Hesham Abdel-Hady

Early weaning from CPAP to high flow nasal cannula in preterm infants is associated with prolonged oxygen requirement: A randomized controlled trial

OBJECTIVE To determine the better approach for weaning preterm infants from nasal continuous positive airway pressure (NCPAP) with or without transitioning to nasal cannula (NC). DESIGN/METHODS This is a randomized, open label, controlled trial. Preterm infants born at ≥28 weeks gestation who were clinically stable on NCPAP of 5 cm H(2)O with FiO(2)<0.30 for at least 24 h were randomly assigned to one of 2 groups. The no-NC group were kept on NCPAP until they were on FiO(2)=0.21 for 24 h, and then were weaned off NCPAP completely without any exposure to NC. If they met failing criteria, NCPAP was re-instituted. The NC-group was weaned off NCPAP when FiO(2) was ≤0.30 to NC (2 L/min) followed by gradual weaning from oxygen. Infants who failed NC were supported back with NCPAP for 24 h before making a second attempt of NC. RESULTS Sixty neonates were enrolled; 30 in each group. The two groups were similar in birthweight, gestational age, sex, antenatal steroids, mode of delivery, use of surfactant and xanthines, and duration of mechanical ventilation. After randomization, the no-NC group had fewer days on oxygen [median (interquartile range): 5 (1-8) vs 14 (7.5-19.25) days, p<0.001] and shorter duration of respiratory support [10.5 (4-21) vs 18 (11.5-29) days, p=0.03]. There were no differences between groups regarding success of weaning from NCPAP. CONCLUSIONS Weaning preterm infants from NCPAP to NC is associated with increased exposure to oxygen and longer duration of respiratory support.

A randomized controlled trial on parenteral nutrition, oxidative stress, and chronic lung diseases in preterm infants.

Objectives:To evaluate the effect of trace elements (TEs), when added to total parenteral nutrition (TPN) solutions, on peroxides load, and to test the hypothesis that protection of TPN from light can decrease peroxides load and is associated with improvement in oxidant-related clinical outcomes in preterm infants. Subjects and Methods:A total of 80 preterm infants were randomized to 1 of 4 groups (n = 20 each): group 1 received a mixture of dextrose and amino acids; group 2 received a mixture of dextrose, amino acids, and lipid emulsion; group 3 received dextrose, amino acids, lipid emulsion, and multivitamins (MVP); and group 4 received dextrose, amino acids, lipid emulsion, MVP, and TEs. Each group was subdivided into photo-protected and photo-exposed subgroups (n = 10 each). Using ferrous oxidation of xylenol orange technique, we measured the baseline level of excreted urinary peroxides before and 48 hours after starting TPN. We examined the association among light protection, urinary peroxides, and clinical outcomes of these infants. Results:Baseline urinary peroxides ranged between 5.5 and 24.8 μmol/L. A significant increase in urinary peroxides was observed in all groups after receiving TPN. The use of TEs did not affect peroxide production. In regression analysis, the addition of MVP (P < 0.0001) and the exposure to light (P = 0.02) were significantly associated with increased urinary peroxides. In the overall population, light exposure was associated with a significant increase in the incidence of chronic lung disease (adjusted OR 9.26, confidence interval 1.2–73; P = 0.03) but had no effect on mortality, necrotizing enterocolitis, or sepsis. Conclusions:TEs in TPN solutions have no effect on the production of urinary peroxides. Addition of MVP and exposure of TPN to light are the 2 major sources of peroxides in TPN. Protection from ambient light is associated with a decrease in chronic lung disease.

