early after RIP, which was possibly induced by transient ventilation-perfusion inequality. Studies II, III, and IV were performed in a porcine OLV model. In Study II, we found that RIP possibly enhances alveolar injury, but attenuates the immune response. In Study III, we confirmed that an immune response to RIP takes place, which shows a different time pattern in each cytokine, depending on the site of measurement as well. In Study IV, we studied the porcine model for eight hours and found that RIP improved oxygenation after two hours of OLV and impeded the decline of exhaled nitric oxide (NO) during and after OLV. These findings indicate that RIP mitigates hypoxic pulmonary vasoconstriction (HPV).In summary, RIP has a complex effect on the respiratory system, which partly explains the previous contradictory findings.
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| 8. |
- Pösö, Tomi, 1972-
(författare)
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Assessment and management of bariatric surgery patients
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: In morbidly obese individuals (MO) cardiorespiratory comorbidities and body habitus challenge the perioperative management of anesthesia. To implement safe and reproducible routines for anesthesia and fluid therapy is the cornerstone in order to minimize anesthesia-related complications and to meet individual variability in rehydration needs. Methods: Paper I: Impact of rapid-weight-loss preparation prior to bariatric surgery was investigated. Prevalence of preoperative dehydration and cardiac function were assessed with transthoracic echocardiography (TTE). Paper II: The anesthetic technique for rapid sequence induction (RSI) in MO based on a combination of volatile and i.v. anesthetics was developed. Pre- and post-induction oxygenation, blood pressure levels and feasibility of the method was evaluated. Paper III: The preoperative ideal body weight based rehydration regime was evaluated by TTE. Paper IV: Need of rehydration during bariatric surgery was evaluated by comparing conventional monitoring to a more advanced approach (i.e. preoperative TTE and arterial pulse wave analysis).Results: Rapid-weight-loss preparation prior to bariatric surgery may expose MO to dehydration. TTE was shown to be a robust modality for preoperative screening of the level of venous return, assessment of filling pressures and biventricular function of the heart in MO. The combination of sevoflurane, propofol, alfentanil and suxamethonium was demonstrated to be a safe method for RSI regardless of BMI. The preoperative rehydration regime implemented by colloids 6 ml/kg IBW was an adequate treatment to obtain euvolemia. In addition, preoperative rehydration seems to increase hemodynamic stability during intravenous induction of anesthesia and even intraoperatively. Conclusion: This thesis describes a safe and comprehensive perioperative management of morbidly obese individuals scheduled for bariatric surgery. Hemodynamic and respiratory stability can be achieved by implementation of strict and proven methods of anesthesia and fluid therapy. Much focus should be placed on feasible monitoring and preoperative optimization in morbidly obese individuals for increased perioperative safety.
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| 9. |
- Sehlin, Maria, 1967-
(författare)
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Resistance breathing with PEP and CPAP : effects on respiratory parameters
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Positive expiratory pressure (PEP) and continuous positive airway pressure (CPAP) are two forms of resistance breathing used in spontaneously breathing patients. With a threshold resistor or a flow resistor, both PEP and CPAP provide a positive (elevated) pressure level during the expiratory phase. With PEP, inspiratory pressure is negative, i.e. lower than ambient air pressure, as during a normal inspiration, but with CPAP, the inspiratory pressure is positive, i.e. higher than ambient air pressure.Methods: This thesis is based on four separate studies in which four different breathing devices, a PEP-bottle (threshold resistor device), a PEP-mask (flow resistor device), a threshold resistor CPAP and a flow resistor device were investigated. Paper I, II and III are based on studies in healthy volunteers. Paper IV is a bench study performed in a hypobaric chamber. Paper I examined differences between two PEP devices, the PEP-bottle and the PEP-mask. Paper II evaluated the performance of a flow resistor CPAP device, (Boussignac CPAP). Paper III investigated the effect of two PEP-devices, a PEP-bottle and a PEP-mask and two CPAP devices, a threshold resistor CPAP and a flow resistor CPAP, on inspiratory capacity (IC). In paper IV, the effect of changes in ambient pressure on preset CPAP levels in two different CPAP devices was compared.Results: With the PEP bottle, both expiration and inspiration began with a zero-flow period during which airway pressure changed rapidly. With the PEP-mask, the zero-flow period was very short and the change in airway pressure almost non-existent (paper I). During normal breathing with the Boussignac CPAP, changes in airway pressure were never large enough to reduce airway pressure below zero. During forced breathing, as airflow increased, both the drop in inspiratory airway pressure and the increase in expiratory airway pressure were potentiated (paper II). IC decreased significantly with three of the breathing devices, the PEP-mask and the two CPAP devices (paper III). With the threshold resistor CPAP, measured pressure levels were close to the preset CPAP level. With the flow resistor CPAP, as the altitude increased CPAP produced pressure levels increased (paper IV).Conclusion: The effect on airway pressure, airflow, IC and the effect of changes in ambient air pressure differ between different kinds of resistance breathing devices. These differences in device performance should be taken into consideration when choosing the optimal resistance breathing device for each patient.
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| 10. |
- Thurm, Mascha, et al.
(författare)
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Spinal anaesthesia with clonidine: pain relief and earlier mobilisation after open nephrectomy – a randomised clinical trial
- 2022
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Ingår i: Journal of international medical research. - : Sage Publications. - 0300-0605 .- 1473-2300. ; 50:9, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Early mobilisation and effective pain management after open nephrectomy for renal cell carcinoma often include epidural analgesia (EDA), requiring an infusion pump and a urinary catheter, thus impeding mobilisation. Spinal anaesthesia (SpA) may be an alternative. This randomised clinical trial evaluated whether SpA improves analgesia and facilitates mobilisation over EDA and which factors influence mobilisation and length of stay (LOS).Methods: Between 2012 and 2015, 135 patients were randomised and stratified by surgical method to either SpA with clonidine or EDA. Mobility index score (MobIs), pain scale, patient satisfaction questionnaire, and LOS were the main outcome measures.Results: SpA patients exhibited an increase in MobIs significantly earlier than EDA patients. Among SpA patients >50% reached MobIs ≥13 by postoperative day 3, while 29% of EDA patients never reached MobIs ≥13 before discharge. SpA patients had higher maximum pain scores on postoperative days 1 and 2, but both groups had similar patient satisfaction. One day before discharge, 36/64 SpA versus 22/67 EDA patients (56% and 33%, respectively) were opioid-free. SpA patients were discharged significantly earlier than EDA patients.Conclusions: SpA facilitates postoperative pain management and is associated with faster mobilisation and shorter LOS.The trial was registered at ClinicalTrials.org (ID-NCT02030717).
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