Search

Background: Near-term neonates (Babies of 36 to 37 weeks GA and with BW [is greater than] 2000g as well as those of 35 weeks GA and BW [is greater than] 2500g) are frequently managed as healthy, well newborns. They are subject to early discharge without mandated specialized pre or post discharge care. Epidemiologic studies have placed them at risk for higher rate of readmission, excessive weight loss, feeding difficulties and varying risk of dehydration and hyperbilirubinemia. Objective: To determine and characterize the level of risk and outcome of neonatal hyperbilirubinemia in these infants. Methods: Identification of a cohort of 326 near-term (n-term) newborns who were enrolled in the bilirubin database that was used to develop the hour-specific bilirubin nomogram (Pediatrics. 1999). Percentile based predischarge risk assessment and subsequent neonatal hyperbilirubinemia, readmission and association with other concomitant epidemiological risk factors were determined from the database. These data were compared to those determined in concurrently enrolled term population (n = 1624). Results: These data show that pre-discharge risk distribution is shifted (*p [is less than] 01) for babies with assisted vaginal deliveries (vacuum/forceps, AVD). Distribution of babies (%) is tabulated below as per their percentile-based risk assignment: Risk All Breast- Status Babies Fed Term N-Term Term N-Term Total (n) 1624 326 827 326 >95 %tile 3.9 4.9 3.9 4.3 40 to 95 53.4 59.9 60.5 61.3 95 %tile 5.2 16.3 27% 50%(*) 40 to 95 59.1 61.3 3.6% 12% Conclusions: These data define the increased risk that near-term babies have for severe bilirubinemia. The magnitude of this risk may be assessed by universal pre-discharge bilirubin screening and efficiently managed by prospective tracking of serial hourspecific post-discharge bilirubin values which designate the ongoing percentile-based risk status. VK Bhutani, MD, FAAP, LH Johnson, MD, FAAP, EM Sivieri, MS; Newborn Pediatrics, Pennsylvania, Hospital, Department of Pediatrics, University of Pennsylvania, Philadelphia, PA3, VK Bhutani, MD, FAAP, LH Johnson, MD, FAAP, EM Sivieri, MS; Newborn Pediatrics, Pennsylvania, Hospital, Department of Pediatrics, University of Pennsylvania, Philadelphia, [...]

Background: Newborn babies can be evaluated and assessed for risk for severe hyperbilirubinemia prior to discharge and effectively targeted for follow-up and interventional strategies (Pediatrics, 1999). Objective: To develop practical and physician-friendly tools for hospital and office based application of the bilirubin nomogram. Methods: Healthy babies, both term and near-term (N-Term, [is less than or equal to] 37 weeks, 36 weeks with BW [is greater than] 2000 g, and 35 weeks with BW [is greater than] 2500 g), had a pre-discharge total serum bilirubin (TSB) test and were also evaluated for known epidemiologic and clinical risk factors for excessive hyperbilirubinemia. Babies were assigned to percentile based risk tracts on their pre-discharge TSB values = high ([is greater than] 95th percentile zone), intermediate (40 to 75th percentile zone) and low ([is less than] 40th percentile). Results: Percent of babies in each risk zone were compared for known risk groups: breast-fed (BF), N-Term, vacuum/forceps (assisted) vaginal delivery (AVD), gender, ancestry, as well as ABO ([+ or -] Coombs) sensitization. Risk Status Term Term Term N-Term ABO (BF) (AVD) Total (n) (1624) (827) (232) (326) (553) >95th %lie 3.9 3.9 5.2 4.9 9.9%(*) 40-95th %ile 53.4 60.5 59.1 59.9 42.1% >40th %ile 42.7 35.6 35.7 35.2 49.0% These data described distribution of risk status for babies based on their epidemiologic/clinical risk factors. As anticipated, a significant shift in risk pattern (p [is less than] 0.01) was seen for the ABO population, and a trend for increased risk distribution is evident for the AVD and near term population. These singled them out for closer follow-up. With the use of a software based program, predischarge coupled with hour-specific TSB values, when expressed in percentiles or visually tracked on the nomogram, facilitated risk assessment by indicating rate of rise and upward or downward change in percentile track. Thus, the impact of epidemiologic and clinical factors may be individualized for each baby. Direct reporting of TSB data from laboratories as percentile values (actual percentile or in quintiles) is also possible. Conclusion: Individualized care and risk assessment for each baby can be achieved in a practical and efficient manner by reporting TSB as hour-specific percentile values, so that they can be tracked by a busy pediatrician's office for safe, efficient, targeted management. VK Bhutani, MD, FAAP, LH Johnson. MD, FAAP, EM Sivieri, MS; Newborn Pediatrics, PA Hospital, Department of Pediatrics, University of PA, Phila, PA3, VK Bhutani, MD, FAAP, LH Johnson. MD, FAAP, EM Sivieri, MS; Newborn Pediatrics, PA Hospital, Department of Pediatrics, University of PA, Phila, [...]

