Efficacy of a single dose of esmolol to prevent extubation-related complications during emergence from anesthesia: a randomized, double-blind, placebo-controlled trial

Abstract Background Few trials have examined the efficacy of esmolol to attenuate hemodynamic and respiratory responses during extubation. However, the most appropriate dose of esmolol and an optimal protocol for administering this beta-blocker are uncertain. Methods Ninety patients ASA physical status I, II, and III (aged 18-60 years) scheduled to procedures with general anesthesia and tracheal extubation were selected. Patients were randomized into esmolol and placebo group to evaluate the efficacy and safety of a single bolus dose of esmolol (2 mg.kg-1) on cardiorespiratory responses during the peri-extubation period. The primary outcome was the rate of tachycardia during extubation. Results The rate of tachycardia was significantly lower in esmolol-treated patients compared to placebo-treated patients (2.2% vs. 48.9%, relative risk (RR): 0.04, 95% confidence interval (95% CI) = 0.01 to 0.32, p= 0.002). The rate of hypertension was also significantly lower in the esmolol group (4.4% vs. 31.1%, RR: 0.14, 95% CI 0.03 to 0.6, p= 0.004). Esmolol-treated patients were associated with higher extubation quality compared to patients who received placebo (p< 0.001), with an approximately two-fold increase in the rate of patients without cough (91.1%) in the esmolol group compared to the placebo group (46.7%). The rate of bucking was approximately 5-fold lower in the esmolol group (8.9% vs. 44.5%, respectively, RR: 0.20 (95% CI, 0.1 to 0.5, p= 0.002, with an NNT of 2.8). Conclusion A single bolus dose of esmolol is an effective and safe therapeutic strategy to attenuate cardiorespiratory responses during the peri-extubation period.

The efficacy of esmolol, remifentanil and nitroglycerin in controlled hypotension for functional endoscopic sinus surgery / Eficácia do esmolol, remifentanil e nitroglicerina na hipotensão controlada para cirurgia sinusal endoscópica funcional

Abstract Introduction Controlled hypotension is a reversible procedure in which the patient's baseline mean arterial blood pressure is reduced by 30% and sustained at 60-70 mmHg during the procedure. It decreases blood loss and provides clear surgical field during the procedures. Objectives The purpose of this study was to compare the efficacy of controlled hypotension agents esmolol, remifentanil, and nitroglycerin in functional endoscopic sinus surgery, in terms of hemodynamic changes and impact on the surgical efficiency. Methods The research was carried out as a cohort study. Patients who underwent functional endoscopic sinus surgery were randomized into 3 groups. Controlled hypotension was achieved with remifentanil (Group R), esmolol (Group E) and nitroglycerin (Group N). The efficacy of the drugs was tested by comparing the length of time with the targeted mean arterial pressure, the amount of anesthetics used, surgical field bleeding score and surgeon's satisfaction. Results Between May to December 2015, 60 patients were included and randomized equally into 3 different study groups. The median of the length of time with the targeted mean arterial pressure was shorter in the Group R when compared with Group E (p = 0.01) and Group N (p = 0.14). The amount of volatile anesthetics used was 25.0 mL (15-51), 43.0 mL (21-105) and 40.0 mL (26-97) in Groups R, E and N, respectively (p < 0.001). While there was more bleeding with nitroglycerin, surgical field bleeding scores were lower in Group R when compared with esmolol (p = 0.001) and nitroglycerin (p < 0.001). The analysis of surgeon's satisfaction scores concluded that surgeons were more satisfied with the group R (100%), when compared with group E (60%) and group N (30%) (p < 0.001). Conclusion Less volatile agent, short time to achieve controlled hypotension, stable blood pressure, lower surgical field bleeding scores and larger length of time with the targeted mean arterial pressure were found as the advantages of Remifentanil. Less costly, efficiency of achieving the targeted median arterial pressure and less postoperative complications were the advantages of nitroglycerin. In functional endoscopic sinus surgery procedures, appropriate controlled hypotensive agents should be selected according to the patients' characteristics and advantages/disadvantages of the drugs.

