京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21624号 / 医博第4430号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 福田 和彦, 教授 坂井 義治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Extracorporeal membrane oxygenation (ECMO) is a method that allows extracorporeal life support in potentially reversible life-threatening conditions affecting the heart or lungs which are refractory to conventional treatment. Depending on the parameters of its setting, this method affects the haemodynamics of the cardiovascular system and the perfusion of the target organ. From the point of view of its character, the necessity for invasive application, and the function thereof in the conditions of the cardiovascular system, ECMO is regarded as a risky method accompanied by a number of complications. Among the critical complications are thromboembolic complications affecting the central nervous system (CNS) and haemorrhagic complications. The goal of this paper is to present and verify the prerequisites for the formation of periprocedural embolisms affecting the CNS and to evaluate the regional haemodynamics of the CNS. This is done by analysing the presence of embolisms and by analysing the parameters of blood flow rates in the right common carotid artery (arteria carotis communis-ACC) and the corresponding oxygenation of the brain tissue during various flow rate parameters generated by the ECMO support on induced heart failure in a biological porcine model. In the first section of the paper, 8...

ExtraCorporeal Membran Oxygenering (framgent ECMO) är en mycket användbar behandling i situationer där patientens tillstånd är kritiskt. ECMO kan potentiellt öka chanserna att överleva avsevärt för patienter som annars skulle avlida till följd av sina hjärt- eller lungproblem. Behandlingen är dock inte helt riskfri, utan komplikationer såsom tromboembolism och invärtes blödningar är vanliga. Dessa associeras båda med rapportens huvudsakliga ämne, nämligen blodplättsaktivering. Denna företeelse är en konsekvens av den icke fysiologiska miljö som slangsystemet utgör. Trombocyter (blodplättar) som utsätts för de höga skjuvspänningar och hastigheter i kombination med långa stillestånd i stagnationspunkter, löper ökad risk att aktiveras och därmed producera ansamlingar av koagulerat blod runtom i olika delar av systemet. I den här rapporten var kopplingarna, som utgör skarvar där olika delar av systemet kopplas samman, av intresse. Simuleringarna för att analysera kopplingarna i olika konfigurationer utfördes med hjälp av ANSYS Fluent på Parallelldatorcentrums (PDC) Beskow och Tegner. Det visade sig att flera kopplingar på rad ökade residenstiden för en individuell partikel mer än vad som vore väntat ifall resultaten från lika många enskilda koppling adderades. Från detta drogs slutsatsen att ett reducerat antal kopplingar är att föredra då det bidrar till att minska den totala blodplättsaktiveringen och därmed minska risken att patienten får komplikationer.

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Objectives: To compare optical values in the osteotomy gap created after a Tibial Tuberosity Advancement (TTA) treated with autogenous cancellous bone graft (ACBG), extracorporeal shock wave therapy (ESWT), a combination of ACBG and ESWT, and absence of both ACBG and ESWT using densitometry. Methods: Dogs presenting for surgical repair of a cranial cruciate ligament rupture were randomly assigned to one of four groups; TTA with ACBG (TTA-G), TTA with ACBG and ESWT (TTA-GS), TTA with ESWT (TTA-S), and TTA with no additional therapy (TTA-O). Mediolateral radiographs at 0, 4 and 8 weeks after surgery were evaluated to compare healing of the osteotomy gap via densitometry. An analysis of variance (ANOVA) statistical analysis was used to