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1.
Artigo em Inglês | MEDLINE | ID: mdl-31358329

RESUMO

OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS: Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.

2.
Sci Rep ; 8(1): 1262, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29352162

RESUMO

We evaluated a standard subcutaneous microdialysis technique for glucose monitoring in two critically ill patient populations and tested whether a prolonged run-in period improves the quality of the interstitial glucose signal. 20 surgical patients after major cardiac surgery (APACHE II score: 10.1 ± 3.2) and 10 medical patients with severe sepsis (APACHE II score: 31.1 ± 4.3) were included in this investigation. A microdialysis catheter was inserted in the subcutaneous adipose tissue of the abdominal region. Interstitial fluid and arterial blood were sampled in hourly intervals to analyse glucose concentrations. Subcutaneous adipose tissue glucose was prospectively calibrated to reference arterial blood either at hour 1 or at hour 6. Median absolute relative difference of glucose (MARD), calibrated at hour 6 (6.2 (2.6; 12.4) %) versus hour 1 (9.9 (4.2; 17.9) %) after catheter insertion indicated a significant improvement in signal quality in patients after major cardiac surgery (p < 0.001). Prolonged run-in period revealed no significant improvement in patients with severe sepsis, but the number of extreme deviations from the blood plasma values could be reduced. Improved concurrence of glucose readings via a 6-hour run-in period could only be achieved in patients after major cardiac surgery.


Assuntos
Glicemia/metabolismo , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Microdiálise/normas , Monitorização Fisiológica/normas , Complicações Pós-Operatórias/sangue , Sepse/sangue , Idoso , Ensaios Clínicos como Assunto , Estado Terminal , Líquido Extracelular/metabolismo , Feminino , Humanos , Masculino , Microdiálise/métodos , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos
3.
Wien Klin Wochenschr ; 129(9-10): 303-316, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28432428

RESUMO

Uncontrolled massive bleeding with subsequent derangement of the coagulation system is a major challenge in the management of both surgical and seriously injured patients. Under physiological conditions activators and inhibitors of coagulation regulate the sensitive balance between clot formation and fibrinolysis. In some cases, excessive and diffuse bleeding is caused by systemic activation of fibrinolysis, i. e. hyperfibrinolysis (HF). Uncontrolled HF is associated with a high mortality. Polytrauma patients and those undergoing surgical procedures involving organs rich in plasminogen proactivators (e. g. liver, kidney, pancreas, uterus and prostate gland) are at a high risk for HF. Antifibrinolytics, such as tranexamic acid (TXA) are used for prophylaxis and treatment of bleeding caused by a local or generalized HF as well as other hemorrhagic conditions. TXA is a synthetic lysine analogue that has been available in Austria since 1966. TXA is of utmost importance in the prevention and treatment of traumatic and perioperative bleeding due to the resulting reduction in perioperative blood loss and blood transfusion requirements. The following article presents the different fields of application of TXA with particular respect to indications and dosages, based on a literature search and on current guidelines.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Hematologia/normas , Hemorragia/prevenção & controle , Guias de Prática Clínica como Assunto , Ácido Tranexâmico/administração & dosagem , Antifibrinolíticos/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Resultado do Tratamento
4.
N Engl J Med ; 376(21): 2032-2042, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28316276

RESUMO

BACKGROUND: Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery. METHODS: In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 µg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 µg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5. RESULTS: A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups. CONCLUSIONS: Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS ClinicalTrials.gov number, NCT02025621 .).


Assuntos
Baixo Débito Cardíaco/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos , Cardiotônicos/uso terapêutico , Hidrazonas/uso terapêutico , Mortalidade , Piridazinas/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Cardiotônicos/efeitos adversos , Método Duplo-Cego , Feminino , Coração Auxiliar/estatística & dados numéricos , Humanos , Hidrazonas/efeitos adversos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Período Perioperatório , Complicações Pós-Operatórias/tratamento farmacológico , Piridazinas/efeitos adversos , Terapia de Substituição Renal/estatística & dados numéricos , Simendana , Volume Sistólico/efeitos dos fármacos , Falha de Tratamento
5.
Am Heart J ; 182: 62-71, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27914501