Resumo Introdução Hipotensão controlada é um procedimento reversível no qual a pressão arterial média basal do paciente é reduzida em 30% e mantida em 60-70 mmHg durante o procedimento. Isso diminui a perda de sangue e propicia um campo cirúrgico limpo durante os procedimentos. Objetivo Comparar agentes usados para hipotensão controlada: esmolol, remifentanil e nitroglicerina em cirurgia sinusal endoscópica funcional, em termos de alterações hemodinâmicas e impactos na eficácia cirúrgica. Método O estudo foi feito como de coorte. Pacientes submetidos à cirurgia sinusal endoscópica funcional foram randomizados em 3 grupos. A hipotensão controlada foi feita com remifentanil (Grupo R), esmolol (Grupo E) e nitroglicerina (Grupo R). A eficácia dos medicamentos foi testada com a comparação do período de tempo com a pressão arterial média desejada, a quantidade de anestésicos usados, o escore de sangramento no campo cirúrgico e a satisfação do cirurgião. Resultados Entre maio e dezembro de 2015, 60 pacientes foram incluídos e randomizados igualmente nos três grupos de estudo. A mediana do período com a pressão arterial desejada foi menor no Grupo R quando comparado ao Grupo E (p = 0,01) e Grupo N (p = 0,14). A quantidade de anestésicos voláteis usados foi de 25,0 mL (15 ± 51), 43,0 mL (21 ± 105) e 40,0 mL (26 ± 97) nos Grupos R, E e N, respectivamente (p < 0,001). Houve mais sangramento com nitroglicerina e escores de sangramento no campo cirúrgico foram menores no Grupo R quando comparados com esmolol (p = 0,001) e nitroglicerina (p < 0,001). A análise dos escores da satisfação do cirurgião concluiu que os cirurgiões estavam mais satisfeitos com o grupo R (100%) quando comparados ao grupo E (60%) e o grupo N (30%) (p < 0,001). Conclusão Agente menos volátil, pouco tempo para obter a hipotensão controlada, pressão arterial estável, menor escore de sangramento no campo cirúrgico e período de pressão arterial desejada curto foram considerados como vantagens do remifentanil. Menor custo, eficácia de obtenção da pressão arterial média desejada e menos complicações pós-operatórias foram as vantagens da nitroglicerina. Nos procedimentos de cirurgia sinusal endoscópica funcional, os agentes apropriados para obtenção de hipotensão controlada devem ser selecionados de acordo com as características dos pacientes e as vantagens/desvantagens dos fármacos.

Randomized, double-blind, placebo-controlled study of the analgesic effect of intraoperative esmolol for laparoscopic gastroplasty

Abstract 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.

Effect of esmolol and lidocaine on agitation in awake phase of anesthesia among children: a double-blind, randomized clinical study / 中华医学杂志(英文版)

BACKGROUND@#Sevoflurane is widely used to anesthetize children because of its rapid action with minimal irritation of the airways. However, there is a high risk of agitation after emergence from anesthesia. Strabismus surgery, in particular, can trigger agitation because patients have their eyes covered in the postoperative period. The aim of this study was to determine whether or not esmolol and lidocaine could decrease emergence agitation in children.@*METHODS@#Eighty-four patients aged 3 to 9 years undergoing strabismus surgery were randomly assigned to a control group (saline only), a group that received intravenous lidocaine 1.5 mg/kg, and a group that received intravenous esmolol 0.5 mg/kg and lidocaine 1.5 mg/kg. Agitation was measured using the objective pain score, Cole 5-point score, and Richmond Agitation Sedation Scale score at the end of surgery, on arrival in the recovery room, and 10 and 30 min after arrival.@*RESULTS@#The group that received the combination of esmolol and lidocaine showed lower OPS and RASS scores than the other two groups when patients awoke from anesthesia (OPS = 0 (0-4), RASS = -4 [(-5)-1]) and were transferred to the recovery room (OPS = 0 (0-8), RASS = -1 [(-5)-3]) (P  0.05).@*CONCLUSIONS@#When pediatric strabismus surgery is accompanied by sevoflurane anesthesia, an intravenous injection of esmolol and lidocaine could alleviate agitation until arrival in the recovery room.@*TRIAL REGISTRATION@#Clinical Research Information Service, No. KCT0002925; https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=11532.

Application of esmolol in severe hand, foot, and mouth disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease (HFMD).</p><p><b>METHODS</b>A prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups (n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate (HR), systolic blood pressure (SBP), and respiratory rate (RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before treatment and after 5 days of treatment.</p><p><b>RESULTS</b>There were no significant differences in HR, SBP, RR, NE, TNF-α, IL-6, NF-κB p65, serum myocardial enzymes, and NT-proBNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point (P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment (P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-proBNP compared with the conventional treatment group (P<0.05).</p><p><b>CONCLUSIONS</b>Early application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.</p>

Effects of lidocaine and esmolol infusions on hemodynamic changes, analgesic requirement, and recovery in laparoscopic cholecystectomy operations / Efeitos das infusões de lidocaína e esmolol sobre as alterações hemodinâmicas, necessidade de analgésicos e recuperação após colecistectomia laparoscópica

ABSTRACT OBJECTIVE: We compared the effects of lidocaine and esmolol infusions on intraoperative hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery in laparoscopic cholecystectomy surgery. METHODS: The first group (n = 30) received IV lidocaine infusions at a rate of 1.5 mg/kg/min and the second group (n = 30) received IV esmolol infusions at a rate of 1 mg/kg/min. Hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery characteristics were evaluated. RESULTS: In the lidocaine group, systolic arterial blood pressures values were lower after the induction of anesthesia and at 20 min following surgical incision (p < 0.05). Awakening time was shorter in the esmolol group (p < 0.001); Ramsay Sedation Scale scores at 10 min after extubation were lower in the esmolol group (p < 0.05). The modified Aldrete scores at all measurement time points during the recovery period were relatively lower in the lidocaine group (p < 0.05). The time to attain a modified Aldrete score of ≥9 points was prolonged in the lidocaine group (p < 0.01). Postoperative resting and dynamic VAS scores were higher in the lidocaine group at 10 and 20 min after extubation (p < 0.05, p < 0.01, respectively). Analgesic supplements were less frequently required in the lidocaine group (p < 0.01). CONCLUSION: In laparoscopic cholecystectomies, lidocaine infusion had superiorities over esmolol infusions regarding the suppression of responses to tracheal extubation and postoperative need for additional analgesic agents in the long run, while esmolol was more advantageous with respect to rapid recovery from anesthesia, attenuation of early postoperative pain, and modified Aldrete recovery (MAR) scores and time to reach MAR score of 9 points.

