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.

Resuscitators' opinions on using a respiratory function monitor during neonatal resuscitation.

AIM: The aim of this study was to assess the resuscitators' opinions of the usefulness and clinical value of using a respiratory function monitor (RFM) when resuscitating extremely preterm infants with positive pressure ventilation. METHODS: The link to an online survey was sent to 106 resuscitators from six countries who were involved in a multicentre trial that compared the percentage of inflations within a predefined target range with and without the RFM. The resuscitators were asked to assess the usefulness and clinical value of the RFM. The survey was online for 4 months after the trial ended in May 2019. RESULTS: The survey was completed by 74 (70%) resuscitators of which 99% considered the RFM to be helpful during neonatal resuscitation and 92% indicated that it influenced their decision-making. The majority (76%) indicated that using the RFM improved their practice and made resuscitation more effective, even when the RFM was not available. Inadequate training was the key issue that limited the effectiveness of the RFM: 45% felt insufficiently trained, and 78% felt more training in using and interpreting the RFM would have been beneficial. CONCLUSION: Resuscitators considered the RFM to be helpful to guide neonatal resuscitation, but sufficient training was required to achieve the maximum benefit.

Postnatal Cytomegalovirus Infection of Preterm and Very-low-birth-weight Infants Through Maternal Breast Milk: Does It Matter?

BACKGROUND: Postnatal infection with cytomegalovirus (CMV) in very-preterm and very-low-birth-weight infants, transmitted through breast milk (BM), is potentially associated with adverse outcomes. This study aimed to investigate the incidence and clinical significance of postnatal CMV infection in a tertiary neonatal intensive care unit. METHODS: Infants of CMV-seropositive mothers born in a neonatal intensive care unit in Melbourne, Australia, were observed for 14 weeks from birth in a prospective cohort study. Maternal BM and infant urine were tested weekly for CMV by culture and polymerase chain reaction, respectively. Clinical and laboratory data were collected and analyzed in relation to the infants' CMV infection status. RESULTS: Data from 65 infants of 56 CMV-seropositive mothers were available for analysis. Of these mothers, 88% (49/56) shed CMV in their BM. Of the 58 infants exposed to CMV-positive BM, 27 (47%) became urine polymerase chain reaction CMV-positive. There was no significant difference in gestational age, birth weight, incidence of bronchopulmonary dysplasia, or necrotizing enterocolitis between the CMV-positive and CMV-negative groups. However, CMV-positive infants had a longer length of hospital stay and more episodes of prolonged neutropenia. Of the CMV-positive infants, 30% (8/27) remained asymptomatic, 48% (13/27) had symptoms categorized as mild and 22% (6/27) as severe. CONCLUSIONS: About half of preterm and very-low-birth-weight infants exposed to CMV-positive BM become infected, and a fifth develop significant clinical symptoms. Future studies should address the maternal and neonatal factors that determine the risk of mother-to-infant CMV transmission, as well as those leading to clinical deterioration and long-term sequelae.

Volume-Targeted Ventilation.

Volume-targeted ventilation (VTV) has been increasingly used in neonatology. In systematic reviews, VTV has been shown to reduce the risk of neonatal morbidities and improve long-term outcomes. It is adaptive ventilation using complex computer algorithms to deliver ventilator inflations with expired tidal volumes close to a target set by clinicians. Significant endotracheal tube leak and patient-ventilator interactions may complicate VTV and make ventilator parameters and waveforms difficult to interpret. In this article, we review the rationale for using VTV and the evidence supporting its use and provide practical advice for clinicians ventilating newborn infants.

A multi-centre randomised controlled trial of respiratory function monitoring during stabilisation of very preterm infants at birth.

AIM: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range. METHODS: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes. RESULTS: Among 288 infants randomised (median (IQR) gestational age 26+2 (25+3-27+1) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO2. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028). CONCLUSION: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. TRIAL REGISTRATION: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.

Gas flow in preterm infants treated with bubble CPAP: an observational study.

