Paola Papoff

Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (nCPAP) after extubation in very low birth weight infants.

In this study we hypothesized that nasal synchronized intermittent positive pressure ventilation (nSIPPV) would provide more ventilatory support than nasal continuous positive airway pressure (nCPAP) in the immediate post-extubation period in very low birth weight (VLBW) infants. We tested this hypothesis by comparing the effects of these two ventilatory techniques on ventilation, gas exchange, and patient inspiratory effort in 11 preterm infants immediately after extubation. All neonates studied (BW: 1141+/-(SEM) 53 g; GA: 28.1+/-(SEM) 0.5 wks) had received mechanical ventilation because of respiratory distress at birth and were extubated by day 14 of life. Nasal SIPPV and nCPAP were applied in random order to each infant after extubation so that each was his/her own control. Both nCPAP and nSIPPV were delivered at end-expiratory pressures (PEEP) of 3 cm H2O. Inspiratory times (Ti) and peak inspiratory pressures set during nSIPPV were the same as those used at the time of extubation. Recordings lasted 45 min in each mode of ventilation. Tidal volume (Vt), minute volume (Ve), respiratory rate (RR), airway pressure (Paw), transcutaneous PO2 (TcPO2) and PCO2 (TcPCO2) as well as phasic esophageal pressure deflections (Pe), as an estimate of inspiratory effort, were measured. The measurements obtained during both modes of ventilation indicated significant differences between the two techniques. Indeed, application of nSIPPV was associated with a statistically significant increase in Vt and Ve. In addition, Pe decreased by 30% during nSIPPV (P<0.01). TcPCO2 was statistically significantly lower during nSIPPV than nCPAP, and RR as well. These data therefore suggest that nSIPPV may provide more ventilatory support than nCPAP in the post-extubation period with less patient inspiratory effort.

Nasal flow-synchronized intermittent positive pressure ventilation to facilitate weaning in very low-birthweight infants: Unmasked randomized controlled trial

Background: Nasal flow‐synchronized intermittent positive pressure ventilation (NFSIPPV) is a new non‐invasive ventilatory mode that delivers synchronized mechanical breaths through the nasal prongs. An unmasked, prospective randomized controlled trial was conducted to compare the efficacy of NFSIPPV and conventional nasal continuous positive airway pressure (NCPAP) in increasing the likelihood for successful extubation in very low‐birthweight infants.

Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up

The association between bronchiolitis and recurrent wheezing remains controversial. In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised for their first episode of bronchiolitis. Demographic, clinical and laboratory data were obtained with a questionnaire and from medical files. A total of 14 respiratory viruses were concurrently assayed in nasal washings. Parents were interviewed 12 months after hospitalisation to check whether their infants experienced recurrent wheezing. The rate of recurrent wheezing was higher in infants with bronchiolitis than in controls (52.7 versus 10.3%; p<0.001). Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0–11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2–4.9) as major independent risk factors for recurrent wheezing. In conclusion, the virus most likely to be associated with recurrent wheezing at 12 months after initial bronchiolitis is RV, a viral agent that could predict infants prone to the development of recurrent wheezing.

Circulating thrombopoietin levels in neonates with infection

Thrombocytopenia is a commonly encountered hematologic complication in neonates with sepsis. Thrombopoietin (TPO) is the principal physiologic regulator of megakariocytopoiesis and platelet production. This study was carried out to determine whether variations in circulating TPO levels would occur in infected neonates and/or if they would correlate with platelet counts. In a prospective study of 36 sick neonates (gestational age 24–42 wk) admitted to a regional Neonatal Intensive Care Unit (NICU), blood was collected for TPO measurements and platelet counts on admission to the NICU, if infection was inferred, and at recovery before discharge. An additional group of 15 apparently healthy neonates was also studied (median postnatal age at the time of blood sampling for TPO assessment: 4 d, range 1–10) as control. TPO was measured on plasma samples using a commercially available enzyme‐immunosorbent assay (ELISA). On admission, the majority (21/36) of the sick neonates had non‐infectious diseases, 2 had early onset sepsis, and 13 had infection (defined as the presence of clinical signs of sepsis, abnormal leukocyte counts or C‐reactive protein values, and positive results on local cultures, but negative blood culture results). During the hospital stay, 5 neonates developed sepsis (positive blood culture) and 6 had infection (as previously defined) or necrotizing enterocolitis (NEC). The median TPO level (1704pg/ml, range 51–3912) was higher during sepsis (either early or late) than during infection (included NEC) (198pg/ml, range 21–2504), or non‐infectious disease (659 pg/ml, range 0–2533), while platelet counts (median value 37,000 cells/μl, range 15,000‐486,000) were lower than during either infection (included NEC) (median value 238,000 cells/μl, range 49,000‐655,000) or noninfectious disease (median value 110,000 cells/μl, range 45,000‐549,000). When infants had recovered from these illnesses, TPO concentrations markedly dropped (median value 59 pg/ml, range 0–825). These values were similar to those found in the control neonates (median TPO level 85 pg/ml, range 43–620). In infected neonates (sepsis plus infection), TPO levels inversely correlated with platelet counts (r= ‐0.634, p= 0.001) as did those of infants with non‐infectious disease (r= ‐0.574, p= 0.006), while there was no significant correlation between TPO levels and platelet counts in the samples obtained after recovery or in the control infants. We conclude that infected neonates have high circulating TPO levels in the face of low platelet counts. Whether larger TPO concentrations following exogenous administration of recombinant TPO would restore the number of circulating platelets warrants further investigation.

