Indomethacin: continuous versus bolus administration.
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Blood Flow Velocity↗
Biomedical subjects
R B Cotton
Publications and source records attributed to R B Cotton.
Outcome of preterm infants with congenital heart disease.
OBJECTIVES AND STUDY DESIGN: To evaluate the morbidity and mortality of preterm infants with congenital heart disease (CHD), a chart review was performed for infants with CHD, excluding isolated patent ductus arteriosus, who were <37 weeks' gestation, weighed <2500 g, and were admitted to our neonatal intensive care unit from 1976 to 1999 (N = 201). RESULTS: Patients in the study represented 1.9% of the total neonatal intensive care unit population <37 weeks' gestation and <2500 g. The median gestational age was 33 weeks, and the mean birth weight was 1852 g. CHD diagnosis frequencies were similar to those reported in other large incidence studies, except for a higher percentage of conotruncal defects. The risk of necrotizing enterocolitis was 1.7 times higher and the overall mortality twice as high in our patients compared with patients in the neonatal intensive care unit who did not have CHD. Cardiac surgery (n = 133) was performed on 108 patients. During the recent period of 1985 to 1999, compared with our institution's overall results for CHD surgery, the operative mortality rate was 10.4% versus 5.4% for closed procedures and 25.4% versus 10.5% for open procedures. The actuarial survival rate is 51% at 10 years; survival improved as the study period progressed. CONCLUSIONS: Infants with both CHD and prematurity did significantly worse than either group alone. Such outcome data are required for proper allocation of resources to care for this high-risk pediatric population.
Cardiac Surgical Procedures↗
Don't discard your indomethacin yet.
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Anti-Inflammatory Agents, Non-Steroidal↗
Quantitative analysis of cimetidine in human plasma using LC/APCI/SRM/MS.
A quantitative method was developed and validated for rapid and sensitive analysis of cimetidine in human plasma. The method involved the use of liquid chromatography (LC) coupled with atmospheric pressure chemical ionization (APCI) and selected reaction monitoring (SRM) mass spectrometry (MS). A cimetidine analog, SKF92374, was used as the internal standard. Separation of cimetidine and the internal standard was accomplished using a reverse-phase HPLC column (C18). The eluted components were ionized by the APCI source and subsequently detected by a highly selective triple quadrupole mass spectrometer in the SRM mode. Linear standard curves were obtained from 5 ng/mL (lower limit of quantitation) to 10,000 ng/mL. The results demonstrated excellent precision (%RSD 1. 1-8.9%) and accuracy (94.7-108.0%) over this range. In addition, the amount of plasma sample needed for analysis was small (50 muL), and the plasma pretreatment (analyte recovery >94%) was simple and time saving. This assay was used to evaluate cimetidine levels in premature infants following intravenous infusion of cimetidine.
Child↗
Surfactant replacement therapy improves ventilation inhomogeneity in infants with respiratory distress syndrome.
Surfactant deficiency in newborn infants with hyaline membrane disease (HMD) reduces peripheral airway stability, leading to lung atelectasis, inhomogeneity of distribution of ventilation, ventilation/perfusion mismatch, and hypoxemia. The aim of this study was to evaluate the immediate effect of exogenous surfactant treatment on ventilation inhomogeneity (VIH) in infants with HMD. Homogeneity of ventilation was measured repeatedly in ten infants (median gestational age 30 weeks and birthweight 1.50 kg) after Exosurf, and in six infants (median gestational age 30 weeks and birthweight 1.42 kg) after Survanta treatment. Lung function was measured before and 0.5, 2, and 6 hours after administration of a single dose of surfactant. The multiple breath nitrogen washout method was used to measure the time pattern of nitrogen elimination from the lungs. VIH was evaluated by using both a compartmental lung model and a model-independent moment analysis. The two-compartment lung model was found to dominate before surfactant treatment, while a single-compartment model (implying homogeneous ventilation) fitted the washout data best 6 hours after Exosurf treatment (P < 0.01). The same pattern occurred 2 hours after Survanta administration. Moment analysis confirmed the reduction in VIH by both surfactants. This study supports the hypothesis that the improved oxygenation after surfactant treatment in infants with HMD results from a reduction in VIH and an increase in functional residual capacity (FRC).