compare the densitometric values between groups. Results: At 4 weeks after surgery, a significant difference in osteotomy gap density was noted between TTA-GS (8.4 millimeters of Aluminum equivalent [mmAleq]) and TTA-S (6.1mmAleq), and between TTA-GS (8.4 mmAleq) and TTA-O (6.4 mmAleq). There were no significant differences noted between groups at the 8 week recheck. Clinical Significance: There were no significant differences in the osteotomy gap density at 8 weeks after surgery regardless of the treatment modality used. The combination of ACBG and ESWT may lead to increased density of the osteotomy gap in the first 4 weeks after surgery. Densitometry using an aluminum step wedge is a feasible method for comparison of bone healing after TTA in dogs. / Master of Science

INTRODUÇÃO E OBJETIVO: A disfunção erétil (DE) em pacientes transplantados renais é frequente. A modalidade de tratamento ideal não deve interferir com a função do enxerto. A terapia de onda de choque extracorpórea de baixa intensidade (TOCE) tem atraído interesse devido às suas propriedades angiogênicas e mostrou resultados interessantes quando usada para tratar pacientes com doença cardiovascular e em homens com DE. Nosso objetivo é estudar a eficácia e segurança da TOCE para o tratamento da DE de provável etiologia vascular em homens transplantados renais. MÉTODOS: Foram selecionados 20 homens (média de idade = 53,7 anos, 46 a 61 anos) que foram submetidos a transplante de rim há pelo menos 6 meses e com DE há pelo menos 6 meses. O estudo foi duplo-cego, realizado em um único centro, prospectivo, randomizado e placebo-controlado. Dez pacientes foram randomizados para o grupo de terapia placebo e 10 pacientes para o grupo TOCE .O protocolo da TOCE consistiu em 2 sessões de tratamento por semana durante 3 semanas. O tratamento placebo foi realizado utilizando o mesmo dispositivo, porém com substituição do probe eficaz por um sem emissão de energia, mas que proporcionava um som e uma sensação de pulso durante o tratamento. A avaliação pré-tratamento e do seguimento foi realizada com o Índice Internacional de Função Erétil-5 (IIEF-5) e Escore de Rigidez Peniana (EHS) após 1, 3 e 12 meses. Ultra-sonografia Doppler do pênis com fármaco ereção foi realizada antes da terapia e após o tratamento (3 meses). RESULTADOS: Não houve diferença entre estes dois grupos no escore basal do IIEF-5 e EHS. No início do estudo, 1 e 3 meses após o último tratamento, o IIEF-5 no grupo TOCE foi de 10,9 ± 5,1, 15,6 ± 6,1 e 17,2 ± 5,7, respectivamente. O IIEF-5 no grupo placebo foi de 14,9 ± 3, 16,6 ± 5,4 e 16,5 ± 5, respectivamente. O comportamento entre os 2 grupos ao longo do tempo foi significativamente estatistico (p=0,0177). A melhora do escore IIEF-5 foi superior a 5 pontos em 70% (variou de 1-14) dos pacientes no grupo TOCE e em 10% (variou de 0-10) dos pacientes no grupo placebo, 3 meses após o tratamento. A análise após 12 meses foi realizada exclusivamente no grupo TOCE. A alteração média no IIEF-5 após 12 meses foi de 4,8 no grupo TOCE. A média do IIEF-5 após 12 meses foi de 15,7 ± 6,45, mostrando estabilidade da melhora inicial. No início do estudo, 1 e 3 meses após o último tratamento, o EHS no grupo TOCE foi de 2 ± 1,05, 2,5 ± 0,85 e 2,6 ± 0,84, respectivamente. O EHS no grupo placedo foi de 2 ± 0,67, 2,4 ± 0,7 e 2,4 ± 0,7, respectivamente. Percebemos um comportamento semelhante nos dois grupos (p=0,724). No grupo TOCE, notamos um EHS médio um pouco maior após 3 meses. Os parâmetros da ultra-sonografia doppler peniana não diferiram entre os grupos e não apresentaram melhoras significativas. CONCLUSÕES: A TOCE é um tratamento não farmacológico com eficácia clínica em homens transplantados renais com DE. Além do seu potencial de reabilitação, é viável e eficaz. Não