Selenium in the full-term and premature newborn infant

The following observations can be made on the basis of findings relating to selenium in serum samples taken from 55 neonates (35 born at term and 20 born pre-term): 1) the blood concentration of selenium in neonates born at term showed no substantial difference to that reported by other authors; moreover, there were no sex or birthweight-dependent variations, and no correlations were found with either the mother's age or the mode of engendering procreation; 2) the blood concentration of selenium in neonates born pre-term was 30% lower than that found in neonates born at term; it was correlated with gestational age and birthweight, but not with sex, mother's age or the mode of engendering procreation. It will be worthwhile continuing these tests in order to identify possible therapeutic uses of selenium in cases of deficiency.     

Morphine pharmacokinetics in premature and mature newborn infants

The pharmacokinetics of a single dose of morphine was investigated in five term infants (gestational age 37–40 weeks) and eight preterm infants (gestational age 25–32 weeks). In the five term infants, median (range) volume of distribution at steady state (Vd_β) was 1758 (634–2700) ml/kg, plasma clearance (Cl) was 4.73 (1–75–6.61) ml/kg/min and terminal half-life (T1/2) was 224 (107–394) min. In the eight preterm infants, Vd_β was 2366 (1662–2876) ml/kg, Cl was 2.82 (1.88–6.60) ml/kg/min and T1/2 was 556 (248–834) min. No correlation was found between clearance and gestational age, but we found a significant negative correlation between T1/2 and gestational age. We conclude that there is considerable variation in the pharmacokinetic properties of morphine in both term and preterm newborn infants. Because of this variation, careful individual assessment of the clinical effect of therapy with morphine in newborn infants should be exercised.     

Nonnutritive sucking during heelstick procedures decreases behavioral distress in the newborn infant

We investigated if nonnutritive sucking (NNS) during heelstick procedures alleviates behavioral distress in neonates. In our NICU, 26 neonates without severe complications (mean Minde score 0.8, range 0-3), undergoing heelstick procedures at least twice a day, in the first 2 weeks of life, were enrolled in the trial (mean gestational age 33.9 weeks, range 26-39 weeks, mean birth weight 1, 988.5 g, range 1,200-4,010 g, mean Apgar score at the first minute 6. 7, range 4-10, at the fifth minute 8.5, range 6-10). Two heelpricks were performed in each neonate with NNS randomly assigned. Behavioral states, transcutaneous oxygen tension (TcPO(2)), heart rate, and respiratory rate were monitored before, during and after the heelstick procedures. Heelstick procedures lasted for a mean of 109 s (range 50-230 s) with NNS, and a mean of 128.8 s (range 20-420 s) without NNS. Compared with baseline, heart rate and behavioral distress increased and respiratory rate decreased during heelstick and after heelstick. Oxygen tension did not change. Nonnutritive sucking had no effect on respiratory rate or transcutaneous oxygen tension, but reduced the time of crying and the heart rate increase during the procedure. In conclusion, NNS can be recommended to reduce distress in newborns undergoing invasive routine procedures. Further studies are needed to evaluate the effects of NNS on respiratory rate and blood gas levels.     

Pharmacokinetic-therapeutic studies of ceftriaxone in premature and mature newborn infants

Ceftriaxone a third generation Cephalosporine exhibits a high degree of antimicrobial activity against the most common pathogens causing life threatening infections in premature and newborn infants. Ceftriaxone was used therapeutically in 16 premature and newborn infants with proven or suspected bacterial infections. Pharmakokinetic investigations were performed during this therapeutic trial. 0.1 ml of blood was taken at 2, 6 and 10 hours after intravenous administration of 50 mg/kg BW Ceftriaxone administered as a single daily bolus injection. Again on day two and four 2 hours after readministration of the same dose, serum concentrations were determined by a biologic test method. With these five samples only, we were able to calculate all clinically relevant pharmakokinetic parameters. There was a high degree of agreement between the experimentally determined and the calculated parameters. Premature infants showed a lower Cmax (115 micrograms/ml) which corresponded to the higher volume of distribution of 44% in this age group. Newborn infants in contrast showed a Cmax of 129 micrograms/ml corresponding to a volume of distribution of 39%. The halflife of elimination was 10.4 and 9.6 hours resp. for premature and mature newborn infants. Cumulation of the drug was seen during the first two days of treatment. A steady state however ensued on day three in both age groups after which no further increase in maximum serum concentrations was seen. Our data suggest, that 50 mg/kg BW once daily given intravenously by bolus-injection or short infusion over 30 minutes constitutes sufficient therapy for serious bacterial infections in premature and newborn infants with susceptible organisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early neonatal hyperkalaemia in the extremely premature newborn infant

The incidence of hyperkalaemia in 43 consecutive infants born at less than 28 weeks gestation and cared for in our neonatal intensive care unit was documented. Plasma K levels were related to indices of renal function as well as to the degree of illness in the infants. The mean gestational age was 26.0 weeks (range 24-27 weeks) and the mean birthweight was 815 g (range 395-1170 g). Twenty-six of the infants (60%) had at least one plasma K greater than 5.5 mmol/L and 13 (30%) had a maximum plasma K greater than 7 mmol/L. The mean postnatal age at which the plasma K exceeded 7 mmol/L was 25 h (range 10-39 h). Five infants with plasma K greater than 7 mmol/L developed cardiac arrhythmias and four died of this complication. Only one infant had a large intraventricular haemorrhage. Only two of 16 infants with an initial plasma K less than 5 mmol/L had a maximum plasma K greater than 7 mmol/L, compared with eight of 10 with an initial plasma K greater than 6 mmol/L (P less than 0.005). Plasma K also correlated directly with plasma urea (P less than 0.001) and plasma creatinine (P less than 0.025), and inversely with urine volume (P less than 0.05). Plasma K did not correlate with K intake, arterial pH, presence of asphyxia, severity of respiratory illness, gestation or birthweight. The rapidity with which the plasma K concentration reached potentially hazardous levels in some infants makes it imperative to measure plasma K within 6 h of birth and to continue to monitor levels at least every 6 h for the first 48 h in all infants born at less than 28 weeks gestation.     

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.