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1.
Zhonghua Nei Ke Za Zhi ; 60(4): 314-320, 2021 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-33765700

RESUMO

ß-receptor blocker is the cornerstone for the treatment of many cardiovascular diseases. Esmolol, an ultra-short-acting intravenous ß-receptor blocker, is characterized with rapid onset of action, a fast metabolism process and convenience in adjusting its effect. It is an important drug in the treatment of acute arrhythmia. By blocking sympathetic excitation, esmolol has other multiple effects, such as negative inotropic action, negative chronotropic action, lowering blood pressure etc. Relative contraindications of its application may occur in clinical practice. Thus, it is of great necessity to master the indications and contraindications for the standard prescriptions and rational administration of the drug.


Assuntos
Propanolaminas , Antagonistas Adrenérgicos beta/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , China , Humanos , Propanolaminas/uso terapêutico
2.
Cochrane Database Syst Rev ; 12: CD013154, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33331670

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is a highly prevalent condition in an ever-increasing elderly population. Although insidious in the early stages, advanced AMD (neovascular and atrophic forms) can cause significant visual disability and economic burden on health systems worldwide. The most common form, geographic atrophy, has no effective treatment to date, whereas neovascular AMD can be treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Geographic atrophy has a slow disease progression and patients tend to have preserved central vision until the final stages. This tendency, coupled with the use of modern imaging modalities, provides a large window of opportunity to intervene with validated methods to assess treatment efficacy. As geographic atrophy is an increasingly common condition with no effective intervention, many treatments are under investigation, one of which is visual cycle modulators. These medications have been shown to reduce lipofuscin accumulation in pre-clinical studies that have led to several clinical trials, reviewed herein. OBJECTIVES: To assess the efficacy and safety of visual cycle modulators for the prevention and treatment of geographic atrophy secondary to AMD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); MEDLINE Ovid; Embase Ovid; Web of Science Core Collection; Scopus; Association for Research in Vision and Ophthalmology (ARVO) website; ClinicalTrials.gov and the WHO ICTRP to 11 January 2020 with no language restrictions. We also searched using the reference lists of reviews and existing studies and the Cited Reference Search function in Web of Science to identify further relevant studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-randomised clinical studies (if available) that compared visual cycle modulators to placebo or no treatment (observation) in people diagnosed with AMD (early, intermediate or geographic atrophy). DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias in the included studies and extracted data. Both authors entered data into RevMan 5. We resolved discrepancies through discussion. We graded the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included three RCTs from the USA; one of these had clinical sites in Germany. Two studies compared emixustat to placebo while the other compared fenretinide to placebo. All assigned one study eye per participant and, combined, have a total of 821 participants with a majority white ethnicity (97.6%). All participants were diagnosed with geographic atrophy due to AMD based on validated imaging modalities. All three studies have high risk of attrition bias mainly due to ocular adverse effects of emixustat and fenretinide. We considered only one study to be adequately conducted and reported with high risk of bias in only one domain (attrition bias). We considered the other two studies to be poorly reported and to have high risk of attrition bias and reporting bias. People with geographic atrophy treated with emixustat may not experience a clinically important change in best-corrected visual acuity (BCVA) between baseline and 24 months compared to people treated with placebo (mean difference (MD) 1.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% confidence interval (CI) -2.34 to 6.14, low-certainty evidence). Emixustat may also result in little or no difference in loss of 15 ETDRS letters or more of BCVA compared with placebo at 24 months (16.4% versus 18%) (risk ratio (RR) 0.91, 95% CI 0.59 to 1.4, low-certainty evidence). In terms of disease progression, emixustat may result in little or no difference in the annual growth rate of geographic atrophy compared with placebo (mean difference MD 0.09 mm2/year (95% CI -0.26 to 0.44, low-certainty evidence). All three studies reported adverse events of both drugs (emixustat: moderate-certainty evidence; fenretinide: low-certainty evidence). The main adverse events were ocular in nature and associated with the mechanism of action of the drugs. Delayed dark adaptation (emixustat: 54.5%; fenretinide: 39.3%) and chromatopsia (emixustat: 22.6%; fenretinide: 25.2%) were the most common adverse events reported, and were the most prevalent reasons for study dropout in emixustat trials. These effects were dose-dependent and resolved after drug cessation. No specific systemic adverse events were considered related to emixustat; only pruritus and rash were considered to be due to fenretinide. One emixustat study reported six deaths, none deemed related to the drug. None of the included RCTs reported the other pre-specified outcomes, including proportion of participants losing 10 letters or more, and mean change in macular sensitivity. We planned to investigate progression to advanced AMD (geographic atrophy or neovascular AMD) in prevention studies, including participants with early or intermediate AMD, but we identified no such studies. Two of the included studies reported an additional outcome - incidence of choroidal neovascularisation (CNV) - that was not in our published protocol. CNV onset may be reduced in those treated with emixustat but the evidence was uncertain (risk ratio (RR) 0.67, 95% CI 0.27 to 1.65, low-certainty evidence), or fenretinide (RR 0.5, 95% CI 0.26 to 0.98, low-certainty evidence) compared to placebo. A dose-dependent relationship was observed with emixustat. AUTHORS' CONCLUSIONS: There is limited evidence to support the use of visual cycle modulators (emixustat and fenretinide) for the treatment of established geographic atrophy due to AMD. The possible reduction in the incidence of CNV observed with fenretinide, and to a lesser extent, emixustat, requires formal assessment in focused studies.


