Constant-flow nasal continuous positive airway pressure (NCPAP) often is used in preterm neonates to recruit and maintain lung volume. Physical model studies indicate that a variable-flow NCPAP ...device provides more stable volume recruitment with less imposed work of breathing (WOB). Although superior lung recruitment with variable-flow NCPAP has been demonstrated in preterm neonates, corroborating WOB data are lacking.
To measure and compare WOB associated with the use of variable-flow versus constant-flow NCPAP in preterm neonates.
Twenty-four preterm infants who were receiving constant-flow NCPAP (means, SD) and had birth weight of 1024 +/- 253 g, gestational age of 28 +/- 1.7 weeks, age of 14 +/- 13 days, and FIO(2) of 0.3 +/- 0.1 were studied. Variable-flow and constant-flow NCPAP were applied in random order. We measured changes in lung volume and tidal ventilation (V(T)) by DC-coupled/calibrated respiratory inductance plethysmography as well as esophageal pressures at NCPAP of 8, 6, 4, and 0 cm H(2)O. Inspiratory WOB (WOB(I)) and lung compliance were calculated from the esophageal pressure and V(T) data using standard methods. WOB was divided by V(T) to standardize the results.
WOB(I) decreased at all CPAP levels with variable-flow NCPAP, with a maximal decrease at 4 cm H(2)O. WOB(I) increased at all CPAP levels with constant-flow CPAP. Lung compliance increased at all NCPAP levels with variable-flow, with a relative decrease at 8 cm H(2)O, whereas it increased only at 8 cm H(2)O with constant-flow NCPAP. Compared with constant-flow NCPAP, WOB(I) was 13% to 29% lower with variable-flow NCPAP.
WOB(I) is decreased with variable-flow NCPAP compared with constant-flow NCPAP. The increase in WOB(I) with constant-flow NCPAP indicates the presence of appreciable imposed WOB with this device. Our study, performed in neonates with little lung disease, indicates the possibility of lung overdistention at CPAP of 6 to 8 cm H(2)O with the variable-flow device. Further study is necessary to determine the efficacy of variable-flow NCPAP in neonates with significant lung disease and its use over extended periods of time.continuous-flow and variable-flow NCPAP, work of breathing, premature neonates, lung compliance.
IMPORTANCE: Understanding why and how extremely preterm infants die is important for practitioners caring for these infants. OBJECTIVE: To examine risk factors, causes, timing, and circumstances of ...death in a modern cohort of extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort review of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial between December 13, 2013, and September 26, 2016, was conducted. A total of 941 infants born between 24 0/7 and 27 6/7 weeks of gestation enrolled at 19 US sites comprising 30 neonatal intensive care units were included. Data analysis was performed from October 16, 2020, to December 1, 2021. MAIN OUTCOMES AND MEASURES: Risk factors, proximal causes, timing, and circumstances of in-hospital death. RESULTS: Of the 941 enrolled infants, 108 died (11%) before hospital discharge: 38% (n = 41) at 24 weeks’ gestation, 30% (n = 32) at 25 weeks’ gestation, 19% (n = 20) at 26 weeks’ gestation, and 14% (n = 15) at 27 weeks’ gestation. An additional 9 infants (1%) died following hospital discharge. In descending order, the primary causes of death included respiratory distress or failure, pulmonary hemorrhage, necrotizing enterocolitis, catastrophic intracranial hemorrhage, sepsis, and sudden unexplained death. Fifty percent of deaths occurred within the first 10 days after birth. The risk of death decreased with day of life and postmenstrual age such that an infant born at 24 weeks’ gestation who survived 14 days had the same risk of death as an infant born at 27 weeks’ gestation: conditional proportional risk of death, 0.08 (95% CI, 0.03-0.13) vs 0.06 (95% CI, 0.01-0.11). Preterm labor was associated with a decreased hazard of death (hazard ratio HR, 0.45; 95% CI, 0.31-0.66). Infant clinical factors associated with death included birth weight below the tenth percentile for gestational age (HR, 2.11; 95% CI, 1.38-3.22), Apgar score less than 5 at 5 minutes (HR, 2.19; 95% CI, 1.48-3.24), sick appearance at birth (HR, 2.49; 95% CI, 1.69-3.67), grade 2b-3 necrotizing enterocolitis (HR, 7.41; 95% CI, 5.14-10.7), pulmonary hemorrhage (HR, 10.0; 95% CI, 6.76-18.8), severe intracranial hemorrhage (HR, 4.60; 95% CI, 3.24-5.63), and severe sepsis (HR, 4.93; 95% CI, 3.67-7.21). Fifty-one percent of the infants received comfort care before death. CONCLUSIONS AND RELEVANCE: In this cohort study, an association between mortality and gestational age at birth was noted; however, for each week that an infant survived, their risk of subsequent death approximated the risk observed in infants born 1 to 2 weeks later, suggesting the importance of an infant’s postmenstrual age. This information may be useful to include in counseling of families regarding prognosis of survival.
