Judith M. Collinge

Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.

The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule. Mean (+/- SE) AV d, t 1/2, ke1, and clearance following a single intravenous dose were 0.916 +/- 0.070 1/kg, 102.9 +/- 17.9 hours, 0.009 +/- 0.001/hours and 8.9 +/- 1.5 ml/kg/hour, respectively. Rapid absorption was noted with plasma concentrations of 6 to 10 mg/l achieved within 30 minutes to two hours following an oral dose of 10 mg/kg. Cpss of caffeine in infants given a high empirical dose (11.2 +/- 1.5 mg/kg/day) ranged from 22.5 to 84.2 mg/l (mean = 45.3) whereas a dose schedule based on kinetic data (2.5 mg/kg/day) yielded plasma concentrations ranging from 7.4 to 19.4 mg/l (mean = 13.7). We suggest a loading dose of 10 mg/kg intravenously or orally followed by a daily maintenance dose of 2.5 mg/kg/day administered as a single dose for the treatment and prevention of neonatal apnea.

Pharmacokinetic disposition and protein binding of furosemide in newborn infants

Using a one-compartment model, the pharmacokinetic disposition of furosemide was studied in eight premature and term neonates with fluid overload. Following a single intravenous injection of furosemide (1 to 1.5 mg/kg), multiple blood samples were obtained from a heelstick or an arterial catheter and analyzed for furosemide by gas liquid chromatography. The mean (+/- SE) apparent volume of distribution was 829.2 +/- 118.9 ml/kg; t1/2 was 7.7 +/- 1.0 hour; elimination rate constant was 0.102 +/- 0.013/hour and plasma clearance was 81.61 +/- 14.98 ml/kg/hour. Compared to the disposition of furosemide in normal adults. AVd is almost fourfold greater in the neonate with an eightfold prolongation in plasma t1/2, an eightfold decrease in Ke1, and a twofold decrease in plasma clearance. Neither gestational and postnatal age nor birth weight correlated with the pharmacokinetic variables. No significant change in reserve bilirubin-binding capacity after an intravenous dose of furosemide was noted. Slow elimination of furosemide may partly explain the prolonged diuretic and saluretic effect of furosemide in the neonate.

Effects of furosemide in the newborn

The effects of furosemide on electrolyte and water excretion were determined in 9 neonates with fluid overload states. Hourly measurements of urine volume, serum and urine Na+, K+, Cl−, creatinine, and blood urea nitrogen were done before and after the intravenous or intramuscular injection offurosemide (1 mg/kg). Mean (±SE) birth weight was 2,261.7 ± 284.4 gm; gestational age was 35.1 ± 1.4 wk, postnatal age was 13.8 ± 6.9 days, blood urea nitrogen was 10.0 ± 1.0 mg%, creatinine was 0.7 ± 0.1 mg%, and glomerular filtration rate was 21.9 ± 3.8 ml · min−1/1.73 m2. Compared with the values obtained before the administration of furosemide, there were significant increases in percent fractional Na+ excretion, percent fractional Cl− excretion, urine volume (ml · hr−1), and free water clearance (ml · hr−1), each of which peaked within 1 hr of furosemide administration and were sustained for another hour thereafter. These effects were discernible for about 5 hr and returned to baseline by 6 hr after administration of the drug. A 2.5‐fold increase in K+ excretion (µEq · hr−1) was noted I hr after furosemide; this increase was sustained for 2 hr and decreased to the predrug level in 4 hr. Although all infants showed increases in urine volume and electrolyte excretion within 1 hr of furosemide administration, the magnitude of the response exhibited remarkable variability. There is some suggestion that perinatal asphyxia may decrease the response to furosemide.

