INTRODUÇÃO: Complicações pulmonares são frequentes no pós-operatório da cirurgia de revascularização do miocárdio (RM) e a ventilação não-invasiva (VNI) tem sido utilizada nos cuidados pós-operatórios de forma profilática e terapêutica. A manobra de recrutamento alveolar (MRA) consiste no aumento sustentado de pressão na via aérea utilizando um alto nível de pressão expiratória final positiva (PEEP) em indivíduos hipoxêmicos, garantindo uma ventilação pulmonar homogênea e, com isso melhorando a oxigenação arterial. O objetivo desse estudo foi de avaliar se o uso da VNI associada à MRA pode melhorar a oxigenação e se pode ser aplicada de forma segura nos pacientes pós-operatório de RM. MÉTODOS: Foram incluídos 34 pacientes internados na unidade de terapia intensiva (UTI) ventilados mecanicamente após RM com relação Pa02/Fi02 < 300 e escore radiológico de atelectasia ;:: 2. Os pacientes foram randomizados 16 para o grupo controle (GC) e 18 para o grupo recrutamento (GR), após a extubação a VNI foi aplicada por 30 minutos três vezes ao dia de acordo com a rotina da UTI. No GC a VNI era realizada com PEEP de 8 cm H20 e no GR foi aplicada PEEP de 15 cm H20 e 20 cm H20 durante 2 minutos cada e depois ficava com PEEP de 8 cm H20. Analisamos a Pa02 pela gasometria arterial em ar ambiente e o escore radiológico de atelectasia, estabilidade hemodinâmica e evento adverso até a alta da UTI. RESULTADOS: Aumento de Pa02 12,6 ± 6,8% GC e 23,3 ± 8,5% GR com p < 0,001, o escore radiológico de atelectasia apresentou resolução completa em 94,4% GR, enquanto que no GC, 87,5% apresentou algum grau de atelectasia, p < 0,001. Não houve eventos adversos relacionados. CONCLUSÃO: o uso por 30 minutos da VNI associada à MRA foi seguro, melhorou a oxigenação e reduziu a atelectasia / BACKGROUND: Postoperative pulmonary impairment is common in the early period after coronary artery bypass grafting (CABG) and noninvasive ventilation (NIV) has been used in postoperative care to prevent and treatment. Recruitment maneuver (RM) consists in a sustained raise of airway pressure with high levei of positive end-expiratory pressure (PEEP) in hypoxemic subjects, insuring a homogeneous pulmonary ventilation and enhancing oxygenation. The aims of this study were to evaluate if the use of NIV associated with RM could improve oxygenation and if it could be safely applied in CABG postoperative patients. METHODS: Were included 34 patients admitled to the intensive care unit (ICU) mechanically ventilated after CABG with Pa02/Fi02 ratio < 300 and radiological atelectasis score (RAS) ~ 2. Patients were randomized 16 to the control group (CG) and 18 to the recruitment group (RG), after extubation NIV was applied for 30 minutes three times a day according to ICU routine. In the CG, NIV was performed with PEEP 8 cm H20 and in the RG, was applied PEEP 15 cm H20 and 20 cm H20 for 2 minutes each and then was with PEEP 8 cm H20. We analyzed Pa02 from arterial blood gas at room air and RAS, hemodynamic stability and adverse event until discharged from the ICU. RESUL TS: Increased of Pa02 12.6±6.8% CG and 23.3±8.5% RG p < 0,001, RAS presented complete improvement for 94.4% RG, whereas in the CG, 87.5% presented some degree of atelectasis, p < 0,001. There was no adverse event related. CONCLUSION: The use of 30 minutes of NIV associated with RM was safe, improved oxygenation and reduced atelectasis

Introdução: A falta de sistemas estruturados de custeio nas organizações hospitalares, principalmente filantrópicas, tem dificultado a análise da cobertura dos custos pelo repasse do Sistema Único de Saúde (SUS) aos procedimentos realizados. Objetivo: Identificar a percentagem de cobertura do repasse de verba do SUS para a cirurgia de revascularização miocárdica (CRM), em um hospital filantrópico do município de São Paulo, que possui um sistema de custeio consolidado. Método: Estudo de abordagem quantitativa, transversal e descritiva. Utilizou-se um banco de dados com registro de CRM denominado REVASC, criado pela instituição em 2009 e de inclusão contínua. As informações para a pesquisa foram coletadas de 13 de março a 30 de setembro de 2012. A escolha do período foi devido ao início da inclusão de informações sobre custo e repasse do SUS. A população alvo foi de 1913 pacientes e amostra de 1362 (71,2%). Resultados: O custo total médio da internação por paciente foi de R$16.196,91. A média de repasse pelo SUS foi de R$6.992,91(48,66%), observando-se um déficit de 9.204,00 (51,34%). A média de idade foi de 61,4 anos e 69,9% eram do sexo masculino. A média do tempo de permanência hospitalar (TPH) foi de 11,23 dias, sendo 2,42 dias na terapia intensiva e 8,49 dias no pós-operatório. A maioria dos pacientes (69,5%) apresentou um TPH maior que sete dias, considerada prolongada pela instituição. Ao comparar o Grupo 1 (TPH7dias) e Grupo 2 (TPH>7dias), este apresentou custo, receita, diferença entre custo-receita e diferença percentual significativamente maiores que os pacientes do Grupo1. Ao associar o TPH