Introdução: O objetivo deste estudo foi avaliar o efeito de uma estratégia restritiva de transfusão de hemácias comparada a uma estratégia liberal na evolução clínica de pacientes submetidos à cirurgia cardíaca com circulação extracorpórea. Métodos: Estudo prospectivo, randomizado, e controlado. Foram randomizados 512 pacientes para uma estratégia liberal de transfusão (hematócrito 30%) ou restritiva (hematócrito 24%). Resultados: Os pacientes apresentaram idade média de 60,7 ± 12,5 anos no grupo liberal e 58,6 ± 12,5 anos no grupo restritivo. Em ambos, houve predomínio de pacientes com fração de ejeção normal, mas 13% dos pacientes do grupo liberal e 15% do grupo restritivo apresentavam fração de ejeção abaixo de 40%. A mortalidade ou a morbidade grave em 30 dias foi semelhante nos dois grupos (10% na estratégia liberal e 11% na estratégia restritiva, P=0,518). Não houve diferença entre os grupos em relação às taxas de complicações secundárias. A média da concentração de hemoglobina foi 10,5 0,9 g/dL no grupo liberal e 9,1 1,2 gdL no grupo restritivo (P<0,001). No grupo liberal, 198 pacientes (78%) receberam transfusão de hemácias, e no grupo restritivo 118 pacientes (47%). Independente da estratégia utilizada, o número de transfusão de hemácias foi fator preditor independente para a ocorrência de complicações clínicas graves ou morte em 30 dias (OR=1,21; IC 95%=1,1-1,4, P= 0,002). Conclusão: A estratégia restritiva de transfusão foi tão segura quanto à estratégia liberal em pacientes submetidos à cirurgia cardíaca com circulação extracorpórea. Cada unidade de concentrado de hemácias administrada foi associada a aumento de 1,2 vezes no risco de mortalidade em 30 dias / Introduction: The aim of this study was to evaluate whether a restrictive strategy of red blood cells transfusion is as safe as a liberal one with respect to clinical outcomes. Methods: In this prospective, randomized, controlled clinical trial we randomly assigned 512 patients after cardiac surgery to a liberal strategy of transfusion (to maintain a hematocrit at least at 30%) or to a restrictive one (to maintain a hematocrit at least at 24%). Results: The mean age of patients was 60.7 ± 12.5 year-old in liberal group vs. 58.6 ± 12.5 year-old in restrictive group. In both groups, most patients had normal left ventricular function, but 13% of patients in the liberal group and 15% in the restrictive one presented ejection fraction of less than 40%. The primary end-point - a composite endpoint of 30 day all cause mortality or severe morbidity was similar between groups (10% in the liberal-strategy group vs. 11% in the restrictive-strategy group) (P=0.518). Also, there were no differences between groups with respect to the rates of other complications. Hemoglobin concentrations were maintained at a level of 10.5 ± 0.9 g/dL in the liberal group and 9.1 ± 1.2 g/dL in the restrictive group (P<0.001). A total of 198 patients (78%) in the liberal group and 118 patients (47%) in the restrictive group received a blood transfusion (P<0.001). Independently of the strategy group, the number of transfused RBC units was an independent risk factor for the occurrence of several clinical complications or death at 30 days (HR = 1.21; CI 95%=1.1-1.4, P=0.002). Conclusions: A restrictive transfusion strategy was as safe as a liberal strategy in patients undergoing cardiac surgery. For each RBC unit transfused, transfusion was independently associated with a 1.2-fold higher risk of death at 30 days

Introdução: A desmopressina, análogo sintético do hormônio hipotalâmico vasopressina, é utilizada em determinadas condições hematológicas hereditárias melhorando a função plaquetária e aumentando os níveis dos fatores de von Willebrand (FvW) e Fator VIII. Entretanto, sua administração na população geral é controversa, necessitando de mais estudos para elucidar sua eficácia como agente hemostático. Objetivo: O objetivo do presente estudo foi avaliar a coagulação sanguínea, clínica e laboratorialmente, após administração profilática da desmopressina em cirurgias cardíacas valvares. Métodos: Estudo clínico prospectivo e randomizado realizado no Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). Foram incluídos 108 pacientes adultos submetidos à cirurgia cardíaca valvar, no período de fevereiro de 2015 a novembro de 2016. Os pacientes foram randomizados e alocados para a administração profilática da desmopressina ou para o grupo controle, na admissão hospitalar. Imediatamente após a reversão da heparina, administrouse a demopressina no grupo da intervenção ou solução placebo no grupo controle. O desfecho foi a análise da coagulação