Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Respiratory function monitoring during early resuscitation and prediction of outcomes in prematurely born infants.

OBJECTIVES: Over the last decade, there has been increased use of end-tidal carbon dioxide (ETCO2) and oxygen saturation (SpO2) monitoring during resuscitation of prematurely born infants in the delivery suite. Our objectives were to test the hypotheses that low end-tidal carbon dioxide (ETCO2) levels, low oxygen saturations (SpO2) and high expiratory tidal volumes (VTE) during the early stages of resuscitation would be associated with adverse outcomes in preterm infants. METHODS: Respiratory recordings made in the first 10 min of resuscitation in the delivery suite of 60 infants, median GA 27 (interquartile range 25-29) weeks were analysed. The results were compared of infants who did or did not die or did or did not develop intracerebral haemorrhage (ICH) or bronchopulmonary dysplasia (BPD). RESULTS: Twenty-five infants (42%) developed an ICH and 23 (47%) BPD; 11 (18%) died. ETCO2 at approximately 5 min after birth was lower in infants who developed an ICH, this remained significant after adjusting for gestational age, coagulopathy and chorioamnionitis (p=0.03). ETCO2 levels were lower in infants who developed ICH or died compared to those that survived without ICH, which remained significant after adjustment for gestational age, Apgar score at 10 min, chorioamnionitis and coagulopathy (p=0.004). SpO2 at approximately 5 min was lower in the infants who died compared to those who survived which remained significant after adjusting for the 5-min Apgar score and chorioamnionitis (p=0.021). CONCLUSIONS: ETCO2 and SpO2 levels during early resuscitation in the delivery suite were associated with adverse outcomes.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Anatomical deadspace during resuscitation of infants with congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has a high mortality and morbidity related to pulmonary hypoplasia. AIMS: To test the hypothesis that CDH infants who survived would have a greater anatomical deadspace reflecting less severe pulmonary hypoplasia. Furthermore, infants with CDH who had undergone feto-tracheal occlusion (FETO) would have a greater anatomical deadspace. STUDY DESIGN: Infants were studied during resuscitation in the delivery suite. They were all intubated immediately at delivery, given a neuromuscular blocking agent and underwent respiratory monitoring. The anatomical deadspace was calculated from volumetric capnography measurements. SUBJECTS: Thirty infants born at 32 weeks of gestation or greater and diagnosed antenatally with a CDH were studied. Eleven had undergone FETO and overall five died. OUTCOME MEASURES: Anatomical deadspace (VdANA) and survival to discharge. RESULTS: The median (IQR) gestational age of the infants was 38.1 (35.2-39.3) weeks and birthweight 2.8 (2.3-3.3) kg. The anatomical deadspace was higher in those infants who survived (2.9 (2.8-3.3) mls/kg) compared to those who died (2.2 (2.1-2.7) mls/kg; p = 0.003) and was higher in those who had undergone FETO (3.0 (2.8-3.8) mls/kg) compared to those who had not (2.8 (2.4-3.0) mls/kg; p = 0.032). In predicting survival to discharge, the anatomical deadspace had an AUC of 0.90 (p = 0.006). CONCLUSIONS: CDH infants who survived had a larger anatomical deadspace than those who died suggesting they had less lung hypoplasia. In addition, infants who had undergone FETO had greater anatomical deadspace possibly reflecting distension of the conducting airways.

End-tidal carbon dioxide levels during resuscitation and carbon dioxide levels in the immediate neonatal period and intraventricular haemorrhage.

