Kris Arheart

Indomethacin reduces the risks of severe intraventricular hemorrhage

A prospective, random selection, double-blind clinical trial was carried out to determine the efficacy of indomethacin in preventing periventricular-intraventricular hemorrhage (PV-IVH). Babies who were born in our institution, had birth weights less than or equal to 1500 gm, and had no PV-IVH or grade 1 PV-IVH were given either placebo (n = 70) or indomethacin (n = 71), 0.2 mg/kg intravenously at 6 hours of age and 0.1 mg/kg at 18 and 30 hours. Two major outcomes were determined: the development of grades 2 to 4 PV-IVH and the development of severe PV-IVH (i.e., hemorrhages with blood filling greater than 50% of the ventricles and in some cases with associated parenchymal echodensities). Grades 2 to 4 PV-IVH occurred in 16 (23%) of the indomethacin group and 27 (39%) of the placebo group (p less than 0.03). The incidence of severe PV-IVH was 3% in the indomethacin-treated babies and 14% in the control group (p less than 0.02). The influence of other perinatal factors on the incidence of grades 2 to 4 or severe PV-IVH was determined by stepwise logistic regression. Placebo use, early grade 1 PV-IVH, lower birth weight, and higher fraction of inspired oxygen at 6 hours of life were associated with higher estimated odds of the development of grades 2 to 4 PV-IVH. Placebo use, male gender, lower 5-minute Apgar score, and a large base deficit were predictive of severe PV-IVH. Estimated odds ratios of severe PV-IVH with placebo use and male gender were 11.25:1 and 9:1, respectively. Thus indomethacin prophylaxis reduced the relative risk of grades 2 to 4 PV-IVH and severe PV-IVH, but other perinatal variables contributed significantly to the overall risk of PV-IVH.

Frequent handling in the neonatal intensive care unit and intraventricular hemorrhage

The association between periventricular-intraventricular hemorrhage (PV-IVH) and frequent handling resulting from various neonatal intensive care procedures and routine interventions was evaluated in a prospective clinical study. Inborn premature babies with birth weight less than or equal to 1500 gm (n = 156) who did not have PV-IVH or who had grade 1 PV-IVH at less than or equal to 1 hour were randomly assigned to the reduced manipulation protocol (n = 62) or to standard care (n = 94). A bedside microcomputer-based data acquisition system was used to monitor the duration of rest or the number of interventions per day. Infants assigned to receive reduced manipulation spent a significantly higher percentage of time each day at rest than did those who received standard manipulation (p less than 0.006). However, the incidence of grades 2 to 4 PV-IVH did not differ significantly (30% in the study vs 37% in the standard manipulation group). When we analyzed the effect of manipulation in relation to risk of PV-IVH, while taking into account other perinatal variables, standard manipulation was not associated with increased risk of grades 2 to 4 PV-IVH. However, low birth weight, maternal smoking, general anesthesia, early grade 1 PV-IVH, low hematocrit, lowest arterial oxygen pressure within the first 6 hours of life, and large base deficit at 6 hours of age all increased the relative risk of grades 2 to 4 PV-IVH.

Controlled supplemental oxygenation during tracheobronchial hygiene

The effect of controlled supplemental oxygenation without bag ventilation on transcutaneous partial pressure of oxygen (TcPO2) measurements during tracheobronchial hygiene was evaluated. Procedure A, no supplemental oxygenation, was compared to Procedure B, in which controlled supplemental oxygenation was used. For controlled supplemental oxygenation, the FiO2 was increased until TcPO2 measurements rose to levels between 90 and 100 torr. Sixteen premature infants who required mechanical ventilation were studied in the neonatal center. Both procedures were performed on each patient in random order. In both procedures, a precipitous decrease in TcPO2 was observed during chest vibration, and further decrease in TcPO2 was noted with endotracheal suctioning. Except for baseline readings, throughout the tracheobronchial hygiene TcPO2 measurements were significantly higher and more subjects maintained TcPO2 values greater than 40 torr in Procedure B. In Procedure A corresponding TcPO2 measurements were 40 torr or less. Mean recovery time was shorter in Procedure B, 2.1 ± 2.3 minutes, than in Procedure A, 4.9 ± 2.8 minutes, p < .003. Thus, in most patients, controlled supplemental oxygenation without manual bag ventilation seems sufficient to prevent hypoxia during tracheobronchial hygiene; it also shortens recovery time from hypoxemia as a result of the bronchopulmonary hygiene procedure.

