Effect of Blood Transfusions on Intermittent Hypoxic Episodes in a Prospective Study of Very Low Birth Weight Infants.

OBJECTIVES: To compare the number of intermittent hypoxia events before and after packed red blood cell (pRBC) and non-pRBC transfusions in very low birth weight infants, and to compare the time spent with saturations of ≤85% before and after transfusions in the same population. STUDY DESIGN: This prospective observational study was conducted from April 2014 to August 2017. It included 92 transfusions (81 pRBC, 11 non-pRBC) from 41 very low birth weight infants between 230/7 and 286/7 weeks of gestation. The primary outcome was number of intermittent hypoxia events. Secondary outcomes included the percent time of Peripheral capillary oxygen saturation (SpO2)of ≤85%, ≤80%, and ≤75%. A mixed ANOVA model was used to examine the relationship between event rate and covariates. RESULTS: The mean number of intermittent hypoxia events per hour decreased from 5.27 ± 5.02 events per hour before pRBC transfusion to 3.61 ± 3.17 per hour after pRBC transfusions (P < .01) and intermittent hypoxia did not change after non-RBC transfusions (before, 4.45 ± 3.19 vs after, 4.47 ± 2.78; P = NS). The percent time with saturations of ≤80% and ≤75% significantly decreased after pRBC transfusions (P = .01). The time with saturations of ≤85% did not significantly change after non-pRBC transfusion. CONCLUSIONS: In very low birth weight infants with a hematocrit of 20%-42%, pRBC transfusions are associated with decreased frequency of intermittent hypoxia. No such diminution of intermittent hypoxia events was observed in infants who had received a non-pRBC transfusion. This finding suggests that the observed beneficial effects of RBC transfusions on apnea and its clinical manifestations of intermittent hypoxia are mediated through an enhanced oxygen carrying capacity.

Derivation of a metabolic signature associated with bacterial meningitis in infants.

BACKGROUND: Diagnosis of bacterial meningitis (BM) is challenging in newborn infants. Presently, biomarkers of BM have limited diagnostic accuracy. Analysis of cerebrospinal fluid (CSF) metabolites may be a useful diagnostic tool in BM. METHODS: In a nested case-control study, we examined >400 metabolites in CSF of uninfected infants and infants with culture-confirmed BM using gas and liquid chromatography mass spectrometry. Preterm and full-term infants in a Level III or IV Neonatal Intensive Care Unit were prospectively enrolled when evaluated for serious bacterial infection. RESULTS: Over 200 CSF metabolites significantly differed in uninfected infants and infants with BM. Using machine learning, we found that as few as 6 metabolites distinguished infants with BM from uninfected infants in this pilot cohort. Further analysis demonstrated three metabolites associated with Group B Streptococcal meningitis. CONCLUSIONS: We report the first comprehensive metabolic analysis of CSF in infants with BM. In our pilot cohort, we derived a metabolic signature that predicted the presence or absence of BM, irrespective of gestational age, postnatal age, sex, race and ethnicity, presence of neurosurgical hardware, white blood cell count in CSF, and red blood cell contamination in CSF. Metabolic analysis may aid diagnosis of BM and facilitate clinical decision-making in infants. IMPACT: In a pilot cohort, metabolites in cerebrospinal fluid distinguished infants with bacterial meningitis from uninfected infants.We report the first comprehensive metabolic analysis of cerebrospinal fluid in infants with bacterial meningitis.Our findings may be used to improve diagnosis of bacterial meningitis and to offer mechanistic insights into the pathophysiology of bacterial meningitis in infants.

Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial.

Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P = .29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P = .002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions. Trial Registration: clinicaltrials.gov Identifier: NCT02139800.

Effects of Targeting Higher or Lower Oxygen Saturations in Centers with More Versus Less Separation between Median Saturations.

Subgroup analysis of the Canadian Oxygen Trial to compare outcomes of extremely preterm infants in centers with more versus less separation between median arterial oxygen saturations in the two target ranges. Centers with more separation observed lower rates of death or disability in the 85%-89% range than in the 91%-95% target range.

Cerebrospinal fluid cytokines in the diagnosis of bacterial meningitis in infants.

