Ultrashort-acting Beta-blocker Research Articles

Heart rate control with landiolol hydrochloride in infants with ventricular dysfunction and pulmonary hypertension.

Sinus tachycardia potentially leads to a deterioration of cardiac function in critically ill infants. The ultrashort-acting beta-blocker landiolol hydrochloride is a new pharmacological option for a selective heart rate (HR) control in patients with sinus tachycardia and heart failure. This study was a monocentric retrospective medical chart review study at the University Children's Hospital Bonn (Germany) from 01 January 2018 until 30 June 2020. This study included a cohort of 62 term and preterm infants with a diagnosis of ventricular dysfunction and/or pulmonary hypertension (PH), in combination with preexisting tachycardia and treatment with landiolol hydrochloride. Infants were allocated to subgroups according to weeks of gestational age (GA): born at <35weeks of GA (Group A) and born at >35weeks of GA (Group B). Tachycardia was defined depending on GA (<35weeks of GA: >170b.p.m.; 35weeks of GA: >150b.p.m.). The primary endpoint was defined as percentage of patients achieving HR normalization during the first 24h of landiolol treatment. Twenty-nine infants were allocated to Group A and 33 infants to Group B. The overall median GA of the infants was 35.3 (23.3/41.3), with 53% female infants. The primary endpoint was achieved in 57 patients (91.9%). The median time to reach target HR was 1.8 (0.3-24) h. The median starting dose of landiolol was 8.8 (3.9-25.3) μk/kg/min, with a median dosing during the first 24h of landiolol treatment of 9.9 (2.8-35.4) μk/kg/min. The median landiolol dose while achieving the target HR was 10 (2.4-44.4) μk/kg/min. The right ventricular dysfunction improved significantly in both groups 24h after onset of landiolol infusion (P=0.001 in Group A and P=0.045 in Group B). The left ventricular and biventricular dysfunction improved significantly 24h after onset of landiolol infusion in infants of Group B (P=0.004 and P=0.006, respectively). The severity of PH improved significantly after 24h in infants of Group A (P<0.001). During landiolol treatment, no severe drug-related adverse event was noted. The use of landiolol hydrochloride for HR control of non-arrhythmic tachycardia in critically ill infants is well tolerated. Reduction of HR can be guided quickly and landiolol treatment is associated with an improvement of ventricular dysfunction and PH.

Intravenous Dexmedetomidine versus Intravenous Esmolol in Blunting the Laryngoscopy Response in Adult Normotensives Undergoing Elective Surgeries: A Randomised Clinical Trial

Introduction: A wide array of drugs are available for blunting the laryngoscopy response. Amongst them both dexmedetomidine, and esmolol belong to the non-opioid group having least interference with the recovery process without causing significant respiratory depression, thus are suitable intervention for this purpose. Dexmedetomidine a sedative highly selective α2 adrenoceptor agonist and has an anaesthetic-sparing effect at induction. It suppresses the release of catecholamine in response to a noxious stimulant because of its central sympatholytic action. Esmolol with a different pharmacokinetic profile is a water soluble, cardio-selective, an ultrashort acting beta blocker has a short t1/2 thus suited for suppressing the transient pressor reflexes following acute noxious surgical or anesthesia stimuli. Aim: To compare the degree of attenuation of the laryngoscopy response following the use of single preinduction dose (Intravenous infusion at a dose of 1 µg/kg) of dexmedetomidine with that of esmolol (intravenous bolus at a dose of 0.5 mg/kg) in adult normotensives undergoing elective intubations. Materials and Methods: The randomised clinical trial was conducted in Pondicherry Institute of Medical Sciences from September 2016 to March 2018, on 60 patients of either sex, aged between 20-60 years with American Society of Anesthesiologists (ASA) physical status I or II requiring elective intubations for general surgical procedures. The patients were randomly divided into two groups (n=30 each). Prior to induction group A received 1 µg/kg dexmedetomidine IV infusion over 10 min, and group B received 100 mL IV infusion of normal saline over 10 min. Also 2 minute before laryngoscopy group A received 10 mL of normal saline (IV) bolus, whereas, group B received esmolol 0.5 mg/kg IV diluted in 10 mL of normal saline as a bolus. Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) were recorded at baseline i.e, pre-procedure before the study drug infusion, preinduction, at laryngoscopy (0min) and 1,3,5 min after intubation. A rise of MAP and/or HR more than 20% from the baseline was considered as positive laryngoscopy response. Student’s unpaired t-test was used for analysis of inter group variables. Intra group variables were analysed using repeated measures Analysis Of Variance (ANOVA). Results: Mean age of patients in group A was 38.77±13.082 years and group B was 37.20±13.069 years (p-value=0.644). Results revealed that both the groups had an increase in HR and MAP at 1 minute after laryngoscopy and intubation. Mean readings of MAP showed a maximum rise of group A (2.15%) vs group B (7.25%) from the baseline readings at 1min following laryngoscopy which showed no statistical significance. The maximum HR increase following laryngoscopy was at 1 minute in group A (8.28%) vs group B (13.59%), which were below the positive laryngoscopy response. The mean HR, SBP, DBP and MAP recorded at preinduction, at laryngoscopy, 1, 3 and 5 mins following intubation showed no statistical difference (p-value &gt;0.05) between the two groups. Conclusion: Usage of single dose preinduction dexmedetomidine iv infusion 1 µg/kg over 10 min was found to be equally effective in blunting the pressor response to laryngoscopy and intubation when compared to bolus dose of iv esmolol 0.5 mg/kg given 2 min prior to laryngoscopy.

