The effect of imposed resistance in neonatal resuscitators on pressure stability and peak flows: a bench test.

BACKGROUND: The importance of neonatal resuscitator resistance is currently unknown. In this study we investigated peak flows and pressure stability resulting from differences in imposed resistance during positive pressure ventilation(PPV) and simulated spontaneous breathing (SSB) between the r-PAP, low-resistance resuscitator, and Neopuff™, high-resistance resuscitator. METHODS: In a bench test, 20 inflations during PPV and 20 breaths during SSB were analysed on breath-by-breath basis to determine peak flow and pressure stability using the Neopuff™ with bias gas flow of 8, 12 or 15 L/min and the r-PAP with total gas flow of 15 L/min. RESULTS: Imposed resistance of the Neopuff™ was significantly reduced when the bias gas flow was increased from 8 to 15 L/min, which resulted in higher peak flows during PPV and SSB. Peak flows in the r-PAP were, however, significantly higher and fluctuations in CPAP during SSB were significantly smaller in the r-PAP compared to the Neopuff™ for all bias gas flow levels. During PPV, a pressure overshoot of 3.2 cmH2O was observed in the r-PAP. CONCLUSIONS: The r-PAP seemed to have a lower resistance than the Neopuff™ even when bias gas flows were increased. This resulted in more stable CPAP pressures with higher peak flows when using the r-PAP. IMPACT: The traditional T-piece system (Neopuff™) has a higher imposed resistance compared to a new neonatal resuscitator (r-PAP). This study shows that reducing imposed resistance leads to smaller CPAP fluctuations and higher inspiratory and expiratory peak flows. High peak flows might negatively affect lung function and/or cause lung injury in preterm infants at birth. This study will form the rationale for further studies investigating these effects. A possible compromise might be to use the traditional T-piece system with a higher bias gas flow (12 L/min), thereby reducing the imposed resistance and generating more stable PEEP/CPAP pressures, while limiting potentially harmful peak flows.

The Effect of a Higher Bias Gas Flow on Imposed T-Piece Resistance and Breathing in Preterm Infants at Birth.

Objective: The resistance created by the PEEP-valve of a T-piece resuscitator is bias gas flow dependent and might affect breathing in preterm infants. In this study we investigated the effect of a higher bias gas flow on the imposed inspiratory and expiratory T-piece resistance and expiratory breaking manoeuvres (EBM) in preterm infants during spontaneous breathing on CPAP at birth. Methods: In a retrospective pre-post implementation study of preterm infants <32 weeks gestation, who were stabilised with a T-piece resuscitator, a bias gas flow of 12 L/min was compared to 8 L/min. All spontaneous breaths on CPAP within the first 10 min of starting respiratory support were analysed on a breath-by-breath basis to determine the breathing pattern of each breath and to calculate the imposed inspiratory and expiratory T-piece resistance (Ri, Re), flow rates and tidal volume. Results: In total, 54 infants were included (bias gas flow 12 L/min: n = 27, 8 L/min: n = 27) with a median GA of 29+6 (28+4-30+3) and 28+5 (25+6-30+3), respectively (p = 0.182). Ri and Re were significantly lower in the 12 L/min compared to 8 L/min bias flow group [Ri: 29.6 (26.1-33.6) vs. 46.4 (43.0-54.1) cm H2O/L/s, p < 0.001; Re: 32.0 (30.0-35.1) vs. 48.0 (46.3-53.9) cm H2O/L/s, p < 0.001], while the incidence of EBM [77% (53-88) vs. 77% (58-90), p = 0.586] was similar. Conclusion: During stabilisation of preterm infants at birth with a T-piece resuscitator, the use of a higher bias gas flow reduced both the imposed inspiratory and expiratory T-piece resistance for the infant, but this did not influence the incidence of EBMs.

A multi-centre randomised controlled trial of respiratory function monitoring during stabilisation of very preterm infants at birth.

AIM: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range. METHODS: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes. RESULTS: Among 288 infants randomised (median (IQR) gestational age 26+2 (25+3-27+1) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO2. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028). CONCLUSION: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. TRIAL REGISTRATION: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.

The host's genetic background determines the extent of angiogenesis induced by schistosome egg antigens.

Schistosomiasis is characterised by periovular granuloma formation within the portal tract and presinusoidal venules. As inflammation wanes, continued attempts to wall off and repair hepatic injury, lead to the development of extensive fibrosis. The codependence of chronic inflammation and angiogenesis is a well-known phenomenon. Neovascularisation is a complex process of endothelial cell proliferation and remodelling of the extracellular matrix. Previous studies demonstrated the ability of schistosome soluble egg antigens (SEAs) to stimulate endothelial cell activation in vitro. In the present study, we investigated the angiogenic potential of SEA in Swiss and BALb/c mice, after infection with Schistosoma mansoni or S. haematobium and by implanting SEA-coated beads into the murine liver. Anti-CD34 and anti-Ki-67 immunohistochemical stainings demonstrated newly formed blood vessels within and at the periphery of the granulomas. However, in one third of the granulomas the pre-existing portal stroma was not destroyed by the granulomatous inflammation, angiogenesis was minimal or absent and further growth of the granuloma was prevented. In C57BL/6J and C3H/HeN inbred mice, this polarisation was even more pronounced. In 91% of the granulomas in C57BL6/J mice the portal stroma was preserved. These mice had significantly smaller granulomas, less fibrosis and less mortality as compared to the high pathology C3H/HeN mice, where 87% of the granulomas were of the angiogenic type with destruction of the pre-existing stroma, leading to more severe chronic pathology. Thus, host's genetic mechanisms regulating the degree of angiogenesis and fibrosis, determine the severity of schistosome-induced pathology.