Prenatal use of indomethacin for preterm labor and renal function among very low birth weight infants.

BACKGROUND: Indomethacin is administered as a tocolytic agent for threatening preterm labor <28weeks of gestation. Only a few, not conclusive, studies have investigated its nephrotoxicity in very low birth weight (VLBW) infants. We investigated whether indomethacin increases the incidence of acute kidney injury (AKI) among VLBW infants. METHODS: This is a retrospective study including all VLBW infants born at our center between January 1, 2005, and December 31, 2013. Indomethacin was administered to women with preterm labor and intact membranes. Neonatal AKI was defined according to KDIGO classification. Univariate analyses were performed comparing VLBW infants exposed to and not exposed to indomethacin. In the multivariable model, the association of indomethacin and AKI was adjusted for patent ductus arteriosus, use of nephrotoxic medications, birth weight, and gestational age. RESULTS: Five hundred seventy-five VLBW infants were included, 49 (8.5%) of whom were exposed to indomethacin in utero. The univariate analysis showed that infants exposed to indomethacin had lower birth weight, lower gestational age, and higher incidence of AKI than infants not exposed. The multivariable model adjusted for confounding factors confirmed an increased risk of AKI in relation to gestational age at birth <27 weeks, but not to indomethacin. CONCLUSIONS: Our data suggest that extreme prematurity, but not the use of indomethacin, is associated with AKI.

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.

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.

Impacto de la viremia de bajo grado en el riesgo de fallo virológico en pacientes con infección por VIH-1 / Impact of low-grade viremia on the risk of virological failure in patients with HIV-1 infection on antiretroviral therapy

Resumen Introducción: Cargas virales (CV) entre 20-200 copias/mL se consideran cargas virales de bajo grado (CVBG). Su implicancia clínica y manejo no han sido definidos. Objetivo: Evaluar el impacto de CVBG en el riesgo de desarrollo posterior de fallo virológico (FV). Pacientes y Métodos: Se incluyeron pacientes ≥ 18 años, desde enero de 2009 a diciembre de 2019, con infección por VIH-1 con CV< 20 copias/mL, por un mínimo de seis meses y/o en dos muestras consecutivas bajo tratamiento anti-retroviral . Se realizó seguimiento de las CV estrati ficándolas: CV < 20 copias/mL, CVBG (20-50 copias/mL y 51-200 copias/mL) y FV. Mediana de seguimiento 25 meses (IQR 15-31). Resultados: Fueron incluidos 1.416 pacientes con CV < 20 copias/ mL bajo TARV. De ellos, 797 permanecieron con CV< 20 copias/mL durante el seguimiento, 144 presentaron CV entre 20-50 copias/mL, 384 entre 51-200 copias/mL y 91 presentaron FV sin CVBG previa. De los 528 pacientes que tuvieron CVBG, 110 (20,1%) fallaron, riesgo 3,45 veces superior respecto a los que no tuvieron CVBG previa. El riesgo de FV fue 3,27 mayor para aquellos que tuvieron CVBG entre 51-200 copias/mL vs 20-50 copias/mL. Discusión: El estudio permite relacionar la CVBG con el FV posterior, siendo el mayor riesgo CVBG entre 51-200 copias/mL.

Abstract Background: Viral loads (VL) between 20-200 copies/mL are considered low-grade viral loads (LGVL). Its clinical implications and management have not been defined. Aim: To evaluate the impact of LGVL on the risk of subsequent development of virological failure (VF). Methods: Patients ≥ 18 years, with HIV-1 infection who had VL < 20 copies/mL for at least six months and/or in two consecutive samples under antiretroviral therapy (ART) were included, between January 1st, 2009 and December 31, 2019. Follow-up of the VLs was carried out stratifying them in VL < 20 copies/mL, LGVL (20-50 copies/mL and 51-200 copies/mL) and VF. Median follow-up 25 months (IQR 15-31). Results: 1,416 patients were included who reached VL < 20 copies/ml under ART, 797 patients remained with CV < 20 copies/mL during follow-up, 144 patients had VL between 21-50 copies/mL, 384 between 51-200 copies/mL and 91 had VF without previous LGVL. Out of 528 patients who had LGVL, 110 failed, risk 3.45 times higher than those who had no previous LGVL. Risk 3.27 times higher of VF for those who had LGVL between 51-200 copies/mL compared to 20-50 copies/mL. Discussion: The study allows to relate the LGVL with VF. This association was observed more frequently with LGVL between 51-200 copies/mL

[Impact of low-grade viremia on the risk of virological failure in patients with HIV-1 infection on antiretroviral therapy]. / Impacto de la viremia de bajo grado en el riesgo de fallo virológico en pacientes con infección por VIH-1.

BACKGROUND: Viral loads (VL) between 20-200 copies/mL are considered low-grade viral loads (LGVL). Its clinical implications and management have not been defined. AIM: To evaluate the impact of LGVL on the risk of subsequent development of virological failure (VF). METHODS: Patients ≥ 18 years, with HIV-1 infection who had VL < 20 copies/mL for at least six months and/or in two consecutive samples under antiretroviral therapy (ART) were included, between January 1st, 2009 and December 31, 2019. Follow-up of the VLs was carried out stratifying them in VL < 20 copies/mL, LGVL (20-50 copies/mL and 51-200 copies/mL) and VF. Median follow-up 25 months (IQR 15-31). RESULTS: 1,416 patients were included who reached VL < 20 copies/ml under ART, 797 patients remained with CV < 20 copies/mL during follow-up, 144 patients had VL between 21-50 copies/mL, 384 between 51-200 copies/mL and 91 had VF without previous LGVL. Out of 528 patients who had LGVL, 110 failed, risk 3.45 times higher than those who had no previous LGVL. Risk 3.27 times higher of VF for those who had LGVL between 51-200 copies/mL compared to 20-50 copies/mL. DISCUSSION: The study allows to relate the LGVL with VF. This association was observed more frequently with LGVL between 51-200 copies/mL.