sanguínea e do sangramento perioperatório através dos exames laboratoriais, débito sanguíneo dos drenos cirúrgicos e do consumo de hemocomponentes em 48 horas. Resultados: Os níveis sanguíneos do Fator VIII no tempo 2h (236,5 ± 62,9 vs. 232,3 ± 66,7, P=0,015) foram estatisticamente significantes entre os dois grupos (DDAVP e controle), respectivamente. Os demais testes clássicos da coagulação, assim como a análise viscoelástica e de agregação plaquetária mantiveram-se homogêneos em todos os tempos de coleta entre os dois grupos. O débito dos drenos cirúrgicos, balanço sanguíneo e consumo de hemocomponentes não apresentaram diferenças significantes entre os grupos DDAVP e controle. O tempo de ventilação mecânica apresentou diferença relevante entre os grupos DDAVP e o controle [897 (820 - 1011) vs. 1010 (846 - 1268), em mim, P=0,031], respectivamente. Não houve diferença em relação à incidência de complicações, tempo de internação hospitalar e de UTI ou mesmo de mortalidade em 30 dias. Conclusões: A utilização profilática da desmopressina em cirurgias cardíacas valvares não se mostrou eficaz em exercer efeito hemostático em relação ao grupo controle no presente estudo / Introduction: Desmopressin, a synthetic vasopressin analogue, is used in certain hereditary hematologic conditions, improving platelet function and increasing the levels of von Willebrand factor and factor VIII. However, its use in general population is still controversial, requiring further studies to elucidate its efficacy as a haemostatic agent. Objective: To evaluate blood coagulation, through clinical and laboratorial analysis, after prophylactic use of desmopressin in heart valve surgeries. Methods: A prospective and randomized clinical study was performed in the Heart Institute (InCor) of Hospital das Clínicas, from the Faculty of Medicine, University of São Paulo (HC-FMUSP). A total of 108 adult patients undergoing heart valve surgeries were enrolled from February 2015 to November 2016. Patients were randomly assigned to the prophylactic use of desmopressin or to the control group at the time of hospital admission. Immediately after heparin reversal, demopressin was given in the intervention group or placebo solution in the control group. Blood samples were collected at three different times in all study participants. Blood coagulation and perioperative bleeding were analysed using laboratorial tests, blood flow through surgical drains and the consumption of blood components within 48 hours. Results: Blood levels of Factor VIII at Time 2h (236.5 ± 62.9 vs. 232.3 ± 66.7, P=0.015) were significantly different between the two groups (desmopressin and control), respectively. Classical coagulation tests, as well as viscoelastic and platelet aggregation tests, remained homogeneous at all collection times between the two groups. Flow rate of surgical drains, blood balance and consumption of blood components did not present significant differences between the DDAVP and control groups. Mechanical ventilation time presented a significant difference between the desmopressin and control groups [897 (820 - 1011) vs.1010 (846 - 1268), min, P=0.031], respectively. There was no difference in incidence of complications, length of hospital and ICU stay or even mortality in 30 days. Conclusions: The prophylactic use of desmopressin in heart valve surgeries was not effective in exerting haemostatic effect compared to the control group in this study

Made available in DSpace on 2016-08-19T18:16:02Z (GMT). No. of bitstreams: 1 Christiana Leal Salgado.pdf: 2220876 bytes, checksum: 73b3f7e0a903e6f67511018a8a8243df (MD5) Previous issue date: 2010-10-19 / This paper aims to analyze the experience of young children s families in the face of an intensive Care Unit of Cardiology s internment. The presence of parents in the hospital environment contributes to minimize the suffering caused by the child's hospitalization. Understanding the factors that help parents when facing the context of disease treatment and hospitalization of a child can help them to understand the dynamic factors related to hospital, helping them to better cope with the situation of illness, treatment and hospitalization. Qualitative approach was the methodological option, considering the nature of study s subject. Were accomplished six semistructured interviews with mothers and a father besides 100 hours of participant observation during the study, 20 hours of it dedicated to formal observation. We used the thematic analysis, a method of content analysis to understand the data. The results were classified into four units of meaning: feelings and emotions