Alok Bhutada

Inhaled nitric oxide and gentle ventilation in the treatment of pulmonary hypertension of the newborn: a single-center, 5-year experience

OBJECTIVE: To evaluate the effect of inhaled nitric oxide (INO) in pulmonary hypertension of the newborn (PH) in a single center over 5 years using gentle ventilation (GV), without hyperventilation or induced alkalosis.METHODS: Data from 229 consecutive infants with PH of varied etiology treated with INO and GV, and from 67 infants with meconium aspiration syndrome (MAS) and primary PH (PPHN) treated with GV alone were reviewed over a 5-year period (86% outborn). INO was initiated at 25 ppm when PH and severe hypoxemia persisted despite maximal optimal ventilation. Hyperventilation or systemic alkalosis were not attempted.RESULTS: Mean duration of ventilation was 9.9±14 days (median 6.5 days). Average mean airway pressure (MAP) dropped from 17.7±4.3 cm H2O at the referral hospital to 13.2±2.5 cm H2O (p<0.001) following admission to our unit using conventional settings and GV, before starting INO. Mean oxygenation index (OI) dropped from 46.8±24.5 to 22.7±21.4 within 24 hours of INO therapy (p<0.001). Infants with higher baseline pH and lower baseline OI responded better to INO (p<0.02). Overall survival was 72%. Patients with MAS and PPHN had the best response, 92% survived and there was a 46% reduction in need for extracorporeal membrane oxygenation (ECMO) compared to historical pre-INO period controls (23.9% vs. 12.8%, p<0.01). In the infants treated with GV alone, the MAP dropped from 17.2±4.3 cm H2O at the referral hospital to 12.6±2.4 after GV was started in our unit.CONCLUSIONS: We conclude that INO is an effective and well-tolerated therapy for PH in infants receiving GV.

Spontaneous correction of the malpositioned percutaneous central venous line in infants.

Abstract Malpositioning of the percutaneously placed central venous line (PCVL) or percutaneously inserted central catheter (PICC) in infants is not a rare occurrence. It has been occasionally observed that these lines spontaneously correct themselves. This prospective study was done to study the incidence of malposition and spontaneous correction. Using a modification of the standard method, 187 catheters were placed with 98.9 % success. Seven of these were initially malpositioned. All seven corrected themselves within a day when left in and used as a peripheral intravenous line. In many centers malpositioned catheters are taken out and replaced, which imposes great stress on the critically ill infant. Our study suggests that to avoid this stress the catheter should be left in place, since spontaneous correction may occur.

Immediate clinical outcomes in preterm neonates receiving antenatal magnesium for neuroprotection

Abstract Background: Antenatal magnesium sulfate can potentially reduce the risk of cerebral palsy in neonates delivered between 24 and 32 weeks of gestational age. Some studies using high-dose magnesium sulfate for neuroprotection have reported increased perinatal mortality. Methods: A retrospective study was conducted on 475 neonates born between 24 and 32 weeks of gestational age. Serum magnesium level in the first 24 h of life was used to stratify the neonates treated with antenatal magnesium into four subgroups: A (<2.5 mEq/L), B (≥2.5 to <3.5 mEq/L), C (≥3.5 to <4.5 mEq/L), and D (≥4.5 mEq/L). Primary outcome of survival without intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL) along with secondary outcomes, such as Apgar scores, resuscitation, intubation, broncho-pulmonary dysplasia, retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), time to reach full feeds, length of stay (LOS), and mortality during immediate neonatal period were studied. Results: Of the 475 neonates included in the study, 289 (61%) received antenatal magnesium sulfate. Primary outcome of survival without IVH and/or PVL among the preterm neonates was 70.9% in those receiving and 74.2% in those not receiving antenatal magnesium (P=0.25). There were higher incidences of ROP (P=0.02), PDA (P=0.01), greater time to reach full feeds (P=0.03), and increased LOS (P=0.01) in neonates who had received antenatal magnesium. These findings were not statistically significant when the data were corrected for gestational age and birth weight. Among the subgroups, there was a significantly increased mortality rate (P<0.05) with increasing magnesium levels (5% vs. 16.9%, P<0.05 in groups A vs. D) and a trend toward higher intubation rate (P=0.1) and PDA (P=0.14). Conclusion: Antenatal magnesium is safe in the immediate postnatal period; however, in the subset of preterm neonates with serum magnesium levels >4.5 mEq/L, there is increased mortality independent of birth weight and gestational age. Identification of these neonates and appropriate dosing for their antenatal neuroprotection needs to be studied.

