Adverse effects of cyclooxygenase (COX) inhibitors on bone healing have previously been demonstrated in diaphyseal fracture models in animals. In spite of that, they are widely used as postoperative analgesics in orthopaedic surgery. After joint replacement, a bone repair process starts at the interface between bone and cement. If this process is disturbed, the prosthesis may never become rigidly fixed to the bone, leading to migration and with time loosening. This thesis investigates the effects of a selective COX-2 inhibitor (parecoxib or celecoxib) on bone healing in metaphyseal bone in a rat model and on knee prosthesis migration after total knee replacement, as measured with radiostereometric analysis. Blood loss, postoperative recovery, and the 2-year subjective outcome, were also measured. In addition, a hemoglobin dilution method for blood loss estimation, used in this thesis, was evaluated. In the first study, pull-out force of a screw inserted in metaphyseal bone of the tibia in rats was only marginally decreased by parecoxib after 7 days but not after 14 days. In the second and third study, celecoxib treatment resulted in less pain postoperatively in conjunction with total knee replacement (TKR), but no effects were seen on blood loss, range of motion, subjective outcome, or prosthesis migration after 2 years. Comparing the true blood loss of blood donors with the blood loss estimated by the hemoglobin dilution method, this method was found to underestimate the true blood loss. It is therefore not suitable for calculation of the absolute blood loss volume, but may be used for a rough estimate. In summary, celecoxib and presumably other cyclooxygenase inhibitors seems not likely to increase the risk of prosthesis loosening.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 4 uppsatser.

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

Over the last century, physiological signals have been broadly analyzed and processed not only to assess the function of the human physiology, but also to better diagnose illnesses or injuries and provide treatment options for patients. In particular, Electrocardiogram (ECG), blood pressure (BP) and impedance are among the most important biomedical signals processed and analyzed. The majority of studies that utilize these signals attempt to diagnose important irregularities such as arrhythmia or blood loss by processing one of these signals. However, the relationship between them is not yet fully studied using computational methods. Therefore, a system that extract and combine features from all physiological signals representative of states such as arrhythmia and loss of blood volume to predict the presence and the severity of such complications is of paramount importance for care givers. This will not only enhance diagnostic methods, but also enable physicians to make more accurate decisions; thereby the overall quality of care provided to patients will improve significantly. In the first part of the dissertation, analysis and processing of ECG signal to detect the most important waves i.e. P, QRS, and T, are described. A wavelet-based method is implemented to facilitate and enhance the detection process. The method not only provides high detection accuracy, but also efficient in regards to memory and execution time. In addition, the method is robust against noise and baseline drift, as supported by the results. The second part outlines a method that extract features from ECG signal in order to classify and predict the severity of arrhythmia. Arrhythmia can be life-threatening or benign. Several methods exist to detect abnormal heartbeats. However, a clear criterion to identify whether the detected arrhythmia is malignant or benign still an open problem. The method discussed in this dissertation will address a novel solution to this important issue. In the third part, a classification model that predicts the severity of loss of blood volume by incorporating multiple physiological signals is elaborated. The features are extracted in time and frequency domains after transforming the signals with Wavelet Transformation (WT). The results support the desirable reliability and accuracy of the system.

