An observational, prospective, multicenter study on rescue high-frequency oscillatory ventilation in neonates failing with conventional ventilation.

BACKGROUND: To achieve gas exchange goals and mitigate lung injury, infants who fail with conventional ventilation (CV) are generally switched to high-frequency oscillatory ventilation (HFOV). Although preferred in many neonatal intensive care units (NICUs), research on this type of rescue HFOV has not been reported recently. METHODS: An online registry database for a multicenter, prospective study was set to evaluate factors affecting the response of newborn infants to rescue HFOV treatment. The study population consisted of 372 infants with CV failure after at least 4 hours of treatment in 23 participating NICUs. Patients were grouped according to their final outcome as survived (Group S) or as died or received extracorporeal membrane oxygenation (ECMO) (Group D/E). Patients' demographic characteristics and underlying diseases in addition to their ventilator settings, arterial blood gas (ABG) analysis results at 0, 1, 4, and 24 hours, type of device, ventilation duration, and complications were compared between groups. RESULTS: HFOV as rescue treatment was successful in 58.1% of patients. Demographic and treatment parameters were not different between groups, except that infants in Group D/E had lower birthweight (BW) (1655 ± 1091 vs. 1858 ± 1027 g, p = 0.006), a higher initial FiO2 setting (83% vs. 72%, p < 0.001), and a higher rate of nitric oxide exposure (21.8% vs. 11.1%, p = 0.004) in comparison to infants who survived (Group S). The initial cut-offs for a successful response on ABG were defined as pH >7.065 (OR: 19.74, 95% CI 4.83-80.6, p < 0.001), HCO3 >16.35 mmol/L (OR: 1.06, 95% CI 1.01-1.1, p = 0.006), and lactate level <3.75 mmol/L (OR: 1.09%95 CI 1.01-1.16, p = 0.006). Rescue HFOV duration was associated with retinopathy of prematurity (p = 0.005) and moderate or severe chronic lung disease (p < 0.001), but not with patent ductus arteriosus or intraventricular hemorrhage, in survivors (p > 0.05). CONCLUSION: Rescue HFOV as defined for this population was successful in more than half of the patients with CV failure. Although the response was not associated with gestational age, underlying disease, device used, or initial MV settings, it seemed to be more effective in patients with higher BW and those not requiring nitric oxide. Initial pH, HCO3, and lactate levels on ABG may be used as predictors of a response to rescue HFOV.

Sustained inflations and avoiding mechanical ventilation to prevent death or bronchopulmonary dysplasia: a meta-analysis.

Sustained inflations and avoidance of endotracheal mechanical ventilation (eMV) are delivery room interventions aimed at preventing bronchopulmonary dysplasia (BPD). Their effectiveness is the subject of the present meta-analysis.The databases MEDLINE, EMBASE and CENTRAL were searched for randomised controlled trials (RCTs) of preterm infants that compared: 1) sustained inflations with intermittent positive-pressure ventilation; and 2) a non-intubated strategy of respiratory support with one that prescribed eMV at an earlier stage. Data extraction and analysis followed the standard methods of the Cochrane Collaboration. The primary outcome was death or BPD, defined as need for oxygen or positive pressure treatment at 36 weeks' postmenstrual age.Avoiding eMV (nine RCTs, 3486 infants) reduced the risk of death or BPD, with a risk ratio of 0.90 (95% CI 0.84-0.97) and a number needed to treat of 35. After sustained inflations (six RCTs, 854 infants), the risk ratio was 0.85 (95% CI 0.65-1.12). A current multicentre RCT of sustained inflations in very preterm infants was halted for increased early mortality in the sustained inflations arm.While strategies aimed at avoiding eMV had a small but significant impact on preventing BPD, sustained inflations had no effect and may even increase mortality in very preterm infants.

Volume-targeted versus pressure-limited ventilation in neonates.

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

Sustained Aeration of Infant Lungs (SAIL) trial: study protocol for a randomized controlled trial.

BACKGROUND: Extremely preterm infants require assistance recruiting the lung to establish a functional residual capacity after birth. Sustained inflation (SI) combined with positive end expiratory pressure (PEEP) may be a superior method of aerating the lung compared with intermittent positive pressure ventilation (IPPV) with PEEP in extremely preterm infants. The Sustained Aeration of Infant Lungs (SAIL) trial was designed to study this question. METHODS/DESIGN: This multisite prospective randomized controlled unblinded trial will recruit 600 infants of 23 to 26 weeks gestational age who require respiratory support at birth. Infants in both arms will be treated with PEEP 5 to 7 cm H2O throughout the resuscitation. The study intervention consists of performing an initial SI (20 cm H20 for 15 seconds) followed by a second SI (25 cm H2O for 15 seconds), and then PEEP with or without IPPV, as needed. The control group will be treated with initial IPPV with PEEP. The primary outcome is the combined endpoint of bronchopulmonary dysplasia or death at 36 weeks post-menstrual age. TRIAL REGISTRATION: www.clinicaltrials.gov , Trial identifier NCT02139800 , Registered 13 May 2014.