Assuntos
Fenretinida/uso terapêutico , Atrofia Geográfica/tratamento farmacológico , Atrofia Geográfica/prevenção & controle , Degeneração Macular/complicações , Éteres Fenílicos/uso terapêutico , Propanolaminas/uso terapêutico , Conduta Expectante , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/epidemiologia , Ensaios Clínicos Fase II como Assunto , Progressão da Doença , Fenretinida/efeitos adversos , Atrofia Geográfica/etiologia , Humanos , Incidência , Éteres Fenílicos/efeitos adversos , Placebos/uso terapêutico , Propanolaminas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acuidade Visual/efeitos dos fármacos
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2756-2759, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018577

RESUMO

Persisting tachycardia is often observed in resuscitated septic shock patients, and it is an independent risk factor for increased mortality. Recently, several drugs, such as esmolol and ivabradine, have been proved to be beneficial in HR control, but their overall impact on cardiac functions needs further investigation. The aim of this study is to study the effects of the two drugs on heart function in a protocol of polymicrobial septic shock and resuscitation. Twelve pigs were divided into three experimental groups: the esmolol-treated group (n=4), the ivabradine-treated group (n=5) and the control group (n=3). Cardiac autonomic activity was estimated by heart rate variability (HRV) indices and baroreflex sensitivity (BRS). The Buckberg index was adopted to evaluate myocardial oxygenation efficiency. Septic shock induced a severe autonomic dysfunction and a lower cardiac efficiency, not resolved by fluids resuscitation. The administration of the drugs improved both the HRV and the BRS, but this favourable condition was preserved after noradrenaline administration only in the esmolol group. The interaction of esmolol with the autonomic system is beneficial in septic shock to restore an improved condition of HRV and control, while ivabradine is not as effective when administered in adjunction to noradrenaline.


Assuntos
Propanolaminas , Choque Séptico , Animais , Humanos , Ivabradina/uso terapêutico , Propanolaminas/uso terapêutico , Choque Séptico/tratamento farmacológico , Suínos , Taquicardia/tratamento farmacológico
4.
Am J Emerg Med ; 38(9): 1921-1934, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32777667

RESUMO

BACKGROUND: Esmolol has been proposed as a viable adjunctive therapy for pre-hospital refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). OBJECTIVES: We performed a systematic review and meta-analysis to assess the effectiveness of esmolol on pre-hospital refractory VF/pVT, compared with standard of care. METHODS: MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for eligible studies. Two investigators independently extracted relevant data and assessed the methodological quality of each included study using the ROBINS-I tool. The quality of evidence for summary estimates was assessed according to GRADE guidelines. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome of interest were calculated. RESULTS: The search yielded 3253 unique records, of which two studies were found to be in accordance with the research purpose, totaling 66 patients, of whom 33.3% (n = 22) received esmolol. Additional evidence was provided in the paper but was not relevant to the analysis and was therefore not included. Esmolol was likely associated with an increased rate of survival to discharge (RR 2.82, 95% CI 1.01-7.93, p = 0.05) (GRADE: Very low) and survival with favorable neurological outcome (RR 3.44, 95% CI 1.11-10.67, p = 0.03) (GRADE: Very low). Similar results were found for return of spontaneous circulation (ROSC) (RR 2.63, 95% CI 1.37-5.07, p = 0.004) (GRADE: Very low) and survival to intensive care unit (ICU)/hospital admission (RR 2.63, 95% CI 1.37-5.07, p = 0.004) (GRADE: Very low). CONCLUSION: The effectiveness of esmolol for refractory VF/pVT remains unclear. Trial sequential analysis (TSA) indicates that the evidence is inconclusive and that further trials are required in order to reach a conclusion. Therefore, it is imperative to continue to accumulate evidence in order to obtain a higher level of scientific evidence.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Serviços Médicos de Emergência/métodos , Propanolaminas/uso terapêutico , Fibrilação Ventricular/tratamento farmacológico , Humanos , Resultado do Tratamento
5.
Cochrane Database Syst Rev ; 7: CD007037, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32700759

