Hyperglycemia is prevalent in critical care, as patients experience stress-induced hyperglycemia, even with no history of diabetes. Hyperglycemia has a significant impact on patient mortality and other negative clinical outcomes such as severe infection, sepsis and septic shock. Tight glycemic control can significantly reduce these negative outcomes by reducing hyperglycemic episode, but achieving it remains clinically elusive, particularly with regard to what constitutes tight control and what protocols are optimal in terms of results and clinical effort. The model used in this thesis is validated using an independent data and readily be used for different clinical interventions. Moreover, this model also able to accurately predict clinical intervention outcomes given that the model prediction error is very small, which is better than any other reported model. In particular, model-based glycemic control methods is used to capture patient-specific physiological dynamics, such as insulin sensitivity, SI. To date, sepsis diagnosis has been a great challenge despite advancement in technologies and medical research. Critically, septic patients are often classified by practitioners according to their experience before standard test results can be assessed, as to avoid delay in treatment. Moreover, several scoring systems have also been widely used to represent sepsis condition and better standardization of sepsis definition across different centers. In this thesis, insulin sensitivity, SI, a model-based metric is used to identify sepsis condition based on the finding that SI represents metabolic condition of a patient. Additionally, several clinical and physiological variables obtained during patient’s stay in critical care are also investigated using mathematical computation and statistical analysis to identify relevant metric which can be accurately use for sepsis interventions. Even though information on SI, clinical and physiological variables of a patient are insufficient to determine the sepsis status, these informations have brought to a different perspective of diagnosing sepsis. Microcirculation dysfunction is very common in sepsis. Tracking of microcirculation state among septic patient enable better tracking of patient state particularly sepsis status. The tracking can potentially be done by using a pulse oximeter that can extract additional information related to oxygen extraction level. The processed signals are therefore represent relative absorption of oxyhemoglobin and reduced hemoglobin that can be used to assess microcirculation status. In addition, this thesis focus on the real challenge of early treatment of sepsis and sepsis diagnosis where several potential metabolic markers are investigated. Microcirculation conditions are assessed using a non-invasive method that is generally used in typical ICU settings. In particular, the concept and method used to assess microcirculation and metabolic conditions are developed in this thesis. Finally, the work presented in this thesis can act as a starting point for many other glycemic control problems in other environments. These areas include cardiac critical care and neonatal critical care that share most similarities to the environment studied in this thesis, to general diabetes where the population is growing exponentially world wide. Eventually, this added knowledge can lead clinical developments from protocol simulations to better clinical decision making.

Depuis quelques années, les plaquettes sanguines sont reconnues comme un véritable élément de l’immunité. En effet, de nombreux rôles clés lors du processus inflammatoire sont attribués aux plaquettes, tels que la détection d’un signal, la libération de nombreux immunomodulateurs ou une forte interaction avec les autres cellules immunitaires. Le constat clinique d’une corrélation entre le taux plaquettaire et la mortalité du sepsis permet de relever l’importance de cette cellule dans la physiopathologie du sepsis. Ainsi ce travail doctoral a eu pour objectif de mettre en relief la part inflammatoire des plaquettes lors des interactions entre les facteurs de virulence de Staphylococcus aureus (S.aureus) que sont différentes exotoxines ou de souches de S. aureus issues de bactériémies de patients septiques. Un modèle expérimental de sepsis murin nous a permis de comprendre la composante inflammatoire jouée par les plaquettes ainsi que leurs implications dans la dysfonction pulmonaire issue lors du sepsis. Enfin, nous avons évalué la modulation de molécules antiplaquettaires, et particulièrement de l’acide acétylsalicylique, sur les nombreux rôles pathogéniques des plaquettes durant cette pathologie. / During some years, platelets are recognized as an key element of immunity. In fact, platelets play several roles, as signal detection, immunomodulator release and interaction with other immunity cells. The clinical significance of a correlation between platelet rate and sepsis mortality reveals the importance of this cell in the pathophysiology of sepsis. Thus, the purpose of this doctoral work was to highlight the inflammatory role of platelets in the interactions between the virulence factors of Staphylococcus aureus (S. aureus) that are different exotoxins or strains of S. aureus from bacteremia of septic patients. An experimental model of murine sepsis allowed us to understand the inflammatory component played by platelets as well as their implications in pulmonary dysfunction resulting from sepsis. Finally, we evaluated the modulation of antiplatelet molecules, particularly acetylsalicylic acid, on the numerous pathogenic roles of platelets during this pathology.

