Critically ill patients admitted to the intensive care unit (ICU) commonly develop severe muscle wasting and weakness and consequently impaired muscle function. This not only delays respirator weaning and ICU discharge, but has deleterious effects on morbidity, mortality, financial costs, and quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders underlying ICU muscle wasting and paralysis, and is a consequence of modern intensive care interventions, although the exact causes remain unclear. Muscle gene/protein expression, intracellular signalling, post-translational modifications, muscle membrane excitability, and contractile properties at the single muscle fibre level were explored in order to unravel the mechanisms underlying the muscle wasting and weakness associated with AQM and how this can be counteracted by specific intervention strategies. A unique experimental rat ICU model was used to address the mechanistic and therapeutic aspects of this condition, allowing time-resolved studies for a period of two weeks. Subsequently, the findings obtained from this model were translated into a clinical study. The obtained results showed that the mechanical silencing of skeletal muscle, i.e., absence of external strain (weight bearing) and internal strain (myosin-actin activation) due to the pharmacological paralysis or sedation associated with the ICU intervention, is likely to be the primary mechanism triggering the preferential myosin loss and muscle wasting, features specifically characteristic of AQM. Moreover, mechanical silencing induces a specific gene expression pattern as well as post-translational modifications in the motor domain of myosin that may be critical for both function and for triggering proteolysis. The higher nNOS expression found in the ICU patients and its cytoplasmic dislocation are indicated as a probable mechanism underlying these highly specific modifications. This work also demonstrated that passive mechanical loading is able to attenuate the oxidative stress associated with the mechanical silencing and induces positive effects on muscle function, i.e., alleviates the loss of force-generating capacity that underlie the ICU intervention, supporting the importance of early physical therapy in immobilized, sedated, and mechanically ventilated ICU patients.

Thesis (MEd (Curriculum Studies)--University of Stellenbosch, 2005. / Ventilator-associated infections contribute to most of the fatal infections in the intensive care. Considerable intensive care resources are also consumed in the treatment of ventilatorassociated infections. Not only economic costs, but also expenditure of staff energies, physical resources, treatment expenses and admission to the intensive care contribute to the complexity of the problem. Despite the large progress in medical treatment over the past decades, the incidence and case fatality rates of health-care-associated ventilator-associated infections remain high. Patients who require mechanical ventilation have a particularly high risk of healthcare- associated infections. Ventilator-associated infections have been a major complication for years, but the researcher has found that no formal attempts, except for inclusion of the concept as part of critical care nursing curricula, have been made to educate nurses with regard to the active prevention of ventilator-associated infections in adult patients. There are also limited data available regarding infection control education-based interventions targeting healthcare systems, e.g. intensive care units. The research goal was to establish and evaluate a learning programme for nurses caring for adult patients with ventilator-associated infections (Learning Programme). This took place in two Australian hospitals during 2003 and 2004. The objectives of the research were divided into three phases. Evidenced-based literature on the above concepts was utilised by the researcher and deductively implemented and validated by a focus (specialist) group to develop the Learning Programme in Phase One.