RESUMO OBJETIVO: Comparar os efeitos de infusões de lidocaína e esmolol sobre as alterações hemodinâmicas no período intraoperatório, a necessidade de analgésicos intra- e pós-operatoriamente e a recuperação após colecistectomia laparoscópica. MÉTODOS: O primeiro grupo (n = 30) recebeu infusões IV de lidocaína a uma taxa de 1,5 mg/kg/min e o segundo grupo (n = 30) recebeu infusões IV de esmolol a uma taxa de 1 mg kg/min. Alterações hemodinâmicas, necessidade de analgésicos no intra- e pós-operatório e características da recuperação foram avaliadas. RESULTADOS: No grupo lidocaína, os valores da pressão arterial sistólica foram menores após a indução da anestesia e 20 minutos após a incisão cirúrgica (p < 0,05). O tempo até o despertar foi menor no grupo esmolol (p < 0,001), os escores na escala de Sedação de Ramsay 10 minutos após a extubação foram menores no grupo esmolol (p < 0,05). Os escores de Aldrete modificados em todos os tempos mensurados durante o período de recuperação foram relativamente baixos no grupo lidocaína (p < 0,05). O tempo necessário para atingir um escore de Aldrete ≥ 9 pontos foi prolongado no grupo lidocaína (p < 0,01). Os escores Eva em repouso e em movimento no pós-operatório foram maiores no grupo lidocaína nos minutos 10 e 20 após a extubação (p < 0,05,p < 0,01, respectivamente). Analgésicos suplementares foram necessários com menos frequência no grupo lidocaína (p < 0,01). CONCLUSÃO: Em colecistectomia laparoscópica, a infusão de lidocaína foi superior às infusões de esmolol quanto a suprimir as respostas à extubação traqueal e necessidade de analgésicos adicionais no pós-operatório, enquanto esmolol foi mais vantajoso quanto à rápida recuperação da anestesia, à atenuação da dor no pós-operatório imediato e aos escores de recuperação de Aldrete modificado (RAM) e o tempo até atingir o escore RAM de 9 pontos.

Effect of selective beta-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

There is evidence for participation of peripheral β-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether β-adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, β1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, β2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, β3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At (BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that β2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex.

Efficacy and Safety of Esmolol in Treatment of Patients with Septic Shock / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies have suggested that β1-receptor blockers benefit septic shock patients. This study aimed to determine whether β1-receptor blockers benefit tissue perfusion in sepsis and to identify parameters to reduce the risk of this drug in sepsis.</p><p><b>METHODS</b>Consecutive septic shock patients were recruited from the Intensive Care Unit of Peking Union Medical College Hospital within 48 h of diagnosis. All patients were hemodynamically stable and satisfactorily sedated with a heart rate (HR) ≥100 beats/min. Esmolol therapy achieved the target HR of 10-15% lower than the baseline HR. Clinical and physiological data of patients were collected prospectively within 1 h prior to esmolol therapy and 2 h after achieving the targeted HR.</p><p><b>RESULTS</b>Sixty-three patients were recruited. After esmolol therapy, blood pressure was unaltered, whereas stroke volume (SV) was increased compared with before esmolol therapy (43.6 ± 22.7 vs. 49.9 ± 23.7 ml, t = -2.3, P = 0.047). Tissue perfusion, including lactate levels (1.4 ± 0.8 vs. 1.1 ± 0.6 mmol/L, t = 2.6, P = 0.015) and the central venous-to-arterial carbon dioxide difference (5.6 ± 3.3 vs. 4.3 ± 2.2 mmHg, t = 2.6 P = 0.016), was also significantly decreased after esmolol therapy. For patients with increased SV (n = 42), cardiac efficiency improved, and esmolol therapy had a lower risk for a decrease in cardiac output (CO). Therefore, pretreatment cardiac systolic and diastolic parameters with (n = 42)/without (n = 21) an increase in SV were compared. Mitral lateral annular plane systolic excursion (MAPSElat) in patients with increased SV was significantly higher than that in those without increased SV (1.3 ± 0.3 vs. 1.1 ± 0.2 cm, t = 2.4, P = 0.034).</p><p><b>CONCLUSIONS</b>SV of septic shock patients is increased following esmolol therapy. Although CO is also decreased with HR, tissue perfusion is not worse. MAPSElat can be used to predict an increase in SV before esmolol use.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT01920776; https://clinicaltrials.gov/ct2/show/NCT01920776?term=NCT01920776&rank=1.</p>

A rare case of an intracardiac hemangioma causing significant right ventricular outflow tract obstruction

