Definitive peritoneal drainage in the extremely low birth weight infant with spontaneous intestinal perforation: predictors and hospital outcomes.

OBJECTIVE: To identify characteristics associated with definitive peritoneal drainage (PD) in the extremely low birth weight infant diagnosed with spontaneous intestinal perforation (SIP). We also sought to determine whether patients requiring a second operation (salvage laparotomy) following PD are at increased risk of adverse hospital outcomes, including increased times to full enteral feedings and decreased 30-day survival. STUDY DESIGN: We performed a retrospective chart review of infants with a birth weight <1000 g who underwent PD for SIP at a single tertiary neonatal unit from 2003 to 2012. Infants with signs of necrotizing enterocolitis on abdominal plain films, including pneumatosis intestinalis, portal venous gas or fixed, dilated small loops of bowel were excluded from the study. Perinatal and perioperative data and short-term neonatal outcomes prior to hospital discharge were collected. Comparison was made between two groups: infants treated with definitive PD vs infants requiring salvage laparotomy. Data were analyzed using independent samples t-test and Cochrane-Mantel-Haenszel. RESULT: Eighty-nine infants who fit all inclusion criteria were identified during the study period. PD was definitive in 67 (75.3%) patients. Patients who had definitive PD vs those who required salvage laparotomy were significantly more likely to present at a later day of life (9.6±5.3 vs 5.6±2.7, P<0.0001) and to have a lower birth weight (724.6 g±132.5 vs 809.2 g±143.1, P=0.02). The administration of indomethacin or ibuprofen prior to the diagnosis of SIP was also associated with definitive PD (74.6% vs 50%, P=0.03). Comparison of feeding outcomes revealed that the time to achieve full enteral feeds was significantly longer for those who underwent a salvage laparotomy (95.9±30.2 vs 60.4±30.4 days, P<0.005). Short-term survival (>30 days) was not significantly different between the two groups. CONCLUSION: PD was definitive therapy for the majority of neonates included in this study who were referred for surgical evaluation of SIP. Our data point to trends in being able to identify infants with SIP who are at risk for salvage laparotomy following PD, and thus, adverse nutritional outcomes. Larger, prospective studies are needed to further evaluate this specific patient population and identify those patients who are likely to succeed with PD following the diagnosis of SIP.

Developmental susceptibility to intestinal injury by platelet-activating factor in the newborn rat.

Platelet-activating factor (PAF) is an important endogenous mediator of neonatal necrotizing enterocolitis (NEC). Injection of PAF into weanling and adult rats causes ischemic bowel necrosis that is morphologically similar to NEC. The purpose of this study was to adapt the PAF model of intestinal injury to the suckling rat and to attempt to alter susceptibility to PAF-induced bowel necrosis by early weaning and formula feeds. At ages 15 to 20 days, rat pups were selected to be weaned to either formula or 5% dextrose or to nurse ad lib (total n = 54). At ages 16, 18, 20, 21, 23, or 25 days of life, animals received PAF (50 micrograms/kg) and endotoxin (1 mg/kg) by intraperitoneal injection. Animals were sacrificed 2 h after injection. Intestinal samples were submitted to be graded by a pathologist in a blinded fashion. Injury scores ranged from 0 to 10, based on the percentage of villous necrosis. Prior to age 20 days, minimal histologic injury was present (mean scores on days 16, 18 = 1.7 +/- 0.9, 1.7 +/- 0.6). Combined injury scores for weaned and nursed animals on days 20 and 23 were significantly greater than on days 16 and 18 (p = .0001). Histologic injury in the dextrose group was significantly less than the formula-fed group on day 21 and greater on day 25. Suckling rats showed resistance to PAF-induced bowel necrosis prior to 20 days of age, during the middle of the weaning period. Early weaning to formula did not alter susceptibility to injury, which suggests that PAF-acetylhydrolase from breast milk does not confer this resistance to PAF.

The role of luminal nutrients in intestinal injury from mesenteric reperfusion and platelet-activating factor in the developing rat.