OBJECTIVE: To measure the nasal gas flow in infants treated with bubble continuous positive airway pressure (CPAP) and compare it with commonly used flows during nasal high flow (nHF) treatment. DESIGN: This is a prospective, single-centre study. Bubble CPAP pressure was measured at the nasal prongs. Set gas flow was reduced until bubbling in the water chamber just ceased. Set gas flow without bubbling then approximated flow entering the infant's nose ('delivered flow'). SETTING: Neonatal intensive care at The Royal Women's Hospital, Melbourne, Australia. PATIENTS: Clinically stable preterm infants receiving bubble CPAP therapy. MAIN OUTCOME MEASURE: Delivered flow (L/min) when bubbling stopped at a range of clinically set CPAP pressures (cm H2O). RESULTS: Forty-four infants were studied, with a mean (SD) gestational age at birth of 28.4 (2.2) weeks and birth weight of 1154 (419) g. At the time of the study, infants had a median (IQR) age of 4.5 (2-12) days and a mean (SD) weight of 1205 (407) g. Delivered flow ranged from 0.5 to 9.0 L/min, and increased with higher set CPAP pressures (median 3.5 L/min at CPAP 5 cm H2O vs 6.3 L/min at CPAP 8 cm H2O) and heavier weights (median 3.5 L/min in infants <1000 g vs 6.5 L/min for infants >1500 g). CONCLUSIONS: Nasal gas flows during bubble CPAP in preterm infants are similar to flows used during nHF and increase with higher set bubble CPAP pressures and in larger infants. Trial registration number ACTRN12619000197134.

Computational analysis of neonatal ventilator waveforms and loops.

BACKGROUND: Modern neonatal ventilators allow the downloading of their data with a high sampling rate. We wanted to develop an algorithm that automatically recognises and characterises ventilator inflations from ventilator pressure and flow data. METHODS: We downloaded airway pressure and flow data with 100 Hz sampling rate from Dräger Babylog VN500 ventilators ventilating critically ill infants. We developed an open source Python package, Ventiliser, that includes a rule-based algorithm to automatically discretise ventilator data into a sequence of flow and pressure states and to recognise ventilator inflations and an information gain approach to identify inflation phases (inspiration, expiration) and sub-phases (pressure rise, pressure plateau, inspiratory hold etc.). RESULTS: Ventiliser runs on a personal computer and analyses 24 h of ventilation in 2 min. With longer recordings, the processing time increases linearly. It generates a table reporting indices of each breath and its sub-phases. Ventiliser also allows visualisation of individual inflations as waveforms or loops. Ventiliser identified >97% of ventilator inflations and their sub-phases in an out-of-sample validation of manually annotated data. We also present detailed quantitative analysis and comparison of two 1-hour-long ventilation periods. CONCLUSIONS: Ventiliser can analyse ventilation patterns and ventilator-patient interactions over long periods of mechanical ventilation. IMPACT: We have developed a computational method to recognize and analyse ventilator inflations from raw data downloaded from ventilators of preterm and critically ill infants. There have been no previous reports on the computational analysis of neonatal ventilator data. We have made our program, Ventiliser, freely available. Clinicians and researchers can use Ventiliser to analyse ventilator inflations, waveforms and loops over long periods. Ventiliser can also be used to study ventilator-patient interactions.

Effect of pressure rise time on ventilator parameters and gas exchange during neonatal ventilation.

