Ventilatory response to added dead space in infants exposed to second-hand smoke in pregnancy.

Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. In utero nicotine exposure has been shown to blunt the infant ventilatory response to hypercapnia, which could increase the risk of sudden infant death syndrome. The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. The aim of this study was to assess ventilatory response to added dead-space (inducing hypercapnia) in infants with second-hand smoke exposure during pregnancy, in infants whose mothers smoked and in controls (non-smoke exposed). Infants breathed through a face mask and specialised "tube-breathing" circuit, incorporating a dead space of 4.4 ml/kg body weight. The maximum minute ventilation (MMV) during added dead space breathing was determined and the time taken to achieve 63% of the MMV calculated (the time constant (TC) of the response). Infants were studied on the postnatal ward prior to discharge home. Thirty infants (ten in each group) were studied with a median gestational age of 39 [range 37-41] weeks, birthweight of 3.1 [2.2-4.0] kg, and postnatal age of 33 (21-62) h. The infants whose mothers had second-hand smoke exposure (median TC 42 s, p = 0.001), and the infants of cigarette smoking mothers (median TC 37 s, p = 0.002) had longer time constants than the controls (median TC 29 s). There was no significant difference between the TC of the infants whose mothers had second-hand smoke exposure and those whose mothers smoked (p = 0.112).    Conclusion: Second-hand smoke exposure during pregnancy was associated with a delayed newborn ventilatory response. What is Known: • Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. • The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. What is New: • We have assessed the ventilatory response to added dead-space (inducing hypercapnia) in newborns with second-hand smoke exposure during pregnancy, in infants whose mothers smoked, and in controls (non-smoke exposed). • Maternal second-hand smoke exposure, as well as maternal smoking, during pregnancy was associated with a delayed newborn ventilatory response.

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.

Early origins of respiratory disease.

Chronic respiratory morbidity is unfortunately common in childhood, particularly in those born very prematurely or with congenital anomalies affecting pulmonary development and those with sickle cell disease. Our research group, therefore, has focused on the early origins of chronic respiratory disease. This has included assessing antenatal diagnostic techniques and potentially therapeutic interventions in infants with congenital diaphragmatic hernia. Undertaking physiological studies, we have increased the understanding of the premature baby's response to resuscitation and evaluated interventions in the delivery suite. Mechanical ventilation modes have been optimised and randomised controlled trials (RCTs) with short- and long-term outcomes undertaken. Our studies highlighted respiratory syncytial virus lower respiratory tract infections (LRTIs) and other respiratory viral LRTIs had an adverse impact on respiratory outcomes of prematurely born infants, who we demonstrated have a functional and genetic predisposition to respiratory viral LRTIs. We have described the long-term respiratory outcomes for children with sickle cell disease and importantly identified influencing factors. In conclusion, it is essential to undertake long term follow up of infants at high risk of chronic respiratory morbidity if effective preventative strategies are to be developed.

The Role of Maternal Smoking in Sudden Fetal and Infant Death Pathogenesis.

Maternal smoking is a risk factor for both sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death syndrome (SIUDS). Both SIDS and SIUDS are more frequently observed in infants of smoking mothers. The global prevalence of smoking during pregnancy is 1.7% and up to 8.1% of women in Europe smoke during pregnancy and worldwide 250 million women smoke during pregnancy. Infants born to mothers who smoke have an abnormal response to hypoxia and hypercarbia and they also have reduced arousal responses. The harmful effects of tobacco smoke are mainly mediated by release of carbon monoxide and nicotine. Nicotine can enter the fetal circulation and affect multiple developing organs including the lungs, adrenal glands and the brain. Abnormalities in brainstem nuclei crucial to respiratory control, the cerebral cortex and the autonomic nervous system have been demonstrated. In addition, hypodevelopment of the intermediolateral nucleus in the spinal cord has been reported. It initiates episodic respiratory movements that facilitate lung development. Furthermore, abnormal maturation and transmitter levels in the carotid bodies have been described which would make infants more vulnerable to hypoxic challenges. Unfortunately, smoking cessation programs do not appear to have significantly reduced the number of pregnant women who smoke.

