digoxin and Infant--Premature--Diseases

To review the literature on the physiologic changes created by neonatal patent ductus arteriosus (PDA) and the potential impact on drug disposition in these infants.. An Index Medicus and bibliographic search of the English-language literature pertaining to neonatal PDA and drug usage in newborns.. PDA in premature infants is associated with a variety of physiologic changes that could alter drug disposition. Perfusion of drug-elimination organs (i.e., liver and kidney) may be diminished, resulting in decreased drug elimination. Further, the general fluid overload state associated with PDA may result in larger volumes of distribution (Vd), and dilutional effects for many drugs. Drug absorption, Vd, tissue penetration, and clearance may be affected by the physiologic changes incurred by a PDA. Although the pharmacokinetics of several categories of therapeutic agents may be affected by a PDA, disposition changes with the aminoglycosides and indomethacin have been the best documented. The most reliable pharmacokinetic change appears to be related to drug Vd. The interpretation of many of these studies is confounded by a potential drug interaction with the concurrent administration of indomethacin for PDA closure.. Close therapeutic drug monitoring is indicated in newborns with PDAs as abrupt changes in drug disposition can occur with PDA closure. PDA-induced changes in specific pharmacokinetic parameters of agents such as the aminoglycosides, indomethacin, and perhaps vancomycin may prove to be a valuable diagnostic adjunct for the identification of babies with undiagnosed PDA. More research into this pharmacophysiologic aspect of pharmacokinetics is warranted.

Topics: Absorption; Anti-Bacterial Agents; Digoxin; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Pharmacokinetics

Recently there has been a significant reappraisal of the role of PDA in the context of neonatal cardiopulmonary disease. This article reviews surgical intervention, pharmacologic treatment, and assessment of ductal patency in the neonate.

Topics: Alprostadil; Blood Circulation; Clinical Trials as Topic; Digoxin; Ductus Arteriosus; Ductus Arteriosus, Patent; Heart Defects, Congenital; Heart Function Tests; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Ligation; Persistent Fetal Circulation Syndrome; Prostaglandin Antagonists; Random Allocation; Respiratory Distress Syndrome, Newborn

Topics: Aortography; Carbon Dioxide; Digoxin; Diuretics; Ductus Arteriosus, Patent; Echocardiography; Electrocardiography; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Postoperative Complications; Respiration Disorders

Topics: Cardiac Catheterization; Digoxin; Ductus Arteriosus, Patent; Echocardiography; Electrocardiography; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases

Recently there has been a significant reappraisal of the role of PDA in the context of neonatal cardiopulmonary disease. This article reviews surgical intervention, pharmacologic treatment, and assessment of ductal patency in the neonate.

Topics: Alprostadil; Blood Circulation; Clinical Trials as Topic; Digoxin; Ductus Arteriosus; Ductus Arteriosus, Patent; Heart Defects, Congenital; Heart Function Tests; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Ligation; Persistent Fetal Circulation Syndrome; Prostaglandin Antagonists; Random Allocation; Respiratory Distress Syndrome, Newborn

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Digoxin; Female; Follow-Up Studies; Heart Rate; Humans; Hungary; Incidence; Infant, Newborn; Infant, Premature, Diseases; Male; Prognosis; Risk Factors

Through the case report of severe digitalis intoxication in a premature born after 27 weeks of gestation with a birthweight of 800 g, the authors show that anti-digoxin antibodies constitute a very efficacious therapeutic tool which, up to the present, has not been used in prematures.

Topics: Antibodies; Digoxin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Male

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Humans; Immunoglobulin Fab Fragments; Infant, Newborn; Infant, Premature, Diseases; Medication Errors; Sodium-Potassium-Exchanging ATPase

The first use of Fab fragments to treat digoxin toxicity in a premature infant with renal failure, 18 h after the onset of severe arrhythmias, is reported with dramatic results. The development of digoxin toxicity in the context of accepted therapeutic dosing to treat heart failure due to a cerebral arteriovenous malformation is discussed.

Topics: Arrhythmias, Cardiac; Digoxin; Disorders of Sex Development; Humans; Immunoglobulin Fab Fragments; Infant, Newborn; Infant, Premature, Diseases

Topics: Digoxin; Ductus Arteriosus, Patent; Echocardiography; Furosemide; Humans; Infant, Newborn; Infant, Premature, Diseases

Topics: Digoxin; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases

The maturation of the lung is one of the greatest challenges the premature infant must face after birth. Premature infants have been observed to have a higher prevalence of patency of the ductus arterious, presenting the physician with a dilemma and a challenge. This article discusses the clinical and pathophysiologic manifestations and the management of patent ductus arteriosus in the premature infant.

Topics: Blood Transfusion; Cardiac Catheterization; Digoxin; Diuresis; Ductus Arteriosus, Patent; Echocardiography; Heart Murmurs; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases

Left ventricular systolic time intervals were assessed in 16 preterm infants with symptomatic left-to-right ductal shunts, before, during and after digoxin therapy. An intravenous loading dose of digoxin, 20 micrograms/kg, resulted in a serum digoxin concentration of 1.94 +/- 0.44 nmol/l (mean +/- 1 SD) but in no significant change in heart rate or systolic time intervals. Digoxin maintenance, 2.5 micrograms/kg/12 h, led 3-7 days later to serum concentrations of 2.57 +/- 1.06 nmol/l with an associated shortening of left ventricular ejection time (p less than 0.05) which probably reflected a reduced ductal shunt. Digoxin therapy was withdrawn after ductal closure. The terminal serum half-life was 87 +/- 17 h. Decreasing digoxin concentrations were associated with prolongation of left ventricular ejection time (p less than 0.01). Digoxin therapy did not seem to influence left ventricular systolic time intervals while ductal patency persisted. This may be attributed to limitations of the method or the left ventricle already working at its maximum.

