Efeitos protetores do exercício contra a disfunção do metabolismo energético induzida por sepse na musculatura esquelético de ratos

We evaluated effects of aerobic physical preconditioning on general performance and energy metabolism in skeletal muscle of septic rats. Forty-eight 10-wk-old male Wistar rats were randomly assigned to either Untrained or Trained groups. Aerobic exercise training protocol (AETP) consisted of an 8-week treadmill program. After AETP, performance was evaluated by graded treadmill and functional ambulation testing. Afterwards animals from both groups were randomly assigned to Sham or CLP surgery (cecal ligation and perforation), resulting in the following groups: Sham untrained (ShamU), CLP untrained (CLPU), Sham trained (ShamT), and CLP trained (CLPT). Two days after surgery, animals repeated the ambulation test, and were euthanized after this. Diaphragm, soleus and plantaris muscles were harvested. Mitochondrial electron transport chain enzyme (METC) and creatine kinase (CK) activity were measured. AETP led to significant improvement in performance of distance run and in skeletal muscle function of the Trained group. Forty-eight hours after surgery the CLPT group was able to maintain similar muscle performance as Sham groups. Dysfunction was shown in the diaphragm in METC complexes I and II-III and in locomotive soleus muscles in complex I; CK enzyme activity was significantly increased in sedentary CLPU group in soleus and plantaris muscle, but in the diaphragm there was only a tendency (p=0.07). CLPT animals that were submitted to AETP avoided all these negative results. Taken together our results provide evidence of the positive effects obtained with an aerobic physical preconditioning program on METC and CK enzyme activity related to the diaphragm and locomotive muscles mitigating sepsis-induced energy metabolism dysfunction.Foram avaliados os efeitos do pré-condicionamento físico aeróbico no desempenho geral e metabolismo energético na musculatura esquelética de ratos sépticos. Quarenta e oito ratos Wistar machos de dez semanas de idade foram aleatoriamente designados para os grupos "treinado" e "não treinado". O protocolo de treinamento de exercício aeróbico (AETP) consistiu de um programa de esteira de oito semanas. Depois do AETP, o desempenho foi avaliado pela esteira graduada e testes de deambulação funcional. Posteriormente, animais de ambos os grupos foram divididos aleatoriamente em Sham ou cirurgia CLP (ligação cecal e perfuração), resultando nos seguintes grupos: Sham não treinado (ShamU), CLP não treinado (CLPU), Sham treinado (ShamT) e CLP treinado (CLPT). Dois dias após a cirurgia, os animais repetiram o teste de deambulação e logo após foram sacrificados. O diafragma e os músculos sóleo e plantar foram colhidos. A atividade da enzima da cadeia mitocondrial transportadora de elétrons (METC) e da creatina quinase (CK) foi medida. A AETP levou a uma melhoria significativa no desempenho em corridas de longa distância e na função da musculatura esquelética do grupo treinado. Quarenta e oito horas após a cirurgia, o grupo CLPT foi capaz de manter um desempenho muscular semelhante ao dos grupos Sham. Foi mostrada disfunção no diafragma nos complexos METC I e II-III e nos músculos sóleos locomotivos no complexo I; a atividade da enzima CK sofreu aumento significativo no grupo CLPU sedentário em músculo sóleo e plantar, mas no diafragma havia apenas uma tendência (p=0,07). Os animais CLPT que foram submetidos ao AETP evitaram todos estes resultados negativos. Tomados em conjunto, nossos resultados fornecem evidências dos efeitos positivos obtidos com um programa de pré-condicionamento físico aeróbico em relação à atividade das enzimas METC e CK relacionada ao diafragma e aos músculos locomotivos atenuando a disfunção do metabolismo energético induzida por sepse.En este estudio se analizó los efectos del preacondicionamiento físico aeróbico en el rendimiento general y en el metabolismo energético de la musculatura esquelética de ratones sépticas. Se seleccionaron aleatoriamente 48 ratones Wistar con 10 semanas de edad, asignados en los grupos "entrenado" y "no entrenado". El protocolo de entrenamiento del ejercicio aeróbico (AETP) constituyó por un programa de tapiz rodante de ocho semanas. Tras el AETP se evaluó el rendimiento a través de tapiz rodante y de pruebas de deambulación funcional. En seguida, se dividieron aleatoriamente los ratones de ambos grupos en Sham o cirugía CLP (ligadura cecal y perforación), teniendo como resultados los grupos: Sham no entrenado (ShamU), CLP no entrenado (CLPU), Sham entrenado (ShamT) y CLP entrenado (CLPT). Dos días después de la cirugía, se repitió la prueba de deambulación en los animales y, en seguida, se los sacrificaron, recolectando el diafragma y los músculos sóleo y plantar. Se midió la actividad de las enzimas de la cadena mitocondrial de transporte de electrones (METC) y de la creatina quinasa (CK). El AETP tuvo una mejora significativa en el rendimiento en carreras de larga distancia y en la función de la musculatura esquelética del grupo entrenado. Cuarenta y ocho horas tras la cirugía, el grupo CLPT mantuvo un rendimiento muscular semejante al de Sham. Se mostró una disfunción en el diafragma en los complejos METC I y II-III así como en los músculos sóleos locomotores del complejo I; sufrió un aumento la actividad de la enzima CK en el grupo CLPU sedentario con músculo sóleo y plantar, pero en el diagrama hubo sólo una tendencia (p=0,07). Los animales CLPT que fueron sometidos al AETP no tuvieron estos resultados negativos. Los resultados mostraron indicios de efectos positivos obtenidos por preacondicionamiento físico aeróbico sobre la actividad de las enzimas METC y CK relacionada al diafragma y a los músculos locomotores, disminuido, así, la disfunción energética inducida por sepsis

