Data from clinical trials support the use of continuous positive airway pressure (CPAP) for initial respiratory management in preterm infants, but there is concern regarding the potential failure of ...CPAP support. We aimed to examine the incidence and explore the outcomes of CPAP failure in Australian and New Zealand Neonatal Network data from 2007 to 2013.
Data from inborn preterm infants managed on CPAP from the outset were analyzed in 2 gestational age ranges (25-28 and 29-32 completed weeks). Outcomes after CPAP failure (need for intubation <72 hours) were compared with those succeeding on CPAP using adjusted odds ratios (AORs).
Within the cohort of 19 103 infants, 11 684 were initially managed on CPAP. Failure of CPAP occurred in 863 (43%) of 1989 infants commencing on CPAP at 25-28 weeks' gestation and 2061 (21%) of 9695 at 29-32 weeks. CPAP failure was associated with a substantially higher rate of pneumothorax, and a heightened risk of death, bronchopulmonary dysplasia (BPD) and other morbidities compared with those managed successfully on CPAP. The incidence of death or BPD was also increased: (25-28 weeks: 39% vs 20%, AOR 2.30, 99% confidence interval 1.71-3.10; 29-32 weeks: 12% vs 3.1%, AOR 3.62 2.76-4.74). The CPAP failure group had longer durations of respiratory support and hospitalization.
CPAP failure in preterm infants is associated with increased risk of mortality and major morbidities, including BPD. Strategies to promote successful CPAP application should be pursued vigorously.
Background
High flow nasal cannulae (HFNC) are small, thin, tapered binasal tubes that deliver oxygen or blended oxygen/air at gas flows of more than 1 L/min. HFNC are increasingly being used as a ...form of non‐invasive respiratory support for preterm infants.
Objectives
To compare the safety and efficacy of HFNC with other forms of non‐invasive respiratory support in preterm infants.
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 1), MEDLINE via PubMed (1966 to 1 January 2016), EMBASE (1980 to 1 January 2016), and CINAHL (1982 to 1 January 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 trials comparing HFNC with other non‐invasive forms of respiratory support in preterm infants immediately after birth or following extubation.
Data collection and analysis
The authors extracted and analysed data, and calculated risk ratio, risk difference and number needed to treat for an additional beneficial outcome.
Main results
We identified 15 studies for inclusion in the review. The studies differed in the interventions compared (nasal continuous positive airway pressure (CPAP), nasal intermittent positive pressure ventilation (NIPPV), non‐humidified HFNC, models for delivering HFNC), the gas flows used and the indications for respiratory support (primary support from soon after birth, post‐extubation support, weaning from CPAP support). When used as primary respiratory support after birth compared to CPAP (4 studies, 439 infants), there were no differences in the primary outcomes of death (typical risk ratio (RR) 0.36, 95% CI 0.01 to 8.73; 4 studies, 439 infants) or chronic lung disease (CLD) (typical RR 2.07, 95% CI 0.64 to 6.64; 4 studies, 439 infants). HFNC use resulted in longer duration of respiratory support, but there were no differences in other secondary outcomes. One study (75 infants) showed no differences between HFNC and NIPPV as primary support. Following extubation (total 6 studies, 934 infants), there were no differences between HFNC and CPAP in the primary outcomes of death (typical RR 0.77, 95% CI 0.43 to 1.36; 5 studies, 896 infants) or CLD (typical RR 0.96, 95% CI 0.78 to 1.18; 5 studies, 893 infants). There was no difference in the rate of treatment failure (typical RR 1.21, 95% CI 0.95 to 1.55; 5 studies, 786 infants) or reintubation (typical RR 0.91, 95% CI 0.68 to 1.20; 6 studies, 934 infants). Infants randomised to HFNC had reduced nasal trauma (typical RR 0.64, 95% CI 0.51 to 0.79; typical risk difference (RD) −0.14, 95% CI −0.20 to −0.08; 4 studies, 645 infants). There was a small reduction in the rate of pneumothorax (typical RR 0.35, 95% CI 0.11 to 1.06; typical RD −0.02, 95% CI −0.03 to −0.00; 5 studies 896 infants) in infants treated with HFNC. Subgroup analysis found no difference in the rate of the primary outcomes between HFNC and CPAP in preterm infants in different gestational age subgroups, though there were only small numbers of extremely preterm and late preterm infants. One trial (28 infants) found similar rates of reintubation for humidified and non‐humidified HFNC, and two other trials (100 infants) found no difference between different models of equipment used to deliver humidified HFNC. For infants weaning from non‐invasive respiratory support (CPAP), two studies (149 infants) found that preterm infants randomised to HFNC had a reduced duration of hospitalisation compared with infants who remained on CPAP.
