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

Date Published: June 10, 2019

Publisher: Public Library of Science

Author(s): Omer Erdeve, Emel Okulu, Gaffari Tunc, Yalcın Celik, Ugur Kayacan, Merih Cetinkaya, Gokhan Buyukkale, Hilal Ozkan, Nilgun Koksal, Mehmet Satar, Mustafa Akcali, Canan Aygun, Servet Ozkiraz, Umut Zubarioglu, Sezin Unal, Hatice Turgut, Kurthan Mert, Tulin Gokmen, Barıs Akcan, Begum Atasay, Saadet Arsan, Olivier Baud.


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.

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.

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).

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.

Partial Text

The use of conventional ventilation (CV) in newborn infants with respiratory failure saves lives, but its use is associated with lung injury and chronic lung disease (CLD). A newer form of ventilation, high-frequency oscillatory ventilation (HFOV), has been shown to result in less lung injury in both experimental and clinical studies [1,2]. As HFOV has been suggested as a useful element of lung protection strategies to achieve gas exchange goals in addition to mitigation of lung injury, infants who fail with CV are generally switched to HFOV in many neonatal intensive care units (NICUs) [3–5]. Despite its widespread adoption, especially in NICUs without extracorporeal membrane oxygenation (ECMO) capability, there have been no recent reports regarding this type of rescue HFOV.

Given the paucity of data regarding the use of rescue HFOV in newborn infants with severe respiratory insufficiency and the issues of designing and conducting large randomized controlled trials in newborns, we performed a prospective multicenter observational cohort trial using data from a national database with a large sample size. Our results indicated that rescue HFOV was successful in more than half of all cases of CV failure in newborns as defined by response to oxygenation. Although the response was not associated with GA, underlying disease, the device used, or initial ventilator settings, HOFV 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 positive response. We believe that data obtained from our observational prospective study may be helpful in selecting patients for rescue HFOV or refer them for ECMO if it is available. Rescue HFOV seems to be safe except a weak association with ROP and CLD disease. Although we observed an association between ROP and HFOV, it is hard to talk about a correlation, because the lung disease was severe in all patients being submitted to rescue HFOV. FiO2 were high in this patients putting them at risk for ROP, but this might be the same when HFOV would not have been used as a rescue mode, i.e. it would be probably the same with CV only.




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