Efficacy of early intravenous landiolol, an ultrashort-acting beta-blocker on infarct size and its safety in patients with myocardial infarction undergoing primary PCI: a randomized, controlled study

Abstract Background Previous clinical studies showed that early intravenous metoprolol before reperfusion in patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI reduced infarct size. However, intravenous beta-blockers in acute phase of STEMI can be associated with adverse effects such as cardiogenic shock and atrioventricular block. Landiolol is an ultrashort-acting beta-blocker with a half-life of 3 min that is eight times more cardioselective than esmolol. Purpose We evaluate the efficacy of intravenous infusion of landiolol on infarct size and its safety in STEMI patients undergoing primary PCI. Methods This study is a multicenter randomized control trial. A total of 47 patients with Killip class II or less STEMI undergoing PCI within 12 hours of symptoms onset were randomized to receive intravenous landiolol (n=23) or not (control, n=24). Patients allocated to landiolol group delivered an intravenous continuous dose of 3μg/min/kg before reperfusion and then continued until a total dose of 50mg. All patients started oral metoprolol or carvedilol within 12 hours. The primary end point was myocardial salvage index (MSI) on magnetic resonance imaging performed 5 to 7 days after PCI. MSI was defined as the difference between the area at risk and the area of necrosis analyzed using a commercial software. Results Magnetic resonance imaging was performed in 35 patients (17 patients in landiolol group and 18 patients in the control group), and ischemia duration time was 229 minutes in the landiolol group and the 242 minutes in control. In adjusting for confounding variables, the areas of myocardium at risk were not difference in both groups (54.4g in the landiolol group, and 46.8g in the control group; p=0.31). However, MSI in the landiolol group was significantly reduced than that in the control group (36.8% and 57.0%; p&amp;lt;0.001). In both group blood pressure was not difference in recruitment (142mmHg in landiolol group, and 144 in control) and starting PCI (163mmHg in landiolol group, and 165 in control). Regarding safety, the composite of death, malignant ventricular arrhythmia, cardiogenic shock, and atrioventricular block at 24 hours did not differ between the landiolol and the control groups (8.7% and 8.3%, respectively, p=0.93). Conclusion Early intravenous landiolol before starting primary PCI reduced infarct size in STEMI patients without significant hemodynamic adverse effects. Funding Acknowledgement Type of funding source: None

Recurrent takotsubo syndrome with worsening of left ventricular outflow obstruction during haemodialysis: a case report.