Sepsis causes major health care problems in the United States, resulting in long hospitalizations, complications, and even patient death. Lack of nursing knowledge regarding sepsis signs and symptoms is a significant problem at a hospital in the northeast. Local hospital data showed a high patient mortality rate for patients diagnosed with sepsis. The purpose of this project was to develop an educational module on sepsis for intensive care nurses. The educational module was developed using current sepsis evidence-based guidelines. The practice-focused question for the project asked whether an educational module on sepsis would increase the intensive care nurse's knowledge on sepsis recognition and treatment guidelines. The adult learning theory was used as a conceptual model to guide project development. After development, the educational module was evaluated by a panel of 8 experts, including a nurse educator, infection control nurse, a charge nurse, a staff nurse, and an infectious disease physician. Program content evaluations included a 10-question pretest/posttest questionnaire completed by each panel member. Program content was modified based on pretest/posttest results. Results of the panel evaluation indicated agreement that the sepsis module content would benefit nurses on sepsis recognition and management for patients. Improving nursing knowledge on sepsis can provide a positive social change to improve patient outcomes, including mortality rates and complications from sepsis.

Due to increasing incidence and noncompliance with sepsis at a local hospital, an educational deficit was identified on the sepsis bundle in the medical intensive care unit. The purpose of this project was to develop and validate a sepsis bundle education program for all frontline staff in the MICU at a local University Hospital. The goal was for the educational tool to be validated by a multidisciplinary team to increase awareness, education, and ultimately, compliance with the severe sepsis and septic shock guidelines. The diffusion of innovation theory was utilized to support the process of change by encouraging the use of screening tools and best practice guidelines. The research question asked whether the education program meets critical care expert panel standards to educate frontline MICU staff on the sepsis bundle. The research design included a 5-member panel of experts in critical care, utilizing the Likert scale to review the proposed educational project on the sepsis bundle. Results are averaged from each reviewer. Results from the review included a unanimous '5' rating on every issue identified, equating to strongly agree on the Likert scale. This rating supported the validity of the educational project, the use of evidence-based practice and that the educational material was clear and easy to follow. Utilizing this validated tool will guide the education of sepsis, severe sepsis, and septic shock and promote social change by increasing education, awareness, recognition and early deployment of the sepsis bundle to improve patient outcomes.

<p><strong>Bakgrund: </strong>Sepsis är vanligt förekommande inom sjukvården och många patienter blir svårt sjuka och dör i svår sepsis eller septisk chock. Det är ett tillstånd som anses föreligga vid infektion och minst två SIRS-kriterier. Symtomen kan vara diffusa och svåra att identifiera. Sjuksköterskan har en viktig roll att observera försämring för att så snabbt som möjligt identifiera en sannolik sepsis. Vid tidig diagnos och behandling minskar sjuklighet och dödlighet. <strong>Syfte: </strong>Att beskriva sjuksköterskans specifika omvårdnad av patienter med sepsis. <strong>Metod:</strong> En litteraturstudie baserad på tolv vetenskapliga artiklar publicerade mellan år 1998-2008. <strong>Resultat:</strong> Analysen resulterade i fyra huvudkategorier; bedömning, specifik omvårdnad, specifik omvårdnad genom akutteam och kunskap som redskap i omvårdnaden. Specifik omvårdnad kan leda till ett gynnsamt och snabbare omhändertagande av patienter med sepsis. <strong>Diskussion och slutsats: </strong>Det krävs ökad kunskap om omvårdnad vid sepsis. Med en bred kunskap om sepsis kan sjuksköterskan ge en säkrare och tryggare omvårdnad och minska lidandet för patienten och kostader för samhället.</p> / <p><strong>Background:</strong>Sepsis is common within the health care and numerous patients become severely ill and die from severe sepsis or septic chock.Sepsis is acondition which is thought to occur at infection and at least two SIRS-criterions. The symptoms can be diffuse and difficult to identify. The nurse has an important role to observe deterioration in order to quickly as possible identify a probable sepsis. At an early diagnose and treatment the mortality and morbidity decreases. <strong>Purpose: </strong>To describe the nurse-specific care of patients with sepsis.<strong>Method:</strong> A literature study based on twelve scientific articles published between years 1998-2008. <strong>Result:</strong> The analysis resulted in four main categories;assessment, specific nursing,specific nursing by an emergency team and knowledge as a tool within nursing. Specific nursing can lead to a beneficial and faster treatment of patients with sepsis. <strong>Discussion and conclusion: </strong>It is necessary with an increased knowledge of nursing of sepsis. With a wide knowledge of sepsis the nurse is able to establish a more secure and safer nursing and ease the suffering for the patient and also decrease the costs for the society.</p>

