Kari D. Roberts

Premedication for Nonemergent Neonatal Intubations: A Randomized, Controlled Trial Comparing Atropine and Fentanyl to Atropine, Fentanyl, and Mivacurium

OBJECTIVE. The purpose of this work was to investigate whether using a muscle relaxant would improve intubation conditions in infants, thereby decreasing the incidence and duration of hypoxia and time and number of attempts needed to successfully complete the intubation procedure. PATIENTS/METHODS. This was a prospective, randomized, controlled, 2-center trial. Infants requiring nonemergent intubation were randomly assigned to receive atropine and fentanyl or atropine, fentanyl, and mivacurium before intubation. Incidence and duration of hypoxia were determined at oxygen saturation thresholds of ≤85%, ≤75%, ≤60%, and ≤40%. Videotape was reviewed to determine the time and number of intubation attempts and duration of action of mivacurium. RESULTS. Analysis of 41 infants showed that incidence of oxygen saturation ≤60% of any duration was significantly less in the mivacurium group (55% vs 24%). The incidence of saturation level of any duration ≤85%, 75%, and 40%; cumulative time ≥30 seconds; and time below the thresholds were not significantly different. Total procedure time (472 vs 144 seconds) and total laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group. Successful intubation was achieved in ≤2 attempts significantly more often in the mivacurium group (35% vs 71%). CONCLUSIONS. Premedication with atropine, fentanyl, and mivacurium compared with atropine and fentanyl without a muscle relaxant decreases the time and number of attempts needed to successfully intubate while significantly reducing the incidence of severe desaturation. Premedication including a short-acting muscle relaxant should be considered for all nonemergent intubations in the NICU.

Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA‐binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

Laryngeal Mask Airway for Surfactant Administration in a Newborn Animal Model

Premature infants are subjected to adverse effects of intubation to benefit from surfactant. We hypothesized that administration of surfactant through a laryngeal mask airway (LMA) is as effective as administration through an endotracheal tube (ETT) and that time and physiologic changes during instrumentation will be less in the LMA group. This study is a randomized, controlled trial using newborn pigs. Lung injury was induced via surfactant washout. Animals were randomized into groups: 1) LMA placed, no surfactant administered (control; n = 8); 2) surfactant via an LMA (LMA group; n = 8); and 3) surfactant via an ETT (ETT group; n = 8). We demonstrated that partial pressure of oxygen in arterial blood (Pao2) levels of the LMA and ETT groups were not statistically different. Time for successful placement of LMA was 19 ± 1 s versus ETT 123 ± 35 s (mean ± SEM); number of attempts for successful LMA placement was 1.1 (1–2) versus ETT 1.9 (1–7) [mean (range)]. Administration of surfactant via an LMA compared with an ETT resulted in similar improvements in oxygenation. Placement of the device required less time and fewer attempts. These data suggest that further study in human neonates is justified. If proven effective, some infants with respiratory distress may be able to receive surfactant while avoiding intubation.

Improved gas exchange and survival after KL-4 surfactant in newborn pigs with severe acute lung injury

To determine the effectiveness of artificial surfactant therapy using KL‐4 surfactant in newborn pigs with hydrochloric acid (HCl)‐induced acute lung injury (ALI).

Feasibility of Laryngeal Mask Airway Device Placement in Neonates

Background: The laryngeal mask airway (LMA) has been used in adult and pediatric populations for decades. While the familiarity of its use in the neonatal population is increasing, there are few data investigating this. Objective: The objective of this study was to determine the feasibility of LMA placement in neonates by investigating the time and number of attempts required for successful placement and physiologic stability during the placement of the device. Methods: This study is one component of a national, multicenter, randomized controlled trial investigating surfactant administration through an LMA in neonates. Videotape of LMA placement was reviewed to determine the total procedure time and the number of attempts required to successfully place the device. Heart rate and oxygen saturation (SaO2) were analyzed as change from baseline, in order to examine physiologic stability during device placement. Results: Videotape and physiologic data were analyzed for 36 infants. Gestational age ranged from 293/7 to 354/7 weeks (mean 33 ± 1.7) with the birth weight ranging from 1,290 to 3,180 g (mean 2,006 ± 482). Average total procedure time was 88 s (±136) with 64% of the procedures successfully completed in <35 s. Successful placement was achieved on the first attempt in 69% of the cases. Compared to baseline, heart rate increased by an average of 1 bpm (±4.5) and SaO2 decreased an average of 6% (±7). Conclusions: Successful placement was achieved in the majority of patients in <35 s and required only one attempt. Physiologic parameters were maintained close to baseline, measured by minimal fluctuation in heart rate and SaO2 during the procedure. Placement of the LMA is feasible in neonates.