BACKGROUND: Bacterial meningitis poses diagnostic challenges in infants. Antibiotic pretreatment and low bacterial density diminish cerebrospinal fluid (CSF) culture yield, while laboratory parameters do not reliably identify bacterial meningitis. Pro and anti-inflammatory cytokines are elevated in bacterial meningitis and may be useful diagnostic adjuncts when CSF cultures are negative. METHODS: In a prospective cohort study of infants, we used cytometric bead arrays to measure tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), IL-6, IL-8, IL-10, and IL-12 in CSF. Receiver operating characteristic (ROC) analyses and Principal component analysis (PCA) were used to determine cytokine combinations that identified bacterial meningitis. RESULTS: Six hundred and eighty four infants < 6 mo were included; 11 had culture-proven bacterial meningitis. IL-6 and IL-10 were the individual cytokines possessing greatest accuracy in diagnosis of culture proven bacterial meningitis (ROC analyses; area under the concentration-time curve (AUC) 0.91; 0.9103 respectively), and performed as well as, or better than combinations identified using ROC and PCA. CSF cytokines were highly correlated with each other and with CSF white blood cell count (WBC) counts in infants with meningitis. A subset of antibiotic pretreated culture-negative subjects demonstrated cytokine patterns similar to culture positive subjects. CONCLUSION: CSF cytokine levels may aid diagnosis of bacterial meningitis, and facilitate decision-making regarding treatment for culture negative meningitis.

Serial echocardiography in very preterm infants: a pilot randomized trial.

AIM: To determine whether routine echocardiography increases diagnosis and treatment for patent ductus arteriosus (PDA) and whether randomized nondisclosure is a feasible strategy for studying PDA management. METHODS: Two-centre, pilot randomized, controlled trial. 88 infants with birth weights ≤1250 grams and gestational ages ≤30 weeks were randomized to disclosure or nondisclosure of serial echocardiogram findings. Echocardiograms were performed at 3-5 and 7-10 days of life. The primary outcome was time to regain birth weight. RESULTS: 100% of echocardiograms in the disclosure group were disclosed; 16% (echocardiogram #1) and 29% (echocardiogram #2) were disclosed in the nondisclosure group. There was a statistically nonsignificant decrease in drug therapy for PDA in the nondisclosure group (adjusted odds ratio [AOR] 0.56, 95% confidence interval [CI] 0.24-1.34). There was no difference in time to regain birth weight or in other important neonatal outcomes. However, infants in the nondisclosure group were more likely to demonstrate appropriate weight loss and then regain birth weight within 7-14 days (AOR 2.64, 95% CI 1.08-6.44). CONCLUSION: Randomized nondisclosure of echocardiograms is a feasible strategy for evaluation of approaches to PDA management in very preterm infants. Avoidance of routine echocardiography may reduce drug therapy for PDA without adverse clinical effects.

The toxigen initiative: targeting oxygen saturation to avoid sequelae in very preterm infants.

UNLABELLED: Supplemental oxygen plays a critical role in the care of infants born at the lower limits of viability, but not without the risk of morbidity resulting from high levels or prolonged exposure. PURPOSE: The purpose of this quality improvement project was to reduce exposure to hyperoxia as evidenced by SpO2 values within the established target range (88%-92%) among very preterm infants (VPIs) in a level 3 neonatal intensive care unit (NICU). Reducing exposure to hyperoxia in this population of exquisitely vulnerable infants has been associated with reduced morbidity, including retinopathy of prematurity, chronic lung disease, and brain injury. SUBJECTS: Two populations of interest were identified: VPIs receiving supplemental oxygen and NICU clinicians. DESIGN: Interventions were employed to (1) improve knowledge regarding hyperoxia and associated outcome sequelae in an interdisciplinary sample of clinicians (pretest posttest design) and (2) reinforce content of the educational intervention by triggering caregiver behaviors to reduce time the VPIs is above target SpO2 range while receiving supplemental oxygen (cohort design). METHODS: : Retrospective chart review, baseline clinician knowledge assessment, education, posteducation assessment, collaborative rounds with regular feedback citing time VPIs spent above target oxygen saturation levels (SpO2), and evaluation of impact on time infants spent above target SpO2 range aligned with the project purpose. OUTCOME MEASURES: Pre- and postintervention dependent variables included clinician knowledge of hyperoxia and related evidence as measured by a 24-item multiple-choice Knowledge Assessment Tool before and after attending an educational presentation. Time VPIs were exposed to hyperoxia was evaluated using SpO2 readings and calculating the percentage of time readings were above target range before and after the introduction of educational and behavioral interventions. PRINCIPAL RESULTS: Outcome 1 was to increase knowledge about hyperoxia among clinician caregivers. Paired-samples t test showed a significant difference between preintervention and postintervention Knowledge Assessment Tool scores (P = .000). Outcome 2 measured reduction in time spent with SpO2 readings above target range. An independent-samples t test was used to compare outcomes in preintervention and postintervention VPI cohorts. Mean time spent with SpO2 greater than target range increased in the postintervention cohort, reaching statistical significance with P = .047. CONCLUSIONS: Knowledge acquisition on the subject of hyperoxia in VPIs was achieved. Decreasing the percent time VPIs were exposed to hyperoxia was not attained. The postintervention VPI cohort spent more time above the target saturation range despite greater knowledge among clinicians.