verificamos impacto nos parâmetros do doppler peniano apesar do efeito da neoangiogênese do método / INTRODUCTION AND OBJECTIVE: Erectile dysfunction (ED) in kidney transplant patients is frequent. The ideal treatment modality should not interfere with the graft function. Low-intensity Extracorporeal Shock Wave Therapy Extracorporeal (Li-ESWT) has been of interest due to its angiogenic properties and has shown interesting results when used to treat patients with cardiovascular disease and non-transplanted men with ED. Our objective is to study the efficacy of Li-ESWT for the treatment of ED of probable vascular etiology in kidney transplanted men. METHODS: Twenty men (mean age = 53.7 years, range 46 to 61 years) that have been submitted to kidney transplant for at least 6 months and have been suffering from ED for at least 6 months were selected for the treatment. This was a double-blinded, single-center, prospective, randomized, placebo-controlled trial. Ten patients were randomized into the placebo therapy arm and 10 patients into the Li-ESWT arm. The Li-ESWT protocol consisted of a 2 treatment sessions per week for 3 weeks. The placebo treatment was performed using the same device replacing the effective probe for one that emits zero energy, but delivers a sound and pulse sensation during treatment. Initial and follow-up assessment was performed with International Index of Erectile Function Questionnaire-5 (IIEF-5) score and Erection Hardness Score (EHS) after 1, 3 and 12 months. Penile ultrasound Doppler with drug erection was performed before therapy and after treatment (3 months). RESULTS: There was no difference between these 2 groups in baseline IIEF-5 score and EHS. At baseline, 1 and 3 months after the last treatment, the IIEF-5 in the Li-ESWT group were 10.9 ± 5.1, 15.6 ± 6.1 and 17.2 ± 5.7, respectively. The IIEF-5 in the sham therapy group were 14.9 ± 3, 16.6 ± 5.4 and 16.5 ± 5, respectively. The interaction was significant (p = 0.0177), indicating significantly different behaviors between the groups over time. The IIEF-5 score improved to higher than 5 points in 70% (range, 1-14) of the patients in the Li-ESWT group and 10% (range, 0-10) of the patients in the placebo treatment group, 3 months after treatment. The analysis after 12 months was performed exclusively in the Li-ESWT group. The mean change in IIEF-5 after 12 months was 4.8 in the Li-ESWT group. The mean of the IIEF-5 score after 12 months was 15.7 ± 6.45, showing stability of the initial improvement. At baseline, 1 and 3 months after the last treatment, the EHSs in the Li-ESWT group were 2±1.05, 2.5±0.85, and 2.6±0.84, respectively. The EHSs in the sham treatment group were 2±0.67, 2.4±0.7, and 2.4±0.7, respectively. We noticed a similar behavior in both groups (P=0,724). In the Li-ESWT group, we noticed a slightly higher mean EHS after 3 months. Penile Doppler ultrasound parameters did not differ between groups and did not show significant improvements. CONCLUSIONS: Li-ESWT is a non pharmacological treatment with clinical efficacy in kidney transplant recipients with ED. Besides its restorative potential, this treatment is feasible and effective. Despite evidences suggesting neoagiogenesis, our protocol had no impact in penile Doppler parameters

