Abstract Background Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Methods Twenty pigs were randomly assigned to Control group (n = 10), which received saline solution; or to Sildenafil group (n = 10), which received sildenafil orally (100 mg). After 30 minutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4 µg.kg-1.h-1) for 180 minutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNFα, IL-1β, IL6, and IL10) and troponin I response. Results Significant hemodynamic alterations were observed after 30 minutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19 ± 2 mmHg to LPS30 52 ± 4 mmHg, p< 0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411 ± 29 to LPS180 334 ± 49, p< 0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35 ± 4 mmHg at LPS30, p< 0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. Conclusion Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

OBJECTIVES: The anesthetic gas xenon is reported to preserve hemodynamic stability during general anesthesia. However, the effects of the gas during shock are unclear. The objective of this study was to evaluate the effect of Xe on hemodynamic stability and tissue perfusion in a canine model of hemorrhagic shock. METHOD: Twenty-six dogs, mechanically ventilated with a fraction of inspired oxygen of 21% and anesthetized with etomidate and vecuronium, were randomized into Xenon (Xe; n = 13) or Control (C; n = 13) groups. Following hemodynamic monitoring, a pressure-driven shock was induced to reach an arterial pressure of 40 mmHg. Hemodynamic data and blood samples were collected prior to bleeding, immediately after bleeding and 5, 20 and 40 minutes following shock. The Xe group was treated with 79% Xe diluted in ambient air, inhaled for 20 minutes after shock. RESULT: The mean bleeding volume was 44 mL.kg-1 in the C group and 40 mL.kg-1 in the Xe group. Hemorrhage promoted a decrease in both the cardiac index (p<0.001) and mean arterial pressure (p<0.001). These changes were associated with an increase in lactate levels and worsening of oxygen transport variables in both groups (p<0.05). Inhalation of xenon did not cause further worsening of hemodynamics or tissue perfusion markers. CONCLUSIONS: Xenon did not alter hemodynamic stability or tissue perfusion in an experimentally controlled hemorrhagic shock model. However, further studies are necessary to validate this drug in other contexts.

OBJECTIVE: The standard therapy for patients with high-level spinal cord injury is long-term mechanical ventilation through a tracheostomy. However, in some cases, this approach results in death or disability. The aim of this study is to highlight the anesthetics and perioperative aspects of patients undergoing insertion of a diaphragmatic pacemaker. METHODS: Five patients with quadriplegia following high cervical traumatic spinal cord injury and ventilator-dependent chronic respiratory failure were implanted with a laparoscopic diaphragmatic pacemaker after preoperative assessments of their phrenic nerve function and diaphragm contractility through transcutaneous nerve stimulation. ClinicalTrials.gov: NCT01385384. RESULTS: The diaphragmatic pacemaker placement was successful in all of the patients. Two patients presented with capnothorax during the perioperative period, which resolved without consequences. After six months, three patients achieved continuous use of the diaphragm pacing system, and one patient could be removed from mechanical ventilation for more than 4 hours per day. CONCLUSIONS: The implantation of a diaphragmatic phrenic system is a new and safe technique with potential to improve the quality of life of patients who are dependent on mechanical ventilation because of spinal cord injuries. Appropriate indication and adequate perioperative care are fundamental to achieving better results.

BACKGROUND: The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days). A p-value of <0.05 was considered significant. RESULTS: The anthropometric and clinical characteristics of the patients from each group were similar, except for weight and body mass index. The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group (p<0.0016). There were no differences between groups regarding clinical outcomes, including the duration of mechanical ventilation, length of stay in the intensive care unit, blood transfusion, postoperative infection, hypoglycemic event, neurological dysfunction or 30-day mortality (p>0.05). CONCLUSIONS: In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.

The pandemic novel influenza A (H1N1) infection was considered widespread in Brazil on July, 2009. Since then, 9.249 cases were confirmed in Brazil, most of them concentrated in São Paulo. The Hospital das Clínicas of the University of São Paulo is a reference center for H1N1 cases in São Paulo. The purpose of this review is to analyze the evidence concerning diagnosis, prevention, and treatment of novel influenza A (H1N1) infection. In addition, we propose guidelines for the management of this pandemic emphasizing Hospital das Clínicas "bundles" for the control of the pandemic novel influenza A (H1N1).

