RESUMO
The hemodynamic model was inappropriate to explain the disappointing effect of vasodilation and the beneficial effect of beta-blockade in chronic heart failure. A more nuanced hemodynamic analysis, taking both steady and pulsatile hemodynamics into consideration, improves insight into these apparently enigmatic effects. Of particular interest is the velocity of early systolic flow as a determinant of left ventricular afterload. Several drugs, in particular beta-blockers, directly or indirectly, influence the velocity of early systolic flow. Thus, the hemodynamic model in heart failure may deserve reconsideration.
Assuntos
Insuficiência Cardíaca , Hemodinâmica , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêuticoRESUMO
BACKGROUND AND AIMS: Secondary prevention of esophageal variceal bleeding is important to improve prognosis, but uptake of guidelines is unknown in a real-world setting. Here, we determined the proportion of patients receiving appropriate nonselective beta-blocker treatment and repeat upper endoscopy after a first episode of esophageal variceal bleeding within a reasonable time frame. METHODS: Population-based registers were used to identify all patients with a first episode of esophageal variceal bleeding in Sweden from 2006 to 2020. Crosslinkage between registers was performed to receive information on the cumulative incidence of patients with a dispensation of nonselective beta-blockers and repeat upper endoscopy within 120 days from baseline. Overall mortality was investigated using Cox regression. RESULTS: In total, 3592 patients were identified, with a median age of 63 (interquartile range, 54-71) years. The cumulative incidence of a dispensation of nonselective beta-blockers and a repeat endoscopy within 120 days was 33%. A total of 77% received either of these treatments. Overall mortality was high, with 65% of patients dying after esophageal variceal bleeding during the full follow-up period (median 1.7 years). We observed an improved overall mortality during the later years of the study period (adjusted hazard ratio for the 2016-2020 period compared with the 2006-2010 period, 0.80; 95% confidence interval, 0.71-0.89). Patients with receipt of nonselective beta-blockers and repeat upper endoscopy had better overall survival compared with those without (adjusted hazard ratio, 0.80; 95% confidence interval, 0.72-0.90). CONCLUSIONS: Secondary prevention of esophageal variceal bleeding has not been widely undertaken, with many patients not receiving guideline-supported interventions within a reasonable time frame. This highlights a need to raise awareness on appropriate prevention strategies to clinicians and patients.
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Varizes Esofágicas e Gástricas , Hemorragia Gastrointestinal , Humanos , Pessoa de Meia-Idade , Idoso , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/prevenção & controle , Hemorragia Gastrointestinal/etiologia , Varizes Esofágicas e Gástricas/epidemiologia , Varizes Esofágicas e Gástricas/complicações , Prevenção Secundária , Estudos de Coortes , Endoscopia Gastrointestinal/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Cirrose Hepática/complicações , Ligadura/efeitos adversosRESUMO
Bisoprolol and nebivolol are highly selective ß1-adrenoceptor antagonists, with clinical indications in many countries within the management of heart failure with reduced left ventricular ejection fraction (HFrEF), ischaemic heart disease (IHD), and hypertension. Nebivolol has additional vasodilator actions, related to enhanced release of NO in the vascular wall. In principle, this additional mechanism compared with bisoprolol might lead to more potent vasodilatation, which in turn might influence the effectiveness of nebivolol in the management of HFrEF, IHD and hypertension. In this article, we review the therapeutic properties of bisoprolol and nebivolol, as representatives of "second generation" and "third generation" ß-blockers, respectively. Although head-to-head trials are largely lacking, there is no clear indication from published studies of an additional effect of nebivolol on clinical outcomes in patients with HFrEF or the magnitude of reductions of BP in patients with hypertension.
Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Hipertensão , Isquemia Miocárdica , Antagonistas Adrenérgicos beta/uso terapêutico , Benzopiranos/efeitos adversos , Bisoprolol/farmacologia , Bisoprolol/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Etanolaminas/farmacologia , Etanolaminas/uso terapêutico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Nebivolol/efeitos adversos , Volume Sistólico , Vasodilatadores/uso terapêutico , Função Ventricular EsquerdaRESUMO
Beta-blockers are often used in the treatment of patients with stress cardiomyopathy without firm evidence of benefit. We conducted a retrospective case note review investigating the effects of beta-blockers on QT interval and heart rate in patients with stress cardiomyopathy over 3 days of hospital admission. We found no evidence of effects on QT interval from beta-blocker treatment in this condition.