RESUMO

BACKGROUND: Beta-blockers are an essential part of standard therapy in adult congestive heart failure and therefore, are expected to be beneficial in children. However, congestive heart failure in children differs from that in adults in terms of characteristics, aetiology, and drug clearance. Therefore, paediatric needs must be specifically investigated. This is an update of a Cochrane review previously published in 2009. OBJECTIVES: To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS up to November 2015. Bibliographies of identified studies were checked. No language restrictions were applied. SELECTION CRITERIA: Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and assessed data from the included trials. MAIN RESULTS: We identified four new studies for the review update; the review now includes seven studies with 420 participants. Four small studies with 20 to 30 children each, and two larger studies of 80 children each, showed an improvement of congestive heart failure with beta-blocker therapy. A larger study with 161 participants showed no evidence of benefit over placebo in a composite measure of heart failure outcomes. The included studies showed no significant difference in mortality or heart transplantation rates between the beta-blocker and control groups. No significant adverse events were reported with beta-blockers, apart from one episode of complete heart block. A meta-analysis of left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) data showed a very small improvement with beta-blockers. However, there were vast differences in the age, age range, and health of the participants (aetiology and severity of heart failure; heterogeneity of diagnoses and co-morbidities); there was a range of treatments across studies (choice of beta-blocker, dosing, duration of treatment); and a lack of standardised methods and outcome measures. Therefore, the primary outcomes could not be pooled in meta-analyses. AUTHORS' CONCLUSIONS: There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme. However, the sparse data available suggested that children with congestive heart failure might benefit from beta-blocker treatment. Further investigations in clearly defined populations with standardised methodology are required to establish guidelines for therapy. Pharmacokinetic investigations of beta-blockers in children are also required to provide effective dosing in future trials.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Adolescente , Carbazóis/uso terapêutico , Carvedilol , Criança , Pré-Escolar , Insuficiência Cardíaca/mortalidade , Transplante de Coração/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Metoprolol/uso terapêutico , Propanolaminas/uso terapêutico , Propranolol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico
6.
Acta Cir Bras ; 35(4): e202000408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555939

RESUMO

PURPOSE: To evaluate the analgesic effect of esmolol in patients submitted to laparoscopic gastroplasty. METHODS: Forty patients aged between 18 and 50 years with American Society of Anesthesiologists (ASA) physical status scores of II and III who underwent gastric bypass were allocated to two groups. Group 1 patients received a 0.5-mg/kg bolus of esmolol in 30 mL of saline before induction of anesthesia, followed by an infusion at 15 µg/kg/min until the end of surgery. Group 2 patients received 30 mL of saline as a bolus and then an infusion of saline. Anesthesia included fentanyl (3 µg/kg), propofol (2-4 mg/kg), rocuronium (0.6 mg/kg), and 2% sevoflurane, with remifentanil if necessary. The following parameters were evaluated: pain intensity over 24h, remifentanil consumption, the first analgesic request, morphine consumption, and side effects. RESULTS: Pain intensity was lower in the esmolol group except at T0 (after extubation) and 12h postoperatively. Remifentanil supplementation, recovery time, and postoperative morphine supplementation were lower in the esmolol group. No differences in the time to the first analgesic request or side effects were found between the groups. CONCLUSION: Intraoperative esmolol promotes reductions in pain intensity and the need for analgesic supplementation without adverse effects, thus representing an effective drug for multimodal analgesia in gastroplasty.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Gastroplastia/efeitos adversos , Laparoscopia/efeitos adversos , Dor Pós-Operatória/prevenção & controle , Propanolaminas/uso terapêutico , Adolescente , Adulto , Analgesia/métodos , Anestesia/métodos , Anestésicos/uso terapêutico , Método Duplo-Cego , Feminino , Gastroplastia/métodos , Humanos , Período Intraoperatório , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Náusea e Vômito Pós-Operatórios/prevenção & controle , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto Jovem
7.
Am J Physiol Heart Circ Physiol ; 318(2): H283-H294, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834837

