Prashanth Bhat

Conventional Mechanical Ventilation Versus High-frequency Oscillatory Ventilation for Congenital Diaphragmatic Hernia: A Randomized Clinical Trial (The VICI-trial).

Objectives:To determine the optimal initial ventilation mode in congenital diaphragmatic hernia. Background:Congenital diaphragmatic hernia is a life-threatening anomaly with significant mortality and morbidity. The maldeveloped lungs have a high susceptibility for oxygen and ventilation damage resulting in a high incidence of bronchopulmonary dysplasia (BPD) and chronic respiratory morbidity. Methods:An international, multicenter study (NTR 1310), the VICI-trial was performed in prenatally diagnosed congenital diaphragmatic hernia infants (n = 171) born between November 2008 and December 2013, who were randomized for initial ventilation strategy. Results:Ninety-one (53.2%) patients initially received conventional mechanical ventilation and 80 (46.8%) high-frequency oscillation. Forty-one patients (45.1%) randomized to conventional mechanical ventilation died/ had BPD compared with 43 patients (53.8%) in the high-frequency oscillation group. An odds ratio of 0.62 [95% confidence interval (95% CI) 0.25–1.55] (P = 0.31) for death/BPD for conventional mechanical ventilation vs high-frequency oscillation was demonstrated, after adjustment for center, head-lung ratio, side of the defect, and liver position. Patients initially ventilated by conventional mechanical ventilation were ventilated for fewer days (P = 0.03), less often needed extracorporeal membrane oxygenation support (P = 0.007), inhaled nitric oxide (P = 0.045), sildenafil (P = 0.004), had a shorter duration of vasoactive drugs (P = 0.02), and less often failed treatment (P = 0.01) as compared with infants initially ventilated by high-frequency oscillation. Conclusions:Our results show no statistically significant difference in the combined outcome of mortality or BPD between the 2 ventilation groups in prenatally diagnosed congenital diaphragmatic hernia infants. Other outcomes, including shorter ventilation time and lesser need of extracorporeal membrane oxygenation, favored conventional ventilation.

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.

Prediction of infant extubation outcomes using the tension-time index

Objective The tension-time index of the diaphragm (TTdi) is a composite assessment of the load on and the capacity of the diaphragm. TTmus is a non-invasive tension-time index of the respiratory muscles. Our aim was to determine whether TTdi or TTmus predicted extubation outcome and performed better than respiratory muscle strength (Pimax, Pdimax), respiratory drive (P0.1) and work of breathing (transdiaphragmatic pressure-time product (PTPdi)) or routinely available clinical data. Design Prospective study. Setting Tertiary neonatal intensive care unit. Patients Sixty infants, median gestation age 35 (range 23–42) weeks and postnatal age of 55 (range 1–115) days. Interventions Airway occlusions were performed to measure Pimax, Pdimax and P0.1. TTdi and PTPdi were derived from measurements of transdiaphragmatic pressure. TTmus was derived from airway pressure measurements. Measurements were made within 6 h of extubation. Main outcome measures Extubation failure defined as reintubation within 48 h of extubation. Results Twelve infants failed extubation. The infants who failed extubation were significantly more immature (medians 25 vs 37 weeks) and of greater postnatal age (23 vs 5 days) and had higher TTdi (0.15 vs 0.04) and TTmus (0.17 vs 0.08). TTdi and TTmus were only significantly better predictors than the peak inflation pressure immediately prior to extubation and did not perform significantly better than gestational age or birth weight. Conclusions Assessment of TTdi and TTmus cannot be recommended for use in 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 infants 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.

How to ventilate term babies

Infants born at term frequently require mechanical ventilation and suffer significant mortality and morbidity. Yet, there have been few randomised trials (RCTs) exclusively of term born infants and when term born infants have been included in studies, a sub-analysis of their results has rarely been undertaken. The limited evidence demonstrates in term born infants that there are no benefits in using rates >60bpm during conventional mechanical ventilation (CMV) or using synchronous intermittent mandatory ventilation. Pressure support ventilation may reduce their work of breathing (WOB). During volume targeted ventilation, a volume targeted (VT) level of 6mls/kg reduces the WOB compared to a lower level or no VT. High frequency oscillatory ventilation in infants born at or near term with severe respiratory failure does not reduce mortality, oxygen dependency at 28 days or intracranial haemorrhage. RCTs with long term outcome are required to determine the optimum ventilatory modes in term born infants.