Bakgrund: Sepsis är vanligt förekommande inom sjukvården och många patienter blir svårt sjuka och dör i svår sepsis eller septisk chock. Det är ett tillstånd som anses föreligga vid infektion och minst två SIRS-kriterier. Symtomen kan vara diffusa och svåra att identifiera. Sjuksköterskan har en viktig roll att observera försämring för att så snabbt som möjligt identifiera en sannolik sepsis. Vid tidig diagnos och behandling minskar sjuklighet och dödlighet. Syfte: Att beskriva sjuksköterskans specifika omvårdnad av patienter med sepsis. Metod: En litteraturstudie baserad på tolv vetenskapliga artiklar publicerade mellan år 1998-2008. Resultat: Analysen resulterade i fyra huvudkategorier; bedömning, specifik omvårdnad, specifik omvårdnad genom akutteam och kunskap som redskap i omvårdnaden. Specifik omvårdnad kan leda till ett gynnsamt och snabbare omhändertagande av patienter med sepsis. Diskussion och slutsats: Det krävs ökad kunskap om omvårdnad vid sepsis. Med en bred kunskap om sepsis kan sjuksköterskan ge en säkrare och tryggare omvårdnad och minska lidandet för patienten och kostader för samhället. / Background:Sepsis is common within the health care and numerous patients become severely ill and die from severe sepsis or septic chock.Sepsis is acondition which is thought to occur at infection and at least two SIRS-criterions. The symptoms can be diffuse and difficult to identify. The nurse has an important role to observe deterioration in order to quickly as possible identify a probable sepsis. At an early diagnose and treatment the mortality and morbidity decreases. Purpose: To describe the nurse-specific care of patients with sepsis.Method: A literature study based on twelve scientific articles published between years 1998-2008. Result: The analysis resulted in four main categories;assessment, specific nursing,specific nursing by an emergency team and knowledge as a tool within nursing. Specific nursing can lead to a beneficial and faster treatment of patients with sepsis. Discussion and conclusion: It is necessary with an increased knowledge of nursing of sepsis. With a wide knowledge of sepsis the nurse is able to establish a more secure and safer nursing and ease the suffering for the patient and also decrease the costs for the society.

Myeloid progenitor-derived suppressor cells (MDSCs) arise from myeloid progenitors and suppress both innate and adaptive immunity. MDSCs expand during the later phases of sepsis in mice, promote immunosuppression, and reduce survival. Here, we report that the myeloid differentiation-related transcription factor nuclear factor I-A (NFI-A) controls MDSC expansion during sepsis and impacts survival. Unlike MDSCs, myeloid cells with conditional deletion of the Nfia gene normally differentiated into effector cells during sepsis, cleared infecting bacteria, and did not express immunosuppressive mediators. In contrast, ectopic expression of NFI-A in myeloid progenitors from NFI-A myeloid cell-deficient mice impeded myeloid cell maturation and promoted immune repressor function. Importantly, surviving septic mice with conditionally deficient NFI-A myeloid cells were able to respond to challenge with bacterial endotoxin by mounting an acute inflammatory response. Together, these results support the concept of NFI-A as a master molecular transcriptome switch that controls myeloid cell differentiation and maturation and that malfunction of this switch during sepsis promotes MDSC expansion that adversely impacts sepsis outcome.

No description available.

