Hemodynamic evaluation in preterm infants using ultrasonic cardiac output monitor (USCOM).

We aimed to establish reference ranges for USCOM parameters in preterm infants, determine factors that affect cardiac output, and evaluate the measurement repeatability. This retro-prospective study was performed at Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. We included infants below 32 weeks of gestational age (GA) and/or 1500 g of birth weight (BW). We excluded infants with congenital heart diseases or hemodynamic instability. Measurements were performed at 3 ± 1, 7 ± 2, and 14 ± 2 postnatal days. We analyzed 204 measurements from 92 patients (median GA = 30.57 weeks, BW = 1360 g). The mean (SD) cardiac output (CO) was 278 (55) ml/min/kg, cardiac index (CI) was 3.1 (0.5) L/min/m2, and systemic vascular resistance (SVRI) was 1292 (294) d*s*cm-5/m2. CO presented a negative correlation with postmenstrual age (PMA), while SVRI presented a positive correlation with PMA. The repeatability coefficient was 31 ml/kg/min (12%).  Conclusion: This is the first study describing reference values for USCOM parameters in hemodynamically stable preterm infants and factors affecting their variability. Further studies to investigate the usefulness of USCOM for the longitudinal assessment of patients at risk for cardiovascular instability or monitoring the response to therapies are warranted. What is Known: • The ultrasonic cardiac output monitoring (USCOM) has been widely used on adult and pediatric patients and reference ranges for cardiac output (CO) by USCOM have been established in term infants. What is New: • We established reference values for USCOM parameters in very preterm and very-low-birth-weight infants; the reference ranges for CO by USCOM in the study population were 198-405 ml/kg/min. • CO normalized by body weight presented a significant negative correlation with postmenstrual age (PMA); systemic vascular resistance index presented a significant positive correlation with PMA.

Combining lung ultrasound and oscillatory mechanics for assessing lung disease in very preterm infants.

BACKGROUND: We investigated whether combining lung ultrasound scores (LUSs) and respiratory system reactance (Xrs) measured by respiratory oscillometry explains the severity of lung disease better than individual parameters alone. METHODS: We performed a prospective observational study in very preterm infants. Forced oscillations (10 Hz) were applied using a neonatal mechanical ventilator (Fabian HFOi, Vyaire). We used the simultaneous respiratory severity score (RSS = mean airway pressure × FIO2) as a primary outcome. We built linear mixed-effect models to assess the relationship between Xrs z-score, LUS and RSS and compared nested models using the likelihood ratio test (LRT). RESULTS: We enrolled 61 infants (median (Q1, Q3) gestational age = 30.00 (26.86, 31.00) weeks) and performed 243 measurements at a postnatal age of 26 (13, 41) days and postmenstrual age of 33.14 (30.46, 35.86) weeks. Xrs z-score and LUS were independently associated with simultaneous RSS (p < 0.001 for both). The model including Xrs and LUS explained the RSS significantly better than Xrs (p value LRT < 0.001) or LUS alone (p value LRT < 0.001). CONCLUSIONS: Combining LUS and Xrs z-score explains the severity of lung disease better than each parameter alone and has the potential to improve the understanding of the underlying pathophysiology. IMPACT: Combining respiratory system reactance by oscillometry and lung ultrasound score explains the respiratory support requirement (e.g., proxy of the severity of lung disease) significantly better than each parameter alone. We assessed the relationship between lung ultrasound and respiratory system reactance in very preterm infants for the first time. Combining respiratory oscillometry and lung ultrasound has the potential to improve the understanding of respiratory pathophysiology.

Oscillatory mechanics trajectory in very preterm infants: a cohort study.

