Reducing post-extubation failure rates in very preterm infants: is BiPAP better than CPAP?

BACKGROUND AND AIM: Continuous positive airway pressure (CPAP) is currently used in neonates after mechanical ventilation though it may occasionally be associated with air leaks syndromes or it may fail to support the baby. The pressure difference offered by bilevel continuous positive distending pressure (BiPAP) respect to CPAP may be an advantage to the spontaneously breathing patient. In this study, we compared the efficacy of CPAP and BiPAP in the firstweek post-extubation in a series of very preterm infants. METHODS: Inborn neonates less than 30 weeks of gestational age who were intubated shortly after birth from January 2011 to December 2017 were enrolled in a retrospective study. The attending clinician assessed the patients for non-invasive respiratory support readiness and allocated them to CPAP (PEEP 4-6 cmH2O) or BiPAP (PEEP 4-5 cmH2O, rate 10-40; Thigh 0.7-1.2; upper-pressure level 8-10 cmH2O). Both techniques were compared for preventing extubation failure within 7 days from extubation as defined per local protocol (primary outcome). Secondary outcomes were: definitive failure of extubation, pneumothorax during non-invasive respiratory support, periventricular leukomalacia, bronchopulmonary dysplasia, sepsis, patent ductus arteriosus and retinopathy of prematurity at discharge. RESULTS: We enrolled 134 neonates; the CPAP group included 89 babies while 45 received BiPAP. Patients did not differ for their general characteristics (EG, antenatal steroids, incidence of SGA, maternal hypertension, surfactant replacement therapy). Short term extubation failure was significantly higher in the former group (23/89 in CPAP vs 5/45 in BiPAP; p = .005). No infant developed air leak syndrome. Secondary outcomes were comparable between groups. Multivariate analysis showed that on the whole population the extubation failure was correlated to the insurgence of late-onset sepsis. CONCLUSION: BiPAP safely reduced early extubation failure compared to CPAP in our cohort of very preterm neonates within 7 days from extubation.

Neonatal Hyperbilirubinemia: An Updated Appraisal of National Guidelines.

Recent reports from several developed countries have documented a resurgence of bilirubin encephalopathy causing both healthcare and forensic issues. For these reasons, many national pediatric societies have issued recommendations on the diagnosis and the treatment of clinically significant neonatal hyperbilirubinemia. The differences among individual national documents may have an impact on neonatal healthcare. This paper shortly reviews the advantages and the shortcomings of the main international guidelines with a focus on the available evidence.

Neonatal painful stimuli: skin conductance algesimeter index to measure efficacy 24% of sucrose oral solution.

Pain management is one of the main challenges in addressing the improved care of hospitalized newborns. The administration of oral sucrose with and without non-nutritive suction has been proposed as a nonpharmacological intervention to relieve procedural pain in newborns. The effects have not yet been well characterized. The aim of this study is to investigate, using skin conductance algesimeter (SCA) pain monitor index, the effects of 24% sucrose solution on pain perception during capillary and arterial blood sampling. It is a prospective, randomized controlled study: sucrose versus placebo. Sucrose was given orally to infants who were submitted to arterial or capillary sampling. The SCA was measured during, and for 3 min before and after the intervention. Fifty-six infants were enrolled: 31 in the sucrose group and 25 in the placebo group. SCA showed that the measurement of peaks per second of pain during and 3 min after the procedures was lower in the sucrose group than the placebo group and that this difference was statistically significant (p < .05). In conclusion, 24% sucrose administered orally is effective in reducing pain during and after capillary and arterial sampling in newborns and can be used for the prevention and treatment of pain in the Neonatal Intensive Care Unit.Brief rationaleTo treat neonatal pain, a tiered approach with nonpharmacological and pharmacological method can be used.Among nonpharmacological therapies, sucrose administration is safe and effective in reducing single episodes of minor procedural pain. This study aimed to investigate, the effects of 24% sucrose solution on pain perception during capillary and arterial blood withdrawn by using an objective method: skin conductance algesimeter (SCA) pain monitor index.This randomized controlled trial in which term and/or preterm neonates (postnatal age maximum of 28 days corrected for postmenstrual age) received sucrose for procedural pain. Oral sucrose was administered directly by a disposable plastic vial. SCA was measured by means of a specific device.We demonstrated, using SCA pain monitor index, the efficacy of 24% sucrose solution on pain perception during capillary and arterial blood withdrawn. The results of this study provide an objective evidence of sucrose efficacy for the prevention and treatment of neonatal painful procedures.

The intracavitary electrocardiography method for positioning the tip of epicutaneous cava catheter in neonates: Pilot study.

