Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birth weight infants.

OBJECTIVE: Magnesium sulfate (MgSO(4)) is the most commonly used tocolytic agent in the US and is also employed as a prophylactic agent against seizures in pre-eclamptic women. MgSO(4) crosses the placenta and its concentration in the newborn usually exceeds that of maternal levels. The purpose of this study was to explore the relationship between antenatal exposure to MgSO(4) and the incidence of patent ductus arteriosus (PDA) in extremely low birth weight infants. STUDY DESIGN: A total of 954 neonates with birth weights between 500 and 1000 g, born at the University of Miami/Jackson Memorial Hospital between January 1995 and December 2004 and surviving for more than 3 days, were followed until death or discharge from the hospital. The incidence of PDA in infants exposed to MgSO(4) was compared with those not exposed and comparisons were also made between infants exposed to different maternal doses of MgSO(4). RESULTS: The incidence of PDA was significantly higher in the group of infants exposed to MgSO(4) compared with the unexposed control group (67 vs. 60%, P<0.018). When stratified by gestational age the differences were significant only in the group of infants with a gestational age of >or=26 weeks (58 vs. 49%, P<0.039). Logistic regression analysis to adjust for co-variables indicated an increased risk of PDA with higher doses of MgSO(4) (odds ratio 1.33 confidence interval (CI) 1.12 to 1.58, per 50 g of MgSO(4)). CONCLUSION: Antenatal exposure to MgSO(4) is associated with a higher risk of PDA in extremely low birth weight infants and this effect is more significant and dose-related in more mature infants.

Continuous positive airway pressure: early, late, or stay with synchronized intermittent mandatory ventilation?

Mechanical ventilation is associated with significant short- and long-term morbidity in small preterm infants. Continuous positive airway pressure applied through nasal prongs is an effective, less-invasive method to improve gas exchange and reduce apnea in these infants. A large number of studies have evaluated the possibility of reducing the need or duration of mechanical ventilation by early use of nasal continuous positive airway pressure shortly after birth and by applying it after extubation. Although results of these trials have not been consistent, most of the evidence suggests that nasal continuous positive airway pressure is a viable alternative to mechanical ventilation in many preterm infants and that its use after extubation contributes to maintain better lung function and reduces apnea. Despite this, there is no evidence that these beneficial short-term effects translate into lower rates of long-term morbidity such as bronchopulmonary dysplasia and neurologic sequelae or mortality rates.

Bronchopulmonary dysplasia and surfactant.

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in preterm infants who survive prolonged mechanical ventilation. Exogenous surfactant administration clearly reduces the severity of respiratory distress syndrome (RDS) and consequently the need for aggressive ventilation and prolonged oxygen therapy. However, the overall incidence of BPD has not decreased but in fact may even have increased after the introduction of surfactant therapy. There are several reasons for the lack of effect on the incidence of BPD. First, surfactant therapy and antenatal steroids have markedly increased survival of the smallest infants, i.e. those at higher risk of BPD. Second, there has been a change in the pathogenesis and the presentation of BPD. While the classic BPD was mainly the consequence of barotrauma and oxygen toxicity, the new BPD seen in the surfactant era results from the interaction of many factors that lead to prolonged mechanical ventilation and colonization of the airway with pathogens that may trigger an inflammatory cascade. While the overall incidence of BPD has not been substantially modified by surfactant therapy, the more severe cases of BPD have become less common. The data regarding the effect of surfactant administration on the incidence and severity of BPD is conflicting. There is substantial evidence that the administration of exogenous surfactant, either as prophylaxis or as a treatment in infants with established RDS, can reduce neonatal mortality and the occurrence of BPD or death. The data also suggest that prophylactic or early administration is more effective than late treatment in reducing mortality and BPD or death. No clear difference has been documented between natural or synthetic surfactant treatment in terms of their effect on incidence of BPD or mortality. The lack of consistency in the results with surfactant replacement may reflect the changing pathogenesis of BPD and the multiplicity of factors involved among which surfactant deficiency is only one.

Effects of treatment with pentoxifylline on the cardiovascular manifestations of group B streptococcal sepsis in the piglet.

