Os Sistemas de Informação Hospitalar podem ser definidos como uma rede integrada de informações, projetada para gerenciar aspectos assistenciais, administrativos e jurídicos em organizações de saúde. No contexto da busca pela melhoria da qualidade na assistência à saúde, proporcionada pelos avanços significativos das tecnologias da informação e comunicação, insere-se a necessidade da abordagem da sepse enquanto importante tema de saúde pública mundial. A sepse pode ser definida como síndrome de anormalidades fisiológicas, patológicas e bioquímicas induzidas por um processo infeccioso. A equipe multiprofissional de saúde deve atuar no reconhecimento precoce dos pacientes com quadro sugestivo de infecção e suas potenciais complicações, que podem culminar em síndrome séptica, estabelecendo medidas que garantam seu controle, manuseio precoce, intervenção eficaz e segura, por meio de uma assistência integral e contínua. O objetivo neste estudo foi verificar a contribuição dos Sistemas de Informação Hospitalar para a identificação precoce e o manejo da sepse em pacientes cirúrgicos de um hospital universitário. Trata-se de pesquisa com delineamento quantitativo, retrospectivo, descritivo e correlacional. A coleta de dados foi realizada por meio dos Sistemas de Informação Hospitalar, mediante aprovação do Comitê de Ética em Pesquisa. A população foi composta de 28 pacientes que atenderam os critérios de inclusão da pesquisa. Na caracterização sociodemográfica desses pacientes, constatou-se predominância do sexo masculino (17; 60,7%), brancos (26; 92,9%), com 60 anos ou mais (21; 75,0%). Quanto à análise clínica do paciente, 11 apresentaram predominância do diagnóstico oncológico (39,3%) na admissão hospitalar, assim como 24 (85,7%) tiveram histórico de somente uma internação hospitalar no período. No final do período de internação (desfecho), predominantemente 20 pacientes (71,4%) evoluíram para óbito. Quanto ao tempo de internação, 13 pacientes (46,4%) permaneceram internados por tempo superior a 30 dias, com média de 30,5 (DP=25,0), a maioria dos pacientes (18; 64,8%) passou pelo procedimento cirúrgico até o quinto dia de internação, com média de 8,25 dias (DP=15,2). Da mesma forma, apresentaram predominância de desenvolvimento dos primeiros sinais de SIRS e de disfunção orgânica também até o quinto dia de internação 19 pacientes (67,8%), com média de 5,2 dias (DP=4,8), e 15 (53,6%), com média de 9,14 dias (DP=12,23), respectivamente. A confirmação ou hipótese do diagnóstico de sepse ocorreu até o décimo dia de internação com 15 pacientes (53,5%), com média de 11,6 (DP=13,4). Na análise da evolução dos pacientes para óbito, identificou-se significância estatística em relação à idade, à especialidade do diagnóstico na admissão e ao tempo de internação. O conteúdo dos registros realizados diariamente pela equipe multidisciplinar evidenciou que os primeiros sinais de SIRS foram identificados, predominantemente, no sistema de monitorização dos pacientes (26; 92,9%), enquanto os primeiros sinais de disfunção orgânica foram descritos nas evoluções da equipe de enfermagem (24; 85,7%). Os resultados evidenciam a importância da qualidade dos registros de enfermagem nos Sistemas de Informações Hospitalares, para identificação dos riscos, reconhecimento precoce e manejo adequado da sepse em pacientes submetidos a procedimentos cirúrgicos, enquanto integrantes da equipe multidisciplinar, visando o alcance de maior efetividade das ações de gerenciamento dos processos de assistência à saúde / Hospital information systems can be defined as an integrated network of information, designed to manage assistance, administrative and legal aspects in healthcare organizations. In the context of the quest for quality improvement in health care, provided by the significant advances of information and communication technologies, the need of sepsis as an important theme of global public health. Sepsis can be defined as abnormalities syndrome, pathological and physiological biochemical induced by an infectious process. The multidisciplinary team of health should act in the early recognition of patients with suggestive of infection and its potential complications, which can lead to septic syndrome, establishing measures to ensure the control, early intervention handling effective and safe, through a full and continuous assistance. The objective of this study was to verify the contribution of hospital information systems for early identification and management of sepsis in surgical patients in a university hospital. This is a quantitative, descriptive, retrospective and correlational research. The data collection was performed through hospital information