Markers of Tissue Perfusion as Predictors of Adverse Outcomes in Patients with Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery. / Marcadores de Perfusão Tecidual como Preditores de Desfechos Adversos em Pacientes com Disfunção Ventricular Esquerda Submetidos à Revascularização Miocárdica (Bypass Coronário).

BACKGROUND: Cardiac surgery patients may be exposed to tissue hypoperfusion and anaerobic metabolism. OBJECTIVE: To verify whether the biomarkers of tissue hypoperfusion have predictive value for prolonged intensive care unit (ICU) stay in patients with left ventricular dysfunction who underwent coronary artery bypass surgery. METHODS: After approval by the institution's Ethics Committee and the signing of informed consent, 87 patients with left ventricular dysfunction (ejection fraction < 50%) undergoing coronary artery bypass surgery were enrolled. Hemodynamic and metabolic biomarkers were collected at five time points: after anesthesia, at the end of the surgery, at ICU admission, and at six and twelve hours after. An analysis of variance for repeated measures followed by a Bonferroni post hoc test was used for repeated, continuous variables (hemodynamic and metabolic variables) to determine differences between the two groups over the course of the study period. The level of statistical significance adopted was 5%. RESULTS: Thirty-eight patients (43.7%) who presented adverse outcomes were older, higher Euro score (p<0.001), and elevated ΔpCO2 as analyzed 12 hours after ICU admission (p<0.01), while increased arterial lactate concentration at 6 hours postoperatively was found to be a negative predictive factor (p<0.01). CONCLUSIONS: Euro SCORE, six-hour postoperative arterial lactate, 12-hour postoperative ΔPCO2, and eRQ are independent predictors of adverse outcomes in patients with left ventricular dysfunction after cardiac surgery.

FUNDAMENTO: Pacientes submetidos à cirurgia cardíaca podem estar expostos à hipoperfusão tecidual e metabolismo anaeróbico. OBJETIVO: Verificar se os biomarcadores de hipoperfusão tecidual têm valor preditivo para permanência prolongada na Unidade de Terapia Intensiva (UTI) em pacientes com disfunção ventricular esquerda submetidos à cirurgia de bypass da artéria coronária. MÉTODOS: Após aprovação pelo comitê de ética institucional e assinatura do termo de consentimento, 87 pacientes com disfunção ventricular esquerda (fração de ejeção <50%) submetidos à cirurgia de bypass coronário foram incluídos. Biomarcadores hemodinâmicos e metabólicos foram coletados em cinco momentos: após anestesia, ao final da cirurgia, na admissão na UTI, e a seis e 12 horas depois. Uma análise de variância para medidas repetidas seguida de um teste post-hoc de Bonferroni foi usado para variáveis contínuas repetidas (variáveis metabólicas e hemodinâmicas) para determinar diferenças entre os dois grupos ao longo do estudo. O nível de significância adotado foi de 5%. RESULTADOS: Trinta e oito pacientes (43,7%) que apresentaram desfechos adversos eram mais velhos, apresentaram um Euroscore mais alto (p<0,001), e gradiente venoarterial de CO2 (ΔPCO2) elevado, analisados 12 horas após a admissão na UTI (p<0,01), enquanto uma concentração de lactato arterial aumentada seis horas após a cirurgia foi um fator preditivo negativo (p<0,01). CONCLUSÕES: EuroSCORE, lactato arterial seis horas após a cirurgia, ΔPCO212 horas após a cirurgia e QRe são preditores independentes de desfechos adversos em pacientes com disfunção ventricular esquerda após cirurgia cardíaca.

