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EBNEO COMMENTARY: REDUCING EXTUBATION FAILURE IN EXTREME PRETERM INFANTS – HIGHER VS STANDARD NCPAP


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Rashida Javed and Harsha Gowda from University Hospitals, Birmingham, UK review EbNeo October Article of the Month "Kidman AM, Manley BJ, Boland RA, et al. Higher versus lower nasal continuous positive airway pressure for extubation of extremely preterm infants in Australia (ÉCLAT): a multicentre, randomised, superiority trial. Lancet Child Adolesc Health. 2023 Dec;7(12):844-851. https://doi.org/10.1016/S2352-4642(23)00235-3. Epub 2023 Oct 27. PMID: 38240784."

READ HERE!

Hear it discussed on the Incubator Podcast!

Acta Commentary:

Acta Paediatrica - 2024 - Javed - EBNEO Commentary Reducing extubation failure in extreme preterm infants higher vs.pdf

Despite advances in non-invasive respiratory support, extremely preterm infants experience extubation failure frequently which can be associated with morbidity and mortality1. The increased risk of extubation failure is due to lung immaturity, poor chest compliance and immature respiratory drive2.

Nasal continuous positive airway pressure (nCPAP) or high flow have been the mainstay of post extubation respiratory support3. Following extubation, nCPAP settings vary between centers. Higher set nCPAP levels post extubation may help to maintain end expiratory lung volume and reduce atelectasis. But, a small pilot RCT by Kitsommart et al in 2013 comparing high vs low nCPAP pressures showed no difference in extubation failure rates4.

In the ECLAT study, extubating infants less than 28-week gestation to a higher nCPAP of 10cmH2O reduced extubation failure (35% – 24/69 infants) compared to standard nCPAP group (57% – 39/69 infants) with risk difference of -21.7%, 95% CI -38.5% to -3.7%. The number needed to treat was 5 infants meaning five infants needed to receive higher nCPAP to standard nCPAP to prevent one additional extubation failure. Stratification for gestational age subgroups (22-25 and 26-27 completed weeks) also showed a lower extubation failure rate in the nCPAP group receiving higher pressures, especially in the more mature subgroup. However, the study was underpowered for subgroup analysis. The secondary outcomes showed no significant differences between groups which was also underpowered. The most common adverse events, such as pneumothorax, pulmonary interstitial emphysema, spontaneous intestinal perforation, and death were similar in both groups. All infants had exogenous surfactant prior to recruitment which might had contributed to minimal incidence of pneumothorax in higher nCPAP group.

13(19%) infants in standard nCPAP group and 2(3%) in higher nCPAP deviated from protocol to increased nCPAP level above the prescribed level. All these infants were eventually re-intubated within the primary outcome period. Recruitment ceased at 74% of planned sample size due to recurrent pauses during COVID-19 pandemic.  Other limitations are clinicians were not blinded and actual distending pressure in alveoli was not measured. Also, there were no standardized criteria for readiness for extubation.

Inspite of above limitations, it is a well-designed randomized control trial showing benefits of higher nCPAP reducing extubation failure. Buzzella et al did randomized control trial in 93 infants of less than 30 weeks gestational age to a higher nCPAP of 7-9 cmH2O or a lower nCPAP of 4-6 cmH2O and found a significant reduction in extubation failure in higher nCPAP group5. But in the ECLAT trial, a much higher nCPAP was used and more immature infants were included. All the extubation failure in higher nCPAP group occurred in first 72hours and nil between 73-168 hours compared to 12 in standard nCPAP group. Probably this suggests the importance of high alveoli end expiratory pressure after extubation to prevent later atelectasis and extubation failure.

To conclude, the ECLAT study provides evidence for the use of higher nCPAP in infants less than 28 weeks’ gestation to reduce extubation failure compared to standard nCPAP. There was no difference in BPD rates observed, so the benefit of higher nCPAP (9-11 cmH2O) is questionable. Further large RCT adequately powered to compare BPD rates is required to better evaluate the safety and efficacy of higher post-extubation nCPAP levels on outcomes of greater importance to clinicians and families.'

References:

Razak A, Shah PS, Ye XY, Mukerji A. Post‐extubation use of non‐invasive respiratory support in preterm infants: a network meta‐analysis. Cochrane Database Syst Rev. 2021;2021(10):CD014509. Published 2021 Oct 25.

Kidman AM, Manley BJ, Boland RA, Davis PG, Bhatia R. Predictors and outcomes of extubation failure in extremely preterm infants. J Paediatr Child Health. 2021;57(6):913–9.

Awanti, Srinivas & Pol, Ramesh & Katti, Arun. (2023). A randomized controlled trial to compare the success rates and efficacy of high flow nasal cannulae versus nasal continuous positive airway pressure in post extubation period in neonates. International Journal of Contemporary Pediatrics. 10. 510-513. 10.18203/2349-3291.ijcp20230728.

Kitsommart R, MHSc AK, Al-Saleem N. Levels of nasal CPAP applied during the immediate post- extubation phase. A Randomized Controlled Pilot Trial2013;3:9.

Buzzella B, Claure N, D’Ugard C, Bancalari E. A randomized controlled trial of two nasal continuous positive airway pressure levels after extubation in preterm infants. J Pediatr 2014; 164: 46–51.

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  • 1 month later...

So, despite observing a decrease in extubation failures, there was no discernible effect on BPD. Nevertheless, considering the established association between invasive ventilation and BPD, how do we reconcile these two outcomes?

Could it be a matter of sample size, or perhaps it relates to the specific method of invasive ventilation employed?

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