PURPOSE:: The neonatologists of Sant'Anna and San Sebastiano Hospital of Caserta have carried out a pilot study investigating the safety, feasibility, and accuracy of intracavitary electrocardiography for neonatal epicutaneous cava catheter tip positioning. PATIENTS AND METHODS:: We enrolled 39 neonates (1-28 days of postnatal age or correct age lower than 41 weeks) requiring epicutaneous cava catheter in the district of superior vena cava (head-neck or upper limbs). Intracavitary electrocardiography was applicable in 38 neonates. RESULTS:: No significant complications related to intracavitary electrocardiography occurred in the studied neonates. The increase in P wave on intracavitary electrocardiography was detected in 30 cases. Of the remaining eight cases, six malpositioned catheters tipped out of cavoatrial junction-target zone (chest x-ray and echocardiographical control) and two were false negative (tip located in target zone). The match between intracavitary electrocardiography and x-ray was observed in 29/38 cases, and the same ratio between intracavitary electrocardiography and echocardiography was detected. CONCLUSION:: We conclude that the intracavitary electrocardiography method is safe and accurate in neonates as demonstrated in pediatric and adult patients. The applicability of the method is 97% and its feasibility is 79%. The overall accuracy is 76% but it rises to 97% if "peak" P wave is detected.

HGF stimulation of Rac1 signaling enhances pharmacological correction of the most prevalent cystic fibrosis mutant F508del-CFTR.

Cystic fibrosis (CF), a major life-limiting genetic disease leading to severe respiratory symptoms, is caused by mutations in CF transmembrane conductance regulator (CFTR), a chloride (Cl(-)) channel expressed at the apical membrane of epithelial cells. Absence of functional CFTR from the surface of respiratory cells reduces mucociliary clearance, promoting airways obstruction, chronic infection, and ultimately lung failure. The most frequent mutation, F508del, causes the channel to misfold, triggering its premature degradation and preventing it from reaching the cell surface. Recently, novel small-molecule correctors rescuing plasma membrane localization of F508del-CFTR underwent clinical trials but with limited success. Plausibly, this may be due to the mutant intrinsic plasma membrane (PM) instability. Herein, we show that restoration of F508del-CFTR PM localization by correctors can be dramatically improved through a novel pathway involving stimulation of signaling by the endogenous small GTPase Rac1 via hepatocyte growth factor (HGF). We first show that CFTR anchors to apical actin cytoskeleton (via Ezrin) upon activation of Rac1 signaling through PIP5K and Arp2/3. We then found that such anchoring retains pharmacologically rescued F508del-CFTR at the cell surface, boosting functional restoration by correctors up to 30% of wild-type channel levels in human airway epithelial cells. Our findings reveal that surface anchoring and retention is a major target pathway for CF pharmacotherapy, namely, to achieve maximal restoration of F508del-CFTR in patients in combination with correctors. Moreover, this approach may also translate to other disorders caused by trafficking-deficient surface proteins.

Control of TMEM16A by INO-4995 and other inositolphosphates.

BACKGROUND AND PURPOSE: Ca(2+)-dependent Cl(-) secretion (CaCC) in airways and other tissues is due to activation of the Cl(-) channel TMEM16A (anoctamin 1). Earlier studies suggested that Ca(2+) -activated Cl(-) channels are regulated by membrane lipid inositol phosphates, and that 1-O-octyl-2-O-butyryl-myo-inositol 3,4,5,6-tetrakisphosphate octakis(propionoxymethyl) ester (INO-4995) augments CaCC. Here we examined whether TMEM16A is the target for INO-4995 and if the channel is regulated by inositol phosphates. EXPERIMENTAL APPROACH: The effects of INO-4995 on CaCC were examined in overexpressing HEK293, colonic and primary airway epithelial cells as well as Xenopus oocytes. We used patch clamping, double electrode voltage clamp and Ussing chamber techniques. KEY RESULTS: We found that INO-4995 directly activates a TMEM16A whole cell conductance of 6.1 ± 0.9 nS pF(-1) in overexpressing cells. The tetrakisphosphates Ins(3,4,5,6)P(4) or Ins(1,3,4,5)P(4) and enzymes controlling levels of InsP(4) or PIP(2) and PIP(3) had no effects on the magnitude or kinetics of TMEM16A currents. In contrast in Xenopus oocytes, human airways and colonic cells, which all express TMEM16A endogenously, Cl(-) currents were not acutely activated by INO-4995. However incubation with INO-4995 augmented 1.6- to 4-fold TMEM16A-dependent Cl(-) currents activated by ionomycin or ATP, while intracellular Ca(2+) signals were not affected. The potentiating effect of INO-4995 on transient ATP-activated TMEM16A-currents in cystic fibrosis (CF) airways was twice of that observed in non-CF airways. CONCLUSIONS AND IMPLICATIONS: These data indicate that TMEM16A is the target for INO-4995, although the mode of action appears different for overexpressed and endogenous channels. INO-4995 may be useful for the treatment of CF lung disease.