INTRODUCTION: Cardiac hemangiomas are rare benign primary tumors.We present the successful management of a patient with a hemangioma causing significant right ventricular outflow tract (RVOT) obstruction.CLINICAL PRESENTATION: A 54-year-old  female  with  no  co-morbidities  presented  with  progressive  right-sided  heart failure  symptoms.Examination  revealed  a  prominent right  ventricular  heave,  irregular  cardiac  rhythm,murmurs  consistent  with  pulmonic  stenosis  and  tricuspid regurgitation,  ascites,  and  bipedal  edema.  Given the echo features of the mass and the patient's clinical course,we  favored  a  benign  cardiac  tumor  over  malignancy.Differentials included  myxoma,  fibroma,  and  papillary fibroelastoma. Medical management included enoxaparin and carvedilol as anticoagulation and rate control for the atrial flutter, respectively. Surgical treatment consisted of tumor excision and tricuspid valve annuloplasty.RESULTS: Intra-operatively, the stalk was indeed attached to the RV free wall. Histopathology was consistent with primary cardiac hemangioma. The patient's post-operative course was complicated by pneumonia, acute kidney injury, and tracheostomy, but she was eventually discharged improved after a month in the ICU.SIGNIFICANCE: This report highlights a rare primary cardiac tumor in an unusual location. While there have been several reports in the world literature on cardiac hemangiomas, less than ten cases have been shown to have significant RVOT obstruction as in our patient.CONCLUSION: Cardiac hemangiomas should be part of the differential diagnosis for an intracardiac mass in the right ventricle.  Meticulous  echocardiography  can  be  a  non-invasive and inexpensive aid to diagnosis and pre-operative planning.

Effects 'of β3 adrenoceptors on the contractility of rat thoracic aorta smooth muscle and the mechanism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effect of β₃adrenoceptors (β₃-AR) activation on rat thoracic aorta smooth muscle contractility and the possible related mechanism.</p><p><b>METHODS</b>The endothelium removed thoracic aorta was pre-contracted with 30 mmol/L KCl physiological saline solution (PSS). Then the tension of the thoracic aorta was recorded in presence of BRL37344 (BRL) to determine the action of β₃-AR. The tension of the thoracic aorta was also recorded in the presence of Propranolol (PRA), SR59230A (SR), L-NNA, H-89 and Iberiotoxin (IBTX) respectively to reveal the underling mechanism of β₃-AR activation on rat vascular smooth muscle. Immunohistochemistry was adopted to confirm the existence and the distribution of β₃-AR in rat thoracic aorta.</p><p><b>RESULTS</b>The results showed that: (1) The thoracic aorta was relaxed by β₃-AR activation, with a relaxation percentage of (10.59 ± 0.79). (2) β₃-AR was expressed in both endothelial and smooth muscle layer in thoracic aorta sections of rats. (3) PRA did not block the effect of BRL on the thoracic aorta. The relaxation actions of BRL could be antagonized by pre-incubating the thoracic aorta with SR. (4) L-NNA (a NOS inhibitor) and H-89 (a PKA inhibitor) reversed the relaxation effect of BRL on vascular smooth muscle. (5) The effect of BRL was decreased after application of Ibriotoxin (IBTX), a large conductance calcium dependent potassium channel blocker.</p><p><b>CONCLUSION</b>The results confirmed that activation of β₃-AR led to relaxation of thoracic aorta smooth muscle. The relaxation action of β₃-AR on smooth muscle of rat thoracic aorta was related to activation of NOS and PKA signaling pathway. Large conductance Ca²⁺-K⁺ channels were involved in the relaxation action of β₃-AR activation on rat thoracic aorta smooth muscle.</p>

Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.

Short-term follow-up of exercise training program and beta-blocker treatment on quality of life in dogs with naturally acquired chronic mitral valve disease

This study aimed to evaluate the effects of carvedilol treatment and a regimen of supervised aerobic exercise training on quality of life and other clinical, echocardiographic, and biochemical variables in a group of client-owned dogs with chronic mitral valve disease (CMVD). Ten healthy dogs (control) and 36 CMVD dogs were studied, with the latter group divided into 3 subgroups. In addition to conventional treatment (benazepril, 0.3-0.5 mg/kg once a day, and digoxin, 0.0055 mg/kg twice daily), 13 dogs received exercise training (subgroup I; 10.3±2.1 years), 10 dogs received carvedilol (0.3 mg/kg twice daily) and exercise training (subgroup II; 10.8±1.7 years), and 13 dogs received only carvedilol (subgroup III; 10.9±2.1 years). All drugs were administered orally. Clinical, laboratory, and Doppler echocardiographic variables were evaluated at baseline and after 3 and 6 months. Exercise training was conducted from months 3-6. The mean speed rate during training increased for both subgroups I and II (ANOVA, P>0.001), indicating improvement in physical conditioning at the end of the exercise period. Quality of life and functional class was improved for all subgroups at the end of the study. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level increased in subgroup I from baseline to 3 months, but remained stable after training introduction (from 3 to 6 months). For subgroups II and III, NT-proBNP levels remained stable during the entire study. No difference was observed for the other variables between the three evaluation periods. The combination of carvedilol or exercise training with conventional treatment in CMVD dogs led to improvements in quality of life and functional class. Therefore, light walking in CMVD dogs must be encouraged.