systems, subject to the approval of the Research Ethics Committee. The population was composed of 28 patients who attended the inclusion criteria of the survey. In demographic characterization of these patients, there was a predominance of males (17; 60.7%), white (26; 92.9%), 60 years or older (21; 75.0%). For the clinical analysis of patient, 11 showed predominance of oncological diagnostics (39.3%) in hospital admission, as well as 24 (85.7%) had a history of only one hospitalization. At the end of the period of hospitalization (outcome), predominantly 20 patients (71.4%) evolved to death. Regarding length of stay 13 patients (46.4%) remained hospitalized for more than 30 days, with an average of 30.5 (SD = 25.0), most patients (18; 64.8%) passed the surgical procedure until the fifth day of hospitalization, averaging 8.25 days (SD = 15.2). Similarly, showed a predominance of development of the first signs of SIRS and organic dysfunction, too, until the fifth day of hospitalization 19 patients (67.8%), with an average of 5.2 days (DP = 4.8), and 15 (53.6%), with an average of 9.14 days (SD = 12.23), respectively. Confirmation or chance of diagnosis of sepsis occur until the tenth day of hospitalization with 15 patients (53.5%), with an average of 11.6 (SD = 13.4). In the analysis of the evolution of the patients to death, statistical significance was identified in relation to age, the speciality of the diagnosis on admission and length of stay. The contents of the records held daily by the multidisciplinary team showed that the first signs of SIRS were identified, predominantly, in the system of monitoring of the patients (92.9%), while 26; the first signs of organic dysfunction were described in the evolutions of the nursing staff (24; 85.7%). The results highlight the importance of the quality of nursing records in hospital information systems, to identify the risks, early recognition and appropriate management of sepsis in patients undergoing surgical procedures, while members of the multidisciplinary team, aiming at the achievement of greater effectiveness of the actions of management of care processes health

A sepse é uma disfunção orgânica causada por uma resposta do hospedeiro à infecção desregulada, com risco de morte. Quando o tratamento da sepse não é efetivo, o quadro pode progredir para hipotensão severa. O tecido adiposo perivascular (perivascular adipose tissue - PVAT) é reconhecido como um elemento regulador na biologia vascular, com implicações na fisiopatologia de doenças cardiovasculares. No entanto, em relação à sepse, pouco se sabe acerca dos efeitos desta sobre a ação modulatória que o PVAT exerce no tônus vascular. Dessa maneira a hipótese do presente trabalho foi a de que a sepse poderia aumentar o efeito anti-contrátil do PVAT. Portanto, o objetivo do trabalho foi avaliar o efeito da sepse experimental na ação modulatória que o PVAT exerce sobre tônus vascular e os possíveis mecanismos envolvidos nessa resposta. Para isso foram utilizados ratos Wistar Hannover com idade entre 60 e 70 dias (270 a 300g). Os ratos foram distribuídos aleatoriamente em 2 grupos: 1) Grupo Sham: foi realizada apenas uma laparotomia sem os procedimentos de ligadura e punção do ceco; 2) Grupo CLP (Cecal Ligation and Puncture) : a sepse letal foi induzida utilizando o modelo CLP no qual foi realizada uma laparotomia para exposição do ceco, onde foi feito uma ligadura e 20 punções intermediárias entre a ligadura e a ponta do ceco com agulha de calibre 18 gauge (G). Os animais foram anestesiados com quetamina/xilasina (80/10 mg/kg, i.p.) e mortos 6 h após a indução da sepse. A aorta torácica foi coletada para realização das análises bioquímicas e funcionais. A sepse letal reduziu a taxa de sobrevida, a pressão arterial média (PAM), não alterou os níveis de leucócitos e neutrófilos, mas aumentou a contagem de bactérias no sangue e no lavado peritoneal, aumentou os níveis plasmáticos de nitrato, uréia e CK-MB. A sepse diminuiu a contração induzida pela fenilefrina e serotonina nas aortas PVAT(-)/Endo(+) ou Endo (-) do grupo CLP, quando comparada ao Sham. Porém nas artérias PVAT(+)/Endo(+) ou Endo (-), o CLP induziu redução mais pronunciada da contração induzida tanto pela fenilefrina, quanto pela serotonina. O aumento do efeito anti-contrátil do PVAT na condição séptica não foi encontrado nas artérias após a incubação com L-NAME, 7-nitroindazol, 1400W, A779, carboxy-PTIO, ODQ, apamina, RO11384552 e indometacina. Tiron, catalase, 4-aminopiridina, glibenclamida e caribdotoxina não alteraram a contração induzida pela fenilefrina no grupo CLP. A sepse aumentou a concentração de H2O2 na aorta, mas não afetou a concentração no PVAT. Aumento dos