against the child's illness; heart disease under the maternal staring; the mother and child in the dynamics of the Intensive Care Unit; resources to face the situation; It follows that the heart s symbolism enhances the mothers emotional fragility regarding their children's illness; religiosity; spirituality and a consistent social support network were contributing factors for demonstration and maintenance of adaptive behavior. The presence of the mother and her stay in all stages of children s treatment in the studied Unit does not always happen. / Este trabalho objetiva analisar a vivência de famílias de crianças frente à internação em uma Unidade de Terapia Intensiva Cardiológica. A presença dos pais no ambiente hospitalar contribui para a minimização do sofrimento gerado na criança pela internação. A compreensão dos fatores que auxiliam os pais no enfrentamento diante do contexto doença-tratamento e hospitalização do filho pode ajudá-los a compreender os fatores ligados à dinâmica hospitalar, contribuindo para um melhor enfrentamento da situação de adoecimento, tratamento e hospitalização. A abordagem qualitativa foi a opção metodológica, considerando-se a natureza do objeto de estudo. Foram realizadas seis entrevistas semi-estruturadas com as mães e uma com o pai e 100 horas de observação participante durante o estudo, sendo 20 horas de observação formal. Foi utilizada a análise temática, uma modalidade da análise de conteúdo para a compreensão dos dados. Os resultados foram classificados em quatro núcleos de sentido: sentimentos e emoções frente ao adoecimento do filho; a doença do coração sob o olhar materno; a mãe e o filho na dinâmica da Unidade de Terapia Intensiva; recursos de enfrentamento; Concluiu-se que o simbolismo do coração potencializa a fragilidade emocional das mães diante do adoecimento dos seus filhos; a religiosidade, a espiritualidade e uma consistente rede social de apoio foram fatores contribuintes para a emissão e a manutenção de comportamentos adaptativos. A presença da mãe e a sua permanência em todas as etapas do tratamento da criança, na Unidade estudada, nem sempre acontece.

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Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2016-11-18T14:26:17Z No. of bitstreams: 1 Ariele Priebe Reisdorfer_.pdf: 1985228 bytes, checksum: 076794974edc775959e935820eee2c49 (MD5) / Made available in DSpace on 2016-11-18T14:26:17Z (GMT). No. of bitstreams: 1 Ariele Priebe Reisdorfer_.pdf: 1985228 bytes, checksum: 076794974edc775959e935820eee2c49 (MD5) Previous issue date: 2016-10-14 / Nenhuma / A cirurgia cardíaca é indicada como tratamento para doenças cardiovasculares. A realização desse procedimento é complexa e exige que todo o cuidado do pós-operatório imediato e parte do mediato sejam realizados na Unidade de Terapia Intensiva (UTI). Nesse sentido, o serviço prestado pela equipe de enfermagem contribui para garantir a recuperação do indivíduo submetido à cirurgia cardíaca. O objetivo desta pesquisa é elaborar um programa de Educação Permanente em Saúde para a equipe de enfermagem da UTI Adulto do Hospital Geral de Caxias do Sul/RS acerca do cuidado ao paciente no pós-operatório de cirurgia cardíaca. Esta pesquisa, de caráter qualitativo, contou com a participação de vinte e sete integrantes da equipe de enfermagem (enfermeiros e técnicos) que prestam cuidado ao paciente no pós-operatório do hospital em estudo. A coleta de dados ocorreu por meio de uma entrevista semiestruturada. Para o tratamento dos dados, foi utilizada a análise temática, da qual emergiram quatro categorias: desafios da equipe em relação aos cuidados específicos ao paciente no pós-operatório de cirurgia cardíaca; o medo da admissão na UTI de paciente no pós-operatório de cirurgia cardíaca; relações multiprofissionais; e necessidade de educação permanente em saúde. Os resultados apontaram que os profissionais que iniciaram suas atividades nesse cenário há pouco tempo sentem dificuldade na prestação de cuidados ao paciente, enquanto os mais antigos percebem a fragilidade dos novos colegas e relembram das suas quando iniciaram. Além disso, todos sentem a necessidade de qualificar a prática profissional. Nesse contexto, as propostas de intervenção deste estudo foram a elaboração do Programa de Educação Permanente em Saúde, uma cartilha de orientação sobre os cuidados no pós-operatório de cirurgia cardíaca e um checklist para guiar a passagem do plantão do bloco cirúrgico para a UTI. / The cardiac surgery is indicated as a treatment for cardiovascular diseases. This procedure is complex and its recuperation on the immediate postoperative