The pandemic novel influenza A (H1N1) infection was considered widespread in Brazil on July 16, 2009. Since then, 46,810 cases of acute respiratory syndrome have been reported in Brazil, most of them concentrated in São Paulo. Through September 16, we have confirmed 9,249 cases of novel influenza A H1N1in Brazil, including 699 deaths. The mortality rate observed in Brazil is 0.47/100,000 inhabitants and varies according to region. In this period, São Paulo registered 3733 cases (40.3% of the total) of novel influenza A (H1N1) infection and 327 deaths, reflecting a mortality rate of 0.79/100,000 inhabitants. The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC) is a reference center for H1N1 cases in São Paulo. During the winter of 2009, 472 patients in this hospital were diagnosed with H1N1 infection; of these, 210 were admitted, and 16 died. To control this pandemic and to provide adequate care for these patients, the Hospital das Clínicas implemented "bundles" including prevention strategies, an epidemiologic surveillance service, availability of fast diagnosis, antiviral treatment and training of staff. The purpose of this manuscript is to describe the epidemiologic features of novel human influenza A (H1N1) infection in the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo during the winter period of the 2009 pandemic.

JUSTIFICATIVA E OBJETIVO: A isquemia miocárdica perioperatória é um evento comumente observado no período perioperatório podendo aumentar significativamente a morbimortalidade pós-cirúrgica. As propriedades cardioprotetoras dos anestésicos voláteis e dos opióides têm sido estudadas durante algumas décadas e hoje constituem poderosas ferramentas no manuseio de pacientes com doença coronariana isquêmica. O objetivo desta revisão foi fornecer fundamentos da proteção miocárdica por precondicionamento. CONTEÚDO: Serão discutidos os conceitos sobre lesão celular decorrente de isquemia e reperfusão, precondicionamento isquêmico (PCI), precondicionamento anestésico (PCA), assim como os mecanismos de proteção miocárdica. Estudos recentes em cirurgia cardíaca demonstram que a aplicação de curtos períodos de isquemia, durante a reperfusão, podem reduzir a área de infarto do miocárdio. Os anestésicos voláteis também podem apresentar efeito protetor na reperfusão miocárdica. Independentemente da via de sinalização que leva ao precondicionamento, tanto aqueles que envolvem anestésicos quanto o isquêmico, considera-se que os canais de KATP dependentes mitocondriais sejam os mediadores finais de cardioproteção por controlarem o influxo de cálcio na mitocôndria e prevenirem a indução da necrose e apoptose. Apesar do PCI e PCA efetivamente reduzirem a área de infarto do miocárdio e melhorarem a função ventricular pós-operatória, é importante salientar que esses tratamentos devem ser anteriores ao evento isquêmics no sentido de justificar sua aplicabilidade clínica. CONCLUSÕES: Os fenômenos conhecidos como precondicionamento isquêmico e precondicionamento anestésico do miocárdi, são bem conhecidos, sendo o mecanismo de proteção similar em ambas as situações, porém nem todos os passos que levam a esta proteção foram completamente esclarecidos. Mais investigações são necessária, para que as propriedades cardioprotetoras dos agentes anestésicos possam ter aplicabilidade clínica crescente.