RESUMO

BACKGROUND: Low cardiac output syndrome is associated with increased mortality and occurs in 3% to 14% of patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). Levosimendan, a novel calcium sensitizer and KATP channel activator with inotropic, vasodilatory, and cardioprotective properties, has shown significant promise in reducing the incidence of low cardiac output syndrome and related adverse outcomes in patients undergoing cardiac surgery on CPB. METHODS: LEVO-CTS is a phase 3 randomized, controlled, multicenter study evaluating the efficacy, safety, and cost-effectiveness of levosimendan in reducing morbidity and mortality in high-risk patients with reduced left ventricular ejection fraction (≤35%) undergoing cardiac surgery on CPB. Patients will be randomly assigned to receive either intravenous levosimendan (0.2 µg kg-1 min-1 for the first hour followed by 0.1 µg/kg for 23hours) or matching placebo initiated within 8hours of surgery. The co-primary end points are (1) the composite of death or renal replacement therapy through day 30 or perioperative myocardial infarction, or mechanical assist device use through day 5 (quad end point tested at α<.01), and (2) the composite of death through postoperative day 30 or mechanical assist device use through day 5 (dual end point tested at α<.04). Safety end points include new atrial fibrillation and death through 90days. In addition, an economic analysis will address the cost-effectiveness of levosimendan compared with placebo in high-risk patients undergoing cardiac surgery on CPB. Approximately 880 patients will be enrolled at approximately 60 sites in the United States and Canada between July 2014 and September 2016, with results anticipated in January 2017. CONCLUSION: LEVO-CTS, a large randomized multicenter clinical trial, will evaluate the efficacy, safety, and cost-effectiveness of levosimendan in reducing adverse outcomes in high-risk patients undergoing cardiac surgery on CPB. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02025621).


Assuntos
Procedimentos Cirúrgicos Cardíacos , Hidrazonas , Complicações Pós-Operatórias , Piridazinas , Disfunção Ventricular Esquerda/terapia , Administração Intravenosa , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/métodos , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Hidrazonas/administração & dosagem , Hidrazonas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Piridazinas/administração & dosagem , Piridazinas/efeitos adversos , Simendana , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia
6.
Ann Thorac Surg ; 102(6): 2010-2017, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27378554

RESUMO

BACKGROUND: Up to 15% of patients require coronary artery bypass grafting (CABG) during dual antiplatelet therapy. Available evidence suggests an association between platelet reactivity and CABG-related bleeding. However, platelet reactivity cutoffs for bleeding remain elusive. We sought to explore the association between platelet reactivity and bleeding. METHODS: Patients on aspirin and a P2Y12 receptor inhibitor within 48 hours before isolated CABG (n = 149) were enrolled in this prospective study. Blood was drawn 2 to 4 hours preoperatively and platelet reactivity assessed by light transmittance aggregometry (LTA), vasodilator-stimulated phosphoprotein (VASP) assay, Multiplate analyzer and Innovance PFA2Y. The primary endpoint was calculated red blood cell loss computed as follows: (blood volume × preoperative hematocrit × 0.91) - (blood volume × hematocrit × 0.91 on postoperative day 5) + (mL of transfused red blood cells × 0.59). RESULTS: Preoperative platelet reactivity was low [median (interquartile range): LTA: 20 (9-28)%; VASP-PRI: 39 (15-73)%; Multiplate adenosine phosphate test: 16 (12-22) U∗min]. Innovance PFA2Y ≥300 seconds, 72%. Median (IQR) red blood cell loss in patients in first the LTA tertile was 1,449 (1,020 to 1,754) mL compared with 1,107 (858 to 1,512) mL and 1,075 (811 to 1,269) mL in those in the second and third tertiles, respectively (p < 0.004). Bleeding Academic Research Consortium (BARC)-4 bleeding differed between tertiles (62% versus 46% versus 36%; p = 0.037). In a multivariable linear regression model, aspirin dose ≥300 mg, cardiopulmonary bypass time, EuroSCORE, and tertile distribution of platelet reactivity were significantly associated with red blood cell loss. CONCLUSIONS: A gradual decrease in red blood cell loss and BARC-4 bleeding occurs with increasing platelet reactivity in patients on antiplatelet therapy undergoing CABG. Our findings support current guidelines to determine time of surgery based on an objective measurement of platelet function (Platelet Inhibition and Bleeding in Patients Undergoing Emergent Cardiac Surgery; clinicaltrials.gov NCT01468597).