Neonatal serum magnesium concentrations are determined by total maternal dose of magnesium sulfate administered for neuroprotection.

Abstract Background: Antenatal magnesium in preterm labor for neuroprotection decreases the incidence of cerebral palsy. However, there are no guidelines on the dose and duration of magnesium infusion for neuroprotection. As increased neonatal serum magnesium concentrations may be related to higher risk of morbidity and mortality, the role of total amount of magnesium and maternal serum magnesium concentrations associated with safe neonatal serum magnesium concentrations is not known. Methods: A retrospective study was conducted on 289 mothers who received antenatal magnesium for neuroprotection as a loading dose of 4–6 g infused over 30 min, followed by a maintenance infusion of 1–2 g/h. Total magnesium dose infused to the mother and maternal serum magnesium concentrations were correlated with neonatal serum magnesium concentrations. Results: Of the 289 mothers, 192 mother/baby dyads had all three measurements (maternal total magnesium dose, and maternal and neonatal serum magnesium concentrations). Magnesium infusion was continued beyond 24 h in 60 mothers. Total maternal magnesium dose at 24 and 48 h of infusion correlated with neonatal serum magnesium concentrations (r=0.55, P<0.0001 and r=0.35, P<0.0001, respectively), but not with maternal serum magnesium concentrations (r=0.004, P=0.98 and r=0.14, P=0.21). However, there was no correlation between the maternal and neonatal serum magnesium concentrations (r=0.10, P=0.15). Conclusion: Total dose of magnesium infused to the mother correlates with neonatal serum magnesium concentrations. To keep neonatal serum magnesium concentrations within a range that is effective for neuroprotection and safe for the neonates, the total dose received by the mother needs to be monitored and limited.

Factors Affecting the Weaning from Nasal CPAP in Preterm Neonates

Objective. Identification of the weight and postmenstrual age (PMA) at successful weaning of NCPAP in preterm neonates and the factors influencing the successful wean. Study Design. Retrospective review of 454 neonates ≤32 weeks of gestational age (GA) who were placed on NCPAP and successfully weaned to room air was performed. Results. Neonates had a mean birth weight (BW) of 1357 ± 392 grams with a mean GA of 29.3 ± 2.2 weeks. Neonates were weaned off NCPAP at mean weight of 1611 ± 432 grams and mean PMA of 32.9 ± 2.4 weeks. Univariate analysis showed that chorioamnionitis, intubation, surfactant use, PDA, sepsis/NEC, anemia, apnea, GER and IVH were significantly associated with the time to NCPAP wean. On multivariate analysis, among neonates that were intubated, BW was the only significant factor (P < 0.001) that was inversely related to time to successful NCPAP wean. Amongst non-intubated neonates, along with BW (P < 0.01), chorioamnionitis (P < 0.01), anemia (P < 0.0001), and GER (P < 0.02) played a significant role in weaning from NCPAP. Conclusion. Neonates were weaned off NCPAP at mean weight of 1611 ± 432 grams and mean PMA of 32.9 ± 2.4 weeks. BW significantly affects weaning among intubated and non-intubated neonates, though in neonates who were never intubated chorioamnionitis, anemia and GER also significantly affected the duration on NCPAP.

Drop in platelet counts in extremely preterm neonates and its association with clinical outcomes.