BACKGROUND: Pressure rise time (PRT), also known as slope time to the peak inflating pressure can be set on some modern neonatal ventilators. On other ventilators, PRT is determined by the set circuit flow. Changing slope time can affect mean airway pressure (MAP), oxygenation, and carbon dioxide elimination. Our aim was to investigate the effect of PRT on ventilator parameters and gas exchange during volume-guaranteed ventilation. METHODS: In a crossover study, 12 infants weighing greater than 2 kg were ventilated using a Dräger Babylog VN500 ventilator with synchronized intermittent positive pressure ventilation with volume guarantee (SIPPV-VG) and pressure support ventilation with volume guarantee (PSV-VG). During both modes PRTs between 0.08 and 0.40 seconds were used in 15-minute epochs. Data from the ventilator and patient monitors were downloaded with 1- and 100-Hz sampling rate and analyzed using the Python computer language. RESULTS: During PSV-VG, longer PRTs were associated with longer inspiratory time (P < .0001) and with lower peak inflating pressure (PIP; P = .003), but the MAP was similar. During SIPPV-VG the PIP was not significantly different; however, MAP was lower with longer PRT (P = .001). With a short PRT (0.08 seconds), the PIP was higher during PSV-VG than during SIPPV-VG (19.8 vs 16.5 mbar; P = .042). There were no significant differences in tidal volume delivery, respiratory rate, minute volume, oxygen saturations, or end-tidal CO2 with different PRTs in either mode. CONCLUSIONS: During SIPPV-VG or PSV-VG, using short or long PRTs affects some ventilation parameters but does not significantly change oxygenation or carbon dioxide elimination.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. OBJECTIVES: To assess the benefits and harms of an initial sustained lung inflation (SLI) (> 1 second duration) versus standard inflations (≤ 1 second) in newborn infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3), MEDLINE via PubMed (1966 to 1 April 2019), Embase (1980 to 1 April 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 1 April 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean standard deviation (SD), and weighted mean difference (WMD) for continuous data. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Ten trials enrolling 1467 infants met our inclusion criteria. Investigators in nine trials (1458 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review: mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40 (I² not applicable); typical RD 0.00, 95% CI -0.02 to 0.02; I² = 0%; 5 studies, 479 participants); and mortality during hospitalisation (typical RR 1.09, 95% CI 0.83 to 1.43; I² = 42%; typical RD 0.01, 95% CI -0.02 to 0.04; I² = 24%; 9 studies, 1458 participants). The quality of the evidence was low for death in the delivery room because of limitations in study design and imprecision of estimates (only one death was recorded across studies). For death before discharge the quality was moderate: with longer follow-up there were more deaths (n = 143) but limitations in study design remained. Among secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; I² = 95%; 5 studies, 524 participants; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study at high risk of bias: when this study was removed from the analysis, the size of the effect was reduced (MD -1.71 days, 95% CI -3.04 to -0.39; I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. risk of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.91, 95% CI 0.79 to 1.04; I² = 65%; 5 studies, 811 participants); risk of surfactant administration during hospital admission (typical RR 0.99, 95% CI 0.91 to 1.08; I² = 0%; 9 studies, 1458 participants); risk of chronic lung disease (typical RR 0.99, 95% CI 0.83 to 1.18; I² = 0%; 4 studies, 735 participants); pneumothorax (typical RR 0.89, 95% CI 0.57 to 1.40; I² = 34%; 8 studies, 1377 infants); or risk of patent ductus arteriosus requiring pharmacological treatment (typical RR 0.99, 95% CI 0.87 to 1.12; I² = 48%; 7 studies, 1127 infants). The quality of evidence for these secondary outcomes was moderate (limitations in study design ‒ GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates ‒ GRADE). We could not perform any meta-analysis in the comparison of the use of initial sustained inflation versus standard inflations in newborns receiving resuscitation with chest compressions because we identified only one trial for inclusion (a pilot study of nine preterm infants). AUTHORS' CONCLUSIONS: Our meta-analysis of nine studies shows that sustained lung inflation without chest compression was not better than intermittent ventilation for reducing mortality in the delivery room (low-quality evidence ‒ GRADE) or during hospitalisation (moderate-quality evidence ‒ GRADE), which were the primary outcomes of this review. However, the single largest study, which was well conducted and had the greatest number of enrolled infants, was stopped early for higher mortality rate in the sustained inflation group. When considering secondary outcomes, such as rate of intubation, rate or duration of respiratory support, or bronchopulmonary dysplasia, we found no benefit of sustained inflation over intermittent ventilation (moderate-quality evidence ‒ GRADE). Duration of mechanical ventilation was shortened in the SLI group (low-quality evidence ‒ GRADE); this result should be interpreted cautiously, however, as it might have been influenced by study characteristics other than the intervention. There is no evidence to support the use of sustained inflation based on evidence from our review.

Volume-targeted ventilation with a Fabian ventilator: maintenance of tidal volumes and blood CO2.

