RESUMO
OBJECTIVES: NHS Digital issued new guidance on sepsis coding in April 2017 which was further modified in April 2018. During these timeframes some centres reported increased sepsis associated mortality, whilst others reported reduced mortality, in some cases coincident with specific quality improvement programmes. We hypothesised that changes in reported mortality could not be separated from changes in coding practice. METHODS: Hospital Episode Statistics from the Admitted Patient Care dataset for NHS hospitals in England, from April 2016 to March 2020 were analysed. Admissions of adults with sepsis: an International Classification of Diseases 10 (ICD-10) code associated with the Agency for Healthcare Research and Quality Clinical Classifications Software class 'Septicaemia (except in labour)', were assessed. Patient comorbidities were defined by other ICD-10 codes recorded within the admission episode. RESULTS: 1,081,565 hospital episodes with a coded diagnosis of sepsis were studied. After April 2017 there was a significant increase in admission episodes with sepsis coded as the primary reason for admission. There were significant changes in the case-mix of patients with a primary diagnosis of sepsis after April 2017. An analysis of case-mix, hospital and year treated as random effects, defined a small reduction in sepsis associated mortality across England following the first change in coding guidance. No centre specific improvement in outcome could be separated from these random-effects. CONCLUSION: Changes in sepsis coding practice altered case-mix and case selection, in ways that varied between centres. This was associated with changes in centre-specific sepsis associated mortality, over time. According to the direction of change these may be interpreted either as requiring local investigation for cause or as supporting coincident changes in clinical practice. A whole system analysis showed that centre specific changes in mortality cannot be separated from system-wide changes. Caution is therefore required when interpreting sepsis outcomes in England, particularly when using single centre studies to inform or support guidance or policy.
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Sepse , Adulto , Comorbidade , Inglaterra/epidemiologia , Mortalidade Hospitalar , Hospitalização , Humanos , Classificação Internacional de Doenças , Sepse/diagnósticoRESUMO
PURPOSE: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. METHOD: Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. RESULTS: Myocardial uptake of both (+) and (-) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (-) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (-) perhexiline were the plasma concentrations [(+) perhexiline: ß = -0.256, p = 0.015; (-) perhexiline: ß = -0.347, p = 0.001] and patients' age [(+) perhexiline: ß = 0.300, p = 0.004; (-) perhexiline: ß = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (ß = 0.228, p = 0.025), while atrial uptake of (-) perhexiline varied inversely with simultaneous heart rate (ß = -0.240, p = 0.015). CONCLUSION: (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (-) perhexiline may selectively modulate heart rate reduction.
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Fármacos Cardiovasculares/farmacocinética , Miocárdio/metabolismo , Perexilina/farmacocinética , Administração Oral , Idoso , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/química , Átrios do Coração/metabolismo , Ventrículos do Coração/metabolismo , Humanos , Pessoa de Meia-Idade , Perexilina/administração & dosagem , Perexilina/química , Estereoisomerismo , Distribuição TecidualRESUMO
AIM: Little is known regarding the steady-state uptake of drugs into the human myocardium. Perhexiline is a prophylactic anti-anginal drug which is increasingly also used in the treatment of heart failure and hypertrophic cardiomyopathy. We explored the relationship between plasma perhexiline concentrations and its uptake into the myocardium. METHODS: Blood, right atrium ± left ventricle biopsies were obtained from patients treated with perhexiline for a median of 8.5 days before undergoing coronary surgery in the perhexiline arm of a randomized controlled trial. Perhexiline concentrations in plasma and heart tissue were determined by HPLC. RESULTS: Atrial biopsies were obtained from 94 patients and ventricular biopsies from 28 patients. The median plasma perhexiline concentration was within the therapeutic range at 0.24 mg l⻹ (IQR 0.12-0.44), the median atrial concentration was 6.02 mg kg⻹ (IQR 2.70-9.06) and median ventricular concentration was 10.0 mg kg⻹ (IQR 5.76-13.1). Atrial (r² = 0.76) and ventricular (r² = 0.73) perhexiline concentrations were closely and directly correlated with plasma concentrations (both P < 0.001). The median atrial : plasma ratio was 21.5 (IQR 18.1-27.1), ventricular : plasma ratio was 34.9 (IQR 24.5-55.2) and ventricular : atrial ratio was 1.67 (IQR 1.39-2.22). Using multiple regression, the best model for predicting steady-state atrial concentration included plasma perhexiline, heart rate and age (r² = 0.83). Ventricular concentrations were directly correlated with plasma perhexiline concentration and length of therapy (r² = 0.84). CONCLUSIONS: This study demonstrates that plasma perhexiline concentrations are predictive of myocardial drug concentrations, a major determinant of drug effect. However, net myocardial perhexiline uptake is significantly modulated by patient age, potentially via alteration of myocardial:extracardiac drug uptake.