Background Thrombocytopenia is a common finding among preterm neonates and has been associated with mortality and morbidities. In recent studies in adults, the drop in platelet numbers has been shown to be a predictor of clinical outcomes. Although drop in the platelet counts with or without thrombocytopenia has also been observed in neonates, its association with mortality and morbidity has not been investigated in the preterm population. Objective To study the prevalence of a ≥30% drop in platelet counts in preterm neonates and its association with clinical outcomes. Methods Retrospective chart review was done on neonates born at gestational age ⩽28 weeks and survived for ≥7 days. As with the adult studies, a ≥30% drop in platelet numbers were identified at 7 days and 28 days of age and their association with mortality, morbidities, and length of stay (LOS) was investigated. Results Two hundred eighty-six patients included in the study had a mean gestational age of 26.3 weeks (range, 23 to 28 wk) and birth weight of 899±215 grams. A ≥30% drop in platelet counts occurred in 68.1% neonates. It was significantly associated with mortality (P<0.001), morbidities at both 7 and 28 days [intraventricular bleed (P<0.01)], retinopathy of prematurity (P<0.01), necrotizing enterocolitis (P<0.05) and gram-positive infections (P<0.05), and LOS (P<0.01). Only those neonates who had a ≥30% drop in the platelet numbers developed gram negative and fungal infections. These associations of clinical morbidities and mortality with a ≥30% drop in platelet counts were independent of thrombocytopenia. Conclusions A ≥30% drop in platelet counts is associated with increased mortality, morbidities, and LOS in preterm neonates, independent of thrombocytopenia. As the drop occurs before the onset of clinical morbidity, one potential application is its use to predict the onset of morbidities including necrotizing enterocolitis, intraventricular hemorrhage, and retinopathy of prematurity, and a prolonged LOS and mortality.

Sudden versus gradual pressure wean from Nasal CPAP in preterm infants: a randomized controlled trial

Objective:In preterm infants, nasal continuous positive airway pressure (NCPAP) is widely used for treatment of respiratory distress syndrome. However, the strategies for successfully weaning infants off NCPAP are still not well defined and there remains considerable variation between the methods. The objective of this study is to determine whether gradual weaning of NCPAP pressure is more successful than sudden weaning off NCPAP to room air.Study Design:A randomized controlled trial was conducted in a level 3 neonatal intensive care unit on 70 preterm neonates who were born between 26 and 32 weeks gestation and required NCPAP for at least 48 h. When infants were stable on NCPAP at 0.21 FiO2 and 5 cm H2O positive end expiratory pressure, neonates were randomized to the gradual wean group (reduction in pressure by 1 cm every 8 h until 3 cm H20 was reached) or to sudden wean group (one time NCPAP removal to room air). The primary outcome was a success at the first trial to wean to room air. Secondary outcomes were a number of trials, and weight and postmenstrual age (PMA) at the time of successful wean. Total number of days on NCPAP and length of stay (LOS) in the hospital were also compared between the groups.Results:Of the 70 infants included in the study, 35 were randomized to sudden group and 33 infants to gradual group (2 excluded for protocol deviation). In sudden and gradual groups, 14 and 22 infants, respectively, were weaned successfully in the first attempt (P=0.03). The infants were successfully weaned at 32.7±1.7 weeks versus 33.1±2.4 weeks (P=0.39) PMA and at a weight of 1651±290 g versus 1589±398 g (P=0.46) in the sudden and gradual groups, respectively. The total number of days on NCPAP was 27±19 days versus 32±24 days (P=0.38) and LOS was 63±25 days versus 63±22 days (P=0.99) in the sudden and gradual groups, respectively.Conclusions:Gradual weaning method was more successful as compared to sudden weaning method in the initial trial off NCPAP. There was no difference in the PMA, weight at the time of successful wean, total days on NCPAP and LOS between the two groups.