Abnormal levels of end-tidal carbon dioxide (EtCO2) during resuscitation in the delivery suite are associated with intraventricular haemorrhage (IVH) development. Our aim was to determine whether carbon dioxide (CO2) levels in the first 3 days after birth reflected abnormal EtCO2 levels in the delivery suite, and hence, a prolonged rather than an early insult resulted in IVH. In addition, we determined if greater EtCO2level fluctuations during resuscitation occurred in infants who developed IVH. EtCO2 levels during delivery suite resuscitation and CO2 levels on the neonatal unit were evaluated in 58 infants (median gestational age 27.3 weeks). Delta EtCO2 was the difference between the highest and lowest level of EtCO2. Thirteen infants developed a grade 3-4 IVH (severe group). There were no significant differences in CO2 levels between those who did and did not develop an IVH (or severe IVH) on the NICU. The delta EtCO2 during resuscitation differed between infants with any IVH (6.2 (5.4-7.5) kPa) or no IVH (3.8 (2.7-4.3) kPA) (p < 0.001) after adjusting for differences in gestational age. Delta EtCO2 levels gave an area under the ROC curve of 0.940 for prediction of IVH.Conclusion: The results emphasize the importance of monitoring EtCO2 levels in the delivery suite.What is Known:• Abnormal levels of carbon dioxide (CO2) in the first few days after birth and abnormal end-tidal CO2levels (EtCO2) levels during resuscitation are associated in preterm infants with the risk of developing intraventricular haemorrhage (IVH).What is New:• There were no significant differences in NICU CO2levels between those who developed an IVH or no IVH.• There was a poor correlation between delivery suite ETCO2levels and NICU CO2levels.• Large fluctuations in EtCO2during resuscitation in the delivery suite were highly predictive of IVH development in preterm infants.

Tidal volume monitoring during initial resuscitation of extremely prematurely born infants.

Background Airway obstruction can occur during facemask (FM) resuscitation of preterm infants at birth. Intubation bypasses any upper airway obstruction. Thus, it would be expected that the occurrence of low expiratory tidal volumes (VTes) would be less in infants resuscitated via an endotracheal tube (ETT) rather than via an FM. Our aim was to test this hypothesis. Methods Analysis was undertaken of respiratory function monitoring traces made during initial resuscitation in the delivery suite to determine the peak inflating pressure (PIP), positive end expiratory pressure (PEEP), the VTe and maximum exhaled carbon dioxide (ETCO2) levels and the number of inflations with a low VTe (less than 2.2 mL/kg). Results Eighteen infants were resuscitated via an ETT and 11 via an FM, all born at less than 29 weeks of gestation. Similar inflation pressures were used in both groups (17.2 vs. 18.8 cmH2O, P = 0.67). The proportion of infants with a low median VTe (P = 0.6) and the proportion of inflations with a low VTe were similar in the groups (P = 0.10), as was the lung compliance (P = 0.67). Infants with the lowest VTe had the stiffest lungs (P < 0.001). Conclusion Respiratory function monitoring during initial resuscitation can objectively identify infants who may require escalation of inflation pressures.

Detection of exhaled carbon dioxide following intubation during resuscitation at delivery.

OBJECTIVES: End tidal carbon dioxide (ETCO2) monitoring can facilitate identification of successful intubation. The aims of this study were to determine the time to detect ETCO2 following intubation during resuscitation of infants born prematurely and whether it differed according to maturity at birth or the Apgar scores (as a measure of the infant's condition after birth). DESIGN: Analysis of recordings of respiratory function monitoring. SETTING: Two tertiary perinatal centres. PATIENTS: Sixty-four infants, with median gestational age of 27 (range 23-34)weeks. INTERVENTIONS: Respiratory function monitoring during resuscitation in the delivery suite. MAIN OUTCOME MEASURES: The time following intubation for ETCO2 levels to be initially detected and to reach 4 mm Hg and 15 mm Hg. RESULTS: The median time for initial detection of ETCO2 following intubation was 3.7 (range 0-44) s, which was significantly shorter than the median time for ETCO2 to reach 4 mm Hg (5.3 (range 0-727) s) and to reach 15 mm Hg (8.1 (range 0-827) s) (both P<0.001). There were significant correlations between the time for ETCO2 to reach 4 mm Hg (r=-0.44, P>0.001) and 15 mm Hg (r=-0.48, P<0.001) and gestational age but not with the Apgar scores. CONCLUSIONS: The time for ETCO2 to be detected following intubation in the delivery suite is variable emphasising the importance of using clinical indicators to assess correct endotracheal tube position in addition to ETCO2 monitoring. Capnography is likely to detect ETCO2 faster than colorimetric devices.

UK neonatal resuscitation survey.

