A novel technique for difficult removal of a neonatal peripherally inserted central catheter (PICC).

Peripherally inserted central catheters have become commonplace in the neonatal intensive care unit for long-term hyperalimentation and medication administration. Removal of the catheter at the conclusion of therapy is routinely relatively easy. We describe a case of a retained catheter that was unresponsive to typical noninvasive interventions and was subsequently removed using a unique non-surgical approach.

Enteral glutamine supplementation for very-low-birth-weight infants decreases hospital costs.

BACKGROUND: There is growing evidence that glutamine may be a conditionally essential amino acid for critically ill patients, including preterm infants cared for in neonatal intensive care units (NICUs). In a randomized study of 68 very-low-birth-weight (VLBW) infants, we found evidence of lower morbidity in a group fed glutamine-supplemented preterm infant formula from postnatal day 3 to day 30 than in a group fed a standard formula. We report here the effects of the glutamine supplementation on hospital costs in these infants. METHODS: The costs were analyzed by log-rank tests and Kaplan-Meier plots. RESULTS: The median costs for hospitalization, radiology, pharmacy, laboratory, and the NICU, and the median number of utilization units were reduced with glutamine supplementation. CONCLUSIONS: This study provides the first evidence for decreased hospital costs in VLBW neonates who receive enteral glutamine supplementation.

Enteral glutamine supplementation for very low birth weight infants decreases morbidity.

Glutamine, described as a "conditionally essential" amino acid for critically ill patients, has not been routinely added to parenteral amino acid formulations for critically ill neonates and is provided in only small quantities by the enteral route when enteral intake is low. We conducted a blinded, randomized study of enteral glutamine supplementation in 68 very low birth weight neonates randomly assigned to receive glutamine-supplemented premature formula versus premature formula alone between days 3 and 30 of life. Primary end points consisted of hospital-acquired sepsis, tolerance to subsequent enteral feedings (days with no oral intake), and duration of hospital stay. Hospital acquired sepsis was 30% (control group) and 11% (glutamine group). Logistic regression with birth weight as a covariate showed that: (1) feeding group was significant (p = 0.048) in determining the probability of developing proven sepsis over the course of hospitalization and (2) the estimated odds of developing sepsis were 3.8 times higher for infants in the control group than for those treated with glutamine. Glutamine-supplemented infants had better tolerance to enteral feedings as measured by percent of days on which feedings needed to be withheld (mean percentage of 8.8 vs 23.8, p = 0.007). Analysis of T cells demonstrated a blunting of the rise in HLA-DR+ and CD16 subsets in glutamine-supplemented infants. There were no differences in growth; in serum ammonia, urea, liver transaminase, or prealbumin concentrations; or in mean hospital stay. This study provides evidence for decreased morbidity in very-low-birth-weight neonates who receive enteral glutamine supplementation.

Glutamine metabolism in very low birth weight infants.

To quantitate glutamine kinetics in premature infants and determine whether glutamine affects leucine metabolism. 11 very low birth weight (< 1250 g) neonates received 4-h i.v. infusions of L-[2H3]leucine and L-[13C5]glutamine, along with orogastric infusion of L-[I-13C]leucine and L-[I-13C]glutamine on the 10th d of life and in the fed state. Patients were receiving parenteral nutrition and were randomized to receive either hypocaloric, enteral preterm formula alone (controls; n = 5), or glutamine (0.2 g.kg-1.d-1 on the day of the study) supplemented formula (GL.n; n = 6). The rates of appearance (Ra) of leucine and glutamine, and their rates of splanchnic extraction were determined from isotopic enrichments in plasma at steady state. Leucine release from protein breakdown did not differ between groups (123 +/- 51 versus 162 +/- 94 mumol.kg-1h-1 in the controls and GLN group, respectively). Glutamine de novo synthesis accounted for > 80% of overall glutamine Ra, and was similar in both groups (626 +/- 177 versus 525 +/- 86 mumol.kg-1.h-1; NS); 46 +/- 16% and 53 +/- 31% of the enteral glutamine underwent first-pass splanchnic extraction in the controls and GLN group, respectively. These findings indicate that the pathways of glutamine de novo synthesis and glutamine utilization in the splanchnic bed are functional in very low birth weight humans by the 10th d of life. Glutamine supplementation provided at low doses on a hypocaloric regimen results in no apparent differences in flux of glutamine or leucine.

Ontogeny of glutamine synthetase in rat small intestine.

Glutamine synthetase (GS) is a key enzyme involved in the endogenous biosynthesis of glutamine, an amino acid known to be essential for small intestinal metabolism and function. This study describes the ontogeny of rat small intestinal GS from fetal life through adulthood with enzyme activities, protein immunoblotting, and steady state levels of GS mRNA by RNA gel blots and dot blots. Enzyme activities progressively increased from 21 d of fetal life to 32 d postnatally, then decreased in adulthood. The amount of GS immunoreactive protein in the small intestine increased from fetal life to 10-day-old infants and persisted into adulthood. GS mRNA, as quantified by dot blots was highest at 19 d postnatally. The ontogenic changes in rat small intestinal GS appear to correspond temporally with rapid growth and weaning. The steady increase in GS enzyme activity up to 32 d of age with a subsequent drop in adulthood is not paralleled by an increase in GS mRNA or protein. These findings suggest an apparent complex regulation of the enzyme activity at a transcriptional or translational levels.