RESUMO

The ß3-adrenergic receptor (ß3AR) is related to myocardial fatty acid metabolism and its expression has been implicated in heart failure. In this study, we investigated the role of ß3AR in sepsis-related myocardial dysfunction using lipopolysaccharide (LPS)-induced endotoxemia as a model of cardiac dysfunction. We placed mice into three treatment groups and treated each with intraperitoneal injections of the ß3AR agonist CL316243 (CL group), the ß3AR antagonist SR59230A (SR group), or normal saline (NS group). Survival rates were significantly improved in the SR group compared with the other treatment groups. Echocardiography analyses revealed cardiac dysfunction within 6-12 h of LPS injections, but the outcome was significantly better for the SR group. Myocardial ATP was preserved in the SR group but was decreased in the CL-treated mice. Additionally, quantitative PCR analysis revealed that expression levels of genes associated with fatty acid oxidation and glucose metabolism were significantly higher in the SR group. Furthermore, the expression levels of mitochondrial membrane protein complexes were preserved in the SR group. Electron microscope studies showed significant accumulation of lipid droplets in the CL group. Moreover, inducible nitric oxide synthase (iNOS) protein expression and nitric oxide were significantly reduced in the SR group. The in vitro study demonstrated that ß3AR has an independent iNOS pathway that does not go through the nuclear factor-κB pathway. These results suggest that blockading ß3AR improves impaired energy metabolism in myocardial tissues by suppressing iNOS expression and recovers cardiac function in animals with endotoxin-induced heart failure.NEW & NOTEWORTHY Nitric oxide production through stimulation of ß3-adrenergic receptor (ß3AR) may improve cardiac function in cases of chronic heart failure. We demonstrated that the blockade of ß3AR improved mortality and cardiac function in endotoxin-induced heart failure. We also determined that LPS-induced inducible nitric oxide synthase has a pathway that is independent of nuclear factor-κB, which worsened cardiac metabolism and mortality in the acute phase of sepsis. Treatment with the ß3AR antagonist had a favorable effect. Thus, the blockade of ß3AR could offer a novel treatment for sepsis-related heart failure.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Propanolaminas/uso terapêutico , Trifosfato de Adenosina/metabolismo , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Animais , Ácidos Graxos/metabolismo , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/mortalidade , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética
8.
Physiol Rep ; 7(23): e14301, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31814327

RESUMO

Clinical data suggests that heart rate (HR) control with selective ß1-blockers may improve cardiac function during septic shock. However, it seems counterintuitive to start ß-blocker infusion in a shock state when organ blood flow is already low or insufficient. Therefore, we studied the effects of HR control with esmolol, an ultrashort- acting ß1-selective adrenoceptor antagonist, on renal blood flow (RBF) and renal autoregulation during early septic shock. In 10 healthy sheep, sepsis was induced by continuous i.v. administration of lipopolysaccharide, while maintained under anesthesia and mechanically ventilated. After successful resuscitation of the septic shock with fluids and vasoactive drugs, esmolol was infused to reduce HR with 30% and was stopped 30-min after reaching this target. Arterial and venous pressures, and RBF were recorded continuously. Renal autoregulation was evaluated by the response in RBF to renal perfusion pressure (RPP) in both the time domain and frequency domain. During septic shock, ß-blockade with esmolol significantly increased the pressure dependency of RBF to RPP. Stopping esmolol showed the reversibility of the impaired renal autoregulation. Showing that clinical diligence and caution are necessary when treating septic shock with esmolol in the acute phase since esmolol reduced RPP to critical values thereby significantly reducing RBF.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Frequência Cardíaca , Propanolaminas/uso terapêutico , Circulação Renal , Choque Séptico/tratamento farmacológico , Lesão Renal Aguda/etiologia , Antagonistas Adrenérgicos beta/administração & dosagem , Animais , Feminino , Infusões Intravenosas , Lipopolissacarídeos/toxicidade , Propanolaminas/administração & dosagem , Ovinos , Choque Séptico/complicações , Choque Séptico/etiologia
9.
Ann Card Anaesth ; 22(4): 353-357, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621668

RESUMO

Background: The aim of this study was to compare the effects of dexmedetomidine, esmolol, and combination of both on control of sympathetic response to laryngoscopy and tracheal intubation in coronary artery disease patients. Material and Methods: A prospective, randomized, double-blinded clinical study included 90 patients scheduled for elective coronary artery bypass surgery. Patients were randomly allocated into three groups of 30 each: dexmedetomidine group (Group D) 1 µg/kg, esmolol group (Group E) 2 mg/kg, and group dexmedetomidine with esmolol (Group DE) 0.5 µg/kg of dexmedetomidine with 1 mg/kg of esmolol. Each drug was diluted with 0.9% normal saline to 20 ml volume and infused in 10 min before induction of anesthesia. Hemodynamic changes (heart rate [HR], arterial blood pressure, and pulmonary artery pressure) were compared at various time intervals as follows-baseline, after study drug, after induction, and 1, 3, and 5 min after intubation. Statistical analysis included analysis of variance, Chi-square, and Fisher's exact test. Results: In Group DE, there was no significant increase in HR at all-time intervals, and the HR was stable compared to Group D and Group E. Blood pressure values were comparable in all groups except in Group E at 5 min. The pulmonary arterial pressures were statistically less in DE group except at 3 and 5 min. Conclusions: The combination of dexmedetomidine and esmolol group has beneficial effect on HR and pulmonary arterial pressures but has no additional advantage with respect to arterial blood pressure when compared with dexmedetomidine and esmolol groups in patients undergoing elective coronary artery bypass grafting.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Doenças do Sistema Nervoso Autônomo/prevenção & controle , Ponte de Artéria Coronária/efeitos adversos , Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Complicações Intraoperatórias/prevenção & controle , Intubação Intratraqueal/efeitos adversos , Laringoscopia/efeitos adversos , Propanolaminas/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
10.
Dtsch Med Wochenschr ; 144(18): 1280-1285, 2019 09.
Artigo em Alemão | MEDLINE | ID: mdl-31514219