and a part of the mediate postoperative is realized on the Intensive Care Unit (ICU). The nursing assistance contributes for the patient recovery after cardiac surgery. The objective of this search is to prepare a Health Permanent Education Program for the nursing team that work at the ICU Adult of this hospital, about the assistance to the patient that realized cardiac surgery. The study is qualitative and twenty-seven people from the nursing team that care of this patient participated of the search. It was utilized a semi structured interview to collect data. The analysis of the data were realized through the thematic analysis. Four categories emerged from the study: team challenges for specifically providing care on the postoperative of cardiac surgery; the fear of the patient admission on the ICU; multi professional relationships and necessity of health permanent education. This study indicated that the new professionals face difficulties to care of the patient that realized this surgery. The professionals that work for longer at this place observe the fragilities on the new coworkers and also remember their difficulties when they started to work. All of them related that is necessary to qualify their professional practice. Therefore, the proposal of this study were the elaboration of the Health Permanent Education Program; a guidance booklet about the care on the postoperative of cardiac surgery; and a checklist to guide the shift change from the surgical ward to the ICU.

INTRODUÇÃO: Existem poucas evidências de benefícios da analgesia regional na disfunção respiratória observada no pós-operatório (PO) de cirurgia cardíaca. Os objetivos deste estudo foram avaliar os efeitos da morfina intratecal sobre a função respiratória, a analgesia, o consumo de morfina e seus níveis plasmáticos no PO de pacientes submetidos à anestesia geral para revascularização do miocárdio (RM). MÉTODOS: Foram estudados 42 pacientes submetidos à RM com circulação extracorpórea e randomizados para receberem anestesia geral associada ou não a morfina intratecal na dose de 400 g (grupo controle, n=22 e grupo morfina, n=20). A anestesia geral foi padronizada com sufentanil e isoflurano e no PO imediato, instalou-se dispositivo de analgesia controlada pelo paciente, com bolus de 1 mg, em livre demanda e dipirona se necessário. Com espirômetro digital, avaliou-se a capacidade vital forçada (CVF), o volume expiratório forçado no primeiro segundo (VEF1), a relação VEF1/CVF e, pela análise da gasometria artérial, calculou-se a relação PaO2/FIO2 no pré-operatório, primeiro e segundo dias de PO. A intensidade da dor, avaliada com escala visual numérica (0-10), o número de solicitações e o consumo de morfina venosa, assim como seus níveis plasmáticos, foram avaliados até 36 horas de PO. A análise estatística consistiu de análise de variância para medidas repetidas e teste de Mann-Whitney, considerando-se significativo p<0,05. RESULTADOS: Em ambos os grupos houve redução da CVF (grupo controle=1,45 L e 1,38 L, grupo morfina= 1,18 L e 1,26 L no primeiro e segundo dias de PO, respectivamente), sem diferença entre os mesmos (p=0,06). Não foram observadas diferenças entre os grupos no VEF1 (p=0,085), nas relações VEF1/CVF (p=0,68) e PaO2/FiO2 (p=0,08) nos tempos avaliados. O grupo morfina apresentou valores significativamente menores de dor no repouso e inspiração profunda e, principalmente, durante a tosse após 18 horas (grupo controle=4,73 e grupo morfina=1,80, p=0,001), 24 horas (grupo controle=4,41 e grupo morfina=1,40, p=0,022) e 36 horas (grupo controle=3,09 e grupo morfina=1,55, p=0,015) de PO. Observou-se redução do consumo cumulativo de morfina venosa após 18 horas (grupo controle=20,14 mg e grupo morfina=14,10 mg, p=0,037) e 24 horas de PO (grupo controle= 27,8 mg e grupo morfina= 13,55 mg, p=0,028). Após 24 horas de PO, o grupo que recebeu opióide intratecal apresentou menores níveis plasmáticos de morfina (grupo controle=16,41 ng/mL e grupo morfina=4,08 ng/mL, p=0,029). CONCLUSÕES: O efeito central da morfina intratecal não minimizou a disfunção respiratória mas promoveu redução da intensidade da dor, com diminuição do consumo venoso e menores níveis plasmáticos de morfina no PO de pacientes submetidos à cirurgia de RM. / BACKGROUNDS: Few evidence exists on beneficial effects of intrathecal analgesia in lung dysfunction observed in postoperative (PO) of cardiac surgery. The objective of this study was to evaluate the effects of intrathecal morphine on pulmonary function, analgesia, morphine consumption and plasma morphine levels in PO of patients undergoing coronary artery bypass graft