Variation and comparative effectiveness of patent ductus arteriosus pharmacotherapy in extremely low birth weight infants.

BACKGROUND: Patent ductus arteriosus (PDA) occurs in 70% of extremely low birth weight (ELBW, birth weight <1000 g) infants. Approximately 34% of ELBW infants with a PDA have spontaneous closure. Failure of the ductus arteriosus to close has been associated with multiple morbidities. OBJECTIVE: To examine variability over time and across hospitals in early therapeutic (2-7 day) use of indomethacin (INDO) vs ibuprofen (IBU) for PDA treatment in outborn ELBW infants and examine the outcomes and side effects of both pharmacological agents in this population. METHODS: Data were extracted from the Pediatric Health Information System. ELBW infants born between January 1, 2007 and December 31, 2010 and admitted on day of life 0 were eligible for inclusion. 732 infants had a PDA diagnosis and met inclusion criteria. We explored the variability in PDA pharmacotherapy over time and across hospitals. We compared outcomes of both agents for in-hospital mortality, need for surgical ligation, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leukomalacia, renal failure, and persistent pulmonary hypertension. Statistical methods included chi square and multivariable regression analysis. Instrumental variable analysis was used to control for selection bias and omitted variables. RESULTS: There was large variability in PDA pharmacotherapy over time and across hospitals. INDO use declined as IBU use grew from 12.8 to 38.9%. There was no difference in hospital or NICU characteristics between high and low IBU using NICUs. Renal failure was more common in infants receiving INDO compared to IBU. CONCLUSION: We noted large variability in PDA pharmacotherapy. Renal failure was more common with INDO use. Until further studies to compare the long-term effects of both drugs, our data support IBU as the preferred medication for PDA pharmacotherapy in ELBW infants.

The ontogeny of cerebrovascular pressure autoregulation in premature infants.

OBJECTIVE: To quantify cerebrovascular autoregulation as a function of gestational age (GA) and across the phases of the cardiac cycle. STUDY DESIGN: The present study is a hypothesis-generating re-analysis of previously published data. Premature infants (n=179) with a GA range of 23 to 33 weeks were monitored with umbilical artery catheters and transcranial Doppler insonation of the middle cerebral artery for 1-h sessions over the first week of life. Autoregulation was quantified by three methods, as a moving correlation coefficient between: (1) systolic arterial blood pressure (ABP) and systolic cerebral blood flow (CBF) velocity (Sx); (2) mean ABP and mean CBF velocity (Mx); and (3) diastolic ABP and diastolic CBF velocity (Dx). Comparisons of individual and cohort cerebrovascular pressure autoregulation were made across GA for each aspect of the cardiac cycle. RESULTS: Systolic, mean and diastolic ABP increased with GA (r=0.3, 0.4 and 0.4; P<0.0001). Systolic CBF velocity was pressure-passive in infants with the lowest GA, and Sx decreased with advancing GA (r=-0.3; P<0.001), indicating increased capacity for cerebral autoregulation during systole during development. By contrast, Dx was elevated, indicating dysautoregulation, in all subjects and showed minimal change with advancing GA (r=-0.06; P=0.05). Multivariate analysis confirmed that both GA (P<0.001) and 'effective cerebral perfusion pressure' (ABP minus critical closing pressure (CrCP); P<0.01) were associated with Sx. CONCLUSION: Premature infants have low and usually pressure-passive diastolic CBF velocity. By contrast, the regulation of systolic CBF velocity by pressure autoregulation developed in this cohort between 23 and 33 weeks GA. Elevated effective cerebral perfusion pressure derived from the CrCP was associated with dysautoregulation.

Impaired white matter development in extremely low-birth-weight infants with previous brain hemorrhage.

BACKGROUND AND PURPOSE: Brain hemorrhage is common in premature infants. The purpose of the study is to evaluate white matter development in extremely low-birth-weight infants with or without previous brain hemorrhage. MATERIALS AND METHODS: Thirty-three extremely low-birth-weight infants were prospectively enrolled and included in this institutional review board-approved study. Another 10 healthy term infants were included as controls. The medical records of the extremely low-birth-weight infants were reviewed for sonography diagnosis of intraventricular hemorrhage. All infants had an MR imaging examination at term-equivalent age for detection of previous hemorrhage, and their white matter was scored and compared among different groups. DTI measured fractional anisotropy values were also compared voxelwise by tract-based spatial statistics. RESULTS: Compared with controls, the white matter score was not significantly different in extremely low-birth-weight infants without blood deposition on MR imaging (P = .17), but was significantly worse in extremely low-birth-weight infants with blood deposition on MR imaging but no intraventricular hemorrhage diagnosis by sonography (P = .02), in extremely low-birth-weight infants with grade 1 or 2 intraventricular hemorrhage on sonography (P = .003), and in extremely low-birth-weight infants with grade 3 or 4 intraventricular hemorrhage on sonography (P = .0001). Extremely low-birth-weight infants without blood deposition on MR imaging did not show any white matter regions with significantly lower fractional anisotropy values than controls. Extremely low-birth-weight infants with blood deposition on MR imaging, but no intraventricular hemorrhage diagnosis, did show white matter regions with significantly lower fractional anisotropy values, and extremely low-birth-weight infants with intraventricular hemorrhage diagnosis had widespread white matter regions with lower fractional anisotropy values. CONCLUSIONS: Previous brain hemorrhage is associated with abnormal white matter in extremely low-birth-weight infants at term-equivalent age, and sonography is not sensitive to minor hemorrhages that are sufficient to cause white matter injury.