Bakgrund: Sambandet mellan hjärtkirurgi med extracorporeal cirkulation (ECC) och blodtransfusion visar risker så som ökad morbiditet och mortalitet. Detta kan orsaka lidande för patienten och leda till kostnader för samhället. Att hantera och administrera blodprodukter är en omvårdnadshandling som sjuksköterskan ansvarar för och detta ställer därför krav på dennes kompetens.   Syftet: Syftet med denna studie var att studera intensivvårdssjuksköterskors kunskap om att ge blodtransfusion till patienter som genomgått hjärtkirurgi med ECC och om de ansåg sig ha kunskap om hur blodprodukter ska handhas och administreras på ett patientsäkert sätt, samt vilket behov av kompetensutveckling de ansåg sig ha.   Metod: Studien som utfördes hade en kvantitativ design med deskriptiv ansats. Ett icke-slumpmässigt urval gjordes på en Thoraxintensivvårdsavdelningen vid ett universitetssjukhus i Mellansverige och 30 intensivvårdssjuksköterskor inkluderades.   Resultat: Intensivvårdsjuksköterskorna hade en mycket låg till låg kunskap om de postoperativa komplikationer vid hjärtkirurgi med ECC som kan ha ett samband med blodtransfusion. Inget statistiskt signifikant samband kunde fastställas mellan intensivvårdsjuksköterskornas upplevda kunskap och faktiska kunskap om dessa postoperativa komplikationer. I resultatet sågs också att de önskade ytterligare utbildning.   Slutsats: Det fanns ett behov av vidare forskning inom området för att kunna uttala sig om intensivvårdssjuksköterskors kunskap och behov av ytterligare utbildning avseende risker med blodtransfusion till patienter som genomgått hjärtkirurgi med ECC. / Background: The relationship between cardiac surgery with extracorporeal circulation (ECC) and blood transfusion demonstrates risks like increased morbidity and mortality. This may cause suffering for the patient and further costs on society. To manage and administer blood products is a nursing act which the nurse is responsible for, and therefore it requires specific competence. Purpose: The purpose of this study was to study critical care nurses' knowledge of giving blood transfusion in patients undergoing cardiac surgery with ECC. Also if they felt they had knowledge of how blood products should be handled and administered safely for the patient, as well as the need for further education they felt they had.  Method: The study had a quantitative design with descriptive approach. A non - random selection was made on the Cardiothoracic Intensive Care Unit at an University Hospital in Sweden and 30 intensive care nurses were included.  Results: Intensive care nurses had a very low to low knowledge of the postoperative complications in cardiac surgery with ECC that may be related to blood transfusion. No statistically significant correlation could be established between critical care nurses' perceived knowledge and actual knowledge of these postoperative complications. In the result there was also possible to see that they wanted further education.   Conclusion: There was a need for further research in the area to give an opinion on critical care nurses' knowledge and the need for further education about the risks of blood transfusion in patients undergoing cardiac surgery with ECC.

Cardiovascular disease is a large problem in the intensive care unit (ICU) due to its high prevalence in modern society. In the ICU, intensive monitoring is required to help diagnose cardiac and circulatory dysfunction. However, complex interactions between the patient, disease, and treatment can hide the underlying disorder. As a result, clinical staff must often rely on their skill, intuition, and experience to choose therapy, increasing variability in care and patient outcome. To simplify this clinical scenario, model-based methods have been created to track subject-specific disease and treatment dependent changes in patient condition, using only clinically available measurements. The approach has been tested in two pig studies on acute pulmonary embolism and septic shock and in a human study on surgical recovery from mitral valve replacement. The model-based method was able to track known pathophysiological changes in the subjects and identified key determinants of cardiovascular health such as cardiac preload, afterload, and contractility. These metrics, which can be otherwise difficult to determine clinically, can be used to help provide targets for goal-directed therapies to help provide deliver the optimal level of therapy to the patient. Hence, this model-based approach provides a feasible and potentially practical means of improving patient care in the ICU.