Citrulline: Is it Ready for Primetime. Its Uses and Limitations in Neonatal Medicine

Citrulline is a non-protein amino acid produced almost exclusively by the gut and present only in small amounts in the diet. Since the gut is the main source of citrulline, it could be used as a potential biomarker of intestinal function. Necrotizing Enterocolitis is an intestinal dysfunction in neonates leading to significant morbidity and mortality. This review discusses the various aspects of intestinal injury and the association of citrulline with bowel disorders, as well as recent developments with citrulline in the pediatric population. As citrulline is directly related to small bowel length, it has been recently shown that its levels are an efficient marker when the active mass of the bowel is affected. This could be used as a prognostic marker for parenteral nutrition weaning and development of enteral tolerance. Lower levels of citrulline are found in preterm neonates with necrotizing enterocolitis and such neonates demonstrate a more prolonged course of the disease. The concomitant increase in citrulline levels along with clinical improvement in neonates and progression of enteral feeds suggest that citrulline levels may be a sensitive marker of intestinal recovery. Studies have shown that citrulline levels are well correlated with the length of the bowel as well as intestinal function. Citrulline levels used as a sensitive biomarker for intestinal absorptive function would be clinically useful in diagnosis of necrotizing enterocolitis and detection of bowel function and recovery from intestinal disorders such as necrotizing enterocolitis, although more studies are needed in newborns affected with these diseases.

Randomized control trial comparing physiologic effects in preterm infants during treatment with nasal continuous positive airway pressure (NCPAP) generated by Bubble NCPAP and Ventilator NCPAP: a pilot study.

Abstract Objectives: Nasal continuous positive airway pressure (NCPAP) is an accepted form of non-invasive ventilation in preterm infants. Few, if any, studies have shown an advantage of one type of NCPAP over another. It has been theorized that bubble-generated NCPAP may be advantageous for the preterm neonate versus traditionally used ventilator-generated NCPAP. The aim of this study was to examine for any short-term differences in physiologic parameters in preterm subjects receiving these two different methods of NCPAP. Methods: We conducted a randomized, prospective, cross-over pilot study of preterm infants being treated with NCPAP in the neonatal intensive care unit. Subjects were continuously monitored for several physiologic parameters including heart rate, respiratory rate, oxygen saturation, cerebral tissue oxygen saturation and cerebral fractional oxygen extraction using routine neonatal monitors and near-infrared spectroscopy (NIRS) while on 2 h of bubble NCPAP and 2 h of ventilator NCPAP. Subjects were randomized to be monitored while either starting on bubble NCPAP and then switching to ventilator NCPAP or starting on ventilator NCPAP and switching to bubble NCPAP. Results: Eighteen subjects were included. We found no statistically significant difference in any of the physiologic parameters while subjects were receiving bubble NCPAP versus ventilator NCPAP during the monitoring time periods. While on bubble NCPAP, subjects showed a trend toward decreasing respiratory rate and decreasing cerebral fractional oxygen extraction over time, but this did not reach statistical significance. Conclusion: There appears to be no difference in immediate physiologic effects between bubble NCPAP and ventilator NCPAP. This does not preclude the possibility of potential long-term differences, but any differences seen would likely be based on mechanisms that take more time to develop. A larger prospective trial is warranted to confirm our findings.

A Unique Preparation and Delivery Method for Acitretin for Neonatal Harlequin Ichthyosis

Harlequin ichthyosis is a rare form of congenital ichthyosis with a distinct phenotypic appearance. We describe a case of a newborn baby with harlequin ichthyosis who was treated with an oral formulation of acitretin. The treatment resulted in a satisfactory improvement in the skin condition of the patient. The tolerance to the drug was good with no side effects in the patient. The aim of this case report is to highlight an extemporaneous preparation of acitretin from the commonly available capsule form, which is effective for use in neonates with harlequin ichthyosis. It also highlights the risk of exposure to health care providers to acitretin.