RESUMO

Supraventricular tachyarrhythmias, especially atrial fibrillation, are common in cardiac and non-cardiac patients with or without surgery. Prolonged rhythm disturbances may impair cardiac function and worsen the clinical outcome and prognosis. Therefore, heart rate control may be necessary to prevent cardiovascular events.Esmolol and landiolol as ultrashort and rapid acting highly selective ß 1 -adrenergic blockers are of particular interest in the prevention and management of cardiac arrhythmias. This review gives an update on both betablockers and their role in the management of arrhythmias in emergency medicine and perioperative setting.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Estado Terminal/terapia , Morfolinas/uso terapêutico , Propanolaminas/uso terapêutico , Ureia/análogos & derivados , Fibrilação Atrial/tratamento farmacológico , Humanos , Ureia/uso terapêutico
11.
Zhonghua Yi Xue Za Zhi ; 99(17): 1317-1322, 2019 May 07.
Artigo em Chinês | MEDLINE | ID: mdl-31091579

RESUMO

Objective: To investigate the effect of esmolol in septic shock patients with tachycardia. Methods: A prospective randomized controlled trial was conducted. Screening septic shock patients that admitted to Department of General Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from June 2016 to August 2017. After 24 h resuscitation therapy, 100 cases of septic shock patients with tachycardia (heart rate>100 bpm) were divided into esmolol group (n=50) and control group (n=50) with random number table. Patients in esmolol group accepted standard treatment plus esmolol injection with an initial dose of 25 mg/h. Heart rate target is 80 to 100 bpm. Patients in esmolol group continued to use esmolol for 7 days or to the day the patient left the ICU when the heart rate didn't achieve the target. Patients in control group were given standard treatment. Primary outcome was 28 d mortality. Secondary outcomes included heart rate, norepinephrine dosages, lactate level, inflammatory markers in per day during the trial; acute physiology and chronic health evaluation (APACHE Ⅱ) and sequential organ failure assessment (SOFA) on day 1, 3, 5, 7; length of hospital stay, length of mechanical ventilation, medication time of vasoactive agent. The data were compared with t test or rank sum test between the two groups. Results: The 28 d mortality of esmolol group and control group was 62%, 68%, respectively(χ(2)=0.529, P=0.529). Logistic regression analysis showed that primary heart rate (increase of 10 bpm, OR=1.568, 95%CI: 1.039-1.238, P=0.027), primary APACHEⅡ (OR=1.134, 95%CI: 1.026-1.239, P=0.005), integral heart rate (per 10 bpm, OR=2.207, 95%CI: 1.400-3.479, P=0.001) were independent risk factors for 28 d mortality. Compared with control group, the esmolol group had a lower heart rate on day 1-7; but over all, there was no statistically significant difference in heart rate between the two groups (P>0.05). There was no significant difference in total does of norepinephrine, lactate level, inflammatory markers, APACHE Ⅱ, SOFA, length of hospital stay between the two groups (all P>0.05). Conclusion: Tachycardia significantly increases the risk of death in patients with septic shock, esmolol may decrease the mortality by controlling heart rate.


Assuntos
Propanolaminas/uso terapêutico , Choque Séptico , Humanos , Estudos Prospectivos , Choque Séptico/tratamento farmacológico , Taquicardia
12.
JACC Heart Fail ; 7(7): 586-598, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31042551

RESUMO

OBJECTIVES: The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF). BACKGROUND: Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta1-adrenergic receptor (ADRB1) Arg389Arg genotype. METHODS: A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period. RESULTS: The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011). CONCLUSIONS: Pharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Propanolaminas/uso terapêutico , Idoso , Fibrilação Atrial/complicações , Eletrocardiografia , Feminino , Genótipo , Insuficiência Cardíaca/complicações , Humanos , Masculino , Metoprolol/uso terapêutico , Pessoa de Meia-Idade , Mortalidade , Farmacogenética , Variantes Farmacogenômicos , Medicina de Precisão , Modelos de Riscos Proporcionais , Receptores Adrenérgicos beta 1/genética , Volume Sistólico
13.
BMJ Open ; 9(4): e028111, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-31023764