Authors' conclusions
HFNC has similar rates of efficacy to other forms of non‐invasive respiratory support in preterm infants for preventing treatment failure, death and CLD. Most evidence is available for the use of HFNC as post‐extubation support. Following extubation, HFNC is associated with less nasal trauma, and may be associated with reduced pneumothorax compared with nasal CPAP. Further adequately powered randomised controlled trials should be undertaken in preterm infants comparing HFNC with other forms of primary non‐invasive support after birth and for weaning from non‐invasive support. Further evidence is also required for evaluating the safety and efficacy of HFNC in extremely preterm and mildly preterm subgroups, and for comparing different HFNC devices.
Background
Non‐invasive respiratory support is increasingly used for the management of respiratory dysfunction in preterm infants. This approach runs the risk of under‐treating those with respiratory ...distress syndrome (RDS), for whom surfactant administration is of paramount importance. Several techniques of minimally invasive surfactant therapy have been described. This review focuses on surfactant administration to spontaneously breathing infants via a thin catheter briefly inserted into the trachea.
Objectives
Primary objectives
In non‐intubated preterm infants with established RDS or at risk of developing RDS to compare surfactant administration via thin catheter with:
1. intubation and surfactant administration through an endotracheal tube (ETT); or
2. continuation of non‐invasive respiratory support without surfactant administration or intubation.
Secondary objective
1. To compare different methods of surfactant administration via thin catheter
Planned subgroup analyses included gestational age, timing of intervention, and use of sedating pre‐medication during the intervention.
Search methods
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 30 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi‐randomised trials.
Selection criteria
We included randomised trials comparing surfactant administration via thin catheter (S‐TC) with (1) surfactant administration through an ETT (S‐ETT), or (2) continuation of non‐invasive respiratory support without surfactant administration or intubation. We also included trials comparing different methods/strategies of surfactant administration via thin catheter. We included preterm infants (at < 37 weeks' gestation) with or at risk of RDS.
Data collection and analysis
Review authors independently assessed study quality and risk of bias and extracted data. Authors of all studies were contacted regarding study design and/or missing or unpublished data. We used the GRADE approach to assess the certainty of evidence.
Main results
We included 16 studies (18 publications; 2164 neonates) in this review. These studies compared surfactant administration via thin catheter with surfactant administration through an ETT with early extubation (Intubate, Surfactant, Extubate technique ‐ InSurE) (12 studies) or with delayed extubation (2 studies), or with continuation of continuous positive airway pressure (CPAP) and rescue surfactant administration at pre‐specified criteria (1 study), or compared different strategies of surfactant administration via thin catheter (1 study). Two trials reported neurosensory outcomes of of surviving participants at two years of age. Eight studies were of moderate certainty with low risk of bias, and eight studies were of lower certainty with unclear risk of bias.