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Miocárdio/metabolismo , Perexilina/farmacocinética , Fatores Etários , Idoso , Biópsia , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
INTRODUCTION: Acute kidney injury (AKI) risk prediction scores are an objective and transparent means to enable cohort enrichment in clinical trials or to risk stratify patients preoperatively. Existing scores are limited in that they have been designed to predict only severe, or non-consensus AKI definitions and not less severe stages of AKI, which also have prognostic significance. The aim of this study was to develop and validate novel risk scores that could identify all patients at risk of AKI. METHODS: Prospective routinely collected clinical data (n = 30,854) were obtained from 3 UK cardiac surgical centres (Bristol, Birmingham and Wolverhampton). AKI was defined as per the Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines. The model was developed using the Bristol and Birmingham datasets, and externally validated using the Wolverhampton data. Model discrimination was estimated using the area under the ROC curve (AUC). Model calibration was assessed using the Hosmer-Lemeshow test and calibration plots. Diagnostic utility was also compared to existing scores. RESULTS: The risk prediction score for any stage AKI (AUC = 0.74 (95% confidence intervals (CI) 0.72, 0.76)) demonstrated better discrimination compared to the Euroscore and the Cleveland Clinic Score, and equivalent discrimination to the Mehta and Ng scores. The any stage AKI score demonstrated better calibration than the four comparison scores. A stage 3 AKI risk prediction score also demonstrated good discrimination (AUC = 0.78 (95% CI 0.75, 0.80)) as did the four comparison risk scores, but stage 3 AKI scores were less well calibrated. CONCLUSIONS: This is the first risk score that accurately identifies patients at risk of any stage AKI. This score will be useful in the perioperative management of high risk patients as well as in clinical trial design.
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Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Idoso , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Período Pós-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologiaAssuntos
Anestesia em Procedimentos Cardíacos/normas , Transfusão de Sangue/normas , Procedimentos Cirúrgicos Cardíacos/normas , Guias de Prática Clínica como Assunto/normas , Adulto , Comitês Consultivos/normas , Anestesia em Procedimentos Cardíacos/métodos , Transfusão de Sangue/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Europa (Continente) , HumanosRESUMO
BACKGROUND: Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. METHODS AND RESULTS: Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked ß-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. CONCLUSIONS: Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.
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Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Baixo Débito Cardíaco/epidemiologia , Baixo Débito Cardíaco/prevenção & controle , Próteses Valvulares Cardíacas , Hipertrofia Ventricular Esquerda/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Acetilglucosamina/metabolismo , Idoso , Baixo Débito Cardíaco/metabolismo , Método Duplo-Cego , Feminino , Glucose/uso terapêutico , Humanos , Incidência , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Potássio/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Studies suggest that certain black and Asian minority ethnic groups experience poorer outcomes from COVID-19, but these studies have not provided insight into potential reasons for this. We hypothesised that outcomes would be poorer for those of South Asian ethnicity hospitalised from a confirmed SARS-CoV-2 infection, once confounding factors, health-seeking behaviours and community demographics were considered, and that this might reflect a more aggressive disease course in these patients. METHODS: Patients with confirmed SARS-CoV-2 infection requiring admission to University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK between 10 March 2020 and 17 April 2020 were included. Standardised admission ratio (SAR) and standardised mortality ratio (SMR) were calculated using observed COVID-19 admissions/deaths and 2011 census data. Adjusted HR for mortality was estimated using Cox proportional hazard model adjusting and propensity score matching. RESULTS: All patients admitted to UHB with COVID-19 during the study period were included (2217 in total). 58% were male, 69.5% were white and the majority (80.2%) had comorbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger and have no comorbidities, but twice the prevalence of diabetes than white patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted and they were more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death, both by Cox regression (HR 1.4, 95% CI 1.2 to 1.8), after adjusting for age, sex, deprivation and comorbidities, and by propensity score matching, matching for the same factors but categorising ethnicity into South Asian or not (HR 1.3, 95% CI 1.0 to 1.6). CONCLUSIONS: Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.
