Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis.

OBJECTIVE: To evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial. STUDY DESIGN: Twenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5-25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age. RESULTS: Cardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted. CONCLUSIONS: In this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00724594.

Kinematic measurement of 12-week head control correlates with 12-month neurodevelopment in preterm infants.

BACKGROUND: Although new interventions treating neonatal brain injury show great promise, our current ability to predict clinical functional outcomes is poor. Quantitative biomarkers of long-term neurodevelopmental outcome are critically needed to gauge treatment efficacy. Kinematic measures derived from commonly used developmental tasks may serve as early objective markers of future motor outcomes. AIM: To develop reliable kinematic markers of head control at 12week corrected gestational age (CGA) from two motor tasks: head lifting in prone and pull-to-sit. STUDY DESIGN AND SUBJECTS: Prospective observational study of 22 preterm infants born between 24 and 34weeks of gestation. OUTCOME MEASURES: Bayley Scales of Infant Development III (Bayley) motor scores. RESULTS: Intrarater and interrater reliability of prone head lift angles and pull-to-sit head angles were excellent. Prone head lift angles at 12week CGA correlated with white matter NAA/Cho, concurrent Test of Infant Motor Performance (TIMP) scores, and 12-month Bayley motor scores. Head angles during pull-to-sit at 12-week CGA correlated with TIMP scores. CONCLUSIONS: Poor ability to lift the head in prone and an inability to align the head with the trunk during the pull-to-sit task were associated with poorer future motor outcome scores. Kinematic measurements of head control in early infancy may serve as reliable objective quantitative markers of future motor impairment and neurodevelopmental outcome.

Identifying premature infants at high and low risk for motor delays using motor performance testing and MRS.

PURPOSE: To determine specific motor skills in premature infants, match those that correlate with standards tests of motor performance, and MRS measures of abnormal brain biochemistry. METHODS: Prospective cohort study of preterm infants (n=22). Infant motor assessments were completed at term and 12 weeks corrected gestational age (CGA) using the Test of Infant Motor Performance (TIMP) and Bayley Scales of Infant and Toddler Development-III at 12 months CGA. Infants (n=12) received MRS scans at term CGA. Rasch analysis and MRS findings investigated TIMP items well targeted to high and low risk infants. RESULTS: A 10 item subset of motor skill items correlated strongly with full 42-item TIMP at term and 12 week testing (r> 0.90, p< 0.001 for both), and with Bayley gross motor scores. MRS metabolites in basal ganglia correlated significantly with both TIMP and 10 item motor tests at term, while frontal white matter metabolites correlated with TIMP and 10 item tests at 12 weeks and Bayley motor scores. CONCLUSION: A short motor skill assessment may be representative of a longer standardized test and relate to brain metabolic function in key areas for motor movement and development. Validation of a shortened assessment may improve early identification of high-risk preterm infants.

Utility of computed tomographic angiography in the pre-operative planning for initial and repeat congenital cardiovascular surgery.

OBJECTIVE: To investigate the utility of computed tomographic angiography as an adjunctive imaging modality before congenital cardiac surgery. DESIGN: We evaluated 33 patients who underwent a pre-operative computed tomographic angiogram. They were classified according to the anatomic site of repair. Post-operatively, the surgeon completed a questionnaire assessing the utility of the study. RESULTS: Computed tomographic angiography was found to be either "essential" or "very useful" for pre-operative planning in 94% of the patients. Specifically, the scan was consistently useful for procedures involving the aorta (14/15, 93%) or the pulmonary veins (4/4, 100%) and obviated pre-operative catheterisations in 14 patients (42%). Furthermore, when compared with other diagnostic groups, computed tomographic angiography determined the need for peripheral cannulation in patients undergoing re-operations (6/7; 86%, p = 0.02). CONCLUSIONS: Computed tomographic angiography was found to be useful in the pre-operative planning of virtually all patients undergoing repair of congenital cardiac malformations, regardless of diagnosis. Specifically, the studies were essential in select populations, such aortic arch or pulmonary vein repairs, and helped to determine cannulation sites for repeat operations while significantly reducing the need for invasive imaging.

Pediatric cardiovascular CT angiography: radiation dose reduction using automatic anatomic tube current modulation.

OBJECTIVE: The purpose of this study was to assess the effect of weight-based scanning protocols and automatic tube current modulation on the tube current-time product and image quality at pediatric cardiovascular 64-MDCT angiography. MATERIALS AND METHODS: Our pediatric cardiovascular 64-MDCT protocols use a weight-based algorithm to determine nominal tube voltage settings with 80, 100, and 120 kV. Automatic tube current modulation was used for each case. The mAs, volume CT dose index (CTDI(vol)), and dose-length product (DLP) values were recorded and the effective dose calculated. On the basis of the selected nominal tube current, the dose values that would have been delivered without tube current modulation were also calculated. Scans were compared with 16-MDCT using 120 kVp and 120 mAs. Two radiologists independently rated image quality on a 5-point scale. Image noise was objectively measured within four different regions of interest. Findings at CT were clinically correlated with results of cardiac sonography, angiography, or surgery. RESULTS: Thirty-eight 64-MDCT and 30 16-MDCT scans were evaluated. Mean diagnostic quality for 64-MDCT was rated at 3.6 +/- 0.4 and mean image noise was 8.9 +/- 4.5 H. Results with 16-MDCT were not significantly different: diagnostic quality (3.6 +/- 0.4; p = 0.97) and image noise (9.1 +/- 2.8 H; p = 0.31). Scanning with automatic tube current modulation significantly (p < 0.05) reduced the tube current time-product compared with scanning without automatic tube current modulation (-57.8%/54.1/128 mAs) or with 16-MDCT (-47.9%/54.1/104.37 mAs), respectively. The mAs values were significantly (p < 0.05) lower for 80 kVp than for 100 or 120 kVp scans, but image quality and image noise were not significantly (p = 0.24) different. Agreement between MDCT and clinical findings was excellent. CONCLUSION: Under simulated conditions, automatic tube current modulation combined with low tube voltage settings significantly reduced radiation exposure and thus appears preferable in pediatric cardiovascular 64-MDCT.