Assuntos
Cardiomiopatia de Takotsubo , Antagonistas Adrenérgicos beta , Eletrocardiografia , Frequência Cardíaca , Humanos , Estudos Retrospectivos , Cardiomiopatia de Takotsubo/tratamento farmacológicoRESUMO
PURPOSE: Habitual endurance exercise results in increased erythropoiesis, which is primarily controlled by erythropoietin (EPO), yet studies demonstrating upregulation of EPO via a single bout of endurance exercise have been equivocal. This study compares the acute EPO response to 30 min of high versus 90 min of moderate-intensity endurance exercise and whether that response can be upregulated via selective adrenergic receptor blockade. METHODS: Using a counterbalanced, cross-over design, fifteen participants (age 28 ± 8) completed two bouts of running (30-min, high intensity vs 90-min, moderate intensity) matched for overall training stress. A separate cohort of fourteen participants (age 31 ± 6) completed three bouts of 30-min high-intensity cycling after ingesting the preferential ß1-adrenergic receptor (AR) antagonist bisoprolol, the non-preferential ß1 + ß2 antagonist nadolol or placebo. Venous blood was collected before, during, and after exercise, and serum EPO levels were determined by ELISA. RESULTS: No detectable EPO response was observed during or after high intensity running, however, in the moderate-intensity trial EPO was significantly elevated at both during-exercise timepoints (+ 6.8% ± 2.3% at 15 min and + 8.7% ± 2.2% at 60 min). No significant change in EPO was observed post-cycling or between the trials involving ßAR blockade. CONCLUSION: Neither training mode (running or cycling), nor beta-blockade significantly influenced the EPO response to 30 min of high-intensity exercise, however, 90 min of moderate-intensity running elevated EPO during exercise, returning to baseline immediately post-exercise. Identifying the optimal mode, duration and intensity required to evoke an EPO response to exercise may help tailor exercise prescriptions designed to maximize EPO response for both performance and clinical applications.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Bisoprolol/farmacologia , Eritropoetina/metabolismo , Nadolol/farmacologia , Resistência Física/fisiologia , Adulto , Ciclismo/fisiologia , Estudos Cross-Over , Feminino , Humanos , Masculino , Corrida/fisiologia , Regulação para CimaRESUMO
AIMS: The effects of sympatho-vagal interaction on heart rate (HR) changes are characterized by vagal dominance resulting in accentuated antagonism. Complex autonomic modulation of ventricular electrophysiology may exert prognostic arrhythmic impact. We examined the effects of concurrent sympathetic (SNS) and vagus (VNS) nerve stimulation on ventricular fibrillation threshold (VFT) and standard restitution (RT) in an isolated rabbit heart preparation with intact dual autonomic innervation, with and without beta-blockade. METHODS AND RESULTS: Monophasic action potentials were recorded from left ventricular epicardial surface of dual-innervated isolated heart preparations from New Zealand white rabbits (n = 18). HR, VFT and RT were measured during different stimulation protocols (Protocol 1: VNS-SNS; Protocol 2: SNS-VNS) involving low- and high-frequency stimulations. A sub-study of Protocol 2 was performed in the presence of metoprolol tartrate. In both protocols, HR changes were characterized by vagal-dominant bradycardic component, affirming accentuated antagonism. During concurrent high-frequency VNS (HV), SNS prevails in lowering VFT in a frequency-sensitive manner during low (LS) or high (HS)-frequency stimulations (HV-LS: -2.8 ± 0.8 mA; HV-HS: -4.0 ± 0.9 mA, p < .05 vs. HV), with accompanying steepening of relative RT slope gradients (HV-LS: 223.54 ± 37.41%; HV-HS: 295.20 ± 60.86%, p < .05 vs. HV). In protocol 2, low (LV) and high (HV) vagal stimulations during concurrent HS raised VFT (HS-LV: 1.0 ± 0.4 mA; HS-HV: 3.0 ± 0.6 mA, p < .05 vs HS) with associated flattening of RT slopes (HS-LV: 32.40 ± 4.97%;HS-HV: 38.07 ± 6.37%; p < .05 vs HS). Metoprolol abolished accentuated antagonism in HR changes, reduced VFT and flattened RT globally during SNS-VNS. CONCLUSIONS: Accentuated antagonism is absent in ventricular electrophysiological changes during sympatho-vagal interaction with sympathetic effect prevailing, suggesting a different mechanism at the ventricular level from heart rate effects. Metoprolol nullified accentuated antagonism with additional anti-fibrillatory effect beyond adrenergic blockade during sympatho-vagal stimulations.