com fatores de risco houve diferença apenas no Grupo 2 que apresentou maior idade, maior número de diabetes e de insuficiência renal crônica. Em relação às complicações pós-operatórias houve diferença em relação a transfusão sanguínea, fibrilação atrial, sangramento importante, pneumonia, insuficiência renal aguda, infarto agudo do miocárdio perioperatório, hemodiálise, acidente vascular encefálico, ventilação mecânica prolongada e reoperação por sangramento / mediastinite, também com incidência maior no Grupo2. Conclusão: O repasse do SUS cobriu menos da metade do custo total médio da internação em CRM (48,66%). Embora o valor do repasse do SUS tenha aumentado conforme a elevação do custo, esse ressarcimento foi desproporcional ao custo total, resultando numa diferença percentual de receita cada vez mais negativa a cada aumento do custo e da permanência hospitalar. / Introduction: The lack of structured expense systems in hospital organizations, especially when philanthropic, has hindered the analysis of the coverage of costs by transfer of funds from the Unified Healthcare System (SUS) for the procedures performed. Objective: To identify the percentage of coverage of the transfer of funds from SUS for coronary artery bypass surgery (CABG) in a philanthropic hospital that has a consolidated expense system in the municipality of São Paulo. Method: A quantitative, cross-sectional, and descriptive study. A databank containing data with CABG records called REVASC was used, created by the institution in 2009 with ongoing data inclusion. Information for the research was collected from March 13 to September 30, 2012. The choice of that period was due to the start of inclusion of information on costs and the transfer of funds from SUS. The target population was made up of 1913 patients and a sample of 1362 (71.2%). Results: The total mean cost of hospitalization per patient was R$16,196.91. The mean transfer of funds by SUS was R$6,992.91 (48.66%), with a deficit of 9,204.00 (51.34%). The mean age of the subjects was 61.4 years, and 69.9% of them were men. The mean hospital stay (HS) was 11.23 days, in which 2.42 days were in intensive therapy, and 8.49 days in the postoperative unit. Most of the patients (69.5%) had a HS longer than seven days, considered prolonged by the institution. When comparing Group 1 (HS 7 days) and Group 2 (HS >7 days), the latter group showed costs, revenue, difference between cost and revenue, and percentage difference significantly greater than did the patients from Group 1. In associating the HS with risk factors, there was a greater difference only in Group 2, which showed a higher age, and greater number individuals with diabetes and chronic renal failure. As to postoperative complications, there was a difference as to blood transfusion, atrial fibrillation, significant bleeding, pneumonia, acute renal failure, perioperative acute myocardial infarct, hemodialysis, cerebrovascular accident, prolonged mechanical ventilation, and reoperation due to bleeding/mediastinitis, also with an incidence greater than in Group 2. Conclusion: The financial provision from SUS covered less than half the total mean cost of hospitalization for CABG (48.66%). Although the value transferred from SUS increased according to cost elevation, this reimbursement was disproportional to the total cost, resulting in an increasingly negative percentage difference of revenue for each increase in cost and in hospital stay.

Duas técnicas invasivas para o tratamento da doença aterosclerótica coronariana oclusiva firmaram-se ao longo dos anos: revascularização cirúrgica do miocárdio e angioplastia transcutânea com stents metálicos. O estudo visa comparar as alterações histopatológicas causadas por stents metálicos coronarianos fabricados com a superliga de composição química em porcentagem em peso cromo 20%, tungstênio 15%, níquel 10% e cobalto restante, designada ASTM F.90, revestidos, ou não, com carbeto de silício pelo processo de asperção térmica originando uma superfície hidrofílica. Stents com espessura das hastes entre 80 a 90 nm, área das células entre 1,4 a 2,1 mm² e relação metal-artéria de 13 a 19%, em pacientes reestenosantes que sofreram posteriormente revascularização cirúrgica do miocárdio, com aqueles não submetidos à angioplastia prévia. Foram determinados dois grupos: grupo I ou grupo controle, pacientes que sofreram revascularização cirúrgica do miocárdio sem angioplastia prévia de qualquer natureza; grupo II pacientes submetidos à revascularização cirúrgica do miocárdio, após reestenose intra-stent coronariana. Pacientes de ambos os grupos foram avaliados rotineiramente quanto à indicação e risco cirúrgico e durante o procedimento convencional da revascularização cirúrgica do miocárdio utilizando circulação extracorpórea, antes de realizar a anastomose do enxerto vascular na coronária, amostras contendo pequenos fragmentos de endotélio foram retiradas juntamente com fragmentos dos stents, enviadas para análise histopatológica e