Introduction : L’arrêt cardiaque réfractaire est défini par l’absence du retour à l’activité circulatoire spontané (RACS) après 30 minutes de réanimation cardiopulmonaire médicalisé. ExtraCorporeal Membrane Oxygenation (ECMO) représente une thérapie alternative urgente dans cette population. L’hémodynamique post la réanimation cardiopulmonaire extracorporel (E-CRP) est un entité complexe et le pris en charge dans les premières heures suivant l’implantation d’ECMO n’est pas bien décrit. L’objectif de cette étude est d’évaluer l’effet de deux stratégie de débit d’ECMO dans un modèle porcin d’arrêt cardiaque réfractaire sur les conséquences métaboliques, microcirculatoires et inflammatoires.Matériels et Méthodes : l’arrêt cardiaque a été induit par la ligature l’artère intraventriculaire antérieure (IVA) chez 18 cochons. E-RCP a été initié après 40 minutes de low-flow avec un débit d’ECMO bas de 30-35 ml.kg-1.min-1 ou un débit d’ECMO standard de 65-70 ml.kg-1.min-1, avec la même pression artérielle moyenne (PAM) au niveau de 65 mmHg. Les paramètres hémodynamiques et métaboliques ont été évalués avec la clairance de lactate et le débit sanguin carotidien. Les paramètres microcirculatoires ont été évalués par la microcirculation sublinguale avec l’imagerie de SDF et NIRS. Cytokines inflammatoires ont été mesurés avec un plateforme de ELISA multiplexe. Résultats : Pas de différence entre les deux groups à H basale et à l’initiation d’ECMO (H0). La clairance de lactate était plus faible dans le groupe débit bas comparé au groupe débit standard (6.67[-10.43-18.78] vs. 47.41[19.54, 70.69] %, p=0.04). Le débit carotidien était plus bas significativement (p<0.005) dans le groupe débit bas pendant les dernières quatre heures malgré le même niveau de la pression artérielle moyenne. Pour les paramètres microcirculatoires, le flux microcirculatoire sublingual évalué par SDF et le StO2 par NIRS ont été altéré transitoirement à H3 dans le groupe débit bas. Le niveau de cytokine IL-6 était plus élevé significativement dans le groupe débit bas à la fin d’expérimentation. Conclusions : Une réanimation à objectif de débit d’ECMO bas 35 ml.kg-1.min-1 versus standard 70ml.kg-1.min-1dans les six premières heures d’un ACR réfractaire n’est pas associé à une meilleure réversion des conséquences métaboliques, microcirculatoire et inflammatoire avec un objectif de PAM à 65 mmHg dans un modèle porcin / Introduction : Refractory cardiac arrest is defined by the absence of the return of spontaneous circulation (ROCS) within 30 minutes of cardiopulmonary resuscitation (CRP) under medical supervision. ExtraCorporeal membrane oxygenation (ECMO) is an emerging alternative therapy in this population. The post extracorporeal cardiopulmonary resuscitation (ECPR) hemodynamic state is a complex entity and the critical care management in the first hours following ECMO implantation is not well defined. This study was designed to assess the effect of two veno-arterial Extracorporeal Membrane Oxygenation (ECMO) blood-flow strategies in an experimental model of ECPR (extracorporeal cardio-pulmonary resuscitation) on macrocirculatory, metabolic and microcirculatory parameters in the first six hours of ECMO initiation. Material and methods : Cardiac arrest was induced in 18 pigs by surgical ligature of the left descending coronary artery. ECPR was initiated after 40 minutes of low-flow with an ECMO blood-flow of 30-35 ml.kg-1.min-1 (low-blood-flow group, LBF) or 65-70 ml.kg-1.min-1 (standard-blood-flow group, SBF), with the same mean arterial pressure target (65 mmHg). Macrocirculatory and metabolic parameters were assessed by lactate clearance and carotid blood-flow. Microcirculatory parameters were assessed by sublingual microcirculation with Sidestream Dark Field (SDF) imaging and peripheral Near-InfraRed Spectrometry (NIRS). Inflammatory cytokine levels were measured with a multiplexed ELISA-based array platform. Results : There was no between-group difference at baseline and at ECMO initiation (H0). Lactate clearance at H6 was lower in LBF compared to SBF (6.67[-10.43-18.78] vs. 47.41[19.54, 70.69] %, p=0.04). carotid blood flow was significantly lower (p<0.005) during the last four hours despite similar mean arterial pressure levels. For microcirculatory parameters, SDF and NIRS parameters were transitorily impaired at H3 in LBF. IL-6 cytokine level was significantly higher in LBF at the end of the experiment. Conclusion: In an experimental porcine model of refractory cardiac arrest treated by ECMO, a low-blood-flow strategy during the first six hours of resuscitation was associated with lower lactate clearance and lower cerebral blood-flow with no benefits on ischemia-reperfusion parameters