Association of T190C polymorphism of β3 adrenergic receptor gene with response to carvedilol in patients with chronic heart failure / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of T190C polymorphism of β3 adrenergic receptor gene (β3-AR) with chronic heart failure (CHF), and to evaluate the effect of this polymorphism on clinical response to β-AR blockade among patients with CHF.</p><p><b>METHODS</b>Three hundred and thirty patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 5 months after the maximal tolerated dose of carvedilol was reached, all indices including heart rate (HR), blood pressure (BP), left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) level, 6 min walk distance were measured and compared with the indices of those with a T190C genotype. Distribution of the T190C polymorphisms in the control group and CHF group was compared.</p><p><b>RESULTS</b>The frequencies of T190C genotypes of the β3-AR gene have fit with the Hardy-Weinberg equilibrium. No significant difference was found between the frequencies of T190C alleles and genotypes between the two groups (P > 0.05). Compared with CC-homozygotes, TT-homozygous patients showed substantially greater improvement in LVEF and BNP (all P < 0.01).</p><p><b>CONCLUSION</b>No difference has been detected in the prevalence of the three genotypes between healthy and CHF subjects. The T190C variation of the β3-AR gene was not associated with increased risk for CHF. CHF patients with a T allele have greater response to carvedilol than those carrying a C allele in ethnic Han Chinese.</p>

Cyclodextrine screening for the chiral separation of carvedilol by capillary electrophoresis

Carvedilol is administered as a racemic mixture of the R[+]- and S[-]-enantiomers, although it was demonstrated that the two enantiomers exhibit different pharmacological effects and stereoselective pharmacokinetics. The aim of this study was the evaluation of several native and derivatized cyclodextrines as chiral selectors for the separation of carvedilol enantiomers. Stereoselective interactions were observed with four cyclodextrines [beta-CD, hydroxypropyl-beta-CD, randomly methylated beta-CD and sulfobuthyl ether-beta-CD]. The effects of CD concentration, pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. The method was validated for precision of peak-area response, linearity range and limits of detection and quantification. An efficient stereoselective capillary zone electrophoretic method was developed for the determination of carvedilol enantiomers using a simple 25 mM phosphate buffer at a pH = 2.5 and 10 mM beta-CD as chiral selector, resulting in baseline separation of the two enantiomers with sharp peaks and relatively short analysis time. Highly satisfactory results were obtained from the analysis of carvedilol from tablets, indicating that the method is suitable for routine analysis of carvedilol in pharmaceutical products

Comparison of bolus and continuous infusion of esmolol on hemodynamic response to laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft / Comparação de esmolol em bolus e infusão contínua na resposta hemodinâmica à laringoscopia, intubação orotraqueal e esternotomia em cirurgia de revascularização coronária / Comparación del esmolol en bolos e infusión continua en la respuesta hemodinámica a la laringoscopia, intubación orotraqueal y esternotomía en cirugía de revascularización coronaria

BACKGROUND AND OBJECTIVE: The aim of this randomized, prospective and double blinded study is to investigate effects of different esmolol use on hemodynamic response of laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft surgery. METHODS: After approval of local ethics committee and patients' written informed consent, 45 patients were randomized into three groups equally. In Infusion Group; from 10 min before intubation up to 5th minute after sternotomy, 0.5 mg/kg/min esmolol infusion, in Bolus Group; 2 min before intubation and sternotomy 1.5 mg/kg esmolol IV bolus and in Control Group; %0.9 NaCl was administered. All demographic parameters were recorded. Heart rate and blood pressure were recorded before infusion up to anesthesia induction in every minute, during endotracheal intubation, every minute for 10 minutes after endotracheal intubation and before, during and after sternotomy at first and fifth minutes. RESULTS: While area under curve (AUC) (SAP × time) was being found more in Group B and C than Group I, AUC (SAP × T int and T st) and AUC (SAP × T2) was found more in Group B and C than Group I (p < 0.05). Moreover AUC (HR × T st) was found less in Group B than Group C but no significant difference was found between Group B and Group I. CONCLUSION: This study highlights that esmolol infusion is more effective than esmolol bolus administration on controlling systolic arterial pressure during endotracheal intubation and sternotomy in CABG surgery. .

JUSTIFICATIVA E OBJETIVO: o objetivo deste estudo prospectivo, randômico e duplo-cego foi investigar os efeitos do uso diferente de esmolol na resposta hemodinâmica à laringoscopia, intubação orotraqueal e esternotomia em cirurgia de revascularização coronária. MÉTODOS: após obter a aprovação do Comitê de Ética local e consentimento informado assinado pelos pacientes, 45 pacientes foram randomicamente divididos em três grupos. O Grupo I (infusão) recebeu 0,5 mg/kg/min de esmolol em infusão a partir de 10 min antes da intubação até 5 minutos após a esternotomia; o Brupo B (bolus) recebeu 1,5 mg/kg de esmolol em bolus IV a partir de 2 min antes da intubação e esternotomia; o grupo C (controle) recebeu NaCl a 0,9%. Todos os parâmetros demográficos foram registados. Os valores de frequência cardíaca e pressão arterial foram registrados desde antes da infusão até a indução da anestesia a cada minuto, durante a intubação endotraqueal, a cada minuto durante 10 min após a intubação endotraqueal e antes, durante e após a esternotomia no primeiro e quinto minutos. RESULTADOS: enquanto a área sob a curva (ASC) (SAP × tempo) foi maior nos grupos B e C que no Grupo I, a ASC (SAP × T int e T st) e ASC (SAP × T2) foram maiores nos grupos B e C que no Grupo I (p < 0,05). Além disso, a ASC (FC × T st)) foi menor no Grupo B que no Grupo C, mas não houve diferença significante entre os grupos B e I. CONCLUSÃO: este estudo destaca que a administração de esmolol em infusão é mais eficaz que em bolus para controlar a pressão arterial sistólica durante a intubação endotraqueal e esternotomia em CRC. .

