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L’optimisation hémodynamique péri-opératoire est une stratégie qui vise à maximaliser le transport artériel en oxygène et/ou le volume d’éjection systolique lors de chirurgie à risque. Ce concept a beaucoup évolué lors de ces trente dernières années, vers une approche plus simple, plus réalisable en pratique clinique et moins invasive. Les principales thérapeutiques utilisées dans les différents protocoles d’optimisation hémodynamique sont le remplissage vasculaire, l’administration d’agents inotropes et de vasopresseurs. Cependant, les conséquences physiopathologiques de l’agression chirurgicale peuvent impacter grandement les modalités d’administration et l’efficacité des thérapeutiques précitées. Dans la première étude, nous avons décrit l’impact de l’acidose respiratoire et métabolique (fréquemment rencontrées lors de chirurgie majeure et/ou de coeliochirurgie) sur l’efficacité des agents α et β-adrénergiques sur le myocarde sain de rat. Dans un deuxième travail nous avons mis en évidence que le remplissage vasculaire ne pouvait pas être guidé par des indices dynamiques de précharge dépendance lors du clampage chirurgicale de l’aorte abdominale sous-rénale, dans un modèle porcin. Enfin, dans la troisième étude, nous avons montré dans un modèle clinique, que le positionnement en décubitus ventral lors d’une chirurgie du rachis entrainait des modifications majeures des interactions cardiorespiratoires et que les indices dynamiques devaient être interprétés avec prudence pour guider le remplissage vasculaire dans ce contexte. Ces études translationnelles soulignent trois situations fréquentes impactant l’efficacité et/ou les modalités d’administration des thérapeutiques nécessaires à une optimisation hémodynamique peropératoire / The aim of perioperative haemodynamic optimization is to maximize oxygen delivery and/or stroke volume during high risk surgery. This concept has evolved during the last thirty years, to a simpler, more feasible and less invasive approach. Main treatments used in different hemodynamic optimization protocols are fluid loading, inotropes and vasopressors administration. However, pathophysiological consequences of surgical stress can greatly impact the mode of administration and the efficacy of the above therapeutics. In the first study, we described the impact of respiratory and metabolic acidosis (frequently encountered during major surgery and/or laparoscopic surgery) on the effectiveness of α and β-adrenergic agents in healthy rat myocardium. In a second work, we demonstrated that intravenous fluids cannot be guided by dynamic indices of preload dependency during surgical clamping of the infrarenal abdominal aorta in a porcine model. Finally, in the third study, we demonstrated in a clinical model, that positioning in prone position during spine surgery induced major changes in cardiorespiratory interactions and dynamic indices should be interpreted with caution to guide fluid therapy in this context. These translational studies highlight three common situations impacting the effectiveness and/or administration of therapeutic necessary for intraoperative hemodynamic optimization.

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.

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.

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.

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

<p>Live donor nephrectomy (LDN) is a unique surgical challenge where surgery is performed on healthy individuals. It is of great importance to keep the morbidity of donors as low as possible, as well as harvesting a kidney in optimal condition. Lowering morbidity is the motive for introducing the endoscopic technique in LDN. Oliguria and impaired kidney function can, however, be seen during pneumoperitoneum and endoscopic LDN have been criticized for not yet being proven safe enough.</p><p>The aims of this study were to investigate the changes in renal function during elevated intraabdominal pressure (IAP) in donors and rats and to evaluate donor morbidity and safety of the new endoscopic techniques compared to the open LDN.</p><p>In two studies, a rat model was used. It was found that elevation of IAP diminished glomerular filtration rate (GFR). Cardiac output (CO) and renal blood flow decreased as well. Elevation of IAP activates the renin system and aldosterone was increased. Acute angiotensin II receptor 1 blockade (candesartan) treatment lowered blood pressure significantly and impaired renal function during elevated IAP. Volume expansion prior to, and during, pneumoperitoneum reduces the deleterious effects on renal function.</p><p>Three studies on kidney live donors show that traditional laparoscopic surgery (TLS) takes longer time to perform than open LDN. Hand-assistance facilitates the operation and increases the safety margin as well as shortens the operation by 27% compared to TLS. Evaluation of a hand-assisted retroperitoneoscopy (HARS), performed for the first time ever in Uppsala 2001, show that the operation is short and safe, the donors experience little pain and the renal function is favourable compared to open surgery, TLS and hand-assisted transperitoneal laparoscopic approaches.</p><p>In conclusion, the results indicate that elevated IAP decreases GFR due to decreased CO and activation of the RAAS, which can be avoided with adequate hydration. Endoscopy can be facilitated if hand-assistance is applied and in particular hand-assisted retroperitoneoscopic nephrectomy shows advantages for the donor.</p>

Live donor nephrectomy (LDN) is a unique surgical challenge where surgery is performed on healthy individuals. It is of great importance to keep the morbidity of donors as low as possible, as well as harvesting a kidney in optimal condition. Lowering morbidity is the motive for introducing the endoscopic technique in LDN. Oliguria and impaired kidney function can, however, be seen during pneumoperitoneum and endoscopic LDN have been criticized for not yet being proven safe enough. The aims of this study were to investigate the changes in renal function during elevated intraabdominal pressure (IAP) in donors and rats and to evaluate donor morbidity and safety of the new endoscopic techniques compared to the open LDN. In two studies, a rat model was used. It was found that elevation of IAP diminished glomerular filtration rate (GFR). Cardiac output (CO) and renal blood flow decreased as well. Elevation of IAP activates the renin system and aldosterone was increased. Acute angiotensin II receptor 1 blockade (candesartan) treatment lowered blood pressure significantly and impaired renal function during elevated IAP. Volume expansion prior to, and during, pneumoperitoneum reduces the deleterious effects on renal function. Three studies on kidney live donors show that traditional laparoscopic surgery (TLS) takes longer time to perform than open LDN. Hand-assistance facilitates the operation and increases the safety margin as well as shortens the operation by 27% compared to TLS. Evaluation of a hand-assisted retroperitoneoscopy (HARS), performed for the first time ever in Uppsala 2001, show that the operation is short and safe, the donors experience little pain and the renal function is favourable compared to open surgery, TLS and hand-assisted transperitoneal laparoscopic approaches. In conclusion, the results indicate that elevated IAP decreases GFR due to decreased CO and activation of the RAAS, which can be avoided with adequate hydration. Endoscopy can be facilitated if hand-assistance is applied and in particular hand-assisted retroperitoneoscopic nephrectomy shows advantages for the donor.

No description available.