PubMed Health⌕ Search

Biomedical subjects

J L Ransom

Publications and source records attributed to J L Ransom.

At least 19 recordsLinked to original sources
PubMed2001

A multicenter evaluation of gentamicin therapy in the neonatal intensive care unit.

STUDY OBJECTIVE: To evaluate traditional nomogram (TN) versus individualized pharmacokinetic gentamicin dosing practices in neonatal intensive care units, focusing on achieving target therapeutic concentrations (peak > 8 microg/ml, trough < 2 microg/ml), number of dosing changes, number of concentrations obtained, and evidence of nephrotoxicity. DESIGN: Retrospective chart review. SETTING: Three neonatal intensive care units. PATIENTS: Three hundred nine infants prescribed gentamicin. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of patients receiving pharmacokinetic dosing had initial peak concentrations of 8 microg/ml or greater compared with 7% of patients receiving TN dosing (p<0.001). Trough concentrations exceeding 2 microg/ml were reported in 23% of patients receiving TN dosing compared with 2% of pharmacokinetic-dosed patients (p<0.001). Forty-two percent and 6%, respectively, required dosage adjustments (p<0.01). The mean number of concentrations obtained per patient was 2.8 and 2.1, respectively (p<0.01). Neither group had evidence of gentamicin-related nephrotoxicity. CONCLUSION: Compared with TN dosing, administering gentamicin loading doses and performing initial pharmacokinetic analysis resulted in rapid attainment of desired concentrations and fewer dosage adjustments, and allowed for a decrease in the number of gentamicin concentrations.

Anti-Bacterial Agents↗
PubMed2000

Use of enoxaparin in a preterm infant.

OBJECTIVE: To describe the use of enoxaparin to treat suspected thrombosis in a preterm neonate. CASE DESCRIPTION: A 29-week-gestation white infant with a family history of protein S deficiency lost color and blood flow to the right hand several hours after removal of the umbilical artery catheter. Although normal color returned to all except the distal first, second, and third fingers after warming, Doppler flow showed a radial artery defect, indicating a lack of blood flow. Enoxaparin 1 mg/kg intravenously every eight hours was then started. Heparin concentrations measured via anti-Xa assay drawn four and eight hours after a dose were 0.78 and 0.39 units/mL, respectively. Pharmacokinetic parameters calculated from these concentrations using a one-compartment model were elimination half-life four hours, volume of distribution 0.13 L/kg, and clearance 0.022 L/kg/h. No adverse effects were noted. Blood flow eventually returned, leaving only the third fingertip chronically injured. DISCUSSION: Differences between the neonatal and adult hemostatic systems contribute to an increased risk of thromboembolic events and an altered sensitivity to heparin anticoagulation in the neonate. Although heparin is currently the anticoagulant of choice, it may produce several adverse effects, such as hemorrhage and thrombocytopenia, which may be avoided by use of low-molecular-weight heparins (LMWHs). However, despite the efficacy and improved safety profile of LMWHs in adults, data regarding their use in children and neonates are scarce. This case demonstrates that enoxaparin can be used safely and effectively in a preterm infant through appropriate monitoring of heparin concentrations to adjust dosages. A larger volume of distribution of enoxaparin was noted in this neonate than in adults. CONCLUSIONS: Enoxaparin 1 mg/kg intravenously every eight hours was used safely in this preterm infant with suspected thrombosis, suggesting that more than one dosing regimen may be appropriate in this population.

Anticoagulants↗
PubMed1999

Comparing the delivery of albuterol metered-dose inhaler via an adapter and spacer device in an in vitro infant ventilator lung model.

OBJECTIVE: To compare the delivery of an albuterol metered-dose inhaler (MDI) (Ventolin) via an Aerochamber (Monaghan) with an inline adapter (Medicomp Straight Swivel) in an in vitro infant lung model. METHODS: An in vitro infant lung model was modified to compare the delivery of albuterol MDI 10 inhalations via an Aerochamber with an inline adapter. The adapter and Aerochamber were placed at the endotracheal tube. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm endotracheal tube (10 cm length). An Infant Bear Cub ventilator was used at the following settings: positive inspiratory pressure 20 cm H2O, intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, and inspiratory time 0.5 second. Each device was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data. RESULTS: There was significantly greater delivery of albuterol with the Aerochamber (19.49 +/- 7.23 microg; 2.17% +/- 0.8%) as compared with an inline adapter (1.0625 +/- 1.36 microg; 0.12% +/- 0.15%) (p = 0.001). CONCLUSIONS: The Aerochamber provides a greater delivery of albuterol metered-dose inhalations to the lung than the inline adapter in an in vitro infant lung model.

Albuterol↗
PubMed1999

Evaluating the delivery of nebulized and metered-dose inhalers in an in vitro infant ventilator lung model.