Introdução: Considerando que uma melhor vigilância do estado hemostático dos doentes antes, durante e após o ato cirúrgico pode ter impacto significativo na sua evolução, e sabendo que os testes clássicos da coagulação têm limitações para avaliar a hemóstase na globalidade, e presumindo-se que o ROTEM seja um teste que permite efetuar esta avaliação da coagulação, fizemos hipótese de que este método seria uma ferramenta que teria a habilidade de prever sangramento em cirurgia cardíaca valvar. Objetivos: 1) Verificar se o ROTEM (Tromboelastometria Rotacional) ao analisar o estado da coagulação sanguínea de pacientes submetidos à cirurgia cardíaca valvar tem a capacidade de prever maior risco de sangramento com suas consequentes complicações; 2) Correlacionar comorbidades e história clinica pré-existentes à cirurgia cardíaca valvar com o nível de sangramento apresentado. Métodos: Foram incluídos 100 pacientes consecutivos submetidos à cirurgia cardíaca valvar com circulação extracorpórea (CEC) nos seguintes procedimentos: cirurgia cardíaca valvar em uma ou mais valvas, incluindo reoperações e cirurgias combinadas, realizadas no Instituto do Coração (INCOR) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Estudo prospectivo que buscou avaliar a eficácia do uso da tromboelastometria rotacional na previsão de sangramento em cirurgia cardíaca valvar. Após a indução anestésica foram coletados: Tromboelastometria, coagulograma, fibrinogênio, dímero D e contagem de plaquetas; com a finalidade de verificar potencial risco de sangramento neste paciente. Correspondente ao tempo - 0 (T0). Estes mesmos exames foram recoletados na admissão na Unidade de Terapia Intensiva Cirúrgica (UTIC), onde o paciente foi recebido após o procedimento cirúrgico cardíaco valvar. Correspondente ao tempo - 1 (T1). Optou-se pela coleta de T1 na UTI, pois a CEC já terá sido descontinuada e a heparina revertida com a administração da protamina. Resultados: Os pacientes fora subdivididos em quartis de acordo com o sangramento, configurando um total (n) de 100 pacientes com uma média de sangramento (débitos dos drenos) de 492,95 mL, apresentando um desvio padrão de 388,14 mL e 2260 mL. Não foi encontrada nenhuma variável estatisticamente significante entre os grupos, comparando-se exames laboratoriais pré-operatórios, tempo de CEC, tempo de pinçamento e uso de drogas vaso ativas. Porém, ocorreu diferença significativa (p = 0,015) nos níveis transfusionais de hemocomponentes entre os quartis. Ocorreu uma relação significante (p =0,014) entre o nível adequado de calcemia e tendência a menor sangramento nos grupos estudados. Os resultados do ROTEM - INTEM, ROTEM - EXTEM e ROTEM - FIBTEM não demonstraram diferença estatística significante entre os grupos estudados. Considerando-se os desfechos, baixo débito, choque cardiogênico, arritmia, AVC, insuficiência renal aguda, óbito e reoperação, apenas a reoperação apresentou resultados com diferença significante entre os grupos (p =0,024). Conclusões: 1- O ROTEM não demonstrou a capacidade de prever sangramento em cirurgia cardíaca valvar. 2 - Não houve correlação do sangramento apresentado com as comorbidades pré-existentes / INTRODUCTION: Considering that better monitoring of the haemostatic status of patients before, during and after the surgical procedure can have a significant impact on their evolution, and knowing that classical coagulation tests have limitations in assessing hemostasis overall, and assuming that ROTEM is a test that allows to perform this evaluation, we hypothesized that this method would be a tool that would have the ability to predict bleeding in valve heart surgery. OBJECTIVES: 1) To verify if the ROTEM (Rotational Thromboelastometry) when analyzing the blood coagulation status of patients submitted to valve heart surgery has the capacity to predict a greater risk of bleeding with its consequent complications; 2) To correlate pre-existing comorbidities and clinical history with valve heart surgery with the level of bleeding presented. METHODS: We included 100 consecutive patients submitted to cardiac valve surgery with cardiopulmonary bypass (CPB) in the following procedures: valvular heart surgery in one or more valves, including reoperations and combined surgeries performed at the Heart Institute of the University of São Paulo. It is a prospective study aimed at evaluating the efficacy of rotational thromboelastometry in the prediction of bleeding in valve heart surgery. After the anesthetic induction were collected: thromboelastometry, coagulogram, fibrinogen, D-dimer and platelet count, with the purpose of verifying potential risk of bleeding in this patient. These samples were defined as time - 0 (T0). These same exams were collected on admission to the Intensive Care Unit. These samples were defined as time - 1(T1 We chose to collect T1 in the ICU, because at this moment it is expected that the total reversal of anticoagulation has already occurred .. RESULTS: Patients were subdivided into quartiles according to bleeding, with a total of 100 patients with a mean bleed (drainage rates) of 492.95 mL. No statistically significant variables were found between the groups, comparing preoperative laboratory tests, CPB time, clamping time and use of vasoactive drugs. However, there was a significant difference (p = 0.015) in transfusion levels of blood components between the quartiles. There Abstract was a significant relationship (p = 0.014) between the adequate level of calcemia and tendency to less bleeding in the groups studied. The results of ROTEM - INTEM, ROTEM - EXTEM and ROTEM - FIBTEM did not show a statistically significant difference between the groups studied. Considering the outcomes, low rate, cardiogenic shock, arrhythmia, stroke, acute renal failure, death and reoperation, only reoperation presented results with significant difference between the groups (p = 0.024). CONCLUSIONS: 1 - ROTEM did not demonstrate the ability to predict bleeding in valvular heart surgery. 2 - There was no correlation of bleeding presented with pre-existing comorbidities

Introdução: Considerando que uma melhor vigilância do estado hemostático dos doentes antes, durante e após o ato cirúrgico pode ter impacto significativo na sua evolução, e sabendo que os testes clássicos da coagulação têm limitações para avaliar a hemóstase na globalidade, e presumindo-se que o ROTEM seja um teste que permite efetuar esta avaliação da coagulação, fizemos hipótese de que este método seria uma ferramenta que teria a habilidade de prever sangramento em cirurgia cardíaca valvar. Objetivos: 1) Verificar se o ROTEM (Tromboelastometria Rotacional) ao analisar o estado da coagulação sanguínea de pacientes submetidos à cirurgia cardíaca valvar tem a capacidade de prever maior risco de sangramento com suas consequentes complicações; 2) Correlacionar comorbidades e história clinica pré-existentes à cirurgia cardíaca valvar com o nível de sangramento apresentado. Métodos: Foram incluídos 100 pacientes consecutivos submetidos à cirurgia cardíaca valvar com circulação extracorpórea (CEC) nos seguintes procedimentos: cirurgia cardíaca valvar em uma ou mais valvas, incluindo reoperações e cirurgias combinadas, realizadas no Instituto do Coração (INCOR) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Estudo prospectivo que buscou avaliar a eficácia do uso da tromboelastometria rotacional na previsão de sangramento em cirurgia cardíaca valvar. Após a indução anestésica foram coletados: Tromboelastometria, coagulograma, fibrinogênio, dímero D e contagem de plaquetas; com a finalidade de verificar potencial risco de sangramento neste paciente. Correspondente ao tempo - 0 (T0). Estes mesmos exames foram recoletados na admissão na Unidade de Terapia Intensiva Cirúrgica (UTIC), onde o paciente foi recebido após o procedimento cirúrgico cardíaco valvar. Correspondente ao tempo - 1 (T1). Optou-se pela coleta de T1 na UTI, pois a CEC já terá sido descontinuada e a heparina revertida com a administração da protamina. Resultados: Os pacientes fora subdivididos em quartis de acordo com o sangramento, configurando um total (n) de 100 pacientes com uma média de sangramento (débitos dos drenos) de 492,95 mL, apresentando um desvio padrão de 388,14 mL e 2260 mL. Não foi encontrada nenhuma variável estatisticamente significante entre os grupos, comparando-se exames laboratoriais pré-operatórios, tempo de CEC, tempo de pinçamento e uso de drogas vaso ativas. Porém, ocorreu diferença significativa (p = 0,015) nos níveis transfusionais de hemocomponentes entre os quartis. Ocorreu uma relação significante (p =0,014) entre o nível adequado de calcemia e tendência a menor sangramento nos grupos estudados. Os resultados do ROTEM - INTEM, ROTEM - EXTEM e ROTEM - FIBTEM não demonstraram diferença estatística significante entre os grupos estudados. Considerando-se os desfechos, baixo débito, choque cardiogênico, arritmia, AVC, insuficiência renal aguda, óbito e reoperação, apenas a reoperação apresentou resultados com diferença significante entre os grupos (p =0,024). Conclusões: 1- O ROTEM não demonstrou a capacidade de prever sangramento em cirurgia cardíaca valvar. 2 - Não houve correlação do sangramento apresentado com as comorbidades pré-existentes / INTRODUCTION: Considering that better monitoring of the haemostatic status of patients before, during and after the surgical procedure can have a significant impact on their evolution, and knowing that classical coagulation tests have limitations in assessing hemostasis overall, and assuming that ROTEM is a test that allows to perform this evaluation, we hypothesized that this method would be a tool that would have the ability to predict bleeding in valve heart surgery. OBJECTIVES: 1) To verify if the ROTEM (Rotational Thromboelastometry) when analyzing the blood coagulation status of patients submitted to valve heart surgery has the capacity to predict a greater risk of bleeding with its consequent complications; 2) To correlate pre-existing comorbidities and clinical history with valve heart surgery with the level of bleeding presented. METHODS: We included 100 consecutive patients submitted to