Ventilação mecânica protetora e incidência de complicações pulmonares pós-operatórias em pacientes submetidos a cirurgia vascular periférica

Introdução: Complicações pós-operatórias após cirurgias de grande porte, principalmente em procedimentos vasculares, estão associadas a aumento significativo de custos e de mortalidade. Há evidência crescente de que a ventilação mecânica com estratégia protetora usando baixo volume corrente, com a utilização de pressão positiva expiratória final (PEEP) e manobras de recrutamento alveolar previnem o aparecimento de complicações pulmonares pós-operatórias (CPP). As cirurgias vasculares periféricas incluem, em sua maioria, cirurgias para revascularização de membros inferiores em pacientes acometidos por obstrução vascular periférica crônica e avançada. Tais procedimentos vasculares são considerados cirurgias de grande porte e estão associados a grande morbidade cardiovascular no perioperatório. Neste grupo específico de pacientes, a presença de CPP está associada a piora de desfechos clínicos com consequente aumento significativo da morbidade perioperatória. Objetivo: Neste estudo, objetivamos comparar os efeitos da ventilação mecânica controlada com uso de estratégia protetora (baixo volume corrente associado a PEEP elevado) quando comparado a estratégia ventilatória convencional (volume corrente elevado associado a PEEP reduzido), sobre a taxa de CPP em pacientes submetidos a cirurgia vascular arterial periférica. Metodologia: O estudo foi delineado como um ensaio clínico prospectivo e randomizado, comparado a grupo controle (estratégia ventilatória convencional). Avaliadores e pacientes foram cegados durante a coleta de dados. Foram incluídos apenas pacientes adultos ASA II a IV, com idade maior do que 18 anos, agendados para a realização de cirurgia de revascularização arterial em membros 11 inferiores. Os pacientes agendados para a realização de revascularização de membros inferiores foram alocados aleatoriamente para tratamento com ventilação mecânica convencional (volume corrente entre 9 a 10 mL.kg-1 do peso predito e PEEP entre 3 e 5 cmH 2 O - Grupo I ou controle) ou tratamento com ventilação mecânica protetora (volume corrente de 6 a 7 mL.kg-1 do peso predito e PEEP de 6 a 8 cmH 2 O - Grupo II ou tratamento). O desfecho primário foi composto de complicações pulmonares pós- operatórias diversas e o desfecho secundário incluiu alterações gasométricas no perioperatório. Análise foi realizada através do método intention-to-treat. Resultados: Cinquenta e seis pacientes foram alocados aos grupos de estudo. Não houveram perdas durante o seguimento. Após análise dos resultados, não foram observadas diferenças estatisticamente significativas entre os grupos quanto a taxa de complicações pulmonares pós-operatórias (P > 0.05). Entretanto, os pacientes submetidos a estratégia protetora de ventilação apresentaram incidência aumentada de intercorrências hemodinâmicas no transoperatório e piora de parâmetros gasométricos ao final do procedimento e no pós- operatório imediato. Conclusões: Ventilação protetora com baixo volume corrente associado a PEEP elevado não reduziu a incidência de complicações pulmonares pós- operatórias em pacientes submetidos a cirurgia vascular arterial periférica sob anestesia geral e esteve associada a piora de parâmetros hemodinâmicos e gasométricos no perioperatório.Background and goal of the study: Postoperative complications following major surgeries are associated with a significant increase in costs and mortality. There is increasing evidence that mechanical ventilation with a protective strategy using low tidal volume prevents postoperative pulmonary complications. Peripheral vascular surgeries include particularly surgeries for arterial revascularization of the lower limbs in patients with advanced peripheral vascular disease. These procedures are strongly associated with major cardiovascular morbidity postoperatively. In this specific group of patients, the presence of postoperative pulmonary complications (PPC) may be associated with worsening of clinical outcomes with a consequent significant increase in perioperative morbidity. Objective: In this study, we aimed to compare the effects of controlled mechanical ventilation with the use of a protective strategy (low tidal volume associated with elevated PEEP) when compared to the conventional strategy (higher tidal volume associated with reduced PEEP levels) on the rate of PPC in patients undergoing peripheral vascular surgery. Methods: This study was delineated as a prospective, randomized clinical trial, compared to the control group (conventional ventilation strategy). Patients and researchers were blinded during data collection. We included adult patients, ASA status II to IV, aged over 18 years, scheduled to undergo lower limb arterial bypass surgery. Patients were randomized to treatment with conventional mechanical ventilation (tidal volume between 9 to 10 mL.kg-1 of predicted body weight and PEEP between 3 and 5 cmH 2 O - Group I or control) or treatment with protective ventilation strategy (tidal volume of 6 to 7 mL.kg-1 of predicted body weight and PEEP of 6 to 8 cmH 2 O - Group II or treatment). The 13 primary outcome was PPC and the secondary endpoint included hemodynamic and metabolic changes perioperatively. Statistical analysis was performed using the intention- to-treat method. Results and Discussion: Fifty-six patients were allocated to the study groups. There were no dropouts during follow-up. No statistically significant differences were observed between the groups regarding the rate of PPC (P > 0.05). However, we observed an increased incidence of hemodynamic adverse events during surgery and altered perioperative blood gas parameters in patients submitted to protective ventilation. Conclusions: In the present study, protective ventilation with low tidal volume and elevated PEEP did not reduce the incidence of PPC in patients undergoing peripheral vascular surgery. Notably, patients submitted to protective ventilation had an increased incidence of perioperative hemodynamic and gasometric adverse events

