Comparison of laryngeal mask airway and endotracheal tube placement in neonates.

OBJECTIVE: We hypothesize that the time, number of attempts, and physiologic stability of placement of an LMA would be superior compared to ETT. STUDY DESIGN: Videotape and physiologic parameters of LMA (n = 36) and ETT (n = 31) placement procedures for infants 28-36 weeks gestation were reviewed. RESULTS: Duration of attempts (32 vs 66 s, p < 0.001) and mean total airway insertion time (88 vs 153 s, p = 0.06) was shorter for LMA compared to ETT. Mean number of attempts for successful placement was fewer for LMA (1.5 vs 1.9, p = 0.11). Physiologic parameters remained near baseline in both groups despite very different degrees of premedication. CONCLUSION: Placement of an LMA required less time and fewer number of attempts compared to ETT. Physiologic stability of an LMA was maintained without the use of an analgesic and muscle relaxant. Use of an LMA is a favorable alternative to ETT placement for surfactant delivery in neonates. TRIAL REGISTRATION: NCT01116921.

Alternative routes of surfactant application - An update.

Non-invasive modes of respiratory support have been shown to be the preferable way of primary respiratory support of preterm infants with respiratory distress syndrome (RDS). The avoidance of invasive mechanical ventilation can be beneficial for preterm infants in reduction of morbidity and even mortality. However, it is well-established that some infants managed with non-invasive respiratory support from the outset have symptomatic RDS to a degree that warrants surfactant administration. Infants for whom non-invasive respiratory support ultimately fails are prone to adverse outcomes, occurring at a frequency on par with the group intubated primarily. This raises the question how to combine non-invasive respiratory support with surfactant therapy. Several methods of less or minimally invasive surfactant therapy have been developed to address the dilemma between avoidance of mechanical ventilation and administration of surfactant. This paper describes the different methods of less invasive surfactant application, reports the existing evidence from clinical studies, discusses the limitations of each of the methods and the open and future research questions.

Surfactant delivery strategies to prevent bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is one of the most devastating morbidities of preterm infants. Antenatal factors like growth restriction and inflammation are risk factors for its development. Use of oxygen and positive pressure ventilation, which are often necessary to treat respiratory distress syndrome (RDS), increase the risk for development of BPD. Continuous positive airway pressure (CPAP) as primary respiratory support allows for avoidance of positive pressure ventilation in many cases but may lead to a delay of surfactant administration which is a proven therapy for RDS. Several alternative surfactant delivery strategies, including nebulization of surfactant, pharyngeal instillation of surfactant, delivery of surfactant via supraglottic airway device or surfactant delivery via a thin endotracheal catheter have been described which allow for the benefit of surfactant therapy while on CPAP. This review reports available data and discusses the existing evidence of their value in preventing BPD as well as further research directions.

RDS-NExT workshop: consensus statements for the use of surfactant in preterm neonates with RDS.

OBJECTIVE: To provide the best clinical practice guidance for surfactant use in preterm neonates with respiratory distress syndrome (RDS). The RDS-Neonatal Expert Taskforce (RDS-NExT) initiative was intended to add to existing evidence and clinical guidelines, where evidence is lacking, with input from an expert panel. STUDY DESIGN: An expert panel of healthcare providers specializing in neonatal intensive care was convened and administered a survey questionnaire, followed by 3 virtual workshops. A modified Delphi method was used to obtain consensus around topics in surfactant use in neonatal RDS. RESULT: Statements focused on establishing RDS diagnosis and indicators for surfactant administration, surfactant administration methods and techniques, and other considerations. After discussion and voting, consensus was achieved on 20 statements. CONCLUSION: These consensus statements provide practical guidance for surfactant administration in preterm neonates with RDS, with a goal to contribute to improving the care of neonates and providing a stimulus for further investigation to bridge existing knowledge gaps.

Implementation of Surfactant Administration through Laryngeal or Supraglottic Airways (SALSA): A Jordanian NICU's Journey to Improve Surfactant Administration.

