Intraaortic balloon counterpulsation (IABP) is the most widely used mechanical support in the assistance of a failing heart.1 Despite extensive research in this field no experimental or clinical studies have been undertaken to evaluate the most effective manner to wean IABP.2 The research reported in this thesis examines early recognition of cardiac decompensation and the management of IABP weaning. Conducted in three phases, the aim of this research programme was to determine the best manner by which to wean IABP. Phase 1 utilised a comparative descriptive design to examine IABP practice at a single cardiothoracic tertiary referral hospital. The majority of data collection was prospective, however, the required sample size saw inclusion of some retrospective data. This single centre data were than compared with an international registry to contrast IABP management and outcome. Phase 2 utilised a questionnaire survey to audit all Australasian intensive care units. Survey results were combined and statistically analysed to describe Australasian IABP management, weaning and outcome. Phase 3 utilised a quasi-experimental, one-group, posttest-only design to clinically validate a tool designed to monitor a patient's cardiac function - the 'cardiac decompensation tool'. Phase 1 saw data collected for 669 IABP insertions over an 11 year period at a single Australian hospital. This cohort was compared against the 38,606 patient dataset of The Benchmark Counterpulsation Outcomes Registry. Australian IABP practice saw later application of the device in a higher acuity patient. Australian practice demonstrated a prejudice toward intraoperative use (34.2% versus 16.6%; p=< 0.0001) and an aversion to catheter laboratory support (10.6% versus 19%; p=< 0.0001). Australian mortality while slightly higher, remained comparable (22% versus 20.8%; p=ns). Phase 2 response rate was 60%. The most common Australasian method of IABP support withdrawal was ratio reduction only (61%). Units with a documented weaning policy were less likely to require balloon reinsertion or pharmacologic escalation following IABP removal (p=0.06). Indicators most likely to demonstrate a patient's readiness for IABP weaning were blood pressure (92%), heart rate (76%) and wedge pressure (59%). Phase 3 revealed cardiac decompensation tool scores to increase immediately prior to a treatment escalation (p=0.022) and decrease immediately following this escalation in therapy (p=0.0096). There was also some indication of decreasing scores prior to treatment minimisation (p=0.005). Tool scores demonstrated a corresponding treatment fluctuation up to three hours prior to the treatment intervention. With Phase 1 and 2 revealing many aspects of IABP practice to vary, the need for some direction regarding weaning is evident. Timely recognition of cardiac decompensation during IABP weaning allows an opportunity for the earlier escalation of treatment and consequent provision of increased cardiac support. Application of the Phase 3 cardiac decompensation tool can only assist in ensuring the best manner by which to support IABP weaning.

Il est avéré que les signaux de pléthysmographie par inductance comportent des composantes cardiaques et respiratoires pouvant présenter un intérêt pour un suivi physiologique. Cette technique est largement utilisée chez l’homme et chez les mammifères de taille moyenne, mais n’a jamais été mise en œuvre chez les petits rongeurs de laboratoire comme le rat. Cette thèse vise à apporter la preuve analytique et expérimentale (TRL3) d’une application cardiaque de la pléthysmographie cardiorespiratoire par inductance (PCRI) fondée sur le concept amont de « bague aortique virtuelle » (BAOV). La BAOV permet de mettre en œuvre une mesure externe des débits aortiques « instantanés » à l’aide de la PCRI en lieu et place d’un instrument positionné autour du vaisseau lui-même.La thèse a débuté par une phase de spécification et de conception guidée par l’interdépendance entre la physiologie et les contraintes instrumentales. Les performances métrologiques à atteindre sont dictées par un saut d’échelle entre l’homme et le rat. Le développement d’une chaine de mesure optimisée a permis de repousser les limites des systèmes existants en rendant possible la mesure de variations de volumes de quelques microlitres. En parallèle, l’identification de critères de validation, de méthodes de référence et la mise au point de protocoles expérimentaux ont conduit à la définition d’une stratégie de validation de l’instrument de mesure développé et du concept de BAOV.À l’issue de ces trois années, un système de PCRI à ultra-haute résolution a été mis au point. Après calibration, l’exactitude sur les mesures de variations de section est de 5 % sur un banc de test micrométrique. L’interchangeabilité de la mesure des variations de volume du thorax sur la gamme physiologique a été évaluée par rapport à une mesure pneumotachographique sur 9 animaux anesthésiés. Les limites d’agrément obtenues sont inférieures à 20 %. L’induction d’un challenge hémodynamique sur 11 animaux anesthésiés dont le débit aortique est mesuré en parallèle avec la PCRI et une bague de débit ultrasonique placée au niveau sous-diaphragmatique démontre l’équivalence entre les deux systèmes. Par ailleurs, la grande similitude entre les signaux de débits des deux méthodes valide le concept de bague aortique virtuelle proposé / It is recognized that inductive plethysmographic signals contain cardiac and respiratory components, which can be of interest for physiological monitoring. This technology is widely used in humans and medium mammals, but it has never been implemented in small laboratory rodents. This PhD aims to provide the analytic and experimental proof (TRL3) of a cardiac application of the cardio-respiratory inductive plethysmography (CRIP), based on the upstream concept of an “virtual aortic probe” (VAP). The VAP allows to realize an extern measure of “instantaneous” aortic flows thanks to CRIP instead of an instrument located directly around the vessel.The PhD starts with a phase of specification and conception driven by the interdependency between physiology and instrumental constraints. The expected metrological performances are established by a scale jumping between man and rat. The development of an optimized acquisition line has enabled to stretch the limits of existing systems; it allows to measure volume variations of a few microliters. At the same