BACKGROUND AND OBJECTIVES: Perioperative myocardial ischemia is commonly observed, and it can increase significantly postoperative morbidity and mortality. The cardioprotective properties of volatile anesthetics and opioids have been studied during several decades and currently constitute powerful tools in the management of patients with ischemic coronariopathy. The objective of this review was to provide the fundaments of myocardial protection by preconditioning. CONTENTS: The concepts of cellular damage secondary to ischemia and reperfusion, ischemic preconditioning (IPC), and anesthetic preconditioning (APC), as well as the mechanisms of myocardial protection, are discussed. Recent studies in cardiac surgery demonstrated that the use of short periods of ischemia during reperfusion can reduce the area of myocardial infarction. Volatile anesthetic can also have a protective effect in myocardial reperfusion. Independently of the signaling pathway that leads to preconditioning, both anesthetic and ischemic, mitochondrial dependent KATP channels are considered the final mediators of cardioprotection by controlling the mitochondrial influx of calcium and, therefore, preventing the induction of necrosis and apoptosis. Although IPC and APC effectively reduce the area of myocardial infarction and improve postoperative ventricular function, it is important to stress that those treatments should be instituted before ischemic events to justify their clinical applicability. CONCLUSIONS: Phenomena known as myocardial ischemic preconditioning and anesthetic preconditioning are well known, and the mechanism of protection is similar in both situations; however, not every step that leads to this protection has been fully explained. Further studies are necessary to increase the clinical applicability of the cardioprotective properties of anesthetics.

JUSTIFICATIVA Y OBJETIVO: La isquemia miocárdica perioperatoria es un evento generalmente observado en el período perioperatorio pudiendo aumentar significativamente para la morbi-mortalidad posquirúrgica. Las propiedades cardioprotectoras de los anestésicos volátiles y de los opioides, han sido estudiadas durante algunas décadas y hoy por hoy se han convertido en poderosas herramientas para el manejo de pacientes con enfermedad coronaria isquémica. El objetivo de esta revisión fue el de ofrecer bases sobre la protección miocárdica por precondicionamiento. CONTENIDO: Se discutirán los conceptos sobre lesión celular proveniente de la isquemia y de la reperfusión, precondicionamiento isquémico (PCI), precondicionamiento anestésico (PCA), como también los mecanismos de Protección miocárdica. Recientes estudios en cirugía cardíaca demostraron que la aplicación de cortos períodos de isquemia, durante la reperfusión, puede reducir el área de infarto del miocardio. Los anestésicos volátiles también pueden presentar un efecto protector en la reperfusión miocárdica. Independientemente de la vía de señalización que conlleva al precondicionamiento, tanto los que envuelven anestésicos como el isquémico, se considera que los canales de KATP dependientes mitocondriales sean los mediadores finales de la cardio protección por controlar el influjo de calcio en la mitocondria y prevenir la inducción de la necrosis y de la apoptosis. A pesar de que el PCI y el PCA de hecho reduzcan el área de infarto del miocardio y mejoren la función ventricular postoperatoria, es importante destacar que esos tratamientos deben ser anteriores al evento isquémico en el sentido de justificar su aplicabilidad clínica. CONCLUSIONES: Los fenómenos conocidos como precondicionamiento isquémico y precondicionamiento anestésico del miocardio, son muy conocidos, siendo el mecanismo de protección similar en ambas situaciones, sin embargo no todos los pasos que conllevan a esa protección fueron completamente aclarados. Más investigaciones se hacen necesarias para que las propiedades cardioprotectoras de los agentes anestésicos puedan tener aumentada su aplicabilidad clínica.

JUSTIFICATIVA E OBJETIVOS: O colapso pulmonar intra-operatório é uma complicação de elevada incidência em pacientes submetidos à intervenção cirúrgica sob anestesia geral com relaxamento/paralisia da musculatura. Essa complicação está associada à piora das trocas gasosas no intra-operatório e, em alguns casos, necessidade de suporte respiratório prolongado no período pós-operatório. Os objetivos deste estudo foram revisar os aspectos fisiopatológicos da formação de atelectasias durante anestesia geral e as possíveis manobras terapêuticas para prevenir e tratar essa complicação. CONTEÚDO: Nesta revisão, os conceitos sobre a incidência de atelectasias intra-operatórias, os fatores relacionados com o seu desenvolvimento, tanto mecânicos quanto associados ao ajuste do respirador durante procedimento cirúrgico, os aspectos do diagnóstico e as estratégias de prevenção e tratamento foram abordados de maneira sistemática. CONCLUSÕES: A compreensão dos mecanismos relacionados com o desenvolvimento do colapso pulmonar durante o período intra-operatório, assim como o seu tratamento, pode contribuir para a redução da incidência de complicações pulmonares pós-operatórias, o tempo de recuperação e os custos hospitalares.

