Beta-blockers In Children Research Articles

Effectiveness of beta-blockers in the treatment of idiopathic premature ventricular contractions in children

Aim. To evaluate the effectiveness of beta-blockers (BB) in the treatment of idiopathic premature ventricular contractions (PVCs) in children.Material and methods. BBs were prescribed to 27 children with idiopathic PVCs. In 3 (11,1%) patients, side effects (hypotension, bronchial obstruction) was revealed at the beginning of therapy. A total of 24 children were included in the further study (15 boys (62,5%), 9 girls (37,5%). The mean age was 8,3±5,4 years. Data from anamnesis, electrocardiography (ECG), 24-hour ECG monitoring, and echocardiography were analyzed.Results. The 24-hour PVC rate was 33,2±17,7 thousand/day or 26,6±13,2%. In 14 (58,3%) children, we recorded paired PVCs, in 3 (12,5%) — multiform, in 10 (41,7%) — runs of non-sustained VT. There were complaints in 7 (29,2%) children. The follow-up period lasted 369,8±119,1 days. Propranolol was received by 17 (70,8%) patients, metoprolol — by 7 (29,2%). The therapy was effective in 11 (45,8%) patients, while ineffective in 13 (54,2%), among which 5 (20,8%) had an increase in the number of PVCs. The effectiveness of BBs was higher in children under the age of 1 year (p=0,043). Propranolol showed greater efficacy than metoprolol (p=0,047). Less efficiency was observed in female patients and those with pathological heart rate turbulence parameters (p=0,04).Conclusion. The effectiveness of BBs in children with idiopathic PVCs is 45,8%, higher in children aged <1 year and declines with age, decreasing in adolescents to 25%. The use of BBs is limited by non-cardiac side effects in 11,1% of children. Propranolol is more effective than metoprolol.

Perioperative control of paroxysmal hypertension using esmolol with alpha-blockade in a child with a germline mutated paraganglioma.

SummaryThe use of antihypertensive medications in patients with pheochromocytomas and paragangliomas (PCC/PG) is usually a challenge. We report a case of familial paraganglioma that was successfully treated by esmolol and other antihypertensive medications without associated perioperative complications. Our patient was an 11-year-old girl who presented with classic symptoms and signs of PCC/PG and a CT scan of the abdomen that showed a right-sided paravertebral mass. Her father was diagnosed with paraganglioma a few years ago. Prazosin had been started but she continued to experience uncontrolled paroxysms of blood pressure (BP). She was known to have asthma; hence, she developed serious bronchospasm with atenolol. She was, therefore, switched to esmolol that successfully controlled her BP in addition to prazosin and intermittent doses of hydralazine prior to laparoscopic surgery with no side effects of medications or postoperative complications. Esmolol could be a good alternative to routinely used beta-blockers in children with PCC/PG with labile hypertension and related symptoms in the pre and intra-operative periods. It is titrable, effective, and can be weaned rapidly helping to avoid postoperative complications. Further larger studies on the use of esmolol in children with PCC/PG are needed to confirm our observation.Learning pointsIn addition to alpha-blockers, esmolol could be a good alternative for routinely used beta-blockers to control paroxysmal hypertension and tachycardia in the pre- and intra-operative periods.Esmolol is titrable and an effective beta-blocker. It can be weaned rapidly helping to avoid postoperative complications in children with PCC/PG.Children with PCC/PG and other comorbidity like asthma may particularly benefit from the use of esmolol due to no or less side effects on airway resistance and the advantage of rapid titration of the medication compared to other beta-blockers.

Beta-blockers for congestive heart failure in children.

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. To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure. 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. Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure. Two review authors independently extracted and assessed data from the included trials. 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. 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.

Beta-blockers for congestive heart failure in children.

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. To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure. 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. Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure. Two review authors independently extracted and assessed data from the included trials. 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. 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.

Beta-Blockers in Children with Congenital Heart Disease Before a Corrective Procedure.

The prevalence of heart failure in patients with congenital heart disease, mainly due to large left to right shunts, is as high as 20%. Heart failure has a high impact on prognosis, growth and neurodevelopment. Prior to surgery or after palliative procedures children need a medical heart failure therapy. The traditional therapy with digoxin, diuretics and ACE-inhibitors is not supported by prospective randomized trials. Propranolol had a significant beneficial effect on the clinical heart failure score, neurohormonal activation, heart rate variability and cardiac remodeling in the prospective randomized trial CHF-Pro-Infant. Beta-blocker dosages depend on heart rate with a target between 100 and 110 bpm in infants and an average dose of 2mg/kg/day after a titration period of 2 to 3 weeks. Within the last 18 years after the first case the author treated only infants with severe heart failure and highly elevated Pro-BNP-levels (8879 pg/ml on average). However we never observed serious side effects due to worsening heart failure, severe bradycardia or pulmonary obstruction. Diuretics are given as low as necessary to prevent the activation of the renin-angiotensin-aldosterone system with its detrimental effect on cardiac remodeling.