Mechanical ventilation (MV) is the primary form of therapeutic support for patients with acute respiratory failure (ARF) or acute respiratory distress syndrome (ARDS) until the underlying disease is resolved. However, as patient disease state and response to MV are highly variable, clinicians often rely on experience to set MV. The result is more variable care, as there are currently no standard approaches to MV settings. As a result of the common occurrence of MV and variability in care, MV is one of the most expensive treatments in critical care. Thus, an approach capable of guiding patient-specific MV is required and this approach could potentially save significant cost. This research focuses on developing models and model-based approaches to analyse and guide patient-specific MV care. Four models and metrics are developed, and each model is tested in experimental or clinical trials developed for the purpose. Each builds the understanding and methods necessary for an overall approach to guide MV in a wide range of patients. The first model, a minimal recruitment model, captures the recruitment of an injured lung and its response to positive end expiratory pressure (PEEP). However, the model was only previously validated in diagnosed ARDS patients, and was not proven to capture behaviours seen in healthy patients. This deficiency could potentially negate its ability to track disease state, which is crucial in providing rapid diagnosis and patient-specific MV in response to changes in patient condition. Hence, the lack of validation in disease state progression monitoring from ARDS to healthy, or vice-versa, severely limits its application in real-time monitoring and decision support. To address this issue, an experimental ARDS animal model is developed to validate the model across the transition between healthy and diseased states. The second model, a single compartment linear lung model, models the lung as a conducting airway connected to an elastic compartment. This model is used to estimate the respiratory mechanics (Elastance and Resistance) of an ARDS animal model during disease progression and recruitment manoeuvres. This model is later extended to capture high resolution, patient-specific time-varying respiratory mechanics during each breathing cycle. This extended model is tested in ARDS patients, and was used to titrate patient-specific PEEP using a minimum elastance metric that balances recruitment and the risk of lung overdistension and ventilation-induced injury. Studies have revealed that promoting patients to breathe spontaneously during MV can improve patient outcomes. Thus, there is significant clinical trend towards using partially assisted ventilation modes, rather than fully supported ventilation modes. In this study, the patient-ventilator interaction of a state of the art partially assisted ventilation mode, known as neurally adjusted ventilatory assist (NAVA), is investigated and compared with pressure support ventilation (PS). The matching of patient-specific inspiratory demand and ventilator supplied tidal volume for these two ventilation modes is assessed using a novel Range90 metric. NAVA consistently showed better matching than PS, indicating that NAVA has better ability to provide patient-specific ventilator tidal volume to match variable patient-specific demand. Hence, this new analysis highlights a critical benefit of partially assisted ventilation and thus the need to extend model-based methods to this patient group. NAVA ventilation has been shown to improve patient-ventilator interaction compared to conventional PS. However, the patient-specific, optimal NAVA level remains unknown, and the best described method to set NAVA is complicated and clinically impractical. The Range90 metric is thus extended to analyse the matching ability of different NAVA levels, where it is found that response to different NAVA levels is highly patient-specific. Similar to the fully sedated MV case, and thus requiring models and metrics to help titrate care. More importantly, Range90 is shown to provide an alternative metric to help titrate patient-specific optimal NAVA level and this analysis further highlights the need for extended model-based methods to better guide these emerging partially assisted MV modes. Traditionally, the respiratory mechanics of the spontaneously breathing (SB) patient cannot be estimated without significant additional invasive equipment and tests that interrupt normal care and are clinically intensive to carry out. Thus, respiratory mechanics and model-based methods are rarely used to guide partially assisted MV. Thus, there is significant clinical interest to use respiratory mechanics to guide MV in SB patients. The single compartment model is extended to effectively capture the trajectory of time-varying elastance for SB patients. Results show that without additional invasive equipment, the model was able estimate unique and clinically useful respiratory mechanics in SB patients. Hence, the extended single compartment model can be used as ‘a one model fits all’ means to guide patient-specific MV continuously and consistently, for all types of patient and ventilation modes, without interrupting care. Overall, the model-based approaches presented in this thesis are capable of capturing physiologically relevant patient-specific parameters, and thus, characterise patient disease state and response to MV. With additional, larger scale clinical trials to test the performance and the impact of model-based methods on clinical outcome, the models can aid clinicians to guide MV decision making in the heterogeneous ICU population. Hence, this thesis develops, extends and validates several fundamental model-based metrics, models and methods to enable standardized patient-specific MV to improve outcome and reduce the variability and cost of care.