Marcadores de Perfusão Tecidual como Preditores de Desfechos Adversos em Pacientes com Disfunção Ventricular Esquerda Submetidos à Revascularização Miocárdica (Bypass Coronário) / Markers of Tissue Perfusion as Predictors of Adverse Outcomes in Patients with Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery

Resumo Fundamento: Pacientes submetidos à cirurgia cardíaca podem estar expostos à hipoperfusão tecidual e metabolismo anaeróbico. Objetivo: Verificar se os biomarcadores de hipoperfusão tecidual têm valor preditivo para permanência prolongada na Unidade de Terapia Intensiva (UTI) em pacientes com disfunção ventricular esquerda submetidos à cirurgia de bypass da artéria coronária. Métodos: Após aprovação pelo comitê de ética institucional e assinatura do termo de consentimento, 87 pacientes com disfunção ventricular esquerda (fração de ejeção <50%) submetidos à cirurgia de bypass coronário foram incluídos. Biomarcadores hemodinâmicos e metabólicos foram coletados em cinco momentos: após anestesia, ao final da cirurgia, na admissão na UTI, e a seis e 12 horas depois. Uma análise de variância para medidas repetidas seguida de um teste post-hoc de Bonferroni foi usado para variáveis contínuas repetidas (variáveis metabólicas e hemodinâmicas) para determinar diferenças entre os dois grupos ao longo do estudo. O nível de significância adotado foi de 5%. Resultados: Trinta e oito pacientes (43,7%) que apresentaram desfechos adversos eram mais velhos, apresentaram um Euroscore mais alto (p<0,001), e gradiente venoarterial de CO2 (ΔPCO2) elevado, analisados 12 horas após a admissão na UTI (p<0,01), enquanto uma concentração de lactato arterial aumentada seis horas após a cirurgia foi um fator preditivo negativo (p<0,01). Conclusões: EuroSCORE, lactato arterial seis horas após a cirurgia, ΔPCO212 horas após a cirurgia e QRe são preditores independentes de desfechos adversos em pacientes com disfunção ventricular esquerda após cirurgia cardíaca.

Abstract Background: Cardiac surgery patients may be exposed to tissue hypoperfusion and anaerobic metabolism. Objective: To verify whether the biomarkers of tissue hypoperfusion have predictive value for prolonged intensive care unit (ICU) stay in patients with left ventricular dysfunction who underwent coronary artery bypass surgery. Methods: After approval by the institution's Ethics Committee and the signing of informed consent, 87 patients with left ventricular dysfunction (ejection fraction < 50%) undergoing coronary artery bypass surgery were enrolled. Hemodynamic and metabolic biomarkers were collected at five time points: after anesthesia, at the end of the surgery, at ICU admission, and at six and twelve hours after. An analysis of variance for repeated measures followed by a Bonferroni post hoc test was used for repeated, continuous variables (hemodynamic and metabolic variables) to determine differences between the two groups over the course of the study period. The level of statistical significance adopted was 5%. Results: Thirty-eight patients (43.7%) who presented adverse outcomes were older, higher Euro score (p<0.001), and elevated ΔpCO2 as analyzed 12 hours after ICU admission (p<0.01), while increased arterial lactate concentration at 6 hours postoperatively was found to be a negative predictive factor (p<0.01). Conclusions: Euro SCORE, six-hour postoperative arterial lactate, 12-hour postoperative ΔPCO2, and eRQ are independent predictors of adverse outcomes in patients with left ventricular dysfunction after cardiac surgery.

Blood cell adhesion to arterial filters analysis by scanning electron microscopy and real-time PCR assay: observational clinical study in cardiac surgery patients.

INTRODUCTION: Arterial filter is the part of the cardiopulmonary bypass circuit where blood cells are exposed to high mechanical stress and where cellular aggregates may fasten in large quantities. The aim of this study was to analyse blood cell adhesiveness in the arterial filter through scanning electron microscopy and real-time PCR assay. METHODS: Prospective, clinical and observational study performed on 28 patients undergoing cardiac surgery with cardiopulmonary bypass. Arterial filters were analysed by scanning electron microscopy. Real-time PCR assay was performed in extracted material from the arterial filters for analysis of platelet GPIb and CD45 leucocyte gene expression. Blood coagulation was analysed during cardiopulmonary bypass. Patients were followed until hospital discharge or 28 days after surgery. RESULTS: All studied arterial filters used in the subject patients showed a degree of adhesion from blood elements at scanning electron microscopy. All studied filters were positive for platelets GPIb gene expression and 15% had CD45 leucocyte gene expression. The GPIb platelet gene expression in blood lowered at the end of cardiopulmonary bypass (p = 0.019). There was negative correlation between blood GPIb platelet gene expression and Clot SR (HEPSCREEN2 ReoRox®) (rho = 0.635; p = 0.027). The filter fields count was correlated to the D-dimer dosage (rho = 0.828; p < 0.001). CONCLUSION: There was adhesion of blood elements, especially nucleated platelets, on all arterial filters studied. Although the arterial filter worked as a safety device, that possibly prevented arterial embolisation, it may also have caused greater hyperfibrinolysis during cardiopulmonary bypass.

Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis

Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

Association of the mobility level of critically ill adult patients with the success of extubation: protocol for a cohort study.

INTRODUCTION: Several factors contribute to the reduction of the mobility in ICU), such as the use of sedatives, severity, invasive devices, acute clinical instability, lack of resources, the culture of immobility, architectural barriers and the own weakness developed in the ICU. The need for ventilatory support is common in most of patients, and weaning from mechanical ventilation (MV) is an arduous process that requires the commitment of the entire team. Instruments that objectively assess the mobility of patients admitted to the ICU can be useful to identify the existence or not of an association between mobility and prognosis. OBJECTIVE: To estimate the association between the level of mobility and successful extubation. METHODS AND ANALYSIS: Prospective cohort study with the beginning of follow-up when the patient completes 24 hours of invasive MV in the ICU and ends on the date the patient's hospital discharge. Adult patients (≥18 years old) admitted to the ICU will be included in the first invasive MV event in this hospitalisation. Patients should be independently able to mobilise before current hospital admission. Predictor variables will be collected (age, sex, body mass index, Simplified Acute Physiological Score III (SAPS III), ICU admission type: clinic, elective or emergency surgery postoperative, Charlson Index, number of physiotherapists per patient in each ICU, use of sedation, vasoactive drugs and neuromuscular blocker, ICU mobility scale, time of invasive MV, ICU admission and hospital admission, and outcome. The primary outcome is the result of extubation (success or failure). ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee, certificate number 92878218.1.0000.5505. The protocol was registered on the Registro Brasileiro de Ensaios Clínicos (ReBEC) (registration number RBR-8k4f68). The results will be published in specialised journals and disseminated to the medical society and the general public.

Precision Medicine: Changing the way we think about healthcare.

Health care has changed since the decline in mortality caused by infectious diseases as well as chronic and non-contagious diseases, with a direct impact on the cost of public health and individual health care. We must now transition from traditional reactive medicine based on symptoms, diagnosis and treatment to a system that targets the disease before it occurs and, if it cannot be avoided, treats the disease in a personalized manner. Precision Medicine is that new way of thinking about medicine. In this paper, we performed a thorough review of the literature to present an updated review on the subject, discussing the impact of the use of genetics and genomics in the care process as well as medical education, clinical research and ethical issues. The Precision Medicine model is expanded upon in this article to include its principles of prediction, prevention, personalization and participation. Finally, we discuss Precision Medicine in various specialty fields and how it has been implemented in developing countries and its effects on public health and medical education.

Precision Medicine: Changing the way we think about healthcare

Health care has changed since the decline in mortality caused by infectious diseases as well as chronic and non-contagious diseases, with a direct impact on the cost of public health and individual health care. We must now transition from traditional reactive medicine based on symptoms, diagnosis and treatment to a system that targets the disease before it occurs and, if it cannot be avoided, treats the disease in a personalized manner. Precision Medicine is that new way of thinking about medicine. In this paper, we performed a thorough review of the literature to present an updated review on the subject, discussing the impact of the use of genetics and genomics in the care process as well as medical education, clinical research and ethical issues. The Precision Medicine model is expanded upon in this article to include its principles of prediction, prevention, personalization and participation. Finally, we discuss Precision Medicine in various specialty fields and how it has been implemented in developing countries and its effects on public health and medical education.