Administration of liquid surfactant through an endotracheal tube for the treatment of respiratory distress syndrome has been the standard of care for decades. Surfactant administration through laryngeal or supraglottic airways (SALSA) is a simplified procedure for delivery of surfactant that is less invasive and better tolerated. The Al Bashir Maternity and Children's Hospital NICU in Amman, Jordan, implemented SALSA as a potentially better practice in 2019 with the objective to effectively and efficiently deliver surfactant in a minimally invasive way and to decrease the adverse events associated with intubation−surfactant−extubation (InSurE) and laryngoscopy. The quality improvement initiative was conducted from March 2019 to December 2019. All infants who weighed 750 g or more who required surfactant were eligible. As physicians were trained in the technique and use expanded, we were able to use plan−do−study−act cycles to observe differences between SALSA and InSurE. The primary aim was the optimization of non-invasive ventilation by the effective and efficient delivery of surfactant. Balancing measures included episodes of bradycardia while receiving surfactant or the need for a second dose of surfactant. We evaluated 220 infants who received surfactant by SALSA or InSurE with a mean gestational age of 32 weeks and a mean birth weight of 1.8 kg. The Respiratory Severity Score (RSS) prior to surfactant administration was 2.7 in the SALSA group compared to 2.9 in the InSurE group (p = 0.024). Those in the InSurE group had a lower mean heart rate during the procedure (p =< 0.0001) and were more likely to need a second dose of surfactant (p = 0.026) or require intubation for mechanical ventilation (p = 0.022). Both groups were effectively delivered surfactant as evidenced by improvement in their RSS over an 8 h period. SALSA was a more time efficient surfactant delivery method (93 vs. 111 secs, p =< 0.0001). Implementation of SALSA into the Al Bashir NICU was successful. We found that it was equally effective to InSurE, but was a more efficient method of delivery. Infants who received surfactant by this method tolerated it well.

Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA): A Viable Method for Low-Income and Middle-Income Countries.

Administration of liquid surfactant through an endotracheal tube for the treatment of respiratory distress syndrome has been the standard of care for decades. A skilled health care provider is needed to perform this procedure. In lower-income and middle-income countries (LMICs), healthcare resources are often limited, leading to increased mortality of premature infants, many of whom would benefit from surfactant administration. Therefore, having a simplified procedure for delivery of surfactant without the need for advanced skills could be life-saving, potentially diminish gaps in care, and help ensure more equitable global neonatal survival rates. Modifications to the standard approach of surfactant administration have been put into practice and these include: INtubation-SURfactant-Extubation (INSURE), thin catheter surfactant administration (TCA), aerosolized surfactant, and surfactant administration through laryngeal or supraglottic airways (SALSA). Although there is a need for larger studies to evaluate the comparative effectiveness of these newer methods, these methods are being embraced by the global community and being implemented in various settings throughout the world. Because the SALSA technique does not require laryngoscopy, a provider skilled in laryngoscopy is not required for the procedure. Therefore, because of the ease of use and safety profile, the SALSA technique should be strongly considered as a viable method of delivering surfactant in LMICs.

A systematic review of surfactant delivery via laryngeal mask airway, pharyngeal instillation, and aerosolization: Methods, limitations, and outcomes.

Less invasive surfactant administration methods without laryngoscopy and endotracheal catheterization include delivery via laryngeal mask airway, pharyngeal instillation, and aerosolization. These less invasive techniques are promising and have several advantages over INSURE (Intubation-Surfactant-Extubation) and thin catheter techniques. The objective of this review is to discuss the requisites, techniques, short-term outcomes, and adverse events associated with these methods.

Surfactant Administration Through Laryngeal or Supraglottic Airways.

Noninvasive ventilation is frequently used in the treatment of infants with respiratory distress syndrome. This practice is often effective in higher gestational age neonates, but can be difficult in those with lower gestational ages as surfactant deficiency can be severe. While noninvasive ventilation avoids the negative effects of intubation and ventilator-induced lung injury, failure of this mode of support does occur with relative frequency and is primarily caused by the poorly compliant, surfactant-deficient lung. Because of the potential problems associated with laryngoscopy and intubation, neonatologists have developed various methods to deliver surfactant in minimally invasive ways with the aim of improving the success of noninvasive ventilation. Methods of minimally invasive surfactant administration include various thin catheter techniques, aerosolization/nebulization, and the use of a laryngeal mask airway/supraglottic airway device. The clinician should recognize that currently the only US Food and Drug Administration-approved device to deliver surfactant is an endotracheal tube and all methods reviewed here are considered off-label use. This review will focus primarily on surfactant administration through laryngeal or supraglottic airways, providing a review of the history of this technique, animal and human trials, and comparison with other minimally invasive techniques. In addition, this review provides a step-by-step instruction guide on how to perform this procedure, including a multimedia tutorial to facilitate learning.

Alternative Methods of Surfactant Administration in Preterm Infants with Respiratory Distress Syndrome: State of the Art.