produção de laminas coradas com H-E. Observou-se a presença de arterite crônica caracterizada por infiltrado mononuclear em conjunto com fenômeno de proliferação fibroblástica e de musculatura lisa naqueles pacientes que apresentavam reestenose intra-stent, sendo mais intenso no local do stent. A visualização das superfícies dos stents em escala nanometrica (MFA) é de suma importância para análise estrutural das próteses, avaliando irregularidades nas superfícies recobertas das hastes dos stents. A persistência de arterite crônica coronariana avaliada por infiltrado linfomononuclear e proliferação de fibrocolágeno foi constatada em pacientes reestenosantes. / Two invasive techniques for the treatment of occlusive coronary atherosclerosis disease were signed over the years: coronary artery bypass surgery and transcutaneous angioplasty with bare metal stent. The study attempts to compare the histopathological abnormality caused in patients with implantation of bare metal stent in coronary made with: Chromium 20%, Tungsten 15%, Nickel 10% and Cobalt remainder, ASTM F.90 alloy for surgical implant applications, and covered with a thin layer of amorphous silicon carbide, or not, and its total or partial obstruction, after undergoing coronary artery bypass grafting, with those who had coronary artery bypass surgery with no previous angioplasty. Two groups were studied: group I, or control group, patients who underwent coronary artery bypass grafting without previous angioplasty of any kind; group II of patients undergoing coronary artery bypass surgery after coronary-stent restenosis. Patients in both groups were evaluated for the indication and surgical risk; was done routinely during the procedure of conventional coronary artery bypass grafting with cardiopulmonary bypass. Before performing the anastomosis in coronary vascular graft, a small fragment of the endothelium was removed along whit a fragment of the stent, and sent for analysis with hematoxilin-eosin. The presence of chronic inflammatory coronary reaction was detected, mediated by mononuclear cells with phenomenon of fibroblast and smooth muscle proliferation in patients presenting in-stent restenosis. It w coronary reaction as also observed that the inflammatory and proliferative process is more intense at the site of stent implantation. The analysis of surface of the stents used atomic force microscopy proved to be an important method for the surface analysis for stents, and showed on nanometric scale an irregular coverage of silicon carbide. In conclusion, in the patients with restenosis in-stent occurs persistence of chronic inflammation with mononuclear cells and process of fibroblast proliferation.

Die Beurteilung der Wirkung von Cariporide auf dieEreignis-Wahrscheinlichkeit eines Herzinfarktes oder des Todes imRahmen einer Bypass-Operation ist Gegenstand der Arbeit. DasNHE-Austauschersystem in der Herzmuskelzelle induziert den unterIschämie durch den intrazellulären Protonenüberschusshervorgerufenen Na(+)- und Ca(2+)-Einstrom. Cariporide ist einNHE-Inhibitor, der den unter Ischämie durch die Ca(2+)-Überladunginduzierten Herzmuskelzelltod verzögern soll. In einer kombinierten Phase-II/III-Studie (GUARDIAN, n=11590) war derEinfluss verschiedener intravenöser Dosen von Cariporide auf dieHäufigkeit von Herzinfarkt oder Tod in ACS/NQMI, PTCA undCABG-Patientenkollektiven untersucht worden. Nur die höchstdosierteCABG-Gruppe zeigte eine signifikante Reduktion der Ereignisrate um24,7% (p=0,027) gegenüber Placebo. Diese schwacheDosis-Wirkungs-Beziehung konnte durch eine pharmakokinetische undpharmakodynamische Populationsanalyse in eineKonzentrations-Wirkungs-Beziehung überführt werden. Zur Entwicklungdes Populationsmodells waren verschiedene Submodelle notwendig: 1. Modell für den Zeitverlauf der Ereignisrate: Durch Kombination zweier Weibull-Verteilungen ist es möglich, die beobachteten Daten als Überlebenszeitfunktion nach CABG zu beschreiben. Ein akutes, unmittelbar auf die CABG-Operation zurückzuführendes Risiko wird hier von einem chronischen Risiko unterschieden. 2. Pharmakokinetisches Modell: Ein multiexponentielles populationspharmakokinetisches Modell ist notwendig zur Beschreibung der PK nach iv-Applikation von Cariporide bei Probanden und Patienten. 