Pediatric superior vena cava syndrome: assessment at low radiation dose 64-slice CT angiography.

We report a case of an 8-year-old boy with a history of aortopexy for aortic compression and multiple venous thrombosis. A 64-slice multidetector-row computed tomography examination was performed to evaluate the cause of esophageal varices and the extent of previously reported thrombi. Despite extremely low radiation dose settings, the 64-slice computed tomography angiography was fully diagnostic and showed discontinuity of the superior vena cava and brachiocephalic veins. In addition, the azygous system and large collateral vessels across the anterior, medial, and posterior mediastinum and chest wall were observed. This case shows that in pediatric patients complicated vascular pathology can reliably be assessed and radiation exposure can be safely minimized.

Hypoventilation improves oxygenation after bidirectional superior cavopulmonary connection.

OBJECTIVE: Bidirectional superior cavopulmonary connection may be complicated by systemic hypoxemia. Previous work has shown that hyperventilation worsens systemic oxygenation in patients after bidirectional superior cavopulmonary connection. The likely mechanism is that hyperventilation-induced hypocarbia decreases cerebral, superior vena caval, and pulmonary blood flow. The aim of the current study was to determine whether the converse approach, hypoventilation, improves oxygenation after bidirectional superior cavopulmonary connection. METHODS: This is a prospective, patient-controlled study of 15 patients (median age 8.0 months, range 4.7-15.5) who underwent bidirectional superior cavopulmonary connection. Patients were studied in the intensive care unit, within 8 hours of surgery, while sedated, paralyzed, and mechanically ventilated. To avoid acidosis during hypoventilation, sodium bicarbonate was administered before hypoventilation. Cerebral blood flow velocity was measured by transcranial Doppler sonography of the middle cerebral artery. RESULTS: Hypoventilation following administration of sodium bicarbonate (pH-buffered hypoventilation) produced hypercarbia (mean Pco(2) = 58 mm Hg versus 42 mm Hg at baseline). During hypoventilation, there were significant increases in both mean arterial Po(2) (from 50 mm Hg at baseline to 61 mm Hg; P <.05) and mean systemic oxygen saturation (from 86% at baseline to 90%; P <.05). These increases occurred despite accompanying, small increases in pulmonary artery pressure and transpulmonary gradient. Hypoventilation also produced an increase in mean cerebral blood flow velocity (from 37 cm/s at baseline to 55 cm/s; P <.05) and a decrease in the arteriovenous oxygen saturation difference across the upper body (from 33% at baseline to 23%; P <.05), consistent with increased cerebral blood flow. CONCLUSIONS: This study demonstrates that hypoventilation improves systemic oxygenation in patients after bidirectional superior cavopulmonary connection. The likely mechanism for this effect is that hypoventilation-induced hypercarbia decreases cerebral vascular resistance, thus increasing cerebral, superior vena caval, and pulmonary blood flow. Hypoventilation may be a useful clinical strategy in patients who are hypoxemic in the early postoperative period after bidirectional superior cavopulmonary connection.

Sodium nitroprusside infusion after bidirectional superior cavopulmonary connection: preserved cerebral blood flow velocity and systemic oxygenation.

OBJECTIVE: Systemic hypertension is common in patients after bidirectional superior cavopulmonary connection. It can be treated with a vasodilator, such as sodium nitroprusside. However, it is possible that systemic hypertension is necessary to maintain cerebral blood flow in the face of cerebral venous hypertension. Furthermore, bidirectional superior cavopulmonary connection places the cerebral and pulmonary vascular beds in series. Thus treatment of systemic hypertension by lowering blood pressure might decrease cerebral blood flow, pulmonary blood flow, and systemic oxygen levels. The aim of the current study was to determine the effects of sodium nitroprusside on cerebral blood flow velocity and systemic oxygenation in patients after bidirectional superior cavopulmonary connection. METHODS: This is a prospective patient-controlled study of 9 patients (median age, 7 months; age range, 4 to 12 months) undergoing bidirectional superior cavopulmonary connection. Patients were studied in the intensive care unit within 6 hours of surgical intervention while sedated, paralyzed, and mechanically ventilated. Sodium nitroprusside was infused to achieve a decrease in mean systemic blood pressure of approximately 20%. Cerebral blood flow velocity was measured by means of transcranial Doppler ultrasonography of the middle cerebral artery. RESULTS: During sodium nitroprusside infusion, mean systemic blood pressure decreased (from 69 +/- 6 mm Hg at baseline to 58 +/- 6 mm Hg, P <.05). However, there was no accompanying change in 2 indicators of cerebral blood flow: blood flow velocity in the middle cerebral artery and arteriovenous oxygen saturation difference across the upper body. Both arterial Po(2) and systemic oxygen saturation were also preserved during sodium nitroprusside infusion. CONCLUSIONS: Sodium nitroprusside decreases systemic blood pressure in patients after bidirectional superior cavopulmonary connection. This decrease occurs without accompanying changes in cerebral blood flow velocity or systemic oxygen levels. These findings suggest that cerebral and pulmonary blood flows are preserved during sodium nitroprusside infusion. Sodium nitroprusside appears to be an appropriate agent for the treatment of systemic hypertension after bidirectional superior cavopulmonary connection.