Spontaneous Breathing or Mechanical Ventilation Alters Lung Compliance and Tissue Association of Exogenous Surfactant in Preterm Newborn Rabbits

Abstract

In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant ( 14 C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 Ϯ 10% (mean Ϯ SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml ⅐ cm H 2 O Ϫ1 ⅐ kg Ϫ1, respectively; p Ͻ 0.05). The relative distribution of 14 C-Curosurf in bronchoalveolar lavage fluid and homogenized lung tissue showed a higher degree of tissue association in the spontaneously breathing animals [53 Ϯ 4 versus 26 Ϯ 3% (mean Ϯ SEM)] than in mechanically ventilated animals (p Ͻ 0.01), the latter figure being very similar to that of the control group (25 Ϯ 5%). There was a higher degree of lipid peroxidation and fewer microbubbles in bronchoalveolar lavage fluid from mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation. In neonates with respiratory distress syndrome (RDS), exogenous surfactant has become a standard treatment (1). In humans, the effective mode of administration is instillation into the airways. This requires intubation, which means that surfactant treatment is usually given in conjunction with mechanical ventilation. With increasing knowledge of the detrimental effects of mechanical ventilation on the immature lung, there is a need for alternative treatment approaches. Early nasal continuous positive airway pressure (nCPAP) has been shown to be beneficial as initial treatment of RDS also in very low birth weight infants (2,3). With the administration of exogenous surfactant during a short intubation, followed by immediate extubation to nCPAP, the need for mechanical ventilation is reduced in preterm infants with RDS (4,5). In most of these patients, a single dose of surfactant is sufficient to reverse the clinical course of RDS, whereas in mechanically ventilated infants, multiple doses are often required (6). On the basis of these clinical observations, we hypothesized that the duration of the treatment response would be better and more sustained if infants were allowed to breathe spontaneously after receiving s...

Implementation of surfactant treatment during continuous positive airway pressure

“…We have previously reported the impaired tissue association of exogenous surfactant in preterm rabbits after MV compared with spontaneous breathing. 5 This finding was associated with a lower dynamic compliance and evidence of surfactant inactivation and constitutes a possible explanation to an attenuated treatment response after surfactant administration followed by MV. These data demonstrate that the immediate improvement in oxygenation following INSURE was sustained over the 48 h following treatment, which may have contributed to the low requirement for surfactant re-treatment.…”

“…3,4 We have previously shown that in premature rabbits, surfactant administration followed by MV resulted in impaired treatment response and a greater degree of surfactant inactivation than surfactant treatment followed by spontaneous breathing. 5 Furthermore, MV has been implicated as the single most important risk factor for the later development of bronchopulmonary dysplasia (BPD). 6,7 Surfactant treatment of spontaneously breathing infants by transient intubation was first reported in 1990 in a study performed in Kuwait, where MV was not available at the time.…”

Effects of less-invasive surfactant administration on oxygenation, pulmonary surfactant distribution, and lung compliance in spontaneously breathing preterm lambs

“…It is a surprising result that, despite lower deposition of surfactant in the lungs, oxygenation was similar between the lambs that received LISA and the intubated lambs. This may be caused by the fact that in spontaneous breathing animals, exogenous surfactant has a higher tissue association and leads to a higher dynamic lung compliance compared to the ventilated animals, as was shown in a rabbit model by Bohlin et al (16).…”

Minimally Invasive Surfactant Therapy: New Age

“…This catheter is stiffer than the feeding tube, being easier to guide it through the vocal cords under direct vision without using Magill's forceps [15][16][17][18]. The surfactant administration during a noninvasive respiratory support is associated with a better distribution of the surfactant, as shown in animal models [19].…”