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Biomedical subjects

A Benatar

Publications and source records attributed to A Benatar.

At least 19 recordsLinked to original sources
PubMed2001

Cisapride plasma levels and corrected QT interval in infants undergoing routine polysomnography.

BACKGROUND: Reported QTc prolongation associated with cardiac arrhythmia in a small number of children undergoing cisapride therapy and lack of pharmacokinetic correlation provided the impetus for this prospective study. The authors evaluated the relation between cisapride plasma concentrations, the electrocardiographic QT interval, and cardiac rhythm in infants undergoing routine 8-hour polysomnography. METHODS: A total of 211 infants were enrolled: 84 (17 born prematurely) undergoing cisapride therapy for at least 4 days for suspected gastroesophageal reflux and 127 controls (10 born prematurely), aged between 1 week and 13.5 months. Infants underwent continuous bipolar limb lead I recording during routine 8-hour polysomnography. QT intervals and heart rate were measured at hourly intervals. The morning after polysomnography, 12-lead electrocardiography was performed (1 hour after cisapride administration). Cisapride plasma concentrations were determined immediately before and 1 to 2 hours after administration. Serum electrolyte concentrations were measured. RESULTS: The administered cisapride dose ranged from 0.35 to 1.55 (mean, 0.81, median 0.79) mg. kg-1. d-1. Cisapride plasma concentrations were significantly higher in infants younger than 3 months of age. Cisapride-treated infants younger than 3 months of age had longer QTc intervals compared with age-matched controls. Heart rate was similar for cisapride-treated and control infants. No arrhythmia or atrioventricular conduction abnormalities were observed. CONCLUSIONS: At comparable doses of cisapride and comparable plasma concentrations, the QTc was significantly higher in infants younger than 3 months of age. This confirms age-dependent cisapride pharmacokinetics in the first 10 to 12 weeks strongly correlated with changes in body weight and may also suggest an altered ability of infants younger than 3 months of age to metabolize cisapride. The clinical significance and risk of the increased QTc interval is unclear. Cisapride should be judiciously prescribed in infants younger than the age of 3 months and electrocardiography should be performed before and during therapy.

Age Factors↗
PubMed2001

The effect of cisapride on the corrected QT interval and QT dispersion in premature infants.

BACKGROUND: Cisapride is used frequently in premature neonates as a gastrointestinal prokinetic drug. Concerns exist, however, about its safety because of its effect on the QT interval. Premature infants could be at higher risk for side effects because of their immaturity. This prospective study investigated the pharmacokinetics of cisapride and its effects on corrected QT interval (QTc) and QT dispersion in premature infants. METHODS: Electrocardiogram examination was performed just before and after 72 hours of treatment with cisapride (0.2 mg/kg per dose, four times daily) in 10 premature infants. Trough and anticipated peak plasma level of cisapride and norcisapride were quantified after 72 hours of treatment. Results were compared with a cohort of 41 term infants aged 0 to 3 months receiving cisapride treatment. RESULTS: The QTc interval increased significantly from 423 ms to 461 ms after 72 hours of treatment (P = 0.0007). No effect was seen on QT dispersion (44.3 ms vs. 45.9 ms). The change in QTc interval was inversely related to postnatal age (R2 = 0.52; P = 0.02), whereas there was no correlation with gestational age or plasma levels of cisapride or norcisapride. Trough and anticipated peak plasma levels of cisapride and norcisapride were significantly higher in the premature infants compared with the term infants aged 0 to 3 months (P < 0.001). CONCLUSIONS: Premature infants less than 1 month of age could be at higher risk for cardiac side effects of cisapride when used in the same dosage as in older infants. The daily dose should be reduced (0.1 mg/kg per dose, maximum four times daily), and the QTc interval should be monitored closely. The benefits and safety of cisapride in premature infants less than 1 month of age should be reconsidered.

Age Factors↗
PubMed2001

Comparison of formulae for heart rate correction of QT interval in exercise ECGs from healthy children.

