Continuous infusion versus intermittent bolus doses of indomethacin for patent ductus arteriosus closure in symptomatic preterm infants.

BACKGROUND: Indomethacin is a prostaglandin inhibitor used for the prevention and the treatment of patent ductus arteriosus (PDA). Although a 3-dose schedule has been commonly used, there is no consensus on optimal dosage and duration of indomethacin therapy for PDA closure. There are potential adverse effects of indomethacin use in premature infants such as a reduction in cerebral, mesenteric and renal blood flow and platelet dysfunction. Administering indomethacin continuously over 36-hours has been suggested as a safer and more effective option to prevent such adverse effects. OBJECTIVES: To compare the efficacy and safety of continuous infusion versus bolus administration of indomethacin in closing a symptomatic PDA in preterm infants. SEARCH STRATEGY: The standard search strategy of Cochrane Neonatal Review was used: MEDLINE and EMBASE (1966 - March 2007), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007), bibliographies of reviews and trials were examined for references to other trials, previous symposia proceedings published in Pediatric Research (Pediatric Academic Societies Annual Meeting Abstract Book, 1972 - 2006). No language restrictions were applied. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing continuous indomethacin infusion to bolus doses for closure of a symptomatic PDA in preterm infants with a symptomatic PDA diagnosed clinically and/or by echocardiography. DATA COLLECTION AND ANALYSIS: The methodological quality of each study was assessed. Authors were contacted regarding missing data as well as to inquire about the outcomes that were not reported. Meta-analysis was performed to calculate relative risk (RR), risk difference (RD) and 95% confidence intervals (CI). MAIN RESULTS: Only two small trials comparing continuous versus bolus indomethacin were eligible. Analysis of these studies showed that, although the primary outcome of PDA closure on days two and five slightly favored bolus administration, there was no statistical difference between the two groups. The estimates for PDA closure were RR 1.57 (95% CI 0.54, 4.60), RD 0.10 (95% CI -0.13, 0.33) for day 2 and RR 2.77 (95% CI 0.33, 23.14), RD 0.15 (95% CI -0.13, 0.42) for day five. There was no statistical difference between the bolus and continuous groups for the secondary outcomes of reopening of PDA, neonatal mortality, intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). These analyses were based on a very small number of events reported by these trials. None of the trials reported on outcomes such as requirement for retreatment with indomethacin or surgical ligation, mortality, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), neurodevelopmental outcome and isolated intestinal perforation. The review demonstrated that there was a decrease in cerebral blood flow velocity after bolus injections and that the difference between the bolus and continuous infusion groups remained significant for 12 - 24 hour. In one study (Christmann 2002), the decrease in blood flow was maximum at 10 minutes [MD -46.40 (95% CI -75.41, -17.39)], while the other study (Hammerman 1995) reported a maximum drop at 30 minutes [MD -55.60 (95% CI -62.92, -48.28)]. Similar decrease in blood flow to the renal and mesenteric circulations following bolus administration was reported in one study (Christmann 2002). In both of these circulations, the decrease was maximum 30 minutes after the bolus injection [typical estimates for renal and mesenteric circulations, respectively: MD -42.00 (95% CI -76.59, -7.41) and MD -26.50 (95% CI -45.34, -7.66)] and lasted about two hours. None of the trials detected predefined levels of decreased urine output and increased levels of BUN and creatinine. AUTHORS' CONCLUSIONS: Due to a paucity of events and lack of precision, the available data was found to be insufficient to draw conclusions regarding the efficacy of continuous indomethacin infusion versus bolus injections for the treatment of PDA. Although continuous indomethacin seems to cause less alterations in cerebral, renal and mesenteric circulations, the clinical meaning of this effect is unclear. Definitive recommendations about the preferred method of indomethacin administration i.e. continuous versus bolus infusions for the treatment of PDA in premature infants cannot be made based on the current findings of this review.

Effect of low fat diet on lipid absorption and fatty-acid transport following bowel resection.

