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1.
Diabetes Obes Metab ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372454

RESUMO

It is unknown if the cardioprotective and renal effects of glucagon-like peptide-1 receptor agonists are consistent across blood pressure (BP) categories in patients with type 2 diabetes and at high risk of cardiovascular events. Using data from the LEADER (9340 patients) and SUSTAIN 6 (3297 patients) trials, we evaluated post hoc the cardiorenal effect of liraglutide and semaglutide on major adverse cardiovascular events (MACE) and nephropathy by baseline BP categories using a Cox proportional hazards model (treatment and subgroup as factors; adjusted for cardiorenal risk factors). Data from the two trials were analyzed separately. In the LEADER and SUSTAIN 6 trials, the prevalence of stage 1 hypertension was 30% and 31%, respectively, and of stage 2 hypertension 41% and 43%, respectively. There was no statistical heterogeneity across the BP categories for the effects of liraglutide (p = 0.06 for MACE; p = 0.14 for nephropathy) or semaglutide (p = 0.40 for MACE; p = 0.27 for nephropathy) versus placebo. This implies that liraglutide and semaglutide may be beneficial for patients with type 2 diabetes, irrespective of their baseline BP. Clinical Trial Registrations: ClinicalTrials.gov, NCT01179048 and NCT01720446. This article is protected by copyright. All rights reserved.

3.
Diabetes Obes Metab ; 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32227432

RESUMO

AIM: To investigate the association of the Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Heart Failure in Diabetes (TRS-HFDM ) with mortality using data from the EMPA-REG OUTCOME trial. MATERIALS AND METHODS: In EMPA-REG OUTCOME, patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease (N = 7020) received the sodium-glucose co-transporter-2 inhibitor, empagliflozin, 10 or 25 mg or placebo. Post hoc, patients were stratified into risk categories (low-intermediate, high, very-high risk scores) using baseline TRS-HFDM . Cox regression analyses evaluated the association of TRS-HFDM categories with all-cause mortality (ACM), CV death, hospitalization for heart failure (HHF) and CV death (excluding fatal stroke) or HHF, and whether empagliflozin reduced the risk of CV outcomes across these risk categories. RESULTS: In placebo patients, increasing risk category was associated with a higher risk of ACM, CV death, and HHF. Empagliflozin reduced the risk of ACM (low-intermediate HR 0.68 [95% CI 0.48, 0.97] and very-high 0.69 [0.52, 0.91]), CV death (0.75 [0.48, 1.18] and 0.56 [0.41, 0.78]), HHF (0.53 [0.28, 1.01] and 0.67 [0.48, 0.96]), and CV death or HHF (0.69 [0.46, 1.03]) and (0.64 [0.49, 0.82]) across all risk categories versus placebo. Higher absolute risk reductions (ARRs) were observed for CV death in the very-high versus low-intermediate category (P = 0.01). CONCLUSIONS: Applied to EMPA-REG OUTCOME, higher TRS-HFDM was associated with increased HHF and mortality risk. Empagliflozin reduced CV outcomes across TRS-HFDM categories. Higher ARRs were associated with higher risk scores.

5.
Br J Anaesth ; 124(5): 544-552, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32216957

RESUMO

BACKGROUND: Use of neuraxial anaesthesia for open abdominal aortic aneurysm repair is postulated to reduce mortality and morbidity. This study aimed to determine the 90-day outcomes after elective open abdominal aortic aneurysm repair in patients receiving combined general and neuraxial anaesthesia vs general anaesthesia alone. METHODS: A retrospective population-based cohort study was conducted from 2003 to 2016. All patients ≥40 yr old undergoing open abdominal aortic aneurysm repair were included. The propensity score was used to construct inverse probability of treatment weighted regression models to assess differences in 90-day outcomes. RESULTS: A total of 10 447 elective open abdominal aortic aneurysm repairs were identified; 9003 (86%) patients received combined general and neuraxial anaesthesia and 1444 (14%) received general anaesthesia alone. Combined anaesthesia was associated with significantly lower hazards for all-cause mortality (hazard ratio [HR]=0.47; 95% confidence interval [CI], 0.37-0.61) and major adverse cardiovascular events (HR=0.72; 95% CI, 0.60-0.86). Combined patients were at lower odds for acute kidney injury (odds ratio [OR]=0.66; 95% CI, 0.49-0.89), respiratory failure (OR=0.41; 95% CI, 0.36-0.47), and limb complications (OR=0.30; 95% CI, 0.25-0.37), with higher odds of being discharged home (OR=1.32; 95% CI, 1.15-1.51). Combined anaesthesia was also associated with significant mechanical ventilation and ICU and hospital length of stay benefits. CONCLUSIONS: Combined general and neuraxial anaesthesia in elective open abdominal aortic aneurysm repair is associated with reduced 90-day mortality and morbidity. Neuraxial anaesthesia should be considered as a routine adjunct to general anaesthesia for elective open abdominal aortic aneurysm repair.


