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.

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.

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.

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.

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.

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.

Health literacy of parents of very preterm infants at NICU admission and discharge: a prospective cohort study.

OBJECTIVE: To determine the prevalence of limited health literacy in parents of infants born ≤32 and 0/7 weeks and if health literacy changes during hospitalization. STUDY DESIGN: Multi-site, prospective cohort study measuring health literacy using the Parent Health Literacy Activities Test, which estimates caregivers' ability to complete tasks such as reading prescription labels and preparing bottles. Data were analyzed using parametric and nonparametric comparison tests and multivariable regression to control for confounders. RESULT: Of the 137 participants, 31% missed ≥3 questions of 8. Scores were not associated with admission characteristics or NICU complications. Lower scores were associated with lower nurses' (rho 0.20, p = 0.04) but not parents' (rho -0.12, p = 0.22) ratings of discharge readiness. Scores improved slightly from admission to discharge (p = 0.049). CONCLUSION: Many parents have difficulty answering questions related to basic infant care tasks. NICUs should ensure that communication and discharge planning are mindful of health literacy.

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.

Elevations of novel cytokines in bacterial meningitis in infants.

BACKGROUND: Bacterial meningitis is challenging to diagnose in infants, especially in the common setting of antibiotic pre-treatment, which diminishes yield of cerebrospinal fluid (CSF) cultures. Prior studies of diagnostic markers have not demonstrated sufficient accuracy. Interleukin-23 (IL-23), interleukin-18 (IL-18) and soluble receptor for advanced glycation end products (sRAGE) possess biologic plausibility, and may be useful as diagnostic markers in bacterial meningitis. METHODS: In a prospective cohort study, we measured IL-23, IL-18 and sRAGE levels in CSF. We compared differences between infected and non-infected infants, and conducted receiver operating characteristic (ROC) analyses to identify individual markers and combinations of markers with the best diagnostic accuracy. RESULTS: 189 infants <6 months, including 8 with bacterial meningitis, 30 without meningitis, and 151 with indeterminate diagnosis (due to antibiotic pretreatment) were included. CSF IL-23, IL-18 and sRAGE levels were significantly elevated in infants with culture proven meningitis. Among individual markers, IL-23 possessed the greatest accuracy for diagnosis of bacterial meningitis (area under the curve (AUC) 0.9698). The combination of all three markers had an AUC of 1. CONCLUSIONS: IL-23, alone and in combination with IL-18 and sRAGE, identified bacterial meningitis with excellent accuracy. Following validation, these markers could aid clinicians in diagnosis of bacterial meningitis and decision-making regarding prolongation of antibiotic therapy.

Carbon dioxide washout during high flow nasal cannula versus nasal CPAP support: An in vitro study.

OBJECTIVE: To compare CO2 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% CO2 . 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 H2 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). CO2 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 CO2 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.

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.

Factors influencing delivered mean airway pressure during nasal CPAP with the RAM cannula.

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.

Continuous Positive Airway Pressure treatment of premature infants; application of a computerized decision support system.

The predictions of a computerized decision-support system (CDSS) are compared to clinical data obtained from a group of premature infants. The infants were suffering from respiratory distress syndrome (RDS) and were treated by the Continuous Positive Airway Pressure (CPAP) therapy. The predictions of the CDSS are found to be in general agreement with clinical measurements. The CDSS is also used to determine the effect of low level oxygen treatment on arterial oxygen pressure if the infant׳s oxygenation is low despite CPAP therapy. Based on the computational results, application of low levels of supplemental inspired fraction of oxygen ( [Formula: see text] ) would result in significant improvement in oxygenation of premature infants provided such treatment is carefully controlled to avoid hyperoxemia.

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.

Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates.

BACKGROUND AND OBJECTIVE: Heated, humidified high-flow nasal cannula (HHHFNC) is commonly used as a noninvasive mode of respiratory support in the NICU. The safety and efficacy of HHHFNC have not been compared with other modes of noninvasive support in large randomized trials. The objective was to assess the efficacy and safety of HHHFNC compared with nasal continuous positive airway pressure (nCPAP) for noninvasive respiratory support in the NICU. METHODS: Randomized, controlled, unblinded noncrossover trial in 432 infants ranging from 28 to 42 weeks' gestational age with planned nCPAP support, as either primary therapy or postextubation. The primary outcome was defined as a need for intubation within 72 hours of applied noninvasive therapy. RESULTS: There was no difference in early failure for HHHFNC (23/212 [10.8%]) versus nCPAP (18/220 [8.2%]; P = .344), subsequent need for any intubation (32/212 [15.1%] vs 25/220 [11.4%]; P = .252), or in any of several adverse outcomes analyzed, including air leak. HHHFNC infants remained on the study mode significantly longer than nCPAP infants (median: 4 vs 2 days, respectively; P < .01), but there were no differences between study groups for days on supplemental oxygen (median: 10 vs 8 days), bronchopulmonary dysplasia (20% vs 16%), or discharge from the hospital on oxygen (19% vs 18%). CONCLUSIONS: Among infants ≥28 weeks' gestational age, HHHFNC appears to have similar efficacy and safety to nCPAP when applied immediately postextubation or early as initial noninvasive support for respiratory dysfunction.