OBJECTIVE: To evaluate drug delivery to the lungs of nebulized and metered-dose inhalers (MDIs) in an in vitro infant lung model. METHODS: An in vitro lung model was modified to study drug delivery. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm (12 cm length) endotracheal tube. An inline Marquest Whisper Jet infant circuit nebulizer system delivered 2.5 mg/3 mL albuterol sulfate inhalation solution (Ventolin nebules) at a flow rate of 5 L/min. An Aerochamber (Monaghan) was placed at the endotracheal tube for the delivery of the MDIs. Albuterol MDI (Ventolin) 10 inhalations and beclomethasone MDI (Beclovent) 20 inhalations were delivered. A Servo 900C (Siemens-Elma) was used at the following ventilator settings: positive inspiratory pressure 30 cm H2O), intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, inspiratory time 0.4 sec. Each formulation was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data. RESULTS: There was a significantly greater percentage of drug delivery with MDI albuterol (1.96 +/- 0.50) as compared with nebulized albuterol (1.26 +/- 0.37) (p = 0.002) or beclomethasone diproprionate (0.51 +/- 0.24) (p = 0.001). CONCLUSIONS: Albuterol MDI provides a more efficient delivery of drug to the lung as compared with nebulized albuterol and MDI beclomethasone diproprionate.

Albuterol↗
PubMed1997

Gentamicin pharmacokinetics in neonates with patent ductus arteriosus.

OBJECTIVES: To determine the effect of patent ductus arteriosus on the pharmacokinetics of gentamicin in neonates and to examine whether any particular pharmacokinetic parameter is of value as a marker of patent ductus arteriosus. DESIGN: Cohort study of neonates treated with gentamicin, according to a standard dosing protocol. SETTING: A 24-bed, Level III, neonatal intensive care unit. PATIENTS: Neonates treated with gentamicin at the time of admission to the neonatal intensive care unit, using a standard protocol, and who were < 36 wks of gestational age. INTERVENTIONS: All patients received a gentamicin loading dose, and had gentamicin concentrations measured at 2 and 12 hrs after this dose, in order to determine pharmacokinetic parameters and calculate the optimum maintenance dose. Those neonates subsequently diagnosed to have patent ductus arteriosus, based on clinical suspicion and echocardiographic confirmation, were compared with those neonates without clinically suspected patent ductus arteriosus. Gentamicin pharmacokinetic parameters were calculated using a one-compartment model. MEASUREMENTS AND MAIN RESULTS: A total of 322 courses of gentamicin were administered (patent ductus arteriosus, n = 106; control, n = 216). Gentamicin clearance was decreased in the patent ductus arteriosus group vs. the control group (40.02 vs. 44.73 mL/kg/hr; p < .0108). Volume of distribution was greater for patent ductus arteriosus patients (0.61 L/kg) than for controls (0.54 L/kg) (p < .0002). Also, volume of distribution was a useful marker for presence of patent ductus arteriosus, with a 92% specificity for patent ductus arteriosus. CONCLUSIONS: Gentamicin dosing should be altered in neonates with patent ductus arteriosus to reflect the impact of higher volume of distribution and lower clearance. When the gentamicin volume of distribution exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus arteriosus.

Anti-Bacterial Agents↗
PubMed1994

Ticarcillin-clavulanic acid pharmacokinetics in preterm neonates with presumed sepsis.

The objective of the reported study was to characterize the pharmacokinetics of ticarcillin and clavulanic acid in premature low-birth-weight (less than 2,200 g) neonates with presumed sepsis. Eleven infants received 12 courses of ticarcillin-clavulanic acid at 75 mg/kg of body weight intravenously every 12 h. Blood samples were collected at 0.5, 1.5, 4, and 8 h following the infusion of the initial dose. The concentrations of ticarcillin and clavulanic acid were determined by a microbiologic assay. Median (interpatient coefficients of variation) values for the volume of the central compartment, total steady-state volume, distributional clearance, total clearance, and terminal elimination half-life for ticarcillin were 0.030 liter/kg (21%), 0.26 liter/kg (48%), 0.41 liter/h/kg (47%), 0.047 liter/h/kg (47%), and 4.2 h (45%), respectively. For clavulanic acid the parameters were 0.28 liter/kg (32%), 0.36 liter/kg (34%), 11 liters/h/kg (36%), 0.12 liters/h/kg (72%), and 1.95 h (40%), respectively. Our results suggest that the current dosing recommendations of 75 mg/kg every 12 h risk subtherapeutic clavulanic acid concentrations and that 50 mg/kg every 6 h is a more rational dosing strategy.

Anti-Bacterial Agents↗
PubMed1994

The role of inhaled steroids in the treatment of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia has been well described in premature infants requiring mechanical ventilation. Systemic steroids are one of many treatment modalities used in the management of these infants, but these agents have been associated with a number of adverse effects. Aerosolized therapy has been proposed as an alternative in order to minimize the systemic complications that occur with the parenteral route. The initial reports of inhaled steroids, although limited, have shown promising results with minimal side effects. This article addresses the mechanism of action, the role in therapy, and potential complications associated with the use of inhaled steroids in the treatment of bronchopulmonary dysplasia.