BackgroundThe recurrence rate of takotsubo syndrome (TS) has been reported as 1.8% per patient-year while left ventricular outflow tract (LVOT) obstruction is comorbid in 10–25% of all instances of TS. The clinical course of recurrent TS with associated LVOT while on haemodialysis has rarely been reported.Case summaryThis case report involves a 60-year-old female patient receiving regular haemodialysis who was admitted for chest pain during ballroom dancing. Four years prior, she had suffered TS, and fully recovered after the hospitalization. An emergent coronary angiogram done during the second hospitalization showed no significant stenosis, and left ventriculography demonstrated mid-apical akinesia and basal hyperkinesia. Based on these findings, we diagnosed the recurrence of TS. Later in the admission, chest pain reappeared with the start of haemodialysis. A transthoracic echocardiogram demonstrated mean pressure gradient (PG) of LVOT was 58 mmHg, with systolic anterior motion of the mitral valve and basal-wall hyperkinesia. The main aetiology for her symptoms was considered as an exacerbation of LVOT obstruction due to removing intravascular volume by haemodialysis. After starting landiolol at 3 μg/kg/min, PG of LVOT and symptoms gradually improved with uptitration of landiolol. Finally, her chest pain resolved when mean PG of LVOT was down to 38 mmHg using 10 μg/kg/min of landiolol.DiscussionTo our knowledge, this is the first report of a recurrent TS case comorbid with LVOT obstruction while on regular haemodialysis. Landiolol, the ultrashort-acting beta-blocker, may be a promising therapeutic option for rapid recovery of increased PG due to LVOT obstruction.

Cost-Effectiveness Analysis of Landiolol, an Ultrashort-Acting Beta-Blocker, for Prevention of Postoperative Atrial Fibrillation for the Germany Health Care System

Landiolol is an ultrashort-acting beta-blocker with high beta-1 receptor affinity and less blood pressure-lowering properties than other beta-blockers available for intravenous use in Germany. The present analysis aimed to determine whether perioperative treatment with landiolol in cardiac surgical patients is cost-effective under the conditions of the German Diagnosis-Related Groups health cost reimbursement system. On the basis of clinical outcome data from a meta-analysis that included 622 patients from 7 randomized controlled trials, a decision-model was developed to determine the cost-effectiveness of landiolol versus standard-of-care (SoC). Hospital setting. Hospital patients undergoing a representative mix of cardiac surgical procedures (MIX-CS) and isolated coronary artery bypass grafting (CABG). Landiolol versus SoC in prevention of atrial fibrillation immediately after cardiac surgery. The model benefit was expressed in a reduction of postoperative atrial fibrillation (POAF) episodes and reduced complications. The model calculated total inpatient costs over the hospital length of stay.Costs from published sources were used for the German hospital perspective. SoC was associated with POAF rates of 36.0% to 39.2% and 24.4% to 30.1% in the MIX-CS and CABG populations, respectively.Patients with POAF had a higher morbidity and mortality. Estimated total costs for SoC patients in the MIX-CS and CABG groups were 28.792 € and 25.630 €, respectively. Landiolol reduced the incidence of POAF to 12.6% in the MIX-CS and 12.1% in the CABG groups. This was associated with a cost reduction of 2.209 € and 1.470 €. This analysis suggests that preventing POAF with landiolol is highly cost-effective. Additional studies are needed to assess whether a comparable reduction in POAF and associated cost savings may be achieved using conventional intravenous beta-blockers or amiodarone.

Landiolol in patients with septic shock resident in an intensive care unit (LANDI-SEP): study protocol for a randomized controlled trial

BackgroundIn patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ≥ 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements.MethodsA phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization period of 24–36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80–94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80–94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment.DiscussionDespite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock.Trial registrationEU Clinical Trials Register; EudraCT, 2017-002138-22. Registered on 8 August 2017.

Effect of intravenous esmolol on analgesic requirements in laparoscopic cholecystectomy.

Background and Aims:Perioperative beta blockers are also being advocated for modulation of acute pain and reduction of intraoperative anesthetic requirements. This study evaluated the effect of perioperative use of esmolol, an ultra short acting beta blocker, on anesthesia and modulation of post operative pain in patients of laproscopic cholecystectomy.Material and Methods:Sixty adult ASA I & II grade patients of either sex, scheduled for laparoscopic cholecystectomy under general anesthesia, were enrolled in the study. The patients were randomly allocated to one of the two groups E or C according to computer generated numbers. Group E- Patients who received loading dose of injection esmolol 0.5 mg/kg in 30 ml isotonic saline, before induction of anesthesia, followed by an IV infusion of esmolol 0.05 μg/kg/min till the completion of surgery and Group C- Patients who received 30 ml of isotonic saline as loading dose and continuous infusion of isotonic saline at the same rate as the esmolol group till the completion of surgery.Results:The baseline MAP at 0 minute was almost similar in both the groups. At 8th minute (time of intubation), MAP increased significantly in group C as compared to group E and remained higher than group E till the end of procedure. Intraoperatively, 16.67% of patients in group C showed somatic signs as compared to none in group E. The difference was statistically significant. 73.33% of patients in group C required additional doses of Inj. Fentanyl as compared to 6.67% in group E.Conclusions:We conclude that intravenous esmolol influences the analgesic requirements both intraoperatively as well as postoperatively by modulation of the sympathetic component of the pain i.e. heart rate and blood pressure.