Volume-targeted versus pressure-limited ventilation in the neonate.

BACKGROUND: Damage caused by lung overdistension (volutrauma) has been implicated in the development bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation using a fixed inflation pressure. Volume targeting aims to produce a more stable tidal volume in order to reduce lung damage and stabilise pCO(2) OBJECTIVES: To determine whether volume-targeted ventilation (VTV) compared with pressure-limited ventilation (PLV) leads to reduced rates of death and BPD in newborn infants. Secondary objectives were to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment. SEARCH STRATEGY: The search strategy comprised searches of the Cochrane Central Register of Controlled Trials, MEDLINE PubMed 1966 to January 2010, and hand searches of reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised and quasi-randomised trials comparing the use of volume-targeted versus pressure-limited ventilation in infants of less than 28 days corrected age. DATA COLLECTION AND ANALYSIS: Two review authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR) and risk difference (RD) were calculated with 95% confidence intervals. Number needed to treat was calculated when RD was statistically significant. Continuous data were analysed using weighted mean difference. MAIN RESULTS: Twelve randomised trials met our inclusion criteria; nine parallel trials (629 infants) and three crossover trials (64 infants).The use of VTV modes resulted in a reduction in the combined outcome of death or bronchopulmonary dysplasia [typical RR 0.73 (95% CI 0.57 to 0.93), NNT8 (95% CI 5 to 33)]. VTV modes also resulted in reductions in pneumothorax [typical RR 0.46 (95% CI 0.25 to 0.84), NNT 17 (95% CI 10 to 100)], days of ventilation [MD -2.36 (95% CI -3.9 to -0.8)], hypocarbia [typical RR 0.56 (95%CI 0.33 to 0.96), NNT 4 (95% CI 2 to 25)] and the combined outcome of periventricular leukomalacia or grade 3-4 intraventricular haemorrhage [typical RR 0.48 (95% CI 0.28 to 0.84), NNT 11 (95% CI 7 to 50)]. AUTHORS' CONCLUSIONS: Infants ventilated using VTV modes had reduced death and chronic lung disease compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.

Volume-targeted versus pressure-limited ventilation in the neonate.

BACKGROUND: Inflammation caused by lung overdistension (volutrauma) is thought to be important in the pathogenesis of bronchopulmonary dysplasia (BPD). Preterm infants with variable lung compliance are particularly at risk. Volume-targeted neonatal ventilators have been developed as alternatives to traditional pressure-limited ventilators. They deliver consistent, appropriate tidal volumes with the aim of reducing lung damage. It is suggested that these would provide an effective, safer means of ventilating the newborn infant. OBJECTIVES: To determine whether volume-targeted ventilation compared with pressure-limited ventilation leads to reduced rates of death and BPD in newborn infants. Secondary objectives were to determine whether use of volume modes affected clinical outcomes such as incidence of airleak, growth, duration of ventilation or cranial ultrasound findings. SEARCH STRATEGY: The search strategy comprised searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), MEDLINE PubMed 1966 to November 2004, and hand searches of reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised and quasi-randomised trials comparing the use of volume-targeted versus pressure-limited ventilation in neonates in the first 28 days of life. DATA COLLECTION AND ANALYSIS: Two authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR) and risk difference (RD) were calculated with 95% confidence intervals. Number needed to treat was calculated when RD was statistically significant. Continuous data were analysed using weighted mean difference (WMD). MAIN RESULTS: Four randomised trials were identified that addressed the outcomes of this review, recruiting a total of 178 preterm infants. All were recruited during the first 72 hours of life. Caregivers and those evaluating the outcomes of trials were not masked. All trials report high rates of follow-up, although one trial with uneven patient distribution may have had some post-randomisation attrition. No significant difference was found for death by hospital discharge, and no trials reported the combined outcome of death or BPD. When secondary outcomes were examined, pooled analysis of the trials showed that volume-targeted ventilation resulted in significant reductions in duration of ventilation [WMD -2.93 days (-4.28, -1.57)] and rates of pneumothorax [typical RR 0.23 (0.07, 0.76), RD -0.11 (-0.20, -0.03), NNT 9]. There was also a significant difference in rates of severe (Grade 3 or 4) intraventricular haemorrhage favouring the volume-targeted group [typical RR 0.32 (0.11, 0.90), RD -0.16 (-0.29, -0.03), NNT 6]. There was a reduction in the incidence of BPD (supplemental oxygen at 36 weeks) amongst surviving infants, of borderline statistical significance [typical RR 0.34 (0.11, 1.05), RD -0.14 (-0.27, 0.00), NNT=7]. No significant differences were found for failure of mode of ventilation, use of neuromuscular paralysis, patent ductus arteriosus, airleak of any sort or pulmonary interstitial emphysema alone, cranial ultrasound abnormalities or periventricular leucomalacia. None of the trials addressed growth, death after discharge from hospital or neurodevelopmental outcome. AUTHORS' CONCLUSIONS: Although rates of death and BPD were not significantly different between the two ventilator strategies, statistically significant effects favouring volume targeting were shown for some clinically important outcomes. However, the numbers of trials and infants randomised are small and further studies are required to confirm the role of volume targeting in neonatal ventilation.