Efeitos antinociceptivos do alopurinol no modelo de dor induzida por capsaicina em camundongos

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Elevated glutamate and lactate predict brain death after severe head trauma

Objective: Clinical neurological assessment is challenging for severe traumatic brain injury (TBI) patients in the acute setting. Waves of neurochemical abnormalities that follow TBI may serve as fluid biomarkers of neurological status. We assessed the cerebrospinal fluid (CSF) levels of glutamate, lactate, BDNF, and GDNF, to identify potential prognostic biomarkers of neurological outcome. Methods: This cross-sectional study was carried out in a total of 20 consecutive patients (mean [SD] age, 29 [13] years; M/F, 9:1) with severe TBI Glasgow Coma Scale ≤ 8 and abnormal computed tomography scan on admission. Patients were submitted to ventricular drainage and had CSF collected between 2 and 4 h after hospital admission. Patients were then stratified according to two clinical outcomes: deterioration to brain death (nonsurvival, n = 6) or survival (survival, n = 14), within 3 days after hospital admission. CSF levels of brain-derived substances were compared between nonsurvival and survival groups. Clinical and neurological parameters were also assessed. Results: Glutamate and lactate are significantly increased in nonsurvival relative to survival patients. We tested the accuracy of both biomarkers to discriminate patient outcome. Setting a cutoff of >57.75, glutamate provides 80.0% of sensitivity and 84.62% of specificity (AUC: 0.8214, 95% CL: 54.55–98.08%; and a cutoff of >4.65, lactate has 100% of sensitivity and 85.71% of specificity (AUC: 0.8810, 95% CL: 54.55–98.08%). BDNF and GDNF did not discriminate poor outcome. Interpretation: This early study suggests that glutamate and lactate concentrations at hospital admission accurately predict death within 3 days after severe TBI

Correlação do Escore de Oxford Modificado com as Medidas Perineométricas em Pacientes Incontinentes

Introdução: diversas técnicas foram propostas para avaliação da musculatura do assoalho pélvico, porém, nenhum método mostrou-se capaz de medir as duas funções desses músculos: elevação e força de compressão. Na rotina de avaliação clínica é comumente empregada a palpação vaginal e, especialmente, o escore de Oxford modificado; entretanto, alguns trabalhos questionam a sensibilidade da escala de Oxford e sua correlação com medidas objetivas de força de contração muscular.Objetivo: neste estudo, propõe-se correlacionar as variáveis medidas na perineometria com o escore de Oxford modificado.Métodos: foram incluídas no estudo 45 pacientes com incontinência urinária que procuraram o ambulatório de Uroginecologia do Hospital de Clínicas de Porto Alegre. As pacientes foram submetidas à palpação vaginal, realizada por uma fisioterapeuta treinada na escala de Oxford, e a medição da força de compressão da musculatura pélvica por meio de balonete conectado a transdutor de pressão. As duas avaliações foram realizadas no mesmo dia.  Resultados: encontrou-se correlação significativa (