Comparison of the efficacy of dexmedetomidine with that of esmolol in attenuating laryngoscopic and intubation response after rapid sequence induction.

Context:Laryngoscopy and tracheal intubation produce sympathetic overdrive by catecholamine release resulting in hypertension and tachycardia. Various agents are being tried to combat the intubation response over years.Aims:This study is aimed at comparing dexmedetomidine which is a highly selective alpha-2 agonist with an ultra-short acting beta blocker, esmolol to see which among the two is better in attenuating the hemodynamic response to laryngoscopy and tracheal intubation.Settings and Design:This was a prospective randomized double-blind control study.Subjects and Methods:Sixty patients scheduled for general anesthesia were divided into two groups, D and E with 30 patients in each group. Group-D patients received dexmedetomidine 0.5 mcg/kg and Group-E patients received esmolol 0.5 mg/kg as intravenous premedication over 5 min before a rapid sequence induction and tracheal intubation. Systolic, diastolic and mean arterial pressures along with heart rate were measured using invasive arterial line at various time points. The percentage change of hemodynamic parameters at those time points from the baseline was compared between the groups.Statistical Analysis Used:Descriptive and inferential statistical methods were used to analyze the data.Results:The percentage change of all hemodynamic parameters from base line were less in the dexmedetomidine group than in esmolol group at all-time points of measurement. However, a statistically significant difference was observed often at the time points within 1 min after tracheal intubation.Conclusions:Dexmedetomidine is superior to esmolol in attenuating the hemodynamic response to laryngoscopy and tracheal intubation.

Abstract 18612: Intravenous Infusion of Ultrashort-acting Beta-blocker, Landiolol, for Prevention of Immediate Recurrence of Atrial Fibrillation after Catheter Ablation

BACKGROUND: Immediate recurrence of atrial fibrillation (AF) after catheter ablation (CA) troubles with patients. We investigated whether intraveneous infusion of landiolol, an ultrashort-acting beta-blocker, could inhibit immediate AF recurrence after CA by randomized controlled trial. METHOD: atients with drug-resistant AF treated by CA were assigned to receive either landiolol or placebo after the procedure. In the landiolol group, landiolol was infused ntraveneously at speed of 1 μg/kg/min and continued for 3 days after the CA. The primary end point was occurrence/non-occurrence of AF, defined as supra-ventricular arrhythmia more than 5 min, up to 3-day after CA. Logistic regression analysis was performed to investigate risk factor. RESULT: 31 and 24 patients were assigned to landiolol group and placebo group, respectively. There were no significant difference between both groups in systolic blood pressure (SBP) before CA, diastolic blood pressure (DBP) before CA and changes from pre-CA to post-CA of SBP and DBP. AF recurrence occurred in 5 patients (10%) in landiolol group versus 11 patients (45%) in the placebo group (P=0.016, Figure). Multivariable analysis revealed that landiolol infusion significantly reduced the risk of transient AF recurrence after procedure (Hazard ratio: 0.208, 95% confidence interval of hazard ratio: 0.048-0.897, P=0.035). CONCLUSIONS: Short-term landiolol infusion successfully decreased immediate AF recurrence after CA without changing SBP and DBP. Administration of landiolol may become a new strategy to facilitate management after CA.

Landiolol hydrochloride for prevention of atrial fibrillation after coronary artery bypass grafting: New evidence from the PASCAL trial