surgery (CABG). METHODS: Were studied 42 patients undergoing on-pump CABG randomized (control group, n=22 and morphine group, n=20) to receive general anesthesia with or not 400 g of intrathecal morphine. Anesthesia was standardized and in immediate PO, patients received a patient controlled-analgesia pump, 1 mg bolus of morphine, free demand and dipirone if necessary. Forced vital capacity (CVF), expiratory forced volume in first second (EFV1) and EFV1/FVC ratio were measured using spirometry and arterial blood samples obtained preoperatively, in first and second PO days. Intensity of pain, evaluated using visual numeric scale (0-10), morphine solicitation and consumption and plasma morphine levels were evaluated until 36 hours of PO. Statistical analysis was done with repeated measures analysis of variance and Mann-Whiney test (*p<0.05). RESULTS: Both groups had reduction of FVC in PO (control group=1.45 L and 1.38 L, and morphine group=1.18 L and 1.26 L, respectively in first and second PO (p= 0.06) without differences between them. There were no differences in EFV1 (p=0.085), VEF1/CVF (p=0.68) and PaO2/FiO2 ratio between groups (p=0.08). In morphine group was observed reduction in intensity of pain at rest and profound inspiration but most significatively at cough after 18 hours PO (control group=4.73 and morphine group=1.80, p=0.001), 24 hours (control group=4.41 and morphine group=1.40, p=0.022) and 36 hours (control group=3.09 and morphine group=1.55, p=0.015). Was observed reduction in morphine consumption after 18 hours PO (control group=20.14 mg and morphine group=14.10 mg, p=0.037) and after 24 hours (control group=27.8 mg and morphine group= 13.55, p=0.028). After 24 hours of PO, morphine group has reduced plasma morphine levels (control group=16,41 ng/mL and morphine group=4.08 ng/mL, p=0.029). CONCLUSIONS: Central neuraxial effect of morphine did not reduced postoperative pulmonary dysfunction but promoted better postoperative analgesia, reducing pain scores, venous morphine consumption and lower plasma morphine levels in CABG.

Background: The 30-day readmission rate is considered a quality of care measure for providers and has become important because providers might face reduced reimbursement from any increase in unplanned readmissions Objective: The aim of the first chapter is to investigate the waiting-length of stay (WLOS) and post-length of stay (PLOS) on the 30-day readmission. In the second chapter, we examined the hospital procedural volume and hospital quality on the 30-day readmission. Our objective in the third chapter is to examine the zip code-level SES factors on the 30-day readmission rates. Participants: patients undergoing isolated coronary artery bypass grafting (CABG) in Virginia Methods: A retrospective study design has been conducted using a multi-level logistic model of increasing complexity for all three chapters. The sample used was from the Virginia Cardiac Surgery Quality Initiative (VCSQI) of the periods 2008-2014, the dataset included patient characteristics. Afterward, we merged the sample with both the Virginia Health Information (VHI) to obtain hospital characteristics (ownership, teaching status, and location), and Agency for Healthcare Research and Quality (AHRF) to obtain county-socio-economic status (SES) characteristics (education, employment, and median household income), the previous SES was used for chapter’s one and two. In chapter three, instead of AHRF, we merged the sample with the American Community Survey (ACS) to obtain zip code-SES characteristics (employment, median household income, education, median house price). The main outcome was the 30-day readmission rate. The analytical sample of chapter one n = 22,097, in chapter two the sample n = 25,531, while in chapter three the sample n= 25,829. We conducted a sensitivity analysis in all three chapters. In chapter one we analyzed the data at the patient level, in chapter two we analyzed the data at the hospital level, while in chapter three we conducted the analysis at the area zip code level. Results: In chapter one, we found that readmitted patients after a prolonged PLOS had increased odds of readmission, by 68.7%, compared to readmitted patients with a shorter PLOS in the fully adjusted model; while, WLOS was not significant at the P < 0.05. In chapter two, the fully adjusted model displayed significant results with a reduced odds in readmissions by 22.8% in the middle-volume hospitals compared to the low-volume hospitals, while the middle-quality hospitals had increased odds of readmission by 23.5% compared to the low-quality hospitals. In chapter