Chylothorax: A Stepwise Approach to Diagnosis and Treatment

Chylothorax, a lymphatic flow disorder characterized by an abnormal circulation of lymph fluid into the pleural cavity, is the most common cause of pleural effusions during the neonatal period. This condition affects 1/15,000 neonates every year. Affected neonates often manifest with respiratory distress, electrolyte imbalances, sepsis, and even immunodeficiencies. Mortality risk is highest among neonates undergoing cardiac surgery as well as those with associated hydrops fetalis. Conservative treatment options include bowel rest with administration of parenteral nutrition, followed with medium-chain triglyceride enteral feedings, and octreotide therapy. Severe or persistent cases require surgical intervention. This can involve a unilateral or bilateral pleurectomy and thoracic duct ligation, with or without pleurodesis. Early identification and successful treatment of this condition is contingent upon awareness of the most current evidence and a timely cross-disciplinary approach to care.

Postnatal Hepatobiliary and Gastrointestinal Systems Development and Impact on ADME

Toxicity can result from variable target organ sensitivity and exposure based on postnatal development. Changes in the gastrointestinal tract (GIT) in neonates are driven by initial enteral feedings. These are important for nutrient uptake as well as drug disposition and include motility, expansion of enzyme and transporter function, permeability, intestinal microbiome, and species-specific maturation. Some aspects of GIT function do not mature until driven by increased dietary complexity. As with the GIT, postnatal hepatic maturation in the rat includes a variety of anatomic and functional changes that include refinements in the activities or expression of drug transporters and drug-metabolizing enzymes. These changes may impact rodent pharmacokinetics, nonclinical toxicity profiles, and estimation of safe pediatric doses. Pilot or dose range finding studies can help characterize and mitigate toxicity related to drug disposition, especially in juvenile rodents. Interpretation of developmental toxicity requires knowledge of developing systems in humans and nonclinical models.

Automated Self-Adjusting Subcutaneous Insulin Algorithm for Patients NPO or on TPN or Enteral Feedings

Background: Perioperative diabetes patients are often treated with sliding-scale insulin, despite a lack of evidence to support therapeutic effectiveness. We introduced an automated subcutaneous insulin algorithm (SQIA) to improve glycemic control in these patients while maintaining the simplicity of a q4 hour adjustable sliding-scale insulin order set. Methods: In this pilot study, we implemented a fully programmed, self-adjusting SQIA as part of a structured order set in the electronic medical record for adult patients who are nil per os, or on continuous enteral tube feedings or total parenteral nutrition. The nurse only enters the current glucose in the Medication Administration Record, and then the calculated dose is shown. The new dose is based on previous dose, and current and previous glucoses. The SQIA titrates the glucose to 120-180 mg/dL. For this pilot, this order set was utilized for complex perioperative oncologic patients. Results: The median duration on the SQIA was 58 hours. Glucoses at titration initiation were highest at 206 ± 63 mg/dL, and came down to 156 ± 29 mg/dL by 72 hours. The majority of measured glucoses (66.8%, n = 647) were maintained between 80 and 180 mg/dL. There were no glucoses lower than 60 mg/dL, and only 0.3% (n = 3) were below 70 mg/dL. There was a low rate of errors (1%). Conclusions: A simple automated SQIA can be used to titrate insulin to meet the changing metabolic requirements of individuals perioperatively and maintain glucose within the target range for these hospitalized patients.

Maltodextrin-induced intestinal injury in a neonatal mouse model

ABSTRACTPrematurity and enteral feedings are major risk factors for intestinal injury leading to necrotizing enterocolitis (NEC). An immature digestive system can lead to maldigestion of macronutrients and increased vulnerability to intestinal injury. The aim of this study was to test in neonatal mice the effect of maltodextrin, a complex carbohydrate, on the risk of intestinal injury. The goal was to develop a robust and highly reproducible murine model of intestinal injury that allows insight into the pathogenesis and therapeutic interventions of nutrient-driven intestinal injury. Five- to 6-day-old C57BL/6 mice were assigned to the following groups: dam fed (D); D+hypoxia+Klebsiella pneumoniae; maltodextrin-dominant human infant formula (M) only; M+hypoxia; and M+hypoxia+K. pneumoniae. The mice in all M groups were gavage fed five times a day for 4 days. Mice were exposed to hypoxia twice a day for 10 min prior to the first and last feedings, and K. pneumoniae was added to feedings as per group assignment. Mice in all M groups demonstrated reduced body weight, increased small intestinal dilatation and increased intestinal injury scores. Maltodextrin-dominant infant formula with hypoxia led to intestinal injury in neonatal mice accompanied by loss of villi, increased MUC2 production, altered expression of tight junction proteins, enhanced intestinal permeability, increased cell death and higher levels of intestinal inflammatory mediators. This robust and highly reproducible model allows for further interrogation of the effects of nutrients on pathogenic factors leading to intestinal injury and NEC in preterm infants.This article has an associated First Person interview with the first author of the paper.

Achievement of full enteral feeding using volume advancement in infants with birth weight 1,000 to <2,000 grams

Background Early enteral feeding is one of the efforts to improve gastrointestinal adaptability in preterm infants. Volume advancement (VA) enteral feeding has been associated with less time to reach full feeding, which can improve outcomes. Objective To evaluate the duration of VA needed to achieve full enteral feeding (FEF) in low birth weight (LBW) and very low birth weight (VLBW) infants and related factors. Methods This prospective study was done in infants with birth weight 1,000 to <2,000 grams in the Neonatal Ward and NICU of Dr. Moh. Hoesin General Hospital, Palembang, South Sumatera. All infants underwent VA feeding. The time needed to achieve FEF (150 ml/kg/day) was recorded. Several clinical factors were analyzed for possible associations with the success rate of achieving FEF within 10 days of feeding. Results Thirty-five infants were included in this study with a mean gestational age of 31.83 (SD 2.67) weeks. Their median body weight at the start of protocol was 1,400 (range 1,000 – 1,950) grams and 80% had hyaline membrane disease. Median time to achieve FEF was 11 (range 8–21) days, with 48.6% subjects achieving FEF in ≤10 days. Gestational age <32 weeks (OR 5.404, 95%CI 0.963 to 30.341), birth weight <1,500 grams (OR 5.248, 95%CI 0.983 to 28.003), and male (OR 4.751, 95%CI 0.854 to 26.437) gender were associated with the failure of achieving FEF within 10 days of feeding, however, no factors remained statistically significant after multivariate analysis. Conclusion Full enteral feedings in infants with birth weight 1,000 to <2,000 grams with VA feeding are achieved within a median of 11 days. Gestational age, birth weight, and gender are not associated with time needed to achieve FEF.