Use of ventilation/perfusion mismatch to guide individualised CPAP level selection in preterm infants: a feasibility trial.

OBJECTIVE: To measure within-subject changes in ventilation/perfusion (V'/Q') mismatch in response to a protocol of individualised nasal continuous positive airway pressure (CPAP) level selection. DESIGN: Single-arm, non-randomised, feasibility trial. SETTING: Three centres in the Children's Hospital of Philadelphia neonatal care network. PATIENTS: Twelve preterm infants of postmenstrual age 27-35 weeks, postnatal age >24 hours, and receiving a fraction of inspired oxygen (FiO2) >0.25 on CPAP of 4-7 cm H2O. INTERVENTIONS: We applied a protocol of stepwise CPAP level changes, with the overall direction and magnitude guided by individual responses in V'/Q' mismatch, as determined by the degree of right shift (kilopascals, kPa) in a non-invasive gas exchange model. Best CPAP level was defined as the final pressure level at which V'/Q' improved by more than 5%. MAIN OUTCOME MEASURES: Within-subject change in V'/Q' mismatch between baseline and best CPAP levels. RESULTS: There was a median (IQR) within-subject reduction in V'/Q' mismatch of 1.2 (0-3.2) kPa between baseline and best CPAP levels, p=0.02. Best CPAP was observed at a median (range) absolute level of 7 (5-8) cm H2O. CONCLUSIONS: Non-invasive measures of V'/Q' mismatch may be a useful approach for identifying individualised CPAP levels in preterm infants. The results of our feasibility study should be interpreted cautiously and replication in larger studies evaluating the impact of this approach on clinical outcomes is needed. TRIAL REGISTRATION NUMBER: NCT02983825.

Cerebrospinal fluid reference ranges in term and preterm infants in the neonatal intensive care unit.

OBJECTIVE: To determine reference ranges of cerebrospinal fluid (CSF) laboratory findings in term and preterm infants in the neonatal intensive care unit. STUDY DESIGN: Data were collected prospectively as part of a multisite study of infants aged <6 months undergoing lumbar puncture for evaluation of suspected sepsis. Infants with a red blood cell count >500 cells/µL or a known cause of CSF pleocytosis were excluded from the analysis. RESULTS: A total of 318 infants met the inclusion criteria. Of these, 148 infants (47%) were preterm, and 229 (72%) received antibiotics before undergoing lumbar puncture. The upper reference limit of the CSF white blood cell (WBC) count was 12 cells/µL in preterm infants and 14 cells/µL in term infants. CSF protein levels were significantly higher in preterm infants (upper reference limit, 209 mg/dL vs 159 mg/dL in term infants; P < .001), and declined with advancing postnatal age in both groups (preterm, P = .008; term, P < .001). CSF glucose levels did not differ in term and preterm infants. Antibiotic exposure did not significantly affect CSF WBC, protein, or glucose values. CONCLUSIONS: CSF WBC counts are not significantly different in preterm and term infants. CSF protein levels are higher and decline more slowly with postnatal age in preterm infants compared with term infants. This study provides CSF reference ranges for hospitalized preterm and term infants, particularly in the first month of life.

Accuracy of tidal volume, compliance, and resistance measurements on neonatal ventilator displays: an in vitro assessment.