OBJECTIVE: To investigate the differences in four formulae for heart rate correction of the QT interval in serial ECG recordings in healthy children undergoing a graded exercise test. SUBJECTS: 54 healthy children, median age 9.9 years (range 5.05-14.9 years), subjected to graded physical exercise (on a bicycle ergometer or treadmill) until heart rate reached > 85% of expected maximum for age. DESIGN: ECG was recorded at baseline, at maximum exercise, and at one, two, four, and six minutes after exercise. For each stage, a 12 lead digital ECG was obtained and printed. In each ECG, QT and RR interval were measured (lead II), heart rate was calculated, and QTc values were obtained using the Bazett, Hodges, Fridericia, and Framingham formulae. A paired t test was used for comparison of QTc, QT, and RR interval at rest and peak exercise, and analysis of variance for all parameters for different stages for each formula. RESULTS: From peak exercise to two minutes recovery there was a delay in QT lengthening compared with RR lengthening, accounting for differences observed with the formulae after peak exercise. At peak exercise, the Bazett and Hodges formulae led to prolongation of QTc intervals (p < 0.001), while the Fridericia and Framingham formulae led to shortening of QTc intervals (p < 0.001) until four minutes of recovery. The Bazett QTc shortened significantly at one minute after peak exercise. CONCLUSIONS: The practical meaning of QT interval measurements depends on the correction formula used. In studies investigating repolarisation changes (for example, in the long QT syndromes, congenital heart defects, or in the evaluation of new drugs), the use of an ad hoc selected heart rate correction formula may bias the results in either direction. The Fridericia and Framingham QTc values at one minute recovery from exercise may be useful in the assessment of long QT syndromes.

Adolescent↗
PubMed2001

Efficacy and tolerability of cisapride in children.

As gastro-oesophageal reflux disease (GORD) in infants and children is a motility disorder which differs in pathophysiology and clinical course from GORD in adults, prokinetics should be considered the drug of choice in certain circumstances. Indeed, cisapride may result in improvement of feeding tolerance in premature infants. Cisapride has a better tolerability profile than a 'wait-and-see-if-improvement-comes-spontaneously' policy or the other therapeutic options available. A careful and critical review of published data suggests that cisapride may have a QTc-prolonging effect. However, provided the precautions for cisapride administration are followed, the QTc-prolonging effect remains consistently without clinically relevant adverse effects. Correct dosage and avoidance of concurrent treatment with macrolides and/or azoles are the most relevant tolerability recommendations in children. Although there is a need for a prokinetic with better efficacy, cisapride is currently the prokinetic with the best benefit-to-risk ratio available. Thus, withdrawal of cisapride would result in a significantly increased risk for severe complications in infants and children with GORD or other gastrointestinal motility disorders such as chronic intestinal pseudo-obstruction, gastroparesis and feed intolerance in premature infants.

Child↗
PubMed2000

Effects of cisapride on corrected QT interval, heart rate, and rhythm in infants undergoing polysomnography.

OBJECTIVE: To evaluate the effects of cisapride, a prokinetic gastrointestinal drug, on the electrocardiographic QT interval, heart rate, and rhythm in infants during routine 8-hour polysomnography. Reported electrocardiogram (ECG) and rhythm disturbances in a small number of patients with the use of cisapride provided the impetus for this prospective study. STUDY DESIGN: Two hundred fifty-two infants born at term were enrolled. Of these, 134 were on cisapride therapy for suspected gastroesophageal reflux and 118 were not on cisapride and served as controls. Cisapride-treated and control infants were from the outset divided into 3 age groups; group 1: under 3 months of age; group 2: between 3 and 6 months of age; and group 3: >6 months of age. Continuous ECG bipolar limb lead I recording, saturation monitoring, and electroencephalography were conducted. QT intervals and heart rate were measured at hourly intervals. RESULTS: Cisapride doses were: group 1 mean, 0.80 mg/kg/day (range: 0.38-1.55); group 2 mean, 0.80 mg/kg/day (range: 0. 23-1.38); and group 3 mean, 0.72 mg/kg/day (range: 0.32-1.41). Heart rate was higher in the younger infants, with a gradual decrease with age. No difference in heart rate was detected between the cisapride and control groups. The QTc interval in patients in group 1 was statistically longer than the controls, when applying both Bazett's and Hodges' formulae for QT correction. The other age groups did not differ. No arrhythmia or atrioventricular conduction abnormalities were observed. CONCLUSION: Infants under 3 months of age on cisapride treatment had significantly longer QTc intervals (with Bazett's formula, the 98th percentile was 504 ms in the cisapride group vs 447 ms in controls). The clinical significance and risk of the increased QTc interval in these infants are unclear and need further evaluation and risk stratification. Meanwhile, cisapride should be judiciously prescribed in infants <3 months of age.

Arrhythmias, Cardiac↗
PubMed1999

Left-ventricular inflow obstruction due to a dilated coronary sinus mimicking Cor Triatriatum.

Persistence of the left superior vena cava with drainage to the coronary sinus is a common congenital anomaly. We report an infant with such a malformation associated with marked enlargement of the coronary sinus, which produced partial supramitral obstruction and consequently impairment to the left-ventricular inflow. The patient pre-sented with cardiac failure in infancy and features mimicking cor triatriatum. Surgical relief of the supramitral obstruction resulted in immediate reversal of the pulmonary hypertension, with clinical improvement. This rare entity, only once previously reported, is an unusual cause of pulmonary hypertension in infancy.