Hemodynamic Changes During Weaning From Nasal Continuous Positive Airway Pressure

BACKGROUND. Nasal continuous positive airway pressure is frequently used to support preterm infants with respiratory distress syndrome. Little is known about the hemodynamic changes that occur, particularly during the weaning phase when lung compliance has improved and most of the airway pressure can be transmitted to the heart and major blood vessels. METHODS. We conducted a prospective study on preterm infants (gestational age ≤32 weeks) with resolving respiratory distress syndrome, who were receiving nasal continuous positive airway pressure of 5 cm H2O and 21% oxygen. While cycling nasal continuous positive airway pressure, we performed 2-dimensional M-mode and pulsed Doppler echocardiography on all infants during nasal continuous positive airway pressure and 1 hour after being off nasal continuous positive airway pressure. RESULTS. A total of 25 preterm infant were studied. The use of nasal continuous positive airway pressure significantly decreased right ventricular output (320 ± 22.7 vs 410.5 ± 44.1 mL/kg per min); right ventricular end diastolic diameter (6 ± 0.7 vs 6.4 ± 0.4 mm), left ventricular end diastolic diameter (11.6 ± 0.9 vs 13.6 ± 0.7 mm), left ventricular end systolic diameter (7.1 ± 0.6 vs 8.3 ± 0.4 mm), left atrial diameter (6.3 ± 0.5 vs 8 ± 0.5 mm), aortic root diameter (6.4 ± 0.3 vs 6.6 ± 0.4 mm), superior vena cava flow (70.2 ± 8.5 vs 91.1 ± 4 mL/kg per minute), and pulmonary maximum velocity (0.6 ± 0.1 vs 0.7 ± 0.1 m/seconds). It significantly increased mean inferior vena cava diameter (4.3 ± 0.5 vs 3.5 ± 0.6 mm), whereas nasal continuous positive airway pressure did not influence left ventricular output, aortic maximum velocity, fractional shortening, heart rate, or mean arterial blood pressure. Changes associated with nasal continuous positive airway pressure were similar in infants with (n = 8) and without (n = 17) patent ductus arteriosus. CONCLUSIONS. In infants with resolving respiratory distress syndrome, nasal continuous positive airway pressure can impede systemic and pulmonary venous return, but it does not compromise systemic arterial pressure or heart rate. It is not clear whether the degree of these hemodynamic changes can affect the success of weaning off nasal continuous positive airway pressure.

Patent ductus arteriosus in preterm infants: do we have the right answers?

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants. Preterm newborns with PDA are at greater risk for several morbidities, including higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical interventions for ligation of PDA are widely used. However, these interventions were reported to be associated with side effects. In the absence of clear restricted rules for application of these interventions, different strategies are adopted by neonatologists. Three different approaches have been investigated including prophylactic treatment shortly after birth irrespective of the state of PDA, presymptomatic treatment using echocardiography at variable postnatal ages to select infants for treatment prior to the duct becoming clinically significant, and symptomatic treatment once PDA becomes clinically apparent or hemodynamically significant. Future appropriately designed randomized controlled trials (RCTs) to refine selection of patients for medical and surgical treatments should be conducted. Waiting for new evidence, it seems wise to employ available clinical and echocardiographic parameters of a hemodynamically significant (HS) PDA to select patients who are candidates for medical treatment. Surgical ligation of PDA could be used as a back-up tool for those patients who failed medical treatment and continued to have hemodynamic compromise.

Myocardial dysfunction in neonatal sepsis: a tissue Doppler imaging study.

Objectives: To assess myocardial performance in septic full-term infants and to correlate it with serum cardiac troponin T concentrations. Design: Prospective, case-control, clinical study. Setting: Neonatal intensive care unit in a university hospital. Patients: Twenty septic and 20 nonseptic full-term neonates. Interventions: None. Measurements and Main Results: Conventional echocardiography, tissue Doppler imaging, and serum cardiac troponin T concentration tests were performed as soon as diagnosis was made. On tissue Doppler imaging measurements, right ventricular and left ventricular Tei indexes were significantly higher in septic neonates compared to nonseptic neonates (mean ± SD: 0.51 ± 0.09 vs. 0.28 ± 0.05, p < .001, and 0.56 ± 0.07 vs. 0.39 ± 0.04, p < .001, respectively). Mitral and tricuspid peak annular systolic velocities were significantly lower in septic neonates (mean ± SD: 4.35 ± 0.68 vs. 6.89 ± 0.94 cm/sec, p < .0001, and 5.55 ± 0.66 vs. 6.69 ± 0.87 cm/second, p < .0001, respectively). On conventional echocardiography measurements, left ventricular internal diameter at end-diastole was significantly higher in septic neonates (p = .04), whereas cardiac index and left ventricular and right ventricular diastolic functions were not significantly different between septic and nonseptic neonates. Cardiac troponin T concentrations were significantly higher in septic neonates (median [range], 0.19 [0.12– 0.32] vs. 0.03 [0–0.07] mg/L, p < .0001), and they correlated positively with left ventricular Tei index (r = .80; p < .0001) and right ventricular Tei index (r = .73; p < .0001), and correlated negatively with mitral peak annular systolic velocity (r = −.70; p < .0001) and tricuspid peak annular systolic (r = −.39, p = .012). Nonsurvivors had significantly higher serum cardiac troponin T concentrations and left ventricular Tei index. Conclusions: Neonatal sepsis is associated with systolic and diastolic myocardial dysfunction. This study provides proof-of-concept data for the use of tissue Doppler imaging in assessment of myocardial dysfunction in septic neonates. Tissue Doppler imaging appears to be more sensitive than conventional echocardiography in the detection of this dysfunction. Serum cardiac troponin T and left ventricular Tei index may have prognostic value in these patients.