Assuntos
Anestesia Epidural/métodos , Anestesia Geral/métodos , Raquianestesia/métodos , Aneurisma da Aorta Abdominal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Epidural/mortalidade , Anestesia Geral/mortalidade , Raquianestesia/mortalidade , Anestésicos Combinados , Aneurisma da Aorta Abdominal/mortalidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
6.
Artigo em Inglês | MEDLINE | ID: mdl-32130021

RESUMO

The mechanism by which the kidney senses changes in hemoglobin concentration (Hb) may inform decisions regarding the optimal fluid for intravascular volume resuscitation in critical care settings where starch solution may be nephrotoxic. We hypothesized that hemodilution with starch solutions would reduce renal PktO2 to a more severe degree than other diluents. Anesthetized Sprague Dawley rats (n=61) were block-randomized to undergo hemodilution with either colloid (6% hydroxyethyl starch or 5% albumin), crystalloid (saline), or a sham procedure (control) (n=6-12 rats/group). We measured mean arterial pressure (MAP), arterial blood gases, Hb (cooximetry), cardiac output (CO, echocardiography), renal PktO2 and hypoxic gene expression (mRNA qRT-PCR). Following hemodilution, MAP decreased in the saline group while Hb and blood oxygen content (CaO2) decreased in all groups. Cardiac output increased (~50%) after colloid, but not after saline hemodilution. Renal PktO2 decreased in proportion to the reduction in Hb in all treatment groups. At comparably reduced Hb and PaO2 values, hemodilution with starch resulted in a larger decrease in kidney PktO2 relative to animals hemodiluted with albumin or saline (p<0.008). Renal erythropoietin (EPO) mRNA levels increased after hemodilution in all groups, but other HIF-dependent molecules did not increase (Glut-1, GAPDH, VEGF). This suggests that EPO expression is highly responsive to changes in CaO2 and demonstrates the capacity for the kidney as a biosensor of CaO2. Our data demonstrates that PktO2 reflects proportional changes in CaO2 and supports the hypothesis that hemodilution with starch colloid solution impairs renal PktO2, relative to hemodilution with albumin and saline.

8.
Diabetes Obes Metab ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32030863

RESUMO

In the EMPA-REG OUTCOME trial, we explored the association between pre-randomization uric acid level tertile (<309.30 µmol/L; 309.30 to <387.21 µmol/L; ≥387.21 µmol/L) and cardiovascular (CV) death, hospitalization for heart failure (HHF), HHF or CV death, all-cause mortality, three-point major adverse CV events (MACE), and incident or worsening nephropathy. Patients with type 2 diabetes and CV disease received empagliflozin or placebo. The median baseline plasma uric acid level was 344.98 µmol/L, and patients' baseline characteristics were mainly balanced across tertiles. Baseline uric acid levels were associated with cardio-renal outcomes: in the placebo group, for the highest versus lowest tertile, the multivariable hazard ratios for three-point MACE, HHF or CV death, and incident or worsening nephropathy were 1.22 (95% confidence interval [CI] 0.89-1.67; P = 0.2088), 1.51 (95% CI 1.02-2.23; P = 0.0396) and 1.77 (95% CI 1.33-2.34; P < 0.0001), respectively. When tested as a continuous variable, baseline uric acid was associated with all outcomes in the placebo group. Empagliflozin improved all cardio-renal outcomes across tertiles, with all interaction P values >0.05. Further investigation of these relationships is required.

9.
Biochem Biophys Res Commun ; 524(1): 50-56, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-31980166

RESUMO

Pulmonary arterial hypertension (PAH) is a rare, but progressive and devastating vascular disease with few treatment options to prevent the advancement to right ventricular dysfunction hypertrophy and failure. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion as well as reduces cardiovascular events and mortality in individuals with type 2 diabetes. While empagliflozin has been reported to lower systemic hypertension due to increased diuresis, the effect of empagliflozin on PAH is unknown. We used monocrotaline (MCT)-treated Sprague-Dawley rats to determine if empagliflozin alters PAH-associated outcomes. Compared to vehicle control, daily empagliflozin administration significantly improved survival in rats with severe MCT-induced PAH. Hemodynamic assessments showed that empagliflozin treatment significantly reduced mean pulmonary artery pressure, right ventricular systolic pressure, and increased pulmonary acceleration time. Empagliflozin treatment resulted in reduced right ventricular hypertrophy and fibrosis. Histological and molecular assessments of lung vasculature revealed significantly reduced medial wall thickening and decreased muscularization of pulmonary arterioles after empagliflozin treatment compared to vehicle-treated rats. In summary, SGLT2 inhibition with empagliflozin lowered mortality, reduced right ventricle systolic pressure, and attenuated maladaptive pulmonary remodeling in MCT-induced PAH. Clinical studies evaluating the efficacy of SGLT-2 inhibition should be considered for patients with PAH.

