Blood group AB increases risk for surgical necrotizing enterocolitis and focal intestinal perforation in preterm infants with very low birth weight.

Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07-2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06-3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10-2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.

Hypertrophic intraventricular flow obstruction after very-low-dose dexamethasone (Minidex) in preterm infants: case presentation and review of the literature.

The use of dexamethasone in preterm infants developing bronchopulmonary dysplasia has been proven to be effective. Hypertrophic cardiomyopathy is a frequently reported, although transient, side effect of high-dose dexamethasone administration. The recent introduction of very low dexamethasone dose, called 'Minidex', promised equal effectiveness compared to high-dose dexamethasone without relevant side effects. Our study presents two patients developing hypertrophic cardiomyopathy with intraventricular cardiac obstruction after administration of 'Minidex'. Marked cardiac side effects may occur even during very-low-dose dexamethasone treatment in preterm neonates. Betablocker and discontinuation of dexamethasone seem to allow spontaneous reversal of myocardial hypertrophy and obstruction. After all, systematic surveys of the incidence of cardiac complications in a larger population of preterm infants treated with very low doses of dexamethasone are needed.

Benzimidazolones enhance the function of epithelial Na⁺ transport.

BACKGROUND AND PURPOSE: Pharmacological enhancement of vectorial Na⁺ transport may be useful to increase alveolar fluid clearance. Herein, we investigated the influence of the benzimidazolones 1-ethyl-1,3-dihydro-2-benzimidazolone (1-EBIO), 5,6-dichloro-1-EBIO (DC-EBIO) and chlorzoxazone on vectorial epithelial Na⁺ transport. EXPERIMENTAL APPROACH: Effects on vectorial Na⁺ transport and amiloride-sensitive apical membrane Na⁺ permeability were determined by measuring short-circuit currents (I(SC)) in rat fetal distal lung epithelial (FDLE) monolayers. Furthermore, amiloride-sensitive membrane conductance and the open probability of epithelial Na⁺ channels (ENaC) were determined by patch clamp experiments using A549 cells. KEY RESULTS: I(SC) was increased by approximately 50% after addition of 1-EBIO, DC-EBIO and chlorzoxazone. With permeabilized basolateral membranes in the presence of a 145:5 apical to basolateral Na⁺ gradient, the benzimidazolones markedly increased amiloride-sensitive I(SC). 5-(N-Ethyl-N-isopropyl)amiloride-induced inhibition of I(SC) was not affected. The benzamil-sensitive I(SC) was increased in benzimidazolone-stimulated monolayers. Pretreating the apical membrane with amiloride, which inhibits ENaC, completely prevented the stimulating effects of benzimidazolones on I(SC). Furthermore, 1-EBIO (1 mM) and DC-EBIO (0.1 mM) significantly increased (threefold) the open probability of ENaC without influencing current amplitude. Whole cell measurements showed that DC-EBIO (0.1 mM) induced an amiloride-sensitive increase in membrane conductance. CONCLUSION AND IMPLICATIONS: Benzimidazolones have a stimulating effect on vectorial Na⁺ transport. The antagonist sensitivity of this effect suggests the benzimidazolones elicit this action by activating the highly selective ENaC currents. Thus, the results demonstrate a possible new strategy for directly enhancing epithelial Na⁺ transport.

Ventilation strategies and outcome in randomised trials of high frequency ventilation.

OBJECTIVE: Randomised controlled trials comparing elective use of high frequency ventilation (HFV) with conventional mechanical ventilation (CMV) in preterm infants have yielded conflicting results. We hypothesised that the variability of results may be explained by differences in study design, ventilation strategies, delay in initiation of HFV, and use of permissive hypercapnia. METHODS: Randomised controlled trials comparing the elective use of HFV with any form of CMV were identified. Trials were classified according to the ventilation strategies used for HFV and CMV and oscillator device employed. For cumulative meta-analyses, trials were arranged by the following covariables: mean duration until randomisation, Paco(2) limits, publication date, and sample size. Odds ratios (OR) and 95% confidence intervals were calculated using fixed and random effects models. RESULTS: Seventeen randomised trials enrolling 3776 patients were included. Unlike previous meta-analyses, there was no significant difference in the incidence of bronchopulmonary dysplasia or death (OR 0.87, 0.75-1.00) and severe intraventricular haemorrhage grade 3-4 (1.14, 0.96-1.37). The incidence of air leaks (OR 1.23, 1.06-1.44) was significantly increased with HFV. Subgroup analyses and cumulative meta-analyses demonstrated that trial results were related to the ventilation strategies used for HFV and CMV. No influence was found for mean time to randomisation, degree of permissive hypercapnia, or sample size. CONCLUSIONS: Heterogeneity among trials of elective HFV compared to CMV in preterm infants is mainly due to differences in ventilatory strategies. Optimising CMV strategy appeared to be as effective as using HFV in improving pulmonary outcome in preterm infants.

Partial liquid ventilation in severely surfactant-depleted, spontaneously breathing rabbits supported by proportional assist ventilation.

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.

High-frequency ventilation in neonates.

High-frequency ventilation (HFV) has been advocated to reduce lung injury and chronic lung disease (CLD) in preterm infants. Several randomized controlled trials have compared HFV with conventional mechanical ventilation (CMV) in preterm and term infants. This review first discusses animal data pertinent to optimizing the application of HFV in preterm infants. Second, a meta-analysis of all randomized controlled trials using HFV as an early intervention is presented. Finally, rescue use of HFV in preterm and term infants with respiratory failure or air leak syndromes is summarized. Eleven trials of early intervention with HFV are included in the meta analysis. Overall, chronic lung disease at 36 weeks postmenstrual age was reduced in patients treated with HFV, but mortality was not changed. The decrease in CLD, however, is confounded, as it is only based on small trials, whereas no pulmonary benefit was found in the three largest trials. Furthermore, HFV appears to increase the incidence of severe intracranial hemorrhages and periventricular leukomalacia. Therefore, routine elective use of HFV cannot be recommended at the present time. Limited data on rescue use of HFV suggest some benefits over continued CMV.