Pulse Oximetry Wave Variation as a Noninvasive Tool to Assess Volume Status in Cardiac Surgery

OBJECTIVE: To compare variations of plethysmographic wave amplitude (&#916;Ppleth) and to determine the percent difference between inspiratory and expiratory pulse pressure (&#916;Pp) cutoff values for volume responsiveness in a homogenous population of postoperative cardiac surgery patients. INTRODUCTION: Intra-thoracic pressure variations interfere with stroke volume variation. Pulse pressure variations through arterial lines during mechanical ventilation have been recommended for the estimation of fluid responsiveness. Pulse oximetry may offer a non-invasive plethysmographic method to evaluate pulse pressure; this may be useful for guiding fluid replacement. METHODS: Controlled, prospective study in cardiac surgery patients under controlled ventilation. Simultaneous digital recordings of arterial pressure and plethysmographic waves were performed. &#916;Pp, systolic pressure (&#916;Ps), DPpleth, and systolic component (&#916;Spleth) were calculated. A DPp > 13% identified fluid-responsive patients. Volume expansion was performed in responsive subjects. Systolic and amplitude components of pressure and plethysmographic waves were compared. RESULTS: In 50 measurements from 43 patients, &#916;Pp was correlated with (Ppleth (r=0.90, p<0.001), (Ps (r=0.90, p<0.001), and (Spleth (r=0.73, p<0.001). An aArea under ROC curve (AUC) identified the fluid responsiveness thresholds: (Ppleth of 11% (AUC = 0.95±0.04), (Ps of 8% (AUC=0.93±0.05), and (Spleth of 32% (AUC=0.82±0.07). A (Ppleth value > 11% predicted (Pp > 13% with 100% specificity and 91% sensitivity. Volume expansion, performed in 20 patients, changed (Pp, (Ppleth, (Ps and (Spleth significantly (p<0.008). CONCLUSIONS: &#916;Ppleth is well correlated with DPp and constitutes a simple and non-invasive method for assessing fluid responsiveness in patients following cardiac surgery

Vasodilation increases pulse pressure variation, mimicking hypovolemic status in rabbits