níveis de ânion superóxido (O2-) e prostaglandina (PG)I2 foram detectados tanto na aorta, quanto no PVAT do grupo CLP. A sepse não alterou os níveis de PGE2 ou angiotensina (1-7) na aorta ou PVAT. Portanto, a sepse letal induzida por CLP aumenta a ação anti-contrátil do PVAT por um mecanismo que envolve a produção de NO pelas enzimas iNOS e nNOS, a participação de canais para KCa de baixa condutância e ativação da enzima guanilato ciclase solúvel. Além disso, sugere-se o envolvimento da PGI2 e angiotensina (1-7) na hiporresponsividade vascular mediada pelo PVAT durante a sepse / Sepsis is an organic dysfunction caused by an unregulated host response to lifethreatening infection. When treatment of sepsis is ineffective, the condition may progress to severe hypotension that is drug-irresponsive. Perivascular adipose tissue (PVAT) is recognized as a regulatory element in vascular biology that is implicated in the pathophysiology of cardiovascular diseases. However, little is known about the effects of sepsis in the modulatory action of PVAT. Thus, the hypothesis of the present study was that sepsis could increase the anti-contractile effect of PVAT. Therefore, the objective of the study was to evaluate the effect of experimental (lethal) sepsis in the modulatory action that PVAT exerts on vascular tone and the possible mechanisms underlying this response. With this purpose, male Wistar Hannover rats (250-300g) were divided in 2 groups: 1) Sham: the cecum was exteriorized without ligation and puncture; 2) CLP: lethal sepsis was induced using the cecal ligation and puncture (CLP) model. The thoracic aorta was isolated 6 h after sepsis for functional and biochemical assays. Lethal sepsis reduced survival rate, mean arterial pressure (MAP), did not alter leukocytes and neutrophils migration, but increased bacterial count in the blood and peritoneal cavity, increased plasma levels of nitrate, urea and CK-MB. We found that in aortas PVAT(-)/Endo(+) or Endo(-), sepsis decreased the contraction induced by phenylephrine or serotonin, when compared to sham. In PVAT(+)/Endo(+) or Endo (-) arteries sepsis induced a more pronounced reduction of phenylephrine-induced contraction. Sepsis-induced increase of anti-contractile action of PVAT was not found after incubation of arteries with L-NAME, 7-nitroindazole, 1400W, A779, carboxyPTIO , ODQ, apamin, indomethacin and RO1138452. Tiron, catalase, charybdotoxin, 4- aminopyridine and glibenclamide did not alter phenylephrine-induced contraction in the CLP group. Sepsis increased H2O2 concentration in the aorta, but did not affect H2O2 concentration in PVAT. Increased levels of superoxide anion (O2-) and prostaglandin (PG) I2 were detected in both aorta and PVAT. Sepsis did not alter the levels of PGE2 or angiotensin (1-7) in the aorta or PVAT. Conclusion: Lethal sepsis increases the anticontractile action of PVAT by a mechanism that involves the production of nitric oxide (NO) by iNOS and nNOS, the participation of calcium-dependent K+ channel of low conductance and activation of the enzyme soluble guanylate cyclase. Angiotensin (1-7) and PGI2 also contribute to the increased anti-contractile effect displayed by PVAT during sepsis. Financial Support: CAPES

Abstrakt: Sepsis (blodförgiftning) är ett livshotande tillstånd som innebär att bakterier eller svampar tar sig in i blodbanan. Det sker ofta genom njurarna, lungorna eller sår i skadad hud. Symptom innefattar feber och allmän sjukdomskänsla. Positiva blododlingar prepareras och analyseras med Matrix assisted laser desorption ionisation time-of-flight (MALDI-TOF MS) där blandas preparerade prov med matrix och bestrålas sedan med en laser. Bestrålningen medför att proteinerna i provet joniseras och rör sig mot en detektor. Proteinerna detekteras som ett spektrum som i sin tur jämförs med ett referensspektrum av en känd bakterie/svamp som finns lagrat i en databas. Dessutom erhålls ett score-värde över hur väl provet liknar ett referensprov. Arbetets syfte var att se vilken provberedningsmetod som gav ett tillförlitligt resultat i MALDI-TOF och ett bra score-värde för identifiering av bakterier till art-nivå på kortast tid. Preparationsmetoderna innefattar rening av blod från röda blodkroppar och andra partiklar som stör MALDI TOF-instrument. Metoderna jämfördes med nuvarande Saponinmetod. Två av metoderna (Ferroni och Huang) gav dåliga resultat och jämförelsen avbröts efter två försök. Ett kommersiellt kit Sepsityper extraktion gav bra resultat där 79 % av analyserna gav identifiering till art-nivå. Motsvarande resultat med saponin-metoden var 33 %. Slutsatsen är att Sepsityper-extraktion-metoden gav betydligt bättre resultat än nuvarande