Cardiac Catheterization↗
PubMed1999

The role of cisapride in the treatment of pediatric gastroesophageal reflux. The European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND: Cisapride is a gastrointestinal prokinetic agent that is used worldwide in the treatment of gastrointestinal motility-related disorders in premature infants, full-term infants, and children. Efficacy data suggest that it is the most effective commercially available prokinetic drug. METHODS: Because of recent concerns about safety, a critical and in-depth analysis of all reported adverse events was performed and resulted in the conclusions and recommendations that follow. RESULTS: Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisapride is given to pediatric patients who can be considered healthy except for their gastrointestinal motility disorder, and the maximum dose does not exceed 0.8 mg/kg per day in 3 to 4 administrations of 0.2 mg/kg (not exceeding 40 mg/d), no special safety procedures regarding potential cardiac adverse events are recommended. However, if cisapride is prescribed for patients who are known to be or are suspected of being at increased risk for drug-associated increases in QTc interval, certain precautions are advisable. Such patients include those:(1) with a previous history of cardiac dysrhythmias, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or disease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc interval should be used before initiation of therapy and after 3 days of treatment to ascertain whether a cisapride-induced cardiac adverse effect is present. CONCLUSIONS: With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced doses. If higher doses than this are given, the precautions above are advisable. In any patient in whom a prolonged QTc interval is found, the dose of cisapride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and the administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be restarted at half dose with control of the QTc interval. Unfortunately, at present, normal ranges of QTc interval in children are unknown. However, a critical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater than 470 milliseconds as outside it.

Arrhythmias, Cardiac↗
PubMed1998

Tetralogy of Fallot with absent pulmonary valve. A continuing challenge.

Absent pulmonary valve syndrome (APVS); the combination of tetralogy of Fallot (TOF) with agenesis of the pulmonary valve, is a relatively rare cardiac malformation. Despite the anatomic similarity with classic TOF, the pathophysiology is strikingly different. Data on 10 patients (3 male, 7 female) with APVS, treated between January 1978 and December 1995, were retrospectively reviewed. During this period a total of 2920 children underwent correction of a variety of congenital cardiac anomalies, of which 246 patients (8%) had a correction for TOF. Two patients with APVS presented within the first four months of life with severe cardiorespiratory distress and required several operative procedures. The remaining eight patients had only mild to moderate respiratory and/or cardiac symptoms and elective intracardiac repair was performed on those between the ages of 10 months and 9.5 years. Associated cardiac anomalies seen in five patients included aberrant coronary artery, absent or interrupted left pulmonary artery, partial AVSD and aberrant azygos continuation. In those electively corrected, the strategies used were ventriculotomy (7), pulmonary homograft (3) and aneurysmorrhaphy (2). There were two deaths, one in each group of patients, as a result of progressive respiratory insufficiency and cardiac tamponade, respectively. The follow-up of the eight survivors ranged from 2 to 11 years (median 6.75). All have a normal effort tolerance; only one child is on digoxin therapy, and one child continues to suffer bronchospastis episodes. Our experience with infants with this lesion is limited but underlines the different approaches required, depending on the age of presentation.

Child↗
PubMed1998

Successful use of an intraosseous infusion in an 800 grams preterm infant.

An intravascular access line for the administration of life support drugs and volume expanders may be particularly difficult, especially in very small premature babies. We report on the successful use of an intraosseous accessline in an 800 grams preterm infant for the administration of drugs and fluid. The use and technique of an intraosseous access is an important emergency alternative which may be lifesaving, even in very preterm babies, when other methods fail.

Atropine↗
PubMed1995

Mid-term results of the modified Senning operation for cavopulmonary connection with autologous tissue.

UNLABELLED: The aim of this study was to determine the results and mid-term outcome of a modified Senning technique using autologous tissue for total cavopulmonary connection. The study involved 31 children, 8 with tricuspid atresia and 23 with complex congenital heart disease. In this operation, a flap of autologous atrial free wall tissue was used to tunnel inferior vena caval blood to the pulmonary arteries. An additional Damus-Kay-Stansel operation was required in 9 patients with subaortic obstruction. RESULTS: the early mortality rate was 16% (5 out of 31 patients) and there were four late deaths. COMPLICATIONS: Pleural effusions were encountered in 17 patients, of whom 4 had a concomitant pericardial effusion. Diaphragmatic paralysis was diagnosed in five patients, one of whom underwent surgical plication. Median hospital stay was 26 days. The 1- to 5-year actuarial survival was 68.6%. Follow-up ranged from 10 months to 7.1 years, mean 3.2 years. A serious atrial arrhythmia was diagnosed in one patient and another one died, possibly from rhythm disorders. Exercise tolerance and quality of life has improved in all but one of the survivors. Although follow-up is short, we have thus far witnessed a low incidence of hemodynamic and rhythm disturbances with this modification of the cavopulmonary connection.