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Povo Asiático/estatística & dados numéricos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus , Hospitalização/estatística & dados numéricos , Mortalidade/etnologia , Pandemias , Pneumonia Viral , COVID-19 , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/etnologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/etnologia , Pneumonia Viral/terapia , Modelos de Riscos Proporcionais , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Reino Unido/epidemiologiaRESUMO
The influence of registries in medicine is large. However, there has been no systematic assessment conducted to quantify the impact of benchmarking with registries focused on cardiothoracic surgery. Numerous publications conclude that registry participation leads to improvement of outcomes for patients. A large number of registries provide evidence sub-structured by statistics that show decreases in morbidity and mortality in the participants' clinical units. Many authors praise the benchmarking method making use of databases of registries as having a positive effect on outcome of care. However, studies proving the direct causal relation between the use of cardiothoracic surgery-oriented registries and improvement of clinical in-hospital outcomes are extremely scarce. We aimed to analyse the causal relation between the use of cardiothoracic surgery-oriented registries and improvement of clinical outcomes. In a systematic literature review, publications demonstrating the use of registry data to obtain consolidated quality improvements were selected. After analysis of 2990 scientific publications, 6 studies filled the inclusion criteria. The selected studies acknowledged that benchmarking of data against registries was used for a focused and methodologically organized improvement in cardiothoracic departments. In conjunction with the impact of the applied methods on healthcare, their results demonstrate quantifiable enhanced local outcomes over time.
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Benchmarking , Melhoria de Qualidade , Atenção à Saúde , Hospitais , Humanos , Sistema de RegistrosRESUMO
Titin is a giant sarcomeric protein that plays a major role in determining passive myocardial stiffness. The shorter N2B isoform results in a higher passive myocardial stiffness than the longer N2BA isoform. We hypothesised that the expression of the short N2B isoform would be increased in patients with aortic stenosis compared with healthy controls in response to pressure overload, in order to act as a modulator for the increased demand placed on the left ventricle during the early stages of the hypertrophic response. Myocardial biopsies were obtained from the left ventricle of 19 patients undergoing aortic valve replacement for aortic stenosis who had no significant co-existing coronary artery disease. Left ventricular biopsies were also obtained from 13 donor hearts for comparison. SDS-agarose gels revealed small N2B and large N2BA cardiac titin isoforms, with a mean N2BA/N2B ratio that was significantly decreased in the 19 aortic stenotic patients compared with the 13 controls (0.66+/-0.04 in the normal donor hearts compared with 0.48+/-0.03 in patients with aortic stenosis; P=0.02). However, total titin remained unchanged (0.28+/-0.02 compared with 0.24+/-0.02 respectively; P=0.29). In conclusion, the expression of less N2BA and more N2B titin in response to pressure overload may result in the generation of higher passive tension upon stretch to a given sarcomere length and this might affect cardiac performance.
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Estenose da Valva Aórtica/metabolismo , Proteínas Musculares/metabolismo , Proteínas Quinases/metabolismo , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Conectina , Feminino , Implante de Prótese de Valva Cardíaca , Ventrículos do Coração/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/metabolismo , Sarcômeros/metabolismo , Fatores Sexuais , Estresse Mecânico , Ultrassonografia , Função Ventricular Esquerda/fisiologiaRESUMO
OBJECTIVES: Administrative databases with dedicated coding systems in healthcare systems where providers are funded based on services recorded have been shown to be useful for clinical research, although their reliability is still questioned. We devised a custom classification of procedures and algorithms based on OPCS, enabling us to identify open heart surgeries from the English administrative database, Hospital Episode Statistics, with the objective of comparing the incidence of cardiac procedures in administrative and clinical databases. DESIGN: A comparative study of the incidence of cardiac procedures in administrative and clinical databases. SETTING: Data from all National Health Service Trusts in England, performing cardiac surgery. PARTICIPANTS: Patients classified as having cardiac surgery across England between 2004 and 2015, using a combination of procedure codes, age >18 and consultant specialty, where the classification was validated against internal and external benchmarks. RESULTS: We identified a total of 296 426 cardiac surgery procedures, of which majority of the procedures were coronary artery bypass grafting (CABG), aortic valve replacement (AVR), mitral repair and aortic surgery. The matching at local level was 100% for CABG and transplant, >90% for aortic valve and major aortic procedures and >80% for mitral. At national level, results were similar for CABG (IQR 98.6%-104%), AVR (IQR 105%-118%) and mitral valve replacement (IQR 86.2%-111%). CONCLUSIONS: We set up a process which can identify cardiac surgeries in England from administrative data. This will lead to the development of a risk model to predict early and late postoperative mortality, useful for risk stratification, risk prediction, benchmarking and real-time monitoring. Once appropriately adjusted, the system can be applied to other specialties, proving especially useful in those areas where clinical databases are not fully established.