Saponin-metod. Metoden var robust, användarvänlig, snabb och gav bra resultat både för gramnegativa och grampositiva bakterier. / Abstract: Sepsis (blood poisoning) is a life-threatening condition caused by bacteria or fungi entering the bloodstream. Pathogens often again access through the kidneys, lungs or wounds in damaged skin. Symptoms include fever, chills and general feeling of illness. Positive blood cultures are prepared and analyzed with Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF MS) prepared samples are mixed with matrix and then irradiated with laser beam. The laser beam will be directed to each position in the MALDI plate that causes the proteins in the sample to ionize and move towards a detector. The protein pattern is presented in a spectrum that is compared with a reference spectrum of known bacteria / fungi, stored in a database. In addition, a score value was obtained on how well the sample is aligned to the reference sample. The aim of this study was to compare three methods in order to achieve the best score value for identification to species level. The time factor was also important. The preparation methods include purification of blood removing red blood cells and other particles that interfere with MALDI analysis. The methods were compared with the current Saponinmethod. The results of two methods (Ferroni and Huang) were not satisfactory and further comparison was interrupted after two experiments. A commercial kit Sepsityper with extraction gave good results with 79 % identification to species level. Corresponding results for the current Saponin-method was 33 %. In conclusion, the Sepsityper-extraction-method was superior to the current Saponin-method. The method was robust, user-friendly, rapid and gave good results from both gramnegative and grampositive bacteria.

Myeloid-derived suppressor cells (MDSC) expand during sepsis, suppress both innate and adaptive immunity, and promote chronic immunosuppression, which characterizes the late/chronic phase of sepsis. We previously reported that the transcription factors Stat3 and C/EBPb synergize to induces the expression of microRNA (miR)-21 and miR-181b to promote MDSC expansion in a mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive stage. We also showed that Gr1+CD11b+ cells, the precursors of MDSCs, from mice genetically deficient in the inflammatory protein S100A9 lack miR-21 or miR-181b in late sepsis, and are not immunosuppressive. In the present study, we show that S100A9 induces miR-21 and miR-181b during the late sepsis phase. We find that S100A9 associates with and stabilizes the Stat3-C/EBPb protein complex that activates the miRNA promoters. Reconstituting Gr1+CD11b+ cells from the S100A9 knockout mice with late sepsis with S100A9 protein restores the Stat3-C/EBPb protein complex and miRNA expressions, and switches the Gr1+CD11b+ cells into the immunosuppressive, MDSC phenotype. Importantly, we find that this process requires IL-10 mediated signaling, which induces S100A9 translocation from the cytosol to the nucleus. These results demonstrate that S100A9 promotes MDSC expansion and immunosuppression in late/chronic sepsis by inducing the expression of miR-21 and miR-181b.

Necroptosis, a type of regulated necrotic cell death, involves cell membrane permeabilization and has been implicated in various acute and chronic pro-inflammatory diseases, including ischemia-reperfusion injury and neurodegenerative diseases. By using in vitro reconstitution studies and a chemical inhibitor, the kinase activity of the serine/threonine kinase RIPK1 had been shown to regulate necroptotic signaling downstream of TNF and Toll-like receptors (TLRs). To investigate the contribution of RIPK1 kinase activity to inflammation and necroptosis in vivo, we generated kinase inactive RIPK1 knock-in mice. Utilizing fibroblasts and macrophages from these mice, we demonstrate that RIPK1 kinase activity is required for necroptotic complex formation and death induction downstream of TNFR1 and TLRs 3 and 4. We show that RIPK1 kinase inactive mice are resistant to TNF-induced shock and exhibit impaired upregulation of TNF-induced cytokines and chemokines in vitro and in vivo. By using bone marrow reconstitution experiments, we demonstrate that RIPK1 kinase activity in a non-hematopoietic lineage drives TNF-induced lethality. We establish that RIPK1 kinase activity is required for TNF-induced increases in intestinal and vascular permeability and clotting, and implicate endothelial cell necroptosis as an underlying factor contributing to TNF/zVAD-induced shock. Thus, work in this thesis reveals that RIPK1 kinase inhibitors may have promise in treating shock and sepsis.