Effect of continuous positive airway pressure on breathing variability in early preterm lung disease.

OBJECTIVES: In preterm infants, the application of nasal Continuous Positive Airway Pressure (nCPAP) improves lung function through several mechanisms and may interact with the control of breathing. Our aim was to evaluate the effect of increasing/decreasing nCPAP on gas exchange, breathing pattern, and its variability in preterm infants. METHODS: Fifeteen infants with mild to moderate respiratory distress syndrome (RDS) were studied on the first day of life. Infants had a mean (SD) gestational age of 30 + 4 (3 + 4) weeks + day and body weight of 1405 (606) g. nCPAP was increased every 10 min stepwise (0-4-8-10 cmH2 O) and then decreased every 20 min (8-6-4-2 cmH2 O). At each step, vital parameters, oxygenation, and chest wall volume changes (optoelectronic plethysmography) were evaluated. Tidal volume (VT ), inter-breath interval (IBI), end-expiratory lung volume (EELV) changes, and other breathing pattern parameters were computed breath-by-breath. The correlation properties of VT , IBI, and EELV were quantified by detrended fluctuation analysis, computing the scaling exponent α. RESULTS: During nCPAP, oxygenation improved and VT decreased significantly compared with no nCPAP. No significant changes in breathing pattern were observed between nCPAP levels. α of EELV was significantly higher off nCPAP than during nCPAP, suggesting that nCPAP helps stabilize EELV control mechanisms. CONCLUSIONS: In our population of preterm infants with mild to moderate RDS, in the first day of life, nCPAP improved gas exchange, VT , and EELV stability independent of nCPAP level.

Assessment of dynamic mechanical properties of the respiratory system during high-frequency oscillatory ventilation*.

OBJECTIVES: 1) To investigate the possibility of estimating respiratory system impedance (Zrs, forced oscillation technique) by using high-amplitude pressure oscillations delivered during high-frequency oscillatory ventilation; 2) to characterize the relationship between Zrs and continuous distending pressure during an increasing/decreasing continuous distending pressure trial; 3) to evaluate how the optimal continuous distending pressure identified by Zrs relates to the point of maximal curvature of the deflation limb of the quasi-static pressure-volume curve. DESIGN: Prospective laboratory animal investigation. SETTING: Experimental medicine laboratory. SUBJECTS: Eight New Zealand rabbits. INTERVENTIONS: The rabbits were ventilated with high-frequency oscillatory ventilation. Zrs was measured while continuous distending pressure was increased and decreased between 2 and 26 cm H2O in 1-minute steps of 4 cm H2O. At each step, a low-amplitude (6 cm H2O) sinusoidal signal was alternated with a high-amplitude (18 cm H2O) asymmetric high-frequency oscillatory ventilation square pressure waveform. Pressure-volume curves were determined at the end of the continuous distending pressure trial. All measurements were repeated after bronchoalveolar lavage. MEASUREMENTS AND MAIN RESULTS: Zrs was estimated from flow and pressure measured at the inlet of the tracheal tube and expressed as resistance (Rrs) and reactance (Xrs). Linear correlation between the values, measured by applying the small-amplitude sinusoidal signal and the ventilator waveform, was good for Xrs (r = 0.95 ± 0.04) but not for Rrs (r = 0.60 ± 0.34). Following lavage, the Xrs-continuous distending pressure curves presented a maximum on the deflation limb, identifying an optimal continuous distending pressure that was, on average, 1.1 ± 1.7 cm H2O below the point of maximal curvature of the deflation limb of the pressure-volume curves. CONCLUSIONS: Xrs can be accurately measured during high-frequency oscillatory ventilation without interrupting ventilation and/or connecting additional devices. An optimal continuous distending pressure close to the point of maximal curvature of the deflation limb of quasi-static pressure-volume curve can be identified by measuring Zrs during a decreasing continuous distending pressure trial. Zrs might constitute a useful bedside tool for monitoring lung mechanics and improving the continuous distending pressure optimization during high-frequency oscillatory ventilation.

Measurement of total and compartmental lung volume changes in newborns by optoelectronic plethysmography.

The study of respiratory mechanics in infants requires a noninvasive accurate measurement of the lung volume changes (DeltaVL). Optoelectronic plethysmography (OEP) allows the assessment of DeltaVL through the measurement of the chest wall surface motion and it has been proved to be accurate in adults. The aim of this study was to apply OEP to newborns and to validate it by comparison to pneumotachography. Twenty term and preterm newborns (GA = 34 +/- 5 wk) in stable condition were studied during 1 to 2 min periods of quiet breathing in supine position. Airway opening flow was measured by applying a facemask connected to a pneumotachograph (PNT) and integrated to provide the DeltaVL. Chest wall volume changes were simultaneously measured by OEP. The tidal volume values measured by pneumotachography and by OEP were compared for each breath. A total of 771 breaths from all patients were considered. Bland-Altmann analysis showed a mean difference of -0.08 mL and a limit of agreement ranging from -2.98 to 2.83 mL. Linear regression analysis demonstrated good correlation between the two techniques (r = 0.95, q = 1.00 mL, m = 0.96). OEP provides accurate measurements of DeltaVL in newborns and may be useful to study respiratory mechanics and breathing patterns during spontaneous breathing and mechanical ventilation.