S‐TC versus S‐ETT in preterm infants with or at risk of RDS
Meta‐analyses of 14 studies in which S‐TC was compared with S‐ETT as a control demonstrated a significant decrease in risk of the composite outcome of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.48 to 0.73; risk difference (RD) ‐0.11, 95% CI ‐0.15 to ‐0.07; number needed to treat for an additional beneficial outcome (NNTB) 9, 95% CI 7 to 16; 10 studies; 1324 infants; moderate‐certainty evidence); the need for intubation within 72 hours (RR 0.63, 95% CI 0.54 to 0.74; RD ‐0.14, 95% CI ‐0.18 to ‐0.09; NNTB 8, 95% CI; 6 to 12; 12 studies, 1422 infants; moderate‐certainty evidence); severe intraventricular haemorrhage (RR 0.63, 95% CI 0.42 to 0.96; RD ‐0.04, 95% CI ‐0.08 to ‐0.00; NNTB 22, 95% CI 12 to 193; 5 studies, 857 infants; low‐certainty evidence); death during first hospitalisation (RR 0.63, 95% CI 0.47 to 0.84; RD ‐0.02, 95% CI ‐0.10 to 0.06; NNTB 20, 95% CI 12 to 58; 11 studies, 1424 infants; low‐certainty evidence); and BPD among survivors (RR 0.57, 95% CI 0.45 to 0.74; RD ‐0.08, 95% CI ‐0.11 to ‐0.04; NNTB 13, 95% CI 9 to 24; 11 studies, 1567 infants; moderate‐certainty evidence). There was no significant difference in risk of air leak requiring drainage (RR 0.58, 95% CI 0.33 to 1.02; RD ‐0.03, 95% CI ‐0.05 to 0.00; 6 studies, 1036 infants; low‐certainty evidence). None of the studies reported on the outcome of death or survival with neurosensory disability.
Only one trial compared surfactant delivery via thin catheter with continuation of CPAP, and one trial compared different strategies of surfactant delivery via thin catheter, precluding meta‐analysis.
Authors' conclusions
Administration of surfactant via thin catheter compared with administration via an ETT is associated with reduced risk of death or BPD, less intubation in the first 72 hours, and reduced incidence of major complications and in‐hospital mortality. This procedure had a similar rate of adverse effects as surfactant administration through an ETT. Data suggest that treatment with surfactant via thin catheter may be preferable to surfactant therapy by ETT. Further well‐designed studies of adequate size and power, as well as ongoing studies, will help confirm and refine these findings, clarify whether surfactant therapy via thin tracheal catheter provides benefits over continuation of non‐invasive respiratory support without surfactant, address uncertainties within important subgroups, and clarify the role of sedation.
Background
Nasal continuous positive airway pressure (NCPAP) is used to support preterm infants recently extubated, those experiencing significant apnoea of prematurity and those with respiratory ...distress soon after birth as an alternative to intubation and ventilation. This review focuses exclusively on identifying the most effective pressure source and interface for NCPAP delivery in preterm infants.
Objectives
To determine which technique of pressure generation and which type of nasal interface for NCPAP delivery most effectively reduces the need for additional respiratory support in preterm infants extubated to NCPAP following intermittent positive pressure ventilation (IPPV) for respiratory distress syndrome (RDS) or in those treated with NCPAP soon after birth.
Search methods
The strategy included searches of MEDLINE (1966 ‐ 2006), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006) CINAHL, s from conference proceedings, cross‐referencing of previous reviews and the use of expert informants.
Selection criteria
Randomised or quasi‐randomised trials comparing different techniques of NCPAP pressure generation and/or nasal interfaces in preterm infants extubated to NCPAP following IPPV for RDS or treated with NCPAP soon after birth.
Data collection and analysis
Data was extracted and analysed by the first three authors. Dichotomous results were analysed using the relative risk (RR), risk difference (RD) and number needed to treat (NNT).
Main results
1. Preterm infants being extubated to NCPAP following a period of IPPV for RDS:
Meta‐analysis of the results from Davis 2001 and Roukema 1999a demonstrated that short binasal prongs are more effective at preventing re‐intubation than single nasal or nasopharyngeal prongs typical RR 0.59 (CI: 0.41, 0.85), typical RD ‐0.21 (CI: ‐0.35, ‐0.07), NNT 5 (CI: 3, 14). In one study comparing short binasal prong devices (Sun 1999), the re‐intubation rate was significantly lower with the Infant Flow Driver than with the Medicorp prong RR 0.33 (CI: 0.17, 0.67), RD ‐0.32 (CI: ‐0.49, ‐0.15), NNT 3 (CI: 2, 7). The other study comparing short binasal prong devices (Infant Flow Driver versus INCA prongs, Stefanescu 2003) demonstrated no significant difference in the re‐intubation rate but did show a significant reduction in the total days in hospital in the Infant Flow Driver group MD ‐12.60 (95% CI: ‐22.81, ‐2.39) days. 2. Preterm infants primarily treated with NCPAP soon after birth:
In the one trial identified, Mazzella 2001 found a significantly lower oxygen requirement and respiratory rate in those randomised to short binasal prongs when compared with CPAP delivered via nasopharyngeal prong. The requirement for intubation beyond 48 hours from randomisation was not assessed.