Volutrauma has been established as the key factor in ventilator-induced lung injury and can only be avoided if tidal volume (V
) is accurately displayed and delivered. The purpose of this study was ...to investigate the accuracy of displayed exhaled V
in a ventilator commonly used in small infants with or without a proximal flow sensor and using 3 methods to achieve a target V
in both a healthy and lung-injured neonatal pig model.
This was a prospective animal study utilizing 8 male pigs, approximately 2.0 kg (range 1.8-2.2 kg). Intubated, sedated, neonatal pigs were studied with both healthy and injured lungs using the Servo-i ventilator. In pressure-regulated volume control, both with and without a proximal flow sensor, we used 3 methods to set V
: (1) circuit compliance compensation (CCC) on, set V
6-8 mL/kg; (2) CCC off, calculated V
using the manufacturer's circuit compliance factor; and (3) CCC off, set V
10-12 mL/kg to approximate a target V
of 6-8 mL/kg. Ventilator-displayed exhaled V
measurements were compared with exhaled V
measured at the airway opening by a calibrated pneumotachograph. Bland-Altman plots were constructed to show the level of agreement between the two.
CCC improved accuracy and precision of displayed exhaled V
when the sensor was not used, more markedly in the lung-injured model. Without CCC, the sensor improved accuracy and precision of displayed exhaled V
, again more markedly in the lung-injured model.
When the Servo-i ventilator is used in neonates, CCC or the in-line sensor should be employed due to the large positive bias and imprecision seen with CCC off and no sensor in-line.
Nasal continuous-positive-airway-pressure (NCPAP) is popular for infant respiratory support. We compared delivered to intended intra-prong, proximal-airway, and distal-airway pressures using ...ventilator (V-NCPAP) and bubble (B-NCPAP) devices. Measurements were repeated at five flows (4, 6, 8, 10, and 12 L/min) and three NCPAP (4, 6, and 8 cm H2O) under no, small, and large nares-prong interface leak conditions. With no-leak, delivered B-NCPAP was systematically greater than intended levels at all pressure sites. The corresponding V-NCPAP flow-dependence was none-to-minimal. Prong and intra-airway B-NCPAP overshoots were also observed with small-leak, while only prong B-NCPAP showed a flow-dependent overshoot for large-leak. Leaks did not affect intra-prong V-NCPAP but resulted in progressively lower than desired, flow-independent intra-airway V-NCPAP. We conclude that the self-adjusting capability of ventilators allows closely matched actual versus intended V-NCPAP. Alternatively, for the range of flows used clinically, intra-prong and intra-airway B-NCPAP are systematically higher at increasing flows than operator-intended levels, even when appreciable nares-prong leak is present. Additionally, the oscillations (noise) characterizing B-NCPAP are substantially attenuated between the proximal and distal airways; therefore, it is unlikely that B-NCPAP engenders ventilation or lung recruitment via this phenomenon. Tubing submersion depth for setting the level of B-NCPAP is highly inaccurate, and operators should instead rely on intra-prong pressure measurement.
Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized ...that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome.
Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20-2 ppm. A control group of 19 infants did not receive iNO.