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Fenômenos Eletrofisiológicos , Ventrículos do Coração/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Nervo Vago/fisiopatologia , Animais , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Masculino , Metoprolol , Perfusão , Coelhos , Sistema Nervoso Simpático/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Estimulação do Nervo VagoRESUMO
BACKGROUND: The aim of this double-blind, placebo-controlled, single-ascending-dose study was to determine the safety and tolerability of intranasal dexmedetomidine in the elderly. METHODS: We randomly assigned 48 surgical patients ≥65 yr of age to receive single intranasal doses of dexmedetomidine or placebo (5:1 ratio) in four sequential dose cohorts: 0.5, 1.0, 1.5, and 2.0 µg kg-1. Each dose cohort comprised two groups of six subjects: a group of subjects using ß-blockers and a group not taking ß-blockers. Vital signs and sedation depth (Modified Observer's Assessment of Alertness and Sedation [MOAA/S] and bispectral index) were measured for 2 h after administration. Blood samples were taken to determine dexmedetomidine plasma concentrations. RESULTS: One subject (1.0 µg kg-1) had acute hypotension requiring ephedrine. Systolic arterial BP decreased >30% in 15 of 40 subjects (37.5%) receiving dexmedetomidine, lasting longer than 5 min in 11 subjects (27.5%). The MAP decreased >30% (>5 min) in 10%, 20%, 50%, and 30% of subjects receiving dexmedetomidine 0.5, 1.0, 1.5, and 2.0 µg kg-1, respectively, irrespective of ß-blocker use. HR decreased 10-26%. MOAA/S score ≤3 occurred in 18 (45%) subjects; eight (20%) subjects receiving dexmedetomidine showed no signs of sedation. Tmax was 70 min. Cmax was between 0.15 ng ml-1 (0.5 µg kg-1) and 0.46 ng ml-1 (2.0 µg kg-1). CONCLUSIONS: Intranasal dexmedetomidine in elderly subjects had a sedative effect, but caused a high incidence of profound and sustained hypotension irrespective of ß-blocker use. The technique is unsuitable for routine clinical use. CLINICAL TRIAL REGISTRATION: NTR5513 (The Netherlands Trial Registry 5513).
RESUMO
BACKGROUND: Electrical storm is a dangerous condition presenting to the Emergency Department that requires rapid diagnosis and management. OBJECTIVE: This article provides a review of the diagnosis and management of electrical storm for the emergency clinician. DISCUSSION: Electrical storm is defined as ≥3 episodes of sustained ventricular tachycardia, ventricular fibrillation, or shocks from an implantable cardioverter defibrillator within 24 h. Patients may present with a wide array of symptoms. Initial evaluation should include an electrocardiogram with a rhythm strip and continuous cardiac monitoring, a medication history, assessment of hemodynamic stability, and identification of potential triggers. Management includes an antiarrhythmic and a beta blocker. Refractory patients may benefit from double-sequential defibrillation or more invasive procedures such as intra-aortic balloon pumps, catheter ablation and extracorporeal membrane oxygenation for critically ill patients. These patients will typically require admission to an intensive care unit. CONCLUSION: Electrical storm is a condition associated with significant morbidity and mortality. It is important for clinicians to be aware of the current evidence regarding the evaluation and management of these patients.
