Eugene W. Outerbridge

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.

Long-term pulmonary sequelae of severe bronchopulmonary dysplasia.

OBJECTIVE To evaluate the long-term pulmonary sequelae of survivors of bronchopulmonary dysplasia (BPD) of sufficient severity to have required supplemental oxygen for at least 1 month after term. STUDY DESIGN Fifteen patients with a mean age of 1.1 years were matched to preterm infants of similar gestational age and age at time of study. Pulmonary function testing included spirometry, plethysmographic lung volumes, carbon monoxide diffusion capacity, and in 9 of 15 subjects with BPD, measurement of lung static elastic recoil pressures. RESULTS The subjects with BPD had a mean expiratory volume in 1 second (FEV1) of 64% +/- 21% predicted (4 had an FEV1 < 50% predicted) compared with 85% +/- 11% (P < .01) for the preterm children in the control group. Subjects with BPD had a significant degree of gas trapping with a residual volume to total lung capacity ratio of 37% +/- 13% compared with 25% +/- 4% for the control group (P < .01). An inverse relationship was seen between the FEV1 and the time on supplemental oxygen (r = -0.84, P < .0001), with 3 of the 4 children whose FEV1 was < 50% requiring oxygen for more than 900 days. Those with the greatest degree of airflow limitation and gas trapping had the greatest abnormalities in both shape and position of the pressure volume curves of the lung. CONCLUSION Severe BPD may result in moderate to severe long-term abnormalities in pulmonary function tests.

Long-term pulmonary sequelae of premature birthwith and without idiopathic respiratory distress syndrome

Seven children born prematurely who survived the respiratory distress syndrome, seven children born prematurely who had no neonatal lung disease, and seven normal children born at term were studied by comparison of flow volume curves obtained while breathing air to those obtained while breathing 80% helium and 20% oxygen. Expiratory flow rates in air both groups of prematurely born children were lower than flow rates of the children born at term, and the volumes of iso-flow were higher in the survivors of RDS than those of the children born at term. The differences in flow rates in air suggest an increase in large airway resistance in both groups of prematurely born children. It is speculated that this may be secondary to growth retardation related to prematurity. The elevated Viso V in the RDS group suggests an increase in small airway resistance secondary to the disease or to its therapy.

Peripheral total parenteral nutrition for premature infants with the respiratory distress syndrome: A controlled study

In 40 premature infants, in whom severe respiratory distress precluded oral feeding, peripheral total parenteral nutrition consisting of casein hydrosylate, dextrose, and soybean emulsion was compared to nutrition with dextrose and electrolytes. The TPN group received more calories, and the total serum protein in them increased significantly. Metabolic complications did not occur. Transient thrombocytosis occurred in six infants who received TPN and eosinophilia occurred in nine. The case fatality rate in the TPN group (three of 20) was not significantly less than in the glucose group (six of 20). The differences suggested that infants who weigh less than 1,500 gm may receive the greater benefit from TPN.

BLOOD TRANSFUSION: A POSSIBLE RISK FACTOR IN RETROLENTAL FIBROPLASIA

ABSTRACT. Clark, C, Gibbs, J. A. H., Maniello, R., Outerbridge, E. W., and Aranda, J. V. (Department of Newborn Medicine, McGill University, Montreal Childrens Hospital Research Institute, Montreal, Quebec, Canada). Blood transfusion: A possible risk factor in retrolental Fibroplasia. Acta Paediatr Scand, 70:535,.–The effect of blood transfusion on the occurrence of RLF was evaluated in 58 infants who weighed less than 1 001 g at birth (Group I) and 70 oxygen treated infants of various birth weights (Group 11). Although there was no significant difference between Group 1 infants with or without exchange transfusion as to birth weight, gestational age, duration of oxygen therapy, peak Po2s, or multiple births, there was a significantly increased incidence of pre‐retrolental fibroplasia in transfused over non‐transfused Group II infants. When Group II infants were stratified for prematurity and oxygen duration, this difference persisted in those not already at risk for RLF. This increased incidence of retinopathy in transfused infants suggests that blood transfusion may be a risk factor in the pathogenesis of RLF.

Continuous negative pressure in themanagement of severe respiratory distress syndrome

Fourteen infants with severe idiopathic respiratory distress syndrome were treated with a continuous negative pressure of −4 to −8 cm. H 2 O about the chest. Arterial oxygen tension rose significantly by a mean of 23.3±4.2 mm. Hg (p

PHARMACOKINETIC DISPOSITION OF CAFFEINE IN PREMATURE NEONATES WITH APNEA

The newborn infant is exposed to caffeine either transplacentally or postnatally for the treatment of apnea. Using a one-compartment model, the pharmacokinetic disposition of caffeine in the neonate was determined. Caffeine (as the citrate salt) was given to 10 premature infants with apnea at a dose of 5 to 20 mg/kg via intravenous infusion for 10 to 20 min. Caffeine was measured in 10 μl of plasma by radioimmunoassay (Cook, Research Triangle Park, N.C). Blood samples were obtained by heelsticks at 2 to 8h interval for 72 to 86h. Relative to adult whose T4 is 3 to 5h, caffeine was eliminated slowly.Neither AVd, T4, kel nor clearance correlated with birth weight or postnatal, gestational or postconceptional age. The data show that a loading dose of 10 mg/kg of caffeine (or 20 mg/kg of caffeine citrate) achieves a peak plasma concentration (Cp) of 8 to 14 mg/L. Maintenance dose of 2.2 mg/kg/24 h maintained Cp of 10 mg/L. The 7-fold range of individual caffeine clearance makes monitoring of Cp mandatory during maintenance therapy for apnea.

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.

Developmental follow-up of survivors of neonatal respiratory failure.

Follow-up evaluation was carried out in 109 (86%) of 126 children who required ventilatory support in the newborn period for respiratory failure; the commonest cause of which was the respiratory distress syndrome. The children are currently between 1 and 6 years of age. Their gestational ages ranged from 27 to 42 weeks and their birth weights from 1050 to 4360 g.The number of major abnormalities in the RDS group was small, occurring primarily in infants who were less than 1500 g birth weight, or in children who have had neonatal insults such as asphyxia or hyperbilirubinemia. The survivors of other causes of neonatal respiratory failure are too small in number to make a valid comparison with RDS survivors, but all appear to be developing normally. The data presented here suggest that RDS itself, even in its most severe form, does not in the large majority result in impaired development of the survivors, and that the overall outlook for this group of infants is an extremely encouraging one, and indicates that life-support efforts are warranted.

OUTCOME AT SCHOOL-AGE AFTER NEONATAL MECHANICAL VENTILATION

103 school‐age children (5 to 12 years) who survived mechanical ventilation for neonatal respiratory failure were evaluated for growth, neurological, intellectual, psychological and school function in order to determine those children most at risk for handicap. A major handicap occurred in seven children, preventing attendance at normal school or normal classes. Neurological sequelae were significantly associated with perinatal asphyxia and with birthweights of 1500g or less, and neurological sequelae and socio‐economic factors were the major determinants of ability. The effects of the Neonatal Intensive Care Unit (NICU) experience on parents and subsequent parent‐child relationships were also investigated: 67 per cent of the mothers were very upset by the experience and many continue to worry excessively about the health of their child. Parents who visited their child in the NICU frequently were significantly more anxious and overprotective, restricting many activities even when the child was of school age.