To identify antecedent clinical and health services events in infants (>35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants >35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n = 118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 µmol l-¹; range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age <1 week. Along with a rapid rise of TSB (>0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age <5 days in 81 of 118 (69%) infants and <10 days in 101 of 118 (86%) infants. TSB levels were <35 mg per 100 ml (598 µmol l-¹) in 46 (39%) infants, of whom one died before exchange transfusion, one was untreated and one was lost to follow-up. Timely and efficacious bilirubin reduction interventions defined by 'crash-cart' initiation of immediate intensive phototherapy and urgent exchange transfusion were accomplished in 11 of 43 infants, which were compared with 12 of 43 infants in whom a timely exchange sometimes could not be accomplished. No overt sequelae were found in 8 of 11 infants (73%) treated with a 'crash-cart' approach compared with none without sequelae when exchange was delayed by pre-admission delays, technical factors or need to transfer to a tertiary facility. None of the remaining 20 of 43 infants treated only with phototherapy escaped sequelae. Regardless of age at readmission and intervention, infants with peak measured TSB >35mg per 100 ml had post-icteric sequelae (n = 73). There was a narrow margin of safety between birthing hospital discharge or home birth and readmission to a tertiary neonatal/pediatric facility. Progression of hyperbilirubinemia to hazardous levels and onset of neurological signs were often not identified as infant's care and medical supervision transitioned during the first week after birth. The major underlying root cause for kernicterus was systems failure of services by multiple providers at multiple sites and inability to identify the at-risk infant and manage severe hyperbilirubinemia in a timely manner. [ABSTRACT FROM AUTHOR]

Male fertility is strongly affected by the overexpression of free radicals induced by heavy metals. The aim of this study was to evaluate the potential antioxidant, anti-inflammatory, and gonado-protective effects of natural compounds. Biochemical and morphological assays were performed on male albino rats divided into five groups: a control group (water only), a group orally exposed to a metal mixture of Pb-Cd-Hg-As alone and three groups co-administered the metal mixture and an aqueous extract of the Nigerian medicinal plant, Anonychium africanum ( Prosopis africana , PA ), at three different concentrations (500, 1000, and 1500 mg/kg) for 60 days. The metal mixture induced a significant rise in testicular weight, metal bioaccumulation, oxidative stress, and pro-inflammatory and apoptotic markers, while the semen analysis indicated a lower viability and a decrease in normal sperm count, and plasma reproductive hormones showed a significant variation. Parallel phytochemical investigations showed that PA has bioactive compounds like phlobatannins, flavonoids, polyphenols, tannins, saponins, steroids, and alkaloids, which are protective against oxidative injury in neural tissues. Indeed, the presence of PA co-administered with the metal mixture mitigated the toxic metals' impact, which was determined by observing the oxido-inflammatory response via nuclear factor erythroid 2-related factor 2, thus boosting male reproductive health.

Introduction: Noninvasive ventilation has become a staple in the care of premature infants. However, failure rates continue to be high in this population. Modifications to noninvasive support, such as nasal intermittent positive pressure ventilation (NIPPV), are used clinically to reduce such failure. Previous in vitro studies have shown improved CO 2 clearance when superimposing high-frequency oscillations onto bubble continuous positive airway pressure (BCPAP)., Objective: To compare the CO 2 clearance of NIPPV to BCPAP with an in-line high-frequency interrupter (HFI) in a premature infant lung model., Methods: A premature infant lung model was connected to either a Dräger VN500 for delivery of NIPPV or a BCPAP device with superimposed high-frequency oscillations generated by an in-line HFI. Change in end-tidal CO 2  (ETCO 2 ) and mean airway pressure at the simulated trachea were measured and compared for both noninvasive modalities., Results: Superimposing HF oscillations onto BCPAP with an in-line HFI resulted in improved CO 2 clearance relative to BCPAP alone for all tested oscillation frequencies at all CPAP levels (p < 0.001). NIPPV also resulted in improved CO 2  clearance relative to nasal CPAP (NCPAP) alone (p < 0.001). Among the tested settings, BCPAP with an in-line HFI resulted in decreased ETCO 2 relative to BCPAP ranging from -14% to -36%, while NIPPV resulted in decreased ETCO 2  relative to NCPAP ranging from -2% to -12%., Conclusion: Superimposing high-frequency oscillations onto BCPAP using a novel in-line HFI was found to be more effective at clearing CO 2 than NIPPV in a premature infant lung model., (© 2022 Wiley Periodicals LLC.)