OBJECTIVE: To test the hypothesis that pulse pressure respiratory variation (PPV) amplification, observed in hypovolemia, can also be observed during sodium nitroprusside (SNP)-induced vasodilation. INTRODUCTION: PPV is largely used for early identification of cardiac responsiveness, especially when hypovolemia is suspected. PPV results from respiratory variation in transpulmonary blood flow and reflects the left ventricular preload variations during respiratory cycles. Any factor that decreases left ventricular preload can be associated with PPV amplification, as seen in hypovolemia. METHODS: Ten anesthetized and mechanically ventilated rabbits underwent progressive hypotension by either controlled hemorrhage (Group 1) or intravenous SNP infusion (Group 2). Animals in Group 1 (n = 5) had graded hemorrhage induced at 10% steps until 50% of the total volume was bled. Mean arterial pressure (MAP) steps were registered and assumed as pressure targets to be reached in Group 2. Group 2 (n = 5) was subjected to a progressive SNP infusion to reach similar pressure targets as those defined in Group 1. Heart rate (HR), systolic pressure variation (SPV) and PPV were measured at each MAP step, and the values were compared between the groups. RESULTS: SPV and PPV were similar between the experimental models in all steps (p >; 0.16). SPV increased earlier in Group 2. CONCLUSION: Both pharmacologic vasodilation and graded hemorrhage induced PPV amplification similar to that observed in hypovolemia, reinforcing the idea that amplified arterial pressure variation does not necessarily represent hypovolemic status but rather potential cardiovascular responsiveness to fluid infusion

Vasodilation increases pulse pressure variation, mimicking hypovolemic status in rabbits

OBJECTIVE: To test the hypothesis that pulse pressure respiratory variation (PPV) amplification, observed in hypovolemia, can also be observed during sodium nitroprusside (SNP)-induced vasodilation. INTRODUCTION: PPV is largely used for early identification of cardiac responsiveness, especially when hypovolemia is suspected. PPV results from respiratory variation in transpulmonary blood flow and reflects the left ventricular preload variations during respiratory cycles. Any factor that decreases left ventricular preload can be associated with PPV amplification, as seen in hypovolemia. METHODS: Ten anesthetized and mechanically ventilated rabbits underwent progressive hypotension by either controlled hemorrhage (Group 1) or intravenous SNP infusion (Group 2). Animals in Group 1 (n = 5) had graded hemorrhage induced at 10% steps until 50% of the total volume was bled. Mean arterial pressure (MAP) steps were registered and assumed as pressure targets to be reached in Group 2. Group 2 (n = 5) was subjected to a progressive SNP infusion to reach similar pressure targets as those defined in Group 1. Heart rate (HR), systolic pressure variation (SPV) and PPV were measured at each MAP step, and the values were compared between the groups. RESULTS: SPV and PPV were similar between the experimental models in all steps (p > 0.16). SPV increased earlier in Group 2. CONCLUSION: Both pharmacologic vasodilation and graded hemorrhage induced PPV amplification similar to that observed in hypovolemia, reinforcing the idea that amplified arterial pressure variation does not necessarily represent hypovolemic status but rather potential cardiovascular responsiveness to fluid infusion

Diretrizes brasileiras para o manejo de potenciais doadores de órgãos em morte encefálica. Uma força-tarefa composta por Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network e Coordenação Geral do Sistema Nacional de Transplantes

Objective: To contribute to updating the recommendations for brain-dead potential organ donor management. Methods: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, answered questions related to the following topics were divided into mechanical ventilation, hemodynamics, endocrine-metabolic management, infection, body temperature, blood transfusion, and checklists use. The outcomes considered were cardiac arrests, number of organs removed or transplanted as well as function / survival of transplanted organs. The quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system to classify the recommendations. Results: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong, 11 as weak and 1 was considered a good clinical practice. Conclusion: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak.Objetivo: Fornecer recomendações para nortear o manejo clínico do potencial doador em morte encefálica. Métodos: O presente documento foi formulado em dois painéis compostos por uma força tarefa integrada por 27 especialistas de diferentes áreas que responderam a questões dirigidas aos seguintes temas: ventilação mecânica, hemodinâmica, suporte endócrino-metabólico, infecção, temperatura corporal, transfusão sanguínea, e uso de checklists. Os desfechos considerados foram: parada cardíaca, número de órgãos retirados ou transplantados e função/sobrevida dos órgãos transplantados. A qualidade das evidências das recomendações foi avaliada pelo sistema Grading of Recommendations Assessment, Development, and Evaluation. Resultados: Foram geradas 19 recomendações a partir do painel de especialistas. Dessas, 7 foram classificadas como fortes, 11 fracas e uma foi considerada boa prática clínica. Conclusão: Apesar da concordância entre os membros do painel em relação à maior parte das recomendações, o grau de recomendação é fraco em sua maioria