Ziel der Arbeit ist die Beurteilung der biochemischen Stoffwechselaktivität eines hybriden, extrakorporalen Leberunterstützungssystems während initialer therapeutischer Anwendungen. Das System basiert auf der Nutzung porciner Hepatozyten, die in einem Bioreaktor kultiviert werden. Acht Patienten in akutem Leberversagen, Komagrad III-IV, wurden unter kontinuierlicher Plasmaseparation mit dem System behandelt. Es wird ein Modell zur Bestimmung der Netto-Stoffwechselbilanz des Bioreaktors vorgestellt. Dieses Modell basiert auf der gleichzeitigen Bestimmung von Stoffkonzentrationen im Patientenplasma, gewonnen vom Patienten direkt und nach Durchfließen des Bioreaktors in bestimmten Zeitintervallen. Die Stoffwechselaktivität des Bioreaktors bezüglich der Stoffe Ammonium, Glutamin, Harnstoff, porcines Albumin, Glucose und Laktat wird dargestellt. Fünf der sieben eingesetzten Bioreaktoren nahmen kontinuierlich Ammonium auf, sechs von sieben Bioreaktoren synthetisierten Harnstoff und alle Bioreaktoren synthetisierten porcines Albumin. Die Ergebnisse zeigen, daß die Parameter Harnstoff und Ammonium am besten geeignet sind, Aussagen über die Stoffwechselaktivität der Bioreaktoren während der Therapie zu liefern. Porcines Albumin kann retrospektiv als Kontrolle der Syntheseleistung eingesetzt werden, steht aber nicht während der Therapie zur Verfügung. Die Bilanzierung von Glucose wird am stärksten durch äußere Einflußfaktoren gestört. Laktat stellt sich als ungeeignet für eine Verlaufskontrolle heraus, weil die Bioreaktoren die stark schwankenden Patientenplasmaspiegel nur unwesentlich beeinflussen konnten. / A hybrid liver support system based on porcine liver cells was investigated in patients suffering from acute liver failure, coma stage III-IV. The biochemical activity of the system during the application was studied. Patient plasma was drawn systemically and after circulation through the bioreactor system at four hour intervals. A method is introduced that takes into account the rate of plasma flow and the differences in plasma concentration systemically and after circulation through the liver support system to determine the net release or uptake of metabolites such as ammonia, urea and glucose, glutamine, porcine albumine, lactate. Urea release was seen in 6 out of 7 bioreactors at all time points during treatment. Continuous ammonia uptake was seen in 5 out of 7 bioreactors used for treatment. Porcine albumine was seen in all patients. An active role of the system in glucose metabolism was observed. Lactate levels did not yield any information on bioreactor metabolic activity. All patients were bridged successfully to liver transplantation.

INTRODUÇÃO: Técnicas cirúrgicas de revascularização miocárdica sem o uso de circulação extracorpórea (CEC) trouxeram esperanças de resultados operatórios com menor dano sistêmico, menor ocorrência de complicações clínicas e menor tempo de internação hospitalar gerando expectativas de menor custo hospitalar. OBJETIVOS: Avaliar o custo hospitalar em pacientes submetidos à cirurgia de revascularização miocárdica com e sem o uso de CEC, em portadores de doença multiarterial coronária estável com função ventricular preservada. MÉTODOS: Os custos hospitalares foram baseados na remuneração governamental vigente. Foram acrescentados nos custos, o