BACKGROUND: The aim of this study was to describe the trajectory of oscillatory mechanics from the first week of life to term equivalent and evaluate whether oscillatory mechanics are associated with simultaneous lung disease in infants ≤32 weeks gestation. METHODS: In this observational, longitudinal study, we enrolled 66 infants. Forced oscillations were applied using a neonatal mechanical ventilator (Fabian HFOi) that superimposed oscillations (10 Hz, amplitude 2.5 cmH2O) on a positive end-expiratory pressure (PEEP). Measurements were performed at 5-7-9 cmH2O of PEEP or the clinical pressure ±2 cmH2O; they were repeated at 7, 14, 28 post-natal days, and 36 and 40 weeks post-menstrual age (PMA). RESULTS: The mean (range) gestational age of study participants was 29.2 (22.9-31.9) weeks. Nineteen infants (29%) developed bronchopulmonary dysplasia (BPD). Respiratory system reactance was significantly lower (lower compliance), and respiratory system resistance was significantly higher in infants with developing BPD from 7 post-natal days to 36 weeks PMA. All oscillatory mechanics parameters were significantly associated with the simultaneous respiratory severity score (p < 0.001 for all). CONCLUSIONS: Serial measurements of oscillatory mechanics allow differentiating lung function trajectory in infants with and without evolving BPD. Oscillatory mechanics significantly correlate with the severity of simultaneous lung disease. IMPACT: The results of the present study suggest that respiratory system reactance, as assessed by respiratory oscillometry, allows the longitudinal monitoring of the progression of lung disease in very premature infants. This paper describes for the first time the trajectory of oscillatory mechanics in very preterm infants with and without evolving bronchopulmonary dysplasia from the first week of life to term equivalent. Serial respiratory oscillometry measurements allow the identification of early markers of evolving bronchopulmonary dysplasia and may help personalizing the respiratory management strategy.

Oscillatory mechanics in very preterm infants on continuous positive airway pressure support: Reference values.

OBJECTIVE: To create reference values for respiratory system resistance (Rrs) and reactance (Xrs) measured by the forced oscillation technique (FOT) in nonintubated very preterm infants. DESIGN: Retrospective analysis of data collected as part of prospective observational studies in two centers. SETTING: Tertiary neonatal intensive care units. PATIENTS: Non-intubated infants below 32 weeks' gestation age who did not develop bronchopulmonary dysplasia. INTERVENTIONS: We applied FOT using a mechanical ventilator (Fabian HFOi; Vyaire) that superimposed small-amplitude oscillations (10 Hz) on a continuous positive airway pressure of 3 and 5 cmH2 O. Measurements were performed during regular tidal breathing using a face mask. MAIN OUTCOME MEASURES: We analyzed 198 measurements performed between 7 postnatal days and 40 weeks postmenstrual age (PMA) in 85 infants, with a median (Q1, Q3) gestational age of 30.43 (29.14, 31.18) weeks. Logarithmic transformations were applied to Rrs and Xrs, and the relationship between transformed impedance values and demographic factors was examined by backwards stepwise linear regression. RESULTS: In univariable analysis, transformed Xrs was significantly associated with PMA, postnatal age, weight, and length, while Rrs was not. The best multivariable regression model estimating transformed Xrs (cmH2 O*s/L) at continuous positive airway pressure (CPAP) = 5 cmH2 O was: Ln(50 - Xrs) = 4.536 - 0.009 x PMA - 0.014 x weight z-score. SEE = 0.053, R2 = 0.36. The mean (SD) Rrs at CPAP = 5 cmH2 O was 33.63 (5.28) cmH2 O*s/L. CONCLUSION: We have established reference values for Rrs and Xrs at 10 Hz in nonintubated preterm neonates on continuous positive airway pressure support.

Left ventricular diastolic function and respiratory outcomes in preterm infants: a retrospective study.

BACKGROUND: The role of left ventricular (LV) diastolic pressure in the pathophysiology of bronchopulmonary dysplasia (BPD) is unclear. We evaluated the trajectory of echocardiographic parameters of LV diastolic function and the association with respiratory outcomes in preterm infants. METHODS: We retrospectively analysed measurements of LV diastolic function (E, e', A, Ee' and E/A ratios) in infants below 32 weeks' gestation (GA). We compared infants with and without BPD by two-way RM ANOVA. We considered Ee' ratio as a proxy of LV filling pressure and identified a cut-off value using ROC analysis. We divided infants using such threshold and compared respiratory outcomes between groups by Mann-Whitney or Chi-square tests. RESULTS: We included 72 infants. Ee' ratio at 28 days was significantly associated with the duration of respiratory support (beta (std. error) = 5.32 (1.82), p = 0.005) and BPD (beta = 0.27 (0.10), p = 0.008). Infants with Ee' ratio > 12 at 28 days had longer respiratory support, oxygen requirement, and higher BPD rates than infants with Ee' ratio ≤ 12. CONCLUSION: LV diastolic function associated with elevated LV filling pressure may contribute to the pathophysiology of BPD. Serial echocardiographic measurements could identify infants at risk of worse respiratory outcomes. IMPACT: In very preterm infants, we assessed the trajectory of left ventricular diastolic function by serial echocardiographic evaluations and evaluated its association with respiratory outcomes. On average, infants who developed bronchopulmonary dysplasia had higher Ee' at 28 postnatal days and 36 weeks postmentrual age than infants who did not develop the disease. Infants with elevated Ee' at 28 postnatal days, suggestive of elevated left atrial pressure, required longer respiratory support.