G104 Inflation pressures and times during the resuscitation of prematurely born infants

Aim We have previously demonstrated that using the UK recommended inflation pressures (20/5 cmH2O) for the first five inflations, expiratory tidal volumes (TVe) rarely exceeded the anatomical dead space (1) and end tidal carbon dioxide (CO2) levels were low (2). The inflation times, however, were usually much shorter than recommended.1,2 Our aim was to assess the effects of higher inflation pressures and longer inflation times. Methods The responses to the first five inflations of infants of gestational age < 34 weeks resuscitated via a face mask were studied. Infants resuscitated using peak inflation pressures of 25 cmH2O and short (<1.5 seconds) or long (>1.5 seconds) inflation times were matched by gestational age to infants resuscitated with peak pressures of 20 cmH2O with short or long inflation times. A NM3 respiratory profile monitor was used to record the inflation pressures, flow, tidal volumes and end tidal CO2 levels. Active inflations were excluded from the analysis. Results There were 12 infants in each of the four groups; the median gestational age of the infants was 31 (range 24–34) weeks. Infants resuscitated with short inflation times had higher expiratory tidal volumes when resuscitated at 25/5 cmH2O compared to 20/5 cmH2O (0.12 (range 0.10–6.8) mls/kg versus 3.21 (range 0.16 –12.20) mls/kg respectively), p= <0.001 and higher ETCO levels (2.05 (range 0.2–35.6) mm Hg versus 8.30 (range 0.3 –61) mm Hg respectively), p = 0.030. Infants resuscitated with long inflation times had higher expiratory tidal volumes when resuscitated at 25/5 cmH2O compared to 20/5 cmH2O (2.06 (range 0.18–13.2) mls/kg versus 1.94 (range 0.01–8.4) mls/kg respectively), p = 0.011, but similar ETCO levels. Conclusion Increasing inflation pressures from 20/5 to 25/5 cmH2O improved tidal volumes regardless of the inflation time used. References Murthy V, Dattani N, Peacock JL, Fox GF, Campbell ME, Milner AD, Greenough A. The first five inflations during resuscitation of prematurely born infants. Arch Dis Child Fetal Neonatal Ed 2012 97: F249-F253 Murthy V, O’Rourke–Potocki A, Dattani N, Fox GF, Campbell ME, Milner AD, Greenough A. End tidal carbon dioxide levels during the resuscitation of prematurely born infants. Early Hum Dev 2012 Oct; 88(10):783-7.

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.

Inflation pressures and times during initial resuscitation in preterm infants

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.

G416(P) Response to resuscitation and outcome of infants with congenital diaphragmatic hernia

Aims Approximately 1 in 3000 live births have a congenital diaphragmatic hernia (CDH). Affected infants have a high mortality and morbidity. The aim of this study was to determine whether the response to resuscitation differed between CDH infants who did and did not survive. Methods Infants born at 34 weeks of gestation or greater and diagnosed antenatally with a CDH were eligible for entry into this study. All underwent our standard resuscitation protocol for CDH infants. None of the infants were subjected to face mask resuscitation. The infants were intubated as soon as possible after birth.. A neuromuscular blocking agent was given as soon as access was established and as soon as possible after intubation. The response to resuscitation was recorded using a respiratory function monitor which began as soon as the infants were intubated. Flow, airway pressure, tidal volume (VTe), compliance and end tidal carbon dioxide (ETCO2) were simultaneously recorded using the respiratory monitor. Oxygen saturation was also continuously recorded. Results Thirty seven CDH infants were included in the study. Eleven infants died, their median gestational age and birthweight did not significantly differ from those who survived. During the first minute of recorded resuscitation, the peak inflation pressure (PIP) did not differ significantly between non survivors and survivors, but the VTe (median 1.89 vs. 2.81 ml/kg) (p = 0.010), the ETCO2 (median 11.7 vs. 42.2 mm Hg) (p = 0.025) and the compliance (0.06 vs. 0.09 ml/cmH2O/kg) (p = 0.02) were significantly lower in the non survivors. In the last minute of resuscitation, the PIP was higher (32.5 vs. 30.3 cm H2O) (p = 0.03), the VTe (3.23 vs. 4.66 ml/kg) (p = 0.004) and the compliance (0.10 vs. 0.16 ml/cmH2O/kg) (p = 0.004) were lower in the non survivors. The maximum oxygen saturation (93 vs. 100%) achieved in the labour suite was lower in the non survivors (p = 0.044). Conclusion Infants with CDH who did not survive responded less well even to initial resuscitation, as indicated by lower tidal volumes and ETCO2 levels despite similar inflation pressures.

Orphan drugs in bronchopulmonary dysplasia

Introduction: Bronchopulmonary dysplasia (BPD) is a common adverse outcome of very premature birth. It has a multifactorial aetiology which includes oxygen toxicity. In this review the potential of antioxidants to reduce BPD is explored. Areas covered: The aim of the review is to determine the potential of agents which reduce oxygen toxicity to prevent BPD development. A literature review was undertaken using PubMed using the terms: BPD, prevention of BPD, antioxidants, superoxide dismutase (SOD), N-acetyl cysteine, allopurinol, melatonin, cimetidine, α-1-protease inhibitor, pentoxifylline and macrolides. Expert opinion: There are several therapies which reduce oxygen toxicity that have shown promising results with regard to improving the respiratory outcome of prematurely born infants. However, further work is necessary to identify the optimum antioxidant which reduces BPD and improves long-term respiratory outcome.