Assuntos
Aspirina/uso terapêutico , Perda Sanguínea Cirúrgica , Ponte de Artéria Coronária , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/uso terapêutico , Hemorragia Pós-Operatória/sangue , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Aspirina/administração & dosagem , Aspirina/farmacologia , Quimioterapia Combinada , Emergências , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/farmacologia , Testes de Função Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/etiologia , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/farmacologia
7.
Clin Chem Lab Med ; 54(3): 453-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26351930

RESUMO

BACKGROUND: Fibrinogen-based clot firmness is reported as the maximum amplitude (MA) when using the citrated functional fibrinogen (CFF) assay in thrombelastography (TEG), and as the maximum clot firmness (MCF) together with several clot amplitude parameters when using the FIBTEM assay in thromboelastometry (ROTEM). Concern is currently being raised that these two tests have different platelet inhibiting performance and consequently provide different values. This is relevant for the clinical setting of fibrinogen replacement. We aim herein to compare the parameters of these two fibrinogen-based clot quality tests and their correlation with the plasma fibrinogen level as determined by the Clauss method. METHODS: In total 261 whole blood samples taken from 163 clinical routine surgical patients were analyzed with TEG 5000 and ROTEM tests, and correlation with Clauss fibrinogen level was assessed. RESULTS: Using TEG, the overall fibrin-based clot firmness measured in the CFF assay was significantly higher than the MCF measured by FIBTEM assay. Both assays showed significantly positive correlations with the fibrinogen levels measured using the Clauss method. However, individual values of Clauss fibrinogen concentration corresponded with different values for the two viscoelastometric tests; e.g. within the range of 1.9-2.1 g/L Clauss fibrinogen the median of CFF MA was 16.3 mm whereas FIBTEM MCF was 12.0 mm. CONCLUSIONS: We showed herein by measurements of citrated whole blood samples from surgical patients that CFF MA values were different from FIBTEM MCF values measured in the same sample. Awareness that these whole blood assays provide different clot amplitude results is mandatory, particularly if they are being considered as tools for guiding fibrinogen supplementation. Thromboembolic side effects caused by a potentially too high fibrinogen substitution must also kept in mind in this context.


Assuntos
Testes de Coagulação Sanguínea/normas , Fibrinogênio/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Fibrinogênio/química , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Projetos de Pesquisa , Estudos Retrospectivos
8.
JAMA ; 312(15): 1520-30, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25268295

RESUMO

IMPORTANCE: Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal. OBJECTIVE: To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs. DESIGN, SETTING, AND PARTICIPANTS: A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243). INTERVENTIONS: Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months. MAIN OUTCOMES AND MEASURES: The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis. RESULTS: A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). CONCLUSIONS AND RELEVANCE: Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130181.


Assuntos
Colecalciferol/uso terapêutico , Estado Terminal , Tempo de Internação , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade
12.
Crit Care ; 14(2): 201, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20497611

RESUMO

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência Cardíaca/etiologia , Assistência Perioperatória/organização & administração , Guias de Prática Clínica como Assunto , Humanos , Valor Preditivo dos Testes , Prognóstico
13.
Curr Opin Anaesthesiol ; 21(1): 78-84, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18195615