Editorial: The Long Way to a Successful Medical Therapy of Heart Failure with Beta-blockers in Children with Heart Disease

Editorial: The Long Way to a Successful Medical Therapy of Heart Failure with Beta-blockers in Children with Heart Disease

Beta-blockers in Children with Duchenne Cardiomyopathy.

Respiratory failure and heart failure are inevitable complications in Duchenne muscular dystrophy (DMD). Respiratory failure and heart failure undergo simultaneously and affect each other. After dissemination of mechanical ventilation, heart failure is the main cause of death in DMD. Regular assessment of cardiopulmonary function, early introduction of cardioprotective therapy and intensive respiratory care are the key issues in medical managements of DMD. In DMD, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) are used as the first line drugs. Beta-blockers (BB) are usually added to ACEI/ARB, when they cannot achieve sufficient effects. Although high dose of BB might be required for functional improvements, even a low dose BB can reduce cardiac events. Recent meta-analyses reported heart rate reduction is more important than BB dose for reducing mortality. Thus heart rate monitoring is essential for titration of BB. Tachycardia under optimal respiratory care can also be an indicator of BB. Although the introduction of BB is relatively safe under gradual dose-escalation from a low dose, hospitalization during uptitration should be considered in advanced cases.

Inpatient Initiation and Target Dosing of ACE Inhibitors and Beta-Blockers in Children with Heart Failure

Introduction: Angiotensin converting-enzyme (ACE) inhibitors and beta-blockers are considered standard pharmacologic therapy in adults and children with congestive heart failure (CHF). Prescribing these medications prior to hospital discharge and subsequent uptitration to target doses improves patient compliance and therapeutic efficacy in adults. To date, performance standards measuring prescriber compliance in utilizing these agents in children with CHF have not been evaluated. Hypothesis: We hypothesized that the rates of inpatient prescribing and subsequent outpatient target dosing of ACE inhibitors, angiotensin receptor blockers (ARB) and beta-blockers in children with CHF were low. Methods: We performed a retrospective analysis of children discharged from our institution with a diagnosis of CHF from 2004e2011. Patients (pts) with acute graft rejection, hypertrophic or restrictive cardiomyopathy and shunt lesions were excluded. CHF had to be attributable to ventricular dysfunction only. Etiologies included dilated cardiomyopathy (n558), acute viral myocarditis (n59) and ischemic cardiomyopathy (n53). Medication dosages, as defined by institutional practice and formulary, were collected to determine target dose at discharge (DC), 90 days and 1 year post-discharge. Target dosages of beta-blockers were: carvedilol 0.8 mg/kg/day or 25e50 mg/day; metoprolol 2 mg/kg/day or 100e200 mg/day. Target dosages of ACE inhibitors were: captopril 2 mg/kg/day or 150 mg/day; enalapril 0.4 mg/kg/day or 10e20 mg/day. Results: The study included 70 pts, with a mean age of 6.4 6 6.3 years. Pts (%) received an ACE inhibitor or ARB at DC (97), 90 days (90) and 1 year (77). Target doses (% of time) were met at DC (46), 90 days (50) and 1 year (39). Pts (%) received a beta-blocker at DC (70), 90 days (76) and 1 year (64). Target doses (% of time) were met at DC (11), 90 days (14) and 1 year (16). At 1 year, 37 pts had been readmitted (23%), transplanted (20%) or died (10%). Six pts (9%) were no longer followed by us. The mean shortening fraction at DC, 90 days, and 1 year was 21, 27 and 34%, respectively. Conclusion: Prescription rates of ACE inhibitors and beta-blockers at hospital discharge are high for children with CHF and comparable to adult practice. However, improvement is needed to ensure these children receive appropriate doses of ACE inhibitors and beta-blockers in follow up.

Medical and surgical management of portal hypertension in children

The treatment of portal hypertension in children has undergone considerable evolution in the past decade. The treatment offered depends on the cause of the hypertension and the underlying health of the liver. The diagnosis of portal hypertension often can be made by the history and physical examination. Upper gastrointestinal bleeding in the presence of splenic enlargement is pathognomonic for portal hypertension. Bleeding and hypersplenism are the principal symptoms. Treatment of bleeding starts with confirming the diagnosis with esophageal and gastric endoscopy. The patient is admitted to an intensive care unit and started on intravenous octreotide. Banding or sclerosis of esophageal varices will result in cessation of the bleeding but not a permanent cure. A careful investigation for the cause of the portal hypertension should be done. This includes imaging studies of intra-abdominal arteries and veins, a liver biopsy, and liver function tests, including coagulation studies. For patients with extrahepatic portal vein thrombosis, early consideration should be given to surgical treatment with a meso-Rex bypass. Patients with liver disease should be treated for the underlying disorder and undergo regular endoscopic monitoring for recurrence of varices. Patients with well-compensated cirrhosis should be considered for selective surgical shunting, and those with advanced disease for liver transplantation. The benefit of long-term beta blockers in children has not been proven by clinical trials.