Anasarca: not a nephrotic syndrome but dermatomyositis

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterized by inflammation of the muscle, connective tissue, skin, gastrointestinal tract, and small nerves. Periorbital and facial edema may also be associated. Although localized edema is a common feature of JDM, generalized edema has rarely been reported. Here, we report a 3.5-year-old boy with JDM presenting with generalized edema. The diagnostic criteria of JDM rely on typical clinical manifestations that include: severe symmetric weakness of the proximal musculature, characteristic cutaneous changes, elevated serum skeletal muscle enzymes, and myopathic electromyographic pattern. Our patient initially received methylprednisolone and intravenous immunoglobulin (IVIG) without significant improvement, so he was given azathioprine and a prolonged course of oral prednisolone. We conclude that JDM should be suspected in patients presenting with anasarca in the absence of laboratory parameters of other causes of generalized edema and an appearance of heliotrope rash with muscle weakness. Also, we suggest that muscle magnetic resonance imaging (MRI) should be considered among the diagnostic tools of JDM.

Pentoxifylline therapy for late-onset sepsis in preterm infants: a randomized controlled trial.

Background: The role of pentoxifylline (PTX) in reducing mortality associated with neonatal sepsis is not well established. We aimed to assess the efficacy and safety of PTX as an adjunct to antibiotics on mortality and morbidity in preterm infants with late-onset sepsis (LOS). Methods: Double blind, randomized controlled trial was conducted on 120 preterm infants with LOS. They were randomly assigned to receive either intravenous PTX 5 mg/kg/hr for 6 hours on 6 successive days or placebo. Death before hospital discharge was our primary outcome and secondary outcomes were length of hospital stay, duration of respiratory support, duration of antibiotics use, short-term morbidity of preterm infants, tumor necrosis factor-alpha concentrations, C-reactive protein concentrations, and adverse effects of PTX. Results: A total of 120 infants were enrolled, 60 in each group, 78 (65%) infants had confirmed and 42 (35%) had suspected LOS. There were no significant differences between groups regarding mortality [6 (10%) in PTX vs. 10 (16.5%) in placebo, P = 0.44], short-term morbidity and combined mortality and/or short-term morbidity [18 (30%) vs. 24 (40%), P = 0.23]. PTX therapy was associated with significant reduction of serum tumor necrosis factor-alpha and C-reactive protein concentrations. The length of hospital stay, durations of respiratory support and antibiotic therapy were significantly shorter in the PTX group. Patients in PTX group had less need for vasopressors, lower incidence of metabolic acidosis, disseminated intravascular coagulopathy and thrombocytopenia. No adverse effects to PTX were reported. Conclusions: PTX has a beneficial adjuvant effect to antibiotic therapy in preterm infants with LOS without significant impact on neonatal mortality and morbidity.