RESUMO

PURPOSE OF REVIEW: While patients with acute heart failure typically receive diuretics and vasodilators, contractile dysfunction and peripheral hypoperfusion also leads to a widespread use of inotropic agents despite the lack of evidence for efficacy or safety. Levosimendan, a calcium sensitizer and vasodilator, has been proposed to be superior to standard inotropes. In addition, further possible indications for levosimendan have been described, such as perioperative use, cardioprotection, cardiogenic shock, sepsis, and right ventricular dysfunction. RECENT FINDINGS: The mortality benefit of levosimendan has not been confirmed in two recent trials but the substance improves symptoms, decreases brain natriuretic peptide and is effective during beta-blocker treatment. The use of levosimendan as an add-on therapy in acute heart failure has been encouraged as well as its perioperative use. Levosimendan may also be useful during right ventricular dysfunction and septic shock due to its favorable effects on splanchnic perfusion. SUMMARY: Levosimendan is an established substance in the treatment of acute heart failure in several countries despite disappointing findings concerning a possible survival benefit in two recent clinical trials. Owing to its alternative mechanisms of action as compared with traditional cardiotonic agents, several promising clinical applications have arisen. Available evidence for the use of levosimendan in settings other than decompensated heart failure is currently limited.


Assuntos
Cardiotônicos/uso terapêutico , Hidrazonas/uso terapêutico , Piridazinas/uso terapêutico , Doença Aguda , Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hidrazonas/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Piridazinas/efeitos adversos , Choque Séptico/tratamento farmacológico , Simendana , Disfunção Ventricular Direita/tratamento farmacológico
14.
Anesthesiology ; 106(6): 1088-95, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17525582

RESUMO

BACKGROUND: Preoperative N-terminal pro-BNP (NT-proBNP) is independently associated with adverse cardiac outcome but does not anticipate the dynamic consequences of anesthesia and surgery. The authors hypothesized that a single postoperative NT-proBNP level provides additional prognostic information for in-hospital and late cardiac events. METHODS: Two hundred eighteen patients scheduled to undergo vascular surgery were enrolled and followed up for 24-30 months. Logistic regression and Cox proportional hazards model were performed to evaluate predictors of in-hospital and long-term cardiac outcome. The optimal discriminatory level of preoperative and postoperative NT-proBNP was determined by receiver operating characteristic analysis. RESULTS: During a median follow-up of 826 days, 44 patients (20%) experienced 51 cardiac events. Perioperatively, median NT-proBNP increased from 215 to 557 pg/ml (interquartile range, 83/457 to 221/1178 pg/ml; P<0.001). The optimum discriminate threshold for preoperative and postoperative NT-proBNP was 280 pg/ml (95% confidence interval, 123-400) and 860 pg/ml (95% confidence interval, 556-1,054), respectively. Adjusted for age, previous myocardial infarction, preoperative fibrinogen, creatinine, high-sensitivity C-reactive protein, type, duration, and surgical complications, only postoperative NT-proBNP remained significantly associated with in-hospital (adjusted hazard ratio, 19.8; 95% confidence interval, 3.4-115) and long-term cardiac outcome (adjusted hazard ratio, 4.88; 95% confidence interval, 2.43-9.81). CONCLUSION: A single postoperative NT-proBNP determination provides important additional prognostic information to preoperative levels and may support therapeutic decisions to prevent subsequent structural myocardial damage.


Assuntos
Infarto do Miocárdio/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/sangue , Idoso , Comorbidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/diagnóstico , Cuidados Pré-Operatórios , Prognóstico , Procedimentos Cirúrgicos Vasculares
16.
Diabetes Care ; 29(6): 1275-81, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16732008

RESUMO

OBJECTIVE: Tight glycemic control improves outcome in critically ill patients but requires frequent glucose measurements. Subcutaneous adipose tissue (SAT) has been characterized as promising for glucose monitoring in diabetes, but it remains unknown whether it can also be used as an alternative site in critically ill patients. The present study was performed to clinically evaluate the relation of glucose in SAT compared with arterial blood in patients after major cardiac surgery. RESEARCH DESIGN AND METHODS: Forty critically ill patients were investigated at two clinical centers after major cardiac surgery. Arterial blood and SAT microdialysis samples were taken in hourly intervals for a period of up to 48 h. The glucose concentration in dialysate was calibrated using a two-step approach, first using the ionic reference technique to calculate the SAT glucose concentration (SATg) and second using a one-point calibration procedure to obtain a glucose profile comparable to SAT-derived blood glucose (BgSAT). Clinical validation of the data was performed by introducing data analysis based on an insulin titration algorithm. RESULTS: Correlation between dialysate glucose and blood glucose (median 0.80 [interquartile range 0.68-0.88]) was significantly improved using the ionic reference calibration technique (SATg vs.blood glucose 0.90 [0.83-0.94]; P < 0.001). Clinical evaluation of the data indicated that 96.1% of glucose readings from SAT would allow acceptable treatment according to a well-established insulin titration protocol. CONCLUSIONS: The results indicate good correlation between SATg and blood glucose in patients after major cardiac surgery. Clinical evaluation of the data suggests that with minor limitations, glucose from SAT can be used to establish tight glycemic control in this patient group.