JUSTIFICACIÓN Y OBJETIVO: el objetivo de este estudio prospectivo, aleatorizado y doble ciego fue investigar los efectos del diferente uso del esmolol en la respuesta hemodinámica a la laringoscopia, intubación orotraqueal y esternotomía en cirugía de revascularización coronaria. MÉTODOS: después de obtener la aprobación del Comité de Ética local y el consentimiento informado firmado por los pacientes, 45 de ellos fueron aleatoriamente divididos en 3 grupos. El grupo I (infusión) recibió 0,5 mg/kg/min de esmolol en infusión desde 10 min antes de la intubación hasta 5 min después de la esternotomía; el grupo B (bolo), que recibió 1,5 mg/kg de esmolol en bolo iv a partir de 2 min antes de la intubación y esternotomía; el grupo C (control) recibió NaCl al 0,9%. Todos los parámetros demográficos fueron registrados. Los valores de frecuencia cardíaca y presión arterial fueron registrados ya antes de la infusión y hasta la inducción de la anestesia cada minuto durante la intubación endotraqueal, cada minuto durante 10 min después de la intubación endotraqueal, y antes, durante y después de la esternotomía en el primer y quinto minutos. RESULTADOS: mientras que el área bajo la curva (AUC) (presión arterial sistólica [PAS] × tiempo) fue mayor en los grupos B y C que en el grupo I, el AUC (PAS ×T int y T st ) y AUC (PAS × T 2 ) fueron mayores en los grupos B y C que en el grupo I (p < 0,05). Además, el AUC (frecuencia cardíaca × T st ) fue menor en el grupo B que en el grupo C, pero no hubo diferencia significativa entre los grupos B e I. CONCLUSIÓN: este estudio destaca que la administración del esmolol en infusión es más eficaz que en bolos para controlar la PAS durante la intubación endotraqueal ...

The effects of carvedilol on ischemia-reperfusion injury in the rat testis

Objective: To analyze the oxidative damage and histopathological alterations caused by ischemia-reperfusion (I/R) injury and ameliorative effects of carvedilol (CVD) in the rat testis. Materials and Methods: Twenty-one male rats were randomized into 3 groups as follows: Group I (n = 7); control (sham) group, Group II (n = 7); I/R group, in which I/R injury was performed by torsing the left testis 720º clockwise for 2 hours and detorsing for 2 hours. Group III (n = 7); CVD treatment group; in addition to I/R process, one-dose of CVD was administered (2mg/kg, i.p) 30 min. before detorsion. Levels of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and levels of malondialdehyde (MDA) and protein carbonyl (PC) were determined in testicular tissues and serum of rats. Testicular tissues were also examined histopathologically and Johnsen scores were determined. Results: Activities of SOD and GSH-Px in serum and testicular tissues were increased by I/R, but administration of CVD decreased these levels (p < 0.001 and p = 0.001). Significantly increased MDA levels in serum and testicular tissues were decreased by CVD treatment (p < 0.001 and p = 0.001). Concerning PC levels in serum and testicular tissues, there was no statistically significant difference between the groups (p = 0.989 and p = 0.428). There was not a statistically significant difference in terms of mean Johnsen scores between the groups (p = 0.161). Conclusions: Administration of CVD decreased oxidative damage biochemically in the rat testis caused by I/R injury, but histopathologically no change was observed between all of the groups. .

O carvedilol potencializa o efeito antioxidante das vitaminas E e C na cardiopatia chagásica crônica / Carvedilol enhances the antioxidant effect of vitamins E and C in chronic chagas heart disease

