When spontaneous breathing (SB) is allowed during mechanical ventilation (MV), atelectatic lung areas are recruited and oxygenation improves thereby. Whether unsupported SB at its natural pattern (without PEEP and at low pressure/small tidal volume) equally recruits and improves oxygenation, and if so by which mechanism, has not been studied. A porcine lung collapse model was designed to study this question. The cardiac output dependency of the pulmonary shunt was investigated with healthy lungs and with major shunt (during one-lung ventilation) and with SB, MV and continuous positive airway pressure (CPAP). The hypoxic pulmonary vasoconstriction (HPV) was blocked with sodium nitroprusside (SNP) to see whether HPV is the only mechanism available for ventilation/perfusion (VA/Q) matching during MV and SB. In all experiments, respiratory rate and tidal volume during MV were matched to SB. Oxygenation was assessed by serial blood gas measurements, recruitment by thoracic CTs; pulmonary shunt was assessed by multiple inert gas elimination or venous admixture. SB attained better oxygenation and lower pulmonary shunt compared with MV, although it did not recruit collapsed lung. Pulmonary shunt did not correlate with cardiac output during SB, whereas a correlation was found during MV and CPAP. With blocked HPV, pulmonary shunt was considerably lower during SB than MV. In conclusion, SB improves VA/Q matching as compared with MV, even when no recruitment occurs. In contrast to MV and CPAP, cardiac output has no major effect on pulmonary shunt during SB. The improved VA/Q matching during SB despite a blocked HPV might indicate the presence of a SB-specific mechanism that improves pulmonary blood flow redistribution towards ventilated lung regions independent of or supplementary to HPV.

In patients affected by acute respiratory failure or acute respiratory distress syndrome (ARDS) the leading cause of death is failure of different vital organs other than the lungs, so called multiple organ dysfunction syndrome (MODS). The abdominal organs have a crucial role in the pathogenesis of this syndrome. There is a lack of knowledge regarding the mechanisms by which mechanical ventilation can affect the abdominal compartment. One hypothesis is that mechanical ventilation can interfere with abdominal fluid balance causing edema and inflammation. We addressed the question whether different levels of ventilatory support (mechanical ventilation with different levels of positive end-expiratory pressure, PEEP, and spontaneous breathing with or without PEEP) can influence abdominal edema and inflammation in both healthy and endotoxin-exposed animals. The effect on lymphatic drainage from the abdomen exerted by different degrees of ventilatory support was evaluated (paper I). We demonstrated that endotoxin increases abdominal lymph production, that PEEP and mechanical ventilation increase lymph production but also impede lymphatic drainage; spontaneous breathing improves lymphatic drainage from the abdomen. By adapting a non-invasive nuclear medicine imaging technique and validating it (paper II), we have been able to evaluate extravascular fluid accumulation (edema formation) in the abdomen over time (paper III) demonstrating that edema increases during endotoxemia, mimicking a sepsis-like condition, and that spontaneous breathing, compared to mechanical ventilation, reduces extravascular fluid. Pro-inflammatory cytokines TNF-α and IL-6 in intestinal biopsies are reduced during spontaneous breathing compared to mechanical ventilation. Abdominal edema results in increased intra-abdominal pressure (IAP): in paper IV we analyzed the effect of increased intra-abdominal pressure on the respiratory system. Pulmonary shunt fraction increased with high IAP both in healthy and LPS animals, resulting in decreased level of oxygenation. These changes are only partially reversible by reducing IAP. In conclusion, mechanical ventilation is a life-saving tool but the possible side effect at the extra-pulmonary level should be considered, and the introduction of some degree of spontaneous breathing when clinically possible is a suggested choice.