Atrial fibrillation occurs frequently after cardiac surgery and not only prolongs hospitalization but also influences the prognosis. We investigated whether landiolol hydrochloride, an ultrashort-acting beta-blocker, could reduce postoperative atrial fibrillation in a randomized controlled trial. The subjects were 140 patients undergoing coronary artery bypass grafting at the Nihon University School of Medicine. The primary end point was occurrence/non-occurrence of atrial fibrillation up to 1 week postoperatively. Logistic regression analysis was performed to investigate risk factors for atrial fibrillation among preoperative, perioperative, and postoperative variables. Atrial fibrillation occurred in 7 patients (10%) in the landiolol group versus 24 patients (34.3%) in the placebo group; the landiolol group had a significantly lower incidence (P=.0006). Postoperative heart rate was significantly lower in the landiolol group than in the placebo group. On returning to the intensive care unit, the landiolol group had significantly lower inflammatory and ischemic parameters. Medical costs were also significantly lower in the landiolol group. Multivariate analysis revealed that significant risk factors for atrial fibrillation were a European System for Cardiac Operative Risk Evaluation of 10 or more, preoperative non-use of angiotensin receptor blockers, and non-use of landiolol. Postoperative atrial fibrillation was reduced by treatment with landiolol hydrochloride. Amelioration of ischemia, an anti-inflammatory effect, and inhibition of sympathetic hypertonia by landiolol presumably reduced the occurrence of atrial fibrillation. Hypotension or bradycardia did not develop in any of the patients, indicating the safety of this beta-blocker. These findings suggest that landiolol hydrochloride could be useful in the perioperative management of patients undergoing cardiac surgery.

Effect of Esmolol, an Ultra-short Acting Beta Blocker on Oxidant Status and Antioxidant Activity in Acute Myocardial Infarction: Results of a Randomized Double-blind, Controlled, Prospective Clinical Study

Effect of Esmolol, an Ultra-short Acting Beta Blocker on Oxidant Status and Antioxidant Activity in Acute Myocardial Infarction: Results of a Randomized Double-blind, Controlled, Prospective Clinical Study

Application of ultra short acting beta blockade (esmolol) in pediatric open heart surgery: a trial in total anomalous pulmonary venous return.

In the repair of total anomalous pulmonary venous return (TAPVR) under cardiopulmonary bypass, esmolol, ultra short acting beta blocker, was applied to obtain low heart rate and weak ventricular contraction under mild hypothermic cardiopulmonary bypass. Five infants aged from 14 to 158 days with an average of 70 days, underwent a primary or palliative repair of TAPVR. The type of anomalous return was supracardiac type (2), infracardiac (2), and intracardiac (1). A primary repair was done in three for isolated TAPVR with bypass time of 65 to 76 minutes, and a palliative repair for two with complex anomalies with bypass time of 64 and 87 minutes. There was one operative death from cerebral bleeding in an infant with complex TAPVR who underwent simultaneous pulmonary banding. This strategy seems to be applicable in pediatric cardiac surgery when aortic cross-clamping is better to be avoided and the surgery is mainly limited to the atrial level.

Esmolol tilt testing with esmolol withdrawal for the evaluation of syncope in the young.

Head-upright tilt (HUT) testing is valuable in evaluating syncope. Isoproterenol is used to increase sensitivity. However, isoproterenol is contraindicated or dangerous in undiagnosed heart disease and produces false-positives. We introduced esmolol withdrawal during esmolol HUT, hypothesizing that (1) acute withdrawal of the ultrashort-acting beta-blocker induces beta-adrenergic effects by unmasking endogenous catecholamines and may provoke syncope with fewer risks, and (2) response to esmolol/esmolol withdrawal may predict effective therapy. Thirty-six patients with unexplained recurrent syncope/presyncope (7 to 35 years old, known heart disease or arrhythmia in 14) underwent 2 to 4 HUT tests (60 degrees, 49 minutes): (1) baseline, (2) esmolol (500 micrograms/kg plus 50 micrograms.kg-1.min-1), (3) esmolol withdrawal (HUT continued after esmolol stopped), and (4) isoproterenol if tests 1 through 3 were negative and isoproterenol was not contraindicated. A positive test reproduced symptoms with hypotension or bradycardia, requiring recumbency for recovery. Twenty-five had positive tests, and 11 had negative tests. In 5, only the baseline test was positive; in 15, esmolol/esmolol withdrawal tests were also positive, with 3 in whom esmolol withdrawal was positive although negative at baseline. Two isoproterenol tilts were positive. Esmolol withdrawal and isoproterenol tilts had the highest initial heart rate and similar maximal heart rate increment. Only isoproterenol caused hypertension. One isoproterenol test was false-positive, with hypertension-induced arterial baroreflex. Treatment was beta-blockers (8), Na/fludrocortisone (9), both (6), and DDD pacemakers (2). Esmolol/esmolol withdrawal accurately predicted therapeutic response in 15; isoproterenol predicted therapeutic response in none. Esmolol withdrawal tilt testing is preferable to isoproterenol for provocative testing of syncope in the young, and it appears to be safer. Esmolol withdrawal testing has clinical utility before invasive testing as a first-line investigation for syncope in patients with or without heart disease.

