Surfactant Delivery Without Intubation in Preterm Infants
2022; American Academy of Pediatrics; Volume: 47; Issue: 4 Linguagem: Inglês
10.1542/gr.47-4-46
ISSN1556-326X
Tópico(s)Respiratory Support and Mechanisms
ResumoSource: Dargaville PA, Kamlin COF, Orsini F, et al. Effect of minimally invasive surfactant therapy vs sham treatment on death or bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome: the OPTIMIST-A randomized clinical trial. JAMA. 2021;326(24):2478-2487. doi:10.1001/jama.2021.21892Investigators from multiple institutions conducted a blinded randomized controlled trial to assess the effectiveness of intra-tracheal administration of surfactant via a thin catheter (minimally invasive surfactant treatment [MIST]) in premature infants treated with continuous positive airway pressure (CPAP) for respiratory distress syndrome. Participants were neonates born at 25-28 weeks’ gestation, treated with CPAP of 5-8 cm H2O and requiring a FiO2 of ≥0.30, and who were receiving care at 1 of 33 NICUs in 11 countries between 2011 and 2020. Study infants were randomized to MIST or a sham treatment (control) group; those in the MIST group received surfactant (200 mg/kg of poractant alfa) intratracheally via a 16-gauge catheter. The primary outcome was a composite of death or development of bronchopulmonary dysplasia (BPD) by 36 weeks postmenstrual age. Infants who were receiving mechanical ventilation, CPAP, or high-flow nasal cannula therapy, or required supplemental oxygen at an FiO2 of ≥0.30, or did not pass a room air test at 36 weeks post-menstrual age, were classified as having BPD. The main secondary outcomes were individual measures for death and BPD. There were multiple other secondary outcomes, including need for intubation within 72 hours of birth, pneumothorax, and development of patent ductus arteriosus (PDA). Generalized linear models were used to compare outcomes among neonates in the MIST and control groups, with gestational age included in the model. The investigators planned to enroll 606 participants in the study, but enrollment was discontinued in March 2020 due to the COVID-19 pandemic.A total of 488 neonates were enrolled in the study, and 485 were included in the primary analysis. The median gestational age of participants was 27.3 weeks; 241 were randomized to MIST and 244 to the control group. The primary outcome of death or BPD at 36 weeks postmenstrual age occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) of those randomized to the control group (risk reduction [RR], 0.87; 95% CI, 0.74, 1.03; P = 0.10). Among those randomized to MIST, 24 (10%) died prior to 36 weeks postmenstrual age compared to 19 (7.8%) of controls (RR, 1.27; 95% CI, 0.63, 2.57; P = 0.51). However, the rate of BPD was significantly lower in infants treated with MIST than controls (rates 37.3% and 45.3%, respectively; RR, 0.83; 95% CI, 0.70, 0.98; P = 0.03). The need for intubation by 72 hours, rate of pneumothorax, and incidence of PDA all were significantly lower among infants in the MIST group than in control infants.The authors conclude that MIST treatment was not associated with a decreased risk of death or BPD by 36 weeks postmenstrual age as a composite measure in premature infants receiving CPAP for respiratory distress syndrome.Dr Lesser has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Surfactant treatment for respiratory distress syndrome in premature infants decreases risk of BPD.1 Administration of surfactant has traditionally been achieved via intubation and mechanical ventilation, itself a risk factor for BPD.2 Methods of delivering surfactant that avoid intubation, if effective, may be an ideal strategy to reduce incidence of BPD.For the primary outcome, the current researchers used a composite of death or BPD assessed at 36 weeks’ gestation. Of note, only 1,192 of 5,187 infants screened were eligible, of which 488 were enrolled. Thus, within the necessary confines of the trial design, only a small segment of premature infants were ideal candidates for MIST. The trial occurred over a 10-year period and was halted at 81% of the target recruitment due to the COVID-19 pandemic. While the intervention did not reduce the primary outcome, this could have been due to underpowering. The authors point to the possibility of 14% absolute reduction in death or BPD based on the 95% CI. Several clinically meaningful secondary outcomes were improved in the treatment group. Incidence of BPD, pneumothorax, intubation within 72 hours, and duration of mechanical ventilation and CPAP all decreased in the treatment group compared to controls.The author of an accompanying editorial points out that while 72.1% of controls required intubation, it is unknown how many received surfactant or for how long they required intubation.3 Notably, the treatment group had an increase in death amongst the lowest gestational age (25-26 weeks). However, the causes of death were varied and could not be tied directly to the treatment. Although this finding could be related to a chance imbalance, the authors suggest caution in application of MIST in the most preterm infants, especially in regions facing high mortality within this gestational age.While the results of the current study do not definitively show efficacy of MIST for preterm infants based on the outcome of death or BPD, the improvement in secondary outcomes (eg, incidence of PDA) suggest it may have a role in care of neonates with RDS.
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