Background: Recent in vitro testing of high frequency (HF) oscillation applied to bubble continuous positive airway pressure (BCPAP) using a novel flow interrupter device (HFI) demonstrated significantly improved CO2 washout while not altering delivered mean airway pressure (MAP) in a premature infant lung model. This study's aim was to evaluate the safety and efficacy of the HFI paired with BCPAP in an animal model of prematurity prior to clinical testing., Design/methods: Twelve fetal lambs, 131-135 days gestation, weight 3.51±0.42 kg, were delivered by Cesarean section. The lambs were supported by mechanical ventilation and weaned to spontaneous breathing with BCPAP at 6 cmH2O. A combined CO2/airflow sensor measured end-tidal (EtCO2) and tidal volume (VT). Blood gases, heart rate (HR), arterial pressure (Part), minute ventilation (MV), MAP, ventilatory efficiency index (VEI), thoracoabdominal phase angle and labored breathing index (LBI) were recorded over a 10-minute baseline period followed by four randomized 10-minute intervals with HFI set to either 8, 10, 12 or 15 Hz., Results: EtCO2 decreased from baseline by 11.1±2.2SE%, 16.6±4.3SE%, 13.5±4.9SE%, and 19.5±4.5SE% at 8, 10, 12, and 15 Hz respectively (p < 0.001). Blood gases, SpO2, HR, Part, MAP, VT, MV, esophageal pressure, phase angle, and LBI underwent no significant change with HF. Respiratory rate decreased, and VEI increased, by 14.9±4.5SD% (p = 0.037) and 83±22SD% (p < 0.011) respectively, averaged over all frequencies., Conclusions: We demonstrated the safety and efficacy of a novel BCPAP flow interrupter device. HF applied to the respiratory system resulted in significantly improved CO2 clearance and ventilation efficiency with no deleterious physiological effects in a pre-term lamb model.

Background: Bubble continuous positive airway pressure (BCPAP) generates pressure oscillations which are suggested to improve gas exchange through mechanisms similar to high frequency (HF) ventilation. In a previous in-vitro lung model with normal lung mechanics, significantly improved CO 2 washout was demonstrated using an HF interrupter in the supply flow of a BCPAP system. The effect of HF with BCPAP on delivered airway pressure (Paw) has not been fully investigated in a lung model having abnormal pulmonary mechanics., Objective: To measure Paw in an infant lung model simulating normal and abnormal pulmonary compliance and resistance while connected to a BCPAP system with superimposed HF oscillations created using an in-line flow interrupter., Design/methods: A premature infant lung model with either: normal lung mechanics, compliance 1.0 ml/cm H 2 O, airway resistance 56 cm H 2 O/(L/s); or abnormal mechanics, compliance 0.5 ml/cm H 2 O, airway resistance 136 cm H 2 O/(L/s), was connected to BCPAP with HF at either 4, 6, 8, 10, or 12 Hz. Paw was measured at BCPAPs of 4, 6, and 8 cm H 2 O and respiratory rates (RR) of 40, 60, and 80 breaths/min and 6.0 ml tidal volume., Results: Mean Paw averaged over all five frequencies showed no significant change from non-oscillated levels at all BCPAPs and RRs for both lung models. Paw amplitudes (peak-to-trough) during oscillation were significantly greater than the non-oscillated levels by an average of 1.7 ± 0.5 SD and 2.6 ± 0.5 SD cm H 2 O (p < .001) for the normal and abnormal models, respectively., Conclusions: HF oscillation of BCPAP using a flow interrupter did not alter mean delivered Paw compared to non-oscillated BCPAP for both normal and abnormal lung mechanics models. This simple modification to BCPAP may be a useful enhancement to this mode of non-invasive respiratory support., (© 2021 Wiley Periodicals LLC.)

Background: High-frequency (HF) oscillatory ventilation has been shown to improve carbon dioxide (CO 2 ) clearance in premature infants. In a previous in vitro lung model with normal lung mechanics we demonstrated significantly improved CO 2 washout by HF oscillation of bubble continuous positive airway pressure (BCPAP)., Objective: To examine CO 2 clearance in a premature infant lung model with abnormal lung mechanics via measurement of end-tidal CO 2 levels (EtCO 2 ) while connected to HF oscillated BCPAP., Design and Methods: A 40 mL premature infant lung model with either: normal lung mechanics (NLM): compliance 1.0 mL/cm H 2 O, airway resistance 56 cm H 2 O/(L/s); or abnormal lung mechanics (ALM): compliance 0.5 mL/cm H 2 O, airway resistance 136 cm H 2 O/(L/s), was connected to BCPAP with HF oscillation at either 4, 6, 8, 10, or 12 Hz. EtCO 2 was measured at BCPAPs of 4, 6, and 8 cm H 2 O and respiratory rates (RR) of 40, 60, and 80 breaths/min and 6 mL tidal volume., Results: HF oscillation decreased EtCO 2 levels at all BCPAPs, RRs, and oscillation frequencies for both lung models. Overall mean ± SD EtCO 2 levels decreased (P < .001) from nonoscillated baseline by 19.3 ± 10.2% for NLM vs 14.1 ± 8.8% for ALM. CO 2 clearance improved for both lung models (P < .001) as a function of oscillation frequency and RR with greatest effectiveness at 40 to 60 breaths/min and HF at 8 to 12 Hz., Conclusions: In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO 2 clearance as compared with nonoscillated BCPAP for both NLM and ALM. The significant improvement in CO 2 clearance in an abnormal lung environment is an important step towards clinical testing of this novel respiratory support modality., (© 2020 Wiley Periodicals LLC.)