OBJECTIVE: To analyse the performance of the Fabian +NCPAP evolution ventilator during volume guarantee (VG) ventilation in neonates at maintaining the target tidal volume and what tidal and minute volumes are required to maintain normocapnia. METHODS: Clinical and ventilator data were collected and analysed from 83 infants receiving VG ventilation during interhospital transfer. Sedation was used in 26 cases. Ventilator data were downloaded with a sampling rate of 0.5 Hz. Data were analysed using the Python computer language and its data analysis packages. RESULTS: ~107 hours of ventilator data were analysed, consisting of ~194 000 data points. The median absolute difference between the actual expiratory tidal volume (VTe) of the ventilator inflations and the target tidal volume (VTset) was 0.29 mL/kg (IQR: 0.11-0.79 mL/kg). Overall, VTe was within 1 mL/kg of VTset in 80% of inflations. VTe decreased progressively below the target when the endotracheal tube leak exceeded 50%. When leak was below 50%, VTe was below VTset by >1 mL/kg in less than 12% of inflations even in babies weighing less than 1000 g. Both VTe (r=-0.34, p=0.0022) and minute volume (r=-0.22, p=0.0567) showed a weak inverse correlation with capillary partial pressure of carbon dioxide (Pco2) values. Only 50% of normocapnic blood gases were associated with tidal volumes between 4 and 6 mL/kg. CONCLUSIONS: The Fabian ventilator delivers volume-targeted ventilation with high accuracy if endotracheal tube leakage is not excessive and the maximum allowed inflating pressure does not limit inflations. There is only weak inverse correlation between tidal or minute volumes and Pco2.

Enhanced monitoring during neonatal resuscitation.

Immediately after birth through spontaneous breaths, infants' clear lung liquid replacing it with air, and gradually establishing a functional residual capacity to achieve gas exchange. Most infants start breathing independently after birth and ~3% of infants who require positive pressure ventilation. When newborns fail to start breathing the current neonatal resuscitation guidelines recommend initiatingpositive pressure ventilationusing a face mask and a ventilation device. Adequate ventilation is the cornerstone of successful neonatal resuscitation; therefore, it is mandatory that anybody involved in neonatal resuscitation is trained in mask ventilation techniques. One of the main problems with mask ventilation is that it is very subjective with direct feedback lacking and not uncommonly, the resuscitator does not realise that their technique is unsatisfactory. Many studies have shown that monitoring tidal volume and leak around the mask or endotracheal tube enables the resuscitator to identify the problem and adjust their technique to reduce the leak and deliver and appropriate tidal volume. This chapter discusses the currently available monitoring devices used during stabilization/resuscitation in the delivery room.

Analysis of peak inflating pressure and inflating pressure limit during neonatal volume guaranteed ventilation.

OBJECTIVES: To report how peak inflating pressure (PIP), tidal volume (VT) and low-tidal volume alarms are affected by maximum allowed inflating pressure (Pmax) during volume guarantee (VG) ventilation. STUDY DESIGN: Ventilation data were analysed with 1 Hz sampling rate from 25 neonates receiving synchronised intermittent positive pressure ventilation with VG for >12 h. RESULTS: The difference between Pmax and PIP (Pdiff) ranged between 5 and 20 mbar (median = 11 mbar) despite a protocol to keep Pmax 5 mbar above the "working PIP". Pmax was reached in 5.2% of inflations. Computational modelling demonstrated that had Pdiff been kept at 5 mbar more consistently, >10% of inflations would have reached Pmax. The frequency of low-tidal volume alarms showed inverse correlation with Pdiff. CONCLUSIONS: It is difficult to implement a simple Pmax strategy due to variability of PIP. Setting Pmax close to the "working PIP" limits VT delivery and triggers frequent alarms.

High-frequency oscillatory ventilation with volume guarantee: a single-centre experience.

OBJECTIVE: High-frequency oscillatory ventilation (HFOV) is widely used in neonatology. The Dräger Babylog VN500 ventilator offers volume-guaranteed HFOV (HFOV-VG) mode when the high-frequency tidal volume (VThf) to be delivered can be set. We investigated how HFOV-VG maintains VThf in the short and longer term and how it affects other ventilator parameters and blood gases. METHODS: We downloaded ~3.2 million seconds (36.7 days) of ventilator data from 17 infants ventilated using HFOV-VG during clinical care with 1 Hz sampling rate. To process and analyse the data, we used the Python computer language. RESULTS: Overall, the median VThf was 1.93 mL/kg (IQR 1.64-2.45 mL/kg). The difference between set and delivered tidal volume was <0.2 mL/kg for 83% of time. In the individual recordings, the median VThf ranged between 1.44 and 3.31 mL/kg. During HFOV-VG, the VThf varied from 1 second to another, but it was very close to the target value when averaged over 5 min periods. After weight correction, the VThf or the diffusion coefficient of carbon dioxide (DCO2) showed weak inverse correlation with partial pressure of CO2(pCO2) (for VThf, r=-0.162, 95% CI -0.282 to -0.037, p=0.01). Uncorrected values showed no correlation. Of the 53 blood gas measurements taken when VThf was >2.5 mL/kg, there were only six (11%) with a pCO2 >8 kPa. CONCLUSIONS: During HFOV-VG, the tidal volume of oscillations varies in the short term but is maintained very close to the target over the longer term. VThf or DCO2 have poor correlation with CO2 levels but a volume of >2.5 mL/kg VThf is rarely needed.

Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration.

Importance: There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen. Objective: To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity. Design, Setting, and Participants: Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation. Exposures: Spo2 target range that was lower (85%-89%) vs higher (91%-95%). Main Outcomes and Measures: The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities. Results: A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003). Conclusions and Relevance: In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.

Leak Compensation During Volume Guarantee With the Dräger Babylog VN500 Neonatal Ventilator.

OBJECTIVES: To investigate how compensating for endotracheal tube leaks by targeting the leak-compensated tidal volume affects measured physiologic and ventilator variables during neonatal mechanical ventilation. DESIGN: Retrospective observational study. SETTING: A level III Neonatal ICU. PATIENTS: We enrolled 30 neonates who were ventilated using synchronized intermittent positive pressure mode with volume guarantee and had at least 12 hours of continuous detailed recording of ventilation variables. INTERVENTIONS: Infants were treated using the Dräger VN500 ventilator (Dräger, Lübeck, Germany), which uses a proprietary algorithm to measure and compensate for endotracheal tube leaks. Eleven were ventilated without leak compensation and 19 with leak compensation. MEASUREMENTS AND MAIN RESULTS: Detailed ventilation data were collected and analyzed at 1 Hz, with intermittent blood gas values. The percentage of leak was less than 20% in 73% of leak-compensated inflations, and the volume of the leak compensation was less than 1 mL/kg in 97.3% of inflations. Between the two groups, ventilation variables were comparable, except the percentage of leak that was significantly (p = 0.005) higher in the recordings with leak compensation. Without leak compensation, the mean expired tidal volume was maintained very close to the set level up to 50% leak, but with leaks greater than 50%, it declined progressively. With leak compensation, the mean leak-compensated expired tidal volume was well maintained even with leak greater than 90% although with large variability. Without leak compensation, the difference between the maximum allowed inflating pressure and the peak inflating pressure decreased progressively as the leak increased. This did not occur with leak compensation. The median PCO2 was slightly higher with leak compensation. CONCLUSIONS: During volume guarantee ventilation with a Dräger VN500 ventilator, without leak compensation the expired tidal volume declined after 50% leak. With leak compensation, the tidal volume was maintained even with a large leak. With leak compensation, there was a more stable peak inflating pressure, although the PCO2 was slightly higher.

Monitoring Neonatal Resuscitation: Why Is It Needed?

Stabilisation and resuscitation of babies at birth is one of the most frequently performed procedures and requires considerable skill. If it is not done well, the baby may suffer prolonged hypoxia and bradycardia. Over the last few years there has been a growing interest in carefully evaluating an infant's condition at birth and the details of what is happening during resuscitation. Clinical assessment of an infant at this time is difficult and often inaccurate. Assessments of heart rate, colour, chest excursions, mask leak, tidal volume, inflation and expiration times, endotracheal intubation, and spontaneous breathing are imprecise. Detailed monitoring of gas flow in and out of the baby, integrated to tidal volume and used to calculate the leak around the face mask or endotracheal tube, together with ventilation pressures, pulse oximetry, ECG, and capnography add objectivity to the clinical assessments. These physiological parameters can be used directly to guide care but are also very useful for debriefing, feedback, audit, teaching, and research. With simultaneous video recording of the resuscitation it is possible to see exactly what is happening during the procedure. Endotracheal intubation is a difficult skill to learn and teach. However, this is now much easier with video laryngoscopy showing the intubator and supervisors exactly what is happening at the larynx.

Frequency, duration and cause of ventilator alarms on a neonatal intensive care unit.

