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OBJECTIVES: The objectives of this study were to determine the pharmacokinetics of milrinone lactate in pediatric patients with septic shock and to determine whether a relationship exists between steady-state plasma milrinone concentrations and changes in hemodynamic variables. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled, interventional study. In study phase 1 patients were randomized and underwent loading and infusion with milrinone lactate (50 microg/kg, then 0.5 microg/kg/min), and invasive hemodynamic values were determined. Steady-state was determined by obtaining plasma samples at 30, 15, and 0 minutes before the end of the milrinone infusion. Study phase 2 started when milrinone was discontinued by the patient care team. Steady-state was reaffirmed and plasma samples were obtained at 0.5, 1, 2, 4, 6, and 8 hours after the end of the infusion. RESULTS: The average plasma concentration at steady-state (Css avg) and total body clearance for phase 1 were 81.3+/-38.6 ng/ml (mean +/- SD) and 0.0106+/-0.0053 L/kg/min, respectively (n = 9). All but two patients underwent reloading with milrinone. In phase 2 Css avg and total body clearance were 65.8+/-42.1 ng/ml and 0.0110+/-0.0096 L/kg/min, respectively (n = 11). The average time of infusion was 51+/-21 hours. Eight patients were evaluated for phase 2 elimination. The mean elimination rate constant was 0.0091+/-0.0061 min(-1) (n = 8). The median half-life was 1.47 hours (range, 0.62 to 10.85 hours). All patients had creatinine clearances greater than 61 ml/min/1.73 m2. The volume of distribution at steady-state was 1.47+/-1.03 L/kg. No correlation existed between age and the elimination rate constant or the volume of distribution at steady-state. All patients achieved at least a 20% change in cardiac index and systemic vascular resistance index while maintaining a Css avg of 35 to 160 ng/ml. No adverse effects were noted. All patients achieved primary hemodynamic end points (cardiac index and systemic vascular resistance index) during the milrinone infusion. CONCLUSIONS: Loading doses of 75 microg/kg milrinone lactate and starting infusion rates of 0.75 to 1.0 microg/kg/min for patients with normal renal function should be used; the infusion rate should then be titrated to effect. We recommend that for every increase of 0.25 microg/kg/min, a 25 microg/kg bolus dose be given. Because the median half-life is 1.47 hours, immediate hemodynamic effects may not be seen unless appropriate loading doses and infusion adjustments are made.

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OBJECTIVE: Our purpose was to examine the differences in body composition in infants of women who smoke compared with those of nonsmokers. STUDY DESIGN: Within 24 hours of birth anthropometric measurements and total body electrical conductivity estimates of body composition were obtained on 129 term infants (30 born to women who smoked tobacco during pregnancy and 99 born to women who did not smoke). Anthropometric measurements included weight, skinfolds, circumferences, and crown-heel and extremity lengths. RESULTS: There was a significant decrease in weight in the infants of smokers (3145 +/- 414 gm vs 3354 +/- 525 gm, p = 0.05). There was a decrease in crown-heel length (49.2 +/- 2.0 cm vs 50.1 +/- 2.2 cm, p = 0.03), the length of the lower leg (7.9 +/- 0.6 cm vs 8.4 +/- 0.6 cm, p = 0.0001), upper leg (9.1 +/- 0.7 cm vs 9.9 +/- 0.8 cm, p = 0.0001), and the lower arm (7.2 +/- 0.5 cm vs 7.5 +/- 0.4 cm, p = 0.0001). There were no significant differences in the skinfold and limb circumference measurements. Infants of smokers had significantly decreased fat-free mass as estimated by total body electrical conductivity (2799 +/- 292 gm vs 2965 +/- 359 gm, p = 0.02) but no significant difference in fat mass (343 +/- 164 gm vs 387 +/- 216 gm, p = 0.32). CONCLUSIONS: The decrease in birth weight in infants of women who smoked is primarily due to a decrease in fat-free mass.

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Intravenously administered ribavirin (20 mg/kg per day) was given to a neonate with disseminated adenovirus infection requiring extracorporeal membrane oxygenation and hemofiltration. Plasma concentrations at steady state were 4.81 to 8.47 micrograms/ml, hemofiltration sieving-coefficient was 0.85, and hemofiltration clearance (0.046 L/kg per hour) was similar to the renal clearance reported with normal kidney function. Despite low plasma concentrations, results of viral cultures were negative within 48 hours of initiation of ribavirin therapy, suggesting that plasma concentrations may not adequately predict inhibition of adenovirus replication in vivo.