Assuntos
Desfibriladores Implantáveis , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/terapia , Agonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Algoritmos , Antiarrítmicos/uso terapêutico , Diagnóstico Diferencial , Eletrocardiografia , Serviço Hospitalar de Emergência , Humanos , Anamnese , Exame Físico , Fatores de Risco , Taquicardia Supraventricular/diagnósticoRESUMO
BACKGROUND: The aim of study was to investigate effects of beta-blockade on microvolt T-wave alternans (TWA), a precursor of lethal arrhythmia, in patients with long QT syndrome (LQTS). METHODS: Eleven consecutive LQTS patients, types 1 (n = 6), 3 (n = 2), and "non-1, non-2, non-3" (n = 3) were enrolled. All patients underwent 24-hr continuous 12-lead ECG monitoring before and after initiation of beta-blockade therapy. TWA was measured using the modified moving average method. RESULTS: Seven (63.6%) of the 11 patients studied were symptomatic, with history of cardiac arrest or documented Torsade de Pointes (TdP) in 4 and syncope in three patients. After a median follow-up of 34 months, beta-blockade reduced the number of symptomatic patients to 1 with TdP (p < 0.02), in whom TdP frequency decreased from 25 events/60 months (0.42 event/month) to seven events/69 months (0.1 event/month). In association with this reduction in symptoms, peak TWA decreased by 47% in the cohort after a median of eight months of beta-blockade therapy [from 95 (74-130) to 50 (39.5-64.5) µV, p = 0.01]. All patients exhibited TWA ≥42 µV before beta-blockade therapy, which eliminated these episodes in four patients. Daily frequency of TWA ≥42 µV episodes decreased by 87% [from 15 (6-26) to 2 (0-5) episodes/day, p = 0.009]. CONCLUSIONS: This study is limited by the small sample size and is mainly hypothesis generating. TWA monitoring deserves further evaluation as a risk marker and a guide to therapy in LQTS patients in future large-scale studies.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Arritmias Cardíacas/complicações , Arritmias Cardíacas/prevenção & controle , Eletrocardiografia Ambulatorial/métodos , Síndrome do QT Longo/complicações , Síndrome do QT Longo/tratamento farmacológico , Adolescente , Adulto , Arritmias Cardíacas/fisiopatologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Nonselective Beta blockade (NSBB) is commonly prescribed for liver transplantation (LT) candidates, but its impact on intraoperative hemodynamics is not well understood. In this study, we investigated if preoperative NSBB was associated with severe bradycardia during LT and if severe intraoperative bradycardia was associated with 30-day mortality. Adult patients undergoing LT between 2005 and 2014 were included. Propensity matching was used to control selection bias. Intraoperative hemodynamics were compared between patients with and without preoperative NSBB. Univariate and multivariate methods were used in statistical analysis. Of 1452 patients, 370 who received preoperative NSBB were matched in a 1:1 ratio with those who did not. Propensity matching eliminated all significant differences between the two groups. Patients who received preoperative NSBB had a significantly higher incidence of severe intraoperative bradycardia compared with the non-BB group (9.6% vs 3.2%, P = 0.001, OR 2.95, 95% CI 1.42-6.12, P = 0.004). Intraoperative hypotension and postreperfusion syndrome were not significantly different between the two groups. Severe intraoperative bradycardia was associated with increased 30-day mortality. In conclusion, preoperative NSBB was associated with severe intraoperative bradycardia in LT. In patients who receive preoperative NSBB, severe intraoperative bradycardia should be closely monitored in LT. Further studies assessing safety of preoperative NSBB and intraoperative bradycardia in LT are warranted.
Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Bradicardia/etiologia , Complicações Intraoperatórias/etiologia , Transplante de Fígado/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Cytomegalovirus (CMV) has been implicated as a factor in immunosenescence, including poor antibody response to vaccination and higher immune activation and inflammation. Some people may be more or less vulnerable to the negative effects of CMV. The present investigation tested the effects of beta-blocker use and chronological age on the associations between CMV and immunity in adults aged 60-91 (N=98; 69% CMV seropositive) who were administered the trivalent influenza vaccine for up to 5years. Peak antibody response, corrected for baseline, and spring (persistent) antibody response, corrected for peak, were assessed, as well as beta-2 microglobulin (ß2µ) and interleukin-6 (IL-6). In multi-level models with years at Level 1 and people at Level 2, CMV serostatus did not predict peak antibody response, but there was a 3-way interaction between CMV serostatus, age, and beta-blockers. Age was negatively associated with peak antibody, but only among adults who were CMV seropositive and taking beta-blockers. CMV seronegative adults who were not taking beta-blockers had the highest antibody persistence. CMV serostatus was not associated with ß2µ or IL-6. Results suggest that CMV+ serostatus may negatively compromise antibody response to a greater degree than inflammatory markers in older adults. Furthermore, older adults who take beta-blockers may be more vulnerable to negative effects of age and CMV on peak antibody response, perhaps by virtue of their underlying health condition.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Envelhecimento/imunologia , Formação de Anticorpos/efeitos dos fármacos , Infecções por Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Vacinas contra Influenza/imunologia , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais , Formação de Anticorpos/imunologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Inflamação , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , VacinaçãoRESUMO
The size of the myocardial infarction remains an important therapeutic target, because heart attack size correlates with mortality and heart failure. In this era, myocardial infarct size is reduced primarily by timely reperfusion of the infarct related coronary artery. Whereas numerous pre-clinical studies have shown that certain pharmacologic agents and therapeutic maneuvers reduce myocardial infarction size greater than reperfusion alone, very few of these therapies have translated to successful clinical trials or standard clinical use. In this review we discuss both the recent successes as well as recent disappointments, and describe some of the newer potential therapies from the preclinical literature that have not yet been tested in clinical trials.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Precondicionamento Isquêmico Miocárdico/métodos , Infarto do Miocárdio/terapia , Reperfusão Miocárdica/métodos , Miocárdio/patologia , Antagonistas Adrenérgicos beta/efeitos adversos , Animais , Fármacos Cardiovasculares/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Hipotermia Induzida/efeitos adversos , Precondicionamento Isquêmico Miocárdico/efeitos adversos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Reperfusão Miocárdica/efeitos adversos , Pesquisa Translacional Biomédica , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the association between positive blood alcohol level (BAL) and functional outcome in patients suffering severe traumatic brain injury. STUDY DESIGN: The brain trauma registry of an academic trauma centre was queried for patients admitted between January 2007 and December 2011. All patients (≥ 18 years) with a neurosurgical intensive care length of stay beyond 2 days were included. Patient demographics, clinical characteristics, injury profile, laboratory test and outcomes were abstracted for analysis. Primary outcome was unfavourable functional outcome defined as Glasgow Outcome Score (GOS) ≤ 3. Multivariable regression models were used for analysis. RESULTS: Of the 352 patients, 39% were BAL (+) at admission. Patients with (+) BAL were significantly younger with less co-morbidities. The cohorts exhibited no significant difference in the severity of the intra-cranial injury and the use of intra-cranial monitoring or surgical interventions. Further, the groups presented no difference in in-hospital mortality (p = 0.1) or 1-year mortality (p = 0.5). There was a worse long-term functional outcome in (-) BAL patients compared to their BAL (+) counterparts after adjustment for confounders (GOS ≤ 3: AOR = 2.0, 95% CI = 1.1-3.5, p = 0.02). CONCLUSION: Positive BAL on admission is associated with a better long-term functional outcome in patients suffering severe traumatic brain injury.
