Delivering Low Tidal Volume With Anesthesia and ICU Ventilators in a Neonatal Lung Model.

BACKGROUND: Mechanical ventilation of the neonate requires ventilators than can deliver precise and accurate tidal volume (VT) and PEEP to avoid lung injury. Due to small neonatal VT and the disproportionate effect of endotracheal tube leak in these patients, accomplishing precise and accurate VT delivery is difficult. Whereas neonatal ICU ventilators are validated in this population, thorough studies testing the performance of anesthesia ventilators in delivering small VT in neonates are lacking. METHODS: Three anesthesia ventilators, Dräger Apollo, GE Avance, and Getinge Flow-i; and 2 ICU ventilators, Medtronic PB980 and Nihon Kohden NKV-550, were tested under volume control mode at VT of 5, 20, 40, and 60 mL. Three combinations of lung compliance and airway resistance were tested using a Servo ASL 5000 lung simulator. RESULTS: In a scenario without leak, the measured VT was greater than the set VT by > 10% in the Apollo (21.0% [18.8-26.0]); measured VT was less than the set VT by > 10% in the Flow-i (-19% [-20.8 to -18.7]). The Avance, PB980, and NKV-550 presented a volume error < 10% (-9.50% [-10.8 to -4.4], -5.8% [-11.8 to -3.5], and 5.4% [-4.5 to 18.9], respectively). Considering all combinations of set VT, leaks, and respiratory mechanics, none of the anesthesia ventilators were able to deliver a median measured VT within a 10% error. The bias between measured VT and set VT varied widely among ventilators (from 4.27 mL to -10.59 mL). Additionally, in the Apollo ventilator, PEEP was underdelivered with the largest leak value. CONCLUSIONS: Our results suggest that in comparison with the 2 neonatal ICU ventilators tested, the anesthesia ventilators did not greatly differ in terms of VT delivery in the presence of a gas leak.

Diagnostic Performance and Patient Outcomes With C-Reactive Protein Use in Early-Onset Sepsis Evaluations.

OBJECTIVES: To determine performance of C-reactive protein (CRP) in the diagnosis of early-onset sepsis, and to assess patient outcomes with and without routine use of CRP. STUDY DESIGN: This was a retrospective cohort study of infants admitted to 2 neonatal intensive care units. CRP was used routinely in early-onset sepsis evaluations during 2009-2014; this period was used to determine CRP performance at a cut-off of ≥10 mg/L in diagnosis of culture-confirmed early-onset sepsis. Routine CRP use was discontinued during 2018-2020; outcomes among infants admitted during this period were compared with those in 2012-2014. RESULTS: From 2009 to 2014, 10 134 infants were admitted; 9103 (89.8%) had CRP and 7549 (74.5%) had blood culture obtained within 3 days of birth. CRP obtained ±4 hours from blood culture had a sensitivity of 41.7%, specificity 89.9%, and positive likelihood ratio 4.12 in diagnosis of early-onset sepsis. When obtained 24-72 hours after blood culture, sensitivity of CRP increased (89.5%), but specificity (55.7%) and positive likelihood ratio (2.02) decreased. Comparing the periods with (n = 4977) and without (n = 5135) routine use of CRP, we observed lower rates of early-onset sepsis evaluation (74.5% vs 50.5%), antibiotic initiation (65.0% vs 50.8%), and antibiotic prolongation in the absence of early-onset sepsis (17.3% vs 7.2%) in the later period. Rate and timing of early-onset sepsis detection, transfer to a greater level of care, and in-hospital mortality were not different between periods. CONCLUSIONS: CRP diagnostic performance was not sufficient to guide decision-making in early-onset sepsis. Discontinuation of routine CRP use was not associated with differences in patient outcomes despite lower rates of antibiotic administration.

Comparison of nasal intermittent positive pressure ventilation and bubble CPAP with an in-line high-frequency interrupter in a premature infant lung model.

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 CO2 clearance when superimposing high-frequency oscillations onto bubble continuous positive airway pressure (BCPAP). OBJECTIVE: To compare the CO2 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 CO2  (ETCO2 ) 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 CO2 clearance relative to BCPAP alone for all tested oscillation frequencies at all CPAP levels (p < 0.001). NIPPV also resulted in improved CO2  clearance relative to nasal CPAP (NCPAP) alone (p < 0.001). Among the tested settings, BCPAP with an in-line HFI resulted in decreased ETCO2 relative to BCPAP ranging from -14% to -36%, while NIPPV resulted in decreased ETCO2  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 CO2 than NIPPV in a premature infant lung model.