Family support system in newborn medicine: Does it work? follow-up study of infants at risk

Acute illness in early childhood generates chronic anxiety in parents, which may manifest itself in part by inappropriate use of health care. To minimize this and the development of other psychosocial sequelae associated with neonatal illness, a family support system (FSS) was developed and implemented in a neonatal intensive care unit. The effectiveness of the FSS was assessed by the evaluation of emergency room and inpatient hospital service utilization in 80 patients born before, and 90 patients born after the institution of the program. At the outset, the groups had similar medical and social characteristics. There was no difference between the two groups in the utilization of emergency services in the first year after discharge. However, during the second year the control group used the emergency room twice as often as the study group did (P less than 0.025). During the first 2 years, half of the control group was readmitted, compared with less than a third of the study group (P less than 0.005). Overall, after discharge from the neonatal intensive care unit the control group spent an average of 9 days per patient in hospital, compared with a mean of 3 days per patient in the study group (P less than 0.025). It appears, therefore, that the FSS may be an effective way to reduce some of the psychosocial sequelae of illness in newborn infants requiring intensive care.

1275 EPIDEMIOLOGY OF ADVERSE REACTIONS TO TOTAL PARENTERAL NUTRITION (TPN)

To determine the magnitude of the risks in TPN delivered via peripheral vein, the incidence of adverse reactions to TPN was evaluated as a part of on-going prospective study on neonatal adverse drug reactions. Data on 456 neonates admitted to the Neonatal Intensive Care Unit were analyzed. Of these, 105 babies (23%) had TPN(glucose, amigen, intralipid) for 3024 days with a mean TPN duration of 28.3 days per patient (range 1174 d). TPN was started at age 5.1 d (range 1-48) for GI abnormalities (33.3%,e.g. necrotizing enterocolitis omphalocoele), severe prematurity (13.3%) and respiratory disorders (39.0%). 96 neonates survived (91.4%). 7 had a total of 9 central venous lines. The average weight gain per day was 8.36 g (range- 35 to 30.5 g). Hyperglycemia (>150 mg/dl, peak 695 mg/dl) occurred in 28 babies (26.7%), glycosuria in 19.0% and significant lipidemia in 18.1%. Abnormal liver function tests and liver disease were noted in 20 babies (19.0%); due to cytomegalovirus in one with no definitive cause in the others. 324 skin necrosis or sloughs (>0.5 cm) occurred in 71 babies (67.6%) while on TPN. 2 neonates developed severe trace metal deficiency, 1 died. Data underscore need for close surveillance and improvement of TPN techniques in the neonate.

308 DETERMINANTS OF DRUG EXPOSURE IN A NEWBORN INTENSIVE CARE UNIT (NICU)

Factors possibly associated with increased use of drug exposure in a NICU were evaluated prospectively in all neonates admitted to NICU since Feb 1977. Demographic, clinical and laboratory data on all babies (Bb) were recorded by a physician/nurse monitor team and stored in the computer. Analyses of data from the first 461 neonates (bt wgt range 734-4850 g, gestational age (GA) 24-43 wks) show that 128 different drugs were used. 76.1% of babies received 1 to 35 drugs (excluding routine Vit K and AgNO3) with a mean exposure of 4.6/Bb. Babies with GA <32 wks (18%) had 3X more drug exposure than those with GA >32 wks (9.7 vs 3.4 drugs/Bb). GA and bt wgt were inversely related with drug exposure (number of drugs/Bb). Drug exposure was greater in disease states more commonly associated with prematurity; 14.2 drugs/Bb in PDA, 16.8 in necrotizing enterocolitis, 14.5 in persistent fetal circulation, 12.5 in renal failure, 13.1 in liver disease. 17 different antimicrobials were used in 47.7% of Bb, diuretics in 17.4%, cardiovascular drugs in 9.8%, steroids in 4.3% and sedatives and narcotics for palliation in 13.0%. Mean bt wgts and GA were significantly lower in babies who received antimicrobials, diuretics, and methylxanthines. Data underscore the necessity of requisite pharmacologic studies in the low bt wgt infants who are at greater risk of drug exposure.