Background: Noninvasive respiratory support continues to have high failure rates in small preterm infants. We previously demonstrated significantly improved in vitro CO 2 washout by applying oscillations to a high flow nasal cannula system., Objective: To develop a high frequency flow interrupter that could be applied to commonly used nasal continuous positive airway pressure (NCPAP) devices and to determine the effect of oscillations on end-tidal carbon dioxide (EtCO 2 ) levels in an infant lung model., Design/methods: NCPAP was applied to a premature infant lung simulator using either bubble (BCPAP) or variable-flow (VCPAP) CPAP. Supply gas was interrupted with a solenoid pinch valve. EtCO 2 was measured before and during oscillation and repeated at 4, 6, 8, 10, and 12 Hz oscillation and CPAP pressures of 4, 6, and 8 cm H 2 O., Results: BCPAP and VCPAP EtCO 2 levels decreased with oscillation (P < .001). BCPAP EtCO 2 was significantly dependent on oscillation frequency (P < .001) with decreases of 18% to 47% and maximum effect at 10 Hz. Optimum VCPAP CO 2 clearance occurred at 6 Hz with reductions of 30% and 39% at 6 and 8 cm H 2 O CPAP respectively. BCPAP and VCPAP mean airway pressures remained unchanged transitioning from nonoscillation to oscillation. Oscillated BCPAP and VCPAP average amplitudes were 8.3 ± 0.5 and 8.4 ± 2.3 SD cm H 2 O, respectively. Power spectrum analysis of non-oscillated BCPAP showed bubbling-only dominant peaks at 10 to 12 Hz corresponding with the maximum BCPAP EtCO 2 reductions., Conclusion: Application of high frequency oscillation to NCPAP improves CO 2 clearance in a premature infant lung model. This simple modification to NCPAP delivery devices may prove to be an effective enhancement of this mode of noninvasive respiratory support., (© 2019 Wiley Periodicals, Inc.)

Objective: This study describes the effect of high-frequency oscillation on airway pressure generated by high flow nasal cannula (HFNC) in a premature infant lung model., Design/methods: A premature in 0.5 or 1.0 mL/cmH 2 O, respiratory rate (RR) of 40 or 60 breaths per min, and tidal volume of 6 mL. Oscillation was achieved by passing the HFNC supply flow through a 3-way solenoid valve operating at 4, 6, 8, or 10 Hz. Airway pressure at the simulated trachea was recorded following equilibration of end-tidal CO 2 both with and without oscillation., Results: Superimposing high-frequency oscillations onto HFNC resulted in an average decrease in mean airway pressure of 17.9% (P = .011). The difference between the maximum and minimum airway pressures, ∆ P min-max, significantly increased as oscillation frequency decreased ( P < .001). Airway pressure during oscillation was 12.8% greater with the 1.0 vs the 0.5 mL/cmH 2 O compliance at flows > 4 L/min ( P = .031). CO 2 clearance was 13.1% greater with the 1.0 vs 0.5 mL/cmH 2 O compliance at oscillation frequencies less than 8 Hz ( P = .015)., Conclusion: In this in-vitro study we demonstrate that delivered mean airway pressure decreases when applying high-frequency oscillation to HFNC, while still improving CO 2 clearance. The combination of improved CO 2 clearance and reduced pressure delivery of this novel noninvasive modality may prove to be a useful improvement in the respiratory care of infants in respiratory distress., (© 2019 Wiley Periodicals, Inc.)

Objective: This study compared CO 2 clearance in a premature infant lung model connected to a high flow nasal cannula (HFNC) system supplied with oscillatory versus non-oscillatory flow., Design/methods: The lung model was set to compliance 1.0 mL/cmH 2 O, RR 60 breaths/min, and 6 mL tidal volume. A 100% CO 2 was injected at a constant 15 mL/min. To create oscillation, HFNC flow was interrupted at rates of 4-6-8 and 10 Hz. equilibrated end-tidal CO 2 (ETCO 2 ) was recorded with and without oscillation at set flows of 2-8 L/min and repeated for each oscillation frequency., Results: Overall ETCO 2 decreased significantly (P < 0.001) during both non-oscillatory and oscillatory HFNC as set flow increased from 2 to 8 L/min by 26.3% and 60.8%, respectively. Oscillatory ETCO 2 levels decreased linearly compared to non-oscillatory HFNC with negligible difference at 2 L/min and a 48.4% difference at 8 L/min (P < 0.001). There were no differences in ETCO 2 levels between oscillation frequencies at any flow except at 6 Hz for which ETCO 2 was significantly lower (P < 0.01) than at 4, 8, and 10 Hz for 5-8 L/min HFNC flows. Amplitude of volume oscillations increased with increasing flow from 0.5 mL at 2 L/min to 4.0 mL at 8 L/min (P < 0.001), and decreased with increasing oscillation frequency., Conclusion: Oscillatory HFNC as compared to non-oscillatory was associated with significantly improved CO 2 clearance in this premature infant lung model. This simple modification of the HFNC system may prove to be a useful enhancement to this mode of non-invasive respiratory support for preterm infants at high risk for respiratory failure., (© 2018 Wiley Periodicals, Inc.)