In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10-20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses.
Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO-cGMP pathway in lung development.
Surfactant dysfunction may contribute to the development of bronchopulmonary dysplasia (BPD) in persistently ventilated preterm infants. We conducted a multicenter randomized, blinded, pilot study to ...assess the safety and efficacy of late administration of doses of a surfactant protein-B (SP-B)-containing surfactant (calfactant) in combination with prolonged inhaled nitric oxide (iNO) in infants ≤1,000 g birth weight (BW).
We randomized 85 preterm infants ventilated at 7-14 d after birth to receive either late administration of surfactant (up to 5 doses) plus prolonged iNO or iNO alone. Large aggregate surfactant was isolated from daily tracheal aspirates (TAs) for measurement of SP-B content, total protein, and phospholipid (PL).
Late administration of surfactant had minimal acute adverse effects. Clinical status as well as surfactant recovery and SP-B content in tracheal aspirate were transiently improved as compared to the controls; these effects waned after 1 d. The change in SP-B content with surfactant dosing was positively correlated with SP-B levels during treatment (r = 0.50, P = 0.02).
Low SP-B values increased with calfactant administration, but the relationship of this response to SP-B levels suggests that degradation is a contributing mechanism for SP-B deficiency and surfactant dysfunction. We conclude that late therapy with surfactant in combination with iNO is safe and transiently increases surfactant SP-B content, possibly leading to improved short- and long-term respiratory outcomes.
To determine whether lung volume changes and breathing pattern parameters differ among 3 devices for delivery of nasal continuous positive airway pressure (CPAP) in premature infants.
Thirty-two ...premature infants receiving nasal CPAP for apnea or mild respiratory distress were enrolled. Birth weight was (mean +/- standard deviation) 1081 +/- 316 g, gestational age 29 +/- 2 weeks, age at study 13 +/- 12 days, and fraction of inspired oxygen (FIO(2)) at study.29 +/-.1. Three devices, applied in random order, were studied in each infant: continuous flow nasal CPAP via CPAP prongs, continuous flow nasal CPAP via modified nasal cannula, and variable flow nasal CPAP. After lung recruitment to standardize volume history, changes in lung volume (DeltaV(L)) were assessed at nasal CPAP of 8, 6, 4, and 0 cm H(2)O using calibrated direct current-coupled respiratory inductance plethysmography.
DeltaV(L) was significantly greater overall with the variable flow device compared with both the nasal cannula and CPAP prongs. However, DeltaV(L) was not different between the cannula and the prongs. Respiratory rate, tidal volume, thoraco-abdominal asynchrony, and FIO(2) were greater with the modified cannula than for either of the other 2 devices.
Compared with 2 continuous flow devices, the variable flow nasal CPAP device leads to greater lung recruitment. Although a nasal cannula is able to recruit lung volume, it does so at the cost of increased respiratory effort and FIO(2).
To compare work of breathing and breathing asynchrony during bubble nasal continuous positive airway pressure (NCPAP) vs variable-flow (VF)-NCPAP in premature infants.
We studied 18 premature infants ...of birth weight <1500 g who required NCPAP for mild respiratory distress. Each infant was studied on bubble and VF-NCPAP at 8, 6, 4, and 0 cm H2O. Tidal volumes were obtained by calibrated respiratory inductance plethysmography. Esophageal pressure estimated intrapleural pressure. Inspiratory and resistive work of breathing were calculated from pressure-volume data. Breathing asynchrony was assessed with phase angle. The results at all NCPAP levels were referenced to VF-NCPAP values at 8 cm H2O.
Provision of NCPAP with either device decreased inspiratory work of breathing, tidal volume, and minute ventilation relative to NCPAP of 0 cm H2O. Bubble NCPAP did not decrease resistive work of breathing relative to 0 cm H2O. Resistive work of breathing (p=0.01), respiratory rate (p<0.03), and phase angle (p=0.002) were all greater with bubble compared to VF-NCPAP.
The more labored and asynchronous breathing seen with bubble NCPAP may lead to higher failure rates over the long term than with VF-NCPAP.
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