Enhanced INSURE (ENSURE): an updated and standardised reference for surfactant administration.

There is no firm consensus about the optimal technique for the administration of exogenous surfactant in preterm neonates, and different techniques may be equally effective. The intubation-surfactant-extubation (INSURE) procedure has not been fully described, and important details, such as duration and mode of ventilation, remain unclear, leading to significant clinical practice variations and influencing its suitability and feasibility. Since the first INSURE description, our knowledge in respiratory care has largely progressed, but the technique has not been updated according to current evidence-based practice. Thus, our aim is to formally describe a modern way to perform INSURE, based on the current knowledge and technology, to increase its feasibility and patients' safety. We offer ENSURE (Enhanced INSURE) as an updated and standardised technique for surfactant administration, clarifying crucial issues of the original method by applying current state-of-the-art concepts of respiratory care. We performed a cross-sectional observational study enrolling 57 preterm neonates describing ENSURE feasibility and safety.   Conclusion: ENSURE can be used as a reference technique in clinical practice, teaching and research. What is Known: • There is no consensus about the optimal method for surfactant administration. INSURE technique has been originally described many years ago without considering modern principles of neonatal respiratory care and the available state-of-the-art technology. What is New: • We here describe a modern way to perform INSURE, based on the current knowledge and technology. We called it ENSURE (Enhanced INSURE) and clarified crucial points of the original technique, in light of the current knowledge. We verified feasibility and safety of ENSURE in a cross-sectional observational study enrolling 57 preterm neonates.

Echography-Guided Surfactant Therapy to Improve Timeliness of Surfactant Replacement: A Quality Improvement Project.

OBJECTIVE: To improve time of surfactant administration with a surfactant replacement protocol based on semiquantitative lung ultrasound score (LUS) thresholds. STUDY DESIGN: Quality improvement (QI), prospective, before-after, pilot study. In a 6-month period surfactant replacement was based only on inspired oxygen fraction (FiO2) thresholds. In the second 6-month period, surfactant was given when either the FiO2 or LUS exceeded the limits. The main QI measures were the proportion of neonates receiving surfactant within the first 3 hours of life and maximal FiO2 reached before surfactant replacement. Secondary QI measures were the duration of respiratory support and ventilator-free days. Data were also collected for 1 year after the study to verify sustainability. RESULTS: Echography-guided Surfactant THERapy (ESTHER) increased the proportion of neonates receiving surfactant within the first 3 hours of life (71.4%-90%; P < .0001) and reduced the maximal FiO2 reached before surfactant replacement (0.33 [0.26-0.5]) vs 0.4 [0.4-0.55]; P = .005). The global need for surfactant did not significantly change. ESTHER also resulted in a significant decrease in duration of invasive ventilation and ventilator-free days. CONCLUSIONS: ESTHER improved the timeliness of surfactant administration and secondary QI indicators related to surfactant replacement.

Effect of preterm chorioamnionitis on lung ultrasound score used to guide surfactant replacement.

OBJECTIVE: Lung ultrasound score (LUS) accurately guides surfactant replacement in preterm neonates with respiratory distress syndrome due to surfactant deficiency. However, surfactant deficiency is not the unique pathobiological feature, as there may be relevant lung inflammation, such as in certain cases of clinical chorioamnionitis (CC). We aim to investigate if CC influences LUS and ultrasound-guided surfactant treatment. DESIGN: Retrospective (2017-2022), large, cohort study targeted to recruit a homogeneous population treated with unchanged respiratory care policy and lung ultrasound protocol. Patients with (CC+: 207) and without (CC-: 205) chorioamnionitis were analyzed with propensity score matching and subsequent additional multivariate adjustments. RESULTS: LUS was identical at unmatched and matched comparisons. Consistently, at least one surfactant dose was given in 98 (47.3%) and 83 (40.5%) neonates in the CC+ and CC- matched cohorts, respectively (p = .210). Multiple doses were needed in 28 (13.5%) and 21 (10.2%) neonates in the CC+ and CC- cohorts, respectively (p = .373). Postnatal age at surfactant dosing was also similar. LUS was higher in patients who were diagnosed with neonatal acute respiratory distress syndrome (NARDS) (CC+ cohort: 10.3 (2.9), CC- cohort: 11.4 (2.6)), than in those without NARDS (CC+ cohort: 6.1 (3.7), CC- cohort: 6.2 (3.9); p < .001, for both). Surfactant use was more frequent in neonates with, than in those without NARDS (p < .001). Multivariate adjustments confirmed NARDS as the variable with greater effect size on LUS. CONCLUSIONS: CC does not influence LUS in preterm neonates, unless inflammation is enough severe to trigger NARDS. The occurrence of NARDS is key factor influencing the LUS.