3. Pharmakodynamisches Modell: Über ein empirisches logistisches Modell wird die Reduktion des akuten Risikos mit der mittleren Cariporide Plasmakonzentration unter der Bypass-Operation verknüpft. In einer Substudie der GUARDIAN-Hauptstudie konnte daspopulationspharmakokinetische Modell aus der früherenPhase-I-Entwicklung mit Probanden für die Patienten validiert werden.Die mit Hilfe der individüllen Dosierung, der demographischen Datenund dem Populationsmodell für die Periode mit dem höchsten Risikowährend der CABG-Operation vorhergesagten mittlerenPlasmakonzentrationen flossen in die Analyse derKonzentrations-Zeit-Abhängigkeit der Ereignis-Wahrscheinlichkeit ein. Eine untere Schwellenkonzentration (0,5mg/l), unterhalb der mitkeinem Effekt zu rechnen ist, wurde bestimmt. Die Daten erlaubten dieSchätzung des maximalen Effekts nur unzureichend. Die maximaleRisikoreduktion von 60% wurde mit einem Konfidenzintervall von29% bis 100% geschätzt. Unter Einsatz einer linearen Näherungdes Hill-Modells wurde eine obere Schwellenkonzentration bei 0,9mg/lbestimmt. Nur 37% aller Patienten der 80mg-Dosisgruppe erreichtenmittlere Konzentrationen oberhalb der unteren Schwellenkonzentration,in der 120mg-Dosisgruppe waren es immerhin schon 75% allerPatienten. Die Infusion von 120mg Cariporide über eine Stunde gefolgt voneiner Erhaltungsdosis von 20mg/h für weitere 47 Stunden sollte bei95% der Patienten während der CABG-Operation zu mittlerenKonzentrationen über der minimal effektiven Konzentration von0,5mg/l führen. Eine auf diese Weise mittels Simulationenoptimierte Dosierungsregel sollte während der CABG-Operation zu einemerhöhten Schutz der Patienten gegen die Folgen ischämischerEreignisse führen. Eine weitere Erhöhung der Erhaltungsdosis aufbis zu 40mg/h mit einer entsprechenden Anpassung der Initialdosissollte 95% der Patienten sogar über die bisher nur unsicher zubestimmende obere Grenzkonzentration von 0,9mg/l bringen. Solltenkeine dosislimitierenden Nebenwirkungen auftreten, kann dieseErhöhung sowohl der Initialdosis als auch der Erhaltungsdosis zueiner weiteren Verbesserung während der Risikoperiode führen undeinen weiteren potentiellen klinischen Vorteil für Cariporideerbringen. / Subject of this analysis is the assessment of the effect of cariporideon the event probability of a myocardial infarction (MI) or death inthe scope of a coronary artery bypass graft. Thesodium-hydrogen-exchange system (NHE) in the myocardial cell inducesthe sodium and calcium influx caused by an ischaemia induced hydrogenoverload. Cariporide is a NHE-inhibitor which is seen to be delayingthe necrosis of myocardial cells caused by the ischaemia inducedcalcium influx. The influence of different intravenous doses of cariporide on thefrequency of MI and death in ACS/NQMI, PTCA, and CABG patients hadbeen investigated in a combined phase II/III trial (GUARDIAN,n=11590). Only the highest dosed CABG-subgroup showed a significantreduction of the event-rate compared to placebo of 24.7% (p=0.027).This weak dose-effect-relationship could be translated into aconcentration-effect relationship by using a populationpharmacokinetic/pharmacodynamic (PK/PD) analysis. To develop thispopulation model a series of sub-models were established: 1) Model for the time-to-event progression: using a combination of two Weibull-distributions, it was possible to describe the observed data following the CABG procedure by means of a survival-function. An acute risk, likely to be related to the CABG-procedure could be discriminated from a chronic risk. 2) Pharmacokinetic model: a multi-exponential population PK model was necessary to describe the PK after iv-application of cariporide in volunteers as well patients. 3) Pharmacodynamic model: using an empirical logistic model the reduction of the acute risk was linked to the cariporide plasma-concentrations. In a sub-study of the GUARDIAN-main study, the population PK model ofthe phase I development in volunteers had been be validated. Usingthe individual dosing, the individual demographic information and thepopulation PK model mean concentrations were calculated for the periodof the highest risk during the CABG procedure. Those concentrationswere then introduced into the analysis of the concentration timedependency of the event probability. A lower threshold concentration (0.5mg/l) was estimated beneath thatno effect would be expected. The data permitted the estimation of themaximum effect only insufficiently. A maximum risk reduction of 60%was estimated with a confidence interval from 29% to 100%. Using thelinear approximation of the Hill-model an upper thresholdconcentration of 0.9mg/l could be determined. Mean concentrationsunder risk were reached above the lower threshold concentration inonly 37% of all patients in the 80mg dose group, whereas in the 120mgdose-group already 75% of the patients exceeded the lower thresholdconcentration. The infusion of 120mg cariporide for an hour followed by a maintenancedose of 20mg/h for further 47 hours should maintain in 95% of thepatients during the CABG-procedure mean concentrations above theminimal effective concentration of 0.5mg/l. A dose regimen optimisedin this sense by means of simulations should lead to an increasedprotection against ischemic events during and after theCABG-operation. A further increase of the maintenance dose up to40mg/h with a corresponding adaptation of the initial dose shouldshift at least 95% of the patients above the so far impreciseestimated upper threshold concentration of 0.9mg. If no dose limitingside-effects occur, this increase of both the initial dose and themaintenance dose may lead to a further improvement during the riskperiod and may result in a further potential clinical advantage forcariporide.