Assuntos
Glicemia/análise , Procedimentos Cirúrgicos Cardíacos , Monitorização Fisiológica/métodos , Idoso , Pressão Sanguínea , Calibragem , Estado Terminal , Feminino , Frequência Cardíaca , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Período Pós-Operatório
17.
Anesthesiology ; 104(3): 556-69, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16508404

RESUMO

Several clinical studies suggest substantial limitations of currently available positive inotropic substances, including beta1-adrenoceptor agonists and phosphodiesterase III inhibitors in the short- and long-term treatment of heart failure. The reasons for these detrimental effects are related to the mechanism of action of these drugs, including increases in intracellular Ca2+ with subsequent increases in myocardial oxygen demand and arrhythmogenesis. Levosimendan, a myofilament Ca2+ sensitizer with inotropic effects, increases myocardial performance without substantial changes in oxygen consumption and with neutral effects on heart rhythm. In addition, levosimendan has vasodilatory effects that are achieved by stimulation of adenosine triphosphate-dependent potassium channels. This action may be of specific interest in the setting of myocardial ischemia. To date, levosimendan is approved in 31 countries worldwide, and more patients with heart failure have participated in randomized controlled trials with levosimendan than with any other intravenous inotropic agent.


Assuntos
Cardiotônicos/farmacologia , Hidrazonas/farmacologia , Piridazinas/farmacologia , Vasodilatadores/farmacologia , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Animais , Cálcio/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3 , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidrazonas/efeitos adversos , Hidrazonas/farmacocinética , Hidrazonas/uso terapêutico , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Inibidores de Fosfodiesterase/farmacologia , Canais de Potássio/efeitos dos fármacos , Piridazinas/efeitos adversos , Piridazinas/farmacocinética , Piridazinas/uso terapêutico , Simendana
18.
Paediatr Anaesth ; 16(3): 266-74, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16490090

RESUMO

BACKGROUND: This study evaluated a propofol-based anesthesia regimen with spontaneous breathing in pediatric patients scheduled for magnetic resonance imaging (MRI). METHODS: In this prospective, randomized, double-blind study propofol formulated with long-chain triglycerides (LCT) and mixed medium-chain/long-chain triglycerides (MCT/LCT) were used. Ninety patients aged 2.4 months to 7.3 years were premedicated with intravenous midazolam. Lidocaine was injected prior to propofol to reduce injection pain. Anesthesia was induced and maintained by propofol. Glycopyrronium bromide was administered for saliva reduction. Hemodynamics, blood oxygen saturation and endtidal capnography were continuously monitored. All patients received additional oxygen. The aggregated propofol dose for induction and maintenance of anesthesia was analyzed for therapeutic equivalence. Incidence of injection pain, laboratory safety values, vital signs, and the adverse event profile were analyzed to compare tolerability and safety. RESULTS: Propofol anesthesia was safe and successful in all children. Both propofol formulations were equivalent regarding dose requirements (mean induction and maintenance doses for anesthesia 2.0-4.0 mg.kg(-1) and 6.0-8.8 mg.kg(-1).h(-1) respectively; aggregated doses 8-13.26 mg.kg(-1)). There were no differences in drug safety such as hemodynamics, spontaneous breathing, injection pain, and laboratory values. Duration of induction and of recovery from anesthesia were short and all examinations were completed with minimal interruption. CONCLUSIONS: Propofol-based short-term anesthesia was well suited for anesthesia during MRI procedures in the studied pediatric patients. There were no clinically relevant differences between the two propofol formulations.