BACKGROUND: Previous surveys have demonstrated that neonatal resuscitation practices on the delivery suite vary between UK units, particularly according to the hospital's neonatal unit's level. Our aim was to determine if recent changes to the Resuscitation Council guidelines had influenced clinical practice. METHODS: Surveys of resuscitation practices at UK delivery units carried out in 2012 and 2017 were compared. RESULTS: Comparing 2017 with 2012, initial resuscitation using air was more commonly used in both term (98% vs 75%, p<0.001) and preterm (84% vs 34%, p<0.001) born infants. Exhaled carbon dioxide monitoring was more frequently employed in 2017 (84% vs 19%, p<0.001). There were no statistically significant differences in practices according to the level of neonatal care provided by the hospital. CONCLUSION: There have been significant changes in neonatal resuscitation practices in the delivery suite since 2012 regardless of the different levels of neonatal care offered.

Relationship of resuscitation, respiratory function monitoring data and outcomes in preterm infants.

Intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD) are major complications of premature birth. We tested the hypotheses that prematurely born infants who developed an IVH or BPD would have high expiratory tidal volumes (VTE) (VTE > 6 ml/kg) and/or low-end tidal carbon dioxide (ETCO2) levels (ETCO2 levels < 4.5 kPa) as recorded by respiratory function monitoring or hyperoxia (oxygen saturation (SaO2) > 95%) during resuscitation in the delivery suite. Seventy infants, median gestational age 27 weeks (range 23-33), were assessed; 31 developed an IVH and 43 developed BPD. Analysis was undertaken of 31,548 inflations. The duration of resuscitation did not differ significantly between the groups. Those who developed an IVH compared to those who did not had a greater number of inflations with a high VTE and a low ETCO2, which remained significant after correcting for differences in gestational age and birth weight between groups (p = 0.019). Differences between infants who did and did not develop BPD were not significant after correcting for differences in gestational age and birth weight. There were no significant differences in the duration of hyperoxia between the groups.Conclusions: Avoidance of high tidal volumes and hypocarbia in the delivery suite might reduce IVH development. What is known • Hypocarbia on the neonatal unit is associated with the development of intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD). What is new • Infants who developed an IVH compared to those who did not had significantly more inflations with high expiratory tidal volumes and low ETCO2s.

Inflation pressures and times during initial resuscitation in preterm infants.

BACKGROUND: The optimal combination of inflation pressures and times to produce adequate expiratory tidal volumes during initial resuscitation in prematurely born infants has not been determined. The aim of this study was therefore to assess combinations of inflation pressures and times and the resulting expiratory tidal volume levels using a respiratory function monitor. METHODS: Sixty-four infants born before 34 weeks of gestation were studied. The infants were divided according to whether the inflation pressure (peak inflation pressure minus positive end expiratory pressure) was < or ≥20 cmH2 O during the first five inflations delivered by a face mask, and those groups were then subdivided according to whether the inflation time was < or ≥1.5 s. RESULTS: Inflation pressure ≥20 cmH2 O compared with lower pressure at both inflation times produced significantly higher expiratory tidal volume. Longer compared with shorter inflation times when the inflation pressure was ≥20 cmH2 O resulted in no significant difference in expiratory tidal volume. At <20 cmH2 O inflation pressure, longer inflation time overall resulted in higher end tidal volume, but the majority of infants had a tidal volume less than the anatomical dead space. CONCLUSIONS: At higher inflation pressure, a longer inflation time was not necessary to increase expiratory tidal volume.

Resuscitation of infants with congenital diaphragmatic hernia.

OBJECTIVE: To determine whether the respiratory response to resuscitation in infants with congenital diaphragmatic hernia (CDH) as measured by a respiratory function monitor differed between those who did and did not survive. DESIGN: Observational study. SETTING: Tertiary perinatal centre. PATIENTS: Thirty-eight infants born at 34 weeks of gestation or greater and diagnosed antenatally with a CDH. INTERVENTIONS: Expiratory tidal volume (VTe), peak inflation pressure (PIP) and end-tidal carbon dioxide level (ETCO2) were simultaneously recorded during resuscitation using a respiratory function monitor. Oxygen saturation was also monitored. MAIN OUTCOME MEASURES: Mortality related to the median VTe, PIP, compliance (VTe divided by PIP) and ETCO2 levels in the first and last minute of recorded resuscitation and the maximum oxygen saturation. RESULTS: The median gestational age, birth weight and duration of resuscitation of the 11 infants who died did not differ significantly from those who survived. During the first minute of recorded resuscitation, the VTe (median 1.89 vs 2.68 mL/kg) (p=0.009)), the ETCO2 (median 11.7 vs 41.7 mm Hg) (p=0.023)) and the compliance (0.06 vs 0.08 mL/cm H2O/kg) (p=0.018)) were lower in the non-survivors. In the last minute, the PIP was higher (32.5 vs 30.3 cm H2O) (p=0.03)), the VTe (3.22 vs 4.66 mL/kg) (p=0.003)) and compliance (0.10 vs 0.15 mL/cm H2O/kg) (p=0.004)) were lower in the non-survivors. The maximum oxygen saturation achieved in the labour suite was lower in the non-survivors (93% vs 100%) (p=0.037). CONCLUSIONS: Infants with CDH who did not survive responded less well even to initial resuscitation.