10.
Curr Opin Cardiol ; 35(2): 178-186, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31804229

RESUMO

PURPOSE OF REVIEW: The aim of this article is to provide practical recommendations on safe initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors to in-patients as well as management of those who are already on SGLT2 inhibitors. RECENT FINDINGS: Robust data from stable outpatient cohorts indicate that the SGLT2 inhibitors are associated with clinically meaningful reductions in major adverse cardiovascular events, lower rates of hospitalization for heart failure, and a reduction in major kidney outcomes There is however a lack of information on how to initiate and manage SGLT2 inhibitors in an acute in-patient setting. SUMMARY: SGLT2 inhibitors may be cautiously appropriate for in-patients if all the criteria for safe use are met but good clinical judgment must prevail. Temporary withholding of SGLT2 inhibitors is appropriate in hospitalized patients during a period of stress and/or insulinopenia.

14.
Can J Anaesth ; 67(4): 452-461, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31879855

RESUMO

PURPOSE: Post-craniotomy pain is a common clinical issue and its optimal management remains incompletely studied. Utilization of a regional scalp block has the potential advantage of reducing perioperative pain and opioid consumption, thereby facilitating optimal postoperative neurologic assessment. The purpose of this study was to assess the efficacy of regional scalp block on post-craniotomy pain and opioid consumption. METHODS: We performed a prospective randomized-controlled trial in adults scheduled to undergo elective supratentorial craniotomy under general anesthesia to assess the efficacy of postoperative bilateral scalp block with 0.5% bupivacaine with 1:200,000 epinephrine compared with placebo on postoperative pain and opioid consumption. The primary outcome was the visual analogue scale (VAS) for pain at 24 hr postoperatively. RESULTS: Eighty-nine patients were enrolled (n = 44 in block group; n = 45 in control group). There was no difference in the mean (standard deviation) VAS score at 24 hr postoperatively between the treatment group and the control group [31.2 (21.4) mm vs 23.0 (19.2) mm, respectively; mean difference, 6.6; 95% confidence interval, -2.3, 15.5; P = 0.15]. There was also no significant difference in postoperative opioid consumption. Distribution of individual VAS score and opioid consumption revealed that postoperative pain was highly variable following craniotomy. Time to hospital discharge was not different between treatment and placebo groups. No adverse events associated with scalp block were identified. CONCLUSION: These data show that bilateral scalp blocks using bupivacaine with epinephrine did not reduce mean postoperative VAS score or overall opioid consumption at 24 hr nor the time-to-discharge from the postanesthesia care unit or from hospital. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT00972790; registered 9 September, 2009.

15.
Br J Anaesth ; 124(3): 261-270, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31864719

RESUMO

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.


Assuntos
Tolerância ao Exercício/fisiologia , Indicadores Básicos de Saúde , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Biomarcadores/sangue , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/mortalidade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Autorrelato , Inquéritos e Questionários
16.
Anesthesiol Clin ; 37(4): 801-813, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677692

RESUMO

This article provides an overview of knowledge gaps that need to be addressed in cardiac anesthesia, including mitigating the inflammatory effects of cardiopulmonary bypass, defining myocardial infarction after cardiac surgery, improving perioperative neurologic outcomes, and the optimal management of patients undergoing valve replacement. In addition, emerging approaches to research conduct are discussed, including the use of new analytical techniques like machine learning, pragmatic trials, and adaptive designs.

17.
Anesth Analg ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596738

RESUMO

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point-of-care (POC) coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, have increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has only modestly declined over the last decade, remaining at ≥50% in high-risk patients. Given these limitations, and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists (SCA) has formed the Blood Conservation in Cardiac Surgery Working Group to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

18.
Anesth Analg ; 129(5): 1209-1221, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31613811

RESUMO

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point-of-care (POC) coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, have increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has only modestly declined over the last decade, remaining at ≥50% in high-risk patients. Given these limitations, and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists (SCA) has formed the Blood Conservation in Cardiac Surgery Working Group to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

19.
J Cardiothorac Vasc Anesth ; 33(11): 2887-2899, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31604540

RESUMO

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point of care coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, has increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has declined only modestly over the last decade, remaining at 50% or greater in high-risk patients. Given these limitations and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists has formed the Blood Conservation in Cardiac Surgery Working Group in order to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

20.
Trials ; 20(1): 595, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619260

RESUMO

Following publication of the original article [1], we have been notified of a few mistakes in the "Sample size calculations" section, second paragraph.

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