uso de orteses, próteses, complicações e intercorrências clinicas. Foram considerados o tempo e os custos da permanência na UTI e de internação hospitalar. Não foram consideradas remuneração de profissionais médicos e equipe multiprofissional, bem como depreciação de materiais, taxa de administração predial, água luz, telefone, alimentação, exames laboratoriais de admissão e medicamentos. RESULTADOS: Entre janeiro de 2002 a Agosto de 2006 foram randomizados 131 pacientes para cirurgia com CEC e 128 pacientes sem CEC. As características clínicas basais foram semelhantes para os dois grupos. Os custos das intercorrências cirúrgicas foram significantemente menores (p<0,001) para pacientes do grupo SCEC comparados ao grupo CCEC (606,00 ± 525,00 vs 945,90 ± 440,00) bem como, os custos na UTI (432,20 ± 391,70 vs 717,70 ± 257,70) respectivamente. Entretanto, o custo final foi maior no grupo SCEC (6.877,00 ± 525,20 vs 5.305,00 ± 440,11; p<0.001) devido ao preço do estabilizador utilizado. Os tempos de permanência na sala cirúrgica foram (4,9 ± 1,1h vs 3,9 ± 1,0h), (p<0,001), na UTI (48,25 ± 17,2h vs 29,20 ± 26,1h) (p<0,001), com tempo de entubação (9,2 ± 4,5h vs 6,4 ± 5,1h) (p<0,001) para pacientes do grupo com CEC e sem CEC respectivamente. CONCLUSÃO: Esses resultados permitem concluir que a cirurgia de revascularização miocárdica sem circulação extracorpórea, proporcionou diminuição de custos operacionais relacionados com a diminuição de tempo de permanência em cada setor do tratamento cirúrgico. Todavia, o alto custo do estabilizador, determinou o aumento do custo final da cirurgia SCEC. / INTRODUCTION: Techniques of coronary artery bypass grafting without the use of cardiopulmonary bypass (CPB) aim surgical results with less systemic damage, lower incidence of clinical complications and shorter hospitalization, generating expectations of lower hospital costs. OBJECTIVE: To evaluate the hospital cost in patients undergoing coronary artery bypass grafting with and without the use of CPB, in patients with multivessel coronary disease with stable preserved ventricular function. METHODS: Hospital costs were based on the current local government payment for the cardiac surgery. The use of orthoses, prostheses, and the clinical complications events were added in the cost. It was also added the duration of staying at ICU and total hospitalization period in the final cost. Yet, it was not considered remuneration of medical professionals as well as the cost of the depreciation of equipment, administration fee of land, water, electricity, phone, food, laboratory tests for admission and medicines. RESULTS: From January 2002 to August 2006, 131 patients and 128 patients were randomized for surgery with CPB and without CPB, respectively. The baseline characteristics were similar for both groups. The cost of surgical complications of the group without CPB were significantly lower compared to the group with CPB (606.00 ± 525.00 vs 945, 90 ± 440.00, p <0,001); as well as, the costs of ICU (432, 20 ± 391.70 vs 717.70 ± 257.70, p<0,001). Yet, the final cost was higher in the without CPB group (6.877,00 ± 525,20 vs 5.305,00 ± 440,11; p<0.001) due to the price of the Octopus stabilizer. Additionally, the occupation time at the operating room was (4.9 ± 1.1h vs 3, 9 ± 1.0h, p<0,001), at the ICU was (48.25 ± 17.2h vs 29, 20 ± 26.1h, p<0001) with intubations time (9.2 ± 4.5h vs 6, 4 ± 5.1h, p <0001) in the group with CPB and without CPB, respectively. CONCLUSION: These results showed that the coronary artery bypass grafting without cardiopulmonary bypass has decreased operational costs related to reduce length of stay in each sector of the surgical procedure. However, the high cost of the stabilizer lead to increased final cost of SCEC surgery.