Synchronized mechanical ventilation for respiratory support in newborn infants.

BACKGROUND: During synchronised mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. If synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing baro/volutrauma, air leak and bronchopulmonary dysplasia. Synchronous ventilation can potentially be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient-triggered ventilation. OBJECTIVES: To compare the efficacy of:(i) synchronised mechanical ventilation, delivered as high-frequency positive pressure ventilation (HFPPV) or patient-triggered ventilation (assist control ventilation (ACV) and synchronous intermittent mandatory ventilation (SIMV)), with conventional ventilation or high-frequency oscillation (HFO);(ii) different types of triggered ventilation (ACV, SIMV, pressure-regulated volume control ventilation (PRVCV), SIMV with pressure support (PS) and pressure support ventilation (PSV)). SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to June 5 2016), EMBASE (1980 to June 5 2016), and CINAHL (1982 to June 5 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials comparing synchronised ventilation delivered as HFPPV to CMV, or ACV/SIMV to CMV or HFO in neonates. Randomised trials comparing different triggered ventilation modes (ACV, SIMV, SIMV plus PS, PRVCV and PSV) in neonates. DATA COLLECTION AND ANALYSIS: Data were collected regarding clinical outcomes including mortality, air leaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intraventricular haemorrhage (grades 3 and 4), bronchopulmonary dysplasia (BPD) (oxygen dependency beyond 28 days), moderate/severe BPD (oxygen/respiratory support dependency beyond 36 weeks' postmenstrual age (PMA) and duration of weaning/ventilation.Eight comparisons were made: (i) HFPPV versus CMV; (ii) ACV/SIMV versus CMV; (iii) SIMV or SIMV + PS versus HFO; iv) ACV versus SIMV; (v) SIMV plus PS versus SIMV; vi) SIMV versus PRVCV; vii) SIMV vs PSV; viii) ACV versus PSV. Data analysis was conducted using relative risk for categorical outcomes, mean difference for outcomes measured on a continuous scale. MAIN RESULTS: Twenty-two studies are included in this review. The meta-analysis demonstrates that HFPPV compared to CMV was associated with a reduction in the risk of air leak (typical relative risk (RR) for pneumothorax was 0.69, 95% confidence interval (CI) 0.51 to 0.93). ACV/SIMV compared to CMV was associated with a shorter duration of ventilation (mean difference (MD) -38.3 hours, 95% CI -53.90 to -22.69). SIMV or SIMV + PS was associated with a greater risk of moderate/severe BPD compared to HFO (RR 1.33, 95% CI 1.07 to 1.65) and a longer duration of mechanical ventilation compared to HFO (MD 1.89 days, 95% CI 1.04 to 2.74).ACV compared to SIMV was associated with a trend to a shorter duration of weaning (MD -42.38 hours, 95% CI -94.35 to 9.60). Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of BPD. There was a non-significant trend towards a lower mortality rate using HFPPV versus CMV and a non-significant trend towards a higher mortality rate using triggered ventilation versus CMV. No disadvantage of HFPPV or triggered ventilation was noted regarding other outcomes. AUTHORS' CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in air leak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronised ventilation. Triggered ventilation in the form of SIMV ± PS resulted in a greater risk of BPD and duration of ventilation compared to HFO. Optimisation of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials. It is essential that newer forms of triggered ventilation are tested in randomised trials that are adequately powered to assess long-term outcomes before they are incorporated into routine clinical practice.

Synchronized mechanical ventilation for respiratory support in newborn infants.