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Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Sistemas de Informação Hospitalar , Modelos Estatísticos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/mortalidade , Ponte de Artéria Coronária/estatística & dados numéricos , Inglaterra , Feminino , Implante de Prótese de Valva Cardíaca/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To assess the impact of deep sternal wound infection on in-hospital mortality and mid-term survival following adult cardiac surgery. METHODS: Prospectively collected data on 4586 consecutive patients who underwent a cardiac surgical procedure via a median sternotomy from 1st January 2001 to 31st December 2005 were analysed. Patients with a deep sternal wound infection (DSWI) were identified in accordance with the Centres for Disease Control and Prevention guidelines. Nineteen variables (patient-related, operative and postoperative) were analysed. Logistic regression analysis was used to calculate a propensity score for each patient. Late survival data were obtained from the UK Central Cardiac Audit Database. Mean follow-up of DSWI patients was 2.28 years. RESULTS: DSWI requiring revision surgery developed in 1.65% (76/4586) patients. Stepwise multivariable logistic regression analysis identified age, diabetes, a smoking history and ventilation time as independent predictors of a DSWI. DSWI patients were more likely to develop renal failure, require reventilation and a tracheostomy postoperatively. Treatment included vacuum assisted closure therapy in 81.5% (62/76) patients and sternectomy with musculocutaneous flap reconstruction in 35.5% (27/76) patients. In-hospital mortality was 9.2% (7/76) in DSWI patients and 3.7% (167/4510) in non-DSWI patients (OR 1.300 (0.434-3.894) p=0.639). Survival with Cox regression analysis with mean propensity score (co-variate) showed freedom from all-cause mortality in DSWI at 1, 2, 3 and 4 years was 91%, 89%, 84% and 79%, respectively compared with 95%, 93%, 90% and 86%, respectively for patients without DSWI ((p=0.082) HR 1.59 95% CI (0.94-2.68)). CONCLUSION: DSWI is not an independent predictor of a higher in-hospital mortality or reduced mid-term survival following cardiac surgery in this population.
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Procedimentos Cirúrgicos Cardíacos/mortalidade , Infecções Estafilocócicas/cirurgia , Esterno/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Idoso , Feminino , Humanos , Masculino , Estudos Prospectivos , Reoperação , Fatores de Risco , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Esterno/microbiologia , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/mortalidade , Análise de SobrevidaRESUMO
OBJECTIVES: To assess the impact of preoperative renal dysfunction on in-hospital mortality and late survival outcome following adult cardiac surgery. METHODS: Prospectively collected data were analysed on 7621 consecutive patients not requiring preoperative renal-replacement therapy, who underwent CABG, valve surgery or combined procedures from 1/1/98 to 1/12/06. Preoperative estimated glomerular filtration rate was calculated using Cockcroft-Gault formula. Patients were classified in the four chronic kidney disease (CKD) stage classes defined by the National Kidney Foundation Disease Outcome Quality Initiative Advisory Board. Late survival data were obtained from the UK Central Cardiac Audit Database. RESULTS: There were 243 in-hospital deaths (3.2%). There was a stepwise increase in operative mortality with each CKD class independent of the type of surgery. Multivariate analysis confirmed CKD class to be an independent predictor of in-hospital mortality (class 2 OR 1.45, 95% CI 1.1-2.35, p=0.001; class 3 OR 2.8, 95% CI 1.68-4.46, p=0.0001; class 4 OR 7.5, 95% CI 3.76-15.2, p=0.0001). The median follow-up after surgery was 42 months (IQR 18-74) and there were 728 late deaths. Survival analysis using a Cox regression model confirmed CKD class to be an independent predictor of late survival (class 2 HR 1.2, 95% CI 1.1-1.6, p=0.0001; class 3 HR 1.95, 95% CI 1.6-2.4, p=0.0001; and class 4 HR 3.2, 95% CI 2.2-4.6, p=0.0001). Ninety-eight percent (7517/7621) of patients had a preoperative creatinine <200 micromol/l, which is not included as a risk factor in most risk stratification systems. CONCLUSIONS: Mild renal dysfunction is an important independent predictor of in-hospital and late mortality in adult patients undergoing cardiac surgery.