time, validation criteria and reference methods have been identified and experimental protocols have been specified in order to define the validation strategy of the developed instrument and VAP concept.At the end of these 3 years, an ultra-high resolution CRIP system has been developed. After calibration, the accuracy on the section variation measurements is 5% on a micrometric test-bench. The interchangeability of the thorax volume variation measure on a physiological range has been evaluated by comparison with a pneumotachographic measure on 9 anesthetized animals and the limits of agreement are lower than 20%. A hemodynamic challenge has been induced on 11 anesthetized animals, and the aortic flow has been simultaneously measured by CRIP and with an ultrasonic flow probe at under diaphragm level. This demonstrates the equivalence between both systems. And the high similarity between flow signals from both methods validates the proposed concept of virtual aortic probe

INTRODUÇÃO: A cirurgia de revascularização miocárdica sem utilização de circulação extracorpórea (CEC) tem sido cada vez mais utilizada, especialmente após a introdução de dispositivos estabilizadores da parede cardíaca. Entretanto, a técnica pode causar alterações hemodinâmicas durante a realização das anastomoses coronárias. OBJETIVOS: Analisar as alterações hemodinâmicas decorrentes das mudanças de posição do coração para abordar as artérias coronárias sem CEC e comparar os monitores de débito cardíaco semi-contínuo e de ecodoppler transesofágico quanto à precisão das medidas hemodinâmicas. MATERIAL E MÉTODOS: Foram selecionados aleatoriamente 20 pacientes adultos com idade inferior a 80 anos, candidatos a cirurgia eletiva de revascularização miocárdica sem utilização de circulação extracorpórea. A avaliação hemodinâmica incluiu a utilização de ecodopppler com transdutor esofágico e de cateter de artéria pulmonar com filamento térmico. A coleta de dados foi realizada: 1 - após a indução da anestesia, antes do início da revascularização propriamente dita, 2 - durante a realização das anastomoses distais, logo após o posicionamento e estabilização do coração e 3 - após cinco minutos do início da anastomose. Os dados hemodinâmicos foram analisados por análise de variância de duplo fator com repetição, complementada por teste de Newman-Keuls. O nível de significância considerado foi de 5%. Os valores de débito cardíaco foram comparados segundo método proposto por Bland e Altman, analisando a correlação intraclasses, diferenças médias e intervalos de confiança de 95%. RESULTADOS: Alterações hemodinâmicas significativas foram detectadas para o aumento de pressão de oclusão de artéria pulmonar (de 17,7 ± 6,1 para 19,2 ± 6,5 mmHg - p<0,001 e para 19,4 ± 5,8 mmHg - p<0,001) e pressão venosa central (de 13,9 ± 5,4 para 14,9 ± 5,9 mmHg - p=0,007 e para 15,1 ± 6,0 mmHg - p=0,006), além de diminuição do débito cardíaco obtido por termodiluição intermitente (de 4,70 ± 1,43 para 4,23 ± 1,22 L/min - p<0,001 e para 4,26 ± 1,27 L/min - p<0,001). Houve interação grupo-tempo estatisticamente significativa no débito cardíaco por Doppler esofágico, que apresentou redução no grupo lateral de 4,08 ± 1,99 para 2,84 ± 1,81 L/min (p=0,02) e para 2,86 ± 1,73 L/min (p=0,02), e no fluxo sanguíneo aórtico, que diminuiu de 2,85 ± 1,39 para 1,99 ± 1,26 L/min (p=0,02) e para 2,00 ± 1,21 L/min (p=0,02). As medidas de débito cardíaco intermitente, semicontínuo e por Doppler esofágico apresentaram diferenças médias e intervalos de confiança de 95% acima de limites aceitáveis clinicamente. CONCLUSÕES: Houve deterioração hemodinâmica significativa durante a revascularização miocárdica sem CEC. Pelo Doppler esofágico, o débito cardíaco apresentou redução detectada apenas na parede lateral. As diferenças nos valores de débito cardíaco foram muito amplas para considerar os métodos concordantes, em quaisquer das condições hemodinâmicas estudadas. / INTRODUCTION: Coronary artery bypass graft (CABG) surgeries have been performed increasingly without cardiopulmonary bypass (off-pump CABG), specially with introduction of cardiac wall stabilizing devices. However, hemodynamic changes can occur during coronary anastomosis. OBJECTIVES: To study hemodynamic alterations caused when cardiac position is changed to operate coronary arteries and to compare continuous cardiac output and esophageal Doppler monitor regardig accuracy of hemodynamic measurements. MATERIALS AND METHODS: Twenty adult patients under age of 80 undergoing elective off-pump CABG were enrolled. Hemodynamic evaluation was performed with esophageal echodoppler and continuous thermodilution pulmonary artery catheter. Data were collected 1 - after induction of anesthesia, before revascularization, 2 - during distal anastomosis, right after heart positioning and stabilization, and 3 - five minutes following the beginning of anastomosis. Repeated measures two-way ANOVA with post hoc Newman-Keuls tests were used to analyse hemodynamic data and level of significance was set at 0.05. Cardiac output values were compared using the method proposed by Bland and Altman, and included analysis of correlation, mean differences and 95% confidence intervals. RESULTS: Significant hemodynamic alterations were detected during revascularization of coronary arteries as elevation of pulmonary artery occlusion pressure (from 17.7 ± 6.1 to 19.2 ± 6.5 mmHg - P <0.001, and to 19.4 ± 5.8 mmHg - P <0.001) and of central venous pressures (from 13.9 ± 5.4 to 14.9 ± 5.9 mmHg - P =0.007, and to 15.1 ± 6.0 mmHg - P =0.006), and as reduction of intermittent cardiac output (from 4.70 ± 1.43 to 4.23 ± 1.22 l/min - P <0.001, and to 4.26 ± 1.27 l/min - P <0.001). Statistically significant group-time interaction was observed in esophageal Doppler cardiac output, that decreased in the lateral wall from 4.08 ± 1.99 to 2.84 ± 1.81 l/min (P =0.02) and to 2.86 ± 1.73 l/min (P =0.02), and in aortic blood flow, that decreased from 2.85 ± 1.39 to 1.99 ± 1.26 l/min (P =0,02) and to 2.00 ± 1.21 l/min (P =0.02). Intermittent, STAT-mode or esophageal Doppler cardiac output mean differences and 95% confidence intervals were beyond clinically acceptable limits. CONCLUSIONS: There was significant hemodynamic deterioration during off-pump CABG. On the esophageal Doppler monitor, cardiac output decrease was detected only in the lateral wall. Differences in cardiac output measurements were too wide to say methods agreed, in all hemodynamic conditions studied.