Background: Infants are commonly supported with non-invasive ventilation (NIV) such as nasal CPAP and high flow nasal cannula (HFNC). These modes utilize a nasal/oral interface precluding use of a traditional airway flow sensor, such as a pneumotachometer (PNT), needed for pulmonary mechanics (PM) measurements. Respiratory Inductive Plethysmography (RIP), when properly calibrated, records tidal volume non-invasively from chest wall movements. Our aim was to integrate RIP into an existing neonatal pulmonary function testing system to measure PM in infants on NIV and to compare measurements of dynamic lung compliance (CL) and resistance (RL) using RIP with those obtained using a PNT., Design/methods: RIP ribcage (RC) and abdominal (ABD) signals were recorded simultaneously with the flow signal from a PNT; transpulmonary pressure was estimated using an esophageal catheter. Two calibration algorithms were applied to obtain RC and ABD scaling factors., Results: Forty PM measurements were performed on 25 infants (GA 31.5±2.9 weeks; birth weight 1598±510 g; median age 7 days). Correlation coefficients for RIP- vs. PNT-based PM were r2 = 0.987 for CL and r2 = 0.997 for RL. From Bland-Altman analysis, the mean bias (±95% CI) between RIP and PNT methods was -0.004±0.021 ml/cmH2O/kg for CL and 0.7±2.9 cmH2O/(L/sec) for RL. The upper, lower limits of agreement (±95% CI) were 0.128±0.037, -0.135±0.037 ml/cmH2O/kg for CL and 18.6±5.1, -17.2±5.1 cmH2O/(L/sec) for RL., Conclusion: Properly calibrated RIP may be a useful tool with sufficient diagnostic accuracy for PM measurements without need for a nasal/oral airflow sensor in infants receiving NIV.

Objective: To compare CO 2 washout time at different levels of HFNC versus NCPAP in a premature infant lung model with simulated mouth-closed and mouth-open conditions using two sizes of nasal cannula and full- and half-prong HFNC insertion depths., Design/methods: A piston-cylinder lung simulator, having a fixed volume of 30 ml and a 4.8 ml dead space, simulated spontaneous breathing (6.5 ml tidal volume, 50 br/min, Ti = 0.5 sec). Two Fisher & Paykel™ cannulas (Fisher & Paykel Healthcare Ltd., Auckland, New Zealand) (2.8 and 3.2 mm O.D.) and two Infant-Flow™ (CareFusion, Yorba Linda, CA) NCPAP cannulas (3.4 and 4.1 mm O.D.) were applied to simulated airways having either 3.5 or 4.5 mm I.D. nares. Simulated mouth opening was a 5 mm I.D. side tap below the nasal interface. The lung was primed with 5% CO 2 . Washout times were determined at HFNC settings of 3, 4, 5, 6, and 8 L/min and NCPAP at 3, 4, 5, 6, and 8 cm H 2 O with simulated open and closed-mouth conditions and full- and half-inserted HFNC prongs., Results: Overall combined mean washout times for NCPAP with mouth-closed were significantly longer than HFNC over all five pressure and flow device settings by 16.2% (P < 0.001). CO 2 washout times decreased as flow or pressure device settings were increased. There were negligible differences in washout times between NCPAP and HFNC with mouth-open. Mouth-open washout times were significantly less than mouth-closed for all conditions. Overall closed-mouth washout times for HFNC half-prong insertion were longer than for full-prong insertion by 5.3% (P < 0.022)., Conclusions: Significantly improved CO 2 elimination using HFNC versus NCPAP should be a particularly important consideration in premature infants having very high dead space-to-tidal volume ratio compared to larger infants. Pediatr Pulmonol. 2017;52:792-798. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objective: To measure mean airway pressure (MAP) delivered through the RAM Cannula® when used with a ventilator in CPAP mode as a function of percent nares occlusion in a simulated nasal interface/test lung model and to compare the results to MAPs using a nasal continuous positive airway pressure (NCPAP) interface with nares fully occluded., Study Design: An artificial airway model was connected to a spontaneous breathing lung model in which MAP was measured at set NCPAP levels between 4 and 8 cmH2 O provided by a Dräger Evita XL® ventilator and delivered through three sizes of RAM cannulae. Measurements were performed with varying leakage at the nasal interface by decreasing occlusion from 100% to 29%, half-way prong insertion, and simulated mouth leakage. Comparison measurements were made using the Dräger BabyFlow® NCPAP interface with a full nasal seal., Results: With simulated mouth closed, the Dräger interface delivered MAPs within 0.5 cmH2 O of set CPAP levels. For the RAM cannula, with 60-80% nares occlusion, overall delivered MAPs were 60 ± 17% less than set CPAP levels (P < 0.001). Further, MAP decreased progressively with decreasing percent nares occlusion. The simulated open mouth condition resulted in significantly lower MAPs to <1.7 cmH2 O. The one-half prong insertion depth condition, with closed mouth, yielded MAPs approximately 35 ± 9% less than full insertion pressures (P < 0.001)., Conclusions: In our bench tests, the RAM interface connected to a ventilator in NCPAP mode failed to deliver set CPAP levels when applied using the manufacturer recommended 60-80% nares occlusion, even with closed mouth and full nasal prong insertion conditions., (© 2015 Wiley Periodicals, Inc.)