Effects of single low dose of dexamethasone before noncardiac and nonneurologic surgery and general anesthesia on postoperative cognitive dysfunction : a phase III double blind, randomized clinical trial

Postoperative cognitive dysfunction (POCD) is a multifactorial adverse event most frequently in elderly patients. This study evaluated the effect of dexamethasone on POCD incidence after noncardiac and nonneurologic surgery. METHODS: One hundred and forty patients (ASA I-II; age 60–87 years) took part in a prospective phase III, double blind, randomized study involving the administration or not of 8 mg of IV dexamethasone before general anesthesia under bispectral index (BIS) between 35–45 or 46–55. Neuropsychological tests were applied preoperatively and on the 3rd, 7th, 21st, 90th and 180th days after surgery and compared with normative data. S100β was evaluated before and 12 hours after induction of anesthesia. The generalized estimating equations (GEE) method was applied, followed by the posthoc Bonferroni test considering P<0.05 as significant. RESULTS: On the 3rd postoperative day, POCD was diagnosed in 25.2% and 15.3% of patients receiving dexamethasone, BIS 35–45, and BIS 46–55 groups, respectively. Meanwhile, POCD was present in 68.2% and 27.2% of patients without dexamethasone, BIS 35–45 and BIS 46–55 groups (p<0.0001). Neuropsychological tests showed that dexamethasone associated to BIS 46–55 decreased the incidence of POCD, especially memory and executive function. The administration of dexamethasone might have prevented the postoperative increase in S100β serum levels. CONCLUSION: Dexamethasone can reduce the incidence of POCD in elderly patients undergoing surgery, especially when associated with BIS 46–55. The effect of dexamethasone on S100β might be related with some degree of neuroprotection

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Anestesia geral versus regional em cirurgia arterial periférica : estudo sobre a incidência de complicações pulmonares pós-operatórias