Analysis of Variance↗
Effect of volume recruitment on response to surfactant treatment in rabbits with lung injury.
We determined if surfactant treatment effect can be enhanced by mechanical volume recruitment during surfactant administration by measuring functional residual capacity, tidal volume, the alveolar portion of tidal volume, dynamic compliance of the respiratory system, a/A ratio, and PaCO2 by measuring before and after surfactant administration to rabbits with lung injury induced by airway lavage. There was improvement in all lung function indices when surfactant was given with volume recruitment, but when surfactant was given without volume recruitment, the only index to show significant improvement was a/A ratio of oxygenation. These results support the hypothesis that mechanical recruitment of terminal airspaces from a previously unventilated compartment will enhance the effectiveness of surfactant replacement by facilitating the distribution of instilled surfactant to this compartment.
Animals↗
Evidence from twin study implies possible genetic susceptibility to bronchopulmonary dysplasia.
To investigate the possibility that susceptibility to bronchopulmonary dysplasia (BPD) is affected by genetic factors, we analyzed risk factors for BPD in 108 twin pairs of infants having birth weight < or = 1,500 g. When BPD occurred in a first born twin (n = 23), it also occurred in 65% (n = 15) of the second born twins, and when BPD did not occur in the first twin (n = 85), it only occurred in 8% (n = 7) of the second twins (crude odds ratio = 20.9). After adjusting for potentially significant risk factors including birth weight, gestational age, gender, diagnosis of hyaline membrane disease, pneumothorax, symptomatic patent ductus arteriosus, and year of admission, using multiple logistic regression on the entire database (1,872 admissions < or = 1,500 g), BPD status of a first twin remained a highly significant predictor of BPD in the second twin (adjusted odds ratio = 12.3, P < .001). Other factors including birth order of twins, twin gestation, inborn/outborn status, cesarean section delivery, 1- and 5-minute Apgar scores, maternal race, maternal diabetes, and antepartum corticosteroid treatment were not significant predictors of BPD. These results are consistent with genetic factors affecting the susceptibility of very low birth weight premature infants to BPD, but we cannot exclude the possibility that factors not included in our analysis are also involved.
Birth Weight↗
Presentation of the 1996 American Pediatric Society John Howland Award to Mildred T. Stahlman.
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Awards and Prizes↗
Validation of a nitrogen washout system to measure functional residual capacity in premature infants with hyaline membrane disease.
A multiple-breath nitrogen washout system designed to measure lung volume in mechanically ventilated infants was validated by assessing three performance criteria: 1) accuracy of lung volume measurements in the presence of an endotracheal tube leak was assessed by comparing the measurements of functional residual capacity (FRC) in a mechanical lung model with and without airway leak; 2) in vivo accuracy was assessed in rabbits by comparing FRC measurements obtained by this system with measurements obtained by helium dilution; and 3) in vivo precision was assessed by analyzing measurements of FRC obtained in replicate measurements at different times in ventilator-dependent premature infants with hyaline membrane disease. The average difference between the measurements of FRC in a mechanical lung model with airway leak and without leak was 3.0 +/- 9.4% (mean +/- SD, P > 0.2), and no difference was greater than 20%. There was a significant correlation between the measurements of FRC in rabbits by nitrogen washout and by helium dilution (r = 0.93, P < 0.0001), and 65.4% of the paired measurements were within 20% of their average. The 95% limits of agreement within pairs of measurements by the two techniques ranged from -4.0 to + 6.5 mL/kg. FRC measured by helium dilution was slightly higher (1.3 +/- 2.7 mL/kg, P < 0.01) than FRC measured by nitrogen washout, and positive end-expiratory pressure was a significant predictor of this difference (P < 0.0001). The regression between the individual FRC measurements obtained in premature infants and the average of the other replicates was significant (r2 > 0.98, P < 0.0001). The coefficient of variation was 12.3%. These findings provide further validation of this multiple-breath nitrogen washout system for measuring FRC in premature infants during mechanical ventilation.