Increased use of non-invasive forms of respiratory support such as CPAP and HFNC in premature infants has generated a need for further investigation of the pulmonary effects of such therapies. In a series of in vitro tests, we measured delivered proximal airway pressures from a HFNC system while varying both the cannula flow and the ratio of nasal prong to simulated nares diameters. Neonatal and infant sized nasal prongs (3.0 and 3.7 mm O.D.) were inserted into seven sizes of simulated nares (range: 3-7 mm I.D. from anatomical measurements in 1-3 kg infants) for nasal prong-to-nares ratios ranging from 0.43 to 1.06. The nares were connected to an active test lung set at: TV 10 ml, 60 breaths/min, Ti 0.35 sec, compliance 1.6 ml/cm H₂O and airway resistance 70 cm H₂O/(L/sec), simulating a 1-3 kg infant with moderately affected lungs. A Fisher & Paykel Healthcare HFNC system with integrated pressure relief valve was set to flow rates of 1-6 L/min while cannula and airway pressures and cannula and mouth leak flows were measured during simulated mouth open, partially closed and fully closed conditions. Airway pressure progressively increased with both increasing HFNC flow rate and nasal prong-to-nares ratio. At 6 L/min HFNC flow with mouth open, airway pressures remained <1.7 cm H₂O for all ratios; and <10 cm H₂O with mouth closed for ratios <0.9. For ratios >0.9 and 50% mouth leak, airway pressures rapidly increased to 18 cm H₂O at 2 L/min HFNC flow followed by a pressure relief valve limited increase to 24 cm H₂O at 6 L/min. Safe and effective use of HFNC requires careful selection of an appropriate nasal prong-to-nares ratio even with an integrated pressure relief valve., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To compare calfactant (CA) and poractant alfa (PA) administration traits, short-term clinical responses, and resource use in the neonatal respiratory distress syndrome (RDS) setting., Methods: An open label series of 277 (213 PA and 64 CA) infants was evaluated for 445 administrations. Registered respiratory therapists collected patient, surfactant administration, and postadministration clinical data. Economic analysis involved labor costs of surfactant administration and usage, wastage, and product average wholesale price. Analysis utilized the Mann-Whitney rank sum test for differences in administration time and either the chi-square or Fisher's exact test for categorical variables., Results: PA had a statistically lower bedside administration time than CA (3.8 minutes vs. 5.3 minutes; P = .006) and a higher percentage of doses administered in less than five minutes (58.9% vs. 4.3%; P < .001). Doses administered per patient were similar (1.67 vs. 1.72). PA and CA were similar in time to recovery (81.4% vs. 74.3%), percent desaturation (24.8% vs. 26.7%), and bradycardia (3.8% vs. 8.5%). Reflux was significantly higher (13.2% vs. 3.5%; P < .001) with CA. Economic analyses found total administration costs per dose were $2.21 for PA and $3.08 for CA. Mean wastage costs were $141.21 for PA and $337.34 for CA (P < .001)., Conclusions: PA appeared to utilize fewer neonatal intensive care unit resources than CA due to reduced administration time and less wastage of drug product. Future studies should more closely evaluate time, resource, wastage, and post-administrative clinical effects to fully assess the impact of surfactant products in this setting.

Background: Postnatal alterations in pulmonary mechanics, energetics and functional residual capacity (FRC) describe the structural maturation of the preterm respiratory system., Objective: To evaluate longitudinal changes in pulmonary function in infants with respiratory distress syndrome (RDS) treated with oxygen, positive pressure ventilation and synthetic surfactant (Exosurf)., Methods: Serial pulmonary function tests were performed in surfactant-treated infants [mean +/- SD birth weight (BW) = 1,112 +/- 276 g, gestational age (GA) = 29 +/- 3 weeks] at postnatal ages: <3 days, 1, 2, 3, 4 and 6-8 weeks until term postmenstrual age (PMA). Tidal volume, pulmonary compliance (C(L)), pulmonary resistance (R(T)) and flow-resistive work were analyzed following simultaneous measurements of airflow and transpulmonary pressure signals. Serial FRC measurements were made in a randomly selected group., Results: Prior to 28 weeks' PMA, C(L) was unchanged irrespective of GA. At age 1 week the likelihood ratio (LR) for bronchopulmonary dysplasia (BPD) based on C(L), R(T) and GA was predicted to be >90% for those with BW <750 g (LR >100) as compared to <10% probability (LR = 0.3) for infants >1,500 g. Significant linear increase in C(L) to PMA was evident >28 weeks' PMA (r = 0.86, p < 0.01) at 0.17 ml/cm H2O/kg/week. By term PMA, mean C(L) was 2.60 +/- 0.07 ml/cm H2O. Improvements in FRC of preterm infants with RDS who recovered occur at a more rapid rate ( approximately 25 ml/kg) compared to those who developed BPD ( approximately 20 ml/kg)., Conclusions: Slow but incremental postnatal pulmonary improvement, minimal <28 weeks' PMA, were comparable for all infants. Along with diminished FRC, these changes reflect persistent deleterious effects of positive pressure ventilation, alveolar hyperoxia and unrecognized pulmonary overdistension., (Copyright 2005 S. Karger AG, Basel)