3. Studies randomising preterm infants to different NCPAP systems using broad inclusion criteria
The studies of Rego 2002 and Buettiker 2004 did not examine the primary outcomes of this review. Of the secondary outcomes, Rego 2002 demonstrated a significantly higher incidence of nasal hyperaemia with the use of the Argyle prong compared with Hudson prongs RR 2.39 (95% CI: 1.27, 4.50), RD 0.28 (95% CI: 0.10, 0.46).
One study comparing different techniques of pressure generation is awaiting further assessment as it is currently available in form only.
Authors' conclusions
Short binasal prong devices are more effective than single prongs in reducing the rate of re‐intubation. Although the Infant Flow Driver appears more effective than Medicorp prongs the most effective short binasal prong device remains to be determined. The improvement in respiratory parameters with short binasal prongs suggests they are more effective than nasopharyngeal CPAP in the treatment of early RDS. Further studies incorporating longer‐term outcomes are required. Studies are also needed to determine the optimal pressure source for the delivery of NCPAP.
Background
Nasal continuous positive airway pressure (NCPAP) is a useful method for providing respiratory support after extubation. Nasal intermittent positive pressure ventilation (NIPPV) can ...augment NCPAP by delivering ventilator breaths via nasal prongs.
Objectives
Primary objective
To determine the effects of management with NIPPV versus NCPAP on the need for additional ventilatory support in preterm infants whose endotracheal tube was removed after a period of intermittent positive pressure ventilation.
Secondary objectives
To compare rates of abdominal distension, gastrointestinal perforation, necrotising enterocolitis, chronic lung disease, pulmonary air leak, mortality, duration of hospitalisation, rates of apnoea and neurodevelopmental status at 18 to 24 months for NIPPV and NCPAP.
To compare the effect of NIPPV versus NCPAP delivered via ventilators versus bilevel devices, and assess the effects of the synchronisation of ventilation, and the strength of interventions in different economic settings.
Search methods
We used standard, extensive Cochrane search methods. The latest search date was January 2023.
Selection criteria
We included randomised and quasi‐randomised trials of ventilated preterm infants (less than 37 weeks' gestational age (GA)) ready for extubation to non‐invasive respiratory support. Interventions were NIPPV and NCPAP.
Data collection and analysis
We used standard Cochrane methods. Our primary outcome was 1. respiratory failure. Our secondary outcomes were 2. endotracheal reintubation, 3. abdominal distension, 4. gastrointestinal perforation, 5. necrotising enterocolitis (NEC), 6. chronic lung disease, 7. pulmonary air leak, 8. mortality, 9. hospitalisation, 10. apnoea and bradycardia, and 11. neurodevelopmental status.
We used GRADE to assess the certainty of evidence.
Main results
We included 19 trials (2738 infants). Compared to NCPAP, NIPPV likely reduces the risk of respiratory failure postextubation (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.67 to 0.84; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 8 to 17; 19 trials, 2738 infants; moderate‐certainty evidence) and endotracheal reintubation (RR 0.78, 95% CI 0.70 to 0.87; NNTB 12, 95% CI 9 to 25; 17 trials, 2608 infants, moderate‐certainty evidence), and may reduce pulmonary air leaks (RR 0.57, 95% CI 0.37 to 0.87; NNTB 50, 95% CI 33 to infinite; 13 trials, 2404 infants; low‐certainty evidence). NIPPV likely results in little to no difference in gastrointestinal perforation (RR 0.89, 95% CI 0.58 to 1.38; 8 trials, 1478 infants, low‐certainty evidence), NEC (RR 0.86, 95% CI 0.65 to 1.15; 10 trials, 2069 infants; moderate‐certainty evidence), chronic lung disease defined as oxygen requirement at 36 weeks (RR 0.93, 95% CI 0.84 to 1.05; 9 trials, 2001 infants; moderate‐certainty evidence) and mortality prior to discharge (RR 0.81, 95% CI 0.61 to 1.07; 11 trials, 2258 infants; low‐certainty evidence).