Aims: Coronary Revascularization (CR) has increased patients' survival rate globally. However, the lack of a consensus definition of Health Related Quality of Life (HRQoL) and the different methodological and conceptual approaches adopted by researchers in the cardio-revascularization field create an incomplete picture of the influence of CR on individuals' HRQoL. By using mixed methodology, the current research aimed to explore Greek CHD patients' perspectives of their HRQoL after CR (Coronary Artery Bypass Grafting (CABG) or Percutaneous Coronary Interventions (PCI)), as well as detect and explain individual disparities. Method: Two studies were conducted with a total sample of 487 individuals: (1) The translation and validation of the Coronary Revascularization Outcome Questionnaire (CROQ) into Greek and (2) The longitudinal mixed methods study, the main study of the thesis, following a sequential explanatory design with two research components: a) the longitudinal quantitative component aimed to detect changes in patients' HRQoL (both overall and its subdomains) following CR over a 12-month period based on individuals' subjective evaluation as captured by the CROQ, detect the influence of CR type on the outcome and to explore potential predictors (individuals' demographic, clinical and behavioural features). Data were analysed using multilevel modelling; b) the qualitative component aimed to capture individuals' lived experience, their view and understanding of themselves and their life approximately 12 months after treatment using Interpretive Phenomenological Analysis (IPA). Results/findings: Based on participants' subjective evaluations as captured by the validated Greek version of the CROQ, one year after CR Greek Coronary Heart Disease (CHD) patients experience an increase in their HRQoL level compared to prior to CR. The pattern of change though is not constant; initially HRQoL increases with time, and then decreases again, however, remaining much greater compared to prior to CR one year after CR. Regarding the influence of the CR type of treatment on patients' HRQoL level, a year after CR mixed findings are revealed. In the symptoms and physical functioning subdomain, patients treated with CABG demonstrate a greater increase compared to patients treated with PCI. In the psychosocial functioning subdomain no difference is found. In the cognitive functioning subdomain, patients treated with CABG demonstrate a decline compared to their cognitive functioning prior to the CR. Various demographic, clinical and behavioural features are demonstrated to be predictors of the outcome though not consistent for all subdomains. The main predictors associated with larger positive changes following CR seem to be sex, BMI and smoking; females with low BMI that do not smoke tend to demonstrate a greater increase in HRQoL after CR. According to individuals' lived experience, participants, reflecting on their experience one year after treatment, perceive CR as a simple process and their negative experience is mostly related to medical care. Many participants with no symptoms or adverse effects tend to misperceive CHD, viewing their health condition as an acute disease treated with CR. Trying to understand disease causality they tend to adopt medical discourse especially in relation to stress as a factor that can be controlled by themselves and reflect on their own responsibility as a causal factor. Feeling grateful for being alive, sensing a different body, a 'revitalized body' as many participants suggest, as well as a fear of re-occurrence or disease progression motivate individuals to work on aspects of the self related to the CHD development in an effort to regain control over their life which has been reduced after the CHD diagnosis. In effect a dramatic change in how the self and life are viewed is reported, highlighting a positive growth; a greater appreciation of life, a personal growth and effort to build more meaningful relationships. Challenges that participants face in modification of their lifestyle are attributed to both external and internal factors. Concerning smoking participants' accounts point to a lack of knowledge regarding the relationship between smoking and CHD, a lack of support (by experts or family members) and conscious denial as a way to cope with every day anxiety and stress, but also a pleasure in everyday life. The findings provide a complementary insight into perceptions of individuals with CHD about their quality of life one year after CR, suggesting that other factors beyond CR may influence their perspectives. Conclusions/implications: This study highlights the benefits of using a mixed methods longitudinal design in exploring HRQoL. Both the quantitative and qualitative findings support the notion that HRQoL is a multidimensional, continuously changing concept, providing support for the Wold Health Organization's definition. Also, the findings suggest that CR has a positive influence on individuals' HRQoL. The effect of the CR type needs further investigation as mixed findings are observed in the present thesis. Moreover, it seems difficult to investigate the pure effect of CR on individuals' HRQoL without taking into consideration individuals' adjustment processes and positive growth triggered by the CR. The self regulation model (SRM) might be considered a useful theoretical framework for developing theory-based interventions aiming to alter patients' false beliefs since individuals' making-meaning process seems to be aligned with it. Finally, the complementary insights concerning smoking may help health care providers to develop smoking cessation interventions tailored to cardiac patients.