Background: In morbidly obese individuals (MO) cardiorespiratory comorbidities and body habitus challenge the perioperative management of anesthesia. To implement safe and reproducible routines for anesthesia and fluid therapy is the cornerstone in order to minimize anesthesia-related complications and to meet individual variability in rehydration needs. Methods: Paper I: Impact of rapid-weight-loss preparation prior to bariatric surgery was investigated. Prevalence of preoperative dehydration and cardiac function were assessed with transthoracic echocardiography (TTE). Paper II: The anesthetic technique for rapid sequence induction (RSI) in MO based on a combination of volatile and i.v. anesthetics was developed. Pre- and post-induction oxygenation, blood pressure levels and feasibility of the method was evaluated. Paper III: The preoperative ideal body weight based rehydration regime was evaluated by TTE. Paper IV: Need of rehydration during bariatric surgery was evaluated by comparing conventional monitoring to a more advanced approach (i.e. preoperative TTE and arterial pulse wave analysis). Results: Rapid-weight-loss preparation prior to bariatric surgery may expose MO to dehydration. TTE was shown to be a robust modality for preoperative screening of the level of venous return, assessment of filling pressures and biventricular function of the heart in MO. The combination of sevoflurane, propofol, alfentanil and suxamethonium was demonstrated to be a safe method for RSI regardless of BMI. The preoperative rehydration regime implemented by colloids 6 ml/kg IBW was an adequate treatment to obtain euvolemia. In addition, preoperative rehydration seems to increase hemodynamic stability during intravenous induction of anesthesia and even intraoperatively. Conclusion: This thesis describes a safe and comprehensive perioperative management of morbidly obese individuals scheduled for bariatric surgery. Hemodynamic and respiratory stability can be achieved by implementation of strict and proven methods of anesthesia and fluid therapy. Much focus should be placed on feasible monitoring and preoperative optimization in morbidly obese individuals for increased perioperative safety.

Objetivo: avaliar a eficácia da aplicação do teste de respiração espontânea (TRE) em predizer o sucesso da extubação em crianças com cardiopatia congênita no pósoperatório de cirurgia cardíaca, comparando-se com a aplicação do protocolo de desmame atualmente utilizado em centro de terapia intensiva pediátrico de hospital terciário. Desenho do estudo: ensaio clínico prospectivo randomizado controlado Pacientes: Foram elegíveis para o estudo pacientes de 0 a 18 anos de idade, no pósoperatório de cirurgia cardíaca para correção de cardiopatias congênitas, submetidos à ventilação mecânica (VM) pós-operatória por > 12 horas. Métodos: Os pacientes foram avaliados por um médico da equipe e os considerados aptos ao desmame foram selecionados para o estudo. Os pacientes randomizados ao grupo intervenção foram submetidos ao TRE (com PS de 10 cm H2O, PEEP de 5 cm H2O e FiO2 <= 50%, durante duas horas). Este teste foi realizado com ventilação em CPAP+PS. Os pacientes do grupo controle seguiram o desmame ventilatório de acordo com o protocolo vigente no CTIP do HCFMRP/USP. O desfecho primário foi considerado o sucesso da extubação, avaliado pela necessidade ou não de reintubação nas primeiras 48 horas após a extubação. Os desfechos secundários foram a duração da internação na UTI e no hospital, a incidência de pneumonia associada à ventilação e a mortalidade. Resultados: Foram alocadas no estudo 110 crianças (54 no grupo controle e 56 no grupo intervenção). Os dados demográficos, clínicos, as características cirúrgicas e os escores de gravidade, complexidade cirúrgica e de disfunção orgânica foram semelhantes nos dois grupos. Os pacientes submetidos ao TRE comparados ao grupo controle apresentaram maior sucesso de extubação (83% vs. 68.5%, p=0,02) e menor tempo de internação no CTIP (mediana 85 h vs. 367 h, p< 0,0001), respectivamente. Não houve diferença significativa entre os grupos no tempo de internação hospitalar, incidência de pneumonia associada à ventilação e mortalidade. Conclusões: O estudo mostra que o TRE é uma importante ferramenta de avaliação de prontidão à extubação. Os pacientes que foram alocados ao grupo de intervenção apresentaram maior sucesso de extubação e menor tempo de internação na UTI. / Objective: To evaluate the efficacy of the spontaneous breathing test (SBT) in predicting the success of extubation in children with congenital heart disease in the postoperative period of cardiac surgery compared with the application of the weaning protocol currently used in a pediatric intensive care unit. Study design: randomized controlled trial. Patients: Patients 0 to 18 years of age in the postoperative period following congenital heart surgery and on, mechanical ventilation (MV) for> 12 hours were eligible for the study. Methods: Patients were evaluated by a staff physician and those considered ready for weaning were selected for the study. Patients randomized to the intervention group underwent the SBT (with PS of 10 cm H2O, PEEP of 5 cm H2O and FiO2 <= 50% for two hours). This test was performed with CPAP + PS ventilation. The patients in the control group underwent ventilator weaning according to the current protocol in the PICU. The primary endpoint was success of extubation, defined as no need for reintubation in the first 48 hours following extubation. Secondary outcomes were duration of PICU and hospital stay, incidence of ventilator-associated pneumonia, and mortality. Results: 110 children (54 in the control group and 56 in the intervention group) were included in the study. Demographic, clinical, surgical, and severity scores, surgical complexity, and organ dysfunction were similar in both groups. Patients submitted to SBT compared to the control group had greater extubation success (83% vs. 68.5%, p = 0.02) and shorter length of stay in the PICU (median 85 h vs. 367 h, p <0.0001), respectively. There was no significant difference between the groups in length of hospital stay, incidence of ventilator-associated pneumonia and mortality. Conclusions: The study shows that the SBT is an important tool for assessment of extubation readiness. Patients who were allocated to the intervention group had greater extubation success and shorter PICU stay.