Administration, Inhalation↗
PubMed1991

Population pharmacokinetics of intravenous indomethacin in neonates with symptomatic patent ductus arteriosus.

The population pharmacokinetics of intravenous indomethacin were investigated with 665 indomethacin serum concentrations from 83 neonates (mean +/- SD: gestational age, 28.8 +/- 2.5 weeks; postnatal age, 5.7 +/- 4.7 days; birth weight, 1.13 +/- 0.40 kg) receiving indomethacin for symptomatic patent ductus arteriosus. A one-compartment open model was used for pharmacokinetic analysis. Hypotheses were tested to determine which developmental and demographic data influenced clearance (CL) and volume of distribution (V(area)). In the final regression equation CL and V(area) were modeled as a function of body weight and postnatal age (PNA) from 0 to 20 days. Final estimates were as follows: CL (ml/hr) = 2.63.weight (kg) + 0.244.PNA (days) and V(area) (L) = 0.28.weight (kg) + 0.0041.PNA (days). The coefficients of variation for interindividual variability in CL and V(area) were 77% and 28%, respectively. Intraindividual variability was 19%. These mean population parameter estimates should prove useful in designing dosage regimens to achieve desired indomethacin concentrations for neonates from 0 to 20 days of age with symptomatic patent ductus arteriosus.

Birth Weight↗
PubMed1991

Indomethacin pharmacokinetics in neonates: the value of volume of distribution as a marker of permanent patent ductus arteriosus closure.

Indomethacin (INDO) pharmacokinetics were examined in 18 neonates on 19 occasions, before and after patent ductus arteriosus (PDA) closure. Patients received INDO as an initial dose of 0.25 mg/kg intravenously, and INDO serum concentrations were measured 2 and 8 h after the dose. Subsequent doses were individualized based on clinical response, toxicity, and INDO pharmacokinetics. PDA status was confirmed echocardiographically at the start and end of therapy. INDO pharmacokinetic parameters varied from dose-to-dose within the same patient, and wide interpatient variability was also observed. Pre- and post-PDA closure, only INDO volume of distribution differed significantly (p less than 0.001) with mean values of 0.36 (+/- 0.06) L/kg and 0.26 (+/- 0.08) L/kg. The reason for this occurrence remains unclear. However, a new application for pharmacokinetics as a probe of physiology is demonstrated.

Biomarkers↗
PubMed1990

Gentamicin in neonates: the need for loading doses.

One hundred eighty-four neonates had gentamicin serum concentrations measured twice after an initial loading dose of 5 mg/kg infused over 1 hour. Gentamicin concentrations immediately postinfusion were calculated using a one-compartment pharmacokinetic model. The extrapolated peak gentamicin concentrations achieved with the 5 mg/kg loading dose was optimal (between 5 and 12 micrograms/ml) in 94% of cases. Had an initial dose of 2.5 mg/kg been given as suggested in most references, peak concentrations 5 mg/kg or higher would only have been achieved in 5% of neonates less than 28 weeks' gestation, 10% of neonates 28 to 30 weeks' gestation, 11% of neonates 31 to 34 weeks' gestation, and 36% of neonates more than 34 weeks' gestation. Our data support the need for greater loading doses of gentamicin in newborns. Our recommendation of 5 mg/kg achieves gentamicin concentrations known to be safe and effective.

Dose-Response Relationship, Drug↗
PubMed1990

Effect of phenobarbital administration on theophylline clearance in premature neonates.

The effect of phenobarbital administration on theophylline clearance was studied in 24 premature neonates. Aminophylline was administered according to a standard protocol of 6 mg/kg loading dose followed by a maintenance dose of 2.5-5 mg/kg/12 h. Of the 24 neonates studied, 12 received a mean phenobarbital dose of 26.34 mg/kg/d (ranging from 2 mg every 24 h to 25 mg every 12 h) and the mean phenobarbital concentration was 56.12 micrograms/ml (range 22-112 micrograms/ml). The remaining 12 patients did not require phenobarbital therapy but did receive aminophylline alone. The two groups were closely matched for gestational age, 5-min Apgar scores, and sex (p greater than 0.2). Steady-state theophylline clearance was determined at least once a week for four or more separate weeks. The study lasted a minimum of 8 wk and if more than one theophylline clearance was determined in any given week, the mean of these clearances was used. Both groups demonstrated an increase in mean theophylline clearance over time (from 15.75 and 16.67 ml/h/kg to 30.33 and 35.42 ml/h/kg for the aminophylline and aminophylline plus phenobarbital groups, respectively). The mean slope, an indicator of the average change in theophylline clearance, was 2.19 for the aminophylline group and 3.27 for the aminophylline plus phenobarbital group (p greater than 0.2), indicating that the theophylline clearance for neonates receiving phenobarbital was not significantly different from that for neonates receiving aminophylline alone. Based on this information, aminophylline does not need to be adjusted solely based on concomitant phenobarbital administration; however, theophylline concentrations should be monitored since theophylline clearance can change rapidly and unpredictably in neonates.

Critical Care↗