FUNDAMENTO: A doença de Chagas continua a ser uma importante doença endêmica no país, sendo o acometimento cardíaco a sua manifestação mais grave. OBJETIVO: Verificar se o uso concomitante de carvedilol potencializará o efeito antioxidante das vitaminas E e C na atenuação do estresse oxidativo sistêmico na cardiopatia chagásica crônica. MÉTODOS: Foram estudados 42 pacientes com cardiopatia chagásica, agrupados de acordo com a classificação modificada de Los Andes, em quatro grupos: 10 pacientes no grupo IA (eletrocardiograma e ecocardiograma normais: sem envolvimento do coração), 20 pacientes do grupo IB (eletrocardiograma normal e ecocardiograma anormal: ligeiro envolvimento cardíaco), oito pacientes no grupo II (eletrocardiograma e ecocardiograma anormais, sem insuficiência cardíaca: moderado envolvimento cardíaco) e quatro pacientes no grupo III (eletrocardiograma e ecocardiograma anormais com insuficiência cardíaca: grave envolvimento cardíaco). Os marcadores de estresse oxidativo foram medidos no sangue, antes e após um período de seis meses de tratamento com carvedilol e após seis meses de terapia combinada com vitaminas E e C. Os marcadores foram: atividades da superóxido dismutase, catalase, glutationa peroxidase, glutationa S-transferase e redutase, mieloperoxidase e adenosina deaminase, e os níveis de glutationa reduzida, de espécies reativas do ácido tiobarbitúrico, proteína carbonilada, vitamina E e óxido nítrico. RESULTADOS: Após o tratamento com carvedilol, todos os grupos apresentaram diminuições significativas dos níveis de proteína carbonilada e glutationa reduzida, enquanto os níveis de óxido nítrico e atividade da adenosina aumentaram significativamente apenas no grupo menos acometido (IA). Além disso, a maioria das enzimas antioxidantes mostrou atividades diminuídas nos grupos menos acometidos (IA e IB). Com a adição das vitaminas ao carvedilol houve diminuição dos danos em proteínas, nos níveis de glutationa e na maior parte da atividade das enzimas antioxidantes. CONCLUSÕES: A queda dos níveis de estresse oxidativo, verificada pelos marcadores testados, foi mais acentuada quando da associação do fármaco carvedilol com as vitaminas antioxidantes. Os dados sugerem que tanto o carvedilol isoladamente como sua associação com as vitaminas foram eficazes em atenuar o dano oxidativo sistêmico em pacientes com CC, especialmente aqueles menos acometidos, sugerindo a possibilidade de sinergismo entre esses compostos.

BACKGROUND: Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. OBJECTIVE: To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. METHODS: A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. RESULTS: After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. CONCLUSIONS: The decrease in oxidative stress levels observed by means of the markers tested was more significant when carvedilol was used in combination with the antioxidant vitamins. The findings suggest that both carvedilol alone and in combination with the vitamins were effective in attenuating the systemic oxidative stress in patients with Chagas heart disease, especially those less severely affected, thus suggesting the possibility of synergism between these compounds.

Efeitos de esmolol, lidocaína e fentanil nos intervalos dispersão da onda P, QT, QTc e respostas hemodinâmicas à intubação endotraqueal durante indução com propofol: um estudo comparativo / Effects of esmolol, lidocaine and fentanyl on P wave dispersion, QT, QTc intervals and hemodynamic responses to endotracheal intubation during propofol induction: a comparative study / Efectos del esmolol, de la lidocaína y del fentanilo en los intervalos dispersión de la onda, QT, QTc y respuestas hemodinámicas a la intubación endotraqueal durante inducción con propofol: un estudio comparativo

JUSTIFICATIVA E OBJETIVOS: Investigar o efeito de esmolol, lidocaína e fentanil na dispersão da onda P (DP), durações dos intervalos QT e QT corrigido (QTc) e as respostas hemodinâmicas à intubação endotraqueal durante a indução com propofol. MÉTODOS: Foram incluídos 80 pacientes adultos, estado físico ASA I ou II, idade entre 18 e 60 anos, neste estudo prospectivo, randômico e duplo-cego. Todos os pacientes foram submetidos a exame eletrocardiográfico (ECG) antes da indução da anestesia. Os pacientes foram randomicamente alocados em quatro grupos iguais. O grupo controle (Grupo C) recebeu 5 mL de solução salina; o grupo esmolol (Grupo E) recebeu 0,5 mg.kg-1 de esmolol; o grupo fentanil (Grupo F) recebeu 2 µg.kg-1 de fentanil e o grupo lidocaína (Grupo L) recebeu 1,5 mg.kg-1 de lidocaína antes da indução anestésica. A anestesia foi induzida com propofol. ECG foi feito em todos os pacientes durante o primeiro e o terceiro minutos de indução, 3 minutos após a administração de relaxante muscular e 5 e 10 minutos após intubação. A DP e intervalos QT foram medidos em todos os ECGs. Os intervalos QTc foram determinados com o uso da fórmula de Bazett. Frequência cardíaca (FC) e pressão arterial média (PAM) foram registradas antes e depois da indução anestésica, imediatamente após a intubação e em 1, 3, 5, 7 e 10 minutos após a intubação. RESULTADOS: Após a intubação, a FC aumentou significativamente nos Grupos C, L e F em comparação com o grupo controle. Porém, não houve diferença significativa nos valores da FC após a intubação entre os grupos E e controle. Nos Grupos C e L, a PAM aumentou significativamente após a intubação em comparação com o grupo controle. No entanto, nos Grupos L, F e E não houve diferença significativa entre os valores da PAM após a intubação em comparação com o grupo controle. A DP foi significativamente mais longa no Grupo C após a intubação em comparação com o grupo controle. Porém, nos grupos L, F e E não houve diferença significativa entre os valores de DP após a intubação em comparação com o grupo controle. A duração do intervalo QTc foi significativamente maior nos grupos C e L após a intubação em comparação com o grupo controle. Porém, não houve diferença significativa na duração do QTc nos grupos F e E após a intubação em comparação com o grupo controle. CONCLUSÃO: Concluímos que a administração de esmolol antes da intubação previne a taquicardia, o aumento da PAM e as durações da onda P e intervalo QTc causados pela laringoscopia e intubação traqueal.