RESUMO

INTRODUCTION AND AIMS: Esmolol is an ultra-short-acting ß1 antagonist that has been shown to attenuate the corrected QT (QTc) interval prolongation associated with laryngoscopy and endotracheal intubation (LTI). Prolongation of the QTc interval can precipitate arrhythmias, the most serious of which is torsades de pointes . The aim of this systematic review was to compare esmolol and placebo on QTc changes occurring during LTI. MATERIALS AND METHODS: PubMed, EMBASE, Cochrane Registry of Clinical Trials and CINAHL databases (up to August 2018) were screened for randomised controlled trials comparing esmolol and placebo on QTc changes during LTI in cardiac and non-cardiac surgeries. The primary outcome was QTc changes during LTI and secondary outcome was related to adverse effects from esmolol such as bradycardia and hypotension. RESULTS: Seven trials were identified involving 320 patients, 160 patients receiving esmolol or placebo apiece. A shortening of the QTc post-LTI was evident in the esmolol group compared with the placebo in four studies. Compared with the baseline, the QTc was reduced post-LTI in the esmolol group. In the placebo group, the QTc was prolonged compared with the baseline post LTI. Nonetheless, esmolol did not prevent QTc prolongation in the remaining three studies, and much of this was attributed to employing QTc prolonging agents for premedication and anaesthetic induction. No significant adverse events were noted. CONCLUSION: Compared with placebo, esmolol reduced the LTI-induced QTc prolongation when current non-QTc prolonging agents were chosen for tracheal intubation. Future studies should explore whether transmural dispersion (a marker of torsadogenicity) is also affected during LTI by analysing parameters such as the Tp-e interval (interval between the peak to the end of the T-wave) and Tp-e/QTc (rate corrected Tp-e interval). TRIAL REGISTRATION NUMBER: CRD42018090282.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Arritmias Cardíacas/prevenção & controle , Frequência Cardíaca/efeitos dos fármacos , Intubação Intratraqueal/métodos , Propanolaminas/uso terapêutico , Eletrocardiografia/efeitos dos fármacos , Humanos
14.
BMJ Case Rep ; 12(3)2019 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-30852502

RESUMO

Current advanced cardiac life support (ACLS) guidelines for the management of ventricular fibrillation (VF) and pulseless ventricular tachycardia is defibrillation. However, refractory VF, which is defined as VF that persists despite three defibrillation attempts, is challenging for all ACLS providers; the best resuscitation strategy for patients that persist in refractory VF remains unclear. We report on a 51-year-old man who presented to the emergency department with chest pain and subsequently went into witnessed VF cardiac arrest. Despite standard ACLS management consisting of high-quality cardiopulmonary resuscitation, serial epinephrine and serial defibrillation, the return of spontaneous circulation (ROSC) was unable to be achieved. Double sequential defibrillation (DSD) was attempted multiple times unsuccessfully. After administration of low-dose esmolol, he immediately achieved ROSC. DSD and ß-blockade are increasingly recognised in the literature and practice for refractory VF. However, to the best of our knowledge, this is the first case of refractory VF that responded to low-dose esmolol ß-blockade.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Propanolaminas/uso terapêutico , Fibrilação Ventricular/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
J Emerg Med ; 56(3): 308-318, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30711368

RESUMO

BACKGROUND: Recent-onset atrial fibrillation (RAF) is the most frequent supraventricular dysrhythmia in emergency medicine. Severely compromised patients require acute treatment with injectable drugs OBJECTIVE: The main purpose of this external validity study was to compare the short-term efficacy of esmolol with that of amiodarone to treat severe RAF in an emergency setting. METHODS: This retrospective survey was conducted in mobile intensive care units by analyzing patient records between 2002 and 2013. We included RAF with (one or more) severity factors including: clinical shock, angina pectoris, ST shift, and very rapid ventricular rate. A blind matching procedure was used to constitute esmolol group (n = 100) and amiodarone group (n = 200), with similar profiles for age, gender, initial blood pressure, heart rate, severity factors, and treatment delay. The main outcome measure was the percentage of patients with a ventricular rate control defined as heart frequency ≤ 100 beats/min. More stringent (rhythm control) and more humble indicators (20% heart rate reduction) were analyzed at from 10 to 120 min after treatment initiation. RESULTS: Patient characteristics were comparable for both groups: age 66 ± 16 years, male 71%, treatment delay < 1 h 36%, 1-2 h 29%, > 2 h 35%, chest pain 61%, ST shift 62%, ventricular rate 154 ± 26 beats/min, and blood pressure 126/73 mm Hg. The superiority of esmolol was significant at 40 min (64% rate control with esmolol vs. 25% with amiodarone) and for all indicators from 10 to 120 min after treatment onset. CONCLUSION: In "real life emergency medicine," esmolol is better than amiodarone in the treatment of RAF.