Animals↗
Effects of morphine and pancuronium on lung volume and oxygenation in premature infants with hyaline membrane disease.
To determine the effect of analgesia and paralysis on lung volume and oxygenation in premature infants supported by mechanical ventilation because of hyaline membrane disease, functional residual capacity (FRC), and arterial/alveolar oxygen tension ratio were measured in nine premature infants with hyaline membrane disease before and after the administration of morphine sulfate and pancuronium bromide. Without a change of positive end-expiratory pressure, ventilator rate and peak inspiratory pressure were increased before the first set of measurements to minimize the contribution of the infants' own respiratory effort to total ventilation. These ventilator settings were then held constant (except fraction of inspired oxygen) before and after the administration of the drugs. The FRC was measured with a multiple-breath N2 washout technique by means of whole-body plethysmography to measure airway flow. The FRC and the ratio of arterial to alveolar oxygen tension decreased in seven of nine patients after treatment with morphine and pancuronium. The decrease in FRC for all patients was significant (2.4 +/- 2.9 ml/kg; p < 0.05), and a significant correlation was demonstrated between the change in the arterial/alveolar oxygen tension ratio and the change in FRC (r = 0.82; p < 0.01). Gestational age, birth weight, postnatal age, severity of lung disease, and time after the administration of morphine and pancuronium were not significantly correlated with the change in FRC. We believe that a decrease in oxygenation caused by alveolar derecruitment occurred even though the ventilator settings had been increased before the first set of measurements. The decrease in FRC in these infants, who are thought to have alveolar instability because of surfactant deficiency, may have resulted from the loss of expiratory braking mechanisms. We conclude that analgesia and paralysis should be used with caution under these circumstances.
Functional Residual Capacity↗
A model of the effect of surfactant treatment on gas exchange in hyaline membrane disease.
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Animals↗
The physiologic effects of surfactant treatment on gas exchange in newborn premature infants with hyaline membrane disease.
To describe the physiologic effects of surfactant treatment on gas exchange in human premature infants with hyaline membrane disease, functional residual capacity (FRC), tidal volume (VT), the alveolar portion of tidal volume (VA), alveolar ventilation (VA), nitrogen clearance index, effective breath fraction calculated as VA/VT, compliance of the respiratory system, and arterial oxygen and carbon dioxide tensions were measured in 17 patients before and 0.5, 2, and 6 h after the administration of a single dose of either a synthetic surfactant (SS), Exosurf (n = 10), or a bovine surfactant (BS), Survanta (n = 7). By 2 h, treatment with either BS or SS was followed by an increase in the arterial/alveolar ratio of PO2 (a/A) and in FRC (p < 0.01 for both a/A and FRC). The a/A and FRC improved sooner (p < 0.001) and to a greater extent (p < 0.01) after BS than after SS. Compliance of the respiratory system and VT were decreased after either BS or SS at 0.5 h (p < 0.01) and remained decreased after SS at 2 h (p < 0.01). There was no significant change in VA or VA after either BS or SS. Because FRC and a/A increased without an accompanying increase in VA, VA, or compliance of the respiratory system, we believe that the immediate increase in FRC in this study was caused by stabilization of gas exchange units already being ventilated in addition to recruitment of new units.(ABSTRACT TRUNCATED AT 250 WORDS)
Biological Products↗
Improved survival accounts for most, but not all, of the increase in bronchopulmonary dysplasia.
