The clinical effects of high-frequency oscillatory ventilation in the treatment of neonatal severe meconium aspiration syndrome complicated with severe acute respiratory distress syndrome

Neonatal meconium aspiration syndrome (MAS) is a type of postnatal dyspnoea resulting from the inhalation of meconium-contaminated amniotic fluid in utero or during delivery [1]. As a serious lung disease caused by meconium, MAS leads to airway obstruction and, subsequently, pulmonary surfactant (PS) inactivation, chemical pneumonia, and persistent pulmonary hypertension of the newborn (PPHN) [2].

In China, the mortality rate of infants with MAS is 7.0%–15.8% [3]. Severe MAS is often complicated by acute respiratory distress syndrome (ARDS), which leads to additional severe clinical symptoms, making treatment more difficult and increasing the fatality rate [4]. For uneven ventilation with partial alveolar collapse and excessive expansion, conventional mechanical ventilation (CMV) often fails to achieve the anticipated clinical effect.

Compared with CMV, high-frequency oscillatory ventilation (HFOV) has the advantages of low tidal volume, low airway pressure, and reduced alveolar injury; therefore, it is an ideal means of lung-protective ventilation.

Few domestic and foreign studies have been conducted on the therapeutic effects of different ventilation methods for children with severe MAS complicated with ARDS. Accordingly, this study aimed to compare the effects of the CMV and HFOV methods on infants with these conditions.

The small airways of children with MAS can become partially blocked by meconium, generating a valve effect. As a result, air is not easily discharged when exhaling; as a result, the alveoli can become over-inflated, leading to localised emphysema. Once scattered atelectasis is formed, if the small airway is completely blocked by meconium atelectasis, the child will be born with severe lung ventilation dysfunction. Due to a variety of factors including inactivated PS and chemical inflammation, acute and widespread destruction of the pulmonary alveolar–capillary barrier occurs, eventually causing ARDS [7]. The CMV method is the primary clinical technique for the treatment of severe MAS. In contrast, HFOV is recommended as a salvage treatment for severe respiratory failure in neonates, using low tidal volume (tidal volume <8 ml/kg), supra-physiologically high respiratory rate, and ventilation at a low respiratory pressure to improve gas exchange [8].

The results of this study showed that at 6, 12, 24 and 48 h after the start of mechanical ventilation, PaO₂ in the HFOV group was higher than in the CMV group, while PaCO₂ was lower in the HFOV group than in the CMV group, and all of these differences were statistically significant. Uneven airway ventilation and decreased pulmonary compliance are important pathological changes in severe MAS cases that initially manifest as severe hypoxaemia and/or carbon dioxide retention. Pulmonary gas distribution is more uniform when HFOV is adopted; thus, balanced alveolar ventilation can be better maintained and, accordingly, has an important role in improving poor oxygenation [9]. Additionally, when exhalation is still active, HFOV can reduce the occurrence of dynamic overinflation, which is conducive to the discharge of CO₂ and can effectively alleviate the occurrence of hypoxia and hypercapnia within a short time.

In the CMV group, the tidal volume was typically 8~10 ml/kg in the early stage of ARDS to maintain the SpO₂ fluctuation at 90%~95%. We believe that CMV requires a higher tidal volume and higher PIP to ensure ventilation in patients compared with relatively uniform and low-lung-volume disease. However, this can increase the risk of pulmonary air leakage, which is contrary to the treatment principles of neap tidal volume and low plateau pressure for ARDS [10, 11].

In a multi-centre study of 482 adults treated with mechanical ventilation, Needham et al. [12] found that the ARDS fatality rate increased by 23% for each 1 ml/kg of initially set tidal volume and by 15% for each 1 ml/kg increase in the tidal volume set by subsequent parameters. Zimova et al. [13] found that the median tidal volume of HFOV for maintaining a normal CO₂ level in neonatal non-interstitial pneumonia was 1.67 ml/kg. In a study of 53 preterm infants who received HFOV for neonatal RDS, Tuzud et al. [14] reported that a tidal volume >2.4 ml/kg was rarely needed to maintain normal PaCO₂ levels. This was consistent with our finding that normal blood gas could be maintained by setting an HFOV tidal volume <2.5 ml/kg. This indicated that the neap tide ventilation strategy of HFOV was suitable for the pathophysiological changes of MAS and ARDS.