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.

Sustained inflations during delivery suite stabilisation in prematurely-born infants - A randomised trial.

BACKGROUND: Sustained inflations at initial stabilisation in the delivery suite may reduce the need for intubation and result in a shorter duration of initial ventilation, but have not been compared to routine UK practice. AIMS: To compare the early efficacy of sustained inflation during stabilisation after delivery to UK practice. STUDY DESIGN: A randomised trial was performed of a fifteen second sustained inflation compared to five inflations lasting 2 to 3 s, each intervention could be repeated once if no chest rise was apparent. Respiratory function monitoring was undertaken. SUBJECTS: Infants born prior to 34 weeks of gestation. OUTCOME MEASURES: The minute volume and maximum end-tidal carbon dioxide level in the first minute after the interventions, the time to the first spontaneous breath after the beginning of stabilisation and the duration of ventilation in the first 48 h. RESULTS: There were no significant differences in the minute volume or maximum end tidal carbon dioxide level between the groups. Infants in the sustained inflation group made a respiratory effort sooner (median 3.5 (range 0.2-59) versus median 12.8 (range 0.4-119) s, p = 0.001). The sustained inflation group were ventilated for a shorter duration in the first 48 h (median 17 (range 0-48) versus median 32.5 (range 0-48) h, p = 0.025). CONCLUSIONS: A sustained inflation of 15 s compared to five two to three second inflations during initial stabilisation was associated with a shorter duration of mechanical ventilation in the first 48 h after birth.

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.

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.

Sustained inflations versus UK standard inflations during initial resuscitation of prematurely born infants in the delivery room: a study protocol for a randomised controlled trial.

BACKGROUND: Many infants born at less than 34 weeks of gestational age will require resuscitation in the delivery suite. Yet, different resuscitation techniques are specified in different national guidelines, likely reflecting a limited evidence base. One difference is the length of mechanical inflation initially delivered to infants either via a facemask or endotracheal tube. Some guidelines specify short inflations delivered at rates of 40-60/min, others recommend initial inflations lasting 2-3 s or sustained inflations lasting for ≥ 5 s for initial resuscitation. Research has shown that tidal volumes > 2.2 mL/kg (the anatomical dead space) are seldom generated unless the infant's respiratory effort coincides with an inflation (active inflation). When inflations lasting 1-3 s were used, the time to the first active inflation was inversely proportional to the inflation time. This trial investigates whether a sustained inflation or repeated shorter inflations is more effective in stimulating the first active inflation. METHODS: This non-blinded, randomised controlled trial performed at a single tertiary neonatal unit is recruiting 40 infants born at < 34 weeks of gestational age. A 15-s sustained inflation is being compared to five repeated inflations of 2-3 s during the resuscitation at delivery. A respiratory function monitor is used to record airway pressure, flow, expiratory tidal volume and end tidal carbon dioxide (ETCO2) levels. The study is performed as emergency research without prior consent and was approved by the NHS London-Riverside Research Ethics Committee. The primary outcome is the minute volume in the first minute of resuscitation with secondary outcomes of the time to the first active inflation and ETCO2 level during the first minute of recorded resuscitation. DISCUSSION: This is the first study to compare a sustained inflation to the current UK practice of five initial inflations of 2-3 s. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02967562 . Registered on 15 November 2016.

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.

In vitro assessment of the effect of proportional assist ventilation on the work of breathing.