BACKGROUND AND METHODS: The incidence of intraoperative pulmonary collapse is elevated in patients undergoing surgery under general anesthesia with muscle relaxation/paralysis. This complication is associated with worsening intraoperative gas exchange and, in some cases, the need for prolonged postoperative respiratory support. The objective of this report was to review the pathophysiological aspects of atelectasis during general anesthesia and possible therapeutic maneuvers that could prevent and treat this complication. CONTENTS: This review discusses the concepts about the incidence of intraoperative atelectasis, factors that influence their development, both mechanical and those related to mechanical ventilator settings during the surgery, diagnostic criteria, and strategies to prevent and treat this complication. CONCLUSIONS: Understanding of the mechanisms related with the development of intraoperative pulmonary collapse, as well as its treatment, can contribute to reduce the incidence of postoperative pulmonary complications, the length of recovery and hospital costs.

JUSTIFICATIVA Y OBJETIVOS: El colapso pulmonar intraoperatorio es una complicación de elevada incidencia en pacientes sometidos a la intervención quirúrgica bajo anestesia general con relajamiento/parálisis de la musculatura. Esta complicación está asociada al empeoramiento de los cambios de gas en el intraoperatorio y en algunos casos, necesidad de soporte respiratorio prolongado en el período postoperatorio. Los objetivos de este estudio fueron los de revisar los aspectos fisiopatológicos de la formación de atelectasias durante anestesia general y las posibles maniobras terapéuticas para prevenir y tratar esa complicación. CONTENIDO: En esta revisión, los conceptos sobre la incidencia de atelectasias intraoperatorias, los factores relacionados a su desarrollo, tanto mecánicos como los relacionados al ajuste del respirador durante el procedimiento quirúrgico, los aspectos del diagnóstico y las estrategias de prevención y tratamiento fueron abordados de manera sistemática. CONCLUSIONES: La comprensión de los mecanismos relacionados al desarrollo del colapso pulmonar durante el período intraoperatorio, como también su tratamiento, pueden contribuir para la reducción de la incidencia de complicaciones pulmonares postoperatorias, el tiempo de recuperación y los costes de las internaciones en los hospitales.

O Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo é centro de excelência para tratamento das cardiopatias congênitas que abranjam o período neonatal e pediátrico. Nos últimos anos, parte dos excelentes resultados cirúrgicos da Instituição devem-se ao progresso da anestesia e a estruturação dos cuidados pós-operatórios por meio de protocolos bem definidos. Este artigo se propõe a revisar aspectos de interesse da fisiologia cardiovascular do neonato, as repercussões orgânicas da circulação extra-corpórea, o pós-operatório imediato, incluindo avaliação cardiovascular e a terapia farmacológica desta Unidade. Será apresentada uma revisão das causas mais comuns de baixo débito; cirurgias para a correção das cardiopatias congênitas e propostas de métodos diagnósticos e terapêuticos, baseados na literatura especializada e protocolos da Unidade.

The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

A associação de paralisia diafragmática bilateral e paralisia da cintura escapular é uma complicação rara após correção de aneurisma de aorta ascendente. Esta associação leva à uma forma grave de insuficiência respiratória cujo sucesso do desmame da ventilação mecânica é dependente da capacidade da musculatura respiratória remanescente em compensar o trabalho respiratório excedente. Fisioterapia respiratória intensiva com treinamento da musculatura, correção dos distúrbios metabólicos, tratamento das infecções respiratórias associadas à ventilação mecânica e otimização do suporte nutricional foram fundamentais para o sucesso do desmame.

The association of bilateral diaphragmatic paralysis and scapular girdle paralysis is a rare complication after aortic aneurysm correction. Such a complication induces to a severe form of hypercapnic respiratory failure in which the success of weaning from mechanical ventilation depends on the capacity of remaining respiratory muscles to compensate extra respiratory work load. Intensive respiratory physiotherapy with muscle training, hydroelectrolityc inbalances correction, treatment of ventilation associated infections and a well planned nutritional support were essential to the successful weaning of mechanical ventilation.