OBJECTIVE: To investigate the frequency and cause of neonatal ventilator alarms. Neonatal ventilators frequently alarm and also disturb babies, parents and nurses. If frequent they may cause alarm fatigue and be ignored. The number, frequency and details of neonatal ventilator alarms are unreported. METHODS: We developed programs for retrieving and analysing ventilator data each second on alarms and ventilation parameters from 46 babies ventilated with Dräger Babylog VN500 ventilators using various modes. RESULTS: A mean of 60 hours was recorded per baby. Over 116 days, 27 751 alarms occurred. On average, that was 603 per baby and 10 per hour. Median (IQR) alarm duration was 10 (4-21) s. Type, frequency and duration varied between infants. Some babies had >10% of their time with alarms. Eight alarm types caused ~99% of all alarms. Three alarms, 'MV high limit' and 'respiratory rate >high limit', caused 46.6%, often due to inappropriate settings. 49.9% were due to a low expired tidal volume during volume guarantee ventilation, often due to the maximum pressure being set too low. 26 106 (94.1%) of all alarms lasted <1 min. However, 86 alarms lasted >10 min and 16 alarms >1 hour. Similar alarms were frequently clustered, sometimes >100/hour. CONCLUSIONS: Frequent ventilator alarms are caused by physiological variability in the respiratory rate or minute volume, inappropriate alarm limits or too low maximum peak inflating pressure during volume-targeted ventilation. While most alarms were very short, sometimes alarms were ignored by neonatal intensive care unit staff for long periods.

Volume-targeted versus pressure-limited ventilation in neonates.

BACKGROUND: Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO2). OBJECTIVES: To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes. DATA COLLECTION AND ANALYSIS: We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes. STATISTICS: for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis. MAIN RESULTS: Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes. AUTHORS' CONCLUSIONS: Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. OBJECTIVES: To assess the efficacy of an initial sustained (> 1 second duration) lung inflation versus standard inflations (≤ 1 second) in newly born infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 17 February 2017), Embase (1980 to 17 February 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 17 February 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and weighted mean difference (WMD) for continuous data. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. MAIN RESULTS: Eight trials enrolling 941 infants met our inclusion criteria. Investigators in seven trials (932 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review - mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40; participants = 479; studies = 5; I² not applicable) and mortality during hospitalisation (typical RR 1.01, 95% CI 0.67 to 1.51; participants = 932; studies = 7; I² = 19%); the quality of the evidence was low for death in the delivery room (limitations in study design and imprecision of estimates) and was moderate for death before discharge (limitations in study design of most included trials). Amongst secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; participants = 524; studies = 5; I² = 95%; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study: When this study was removed from the analysis, the effect was largely reduced (MD -1.71 days, 95% CI -3.04 to -0.39, I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. rate of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 811; studies = 5; I² = 0%); need for surfactant administration during hospital admission (typical RR 0.97, 95% CI 0.86 to 1.10; participants = 932; studies = 7; I² = 0%); rate of chronic lung disease (typical RR 0.95, 95% CI 0.74 to 1.22; participants = 683; studies = 5; I² = 47%); pneumothorax (typical RR 1.44, 95% CI 0.76 to 2.72; studies = 6, 851 infants; I² = 26%); or rate of patent ductus arteriosus requiring pharmacological treatment (typical RR 1.08, 95% CI 0.90 to 1.30; studies = 6, 745 infants; I² = 36%). The quality of evidence for these secondary outcomes was moderate (limitations in study design of most included trials - GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates - GRADE). AUTHORS' CONCLUSIONS: Sustained inflation was not better than intermittent ventilation for reducing mortality in the delivery room and during hospitalisation. The number of events across trials was limited, so differences cannot be excluded. When considering secondary outcomes, such as need for intubation, need for or duration of respiratory support, or bronchopulmonary dysplasia, we found no evidence of relevant benefit for sustained inflation over intermittent ventilation. The duration of mechanical ventilation was shortened in the SLI group. This result should be interpreted cautiously, as it can be influenced by study characteristics other than the intervention. Future RCTs should aim to enrol infants who are at higher risk of morbidity and mortality, should stratify participants by gestational age, and should provide more detailed monitoring of the procedure, including measurements of lung volume and presence of apnoea before or during the SLI.