Pentoxifylline (PTXF) is a methylxanthine derivative which modifies leukocyte function and inhibits tumor necrosis factor (TNF)-alpha release. As TNF-alpha is considered a proximal mediator in the cascade leading to septic shock, we evaluated the ability of PTXF to attenuate the cardiovascular manifestations of sepsis secondary to an infusion of group B beta-hemolytic streptococci (GBS). Fifteen anesthetized, mechanically ventilated piglets (weight, 2815 +/- 552 g) were randomly assigned to a treatment group which received a continuous infusion of PTXF (5 mg/kg/h) beginning 30 min after GBS (7.5 x 10(8) colony-forming units/kg/min) administration was started or to a control group which received GBS plus saline as placebo. Comparison of the hemodynamic measurements and arterial blood gases over the first 120 min of bacterial infusion for treatment and control groups revealed the following statistically significant differences (120-min values presented): cardiac output was significantly higher in the PTXF group (0.159 +/- 0.035 versus 0.09 +/- 0.026 L/kg/min; p < 0.05) as was stroke volume (0.54 +/- 0.11 versus 0.27 +/- 0.126 mL/kg/beat; p < 0.01). Pulmonary and systemic vascular resistances remained lower in the PTXF-treated animals (167 +/- 45 versus 233 +/- 69 mm Hg/L/kg/min; p < 0.03) and (427 +/- 162 versus 828 +/- 426 mm Hg/L/kg/min; p < 0.03, respectively). Median survival time was significantly longer in the PTXF group (180 versus 120 min; p < 0.05). In an additional group of animals, PTXF administration before GBS infusion revealed no attenuation in the rise of TNF-alpha, accompanying sepsis. These data demonstrate that treatment with PTXF may ameliorate some of the deleterious hemodynamic manifestations of GBS sepsis and result in improved survival in a young animal model without significantly modifying plasma TNF-alpha levels.

Effect of an interleukin-1 receptor antagonist on the hemodynamic manifestations of group B streptococcal sepsis.

IL-1 is purported to be a proximal mediator in the cascade leading to septic shock. To characterize its hemodynamic effects and to ascertain whether its blockade would ameliorate the deleterious consequences of sepsis, an IL-1 receptor antagonist (IL-1ra) was administered to 16 anesthetized, mechanically ventilated piglets that received a continuous infusion of group B streptococci (GBS) (7.5 x 10(7) colony-forming units/kg/min). Systemic (Psa), pulmonary artery (Ppa), and wedge (Pwp) pressures and cardiac output were measured pre-GBS and every 30 min during GBS infusion. After 15 min of bacterial infusion the control group received normal saline, whereas the treatment group received a bolus of IL-1ra (40 mg/kg) followed by a continuous infusion of IL-1ra (60 micrograms/kg/min). In comparing IL-1ra-treated animals with controls from the 15-min GBS baseline to the succeeding septic study period (45-120 min), the following treatment effects were noted (120-min values shown): mean Psa remained elevated in treatment compared with control animals (12.7 +/- 2.5 versus 9 +/- 3.5 kPa; p < 0.001) as did CO (0.21 +/- 0.07 versus 0.13 +/- 0.08 L/min/kg; p < 0.001). Pwp decreased in the treatment compared to the control group over the study period (1 +/- 0.3 versus 1.6 +/- 0.7 kPa; p < 0.02). Mean Ppa and mean Pra were not different between groups over time. Median length of survival was significantly longer (p = 0.04) in treated (226 min) compared with control animals (150 min). These data suggest that IL-1 plays an important role in GBS sepsis and septic shock, and that IL-1ra may in part ameliorate the cardiovascular alterations associated with GBS sepsis in the neonate.

Effects of pentoxifylline on the cardiovascular manifestations of group B streptococcal sepsis in the piglet.

Pentoxifylline (PTXF) is a methylxanthine that modifies leukocyte function and inhibits cytokine release. To evaluate its effects on the cardiovascular manifestations of sepsis secondary to group B streptococci, 14 anesthetized, mechanically ventilated piglets were studied over a 240-min period. Animals were randomly assigned to a treatment group that received a PTXF bolus (20 mg/kg) followed by a continuous infusion of 5 mg/kg/h before and during group B streptococci (1 x 10(8) colony forming units/kg/min) administration and a control group that received saline as a placebo. Comparison of the hemodynamic measurements and arterial blood gases during the first 90 min of PTXF treatment with those of the control group resulted in the following 90 min values: systemic arterial blood pressure was significantly higher in the PTXF group (89 +/- 10 versus 56 +/- 30 mm Hg; p less than 0.005) as was cardiac output (0.18 +/- 0.04 versus 0.10 +/- 0.07 L/kg/min; p less than 0.005). Pulmonary vascular resistance remained lower in the PTXF-treated animals (135 +/- 117 versus 248 +/- 119 mm Hg/L/min/kg; p less than 0.001), and these animals were less acidotic as measured by pH (7.07 +/- 0.2 versus 7.31 +/- 0.1; p less than 0.05) and base deficit (-15 +/- 9 versus -5 +/- 2 mmol/L; p less than 0.05). Median survival time was significantly longer in the PTXF group (210 versus 90 min; p less than 0.002). These data demonstrate that PTXF can ameliorate some of the deleterious hemodynamic manifestations of group B streptococci sepsis and result in improved survival in a young animal model.