Absence of inspiratory laryngeal constrictor muscle activity during nasal neurally adjusted ventilatory assist in newborn lambs

It has been demonstrated that a progressive increase in nasal pressure support ventilation (nPSV) leads to an active inspiratory glottal closure in non-sedated newborn lambs, which limits lung ventilation (24, 33). Unlike nPSV, the pressure delivered during nasal Neurally Adjusted Ventilatory Assist (nNAVA) is synchronized to the diaphragm electrical activity on inspiration (36). Given the tight neural integration of the glottal dilators and constrictors with diaphragm activity on inspiration and expiration respectively, the aim of the present study was to test the hypothesis that inspiratory glottal closure does not develop during nNAVA. Polysomnographic recordings were performed in eight non-sedated, chronically instrumented lambs, which were ventilated with progressively increasing levels of nPSV and nNAVA, in random order. States of alertness, diaphragm and glottal muscle electrical activity, tracheal pressure, SpO2, tracheal PETCO2 and respiratory inductive plethysmography were continuously recorded. While phasic inspiratory glottal constrictor electrical activity appeared with increasing levels of nPSV in 5 out of 8 lambs, it was never observed at any nNAVA level in any lamb, even at maximal achievable nNAVA levels. In addition, a decrease in arterial PCO2 was neither necessary nor sufficient for the development of phasic inspiratory glottal constrictor activity. In conclusion, nNAVA does not induce active glottal closure in non-sedated newborn lambs at high-pressure levels, in contrast to nPSV

Effects of caffeine and/or nasal CPAP treatment on laryngeal chemoreflexes in preterm lambs

Current knowledge suggests that laryngeal chemoreflexes (LCR) are involved in the occurrence of certain neonatal apneas/bradycardias, especially in the preterm newborn. While caffeine and/or nasal continuous positive airway pressure (nCPAP) are the most frequent options used for treating apneas in preterm newborns, their effects on LCR-related apneas/bradycardias are virtually unknown. The aim of the present study was to test the hypothesis that caffeine and/or nCPAP decreases LCR-related cardiorespiratory inhibition in a preterm ovine model. Seven preterm lambs were born vaginally on gestational day 133 (normal gestation: 147 days) after intramuscular injections of betamethasone and mifepristone. Five days after birth, a chronic surgical instrumentation was performed to record states of alertness, electrocardiogram, systemic arterial pressure, and electromyographic activity of a laryngeal constrictor muscle, as well as to insert a transcutaneous supraglottal catheter. LCR were induced in quiet sleep under four conditions: 1) control (without caffeine or nCPAP); 2) nCPAP (5 cmH2O, without caffeine); 3) caffeine (10 mg/kg infused intravenously for 30 min, without nCPAP); and 4) nCPAP + caffeine. Our results showed that nCPAP consistently blunted LCR-related cardiorespiratory inhibition vs. control condition, contrary to caffeine whose overall effect was nonsignificant. In addition, nCPAP condition was characterized by a more consistent and rapid arousal after HCl injection. No significant differences were observed between all tested conditions with regard to swallowing and cough. It is concluded that nCPAP should be further assessed for its usefulness in treating neonatal apneas linked to LCR

A High-Value, Low-Cost Bubble Continuous Positive Airway Pressure System for Low-Resource Settings: Technical Assessment and Initial Case Reports

Acute respiratory infections are the leading cause of global child mortality. In the developing world, nasal oxygen therapy is often the only treatment option for babies who are suffering from respiratory distress. Without the added pressure of bubble Continuous Positive Airway Pressure (bCPAP) which helps maintain alveoli open, babies struggle to breathe and can suffer serious complications, and frequently death. A stand-alone bCPAP device can cost $6,000, too expensive for most developing world hospitals. Here, we describe the design and technical evaluation of a new, rugged bCPAP system that can be made in small volume for a cost-of-goods of approximately$350. Moreover, because of its simple designﾗconsumergrade pumps, medical tubing, and regulators—it requires only the simple replacement of a ,$1 diaphragm approximately every 2 years for maintenance. The low-cost bCPAP device delivers pressure and flow equivalent to those of a reference bCPAP system used in the developed world. We describe the initial clinical cases of a child with bronchiolitis and a neonate with respiratory distress who were treated successfully with the new bCPAP device

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders

Respiratory care year in review 2010: part 2. Invasive mechanical ventilation, noninvasive ventilation, pediatric mechanical ventilation, aerosol therapy

The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, NIV, pediatric mechanical ventilation, and aerosol therapy. Topics covered related to invasive mechanical ventilation topics include the role of PEEP in providing lung protection during mechanical ventilation, unconventional modes for severe hypoxemia, and strategies to improve patient-ventilator interactions. Topics covered related to NIV include real-life NIV use, NIV and extubation failure, and NIV and pandemics. For pediatric mechanical ventilation, the topics addressed are NIV, invasive respiratory support, and inhaled nitric oxide. Topics covered related to aerosol therapy include short-acting β-adrenergic agents, long-acting β-adrenergic agents, long-acting antimuscarinic agents, inhaled corticosteroid therapy, phosphodiesterase type 4 (PDE4) inhibitors, long-acting β-adrenergic plus inhaled corticosteroid, long-acting antimuscarinic plus inhaled corticosteroid, nebulized hypertonic saline, inhaled mannitol, and inhaled antibiotic therapy. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Car