Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

Assessment of age-related changes in pediatric gastrointestinal solubility

PurposeCompound solubility serves as a surrogate indicator of oral biopharmaceutical performance. Between infancy and adulthood, marked compositional changes in gastrointestinal (GI) fluids occur. This study serves to assess how developmental changes in GI fluid composition affects compound solubility.MethodsSolubility assessments were conducted in vitro using biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2, and FeSSIF.v2) were employed as references for pediatric media development. Investigations assessing age-specific changes in GI fluid parameters (i.e., pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and served to define the composition of neonatal and infant media. Solubility assessments at 37°C were conducted for seven BCS Class II compounds within the developed pediatric and reference adult media.ResultsFor six of the seven compounds investigated, solubility fell outside an 80–125% range from adult values in at least one of the developed pediatric media. This result indicates a potential for age-related alterations in oral drug performance, especially for compounds whose absorption is delimited by solubility (i.e., BCS Class II).ConclusionDevelopmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.<br/

Effect of bolus volume and viscosity on pharyngeal automated impedance manometry variables derived for broad dysphagia patients

Automated impedance manometry (AIM) analysis measures swallow variables defining bolus timing, pressure, contractile vigour, and bolus presence, which are combined to derive a swallow risk index (SRI) correlating with aspiration. In a heterogeneous cohort of dysphagia patients, we assessed the impact of bolus volume and viscosity on AIM variables. We studied 40 patients (average age = 46 years). Swallowing of boluses was recorded with manometry, impedance, and videofluoroscopy. AIMplot software was used to derive functional variables: peak pressure (PeakP), pressure at nadir impedance (PNadImp), time from nadir impedance to peak pressure (TNadImp-PeakP), the interval of impedance drop in the distal pharynx (flow interval, FI), upper oesophageal sphincter (UES) relaxation interval (UES RI), nadir UES pressure (Nad UESP), UES intrabolus pressure (UES IBP), and UES resistance. The SRI was derived using the formula SRI = (FI * PNadImp)/(PeakP * (TNadImp-PeakP + 1)) * 100. A total of 173 liquid, 44 semisolid, and 33 solid boluses were analysed. The SRI was elevated in relation to aspiration. PeakP increased with volume. SRI was not significantly altered by bolus volume. PNadImp, UES IBP, and UES resistance increased with viscosity. SRI was lower with increased viscosity. In patients with dysphagia, the SRI is elevated in relation to aspiration, reduced by bolus viscosity, and not affected by bolus volume. These data provide evidence that pharyngeal AIM analysis may have clinical utility for assessing deglutitive aspiration risk to liquid boluses.Taher I. Omari, Eddy Dejaeger, Jan Tack, Dirk Van Beckevoort, Nathalie Romme