Significance of the endogenous digoxin-like substance in infants and mothers.

Digoxin serum concentrations were measured by a routine radioimmunoassay in 30 neonates not receiving digoxin; nonetheless, digoxin levels were between 0.17 nM and 1.64nM (means = 0.64nM +/- 0.27 nM). There was a negative correlation between gestational age and concentration of an endogenous digoxin-like substance (EDLS). Neonates less than or equal to 32 wk gestational age had higher levels of EDLS than neonates greater than 32 wk old. EDLS concentrations were compared in 22 mothers and their 24 offspring and were higher in all newborn infants (0.34nM +/- 0.09nM and 0.15nM +/- 0.08nM). EDLS was shown to inhibit Na+-K+-adenosinetriphosphatase activity by measurement of 86Rb uptake in erythrocytes exposed to sera samples from 30 infants in the study. EDLS levels greater than 0.6 ng/ml were associated with lesser 86Rb uptake. Simulation kinetics suggest that the presence of 0.6nM EDLS would lengthen the digoxin t1/2 by 64%, reduce the volume of distribution by 23%, and lower clearance by 53% if the peak "true" digoxin level were 2 ng/ml. EDLS concentrations of 1.5 ng/ml would increase the t1/2 by 207% while reducing the volume of distribution by 43% and clearance by 81%. These considerations cast serious doubts on the validity of currently accepted digoxin kinetics and dosing in preterm infants.

Adverse reactions to diphtheria, tetanus, pertussis-polio vaccination at 18 months of age: effect of injection site and needle length.

Adverse reactions after diphtheria, pertussis, tetanus, polio vaccination at 18 months of age were investigated in three groups: 74 children injected in the deltoid muscle with a 16-mm (5/8-in) needle, 64 in the anterolateral thigh with a 16-mm needle, and 67 in the anterolateral thigh with a 25-mm (1-in) needle. No significant differences in systemic reactions were observed. Severe pain occurred in 30.5% of the groups injected in the thigh compared with only 8.1% of the group injected in the arm (P less than .001). Children vaccinated in the thigh had decreased movement of the extremity significantly more often than those injected in the arm (49.9% v 25.6%, P less than .0005), and two thirds of the former limped for 24 to 48 hours. Redness and swelling were observed more often after injection in the arm than in the thigh (58.1% v 26.7%, P less than .0005). The only effect of changing needle length in the groups injected in the thigh was the occurrence of more redness and swelling in children vaccinated with the 16-mm needle compared with the 25-mm needle. Overall, parents rated more reactions as moderate to severe among children injected in the thigh than among children injected in the arm (64.2% v 37.9%, P less than .001). The deltoid muscle appears to be the preferred site for administration of diphtheria, pertussis, tetanus, polio vaccine at 18 months of age.

Acetaminophen prophylaxis of adverse reactions following vaccination of infants with diphtheria-pertussis-tetanus toxoids-polio vaccine.

The effect of acetaminophen on reducing the frequency and severity of adverse reactions following diphtheria-pertussis-tetanus toxoids-polio vaccine was studied in a randomized clinical trial involving 519 vaccinations in 383 infants 2 to 6 months of age and 70 infants 18 months of age. Significantly fewer local and systemic reactions were reported in acetaminophen-treated infants at 2 to 6 months of age. Acetaminophen also reduced the incidence of fever greater than 38.0 degrees C from 44% to 27%. Only 0.9% of acetaminophen-treated infants had overall behavioral changes rated as severe by parents compared to 13% of the placebo group. Infants vaccinated at 18 months of age had higher rates of systemic and local reactions than younger infants. Acetaminophen did not result in significant reductions in reaction rates after the booster at 18 months. We conclude that acetaminophen administered at the time of primary vaccination with diphtheria-pertussis-tetanus toxoids-polio can significantly reduce the frequency and severity of common adverse reactions.

Pharmacokinetics of intravenous clindamycin in newborn infants.

We studied 12 newborn infants (gestational ages 26-39 wk [mean +/- SD, 30.6 +/- 4.7]; birth weight 640-2700 g, [mean, 1,322 +/- 688]; postnatal age 1-24 days [mean, 9.6 +/- 8.5]) who received clindamycin phosphate for suspected or proven necrotizing enterocolitis (ten patients) or suspected anaerobic septicemia (two patients) in doses of 3.2-11 mg/kg every six hours. Range of mean serum concentration of clindamycin at steady state was between 12.7 and 40 micrograms/ml (therapeutic range = 2-10 micrograms/ml). High concentrations could be attributed to elimination T1/2 (6.3 +/- 2.1 hr) 100% longer than in older children or adults. Clindamycin clearance (61.6 +/- 31.6 hr ml/kg/hr) was lower than in older children or adults. Because of the observed prolongation in T1/2 and correspondingly lower clearance, the IV dose of clindamycin in newborn infants should be reduced to 15-20 mg/kg/day given in four daily doses.