Early and late intraventricular hemorrhage: The role of obstetric factors

Objective: To evaluate the influence of active phase labor and other obstetric factors on the development of periventricular- intraventricular hemorrhage in the neonate. Methods: A total of 230 infants were studied. Antenatal enrollment was carried out when estimated fetal weight was 1750 g or less. Serial head ultrasound scans were performed to screen for periventricular-intraventricular hemorrhage, with the initial scan performed within minutes of birth. Scan findings and obstetric and neonatal variables collected prospectively at scheduled intervals were analyzed to determine the significant factors that predispose to intraventricular hemorrhage. Results: In 47 infants (20%), intraventricular hemorrhage was detected within 1 hour of birth (early) and in another 49 (21%) at a later age (late). The overall incidence of hemorrhage was similar between vaginal and cesarean deliveries (41 and 44%, respectively). Early hemorrhage was more frequent in vaginal (28%) than cesarean deliveries (11%), whereas late hemorrhage was more frequent in cesarean deliveries. When the role of delivery mode and labor was analyzed by stepwise logistic regression, the odds ratios for development of early intraventricular hemorrhage increased in the following order: cesarean delivery with no labor, cesarean delivery with latent phase labor, vaginal delivery with forceps use, cesarean delivery with active phase labor, and vaginal delivery without forceps use. For late hemorrhage, the odds ratios increased in the following order: vaginal delivery with forceps, vaginal delivery without forceps, cesarean delivery with no labor, cesarean delivery with latent phase labor, and cesarean delivery with active phase labor. Conclusions: Active phase labor may predispose to early periventricular-intraventricular hemorrhage, but its influence may be attenuated by use of forceps or by abdominal delivery. The protective effect of forceps remains for late periventricular-intraventricular hemorrhage, but abdominal delivery does not seem to protect against late hemorrhage.

Chronic Prenatal Exposure to Cocaine Alters Cerebrovascular Responses in Newborn Pigs

Maternal cocaine abuse may increase the incidence of perinatal asphyxia. In nonexposed asphyxiated neonates, decreased cerebrospinal fluid (CSF) cAMP concentrations are associated with poor neurological outcome. On the other hand, cocaine increases central nervous system (CNS) cAMP. Therefore, we hypothesized that in utero cocaine exposure may increase brain cAMP and thereby preserve cerebrovascular responses to cAMP-dependent stimuli following asphyxia. Pregnant pigs received either cocaine (1 mg/kg, iv) twice weekly during the last trimester or normal saline vehicle (sham-control) and were allowed to deliver vaginally at term. Cranial windows were implanted in the newborn pigs within the first week of life and used to collect CSF for cAMP determinations and to assess changes in pial arteriolar diameters (PAD). In the first part of the study, pial arteriolar responses to different vasodilator and vasoconstrictor stimuli were evaluated in piglets prior to asphyxia (n = 20). In newborn pigs exposed to cocaine, cerebrovascular responses to hypercapnia and norepinephrine were significantly exaggerated compared to controls. Then, piglets were randomly selected for the second part of the study that involved prolonged asphyxia (n = 12). In cocaine-exposed but not sham-control piglets, CSF cAMP increased markedly during asphyxia. In the sham piglets, but not the cocaine-exposed piglets, CSF cAMP fell progressively below the base-line during recovery. Cerebrovascular reactivity to cAMP-dependent stimuli (hypercapnia and isoproterenol) was preserved during recovery from asphyxia in the cocaine-exposed piglets but significantly attenuated in the sham controls. We conclude that piglets with chronic prenatal exposure to cocaine show exaggerated cerebrovascular responses to vasogenic stimuli and preserved cAMP-dependant cerebral vasoreactivity following asphyxia.