Sepsis is dysregulated host immune response to infection causing life-threatening organ dysfunction. Endothelial cell dysfunction and uncontrolled inflammatory responses are two contributors for sepsis-induced mortality. The crosstalk between endothelial and immune cells plays a critical role in the pathophysiology of sepsis. Therefore, understanding the mechanism of interaction between endothelial and immune cells will provide novel information to develop therapeutic strategies for sepsis. Pathogen associated moleculear patterns (PAMPs) and/or damage associated molecular patterns (DAMPs) produced during sepsis, activate endothelial cells to increase the expression of adhesion molecules, attracting immune cell infiltration into the tissues. Uncontrolled inflammatory responses during the early phase of sepsis contribute to organ failure and lethality. Over 100 clinical trials, targeting inflammatory responses in sepsis, have failed in the past three decades. Thereby, developing novel therapeutic strategies for sepsis are urgent. Heat shock protein A12B (HSPA12B), as one member of HSP70 family, predominately expressed in the endothelial cells, plays important roles in many pathophysiological processes. Currently, we observed endothelial cell specific HSPA12B deficiency (HSPA12B-/-) exacerbates mortality in sepsis induced by cecal ligation puncture (CLP). HSPA12B-/- septic mice exhibits increased expressions of adhesion molecule and infiltrated macrophages in the myocardium and activated macrophages in the peritoneal cavity. In vitro studies show that HSPA12B could be secreted from endothelial cells via exosome. HSPA12B carried by exosomes can be uptaken by macrophages to downregulate macrophage NF-kB activation and pro-inflammatory cytokine production. Trained immunity, induced by β-glucan, causes immune memory in innate immune cells, with an altered response towards another challenge. We have found that mice received β-glucan seven days before CLP sepsis exhibit attenuated mortality with decreased pro-inflammatory responses. We found that β-glucan significantly increased the levels of HSPA12B in endothelial cells and endothelial exosomes. β-glucan induced endothelial exosomes markedly suppress macrophage NF-kB activation and pro-inflammatory responses. The current data suggests that HSPA12B plays a novel role in the regulation of immune and inflammatory responses and that HSPA12B could be an important mediator for the crosstalk between endothelial cells and macrophages during sepsis. β-glucan regulates endothelial cell functions and immune/inflammatory responses, thus improving survival outcome in CLP sepsis.

The global population is rapidly aging. It is estimated that over the next thirty years, the number of individuals >60 years of age will increase by over a billion, and the number of individuals over age 80 may increase by 300 million. As humans age, our immune system becomes progressively weaker through a process called immune senescence. This age-related decrease in immune function increases susceptibility to infection and chronic diseases. Sepsis is a leading cause of death worldwide. Over the past two decades, there has been an increased incidence of sepsis which is due, in part, to our aging population and immune senescence. The gut microbiome, which plays an essential role in health and disease, is altered in aging and sepsis. Specifically, the commensal microorganisms of the gut microbiota are replaced with potentially pathogenic bacteria. This contributes to immune dysfunction and worsened outcomes in critical illness. The innate immune system can be “trained” to respond more effectively to pathogens. We examined trained immunity as an approach to modulating immunosenescence and microbiome diversity in aging. We investigated the effect of trained immunity on: i) immune cells from healthy aging subjects and sepsis patients and ii) the diversity of the microbiome in aging and sepsis. Our results indicate that trained immunity is effective in combatting age-related immunosenescence. We found that β-glucan induced trained immunity enhances monocyte metabolism, increases functionality as well as alters the transcriptome and epigenome in aging individuals and sepsis patients. We also found that trained immunity induced the expansion of a unique population of myeloid cells in sepsis. These cells are defined as FSChi, CD11b+, GR-1hi and express high levels of immunosuppressive PD-L1. In addition, we found that trained immunity reversed age-related changes to the microbiome and prevented alterations to the microbiome in septic mice. We found that the Firmicutes/Bacteroidetes ratio increased in aging; however, trained immunity reversed this increase and increased Clostridia in aged mice. In sepsis, trained immunity prevented expansion of Proteobacteria observed in control mice. Thus, our results indicate that trained immunity may be effective in modulating immune senescence and the microbiome in aging and sepsis.