BACKGROUND: During synchronised mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. If synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing baro/volutrauma, air leak and bronchopulmonary dysplasia. Synchronous ventilation can potentially be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient-triggered ventilation. OBJECTIVES: To compare the efficacy of:(i) synchronised mechanical ventilation, delivered as high-frequency positive pressure ventilation (HFPPV) or patient-triggered ventilation (assist control ventilation (ACV) and synchronous intermittent mandatory ventilation (SIMV)), with conventional ventilation or high-frequency oscillation (HFO);(ii) different types of triggered ventilation (ACV, SIMV, pressure-regulated volume control ventilation (PRVCV), SIMV with pressure support (PS) and pressure support ventilation (PSV)). SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to June 5 2016), EMBASE (1980 to June 5 2016), and CINAHL (1982 to June 5 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials comparing synchronised ventilation delivered as HFPPV to CMV, or ACV/SIMV to CMV or HFO in neonates. Randomised trials comparing different triggered ventilation modes (ACV, SIMV, SIMV plus PS, PRVCV and PSV) in neonates. DATA COLLECTION AND ANALYSIS: Data were collected regarding clinical outcomes including mortality, air leaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intraventricular haemorrhage (grades 3 and 4), bronchopulmonary dysplasia (BPD) (oxygen dependency beyond 28 days), moderate/severe BPD (oxygen/respiratory support dependency beyond 36 weeks' postmenstrual age (PMA) and duration of weaning/ventilation.Eight comparisons were made: (i) HFPPV versus CMV; (ii) ACV/SIMV versus CMV; (iii) SIMV or SIMV + PS versus HFO; iv) ACV versus SIMV; (v) SIMV plus PS versus SIMV; vi) SIMV versus PRVCV; vii) SIMV vs PSV; viii) ACV versus PSV. Data analysis was conducted using relative risk for categorical outcomes, mean difference for outcomes measured on a continuous scale. MAIN RESULTS: Twenty-two studies are included in this review. The meta-analysis demonstrates that HFPPV compared to CMV was associated with a reduction in the risk of air leak (typical relative risk (RR) for pneumothorax was 0.69, 95% confidence interval (CI) 0.51 to 0.93). ACV/SIMV compared to CMV was associated with a shorter duration of ventilation (mean difference (MD) -38.3 hours, 95% CI -53.90 to -22.69). SIMV or SIMV + PS was associated with a greater risk of moderate/severe BPD compared to HFO (RR 1.33, 95% CI 1.07 to 1.65) and a longer duration of mechanical ventilation compared to HFO (MD 1.89 days, 95% CI 1.04 to 2.74).ACV compared to SIMV was associated with a trend to a shorter duration of weaning (MD -42.38 hours, 95% CI -94.35 to 9.60). Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of BPD. There was a non-significant trend towards a lower mortality rate using HFPPV versus CMV and a non-significant trend towards a higher mortality rate using triggered ventilation versus CMV. No disadvantage of HFPPV or triggered ventilation was noted regarding other outcomes. AUTHORS' CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in air leak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronised ventilation. Triggered ventilation in the form of SIMV ± PS resulted in a greater risk of BPD and duration of ventilation compared to HFO. Optimisation of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials. It is essential that newer forms of triggered ventilation are tested in randomised trials that are adequately powered to assess long-term outcomes before they are incorporated into routine clinical practice.

The first breath during resuscitation of prematurely born infants.

BACKGROUND: The first five initial inflation pressures and times during resuscitation of prematurely born infants are frequently lower than those recommended and rarely result in tidal volumes exceeding the anatomical dead space. Greater volumes were produced when the infant was provoked to inspire by an inflation (active inflation). AIMS: To assess factors associated with a shorter time to the first active inflation. STUDY DESIGN: Respiratory function monitoring was undertaken during resuscitation, peak inflation pressures (PIP), inflation times and the infant's respiratory activity were simultaneously recorded. SUBJECTS: Infants with a gestational age<34weeks requiring resuscitation at birth. OUTCOME MEASURES: The relationships of the PIP and inflation time of the first five inflations and first active inflation to the time to the first active inflation. RESULTS: Recordings from 47 infants, median gestational age of 29 (23-34) weeks, were analysed. The median PIP of the first five inflations was 27 (range 9-37) cmH2O and inflation time 1.22 (range 0.32-4.08) s. The median PIP of the first active inflation was 25 (range 19-37) cmH2O and inflation time 1.35 (0.35-3.67) s. The median time to the first active inflation was 7 (range 0-50) seconds and was inversely correlated with the PIP (p=0.001) and inflation time (p=0.018) of the first five inflations and the PIP (p=0.001) and inflation time (p=0.008) of the first active inflation. CONCLUSION: The magnitude of the inflation pressures and times of the first five inflations inversely correlate with the time to the first breath during resuscitation.