Introdução: A Variação da Pressão Sistólica (VPS) e da Pressão de Pulso (VPP) têm sido propostas como métodos efetivos para monitoração hemodinâmica, em predizer a resposta à reposição da volemia durante a ventilação mecânica. A primeira é calculada pela diferença entre a pressão sistólica máxima e mínima em um ciclo respiratório, e composta pela somatória dos componentes delta up e delta down; e a VPP obtida pela diferença entre a pressão sistólica e diastólica também em um ciclo respiratório. O objetivo deste estudo foi avaliar a VPS e seus componentes, e a VPP durante a ventilação com volume (VCV) e pressão (PCV) controlados, em coelhos normovolêmicos ou submetidos à hemorragia controlada. Método: Trinta e dois coelhos foram distribuídos de forma aleatória em quatro grupos: G1-ConPCV, G2-HemPCV, G3-ConVCV e G4-HemVCV. Foram ventilados em PCV ou VCV, com volume corrente entre 10 e 12 ml.kg-1 e freqüência respiratória para manter normocapnia. Nos grupos controle (G1-ConPCV e G3-ConVCV), sangue não foi retirado, e cada momento foi avaliado por 30 minutos (M0, M1 e M2); nos grupos com hemorragia (G2-HemPCV e G4-HemVCV), não houve perda sangüínea em M0, em M1 retirou-se 15% da volemia estimada, assim como em M2, de forma gradual. Os dados foram submetidos à análise de variância para medidas repetidas (ANOVA), sendo considerados significativos para um valor de p<0,05, e apresentados na forma de média e desvio-padrão. Resultados: Não houve diferença em M0 entre os grupos estudados. Em M1, os grupos com perda sanguínea apresentaram maiores variações na VPS, em seu componente delta down e na VPP, diferindo significativamente apenas dos grupos controle. Quando a volemia foi reduzida em 30% (M2), G4-HemVCV apresentou maior variação na pressão sistólica, no componente delta down e na pressão de pulso; bem como ambos grupos submetidos à hemorragia apresentaram valores significativamente maiores do que os grupos controle. O débito cardíaco não apresentou variação significativa (p>0,05) entre os momentos e grupos estudados. Conclusões: Em coelhos normovolêmicos ou com hipovolemia leve, ambos modos de ventilação se comportam de forma semelhante sobre as variáveis estudadas, ao passo que na hipovolemia moderada pôde-se observar menor comprometimento hemodinâmico durante a PCV / Rationale: Systolic pressure variation (SPV) and pulse pressure variation (PPV) indices have been proposed as effective methods of hemodynamic monitoring to predict fluid responsiveness during mechanical ventilation. SPV is calculated by the difference between the maximum and minimum values of systolic blood pressure following a single positive pressure breath, and it is made up of the sum of their components delta up and delta down; PPV is obtained by the difference between systolic and diastolic blood pressure also in a single positive pressure breath. The purpose of this study was to evaluate SPV and its components, and PPV during volume (VCV) and pressure (PCV) controlled ventilation in normovolemic rabbits or ones submitted to graded hemorrhage. Method: Thirty two rabbits were randomly allocated in four groups: G1- ConPCV, G2-HemPCV, G3-ConVCV and G4-HemVCV. They were ventilated in PCV or VCV; tidal volume was fixed between 10 to 12 mL.kg-1 and respiratory rate was monitored in order to maintain normocapnia. In control groups (G1- ConPCV and G3-ConVCV) blood was not withdrawn and each moment was evaluated for 30 minutes (M0, M1 and M2); in hemorrhage groups (G2-HemPCV and G4-HemVCV) there was no blood loss in M0; in M1 and M2 15% of estimated volemia was graded withdrawn. Data were submitted to analysis of variance for repeated measures (ANOVA); significance level was p<0,05 and results were expressed as mean ± standard deviation. Results: In M0, no significant differences were observed among all groups. Hemorrhagic groups (G2-HemPCV and G4-HemVCV) presented higher SPV, delta down and PPV in M1, differing significantly (p<0,05) only from control groups. When 30% of estimated blood volume was removed, higher SPV, delta down and PPV were observed mainly in G4-HemVCV. Cardiac output did not vary significantly (p>0,05) among groups and moments. Conclusions: In rabbits with normovolemia or slight hemorrhage, both modes of ventilation had similar behavior over studied parameters, while in the ones undergoing moderate hemorrhage PCV determined less hemodynamic compromising