When considering subgroup analysis, ventilator‐generated NIPPV likely reduces respiratory failure postextubation (RR 0.49, 95% CI 0.40 to 0.62; 1057 infants; I2 = 47%; moderate‐certainty evidence), while bilevel devices (RR 0.95, 95% CI 0.77 to 1.17; 716 infants) or a mix of both ventilator‐generated and bilevel devices likely results in little to no difference (RR 0.87, 95% CI 0.73 to 1.02; 965 infants).
Authors' conclusions
NIPPV likely reduces the incidence of extubation failure and the need for reintubation within 48 hours to one‐week postextubation more effectively than NCPAP in very preterm infants (GA 28 weeks and above). There is a paucity of data for infants less than 28 weeks' gestation. Pulmonary air leaks were also potentially reduced in the NIPPV group. However, it has no effect on other clinically relevant outcomes such as gastrointestinal perforation, NEC, chronic lung disease or mortality. Ventilator‐generated NIPPV appears superior to bilevel devices in reducing the incidence of respiratory failure postextubation failure and need for reintubation. Synchronisation used to deliver NIPPV may be important; however, data are insufficient to support strong conclusions.
Future trials should enrol a sufficient number of infants, particularly those less than 28 weeks' GA, to detect differences in death or chronic lung disease and should compare different categories of devices, establish the impact of synchronisation of NIPPV on safety and efficacy of the technique as well as the best combination of settings for NIPPV (rate, peak pressure and positive end‐expiratory). Trials should strive to match the mean airway pressure between the intervention groups to allow a better comparison. Neurally adjusted ventilatory assist needs further assessment with properly powered randomised trials.
Background
Several types of pressure sources, including underwater bubble devices, mechanical ventilators, and the Infant Flow Driver, are used for providing continuous positive airway pressure ...(CPAP) to preterm infants with respiratory distress. It is unclear whether the use of bubble CPAP versus other pressure sources is associated with lower rates of CPAP treatment failure, or mortality and other morbidity.
Objectives
To assess the benefits and harms of bubble CPAP versus other pressure sources (mechanical ventilators or Infant Flow Driver) for reducing treatment failure and associated morbidity and mortality in newborn preterm infants with or at risk of respiratory distress.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2023, Issue 1); MEDLINE (1946 to 6 January 2023), Embase (1974 to 6 January 2023), Maternity & Infant Care Database (1971 to 6 January 2023), and the Cumulative Index to Nursing and Allied Health Literature (1982 to 6 January 2023). We searched clinical trials databases and the reference lists of retrieved articles.
Selection criteria
We included randomised controlled trials comparing bubble CPAP with other pressure sources (mechanical ventilators or Infant Flow Driver) for the delivery of nasal CPAP to preterm infants.
Data collection and analysis
We used standard Cochrane methods. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of the evidence for effects on treatment failure, all‐cause mortality, neurodevelopmental impairment, pneumothorax, moderate‐severe nasal trauma, and bronchopulmonary dysplasia.
Main results
We included 15 trials involving a total of 1437 infants. All trials were small (median number of participants 88). The methods used to generate the randomisation sequence and ensure allocation concealment were unclear in about half of the trial reports. Lack of measures to blind caregivers or investigators was a potential source of bias in all of the included trials. The trials took place during the past 25 years in care facilities internationally, predominantly in India (five trials) and Iran (four trials). The studied pressure sources were commercially available bubble CPAP devices versus a variety of mechanical ventilator (11 trials) or Infant Flow Driver (4 trials) devices.