cardiac valve surgery with cardiopulmonary bypass (CPB) in the following procedures: valvular heart surgery in one or more valves, including reoperations and combined surgeries performed at the Heart Institute of the University of São Paulo. It is a prospective study aimed at evaluating the efficacy of rotational thromboelastometry in the prediction of bleeding in valve heart surgery. After the anesthetic induction were collected: thromboelastometry, coagulogram, fibrinogen, D-dimer and platelet count, with the purpose of verifying potential risk of bleeding in this patient. These samples were defined as time - 0 (T0). These same exams were collected on admission to the Intensive Care Unit. These samples were defined as time - 1(T1 We chose to collect T1 in the ICU, because at this moment it is expected that the total reversal of anticoagulation has already occurred .. RESULTS: Patients were subdivided into quartiles according to bleeding, with a total of 100 patients with a mean bleed (drainage rates) of 492.95 mL. No statistically significant variables were found between the groups, comparing preoperative laboratory tests, CPB time, clamping time and use of vasoactive drugs. However, there was a significant difference (p = 0.015) in transfusion levels of blood components between the quartiles. There Abstract was a significant relationship (p = 0.014) between the adequate level of calcemia and tendency to less bleeding in the groups studied. The results of ROTEM - INTEM, ROTEM - EXTEM and ROTEM - FIBTEM did not show a statistically significant difference between the groups studied. Considering the outcomes, low rate, cardiogenic shock, arrhythmia, stroke, acute renal failure, death and reoperation, only reoperation presented results with significant difference between the groups (p = 0.024). CONCLUSIONS: 1 - ROTEM did not demonstrate the ability to predict bleeding in valvular heart surgery. 2 - There was no correlation of bleeding presented with pre-existing comorbidities

Abstract Cardiovascular diseases are the leading cause of death worldwide, and coronary artery disease accounts for the majority of them. The treatment of choice for complex coronary artery disease is coronary artery bypass grafting. However, as surgery in general, cardiac surgery is associated with an increased risk of perioperative bleeding and utilization of blood products. The present study aimed to investigate the impact of preoperative anemia, perioperative bleeding and retained blood syndrome as well as blood transfusion on the outcomes after isolated coronary surgery. The severity of perioperative bleeding was assessed mainly using the E-CABG and UDPB stratification criteria. Our analyses showed that severe bleeding is associated with a significantly increased risk of stroke. Furthermore, severe bleeding increased the risk of several adverse events even in low-risk patients. Retained blood syndrome was observed to be a common complication after coronary surgery and was associated with an increased risk of postoperative complications. Preoperative anemia seems to have no significant impact on patient early and late survival. Instead, the frequent exposure to blood products may be the determinant of poorer survival observed among anemic patients. Perioperative blood loss and exposure to allogeneic blood has been shown to increase adverse events. Therefore, prevention of bleeding and measures to optimize patient blood management could improve patient outcomes after cardiac surgery. / Tiivistelmä Sydän ja verisuonitaudit ovat maailmanlaajuisesti yleisin kuoleman aiheuttaja, joista sepelvaltimotaudilla on suurin vaikutus. Sepelvaltimoiden ohitusleikkaus on käypä hoito vakavassa sepelvaltimotaudissa. Kuten kirurgiassa yleisestikin, erityisesti sydänkirurgia on yhdistetty suurentuneeseen verenevuodon ja verituotteiden saannin riskiin. Tutkimukseni tavoitteena oli selvittää preoperatiivisen anemian, perioperatiivisen verenvuodon, verituotteiden annon, sekä leikkausalueelle jääneen veren itsenäisiä vaikutuksia potilaiden lopputulemiin sepelvaltimoiden ohitusleikkauksen jälkeen. Verituotteiden ja perioperatiivisen verenvuodon määrää arvioitiin pääsääntöisesti käyttäen E-CABG ja UDPB verenvuotoluokituksia. Tuloksenamme oli, että vakava verenvuoto lisää merkitsevästi aivoinfarktin riskiä. Lisäksi vakava perioperatiivinen verenvuoto on yhteydessä useisiin komplikaatioihin myös matalan leikkausriskin potilailla. Leikkausalueelle jääneen veren huomattiin olevan yleinen ongelma sepelvaltimoiden ohitusleikkauksen jälkeen, minkä lisäksi se lisäsi riskiä useille haitta-tapahtumille. Preoperatiivisella anemialla ei ollut tilastollisesti merkitsevää vaikutusta potilaiden lyhyen ja pitkän aikavälin ennusteisiin. Sen sijaan, aneemisille potilaille annetut verensiirrot saattaisivat aiheuttaa näillä potilailla huomatun alentuneen elinajan ennusteen. Perioperatiivisen verenvuodon ja altistumisen verituotteille on osoitettu lisäävän haittatapahtumia. Siispä verenvuodon vähentäminen ja verituotteiden säästäminen voisi parantaa potilaiden ennustetta sydänkirurgiassa.