UNLABELLED: During proportional assist ventilation, elastic and resistive unloading can be delivered to reduce the work of breathing (WOB). Our aim was to determine the effects of different levels of elastic and resistive unloading on the WOB in lung models designed to mimic certain neonatal respiratory disorders. Two dynamic lung models were used, one with a compliance of 0.4 ml/cm H2O to mimic an infant with respiratory distress syndrome and one with a resistance of 300 cm H2O/l/s to mimic an infant with bronchopulmonary dypslasia. Pressure volume curves were constructed at each unloading level. Elastic unloading in the low compliance model was highly effective in reducing the WOB measured in the lung model; the effective compliance increased from 0.4 ml/cm H2O at baseline to 4.1 ml/cm H2O at maximum possible elastic unloading (2.0 cm H2O/ml). Maximum possible resistive unloading (200 cm H2O/l/s) in the high-resistance model only reduced the effective resistance from 300 to 204 cm H2O/l/s. At maximum resistive unloading, oscillations appeared in the airway pressure waveform. CONCLUSION: Our results suggest that elastic unloading will be helpful in respiratory conditions characterised by a low compliance, but resistive unloading as currently delivered is unlikely to be of major clinical benefit. WHAT IS KNOWN: • During PAV, the ventilator can provide elastic and resistive unloading. What is New: • Elastic unloading was highly effective in reducing the work of breathing. • Maximum resistive unloading only partially reduced the effective resistance.

Proportional assist versus assist control ventilation in premature infants.

During proportional assist ventilation (PAV), the applied pressure is servo-controlled based on continuous input from the infant's breathing. In addition, elastic and resistive unloading can be employed to compensate for the abnormalities in the infant's lung mechanics. The aim of this study was to test the hypothesis that in very prematurely born infants remaining ventilated beyond the first week, PAV compared to assist control ventilation (ACV) would be associated with superior oxygenation. A randomised crossover study was undertaken. Infants were studied for 4 hours each on PAV and ACV in random order; at the end of each 4-h period, the oxygenation index (OI) was calculated. Eight infants, median gestational age of 25 (range 24-33) weeks, were studied at a median of 19 (range 10-105) days. It had been intended to study 18 infants but as all the infants had superior oxygenation on PAV (p = 0.0039), the study was terminated after recruitment of eight infants. The median inspired oxygen concentration (p = 0.049), mean airway pressure (p = 0.012) and OI (p = 0.012) were all lower on PAV. CONCLUSION: These results suggest that PAV compared to ACV is advantageous in improving oxygenation for prematurely born infants with evolving or established BPD. WHAT IS KNOWN: During proportional assist ventilation (PAV), the applied pressure is servo controlled throughout each spontaneous breath. Elastic and resistive unloading can compensate for the infant's abnormalities in lung mechanics. WHAT IS NEW: In a randomised crossover study, infants with evolving/established BPD were studied on PAV and ACV each for 4 h. The oxygenation index was significantly lower on PAV in all infants studied.

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.

Crossover study of proportional assist versus assist control ventilation.

OBJECTIVE: To test the hypothesis that in very prematurely born infants remaining ventilated beyond the first week, proportional assist ventilation (PAV) compared with assist control ventilation (ACV) would be associated with reduced work of breathing, increased respiratory muscle strength and less ventilator-infant asynchrony which would be associated with improved oxygenation. DESIGN: Randomised crossover study. SETTING: Tertiary neonatal unit. PATIENTS: 12 infants with a median gestational age of 25 (range 24-26) weeks were studied at a median of 43 (range 8-86) days. INTERVENTIONS: Infants were studied for 1 h each on PAV and ACV in random order. MAIN OUTCOME MEASURES: At the end of each hour, the work of breathing (assessed by measuring the diaphragmatic pressure time product), thoracoabdominal asynchrony and respiratory muscle strength (maximal inspiratory pressure, maximal expiratory pressure (Pemax) and maximal transdiaphragmatic pressure (Pdimax)) were assessed. Blood gas analysis was performed and the oxygenation index (OI) calculated. RESULTS: After 1 h on PAV compared with 1 h on ACV, the median OI (5.55 (range 5-11) vs 10.10 (range 7-16), p=0.002) and PTP levels were lower (217 (range 59-556) cm H2O.s/min vs 309 (range 55-544) cm H2O.s/min, p=0.005), while Pdimax (44.26 (range 21-66) cm H2O vs 37.9 (range 19-45) cm H2O, p=0.002) and Pemax (25.6 (range 6.5-42) cm H2O vs 15.9 (range 3-35) cm H2O levels p=0.010) were higher. CONCLUSIONS: These results suggest that PAV compared with ACV may have physiological advantages for prematurely born infants who remain ventilated after the first week after birth.