The incidence of bronchopulmonary dysplasia (BPD) increased from 10.6% in 1976 through 1980, to 21.7% (1981 through 1985), and to 32.9% (1986 through 1990) in very low birth weight neonates (1500 g or less) admitted to the Vanderbilt Neonatal Intensive Care Unit, while there was a concurrent decline in incidence of neonatal death (NEOD) during the same periods (26.4%, 18.3%, and 15.9%, respectively). Population changes in risk factors (birth weight, sex, race, location of birth, gestational age, diagnosis of hyaline membrane disease, and 5-minute Apgar score) over time do not account for this increase. To estimate the proportion of the increase in BPD attributable to the concurrent decline in NEOD during these periods, separate logistic regression models for NEOD and BPD were calculated from patients born during 1976 through 1985. These results were used to predict the expected number of cases of NEOD and BPD during 1986 through 1990, assuming that the adjusted incidence of NEOD and BPD remained constant from 1976 through 1985, to 1986 through 1990. The increase in the combined outcome, NEOD/BPD, over the three time periods (34.2%, 36.1%, and 43.5%) remained statistically significant after adjustment for the risk factors listed above. During 1986 through 1990, the predicted number of NEOD was 83 more than the number observed, while the predicted number with BPD was 115 less than the number observed. If all 83 averted cases of NEOD during 1986 through 1990 had developed BPD, then 83 (72%) of the 115 excess cases of BPD could be attributed to averted NEOD. The approximate 95% confidence interval for this estimate was 58% to 87%.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchopulmonary Dysplasia↗
Origin of cardiac-related thoracic electrical impedance variations in lambs.
Cardiac-related deflections in thoracic electrical impedance have been thought to correlate sufficiently well with cardiac stroke volume to be used as the basis for a noninvasive estimation of cardiac output. To determine more precisely the physiological origin of the impedance deflection (DZ), we regarded right ventricular stroke volume (SVa) as the sum of two components: 1) that part of SVa responsible for the transient increment in pulmonary blood volume within a cardiac cycle, SVa-v and 2) the remaining part of SVa, (SVa-SVa-v). SVa-v was measured in lambs by integration of the difference between pulmonary arterial and pulmonary venous flow. SVa and its components were varied experimentally by opening and closing an aorticocaval shunt or by inflating and deflating a cuff implanted around the pulmonary artery. DZ was measured using a tetrapolar disk electrode system. Multivariate linear regression analysis revealed that SVa-v had a significant positive effect on DZ, and, at the same time, (SVa-SVa-v) had a significant negative effect on DZ. In the pulmonary artery occluder model, the positive effect of SVa-v dominated the opposing negative effect of (SVa - SVa-v) so that the net effect of SVa on DZ was positive and significant. In the aorticocaval shunt model, these effects opposed each other to the extent that there was no significant correlation between SVa and DZ. These results shed new light on the physiological origin of DZ. They also demonstrate that use of DZ to measure acute changes in cardiac output may yield misleading results. Changes or the lack of changes in thoracic electrical impedance do not necessarily reflect cardiac output status.
Animals↗
Symptomatic patent ductus arteriosus following prophylactic indomethacin. A clinical and biochemical appraisal.
Seven of 36 premature infants with birth weight less than 1,250 g who had been randomly assigned to either high-frequency ventilatory ventilation or conventional mechanical ventilation developed symptomatic patent ductus arteriosus (PDA) after receiving prophylactic indomethacin, 0.2 mg/kg, i.v. 24 h after birth. Infants who developed symptomatic PDA were more likely to be white and male and have more severe pulmonary insufficiency than infants who did not develop symptomatic PDA. Serum indomethacin levels were similar in both groups of patients. There was no difference in the degree of suppression or subsequent recovery of endogenous eicosanoid biosynthesis between infants who did and did not develop symptomatic PDA. Compared to conventional mechanical ventilation, high-frequency oscillatory ventilation had no significant effect on endogenous eicosanoid biosynthesis. The susceptibility of white male infants to symptomatic PDA following prophylactic indomethacin may represent the influence of maturational factors on ductus patency. Cyclooxygenase products do not appear to be involved in mediating ductus patency when symptomatic PDA occurs immediately following administration of prophylactic indomethacin.
