Abstract The rationale for automatically monitoring anesthetic drug effects on the central nervous system (CNS) is to improve possibilities to gain objective information on a patient's state and to adjust the medication individually. Although monitors have shown their usefulness in practice, there are still a number of unclear issues, especially with respect to the scientific foundations and validity of CNS monitoring techniques, and in monitoring the light hypnotic levels. Current monitors are, for example, often based on heuristics and ad hoc solutions. However, a quantitative index for anesthetic drug effect should have a sound relationship with observations and with the selected control variable. The research objectives are: (1) to explore propofol anesthetic related neurophysiological phenomena that can be applied in the automatic assessment of CNS suppression; (2) to develop a valid control variable for this purpose; (3) by means of digital signal processing and mathematical modeling, to design and to evaluate the performance of an index that correlates with the control variable. This dissertation introduces potentially useful neurophysiological phenomena, such as changes in phase synchronization between different EEG channels due to anesthesia, and painful stimulus evoked responses during the burst suppression. Furthermore, it refines the progression of the time-frequency patterns during the induction of anesthesia and shows their relation to the instant of unresponsiveness. The presented spontaneous and evoked EEG phenomena provide complementary information about the CNS functional suppression. Most significantly, the dissertation proposes a continuous and observation based control variable (r scale) and the means to predict its values by using EEG data. The definition of the scale provides a basis for anticipating the instant of the loss of consciousness. Additionally, the phase synchronization index as an indicator of drug effect is introduced. The approximate entropy descriptor performance is evaluated and optimised with a non-stationary signal recorded during the induction of anesthesia. The results open up opportunities to improve the preciseness, scientific validity and the interpretation of information on the anesthetic effects on CNS, and therefore, to increase the reliability of the anesthesia monitoring. Further work is needed to extend and verify the results in deep anesthesia.

Instituto Dr. Josà Frota / A cirurgia cardÃaca pediÃtrica freqÃentemente necessita de circulaÃÃo extracorpÃrea (CEC) durante a intervenÃÃo cirÃrgica. A combinaÃÃo de estresse cirÃrgico e CEC evoca uma resposta inflamatÃria sistÃmica multifatorial, com ativaÃÃo das cascatas humoral e celular. Somado à isto, a CEC proporciona perÃodos de isquemia-reperfusÃo, levando à condiÃÃes favorÃveis para formaÃÃo de radicais livres e criando uma situaÃÃo de desequilÃbrio que à denominada de estresse oxidativo. As espÃcies reativas do oxigÃnio (ERO) formadas durante o perÃodo de isquemia-reperfusÃo, estÃo intensamente implicadas na patogÃnese da disfunÃÃo miocÃrdica transitÃria (stunning heart), da necrose miocÃrdica devido à peroxidaÃÃo lipÃdica severa, da disfunÃÃo vascular, da morte celular programada (apoptose) e das disritmias pÃs-isquÃmicas. A influÃncia da tÃcnica anestÃsica sobre a resposta metabÃlica e oxidativa foi avaliada em um estudo envolvendo 20 crianÃas portadoras de doenÃas cardÃacas congÃnitas, distribuÃdas aleatoriamente em dois grupos: GP, o grupo em que foi utilizado anestesia venosa total com propofol e GS, grupo em que foi utilizado anestesia balanceada com sevoflurano. Foram determinadas as concentraÃÃes plasmÃticas das SubstÃncias Reativas do Ãcido TiobarbitÃrico (TBARS), glutationa, lactato e piruvato em trÃs tempos: T0 apÃs cateterizaÃÃo da artÃria radial, T1, 30 minutos apÃs o inÃcio da CEC e T2 ao tÃrmino do procedimento. Para a avaliaÃÃo dos marcadores estre os tempos em cada grupo, foi usado o teste de Friedman. A comparaÃÃo das mÃdias entre os dois grupos foi feita atravÃs do teste de Wilcoxon. Realizou-se tambÃm a correlaÃÃo de Pearson, para avaliar os marcadores entre os grupos. Valores de p < 0,05 foram considerados significantes. As concentraÃÃes de TBARS, glutationa, lactato e piruvato nÃo se alteraram significantemente nos tempos observados (p>0,05, teste de Friedman). Ao se comparar os valores mÃdios dos marcadores entre os grupos, nÃo se encontrou diferenÃa significante (p>0,05, teste de Wilcoxon). O quociente obtido da relaÃÃo lactato e piruvato (L/P) foi maior que 10 nos dois grupos, sem significÃncia estatÃstica quando comparado os dois grupos. Encontrou-se uma correlaÃÃo de pearson moderada para o TBARS, durante T1(r=0,50; p=0,13) e T2(r=0,51;p=0,12). Durante a CEC (T1), encontrou-se uma correlaÃÃo alta entre os grupos para o lactato (r=0,68; p=0,02), piruvato (r=o,75; p=0,01) e relaÃÃo L/P (r=0,83; p=0,003). A comparaÃÃo do uso de duas tÃcnicas anestÃsicas com mecanismos de aÃÃo distintos permite confrontar propriedades protetoras jà bem estabelecidas dos anestÃsicos venosos e inalatÃrios. As tÃcnicas anestÃsicas investigadas neste estudo, apresentaram comportamentos semelhantes, nÃo havendo aumento de substratos do estresse metabÃlico e oxidativo, durante a correÃÃo cirÃrgica de cardiopatias congÃnitas em crianÃas acianÃticas. / Pediatric cardiac surgery often requires cardiopulmonary bypass (CPB) during the surgical intervention. CPB and surgical stress combination evokes a multifatorial systemic inflammatory response with activation of the humoral and cellular cascade. In addition, CPB provides ischemia-reperfusion periods, leading to favorable conditions to free radical production and creating an imbalance, knew as oxidative stress. Reactive Oxygen Species (ROS) formed during the ischemia-reperfusion period are strongly implicated in the pathogenesis of the transitory myocardial dysfunction (stunning heart), myocardial necrosis, programmed cell death (apoptosis), vascular dysfunction and postischemic dysrhythmias. The anesthetic technique influence on the metabolic and oxidative response was evaluated in 20 children with congenital heart disease, randomized in two groups: GP, group which used venous total anesthesia with propofol, and GS, the group which used balanced anesthesia with sevoflurano. Thiobarbituric acid-reactive substance (TBARS), glutatione, lactate and pyruvate plasmatic concentrations were determined in three times: T0, after radial artery canulation, T1, 30 minutes after CPB start and T2, at the end of procedure. The markers evaluation in the several times and in each group, the Friedman test was used. The Wilcoxon test was used to compare the medians between the groups. Pearson correlation was done to evaluate the markers between the groups. Values of p<0.05 were considered statistically significant. The TBARS, gluthatione, lactate and pyruvate concentrations did not change significantly in the observed times (p>0,05, Friedman test). When the markerâs median values was compared between the groups, it wasnât significant (p>0,05, Wilcoxon test). The quotient of the relationship between lactate and pyruvate (L/P) was greater than 10 in both groups, with no difference statistically significant. There was a moderate Pearson correlation for TBARS, in T1 (r=0,50; p=0,13) e T2(r=0,51;p=0,12). During the CPB (T1), there was a high Pearson correlation between the groups for lactate (r=0,68; p=0,02), piruvato (r=0,75; p=0,01) e L/P rate (r=0,83; p=0,003). The comparison of two anesthetic techniques with distinct action mechanisms, allow confronting inhalator and venous anesthetic protecting proprieties. The anesthetic techniques investigated in this study were similar, without metabolic and oxidative stress substrates augment, in congenital heart disease surgical correction of acianotic children