Mesenchymal stem cells in the pathogenesis and treatment of bronchopulmonary dysplasia: A clinical review

Advances in neonatal medicine have led to increased survival of infants born at the limits of viability, resulting in an increased incidence of bronchopulmonary dysplasia (BPD). BPD is a chronic lung disease of premature infants characterized by the arrest of alveolarization, fibroblast activation, and inflammation. BPD leads to significant morbidity and mortality in the neonatal period and is one of the leading causes of chronic lung disease in children. The past decade has brought a surge of trials investigating cellular therapies for the treatment of pulmonary diseases. Mesenchymal stem cells (MSCs) are of particular interest because of their ease of isolation, low immunogenicity, and anti-inflammatory and reparative properties. Clinical trials of MSCs have demonstrated short-term safety and tolerability; however, studies have also shown populations of MSCs with adverse pro-inflammatory and myofibroblastic characteristics. Cell-based therapies may represent the next breakthrough therapy for the treatment of BPD, however, there remain barriers to implementation as well as gaps in knowledge of the role of endogenous MSCs in the pathogenesis of BPD. Concurrent high-quality basic science, translational, and clinical studies investigating the fundamental pathophysiology underlying BPD, therapeutic mechanisms of exogenous MSCs, and logistics of translating cellular therapies will be important areas of future research.

Laryngeal Mask Airway for Surfactant Administration in Neonates: A Randomized, Controlled Trial

Objective To determine if preterm infants with moderate respiratory distress syndrome on continuous positive airway pressure (CPAP) who received surfactant via a laryngeal mask airway (LMA) would have a decreased rate of intubation and mechanical ventilation compared with those on CPAP who did not receive surfactant. Study design In this prospective, multicenter, randomized controlled trial, 103 premature infants 280/7‐356/7 weeks gestation, ≥1250 g and ≤36 hours old on CPAP requiring fraction of inspired oxygen 0.30‐0.40 were assigned to receive surfactant administered through an LMA then placed back on CPAP (LMA group) or maintained on CPAP with no surfactant administered (control group). The primary outcome was treatment failure necessitating intubation and mechanical ventilation in the first 7 days of life. Results Surfactant administration through an LMA (n = 50) significantly decreased the rate of intubation and mechanical ventilation compared with controls (n = 53): 38% vs 64%, respectively, OR 0.30 (95% CI 0.13, 0.70), P = .006, number needed to treat: 4). There were no serious adverse events associated with placement of the LMA or surfactant administration. Conclusions In premature neonates with moderate respiratory distress syndrome, surfactant administered through an LMA decreased the rate of intubation and mechanical ventilation. This intervention may have significant impact on clinical care in both high and low resource settings. Trial registration ClinicalTrials.gov: NCT01116921.

Diabetic ketoacidosis, respiratory distress and myocardial dysfunction

This case report describes a patient with respiratory distress, myocardial dysfunction, elevated troponin level, ECG changes and pulmonary oedema secondary to new onset diabetic ketoacidosis (DKA). This case may be unique, but it is possible that less severe cases occur and are underappreciated in the paediatric setting. This report demonstrates the need to closely evaluate and monitor cardiac function in patients with DKA.

PO-0758 Laryngeal Mask Airway Device Placement In Neonates

Background Endotracheal intubation (EI) is currently required for surfactant administration. However, EI is associated with adverse physiologic effects, including bradycardia and hypoxia. The laryngeal mask airway (LMA) may provide a more practical and less invasive alternative to EI for surfactant administration. Aim Determine feasibility of LMA placement in neonates by investigating the time, number of attempts and physiologic stability during placement of the device. Methods Infants ≥1250 g who required surfactant administration were eligible. Videotape of the LMA placement procedure was reviewed to determine number of attempts, duration of attempts, total procedure time, and heart rate and oxygen saturation change from baseline. Results Twenty-two infants were included in analysis. Mean total procedure time was 129 seconds (±187). Duration of attempts was 59 seconds (±81). Successful placement was achieved on the first attempt in 73% of cases. Two attempts were required in 14% of cases and all procedures were successful in ≤3 attempts. As compared to baseline, heart rate increased 3 beats per minute on average (±4, range: -3 to 11) and oxygen saturation decreased by 7% on average (±8, range: -24 to 1), as shown in Figure 1. Abstract PO-0758 Figure 1 Conclusions Successful placement was achieved in the majority of patients in one attempt with an average total procedure time of approximately 2 min. Physiologic parameters were maintained close to baseline with minimal fluctuation in heart rate and oxygen saturation. Placement of the LMA device is feasible in neonates.

Four-year follow-up of megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephalus (MPPH) syndrome

A male infant was born by emergent caesarean section at 39 weeks gestational age secondary to maternal and fetal distress. Initial physical examination was notable for macrocephaly (greater than+2SD), postaxial polydactyly of the hands and facial dysmorphism. Head imaging demonstrated diffuse polymicrogyria without hydrocephalus. All findings were consistent with a diagnosis of megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephalus (MPPH) syndrome. At the 4-year follow-up, megalencephaly persisted without evidence of hydrocephalus. The child was severely delayed with a stable seizure disorder controlled with dual antiepileptic therapy. This case meets the classic criteria for MPPH syndrome, adding to the limited experience with this disease. The 4-year follow-up and absence of hydrocephalus, once thought to be a key diagnostic criterion, adds to our understanding of the long-term sequelae.