Assuntos
Concentração Alcoólica no Sangue , Lesões Encefálicas Traumáticas/sangue , Etanol/sangue , Adulto , Idoso , Lesões Encefálicas Traumáticas/mortalidade , Feminino , Escala de Coma de Glasgow , Mortalidade Hospitalar , Humanos , Tempo de Internação , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , SuéciaRESUMO
OBJECTIVE: This study investigated if the ß-receptor blocking agent esmolol, added to standard oxygenated blood cardioplegia, improved myocardial function after weaning from bypass. DESIGN: A block-randomized, blinded study. SETTING: A university laboratory. PARTICIPANTS: Twenty anesthetized pigs, Norwegian Landrace. INTERVENTIONS: After cardiopulmonary bypass, cardiac arrest was induced with cold (12°C), oxygenated blood cardioplegia, enriched with either esmolol or vehicle, repeated every 20 minutes. After 100 minutes the heart was reperfused and weaned. MEASUREMENTS AND MAIN RESULTS: Left ventricular function was evaluated with pressure-volume loops, local myocardial function with multilayer strain and strain rate by epicardial short-axis tissue Doppler imaging. One hour after declamping, preload recruitable stroke work did not differ between groups, but increased to 72±3 mmHg in esmolol-treated animals v 57±4 mmHg (p<0.001) in controls after 3 hours. Radial peak ejection strain rate also was increased by esmolol; 6.0±1.0 s(-1)v 2.9±0.3 s(-1) (p<0.001) in subendocardium and 3.9±0.5 s(-1)v 2.3±0.2 s(-1) (p<0.005) in the midmyocardium. Cardiac index was increased, 4.0±0.2 L/min/m(2) by esmolol v 3.3±0.1 L/min/m(2) for controls (p<0.05). Isovolumetric relaxation time constant was reduced by esmolol, 23±1 ms v 26±1 ms (p<0.025). Troponin-T did not differ and was 339±48 ng/L for the esmolol group and 357±55 ng/L for the control group (p = 0.81). CONCLUSIONS: Esmolol added to blood cardioplegia preserved systolic cardiac function during the first 3 hours after reperfusion in a porcine model with 100 minutes of cardioplegic arrest.
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Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Ponte Cardiopulmonar/métodos , Temperatura Baixa , Parada Cardíaca Induzida/métodos , Oxigênio/administração & dosagem , Propanolaminas/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/metabolismo , Animais , Soluções Cardioplégicas/administração & dosagem , Soluções Cardioplégicas/metabolismo , Ponte Cardiopulmonar/tendências , Feminino , Parada Cardíaca Induzida/tendências , Masculino , Oxigênio/metabolismo , Propanolaminas/metabolismo , Distribuição Aleatória , SuínosRESUMO
OBJECTIVE: To evaluate the impact of a simple written algorithm of early postoperative beta-blocker administration on daily practices. DESIGN: A prospective, single center observational study. SETTING: A 16-bed cardiac surgical intensive care unit in a university teaching hospital. PATIENTS: One hundred twenty-five consecutive adult patients chronically treated with beta-blockers and scheduled for conventional cardiac surgery. INTERVENTIONS: Two successive 4-month phases: Phase 1 = uncontrolled early postoperative beta-blocker administration (n = 73) and phase 2 = beta-blocker administration by an institutional written algorithm using incremental doses of bisoprolol and/or esmolol (n = 52). MEASUREMENTS AND MAIN RESULTS: The main endpoint was the number of patients receiving beta-blockers on the morning of postoperative day 1. Secondary endpoints were the number of patients receiving beta-blockers on the morning of postoperative day 1 and reaching the targeted therapeutic goal and the incidence of postoperative atrial fibrillation in the intensive care unit. A 79% increase in the number of patients receiving beta-blockers on the morning of postoperative day 1 (42% v 75%, p<0.001) was observed during the second phase of the study. The number of patients receiving beta-blockers on the morning of postoperative day 1 and reaching the targeted therapeutic goal was increased significantly by 127% (33% v 75%, p<0.001). The incidence of atrial fibrillation was similar between both phases of the study: 37% versus 31%, p = 0.567. CONCLUSIONS: A simple written algorithm markedly improved early postoperative continuation of beta-blockers in chronically treated patients undergoing conventional cardiac surgery.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Algoritmos , Procedimentos Cirúrgicos Cardíacos/tendências , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Estudos ProspectivosRESUMO