Assuntos
Anestesia Intravenosa , Anestésicos Intravenosos , Imagem por Ressonância Magnética , Propofol , Anestésicos Intravenosos/efeitos adversos , Criança , Pré-Escolar , Formas de Dosagem , Método Duplo-Cego , Emulsões , Feminino , Humanos , Lactente , Injeções Intravenosas , Masculino , Propofol/efeitos adversos , Equivalência Terapêutica , Triglicerídeos
19.
Diabetes Care ; 29(2): 271-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16443872

RESUMO

OBJECTIVE: To evaluate a fully automated algorithm for the establishment of tight glycemic control in critically ill patients and to compare the results with different routine glucose management protocols of three intensive care units (ICUs) across Europe (Graz, Prague, and London). RESEARCH DESIGN AND METHODS: Sixty patients undergoing cardiac surgery (age 67 +/- 9 years, BMI 27.7 +/- 4.9 kg/m2, 17 women) with postsurgery blood glucose levels >120 mg/dl (6.7 mmol/l) were investigated in three different ICUs (20 per center). Patients were randomized to either blood glucose management (target range 80-110 mg/dl [4.4-6.1 mmol/l]) by the fully automated model predictive control (MPC) algorithm (n = 30, 10 per center) or implemented routine glucose management protocols (n = 30, 10 per center). In all patients, arterial glucose was measured hourly to describe the glucose profile until the end of the ICU stay but for a maximum period of 48 h. RESULTS: Compared with routine protocols, MPC treatment resulted in a significantly higher percentage of time within the target glycemic range (% median [min-max]: 52 [17-92] vs. 19 [0-71]) over 0-24 h (P < 0.01). Improved glycemic control with MPC treatment was confirmed in patients remaining in the ICU for 48 h (0-24 h: 50 [17-71] vs. 21 [4-67], P < 0.05, and 24-48 h: 65 [38-96] vs. 25 [8-79], P < 0.05, for MPC [n = 16] vs. routine protocol [n = 13], respectively). Two hypoglycemic events (<54 mg/dl [3.0 mmol/l]) were observed with routine protocol treatment. No hypoglycemic event occurred with MPC. CONCLUSIONS: The data suggest that the MPC algorithm is safe and effective in controlling glycemia in critically ill postsurgery patients.


Assuntos
Algoritmos , Glicemia/metabolismo , Cardiopatias/cirurgia , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Monitorização Fisiológica/métodos , Cuidados Pós-Operatórios , Idoso , Carboidratos/administração & dosagem , Estado Terminal , Feminino , Cardiopatias/sangue , Humanos , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Unidades de Terapia Intensiva , Masculino
20.
Eur J Pharmacol ; 507(1-3): 199-209, 2005 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-15659310

RESUMO

We evaluated the inotropic actions of levosimendan and epinephrine, both singly and in combination, under isohydric (pH 7.4) and acidotic (pH 7.0) conditions in isolated guinea-pig hearts. Acidosis depressed contractility and myocardial relaxation by 25-30%, and both inotropes were less efficacious at pH 7.0, while their potencies were unaffected. In combination experiments, the presence of levosimendan increased the potency of epinephrine approximately 17-fold (pH 7.4) and 11-fold (pH 7.0), and the presence of epinephrine increased the potency of levosimendan approximately 12-fold (pH 7.4) and approximately 21-fold (pH 7.0). At pH 7.0, both inotropes augmented papillary muscle contraction to a similar extent, but in contrast to epinephrine, levosimendan non-significantly [corrected] raised cAMP levels. In conclusion, combining levosimendan with epinephrine helps to overcome the depressed inotropic actions of epinephrine during acidosis, suggesting that additional studies which might justify clinical evaluation of the concurrent use of the two agents should be performed.


Assuntos
Acidose/tratamento farmacológico , Epinefrina/administração & dosagem , Hidrazonas/administração & dosagem , Contração Miocárdica/efeitos dos fármacos , Piridazinas/administração & dosagem , Acidose/fisiopatologia , Animais , Cardiotônicos/administração & dosagem , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Cobaias , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Técnicas In Vitro , Masculino , Contração Miocárdica/fisiologia , Simendana
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