Assuntos
Amiodarona/normas , Fibrilação Atrial/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Propanolaminas/normas , Antagonistas de Receptores Adrenérgicos beta 1/normas , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Amiodarona/uso terapêutico , Antiarrítmicos/normas , Antiarrítmicos/uso terapêutico , Medicina de Emergência/métodos , Medicina de Emergência/normas , Serviço Hospitalar de Emergência/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propanolaminas/uso terapêutico , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de Tempo
16.
J Immunol Res ; 2019: 5821589, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31930150

RESUMO

Amiselimod (MT-1303) is a novel and selective sphingosine 1-phosphate receptor-1 (S1P1) modulator with a more favorable cardiac safety profile than other S1P1 receptor modulators. In this study, we evaluated the effects of MT-1303 on the progression of lupus nephritis in two well-known murine systemic lupus erythematosus (SLE) models, MRL/lpr and NZBWF1 mice, compared with those of FK506. Daily oral doses of 0.1 and 0.3 mg/kg MT-1303 not only inhibited the development of lupus nephritis when administered before onset in MRL/lpr and NZBWF1 mice but also improved symptoms of lupus nephritis when administered after onset in MRL/lpr mice. Its efficacy in these models was more potent or comparable to that of FK506 (1 and 3 mg/kg). In histological analysis, treatment with MT-1303 inhibited infiltration of T cells into the kidneys, mesangial expansion, and glomerular sclerosis. MT-1303 treatment resulted in a marked reduction in T cells and B cells in the peripheral blood and significantly inhibited increases in the number of plasma cells in the spleen and T cells in the kidneys. In addition, administration of MT-1303 suppressed elevations in serum anti-dsDNA antibody levels in MRL/lpr mice, but not in NZBWF1 mice. Our findings show that MT-1303 exhibits marked therapeutic effects on lupus nephritis in two SLE models, likely by reducing the infiltration of autoreactive T cells into the kidneys. These results suggest that MT-1303 has the potential to be used as a therapeutic agent for patients suffering from SLE, including lupus nephritis.


Assuntos
Rim/efeitos dos fármacos , Nefrite Lúpica/tratamento farmacológico , Propanolaminas/uso terapêutico , Receptores de Esfingosina-1-Fosfato/efeitos dos fármacos , Animais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Rim/citologia , Rim/imunologia , Rim/patologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Masculino , Células Mesangiais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos MRL lpr , Plasmócitos/efeitos dos fármacos , Plasmócitos/imunologia , Receptores de Esfingosina-1-Fosfato/metabolismo , Baço/citologia , Baço/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
18.
Oncol Rep ; 41(1): 341-350, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30542705

RESUMO

The ß2­adrenergic receptor (ß2­AR, encoded by the ADRB2 gene) is a member of the G­protein­coupled receptor superfamily that can be stimulated by catecholamines. Studies in vivo and in vitro have confirmed that ß­blockers (ß­AR antagonists) exert antitumor effects on various tumors. Furthermore, ADRB2 single­nucleotide polymorphisms (SNPs) have been identified to alter the expression and conformation of ß2­AR, which may alter the ß­blocker drug response. The aim of the present study was to investigate the effect of ß­blockers on triple­negative breast cancer cells and determine whether ADRB2 SNPs affect the response to ß­blocker drugs. Propranolol and ICI 118,551 significantly inhibited the viability of MDA­MB­231 cells, arrested cell cycle progression at G0/G1 and S phase and induced cell apoptosis. Western blot analysis indicated that the phosphorylation levels of extracellular­signal­regulated kinase (ERK)1/2 and the expression levels of cyclo­oxygenase 2 (COX­2) were significantly decreased following ß­blocker treatment. Four haplotypes, which comprised ADRB2 SNPs rs1042713 and rs1042714, were transfected into 293 cells. After 24 and 48 h of transfection, ADRB2 mRNA expression was significantly decreased in mutant groups compared with the wild­type group. The ADRB2 SNPs exerted no effect on cell viability, but did affect the drug response of ICI 118,551. Furthermore, ADRB2 SNPs also affected the regulatory function of ICI 118,551 on the ERK/COX­2 signaling pathway. Collectively, propranolol and ICI 118,551 inhibited the viability of MDA­MB­231 cells by downregulating the ERK/COX­2 signaling pathway and inducing apoptosis. The results of the present study indicated that SNPs rs1042713 and rs1042714 of ADRB2 affected the response to ICI 118,551, and the underlying molecular mechanism was elucidated.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Receptores Adrenérgicos beta 2/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Fosforilação/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Propranolol/farmacologia , Propranolol/uso terapêutico , Receptores Adrenérgicos beta 2/metabolismo , Neoplasias de Mama Triplo Negativas/genética
19.
Ann Med ; 51(1): 17-27, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30346213