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No. of bitstreams: 2 Dissertacao - Sandro de Melo Braga - 2014.pdf: 4351893 bytes, checksum: abf7d37b6f843e30fee499929c15eb91 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-07-15 / Agonist drugs α-2 adrenergic receptors are used in veterinary medicine to promote sedation, analgesia and muscle relaxation. In horses with xylazine and detomidine are used in preanesthetic medication such as sedatives for procedures or surgeries in the standing position with the aid of locoregional anesthesia in analgesic infusions associated with general anesthesia for invasive procedures, or associated with dissociative drugs to anesthesia Overall the equine field. In the first study aimed to evaluate the sedative, gastrointestinal, cardiovascular and blood gas of xylazine and detomidine administered at different doses in horses effects. Eight horses, four males and four females, aged between five and 15 years, weighing 276.58±9.23 kg were used. The experimental design was randomized crossover using animals of six different occasions to receive: xylazine 0.5 mg/kg (X05), 1.0 mg/kg (X1), 1.5 mg/kg (X15); 20μg/kg detomidine (D20), 40 mg/kg (D40) and 60μg/kg (D60). The parameters evaluated were heart rate (HR); the electrocardiogram (ECG); respiratory frequency (f); systolic blood pressure (SBP), diastolic (DBP) and mean (MAP) by invasive method; Sedation (RAC); rectal temperature (T); intestinal motility (MI); blood gases and electrolytes. Some showed similar results to those previously reported with xylazine and detomidine as good sedation, significant reduction of HR and f, however, there was an increase in BP lasting with increasing dose of detomidine, as well as a reduction in intestinal motility for periods there are 180 minutes with the same drug. In the review of blood gas analysis showed a decrease in PaO 2 and increase in PaCO 2 in arterial blood, indicative of respiratory depression, increased bicarbonate ion (HCO 3 -) and base excess, however they remained within normal limits for the species. It follows that promotes more efficient detomidine sedation, however promotes a greater depression in cardiac system and intestinal motility compared with xylazine in horses. In the second study aimed to evaluate the sedative, cardiovascular and echodopplercardiographic effects of xylazine and detomidine in horses. Six horses, two males and four females, aged between five and 15 years, weighing 276.58 ± 9.23 kg were used . The animals used in randomized crossover design twice for receiving xylazine 1.0 mg/kg (GX) detomidine or 40 µg/kg (GD), administered intravenously. In addition to the parameters evaluated in the first phase of the study, also cardiac output (CO), cardiac index (CI), aortic diameter (AD), ejection fraction (FE) and fractional shortening (FS) by echocardiography were recorded. The results showed intense cardiorespiratory depression in animals that received detomidine, however with greater sedative effects compared to xylazine group. BP values showed an initial increase only in the detomidine group, lasting approximately 30 minutes and subsequent reduction of the values, without characterizing hypertension and hypotension. In echodopplercardiographic evaluation, the GD had major depression in ventricular function parameters, for the group GX and this review was efficient compared with values obtained in other studies by methods already established. It is concluded that detomidine sedation promotes more efficient compared to xylazine in horses, however the depressive effects on cardiovascular variables are evaluated by echocardiogram greatest method. / Em equinos a xilazina e a detomidina são utilizadas na medicação pré-anestésica, como sedativos para procedimentos ou cirurgias em posição quadrupedal com o auxílio de anestesia locorregional, em infusões analgésicas associadas à anestesia geral para procedimentos invasivos, ou associadas a fármacos dissociativos na manutenção da anestesia geral a campo. No primeiro estudo objetivou-se avaliar os efeitos sedativos, gastrointestinais, cardiovasculares e hemogasométricos da xilazina e da detomidina administradas em diferentes doses em equinos. Foram utilizados oito equinos, quatro machos e quatro fêmeas, com idade entre cinco e 15 anos, pesando 276,58 ± 9,23 kg. O delineamento foi cruzado aleatório, utilizando os animais em seis ocasiões diferentes para receberem: xilazina 0,5 mg/kg (X05), 1,0 mg/kg (X1), 1,5 mg/kg (X15), detomidina 20 µg/kg (D20), 40 µg/kg (D40) e 60 µg/kg (D60). Os parâmetros avaliados foram frequência cardíaca (FC); traçado eletrocardiográfico (ECG); frequência respiratória (f); pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM) pelo método invasivo; grau de sedação (SD); temperatura retal (T); motilidade intestinal (MI); gases sanguíneos e eletrólitos. Foram obtidos resultados similares aos descritos na literatura com xilazina e detomidina, como boa sedação, redução significativa da FC e f, no entanto, observou-se aumento duradouro da PA com o incremento da dose de detomidina, assim como redução na motilidade intestinal por períodos superiores a 180 minutos, com o mesmo fármaco. Houve redução da PaO 2 e aumento da PaCO 2 e do bicarbonato(HCO3) -com déficit de base. No entanto os valores permaneceram dentro dos limites de normalidade para a espécie. Concluiu-se que a detomidina promove sedação mais eficiente, no entanto induz maior