In search of a 'gold standard' for bilirubin toxicity.
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Biomedical subjects
Publications and source records attributed to R L Poland.
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A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia.
The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.
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Forty-six pregnant women less than 35 weeks of gestation were enrolled in a prospective randomized controlled study evaluating the effects of antenatal phenobarbital on neonatal intracerebral hemorrhage. The women were randomly assigned to control (n = 22) or treatment (n = 24) groups; the treatment group received 500 mg of phenobarbital intravenously. The time interval between the dose of phenobarbital and delivery was 5.5 +/- 4.8 hours (mean +/- SD). The infants in the control group (n = 23) and those in the phenobarbital-treated group (n = 25) were comparable regarding birth weight, gestational age, and other obstetric and neonatal risk factors associated with intracerebral hemorrhage. The incidence of intracerebral hemorrhage was 56.5% (13 of 23 infants) in the control group and 32% (eight of 25 infants) in the phenobarbital-treated group (p = 0.08). Moderate or severe hemorrhage was diagnosed in six of 13 control infants and in none of the phenobarbital-treated infants (p less than 0.01). The mortality rate was significantly lower in the phenobarbital-treated group (two of 25 infants) than in the control group (eight of 23 infants; p less than 0.05). Our study suggests that antenatal phenobarbital administration results in a decrease in mortality and in the severity of intracerebral hemorrhage in the preterm neonate.
PAM/NET is a computerized data base and conferencing system used by nine neonatal intensive care units in Michigan and Illinois. The system depends on the timesharing resource of a large university mainframe computer. The data base functions are managed by a sophisticated inverted file relational data base management system capable of mass storage and rapid and specific retrieval of individual cases or summary data. Data stored in the system are used to generate admission, discharge and developmental assessment clinic summaries that serve as such for the medical record and as letters to primary physicians. We report here the early experience in the design and dissemination of this database network to the participating hospitals. Conflicting goals of sharing and confidentiality of clinical data are addressed in the design of this system.
Twenty-one real-time sonographic determinations of endotracheal tube tip position were performed in 16 neonates. Findings were compared with those from simultaneously obtained chest radiographs. Relation of the tube tip to the aortic arch provided a reliable method of determination of appropriate position. Optimal tube tip position was seen when the tube tip was 1 cm above the arch.
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Seventy-three real time sonographic scans were performed through the anterior fontanelle of 67 infants between 28 and 48 weeks post-conception who had no evidence of intracranial disease. Several anatomical measurements were plotted against independent variables such as post-conception age, weight and head circumference at the time of the examination. All of the measurements increased as age, weight and head circumference increased. Ratios formed by dividing transventricular diameters by transcalvarial diameters at the two levels in the coronal plane and by dividing occipital mantle thickness by frontal mantle thickness in the parasagittal planes remained stable as all of the independent variables increased. In 88% of cases the occipital mantle could not be measured since the occipital horns of the lateral ventricles could not be identified. Since dilation of the ventricular system starts in the occipital horns of the lateral ventricles, non-visualization of this area is an important negative finding.
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Length of stay data collected for high-risk newborn infants admitted to a tertiary care children's hospital neonatal unit over a 6-year period were compared with mean and outlier lengths of stay published in the Federal Register as part of a proposed system for prospective payment of hospital cost by diagnosis-related groupings (DRGs). We found that the classification system for newborns markedly underestimated the number of days required for the treatment of these infants. The use of the geometric mean instead of the arithmetic mean as the measure of central tendency was a significant contributor to the discrepancy, especially in those subgroups with bimodal frequency distributions of lengths of stay. Another contributor to the discrepancy was the lack of inborn patients in the children's hospital cohort. The system of prospective payments, as outlined, does not take into account several factors that have a strong influence on length of stay such as birth weight (which requires more than three divisions to serve as an effective predictor), surgery, outborn status, and ventilation. Implementation of the system described in the Federal Register would severely discourage tertiary care referral hospitals from providing neonatal intensive care.
