The effects of sodium bicarbonate infusion on cerebrovascular function in newborn pigs.

BACKGROUND: Sodium bicarbonate (NaHCO3) is no longer recommended by the Neonatal Resuscitation Program (NRP), but is still being used by some neonatologists. The effects of NaHCO3 on cerebral hemodynamics are unclear. Therefore, we investigated the effects of NaHCO3 on cerebral blood flow (CBF) and cerebrovascular function using a newborn piglet model. METHODS: Newborn pigs were anesthetized, intubated, and ventilated. Cranial windows were implanted to evaluate changes in pial arteriolar diameters (PADs) as a surrogate for CBF during a 4-h intravenous infusion of 3% NaHCO3. Cerebrovascular reactivity to vasodilators and vasoconstrictors was investigated during vehicle control and during NaHCO3 infusion. RESULTS: NaHCO3 infusion caused significant and progressive pial arteriolar vasoconstrictions. During NaHCO3 infusion, cerebrovascular reactivity was preserved. Adding vasodilators decreased cerebral vasoconstriction, while adding vasoconstrictors exaggerated cerebral vasoconstriction. CONCLUSIONS: Intravenous infusion of NaHCO3 over 4 h caused progressive vasoconstriction of pial arterioles. Cerebrovascular function evaluated by the responses of pial arterioles to physiologically relevant vasoconstrictors and vasodilators was preserved during NaHCO3 infusion. A notable additional reduction of PADs was observed during NaHCO3 infusion in the presence of vasoconstrictors. Extrapolating our findings to human neonates should alarm the clinicians that using NaHCO3 in neonates may cause cerebral hypoperfusion. IMPACT: Cerebral vasoconstriction occurs during slow infusion of 3% diluted NaHCO3. Cerebral vasoconstriction is exaggerated when another vasoconstrictor is added during NaHCO3 infusion. Cerebrovascular function is preserved during NaHCO3 infusion. Clinicians should be aware of the risk of cerebral hypoperfusion with NaHCO3 infusion in vulnerable neonates.

Role of Transcatheter patent ductus arteriosus closure in extremely low birth weight infants.

BACKGROUND: Patent ductus arteriosus (PDA) is common in extremely low birth weight (ELBW) infants. The objectives of this study were to describe our early clinical experience of transcatheter PDA closure (TCPC) in ELBW infants, compare outcomes with surgical ligation of PDA (SLP), and identify risk factors for prolonged respiratory support. METHODS: A retrospective review was performed comparing infants born <27 weeks, weighing <1 kg at birth and < 2 kg during TCPC with 2:1 propensity-score matched group of infants that underwent SLP. Change in respiratory severity scores (RSS) immediately post-procedure and the time taken for return to pre-procedure RSS for TCPC versus SLP was compared. Factors contributing to prolonged elevation of RSS were identified. RESULTS: Eighty ELBW infants (median procedure weight: 1060 [range 640-2000] grams) that underwent successful TCPC were compared with 40 infants that underwent SLP (procedure weight 650-1760 g). There was greater increase in RSS following SLP compared to TCPC (76% vs. 18%; P < 0.01). It took longer for RSS to return to pre-procedural scores post-SLP compared to post-TCPC (28 vs. 8.4 hr; P < 0.01). Elevated pulmonary artery pressure (PAP) and TCPC at >8 weeks of age were associated with prolonged (>30-days) elevation of RSS ≥ 1 (OR = 5.4, 95%CI: 2.2-9.4, P < 0.01 and OR = 2.86, 95%CI: 1.5-4.2, P = 0.05 respectively). Overall complication rate for TCPC was 3.7%. CONCLUSIONS: TCPC is feasible in infants as small as 640-2000 g and can be performed safely in the majority. TCPC may offer faster weaning of respiratory support compared to SLP when performed earlier in life, and before the onset of elevated PAP.

Does prolonged severe hypercapnia interfere with normal cerebrovascular function in piglets?

BACKGROUND: Hypercapnia causes cerebral vasodilation and increased cerebral blood flow (CBF). During prolonged hypercapnia it is unknown whether cerebral vasodilation persists and whether cerebrovascular function is preserved. We investigated the effects of prolonged severe hypercapnia on pial arteriolar diameters (PAD) and cerebrovascular reactivity to vasodilators and vasoconstrictors. METHODS: Piglets were anesthetized, intubated and ventilated. Closed cranial windows were implanted to measure PAD. Changes in PAD were documented during hypercapnia (PaCO2 75-80 mm Hg). Cerebrovascular reactivity was documented during normocapnia and at 30, 60, and 120 min of hypercapnia. RESULTS: Cerebral vasodilation to hypercapnia was sustained over 120 min. Cerebrovascular responses to vasodilators and vasoconstrictors were preserved during hypercapnia. During hypercapnia, vasodilatory responses to second vasodilators were similar to normocapnia, while exposure to vasoconstrictors caused significant vasoconstriction. CONCLUSIONS: Prolonged severe hypercapnia causes sustained vasodilation of pial arteriolar diameters indicative of hyperperfusion. During hypercapnia, cerebral vascular responses to vasodilators and vasoconstrictors were preserved, suggesting that cerebral vascular function remained intact. Of note, cerebral vessels during hypercapnia were capable of further dilation when exposed to additional cerebral vasodilators and, significant vasoconstriction when exposed to vasoconstrictors. Extrapolating these findings to infants, we suggest that severe hypercapnia should be avoided, because it could cause/increase cerebrovascular injury.

Effect of cue-based feeding on time to nipple feed and time to discharge in very low birth weight infants.