Characterization of glutaminase in the developing rat small intestine.

As a primary substrate in the small intestine, glutamine is a very important source of energy. Glutaminase (GA) is the enzyme involved in the deamination of glutamine to glutamate, which is utilized for energy production via the TCA cycle. Although the enzymatic activity of GA in the small intestine is known to undergo maturational changes, the tissue localization of the protein and its mRNA, the intracellular processing of this enzyme and levels of its mRNA in the small intestine at different maturational stages have not yet been described. In this study, using immuno-histochemical staining, we confirm previous studies using other techniques that suggested GA is localized in the epithelial layer of the rat small intestine. Some GA is also found in cells of the lamina propria and crypt epithelium. Using in situ hybridization studies, we have corroborated the presence of the protein in the epithelial cells of the villi by localizing the mRNA of this protein to the same layer and its precursor layer in the crypt region. An ontogenic analysis of GA mRNA and protein from rat small intestines, using RNA dot blots, gel blots and protein immunoblotting revealed differences in immunoreactive GA protein and mRNA during maturation. Immunoreactive GA and steady-state levels of GA mRNA increased around the 3rd wk of life, coincident with weaning and the endogenous glucocorticoid surge. Whether these findings have nutritional or pathophysiological implications remains speculative.

Localization of rat small intestine glutamine synthetase using immunofluorescence and in situ hybridization.

Glutamine is an important energy source for small intestinal epithelial enterocytes and serves as a key precursor for de novo synthesis of purines and pyrimidines in these rapidly dividing cells. Although glutamine synthetase (GS) is known to be the major enzyme of glutamine biosynthesis, the precise localization of this enzyme in the small intestine is not known. Because glutamine is an important precursor for nucleic acids biosynthesis, we hypothesized that GS is preferentially expressed in the crypt region, which contains the rapidly proliferating cells in the small intestine. Accordingly, immunofluorescence with a specific polyclonal antibody and in situ hybridization using a riboprobe were performed to localize GS protein and mRNA, respectively, in adult rats. Both GS protein and GS mRNA were detected primarily in the crypt region. This finding suggests that GS is located in the region with the highest nucleotide synthesis and cell proliferation. This finding is in support of the use of parenteral glutamine in patients with severe mucosal injury affecting the crypts.

Term neonates with hemolytic disease of the newborn and necrotizing enterocolitis: a report of two cases.

Necrotizing enterocolitis in term infants is uncommon, and when it occurs it is usually associated with risk factors such as asphyxia, congenital heart disease, or polycythemia. It has been reported in term neonates after exchange transfusion for hemolytic disease of the newborn; therefore exchange transfusion is recognized as a risk factor. We report two term neonates with hemolytic disease of the newborn resulting from anti-c rhesus incompatibility in whom necrotizing enterocolitis developed before exchange transfusions. These cases implicate hemolytic disease of the newborn without exchange transfusion as a risk factor for necrotizing enterocolitis in term infants.

Metabolic acidemia with hypoxia attenuates the hemodynamic responses to epinephrine during resuscitation in lambs.

OBJECTIVE: To examine the effects of metabolic acidemia and hypoxia on the hemodynamic responses to epinephrine in an intact neonatal animal model. DESIGN: Multi-experiment, randomized, controlled trial. SETTING: Animal research laboratory of a university hospital. SUBJECTS: Sixteen lambs, ranging in age from 2 to 14 days. INTERVENTIONS: The lambs were chronically catheterized; the ductus arteriosus was ligated; and a pulmonary arterial flow probe was inserted to measure cardiac output, blood pressure (BP), and heart rate. In the first protocol, hemodynamic responses to epinephrine during pure metabolic acidemia or metabolic alkalosis were studied in eight lambs. Each lamb was studied on four different days at a different arterial pH: 6.9, 7.1, 7.4, and 7.6. Ventilation was controlled to maintain PCO2 at 35 to 45 torr (4.66 to 5.99 kPa). Acidemia was induced by the infusion of lactic acid and alkalosis by the infusion of sodium bicarbonate. When the appropriate arterial pH was achieved, 10 micrograms/kg of epinephrine was administered intravenously. In a second protocol, hemodynamic responses to epinephrine during metabolic acidemia or alkalosis plus hypoxia were studied in eight lambs. When the appropriate arterial pH was achieved, hypoxia was induced until cardiac output decreased to 40% of baseline. Epinephrine bolus was given, and after 90 secs, the lambs were resuscitated with oxygen. MEASUREMENTS AND MAIN RESULTS: Epinephrine administered during uncompromised hemodynamics led to hypertension, bradycardia, and decreased cardiac output that were unaffected by arterial pH values between 6.9 and 7.6. Acidemia with hypoxia compromised hemodynamics with decreases in heart rate and cardiac output. Epinephrine administered during this compromised condition did not improve cardiac output, heart rate, or BP before resuscitation with oxygen at any arterial pH studied. Resuscitation with epinephrine and oxygen during hemodynamically compromised states led to increases in heart rate, BP, and cardiac output with significant attenuation of these hemodynamic responses during metabolic acidemia at pH values of 6.9 and 7.1. CONCLUSIONS: During the physiologic conditions associated with neonatal resuscitation, that is, hypoxia with a compromised hemodynamic state, metabolic acidemia significantly attenuates the hemodynamic responses to resuscitation with epinephrine and oxygen. Correction of metabolic acidosis may be warranted in newborn resuscitation.