Objetivo: avaliar a eficácia da aplicação do teste de respiração espontânea (TRE) em predizer o sucesso da extubação em crianças com cardiopatia congênita no pósoperatório de cirurgia cardíaca, comparando-se com a aplicação do protocolo de desmame atualmente utilizado em centro de terapia intensiva pediátrico de hospital terciário. Desenho do estudo: ensaio clínico prospectivo randomizado controlado Pacientes: Foram elegíveis para o estudo pacientes de 0 a 18 anos de idade, no pósoperatório de cirurgia cardíaca para correção de cardiopatias congênitas, submetidos à ventilação mecânica (VM) pós-operatória por > 12 horas. Métodos: Os pacientes foram avaliados por um médico da equipe e os considerados aptos ao desmame foram selecionados para o estudo. Os pacientes randomizados ao grupo intervenção foram submetidos ao TRE (com PS de 10 cm H2O, PEEP de 5 cm H2O e FiO2 <= 50%, durante duas horas). Este teste foi realizado com ventilação em CPAP+PS. Os pacientes do grupo controle seguiram o desmame ventilatório de acordo com o protocolo vigente no CTIP do HCFMRP/USP. O desfecho primário foi considerado o sucesso da extubação, avaliado pela necessidade ou não de reintubação nas primeiras 48 horas após a extubação. Os desfechos secundários foram a duração da internação na UTI e no hospital, a incidência de pneumonia associada à ventilação e a mortalidade. Resultados: Foram alocadas no estudo 110 crianças (54 no grupo controle e 56 no grupo intervenção). Os dados demográficos, clínicos, as características cirúrgicas e os escores de gravidade, complexidade cirúrgica e de disfunção orgânica foram semelhantes nos dois grupos. Os pacientes submetidos ao TRE comparados ao grupo controle apresentaram maior sucesso de extubação (83% vs. 68.5%, p=0,02) e menor tempo de internação no CTIP (mediana 85 h vs. 367 h, p< 0,0001), respectivamente. Não houve diferença significativa entre os grupos no tempo de internação hospitalar, incidência de pneumonia associada à ventilação e mortalidade. Conclusões: O estudo mostra que o TRE é uma importante ferramenta de avaliação de prontidão à extubação. Os pacientes que foram alocados ao grupo de intervenção apresentaram maior sucesso de extubação e menor tempo de internação na UTI. / Objective: To evaluate the efficacy of the spontaneous breathing test (SBT) in predicting the success of extubation in children with congenital heart disease in the postoperative period of cardiac surgery compared with the application of the weaning protocol currently used in a pediatric intensive care unit. Study design: randomized controlled trial. Patients: Patients 0 to 18 years of age in the postoperative period following congenital heart surgery and on, mechanical ventilation (MV) for> 12 hours were eligible for the study. Methods: Patients were evaluated by a staff physician and those considered ready for weaning were selected for the study. Patients randomized to the intervention group underwent the SBT (with PS of 10 cm H2O, PEEP of 5 cm H2O and FiO2 <= 50% for two hours). This test was performed with CPAP + PS ventilation. The patients in the control group underwent ventilator weaning according to the current protocol in the PICU. The primary endpoint was success of extubation, defined as no need for reintubation in the first 48 hours following extubation. Secondary outcomes were duration of PICU and hospital stay, incidence of ventilator-associated pneumonia, and mortality. Results: 110 children (54 in the control group and 56 in the intervention group) were included in the study. Demographic, clinical, surgical, and severity scores, surgical complexity, and organ dysfunction were similar in both groups. Patients submitted to SBT compared to the control group had greater extubation success (83% vs. 68.5%, p = 0.02) and shorter length of stay in the PICU (median 85 h vs. 367 h, p <0.0001), respectively. There was no significant difference between the groups in length of hospital stay, incidence of ventilator-associated pneumonia and mortality. Conclusions: The study shows that the SBT is an important tool for assessment of extubation readiness. Patients who were allocated to the intervention group had greater extubation success and shorter PICU stay.