Oscillation Transmission of Modern High-Frequency Neonatal Ventilators Under Different Lung Mechanics Conditions.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) is widely used in neonatal critical care, and several modern ventilators using different technologies are available to provide HFOV. These devices have different technical characteristics that might interact with patient lung mechanics to influence the effectiveness of ventilation. To verify this, we studied the oscillation transmission of 5 neonatal oscillators in a lung model mimicking the mechanical patterns commonly observed in neonatal practice. METHODS: This was a benchtop, in vitro, physiological, pragmatic study using a model mimicking airways and lung of a 1-kg preterm neonate and the following patterns: normal (compliance: 1.0 mL/cm H2O, resistance: 50 cm H2O/L/s), restrictive (compliance: 0.3 mL/cm H2O, resistance: 50 cm H2O/L/s), and mixed mechanics (compliance: 0.3 mL/cm H2O, resistance: 250 cm H2O/L/s). Several permutations of HFOV parameters (variable mean airway pressure or amplitude or frequency protocols) were tested. Oscillations were measured with a dedicated pressure transducer validated for use during HFOV, and oscillatory pressure ratio (OPR) was calculated to estimate the oscillation transmission. RESULTS: Overall OPR (calculated on all experiments) was significantly different between ventilators and the mechanical patterns (both P < .001). Different ventilators and patterns accounted for 35.6% and 20.6% of the variation in oscillation transmission, respectively. Sub-analyses per changing amplitude or frequency protocols and multivariate regressions showed that VN500 (standardized ß coefficient [St.ß]: 0.548, P < .001) and Fabian HFO (St.ß: 0.421, P < .001; adjusted R2: 0.615) provided the best oscillation transmission. Fabian HFO also delivered oscillations with the lowest variability when increasing amplitude. CONCLUSIONS: In an experimental setting mimicking typical neonatal lung disorders, the oscillation transmission was more dependent on the ventilator model than on the mechanical lung conditions at equal HFOV parameters. Fabian HFO and VN500 provided better oscillation transmission overall, and when increasing amplitude, Fabian HFO delivered oscillations with the lowest variability.

Effect of the measurement of the work of breathing on the respiratory outcome of preterms.

RATIONALE: There are no validated criteria for the choice of the optimal type of noninvasive respiratory support (NRS) and most appropriate settings in preterms. METHODS: The work of breathing (WOB) during oxygen (O2) alone, nasal continuous positive pressure (nCPAP) and high flow nasal cannula (HFNC) was compared in preterm babies (23-30 weeks' gestation, "physiological group") needing any type of noninvasive respiratory support ("baseline" NRS) at 4 weeks of life. Babies were thereafter treated with the NRS associated with the greatest reduction in WOB ("optimal NRS"). The respiratory outcome at 36 weeks" gestation of these babies was compared to a "control" group treated with NRS based on standard noninvasive parameters. Preterm babies were prospectively enrolled in 3 centers and randomized into the "physiological" or "control" group. RESULTS: Thirty babies were randomized. WOB with "baseline" NRS was higher than the "optimal" NRS and the consequent NRS chosen by physicians (p = 0.001). WOB was lower during HFNC than during O2 (p = 0.032) but WOB was comparable between nCPAP and HFNC, and between nCPAP and O2. Notably, WOB was near to normal during spontaneous breathing with O2. Respiratory outcome at 36 week' gestation was comparable between the 2 groups. CONCLUSION: The optimization of NRS by means of the measurement of WOB in preterms requiring any type of NRS at 4 weeks of life was able to decrease the WOB but had no effect on the clinical outcome at 36 weeks' gestation.

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway.

Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates. Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60. Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml). Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.

Lung Ultrasound Score Predicts Surfactant Need in Extremely Preterm Neonates.

BACKGROUND AND OBJECTIVES: There are several lung ultrasound scores (LUS) for evaluating lung aeration in critically ill adults with restrictive lung disorders. A modified LUS adapted for neonates correlates well with oxygenation and is able to be used to predict the need for surfactant in preterm neonates with respiratory distress syndrome (RDS). However, no data are available for extremely preterm neonates for whom timely surfactant administration is especially important. We hypothesized that LUS might be reliable in extremely preterm neonates with RDS who are treated with continuous positive airway pressure. We aimed to determine the diagnostic accuracy of LUS in predicting the need for surfactant treatment and re-treatment in this population. METHODS: We performed a prospective cohort diagnostic accuracy study between 2015 and 2016 in a tertiary-care academic center. Inborn neonates at ≤30 weeks' gestation with RDS treated with continuous positive airway pressure were eligible. Surfactant was given on the basis of oxygen requirement thresholds derived from European guidelines, and a LUS was not used to guide surfactant treatment. We calculated the LUS after admission and analyzed its diagnostic accuracy to predict surfactant treatment and re-treatment. RESULTS: We enrolled 133 infants; 68 (51%) received 1 dose of surfactant and 19 (14%) received 2 surfactant doses. A LUS is significantly correlated with oxygenation index (ρ = 0.6; P < .0001) even after adjustment for gestational age (P < .0001). A LUS can be used to accurately predict the need for the first surfactant dose (area under the curve = 0.94; 95% confidence interval: 0.90-0.98; P < .0001) and also the need for surfactant redosing (area under the curve = 0.803; 95% confidence interval: 0.72-0.89; P < .0001). The global accuracy for the prediction of surfactant treatment and re-treatment is 89% and 72%, respectively. CONCLUSIONS: LUS may be used to predict the need for surfactant replacement in extremely preterm neonates with RDS.