three, statistically, we did not find that area zip code-SES had an effect on the 30-day readmission rate. While, geographically, we found that addresses of individuals were clustered in certain areas of Virginia. Conclusion: In chapter one, patients undergoing CABG and experience a prolonged PLOS of > 6 days are at risk to be readmitted within 30-days of the procedure. In chapter two, the higher volume hospitals (middle-volume) compared to low-volume hospitals showed a significant reduction in odds in the 30-day readmissions, especially after adjusting the model with hospital quality. In chapter three, even though, there was no association of area-SES with 30-day readmission, in the maps, we found a cluster of patient addresses in the southern parts of Virginia with an increased readmission, which is considered underprivileged area; and the fact might be due to the proximity of these areas to cardiovascular hospitals. Policy Implication: In chapter one, the study provided a model for clinicians to stratify patients at risk of readmission, especially patients with risks of staying longer in the hospital after CABG. In chapter two, policymakers and the CMS should find new ways to help hospitals with low-volumes to reduce their isolated-CABG readmission rates and be able to compete with high-volume hospitals. In chapter three, no significant correlation between area-SES and readmission for patients who underwent CABG was found; these backs prior notion that SES should not be adjusted for the reimbursement penalties of the Hospital Readmission Reductions Program (HRRP) on hospitals

<p>Nitric oxide (NO) is expressed in inflammatory tissues. However, NO effects are controversial in inflammation; NO is described as acting in a dose dependent manner and possess both pro-inflammatory and anti-inflammatory properties. </p><p>The present thesis explored the role of NO in relation to white blood cell (WBC) and protein system activation by foreign surfaces in simulated extracorporeal circulation (SECC) using human whole blood from volunteer donors. Three doses of NO, 40 ppm, 80 ppm and 500 ppm, were administered and an array of markers of WBC and protein activation were studied. Neutrophil degranulation was detected with myeloperoxidase (MPO), human neutrophil lipocalin (HNL) and lactoferrin (LF); eosinophil degranulation with eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO); and basophil degranulation with histamine. Furthermore, whole blood and WBC capacity to produce reactive oxygen species (ROS) were studied and cytokine release was measured with IL-1 and IL-10. Complement activation was measured with C3a and C5b-9 complex and contact system activation with FXIIa-C1INH, FXIIa-AT, FXIa-C1INH and FXIa-AT.</p><p>NO increased neutrophil degranulation at all dose levels and 80 ppm NO increased basophil degranulation; whereas, NO exerted no effect on eosinophil degranulation, WBC subset counts, cytokine release or capacity to produce ROS. In addition, while increasing both specific and azurophil degranulation with 40 ppm, 80 ppm and 500 ppm, NO reversed the classical degranulation hierarchy with 500 ppm and azurophil degranulation became predominant. Furthermore, NO effect was greater with 500 ppm than with 80 ppm, indicating a dose response effect. The lack of iNOS mRNA expression in WBC and lack of L-NAME effect on degranulation and nitrite/nitrate production, together with absent increase in nitrite/nitrate in controls, excluded autocrine or paracrine regulation of degranulation. FXIIa-AT and FXIa-AT complexes increased and became predominant during early recirculation, whereas FXIIa-C1INH and FXIa-C1INH complexes were predominant at baseline but remained unaltered, suggesting contact system inhibition predominantly via AT. C3a and C5b-C9 increased. NO had no effect on either contact or complement system activation; however, 500 ppm NO shortened active clotting time.</p><p>In conclusion, the present data suggest that NO has a direct effect on neutrophil and basophil degranulation. Recognition of NO as an enhancer of degranulation may give access to new therapeutic tools for local and systemic inflammatory therapies; whereas, the identification of increased AT mediated inhibition of FXIIa and unchanged C1INH complexes presents new possibilities for therapeutic intervention in conditions such as hereditary angioedema and heart surgery.</p>