depressão cardiorrespiratória e da motilidade intestinal, quando comparada à xilazina em equinos. No segundo ensaio objetivou-se avaliar os efeitos sedativos, cardiovasculares e ecodopplercardiográficos da xilazina e da detomidina em equinos. Foram utilizados seis equinos, dois machos e quatro fêmeas, com idade entre cinco e 15 anos, pesando 276,58 ± 9,23 kg. Os animais foram usados em delineamento cruzado aleatório, para receberem xilazina, 1,0 mg/kg (GX) ou detomidina 40 µg/kg (GD), pela via endovenosa. Além dos parâmetros avaliados na primeira fase do estudo, também foram registrados débito cardíaco (DC), índice cardíaco (IC), diâmetro da aorta (DA), fração de ejeção (FE) e fração de encurtamento (FS), por ecodopplercardiografia. Houve depressão cardiorrespiratória e efeito sedativo mais intensos nos animais que receberam detomidina. Os valores de PA apresentaram aumento inicial apenas no grupo detomidina, com duração de aproximadamente 30 minutos e posterior redução dos valores, sem caracterizar hipertensão ou hipotensão. Na avaliação ecodopplercardiográfica o GD apresentou maior depressão nos parâmetros de função ventricular, em relação ao GX. Com base nos valores obtidos em outros estudos utilizando métodos já consagrados, observou-se que a ecodopplercardiografia foi eficiente na avaliação hemodinâmica de equinos. Conclui-se que a detomidina promove sedação mais eficiente comparada à xilazina em equinos, no entanto os efeitos depressivos sobre as variáveis cardiovasculares são maiores, conforme avaliação ecodopplercardiográfica

Abstract Cardiovascular abnormalities are frequent after non-traumatic intracranial hemorrhage (NT-IH). They have mainly been studied in patients with subarachnoid hemorrhage (SAH), in which they have been reported to be associated with a poorer outcome. The aim of this observational clinical study was to evaluate cardiovascular abnormalities in patients with NT-IH requiring intensive care: clinical picture, predisposing factors and impact on outcome were examined. Additionally, the validity of cardiac output (CO) monitoring via uncalibrated arterial pressure waveform analysis (APCO, FloTrac/Vigileo™) was evaluated. The thesis was comprised of retrospective (n=229) and prospective (n=108) studies. The cardiovascular abnormalities evaluated were repolarization abnormalities (RAs) in electrocardiography (ECG), myocardial injury and dysfunction, and neurogenic pulmonary edema (NPE). Cardiovascular dysfunction severity was assessed using the Sequential Organ Failure Assessment cardiovascular (SOFAcv) score. Predisposing factors for RAs and NPE were examined. The one-year mortality and functional outcome were assessed. APCO was compared with the intermittent bolus thermodilution technique (TDCO). Cardiovascular abnormalities were almost universal after NT-IH and comparable after intracerebral hemorrhage (ICH) and SAH. Each RAs (QT interval prolongation, ischemic-like ECG changes and morphological end-repolarization abnormalities) had characteristic predisposing factors. The Acute Physiology And Chronic Health Evaluation (APACHE) II score &#8805;20 and systemic interleukin 6 concentration &#62;40 pg/mL were independent predictors for NPE. In the retrospective study the mortality rate was 32% after SAH and 44% after ICH. In the prospective study the rates for mortality were 18% vs. 29% and for a poor functional outcome 41% vs. 69%, respectively. Ischemic-like ECG changes were associated with a poorer functional outcome. APCO underestimated CO compared to TDCO and was biased by low systemic vascular resistance (SVR). In conclusion, cardiovascular abnormalities after NT-IH are comparable after SAH and ICH. Predisposing factors for each RAs vary. Inflammatory mechanisms play an important role in NPE development. Ischemic-like ECG changes are associated with a poorer one-year functional outcome. The validity of APCO is insufficient and biased by low SVR in patients with NT-IH. / Tiivistelmä Sydämen ja verenkierron toimintahäiriöt ovat yleisiä ei-traumaattisen aivoverenvuodon (NT-IH) jälkeen. Niitä on tutkittu lähinnä lukinkalvonalaisvuotopotilailla (SAV), joilla niiden on todettu olevan yhteydessä huonompaan ennusteeseen. Tässä havainnoivassa kliinisessä tutkimuksessa selvitettiin tehohoidettujen NT-IH -potilaiden sydämen ja verenkierron toimintahäiriöiden kliinistä oirekuvaa, altistavia tekijöitä ja vaikutusta ennusteeseen. Tutkimuksessa arvioitiin myös valtimopainekäyräanalyysiin perustuvan monitorointimenetelmän (APCO, FloTrac/Vigileo™) luotettavuutta mitattaessa sydämen minuuttitilavuutta. Väitöskirjatyö koostui retrospektiivisesta (n=229) ja prospektiivisesta (n=108) tutkimuksesta. Tutkittavia toimintahäiriöitä olivat elektrokardiografiassa (EKG) nähtävät repolarisaatiohäiriöt (RAs), sydänlihaksen vaurio ja supistumishäiriö sekä keuhkopöhö. Sydämen ja verenkierron toimintahäiriön yleistä vaikeusastetta arvioitiin SOFAcv -pisteytyksellä. RAs:lle ja keuhkopöhölle altistavia tekijöitä määritettiin. Potilaiden kuolleisuus ja toiminnallinen ennuste selvitettiin vuoden seuranta-aikana. APCO:a verrattiin lämpölaimennusmenetelmään (TDCO). Sydämen ja verenkierron toimintahäiriöitä esiintyi lähes kaikilla, eivätkä ne oirekuvaltaan eronneet aivokudoksen sisäistä vuotoa (ICH) ja SAV:a sairastavilla potilailla. Eri RAs:llä (QT-ajan pidentyminen, iskeemistyyppiset EKG-muutokset ja loppurepolarisaation morfologiset poikkeavuudet) oli kullekin ominaiset altistavat tekijät. APACHE II –pisteet &#8805;20 ja veren interleukiini 6 –pitoisuus &#62;40 pg/ml ennustivat keuhkopöhön kehittymistä. Retrospektiivisessä aineistossa kuolleisuus oli 32&#160;% SAV-potilailla ja 44&#160;% ICH-potilailla. Prospektiivisessa aineistossa kuolleisuus ja huono toiminnallinen ennuste olivat vastaavasti 18&#160;% vs. 29&#160;% ja 41&#160;% vs. 69&#160;%. Iskeemistyypiset EKG-muutokset olivat yhteydessä huonompaan toiminnalliseen ennusteeseen. APCO aliarvioi TDCO:a matalan systeemiverenkierron vastuksen (SVR) kasvattaessa harhaa. Yhteenvetona todettakoon, että sydämen ja verenkierron toimintahäiriöt eivät eroa SAV- ja ICH-potilailla. Eri RAs:lle altistavat kullekin ominaiset tekijät. Tulehdukselliset mekanismit ovat keskeisiä keuhkopöhön kehittymisessä. Iskeemistyyppiset EKG-muutokset ovat yhteydessä huonompaan toiminnalliseen ennusteeseen. APCO:n luotettavuus NT-IH -potilailla on riittämätön, ja harhaa lisää matala SVR.

Objetivo: O objetivo do estudo foi avaliar se o uso da terapia hemodinâmica pós-operatória guiada pelo índice cardíaco por método minimamente invasivo reduz o desfecho combinado de mortalidade em 30 dias e de complicações graves durante a internação hospitalar em pacientes com câncer submetidos à cirurgia de alto risco. Desenho: Estudo fase III, de superioridade, unicêntrico, randomizado e controlado realizado no Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, Brasil. População: Pacientes adultos submetidos a cirurgia de alto risco para tratamento de câncer e que necessitaram de cuidados pós-operatórios em unidade de terapia intensiva. Intervenção: Um protocolo de terapia hemodinâmica pós-operatória guiada por metas (incluindo reposição volêmica, fármacos vasoativos e transfusão de hemácias para manter índice cardíaco maior ou igual a 2,5 L/min/m2) foi comparado a uma terapia padrão nas primeiras 8 horas de admissão dos pacientes na Unidade de Terapia Intensiva. Desfecho primário: Desfecho composto por mortalidade em 30 dias e complicações graves durante a internação hospitalar (infarto agudo do miocárdio, síndrome do baixo débito cardíaco, isquemia mesentérica, isquemia vascular periférica, embolia pulmonar, síndrome do desconforto respiratório agudo, acidente vascular cerebral, insuficiência renal aguda, infecção de ferida operatória profunda e reoperação). Resultados: Foram incluídos 128 pacientes, 64 no grupo terapia guiada por metas (TGM) e 64 no grupo terapia padrão (TP). Durante as 8 horas de intervenção, não houve diferença entre os grupos TGM e TP na quantidade de fluidos administrada (1295,1 mL ± 613,2 mL vs 1129 mL ± 557,5 mL, P=0,189), no número de pacientes que receberam norepinefrina (65,5% vs 51,6%, P= 0,211) e no número de pacientes expostos a transfusão de hemácias (3,1% vs 0, P=0,496). Um número maior de pacientes do grupo TGM recebeu dobutamina durante a intervenção quando comparado aos pacientes do grupo TP (54,7% vs 15,65%, P < 0,001. Não houve diferença entre os grupos em relação ao desfecho primário (53,1% no grupo TGM vs 43,8% no grupo TP, P= 0,289). Conclusão: A terapia hemodinâmica guiada pelo índice cardíaco aplicada nas primeiras 8h de pós-operatório não reduziu a mortalidade em 30 dias e as complicações graves durante a internação hospitalar quando comparada a estratégia padrão em pacientes com câncer submetidos a cirurgia de alto risco. A terapia hemodinâmica resultou em maior exposição dos pacientes à dobutamina, sem resultar em redução das complicações. Registro no Clinical Trials: NCT01946269 / Objectives: The aim of this study was to determine whether a postoperative hemodynamic therapy guided by the cardiac index based on minimally invasive cardiac output monitoring decreases the incidence of 30-day mortality and postoperative complications in oncologic patients undergoing high-risk non-cardiac surgery. Design: Phase III, single center, superiority, randomized and controlled trial performed at the Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, Brazil. Population: Adult patients undergoing high-risk cancer surgery who required intensive care unit admission. Intervention: A hemodynamic goal directed therapy protocol (including fluids, vasoactive agents and red blood cells transfusion to reach a cardiac index equal or higher than 2.5 L/min/m2) was compared to usual care during the first 8 h of postoperative. Primary outcome: The primary