Pharmacokinetics of cefoperazone in newborn infants

We studied the disposition of two 100 mg/kg doses of cefoperazone given intravenously 12 hr apart in ten newborn infants. Peak levels were a mean 352 +/- SD 75 and 371 +/- 68 micrograms/ml immediately after the first and second dose, respectively, with corresponding troughs of 60 +/- 10 and 76 +/- 28 mcg/ml 12 hr later. Mean half-life was 6.5 +/- 0.9 hr and decreased with increasing gestational age and birthweight. Steady-state volume of distribution averaged 410 +/- 40 ml/kg and total clearance 0.78 +/- 0.13 ml/min X kg and neither varied with gestational age nor birthweight. No untoward physical or laboratory effects were noted. Additional studies including postnatal age effects on kinetics, efficacy, and cerebrospinal fluid penetrance are necessary prior to widespread use of this potentially valuable antibiotic in newborn infants.     

Pharmacokinetics of dopamine in critically ill newborn infants

Dopamine pharmacokinetics was investigated in 14 critically ill newborn infants ranging from 27 to 43 weeks of gestational age and from 0.9 to greater than 4 kg birth weight. Plasma clearance rate was determined from dopamine levels during controlled infusions under actual clinical conditions. Dopamine was administered in stepwise increasing doses up to 8 micrograms/kg/min. Dopamine concentration and dopamine clearance rate were determined from duplicate samples drawn during each infusion in each patient. Steady-state plasma dopamine concentrations and plasma clearance rates were observed within 20 minutes at each infusion. Plasma dopamine concentration ranged from 0.5 ng/ml before infusion to almost 70 ng/ml at an infusion rate of 4 to 8 micrograms/kg/min. There was a linear correlation between infusion rate and plasma dopamine concentration (r = 0.68, p less than 0.001). Neither plasma dopamine concentration nor infusion rate had a significant effect on clearance rate. These data are consistent with first-order kinetics for administered dopamine in critically ill neonates over the range of concentrations studied.     

The use of in-line intravenous filters in sick newborn infants

AIM: This study assesses the improvement in outcome for newborn infants by decreasing major complications associated with intravenous fluid therapy by using an in-line filter, and evaluates the economical impact this might have in relation to daily changing of i.v. lines. METHODS: In a prospective controlled study, 88 infants were randomly assigned to receive either filtered (except for lipids, blood and blood products) or non-filtered infusions via a central catheter. Main outcome measures such as bacteraemia, phlebitis, extravasation, thrombosis, septicaemia and necrosis were all scored. The costs attributable to patients during a standard 8-day stay were also recorded. RESULTS: Significant reductions were found in major complications such as thrombi and clinical sepsis (control group (21), filter group (8); p < 0.05). Bacterial cultures of the filters showed a contamination rate on the upstream surface of 15/109 filters (14%). The mean costs of disposables were less in the filter group, showing a reduction from 31.17 euros to 23.79 euros. CONCLUSIONS: The use of this in-line filter leads to a significant decrease in major complications and substantial cost savings.     

Pharmacokinetics and dosing of arbekacin in preterm and term newborn infants

BACKGROUND: The objective of the present study was to determine pharmacokinetic variables and to characterize a new initial dosing regimen of arbekacin (ABK) for preterm and term newborn infants. PATIENTS AND METHODS: Subjects were 40 infants treated with ABK in a tertiary care neonatal unit over a period of 18 months. At birth, the infants were 23 5/7-40 0/7 weeks and weighed 530-3428 g. Serum ABK concentration was measured at two points in a course of treatment. Data were analyzed by a one-compartment model to obtain volume of distribution (Vd) and clearance (CL) of ABK. These variables were correlated with the patients' demographic and laboratory data. The new initial dosing regimen was determined based on these data. RESULTS: Sixty pairs of blood samples were taken from the infants. They were divided into three groups: preterm early (PE), gestational age (GA) < 37 weeks and postnatal age (PNA) < 28 days; preterm late (PL), GA < 37 weeks and PNA >or= 28 days; and term (T), GA >or= 37 weeks and PNA < 28 days. The Vd was 0.50 +/- 0.02, 0.48 +/- 0.04, and 0.43 +/- 0.03 L/kg, and CL was 0.59 +/- 0.04, 1.12 +/- 0.10, and 0.78 +/- 0.09 mL/min per kg (mean +/- SEM) in PE, PL, and T, respectively. The new dosing regimen is 5 mg/kg every 48 h, 5 mg/kg every 24 h, and 4 mg/kg every 24 h for PE, PL, and T, respectively. CONCLUSIONS: With the new dosing regimen, more infants achieved serum ABK levels within the optimal range than the conventional one.     

Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575–1450 g; gestational age: 26.8 weeks, range: 22–31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean ± SEM) show that apparent volume of distribution (AVd) was 62.1 ± 3.9 ml/kg, plasma t _1/2 beta was 30.5 ± 4.2 h, elimination rate constant (k_el) was 0.032 ± 0.004 h^-1plasma clearance was 2.06 ± 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 ±11.1 mg/1. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 ± 54.5 mg/1 and 113.6 ± 58.2mg/1, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 ± 0.39%, n = 26) compared to adult plasma protein (mean ± SE = 98.73 ± 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.     

Pharmacokinetics and nephrotoxicity of continuous intravenous infusion of gentamicin in low birth weight infants

We evaluated the pharmacokinetics and renal effects of continuous intravenous infusion of gentamicin compared with multiple-dose therapy given in equivalent daily amounts. Nine infants (mean gestational age 34.7 weeks, mean birth weight 2107 gm) were given intermittent injections of gentamicin and 10 infants (mean gestational age 34.8 weeks, mean birth weight 2078 gm) received gentamicin by continuous infusion. Comparison of gentamicin pharmacokinetic data revealed a larger volume of distribution and AUC, prolonged terminal t1/2, and slower total body clearance of the drug in those infants receiving gentamicin by continuous infusion. During and after therapy the fractional excretion of sodium was significantly increased in the continuous infusion group. After treatment the creatinine clearance and excretion of beta 2-microglobulin were significantly lower in the continuous therapy group. Our results indicate that infants receiving gentamicin by constant infusion are at higher risk of nephrotoxicity. The extent of this nephrotoxic hazard remains to be determined.     

Heparin lock intravenous line. Use in newborn infants. A controlled trial

The heparin lock technique has been available for parenteral access in older children and adults but has not yet been described for use in newborns. We randomized 39 newborns who needed parenteral medication in the intermediate care nursery to receive a heparin lock catheter (17) or an intravenous line kept patent by continuous low infusion rate (22). There were no differences between study groups with regard to birthweight, gestational age, or distribution of diagnoses. Infants in the heparin lock group were enrolled in the study on average 1 day longer than the continuous intravenous group (p less than 0.05). Subcutaneous infiltration occurred twice as frequently with the continuous intravenous line (p = 0.0015), and the life span was significantly less than heparin lock (1.0 +/- 0.5 days versus 2.1 +/- 1.0 days, p = 0.0003). Infants with continuous intravenous lines received approximately 20 ml/kg/day greater quantity of fluid (p less than 0.0001). There was no difference between groups with regard to mean heparin activity level. None of the infants developed hemorrhagic complications, thrombophlebitis, or documented nosocomial infection. Nurses significantly favored heparin locks over continuous intravenous lines for ease of use. The heparin lock technique is a safe and reasonable alternative to a continuous low infusion intravenous line for administering parenteral medications to intermediate care newborns.     

Pharmacokinetics of clindamycin phosphate in the first year of life

The pharmacokinetics of intravenously administered clindamycin phosphate was studied in 40 children less than 1 year of age. Mean peak serum concentrations were 10.92 micrograms/ml in premature infants less than 4 weeks of age, 10.45 micrograms/ml in term infants greater than 4 weeks, and 12.69 micrograms/ml in term infants less than 4 weeks of age. Mean trough concentrations were 5.52, 2.8, and 3.03 micrograms/ml, respectively, in the same groups. Serum half-life was significantly longer (8.68 vs 3.60 hours) in premature compared with term infants less than 4 weeks of age. Both premature and term infants less than 4 weeks had significantly decreased clearance when compared with infants greater than 4 weeks (0.294 and 0.678, respectively, vs 1.58 L/hr). Clearance was significantly greater (1.919 vs 0.310 L/hr) and serum half-life less (1.75 vs 7.57 hours) in infants with body weight greater than 3.5 kg. On the basis of these data it is recommended that in infants greater than 4 weeks or greater than 3.5 kg, intravenous clindamycin dosage be 20 mg/kg/day in four divided doses. In premature neonates less than 4 weeks, the dose should be reduced to 15 mg/kg/day in three divided doses. Term infants greater than 1 week of age may also receive 20 mg/kg/day in four doses.     

