Association between prenatal cocaine exposure and sudden infant death syndrome.
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Biomedical subjects
Publications and source records attributed to D J Durand.
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While cocaine is now used much more frequently than heroin by women of childbearing age, we have found that a significant number of mothers have abused both drugs during their pregnancy. We studied 86 infants who were born to women with a history of cocaine and/or heroin use during pregnancy. The newborns were observed over a 5-day hospital period using a standardized abstinence scoring system and urine drug screening of both mother and infant. Of these, 35 had maternal and/or newborn urine test results that were positive for cocaine only (cocaine group), 14 that were positive for heroin only (heroin group), 17 that were positive for both cocaine and heroin (cocaine/heroin group), and 20 that were negative for both, although the mothers admitted to cocaine use during their pregnancy (cocaine history group). In approximately half of the mother/infant pairs, the results of the urine drug tests were discordant. Microcephaly and growth retardation occurred most frequently in the infants in the cocaine group (17% and 27%, respectively). Microcephaly was also found to be significant in the infants in the cocaine/heroin group. Signs of drug withdrawal occurred in all four drug-exposed groups. Mild withdrawal occurred in 26% of infants in the cocaine group, 21% of the infants in the heroin group, 47% of the infants in the cocaine/heroin group, and in 30% of the infants in the cocaine history group. Withdrawal requiring treatment occurred in 6% of the infants in the cocaine group, 14% of the infants in the heroin group, 35% of infants in the cocaine/heroin group, and 5% of the infants in the cocaine history group. The use of heroin with cocaine has a synergistic effect on the behavior of the newborn.
We determined the short-term variability of pulmonary function in infants recovering from bronchopulmonary dysplasia. Sixteen infants with birth weight of 1,231 +/- 929 grams (mean +/- SD) and gestational age of 29 +/- 4 weeks were studied twice at 17 +/- 8 weeks postnatally at intervals of 4 to 8 days during a period of clinical stability. The infants were still on supplemental oxygen but were off diuretics and bronchodilators. We used a modification of the rapid thoracic compression method to measure forced expiratory flow (Vmax FRC) and the time constant (tau) of expiratory flow at functional residual capacity. Thoracic gas volume (TGV), mean and total airway resistance (RawM and RawT), and mean and total specific airway conductance (SGawM and SGawT) were measured in a whole body pressure plethysmograph. An esophageal balloon was used to measure dynamic pulmonary compliance (Cdyn). Variabilities were defined as the standard deviation of percent changes between the first and second tests. They were 30% for VmaxFRC, 23% for tau, 12% for TGV, 20% for RawM, 35% for RawT, 25% for SGawM, 72% for SGawT, and 23% for Cdyn. All these tests are useful in assessing pulmonary function of infants with BPD; however, their variability must be taken into account when interpreting short-term changes.
We evaluated the individual and combined effects of an inhaled beta-adrenergic agent (metaproterenol) and an inhaled anticholinergic agent (atropine) on the pulmonary function of infants with bronchopulmonary dysplasia. In this randomized, double-blind study we studied 15 infants at a mean postnatal age of 15.8 weeks (range 4-28 weeks). On 4 successive days, pulmonary function tests were measured before and after a single treatment with one of the following four aerosols: placebo, metaproterenol, atropine, and combined metaproterenol and atropine. Following treatment with metaproterenol, atropine, and combined metaproterenol and atropine, airway resistance and maximal expiratory flow at functional residual capacity improved significantly when compared with baseline. Pulmonary function values returned toward baseline by 3 hours after the treatments. We found no significant differences between the effects of metaproterenol and atropine and were unable to show any synergy of the two agents.
To determine whether the high oxygen consumption VO2 in infants with bronchopulmonary dysplasia (BPD) is caused by increased mechanical power of breathing, and if improvement of pulmonary mechanics would reduce mechanical power of breathing and VO2 we gave 16 infants with oxygen-dependent BPD at 19.5 +/- 10.7 (mean +/- SD) weeks of age placebo, theophylline, and orally administered diuretics or theophylline plus diuretics. Pulmonary mechanics, mechanical power of breathing, and VO2 were measured at the beginning and end of each study period. In the placebo group, all infants had elevated VO2 (7.4 +/- 1.4 mL/kg/min) and carbon dioxide production (6.6 +/- 1.2 mL/kg/min), increased airway resistance (59 +/- 30 cm H2O/L/sec), decreased dynamic compliance (0.073 +/- 0.024 mL/cm H2O/cm), increase respiratory rate (52 +/- 11), and increased mechanical power of breathing (2.22 +/- 1.05 kg.cm/kg/min). Treatment with theophylline, diuretics, and theophylline plus diuretics resulted in a significant improvement in pulmonary mechanics and mechanical power of breathing, but not in VO2. These results suggest that the increased VO2 in infants with BPD is not secondary to increased mechanical power of breathing.