Meta‐analyses suggest that the use of bubble CPAP compared with mechanical ventilator or Infant Flow Driver CPAP may reduce the rate of treatment failure (RR 0.76, 95% confidence interval (CI) 0.60 to 0.95; (I² = 31%); RD −0.05, 95% CI −0.10 to −0.01; number needed to treat for an additional beneficial outcome 20, 95% CI 10 to 100; 13 trials, 1230 infants; low certainty evidence). The type of pressure source may not affect mortality prior to hospital discharge (RR 0.93, 95% CI 0.64 to 1.36 (I² = 0%); RD −0.01, 95% CI −0.04 to 0.02; 10 trials, 1189 infants; low certainty evidence). No data were available on neurodevelopmental impairment. Meta‐analysis suggests that the pressure source may not affect the risk of pneumothorax (RR 0.73, 95% CI 0.40 to 1.34 (I² = 0%); RD −0.01, 95% CI −0.03 to 0.01; 14 trials, 1340 infants; low certainty evidence). Bubble CPAP likely increases the risk of moderate‐severe nasal injury (RR 2.29, 95% CI 1.37 to 3.82 (I² = 17%); RD 0.07, 95% CI 0.03 to 0.11; number needed to treat for an additional harmful outcome 14, 95% CI 9 to 33; 8 trials, 753 infants; moderate certainty evidence). The pressure source may not affect the risk of bronchopulmonary dysplasia (RR 0.76, 95% CI 0.53 to 1.10 (I² = 0%); RD −0.04, 95% CI −0.09 to 0.01; 7 trials, 603 infants; low certainty evidence).
Authors' conclusions
Given the low level of certainty about the effects of bubble CPAP versus other pressure sources on the risk of treatment failure and most associated morbidity and mortality for preterm infants, further large, high‐quality trials are needed to provide evidence of sufficient validity and applicability to inform context‐ and setting‐relevant policy and practice.
Background
Nasal high flow (nHF) therapy provides heated, humidified air and oxygen via two small nasal prongs, at gas flows of more than 1 litre/minute (L/min), typically 2 L/min to 8 L/min. nHF is ...commonly used for non‐invasive respiratory support in preterm neonates. It may be used in this population for primary respiratory support (avoiding, or prior to the use of mechanical ventilation via an endotracheal tube) for prophylaxis or treatment of respiratory distress syndrome (RDS). This is an update of a review first published in 2011 and updated in 2016.
Objectives
To evaluate the benefits and harms of nHF for primary respiratory support in preterm infants compared to other forms of non‐invasive respiratory support.
Search methods
We used standard, extensive Cochrane search methods. The latest search date March 2022.
Selection criteria
We included randomised or quasi‐randomised trials comparing nHF with other forms of non‐invasive respiratory support for preterm infants born less than 37 weeks' gestation with respiratory distress soon after birth.
Data collection and analysis
We used standard Cochrane Neonatal methods. Our primary outcomes were 1. death (before hospital discharge) or bronchopulmonary dysplasia (BPD), 2. death (before hospital discharge), 3. BPD, 4. treatment failure within 72 hours of trial entry and 5. mechanical ventilation via an endotracheal tube within 72 hours of trial entry. Our secondary outcomes were 6. respiratory support, 7. complications and 8. neurosensory outcomes. We used GRADE to assess the certainty of evidence.
Main results
We included 13 studies (2540 infants) in this updated review. There are nine studies awaiting classification and 13 ongoing studies. The included studies differed in the comparator treatment (continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NIPPV)), the devices for delivering nHF and the gas flows used. Some studies allowed the use of 'rescue' CPAP in the event of nHF treatment failure, prior to any mechanical ventilation, and some allowed surfactant administration via the INSURE (INtubation, SURfactant, Extubation) technique without this being deemed treatment failure. The studies included very few extremely preterm infants less than 28 weeks' gestation. Several studies had unclear or high risk of bias in one or more domains.