Observational study of cerebral hemodynamics during dopamine treatment in hypotensive ELBW infants on the first day of life.

OBJECTIVE: To evaluate cerebral hemodynamics during dopamine treatment in hypotensive (mean arterial blood pressure (MABP)

The effects of closed tracheal suctioning plus volume guarantee on cerebral hemodynamics.

OBJECTIVE: To compare the effects of open tracheal suctioning (OS) plus intermittent mandatory ventilation (IMV) vs. closed tracheal suctioning (CS) plus volume guarantee ventilation (VG) on changes in mean cerebral blood-flow velocity (CBFv) of ventilated very low birth weight (VLBW) infants. STUDY DESIGN: A total of 75 normotensive, ventilated VLBW infants (with normal cranial ultrasounds) had monitoring of mean CBFv, PCO2 and mean arterial blood pressure (MABP) before, during and after 220 tracheal suctioning sessions during the first week of life. Multiple linear regression analysis was used to determine the factor(s) influencing the magnitude of relative changes from baseline in mean CBFv after suctioning. RESULT: In all, 49 VLBW infants receiving IMV had monitoring during 124 OS sessions between July 2002 and May 2005; 26 VLBW infants receiving VG had monitoring during 96 CS sessions between January 2006 and July 2007. The average magnitude of relative changes in mean CBFv was significantly less with CS+VG, and was associated with the magnitude of relative changes in PCO2 and suctioning-ventilator group. CONCLUSION: The average magnitude of relative changes in mean CBFv was reduced in VLBW infants with CS+VG vs. OS+IMV.

Tracheal suctioning is associated with prolonged disturbances of cerebral hemodynamics in very low birth weight infants.

OBJECTIVES: Examining the effects of tracheal suctioning on cerebral hemodynamics of normotensive ventilated very low birth weight (VLBW) infants with normal cranial ultrasounds; determining the factor(s) influencing changes in mean cerebral blood flow velocity (CBFv) after suctioning. METHODS: Seventy-three VLBW infants had continuous monitoring of mean arterial blood pressure (MABP), PaCO(2), PaO(2) and mean CBFv before, during, and after 202 suctioning sessions during the first week of life. Peak (or nadir) and relative changes of the four variables for 45 min after suctioning were calculated. Multiple linear regression was used to determine the factor(s) influencing changes in mean CBFv after suctioning. RESULT: Birth weight was 928+/-244 g; gestational age was 27.0+/-2.0 weeks. Mean CBFv increased to 31.0+/-26.4% after suctioning and remained elevated for 25 min. PaCO(2) was highly associated with mean CBFv (P<0.001), whereas MABP and PaO(2) were not. CONCLUSION: We observed prolonged increases of mean CBFv following suctioning in ventilated VLBW infants that were previously unrecognized. This is concerning since disturbances of CBF may be associated with subsequent brain injury.

Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants.

OBJECTIVE: To examine whether hypercapnia in very low birth weight (VLBW) infants during the first 3 days of life is associated with severe intraventricular hemorrhage (IVH). STUDY DESIGN: Retrospective cohort study of inborn VLBW infants between January 1999 and May 2004 with arterial access during the first 3 days of life. A multiple logistic regression analysis was used where IVH was dichotomized ((grades 0/1/2) = non-severe; (grades 3/4) = severe). Measures of hypercapnia were entered into the model to ascertain their association with severe IVH. RESULTS: In total, 574 VLBW infants met entry criteria. Worst IVH grade was 0 in 400; 1: 54; 2: 42; 3: 47; and 4: 31 infants. The logistic regression model consisted of the following predictors of severe IVH: gestational age, gender, 1 min Apgar score (dichotomized into two groups: >3 vs < or =3), multifetal gestation, vasopressor use, and maximum PaCO(2). CONCLUSION: In addition to traditional risk factors, it appears maximum PaCO(2) is a dose-dependent predictor of severe IVH during the permissive hypercapnia era.

Laparoscopic management of a large ovarian cyst in an adolescent. A case report.

BACKGROUND: The safety of laparoscopic management of benign ovarian cysts has been demonstrated. The size of the benign ovarian cyst continues to be a limiting factor for laparoscopic surgery, with most surgeons choosing laparotomy for large cysts. CASE: A 15-year-old woman had a 22-cm, benign ovarian cyst extending above the umbilicus that was managed successfully with laparoscopy. We performed prelaparoscopy cyst drainage with a suprapubic Bonanno catheter (Becton Dickinson, Rutherford, New Jersey) followed by laparoscopic cystectomy. Because of its coiled end, the Bonanno catheter is less likely to result in cyst leakage around the aspiration site. CONCLUSION: With proper patient selection, laparoscopic surgery can be safely applied in a select group of patients with large, benign ovarian cysts.