Evaluation of viral load in infants hospitalized with bronchiolitis caused by respiratory syncytial virus

The relationship between viral load, disease severity and antiviral immune activation in infants suffering from respiratory syncytial virus (RSV)-associated bronchiolitis has not been well identified. The main objective of this study was to determine the existence of a correlation between RSV load and disease severity and also between different clinical markers and mRNA levels of the interferon stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also evaluated whether viral load tended to be persistent over the course of the RSV infection. The levels of RSV-RNA were quantified in nasopharyngeal washings, collected from 132 infants infected with RSV as a single (90.15%) or as a dual infection with other respiratory viruses (9.85%). Results indicated that viral load was positively related to the clinical severity of bronchiolitis, the length of hospital stay, the levels of glycemia and the relative gene expression of ISG56, whereas an inverse correlation was observed with the levels of hemoglobin. We also found that the RSV load significantly decreased between the first and second nasopharingeal washings sample in most subjects. These results suggest that infants with high RSV load on hospital admission are more likely to have both more severe bronchiolitis and a higher airway activation of antiviral immune response.

Outcomes after tongue–lip adhesion or mandibular distraction osteogenesis in infants with Pierre Robin sequence and severe airway obstruction

The objective was to review and compare outcomes after tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) in infants with severe breathing difficulties related to Pierre Robin sequence (PRS). A single-centre retrospective (2002-2012) study was carried out; 18 infants with severe breathing difficulties related to PRS resistant to conservative treatment, who underwent TLA or MDO to correct airway obstruction, were enrolled. The primary outcome measures were successful weaning from respiratory support and resumption of full oral feeding. Nine underwent TLA and nine MDO. Eight of the nine infants who underwent MDO and all those treated with TLA were successfully weaned from respiratory support. After discharge, residual respiratory distress was diagnosed more commonly after TLA than after MDO (6/9 vs 1/9, P=0.050). Infants resumed oral feeding sooner after MDO than after TLA (mean days after surgery to full oral feeds 44±24 vs 217±134, P<0.003). The length of hospital stay was longer for infants treated with MDO than for those treated with TLA. The rate of complications was similar. Infants with severe airway obstruction related to PRS can benefit safely from either TLA or MDO. Although MDO lengthens the time to discharge, this option stabilizes airway patency of infants with PRS more efficiently and achieves full oral feeding more rapidly than TLA.

Incidence and predisposing factors for severe disease in previously healthy term infants experiencing their first episode of bronchiolitis.

Aim:  To determine the incidence and predisposing factors for severe bronchiolitis in previously healthy term infants <12 months of age experiencing their first episode of bronchiolitis.

Is synchronised NIPPV more effective than NIPPV and NCPAP in treating apnoea of prematurity (AOP)? A randomised cross-over trial

Background Apnoea, desaturations and bradycardias are common problems in preterm infants which can be treated with nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV). It is unclear whether synchronised NIPPV (SNIPPV) would be even more effective. Objective To assess the effects of flow-SNIPPV, NIPPV and NCPAP on the rate of desaturations and bradycardias in preterm infants and, secondarily, to evaluate their influence on pattern of breathing and gas exchange. Patients and methods Nineteen infants (mean gestational age at study 30 weeks, 9 boys) with apnoeic spells were enrolled in a randomised controlled trial with a cross-over design. They received flow-SNIPPV, NIPPV and NCPAP for 4 h each. All modes were provided by a nasal conventional ventilator able to provide synchronisation by a pneumotachograph. The primary outcome was the event rate of desaturations (≤80% arterial oxygen saturation) and bradycardias (≤80 bpm) per hour, obtained from cardiorespiratory recordings. The incidence of central apnoeas (≥10 s) as well as baseline heart rate, FiO2, SpO2, transcutaneous blood gases and respiratory rate were also evaluated. Results The median event rate per hour during flow-SNIPPV, NIPPV and NCPAP was 2.9, 6.1 and 5.9, respectively (p<0.001 and 0.009, compared with flow-SNIPPV). Central apnoeas per hour were 2.4, 6.3 and 5.4, respectively (p=0.001, for both compared with flow-SNIPPV), while no differences in any other parameter studied were recorded. Conclusions Flow-SNIPPV seems more effective than NIPPV and NCPAP in reducing the incidence of desaturations, bradycardias and central apnoea episodes in preterm infants.

Morphologic evidence of diffuse vascular damage in human and in the experimental model of ethylmalonic encephalopathy

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1, a mitochondrial sulphur dioxygenase. By studying a suitable mouse model, we found that loss of ETHE1 leads to accumulation of sulphide, which is a poison for COX and other enzymatic activities thus accounting for the main features of EE. We report here the first autopsy case of a child with a genetically confirmed diagnosis of EE, and compare the histological, histochemical and immunohistochemical findings with those of the constitutive Ethe1−/− mice. In addition to COX depleted cells, widespread endothelial lesions of arterioles and capillaries of the brain and gastrointestinal tract were the pathologic hallmarks in both organisms. Our findings of diffuse vascular damage of target critical organs are in keeping with the hypothesis that the pathologic effects of ETHE1 deficiency may stem from high levels of circulating hydrogen sulphide rather than the inability of specific organs to detoxify its endogenous production.

Effectiveness and safety of propofol in newborn infants.

To the Editor .— We welcome the recent contribution by Ghanta et al,1 which showed the efficacy of propofol as an induction agent to facilitate neonatal endotracheal intubation. Their article provided convincing evidence that in neonates, as in adults and children, propofol without muscle relaxants provides optimal conditions for endotracheal intubation. Hence, skilled or less experienced physicians may be encouraged to sedate infants before semiurgent endotracheal intubation, a procedure that is still underused in most NICUs. Nevertheless, we would like to raise a note of caution regarding the use of propofol as a single agent before intubation in newborn …