Goal-directed therapy in patients with early acute kidney injury: a multicenter randomized controlled trial

OBJECTIVES: Acute kidney injury is associated with many conditions, and no interventions to improve the outcomes of established acute kidney injury have been developed. We performed this study to determine whether goal-directed therapy conducted during the early stages of acute kidney injury could change the course of the disease. METHODS: This was a multicenter prospective randomized controlled study. Patients with early acute kidney injury in the critical care unit were randomly allocated to a standard care (control) group or a goal-directed therapy group with 8h of intensive treatment to maximize oxygen delivery, and all patients were evaluated during a period of 72h. ClinicalTrials.gov: NCT02414906. RESULTS: A total of 143 patients were eligible for the study, and 99 patients were randomized. Central venous oxygen saturation was significantly increased and the serum lactate level significantly was decreased from baseline levels in the goal-directed therapy group (p=0.001) compared to the control group (p=0.572). No significant differences in the change in serum creatinine level (p=0.96), persistence of acute kidney injury beyond 72h (p=0.064) or the need for renal replacement therapy (p=0.82) were observed between the two groups. In-hospital mortality was significantly lower in the goal-directed therapy group than in the control group (33% vs. 51%; RR: 0.61, 95% CI: 0.37-1.00, p=0.048, number needed to treat=5). CONCLUSIONS: Goal-directed therapy for patients in the early stages of acute kidney injury did not change the disease course.

Effect of Perioperative Goal-Directed Hemodynamic Resuscitation Therapy on Outcomes Following Cardiac Surgery: A Randomized Clinical Trial and Systematic Review.

OBJECTIVES: To evaluate the effects of goal-directed therapy on outcomes in high-risk patients undergoing cardiac surgery. DESIGN: A prospective randomized controlled trial and an updated metaanalysis of randomized trials published from inception up to May 1, 2015. SETTING: Surgical ICU within a tertiary referral university-affiliated teaching hospital. PATIENTS: One hundred twenty-six high-risk patients undergoing coronary artery bypass surgery or valve repair. INTERVENTIONS: Patients were randomized to a cardiac output-guided hemodynamic therapy algorithm (goal-directed therapy group, n = 62) or to usual care (n = 64). In the goal-directed therapy arm, a cardiac index of greater than 3 L/min/m was targeted with IV fluids, inotropes, and RBC transfusion starting from cardiopulmonary bypass and ending 8 hours after arrival to the ICU. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications. Patients from the goal-directed therapy group received a greater median (interquartile range) volume of IV fluids than the usual care group (1,000 [625-1,500] vs 500 [500-1,000] mL; p < 0.001], with no differences in the administration of either inotropes or RBC transfusions. The primary outcome was reduced in the goal-directed therapy group (27.4% vs 45.3%; p = 0.037). The goal-directed therapy group had a lower occurrence rate of infection (12.9% vs 29.7%; p = 0.002) and low cardiac output syndrome (6.5% vs 26.6%; p = 0.002). We also observed lower ICU cumulative dosage of dobutamine (12 vs 19 mg/kg; p = 0.003) and a shorter ICU (3 [3-4] vs 5 [4-7] d; p < 0.001) and hospital length of stay (9 [8-16] vs 12 [9-22] d; p = 0.049) in the goal-directed therapy compared with the usual care group. There were no differences in 30-day mortality rates (4.8% vs 9.4%, respectively; p = 0.492). The metaanalysis identified six trials and showed that, when compared with standard treatment, goal-directed therapy reduced the overall rate of complications (goal-directed therapy, 47/410 [11%] vs usual care, 92/415 [22%]; odds ratio, 0.40 [95% CI, 0.26-0.63]; p < 0.0001) and decreased the hospital length of stay (mean difference, -5.44 d; 95% CI, -9.28 to -1.60; p = 0.006) with no difference in postoperative mortality: 9 of 410 (2.2%) versus 15 of 415 (3.6%), odds ratio, 0.61 (95% CI, 0.26-1.47), and p = 0.27. CONCLUSIONS: Goal-directed therapy using fluids, inotropes, and blood transfusion reduced 30-day major complications in high-risk patients undergoing cardiac surgery.

Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs.

OBJECTIVES: Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid. METHODS: Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis. RESULTS: Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups. CONCLUSIONS: Hypertonic saline infusion after intratracheal hydrochloric acid instillation does not have an effect on inflammatory biomarkers or respiratory gas exchange.