OBJECTIVE: To determine the accuracy of measures of respiratory mechanics derived from neonatal ventilators using an in vitro passive physical lung model to simulate newborn pulmonary conditions. DESIGN: Test lung models. SETTING: Laboratory-based measurements. INTERVENTIONS: Three test lungs were constructed to simulate three severities of neonatal lung disease, with ranges of compliance from 0.5 to 2.0 mL/cm H2O and resistance from 25 to 150 cm H2O/(L/sec). Each ventilator was tested using 27 combinations of peak inspiratory pressure (15-25 cm H2O), positive end-expiratory pressure (5-7 cm H2O), and rate settings (20-60 B/min). Data were compared for five different ventilators across simulated lung severity as the ratio of ventilator readout to test lung reference value. A ratio of 1.0 indicated a completely unbiased result. MAIN RESULTS: Overall, four of the five ventilators under-read expired tidal volume by about 1%-12% across all lung conditions, whereas the VIP Bird readout ranged from -4% to +4% bias. Changes in ventilator settings had only a modest effect on mechanics readout. As peak inspiratory pressure progressed from 15 to 25 cm H2O, bias in tidal volume readout changed from +5.0% to -2.5% (p < .001) in the VIP Bird, and from -11% to -9% (p < .001) in the Draeger Babylog VN500. Between positive end-expiratory pressure levels of 5 and 7 cm H2O, tidal volume bias in the Babylog varied between -13% and -7% (p < .001). In progressing from simulated normal to severely ill lung condition, bias in compliance measurements by the Avea and SLE5000 increased from -18% to -40% whereas in the VIP Bird it remained between -17% to -13%, and in the Draeger Evita XL-neo it changed from +17% to -13% and from -8% to -16% in the Babylog. Ratio of ventilator resistance readout to reference value with progressing simulated lung condition changed from 2.0 to 1.0 for the Draeger Evita, 1.6 to 1.1 for the Babylog, 4.2 to 2.0 for the SLE, and from 11.7 to 5.6 for the VIP Bird. The Avea, by design, did not display resistances >100 cm H2O/(L/sec), but overestimated the simulated normal lung resistance of 25 cm H2O/(L/sec) by a factor of 2.5. CONCLUSIONS: Neonatal ventilator respiratory mechanics measurements and computation methods need further standardization to be useful in clinical settings.

A model-based decision support system for critiquing mechanical ventilation treatments.

A computerized system for critiquing mechanical ventilation treatments is presented that can be used as an aide to the intensivist. The presented system is based on the physiological model of the subject's respiratory system. It uses modified versions of previously developed models of adult and neonatal respiratory systems to simulate the effects of different ventilator treatments on the patient's blood gases. The physiological models that have been used for research and teaching purposes by many researchers in the field include lungs, body tissue, and the brain tissue. The lung volume is continuously time-varying and the effects of shunt in the lung, changes in cardiac output and cerebral blood flow, and the arterial transport delays are included in the system. Evaluation tests were done on adult and neonate patients with different diagnoses. In both groups combined, the differences between the arterial partial pressures of CO(2) predicted by the system and the experimental values were 1.86 ± 1.6 mmHg (mean ± SD), and the differences between the predicted arterial hemoglobin oxygen saturation values, S(aO2), and the experimental values measured by using pulse oximetry, S(pO2), were 0.032 ± 0.02 (mean ± SD). The proposed system has the potential to be used alone or in combination with other decision support systems to set ventilation parameters and optimize treatment for patients on mechanical ventilation.

Relationship of Neonatal Oral Motor Assessment Scale to Feeding Performance of Premature Infants.