Treatment of 2 newborn infants with autoimmune thrombocytopenia by high-dose intravenous gamma globulins

We report 2 cases of neonatal auto-immune thrombocytopenia treated with high-dose intravenous gamma-globulins. Efficacy of treatment was immediate, inducing an increase in platelet levels which was transitory during the first 2 weeks but stabilized in the third week. Tolerance was excellent. Injections of 400 mg/kg/day repeated for 4 to 5 days should be preferred to a single dose of 1 to 2 g/kg.     

Renal control of sodium and fluid balance in newborn infants during intravenous maintenance therapy.

Changes in accumulated fluid and sodium balance during intravenous maintenance fluid therapy has been studied in 38 newborn infants with different clinical disorders and gestational ages 28-42 weeks. The results from the infants born before 36 weeks of gestation (preterm) have been compared with the result from infants born after 36 weeks. Three different saline infusions 10, 20 and 40 mEq Na1/2/1000 ml 5.5% glucose have been given. The infusion rate has in preterm neonates been 3.3 ml/kg and hour and in the more full-term neonates been 3.6 ml/kg and hour. The study lasted for 5-8 hours. Urine was collected by spontaneous voidings in plastic bags. The balances were calculated as the difference between the amount given intravenously, and the amount excreted in the urine. In the more full-term neonates Na1/2 balance became increasingly negative with the 10 mEq solution, just balanced with the 20 mEq solution and increasingly positive with the 40 mEq solution. A different response was found in the preterm neonates. The natriuresis was higher and the sodium balances were increasingly negative with both the 10 and 20 mEq solutions. With the 40 mEq solution the negative balance tended to level off. The fluid balances were fairly well maintained in all infants regardless of the sodium concentration in the infusate.     

Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition in 88 newborn infants.

Ampicillin and gentamicin were dissolved once a day in an L-amino acid solution especially prepared for parenteral nutrition of newborn infants and infused continuously to 88 infants in whom septicaemia was suspected or had been proved. The mean dosages were 162 and 5.3 mg/kg per 24 hours respectively, and the 95% limits for the serum concentrations were 11-133 and 1.3-7.4 micrograms/ml. The treatment results were at least as good as with intermittent intramuscular or intravenous administration. This new mode of giving antibiotics is less painful to the babies and easier for the nurses.     

Triploidy in newborn infants

Human triploidy, a common condition occurring in about 1 to 2% of all clinically recognizable pregnancies, is a rare finding in live-born children. Not more than 44 live-born triploid infants have been reported in the available literature. Triploid infants surviving for more than a few days have been suspected to be hidden mosaicisms and mostly have turned out to be diploid-triploid mosaics. We observed two live-born female infants with a complete triploidy and describe the typical clinical picture.     

新生儿嗜酸性粒细胞增多

目的　探讨新生儿嗜酸性粒细胞增多的原因 ,评价新生儿嗜酸性粒细胞增多的临床特征。方法　对 2 4例新生儿嗜酸性粒细胞增多患儿 ,监测血嗜酸性粒细胞计数 ,检测Ig系列 ,详细记录患儿入院后情况及患儿家属情况 ,并对所有患儿进行随访。结果　在同期住院的 10 5 2例新生儿中 ,2 4例 (2 .3% )患儿存在嗜酸性粒细胞增多。嗜酸性粒细胞轻度增高占 2 9.2 % ,中度增高 5 4 .2 % ,重度增高 16 .7%。嗜酸性粒细胞增多的时间为入院后 0～ 2 0d不等 ,其中 2 5 .0 %患儿入院当时即发现有嗜酸性粒细胞增多 ,2 9.2 %患儿为入院后 1d发现有嗜酸性粒细胞增多 ,2例化脓性脑膜炎患儿在恢复期出现嗜酸性粒细胞增多。在Ig系列中 ,IgA增高 6例 (2 5 .0 % ) ,IgE增高 2例 (8.3% )。嗜酸性粒细胞增多患儿的恢复时间为 2～ 2 1d。患儿出院后 ,对所有患儿进行随访 ,其中 3例(12 .5 % )患儿有湿疹存在。截止至随访日期 ,尚未发现有过敏及哮喘发作。结论　嗜酸性粒细胞增多在新生儿期并不少见 ,常见的原因与新生儿感染有关。