Research Article: Controlled hypothermia may improve surfactant function in asphyxiated neonates with or without meconium aspiration syndrome

Date Published: February 8, 2018

Publisher: Public Library of Science

Author(s): Chiara Autilio, Mercedes Echaide, Daniele De Luca, Jesús Pérez-Gil, Jorge Bernardino de la Serna.


Whole-body hypothermia (WBH) is used to improve neurological outcomes in perinatal asphyxia. Recent studies suggested a beneficial effect of hypothermia for some types of acute respiratory failure. However, no data are available about the biophysical function of human surfactant during WBH. We investigated whether WBH improves surfactant biophysical properties in asphyxiated neonates with or without meconium aspiration syndrome (MAS).

Non-bronchoscopic bronchoalveolar lavage (BAL) has been collected from 10 asphyxiated neonates (2 with MAS, 8 with no lung disease (NLD)) at different time-points (pre-WBH, 24h, 48h, 72h of WBH and post-WBH). Surfactant was extracted and tested by captive bubble surfactometry (CBS) in triplicate, at 37°C and 33.5°C, through initial adsorption and dynamic compression-expansion cycling. Phosphatidylcholine and cholesterol were assayed using enzymatic methods. Clinical data were recorded in real-time.

Minimum surface tension under dynamic testing was significantly improved as assessed at 33.5°C compared with its behavior at 37°C in NLD neonates: the difference was evident after at least 72h of WBH and remained significant at 6h after rewarming (72h: p = 0.009; rewarming: p = 0.040). Similar results were obtained in MAS patients whose surfactant activity improved already at 48h of hypothermia. Total cholesterol showed a trend to increase at the first 24-48h of hypothermia in NLD patients. Conversely, hypothermia seemed to reduce the excess of exogenous cholesterol in MAS surfactant.

Surfactant biophysical properties may improve after 48-72h of WBH in asphyxiated neonates and the improvement is maintained shortly after rewarming. Due to study limitations, further studies are warranted to better clarify the effects of hypothermia on surfactant activity.

Partial Text

Controlled hypothermia is an effective treatment for encephalopathy due to perinatal asphyxia. Cooling is usually applied as whole-body hypothermia (WBH) at a constant servo-controlled temperature of 33.5°C, starting early from birth and continuing for the following 72h [1–3]. The beneficial effect of WBH on the neonatal brain is well known but there are scanty data about its effect on other organs. Short preliminary reports have suggested a possible usefulness of hypothermia for acute respiratory distress syndrome (ARDS) or necrotising enterocolitis [4–7]. In the newborn lung, this effect might be due to the reduction in inflammatory mediators and to the improvement of lung mechanics [8,9]. Thus, controlled hypothermia could be theoretically useful for respiratory conditions characterised by high lung tissue inflammation. For instance, WBH seems to improve short term oxygenation and clinical outcomes in neonates with meconium aspiration syndrome (MAS), which is often associated with perinatal asphyxia [10].

Fig 3 shows that no significant differences are evident in surfactant initial adsorption at different time-points within the patients, irrespective of the experimental temperature (p = 0.484 and p = 0.281, for 37°C and 33.5°C, respectively). During the first 20” of adsorption, there is a quick surface tension decay both at 37°C and 33.5°C, and then a further slow decrease towards the apparent equilibrium (see Fig 3 and Table 2). While reaching the equilibrium, initial adsorption seems slightly worse for the experiment at 33.5°C, than for that at 37°C. Data were significantly different for the fast kinetics (that is, for 1” and 5” of initial adsorption) for the whole cohort [33.5°C (at 1”: 49.2 (5.1) mN/m; at 5”: 46.3 (4.9) mN/m) and 37°C (at 1”: 46.8 (5.1) mN/m, overall p = 0.047; at 5” 43.9 (4.9) mN/m, overall p = 0.046] and for NLD subgroup [33.5°C (at 1”: 48.4 (5.1) mN/m; at 5”: 46.0 (5.0) mN/m) and 37°C (at 1”: 46.2 (5.2) mN/m, overall p = 0.023; at 5” 43.4 (5.1) mN/m, overall p = 0.047]. All data and post-hoc comparisons are shown in Table 2. Once the equilibrium has been reached (that is, beyond the first 20”) no differences are evident between the two temperatures.

To the best of our knowledge, scanty data are available about the effect of WBH on biophysical properties of human surfactant. In a previous preliminary study, we showed improved interfacial adsorption at 48h of hypothermia [9]. However, these data were obtained analysing the mere kinetics of surfactant accumulation into the air/liquid interface in a simplified plate fluorescent assay [33]. This technique can only assess the capability of surfactant to form a surface-associated layer, but it cannot provide any detailed information about surface tension and how surfactant stabilizes the interface during breathing-like compression-expansion cycles.




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