outcome was a composite endpoint of 30-day mortality and severe complications during hospital stay (acute myocardial infarction, low cardiac output syndrome, mesenteric ischemia, peripheral vascular ischemia, pulmonary embolism, acute respiratory distress syndrome, stroke, acute kidney injury, deep wound infection and reoperation). Results: 128 patients were included in the study; 64 were allocated to the goal directed therapy group (GDT) and 64 to the usual care group (UC). During the 8-hour intervention, there were no differences between GDT and UC groups in the amount of administered fluid (1295.1 mL ± 613.2 mL) vs (1129 mL ± 557.5 mL), P=0.189), in the number of patients who received norepinephrine (65.5% vs. 51.6%, P= 0.211) and in the number of patients exposed to red blood cells transfusion (3.1% vs. 0, P= 0,496). However, more patients in GDT group needed dobutamine during intervention when compared to patients from the UC group (54.7% vs. 15.65%, P < 0.001). The primary outcome was reached by a similar proportion of patients in both groups (53.1% in GDT group vs. 43.8% in UC group, P=0.289). Conclusion: Postoperative hemodynamic therapy guided by cardiac index monitoring in the first 8-hour of postoperative does not reduce 30-day mortality and severe complications during hospital stay when compared to the usual care in cancer patients undergoing high-risk surgery. Also, hemodynamic therapy resulted in a higher needing of dobutamine without improving outcomes. Clinical Trials Register: NCT01946269.

Kardiopulmonale Adaptation und Therapie von wachstumsretardierten Frühgeborenen mit intrauteriner Perfusionsstörung im Vergleich zu nicht-wachstumsretardierten Frühgeborenen ohne intrauterine Perfusionsstörung Eingereicht von: Christin Lenk, geb. Demolt angefertigt in der Universitätsklinik und Poliklinik für Kinder und Jugendliche in Leipzig, Neonatologische Intensivstation betreut von Frau Prof. Dr. med. Eva Robel-Tillig Juli 2012 Chronische intrauterine Hypoxie bedingt durch uterine, feto-maternale und fetale Perfusionsstörung führt zur fetalen Wachstumsrestriktion und Erhöhung der fetalen und neonatalen Morbidität und Mortalität. Die pränatale Kreislaufzentralisation stellt einen pathophysiologischen Kompensationsmechanismus dar, der durch Umverteilung des Blutflusses eine Versorgung lebenswichtiger Organe des Feten sichert (Rizzo et al. 2008), (Robel-Tillig 2003), (Robel 1994), (Saling 1966). In den letzten Jahren haben sich Studien mit der postnatalen Adaptation der wachstumsretardierten Neonaten beschäftigt und wesentliche Risiken im Verlauf der ersten Lebenstage definiert. Wenige validierte Aussagen existieren jedoch zur Kreislaufsituation der betroffenen Kinder und der kardialen Leistungsfähigkeit auch über die erste Lebenswoche hinaus. Die vorliegende Studie vergleicht unter dieser Fragestellung eine Gruppe von 43 Frühgeborenen mit intrauteriner Wachstumsrestriktion auf der Grundlage einer Perfusionsstörung und 33 Frühgeborene mit appropriatem Wachstum und ungestörter pränataler Perfusion während der ersten 42 Lebenstage hinsichtlich der unmittelbaren postnatalen pulmonalen und kardialen Adaptationsparameter und des weiteren klinischen Verlaufs. Besonderer Schwerpunkt wird dabei auf die dopplersonographisch erfasste kardiale Funktion der Kinder gelegt. Als wesentlichstes Ergebnis der dopplersonographischen Messungen lässt sich bei den Frühgeborenen mit pränataler Perfusionsstörung ein signifikant erhöhtes Herzminutenvolumen rechts- und linksventrikulär im Vergleich zur Gruppe der Frühgeborenen mit ungestörter Perfusion darstellen (Robel-Tillig 2003), (Leipälä et al. 2003), Martinussen 1997}, (Guajardo, Mandelbaum & Linderkamp 1994), (Lindner et al. 1990). Die unmittelbar postnatale Adaptation zeigt hinsichtlich des arteriellen Nabelschnur-pH-Wertes eine schlechtere Anpassung der Frühgeborenen mit pränataler Perfusionsstörung auf. Im weiteren Verlauf der ersten Tage benötigen diese Frühgeborenen seltener eine maschinelle Beatmung oder CPAP-Atemhilfe als die Frühgeborenen ohne Wachstumsrestriktion. Bis zum 42. Lebenstag kehrt sich dieser Befund jedoch um. Die Frühgeborenen mit Wachstumsrestriktion bedürfen nun signifikant länger und häufiger einer Atemhilfe und zusätzlicher Sauerstoffsupplementierung. Als Komplikation trat bei den wachstumsretardierten Frühgeborenen eine höhere Rate an bronchopulmonaler Dysplasie auf. Ein weiterer Unterschied wird hinsichtlich der Transfusionshäufigkeit dargestellt. Frühgeborene mit Wachstumsrestriktion erhielten häufiger eine Erythrozytentransfusion und länger eine Transfusion von zusätzlichem Volumen. Zusammenfassend weisen die ermittelten Befunde auf ein Persistieren der intrauterin bestehenden Kompensation der beeinträchtigten Kreislaufsituation hin. Eine genaue Kenntnis der speziellen Probleme dieser Patientengruppe ist zur Vermeidung postnatal anhaltender hämodynamischer Störungen erforderlich.