Pacientes submetidos à revascularização do miocárdio (RM), frequentemente utilizam beta-bloqueadores no pré-operatório para o controle da angina pectoris, e continuam o tratamento após a cirurgia, para a redução de mortalidade e complicações cardiovasculares perioperatórias. Entretanto, a circulação extracorpórea (CEC), empregada na maioria das cirurgias cardíacas, pode alterar as concentrações plasmáticas e a disposição cinética de muitos fármacos, e consequentemente seus efeitos terapêuticos. O atenolol é um beta-bloqueador altamente hidrossolúvel, de absorção incompleta e eliminação renal-dependente. O objetivo deste estudo foi o de investigar a influência da CEC sobre as concentrações plasmáticas do atenolol no intra-operatório de cirurgia cardíaca, além de comparar a sua farmacocinética no pré e pós-operatório de RM com CEC, em pacientes com insuficiência coronariana. Investigou-se ainda, a variabilidade das concentrações plasmáticas do atenolol no período que antecede a cirurgia cardíaca. Na primeira etapa, avaliaram-se 19 pacientes coronarianos, em terapia crônica com atenolol PO, submetidos à cirurgia cardíaca com ou sem CEC. Na segunda parte, investigaram-se os períodos pré e pós-cirúrgico de 7 pacientes submetidos à RM com CEC e tratados com atenolol PO em regime de doses múltiplas. Todos os pacientes investigados apresentavam função renal dentro da normalidade ou leve disfunção renal, decorrente da idade e da insuficiência coronariana. O monitoramento do atenolol plasmático no intra-operatório de RM e o estudo farmacocinético realizado antes e após a revascularização, exigiram coletas de amostras sangüíneas seriadas. A quantificação do atenolol em plasma foi realizada através da cromatografia líquida de alta eficiência com detector de fluorescência e consistiu num procedimento analítico rápido, simples e de baixo custo. Apenas 200 L de plasma foram utilizados em cada análise cromatográfica. O estudo de validação demonstrou que o método desenvolvido apresenta alta linearidade, sensibilidade e seletividade adequadas, alta recuperação, boa precisão e exatidão, além de estabilidade e robustez. Conclui-se que a circulação extracorpórea altera as concentrações do atenolol no intra-operatório de RM, visto que o decaimento das concentrações plasmáticas mostrou-se mais pronunciado na ausência da CEC. Entretanto, apesar das maiores concentrações obtidas ao final da cirurgia com CEC, o atenolol mostra-se seguro, em virtude do baixo acúmulo do fármaco administrado em regime de doses múltiplas. Além disso, a disposição cinética do atenolol permaneceu inalterada, quando os períodos pré e pós-operatórios foram comparados; entretanto, registrou-se uma tendência à normalização do volume de distribuição e da depuração plasmática do atenolol após a revascularização. Adicionalmente, a ausência de correlação entre meia-vida biológica e volume aparente de distribuição sugere que, tanto no pré quanto no pós-operatório, as concentrações do atenolol dependem apenas da sua depuração plasmática. Finalmente, verificou-se que o atenolol apresenta baixa variabilidade inter-pacientes nos regimes posológicos empregados no tratamento da insuficiência coronariana. / Patients submitted to coronary artery bypass grafting (CABG) surgery frequently are using beta-blockers agents for the control of angina pectoris, and continue the treatment after the surgery to reduce the mortality and cardiovascular events. However, the technique of cardiopulmonary bypass (CPB), used in most cardiac surgeries with cardioplegia, causes important changes in the plasma concentrations and pharmacokinetics of many drugs and may also alter their therapeutic effects. Atenolol is a hydrophilic beta-blocker characterized by incomplete absorption, a relatively small volume of distribution and a renal function-dependent elimination. The objective of this study was to investigate the effects of CPB on the plasma concentrations of atenolol during the intra-operative period of cardiac surgery, as well as, to compare the pharmacokinetics of atenolol in the pre and post-operative periods of revascularization with CPB, in patients with coronary insufficiency. In addition, it was investigated the variability of plasma atenolol concentrations before the cardiac surgery. In the first part of the study, it was investigated 19 coronary patients, under chronic therapy with atenolol and submitted to cardiac surgery performed with and without CPB. At the second part, it was evaluated the pre and post-operative periods from 7 patients submitted to the CABG surgery with CPB, who were chronically treated with atenolol in a multiple regimen. All enrolled patients presented normal or slightly reduced renal function as a result of age and underlying disease. A serial blood samples collection was required for monitoring of plasma atenolol concentrations at the intra-operative period and also for pharmacokinetic study at the pre and post-CABG. The quantification of plasma atenolol was performed using high-performance liquid chromatography with fluorescence detection and consisted of a relatively rapid, simple and low-cost analytical procedure. Only 200 µL of plasma was used for each chromatographic analysis. Validation of this analytical method showed high linearity, adequate sensitivity and selectivity, high recovery, good accuracy and precision, in addition to stability and a guarantee of robustness. It was concluded that the CPB changes plasma atenolol concentrations in the intra-operative period, since a marked decrease in plasma atenolol concentrations was observed in patients undergoing cardiac surgery without CPB. Thus, despite the lower decline in plasma levels observed in patients submitted to CPB, atenolol can be used safely, due to the low accumulation of the drug administrated at multiple dose regimens. In addition, pharmacokinetics of atenolol remained unaltered when pre and post-operative periods were compared; although it was observed a tendency of normalization of volume of distribution and plasma clearance of atenolol after the revascularization. Moreover, the lack of correlation between biological half-life and apparent volume of distribution suggests that, in both periods, plasma atenolol concentration only depends on its plasma clearance. Finally, it was verified a small inter-patient variability of atenolol in the dose regimens used for the control of coronary insufficiency.