Respiratory failure remains a major cause of morbidity and mortality in the neonatal population. Infants with hypoxemic respiratory failure because of meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN), and pneumonia/sepsis have a potential for increased survival with extracorporeal membrane oxygenation (ECMO). Other treatment options previously limited to inotropic support, conventional ventilatory management, respiratory alkalosis, paralysis and intravenousvasodilators have been replaced by high-frequency oscillatory ventilation (HFOV), surfactant, and inhaled nitric oxide (iNO). HFOV has been advocated for use to improve lung inflation while potentially decreasing lung injury through volutrauma. Other reports describe enhanced efficacy of HFOV when combined with iNO. Subsequent to studies reporting surfactant deficiency or inactivation may contribute to neonatal respiratory failure exogenous surfactant therapy has been implemented with apparent success. Recent studies have shown that iNO therapy in the neonate with hypoxemic respiratory failure can result in improved oxygenation and decreased need for ECMO. In this article, the authors place in context of a system-based strategy the prenatal, natal and postnatal management of babies delivered through meconium stained amniotic fluid (MSAF) so that adverse outcomes are minimized, and the least number of babies require innovative ventilatory support. At Pennsylvania Hospital, over a six-year period (1995 to 2000), 14.5% (3370/23,175 of live births babies were delivered with MSAF. These data show that 4.6% (155/3370) of babies with MSAF sustained MAS. Overall, 26% (40/155) of babies with MAS needed ventilatory support (or 0.17% of all live-births); of these only 20% (8/40 or 0.035% of live births) needed innovative ventilatory support. None died or needed ECMO. These data describe the impact of a system-based approach to prevent and manage adverse outcomes related to MSAF at regional Level III perinatal center.

Decades of research have led to the understanding of neonatal pulmonary physiology and have influenced the clinical care that neonatologists provide to the sick newborn. Advances in microprocessor technology have allowed for clinical access of the research-based measurements of neonatal pulmonary functions. These evaluations are not only the integrated evaluation of the three primary vectors of respiration (driving pressure, air flow, and volume measured over time) but also values calculated by known physiologic equations. Clinical use of these data may not only be relevant and helpful in the bedside management, but also provides a uniquely objective and research-oriented data collection for individual newborns.

Objective: To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week., Methods: Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined., Results: The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (>/=95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and.48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%)., Conclusions: An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels >/=95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction.

The relationship between pulmonary function and the migration of meconium to distal airways was determined in 10 rabbits (mean weight 2.6 kg) after insufflation of a meconium-saline mixture (1--2 ml/kg). Animals were anesthetized, cannulated, intubated, and mechanically ventilated with 100% oxygen. Lung mechanical dysfunction was most severe during the early phase of meconium migration, 15 min postinsufflation. Substantial increases in inspiratory lung resistance (RI) and expiratory lung resistance (RE) suggest that the site of obstruction at 15 min was the large airways. A decrease in dynamic lung compliance with unchanged static compliance characterizes the obstruction as partial. At 15 min and throughout the migration process, RE was greater than RI, demonstrating a check-valve effect. This phenomenon was substantiated by an increased functional residual capacity (FRC) in all rabbits, presumably due to gas trapping. Secondary to these changes, marked hypoxemia, hypercapnea, and acidosis developed in spite of assisted ventilation with 100% oxygen. At 60 and 120 min postinsufflation, both RI and RE decreased as compared to 15 min. This suggests that the predominant site of obstruction shifted to medium and small airways concomitant with the migration of meconium. Widespread and uneven distribution of meconium still produced significant frequency dependence of lung compliance. Static compliance remained unchanged, indicating that meconium does not affect surface-active or tissue properties of the lung within 120 min postinsufflation. These data suggest that effective respiratory management after meconium aspiration is dependent on the degree of meconium migration, as reflected by pulmonary mechanics.

Pulmonary mechanics, using a two factor least mean square analysis technique, were determined in 22 preterm neonates with respiratory failure. The respiratory system is modelled as a linear mechanical system. Concurrent signals of airflow and transpulmonary pressure were utilized to calculate values of dynamic lung compliance and pulmonary resistances; these determinations were made over the entire tidal volume range. In addition, values of resistive work of breathing, pulmonary time constants, scalar records of sequential breaths, pressure-volume and flow-volume relationships were available for data review and interpretation. The mean +/- SEM value of tidal volume was 7.4 +/- 0.6 ml/kg; dynamic lung compliance was 0.44 +/- 0.04 ml/cmH2O/kg; and the pulmonary resistance of the whole breath was 106 +/- 9.1 cmH2O/liter/s. The resistive work of breathing (hysteresis) was 41.8 +/- 5.9 gm.cm/kg. In correlating the measured values of pressure and flow to those predicted by the model, the mean value of the correlation coefficient for the least mean square analysis for all 22 studies was 0.995 +/- 0.001; the standard error of estimate of the predicted pressure was less than 4.4% of the range of pressures measured. Thereby, the model was considered to be appropriate for the neonatal respiratory system. In addition to the traditional procedures of evaluating the respiratory status of a sick neonate, bedside analysis of pulmonary mechanics provide graphical information, and quantitative data which should be useful in day-to-day pulmonary management.