Background: Surgical procedures are invariably accompanied by the use of inhalational and intravenous anesthetics. Both groups have strong influence on cardiovascular system by the interaction with myocardial oxygen supply/demand ratio and cardiomyocyte functions at the level of cell membranes, ion channels and regulatory enzymes. Aims: 1. To examine the effects of different isoflurane concentrations on the left ventricular (LV) dimensions and systolic function in the rat. 2. To examine the effects of isoflurane-induced myocardial preconditioning (APC) on the cardiac tolerance to ischemia- reperfusion (I-R) injury. 3. To compare the influence of anesthesia, based on ketamine- dexmedetomidine (KET-DEX), on the release of biochemical markers of myocardial injury and the early postoperative course with the anesthesia, based on sevoflurane-sufentanil (SEVO), in the patients undergoing coronary artery bypass grafting (CABG). Methods: 1. We carried out transthoracic echocardiographic examination in the rats immobilized by 1.5-3% concentration of isoflurane. 2. After inducing APC by isoflurane (0.5 and 1 MAC), we evaluated ventricular arrhythmias during regional ischemia (45 min), induced by the occlusion of the left anterior descending artery, and subsequent reperfusion (60 min), using the model of...

Background: Surgical procedures are invariably accompanied by the use of inhalational and intravenous anesthetics. Both groups have strong influence on cardiovascular system by the interaction with myocardial oxygen supply/demand ratio and cardiomyocyte functions at the level of cell membranes, ion channels and regulatory enzymes. Aims: 1. To examine the effects of different isoflurane concentrations on the left ventricular (LV) dimensions and systolic function in the rat. 2. To examine the effects of isoflurane-induced myocardial preconditioning (APC) on the cardiac tolerance to ischemia- reperfusion (I-R) injury. 3. To compare the influence of anesthesia, based on ketamine- dexmedetomidine (KET-DEX), on the release of biochemical markers of myocardial injury and the early postoperative course with the anesthesia, based on sevoflurane-sufentanil (SEVO), in the patients undergoing coronary artery bypass grafting (CABG). Methods: 1. We carried out transthoracic echocardiographic examination in the rats immobilized by 1.5-3% concentration of isoflurane. 2. After inducing APC by isoflurane (0.5 and 1 MAC), we evaluated ventricular arrhythmias during regional ischemia (45 min), induced by the occlusion of the left anterior descending artery, and subsequent reperfusion (60 min), using the model of...