Introdução: a revascularização miocárdica (RM) sem circulação extracorpórea (CEC) tem sido associada a menores complicações quando comparadas à com CEC. Objetivos: determinar os efeitos da CEC em marcadores de hemostasia, fibrinólise, inflamação e correlacionar com eventos clínicos. Método: os pacientes foram incluídos de forma prospectiva e randomizada para cirurgia de RM com (n=41) ou sem CEC (n=51). As concentrações de proteína C reativa (PCR), fibrinogênio, dímero-D e inibidor do ativador do plasminogênio tipo 1 (PAI1) foram quantificadas antes e após (1 e 24 horas) a RM. As técnicas cirúrgicas e anestésicas foram padronizadas para ambos os grupos. Eventos clínicos foram avaliados durante a hospitalização inicial e após 1 ano de seguimento. Resultados: as concentrações de PAI1 e dímeros-d foram maiores quando comparados os valores pré-operatórios com os de 1 e 24 h, após a RM em ambos os grupos, porém as concentrações de PAI1 aumentadas estenderam-se por 24 h após a RM com CEC (p<0,01). A concentração de PCR teve um aumento de pequena magnitude imediatamente após a cirurgia em ambos os grupos e aumentou de modo similar 24h após a RM (p<0,01). A RM com CEC foi associada com maior perda sanguínea durante a cirurgia e mais sangramento pós-operatório (p<0,01). A incidência de todas as outras complicações foi similar nos dois grupos. Conclusão: a RM com CEC apresentou evidências bioquímicas de um estado pró-trombótico precoce após a cirurgia, porém, sem evidências no aumento no número de eventos trombóticos. O estado pró-trombótico pode ser consequência do circuito extracorpóreo, resposta compensatória ao sangramento, ou a ambos em pacientes submetidos à cirurgia com CEC. / Objective: To delineate the effects of extracorporeal bypass on biomarkers of hemostasis, fibrinolysis, and inflammation and clinical sequelae. Methods: Patients were assigned prospectively and randomly to either on-pump (n=41) or off-pump (n=51) coronary bypass surgery. The concentrations of C-reactive protein (CRP), fibrinogen, D-dimer, and plasminogen activator inhibitor type 1 (PAI-1) in blood were quantified before and after (1 hour and 24 hours) surgery. Similar surgical and anesthetic procedures were used for both groups. Clinical events were assessed during initial hospitalization and at the end of 1 year. Results: The concentrations of PAI-1 and d-dimer were greater compared with preoperative values 1 hour and 24 hours after surgery in both groups, but their concentrations increased to a greater extent 24 hours after surgery in the on-pump group (p<0.01). The concentration of CRP did not change appreciably immediately after surgery in either group but increased in a parallel fashion 24 hours after either on-pump or off-pump surgery (p<0.01). Bypass surgery in the on-pump group was associated with greater blood loss during surgery and more bleeding after surgery (p0.01). The incidence of all other complications was similar in the 2 groups. Conclusion: On-pump surgery was associated with biochemical evidence of a pro-thrombotic state early after surgery but no greater incidence of thrombotic events. The pro-thrombotic state may have been a consequence of extracorporeal bypass, compensation in response to more bleeding, or both in patients undergoing on-pump surgery.

Objetivo: Novas tendências na avaliação de risco trazem evidências de que modelos externos recalibrados ou remodelados funcionam melhor localmente. O objetivo deste estudo foi validar dois modelos externos e formular um modelo local, comparando-os na predição de mortalidade nos pacientes operados de coronária e/ou valva no InCor-HCFMUSP. Método: Entre 2007 e 2009, 3.000 pacientes foram sequencialmente operados de coronária e/ou valva no InCor-HCFMUSP. No banco de dados, foi realizada a validação dos modelos 2000 Bernstein-Parsonnet (2000BP) e EuroSCORE (ES), mediante testes de calibração e discriminação. O InsCor de 2.000 pacientes foi elaborado mediante a utilização de técnicas de bootstrap. Nos próximos 1.000 pacientes foi realizada a validação interna do modelo, e seu desempenho medido frente ao 2000BP e ES. Resultados: Houve uma diferença significativa na prevalência dos fatores de risco entre as populações do estudo, ES e 2000BP. Na validação externa dos modelos, o ES apresentou uma boa calibração (P=0,596); no entanto, o 2000BP revelou-se inadequado (P=0,047). Na discriminação, a área abaixo da curva ROC revelou-se boa para ambos os modelos, ES (0,79) e 2000BP (0,80). Utilizando a técnica de bootstrap, 10 variáveis: idade >70 anos, sexo feminino, cirurgia associada, infarto do miocárdio <90 dias, reoperação, cirurgia da valva aórtica, cirurgia da valva tricúspide, creatinina <2mg/dl, fração de ejeção <30% e estado pré-operátorio crítico (eventos), foram selecionadas para formulacão do InsCor. Na validação interna do InsCor, a calibração foi adequada, com P=0,184. Na discriminação, a área abaixo da curva ROC foi boa (0,79). Neste grupo, a área abaixo da curva ROC foi de 0,81 e 0,82 para o ES e 2000BP, respectivamente, mostrando-se apropriada para ambos os modelos. Conclusões: O InsCor e o ES tiveram melhor desempenho que o 2000BP em todas as fases da validação; pórem o novo modelo, além de se identificar com os fatores de risco locais, é mais simples e objetivo para a predição de mortalidade nos pacientes operados de coronária e/ou valva no InCor-HCFMUSP / Background: New trends in risk assessment bring evidence that recalibrated or remodeled external models work best locally. The aim of this study was to validate two external models and formulate a local model, comparing them to predict mortality in patients who underwent coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP. Method Between 2007 and 2009, 3.000 patients were sequentially operated to coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP. The database was assessment to validate the models 2000 Bernstein-Parsonnet (2000BP) and EuroSCORE (ES) through calibration and discrimination tests. The InsCor of 2,000 patients (2/3 of database) was elaborated using bootstrap techniques. Over the next 1000 patients (1/3 of database) the internal validation of the InsCor was performed and its performance compared against the 2000BP and ES. Results: Significant difference in the prevalence of risk factors was found among the external and study populations (P<0,001). In the external validation of these models, the ES showed good calibration (P = 0.596); however, 2000BP was inadequate (P = 0.047). In discrimination, the area under the ROC curve was good for both models, ES (0.79) and 2000BP (0.80). With the bootstrap technique, 10 variables: age> 70 years, female, CABG + valve surgery, myocardial infarction <90 days, reoperation, aortic valve surgery, tricuspid valve surgery, creatinine <2mg/dl, ejection fraction <30% and critical preoperative state (events) were chosen to formulate the InsCor. In the validation of InsCor, the calibration was appropriate with P = 0.184. In discrimination, the area under the ROC curve was good (0.79). In this group, the area under the ROC curve was 0.81 and 0.82 for ES and 2000BP, respectively, being suitable for both models. Conclusions: The InsCor and ES outperformed the 2000BP at all stages of validation, but the new model, besides identifying itself with the local risk factors, is more simple and objective for the prediction of mortality in patients who underwent coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP.