Introdução: Complicações pulmonares pós-operatórias (CPP) após cirurgias de grande porte, principalmente em procedimentos vasculares, estão associadas a aumento significativo de custos e de mortalidade. As cirurgias vasculares periféricas incluem, em sua maioria, cirurgias para revascularização de membros inferiores em pacientes acometidos por obstrução vascular periférica crônica e isquemia crítica do membro afetado. Tais procedimentos vasculares são considerados cirurgias de grande porte e estão associados a grande morbidade cardiovascular no perioperatório. Neste grupo específico de pacientes, a presença de CPP está associada a piora de desfechos clínicos com consequente aumento significativo da morbimortalidade perioperatória. Metodologia: Neste estudo, objetivamos comparar os efeitos da anestesia regional (neuroaxial) com a anestesia geral com ventilação mecânica controlada sobre a taxa de CPP em pacientes submetidos a cirurgia arterial periférica. O estudo foi delineado em duas fases, sendo a primeira composta por uma revisão narrativa sobre as principais evidências disponíveis na literatura a respeito dos efeitos da anestesia regional em cirurgia vascular periférica e uma segunda fase composta por um ensaio clínico prospectivo e randomizado. Neste ensaio clínico paralelo com inclusão de dois grupos de estudo, avaliadores foram cegados durante a coleta de dados. Foram incluídos apenas pacientes adultos ASA II a IV, com idade maior do que 18 anos, agendados para a realização de cirurgia de revascularização arterial em membros inferiores. Os pacientes foram alocados aleatoriamente para anestesia geral com estratégia de ventilação protetora (volume corrente de 6 a 8 mL.kg-1 de peso corporal previsto e PEEP de 5 cmH2O) ou 6 anestesia raquidiana sob sedação moderada e oxigênio suplementar por cânula nasal. O desfecho primário foi composto de complicações pulmonares pós-operatórias diversas e os desfechos secundários incluíram alterações gasométricas e hemodinâmicas, complicações cardiovasculares, tempo de internação hospitalar e mortalidade em 30 dias. A análise foi realizada através do método intention-to-treat. Resultados: Cento e vinte e oito pacientes foram alocados aos grupos de estudo, sendo 123 pacientes a amostra final estudada. Não houveram perdas durante o seguimento. Após análise dos resultados, não foram observadas diferenças estatisticamente significativas entre os grupos quanto a taxa de complicações pulmonares pós-operatórias. Aproximadamente 27% dos pacientes que receberam anestesia geral com ventilação mecânica tiveram complicações pulmonares pós-operatórias em comparação a 13% que receberam raquianestesia regional (P = 0,051). Os pacientes submetidos à raquianestesia tiveram menor incidência de episódios de hipotensão e uso intraoperatório de drogas vasoativas (P < 0,001). Conclusões: No presente estudo, a anestesia regional (raquianestesia) não reduziu a incidência de CPP em pacientes submetidos à cirurgia vascular periférica em comparação com a anestesia geral. No entanto, a anestesia neuroaxial parece reduzir a incidência de hipotensão e a necessidade de suporte hemodinâmico perioperatório em pacientes submetidos à cirurgia arterial periférica.Introduction: Postoperative complications (PPC) after major surgeries, especially in vascular procedures, are associated with a significant increase in costs and mortality. Peripheral vascular surgeries often include surgeries for lower limb revascularization in patients affected by chronic peripheral vascular obstruction and limb-threatening ischemia. Peripheral vascular procedures are considered major surgery and are associated with high perioperative cardiovascular morbidity. In this specific group of patients, the presence of CPP is associated with worsening of clinical outcomes with a consequent significant increase in perioperative morbidity. Methodology: In this study, we aimed to compare the effects of regional anesthesia (neuraxial) when compared to general anesthesia with controlled mechanical ventilation on the rate of PPC in patients undergoing peripheral arterial surgery. The study was designed in two phases, the first consisting of a comprehensive narrative review of the main evidence available in the literature regarding the effects of regional anesthesia in peripheral vascular surgery and a second phase consisting of a prospective and randomized clinical trial. In this parallel clinical trial including two study groups, researchers were blinded during data collection. Only adult patients ASA II to IV, aged over 18 years, scheduled to undergo arterial revascularization surgery in the lower limbs, were included. Patients scheduled for lower limb bypass surgery were randomly allocated to treatment with general anesthesia with a protective ventilation strategy (tidal volume of 6 to 8 mL.kg-1 of predicted body weight and PEEP of 5 cmH2O) or spinal anesthesia under moderate sedation and supplemental oxygen via nasal cannula. The primary outcome was a composite of 8 miscellaneous postoperative pulmonary complications, and the secondary outcomes included perioperative blood gas and hemodynamic changes, cardiovascular complications, length of hospital stay, and 30-day mortality. Analysis was performed using the intention-to-treat method. Results: One hundred and twenty-eight patients were allocated to the study groups, with 123 patients ultimately included in the analysis. There were no dropouts during followup. After analyzing the results, no statistically significant differences were observed between the groups regarding the rate of postoperative pulmonary complications. Approximately 27% of patients who received general anesthesia with mechanical ventilation had postoperative pulmonary complications compared with 13% who received spinal anesthesia (P = 0.051). Patients undergoing spinal anesthesia had a lower incidence of hypotension episodes and intraoperative use of vasoactive drugs (P < 0.001). Conclusions: In the present study, regional anesthesia (spinal anesthesia) did not reduce the incidence of PPC in patients undergoing peripheral vascular surgery compared with general anesthesia. However, neuraxial anesthesia appears to reduce the incidence of hypotension and the need for perioperative hemodynamic support in patients undergoing peripheral arterial surgery