Nasal high flow compared with continuous positive airway pressure for primary respiratory support in preterm infants
Eleven studies compared nHF with CPAP for primary respiratory support in preterm infants. When compared with CPAP, nHF may result in little to no difference in the combined outcome of death or BPD (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.74 to 1.60; risk difference (RD) 0, 95% CI −0.02 to 0.02; 7 studies, 1830 infants; low‐certainty evidence). Compared with CPAP, nHF may result in little to no difference in the risk of death (RR 0.78, 95% CI 0.44 to 1.39; 9 studies, 2009 infants; low‐certainty evidence), or BPD (RR 1.14, 95% CI 0.74 to 1.76; 8 studies, 1917 infants; low‐certainty evidence). nHF likely results in an increase in treatment failure within 72 hours of trial entry (RR 1.70, 95% CI 1.41 to 2.06; RD 0.09, 95% CI 0.06 to 0.12; number needed to treat for an additional harmful outcome (NNTH) 11, 95% CI 8 to 17; 9 studies, 2042 infants; moderate‐certainty evidence). However, nHF likely does not increase the rate of mechanical ventilation (RR 1.04, 95% CI 0.82 to 1.31; 9 studies, 2042 infants; moderate‐certainty evidence). nHF likely results in a reduction in pneumothorax (RR 0.66, 95% CI 0.40 to 1.08; 10 studies, 2094 infants; moderate‐certainty evidence) and nasal trauma (RR 0.49, 95% CI 0.36 to 0.68; RD −0.06, 95% CI −0.09 to −0.04; 7 studies, 1595 infants; moderate‐certainty evidence).
Nasal high flow compared with nasal intermittent positive pressure ventilation for primary respiratory support in preterm infants
Four studies compared nHF with NIPPV for primary respiratory support in preterm infants. When compared with NIPPV, nHF may result in little to no difference in the combined outcome of death or BPD, but the evidence is very uncertain (RR 0.64, 95% CI 0.30 to 1.37; RD −0.05, 95% CI −0.14 to 0.04; 2 studies, 182 infants; very low‐certainty evidence). nHF may result in little to no difference in the risk of death (RR 0.78, 95% CI 0.36 to 1.69; RD −0.02, 95% CI −0.10 to 0.05; 3 studies, 254 infants; low‐certainty evidence). nHF likely results in little to no difference in the incidence of treatment failure within 72 hours of trial entry compared with NIPPV (RR 1.27, 95% CI 0.90 to 1.79; 4 studies, 343 infants; moderate‐certainty evidence), or mechanical ventilation within 72 hours of trial entry (RR 0.91, 95% CI 0.62 to 1.33; 4 studies, 343 infants; moderate‐certainty evidence). nHF likely results in a reduction in nasal trauma, compared with NIPPV (RR 0.21, 95% CI 0.09 to 0.47; RD −0.17, 95% CI −0.24 to −0.10; 3 studies, 272 infants; moderate‐certainty evidence). nHF likely results in little to no difference in the rate of pneumothorax (RR 0.78, 95% CI 0.40 to 1.53; 4 studies, 344 infants; moderate‐certainty evidence).
Nasal high flow compared with ambient oxygen
We found no studies examining this comparison.
Nasal high flow compared with low flow nasal cannulae
We found no studies examining this comparison.
Authors' conclusions
The use of nHF for primary respiratory support in preterm infants of 28 weeks' gestation or greater may result in little to no difference in death or BPD, compared with CPAP or NIPPV. nHF likely results in an increase in treatment failure within 72 hours of trial entry compared with CPAP; however, it likely does not increase the rate of mechanical ventilation. Compared with CPAP, nHF use likely results in less nasal trauma and likely a reduction in pneumothorax. As few extremely preterm infants less than 28 weeks' gestation were enrolled in the included trials, evidence is lacking for the use of nHF for primary respiratory support in this population.
Background
Nasal masks and nasal prongs are used as interfaces for providing continuous positive airway pressure (CPAP) for preterm infants with or at risk of respiratory distress, either as primary ...support after birth or as ongoing support after endotracheal extubation from mechanical ventilation. It is unclear which type of interface is associated with lower rates of CPAP treatment failure, nasal trauma, or mortality and other morbidity.
Objectives
To assess the benefits and harms of nasal masks versus nasal prongs for reducing CPAP treatment failure, nasal trauma, or mortality and other morbidity in newborn preterm infants with or at risk of respiratory distress.
Search methods
We used standard, extensive Cochrane search methods. The latest search date was October 2021.
Selection criteria
We included randomised controlled trials comparing masks versus prongs as interfaces for delivery of nasal CPAP in newborn preterm infants (less than 37 weeks' gestation) with or at risk of respiratory distress.