A population-based study of congenital diaphragmatic hernia: impact of associated anomalies and preoperative blood gases on survival.

BACKGROUND/PURPOSE: Although neonatal care has improved over the past 20 years, mortality rate with congenital diaphragmatic hernia (CDH) remains 50% to 60%, possibly reflecting differences in management or selection biases. The authors determined the incidence, outcome, effect of coexisting anomalies, and prognostic indicators for neonates with CDH in a single inborn population older than 13 years. METHODS: Forty-three neonates with CDH, those symptomatic within the first 6 hours of life, were identified using a validated neonatal database and diagnosis coding data from medical records among 180,643 live inborn neonates delivered at Parkland Memorial Hospital between 1983 and 1995. Charts were reviewed for prenatal history, demographic variables, presence of coexisting malformations, preoperative arterial blood gases, surgical findings, and outcome. Survival to hospital discharge was the primary outcome variable. RESULTS: The incidence of CDH was 1 in 4,200 live births; overall survival rate was 51%. Thirty-two (74%) neonates underwent surgical repair, often at less than 8 hours of life; postoperative mortality rate was 31%. Eighteen (42%) had coexisting major anomalies or chromosomal abnormalities. Eighty percent of neonates with isolated CDH survived, whereas 89% with CDH and associated defects died. Nonsurvivors had lower birth weights and Apgar scores, were more acidotic, and had more severe respiratory compromise. When best preoperative pH was > or = 7.25 or PaCO2 < or = 50 mm Hg, 80% of neonates survived. CONCLUSION: In this inborn population-based review of neonatal CDH between 1983 and 1995, the best predictors of survival were the presence or absence of other anomalies and the best preoperative PaCO2 and pH.

Transvaginal ultrasonographic diagnosis of uterine septa.

OBJECTIVE: To ascertain the sensitivity of transvaginal ultrasound as a screening tool in diagnosing patients with uterine septa. STUDY DESIGN: In this descriptive, retrospective study, the medical records of all patients who had hysteroscopic resection of uterine septa between 1990 and 1996 were reviewed. Specific preoperative imaging techniques were noted, and the sensitivity of transvaginal ultrasonography in correctly identifying the septum was calculated. RESULTS: During the seven-year period, 27 of 39 total patients undergoing hysteroscopic metroplasty had preoperative transvaginal ultrasonography. Twenty-two of the 27 ultrasonograms correctly identified the uterine septum, for a sensitivity of 81%. CONCLUSION: This was the largest study to date that specifically assessed the sensitivity of transvaginal ultrasonography as a reliable method of diagnosing uterine septa. It appears justifiable to use it as the initial screening tool for an accurate evaluation of uterine septa.

Differential development of umbilical and systemic arteries. I. ANG II receptor subtype expression.

In fetal sheep umbilical responses to angiotensin II (ANG II) exceed those by systemic vasculature. Two ANG II receptors (AT) exist, AT1 and AT2, but only AT1 mediates vasoconstriction in adult tissues. Thus differences in reactivity could reflect differences in subtype expression. Using competitive radioligand binding assays, we demonstrated AT1 predominance in umbilical arteries and AT2 in femoral arteries. Steady-state responses to intravenous ANG II (0.229-1.72 micrograms/min) were studied in 16 fetuses with umbilical and/or femoral artery flow probes without and with local AT1 (L-158,809) or AT2 (PD-123319) blockade. ANG II dose dependently (P < 0.001) increased umbilical resistance more than arterial pressure (MAP) while decreasing umbilical blood flow. Femoral vascular resistance also increased dose dependently (P = 0.02), but responses were less than umbilical (P = 0.0001) and paralleled increases in MAP; blood flow was unaffected. Cumulative local doses of L-158,809 (125 micrograms) inhibited all responses (P < 0.001); however, 1,000 micrograms of the AT2 antagonist had no effect. Plasma renin activity (PRA) was unaltered by local AT1 blockade, whereas PRA doubled (P = 0.001) after systemic infusion of only 50 micrograms of the AT1 antagonist and remained elevated. Differences in umbilical and femoral vascular responses to ANG II are in large part due to differences in AT subtype expression. Furthermore, in fetal sheep the ANG II negative feedback on PRA is mediated by AT1 receptors, and it is substantially more sensitive to receptor blockade than the vasculature.

Thyroid hormone action on glucose transporter activity in astrocytes.

In astrocytes from rat brain cultured in thyroid hormone-deficient media cytochalasin B-binding was decreased 80%; addition of L-T3 increased binding to 75% of control levels. Saponin-treatment of controls increased accessibility of binding sites to 60% above untreated cells. Saponin also increased binding in deficient cells; however, the level was less than in treated controls, suggesting L-T3 deficiency decreases total glucose transporters. Addition of L-T3 appeared to convert most (90%) of the binding sites from unavailable to accessible status. Changes in binding to plasma membranes in response to L-T3 level were similar to those in intact cells. No binding to Golgi was detectable, thus no evidence for translocation of carriers was obtained. L-T3 may activate the glucose transporter by increasing its accessibility in brain cells.