Topics: Digoxin; Ductus Arteriosus, Patent; Heart Rate; Humans; Infant, Newborn; Infant, Premature, Diseases; Prospective Studies; Systole

Eighteen infants, each weighing less than 1,500 gm, were treated with low dose digoxin therapy for patent ductus arteriosus and signs of circulatory congestion. Nine of the 18 developed one or more signs of clinical deterioration felt to be related to digoxin therapy: eight infants experienced frequent episodes of bradycardia, six had cardiac arrhythmias, and six experienced feeding difficulties. All signs disappeared when digoxin therapy was discontinued. Digoxin, even in relatively low dosages, can have deleterious complications in seriously ill low-birth-weight infants. Alternatives to digoxin in this patient population should be considered before institution of digoxin therapy.

Topics: Arrhythmias, Cardiac; Bradycardia; Digoxin; Ductus Arteriosus, Patent; Feeding Behavior; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases

A retrospective study is made on the results of the treatment of 38 preterm infants with symptomatic PDA; they represented an incidence of 4% of all the admissions to our Unit from June 1978 to March 1980. 30 of the 38 infants (79%) had PDA associated with RDS. Conservative medical treatment failed in 42% of the patients, requiring the administration of indomethacin for pharmacologic closure of their PDA. The different responses to the drug in each of the established groups are commented, being the group with a birth weight less than 1,500 g who presented the highest percentage of re-openings (62.5%) and of therapeutic failures (50%). An early closure of the PDA can contribute to decrease the morbidity and mortality of these infants, specially those with lower birth weight.

Topics: Digoxin; Ductus Arteriosus, Patent; Female; Furosemide; Humans; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Male; Respiratory Distress Syndrome, Newborn; Retrospective Studies

The pharmacokinetics and pharmacodynamics of digoxin in premature infants was studied. During maintenance therapy, after a total digitalizing dose of 30 microgram/kg, the measured digoxin level was related inversely to body weight at birth and to estimated gestational age. The serum digoxin levels found in the immature and smaller infants were two to three times the values usually reported to be toxic in older children. Based on these findings, a second group of premature infants was digitalized with 20 microgram/kg; in this group, the serum digoxin levels were below the toxic range, irrespective of gestational age or birth weight. The cardiac effects of digoxin, i.e., shortened left ventricular pre-ejection period and ejection time as determined by echocardiography, were similar in the two groups. For both groups, the half-life of digoxin in the serum was twice that reported for term infants and children. Since digitalis effect is obtained with lower dose and serum concentration, we recommend that this dose be used in premature infants.

Topics: Birth Weight; Digoxin; Echocardiography; Gestational Age; Half-Life; Heart Failure; Heart Ventricles; Humans; Infant, Newborn; Infant, Premature, Diseases; Kinetics; Prospective Studies

Topics: Digoxin; Humans; Infant, Newborn; Infant, Premature, Diseases; Jaundice, Neonatal; Kinetics; Respiratory Distress Syndrome, Newborn; Time Factors

Topics: Digoxin; Heart Failure; Humans; Infant, Newborn; Infant, Premature, Diseases

Serum concentrations and half-life times of digoxin were determined in ten mature and nine premature newborns. Median serum digoxin concentration was 2.3 ng/ml (1.2 to 3.5 ng/ml) in mature newborns and 2.4 ng/ml (1.5 to 4.5 ng/ml) in premature newborns. Median serum digoxin half-life was 35 hours (17 to 52 hours) in mature newborns and 57 hours (38 to 88 hours) in premature newborns. The difference in serum digoxin half-life between the two groups is statistically significant. The relatively long serum digoxin half-life in premature newborns is probably due to immature renal function in this group. The data emphasize the need for cautious digoxin administration, especially in premature infants.

Topics: Digoxin; Half-Life; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases

Topics: Acute Disease; Biological Transport, Active; Digoxin; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Magnesium; Male; Phenytoin; Poisoning; Potassium; Respiratory Distress Syndrome, Newborn; Sodium; Vomiting

Topics: Asphyxia Neonatorum; Body Weight; Digoxin; Ductus Arteriosus, Patent; Female; Gestational Age; Heart Failure; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Male; Organomercury Compounds; Respiratory Distress Syndrome, Newborn; Sex Factors

The possibility that cardiac failure may be an important contributory or additive factor has led to the sporadic use of digitalis in the treatment of the respiratory distress syndrome in newborn infants. To assess the value of such medication a double-blind controlled study was conducted on 196 newborn infants, using digoxin and a placebo. As a result of the findings in this study the routine use of digoxin for the prevention of the respiratory distress syndrome is not recommended. The toxic effects of digitalis are outlined.

Topics: Asphyxia Neonatorum; Digoxin; Double-Blind Method; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Placebos; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Toxicology