Dinoprostone↗
Endogenous formation of prostanoids in neonates with persistent pulmonary hypertension.
Endogenous formation of thromboxane A2 and prostacyclin were evaluated in seven neonatates with persistent pulmonary hypertension by serial gas chromatographic mass spectrometric determination of their urinary metabolites dinor-thromboxane B2 and dinor-6-keto-prostaglandin F1 alpha, respectively. The patients were studied until their hypertension had resolved on clinical criteria. Urinary excretion of dinor-thromboxane B2 and dinor-6-keto-prostaglandin F1 alpha was increased when the persistent pulmonary hypertension was associated with group B streptococcal (n = 2) and pneumococcal (n = 1) sepsis. Based on urinary metabolite excretion, endogenous formation of thromboxane A2 and prostacyclin did not consistently differ from normal neonates in four patients with non-septic persistent pulmonary hypertension (hyaline membrane disease (n = 2), asphyxia, and meconium aspiration). These data suggest that thromboxane A2 is not a universal mediator of persistent pulmonary hypertension. It may, however, have a role in the pathophysiology of early onset group B streptococcal disease, and persistent pulmonary hypertension of other infectious aetiology. If these findings are confirmed by further studies, thromboxane synthetase inhibition or receptor antagonism may offer a potential therapeutic approach in neonates with persistent pulmonary hypertension associated with sepsis.
6-Ketoprostaglandin F1 alpha↗
Sensitivity, specificity, and predictive value of body surface cultures in a neonatal intensive care unit.
We analyzed 24,584 cultures obtained from 3371 infants during a three-year period to determine how frequently body surface culture isolates matched those obtained subsequently from body fluids. The sensitivity, specificity, and predictive values of surface cultures were calculated daily for the two weeks up to and including the day that a body fluid culture was obtained. Isolates from cultures of material from the ear canal, nasopharynx, axilla, umbilicus, groin, rectum, stomach, and endotracheal tube were rarely the same as those recovered from blood or fluids of the cerebrospinal, joint, pleural, pericardial, and peritoneal spaces. With a frequency of sepsis of 3.3% among patients in our neonatal intensive care unit, the optimum sensitivity, specificity, and positive predictive values of surface cultures were 56%, 82%, and 7.5%, respectively. These values did not improve substantially for any specific times of surface cultures prior to sepsis, for anatomic sites cultured, or for pathogens recovered. We conclude that surface cultures are of limited value in predicting the etiology of sepsis in neonates.
Algorithms↗
Decreased early diastolic function after indomethacin administration in premature infants.
The effect of indomethacin on systolic and diastolic cardiac function was assessed in 15 premature infants. Seven infants (group 1) received indomethacin to treat a clinically significant patent ductus arteriosus (PDA), and eight infants (group 2) received indomethacin prophylactically at 24 hours of age because of their high risk for PDA. Diastolic cardiac function was assessed using instantaneous rates of change of left ventricular (LV) cavity dimension, derived from M-mode echocardiography. The maximum velocity of lengthening of the LV cavity dimension, an index of early diastolic function, fell from 63 +/- 19 mm/sec before indomethacin to 48 +/- 16 mm/sec 1 hour after indomethacin in group 1 (P less than 0.01), with the ductus still patent and the LV chamber still dilated, and also decreased in group 2, from 52 +/- 7 mm/sec to 38 +/- 6 mm/sec (P less than 0.01). This index, when normalized for loading conditions, was decreased 1 hour after indomethacin at 12 +/- 2 sec-1 and 12 +/- 1 sec-1 for groups 1 and 2, respectively, compared with values before indomethacin of 15 +/- 3 sec-1 and 15 +/- 2 sec-1. There was no effect of indomethacin on the indices of systolic function. We conclude that indomethacin decreases early diastolic function in premature infants.
Diastole↗