The objective of this study is to evaluate the effectiveness of a cue-based feeding protocol in improving time to nipple feed and time to discharge in very low birth weight infants in a Level III Neonatal Intensive Care Unit. Demographic, feeding, and discharge data were recorded and compared between the two cohorts. The pre-protocol cohort included infants born from August 2013 through April 2016 and the post-protocol cohort included infants born from January 2017 through December 2019. 272 infants were included in the pre-protocol cohort and 314 infants in the post-protocol cohort. Both cohorts were statistically comparable in gestational age, gender, race, birthweight, prenatal care, antenatal steroid use, and rates of maternal diabetes. There were statistically significant differences between the pre- versus post-protocol cohorts in median post-menstrual age (PMA) in days at first nipple feed (PO) (240 vs 238, p = 0.025), PMA in days at full PO (250 vs 247, p = 0.015), and length of stay in days (55 vs 48, p = 0.0113). Comparing each year in the post-protocol cohort, for each outcome measure, a similar trend was noted in 2017 and 2018, but not in 2019. In conclusion, the cue-based feeding protocol was associated with a decrease in the time to first PO, time to full nipple feeds, and the length of stay in very-low-birthweight infants.

A Newborn Infant with Congenital Central Hypoventilation Syndrome and Pupillary Abnormalities: A Literature Review.

We present a neonate with early onset apnea and bradycardia in the absence of primary cardiorespiratory and central nervous system disorders that eventually required chronic ventilator support starting at 6 hours of life. Molecular testing of paired-like homeobox 2b (PHOX2B) gene mutation confirmed the diagnosis of congenital central hypoventilation syndrome (CCHS). CCHS is a rare genetic disorder characterized by impaired central respiratory control with or without broad spectrum of autonomic nervous system (ANS) dysregulations. Ocular ANS dysregulation is a rare finding in CCHS individuals, and it is usually discovered later in life. However, the ophthalmic evaluation of this neonate on first day of life revealed persistent mild dilated oval pupils with limited light reactivity.

Hemodynamic and clinical consequences of early versus delayed closure of patent ductus arteriosus in extremely low birth weight infants.

OBJECTIVES: To describe changes in hemodynamics, respiratory support, and growth associated with transcatheter PDA closure (TCPC) in ELBW infants, stratified by postnatal age at treatment. STUDY DESIGN: This is an observational study of ELBW infants who underwent TCPC at ≤4 weeks (Group-1; n = 34), 4-8 weeks (Group-2; n = 33), and >8 weeks of age (Group-3; n = 33). Hemodynamic assessment was performed during TCPC. Multivariate Cox-proportionate-hazard modeling was used to identify factors associated with respiratory severity score (RSS) > 2 for >30 days following TCPC. RESULTS: In comparison with Group-1, Group-3 infants had higher pulmonary vascular resistance (PVRi = 3.3 vs. 1.6 WU*m2; P = 0.01), less weight gain between 4 and 8 weeks of age (16 vs. 25 g/day) and took longer to achieve RSS < 2 (median 81 vs. 20 days; P = 0.001). RSS > 2 for >30 days was associated with TCPC > 8 weeks (OR = 3.2, 95% CI: 1.75-5.8; p = 0.03) and PVRi ≥ 3 (OR = 4.5, 95% CI: 2.7-8.9; p < 0.01). CONCLUSION: ELBW infants may benefit from PDA closure within the first 4 weeks of life in order to prevent early onset pulmonary vascular disease, promote faster growth, and for quicker weaning of ventilator and oxygen support.

Effect of patent ductus arteriosus on pulmonary vascular disease.

The hemodynamic effects of a patent ductus arteriosus (PDA) are well known including systemic hypoperfusion and volume overload on the left ventricle. This article aims to provide a review of the long-standing effect of a hemodynamically significant PDA on the pulmonary vasculature and the role of cardiac catheterization in preterm infants with a PDA and pulmonary hypertension.

Can transcatheter PDA closure be performed in neonates ≤1000 grams? The Memphis experience.

OBJECTIVE: Advancements in transcatheter technology have now made it possible to safely close patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. The objective of this article is to describe our technique for transcatheter PDA closure (TCPC) in ELBW infants. DESIGN: The techniques employed are very specific to this population and are drastically different when compared to the procedure performed in patients weighing >5 kg. SETTING: A multidisciplinary team approach should be taken to evaluate and manage ELBW infants in order to achieve success. It is important that specific techniques with venous-only approach outlined in this article be followed to achieve optimal results with low risk of complications. PATIENTS: To date, in Memphis, 55 ELBW infants have had successful TCPC at a weight of ≤1000 g with minimal procedure-related complications. INTERVENTIONS: It is important that specific techniques with venous-only approach outlined in this article be followed to achieve optimal results with low risk of complications. OUTCOME MEASURES: This procedure entails a steep learning curve and should be limited to specialized centers with expertise in these thanscatheter procedures. RESULTS: There has been 100% procedural success of performing TCPC in children ≤1000 g. There have been only two procedure-related complications which happened to the first two patients, ≤1000 g, that we performed TCPC on. CONCLUSIONS: It is feasible and probably safe to perform TCPC in children ≤1000 g. The techniques described in this article represent our institutional experience and have helped us improve clinical outcomes in ELBW infants.

Anatomical Closure of Left-to-Right Shunts in Premature Infants with Bronchopulmonary Dysplasia and Pulmonary Hypertension: A Cautionary Tale.

Closure of a systemic to pulmonary shunt in premature infants with bronchopulmonary dysplasia may be beneficial, but in the presence of pulmonary hypertension is controversial. Here, we discuss two premature infants with pulmonary hypertension who developed acute pulmonary hypertensive crisis after closure of these shunts and hence advise caution.