Pulmonary arterial hypertension (PAH) is an uncommon but serious disease that causes increased pressure in the pulmonary vessels and increased pulmonary vascular resistance (PVR), which in turn leads to right heart failure. At diagnosis, mean pulmonary artery pressure (mPAP) must be &gt;20 mmHg, pulmonary artery wedge pressure (PAWP) ≤15 mmHg and PVR &gt;2 Wood units (WU). Calculation of cardiac output (CO) is an important hemodynamic parameter to be measured and assessed in these patients during a right heart catheterization (RHC). Prevailing ESC guidelines recommend using direct Fick's principle (dFp), which is considered the gold standard, or thermodilution when calculating CO. The aim of this study was to compare these two methods to see if there is a significant difference in the calculation of CO in patients with PAH. The aim was also to see if calculated cardiac index (CI) and PVR differ significantly depending on which of the methods for calculating CO is used. A retrospective study was conducted in which 34 patients who underwent RHC at the University Hospital in Örebro were included. The result showed a significant difference between dFp and thermodilution (p&lt;0,05), where dFp on average measures higher volumes compared to thermodilution. It also showed a low agreement between the two methods. A significant difference was seen between CI and PVR (p&lt;0,05) depending on which of the methods is used. Therefore, dFp and thermodilution cannot be said to have a good agreement in this patient group. It is important to use the same method for follow-up examinations as the assessment of PVR and CI is used as a predictor of whether the disease progresses or remains stable.

High blood pressure, also called hypertension is one of the most common worldwide diseases afflicting humans and is a major risk factor for stroke, myocardial infarction, vascular disease, and chronic kidney disease. If blood pressure is controlled and oscillations in the hemodynamic variables are reduced, patients experience fewer complications after surgery. In clinical practice, this is usually achieved using manual drug delivery. Given that different patients have different sensitivity and reaction time to drugs, determining manually the right drug infusion rates may be difficult. This is a problem where automatic drug delivery can provide a solution, especially if it is designed to adapt to variations in the patient’s conditions. This research work presents an investigation into the development of abnormal blood pressure (hypertension) controllers for postoperative patients. Control of the drugs infusion rates is used to simultaneously regulate the hemodynamic variables such as the Mean Arterial Pressure (MAP) and the Cardiac Output (CO) at the desired level. The implementation of optimal control system is very essential to improve the quality of patient care and also to reduce the workload of healthcare staff and costs. Many researchers have conducted studies earlier on modelling and/or control of abnormal blood pressure for postoperative patients. However, there are still many concerns about smooth transition of blood pressure without any side effect. The blood pressure is classified in two categories: high blood pressure (Hypertension) and low blood pressure (Hypotension). The hypertension often occurred after cardiac surgery, and the hypotension occurred during cardiac surgery. To achieve the optimal control solution for these abnormal blood pressures, many methods are proposed, one of the common methods is infusing the drug related to blood pressure to maintain it at the desired level. There are several kinds of vasodilating drugs such as Sodium Nitroprusside (SNP), Dopamine (DPM), Nitro-glycerine (NTG), and so on, which can be used to treat postoperative patients, also used for hypertensive emergencies to keep the blood pressure at safety level. A comparative performance of two types of algorithms has been presented in chapter four. These include the Internal Model Control (IMC), and Proportional-Integral-Derivative (PID) controller. The resulting controllers are implemented, tested and verified for three sensitivity patient response. SNP is used for all three patients’ situation in order to reduce the pressure smoothly and maintain it at the desire level. A Genetic Algorithms (GAs) optimization technique has been implemented to optimise the controllers’ parameters. A set of experiments are presented to demonstrate the merits and capabilities of the control algorithms. The simulation results in chapter four have demonstrated that the performance criteria are satisfied with the IMC, and PID controllers. On the other hand, the settling time for the PID control of all three patients’ response is shorter than the settling time with IMC controller. Using multiple interacting drugs to control both the MAP and CO of patients with different sensitivity to drugs is a challenging task. A Multivariable Model Reference Adaptive Control (MMRAC) algorithm is developed using a two-input, two-output patient model. Because of the difference in patient’s sensitivity to the drug, and in order to cover the wide ranges of patients, Model Reference Adaptive Control (MRAC) has been implemented to obtain the optimal infusion rates of DPM and SNP. This is developed in chapters five and six. Computer simulations were carried out to investigate the performance of this controller. The results show that the proposed adaptive scheme is robust with respect to disturbances and variations in model parameters, the simulation results have demonstrated that this algorithm cannot cover the wide range of patient’s sensitivity to drugs, due to that shortcoming, a PID controller using a Neural Network that tunes the controller parameters was designed and implemented. The parameters of the PID controller were optimised offline using Matlab genetic algorithm. The proposed Neuro-PID controller has been tested and validated to demonstrate its merits and capabilities compared to the existing approaches to cover wide range of patients. / Libyan Ministry of Higher Education scholarship