Three-year experience with neonatal ventilation from a tertiary care hospital in Delhi.

Ninety neonates were ventilated over a period of 33 months of whom 50 (55.5%) survived. Fifty seven babies received IPPV while 33 CPAP. IPPV mode was being used more frequently recently and survival rates have steadily improved over past 3 years. Survival was cent per cent in babies above 1.5 kg on CPAP mode while 16/26 (57.7%) survived on IPPV mode. Of 22 extremely VLBW (< 1 kg) babies, six survived. HMD was the commonest indication of ventilation (50%), of which 53% (24/45) survived. The other important indications of ventilation were apnea in 13 and transient tachypnea in 11 babies. All babies requiring ventilation for transient tachypnea survived. Nosocomial infections were common in association with ventilation 34/90 (37.7%), out of which in 14 was responsible for about a third of deaths. Pulmonary air leaks developed in 12 babies of which 6 died. Two babies developed BPD and one ROP. Neonatal ventilation should be ventured in centres where basic facilities for level II care already exist. It may not be cost effective to ventilate extremely low birth weight neonates.

PIP: During January 1989-September 1991, in India, neonatologists prescribed assisted ventilation (intermittent positive pressure ventilation [IPPV] and continuous positive airway pressure [CPAP]) for 90 neonates born and treated at a tertiary hospital in Delhi. All neonates requiring more than 168 hours of ventilation received IPPV. The smallest surviving neonate weighed 830 g at birth and was born at 26 weeks' gestation. This neonate received 510 hours of ventilation. One neonate received 48 days of ventilation (gestational age at birth, 28 weeks; birth weight, 800 g). This neonate eventually died due to necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and sepsis. This infant was the only infant to develop NEC. A total of two newborns developed BPD. One infant developed retinopathy of prematurity (ROP). Indications for ventilation were hyaline membrane disease (HMD) (45/90), apnea (13/90), and transient tachypnea of the newborn (TTNB) (11/90). Almost all HMD cases who weighed more than 1.5 kg at birth on CPAP survived. CPAP successfully treated all TTNB cases. Nine neonates developed pneumothorax. Three of them survived. 34 neonates developed sepsis, the most common complication. 20 sepsis cases also had underlying pneumonia. Sepsis was responsible for 35% of deaths (14/40). Five infants on IPPV developed persistent pulmonary hypertension (persistent fetal circulation). 35 infants developed infection during ventilation, 34 of whom had a nosocomial infection. The nosocomial infection rate was 37.7%. Nosocomial infection was responsible for 35% of deaths. 12 babies (13%) developed pulmonary air leaks, 50% of whom died. 25 of the 33 infants on CPAP survived. Few CPAP cases developed pulmonary air leak, BPD, and ROP. Six of 22 very low birth weight (VLBW) infants (1 kg) survived. These findings led the researchers to recommend that medical centers with basic facilities for level II care should provide neonatal ventilation. They proposed that ventilation may not be cost effective for VLBW newborns, however.

Outcome and costs of intensive care. A follow-up study on patients requiring prolonged mechanical ventilation.

This historically prospective study analysed hospital costs and long-term outcome in 249 consecutive patients who required intensive care including intermittent positive pressure ventilation (IPPV) for 48 h or more. The mean age of the patients was 46.7 years and the mean duration on IPPV was 9.1 days. Mortality in hospital was 43%, increasing to 54.6% five years after admission. The mean cost per patient treated was 22,823 US dollars (USD (1980 value]. The mean cost to yield one survivor was 40,035 USD. The mean cost per survivor was 26,056 USD, whereas that of a non-survivor was 18,500 USD. The cost-benefit ratio, i.e. calculated cost per year of extended life until the age of 75 years, averaged 1420 USD (range 360-7980 USD). With the exception of patients suffering from cancerous diseases, the cost-benefit ratio found in this study was favourable in comparison to other high-cost medical care. This is further emphasized by the fact that for the years saved, the quality of life was mostly good.