The use of partial plasma exchange transfusion in newborns with polycythemia and hyperviscosity was evaluated. Ninety-three infants with polycythemia and hyperviscosity were randomly assigned to receive either partial plasma exchange transfusion or symptomatic treatment; the infants were matched with control infants without polycythemia. Neonatal course and outcome at 1 and 2 years were evaluated for each of the three groups. Polycythemic infants had more fine motor and speech problems at 1 year of age than did control infants. At 2 years of age, polycythemic infants had more gross motor delays, neurologic diagnoses, fine motor abnormalities, and speech delays than did the control infants. There was no significant difference at 1 year between the polycythemic infants who had received partial plasma exchange transfusion and those given only symptomatic care. At 2 years, the group receiving partial plasma exchange transfusion had fewer neurologic diagnoses and fine motor abnormalities.
Capillary blood samples obtained from a warmed distal phalanx of the right hand were compared with either temporal or right radial arterial blood samples for PO2, PCO2, and pH in 33 critically ill newborn infants. The blood pressure and skin temperatures of each infant and the ambient oxygen concentration were recorded at the time the blood was sampled. Sixty-eight paired PO2 analyses yielded a regression line close to the line of identity. The mean difference between digital capillary and arterial PO2 was 11.3 +/- 1.4 mm Hg (r = 0.92). The results were similar for the paired PCO2 analyses (r = 0.84) and for the paired pH analyses (r = 0.94). The correlation between arterial PO2 and digital capillary PO2 deteriorated when the systolic blood pressure of the patient was below 35 mm Hg. There was no correlation between skin temperature and capillary-arterial PO2 differences. The frequency of retrolental fibroplasia leading to blindness was not different from that in nurseries that sample umbilical arterial blood routinely.
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Since furosemide, a sulfonamide diuretic, has been recommended for use in the newborn infant, a study was made of its effect on the bilirubin-binding capacity of albumin. Furosemide was compared to sulfisoxazole, a known displacer of bilirubin, by means of three methods. First, aliquots of whole blood from 20 icteric infants were diluted in phosphate buffer along with expected clinical concentrations of furosemide and sulfisoxazole. The red cells and globulins were then isolated and bilirubin concentrations were measured in these two fractions. The addition of Furosemide resulted in the displacement of bilirubin from albumin to red cells and globulins. Mole for mole, furosemide displaced bilirubin about as well as sulfisoxazole. Second, the hydroxybenzeneazobenzoic acid dye binding test of Porter and twaters was performed using the sera of eight jaundiced newborn infants. The mean dye binding capacity of the sera was significantly reduced with the addition of furosemide to a final concentration of 2 mug/ml. Third, the administration of furosemide (5 mg/kg) or sulfisoxazole (50 mg/kg) to adult Gunn rats resulted in a significant fall in mean serum bilirubin concentration compared to saline controls. Furosemide, like sulfisoxazole, is a potent displacer of bilirubin and should be used with caution in jaundiced infants.
The influence of free fatty acids (FFA's) on the albumin binding of bilirubin was studied in vitro in the plasma of infants with neonatal hyperbilirubineamia and in solutions employing crystalline albumin to which bilirubin and FFA (oleic acid) were added. The bilirubin saturation index (SI) was utilized to distinguish between that fraction of bilirubin bound at the primary (high-affinity) site of albumin and bilirubin bound at secondary sites from which it is easily dissociated by salicylate. The relative saturation of albumin with bilirubin was also measured by addition of salicylate to whole blood samples where bilirubin was also measured by addition of salicylate to whole blood samples where bilirubin dissociated from the albumin could be sequestered by the red cells. The present studies indicate that FFA's influence the binding of bilirubin in two ways. At molar ratios of FFA to albumin (2:1 to 4:1), the FFA's compete with bilirubin for binding at the high-affinity site so that a significant portion of the bilirubin is transported at secondary sites, making it susceptible to displacement by water-soluble organic anions. At high molar ratios (greater than 5:1) FFA's compete with bilirubin for albumin binding at the secondary sites as well. In contrast to crystalline albumin where the first two molar equivalents of FFA do not influence the binding of bilirubin to albumin, all FFA concentrations in hyperbilirubinemic plasma reduce the affinity of albumin for bilirubin at its high-affinity site even though there is a molar excess of albumin over bilirubin.