Necrotizing enterocolitis (NEC) develops primarily after the onset of enteral feeds in the premature infant. The purpose of this study was to evaluate the influence of intestinal luminal nutrients on histologic injury and the oxidant response in a rat model of NEC. On postnatal Days 10 and 35, Sprague-Dawley rats (total n = 81) underwent abdominal laparotomy. A control group received sham-injury only. The ischemia groups received a single intraluminal injection of 0.25 ml (Day 10) or 1.0 ml (Day 35) of lactose (8.6 g/dl), casein (2.2 g/dl), corn oil (4.4 g/dl), or infant formula (Similac; 20 g/dl). After injection of the nutrient solutions, ischemia groups underwent mesenteric occlusion for 1 hr and intraluminal injection of platelet-activating factor (50 microgram/kg). Necropsies were performed after 6 hr or at demise. Intestinal samples were taken for histology, total glutathione (GSH; an antioxidant), and conjugated dienes (a lipid peroxidation product). Histologic injury was scored from 0 (normal) to 5 (transmural necrosis). Microscopic injury scores in the oil group were significantly higher than the casein group (P < 0.05) and trended toward being higher in the formula group (P = 0.085) at age 10 days. Total GSH activity was significantly higher in the sham groups than all ischemia groups on Day 10 (P < 0.001) and than the corn oil group on Day 35 (P < 0.05). GSH activity did not differ among ischemia groups. Conjugated diene concentrations were significantly higher in the casein group than the lactose and sham groups at age 10 days (P < 0.05) only. We conclude that intraluminal lipids may augment intestinal ischemic injury in the newborn (age 10 days) but not the weanling rat. While oxygen-free radicals were present during injury, lipid peroxidation from oxygen radicals was not responsible for this increase in histologic injury.

Congenital ventral hernia in association with focal dermal hypoplasia.

Focal dermal hypoplasia is a rare, X-linked dominant syndrome characterized by dysplasia of the skin, skeleton, and central nervous system. We report an infant who was born with severe focal dermal hypoplasia and an epigastric hernia. Operative timing and approach to abdominal wall defects in the presence of severe cutaneous dysplasia are discussed.

Is Phaseolus vulgaris leucoagglutinin (PHA-L) a useful marker for labeling neural grafts?

The lectin Phaseolus vulgaris leucoagglutinin (PHA-L) has come into wide use as an anterograde neuroanatomical tracer. The ability of this lectin to fill entire neurons and remain in place over long periods suggested it might be an ideal marker for donor cells to be grafted into hosts for long survival periods. We have used the lectin PHA-L to mark fetal rat olfactory bulb (OB) cells prior to grafting into host rat OBs. Hosts were sacrificed at various times up to 9 weeks after grafting, and tissue was immunohistochemically processed for PHA reactivity. After 2 and 4 weeks survival, sparse patterns of labeled cells were observed within the host OBs. However, after 9 weeks survival, few if any labeled cells were visible within host tissue. We conclude that PHA-L may be a less than satisfactory marker for fetal rat cells (other than astrocytes) which are to be identified in host tissue after a period of several weeks.

Response to chronic insulin administration: effect of area postrema ablation.

The effects of daily administration of protamine zinc insulin (PZI) on plasma insulin and glucose levels and on food intake and body weight of rats with lesions of the area postrema and adjacent caudal-medial portions of the nucleus of the solitary tract (APX rats) were examined. Prior to insulin treatment, APX rats weighted less and had lower plasma immunoreactive insulin (IRI) levels than nonlesioned controls but did not differ from controls in plasma glucose levels. Five daily injections of 5 U/kg PZI raised plasma IRI and lowered plasma glucose levels similarly for both lesioned and nonlesioned rats. When injected with increasing doses of PZI over a 30-day period, both lesioned and nonlesioned rats showed increases of food intake and rate of weight gain in response to 8 U/kg PZI. These data indicate that APX does not affect either physiological or behavioral responses to chronic peripheral insulin administration.