Introduktion: Patienter med sepsis är en patientkategori för den prehospitala vården som kan vara svåra att upptäcka. Denna patientkategori har en hög mortalitet om sjukdomen inte upptäcks i tid och adekvat behandling sätts in i tid. Tidigt upptäckt av förhöjda laktatvärden hos sepsispatienter kan hjälpa ambulanssjuksköterskan att i tid påbörja adekvat behandling samt rapportera till mottagande akutmottagning som sedan kan fortsätta med den adekvata behandlingen som patienten behöver. Syfte: Syftet var att belysa värdet av prehospital laktatmätning vid misstänkt sepsis. Metod: Systematisk kvalitativ litteraturstudie. Totalt 15 vetenskapliga artiklar inkluderades efter sökning i databaserna PubMed, Cinhal och PsycInfo.   Resultat: Laktatmätning i prehospitalmiljö kan användas som en tidig indikator för sepsis och i samband med patientens symtombild. Detta gör det möjligt för sjuksköterskan att tillse att patienten hamnar på rätt vårdnivå och på så sätt kunna förebygga ökad mortalitet genom att behandling kan sättas in snabbt. Slutsats: Genom att implementera laktatmätning prehospitalt skulle förmågan att identifiera sepsis öka för ambulanspersonal. Möjligheten att transportera patienten till rätt vårdnivå och förebygga mortalitet skulle förbättras. Det behövs fortsatt forskning för att bekräfta slutsatserna. / Introduction: Patients with sepsis is a patient category for prehospital care that can be difficult to detect. These patients have a high risk of mortality if they are not detected in time and adequate treatment is initiated in time. Early detection of elevated lactate levels in sepsis patients can help the ambulance nurse to start adequate treatment in time and report to the receiving emergency department who can then continue with the adequate treatment that the patient needs. Aim: The aim was to shed light on the value of prehospital lactate measurement in suspected sepsis. Method: Systematic qualitative literature study. A total of 15 scientific articles were included after searching the databases PubMed, Cinhal and PsycInfo. Results: Lactate measurement in a prehospital setting can be used as an early indicator of sepsis and in connection with the patient's symptoms. This makes it possible for the nurse to ensure that the patient ends up at the right level of care and this be able to prevent increased mortality by allowing treatment to be started quickly. Conclusion: By implementing lactate measurement prehospital, the ability to identify sepsis would increase for ambulance care giver. The ability to transport the patient to the right level of care and prevent mortality would be improved. Further research is needed to confirm the conclusions.

Bakgrund: Allvarliga infektioner kan sprida sig ut till blodbanan om infektionerna inte behandlas adekvat. Patienter som drabbas av sepsis kan också drabbas av komplikationer som påverkar det vardagliga livet. Syfte: Syftet var att beskriva patienters erfarenheter av genomgången sepsis. Metod: Studien genomfördes som en litteraturstudie med en induktiv ansats där tre kvalitativa och fem kvantitativa artiklar analyserades utifrån en innehållsanalys. Resultat: Två huvudkategorier framkom ur analysen: (1) från milda komplikationer till svåra komplikationer, och (2) att tillfriskna från sepsis. Till första huvudkategorin tillkom tre underkategorier. Patienter som genomgått sepsis och drabbats av komplikationer upplevde att det tog lång tid att tillfriskna. Fysiska komplikationer som muskelsvaghet utgjorde problem i vardagen. Psykiska komplikationer i form av ångest och depression var vanligt förekommande. Även kognitiva komplikationer som nedsatt koncentrationsförmåga lyftes fram. Patienter som genomgått sepsis betonade även vikten av att få information om tillståndet. Konklusion: Hos patienter som genomgått sepsis kunde komplikationer i form av fysiska, psykiska och kognitiva besvär kvarstå och påverkade vardagsfunktionen. Alla som drabbats fick inte komplikationer och patienter som drabbats av allvarligare sepsis, septisk chock, visade sig få svårare komplikationer. Vägen till tillfrisknande beskrevs som lång och patienter kände sig ofta ensamma i sin sjukdoms- och återhämtningsprocess. / Background: Serious infections can develop and spread into the bloodstream if the infection isn’t treated adequately. Patients who suffer from sepsis can also develop complications that affect the everyday life. Aim: To describe patients experiences after suffering from sepsis. Method: In this literature study, an inductive approach was used, where three qualitative and five quantitative articles were used and analyzed through content analysis. Result: Two main categories emerged from the analysis: (1) from mild complications to severe complications and (2) to recover from sepsis. The first main category had three subcategories. Patients who survived sepsis and developed complications experienced a long time to recover. Physical complications like muscle weakness affected the everyday life. Psychological complications in terms of anxiety and depression were common. Cognitive complications such as reduced ability to concentrate were also highlighted. Patients who survived sepsis emphasized the importance of getting information about the condition. Conclusion: In patients who had suffered from sepsis, complications in the form of physical, psychological and cognitive problems often persisted and affected the everyday function. Not everyone who had had sepsis was affected by complications. The recovery was described as a long process and patients often felt on their own in their recovery process.