Sepsis är ett globalt hälsoproblem och en stor del av personerna som överlever får restsymtom som påverkar deras livskvalité. Syftet med denna studie var att sammanställa faktorer som påverkar livskvalitén för personer som överlevt en sepsis. En integrerad kunskapsöversikt genomfördes där 19 artiklar ur den systematiska litteratursökningen valdes ut för analys. Resultatet visar att faktorer såsom psykiska, fysiska och kognitiva funktionsnedsättningar påverkar personernas livskvalité, då det medför en känsla av att inte vara en fri individ. Andra faktorer som påverkade livskvalitén var förändringar i det sociala livet vilket innebar att personer upplevde en känsla av att inte vara en del av gemenskapen. Detta på grund av att relationer påverkades samt svårigheter att återgå till arbetet. Känslomässiga faktorer som framkom och påverkade personer som överlevt en sepsis var rädsla och oro för att drabbas igen samt existentiella funderingar kring varför just dem drabbats. För att sjuksköterskor ska kunna vara ett sådant stöd till återhämtning som behövs utifrån personernas individuella behov, är det av stor vikt att sjuksköterskor har kunskap kring vilka faktorer som påverkar livskvalité för personer som överlevt sepsis. Det är också av stor vikt att möjliggöra tidig upptäckt och adekvat omvårdnad för personer med sepsis. Föreslagna interventioner var arbetsträning, stödjande samtal samt personcentrerad omvårdnad för att stärka empowerment och återhämtning även efter vårdtidens slut. Kvalitativ forskning utifrån personers perspektiv behövs för att öka kunskapen om och möjliggöra en tidig upptäckt och adekvat vård och omvårdnad för personer med sepsis.

Die Sepsis stellt eine pathophysiologisch komplexe systemische Reaktion auf eine zugrundeliegende Infektion dar. Septische Erkrankungen sind die dritthäufigste Todesursache in Deutschland. Um die bisher vorliegenden Erkenntnisse zur Epidemiologie der schweren Sepsis und des septischen Schocks in Deutschland zu aktualisieren und insbesondere erstmals direkte Daten zur Inzidenz zu ermitteln, wurde die INSEP-Studie als prospektive multizentrische Studie auf Intensivstationen in Deutschland durchgeführt. Für die Mitwirkung an der Studie rekrutierten die beteiligten SepNet-Zentren weitere Kliniken außerhalb des SepNet. Die Teilnahme aller Kliniken erfolgte auf freiwilliger Basis. Die im November 2013 durchgeführte Studie umfasste einen Erhebungszeitraum von 4 Wochen. Von allen Patienten, die sich in diesem Zeitraum auf Intensivstation befanden, wurden allgemeine Daten erfasst. Sofern eine schwere Sepsis oder ein septischer Schock (gemäß der zum Zeitpunkt der Studie gültigen Sepsis-1 Definition) auftrat, erfolgte die Dokumentation sepsis-spezifischer Parameter. 133 Intensivstationen aus 95 Krankenhäusern beteiligten sich an der Studie. Insgesamt waren die Daten von 11883 Aufnahmen auf Intensivstation auswertbar. Das Alter der Patienten betrug im Median 69 Jahre (IQR: 57-77), 57,7% der Patienten waren männlich. Bei 1503 (12,6%) Patienten wurde die Diagnose einer schweren Sepsis oder eines septischen Schocks gestellt. Die ermittelte Inzidenzdichte betrug 11,6 pro 1000 Patiententage auf ITS [95%-KI: 10,5-12,9]. Die für den 1. Tag des Erhebungszeitraums bestimmte Punktprävalenz lag bei 17,9% [95%-KI: 16,3-19,7]. Die Sterblichkeit auf Intensivstation betrug für die Patienten mit schwerer Sepsis / septischem Schock 34,3%. Im Vergleich dazu verstarben nur 6% der Patienten, die keine Sepsis hatten, auf ITS. Die Krankenhaussterblichkeit