<p>Many elderly undergo cardiac surgery. The prevalence of malnutrition in elderly is high and increases with comorbidity. This thesis aims to clarify some aspects on performing surgery in elderly concerning nutritional status, nutritional treatment and age-related physiology.</p><p>Study I: 886 patients were assessed preoperatively by body mass index (BMI) and S-albumin and postoperatively for mortality and morbidity.. Low BMI increased the relative hazard for death and low S-albumin increased the risk for infection. BMI and S-albumin are useful in preoperative evaluations</p><p>Study II: we followed energy intake in 31 patients for five postoperative days. Scheduled and unscheduled surgery did not differ in preoperative resting energy expenditure (REE). REE increased by 10-12% postoperatively, more in unscheduled CABG. Nutritional supplementation increased total energy intake. All patients exhibited postoperative energy deficits, less prominent in the supplemented group. There were no differences in protein synthesis or muscle degradation. </p><p>Study III: in 16 patients, .we measured stress hormones and insulin resistance before surgery and for five postoperative days Patients were insulin resistant on the first two days. We saw no clearly adverse or beneficial effects of oral carbohydrate on insulin resistance or stress hormone response. </p><p>Study IV: 73 patients, with early enteral nutrition (EN), were observed until discharge or resumed oral nutrition. EN started within three days in most patients. In a minority, problems occurred (gastric residual volumes, tube dislocation, vomiting, diarrhoea, aspiration pneumonia). In the cardiothoracic ICU individually adjusted early EN is feasible. </p><p>Study V: in 16 patients, splanchnic blood flow (SBF) enhancing treatments (dopexamine (Dpx) or EN) were compared. Dpx increased systemic blood flow, but had only a transient effect on SBF. EN had no effect on systemic blood flow or SBF. Neither Dpx, EN or the combined treatment, exhibited any difference between groups on systemic or splanchnic VO₂ or oxygen extraction ratio. </p>

Nitric oxide (NO) is expressed in inflammatory tissues. However, NO effects are controversial in inflammation; NO is described as acting in a dose dependent manner and possess both pro-inflammatory and anti-inflammatory properties. The present thesis explored the role of NO in relation to white blood cell (WBC) and protein system activation by foreign surfaces in simulated extracorporeal circulation (SECC) using human whole blood from volunteer donors. Three doses of NO, 40 ppm, 80 ppm and 500 ppm, were administered and an array of markers of WBC and protein activation were studied. Neutrophil degranulation was detected with myeloperoxidase (MPO), human neutrophil lipocalin (HNL) and lactoferrin (LF); eosinophil degranulation with eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO); and basophil degranulation with histamine. Furthermore, whole blood and WBC capacity to produce reactive oxygen species (ROS) were studied and cytokine release was measured with IL-1 and IL-10. Complement activation was measured with C3a and C5b-9 complex and contact system activation with FXIIa-C1INH, FXIIa-AT, FXIa-C1INH and FXIa-AT. NO increased neutrophil degranulation at all dose levels and 80 ppm NO increased basophil degranulation; whereas, NO exerted no effect on eosinophil degranulation, WBC subset counts, cytokine release or capacity to produce ROS. In addition, while increasing both specific and azurophil degranulation with 40 ppm, 80 ppm and 500 ppm, NO reversed the classical degranulation hierarchy with 500 ppm and azurophil degranulation became predominant. Furthermore, NO effect was greater with 500 ppm than with 80 ppm, indicating a dose response effect. The lack of iNOS mRNA expression in WBC and lack of L-NAME effect on degranulation and nitrite/nitrate production, together with absent increase in nitrite/nitrate in controls, excluded autocrine or paracrine regulation of degranulation. FXIIa-AT and FXIa-AT complexes increased and became predominant during early recirculation, whereas FXIIa-C1INH and FXIa-C1INH complexes were predominant at baseline but remained unaltered, suggesting contact system inhibition predominantly via AT. C3a and C5b-C9 increased. NO had no effect on either contact or complement system activation; however, 500 ppm NO shortened active clotting time. In conclusion, the present data suggest that NO has a direct effect on neutrophil and basophil degranulation. Recognition of NO as an enhancer of degranulation may give access to new therapeutic tools for local and systemic inflammatory therapies; whereas, the identification of increased AT mediated inhibition of FXIIa and unchanged C1INH complexes presents new possibilities for therapeutic intervention in conditions such as hereditary angioedema and heart surgery.