Preserved pressure delivery during high-frequency oscillation of bubble CPAP in a premature infant lung model with both normal and abnormal lung mechanics.

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 CO2 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 H2 O, airway resistance 56 cm H2 O/(L/s); or abnormal mechanics, compliance 0.5 ml/cm H2 O, airway resistance 136 cm H2 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 H2 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 H2 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.

Role of microbiological tests and biomarkers in antibiotic stewardship.

Laboratory tests are critical in the detection and timely treatment of infection. Two categories of tests are commonly used in neonatal sepsis management: those that identify the pathogen and those that detect host response to a potential pathogen. Decision-making around antibiotic choice is related to the performance of tests that directly identify pathogens. Advances in these tests hold the key to progress in antibiotic stewardship. Tests measuring host response, on the other hand, are an indirect marker of potential infection. While an important measure of the patient's clinical state, in the absence of pathogen detection these tests cannot confirm the appropriateness of antibiotic selection. The overall impact these tests then have on antibiotic utilization depends the test's specificity for bacterial infection, clinical scenario where it is being used and the decision-rule it is being integrated into for use. In this review we discuss common and emerging laboratory tests available for assisting management of neonatal infection and specifically focus on the role they play in optimizing antibiotic utilization.

Carbon dioxide clearance using bubble CPAP with superimposed high-frequency oscillations in a premature infant lung model with abnormal lung mechanics.

BACKGROUND: High-frequency (HF) oscillatory ventilation has been shown to improve carbon dioxide (CO2 ) clearance in premature infants. In a previous in vitro lung model with normal lung mechanics we demonstrated significantly improved CO2 washout by HF oscillation of bubble continuous positive airway pressure (BCPAP). OBJECTIVE: To examine CO2 clearance in a premature infant lung model with abnormal lung mechanics via measurement of end-tidal CO2 levels (EtCO2 ) 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 H2 O, airway resistance 56 cm H2 O/(L/s); or abnormal lung mechanics (ALM): compliance 0.5 mL/cm H2 O, airway resistance 136 cm H2 O/(L/s), was connected to BCPAP with HF oscillation at either 4, 6, 8, 10, or 12 Hz. EtCO2 was measured at BCPAPs of 4, 6, and 8 cm H2 O and respiratory rates (RR) of 40, 60, and 80 breaths/min and 6 mL tidal volume. RESULTS: HF oscillation decreased EtCO2 levels at all BCPAPs, RRs, and oscillation frequencies for both lung models. Overall mean ± SD EtCO2 levels decreased (P < .001) from nonoscillated baseline by 19.3 ± 10.2% for NLM vs 14.1 ± 8.8% for ALM. CO2 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 CO2 clearance as compared with nonoscillated BCPAP for both NLM and ALM. The significant improvement in CO2 clearance in an abnormal lung environment is an important step towards clinical testing of this novel respiratory support modality.

An in-line high frequency flow interrupter applied to nasal CPAP: Improved carbon dioxide clearance in a premature infant lung model.

BACKGROUND: Noninvasive respiratory support continues to have high failure rates in small preterm infants. We previously demonstrated significantly improved in vitro CO2 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 (EtCO2 ) 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. EtCO2 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 EtCO2 levels decreased with oscillation (P < .001). BCPAP EtCO2 was significantly dependent on oscillation frequency (P < .001) with decreases of 18% to 47% and maximum effect at 10 Hz. Optimum VCPAP CO2 clearance occurred at 6 Hz with reductions of 30% and 39% at 6 and 8 cm H2 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 H2 O, respectively. Power spectrum analysis of non-oscillated BCPAP showed bubbling-only dominant peaks at 10 to 12 Hz corresponding with the maximum BCPAP EtCO2 reductions. CONCLUSION: Application of high frequency oscillation to NCPAP improves CO2 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.

Effect of high-frequency oscillation on pressure delivered by high flow nasal cannula in a premature infant lung model.

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 CO2 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.