Retrieval-induced forgetting (RIF) is the phenomenon that 'retrieval-practice', the repeated retrieval of a subset of initially learned material, can impair the recall of episodically related memories. Previous studies showed that RIF is eliminated when retrieval-practice is carried out under psycho-social stress, anxiety, or in negative mood. However, pharmacological manipulation by hydrocortisone did not eliminate the effect. This study investigated the effect of beta-adrenergic blockade on stress-induced modulations of RIF, addressing possible interactive effects of the glucocorticoid and sympatho-adrenomedullary systems. Participants learned categorized word lists and then received either 60 mg propranolol or a placebo. After 90 min they were exposed to the TSST. A third group did not receive any medication and performed a non-stressful control task with the same timing as the other two groups. Finally, all participants underwent retrieval-practice and final recall. Both TSST groups exhibited a stress-induced increase in cortisol-levels, and the placebo group also exhibited large increases in markers of sympathetic nervous system activity and more psychological distress at the time of retrieval-practice. Although, overall recall was poorer under stress, an overall RIF effect emerged irrespective of group and showed no clear modulation by stress with or without beta-adrenergic blockade. In previous demonstrations of RIF elimination by negative emotion, state induction and retrieval-practice followed very briefly after initial learning. Given that both the previous study of hydrocortisone effects on RIF and the present study used longer delays between learning and retrieval-practice, the possibility that stress effects on retrieval-practice eliminate RIF only relatively briefly after learning is discussed.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Rememoração Mental/fisiologia , Propranolol/farmacologia , Estresse Psicológico/psicologia , Adulto , Feminino , Humanos , Hidrocortisona/análise , Masculino , Rememoração Mental/efeitos dos fármacos , Testes Neuropsicológicos , Saliva/química , Fatores de Tempo , Adulto JovemRESUMO
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity amongst trauma patients. Its treatment is focused on minimizing progression to secondary injury. Administration of propranolol for TBI maydecrease mortality and improve functional outcomes. However, it is our sense that its use has not been universally adopted due to low certainty evidence. The literature was reviewed to explore the mechanism of propranolol as a therapeutic intervention in TBI to guide future clinical investigations. Medline, Embase, and Scopus were searched for studies that investigated the effect of propranolol on TBI in animal models from inception until June 6, 2023. All routes of administration for propranolol were included and the following outcomes were evaluated: cognitive functions, physiological and immunological responses. Screening and data extraction were done independently and in duplicate. The risk of bias for each individual study was assessed using the SYCLE's risk of bias tool for animal studies. Three hundred twenty-three citations were identified and 14 studies met our eligibility criteria. The data suggests that propranolol may improve post-TBI cognitive and motor function by increasing cerebral perfusion, reducing neural injury, cell death, leukocyte mobilization and p-tau accumulation in animal models. Propranolol may also attenuate TBI-induced immunodeficiency and provide cardioprotective effects by mitigating damage to the myocardium caused by oxidative stress. This systematic review demonstrates that propranolol may be therapeutic in TBI by improving cognitive and motor function while regulating T lymphocyte response and levels of myocardial reactive oxygen species. Oral or intravenous injection of propranolol following TBI is associated with improved cerebral perfusion, reduced neuroinflammation, reduced immunodeficiency, and cardio-neuroprotection in preclinical studies.
Assuntos
Lesões Encefálicas Traumáticas , Propranolol , Propranolol/farmacologia , Propranolol/uso terapêutico , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Humanos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêuticoRESUMO
BACKGROUND: Angiosarcoma is a rare and aggressive cancer of the endothelial cells. Propranolol, a non-selective ß-blocker, was able to initiate apoptosis in angiosarcoma cell lines and its anti-tumor activity has been described in several case reports. The aim of this trial was to prospectively evaluate the anti-tumor activity of propranolol monotherapy in patients with angiosarcoma before proceeding to standard of care treatment. METHODS: Propranolol was dosed 80 mg to 240 mg/day for 3 to 6 weeks according to a dose titration schedule. The primary endpoint was clinical response (response according to RECIST 1.1 or stable disease with improvement of cutaneous lesions) in at least three patients. Exploratory objectives included histologic response (>30% decrease in Ki-67), FDG PET response, and ß-receptor expression levels. RESULTS: Fourteen patients were enrolled. The median duration of treatment was 26 days (range 21-42 days). The median highest propranolol dose was 160 mg/day (range 80 - 240 mg). Two patients showed clinical response (14%, 95% CI 3-100%). One of these patients showed a partial metabolic response on PET-CT. None of the tumors showed histologic response. The most common adverse event was grade 1/2 bradycardia (86%). There were no grade ≥ 3 adverse events. ADRB2 was overexpressed in 16 out of 18 tumors, in both responders and non-responders. None of the tumors showed ADRB1 overexpression. CONCLUSIONS: This window-of-opportunity trial did not show clinical efficacy of propranolol monotherapy. However, two out of 14 patients did show clinical benefit. ADRB1/2 expression did not correlate with clinical response.