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OBJECTIVE: To determine the longitudinal relationship between body mass index (BMI) and percent body fat in women before and during pregnancy. METHODS: Twenty-seven healthy, nonobese women were evaluated before conception, in early gestation (12-17 weeks), and in late gestation (33-36 weeks). Height and weight were measured and BMI was calculated. Percent body fat was estimated using hydrodensitometry with correction for residual lung volume. RESULTS: The correlation between BMI and percent body fat before conception was r = 0.693 (P < .005); in early gestation it was r = 0.723 (P < .005) and in late gestation r = 0.633 (P < .005). The mean pregravid BMI was 21.54 and the 95% predictive confidence interval (CI) for percent body fat was 18.2, 26.5%. For the mean BMI of 22.26 in early gestation, the predictive 95% CI for percent body fat was 20.0, 29.0%. In late gestation, the mean BMI was 26.04 with a predictive 95% CI for percent body fat 22.5, 30.8%. CONCLUSION: In nonobese women the correlation between BMI and percent body fat remains significant during pregnancy, although the 95% CI for predicting percent body fat from the mean BMI ranges widely.

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Three children were receiving ticarcillin-clavulanic acid by continuous venovenous hemofiltration (CVVH). Two of them were also receiving concomitant extracorporeal membrane oxygenation (ECMO). We collected ultrafiltrate hourly to determine the clearance of ticarcillin-clavulanic acid by CVVH. Serum concentrations were also determined at the midpoint of each ultrafiltrate collection. All samples were collected over one dosing interval. The volume of distribution of ticarcillin and clavulanic acid was 0.26 +/- 0.01 and 0.69 +/- 0.23 L/kg, respectively. Total body clearance of ticarcillin, determined from the elimination rate constant and volume of distribution, was 0.038 +/- 0.003 L/kg/hour and for clavulanic acid was 0.18 +/- 0.03 L/kg/hour. The sieving coefficients for ticarcillin and clavulanic acid were 0.83 +/- 0.11 and 1.69 +/- 0.19, respectively. We attempted to estimate the clearances by ECMO, but the result was uninterpretable.

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OBJECTIVE: To determine in vitro the compatibility of reconstituted intravenous immunoglobulin (IVIG) (Gammagard, Baxter-Hyland) with five different neonatal and pediatric intravenous solutions in Viaflex polyvinyl chloride bags. DESIGN: In vitro compatibility study. INTERVENTIONS: Samples were taken at time = 0, 10, 30, 60, 90, and 120 minutes and at 4, 8, 12, and 24 hours and assayed for total immunoglobulin G content and antibodies to hepatitis B surface antigen. Type III group B Streptococcus (GBS) and opsonic activity for type III GBS were analyzed at time = 0, 60, and 120 minutes and 12 and 24 hours. All results were compared with those from pure IVIG. RESULTS: Our results demonstrate that mixing IVIG with intravenous solutions commonly used in the care of premature infants (dextrose 5% in water [D5W], D15W, D5W/NaCl 0.225%, and total parenteral nutrition [TPN]) does not significantly alter total immunoglobulin G concentrations or concentration of antibodies to hepatitis B surface antigen or type III GBS. As well, the in vitro functional activity for type III GBS of the IVIG, when mixed with these solutions for up to 24 hours, remained intact. An apparent decrease in bactericidal killing was seen with the IVIG/central TPN mixture. This apparent decrease was found to be an artifact of the high concentration of glucose (20 percent) in the solution. CONCLUSIONS: We propose that Gammagard may be mixed with these solutions through Y-site connections without loss of antibody content or functional activity of the IVIG.

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Antibiotic therapy plays a central role in the medical management of patients with cystic fibrosis. While totally convincing efficacy data are lacking, antibiotics probably have a pronounced beneficial effect on both morbidity and mortality. Much has been learned in the past 20 years about antibiotic use in this population. At the same time, new antimicrobial agents with the potential to treat this condition have become available for use. The pharmacokinetics of a number of antibiotic classes, including beta-lactams, aminoglycosides and quinolones, are altered in this patient population. Increased total body clearance is a common occurrence but is not always changed enough to warrant altered dosages. Nonetheless, in light of altered pharmacokinetics in the cystic fibrosis population, appropriate dosage and monitoring parameters for a number of antibiotics have been determined.

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Continuing education has become increasingly important to the professions, including dietetics. There is some concern, however, that continuing education programs too seldom focus on practice-related problems and do not have a large enough impact on daily practice. A research and development endeavor is in progress to create an alternative approach to continuing education programming. Utilizing a process called the Practice Audit Model, this approach brings practitioners (or their representatives) and educators together to develop continuing education programs that focus on learning needs identified through an empirical assessment of practitioner performance.

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Clinical dietitians in Pennsylvania (N = 185) responded to a survey (based on the practice description developed by the Clinical Dietetics Profession Team of the Continuing Professional Education Development Project) in which they rated time spent on and perceived importance of 11 responsibilities and 120 tasks in their practice. Practitioners spent the most time on responsibilities and tasks that they perceived to be most important. Responsibilities rated high in terms of time spent and importance were nutrition care implementation, nutrition care planning, nutrition assessment, and nutrition care evaluation. Dietitians reported spending a considerable amount of time on activities related to documentation.

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