betrug für Patienten mit schwerer Sepsis / septischem Schock 40,4% bzw. 9,6% für Patienten ohne Sepsis. Schwere Sepsis und septischer Schock entwickelten sich bei 860 (57,2%) Patienten auf der Basis einer nosokomialen Infektion. Die häufigsten Infektionen waren Pneumonien, die bei 700 (46,6%) Patienten auftraten. Intraabdominelle und gastrointestinale Infektionen lagen bei 431 (28,7%) und urogenitale Infektionen bei 190 (12,6%) Patienten vor. Sowohl die Sterblichkeit auf Intensivstation, als auch die Sterblichkeit im Krankenhaus war bei Patienten im septischen Schock mit 37,3% bzw. 43,3% signifikant höher (p<0,001) als bei Patienten mit schwerer Sepsis (16,7% bzw. 23,4%). Aufgrund der nicht repräsentativen Stichprobe konnte die Inzidenz nicht auf die Gesamtbevölkerung in Deutschland hochgerechnet werden. In der INSEP-Studie konnte im Rahmen eines pragmatischen Ansatzes gezeigt werden, dass sowohl die schwere Sepsis als auch der septische Schock auf Intensivstationen in Deutschland immer noch häufig auftreten und eine hohe Mortalität aufweisen. Es bleibt zu wünschen, dass insbesondere aufgrund der mittlerweile im Alltag eingeführten neuen Sepsis-Definition (Sepsis-3) die Epidemiologie der Sepsis im Rahmen einer repräsentativen Studie ermittelt werden kann.:1 Abkürzungsverzeichnis 4 2 Einführung 6 2.1 Definition Sepsis 6 2.2 SepNet 10 2.3 Epidemiologie der Sepsis 11 3 Aufgabenstellung 14 4 Material und Methoden 15 4.1 Dokumentierte Fälle 16 4.2 Statistische Auswertung 17 5 Ergebnisse 21 5.1 Beteiligte Krankenhäuser und Intensivstationen 21 5.2 Beschreibung der Patientenpopulation 23 5.3 Inzidenz und Prävalenz 25 5.4 Überlebensstatus 30 5.5 Infektionen und Mikrobiologie der Sepsis 30 5.6 SIRS-Kriterien und Organdysfunktionen 31 5.7 Auswertung gemäß Sepsis-3-Definition 33 6 Diskussion 39 6.1 Inzidenz und Prävalenz 39 6.2 Sterblichkeit 41 6.3 SIRS und Organdysfunktionen 42 6.4 Neue Definition der Sepsis (Sepsis-3) 43 6.5 Limitationen 44 6.6 Zusammenfassung und Ausblick 44 7 Zusammenfassung der Arbeit 45 8 Literaturverzeichnis 49 9 Anlage – Statistischer Analyseplan 55 10 Erklärung über die eigenständige Abfassung der Arbeit 81 Lebenslauf 82 Publikationen 82 Danksagung 85

In dieser retrospektiven Pilotstudie wurde die Aussagekraft klinischer und paraklinischer Parameter in Prä-, Peri- und früher Postnatalphase für die Diagnostik der klinischen Early-Onset Sepsis beim Neugeborenen untersucht. Der postnatal innerhalb von drei Tagen beim Kind gemessene CRP-Wert mit einem Cut-off von 10 mg/l wurde für die Differenzierung klinische Sepsis / keine Sepsis herangezogen. Die Analyse der zwei nach CRP-Werten getrennten Kollektive erfolgte hinsichtlich verschiedener Faktoren (wie z.B. Kreislauf und Laborparameter der Mutter vor der Geburt bzw. Labor – und Kreislaufparameter des Kindes bis 96 h postnatal). In der Auswertung zeigen sich signifikante Unterschiede der einzeln betrachteten Variablen. In einer Multivarianzanalyse konnten keine statistisch relevanten Differenzen bestätigt werden, daher werden weiterführende, prospektive randomisierte Studien zur Evaluation dieses Ansatzes empfohlen. Aufgrund der hohen und signifikanten Unterschiede bei Einzelbetrachtung und der sehr frühen Verfügbarkeit können die mütterlichen Parameter CRP > 12,3 mg/l und Herzfrequenz > 76,5 Schläge pro Minute sowie die unmittelbar postnatal gemessenen kindlichen Laktatwerte > 3,55 mml/l jedoch als wichtige Indikatoren zur Identifikation von Kindern mit einer Early-Onset Sepsis empfohlen werden.