Oscillatory Mechanics Response to Inhaled Bronchodilators in Very Preterm Infants: A Retrospective Study.

OBJECTIVES: To identify short-term repeatability of forced oscillation technique (FOT) measurement of lung function, assess the lung function response to bronchodilators (BDs) by FOT, and prove the concept that only some very preterm infants manifest a change in lung mechanics in response to BD. STUDY DESIGN: We retrospectively analyzed respiratory system resistance and respiratory system reactance measured by FOT (Fabian HFOi). The measurement short-term repeatability was assessed in 43 patients on 60 occasions; BD responsiveness was assessed using a different data set, including 38 measurements in 18 infants. The coefficient of repeatability was calculated as twice the SD of differences between measurements performed 15 minutes apart. We assessed BD responsiveness by measuring respiratory system resistance and respiratory system reactance before and 15 minutes after administering 200 mcg/kg of nebulized salbutamol. A positive response was defined as an improvement in respiratory system resistance or respiratory system reactance greater than the identified coefficient of repeatability. RESULTS: The coefficient of repeatability was 7.5 cmH2O∗s/L (21%) for respiratory system resistance and 6.3 cmH2O∗s/L (21%) for respiratory system reactance. On average, respiratory system resistance did not change significantly following BD administration, though respiratory system reactance increased significantly (from -32.0 [-50.2, -24.4] to -27.9 [-38.1, -22.0] cmH2O∗s/L, P < .001). Changes in respiratory system resistance or respiratory system reactance after BD were greater than the identified coefficient of repeatability in 8 infants (44%) on 13 (34%) occasions. CONCLUSIONS: We identified a threshold to assess BD responsiveness by FOT in preterm infants. We speculate that FOT could be used to assess and personalize treatment with BD.

Assessment of bronchodilator response by forced oscillation technique in a preterm infant with evolving bronchopulmonary dysplasia: A case report.

Inhaled bronchodilators are often given in preterm infants with evolving or established bronchopulmonary dysplasia. However, it is unclear which patients may benefit from it and when it is the best time to start treatment. The forced oscillation technique (FOT) is a noninvasive method for assessing lung mechanics that proved sensitive to airway obstruction reversibility in children and adults. FOT does not need patient cooperation, which is ideal for infants. Bedside tools for applying FOT in infants during spontaneous breathing and different respiratory support modes are becoming available. This case report illustrates for the first time that FOT has potential value in assessing airway obstruction reversibility in preterm infants, informing which infants may manifest a clinical benefit from the treatment with bronchodilators.

Role of ventilator and nasal interface in pressure transmission during neonatal intermittent positive pressure ventilation: A bench study.

We aimed at evaluating pressure transmission and stability during non-synchronized neonatal nasal intermittent positive pressure ventilation (NIPPV) delivered using five mechanical ventilators and three nasal interfaces. An artificial nose-throat model was connected to a mechanical analog of the infant respiratory system and a breath generator. Ventilation was administrated via a nasal mask (NM), short bi-nasal prongs (SBN), or RAM® cannula. We applied positive end-expiratory pressures (PEEP) of 5 and 10 cmH2 O, inspiratory pressures (PIP) of 15 and 30 cmH2 O, inspiratory times of 0.23, 0.42, and 0.57 s. Measurements were performed with leaks of 0, 1.5, and 4 L/min. The pressure was measured at the airways opening (PAW ) and the glottis (PGL ). The difference between set and delivered pressures (PAW ) was less than ±1 cmH2 O for all ventilators. We documented a significant difference between PAW and PGL in the presence of leaks. With 4 L/min leaks, PEEP dropped by 43%, 49%, and 63% with NM, SBP, and RAM® cannula, respectively; PIP dropped by 58%, 64%, and 74%. On average, the SD of PEEP fluctuations was ±0.60 and ±2.50 cmH2 O for PAW and PGL ; the breath-by-breath SD of PIP was ±0.77 and ±2.06 cmH2 O. During NIPPV, the PIP and PEEP transmission to the glottis is markedly lower than the set values and highly variable. The impact of leaks and nasal interface is much more significant than the differences in ventilators' performance on the efficacy of pressure transmission and stability of non-synchronized ventilator-generated NIPPV.