RESUMO

Haemodynamic instability predisposes patients to cardiac complications in non-cardiac surgery. Esmolol, a short-acting cardioselective beta-adrenergic blocker might be efficient in perioperative cardiac protection, but could affect other vital organs, such as the kidneys, and post-discharge survival. We performed a systematic review on the use of esmolol for perioperative cardiac protection. We searched PubMed, Ovid Medline and Cochrane Central Register for Controlled trials. Eligible randomized controlled studies (RCTs) reported a perioperative esmolol intervention with at least one of the primary (major cardiac or renal complications during the first 30 postoperative days) or secondary (postoperative adverse effects and all-cause mortality) outcomes. We included 196 adult patients from three RCTs. Esmolol significantly reduced postoperative myocardial ischaemia, RR =0.43 [95% confidence interval, CI: 0.21-0.88], p = .02. No association with clinically significant bradycardia and hypotension compared to patients receiving control treatment could be confirmed (RR =7.4 [95% CI: 0.29-139.81], p = .18 and RR =2.21 [95% CI: 0.34-14.36], p = .41, respectively). No differences regarding other outcomes were observed. No study reported postoperative renal outcomes. Esmolol seems promising for the prevention of perioperative myocardial ischaemia. However, the association with bradycardia and hypotension remains unclear. Randomized trials investigating the effect of ß1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted. Key messages Short-acting cardioselective esmolol seems efficient in the prevention of perioperative myocardial ischaemia. The possibly increased risk of bradycardia and hypotension with short-acting intravenous beta blockade could not be confirmed or refuted by available data. Future adequately powered trials investigating the effect of ß1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Cardiopatias/tratamento farmacológico , Coração/efeitos dos fármacos , Propanolaminas/administração & dosagem , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/epidemiologia , Administração Intravenosa , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Feminino , Cardiopatias/epidemiologia , Cardiopatias/mortalidade , Cardiopatias/prevenção & controle , Hemodinâmica/efeitos dos fármacos , Humanos , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia , Masculino , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/mortalidade , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Propanolaminas/efeitos adversos , Propanolaminas/uso terapêutico , Substâncias Protetoras/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança
20.
Respir Physiol Neurobiol ; 259: 104-110, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30171906

RESUMO

While alveolar liquid clearance (ALC) mediated by the ß2-adrenergic receptor (ß2-AR) plays an important role in lung edema resolution in certain models of lung injury, in more severe lung injury models, this response might disappear. Indeed, we have shown that in an ischemia-reperfusion-induced lung injury model, ß2-agonists do not enhance ALC. The objective of this study was to determine if downregulation of the ß2-AR could explain the lack of response to ß2-agonists in this lung injury model. In an in vivo canine model of lung transplantation, we observed no change in ß2-AR concentration or affinity in the injured transplanted lungs compared to the native lungs. Furthermore, we could not enhance ALC in transplanted lungs with dcAMP + aminophylline, a treatment that bypasses the ß2-adrenergic receptor and is known to stimulate ALC in normal lungs. However, transplantation decreased αENaC expression in the lungs by 50%. We conclude that the lack of response to ß2-agonists in ischemia-reperfusion-induced lung injury is not associated with significant downregulation of the ß2-adrenergic receptors but is attributable to decreased expression of the ENaC channel, which is essential for sodium transport and alveolar liquid clearance in the lung.


Assuntos
Lesão Pulmonar , Alvéolos Pulmonares/fisiopatologia , Receptores Adrenérgicos beta 2/uso terapêutico , Traumatismo por Reperfusão/complicações , Aminofilina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Broncodilatadores/farmacologia , AMP Cíclico/farmacologia , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Canais Epiteliais de Sódio/metabolismo , Feminino , Frequência Cardíaca/efeitos dos fármacos , Imidazóis/uso terapêutico , Radioisótopos do Iodo/farmacocinética , Iodocianopindolol/farmacocinética , Lesão Pulmonar/etiologia , Lesão Pulmonar/fisiopatologia , Masculino , Propanolaminas/uso terapêutico , Ligação Proteica/efeitos dos fármacos , Edema Pulmonar/etiologia , RNA Mensageiro
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