Data collection and analysis
We used standard Cochrane methods. Our primary outcomes were 1. treatment failure, 2. all‐cause mortality, and 3. neurodevelopmental impairment. Our secondary outcomes were 4. pneumothorax, 5. moderate–severe nasal trauma, 6. bronchopulmonary dysplasia, 7. duration of CPAP use, 8. duration of oxygen supplementation, 9. duration of hospitalisation, 10. patent ductus arteriosus receiving medical or surgical treatment, 11. necrotising enterocolitis, 12. severe intraventricular haemorrhage, and 13. severe retinopathy of prematurity. We used the GRADE approach to assess the certainty of the evidence.
Main results
We included 12 trials with 1604 infants. All trials were small (median number of participants 118). The trials occurred after 2001 in care facilities internationally, predominantly in India (eight trials). Most participants were preterm infants of 26 to 34 weeks' gestation who received nasal CPAP as the primary form of respiratory support after birth. The studied interfaces included commonly used commercially available masks and prongs. Lack of measures to blind caregivers or investigators was a potential source of performance and detection bias in all the trials.
Meta‐analyses suggested that use of masks compared with prongs may reduce CPAP treatment failure (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 8 trials, 919 infants; low certainty). The type of interface may not affect mortality prior to hospital discharge (RR 0.83, 95% CI 0.56 to 1.22; 7 trials, 814 infants; low certainty). There are no data on neurodevelopmental impairment. Meta‐analyses suggest that the choice of interface may result in little or no difference in the risk of pneumothorax (RR 0.93, 95% CI 0.45 to 1.93; 5 trials, 625 infants; low certainty). Use of masks rather than prongs may reduce the risk of moderate–severe nasal injury (RR 0.55, 95% CI 0.44 to 0.71; 10 trials, 1058 infants; low certainty). The evidence is very uncertain about the effect on bronchopulmonary dysplasia (RR 0.69, 95% CI 0.46 to 1.03; 7 trials, 843 infants; very low certainty).
Authors' conclusions
The available trial data provide low‐certainty evidence that use of masks compared with prongs as the nasal CPAP interface may reduce treatment failure and nasal injury, and may have little or no effect on mortality or the risk of pneumothorax in newborn preterm infants with or at risk of respiratory distress. The effect on bronchopulmonary dysplasia is very uncertain. Large, high‐quality trials would be needed to provide evidence of sufficient validity and applicability to inform policy and practice.
To investigate a method of minimally invasive surfactant therapy (MIST) to be used in spontaneously breathing preterm infants on continuous positive airway pressure (CPAP), evaluating the feasibility ...of the technique and the therapeutic benefit after MIST.
Non-randomised feasibility study.
Tertiary neonatal intensive care unit.
Study subjects were preterm infants with respiratory distress supported with CPAP, with early enrolment of 25-28-week infants (n=11) at any CPAP pressure and fractional inspired O(2) concentration (FiO(2)), and enrolment of 29-34-week infants (n=14) at CPAP pressure ≥7 cm H(2)O and FiO(2) ≥0.35. Without premedication, a 16 gauge vascular catheter was inserted through the vocal cords under direct vision. Porcine surfactant (~100 mg/kg) was then instilled, followed by reinstitution of CPAP.
Respiratory indices were documented for 4 h following MIST, and neonatal outcomes ascertained. In all cases, surfactant was successfully administered and CPAP re-established. Coughing (32%) and bradycardia (44%) were transiently noted, and 44% received positive pressure inflations. There was a clear surfactant effect, with lower FiO(2) after MIST (pre-MIST: 0.39±0.092 (mean±SD); 4 h: 0.26±0.093; p<0.01), and a modest reduction in CPAP pressure. Adverse outcomes were few: intubation within 72 h (n=3), pneumothorax (n=1), chronic lung disease (n=3) and death (n=1), all in the 25-28-week group. Outcome was otherwise favourable in both gestation groups, with a trend towards reduction in intubation in the first 72 h in the 25-28-week infants compared with historical controls.
Surfactant can be effectively delivered via a vascular catheter, and this method of MIST deserves further investigation.
Background:
Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed.
Methods:
To ...examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25–28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a ‘study team’ uninvolved in clinical care including decision-making. Procedure duration and the study team’s words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: −0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated.
Results:
From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65–0.70). The Bang index was 0.28 (95% CI 0.23–0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12–0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm.
Conclusion:
Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials.
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