INTRODUÇÃO: Complicações pulmonares são frequentes no pós-operatório da cirurgia de revascularização do miocárdio (RM) e a ventilação não-invasiva (VNI) tem sido utilizada nos cuidados pós-operatórios de forma profilática e terapêutica. A manobra de recrutamento alveolar (MRA) consiste no aumento sustentado de pressão na via aérea utilizando um alto nível de pressão expiratória final positiva (PEEP) em indivíduos hipoxêmicos, garantindo uma ventilação pulmonar homogênea e, com isso melhorando a oxigenação arterial. O objetivo desse estudo foi de avaliar se o uso da VNI associada à MRA pode melhorar a oxigenação e se pode ser aplicada de forma segura nos pacientes pós-operatório de RM. MÉTODOS: Foram incluídos 34 pacientes internados na unidade de terapia intensiva (UTI) ventilados mecanicamente após RM com relação Pa02/Fi02 < 300 e escore radiológico de atelectasia ;:: 2. Os pacientes foram randomizados 16 para o grupo controle (GC) e 18 para o grupo recrutamento (GR), após a extubação a VNI foi aplicada por 30 minutos três vezes ao dia de acordo com a rotina da UTI. No GC a VNI era realizada com PEEP de 8 cm H20 e no GR foi aplicada PEEP de 15 cm H20 e 20 cm H20 durante 2 minutos cada e depois ficava com PEEP de 8 cm H20. Analisamos a Pa02 pela gasometria arterial em ar ambiente e o escore radiológico de atelectasia, estabilidade hemodinâmica e evento adverso até a alta da UTI. RESULTADOS: Aumento de Pa02 12,6 ± 6,8% GC e 23,3 ± 8,5% GR com p < 0,001, o escore radiológico de atelectasia apresentou resolução completa em 94,4% GR, enquanto que no GC, 87,5% apresentou algum grau de atelectasia, p < 0,001. Não houve eventos adversos relacionados. CONCLUSÃO: o uso por 30 minutos da VNI associada à MRA foi seguro, melhorou a oxigenação e reduziu a atelectasia / BACKGROUND: Postoperative pulmonary impairment is common in the early period after coronary artery bypass grafting (CABG) and noninvasive ventilation (NIV) has been used in postoperative care to prevent and treatment. Recruitment maneuver (RM) consists in a sustained raise of airway pressure with high levei of positive end-expiratory pressure (PEEP) in hypoxemic subjects, insuring a homogeneous pulmonary ventilation and enhancing oxygenation. The aims of this study were to evaluate if the use of NIV associated with RM could improve oxygenation and if it could be safely applied in CABG postoperative patients. METHODS: Were included 34 patients admitled to the intensive care unit (ICU) mechanically ventilated after CABG with Pa02/Fi02 ratio < 300 and radiological atelectasis score (RAS) ~ 2. Patients were randomized 16 to the control group (CG) and 18 to the recruitment group (RG), after extubation NIV was applied for 30 minutes three times a day according to ICU routine. In the CG, NIV was performed with PEEP 8 cm H20 and in the RG, was applied PEEP 15 cm H20 and 20 cm H20 for 2 minutes each and then was with PEEP 8 cm H20. We analyzed Pa02 from arterial blood gas at room air and RAS, hemodynamic stability and adverse event until discharged from the ICU. RESUL TS: Increased of Pa02 12.6±6.8% CG and 23.3±8.5% RG p < 0,001, RAS presented complete improvement for 94.4% RG, whereas in the CG, 87.5% presented some degree of atelectasis, p < 0,001. There was no adverse event related. CONCLUSION: The use of 30 minutes of NIV associated with RM was safe, improved oxygenation and reduced atelectasis

No description available.