A closed-circuit fluorocarbon oxygenation system was designed and incorporated into an existing liquid breathing system (LBS) to allow measurement of an animal's oxygen consumption during liquid ventilation. This enabled simultaneous determination of cardiac output by the direct Fick method. A series of seven in-vivo experiments were conducted in which the oxygen consumption and cardiac output of adult cats (2.3 +/- 0.1 kg body wt SEM) were measured during both spontaneous gas breathing (Fio2 = 0.80 in the control animals) and fluorocarbon liquid (FC-80) ventilation using the LBS. On conversion to liquid ventilation, cardiac output and oxygen consumption were found to decrease significantly, by 40% (P less than 0.02) and 18.6% (P less than 0.05), respectively, from control values for gas breathing. Use of the closed-loop fluorocarbon oxygenation system provided for total recovery of vaporized fluorocarbon (greater than 750 ml/h) and of oxygen (18 liter/min STPD), which were otherwise discarded in previous experiments with liquid ventilation.

Cardiopulmonary function was evaluated in very preterm lambs (106 +/- 0.7 S.E. days gestation, 1.66 +/- 0.12 S.E. kg birth weight) during fluorocarbon ventilation. Lambs were delivered by cesarean section after epidural anesthesia. Indwelling arterial, venous, and tracheal cannulae were placed before clamping the cord. Lambs were then mechanically ventilated with oxygenated fluorocarbon for approximately 2 h. During this period it was possible to maintain adequate gas exchange and stable cardiac function. Transpulmonary pressure, liquid flow, and tidal volume tracings enabled determination of lung compliance, CL = 0.58 +/- 0.12 S.E. ml X cmH2O-1 X kg-1, inspiratory resistance, RI = 3600 +/- 604 S.E. cmH2O X liter-1 X sec-1, and expiratory resistance, RE = 4034 +/- 2183 S.E. cmH2O/liter/sec. Lung compliance of the 106-day-old fluorocarbon-filled lung is similar to the more mature 138-143-day-old air-filled lung in preterm lambs. Based on the data presented herein we have extended the viability of the preterm lamb to the limit of pulmonary capillary development rather than that of the pulmonary surfactant system.

Cardiovascular adjustments during liquid ventilation were investigated in seven cats. Cardiac output (CO) and regional blood flow were measured with radioactive microspheres during both spontaneous air breathing (control) and ventilation with fluorocarbon liquid, FC-80. CO was found to decrease 48% (P less than 0.05) during liquid breathing as compared to control. This decrease largely reflected a reduced stroke volume. Despite the decreased CO, mean arterial pressure remained unchanged, indicating a 48% increase (P less than 0.002) in total peripheral resistance (TPR). Secondary to the reduced CO and increased TPR, extensive redistribution of blood flow occurred during liquid ventilation. The arterial lactate concentration and lactate-to-pyruvate ratio (L/P) were significantly increased (P less than 0.02). Furthermore, the increase in L/P correlated with the decrease in CO (r = 0.70; P less than 0.01). In turn, the significant decrease in pH during liquid breathing was found to correlate with the increase in L/P (r = 0.85; P less than 0.001). These data clearly demonstrate signficant alterations in cardiovascular dynamics during liquid ventilation with secondary hyperlactatemia and acidosis.

Pancuronium bromide (Pavulon) is used to induce skeletal muscle paralysis in preterm infants, presumably for effective ventilatory support during acute respiratory failure. Twelve infants with respiratory failure were evaluated for sequential changes in pulmonary mechanics during continuous pancuronium administration (0.1 mg/kg every two to three hours) for more than 48 hours. The study weight of the neonates ranged from 980 to 2,950 g, and the postconceptional age ranged from 27 to 41 weeks. Pulmonary compliance, resistance, and resistive work of breathing were determined, using least mean square analysis technique, daily for three days and after discontinuation of pancuronium (even though there was no clinical improvement in ventilatory management). The dynamic pulmonary compliance decreased from 0.38 +/- 0.05 to 0.30 +/- 0.04 mL/cm H2O/kg (mean +/- SE) (P less than .05) and the total pulmonary resistance increased 51% from 115.6 +/- 21.3 to 174.9 +/- 27.3 cm H2O/L/s (P less than .005) during prolonged skeletal muscle paralysis. Upon discontinuation of pancuronium, the dynamic pulmonary compliance increased 43% to 0.43 +/- 0.4 mL/cm H2O/kg (P less than .05) and the total pulmonary resistance decreased by 41% (P less than .005). These data question the advisability of prolonged skeletal muscle paralysis in neonates and suggest the need for further detailed evaluation of the effects of prolonged paralysis on neonatal pulmonary mechanics.