BACKGROUND AND OBJECTIVES: In our study we aimed to investigate the effect of esmolol, lidocaine and fentanyl on P-wave dispersion (Pwd), QT and corrected QT (QTc) durations and hemodynamic responses to endotracheal intubation during propofol induction. METHODS: A total of eighty adult patients, American Society of Anesthesiologists (ASA) Physical Status I or II aged 18 to 60 years were included in this prospective, randomised, double-blind study. All patients had control electrocardiograms (ECGs) done before anesthesia induction. The patients were randomised into four equal groups. The control group (Group C) received saline 5 mL, the esmolol group (Group E) received esmolol 0.5 mg.kg-1, the fentanyl group (Group F) received fentanyl 2 µg.kg-1 and the lidocaine group (Group L) received lidocaine 1.5 mg.kg-1 before anesthesia induction. Anesthesia was induced with intravenous propofol. ECGs for all patients were performed during the 1st and 3rd minutes of induction, 3 minutes after administration of muscle relaxant, and at 5 minutes and 10 minutes after intubation. Pwd and QT intervals were measured on all ECGs. QTc intervals were determined using the Bazett formula. Heart rate (HR) and mean arterial pressure (MAP) were recorded before and after induction of anesthesia, immediately after intubation, and 1, 3, 5, 7 and 10 minutes after intubation. RESULTS: Compared with control, HR significantly increased in Group C, Group L and Group F after intubation. However, in Group E, there was no significant difference in HR values between control and after intubation. Compared with control, MAP significantly increased in Group C and Group L after the intubation. However, in Group E and Group F, there was no significant difference in MAP values between control and after the intubation. Compared with control, Pwd significantly increased in Group C after intubation. In Group L, Group F and Group E, there was no significant difference in Pwd values between control and after the intubation. Compared with control, QTc duration significantly increased in Group C and L after the intubation. In Group F and Group E, there was no significant difference in QTc durations between control and after the intubation. CONCLUSION: We concluded that administration of esmolol before intubation prevents tachycardia and an increase in MAP, Pwd and QTc duration caused by laryngoscopy and tracheal intubation.

JUSTIFICATIVA Y OBJETIVOS: Investigar el efecto del esmolol, lidocaína y fentanilo en la dispersión de la onda P (DOP), duraciones de los intervalos QT y QT corregido (QTc) y las respuestas hemodinámicas a la intubación endotraqueal durante la inducción con propofol. MÉTODOS: En este estudio prospectivo, aleatorio y doble ciego, fueron incluidos 80 pacientes adultos, con estado físico ASA I o II, y edad entre 18 y 60 años. Todos los pacientes se sometieron al examen electrocardiográfico (ECG) antes de la inducción de la anestesia. Los pacientes fueron aleatoriamente divididos en cuatro grupos iguales. El grupo control (Grupo C) recibió 5 mL de solución salina; el grupo esmolol (Grupo E) recibió 0,5 mg.kg-1 de esmolol; el grupo fentanilo (Grupo F) recibió 2 µg.kg-1 de fentanilo y el grupo lidocaína (Grupo L) recibió 1,5 mg.kg-1 de lidocaína antes de la inducción anestésica. La anestesia fue inducida con propofol. El ECG se hizo en todos los pacientes durante el primero y el tercer minuto de inducción, 3 minutos después de la administración del relajante muscular y 5 y 10 minutos después de la intubación. La DOP y los intervalos QT se midieron en todos los ECGs. Los intervalos QTc fueron determinados con el uso de la fórmula de Bazett. La frecuencia cardíaca (FC) y la presión arterial promedio (PAP) fueron registradas antes y después de la inducción anestésica, inmediatamente después de la intubación y en 1, 3, 5, 7 y 10 minutos después de la intubación. RESULTADOS: Después de la intubación, la FC aumentó significativamente en los Grupos C, L y F en comparación con el grupo control. Sin embargo, no hubo diferencia significativa en los valores de la FC después de la intubación entre los grupos E y control. En los Grupos C y L, la PAP aumentó significativamente después de la intubación en comparación con el grupo control. Sin embargo, en los Grupos L, F y E no hubo diferencia significativa entre los valores de la PAP posteriormente a la intubación en comparación con el grupo control. La DOP fue significativamente más larga en el Grupo C después de la intubación en comparación con el grupo control. No obstante, en los grupos L, F y E no hubo diferencia significativa entre los valores de DOP después de la intubación en comparación con el grupo control. La duración del intervalo QTc fue significativamente mayor en los grupos C y L después de la intubación en comparación con el grupo control. Sin embargo, no hubo diferencia significativa en la duración del QTc en los grupos F y E después de la intubación en comparación con el grupo control. CONCLUSIONES: Llegamos entonces a la conclusión, de que la administración del esmolol antes de la intubación previene la taquicardia, el aumento de la PAP y las duraciones de la onda P e intervalo QTc causados por la laringoscopia y por la intubación traqueal.