Poddutoor et al. [15] demonstrated that the application of HFOV in the emergency treatment of neonatal acute lung injury could rapidly improve oxygenation and blood gas analysis results within 2 h from the start of ventilation. In the current study, we found that PaO₂/FiO₂ was higher in the HFOV compared with the CMV group at 6, 12, 24, 48, and 72 h after the start of mechanical ventilation, while the OI of the HFOV group was lower compared with the CMV group at these time points. The differences were statistically significant.

High-frequency oscillatory ventilation can reopen the small airway and the alveoli that have been occluded in calse of ARDS. This will provide effective ventilation and allow air exchange at a low alveolar inflation pressure and relatively constant pressure and volume, which can improve oxygen and maintain it at a high level for an extended time.

The Canadian Paediatric Society [16] recommends PS treatment for children undergoing mechanical ventilation for MAS. In the current study, both groups were given PS treatment in the early postnatal period, and pulmonary compliance improved rapidly as a result. In addition, the more appropriate ventilation mode effectively alleviated the severity of ARDS, making the mechanical ventilation duration and oxygen use time in the HFOV group shorter.

As a special ventilation method, there remains controversy regarding the safety of the clinical application of HFOV, particularly in terms of the risk of air leakage and intracranial haemorrhage [17]. In this study, there was a lower incidence of air leakage in the HFOV group than in the CMV group, and there were no statistically significant differences in the incidence of intracranial haemorrhage and other complications between the two groups.

Overall, HFOV can reduce the extent of lung injury caused by local lung overexpansion and repeated alveolar opening and closing, optimise the ventilation effect, and reduce the occurrence of air leakage. It can also significantly alleviate PaCO₂ issues and effectively maintain this aspect at normal levels, thus avoiding the risk of cerebral vasodilation and increased cerebral blood flow caused by hypercapnia.

When collecting the data, we found a higher incidence of intermittent hypoxemia in the CMV group, which may have contributed to the occurrence of or further deterioration of cases of PPHN. The superior pulmonary ventilation effect of HFOV could reduce intrapulmonary shunt, which was conducive to the action of NO on pulmonary vessels and improved oxygenation. Although this research was a retrospective study with a small sample size, and large-scale clinical studies are needed to further clarify the optimal application time of HFOV and its influence on the prognosis of ARDS, our findings support HFOV as a safe and effective option for the treatment of MAS.

One of the reasons why HFOV is better suitable for neonates compared with other patient groups is because a smaller body surface area results in improved lung tissue resonance and corresponding ventilation effects. Using HFOV can improve ventilation and oxygenation in patients with severe MAS [18], alleviate lung inflammatory reactions [19], effectively relieve the severity of ARDS [20] and shorten the duration of mechanical ventilation and oxygen use, thereby allowing patients to reach the remission stage quickly. Accordingly, it is more in line with the pulmonary protective ventilation strategy than CMV [21] and is worthy of clinical promotion.

There were several limitations in this study. First, the research was a retrospective study, as opposed to a randomised controlled trial; accordingly, bias was introduced. Second, based on our design, the targeted tidal volumes were 8–10 ml/kg, which may have had some influence on the efficacy of the treatments. Third, although the results regarding OI were statistically significant, few of our additional findings were clinically significant; therefore, further research on this topic is needed in the future.

Overall, HFOV can effectively improve lung ventilation and oxygenation function, shorten ventilator treatment time, and reduce the incidence of air leakage for neonatal MAS, making it a safe and effective treatment method.