Critically ill patients often exhibit abnormal glycaemia that can lead to severe complications and potentially death. In critically ill adults, hyperglycaemia is a common problem that has been associated with increased morbidity and mortality. In contrast, critically ill infants often suffer from hypoglycaemia, which may cause seizures and permanent brain injury. Further complicating the matter, both of these conditions are diagnosed by blood glucose (BG) measurements, often taken several hours apart, and, as a result, these conditions can remain poorly managed or go completely undetected. Emerging ‘continuous’ glucose monitoring (CGM) devices with 1-5 minute measurement intervals have the potential to resolve many issues associated with conventional intermittent BG monitoring. The objective of this research was to investigate and develop methods and models to optimise the clinical use of CGM devices in critically ill patients. For critically ill adults, an in-silico study was conducted to quantify the potential benefits of introducing CGM devices into the intensive care unit (ICU). Mathematical models of CGM error characteristics were implemented with existing, clinically validated, models of the insulin-glucose regulatory system, to simulate the behaviour of CGM devices in critically ill patients. An alarm algorithm was also incorporated to provide a warning at the onset of predicted hypoglycaemia, allowing a virtual dextrose intervention to be administered as a preventative measure. The results of the in-silico study showed a potential reduction in nurse workload of approximately 75% and a significant reduction in hypoglycaemia, while also providing insight into the optimal rescue dose size and resulting dynamics of glucose recovery. During 2012, ten patients were recruited into a pilot clinical trial of CGM devices in critical care with a primary goal of assessing the reliability of CGM devices in this environment, with a specific interest in the effects of CGM device type and sensor site on sensor glucose (SG) data. Results showed the mean absolute relative difference of SG data across the cohort was between 12-24% and CGM devices were capable of monitoring some patients with a high degree of accuracy. However, certain illnesses, drugs and therapies can potentially affect sensor performance, and one particular set of results suggested severe oedema may have affected sensor performance. A novel and first of its kind metric, the Trend Compass was developed and used to assesses trend accuracy of SG in a mathematically precise fashion without approximation, and, importantly, does so independent of glucose level or sensor bias, unlike any other such metrics. In this analysis, the trend accuracy between CGM devices was typically good. A recent hypothesis suggesting that glucose complexity is associated with mortality was also investigated using the clinical CGM data. The results showed that complexity results from detrended fluctuation analysis (DFA) were influenced far more by CGM device type than patient outcome. In addition, the location of CGM sensors had no significant effect on complexity results in this data set. Thus, while this emerging analytical method has shown positive results in the literature, this analysis indicates that those results may be misleading given the impact of technology outweighing that of physiology. This particular result helps to further delineate the range of potential applications and insight that CGM devices might offer in this clinical scenario. In critically ill infants, CGM devices were used to investigate hypoglycaemia during the first 48 hours after birth. More than 50 CGM data sets were obtained from several studies of CGM in infants at risk of hypoglycaemia at the Waikato hospital neonatal ICU (NICU). In light of concerns regarding CGM accuracy, particularly during the first few hours of monitoring and/or at low BG levels, an alternative, novel calibration scheme was developed to increase the reliability of SG data. The recalibration algorithm maximised the value of very accurate calibration BG measurements from a blood gas analyser (BGA), by forcing SG data to pass through these calibration BG measurements. Recalibration increased all metrics of hypoglycaemia (number, duration, severity and hypoglycaemic index) as the factory CGM calibration was found to be reporting higher values at low BG levels due to its least squares calibration approach based on the assumption of a less accurate calibration glucose meter. Thus, this research defined new calibration methods to directly optimise the use of CGM devices in this clinical environment, where accurate reference BG measurements are available. Furthermore, this work showed that metrics such as duration or area under curve were far more robust to error than the typically used counted-incidence metrics, indicating how clinical assessment may have to change when using these devices. The impact of errors in calibration measurements on metrics used to classify hypoglycaemia was also assessed. Across the cohort, measurement error, particularly measurement bias, had a larger effect on hypoglycaemia metrics than delays in entering calibration measurements. However, for patients with highly variable glycaemia, timing error can have a significantly larger impact on output SG data than measurement error. Unusual episodes of hypoglycaemia could be successfully identified using a stochastic model, based on kernel density estimation, providing another level of information to aid decision making when assessing hypoglycaemia. Using the developed algorithms/tools, with CGM data from 161 infants, the incidence of hypoglycaemia was assessed and compared to results determined using BG measurements alone. Results from BG measurements showed that ~17% of BG measurements identified hypoglycaemia and over 80% of episodes occurred in the first day after birth. However, with concurrent BG and SG data available, the SG data consistently identified hypoglycaemia at a higher rate suggesting the BG measurements were not capturing some episodes. Duration of hypoglycaemia in SG data varied from 0-10+%, but was typically in the range 4-6%. Hypoglycaemia occurred most frequently on the first day after birth and an optimal measurement protocol for at risk infants would likely involve CGM for the first week after birth with frequent intermittent BG measurements for the first day. Overall, CGM devices have the potential to increase the understanding of certain glycaemic abnormalities and aid in the diagnosis/treatment of other conditions in critically ill patients. This research has used a range of prospective and retrospective clinical studies to develop methods to further optimise the use of CGM devices within the critically ill clinical environment, as well as delineating where they are less useful or less robust. These latter results clearly define areas where clinical practice needs to adapt when using these devices, as well as areas where device makers could target technological improvements for best effect. Although further investigations are required before these devices are regularly implemented in day-to-day clinical practice, as an observational tool they are capable of providing useful information that is not currently available with conventional intermittent BG monitoring.