Prevention of Late Onset Sepsis and Central-line Associated Blood Stream Infection in Preterm Infants.

AIM: Late onset sepsis (LOS) and central-line associated blood stream infection (CLA-BSI) contribute toward the mortality and morbidity in prematurely born infants. The aim of this study is to investigate the effects of hospital-wide and unit-based interventions on LOS and CLA-BSI in infants born at <32 weeks gestation. METHODS: Intensive care, high dependency days and catheter days were obtained from the unit database and blood culture results from a microbiology laboratory database. Poisson regression was used to evaluate the effects of interventions on LOS and CLA-BSI. RESULTS: Quarterly rates of LOS reduced from 26.1 to 2.9 per 1000 intensive care, high dependency days and CLA-BSI from 31.6 to 4.3 per 1000 catheter days between 2007 and 2012. Appointment of a hospital specialist vascular device nurse, a change in the mode of administration of vancomycin, standardization of the hospital skin and hub disinfection policy and the introduction of a venous infusion phlebitis scoring system were associated with a reduction of LOS to 55% (95% confidence interval: 40-74%) and CLA-BSI 45% (95% confidence interval: 33-61%) of pre-intervention levels. The standardization of the neonatal unit policy for skin disinfection and a move to a new building were associated with reductions of LOS to 64% (47-87%) and 54% (34-88%), respectively, and aseptic no touch technique for infusion access with CLA-BSI to 53% (37-75%) of pre-intervention levels. CONCLUSION: A multifaceted approach involving changes in antimicrobial and skin disinfection policy, training for aseptic no touch technique and surveillance resulted in sustained reduction in LOS and CLA-BSI rates.

Prematurely born infants' response to resuscitation via an endotracheal tube or a face mask.

BACKGROUND: Prematurely born infants may be resuscitated in the labour suite via a face mask or an endotracheal tube. AIMS: To assess prematurely born infants' initial responses to resuscitation delivered via an endotracheal tube or a face mask, to determine if the first five inflations via an endotracheal tube produced expired tidal volumes greater than 4.4ml/kg (twice the anatomical dead space) and whether the outcome of initial resuscitation via an endotracheal tube or via a face mask differed according to the first active inflation (the infant's inspiratory effort coinciding with an inflation). STUDY DESIGN: Prospective observational study. SUBJECTS: Thirty-five infants (median gestational age 25, range 23-27weeks) requiring resuscitation via an endotracheal tube (n=20) or a face mask (n=15) were studied. OUTCOME MEASURES: Inflation pressures, inflation times, expiratory tidal volumes, end tidal carbon dioxide (ETCO2) and leak were recorded. RESULTS: Before the first active inflation, only 27% of infants receiving resuscitation via an endotracheal tube had expiratory volumes greater than 4.4ml/kg. During, both endotracheal and face mask initial resuscitations, during the first active inflation the expired tidal volumes (7.7ml/kg, 5.2ml/kg) and ETCO2 levels (4.8kPa, 3.2kPa) were significantly higher than during the inflations before the first active inflation (2.8ml/kg, 1.6ml/kg; 0.36kPa, 0.2kPa respectively) (all p<0.001). CONCLUSIONS: Initial resuscitation via an endotracheal tube using currently recommended pressures, rarely produced adequate tidal volumes. Resuscitation via an endotracheal tube or a face mask was most effective when the infant's inspiratory effort coincided with an inflation.

Evaluation of respiratory function monitoring at the resuscitation of prematurely born infants.