Assuntos
Hemangiossarcoma , Propranolol , Humanos , Propranolol/uso terapêutico , Hemangiossarcoma/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Células Endoteliais , Antagonistas Adrenérgicos beta/uso terapêuticoRESUMO
BACKGROUND: Out-of-hospital cardiac arrest (OHCA) complicated by refractory ventricular fibrillation (VF) is associated with poor outcome. Beta-1-receptor selective blockade might overcome refractory VF and improve survival. This trial investigates the efficacy and safety of prehospital landiolol in OHCA and refractory VF. METHODS: In this randomized, double-blind, placebo-controlled pilot trial, patients with OHCA and recurrent or refractory VF (at least 3 defibrillation attempts and last rhythm shockable), pretreated with epinephrine and amiodarone, were allocated to receive add-on treatment with landiolol or placebo. Landiolol was given as a 20 mg bolus infusion. The primary efficacy outcome was time from trial drug infusion to sustained return of spontaneous circulation (ROSC). Safety outcomes included the onset of bradycardia and asystole. RESULTS: A total of 36 patients were enrolled, 19 were allocated to the landiolol group and 17 to the placebo group. Time from trial drug infusion to sustained ROSC was similar between treatment groups (39 min [landiolol] versus 41 min [placebo]). Sustained ROSC was numerically lower in the landiolol group compared with the placebo group (7 patients [36.8%] versus 11 patients [64.7%], respectively). Asystole within 15 min of trial drug infusion occurred significantly more often in the landiolol group than in the placebo group (7 patients [36.8%] and 0 patients [0.0%], respectively). CONCLUSION: In patients with OHCA and refractory VF who are pretreated with epinephrine and amiodarone, add-on bolus infusion of landiolol 20 mg did not lead to a shorter time to sustained ROSC compared with placebo. Landiolol might be associated with bradycardia and asystole.
Assuntos
Morfolinas , Parada Cardíaca Extra-Hospitalar , Ureia , Fibrilação Ventricular , Humanos , Masculino , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/complicações , Fibrilação Ventricular/etiologia , Parada Cardíaca Extra-Hospitalar/tratamento farmacológico , Parada Cardíaca Extra-Hospitalar/complicações , Método Duplo-Cego , Feminino , Projetos Piloto , Pessoa de Meia-Idade , Ureia/análogos & derivados , Ureia/administração & dosagem , Ureia/uso terapêutico , Idoso , Morfolinas/administração & dosagem , Morfolinas/uso terapêutico , Morfolinas/efeitos adversos , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Resultado do Tratamento , Amiodarona/administração & dosagem , Amiodarona/análogos & derivados , Amiodarona/uso terapêutico , Amiodarona/efeitos adversos , Antiarrítmicos/administração & dosagem , Antiarrítmicos/uso terapêutico , Epinefrina/administração & dosagemRESUMO
Beta-blockers are currently studied to improve therapeutic options for patients with angiosarcoma. However, most of these patients have no cardiovascular co-morbidity and it is therefore crucial to discuss the most optimal pharmacological properties of beta-blockers for this population. To maximize the possible effectiveness in angiosarcoma, the use of a non-selective beta-blocker is preferred based on in vitro data. To minimize the risk of cardiovascular adverse events a beta-blocker should ideally have intrinsic sympathomimetic activity or vasodilator effects, e.g. labetalol, pindolol or carvedilol. However, except for one case of carvedilol, only efficacy data of propranolol is available. In potential follow-up studies labetalol, pindolol or carvedilol can be considered to reduce the risk of cardiovascular adverse events.