For preterm infants with respiratory distress syndrome, delivery of surfactant via brief intubation (INtubate, SURfactant, Extubate; InSurE) has been the standard technique of surfactant administration. However, this method requires intubation and positive pressure ventilation. It is thought that even the short exposure to positive pressure inflations may be enough to initiate the cascade of events that lead to lung injury in the smallest neonates. In an effort to avoid tracheal intubation and positive pressure ventilation, several alternative and less invasive techniques of exogenous surfactant administration have been developed over the years. These have been investigated in clinical studies, including randomized clinical trials, and have demonstrated advantages such as a decrease in the need for mechanical ventilation and incidence of bronchopulmonary dysplasia. These newer techniques of surfactant delivery also have the benefit of being easier to perform. Surfactant delivery via pharyngeal instillation, laryngeal mask, aerosolization, and placement of a thin catheter are being actively pursued in research. We present a contemporary review of surfactant administration for respiratory distress syndrome via these alternative methods in the hope of guiding physicians in their choices for surfactant application in the neonatal intensive care unit.

Partial gonadal dysgenesis associated with a pathogenic variant of PBX1 transcription factor.

A term neonate was admitted to the Neonatal Intensive Care Unit for respiratory distress, hypotonia and atypical genitalia. Significant findings included a small phallic structure, labial folds, no palpable gonads and two perineal openings. Pelvic ultrasound showed uterine didelphys and a gonad in the right inguinal canal. The right gonad was removed during diagnostic laparoscopy with microscopic evaluation showing infantile testicular tissue and fluorescence in-situ hybridisation showed only XY signal suggesting that the removed gonad was a male-developed testis. Infant was 46,XY, SRY probe positive. The parents chose a female sex assignment prior to gonadectomy. The infant had respiratory insufficiency and central hypotonia that persisted on discharge. Whole exome sequencing showed a heterozygous pathogenic variant of the PBX1 gene. This variant encodes the pre-B-cell leukaemia homeobox PBX transcription factor and has been associated with malformations and severe hypoplasia or aplasia of multiple organs including lungs and gonads. Whole exome sequencing was crucial in providing a unifying diagnosis for this patient.

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.

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.

Current practice of neonatal resuscitation documentation in North America: a multi-center retrospective chart review.

BACKGROUND: To determine the comprehensiveness of neonatal resuscitation documentation and to determine the association of various patient, provider and institutional factors with completeness of neonatal documentation. METHODS: Multi-center retrospective chart review of a sequential sample of very low birth weight infants born in 2013. The description of resuscitation in each infant's record was evaluated for the presence of 29 Resuscitation Data Items and assigned a Number of items documented per record. Covariates associated with this Assessment were identified. RESULTS: Charts of 263 infants were reviewed. The mean gestational age was 28.4 weeks, and the mean birth weight 1050 g. Of the infants, 69 % were singletons, and 74 % were delivered by Cesarean section. A mean of 13.2 (SD 3.5) of the 29 Resuscitation Data Items were registered for each birth. Items most frequently present were; review of obstetric history (98 %), Apgar scores (96 %), oxygen use (77 %), suctioning (71 %), and stimulation (62 %). In our model adjusted for measured covariates, the institution was significantly associated with documentation. CONCLUSIONS: Neonatal resuscitation documentation is not standardized and has significant variation. Variation in documentation was mostly dependent on institutional factors, not infant or provider characteristics. Understanding this variation may lead to efforts to standardize documentation of neonatal resuscitation.

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.

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

OBJECTIVE: To determine the effectiveness of artificial surfactant therapy using KL-4 surfactant in newborn pigs with hydrochloric acid (HCl)-induced acute lung injury (ALI). DESIGN: After induction of ALI via intratracheal HCl instillation, pigs were randomized to receive 5.8 ml/kg KL-4 surfactant or no surfactant prior to extubation to bubble CPAP. SETTING: Clinical laboratory. SUBJECTS: Spontaneously breathing newborn pigs (<1 week of age). INTERVENTIONS: Treatment with KL-4 surfactant on bubble CPAP with PEEP of 6 cmH(2)O for 3.5 hr after extubation compared with controls. MEASUREMENTS: Physiologic parameters and arterial blood gases were measured every 15 min. At the conclusion of the study, the lungs were excised for the analysis of histopathology and morphometric data. MAIN RESULTS: Pigs treated with KL-4 surfactant had arterial blood gases with less acidosis (P < 0.001), higher P(a)O(2) levels (P < 0.001), and lower P(a)CO(2) levels (P < 0.001). Pigs treated with KL-4 surfactant had improved survival compared with controls (6/12 KL-4, 2/12 control, P < 0.05). Postmortem morphometric data demonstrated that pigs treated with KL-4 surfactant had larger (P < 0.05) exchange units in the caudal-dorsal lung as compared to relatively atelectatic region in the control animals. CONCLUSIONS: In newborn pigs with severe HCl-induced ALI, treatment with KL-4 surfactant resulted in improved respiratory parameters, less dependent atelectasis, and improved short-term survival.

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.

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.