Actuarial Analysis↗
PubMed1995

Pulmonary hypertension in infants with chronic lung disease: non-invasive evaluation and short term effect of oxygen treatment.

A total of 45 examinations on 30 premature infants with chronic lung disease (CLD) of prematurity were made using Doppler echocardiography. Pulmonary systolic time intervals and tricuspid regurgitant velocity were measured to assess the prevalence of pulmonary hypertension and short term responsiveness of the pulmonary circulation to oxygen. Twelve preterm infants matched for gestational age, served as controls. Tricuspid regurgitation (TR) was detected in 14 of the patients. Eleven of those with TR had pulmonary hypertension, of whom eight responded to oxygen treatment. Of the remaining three patients with 'fixed' pulmonary hypertension, one subsequently died. The detection of TR was the basis of the preferred method for measuring pulmonary artery pressure (Ppa) non-invasively, but the degree of correlation between the Ppa estimated from TR and pulmonary systolic time intervals was high (r = -0.84, p = 0.001). In the absence of TR, systolic time intervals are an effective way to monitor pulmonary artery pressure in infants with CLD. Without these measurements, it would have been impossible to predict which subjects had pulmonary hypertension, and which might respond to oxygen treatment.

Blood Pressure↗
PubMed1993

Continuous negative extrathoracic pressure and cardiac output--a pilot study.

Continuous negative extrathoracic pressure (CNEP) has been recently reintroduced as therapy for respiratory failure. To determine its effects on cardiac output a pilot study was performed in ten patients aged 2 months-3 years (median 4 months). All had chronic respiratory failure (seven with bronchopulmonary dysplasia). Five were breathing spontaneously and five were intubated and undergoing intermittent positive pressure ventilation. Transcutaneous oxygen saturation and PCO2, together with ECG were continuously monitored. Pulmonary artery blood flow velocity was measured non-invasively using pulsed wave Doppler. The 95% confidence intervals for the changes with and without CNEP in spontaneously breathing and ventilated patients showed no statistically significant changes in heart rate, O2 saturation, transcutaneous PCO2 or cardiac output. This study shows that the use of CNEP, administered in a tank respirator, does not lead to large changes in cardiac output.

Blood Flow Velocity↗
PubMed1992

Subclinical cardiomyopathy in Becker muscular dystrophy.

OBJECTIVE: To investigate the prevalence, age distribution, and spectrum of cardiac involvement in a cohort of patients with Becker muscular dystrophy. DESIGN: A prospective non-invasive study with clinical, electrocardiographic, and echocardiographic assessment. PATIENTS: 19 patients (age range 16-41 years) with Becker muscular dystrophy attending the Muscle Clinic at Hammersmith Hospital and 22 healthy controls (age range 22-36 years). RESULTS: 17 patients (89%) were symptom free; two had exertional dyspnoea. Three had a past history of acute pericarditis. The electrocardiogram was abnormal in 14 patients (74%). Intraventricular conduction delay or right bundle branch block was present in eight (42%). Three (16%) had tall R waves (R/S > 1) in lead V1 in the absence of right bundle branch block and eight (42%) had Q waves in the lateral and inferolateral leads. The PQ interval was significantly shorter in patients with Becker muscular dystrophy (p < 0.01). Echocardiography showed left ventricular dilatation in seven patients (37%) and 12 (63%) had subnormal systolic function caused by global hypokinesia (fractional shortening < 27%). Six of these patients were under the age of 22 years. Patients with Becker muscular dystrophy had significant reduction of both fractional shortening and corrected mean velocity of circumferential shortening compared with controls. No correlation was found between fractional shortening and age. The third filling fraction was significantly reduced in patients with Becker muscular dystrophy (p < 0.05), although other indices of diastolic function (isovolumic relaxation time and E/A ratios) were not significantly different. CONCLUSIONS: Though most patients with Becker muscular dystrophy were symptom free, a high percentage had evidence of a subclinical cardiomyopathy. Electrocardiography showed that the inferolateral and posterior segments of the left ventricle tended to be affected and may show evidence for conduction tissue disease. Echocardiography showed that most patients had left ventricular dilation and global hypokinesia. The severity of left ventricular disease was unrelated to age; some younger patients had severe left ventricular dysfunction. All patients with Becker muscular dystrophy should have echocardiographic assessment of left ventricular function.

Adolescent↗