Introdução: Adrenomedulina, peptídeo recentemente identificado, atua como mediador em diversos estados fisiológicos e patológicos, sendo expresso em inúmeros tecidos. Níveis elevados de adrenomedulina foram observados em quadros inflamatórios e sépticos, além de atividade inibitória da adrenomedulina sobre a liberação de insulina, o que poderia contribuir para a gênese e manutenção dos quadros hipeglicêmicos, situação comum em pacientes pediátricos internados em unidades de terapia intensiva, tendo sido comprovado que o controle glicêmico melhora o prognóstico nesses pacientes. O objetivo do estudo foi relacionar as concentrações de adrenomedulina com alterações de hormônios do eixo hipófise-adrenal e o controle glicêmico de crianças submetidas à cirurgia cardíaca com circulação extracorpórea (CEC) representando modelo de síndrome da resposta inflamatória sistêmica. Material e métodos: Foram incluídas 20 crianças com idade entre 11-84 meses submetidas à cirurgia cardíaca com CEC. Foram avaliadas concentrações sangüíneas de glicose, insulina, peptídeo-C, cortisol, ACTH, interleucina-6 e adrenomedulina nos tempos pré-CEC, pós-CEC, 1ºPO, 2ºPO e 3ºPO. Os resultados foram expressos em medianas e inter-quartis. Todas crianças receberam antibioticoterapia profilática (Cefuroxima 150mg/kg) e metilprednisolona (30mg/kg) na indução anestésica. Resultados: Adrenomedulina aumentou de 1,13 ng/mL (0.83 1.81) pré- CEC a 3,28 ng/mL (1.82 4.25) no 1ºPO (p=0,0005). A insulina e o peptídeo-C apresentaram queda do tempo pré-CEC ao 1ºPO: 10,9 U/mL (10.5 13.6) a 2,88 U/mL (1.68 3.46) (p= 0,0001) e 1,44 (0.93 2.08) a 0.89 ng/mL (0.58 2.06) (p=0,076), respectivamente. Houve aumento da glicemia de 86,5 mg/dL (67 88) pré-CEC a 169 mg/dL (153 201) no 1ºPO (p=0,0001). Não houve alterações significativas das concentrações de cortisol e ACTH. Após a CEC todas as concentrações de interleucina-6 encontravam-se elevadas retornando aos valores normais no 3ºPO. Houve correlação negativa entre as concentrações de peptídeo-C e de adrenomedulina no 1ºPO (R= - 0,70 - p< 0,0009). Conclusão: os resultados deste estudo indicam que a adrenomedulina possa ter contribuído para a gênese e manutenção da hiperglicemia em pacientes pediátricos com SRIS, agindo por intermédio da redução das concentrações de insulina e do peptídeo-C / Background: Adrenomedullin (AM), a recently identified vasoactive peptide, is expressed in a large number of tissues and was found to be increased in some pathophysiologic conditions such as sepsis and Systemic Inflammatory Response Syndrome (SIRS). It has been shown that AM inhibits insulin secretion by means of a direct action on pancreatic -cells thus contributing to the genesis and sustaining of hypeglicemia, a common condition in critically ill pediatric patients. Therefore, the strict control of glucose concentrations has proved beneficial and associated to decrement of morbimortality rates in adults and children. The aim of the present study was to monitor serum adrenomedullin concentration in parallel with interleukin-6, plasma glucose, insulin and C-peptide, as well as ACTH and cortisol in pediatric patients submitted to cardiac surgery and cardiopulmonary bypass (CPB) representing a SIRS model. Methods: Twenty children aged 11-84 months who underwent cardiac surgery requiring cardiopulmonary bypass were prospective studied. Blood glucose, insulin, C-peptide, adrenocorticotropic hormone, cortisol, interleukin- 6 and AM were measured immediately before cardiopulmonary bypass (BCPB), immediately after CPB, on the first (POD1), second (POD2) and third days (POD3) after surgery. Data were expressed by median values and inter quartile range. All children received profilatic antibiotic (cefuroxime 150mg/kg) and methylprednisolone (30mg/kg) during induction of anesthesia. Results: Adrenomedullin increased from 1.13 ng/mL (0.83 1.81) BCPB to 3.28 ng/mL (1.82 4.25) in POD1 (p=0.0005). Insulin dropped from 10.9 U/mL (10.5 13.6) BCPB to 2.88 U/mL (1.68 3.46) in POD1 (p=0.0000). C-peptide decreased from 1.44 (0.93 2.08) BCPB to 0.89 ng/mL (0.58 2.06) in POD1 (p=0.076). Glucose increased from 86.5 mg/dL (67 88) BCPB to 169 mg/dL (153 201) in POD1 (p=0.0000). No significant changes were observed in ACTH and cortisol levels. After CPB, IL-6 concentrations of all patients were significantly increased and returned to basal values in POD3 (p=0.0009). There was a negative correlation between C-peptide an adrenomedullin in POD1 (R= - 0.70 - p< 0.0009). Conclusion: Our results indicate that adrenomedullin might be partly responsible for the genesis and sustaining of hyperglycemia in pediatric SIRS patients, by means of the decrement of insulin and C- peptide levels