Beta-adrenergic blockers in the treatment of pediatric heart failure

Beta-adrenergic blocking agents for the treatment of chronic congestive heart failure in adults have gained wide acceptance. Although the exact mechanism of their effect is still not entirely clear, the preponderance of data support the hypothesis that the primary mechanism of action of beta-blocking agents in chronic heart failure is to prevent and reverse adrenergically-mediated intrinsic myocardial dysfunction and remodeling. Large, multicenter trials in adults with chronic congestive heart failure have definitively shown that beta-blockers improve left ventricular ejection fraction, symptoms, and survival when compared to placebo. Although experience with beta-blockers in children is limited, anecdotal evidence suggests that children with chronic congestive heart failure may also benefit from this therapy. Large trials in children are currently in the planning stages in order to attempt to determine the indications, dosages, and optimal use of beta-blockers in children with chronic congestive heart failure.

PSYCHOPHARMACOLOGIC TREATMENT OF PATHOLOGIC AGGRESSION

Several drugs are apparently effective in treating pathologic anger and aggression. Because many of the studies on aggressive populations allowed the use of concomitant medications, it is unclear whether the efficacy of each drug in a particular population is dependent on the presence of other medications, such as antipsychotic agents. Finally, one needs to be circumspect in inferring efficacy of a particular drug in aggressive patients with neuropsychiatric conditions other than the ones in which some efficacy has been established. Lithium appears to be an effective treatment of aggression among nonepileptic prison inmates, mentally retarded and handicapped patients, and among conduct-disordered children with explosive behavior. Certainly, lithium would be the treatment of choice in bipolar patients with excessive irritability and anger outbursts, and it has been shown to be effective in this population. Anticonvulsant medications are the treatment of choice for patients with outbursts of rage and abnormal EEG findings. The efficacy of these drugs in patients without a seizure disorder, however, remains to be established, with the exception perhaps of valproate and carbamazepine. In fact, dyphenylhydantoin did not appear to be effective in treating aggressive behavior in children with temper tantrums and was found to be effective in only a prison population. There is some evidence for the efficacy of carbamazepine and valproate in treating pathologic aggression in patients with dementia, organic brain syndrome, psychosis, and personality disorders. As Yudofsky et al point out in their review of the literature, although traditional antipsychotic drugs have been used widely to treat aggression, there is little evidence for their effectiveness in treating aggression beyond their sedative effect in agitated patients or their antiaggressive effect among patients whose aggression is related to active psychosis. Antipsychotic agents appear to be effective in treating psychotic aggressive patients, conduct-disordered children, and mentally retarded patients, with only modest effects in the management of pathologic aggression in patients with dementia. Furthermore, at least in one study, these drugs were found to be associated with increased aggressiveness in mentally retarded subjects. On the other hand, atypical antipsychotic agents (i.e., clozapine, risperidone, and olanzapine) may be more effective than traditional antipsychotic drugs in aggressive and violent populations, as they have shown efficacy in patients with dementia, brain injury, mental retardation, and personality disorders. Similarly, benzodiazepines can reduce agitation and irritability in elderly and demented populations, but they also can induce behavioral disinhibition. Therefore, one should be careful in using this class of drugs in patients with pathologic aggression. Beta-blockers appear to be effective in many different neuropsychiatric conditions. These drugs seem effective in reducing violent and assaultive behavior in patients with dementia, brain injury, schizophrenia, mental retardation, and organic brain syndrome. As pointed out by Campbell et al in their review of the literature, however, systematic research is lacking, and little is known about the efficacy and safety of beta-blockers in children and adolescents with pathologic aggression. Although widely used in the management of pathologic aggression, the use of this class of drugs has been limited partially by marked hypotension and bradycardia, which are side effects common at the higher doses. The usefulness of the antihypertensive drug clonidine in the treatment of pathologic aggression has not been assessed adequately, and only marginal benefits were observed with this drug in irritable autistic and conduct disorder children. Psychostimulants seem to be effective in reducing aggressiveness in brain-injured patients as well as in violent adolescents with oppositional or conduct disorders, particu

Beta Blockers for Aggression: A Review of the Pediatrie Experience

ABSTRACT beta-Adrenergic blocking agents have been used successfully to treat intractable aggression in adult psychiatric patients. A review of the adult literature and a summary of the pediatrie treatment experience are presented. There are no double-blind placebo-controlled studies in child or adolescent psychiatric patients. Open studies have reported high improvement rates (75-85%), but actual improvement rates may be lower than the generally uncontrolled reports in the literature suggest to date. Future controlled studies should take advantage of statistical methods that allow determination of meaningful changes within subjects in addition to the more typically analyzed changes within groups. Though these medications may be effective as adjunctive treatments in a multidisciplinary approach to aggression, beta blockers cannot at present be considered to be indicated in the treatment of any child or adolescent psychiatric disorder. There is not enough available information to know whether aggression that is associated with any specific psychiatric diagnosis is predictive of response to beta blockers in children or adolescents, and no other predictors of treatment response have been consistently identified. Judging from the experience in adults, treatment duration may be more important than dose level in attaining a therapeutic response with beta blockers. Empirical clinical and research trials of beta blockers for psychiatric symptoms or disorders should probably be run for a minimum of 12 weeks.