OBJECTIVE: Some premature infants require prolonged tube-feeding, beyond term equivalent gestational age. Tools that could prospectively identify such infants from among otherwise healthy patients are needed. We examined how well the Neonatal Oral Motor Assessment Scale (NOMAS) predicts premature infants' transition from tube to oral feeding. DESIGN: Data from a prospective study of sucking behavior as a predictor of feeding skills were used to examine the relationship of NOMAS and other nominal predictors to pre-defined feeding milestones. SETTING: Neonatal intensive Care Unit PATIENTS: 51 tube-fed, premature infants METHODS: NOMAS was administered soon (<72 hours) after oral feeding was initiated, and weekly thereafter, until infants reached full oral feeding. A timed measure of feeding efficiency was also done as oral feeding was initiated. A standardized, permissive protocol for feeding advance was used. Nonparametric rank sum tests and ANOVA were used to relate NOMAS, feeding efficiency, and other baseline variables to feeding milestones. RESULTS: Gestational age at birth, birth weight, and initial feeding efficiency predicted shorter transition and earlier acquisition to full oral feeding; NOMAS scores did not predict feeding outcomes. CONCLUSIONS: NOMAS was a poor predictor, while feeding efficiency and other baseline traits were better predictors of feeding skills in premature infants.

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.

Antenatal corticosteroids prior to 24 weeks' gestation and neonatal outcome of extremely low birth weight infants.

We sought to determine if antenatal corticosteroid treatment administered prior to 24 weeks' gestation influences neonatal morbidity and mortality in extremely low-birth-weight infants. A retrospective review was performed of all singleton pregnancies treated with one complete course of antenatal corticosteroids prior to 24 weeks' gestation and delivered between 23(0)/(7) and 25(6)/(7) weeks. These infants were compared with similar gestational-age controls. There were no differences in gender, race, birth weight, and gestational age between the groups. Infants exposed to antenatal corticosteroids had lower mortality (29.3% versus 62.9%, P = 0.001) and grade 3 or 4 intraventricular hemorrhage (IVH; 16.7% versus 36%, P < 0.05; relative risk [RR]: 2.16). Grade 3 and 4 IVH was associated with significantly lower survival probability as compared with no IVH or grade 1 and 2 IVH (P < 0.001, RR: 10.6, 95% confidence interval [CI]: 4.4 to 25.6). Antenatal steroid exposure was associated with a 62% decrease in the hazard rate compare with those who did not receive antenatal steroids after adjusting for IVH grade (Cox proportional hazard model, hazard ratio 0.38, 95% CI: 0.152 to 0.957, P = 0.04). The rates of premature rupture of membranes and chorioamnionitis were higher for infants exposed to antenatal corticosteroids. Exposure to a single course of antenatal corticosteroids prior to 24 weeks' gestation was associated with reduction of the risk of severe IVH and neonatal mortality for extremely low-birth-weight infants.

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.

Evaluation of a computerized system for mechanical ventilation of infants.

OBJECTIVE: To evaluate a computerized system for mechanical ventilation of infants. METHODS: FLEX is a computerized system that includes the features of a patented mode known as adaptive-support ventilation (ASV). In addition, it has many other features including adjustment of positive end-expiratory pressure (PEEP), fraction of inspired oxygen (F(IO2)), minute ventilation, and control of weaning. It is used as an open-loop decision support system or as a closed-loop technique. Blood gas and ventilation data were collected from 12 infants in the neonatal intensive care at baseline and at the next round of evaluation. This data were input to open-loop version of FLEX. The system recommendations were compared to clinical determinations. RESULTS: FLEX recommended values for ventilation were on the average within 25% and 16.5% of the measured values at baseline and at the next round of evaluation, respectively. For F(IO2) and PEEP, FLEX recommended values were in general agreement with the clinical settings. FLEX recommendations for weaning were the same as the clinical determinations 50% of the time at baseline and 55% of the time at the next round of evaluation. FLEX did not recommend weaning for infants with weak spontaneous breathing effort or those who showed signs of dyspnea. CONCLUSIONS: A computerized system for mechanical ventilation is evaluated for treatment of infants. The results of the study show that the system has good potential for use in neonatal ventilatory care. Further refinements can be made in the system for very low-birth-weight infants.

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.

Effect of high frequency oscillatory high flow nasal cannula on carbon dioxide clearance in a premature infant lung model: A bench study.

OBJECTIVE: This study compared CO2 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/cmH2 O, RR 60 breaths/min, and 6 mL tidal volume. A 100% CO2 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 CO2 (ETCO2 ) was recorded with and without oscillation at set flows of 2-8 L/min and repeated for each oscillation frequency. RESULTS: Overall ETCO2 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 ETCO2 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 ETCO2 levels between oscillation frequencies at any flow except at 6 Hz for which ETCO2 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 CO2 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.

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.