Brazilian guidelines for the management of brain-dead potential organ donors : the task force of the AMIB, ABTO, BRICNet, and the General Coordination of the National Transplant System

Objective: To contribute to updating the recommendations for brain-dead potential organ donor management. Method: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, joined a task force formed by the General Coordination Ofce of the National Transplant System/Brazilian Ministry of Health (CGSNT-MS), the Brazilian Association of Intensive Care Medicine (AMIB), the Brazilian Association of Organ Transplantation (ABTO), and the Brazilian Research in Intensive Care Network (BRICNet). The questions were developed within the scope of the 2011 Brazilian Guidelines for Management of Adult Potential Multiple-Organ Deceased Donors. The topics were divided into mechanical ventilation, hemodynamic support, endocrine-metabolic management, infection, body temperature, blood transfusion, and use of checklists. The outcomes considered for decision-making were cardiac arrest, number of organs recovered or transplanted per donor, and graft function/sur‑ vival. Rapid systematic reviews were conducted, and the quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Two expert panels were held in November 2016 and February 2017 to classify the recommendations. A systematic review update was performed in June 2020, and the recommendations were reviewed through a Delphi process with the panelists between June and July 2020. Results A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong (lung-protective ventilation strategy, vasopressors and combining arginine vasopressin to control blood pressure, antidiuretic hormones to control polyuria, serum potassium and magnesium control, and antibiotic use), 11 as weak (alveolar recruitment maneuvers, low-dose dopamine, low-dose corticosteroids, thyroid hormones, glycemic and serum sodium control, nutritional support, body temperature control or hypothermia, red blood cell transfusion, and goal-directed protocols), and 1 was considered a good clinical practice (volemic expansion). Conclusion Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak. The observed lack of robust evidence on the topic highlights the importance of the present guideline to improve the management of brain-dead potential organ donors

INTERSEPT study: we still need more clarity

Universidade Federal de São Paulo, Hosp São Paulo, Anesthesiol & Crit Care Dept, BR-04024900 São Paulo, BrazilHosp Dona Helena, BR-89204205 Joinville, SC, BrazilHosp Procardiaco, BR-22280000 Rio de Janeiro, BrazilUniv Fed Paraiba, Univ Hosp, BR-58000000 Joao Pessoa, Paraiba, BrazilHosp Base, Intens Care Div, Dept Internal Med, Fac Med Sao Jose Rio Preto, BR-15090000 Sao Jose Do Rio Preto, SP, BrazilHosp Copa DOr, BR-22031011 Rio de Janeiro, BrazilHosp Santo Amaro, BR-40210320 Salvador, BA, BrazilHosp Portugues, Salvador, BA, BrazilHosp Salvador, Salvador, BA, BrazilCtr Hosp UNIMED, BR-89204060 Joinville, SC, BrazilUniversidade Federal de São Paulo, Hosp São Paulo, Anesthesiol & Crit Care Dept, BR-04024900 São Paulo, BrazilWeb of Scienc

Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial

Introduction: Patients undergoing mechanical ventilation (MV) are frequently administered prolonged and/or high doses of opioids which when removed can cause a withdrawal syndrome and difficulty in weaning from MV. We tested the hypothesis that the introduction of enteral methadone during weaning from sedation and analgesia in critically ill adult patients on MV would decrease the weaning time from MV. Methods: A double-blind randomized controlled trial was conducted in the adult intensive care units (ICUs) of four general hospitals in Brazil. The 75 patients, who met the criteria for weaning from MV and had been using fentanyl for more than five consecutive days, were randomized to the methadone (MG) or control group (CG). Within the first 24 hours after study enrollment, both groups received 80% of the original dose of fentanyl, the MG received enteral methadone and the CG received an enteral placebo. After the first 24 hours, the MG received an intravenous (IV) saline solution (placebo), while the CG received IV fentanyl. For both groups, the IV solution was reduced by 20% every 24 hours. The groups were compared by evaluating the MV weaning time and the duration of MV, as well as the ICU stay and the hospital stay. Results: Of the 75 patients randomized, seven were excluded and 68 were analyzed: 37 from the MG and 31 from the CG. There was a higher probability of early extubation in the MG, but the difference was not significant (hazard ratio: 1.52 (95% confidence interval (CI) 0.87 to 2.64; P = 0.11). The probability of successful weaning by the fifth day was significantly higher in the MG (hazard ratio: 2.64 (95% CI: 1.22 to 5.69; P &lt; 0.02). Among the 54 patients who were successfully weaned (29 from the MG and 25 from the CG), the MV weaning time was significantly lower in the MG (hazard ratio: 2.06; 95% CI 1.17 to 3.63; P &lt; 0.004). Conclusions: The introduction of enteral methadone during weaning from sedation and analgesia in mechanically ventilated patients resulted in a decrease in the weaning time from MV

Exercise training prevents skeletal muscle damage in an experimental sepsis model

OBJECTIVE: Oxidative stress plays an important role in skeletal muscle damage in sepsis. Aerobic exercise can decrease oxidative stress and enhance antioxidant defenses. Therefore, it was hypothesized that aerobic exercise training before a sepsis stimulus could attenuate skeletal muscle damage by modulating oxidative stress. Thus, the aim of this study was to evaluate the effects of aerobic physical preconditioning on the different mechanisms that are involved in sepsis-induced myopathy. METHODS: Male Wistar rats were randomly assigned to either the untrained or trained group. The exercise training protocol consisted of an eight-week treadmill program. After the training protocol, the animals from both groups were randomly assigned to either a sham group or a cecal ligation and perforation surgery group. Thus, the groups were as follows: sham, cecal ligation and perforation, sham trained, and cecal ligation and perforation trained. Five days after surgery, the animals were euthanized and their soleus and plantaris muscles were harvested. Fiber cross-sectional area, creatine kinase, thiobarbituric acid reactive species, carbonyl, catalase and superoxide dismutase activities were measured. RESULTS: The fiber cross-sectional area was smaller, and the creatine kinase, thiobarbituric acid reactive species and carbonyl levels were higher in both muscles in the cecal ligation and perforation group than in the sham and cecal ligation and perforation trained groups. The muscle superoxide dismutase activity was higher in the cecal ligation and perforation trained group than in the sham and cecal ligation and perforation groups. The muscle catalase activity was lower in the cecal ligation and perforation group than in the sham group. CONCLUSION: In summary, aerobic physical preconditioning prevents atrophy, lipid peroxidation and protein oxidation and improves superoxide dismutase activity in the skeletal muscles of septic rats

Revisiting the bi-directional causality between debt and growth:Evidence from linear and nonlinear tests

We revisit the bi-directional causality between public debt and the rate of GDP growth for 10 EMU countries alongside the US, UK and Japan, over sample periods spanning from 1970 up to 2014 whilst accounting for the nonlinear properties of both the individual time series, and their relation in both directions. Our results indicate that the causal relation between debt and growth, in either direction, is weak at best. For most of the countries in our sample, we find no robust evidence of a long-run causal effect using bi-variate Granger causality tests. Bi-directional causality is detected only for Austria, while for France, Luxembourg and Portugal, causality runs solely from debt to growth, but the estimated effects are very small. In Finland, Spain and Italy, Granger causality (from growth to debt in the former two and debt to growth in Italy) appears to be present in the short-run. Our findings cannot be taken as evidence that a high level of public indebtedness is not risky for the economy or as invalidating hypotheses postulating effects in either direction in the relation between debt and growth