The best ventilation strategy to prevent chronic lung disease, one of the most significant complications in preterm infants, has been evaluated in a Canadian meta-analysis.
The study compared seven different ventilation strategies. Based on data collected from 30 different trials and over 5,500 infants younger than 33 weeks’ gestational age, the lead author of the study, Dr Tetsuya Isayama, said one strategy appeared more effective than most.
Using and promoting this strategy will have major global ramifications, he said. “These preterm infants have a high risk of death or severe complications, many of which come from the fact that their lungs have not yet fully developed,” said Isayama, a PhD candidate in department of clinical epidemiology and biostatistics at the Michael G DeGroote School of Medicine,. McMaster University.
“Although a number of factors contribute to long-term breathing problems, or chronic lung disease, one of the major factors is lung injury from too much pressure and expansion from the breathing machine with a large breathing tube in the windpipe. Therefore, it is important to select as gentle breathing assistance as possible for preterm infants – but until this study, the best method was not known.”
The recommended strategy called LISA, or Less Invasive Surfactant Administration (on Continuous Positive Airway Pressure) was the best in preventing the primary outcome of death and/or chronic lung disease as well as other secondary outcomes including severe intra-ventricular haemorrhage and air leak.
LISA is a non-invasive ventilation strategy in which infants are given surfactant – a substance that keeps the tiny air sacs in the lung open – through a soft, thin tube placed in the windpipe while a breathing mask over the baby’s nose supports respiration. The advantage of LISA is that it can maintain pressure to the baby’s lungs to keep them open while surfactant is being given, while avoiding the use of a breathing tube and too much pressure.
The study found that LISA, on average, resulted in 164 fewer pre-term babies per 1000 dying or having long term breathing problems compared to those when a large breathing tube was inserted into a windpipe and a breathing machine was used.
The originator of the study, Dr Sarah McDonald, said that these are very promising results. “This finding is important for all clinicians globally who resuscitate premature infants as well as researchers and clinical guideline developers who are involved in the management of preterm infants,” said McDonald, a professor in McMaster’s department of obstetrics and gynaecology. “The next step is to determine which infants require surfactant and which do not. We also need to determine which babies with gentler breathing assistance get tired and need more breathing support, and need to eventually be placed on a breathing machine.”
Importance: Various noninvasive ventilation strategies are used to prevent bronchopulmonary dysplasia (BPD)of preterm infants; however, the best mode is uncertain.
Objective: To compare 7 ventilation strategies for preterm infants including nasal continuous positive airway pressure (CPAP) alone, intubation and surfactant administration followed by immediate extubation (INSURE), less invasive surfactant administration (LISA), noninvasive intermittent positive pressure ventilation, nebulized surfactant administration, surfactant administration via laryngeal mask airway, and mechanical ventilation.
Data Sources: MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions to June 2016.
Study Selection: Randomized clinical trials comparing ventilation strategies for infants younger than 33 weeks’ gestational age within 24 hours of birth who had not been intubated.
Data Extraction and Synthesis: Data were independently extracted by 2 reviewers and synthesized with Bayesian random-effects network meta-analyses.
Main Outcomes and Measures: A composite of death or BPD at 36 weeks’ postmenstrual age was the primary outcome. Death, BPD, severe intraventricular hemorrhage, and air leak by discharge were the main secondary outcomes.
Results: Among 5598 infants involved in 30 trials, the incidence of the primary outcome was 33% (1665 of 4987; including 505 deaths and 1160 cases of BPD). The secondary outcomes ranged from 6% (314 of 5587) for air leak to 26% (1160 of 4455) for BPD . Compared with mechanical ventilation, LISA had a lower odds of the primary outcome (odds ratio [OR], 0.49; 95% credible interval [CrI], 0.30-0.79; absolute risk difference [RD], 164 fewer per 1000 infants; 57-253 fewer per 1000 infants; moderate quality of evidence), BPD(OR, 0.53; 95% CrI, 0.27-0.96; absolute RD, 133 fewer per 1000 infants; 95% CrI, 9-234 fewer per 1000 infants; moderate-quality), and severe intraventricular hemorrhage (OR, 0.44; 95% CrI, 0.19-0.99; absolute RD, 58 fewer per 1000 births; 95% CrI, 1-86 fewer per 1000 births; moderate-quality). Compared with nasal CPAP alone, LISA had a lower odds of the primary outcome (OR, 0.58; 95% CrI, 0.35-0.93; absolute RD, 112 fewer per 1000 births; 95% CrI, 16-190 fewer per 1000 births; moderate quality), and air leak (OR, 0.24; 95% CrI, 0.05-0.96; absolute RD, 47 fewer per 1000 births; 95% CrI, 2-59 fewer per 1000 births; very low quality). Ranking probabilities indicated that LISA was the best strategy with a surface under the cumulative ranking curve of 0.85 to 0.94, but this finding was not robust for death when limited to higher-quality evidence.
Conclusions and Relevance: Among preterm infants, the use of LISA was associated with the lowest likelihood of the composite outcome of death or BPD at 36 weeks’ postmenstrual age. These findings were limited by the overall low quality of evidence and lack of robustness in higher-quality trials.
Tetsuya Isayama; Hiroko Iwami; Sarah McDonald; Joseph Beyene