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Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Insuficiência Renal/complicações , Idoso , Doença Crônica , Ponte de Artéria Coronária/efeitos adversos , Métodos Epidemiológicos , Feminino , Taxa de Filtração Glomerular , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
AIMS: A variety of antithrombotic regimens have been described for the early postoperative period after bioprosthetic aortic valve replacement (AVR). This study reviews antithrombotic practice for patients undergoing bioprosthetic AVR with or without coronary artery bypass graft (CABG) amongst the centers participating in the ACTION (Anticoagulation Treatment Influence on Postoperative Patients) Registry. METHODS AND RESULTS: An antithrombotic therapy questionnaire was answered by the 49 centers participating in the ACTION Registry located in Europe, Middle East, Canada and Asia. The 43% of centers prescribe vitamin K antagonist (VKA), 20% prescribe VKA and acetyl salicylic acid (ASA), 33% prescribe only ASA and 4% do not prescribe any therapy after bioprosthetic AVR. For patients undergoing bioprosthetic AVR and CABG 39% of the centers prescribe VKA and ASA, 37% prescribe VKA and 24% prescribe ASA. After the first three postoperative months following bioprosthetic AVR, 61% of the centers prescribe only ASA, while 39% do not prescribe any therapy. Patients with bioprosthetic AVR and CABG receive ASA in 90% centers, in 2% centers VKA and ASA, and 8% centers do not prescribe any antithrombotic. CONCLUSION: This study demonstrates that, despite guidelines published by several professional societies, medical practice for the prevention of thrombotic events early after bioprosthetic AVR varies widely among cardiac surgical centers.
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Anticoagulantes/administração & dosagem , Bioprótese , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Sistema de Registros , Anticoagulantes/efeitos adversos , Protocolos Clínicos , Pesquisas sobre Atenção à Saúde , Doenças das Valvas Cardíacas/tratamento farmacológico , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Glucose insulin potassium (GIK) improves hemodynamic performance after coronary artery surgery (CABG). We investigated whether this is associated with changes in gene expression of beta1-adrenergic receptor (ADRB1) or other calcium handling proteins. METHODS AND RESULTS: During a randomized double-blind placebo-controlled trial, 48 patients undergoing on-pump CABG, allocated to receive pre-ischemic placebo (5% dextrose) or GIK (40% dextrose, K+ 100 mmol.L(-1), insulin 70 u.L(-1); 0.75 mL.kg(-1).h(-1)) continued for 6 hours after the removal of the aortic cross-clamp (AXC), underwent left ventricular biopsy for analysis of specific mRNAs immediately before AXC, before release of AXC, and 10 minutes after reperfusion (placebo n=24, GIK n=24). GIK or placebo was infused for a mean of 79+/-21 minutes or 79+/-18 minutes pre-ischemia respectively. Serial hemodynamic measurements were performed. Biopsy samples were snap-frozen and stored at -80 degrees C, mRNA was extracted and TaqMan real-time polymerase chain reaction was performed to investigate expression of ADRB1, sarcoplasmic reticulum Ca-ATPase (SERCA2a), and phospholamban (PLB). GIK significantly increased cardiac index versus placebo (P=0.037). TaqMan reverse-transcriptase polymerase chain reaction showed significantly greater ADRB1 mRNA expression at all time points (4.9-fold, 7.4-fold, and 15.6-fold increase, respectively; P<0.001), significantly greater SERCA2a mRNA expression after reperfusion (13.2-fold; P<0.001), and increased PLB mRNA expression at pre-ischemia and reperfusion (P<0.001 for both time-points) in GIK groups versus placebo. CONCLUSIONS: The beneficial hemodynamic effects of GIK therapy are associated with increased ADRB1 and SERCA2a mRNA expression. Further work is therefore warranted to investigate these mRNA effects at the protein level.