Development of a highly cardioselective ultra short-acting beta-blocker, ONO-1101.

A novel, highly cardioselective ultra short-acting beta-blocker, ONO-1101, has been developed for application in the emergency treatment of tachycardia and better control of heart rate in surgery. This agent is approximately nine times more potent in beta-blocking activity in vivo and eight times more cardioselective in vitro than esmolol. This beta-blocking drug has a short duration of activity, enabling rapid recovery after cessation of administration if side effects occur. It can be used safely in patients suffering from acute heart disease and represents a major therapeutic advance in the treatment of heart disease.

Effect of the ultrashort-acting β-blocker Brevibloc on free-radical-mediated injuries during the early reperfusion state

The left descending coronary artery (LAD) was ligated for 45 min or 90 min followed by 1-h reperfusion. During experiments the animals in Group I (15 dogs) received saline infusion, in Group II (20 dogs) they received the ultrashort-acting beta-blocker Brevibloc (esmolol HCl). The marker of lipid peroxidation the malondialdehyde (MDH) as well as endogen scavengers, the glutathione (GSH), and superoxide dismutase (SOD) were measured in the heart tissue homogenates. In blood and heart tissue samples the 6-keto-prostaglandin F1 alpha (PGF1 alpha) and thromboxane B2 (TXB2) were determined. Biochemical measurements revealed that esmolol HCl has beneficial effect on the free-radical-meduated-damage reducing the MDA content in the ischemic area. In Group I the value of MDA after 90 min of LAD ligature was 138 +/- 5.6%, in Group II the elevation was only 107.4 +/- 3.2%. After treatment with Brevibloc the GSH content of ischemic-reperfused areas decreased slightly (81.75 +/- 3.5% of the normal value), moreover, in Group I the depletion of GSH was considerable (64.5 +/- 4.2%). Coronary reperfusion caused the release of eicosanoids in both groups, mainly in the first 10 min. The highest value of thromboxane in blood samples could be measured in Group I after 90 min of LAD ligature (24.8 +/- 3.6 pmol/ml; the normal value 8-12 pmol/ml). In Group II during the same period of experiments the TXB2 in the blood was 14 +/- 3.7 pmol/ml. In heart tissue samples the amount of endoperoxides increased in ischemic and non-ischemic areas of Group I and II. Nevertheless, the calculated ratio of PGF1 alpha and TXB2 was near to the normal after Brevibloc treatment (0.85-0.9; the normal values were 1-1.2). These results indicate that esmolol HCl can modulate both the free-radical-mediated reaction and arachidonic acid metabolism.

Intravenous Esmolol in Acute Aortic Dissection

Acute aortic dissection is a devastating condition requiring prompt intensive pharmacologic management geared toward control of blood pressure and reduction in myocardial contractility (change in velocity/change in time). The treatment of choice currently is sodium nitroprusside and intravenous propranolol hydrochloride. During acute aortic dissection, hemorrhage may spread into the interatrial septum, extending to the atrioventricular junctional tissues, thus causing conduction abnormalities. Adverse effects of long-acting beta-blockers, including bradycardia, heart failure, and bronchospasm, may limit their usefulness because these effects persist for a long time after discontinuation. This may be detrimental, especially in patients with compromised cardiac function, bronchospastic disease, or both. We report a case of a 64-year-old woman with compromised cardiac function and aortic dissection who was successfully treated with esmolol hydrochloride (an ultrashort-acting beta-blocker) and sodium nitroprusside.

Attenuation of myocardial ischemia during coronary occlusion by ultrashort-acting beta adrenergic blockade