Evaluation of hemodynamics in healthy term neonates using ultrasonic cardiac output monitor.

BACKGROUND: Transition from intrauterine to extrauterine life is a critical phase during which several changes occur in cardiovascular system. In clinical practice, it is important to have a method that allows an easy, rapid and precise evaluation of hemodynamic status of a newborn for clinical management. We here propose a rapid, broadly applicable method to monitor cardiovascular function using ultrasonic cardiac output monitoring (USCOM). METHODS: We here present data obtained from a cohort of healthy term newborns (n = 43) born by programmed cesarean section at Fondazione MBBM, Ospedale San Gerardo. Measurements were performed during the first hour of life, then at 6 + 2, at 12-24, and 48 h of life. We performed a screening echocardiography to identify a patent duct at 24 h and, if patent, it was repeated at 48 h of life. RESULTS: We show that physiologically, during the first 48 h of life, blood pressure and systemic vascular resistance gradually increase, while there is a concomitant reduction in stroke volume, cardiac output, and cardiac index. The presence of patent ductus arteriosus significantly reduces cardiac output (p = 0.006) and stroke volume (p = 0.023). Furthermore, newborns born at 37 weeks of gestational age display significantly lower cardiac output (p < 0.001), cardiac index (p = 0.045) and stroke volume (p < 0.001) compared to newborns born at 38 and ≥ 39 weeks. Finally, birth-weight (whether adequate, small or large for gestational age) significantly affects blood pressure (p = 0.0349), stroke volume (p < 0.0001), cardiac output (p < 0.0001) and cardiac index (p = 0.0004). In particular, LGA infants display a transient increase in cardiac index, cardiac output and stroke volume up to 24 h of life; showing a different behavior from AGA and SGA infants. CONCLUSIONS: Compared to previous studies, we expanded measurements to longer time-points and we analyzed the impact of commonly used clinical variables on hemodynamics during transition phase thus making our data clinically applicable in daily routine. We calculate reference values for each population, which can be of clinical relevance for quick bedside evaluation in neonatal intensive care unit.

Relationship between Mean Airways Pressure, Lung Mechanics, and Right Ventricular Output during High-Frequency Oscillatory Ventilation in Infants.

OBJECTIVE: To characterize changes in lung mechanics and right ventricular output (RVO) during incremental/decremental continuous distending pressure (CDP) maneuvers in newborn infants receiving high-frequency oscillatory ventilation, with the aim of evaluating when open lung maneuvers are needed and whether they are beneficial. STUDY DESIGN: Thirteen infants on high-frequency oscillatory ventilation were studied with a median (IQR) gestational age of 261 (253-291) weeks and median (IQR) body weight of 810 (600-1020) g. CDP was increased stepwise from 8 cmH2O to a maximum pressure and subsequently decreased until oxygenation deteriorated or a CDP of 8 cmH2O was reached. The lowest CDP that maintained good oxygenation was considered the clinically optimal CDP. At each CDP, the following variables were evaluated: oxygenation, respiratory system reactance (Xrs), and RVO by Doppler echocardiography. RESULTS: At maximal CDP reached during the trial, 19 [1] cmH2O (mean [SEM]), oxygenation markedly improved, and Xrs and RVO decreased. During deflation, oxygenation remained stable over a wide range of CDP settings, Xrs returned to the baseline values, and RVO increased but the baseline values were not readily restored in all patients. CONCLUSION: These results suggest that Xrs and RVO are more sensitive than oxygenation to overdistension and they may be useful in clinical practice to guide open lung maneuvers.