Caffeine therapy in preterm infants

Caffeine is the most commonly used medication for treatment of apnea of prematurity. Its effect has been well established in reducing the frequency of apnea, intermittent hypoxemia, and extubation failure in mechanically ventilated preterm infants. Evidence for additional short-term benefits on reducing the incidence of bronchopulmonary dysplasia and patent ductus arteriosus has also been suggested. Controversies exist among various neonatal intensive care units in terms of drug efficacy compared to other methylxanthines, dosage regimen, time of initiation, duration of therapy, drug safety and value of therapeutic drug monitoring. In the current review, we will summarize the available evidence for the best practice in using caffeine therapy in preterm infants.

Neuroprotection for Perinatal Hypoxic Ischemic Encephalopathy in Low- and Middle-Income Countries.

From the Winnipeg Regional Health Authority, Winnipeg, Manitoba, Canada; 2 3 the standard of care for treating newborns with moderate to severe HIE. Therapeutic hypothermia has been found to reduce the risk of death or major neurodevelopmental disability at age 18 months (risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and to increase survival with normal neurologic function (RR, 1.63; 95% CI, 1.36-1.95). Recent studies have confirmed improved neurocognitive outcomes at school age. Those studies involved predominantly developed countries. In contrast, a systematic review of 7 trials including 567 newborns from LMI countries, using mainly low-cost cooling techniques, did not show a significant reduction in neonatal mortality (RR, 0.74; 95% CI, 0.441.25). Although the point estimate is consistent with estimates from the developed world, the wide CI of that result means that a clinically important benefit or harm could not be excluded. Furthermore, there was insufficient long-term follow-up to allow assessment of whether hypothermia had improved neurodevelopmental outcomes. The heterogeneity of outcomes in studies from LMI countries may be an artifact of poorly designed studies, many of which were very small. The largest study in that review, which carried almost one-half of the weight in the primary outcome (neonatal mortality), may have introduced selection bias by including more boys (85%) and violated its protocol by including 20% cases with mild encephalopathy. Overall, 15% of the patients in these studies hadmild encephalopathy, and, consistent with this, only 12% required ventilation. Newborns with mild HIE have a low risk of mortality, reducing the study’s power and potentially leading to a false conclusion that the intervention is not conclusive when the intervention was not applied to the correct target population. It is unclear whether the low frequency of mechanical ventilation reflects only selection for milder cases, or whether resource limitations constrained care. Alternatively, the heterogeneity of outcomes potentially could be “real,” that is, related to medical factors that impair

Conventional Versus Prolonged Infusion of Meropenem in Neonates with Gram Negative Late Onset Sepsis: A Randomized Controlled Trial.

Background: Gram-negative bacteria are associated with significant morbidity and mortality in preterm and term newborns. Meropenem has widespread efficacy and often allows for monotherapy in this group. Prolonged infusion instead of infusion over 30 minutes has been suggested to result in higher microbiologic efficacy. Objective: To compare the clinical and microbiologic efficacy and safety of prolonged infusions versus conventional dosing of meropenem in neonates with Gram-negative late-onset sepsis (GN-LOS). Methods: A prospective, randomized clinical trial was conducted in neonates with GN-LOS admitted to neonatal intensive care unit (NICU), Mansoura University Children’s Hospital, between August 2013 and June 2015. Patients were randomly assigned to receive either intravenous infusion of meropenem over 4 hours (infusion group) or 30 minutes (conventional group) at a dosing regimen of 20 mg/kg/dose every 8 hours and 40 mg/kg/dose every 8 hours in meningitis and Pseudomonas infection. Clinical and microbiologic success in eradication of infection were the primary outcomes. Neonatal mortality, meropenem-related (MR) duration of mechanical ventilation, MR length of NICU stay, total length of NICU stay, duration of respiratory support (RS), duration of mechanical ventilation, MR duration of inotropes and adverse effects were secondary outcomes. Results: A total of 102 infants (51 in each group) were recruited. The infusion group demonstrated a significantly higher rate of clinical improvement and microbiologic eradication 7 days after starting meropenem therapy compared with the conventional group. Mortality and duration of RS were significantly less in the infusion group compared with conventional group. Acute kidney injury after meropenem treatment was significantly less in the infusion group compared with the conventional group. Conclusions: Prolonged infusion of meropenem in neonates with GN-LOS is associated with higher clinical improvement, microbiologic eradication, less neonatal mortality, shorter duration of RS and less acute kidney injury compared with the conventional strategy.