Necrotizing enterocolitis (NEC) is a costly and deadly disease in neonates. Composite risk for NEC is poorly understood and consensus has not been established on the relevance of risk factors. This two-phase study attempted to validate and test a neonatal NEC risk index, GutCheck(NEC). Phase I used an E-Delphi methodology in which experts (n=35) rated the relevance of 64 potential NEC risk factors. Items were retained if they achieved predefined levels of expert consensus or stability. After three rounds, 43 items were retained (CVI=.77). Qualitative analysis revealed two broad themes: individual characteristics of vulnerability and the impact of contextual variation within the NICU on NEC risk. In Phase II, the predictive validity of GutCheck(NEC) was evaluated using a sample from the Pediatrix BabySteps Clinical Data Warehouse (CDW). The sample included infants born<1500 grams, before 36 weeks, and without congenital anomalies or spontaneous intestinal perforation (N=58,818, of which n=35,005 for empiric derivation and n=23,813 for empiric validation). Backward stepwise likelihood-ratio method regression was used to reduce the number of predictive factors in GutCheck(NEC) to 11 and derive empiric weights. Items in the final GutCheck(NEC) were gestational age, history of a transfusion, NICU-specific NEC risk, late onset sepsis, multiple infections, hypotension treated with Inotropic medications, Black or Hispanic race, outborn status, metabolic acidosis, human milk feeding on both day 7 and day 14 (reduces risk) and probiotics (reduces risk).Discrimination was fair in the case-control sample (AUC=.67, 95% CI .61-.73) but better in the validation set (AUC=.76, 95% CI .75-.78) and best for surgical NEC (AUC=.84, 95% CI .82-.84) and infants who died from NEC (AUC=.83, 95% CI .81-.85). A GutCheck(NEC) score of 33 (range 0-58) yielded a sensitivity of .78 and a specificity of .74 in the validation set. Intra-individual reliability was acceptable (ICC (19) =.97, p<.001). Future research is needed to repeat this procedure in infants between 1500 and 2500 grams, complete psychometric testing, and explore unit variation in NEC rates using a comprehensive approach.

No description available.

No description available.

The overall aim of the thesis was to gain a deeper understanding of nutritional nursing care in municipal care and county council care, with specific focus on enteral nutrition (EN) in intensive care. Quantitative and qualitative methods were used. Telephone interviews regarding assessment of the nutritional status of patients were carried out with special medical nurses (CNs) (n = 14) in municipalities in one county and first line managers (CNs) (n = 27) in one county council. Registered nurses (RNs) in municipalities (n = 74) and county councils (n = 57) answered a questionnaire about nutritional assessment and documentation (I). RNs (n = 44) at three different intensive care units answered a questionnaire about responsibility, knowledge, documentation and nursing interventions regarding EN. Observations (n = 40) on nursing care interventions for patients with EN were carried out (II). RNs (n = 8), enrolled nurses (n = 4) (III) and patients (n = 14) (IV) were interviewed and nutritional nursing care was observed (III-IV) at an intensive care unit. The results showed that assessment of nutritional status was not performed on all patients, according to RNs/CNs. Malnourished patients were estimated to occur to a varied extent. Sixty-six percent of RNs/CNs answered that there were no guidelines for nutritional care and 13% that they did not know if there were any. RNs saw the VIPS model as a guide in nursing care, but also as an obstacle to information exchange (I). A majority of RNs answered that there were guidelines for EN. There were differences between the RNs’ opinions about their responsibility, knowledge and documentation. Deviations from recommended nursing care interventions occurred (II). The developed substantive theory of nurses (RNs and enrolled nurses) concerns and strategies of nutritional nursing care for patients with EN, includes the core category ”to have and to hold nutritional control – balancing between individual care and routine care” and the categories ”knowing the patient”, ”facilitating the patients’ involvement”, ”being a nurse in the team”, ”having professional confidence” and ”having a supportive organization”. In order for RNs and enrolled nurses to have a sense of control over the patients’ care in relation to nutrition, a balance between routine care and individual care was required (III). The developed substantive theory regarding the patients’ experiences of nutritional care includes the core category ”grasping nutrition during the recovery process”.  The core category is reflected in, and dependent on, the categories ”facing nutritional changes”, ”making sense of the nutritional situation” and ”being involved with nutritional care”. The patients alternated emotionally between worry, fear and failure, and relief and hope. The patients experienced a turning point and felt an improvement in their condition when their appetite returned, when the stomach and gut were functioning and when the feeding tube was removed (IV). The conclusion is that quality and safety in relation to nutritional nursing care is dependent on the interactions between the nurse and patient, between the nurse and the team, and the nurse and the organization.