We studied the effects of orally administered theophylline and diuretics (chlorothiazide and spironolactone) on pulmonary mechanics in 16 infants with bronchopulmonary dysplasia. Their gestational age (mean +/- SD) was 28.5 +/- 3.4 weeks, and postnatal age at the time of study 19.5 +/- 10.7 weeks. The infants were randomized to two groups. Group 1 received successively placebo, theophylline, and theophylline plus diuretics; Group 2 received theophylline, placebo, and placebo plus diuretics on successive 4-day periods. Pulmonary function was measured before beginning the study (baseline) and at the end of each 4-day period. No significant changes in pulmonary function were noted after treatment with placebo. After treatment with theophylline, dynamic compliance (Cdyn) increased from baseline (mean +/- SD) 0.075 +/- 0.017 to 0.091 +/- 0.028 mL/cm H2O/cm (P less than 0.01), airway resistance (Raw) decreased from 67.19 +/- 36.71 to 41.44 +/- 22.50 cm H2O/L/sec (P less than 0.001), maximal expiratory flow at functional residual capacity (VmaxFRC) increased from 0.261 +/- 0.240 to 0.357 +/- 0.299 thoracic gas volume (TGV)/sec (P less than 0.01), and time constant decreased from 0.312 +/- 0.224 to 0.275 +/- 0.247 sec (P less than 0.02). After treatment with combined placebo and diuretics, Cdyn increased to 0.103 +/- 0.023 mL/cm H2O/cm (P less than 0.05), Raw decreased to 31.76 +/- 24.90 cm H2O/L/sec (P less than 0.001), VmaxFRC increased to 0.638 +/- 0.595 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.141 sec (P less than 0.05). After treatment with combined theophylline and diuretics, Cdyn increased to 0.118 +/- 0.017 mL/cm H2O/cm (P less than 0.001), Raw decreased to 35.98 +/- 25.85 cm H2O/L/sec (P less than 0.02), VmaxFRC increased to 0.479 +/- 0.377 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.137 sec (P less than 0.01). We conclude that theophylline and diuretics have additive effects on the improvement of pulmonary function in infants with bronchopulmonary dysplasia.
The role of theophylline in weaning infants weighing less than 1,250 g at birth from mechanical ventilation was evaluated. Infants were randomized into control or theophylline treatment groups when they required minimal ventilatory support (peak inspiratory pressure 12 cm H2O, positive end-expiratory pressure 2 cm H2O, rate 12 breaths per minute, and FiO2 less than 0.3), and they were extubated 24 hours later. Infants required reintubation if they had (1) PaCO2 greater than 55 mm Hg and pH less than 7.20, (2) FiO2 greater than 0.5, or (3) apnea associated with a heart rate less than 100 beats per minute that required frequent stimulation (more than 20 episodes during a 16-hour period). Among 32 infants (birth weight less than 1,000 g) who reached minimal ventilatory support before seven days after delivery, 13 of 18 (72%) control infants required reintubation, whereas only four of 14 (28%) theophylline-treated infants required reintubation. On the other hand, among infants (birth weight less than 1,000 g) who reached minimal ventilatory support after seven days following delivery, only one of six (17%) of the control group required reintubation and no improvement could be seen with theophylline treatment. Similarly, among control infants (birth weight 1,001 to 1,250 g), only ten of 45 (23%) required reintubation after reaching low intermittent manditory ventilation settings. In summary, most infants recovering from respiratory distress syndrome who had birth weights (1) greater than 1,000 g or (2) less than 1,000 g and who were older than seven days could be successfully extubated from minimal ventilatory support without theophylline treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
We have created a totally synthetic, protein-free surfactant (Exosurf) composed of dipalmitoylphosphatidylcholine, hexadecanol, and tyloxapol. We studied the effects of endotracheal instillation of Exosurf on survival and pulmonary function of preterm lambs delivered at 131 to 133 days gestation (term 148 days). Exosurf treatment was compared with instillation of surface-active material prepared from lung lavages of adult sheep and with no instillation. Lambs were delivered by cesarean section, paralyzed, and mechanically ventilated. The Exosurf group survived longer (80% alive at 11 hours) than did the no instillation group (30% alive at 11 hours) (P less than 0.05). There were no statistically significant differences between the Exosurf and sheep surfactant groups. We conclude that Exosurf, a synthetic surfactant, produces significant improvement in survival and pulmonary function in preterm lambs.