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ATPases Transportadoras de Cálcio/biossíntese , Soluções Cardioplégicas/farmacologia , Cardiotônicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Receptores Adrenérgicos beta 1/biossíntese , Idoso , Aorta , Proteínas de Ligação ao Cálcio/biossíntese , Proteínas de Ligação ao Cálcio/genética , ATPases Transportadoras de Cálcio/genética , Cardiotônicos/uso terapêutico , Estudos de Coortes , Constrição , Ponte de Artéria Coronária , Feminino , Glucose/farmacologia , Parada Cardíaca Induzida/métodos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Insulina/farmacologia , Masculino , Pessoa de Meia-Idade , Reperfusão Miocárdica , Potássio/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Adrenérgicos beta 1/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: Both glucose-insulin-potassium (GIK) and tri-iodothyronine (T3) may improve cardiovascular performance after coronary artery surgery (CABG) but their effects have not been directly compared and the effects of combined treatment are unknown. METHODS AND RESULTS: In 2 consecutive randomized double-blind placebo-controlled trials, in patients undergoing first time isolated on-pump CABG between January 2000 and September 2004, 440 patients were recruited and randomized to either placebo (5% dextrose) (n=160), GIK (40% dextrose, K+ 100 mmol.L(-1), insulin 70 u.L(-1)) (0.75 mL.kg(-1) h(-1)) (n=157), T3 (0.8 microg.kg(-1) followed by 0.113 microg.kg(-1) h(-1)) (n=63) or GIK+T3 (n=60). GIK/placebo therapy was administered from start of operation until 6 hours after removal of aortic cross-clamp (AXC) and T3/placebo was administered for a 6-hour period from removal of AXC. Serial hemodynamic measurements were taken up to 12 hours after removal of AXC and troponin I (cTnI) levels were assayed to 72 hours. Cardiac index (CI) was significantly increased in both the GIK and GIK/T3 group in the first 6 hours compared with placebo (P<0.001 for both) and T3 therapy (P=0.009 and 0.029, respectively). T3 therapy increased CI versus placebo between 6 and 12 hours after AXC removal (P=0.01) but combination therapy did not. Release of cTnI was lower in all treatment groups at 6 and 12 hours after removal of AXC. CONCLUSIONS: Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery. Combination therapy does not provide added hemodynamic effect.
Assuntos
Soluções Cardioplégicas/uso terapêutico , Cardiotônicos/uso terapêutico , Ponte de Artéria Coronária/estatística & dados numéricos , Hemodinâmica/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Tri-Iodotironina/uso terapêutico , Troponina I/sangue , Idoso , Biomarcadores , Soluções Cardioplégicas/administração & dosagem , Soluções Cardioplégicas/farmacologia , Ponte Cardiopulmonar/efeitos adversos , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacologia , Dopamina/administração & dosagem , Dopamina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucose/administração & dosagem , Glucose/farmacologia , Glucose/uso terapêutico , Humanos , Insulina/administração & dosagem , Insulina/farmacologia , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Norepinefrina/administração & dosagem , Norepinefrina/uso terapêutico , Potássio/administração & dosagem , Potássio/farmacologia , Potássio/uso terapêutico , Estudos Prospectivos , Tri-Iodotironina/administração & dosagem , Tri-Iodotironina/farmacologia , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêuticoAssuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Acidente Vascular Cerebral , Tomada de Decisão Clínica/métodos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Humanos , Mortalidade , Seleção de Pacientes , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
OBJECTIVE: To estimate a safe minimum hospital volume for hospitals performing coronary artery bypass graft (CABG) surgery. DATA SOURCE: Hospital data on all publicly funded CABG in five European countries, 2007-2009 (106,149 patients). DESIGN: Hierarchical logistic regression models to estimate the relationship between hospital volume and mortality, allowing for case mix. Segmented regression analysis to estimate a threshold. FINDINGS: The 30-day in-hospital mortality rate was 3.0 percent overall, 5.2 percent (95 percent CI: 4.0-6.4) in low-volume hospitals, and 2.1 percent (95 percent CI: 1.8-2.3) in high-volume hospitals. There is a significant curvilinear relationship between volume and mortality, flatter above 415 cases per hospital per year. CONCLUSIONS: There is a clear relationship between hospital CABG volume and mortality in Europe, implying a "safe" threshold volume of 415 cases per year.