Low-fat diets (LFD) are used extensively in many different clinical conditions. However, the effect of this diet on lipid absorption and cellular long-chain fatty-acid (LCFA) transport is unknown. Fatty-acid translocase (FAT), the rat homologue of human CD36, is one of several LCFA plasma-membrane transport proteins that may play an important role in intestinal lipid uptake. The purpose of this study was to investigate the effects of a LFD on intestinal expression of FAT/CD36, enterocyte fatty-acid transport, and in-vivo lipid absorption in rats following bowel resection. Adult male Sprague-Dawley rats were divided into five experimental groups: normal rats fed normal chow(NR-NC) (10 kcal% fat), normal rats fed a LFD (NR-LFD) (3 kcal% fat), sham rats fed normal chow (Sham-NC), short-bowel syndrome rats fed normal chow (SBS-NC), and SBS rats fed a LFD (SBS-LFD). SBS rats underwent 75% small-bowel resection, while sham animals underwent bowel transection and reanastomosis. Food intake, fecal mass, and fecal fat were measured over the last 3 days before death on day 14. Final body weight, plasma lipids and protein, and tissue total lipids in liver, adipose tissue, and intestine were determined at death. Total RNA from the mucosa of the duodenum, jejunum, and ileum was extracted for Northern blot analysis to determine fatty-acid translocase (FAT)/CD36 mRNA levels. An established cellular LCFA transport assay was used to determine isolated enterocyte [3H]-oleate uptake. Students t-test was used to determine statistical significance (P < 0.05). NR-LFD rats demonstrated a small increase in overall food absorption and no change in fat absorption compared to NR-NC animals. A significant decrease in FAT/CD36 mRNA levels was seen in the duodenum and jejunum in NF-LFD rats (vs NR-NC) and was accompanied by reduced LCFA transport by isolated enterocytes from the jejunum and ileum. SBS-LFD rats demonstrated decreased FAT/CD36 mRNA levels in all three segments and a concomitant decrease in LCFA uptake enterocytes compared to the SBS-NC group. In addition, SBS-LFD rats showed significantly lower final body weight and plasma lipids compared to SBS-NC animals.

The effect of mucin on bacterial translocation in I-407 fetal and Caco-2 adult enterocyte cultured cell lines.

Although the intestinal mucosa forms a crucial barrier between the host and the environment, bacterial translocation (BT) occurs frequently in neonates and may be a source of sepsis. The intestinal mucous gel layer is thought to be a vital component of the gut barrier and is composed, in part, of a family of glycoproteins known as mucins. Our aim was to study the effects of mucin on BT in an enterocyte cell-culture model using a fetal (I-407) and an adult (Caco-2) intestinal cell line. I-407 and Caco-2 cells were grown to confluence on porous filters in a two-chamber Transwell system. The integrity of the monolayers was confirmed by transepithelial electrical resistance (TEER) and permeability using the macromolecule dextran blue. Cells were treated with mucin (40 mg/ml) prior to inoculation of 1 x 10(6) Escherichia coli C25. The magnitude of BT was determined quantitatively by culturing the samples from the basal chamber of the wells and was expressed as log 10 [Colony Forming Units (CFU)/ml]. Statistical analysis was performed by the Mann-Whitney U test with statistical significance at P < 0.05. Mucin inhibited BT across both fetal and adult cultured enterocyte monolayers; however, the inhibitory effect was less on the fetal cells compared to the adult cells. Dextran-blue studies showed that monolayers were intact throughout the experiments. Despite 98% inhibition of BT, mucin had a statistically significant effect on post-bacterial inoculation TEER in Caco-2 cells and no effect in I-407 cells. The ability of mucin, a mucous-barrier glycoprotein, to inhibit BT across immature intestinal enterocytes, as in the neonate, may be diminished compared to mature adult enterocytes.

Pentalogy of Cantrell.

Omphalocele is often associated with various abnormalities. In two patients admitted with omphalocele, we additionally found defects both in the pars stenalis of diaphragm and in the diaphragmatic surface of the pericardium, sternal defect and tetralogy of Fallot. These entities form the components of a syndrome, named pentalogy of Cantrell. It is extremely in the spectrum of midline closure defects that display wide variations and its incidence is very low. Existing cardiac defect is the most important factor influencing morbidity and mortality. Herein we report two cases of pentalogy of Cantrell with the review of the syndrome in the light of literature.