UNLABELLED: Our aim was to determine whether neonatal trainees found respiratory function monitoring (RFM) helpful during the resuscitation of prematurely born infants, what decisions they made on the basis of RFM and whether those decisions were evidence based. Fifty one trainees completed an electronic questionnaire. Eighty-three percent found the tidal volume display useful, 59 % altered the inflation pressure based on the tidal volume: 52 % considered 5 ml/kg adequate; 33 % 4 ml/kg; 13 % 6 ml/kg; and 2 % 7 ml/kg, despite no evidence on which to decide was the optimum tidal volume. If there was no detectable expired carbon dioxide (CO2), 30 trainees said they would reintubate, yet the absence of expired CO2 can indicate inadequate vasodilation of the pulmonary circulation rather than inappropriate placement of the endotracheal tube. If there was no chest wall expansion, but expired CO2, a third of junior trainees would reintubate which is inappropriate. If the oxygen saturation (SaO2) was <85 % at 1 min, no senior trainee, but 50 % of junior trainees would increase the inspired oxygen. The majority of healthy babies have an SaO2 > 85 % by 1 min. CONCLUSIONS: The usefulness of respiratory function monitoring for trainees during neonatal resuscitation is often not evidence based.

Neuromuscular blockade and lung function during resuscitation of infants with congenital diaphragmatic hernia.

BACKGROUND: There is no consensus or evidence as to whether a neuromuscular blocking agent should be used during the initial resuscitation of infants with congenital diaphragmatic hernia (CDH) in the labour ward. OBJECTIVE: To determine if administration of a neuromuscular blocking agent affected the lung function of infants with CDH during their initial resuscitation in the labour ward. METHODS: Fifteen infants with CDH were studied (median gestational age 38 weeks, range 34-41; birth weight 2,790 g, range 1,780-3,976). Six infants had undergone feto-endotracheal occlusion (FETO). Flow, airway pressure, tidal volume and dynamic lung compliance changes were recorded using a respiratory function monitor (NM3, Respironics). Twenty inflations immediately before, immediately after and 5 min after administration of a neuromuscular blocking agent (pancuronium bromide) were analysed. RESULTS: The median dynamic lung compliance of the 15 infants was 0.22 ml/cm H2O/kg (range 0.1-0.4) before and 0.16 ml/cm H2O/kg (range 0.1-0.3) immediately after pancuronium bromide administration (p < 0.001) and remained at a similar low level 5 min after pancuronium bromide administration. The FETO compared to the non-FETO infants had a lower median dynamic compliance both before (p < 0.0001) and 5 min after pancuronium administration (p < 0.001) and required significantly longer durations of ventilation (p = 0.004), supplementary oxygen (p = 0.003) and hospitalisation (p = 0.007). CONCLUSIONS: Infants with CDH, particularly those who have undergone FETO, have a low lung compliance at birth, and this is further reduced by administration of a neuromuscular blocking agent.

End tidal carbon dioxide levels during the resuscitation of prematurely born infants.

BACKGROUND: Successful resuscitation of prematurely born infants is dependent on achieving adequate alveolar ventilation and vasodilation of the pulmonary vascular bed. Elevation of end-tidal carbon dioxide (ETCO(2)) levels may indicate pulmonary vasodilation. AIMS: This research aims to study the temporal changes in ETCO(2) levels and the infant's respiratory efforts during face mask resuscitation in the labour suite, and to determine if the infant's first inspiratory effort was associated with a rise in the ETCO(2) levels, suggesting pulmonary vasodilation had occurred. STUDY DESIGN: This study is an observational one. SUBJECTS: The subjects of the study are forty infants with a median gestational age of 30 weeks (range 23-34). OUTCOME MEASURES: Inflation pressures, expiratory tidal volumes and ETCO(2) levels were measured. RESULTS: The median expiratory tidal volume of inflations prior to the onset of the infant's respiratory efforts (passive inflations) was lower than that of the inflation associated with the first inspiratory effort (active inflation) (1.8 (range 0.1-7.3) versus 6.3 ml/kg (range 1.9-18.4), p<0.001), as were the median ETCO(2) levels (0.3 (range 0.1-2.1) versus 3.4 kPa (0.4-11.5), p<0.001). The median expiratory tidal volume (4.5 ml/kg (range 0.5-18.3)) and ETCO(2) level (2.2 kPa (range 0.3-9.3)) of the two passive inflations following the first active inflation were also higher than the median expiratory tidal volume and ETCO(2) levels of the previous passive inflations (p<0.001, p<0.0001 respectively). CONCLUSION: These results suggest that during face mask resuscitation, improved carbon dioxide elimination, likely due to pulmonary vasodilation, occurred with the onset of the infant's respiratory efforts.