To assess the effect of the ultrashort-acting beta blocker esmolol on ischemia induced by acute coronary occlusion, we studied 16 patients undergoing coronary angioplasty. Doppler echocardiography and ECG monitoring were performed continuously before, during, and after balloon occlusion in the drug-free state and during esmolol infusion. Fourteen of the 16 patients had ST segment elevation during balloon inflation. However, maximal ST segment elevation (2.1 ± 1.5 mm vs 1.7 ± 1.3 mm, p < 0.001) and duration of ST segment elevation (68 ± 20 seconds vs 54 ± 19 seconds, p < 0.05) were both significantly reduced during esmolol infusion. Furthermore, the decrease in ejection fraction seen during drug-free balloon occlusions was significantly blunted during esmolol infusion. In the baseline state ejection fraction decreased from 55% to 38% ( p < 0.05) during coronary occlusion compared with a decrease from 52% to 49% ( p = NS) during esmolol infusion. In addition, esmolol appeared to delay the onset of segmental wall motion abnormalities after coronary occlusion, occurring at a mean of 40 seconds after balloon inflation versus a mean of 31 seconds in the absence of beta blockade ( p < 0.05). Thus the use of ultrashort-acting beta blockade appears to diminish the extent and delay the onset of myocardial ischemia during acute coronary occlusion.

Generalized Convulsions in a Patient Receiving Ultrashort-Acting Beta-Blocker Infusion

Beta-receptor blocking agents are commonly used to treat patients with heart disease, and generalized seizures due to therapy with these agents are rare. All reported cases of seizures due to beta blocking agents have occurred only in those subjects who ingested large doses of the drugs. We observed generalized convulsions in a patient who was receiving therapeutic doses of an ultrashort-acting beta-blocking agent (esmolol hydrochloride) intravenously. A literature survey and possible mechanisms by which these agents induce seizures are presented.

Esmolol: Safety and Efficacy in Postoperative Cardiothoracic Patients with Supraventricular Tachyarrhythmias

Esmolol, an intravenous, ultrashort-acting beta-blocker, was studied for its ability to safely control supraventricular arrhythmias up to 24 hours in 15 postoperative cardiothoracic surgery patients with atrial fibrillation or flutter and rapid ventricular response. Esmolol obtained an initial therapeutic response in nine (60 percent) patients. Mean heart rate for the 15 patients was reduced from 139 +/- 12 beats/min before therapy to 106 +/- 21 beats/min during esmolol infusion (p less than 0.01). The mean time to a therapeutic response after initiation of therapy, using a multistep titration regimen (500 micrograms/kg/min loading infusions over one minute, prior to incremental titration steps from 50 to 300 micrograms/kg/min over 4 to 14 minutes), was 22 +/- 9 minutes, and therapy was continued for 17 +/- 9 hours in responders. Esmolol significantly lowered blood pressure in the group studied and resulted in mild supine or orthostatic hypotension in ten (67 percent) patients. Side effects, including hypotension (10/15 patients), gastrointestinal disturbances (2/15), and weakness or somnolence (6/15), were transient and were not associated with serious clinical sequelae. We conclude that esmolol is effective for rate control in a majority of postoperative cardiothoracic surgery patients with atrial fibrillation or flutter. Side effects, although mild, occur relatively frequently, limiting prolonged infusions and warranting close surveillance of patients.

Clinical electrophysiology of flestolol, a potent ultra short-acting beta blocker

We measured the electrophysiologic effects of flestolol, and ultra short-acting beta blocker, in 15 patients at two infusion rates: a 45 μg/kg loading dose followed by a 5 μg/kg/min infusion and a 60 μg/kg loading dose followed by a 10 μg/kg/min infusion. Electrophysiologic measurements were made after 15 minutes at each infusion rate (plasma concentrations 46 ± 11 and 94 ± 23 ng/ml). Flestolol produced dose-dependent effects on the sinus node, the atrioventricular (AV) node, and right ventricular refractoriness, whereas atrial refractoriness and infranodal conduction were unchanged. At the 10 μg/kg/min dose, flestolol prolonged sinus cycle length by a mean of 20% ( p = 0.0001), corrected sinus node recovery time by 42% ( p = 0.02), AH interval by 21% ( p = 0.0001), AV node effective refractory period by 28%, AV node Wenckebach cycle length by 30% (0.0001), and right ventricular effective refractory period by 5% ( p = 0.03). A significant concentration-effect relationship ( p ≤ 0.03) was present for all variables which had significant dose-effect relationships. No patient developed hypotension, bradyarrhythmias, or other toxicity. Sinus cycle length decreased linearly with time in the post infusion period ( r = 0.99); by 30 minutes post infusion, measured electrophysiologic variables had returned to control values and flestolol plasma concentration had decreased to 4 ± 2 ng/ml. Flestolol's electrophysiologic effects are similar to those of other beta blockers. In doses up to 10 μg/kg/min, it is safe in selected patients, has rapid onset and offset of action, and does not cause acute rebound.